2010ACOG Compendium

THE AMERICAN COLLEGE OF
OBSTETRICIANS AND GYNECOLOGISTS

W OMEN S H EALTH C ARE P HYSICIANS
COMPENDIUM
of Selected Publications
The Compendium of Selected Publications CD-ROM contains all Committee Opinions,

Practice Bulletins, Policy Statements, and Technology Assessments published by the
American College of Obstetricians and Gynecologists (the College) as of December 31,
2009. The information in these documents should not be viewed as establishing standards
or dictating rigid rules. The guidelines are general and intended to be adapted to many
different situations, taking into account the needs and resources particular to the locality, the
institution, or the type of practice. Variations and innovations that improve the quality of
patient care are to be encouraged rather than restricted. The purpose of these guidelines will
be well served if they provide a firm basis on which local norms may be built.
Copyright 2010 by the American College of Obstetricians and Gynecologists. All rights
reserved. No part of this publication may be reproduced, stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permission from the publisher.
The American College of Obstetricians and Gynecologists
409 12th Street, SW
PO Box 96920
Washington, DC 20090-6920
ISBN: 978-1-934946-88-6
Publications can be ordered through the College Distribution Center by calling toll free
800-762-2264. To receive order forms via facsimile, call (732) 885-6364 and follow the audio
instructions. Publications also can be ordered from the College web site at www.acog.org.
The following resources from the College also contain College practice
guidelines and should be considered adjuncts to the documents in the
Compendium of Selected Publications CD-ROM.
Guidelines for Perinatal Care, Sixth Edition
Guidelines for Womens Health Care, Third Edition
Health Care for Adolescents
Special Issues in Womens Health
These documents are available online to members at www.acog.org
SEARCH
Contents
F OREWORD
xi
T HE S COPE
C ODE
OF
OF
P RACTICE
OF
O BSTETRICS
AND
G YNECOLOGY
P ROFESSIONAL E THICS
xii
xiii
C OMMITTEE O PINIONS
C OMMITTEE
302
310
314
344
349
350
351
355
392
415
417
*448
*451
C OMMITTEE
205
249
250
C OMMITTEE
297
321
341
347
352
358
ON
A DOLESCENT H EALTH C ARE
Guidelines for Adolescent Health Research

Endometriosis in Adolescents
Meningococcal Vaccination for Adolescents
Human Papillomavirus Vaccination
(Joint with the ACOG Working Group on Immunization)
Menstruation in Girls and Adolescents: Using the Menstrual Cycle as a Vital Sign
(Joint with the American Academy of Pediatrics)
Breast Concerns in the Adolescent
The Overweight Adolescent: Prevention, Treatment, and ObstetricGynecologic Implications
Vaginal Agenesis: Diagnosis, Management, and Routine Care
Intrauterine Device and Adolescents
Depot Medroxyprogesterone Acetate and Bone Effects
(Joint with Committee on Gynecologic Practice)
Addressing Health Risks of Noncoital Sexual Activities
Menstrual Manipulation for Adolescents with Disabilities
Von Willebrand Disease in Women
ON
C ODING
AND
3
7
14
17
24
30
38
50
55
58
62
65
69
N OMENCLATURE
Tubal Ligation with Cesarean Delivery

Coding Responsibility
Inappropriate Reimbursement Practices by Third-Party Payers
77
78
79
ON E THICS
Nonmedical Use of Obstetric Ultrasonography
Maternal Decision Making, Ethics, and the Law
Ethical Ways for Physicians to Market a Practice
Using Preimplantation Embryos for Research
Innovative Practice: Ethical Guidelines
Professional Responsibilities in ObstetricGynecologic Education
85
87
98
102
115
122
*Published in 2009
iii
iv
COMPENDIUM OF SELECTED PUBLICATIONS
C OMMITTEE
359
360
362
363
364
365
368
369
370
371
373
374
377
385
389
390
395
397
401
403
409
410
422
*439
C OMMITTEE
318
324
325
338
393
399
*430
*432
*442
*446
*449
1
ON E THICS (continued)
Commercial Enterprises in Medical Practice
Sex Selection
Medical Futility
Patient Testing: Ethical Issues in Selection and Counseling
Patents, Medicine, and the Interests of Patients (Joint with Committee on Genetics)
Seeking and Giving Consultation
Adoption
Multifetal Pregnancy Reduction
Institutional Responsibility to Provide Legal Representation
Sterilization of Women, Including Those With Mental Disabilities
Sexual Misconduct
Expert Testimony
Research Involving Women
The Limits of Conscientious Refusal in Reproductive Medicine
Human Immunodeficiency Virus
Ethical Decision Making in Obstetrics and Gynecology
Surgery and Patient Choice
Surrogate Motherhood
Relationships With Industry
End-of-Life Decision Making
Direct-to-Consumer Marketing of Genetic Testing (Joint with Committee on Genetics)
Ethical Issues in Genetic Testing (Joint with Committee on Genetics)
At-Risk Drinking and Illicit Drug Use: Ethical Issues in Obstetric and Gynecologic Practice
Informed Consent
ON
126
129
133
137
140
145
150
154
159
161
165
169
171
177
183
189
198
203
209
215
222
224
232
244
G ENETICS
Screening for TaySachs Disease

Perinatal Risks Associated With Assisted Reproductive Technology
(Joint with Committees on Obstetric Practice and Gynecologic Practice)
Update on Carrier Screening for Cystic Fibrosis
Screening for Fragile X Syndrome
Newborn Screening
Umbilical Cord Blood Banking (Joint with Committee on Obstetric Practice)
Preimplantation Genetic Screening for Aneuploidy
Spinal Muscular Atrophy
Preconception and Prenatal Carrier Screening for Genetic Diseases
in Individuals of Eastern European Jewish Descent
Array Comparative Genomic Hybridization in Prenatal Diagnosis
Maternal Phenylketonuria
Genetics and Molecular Diagnostic Testing
*Published in 2009
Technology Assessment
255
257
261
265
268
272
275
277
280
284
287
289
CONTENTS
C OMMITTEE
240
253
278
280
313
319
322
323
332
334
336
337
345
372
375
378
384
387
388
396
405
407
408
411
412
413
420
*434
*440
*444
*450
*452
4
5
*6
ON
G YNECOLOGIC P RACTICE
Statement on Surgical Assistants (Joint with Committee on Obstetric Practice)

Nongynecologic Procedures
Avoiding Inappropriate Clinical Decisions Based
on False-Positive Human Chorionic Gonadotropin Test Results
The Role of the Generalist ObstetricianGynecologist in the Early
Detection of Ovarian Cancer (Joint with Society of Gynecologic Oncologists)
The Importance of Preconception Care in the Continuum of Womens Health Care
The Role of the ObstetricianGynecologist in the Assessment and Management of Obesity
Compounded Bioidentical Hormones
Elective Coincidental Appendectomy
Hepatitis B and Hepatitis C Virus Infections in ObstetricianGynecologists
Role of the ObstetricianGynecologist in the Screening and Diagnosis of Breast Masses
Tamoxifen and Uterine Cancer
Noncontraceptive Uses of the Levonorgestrel Intrauterine System
Vulvodynia (Joint with American Society for Colposcopy and Cervical Pathology)
The Role of Cystourethroscopy in the Generalist ObstetricianGynecologist Practice
Brand Versus Generic Oral Contraceptives
Vaginal Rejuvenation and Cosmetic Vaginal Procedures
Colonoscopy and Colorectal Cancer Screening and Prevention
Pharmaceutical Compounding
Supracervical Hysterectomy
Intraperitoneal Chemotherapy for Ovarian Cancer
Ovarian Tissue and Oocyte Cryopreservation
Low Bone Mass (Osteopenia) and Fracture Risk
Professional Liability and Gynecology-Only Practice
(Joint with Committees on Obstetric Practice and Professional Liability)
Routine Human Immunodeficiency Virus Screening
Aromatase Inhibitors in Gynecologic Practice
Age-Related Fertility Decline (Joint with American Society for Reproductive Medicine)
Hormone Therapy and Heart Disease
Induced Abortion and Breast Cancer Risk
The Role of Transvaginal Ultrasonography in the Evaluation of Postmenopasual Bleeding
Choosing the Route of Hysterectomy for Benign Diseases
Increasing Use of Contraceptive Implants and Intrauterine Devices to Reduce
Unintended Pregnancy (Joint with the Long Acting Reversible Contraception Working Group)
Primary and Preventive Care: Periodic Assessments
Hysteroscopy
Sonohysterography
Robot-Assisted Surgery
*Published in 2009
Technology Assessment
311
312
313
316
319
321
326
328
330
332
334
338
342
346
350
352
354
358
360
363
366
368
371
372
375
378
381
385
387
390
393
398
406
410
413
vi
C OMMITTEE
307
312
316
317
343
361
391
414
416
*423
*424
*425
*428
*429
*437
C OMMITTEE
*427
C OMMITTEE
125
234
260
267
268
275
276
279
281
284
295
299
305
315
326
333
339
340
ON
H EALTH C ARE
FOR
U NDERSERVED W OMEN
Partner Consent for Participation in Womens Reproductive Health Research

Health Care for Homeless Women
Smoking Cessation During Pregnancy (Joint with Committee on Obstetric Practice)
Racial and Ethnic Disparities in Womens Health
Psychosocial Risk Factors: Perinatal Screening and Intervention
Breastfeeding: Maternal and Infant Aspects (Joint with Committee on Obstetric Practice)
Health Literacy
Human Immunodeficiency Virus and Acquired Immunodeficiency
Syndrome and Women of Color
The Uninsured
Motivational Interviewing: A Tool for Behavior Change
Abortion Access and Training
Health Care for Undocumented Immigrants
Legal Status: Health Impact for Lesbian Couples
Health Disparities for Rural Women
Community Involvement and Volunteerism
ON I NTERNATIONAL
485
O BSTETRIC P RACTICE
Placental Pathology
Scheduled Cesarean Delivery and the Prevention of Vertical Transmission of HIV Infection
Circumcision
Exercise During Pregnancy and the Postpartum Period
Management of Asymptomatic Pregnant or Lactating Women Exposed to Anthrax
Obstetric Management of Patients with Spinal Cord Injuries
Safety of Lovenox in Pregnancy
Prevention of Early-Onset Group B Streptococcal Disease in Newborns
Rubella Vaccination
Nonobstetric Surgery in Pregnancy
Pain Relief During Labor (Joint with American Society of Anesthesiologists)
Guidelines for Diagnostic Imaging During Pregnancy
Influenza Vaccination and Treatment During Pregnancy
Obesity in Pregnancy
Inappropriate Use of the Terms Fetal Distress and Birth Asphyxia
The Apgar Score (Joint with American Academy of Pediatrics)
Analgesia and Cesarean Delivery Rates
Mode of Term Singleton Breech Delivery
*Published in 2009
452
456
460
464
468
472
476
480
A FFAIRS
Misoprostol for Postabortion Care
ON
419
422
428
434
438
447
449
491
492
495
497
500
503
506
508
516
517
518
519
524
526
531
533
537
539
CONTENTS
C OMMITTEE
342
346
348
376
379
381
382
394
402
404
418
419
421
*433
*435
*438
*441
*443
*445
C OMMITTEE
380
406
C OMMITTEE
320
327
328
329
331
353
366
367
398
400
*447
ON
O BSTETRIC P RACTICE (continued)
Induction of Labor for Vaginal Birth After Cesarean Delivery

Amnioinfusion Does Not Prevent Meconium Aspiration Syndrome
Umbilical Cord Blood Gas and Acid-Base Analysis
Nalbuphine Hydrochloride Use for Intrapartum Analgesia
Management of Delivery of a Newborn With Meconium-Stained Amniotic Fluid
Subclinical Hypothyroidism in Pregnancy
Fetal Monitoring Prior to Scheduled Cesarean Delivery
Cesarean Delivery on Maternal Request
Antenatal Corticosteroid Therapy for Fetal Maturation
Late-Preterm Infants
Prenatal and Perinatal Human Immunodeficiency Virus Testing:
Expanded Recommendations
Use of Progesterone to Reduce Preterm Birth
(Joint with Society for Maternal Fetal Medicine)
Antibiotic Prophylaxis for Infective Endocarditis
Optimal Goals for Anesthesia Care in Obstetrics
(Joint with American Society of Anesthesiologists)
Postpartum Screening for Abnormal Glucose Tolerance in Women Who Had
Gestational Diabetes Mellitus
Update on Immunization and Pregnancy: Tetanus, Diphtheria, and Pertussis Vaccination
Oral Intake During Labor
Air Travel During Pregnancy
Antibiotics for Preterm Labor (Joint with Society for Maternal Fetal Medicine)
ON
542
545
548
552
553
554
556
557
561
564
568
572
575
577
580
583
586
587
589
P ROFESSIONAL L IABILITY
Disclosure and Discussion of Adverse Events (Joint with Committee on Patient Safety and
Quality Improvement)
Coping With the Stress of Medical Professional Liability Litigation
ON PATIENT S AFETY AND
593
595
Q UALITY I MPROVEMENT
Partnering With Patients to Improve Safety

Do Not Use Abbreviations
Patient Safety in the Surgical Environment
Tracking and Reminder Systems
Safe Use of Medication
Medical Emergency Preparedness
Disruptive Behavior
Communication Strategies for Patient Handoffs
Fatigue and Patient Safety
Technologic Advances to Reduce Medication-Related Errors
Patient Safety in Obstetrics and Gynecology
*Published in 2009
vii
599
602
604
609
612
616
619
621
624
627
631
viii
R EADING
THE
M EDICAL L ITERATURE
637
P RACTICE B ULLETINS
C OMMITTEE
4
6
9
12
13
17
19
20
22
24
29
30
31
33
36
37
38
40
43
44
48
49
52
54
55
56
60
68
71
75
76
77
78
80
ON
P RACTICE B ULLETINS O BSTETRICS
Prevention of Rh D Alloimmunization
Thrombocytopenia in Pregnancy
Antepartum Fetal Surveillance
Intrauterine Growth Restriction
External Cephalic Version
Operative Vaginal Delivery
Thromboembolism in Pregnancy
Perinatal Viral and Parasitic Infections
Fetal Macrosomia
Management of Recurrent Early Pregnancy Loss
Chronic Hypertension in Pregnancy
Gestational Diabetes
Assessment of Risk Factors for Preterm Birth
Diagnosis and Management of Preeclampsia and Eclampsia
Obstetric Analgesia and Anesthesia
Thyroid Disease in Pregnancy
Perinatal Care at the Threshold of Viability
Shoulder Dystocia
Management of Preterm Labor
Neural Tube Defects
Cervical Insufficiency
Dystocia and Augmentation of Labor
Nausea and Vomiting of Pregnancy
Vaginal Birth After Previous Cesarean Delivery
Management of Postterm Pregnancy
Multiple Gestation: Complicated Twin, Triplet, and High-Order Multifetal Pregnancy
(Joint with Society for MaternalFetal Medicine)
Pregestational Diabetes Mellitus
Antiphospholipid Syndrome
Episiotomy
Management of Alloimmunization During Pregnancy
Postpartum Hemorrhage
Screening for Fetal Chromosomal Abnormalities
(Joint with Committee on Genetics and the Society for MaternalFetal Medicine)
Hemoglobinopathies in Pregnancy
Premature Rupture of Membranes
*Published in 2009
647
655
666
677
689
696
704
714
727
738
750
759
773
781
790
805
815
823
829
838
849
858
868
881
891
899
914
925
934
940
948
957
968
977
CONTENTS
C OMMITTEE
82
86
88
90
92
95
97
*100
*101
*102
*105
*106
*107
251
C OMMITTEE
11
14
15
28
34
35
39
42
46
50
51
53
57
59
61
63
65
67
69
72
73
ON
P RACTICE B ULLETINS O BSTETRICS (continued)
Management of Herpes in Pregnancy

Viral Hepatitis in Pregnancy
Invasive Prenatal Testing for Aneuploidy (Joint with Committee on Genetics)
Asthma in Pregnancy
Use of Psychiatric Medications During Pregnancy and Lactation
Anemia in Pregnancy
Fetal Lung Maturity
Critical Care in Pregnancy
Ultrasonography in Pregnancy
Management of Stillbirth
Bariatric Surgery and Pregnancy
Intrapartum Fetal Heart Rate Monitoring: Nomenclature, Interpretation, and General
Management Principles
Induction of Labor
Obstetric Aspects of Trauma Management
ON
ix
990
1000
1015
1024
1032
1052
1059
1069
1077
1088
1102
1111
1122
1134
P RACTICE B ULLETINS G YNECOLOGY
Medical Management of Endometriosis

Management of Anovulatory Bleeding
Premenstrual Syndrome
Use of Botanicals for Management of Menopausal Symptoms
Management of Infertility Caused by Ovulatory Dysfunction
Diagnosis and Treatment of Cervical Carcinomas
Selective Estrogen Receptor Modulators
Breast Cancer Screening
Benefits and Risks of Sterilization
Osteoporosis
Chronic Pelvic Pain
Diagnosis and Treatment of Gestational Trophoblastic Disease
(Joint with Society of Gynecologic Oncologists)
Gynecologic Herpes Simplex Virus Infections
Intrauterine Device
Human Papillomavirus
Urinary Incontinence in Women
Management of Endometrial Cancer
(Joint with Society of Gynecologic Oncologists)
Medical Management of Abortion
Emergency Contraception
Vaginitis
Use of Hormonal Contraception in Women With Coexisting Medical Conditions
*Published in 2009
1143
1156
1164
1173
1184
1196
1209
1219
1231
1243
1257
1274
1287
1294
1304
1318
1331
1344
1356
1367
1379
C OMMITTEE
ON
P RACTICE B ULLETINS G YNECOLOGY (continued)
81
83
84
85
89
91
93
94
96
99
*103
Endometrial Ablation
Management of Adnexal Masses
Prevention of Deep Vein Thrombosis and Pulmonary Embolism
Pelvic Organ Prolapse
Elective and Risk-Reducing Salpingo-oophorectomy
Treatment of Urinary Tract Infections in Nonpregnant Women
Diagnosis and Management of Vulvar Skin Disorders
Medical Management of Ectopic Pregnancy
Alternatives to Hysterectomy in the Management of Leiomyomas
Management of Abnormal Cervical Cytology and Histology
Hereditary Breast and Ovarian Cancer Syndrome (Joint with the Committee on Genetics
and the Society of Gynecologic Oncologists)
*104 Antibiotic Prophylaxis for Gynecologic Procedures
*108 Polycystic Ovary Syndrome
*109 Cervical Cytology Screening
1399
1415
1429
1441
1454
1465
1475
1486
1493
1507
1533
1543
1553
1567
P OLICY S TATEMENTS
AAFPACOG Joint Statement on Cooperative Practice and Hospital Privileges
(July 1980, Revised and Retitled, March 1998)
Abortion Policy (January 1993, Reaffirmed July 2007)
Access to Womens Health Care (July 1988, Reaffirmed July 2009)
Certification and Procedural Credentialing (February 2008)
Cervical Cancer Prevention in Low-Resource Settings (March 2004)
Home Births in the United States (May 4, 2007)
Joint Statement of ACOG/AAP on Human Immunodeficiency
Virus Screening (May 1999, Reaffirmed July 2006)
Joint Statement of Practice Relationships Between ObstetricianGynecologists
and Certified Nurse-Midwives/Certified Midwives (October 2002)
Midwifery Education and Certification (February 2006, Amended February 2007)
The Role of Obstetrician-Gynecologists in Cosmetic Procedures (November 2008)
Tobacco Marketing Aimed at Women and Adolescents
(July 1990, Amended July 2009)
1581
1583
1586
1587
1589
1591
1592
1594
1595
1596
1597
A PPENDIX C ONTENTS F ROM O THER C OLLEGE R ESOURCES

Guidelines for Perinatal Care, Sixth Edition
Guidelines for Womens Health Care, Third Edition
Health Care For Adolescents
Special Issues in Womens Health
Committee Opinions List of Titles
Practice Bulletins List of Titles
*Published in 2009
1601
1603
1604
1604
1605
1611
Foreword
The Compendium of Selected Publications CD-ROM is a compilation of all Committee Opinions, Practice Bulletins,
Policy Statements, and Technology Assessments current as of December 31, 2009:
Committee Opinions: Brief focused documents that address clinical issues of an urgent or emergent
nature or nonclinical topics such as policy, economics, and social issues that relate to obstetrics and
gynecology. They are consensus statements that may or may not be based on scientific evidence.
Practice Bulletins: Evidence-based guidelines developed to indicate a preferred method of diagnosis

and management of a condition. The evidence is graded, and peer-reviewed research determines the
recommendations in the document.
Policy Statements: Position papers on key issues approved by the Executive Board.
Technology Assessments in Obstetrics and Gynecology: Documents that describe specific technologies and their application.
These series are developed by committees of experts and reviewed by leaders in the specialty and the College.
Each document is reviewed periodically and either reaffirmed, replaced, or withdrawn to ensure its continued
appropriateness to practice. The contribution of the many groups and individuals who participated in the process is
gratefully acknowledged.
Each section of the Compendium is devoted to a particular series, and includes those documents considered
current at the time of publication. A comprehensive table of contents has been added for ease of use with titles listed
numerically by committee. Those published within 2009 are indicated with an asterisk. Also provided are current
Committee Opinion and Practice Bulletin lists of titles, grouped by committee in order of publication.
As the practice of medicine evolves, so do College documents. As a part of the continuing process of review
and revision, many documents initially published as a separate installment of a series evolve to become a part of a
broader effort to educate and inform our Fellows. Books such Guidelines for Perinatal Care or Guidelines for Womens
Health Care carry equal weight as practice guidelines and should be considered adjuncts to the documents in the series.
For ease of reference, the contents of these volumes are included in the appendix.
The Compendium of Selected Publications CD-ROM and the companion 2010 Compendium of Selected
Publications, which includes only 20082009 series documents current as of December 31, 2009, can be purchased by
calling 800-762-2264 (Compendium CD-ROM only: $104, $59 [members]; 2010 Compendium and CD-ROM: $226,
$99 [members]).
Throughout the year, new documents will be published in the Colleges official journal, Obstetrics & Gynecology.
Single copies can be obtained from the Resource Center (202-863-2518), and the series are available for sale as
complete sets or subscriptions (call 800-762-2264 to order). These documents also are available to members on our web
site: www.acog.org. To verify the status of documents, contact the Resource Center or check our web site.
We are making every effort to provide health professionals with current, quality information on the practice of
obstetrics and gynecology. The Compendium of Selected Publications CD-ROM and the 2010 Compendium of Selected
Publications represent still other ways to disseminate material designed to promote womens health.
Ralph W. Hale, MD, Executive Vice President
xi
xii
The Scope of Practice of

Obstetrics and Gynecology
Obstetrics and gynecology is a discipline dedicated to the broad, integrated medical and surgical
care of womens health throughout their lifespan. The combined discipline of obstetrics and gynecology requires extensive study and understanding of reproductive physiology, including the physiologic, social, cultural, environmental and genetic factors that influence disease in women. This
study and understanding of the reproductive physiology of women gives obstetricians and gynecologists a unique perspective in addressing gender-specific health care issues.
Preventive counseling and health education are essential and integral parts of the practice of obstetricians and gynecologists as they advance the individual and community-based health of women
of all ages.
Obstetricians and gynecologists may choose a scope of practice ranging from primary ambulatory
health care to concentration in a focused area of specialization.
Approved by the Executive Board
February 6, 2005
Code of Professional Ethics

of the American College of
Obstetricians and Gynecologists
Obstetrician-gynecologists, as members of the medical profession, have ethical responsibilities not only to patients, but also to society, to other health professionals and to themselves.
The following ethical foundations for professional activities in the field of obstetrics and
gynecology are the supporting structures for the Code of Conduct. The Code implements
many of these foundations in the form of rules of ethical conduct. Certain documents of the
American College of Obstetricians and Gynecologists also provide additional ethical rules,
including documents addressing the following issues: seeking and giving consultation,
informed consent, sexual misconduct, patient testing, human immunodeficiency virus, relationships with industry, commercial enterprises in medical practice, and expert testimony.
Noncompliance with the Code, including the above-referenced documents, may affect an
individuals initial or continuing Fellowship in the American College of Obstetricians and
Gynecologists. These documents may be revised or replaced periodically, and Fellows should
be knowledgeable about current information.
Ethical Foundations
I. The patientphysician relationship: The welfare of the patient (beneficence) is central
to all considerations in the patientphysician relationship. Included in this relationship is the obligation of physicians to respect the rights of patients, colleagues, and
other health professionals. The respect for the right of individual patients to make
their own choices about their health care (autonomy) is fundamental. The principle of
justice requires strict avoidance of discrimination on the basis of race, color, religion,
national origin, or any other basis that would constitute illegal discrimination (justice).
II. Physician conduct and practice: The obstetriciangynecologist must deal honestly
with patients and colleagues (veracity). This includes not misrepresenting himself or
herself through any form of communication in an untruthful, misleading, or deceptive manner. Furthermore, maintenance of medical competence through study,
application, and enhancement of medical knowledge and skills is an obligation of
practicing physicians. Any behavior that diminishes a physicians capability to practice, such as substance abuse, must be immediately addressed and rehabilitative
services instituted. The physician should modify his or her practice until the diminished capacity has been restored to an acceptable standard to avoid harm to patients
(nonmaleficence). All physicians are obligated to respond to evidence of questionable
409 12th Street, SW
PO Box 96920
conduct or unethical behavior by other physicians through appropriate procedures
established by the relevant organization.
xiii
xiv
III. Avoiding conflicts of interest: Potential conflicts of interest are inherent in the practice of medicine.
Physicians are expected to recognize such situations and deal with them through public disclosure.
Conflicts of interest should be resolved in accordance with the best interest of the patient, respecting a
womans autonomy to make health care decisions. The physician should be an advocate for the patient
through public disclosure of conflicts of interest raised by health payer policies or hospital policies.
IV.
Professional relations: The obstetriciangynecologist should respect and cooperate with other physicians,
nurses, and health care professionals.
V.
Societal responsibilities: The obstetriciangynecologist has a continuing responsibility to society as a

whole and should support and participate in activities that enhance the community. As a member of society, the obstetriciangynecologist should respect the laws of that society. As professionals and members
of medical societies, physicians are required to uphold the dignity and honor of the profession.
Code of Conduct
I.
PatientPhysician Relationship
1. The patientphysician relationship is the central focus of all ethical concerns, and the welfare of the
patient must form the basis of all medical judgments.
2. The obstetriciangynecologist should serve as the patients advocate and exercise all reasonable
means to ensure that the most appropriate care is provided to the patient.
3. The patientphysician relationship has an ethical basis and is built on confidentiality, trust, and honesty. If no patientphysician relationship exists, a physician may refuse to provide care, except in
emergencies. Once the patientphysician relationship exists, the obstetriciangynecologist must
adhere to all applicable legal or contractual constraints in dissolving the patientphysician relationship.
4. Sexual misconduct on the part of the obstetriciangynecologist is an abuse of professional power and
a violation of patient trust. Sexual contact or a romantic relationship between a physician and a current patient is always unethical.
5. The obstetriciangynecologist has an obligation to obtain the informed consent of each patient. In
obtaining informed consent for any course of medical or surgical treatment, the obstetriciangynecologist must present to the patient, or to the person legally responsible for the patient, pertinent
medical facts and recommendations consistent with good medical practice. Such information should
be presented in reasonably understandable terms and include alternative modes of treatment and the
objectives, risks, benefits, possible complications, and anticipated results of such treatment.
6. It is unethical to prescribe, provide, or seek compensation for therapies that are of no benefit to the
patient.
7.
The obstetriciangynecologist must respect the rights and privacy of patients, colleagues, and others
and safeguard patient information and confidences within the limits of the law. If during the process
of providing information for consent it is known that results of a particular test or other information
must be given to governmental authorities or other third parties, that must be explained to the
patient.
8. The obstetriciangynecologist must not discriminate against patients based on race, color, national
origin, religion, or any other basis that would constitute illegal discrimination.
II.
Physician Conduct and Practice

1. The obstetriciangynecologist should recognize the boundaries of his or her particular competencies
and expertise and must provide only those services and use only those techniques for which he or she
is qualified by education, training, and experience.
CODE OF PROFESSIONAL ETHICS
2. The obstetriciangynecologist should participate in continuing medical education activities to maintain current scientific and professional knowledge relevant to the medical services he or she renders.
The obstetriciangynecologist should provide medical care involving new therapies or techniques only
after undertaking appropriate training and study.
3. In emerging areas of medical treatment where recognized medical guidelines do not exist, the obstetriciangynecologist should exercise careful judgment and take appropriate precautions to protect
patient welfare.
4. The obstetriciangynecologist must not publicize or represent himself or herself in any untruthful,
misleading, or deceptive manner to patients, colleagues, other health care professionals, or the public.
5. The obstetriciangynecologist who has reason to believe that he or she is infected with the human
immunodeficiency virus (HIV) or other serious infectious agents that might be communicated to
patients should voluntarily be tested for the protection of his or her patients. In making decisions
about patient-care activities, a physician infected with such an agent should adhere to the fundamental professional obligation to avoid harm to patients.
6. The obstetriciangynecologist should not practice medicine while impaired by alcohol, drugs, or physical or mental disability. The obstetriciangynecologist who experiences substance abuse problems or
who is physically or emotionally impaired should seek appropriate assistance to address these problems and must limit his or her practice until the impairment no longer affects the quality of patient
care.
III. Conflicts of Interest
1. Potential conflicts of interest are inherent in the practice of medicine. Conflicts of interest should be
resolved in accordance with the best interest of the patient, respecting a womans autonomy to make
health care decisions. If there is an actual or potential conflict of interest that could be reasonably construed to affect significantly the patients care, the physician must disclose the conflict to the patient.
The physician should seek consultation with colleagues or an institutional ethics committee to determine whether there is an actual or potential conflict of interest and how to address it.
2. Commercial promotions of medical products and services may generate bias unrelated to product
merit, creating or appearing to create inappropriate undue influence. The obstetriciangynecologist
should be aware of this potential conflict of interest and offer medical advice that is as accurate, balanced, complete, and devoid of bias as possible.
3. The obstetriciangynecologist should prescribe drugs, devices, and other treatments solely on the
basis of medical considerations and patient needs, regardless of any direct or indirect interests in or
benefit from a pharmaceutical firm or other supplier.
4. When the obstetriciangynecologist receives anything of substantial value, including royalties, from
companies in the health care industry, such as a manufacturer of pharmaceuticals and medical
devices, this fact should be disclosed to patients and colleagues when material.
5. Financial and administrative constraints may create disincentives to treatment otherwise recommended by the obstetriciangynecologist. Any pertinent constraints should be disclosed to the
patient.
IV. Professional Relations
1. The obstetriciangynecologists relationships with other physicians, nurses, and health care professionals should reflect fairness, honesty, and integrity, sharing a mutual respect and concern for the
patient.
2. The obstetriciangynecologist should consult, refer, or cooperate with other physicians, health care
professionals, and institutions to the extent necessary to serve the best interests of their patients.
XV
xv
xvi
V.
Societal Responsibilities
1. The obstetriciangynecologist should support and participate in those health care programs, practices, and activities that contribute positively, in a meaningful and cost-effective way, to the welfare of
individual patients, the health care system, or the public good.
2. The obstetriciangynecologist should respect all laws, uphold the dignity and honor of the profession, and accept the professions self-imposed discipline. The professional competence and conduct
of obstetriciangynecologists are best examined by professional associations, hospital peer-review
committees, and state medical and licensing boards. These groups deserve the full participation and
cooperation of the obstetriciangynecologist.
3. The obstetriciangynecologist should strive to address through the appropriate procedures the status of
those physicians who demonstrate questionable competence, impairment, or unethical or illegal behavior. In addition, the obstetriciangynecologist should cooperate with appropriate authorities to prevent
the continuation of such behavior.
4. The obstetriciangynecologist must not knowingly offer testimony that is false. The
obstetriciangynecologist must testify only on matters about which he or she has knowledge and
experience. The obstetriciangynecologist must not knowingly misrepresent his or her credentials.
5. The obstetriciangynecologist testifying as an expert witness must have knowledge and experience
about the range of the standard of care and the available scientific evidence for the condition in question during the relevant time and must respond accurately to questions about the range of the standard of care and the available scientific evidence.
6. Before offering testimony, the obstetriciangynecologist must thoroughly review the medical facts of
the case and all available relevant information.
7.
The obstetriciangynecologist serving as an expert witness must accept neither disproportionate

compensation nor compensation that is contingent upon the outcome of the litigation.
Copyright January 2008, The American College of Obstetricians and Gynecologists, 409 12th Street,
SW, PO Box 96920, Washington, DC 20090-6920. This document provides rules for ethical conduct for
obstetricians and gynecologists.
COMMITTEE OPINIONS
COMMITTEE
ON
ADOLESCENT HEALTH CARE
COMMITTEE OPINIONS
COMMITTEE
ON
ADOLESCENT HEALTH CARE
ACOG
Committee on
Adolescent Health Care
The Committee wishes to thank

Abigail English, JD; S. Paige
Hertweck, MD; Susan Kornetsky,
MPH; Audrey Rogers, PhD,
MPH; and John Santelli, MD,
MPH for their assistance in the
development of this opinion. This
document reflects emerging clinical and scientific advances as of
the date issued and is subject to
change. The information should
not be construed as dictating an
exclusive course of treatment or
procedure to be followed.
Copyright October 2004
by the American College of
Obstetricians and Gynecologists.
All rights reserved. No part of
this publication may be reproduced, stored in a retrieval system, or transmitted, in any form
or by any means, electronic,
mechanical, photocopying,
recording, or otherwise, without
prior written permission from
the publisher.
Requests for authorization to
make photocopies should be
directed to:
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ISSN 1074-861X
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409 12th Street, SW
PO Box 96920
Guidelines for adolescent health
research. ACOG Committee Opinion
No. 302. American College of
Obstet Gynecol 2004;104:899902.
Committee
Opinion
Number 302, October 2004
Guidelines for Adolescent Health

Research
ABSTRACT: The risks of exposure to violence, human immunodeficiency
virus, and other sexually transmitted diseases; alcohol, tobacco, and prescribed and illicit drug use; and unintended pregnancy, among others, threaten the health and well-being of adolescents in the United States. Research is
needed in these and other areas to improve adolescent health care and to aid
in health policy decisions. Adolescents often are prevented from participating
in such research because of inadequate understanding of their legal status
and the ethical considerations regarding their participation in research.
There is confusion about what constitutes appropriate levels of protection for
studies involving adolescents as research subjects and uncertainty about the
need for parental permission. This document is designed to clarify the
informed consent and parental permission issues as they pertain to adolescent
health research.
Background
A basic criterion for ethical research is the protection of the rights and welfare of people participating in research. The U.S. federal government has promulgated regulations that govern research involving human subjects when the
research is supported, conducted, or otherwise subject to regulation by the
federal government (1). These federal regulations on protection of human
subjects in research, known as the Code of Federal Regulations: Title 45Public Welfare; Part 46: Protection of Human Subjects (45 CFR Part 46), provide for a nationwide system of local Institutional Review Boards (IRBs).
These IRBs must review and approve all federally funded research involving
human subjects and are regulated by the Office for Human Research
Protections in the Department of Health and Human Services. Most universities and research institutions apply these regulations to privately funded
research as well. These regulations serve as guidelines for IRB review and
approval. They require that risks to research participants are minimized and
that they are reasonable relative to the anticipated benefits and the importance
of the knowledge that may be expected to result from the research. The regulations also require that the selection of research participants is equitable and
that informed consent is provided from each prospective research participant
3
or the participants legally authorized representative.

Informed consent is the ability to understand the
risks and benefits of ones participation in a research
activity and to authorize ones participation in this
activity freely (2). General requirements for informed consent are described in 45 CFR Part 46,
Section 116 (1). Finally, the regulations require that
the research plan makes adequate provisions for
ensuring the safety of research participants and that
adequate provisions are made to protect the privacy
of research participants and to maintain the confidentiality of data. Subpart D of 45 CFR Part 46 contains
special protections for children who participate as
subjects in research.
Research involving adolescents, especially
regarding behaviors related to sexuality, often raises
questions about how to obtain adequate informed
consent and protection of the research participants
confidential receipt of health care services. The
Society for Adolescent Medicine provided early
leadership to address these concerns. In 1995, they
led the development of consensus guidelines to promote the ethical conduct of health research involving adolescents as research participants (3). The
society recently issued a revised position statement
to support the guidelines (4); the Society for
Adolescent medicine also established a code of
research ethics to encourage, enhance, and promote
ethical standards for the conduct of research in adolescent health (5).
When considering the legal complexities of adolescent health research, it is important to recognize
that the age of majority in almost every state is 18
years, and all states recognize the concept of emancipated minors, who generally are allowed to consent
for their own health care. In addition, every state has
enacted some minor consent laws that allow minors
to consent for their own health care, whether or not
they are legally emancipated. Such laws may be
based on the status of the minor or the services they
are seeking. Minors who may consent for their own
health care based on their status include those who
are married, are members of the armed forces, live
apart from their parents, and are parents of a child. In
addition, all states allow adolescents who are minors
to consent for some categories of health care such as
sexually transmitted disease (STD) services (all
states), drug and alcohol care (almost all states), contraceptive services and pregnancy related care (a
majority of states), outpatient mental health counseling (about one half of states), or sexual assault care
(a few states). Some states specify the age at which a
minor can begin to consent (6). Researchers in adolescent health should be familiar with current state
statutes regarding age of majority and emancipation,
as well as with minor consent statutes. An up-to-date
listing of these statutes can be found online at
http://www.guttmacher.org/pubs/spib.html.
Regulations
In the federal regulations governing research, children are defined in 45 CFR 46 Section 102(a) as
persons who have not attained the legal age for
consent to treatments or procedures involved in the
research, under the applicable law of the jurisdiction
in which the research will be conducted(1). This
definition refers to laws, primarily state laws related
to consent for treatment of minors, age of majority,
and emancipation status.
Federal regulations governing human subject
research require parental permission and child
assent for subjects who meet the regulatory definition of children, ie, those who are younger than the
state-mandated age at which people may give legally effective informed consent for treatments or procedures involved in the research. Assent means a
child has given affirmative agreement to participate
in research. Mere failure to object should not, absent
affirmative agreement, be construed as assent.
Assent is required when, in the judgment of the IRB,
the children are capable of providing it (1).The federal regulations deliberately use the terms permission and assent to differentiate this process from
the usual informed consent process. An individual
can provide consent only for himself or herself.
Therefore, parents give only permission for their
child to be involved in research, not consent. Assent
recognizes the importance of the emerging capacity
of children to give informed consent for themselves,
as well as the ethical importance of obtaining their
agreement to participate even if they are not legally
authorized to give informed consent.
In 1977, the National Commission for the
Protection of Human Subjects of Biomedical and
Behavioral Research recommended that individual
IRBs be allowed to determine that parental permission is not appropriate in certain research studies,
including research involving assessment for or care
related to contraception and drug abuse (7).
According to the federal regulations (1), informed
consent may be waived under 45 CFR Part 46
Section 116(d) and parental permission may be
waived under 45 CFR Part 46 Section 408(c).
COMMITTEE OPINIONS
Four criteria set forth by 45 CFR Part 46 116(d)

allow an IRB to waive the requirement to obtain the
informed consent for adult research subjects or permission of a parent or guardian for research subjects
who are children if: 1) the research involves no more
than minimal risk (which means that the probability and magnitude of harm or discomfort anticipated
in the research are not greater in and of themselves
than those ordinarily encountered in daily life or
during the performance of routine physical or psychologic examinations or tests [1]), 2) the waiver
will not adversely affect the rights and welfare of the
subjects, 3) the research could not practically be carried out without a waiver, and 4) whenever appropriate, the subjects will be provided with additional
pertinent information after participation (1). This
section is commonly used when waiving informed
consent for research involving existing data such as
medical records.
In addition, 45 CFR Part 46 Section 408(c)
specifically allows for a waiver of parental permission under Subpart D, which addresses research with
children. Section 408(c) of 45 CFR Part 46 states:
if an IRB determines that a research protocol is
designed for conditions or a subject population for
which parental permission is not a reasonable
requirement to protect subjects (eg, neglected or
abused children), it may waive consent requirements
provided an appropriate mechanism for protecting
the children who will participate as research subjects
is substituted and provided the waiver is not inconsistent with federal, state, or local law. The choice
of an appropriate mechanism would depend on the
nature and purpose of the activities described in the
protocol, the risk and anticipated benefit to the
research subjects, and their age, maturity, status, and
condition (1). In discussing the waiver of parental
permission, the National Commission cited as examples of when the requirement might not be a reasonable one: [r]esearch designed to identify factors
related to the incidence or treatment of certain conditions in adolescents for which, in certain jurisdictions, they legally may receive treatment without
parental consent; [and] research in which the subjects are mature minors and the procedures
involved entail essentially no more than minimal
risk that such individuals might reasonably assume
on their own (7).
Based on these criteria, either 45 CFR Part 46
Section 408(c) or 45 CFR Part 46 Section 116(d)
may be used to waive parental permission in a variety of studies, including, for example, surveys of
adolescents. It is important to note that if these surveys are conducted in a school setting, federal educational law governing certain research conducted in
schools may apply. Health researchers working in
schools are, therefore, advised to become knowledgeable about these laws.
Section 408(c) of 45 CFR Part 46 also may be
used to waive parental permission for research areas
including STDs, birth control usage, high-risk
behaviors, HIV prevention, and situations in which
obtaining parental consent may be dangerous to the
child (abuse situations). Finally, in certain research
studies, adolescent minors would not be considered
children and parental permission would not be
required. Such research includes certain clinical
studies involving pregnancy, family planning, and
treatment of STDs where the adolescent minor can
legally consent to such services. Again, familiarity
with current state statutes on the rights of minors to
consent to health care services is essential.
Researchers conducting and IRBs reviewing
research involving adolescents should be knowledgeable of the federal regulations and the ethical
principles that underlie these regulations. They
should understand when parental permission is
required and when it may be waived. Personal
beliefs and attitudes should not enter into this decision. The Society for Adolescent Medicines
Guidelines for Adolescent Health Research (4) provide a comprehensive approach to understanding
these issues. Parental permission should not be a
barrier to the inclusion of adolescents in studies that
meet federal regulations and are designed to
improve their health.
Conclusions
1. Researchers developing study protocols and
materials for submission for IRB review and
approval and the IRBs themselves should be
familiar with, and adhere to, current federal regulations, 45 CFR Part 46 (1), and federal and
state laws that affect research (including laws
regarding age of majority and emancipation,
minor consent statutes, and federal educational
law governing certain research conducted in
schools).
2. Investigators will communicate better with IRB
panels regarding the involvement of adolescent
participants in research if they understand the
purpose of human subject protection regulations
with respect to minors and review the guidelines

provided by the Society for Adolescent
Medicine (35).
3. Under the following circumstances it is reasonable to waive parental permission when adolescents are involved in studies: a) the waiver
would not adversely affect the rights and welfare of the adolescent, b) the study poses no
more than a minimal risk to adolescents, c) the
study could not be practically carried out without a waiver, and d) requiring permission may
not be reasonable to protect subjects. Parental
permission is not a requirement for research
involving the provision of health care for which
adolescents do not legally need parental consent. It is important to review 45 CFR Part 46
for the necessary details.
References
1. Protection of human subjects. 45 C.F.R 46 (2003). Available at http://www.access.gpo.gov/nara/cfr/cfr-tablesearch.
html#page1. Retrieved July 8, 2004.
2. American College of Obstetricians and Gynecologists.

Ethics in obstetrics and gynecology. 2nd ed. ACOG:
Washington, DC; 2004.
3. Guidelines for adolescent health research. 1995. Society
for Adolescent Medicine. J Adolesc Health 2003;33:
4105.
4. Santelli JS, Smith Rogers A, Rosenfeld WD, DuRant RH,
Dubler N, Morreale M, et al. Guidelines for adolescent
health research: A position paper of the Society for
Adolescent Medicine. J Adolesc Health 2003;33:
396409.
5. Code of Research Ethics: position paper of the Society for
Adolescent Medicine. J Adolesc Health 1999;24:27782;
discussion 283.
6. English A, Kenney KE. State minor consent laws: a summary. 2nd Ed. Chapel Hill (NC): Center for Adolescent
Health & the Law; 2003.
7. The National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research.
Research involving children: report and recommendations. Bethesda (MD): U.S. Department of Health Education and Welfare; 1977.
COMMITTEE OPINIONS
ACOG
ACOG Committee on
This document reflects emerging

clinical and scientific advances as
of the date issued and is subject
to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed.
Marc R. Laufer, MD; Joseph
Sanfilippo, MD; and Jonathon
Solnik, MD; for their assistance
in the development of this document.
Copyright April 2005
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Endometriosis in adolescents. ACOG

Committee Opinion No. 310.
American College of Obstetricians
and Gynecologists. Obstet Gynecol
2005;105:9217.
Committee
Opinion
Number 310, April 2005
Endometriosis in Adolescents
ABSTRACT: Historically thought of as a disease that affects adult women,
endometriosis increasingly is being diagnosed in the adolescent population.
This disorder, which was originally described more than a century ago, still
represents a vague and perplexing entity that frequently results in chronic
pelvic pain, adhesive disease, and infertility. The purpose of this Committee
Opinion is to highlight the differences in adolescent and adult types of
endometriosis. Early diagnosis and treatment during adolescence may decrease
disease progression and prevent subsequent infertility.
Incidence
It has been difficult to establish accurate prevalence rates of endometriosis in
adult and adolescent women. Documented rates in adolescent patients undergoing laparoscopy for chronic pelvic pain range from 19% to 73%. Goldstein
et al (1) reported a 47% prevalence of endometriosis found at laparoscopy in
a prospective study of adolescent females with pelvic pain. Other studies have
shown that 2538% of adolescents with chronic pelvic pain have endometriosis (2, 3). In addition, it has been shown that 5070% of adolescents with
pelvic pain not responding to combination hormone therapy (such as oral
contraceptive pills [OCPs]) and nonsteroidal antiinflammatory drugs
(NSAIDs) have endometriosis at the time of laparoscopy (4, 5).
Endometriosis also has been identified in premenarcheal girls who have
started puberty and have some breast development (6, 7). The occurrence of
endometriosis before menarche contributes to the argument that one etiology
for endometriosis lies in the theory of embryonic mllerian rests or coelomic metaplasia as opposed to retrograde menses. Based on the occurrence
of early endometriosis, some authors have argued that thelarche be recognized as a developmental benchmark, after which endometriosis is included
in the differential diagnosis of chronic pelvic pain (6).
It is common for adult women who have endometriosis to bring in their
adolescent daughters for evaluation and early diagnosis. Data from the
Endometriosis Association indicate that 66% of adult women reported the
onset of pelvic symptoms before age 20 years. Forty-seven percent of these
women reported they had to see a doctor five times or more before receiving
the diagnosis of endometriosis or referral. As the age of the onset of symp-
toms decreases, the number of doctors having to be

seen to reach a diagnosis increases. Specifically, an
average of 4.2 doctors were seen for patients whose
symptoms began before age 15 years compared with
an average of 2.64 doctors for patients whose symptoms began between the ages of 30 years and 34
years. There are, on average, 9.28 years from the
onset of symptoms to the diagnosis (8). Endometriosis is believed to be a progressive disease because the prevalence and severity of the stage of the
disease significantly increase with age (9, 10). With
early diagnosis and treatment, it is hoped that disease progression and infertility can be limited, but
this remains to be proved with prospective research.
Presentation and Characteristics

The typical presentation of an adolescent with
endometriosis may be different from that of an adult.
One significant difference is that adolescents primarily seek medical attention because of pain rather
than a concern for infertility. The most common
symptom noted among published reviews is
acquired or progressive dysmenorrhea, which was
encountered in 6494% of patients (4, 11). Other
common symptoms included acyclic pain (3691%),
dyspareunia (1425%), and gastrointestinal complaints (246%) (11). Adolescents found to have
endometriosis most commonly present with both
cyclic and acyclic pain (62.6%), as opposed to
acyclic pain alone (28.1%), or cyclic pain alone
(9.4%) (11).
In young women, pelvic pain associated with
endometriosis often interferes with school attendance as well as physical and social activities.
Prompt diagnosis and adequate therapy, therefore,
may return normal psychosocial development and
self-esteem, improve scholastic performance, and
lead to a return to normal daily activities.
Diagnosis
History and Physical Examination
A thorough review of history and physical examination are necessary to assess a variety of differential
diagnoses of pelvic pain such as appendicitis, pelvic
inflammatory disease, mllerian anomalies or outflow obstruction, bowel disease, hernias, musculo
skeletal disorders, and psychosocial complaints.
Pelvic examination may be difficult, especially in
patients who have not had vaginal intercourse.
When evaluating an adolescent for suspected

endometriosis or dysmenorrhea, the clinician should
aim to rule out a pelvic mass or a congenital anomaly of the reproductive tract. A bimanual examination may not be necessary to evaluate pelvic pain,
especially in adolescents who are virgins. If a bimanual examination cannot be performed or is
declined, a rectalabdominal examination in the dorsal lithotomy position may be helpful to determine if
a pelvic mass is present, and a cotton-tipped swab
can be inserted into the vagina to evaluate for the
presence of a transverse vaginal septum, vaginal
agenesis, or agenesis of the lower vagina. If a bimanual examination is performed, the clinician should
check for the existence of both diffuse and focal
pelvic tenderness, and evaluate the pelvis for a displaced uterus or an adnexal mass. An ultrasound
examination may be helpful in evaluating the pelvis
of a young adolescent who declines a bimanual or
rectalabdominal examination.
Imaging Studies and Serum Markers
Ultrasonography and magnetic resonance imaging
are helpful in evaluating anatomical structures, but
are not specific for diagnosing endometriosis. An
adolescent will rarely have a pelvic mass from an
endometrioma or uterosacral nodularity. CA 125,
although very sensitive, is not specific and, thus, is
not helpful in the diagnosis of adolescent endometriosis. No data exist regarding the use of CA 125
to monitor the clinical progression or regression of
disease in adolescents with endometriosis.
Empiric Therapy
If an adolescent younger than 18 years has persistent
pain while taking combination hormone therapy and
NSAIDs, endometriosis should be suspected and she
should be offered a laparoscopic evaluation (discussion follows in section on Surgical Diagnosis). If,
however, she is older than 18 years and had a negative assessment for an ovarian mass or tumor, she
can be offered an empiric trial of gonadotropinreleasing hormone (GnRH) agonist therapy (12, 13).
If the pain subsides with the use of GnRH agonist,
then a diagnosis of endometriosis can be made. An
empiric trial of GnRH agonist is not routinely
offered to patients younger than 18 years because
the effects of these medications on bone formation
and long-term bone density have not been adequately studied. For patients younger than 18 years
or who decline empiric therapy, diagnostic and ther-
COMMITTEE OPINIONS
apeutic laparoscopy can be initiated. An algorithm

for therapy is provided in Figure 1 (14).
Surgical Diagnosis
After a comprehensive preoperative evaluation and
trial of combination hormone therapy and NSAIDs
to treat dysmenorrhea, laparoscopy should be rec-
ommended for diagnosing and treating presumed

endometriosis in an adolescent. Laparoscopy can be
safely performed in adolescents. At the time of surgical diagnosis, most adolescents have Stage I disease as classified by the American Society for
Reproductive Medicine classification system (15).
Goldstein et al commented that almost 60% of the
History
Physical examination
Consider radiologic imaging
Pain diary
Cyclic CHT and NSAIDs

If persistent pain
Empiric GnRH agonist (if older than 18 years)

If improveddiagnosis is endometriosis
Laparoscopy
Diagnosis of endometriosis by visualization or biopsy
Surgical treatment (ablation/resection/laser)
of endometriosis
Endometriosis identified visually or by pathology

<16 years
No endometriosisvisually and histologically negative
>16 years
Continuous CHT
Symptoms persist
GnRH agonist
( add-back)*
OR
Continuous CHT
Gastrointestinal or urologic evaluation

Pain management service
Continuous CHT
No pain
Continue CHT
Continued pain
Laparoscopy with resection of endometriosis

and/or
Long-term GnRH agonist with add-back
and
Pain management service
Complementary or alternative therapies
Abbreviations: NSAIDs, nonsteroidal antiinflammatory drugs; CHT, combination hormone therapy (oral contraceptive pills, estrogen/progestin
patch, estrogen/progestin vaginal ring, norethindrone acetate, medroxyprogesterone acetate); GnRH, gonadotropin-releasing hormone.
*Add-back indicates use of estrogen and progestin or norethindrone acetate alone.
Fig. 1. Protocol for evaluation and treatment of adolescent pelvic pain and endometriosis. (Modified with permission
from Bandera CA, Brown LR, Laufer MR. Adolescents and endometriosis. Clin Consult Obstet Gynecol 1995;7:206.)
10
patients in their cohort had Stage I disease (1),

whereas 80% of the cases reported by other
researchers had minimal to mild disease (4).
Gynecologic surgeons who perform laparoscopy in
adolescents with pelvic pain should be familiar with
the typical lesions of endometriosis in adolescents,
which tend to be red, clear, or white (15) as opposed
to the powder-burn lesions seen commonly in adults
who have endometriosis. The use of a liquid medium
in the pelvis may facilitate the identification of clear
lesions, which are very common in adolescents (11).
Mllerian Anomalies and Endometriosis
The development of endometriosis in adolescent
patients has been associated with mllerian anomalies with outflow tract obstruction. The published
incidence of anomalies of the reproductive system
and associated endometriosis has been reported to
be as high as 40%, but most studies quote a rate of
56%. The clinical outcome in patients with outflow
tract obstructions has been reported to differ from
those without such obstruction because regression of
disease usually has been observed once surgical correction of the anomaly has been accomplished (16).
Treatment
The premise for treating the symptomatic adolescent
is based on the concept that endometriosis has been
shown to be a progressive disease without a known
cure. A physician treating an adolescent with endometriosis should adopt a multidimensional approach
and consider the use of the following components:
surgery, hormonal manipulation, pain medications,
mental health support, complementary and alternative therapies, and education.
Patients younger than 18 years with persistent
pelvic pain while taking combination hormone therapy should routinely be offered a laparoscopic procedure for diagnosis and surgical management of
endometriosis. The gynecologic surgeon must be
familiar with the appearance of endometriosis in
adolescents and should remove or destroy all visible lesions of endometriosis. Only procedures that
preserve fertility options should be applied; oophorectomy or hysterectomy should not be offered to
adolescents.
Long-term follow-up studies of treatments for
adolescent endometriosis have not been performed.
Current treatments for adolescents have been extrapolated and adapted from the literature of adult cases
of endometriosis. The goal of therapy for adolescent

endometriosis should be suppression of pain, suppression of disease progression, and preservation of
fertility. Consequently, after surgery, all adolescents
who have endometriosis should be treated with medical therapy until they have completed child bearing
to suppress pain, progression of disease, and resulting potential infertility.
First-line treatment modalities should involve
the use of NSAIDs and hormone therapy. Because
red lesions have been shown to be active producers
of prostaglandins, and adolescents with endometriosis typically report severe dysmenorrhea, NSAIDs
may be used in conjunction with hormonal menstrual suppressive therapy to provide sufficient
relief. Most pharmacologic agents bring about relief
by inducing an anovulatory or a hypoestrogenic
state or both. Continuous combination hormone
therapy (OCPs, combination hormonal contraceptive patch, or vaginal ring) for menstrual suppression
can be used to create a pseudopregnancy state,
which was described more than 40 years ago (17).
This method routinely has been promoted for adolescents who have endometriosis. Although this
method may provide effective relief, the Cochrane
Database Review 2003 provided data suggesting
that further studies are needed to prove long-term
benefits (18). Most clinicians advocate continuous
use of combination hormone therapy to induce
amenorrhea, but this modality can result in significant breakthrough bleeding. One randomized controlled trial compared a 28-day regimen with continuous combination oral contraceptives and found no
increase in spotting days after 9 months of therapy,
with fewer total bleeding days in the group taking
continuous combination oral contraceptives (19).
Thus, continuous use of combination hormone therapy is believed to be both safe and effective for adolescents with endometriosis-related pain and, thus, is
the first-line hormone therapy for adolescents
younger than 16 years with endometriosis. Gonadotropin-releasing hormone agonists are not offered as
first-line therapy for adolescents in this age range.
Progestin-only protocols have been used for the
treatment of adult endometriosis with mixed results.
In a recent critical review, progestins were shown to
be as effective as danazol or GnRH agonists (20).
Common side effects include irregular bleeding and
weight gain. Some studies suggest that these side
effects are well tolerated (20), however in a data set
of 3,751 women who have endometriosis, treatment
COMMITTEE OPINIONS
with medroxyprogesterone acetate or depot medroxyprogesterone acetate was the least well tolerated and
was the least effective in treating pain compared
with combination OCPs, GnRH agonists, and pain
medications (8). Furthermore, depot medroxyprogesterone acetate used for longer than 2 years has
been shown to decrease bone density in adolescents
(21, 22, 23). The U.S. Food and Drug Administration has warned against the long-term use of depot
medroxyprogesterone acetate because of adverse
affects on bone density (24).
Danazol, an androgenic and antiestrogenic
agent, is extremely effective in treating symptomatic
endometriosis in adults. Doses of 400800 mg daily
have been advocated for 6 months followed by continuous OCP use for maintenance suppression of the
hypothalamicpituitary ovarian axis. This choice of
pharmacotherapy was more common in the 1980s,
but the androgenic side effects have made this a poor
option for adolescents.
Gonadotropin-releasing hormone agonists create a hypoestrogenic state by downregulating the
hypothalamicpituitary axis. Whereas these agents
are greatly effective in the treatment of endometriosis-related pain in adolescents, their use alone (without add-back therapy described in the following
paragraph) usually is limited to 6 months because of
the resultant profound hypoestrogenic state and its
subsequent effect on bone mineralization. This is a
major issue for an adolescent who is accruing peak
bone mineral density. Therefore, it has been suggested that this therapy not be offered as a first-line treatment for adolescents younger than 16 years (14). At
6 months, GnRH agonist induces a 5% loss in trabecular bone mineral density and a 2% loss in
femoral neck bone mineral density in adult women.
In a cross-sectional study, researchers collected bone
mineral density test results of 265 females, aged
850 years (25). They determined that the majority
of bone mass growth is achieved by age 20 years and
that after the age 18 years, no significant differences
in bone mass or bone mineral density were noted at
most skeletal sites. This emphasizes that a druginduced hypoestrogenic state could significantly
affect peak bone mineralization that occurs during
adolescence, particularly in females younger than 16
years.
Investigators have determined that to reduce the
symptoms and bone loss related to a hypoestrogenic
state, add-back therapy with norethindrone acetate
(5 mg per day) or conjugated estrogens/medroxy-
11
progesterone acetate (0.625/2.5 mg per day) can

help preserve bone density (26, 27). Add-back therapy has been shown not to influence the primary
therapeutic effect and resulted in less bone loss
12 months after cessation of therapy in adult
women. There is some evidence in adults to suggest
that immediate add-back therapy may result in even
less bone loss (28). No data exist on the long-term
effects of GnRH agonist use with add-back therapy
in the adolescent population and, thus, it should be
reserved for adolescents refractory to continuous
combination hormone therapy (14, 29). Lifestyle
modifications, such as adequate physical exercise
and calcium and vitamin D intake, also are essential
to maintaining proper bone health when taking
GnRH agonists (with or without add-back therapy).
Aside from medical management, surgery also
has proved to be an effective form of treatment for
adult patients with pain (30). Surgery for the management of endometriosis-related pain is an important option for adolescents, but clearly, radical
procedures (oophorectomy, bilateral oophorectomy,
or hysterectomy) should be avoided in this age
group, even in rare cases of severe endometriosis. A
double-blinded randomized controlled trial compared laser vaporization of endometriosis and laser
uterosacral nerve ablation with controls in 63 adult
patients with proven endometriosis. At 6 months of
follow-up, 63% of patients reported significant relief
compared with 23% of controls (31). Patients with
more advanced disease had better outcomes in pain
management compared with those with minimal disease. At 1-year follow-up, 90% of those in the treatment arm who initially responded had continued
pain relief (32). Among the symptomatic controls,
an even distribution of patients was noted to have
progression, regression, and maintenance of disease.
Both new and recurrent disease was noted at second
look. In a Cochrane review of these data, adult
patients were almost 5 times more likely to benefit
from surgical management of endometriosis compared with controls (33). One study demonstrated, in
a prospective review of 643 patients with pain, or
infertility, or both, that there was a significant relationship between pain and the depth of infiltration of
the endometriosis implants (9). This study also confirmed that red implants were more common in
younger patients and that the depth of invasion
increased with age, suggesting that endometriosis is
a progressive disease. The concept that endometriosis is a progressive disease supports the recommen-
12
dation for long-term medical treatment for pain

management of adolescent endometriosis and until
a woman has completed childbearing. Long-term
studies are needed to determine if medical treatment
can inhibit the progression of endometriosis diagnosed in adolescents and preserve future fertility.
In addition to surgery and hormonal manipulation, complementary and alternative medicine has
been used for the treatment of endometriosis. A multidisciplinary pain management service, including
support groups and age-appropriate educational
information, may be beneficial for an adolescent with
chronic pelvic pain caused by endometriosis.
medical interventions. Only procedures that preserve

fertility options should be applied. Long-term endometriosis treatment may be required for chronic pain
relief. Because there is no cure for endometriosis,
long-term treatment should continue until desired
family size is reached or fertility no longer needs to
be preserved. A multidisciplinary team approach to
the adolescent who has endometriosis may be the
most rewarding for the adolescent, her family, and
the clinician.
Summary
The Center for Young Womens Health

(www.youngwomenshealth.org)
Endometriosis can be a debilitating disease that

affects adolescent girls and young women. Pediatricians, adolescent health care providers, and gynecologists should recognize that thelarche and the
presence of endogenous estrogen can be considered
a developmental milestone and benchmark for inclusion of adolescent endometriosis in the differential
diagnosis of postpubertal girls and young women
with chronic pelvic pain. Adolescent patients typically present with progressive and severe dysmenorrhea, but also may present with acylic pelvic pain.
Standard therapy (combination hormone therapy
and NSAIDs) for dysmenorrhea should be initiated,
and if symptoms do not resolve after 3 months, further evaluation for endometriosis is indicated.
Prompt evaluation and consideration of the adverse
effects of endometriosis is, therefore, essential in
this age group.
Findings of the physical examination of adolescents may vary from the adult population because
uterosacral nodularity and endometriomas are found
in more advanced disease and, thus, are uncommon
in adolescents. A bimanual pelvic examination may
not be necessary for further evaluation of pelvic pain
and should not be a requirement before the diagnosis of endometriosis and initiation of therapy for
adolescents. It is important to evaluate the vagina for
a possible obstructive anomaly and the ovaries for a
possible ovarian mass. This can be accomplished
with an evaluation of the vagina with a cotton-tipped
swab and an ultrasound examination of the pelvis.
Endometriosis in adolescents typically presents
as early disease (Stage I) and clear, red, and white
lesions are the most common. Treatment should
focus on conservative measures with surgical and
Resources
Endometriosis Association
(www.endometriosisassn.org)
References
1. Goldstein DP, De Cholnoky C, Emans SJ. Adolescent
endometriosis. J Adolesc Health Care 1980;1:3741.
2. Vercellini P, Fedele L, Arcaini L, Bianchi S, Rognoni MT,
Candiani GB. Laparoscopy in the diagnosis of chronic
pelvic pain in adolescent women. J Reprod Med 1989;34:
82730.
3. Kontoravdis A, Hassan E, Hassiakos D, Botsis D,
Kontoravdis N, Creatsas G. Laparoscopic evaluation and
management of chronic pelvic pain during adolescence.
Clin Exp Obstet Gynecol 1999;26:767.
4. Reese KA, Reddy S, Rock JA. Endometriosis in an adolescent population: the Emory experience. J Pediatr Adolesc
Gynecol 1996;9:1258.
5. Laufer MR, Goitein L, Bush M, Cramer DW, Emans SJ.
Prevalence of endometriosis in adolescent girls with
chronic pelvic pain not responding to conventional therapy. J Pediatr Adolesc Gynecol 1997;10:199202.
6. Batt RE, Mitwally MF. Endometriosis from thelarche to
midteens: pathogenesis and prognosis, prevention and
pedagogy. J Pediatr Adolesc Gynecol 2003;16:33747.
7. Marsh EE, Laufer MR. Endometriosis in premenarcheal
girls without an associated obstructive anomaly. Fertil
Steril 2005;83:75860.
8. Ballweg ML. Big picture of endometriosis helps provide
guidance on approach to teens: comparative historical
data show endo starting younger, is more severe. J Pediatr
Adolesc Gynecol 2003;16(suppl):S216.
9. Koninckx PR, Meuleman C, Demeyere S, Lesaffre E,
Comillie FJ. Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating
endometriosis is associated with pelvic pain. Fertil Steril
1991;55:75965.
10. DHooghe TM, Bambra CS, Raeymaekers BM, Koninckx
PR. Serial laparoscopies over 30 months show that
endometriosis in captive baboons (Papio anubis, Papio
cynocephalus) is a progressive disease. Fertil Steril 1996;
65:6459.
COMMITTEE OPINIONS
11. Laufer MR. Identification of clear vesicular lesions of

atypical endometriosis: a new technique. Fertil Steril 1997;
68:73940.
12. Ling FW. Randomized controlled trial of depot leuprolide
in patients with chronic pelvic pain and clinically suspected endometriosis. Pelvic Pain Study Group. Obstet
Gynecol 1999;93:518.
Medical management of endometriosis. ACOG Practice
Bulletin 11. Washington, DC: ACOG; 1999.
14. Laufer MR, Sanfilippo J, Rose G. Adolescent endometriosis: diagnosis and treatment approaches. J Pediatr Adolesc
Gynecol 2003;16(suppl):S311.
15. Revised American Society for Reproductive Medicine
classification of endometriosis: 1996. Fertil Steril 1997;
67:81721.
16. Sanfilippo JS, Wakim NG, Schikler KN, Yussman MA.
Endometriosis in association with uterine anomaly. Am J
17. Kistner RW. The treatment of endometriosis by inducing
pseudopregnancy with ovarian hormones. Fertil Steril
1959;10:53956.
18. Moore J, Kennedy S, Prentice A. Modern combined oral
contraceptives for pain associated with endometriosis.
The Cochrane Database of Systematic Reviews 1997,
Issue 4. Art. No.: CD001019. DOI: 10.1002/14651858.
CD001019.
19. Miller L, Hughes JP. Continuous combination oral contraceptive pills to eliminate withdrawal bleeding: a randomized trial. Obstet Gynecol 2003;101:65361.
20. Vercellini P, Cortesi I, Crosignani PG. Progestins for
symptomatic endometriosis: a critical analysis of the evidence. Fertil Steril 1997;68:393401.
21. Cromer BA, Blair JM, Mahan JD, Zibners L, Naumovski
Z. A prospective comparison of bone density in adolescent girls receiving depot-medroxyprogesterone acetate
(Depo-Provera), levonorgestrel (Norplant), or oral contraceptives. J Pediatr 1996;129:6716.
22. Berenson AB, Radecki CM, Grady JJ, Rickert VI, Thomas
A. A prospective, controlled study of the effects of hormonal contraception on bone mineral density. Obstet
Gynecol 2001;98:57682.
23. Lara-Torre E, Edwards CP, Perlman S, Hertweck SP. Bone
mineral density in adolescent females using depot
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
13
medroxyprogesterone acetate. J Pediatr Adolesc Gynecol

2004;17:1721.
Black box warning added concerning long-term use of
depo-provera contraceptive injection. FDA talk paper.
Rockville (MD): U.S. Food and Drug Administration;
2004. Available at: http://www.fda.gov/bbs/topics/ANSWERS
/2004/ANS01325.html. Retrieved December 8, 2004.
Matkovic V, Jelic T, Wardlaw GM, Ilich JZ, Goel PK,
Wright JK, et al. Timing of peak bone mass in Caucasian
females and its implication for the prevention of osteoporosis: inference from a cross-sectional model. J Clin
Invest 1994;93:799808.
Barbieri RL. Hormone treatment of endometriosis: the
estrogen threshold hypothesis. Am J Obstet Gynecol
1992;166:7405.
Surrey ES, Hornstein MD. Prolonged GnRH agonist and
add-back therapy for symptomatic endometriosis: longterm follow-up. Obstet Gynecol 2002;99:70919.
Kiesel L, Schweppe KW, Sillem M, Siebzehnrubl E.
Should add-back therapy for endometriosis be deferred
for optimal results? Br J Obstet Gynaecol 1996;103(suppl
14):157.
Lubianca JN, Gordon CM, Laufer MR. Add-back therapy for endometriosis in adolescents. J Reprod Med 1998;
43:16472.
Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R.
Laparoscopic excision of endometriosis: a randomized,
placebo-controlled trial. Fertil Steril 2004;82:87884.
Sutton CJ, Ewen SP, Whitelaw N, Haines P. Prospective,
randomized, double-blind, controlled trial of laser
laparoscopy in the treatment of pelvic pain associated
with minimal, mild and moderate endometriosis. Fertil
Steril 1994;62:696700.
Sutton CJ, Pooley AS, Ewen SP, Haines P. Follow-up
report on a randomized controlled trial of laser laparoscopy in the treatment of pelvic pain associated with
minimal to moderate endometriosis. Fertil Steril 1997;68:
10704.
Jacobson TZ, Barlow DH, Garry R, Koninckx PR.
Laparoscopic surgery for pelvic pain associated with
endometriosis. The Cochrane Database of Systematic
Reviews 2001, Issue 4. Art. No.: CD001300. DOI: 10.1002/
14651858.CD001300.
14
ACOG
Committee on
Committee
Opinion
Number 314, September 2005
Meningococcal Vaccination for

Adolescents
This information should not be
construed as dictating an exclusive course of treatment or procedure to be followed.
Copyright September 2005
All rights reserved. No part of this
publication may be reproduced,
stored in a retrieval system, or
transmitted, in any form or by any
means, electronic, mechanical,
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Meningococcal vaccination for adolescents. ACOG Committee Opinion No.
314. American College of Obstetricians
2005;106:6679.
ABSTRACT: Every year in the United States, approximately 1,4002,800 individuals are infected with meningococcal disease. The Advisory Committee on
Immunization Practices (ACIP) to the Centers for Disease Control and
Prevention (CDC) released recommendations in early 2005 to reduce the incidence of meningococcal disease during adolescence and young adulthood. To
achieve this goal, routine vaccination of preadolescents with meningococcal
conjugate vaccine (MCV4) is now recommended. For adolescents who have
not received MCV4, the CDC now recommends vaccination before entry into
high school, at approximately 15 years of age. The American College of
Obstetricians and Gynecologists supports these recommendations and encourages all health care providers caring for adolescent and young adult patients
to provide meningococcal vaccination with MCV4 when appropriate. This
includes vaccination of college freshmen who live in dormitories. Pregnant
women may be vaccinated with meningococcal polysaccharide vaccine
(MPSV4) as indicated. Health care providers also are encouraged to discuss
meningococcal vaccination with patients whose children have reached preadolescence, adolescence, or young adulthood and to increase awareness of the
signs and symptoms of meningococcal disease.
Background
Meningococcal disease is caused by bacteria (Neisseria meningitidis) that
infect the bloodstream and the meninges, resulting in serious illness. Every
year in the United States, approximately 1,4002,800 individuals are infected with meningococcal disease. Neisseria meningitidis has become a leading
cause of bacterial meningitis in the United States. Ten percent to 14% of individuals with meningococcal disease die, and 1119% percent of those who
survive have permanent disabilities, such as mental retardation, hearing loss,
and loss of limbs (1). The disease often begins with generalized symptoms
that can be mistaken for a common illness, such as the flu. Meningococcal
disease is particularly dangerous because it progresses rapidly and can be
fatal within hours (2). Therefore, it is important to prevent the disease,
through use of meningococcal vaccination, for individuals at highest risk.
Two meningococcal vaccines are available in the United States, meningococcal polysaccharide vaccine (MPSV4) and meningococcal conjugate vac-
COMMITTEE OPINIONS
cine (MCV4). Studies indicate that both vaccines can

prevent four types of meningococcal disease
(serogroups A, C, Y, W-135). Of all cases of
meningococcal disease among individuals 11 years
and older, 75% are caused by serogroups C, Y, or W135. Both vaccines protect approximately 90% of
individuals vaccinated.
Meningococcal polysaccharide vaccine is a
tetravalent meningococcal polysaccharide vaccine
that has been available in the United States since the
1970s. Each dose consists of purified bacterial capsular polysaccharides (50 g each) from serogroups
A, C, Y, and W-135. Meningococcal polysaccharide
vaccine is available in single-dose (0.5 mL) and 10dose (5 mL) vials (1).
Meningococcal conjugate vaccine is a tetravalent meningococcal conjugate vaccine that was
licensed for use in the United States in January
2005. A 0.5-mL single dose of vaccine contains 4 g
each of capsular polysaccharide from serogroups A,
C, Y, and W-135 conjugated to 48 g of diphtheria
toxoid. Meningococcal conjugate vaccine is available only in single-dose vials and is expected to be
more effective, longer lasting, and more capable of
preventing transmission of the disease from person
to person (1).
These vaccines have been shown to be highly
effective at reducing meningococcal disease.
However, they do not protect individuals against
meningococcal disease caused by serogroup B of
N meningitidis. This type of bacteria causes one
third of all meningococcal cases. More than half of
the cases among infants younger than 1 year are
caused by serogroup B, for which no vaccine is
available in the United States (1).
Studies of vaccination with MPSV4 during
pregnancy have not documented adverse effects
among either pregnant women or newborns. On the
basis of these data, the Centers for Disease Control
and Prevention (CDC) states that pregnancy should
not preclude vaccination with MPSV4, if indicated.
No data are available on the safety of MCV4 during
pregnancy (1).
Recommendations of the Advisory

Committee on Immunization Practices to
the Centers for Disease Control and
Prevention
The Advisory Committee on Immunization Practices (ACIP) to the CDC released recommendations
15
in early 2005 to reduce meningococcal disease during adolescence and young adulthood. Routine vaccination of preadolescents 1112 years of age with
MCV4 is now recommended. For adolescents who
have not received MCV4, the CDC now recommends vaccination before entry into high school, at
approximately 15 years of age. The goal is to implement, within 3 years, routine vaccination with
MCV4 of all preadolescents beginning at 11 years of
age. Other adolescents and young adults who want
to decrease their risk for meningococcal disease also
can be given the immunization. The recommendations state that MCV4 is preferred, but MPSV4 is
acceptable (1).
Meningococcal vaccination also is recommended for other high-risk groups including (1):
Anyone traveling to or living in a part of the
world where meningococcal disease is endemic
Anyone who is asplenic or has a damaged
spleen
Anyone who has terminal complement component deficiency (an immune system disorder)
Anyone possibly exposed to meningitis during
an outbreak
Young men and women entering the military
College freshmen living in dormitories
College freshmen who live in dormitories are at
higher risk for meningococcal disease than other
individuals of the same age because lifestyle factors
common among freshman college students appear to
be linked to the disease. These factors include: living
in crowded housing, going to bars, smoking, and
having irregular sleeping habits. Because of the feasibility constraints in targeting freshmen in dormitories, the CDC indicates that colleges may elect to
target their vaccination campaigns to all matriculating freshmen. The risk for meningococcal disease
among nonfreshmen college students is similar to
that for the general population of similar age (1824
years). However, the vaccines are safe and immunogenic and can be provided to nonfreshmen college
students who want to reduce their risk for meningococcal disease (1).
ACOG Recommendations
The American College of Obstetricians and Gynecologists supports the recommendations of the ACIP
for routine vaccination of preadolescents against
meningococcal disease. Several medical profes-
16
sional organizations, including the American Academy of Pediatrics, the Society for Adolescent
Medicine, and the American Academy of Family
Physicians also support the recommendations of the
ACIP (35). The American College of Obstetricians
and Gynecologists encourages all health care
providers caring for adolescent and young adult
patients to provide meningococcal vaccination with
MCV4 when appropriate. Because of the lack of
data regarding the safety of MCV4 during pregnancy, MPSV4 can be considered for adolescents
and young adults who are pregnant and those having
unprotected sex who may be at risk for unintended
pregnancy. Health care providers are encouraged to
discuss meningococcal vaccination with patients
whose children have reached preadolescence, adolescence, or young adulthood. It is important to
increase parents, adolescents, and young adults
awareness of the signs and symptoms of meningococcal disease even though they are frequently nonspecific. This can result in earlier medical care and
improved clinical outcomes.
References
1. Bilukha OO, Rosenstein N. Prevention and control of
meningococcal disease. Recommendations of the
Advisory Committee on Immunization Practices (ACIP).
National Center for Infectious Diseases, Centers for
Disease Control and Prevention (CDC). MMWR
Recomm Rep 2005;54(RR-7):1-21. Available at: http://
www.cdc.gov/mmwr/preview/mmwrhtml/rr5407a1.htm.
Retrieved June 6, 2005.
2. Centers for Disease Control and Prevention. Meningococcal vaccines: what you need to know. Available at
http://www.cdc.gov/nip/publications/vis/vis-mening.rtf.
Retrieved May 18, 2005.
3. American Academy of Family Physicians. Meningococcal immunization. Available at: http://www.aafp.org/
x34406.xml. Retrieved June 8, 2005.
4. Middleman AB, Rickert VI, Rosenthal SL. Meningococcal vaccine: position statement of the Society for
Adolescent Medicine. J Adolesc Health 2005;37:262.
5. Prevention and control of meningococcal disease: recommendations for use of meningococcal vaccines in pediatric patients. Pediatrics 2005;116:496505.
COMMITTEE OPINIONS
ACOG
Committee on
and
The ACOG Working
Group on Immunization
construed as dictating an exclusive
course of treatment or procedure
to be followed.
The College wishes to thank
Eduardo Lara-Torre, MD, Marc
R. Laufer, MD, Abigail English,
JD, Jennifer E. Dietrich, MD,
MSc, Richard S. Guido, MD,
John Santelli, MD, MPH, Stanley
Gall, MD, and Barbara Moscicki,
MD, for their assistance in the
development of this document.
stored in a retrieval system,
posted on the Internet, or transmitted, in any form or by any
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Human papillomavirus vaccination.
ACOG Committee Opinion No. 344.
2006;108:699705.
17
Committee
Opinion
Human Papillomavirus Vaccination

ABSTRACT: The U.S. Food and Drug Administration recently approved a
quadrivalent human papillomavirus (HPV) vaccine for females aged 926
years. The American College of Obstetricians and Gynecologists recommends the vaccination of females in this age group. The Advisory Committee
on Immunization Practices has recommended that the vaccination routinely
be given to girls when they are 11 or 12 years old. Although obstetrician
gynecologists are not likely to care for many girls in this initial vaccination
target group, they are critical to the widespread use of the vaccine for
females aged 1326 years. The quadrivalent HPV vaccine is most effective if
given before any exposure to HPV infection, but sexually active women can
receive and benefit from the vaccination. Vaccination with the quadrivalent
HPV vaccine is not recommended for pregnant women. It can be provided to
women who are breastfeeding. The need for booster vaccination after 5 years
has not been established. Health care providers are encouraged to discuss
with their patients the benefits and limitations of the quadrivalent HPV vaccine and the need for continued routine cervical cytology screening.
The relationship between infection with human papillomavirus (HPV) and

both cervical cancer and genital warts has been recognized for many years
(1). More than 100 genotypes of HPV have been discovered to date with
approximately 30 found in the genital mucosa. However, only 15 have been
shown to be associated with cervical cancer. Approximately 70% of cervical
cancers result from infection with HPV genotypes 16 and 18, and 90% of
cases of genital warts result from infection with HPV genotypes 6 and 11 (2).
The American Cancer Society estimates there will be 9,710 new cases of
cervical cancer and 3,700 deaths from cervical cancer in the United States in
2006 (3). Cervical cancer is the second largest cause of female cancer mortality worldwide (4). Worldwide, an estimated 493,000 new cases occur each
year and of these cases, 274,000 women die annually from cervical cancer
(5). Eighty percent of these deaths occur where resources are the most limited (6). Although the implementation of cervical cytology screening programs
and treatment of precancerous lesions has led to a decrease in cervical cancer
deaths in the United States, there continues to be a significant population of
women not receiving adequate screening. In 2003, only 67% of uninsured
women aged 1864 years obtained cervical cytology screening within the
past 3 years compared with 86% of insured women in that age group (7).
18
The U.S. Food and Drug Administration (FDA)

recently licensed the first vaccine shown to be
effective at preventing infection with some genotypes
of HPV. The prophylactic quadrivalent human papillomavirus L1 virus-like particle vaccine offers protection against cervical cancer, cervical dysplasias,
vulvar or vaginal dysplasias, and genital warts associated with HPV genotypes 6, 11, 16, and 18. The
FDA approval is for administration of this three-dose
vaccine to females aged 926 years at intervals of 0,
2, and 6 months (see the box). The need for booster
doses remains to be demonstrated (8). To date, protection has been shown to last at least 5 years (9).
A second, bivalent formulation of an HPV vaccine is in development. Results of initial studies of
this vaccine indicate that it offers protection similar
to the quadrivalent vaccine against HPV infections
caused by genotypes 16 and 18 (10, 11).
Studies of the quadrivalent HPV vaccine have
shown that in subjects naive to the vaccine genotypes who followed protocol, the vaccine was 100%
effective in preventing cervical intraepithelial neoplasia (CIN) 2, CIN 3, and condylomatous vulvar
disease related to the HPV genotypes covered by the
vaccine (8). In contrast, for a woman with current or
past HPV infection, there is no evidence of protection from disease caused by the HPV genotypes with
which she was infected. There is, however, evidence
of protection from disease caused by the remaining
HPV vaccine genotypes (8, 12).
To be maximally effective against all HPV
genotypes included in the quadrivalent vaccine, it
should be given before any exposure to HPV infection. If the vaccine is given after the onset of sexual
activity, patients may have already been infected
with HPV and develop abnormal cervical cytology
related to the HPV genotypes in the vaccine as well
as to those genotypes not included in the vaccine.
Recommendations
Vaccination of Girls, Adolescents, and Young
Women
The American College of Obstetricians and
Gynecologists (ACOG) Committee on Adolescent
Health Care and the ACOG Working Group on
Immunization recommend the vaccination of
females aged 926 years against HPV. The Advisory
Committee on Immunization Practices has recommended the initial vaccination target of females aged
11 or 12 years (13). Although obstetriciangynecol-
Key Information Regarding Gardasil

Dosage:
The quadrivalent human papillomavirus (HPV) vaccine
should be administered intramuscularly as three separate 0.5-mL doses according to the following schedule:
First dose: at elected date
Second dose: 2 months after the first dose
Third dose: 6 months after the first dose
Storage:
The quadrivalent vaccine should be refrigerated at 28C
(3646F). It should not be frozen and should be protected from light.
Contraindications:
Hypersensitivity to the active substances or to any of
the excipients of the quadrivalent vaccine. Individuals
who develop symptoms indicative of hypersensitivity
after receiving a dose of quadrivalent vaccine should
not receive further doses of the product.
Precautions:
As with any vaccine, vaccination may not result in
protection in all vaccine recipients.
The quadrivalent vaccine is not intended to be used
for treatment of active genital warts; cervical cancer;
cervical intraepithelial neoplasia, vulvar intraepithelial
neoplasia, or vaginal intraepithelial neoplasia.
The quadrivalent vaccine has not been shown to protect against disease due to nonvaccine HPV types.
The vaccine is not recommended for use in pregnant
women. The manufacturer maintains a pregnancy registry to monitor fetal outcomes of pregnant women
exposed to the vaccine. Any exposure to it during
pregnancy can be reported by calling 800-986-8999.
Vaccine Adverse Event Reporting:
To report an adverse event associated with administration of the quadrivalent vaccine, go to
http://vaers.hhs.gov/.
Advisory Committee on Immunization Practices
Recommendations:
For current recommendations by the Advisory
Committee on Immunization Practices, go to
http://www.cdc.gov/nip/ACIP/.
CPT Code:
The American Medical Association has established a
Current Procedural Terminology* code of 90649 for
quadrivalent HPV vaccination.
*Current Procedural Terminology (CPT) is copyright 2006
American Medical Association. All rights reserved. No fee schedules, basic units, relative values or related listings are included
in CPT. The AMA assumes no liability for the data contained
herein. CPT is a trademark of the American Medical Association.
COMMITTEE OPINIONS
ogists are not likely to care for many girls in this initial vaccination target group, they are critical to the
widespread use of the vaccine for females aged
1326 years. The American College of Obstetricians
and Gynecologists has recommended that the first
adolescent reproductive health care visit take place
between ages 13 years and 15 years (14). Adolescents and young women aged 1626 years who are
in the vaccination age groups visit obstetrician
gynecologists for primary care, contraceptive or
other gynecologic needs, or pregnancy-related services. These visits are a strategic time to discuss HPV
and the potential benefit of the HPV vaccine and to
offer vaccination to those who have not already
received it. During a health care visit with a girl or
woman in the age range for vaccination, an assessment of the patients HPV vaccine status should be
conducted and documented in the patient record.
Cervical Cytology Screening
Current cervical cytology screening recommendations remain unchanged and should be followed
regardless of vaccination status (1, 1417). Cervical
cancer screening should begin approximately 3
years after the onset of vaginal intercourse or no
later than age 21 years (16). After the first screening,
annual cervical cytology screening should be conducted for women younger than 30 years (17). It
must be emphasized that the currently approved
quadrivalent vaccine protects against acquisition
of HPV genotypes that account for only 70% of
HPV-related cervical cancer and only 90% of genital warts cases (2). The vaccine is a preventive tool
and is not a substitute for cancer screening.
Human Papillomavirus Testing
Testing for HPV is currently not recommended
before vaccination. Testing for HPV DNA would not
identify past HPV infections, only current HPV
infections. Serologic assays for HPV are unreliable
and currently not commercially available. Requiring
any type of screening test would raise the cost of
vaccination programs dramatically and reduce the
cost-effectiveness of vaccination.
Vaccination of Sexually Active Women
Sexually active women can receive the quadrivalent
HPV vaccine. Women with previous abnormal cervical cytology or genital warts also can receive the
quadrivalent HPV vaccine. These patients should be
counseled that the vaccine may be less effective in
19
women who have been exposed to HPV before vaccination than in women who were HPV naive at the
time of vaccination (8, 12). Women with previous
HPV infection will benefit from protection against
disease caused by the HPV vaccine genotypes with
which they have not been infected. The need for annual cervical cytology screening should be emphasized.
Vaccination of Women With Previous Cervical
Intraepithelial Neoplasia
There is concern that provision of the vaccination to
women with previous CIN may create a false sense
of protection, potentially deterring patients from
continuing their regular screening and management.
The quadrivalent vaccine can be given to patients
with previous CIN, but practitioners need to emphasize that the benefits may be limited, and cervical
cytology screening and corresponding management
based on ACOG recommendations must continue.
Vaccination Is Not Treatment
The quadrivalent HPV vaccine is not intended to
treat patients with cervical cytologic abnormalities
or genital warts. Patients with these conditions
should undergo the appropriate evaluation and treatment. It is important to note that many early cytoloic abnormalities can be detected and managed
conservatively given the significant rate of regression. This is especially true in adolescents and
young women (15, 18).
Vaccination of Pregnant and Lactating Women
The quadrivalent HPV vaccine has been classified
by the FDA as pregnancy category B. Although its
use in pregnancy is not recommended, no teratogenic effects have been reported in animal studies.
In clinical studies, the proportion of pregnancies
with an adverse outcome were comparable in
women who received the quadrivalent HPV vaccine and in women who received a placebo (8).
The manufacturers pregnancy registry should be
contacted if pregnancy is detected during the vaccination schedule. Completion of the series should
be delayed until pregnancy is completed. It is not
known whether vaccine antigens or antibodies
found in the quadrivalent vaccine are excreted in
human milk (8). Lactating women can receive the
quadrivalent HPV vaccine because inactivated vaccines such as this vaccine do not affect the safety
of breastfeeding for mothers or infants (19).
20
Vaccination of Immunosuppressed Patients

The presence of immunosuppression, like that experienced in patients with HIV infection, is not a contraindication to the quadrivalent HPV vaccine.
However, the immune response may be smaller in
the immunocompromised patient than in immunocompetent patients (8).
Vaccination of Women Older Than 26 Years
and Males
Research regarding vaccination of women older than
26 years and males is currently under way. Data
available are insufficient to make recommendations
for these populations.
Other Methods for Prevention of HPV Infection
Abstinence from sexual activity is the most effective
way to avoid sexually transmitted diseases (STDs),
including HPV infection. Limiting the number of
sexual partners also may decrease ones risk for
STDs, including HPV. Use of latex condoms is the
only method currently available for sexually active
individuals to reduce the likelihood of HPV acquisition and HPV-related cervical dysplasia (20, 21).
Research Needs
ACOG supports additional research to evaluate the
need for booster vaccination, the effectiveness of
vaccination in women older than 26 years, and the
effectiveness of vaccination of males.
Educational Efforts
The quadrivalent HPV vaccine is a major breakthrough in efforts to prevent cervical cancer; obstetriciangynecologists can play a critical role in its
widespread use. It is important for clinicians to provide patient education about HPV-related disease
and be prepared to respond to questions from
patients regarding the HPV vaccine. Studies have
shown that physician recommendation plays an
important role in the acceptance of the vaccine by
patients (22). Limitations of the currently approved
quadrivalent vaccine also should be discussed,
including that it provides coverage for only two of
the 15 HPV genotypes associated with cancer and
only two of the genotypes that cause genital warts.
In addition, the health care provider can discuss with
patients that despite the high prevalence of HPV
infection, few infections result in cervical cancer.
As the HPV vaccines have been developed, market research has addressed the acceptability of HPV
vaccination by parents, guardians, and patients. A

study of 880 females aged 1545 years demonstrated that more than 80% of mothers would support
vaccinating their daughters. In most additional studies, a higher level of acceptability was associated
with educating mothers and patients about the consequences of HPV disease and the potential for
decreased rates of cervical cancer (2325). Professional recommendations for HPV vaccination are
essential in ensuring widespread acceptance and use
of the vaccine. Requiring vaccination for child care,
school, or college attendance and multicomponent
interventions that include community education
have been effective in improving the use of vaccination (26, 27).
Consent for HPV Vaccination
As for all immunizations, consent for HPV vaccination must be obtained from someone who is legally
authorized to provide it. Generally, for children and
adolescents who are minors, typically those younger
than 18 years, the consent of a parent is required for
medical care, including vaccinations. There are,
however, numerous exceptions to this requirement
(28). For example, individuals other than a parent
are sometimes authorized to consent for a child or
adolescents care. These may include a legal
guardian, a judge, or an individual who has been
authorized either by a parent or by a court to consent
for a minors care. In addition, in certain situations,
adolescents who are minors are legally allowed to
consent to their own care. This is usually determined
by state law and varies by state. Depending on the
state, certain minors are allowed to consent for care
because of their status; these may include minors
who have reached a certain age or are pregnant, married, parents, living apart from their parents, or
emancipated (28). In all states, minors are allowed to
consent for diagnosis and treatment for STDs; however, many of the laws that authorize them to do so
do not mention vaccinations (28).
Clinicians should be familiar with state and
local statutes regarding the rights of minors to health
care services and the federal and state laws that
affect confidentiality. When necessary, they should
seek appropriate legal advice. Careful analysis
would be required to determine the circumstances in
which an adolescent minor might be able to consent
for her own HPV vaccination in a particular state.
Often, state medical societies can be helpful in this
capacity. A list of state medical society web sites is
COMMITTEE OPINIONS
available at http://www.ama-assn.org/ama/pub/
category/7630.html.
Advocacy Efforts
In the United States, cervical cancer rates are highest for low income and uninsured women. Third
party payers and government agencies are encouraged to assist in covering the costs of HPV vaccination to patients, even if they are underinsured or
uninsured. Pharmaceutical companysponsored
patient assistance programs for vaccines should be
implemented as well as the provision of the vaccine
at significantly discounted rates to the Vaccines for
Children (VFC) program. The VFC program
provides free vaccines to children who are
Medicaid-eligible, uninsured, Native American, or
underinsured children who visit federally qualified
or rural health centers. Health care providers are
encouraged to become VFC providers. (For more
information, go to http://www.cdc.gov/nip/vfc/.)
References
1. Human papillomavirus. ACOG Practice Bulletin No. 61.
American College of Obstetricians and Gynecologists.
2. Bosch FX, Manos MM, Munoz N, Sherman M, Jansen
AM, Peto J, et al. Prevalence of human papillomavirus in
cervical cancer: a worldwide perspective. International
biological study on cervical cancer (IBSCC) Study
Group. J Natl Cancer Inst 1995;87:796802.
3. American Cancer Society. Cancer facts and figures 2006.
Atlanta (GA): ACS; 2006. Available at: http://www.
cancer.org/downloads/STT/CAFF2006PWSecured.pdf.
4. World Health Organization. State of the art new vaccines:
research and development. Initiative for Vaccine
Research. Geneva: WHO; 2003. Available at: http://
www.who.int/vaccine_research/documents/en/stateofart_
excler.pdf. Retrieved November 21, 2003.
5. International Agency for Research on Cancer. GLOBOCAN 2002 database. Lyon (FR): IARC; 2002.
6. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide
incidence of eighteen major cancers in 1985. Int J Cancer
1993;54:594606.
7. National Center for Health Statistics. Health, United
States, 2005 with chartbook on trends in the health of
Americans. Hyattsville (MD): NCHS; 2005.
8. Prescribing information for GARDASIL. Whitehouse
Station (NJ): Merck & Co., Inc.; 2006. Available at:
http://www.merck.com/product/usa/pi_circulars/g/
gardasil/gardasil_pi.pdf. Retrieved June 26, 2006.
9. Centers for Disease Control and Prevention. HPV and
HPV vaccineinformation for healthcare providers.
Available at: http://www.cdc.gov/std/HPV/STDFact-HPVvaccine-hcp.htm#hpvvaccine. Retrieved July 7, 2006.
21
10. Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D,

Schuind A, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised
controlled trial. GlaxoSmithKline HPV Vaccine Study
Group. Lancet 2004;364:175765.
11. Harper DM, Franco EL, Wheeler CM, Moscicki AB,
Romanowski B, Roteli-Martins CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle
vaccine against human papillomavirus types 16 and 18:
follow-up from a randomised control trial. Lancet
2006;367:124755.
12. Mao C, Koutsky LA, Ault KA, Wheeler CM, Brown DR,
Wiley DJ, et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial [published erratum appears in
Obstet Gynecol 2006;107:1425]. Obstet Gynecol 2006;
107:1827.
13. Centers for Disease Control and Prevention. HPV vaccine
[human papillomavirus (HPV) and the HPV vaccine].
Atlanta (GA): CDC. Available at: http://www.cdc.gov/
nip/vaccine/hpv/. Retrieved July 26, 2006.
Primary and preventive health care for female adolescents. In: Health care for adolescents. Washington, DC:
ACOG; 2003. p. 124.
15. Evaluation and management of abnormal cervical cytology and histology in the adolescent. ACOG Committee
Opinion No. 330. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2006:107:9638.
16. Cervical cancer screening in adolescents. ACOG
Committee Opinion No. 300. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2004;
104:8859.
17. Cervical cytology screening. ACOG Practice Bulletin No.
18. Moscicki AB, Shiboski S, Broering J, Powell K, Clayton
L, Jay N, et al. The natural history of human papillomavirus infection as measured by repeated DNA testing in
adolescent and young women. J Pediatr 1998;132:
27784.
19. Atkinson WL, Pickering LK, Schwartz B, Weniger BG,
Iskander JK, Watson JC. General recommendations on
immunization. Recommendations of the Advisory
Committee on Immunization Practices (ACIP) and the
American Academy of Family Physicians (AAFP).
Centers for Disease Control and Prevention. MMWR
Recomm Rep 2002;51(RR-2):135.
20. Hogewoning CJ, Bleeker MC, van den Brule AJ,
Voorhorst FJ, Snijders PJ, Berkhof J, et al. Condom use
promotes regression of cervical intraepithelial neoplasia
and clearance of human papillomavirus: a randomized
clinical trial. Int J Cancer 2003;107:8116.
21. Winer RL, Hughes JP, Feng Q, OReilly S, Kiviat NB,
Holmes KK, et al. Condom use and the risk of genital
human papillomavirus infection in young women. N Engl
J Med 2006;354:264554.
22. Zimet GD, Mays RM, Winston Y, Kee R, Dickes J, Su L.
Acceptability of human papillomavirus immunization. J
Womens Health Gend Based Med 2000;9:4750.
22
23. Lazcano-Ponce E, Rivera L, Arillo-Santillan E, Salmeron

J, Hernandez-Avila M, Munoz N. Acceptability of a
human papillomavirus (HPV) trial vaccine among mothers of adolescents in Cuernavaca, Mexico. Arch Med Res
2001;32:2437.
24. Hoover DR, Carfioli B, Moench EA. Attitudes of adolescent/young adult women toward human papillomavirus
vaccination and clinical trials. Health Care Women Int
2000;21:37591.
25. Davis K, Dickman ED, Ferris D, Dias JK. Human papillomavirus vaccine acceptability among parents of 10- to
15-year-old adolescents. J Low Genit Tract Dis 2004;
8:18894.
26. Centers for Disease Control and Prevention. The guide to
community preventive services. Effectiveness of multicomponent interventions that include education to
increase vaccination coverage. Atlanta (GA): CDC; 2003.
Available at: http://www.thecommunityguide.org/vaccine/
vpd-int-demand-multicomponent-ed.pdf. Retrieved July
11, 2006.
27. Centers for Disease Control and Prevention. The guide to
community preventive services. Effectiveness of requiring
vaccinations for child care, school, and college attendance to
increase vaccination coverage. Atlanta (GA): CDC; 2003.
Available at: http://www.thecommunityguide.org/vaccine/
vpd-int-demand-require.pdf. Retrieved July 11, 2006.
28. English A, Kenney KE. State minor consent laws: a summary. 2nd ed. Chapel Hill (NC): Center for Adolescent
Health & the Law; 2003.
Resources
ACOG Resources
American College of Obstetricians and Gynecologists. Cmo
prevenir las enfermedades de transmisin sexual. ACOG
Patient Education Pamphlet SP009. Washington, DC: ACOG;
2005.
American College of Obstetricians and Gynecologists. Genital
HPV (human papillomavirus) in adolescents fact sheet.
Washington, DC: ACOG; 2005.
American College of Obstetricians and Gynecologists. How to
prevent sexually transmitted diseases. ACOG Patient
Education Pamphlet AP009. Washington, DC: ACOG; 2005.
American College of Obstetricians and Gynecologists. Human
papillomavirus infection. ACOG Patient Education Pamphlet
AP073. Washington, DC: ACOG; 2003.
American College of Obstetricians and Gynecologists. Tool kit
for teen care. Washington, DC: ACOG; 2003.
Cervical cancer screening in adolescents. ACOG Committee
Gynecologists. Obstet Gynecol 2004;104:8859.
Cervical cytology screening. ACOG Practice Bulletin No. 45.
American College of Obstetricians and Gynecologists. Obstet
Gynecol 2003;102:41727.
Human papillomavirus. ACOG Practice Bulletin No. 61.
Gynecol 2005;105:90518.
Sexually transmitted diseases in adolescents. ACOG Committee Opinion No. 301. American College of Obstetricians
and Gynecologists. Obstet Gynecol 2004;104:8918.
Other Resources
The following lists are for information purposes only. Referral
to these sources and web sites does not imply the endorsement
of ACOG. These lists are not meant to be comprehensive. The
exclusion of a source or web site does not reflect the quality of
that source or web site. Please note that web sites are subject to
change without notice. Furthermore, ACOG does not endorse
any commercial products that may be advertised or available
from these organizations or on these web sites.
American Cancer Society
1599 Clifton Rd. NE
Atlanta, GA 30329
1-800-ACS-2345 (or 1-866-228-4327 for TTY)
http://www.cancer.org
The American Social Health Association
PO Box 13827
Research Triangle Park, NC 27709
(919) 361-8400
(919) 361-8488: National Herpes Hotline
http://www.ashastd.org
http://www.iwannaknow.org
http://www.ashastd.org/hpvccrc
American Society for Colposcopy and Cervical Pathology
20 West Washington St., Suite 1
Hagerstown, MD 21740
(301) 733-3640
1-800-787-7227
http://www.asccp.org
Center for Young Womens Health
Childrens Hospital Boston
333 Longwood Ave., 5th Floor
Boston, MA 02115
(617) 355-2994
http://www.youngwomenshealth.org
Centers for Disease Control and Prevention
1600 Clifton Rd.
Atlanta, GA 30333
(404) 639-3311
1-800-311-3435
http://www.cdc.gov
http://www.cdc.gov/std/hpv/STDFact-HPV-vaccine.htm
Go Ask Alice!
Columbia University
7th Floor, Lerner Hall
2920 Broadway, Mail Code 2608
New York, NY 10027
(212) 854-5453
http://www.goaskalice.columbia.edu
Merck Inc.
Make the Connection
1-888-447-8266
http://www.maketheconnection.org
COMMITTEE OPINIONS
National Cervical Cancer Public Education Campaign

1-866-280-6605
http://www.cervicalcancercampaign.org
National Womens Health Resource Center
157 Broad St., Suite 315
Red Bank, NJ 07701
(732) 530-3425
1-877-986-9472
http://www.healthywomen.org
Planned Parenthood Federation of America
434 West 33rd St.
New York, NY 10001
1-800-230-7526
http://www.plannedparenthood.org
http://www.teenwire.org
Society for Adolescent Medicine
1916 Copper Oaks Circle
Blue Springs, MO 64015
(816) 224-8010
http://www.adolescenthealth.org
http://www.adolescenthealth.org/cme/program_hpv
Society of Obstetricians and Gynaecologists of Canada

780 Echo Drive
Ottawa, ON K1S 5R7
Canada
(613) 730-4192
1-800-561-2416
http://www.sogc.org
http://www.sexualityandu.ca
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857-0001
1-888-INFO-FDA (1-888-463-6332)
http://www.fda.gov/cber/products/hpvmer060806.htm
http://www.fda.gov/womens/getthefacts/hpv.html
23
24
ACOG
Committee on
American Academy
of Pediatrics
Committee
Opinion
DEDICATED TO THE HEALTH OF ALL CHILDREN
Committee on Adolescence
Number 349, November 2006
Reaffirmed 2009
This document reflects emerging clinical and scientific advances as of the
date issued and is subject to change.
The information should not be construed as dictating an exclusive
course of treatment or procedure to
be followed.
The committees would like to thank
Lesley Breech, MD; Angela Diaz,
MD; S. Paige Hertwick, MD; Paula
Adams Hillard, MD; and Marc
Laufer, MD, for their assistance in
the development of this document.
Copyright November 2006
by the American Academy of
Pediatrics and the American College
of Obstetricians and Gynecologists.
stored in a retrieval system, posted on
the Internet, or transmitted, in any
form or by any means, electronic,
mechanical, photocopying, recording,
or otherwise, without prior written
permission from the publisher.
Requests for authorization to make
photocopies should be
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Menstruation in girls and adolescents:
using the menstrual cycle as a vital
sign. ACOG Committee Opinion No.
349. American Academy of Pediatrics;
2006;108:13238.
Menstruation in Girls and

Adolescents: Using the Menstrual
Cycle as a Vital Sign
ABSTRACT: Young patients and their parents often are unsure about what
represents normal menstrual patterns, and clinicians also may be unsure
about normal ranges for menstrual cycle length and amount and duration of
flow through adolescence. It is important to be able to educate young
patients and their parents regarding what to expect of a first period and
about the range for normal cycle length of subsequent menses. It is equally
important for clinicians to have an understanding of bleeding patterns in
girls and adolescents, the ability to differentiate between normal and abnormal menstruation, and the skill to know how to evaluate young patients conditions appropriately. Using the menstrual cycle as an additional vital sign
adds a powerful tool to the assessment of normal development and the exclusion of serious pathologic conditions.
Young patients and their parents frequently have difficulty assessing what
constitutes normal menstrual cycles or patterns of bleeding. Girls may be
unfamiliar with what is normal and may not inform their parents about menstrual irregularities or missed menses. Additionally, girls often are reluctant
to discuss this very private topic with a parent, although they may confide in
another trusted adult. Some girls will seek medical attention for cycle variations that actually fall within the normal range. Others are unaware that their
bleeding patterns are abnormal and may be attributable to significant underlying medical issues with the potential for long-term health consequences.
Clinicians also may be unsure about normal ranges for menstrual cycle
length and for amount and duration of flow through adolescence. Clinicians
who are confident in their understanding of early menstrual bleeding patterns
may convey information to their patients more frequently and with less
prompting; girls who have been educated about menarche and early menstrual patterns will experience less anxiety when they occur (1). By including an evaluation of the menstrual cycle as an additional vital sign, clinicians
reinforce its importance in assessing overall health status for both patients
and parents. Just as abnormal blood pressure, heart rate, or respiratory rate
may be key to the diagnosis of potentially serious health conditions, identi-
COMMITTEE OPINIONS
fication of abnormal menstrual patterns through

adolescence may permit early identification of
potential health concerns for adulthood.
Normal Menstrual Cycles

Menarche
From the early 1800s to the mid-1950s, menarche
occurred at increasingly younger ages in the United
States, but there has been no further decline in the
past 4050 years. This finding also has been seen in
international studies of other developed urban populations (2). The U.S. National Health and Nutrition
Examination Surveys have found no significant
change in the median age at menarche over the past
30 years except among the non-Hispanic black population, which has a 5.5-month earlier age at menarche than it did 30 years ago (3). Age at menarche
varies internationally and especially in less developed countries; in Haiti, for example, the mean age
at menarche is 15.37 years (4, 5). This knowledge
may be especially pertinent for practitioners with a
large number of immigrant families in their patient
population. Although onset of puberty and menarche
typically occur at a later age in females from less
well-developed nations, two large studies have confirmed that a higher gain in body mass index (BMI)
during childhood is related to an earlier onset of
puberty (6, 7). This earlier onset of puberty may
result from attainment of a minimal requisite body
mass at a younger age. Other possible explanations
for the perceived trend in timing and progression of
puberty are environmental factors, including socioeconomic conditions, nutrition, and access to preventive health care (8).
Despite variations worldwide and within the
U.S. population, median age at menarche has
remained relatively stable, between 12 and 13 years,
across well-nourished populations in developed
countries. The median age of females when they have
their first period or menarche is 12.43 years (see the
box) (3). Only 10% of females are menstruating at
age 11.11 years; 90% are menstruating by age 13.75
years. The median age at which black females begin
to menstruate is earlier (12.06 years) than the median
age for Hispanic females (12.25 years) and nonHispanic white females (12.55 years) (3). Although
black girls start to mature earlier than non-Hispanic
white and Hispanic girls, U.S. females complete secondary sexual development at approximately the
same ages (9). Menarche typically occurs within 23
25
Normal Menstrual Cycles in Young Females

Menarche (median age):
Mean cycle interval:
Menstrual cycle interval:
Menstrual flow length:
Menstrual product use:
12.43 years
32.2 days in first gynecologic
year
typically 2145 days
7 days or less
three to six pads or tampons
per day
years after thelarche (breast budding), at Tanner stage

IV breast development, and is rare before Tanner
stage III development (10). Menarche correlates with
age at onset of puberty and breast development. In
girls with early onset of breast development, the
interval to menarche is longer (3 years or more) than
in girls with later onset (1113). By age 15 years,
98% of females will have had menarche (3, 14).
Traditionally, primary amenorrhea has been defined
as no menarche by age 16 years; however, many
diagnosable and treatable disorders can and should
be detected earlier, using the statistically derived
guideline of age 1415 years (3, 14). Thus, an evaluation for primary amenorrhea should be considered
for any adolescent who has not reached menarche by
15 years or has not done so within 3 years of thelarche. Accordingly, lack of breast development by
age 13 years also should be evaluated (15).
Cycle Length and Ovulation
Menstrual cycles often are irregular through adolescence, particularly the interval from the first to the
second cycle. According to the World Health Organizations international and multicenter study of 3,073
girls, the median length of the first cycle after menarche was 34 days, with 38% of cycle lengths exceeding 40 days. Variability was wide: 10% of females
had more than 60 days between their first and second
menses, and 7% had a first-cycle length of 20 days
(16). Most females bleed for 27 days during their
first menses (1719). Early menstrual life is characterized by anovulatory cycles (20, 21), but the frequency of ovulation is related to both time since
menarche and age at menarche (2123). Early
menarche is associated with early onset of ovulatory
cycles. When age at menarche is younger than 12
years, 50% of cycles are ovulatory in the first gynecologic year (year after menarche).
By contrast, it may take 812 years after menarche until females with later-onset menarche are fully
26
ovulatory (23). Despite variability, most normal

cycles range from 21 to 45 days, even in the first
gynecologic year (1618), although short cycles of
fewer than 20 days and long cycles of more than 45
days may occur. Because long cycles most often
occur in the first 3 years postmenarche, that overall
trend is toward shorter and more regular cycles with
increasing age. By the third year after menarche,
6080% of menstrual cycles are 2134 days long, as
is typical of adults (16, 18, 24). An individuals normal cycle length is established around the sixth
gynecologic year, at a chronologic age of approximately 19 or 20 years (16, 18).
Two large studies, one cataloging 275,947
cycles in 2,702 females and another reporting on
31,645 cycles in 656 females, support the observation that menstrual cycles in girls and adolescents
typically range from 21 to approximately 45 days,
even in the first gynecologic year (25, 26). In the
first gynecologic year, the fifth percentile for cycle
length is 23 days and the 95th percentile is 90 days.
By the fourth gynecologic year, fewer females are
having cycles that exceed 45 days, but anovulation is
still significant for some, with the 95th percentile for
cycle length at 50 days. By the seventh gynecologic
year, cycles are shorter and less variable, with the
fifth percentile for cycle length at 27 days and the
95th percentile at only 38 days. Thus, during the
early years after menarche, cycles may be somewhat
long because of anovulation, but 90% of cycles will
be within the range of 2145 days (16).
conditions are associated with derangement of hypothalamicpituitary endocrine function (see the box).
Commonly, polycystic ovary syndrome (PCOS) causes prolonged intervals between menstrual periods,
especially in patients with signs of androgen excess.
The pathogenesis of PCOS is unclear; many experts
believe that PCOS results from primary functional
intraovarian overproduction of androgen. Others
believe that excessive luteinizing hormone secretion
from the pituitary gland, which stimulates a secondary ovarian androgen excess, has a role in causing
the disorder. Still others hypothesize that PCOS may
be related to hyperinsulinism. Whatever its origins,
PCOS accounts for 90% of hyperandrogenism among
females and, by definition, is characterized by amenorrhea and oligomenorrhea. Before the diagnosis is
confirmed, hyperprolactinemia, adrenal and ovarian
tumors, and drug effects (such as those caused by
danazol and several psychotropic medications) must
be ruled out. Additionally, although uncommon in the
general population, congenital adrenal hyperplasia
should be ruled out by a negative 17-hydroxyprogesterone test result (serum concentrations of less
than 1,000 ng/dL) (27). Treatment of PCOS should
target menstrual irregularities, hirsutism if present,
obesity, or insulin resistance.
Menstrual irregularities can be caused by disturbance of the central gonadotropin-releasing hormone
pulse generator as well as by significant weight loss,
strenuous exercise, substantial changes in sleeping
or eating habits, and severe stressors. Menstrual disturbances also occur with chronic diseases, such as
Abnormal Menstrual Cycles

Prolonged Interval
A number of medical conditions can cause irregular
or missed menses. Although secondary amenorrhea
has been defined as the absence of menses for 6
months, it is statistically uncommon for girls and
adolescents to remain amenorrheic for more than 3
months or 90 daysthe 95th percentile for cycle
length. Thus, it is valuable to begin evaluation of
secondary amenorrhea after the absence of menses
for 90 days. Therefore, girls and adolescents with
chaotically irregular cycles with more than 3 months
between periods should be evaluated, not reassured
that it is normal to have irregular periods in the
first gynecologic years.
Irregular menses may be associated with many
conditions, including pregnancy, endocrine disorders,
and acquired medical conditions because all of these
Causes of Menstrual Irregularity

Pregnancy
Endocrine causes
Poorly controlled diabetes mellitus
Polycystic ovary syndrome
Cushings disease
Thyroid dysfunction
Premature ovarian failure
Late-onset congenital adrenal hyperplasia
Acquired conditions
Stress-related hypothalamic dysfunction
Medications
Exercise-induced amenorrhea
Eating disorders (both anorexia and bulimia)
Tumors
Ovarian tumors
Adrenal tumors
Prolactinomas
COMMITTEE OPINIONS
poorly controlled diabetes mellitus; with genetic and

congenital conditions, such as Turners syndrome;
and with other forms of gonadal dysgenesis. The
diagnosis of pregnancy always should be excluded,
even if the history suggests the patient has not been
sexually active.
27
form of estrogen therapy, may affect hematologic

factors and mask the diagnosis. Blood collection to
screen for hematologic disorders should be obtained
before initiating treatment. Evaluating the patient
may include referral to a hematologist or a specialized hemophilia treatment center for appropriate
screening.
Excessive Menstrual Flow

A females first period usually is reported to be of
medium flow, and the need for menstrual hygiene
products is not typically excessive. Although experts
typically report that the mean blood loss per menstrual period is 30 mL per cycle and that chronic loss
of more than 80 mL is associated with anemia, this
has limited clinical utility because most females are
unable to measure their blood loss. However, a recent
study in adult women confirms that the perception of
heavy menstrual flow is correlated with a higher
objective volume of blood loss (28).
Attempts to measure menstrual blood loss on
the basis of the number of pads or tampons used per
day or the frequency of pad changes are subject to
variables such as the individuals fastidiousness, her
familiarity or comfort with menstrual hygiene products, and even variation among types and brands
of pads or tampons (29). Most report changing a pad
approximately three to six times a day, although
external constraints such as school rules and limited
time between classes may make menstrual hygiene
more problematic for adolescents than for adults.
Menstrual flow requiring changes of menstrual
products every 12 hours is considered excessive,
particularly when associated with flow that lasts
more than 7 days at a time. This type of acute menorrhagia, although most often associated with
anovulation, also has been associated with the diagnosis of hematologic problems, including von
Willebrands disease and other bleeding disorders,
or other serious problems, including hepatic failure
and malignancy (3033).
The prevalence of von Willebrands disease is
1% in the general population. Von Willebrands
disease is the most common medical disorder associated with menorrhagia at menarche (34). As many
as one in six girls presenting to an emergency
department with acute menorrhagia may have von
Willebrands disease (30). Therefore, hematologic
disorders should be considered in patients presenting with menorrhagiaespecially those presenting
acutely at menarche. Hormonal treatment, in the
Anticipatory Guidance
Because development of secondary sex characteristics begins at ages as young as 8 years, primary care
clinicians should include pubertal development in
their anticipatory guidance to children and parents
from this age on. Clinicians should take an ongoing
history and perform a complete annual examination,
including the inspection of the external genitalia. It
is important to educate children and parents about
the usual progression of puberty. This includes the
likelihood that a childs initial breast growth may be
unilateral and slightly tender. Breast development
will likely then become bilateral, but some asymmetry is normal. Young females and their parents
should understand that the progression of puberty
also includes the development of pubic hair, which
will increase in amount over time and become thicker and curlier. Additionally, clinicians should convey
that females will likely begin to menstruate approximately 22.5 years after breast development begins,
keeping in mind that recent studies have suggested
that the onset of both breast development and
menarche may occur slightly earlier for black girls
than for white girls (35). Young females should
understand that menstruation is a normal part of
development and should be instructed on use of feminine products and on what is considered normal
menstrual flow. Ideally, both parents and clinicians
can participate in this educational process.
Evaluation
Once young females begin menstruating, evaluation
of the menstrual cycle should be included with an
assessment of other vital signs. By including this
information with the other vital signs, clinicians
emphasize the important role of menstrual patterns
in reflecting overall health status. Clinicians should
ask at every visit for the first date of the patients last
menstrual period. Clinicians should convey that the
menstrual cycle is from the first day of a period to the
first day of the next period and may vary in length.
28
Both the American Academy of Pediatrics and

the American College of Obstetricians and Gynecologists recommend preventive health visits during
adolescence to begin a dialogue and establish an environment where a patient can feel good about taking
responsibility for her own reproductive health and
feel confident that her concerns will be addressed in
a confidential setting (36, 37). These visits are also
an opportunity to provide guidance to young females
and their parents on adolescent physical development
based on data that define normal pubertal development, menarche, and menstrual cyclicity (38). Even
during visits with adult patients who interact with
adolescents or have children, education about appropriate expectations and normal patterns for the menstrual cycle may be helpful guidance in the decision
to consider evaluation.
Asking the patient to begin to chart her menses
may be beneficial, especially if the bleeding history is
too vague or considered to be inaccurate. Although
uncommon, abnormalities do occur. Confirming normal internal and external genital anatomy with a
pelvic examination or ultrasonography can rule out
significant abnormalities. Therefore, one might consider the menstrual cycle as a type of vital sign and an
indicator of other possible medical problems. Using
menarche or the menstrual cycle as a sensitive vital
sign adds a powerful tool to the assessment of normal
hormonal development and the exclusion of serious
abnormalities, such as anorexia nervosa, inflammatory bowel disease, and many other chronic illnesses.
Menstrual conditions that suggest the need for further
evaluation are listed in the box.
Because menarche is such an important milestone in physical development, it is important to be
able to educate young females and their parents
regarding what to expect of a first period and about
the range for normal cycle length of subsequent
menses. Girls who have been educated about early
menstrual patterns will experience less anxiety as
development progresses (1). It is equally important
for clinicians to have an understanding of bleeding
patterns of young females, the ability to differentiate
between normal and abnormal menstruation, and the
skill to know how to evaluate the young female
patient appropriately.
References
1. Frank D, Williams T. Attitudes about menstruation among
fifth-, sixth-, and seventh-grade pre- and post-menarcheal
girls. J Sch Nurs 1999;15:2531.
Menstrual Conditions That

May Require Evaluation
Menstrual periods that:
Have not started within 3 years of thelarche
Have not started by 13 years of age with no signs of
pubertal development
Have not started by 14 years of age with signs of
hirsutism
Have not started by 14 years of age with a history
or examination suggestive of excessive exercise or
eating disorder
Have not started by 14 years of age with concerns
about genital outflow tract obstruction or anomaly
Have not started by 15 years of age
Are regular, occurring monthly, and then become
markedly irregular
Occur more frequently than every 21 days or less frequently than every 45 days
Occur 90 days apart even for one cycle
Last more than 7 days
Require frequent pad or tampon changes (soaking
more than one every 12 hours)
2. Wyshak G, Frisch RE. Evidence for a secular trend in age

of menarche. N Engl J Med 1982;306:10335.
3. Chumlea WE, Schubert CM, Roche AF, Kulin HE, Lee
PA, Himes JH, et al. Age at menarche and racial comparisons in US girls. Pediatrics 2003;111:1103.
4. Thomas F, Renaud F, Benefice E, de Meeus T, Guegan JF.
International variability of ages at menarche and menopause: patterns and main determinants. Hum Biol 2001;
73:27190.
5. Barnes-Josiah D, Augustin A. Secular trend in the age at
menarche in Haiti. Am J Hum Biol 1997;7:35762.
6. He Q, Karlberg J. BMI in childhood and its association
with height gain, timing of puberty and final height.
Pediatr Res 2001;49:24451.
7. Wang Y. Is obesity associated with early sexual maturation? A comparison of the association in American boys
versus girls. Pediatrics 2002;110:90310.
8. Apter D, Hermanson E. Update on female pubertal development. Curr Opin Obstet Gynecol 2002;14:47581.
9. Sun SS, Schubert CM, Chumlea WC, Roche AF, Kulin
HE, Lee PA, et al. National estimates of the timing of sexual maturation and racial differences among US children.
Pediatrics 2002;110:9119.
10. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291303.
11. Marti-Henneberg C, Vizmanos B. The duration of puberty in girls is related to the timing of its onset. J Pediatr
1997;131:61821.
12. Llop-Vinolas D, Vizmanos B, Closa Monasterolo R,
Escribano Subias J, Fernandez-Ballart JD, Marti-Henneberg C. Onset of puberty at eight years of age in girls
determines a specific tempo of puberty but does not affect
adult height. Acta Paediatr 2004;93:8749.
COMMITTEE OPINIONS
13. Largo RH, Prader A. Pubertal development in Swiss girls.

Helv Paediatr Acta 1983;38:22943.
14. National Center for Health Statistics. Age at menarche:
United States. Rockville (MD): NCHS; 1973. Available
at: http://www.cdc.gov/nchs/data/series/sr_11/sr11_133.
pdf. Retrieved June 26, 2006.
15. Reindollar RH, Byrd JR, McDonough PG. Delayed sexual development: a study of 252 patients. Am J Obstet
Gynecol 1981;140:37180.
16. World Health Organization multicenter study on menstrual and ovulatory patterns in adolescent girls. II.
Longitudinal study of menstrual patterns in the early postmenarcheal period, duration of bleeding episodes and
menstrual cycles. World Health Organization Task Force
on Adolescent Reproductive Health. J Adolesc Health
Care 1986;7:23644.
17. Flug D, Largo RH, Prader A. Menstrual patterns in adolescent Swiss girls: a longitudinal study. Ann Hum Biol
1984;11:495508.
18. Widholm O, Kantero RL. A statistical analysis of the
menstrual patterns of 8,000 Finnish girls and their mothers. Acta Obstet Gynecol Scand Suppl 1971;14:(suppl
14):136.
19. Zacharias L, Rand WM, Wurtman RJ. A prospective study
of sexual development and growth in American girls: the
statistics of menarche. Obstet Gynecol Surv 1976;31:
32537.
20. Venturoli S, Porcu E, Fabbri R, Magrini O, Paradisi R,
Pallotti G, et al. Postmenarchal evolution of endocrine
pattern and ovarian aspects in adolescents with menstrual
irregularities. Fertil Steril 1987;48:7885.
21. Venturoli S, Porcu E, Fabbri R, Magrini O, Grammi L,
Paradisi R, et al. Longitudinal evaluation of the different
gonadotropin pulsatile patterns in anovulatory cycles of
young girls. J Clin Endocrinol Metab 1992;74:83641.
22. Apter D, Vihko R. Early menarche, a risk factor for breast
cancer, indicates early onset of ovulatory cycles. J Clin
Endocrinol Metab 1983;57:826.
23. Vihko R, Apter D. Endocrine characteristics of adolescent
menstrual cycles: impact of early menarche. J Steroid
Biochem 1984;20:2316.
24. Hickey M, Balen A. Menstrual disorders in adolescence:
investigation and management. Hum Reprod Update
2003;9:493504.
29
25. Treloar AE, Boynton RE, Behn BG, Brown BW. Variation
of the human menstrual cycle through reproductive life.
Int J Fertil 1967;12:77126.
26. Vollman RF. The menstrual cycle. Major Probl Obstet
Gynecol 1977;7:1193.
27. Cowan JT, Graham MG. Polycystic ovary syndrome:
more than a reproductive disorder. Patient Care 2003;37:
2333.
28. Warner PE, Critchley HO, Lumsden MA, CampbellBrown M, Douglas A, Murray GD. Menorrhagia I: measured blood loss, clinical features, and outcome in women
with heavy periods: a survey with follow-up data. Am J
29. Grimes DA. Estimating vaginal blood loss. J Reprod Med
1979;22:1902.
30. Claessens E, Cowell CA. Acute adolescent menorrhagia.
Am J Obstet Gynecol 1981;139:27780.
31. Bevan JA, Maloney KW, Hillery CA, Gill JC, Montgomery RR, Scott JP. Bleeding disorders: a common
cause of menorrhagia in adolescents. J Pediatr 2001;138:
85661.
32. Ellis MH, Beyth Y. Abnormal vaginal bleeding in adolescence as the presenting symptom of a bleeding diathesis.
J Pediatr Adolesc Gynecol 1999;12:12731.
33. Duflos-Cohade C, Amandruz M, Thibaud E. Pubertal
metrorrhagia. J Pediatr Adolesc Gynecol 1996;9:1620.
34. Castaman G, Federici AB, Rodeghiero F, Mannucci PM.
Von Willebrands disease in the year 2003: towards complete identification of gene defects for correct diagnosis
and treatment. Haematologica 2003;88:94108.
35. Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, et al. Secondary sexual
characteristics and menses in young girls seen in office
practice: a study from the Pediatric Research in Office
Settings Network. Pediatrics 1997;99:50512.
36. American Academy of Pediatrics. Guidelines for health
supervision III. Elk Grove Village (IL): AAP; 2002.
Health care for adolescents. Washington, DC: ACOG;
2003.
38. Adams Hillard PJ. Menstruation in young girls: a clinical
perspective. Obstet Gynecol 2002;99:65562.
30
ACOG
Committee on

to change. The information should
The Committee would like to
thank Nichole Zidenberg, MD,
and Patricia S. Simmons, MD,
for their assistance in the development of this document.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Breast concerns in the adolescent.
2006;108:132936
Committee
Opinion
Breast Concerns in the Adolescent

ABSTRACT: Breast disease in the adolescent female encompasses an expansive array of topics. Benign disease overwhelmingly dominates the differential diagnosis and dictates a different protocol for care in the adolescent
compared with the adult patient to avoid inappropriately high assessments of
risk and unnecessary diagnostic procedures and surgery. There also are
emerging issues pertaining to the care of the adolescent breast, such as
breast augmentation, nipple piercing, and management of the adolescent
patient with a family history of breast cancer.
Breast disease in the adolescent female encompasses an expansive array of

topics. Common presenting signs and symptoms in the adolescent patient are
breast pain, nipple discharge, and the discovery of a mass (1, 2). Benign disease overwhelmingly dominates the differential diagnosis and dictates a different protocol for care in the adolescent compared with the adult patient.
Family practitioners, pediatricians, nurse practitioners, and obstetrician
gynecologists most commonly encounter and manage adolescent patients
with breast disease. Many of these adolescents are referred for evaluation to
general surgeons and breast centers with little experience with or familiarity
with the data for this population. Their adult frame of reference can lead to
inappropriately high assessments of risk and unnecessary diagnostic procedures and surgery.
Breast Development
As growth of the pubertal breast begins, it is often asymmetric. A unilateral
breast lump just beneath the areola in an 810-year-old patient is invariably
a developing breast bud. Biopsy in prepubertal girls or girls in early puberty
is rarely indicated and should almost always be avoided because it can irreversibly damage the breast bud. It is estimated that approximately 25% of
adolescent females have breast asymmetry that persists into adulthood (3). In
addition to the most common cause of breast asymmetry, normal variation in
breast size, the differential diagnosis includes unilateral hypoplasia or amastia, unilateral hypertrophy or large breast mass, and Polands syndrome (congenital underdevelopment or absence of the chest muscle on one side of the
body). Failure of bilateral development of the breasts can be caused by
delayed puberty or rarely by bilateral hypoplasia or amastia. Careful assess-
COMMITTEE OPINIONS
31
ment of unilateral or bilateral breast hypoplasia is

important before any surgical intervention is initiated.
educated regarding behavioral changes to avoid nipple stimulation, and observation is recommended.
Common Adolescent Breast Concerns
Breast Mass
Of all breast masses diagnosed in adolescents, recent
retrospective chart reviews demonstrate that approximately 67% are fibroadenomas, 15% are fibrocystic
changes, and 3% are abscess or mastitis (see the
box) (6). In one longitudinal study of adolescent
females with a breast mass, follow-up over a 79
month period demonstrated that 77% of adolescents
had lesions that either resolved or did not enlarge,
and no malignancies were diagnosed (7).
Mastalgia
Breast pain, or mastalgia, is a common symptom in
the adolescent. Symptoms also may include mild
swelling and palpable nodularity, consistent with
fibrocystic changes, usually in the upper outer quadrant. The symptoms are typically cyclic and worse
premenstrually. Supportive measures and reassurance are the best treatment. For adolescent patients
who are smokers, smoking cessation should be
encouraged because nicotine has been shown to
increase breast pain. Some studies suggest that
dietary modifications, such as eliminating coffee,
tea, and caffeinated sodas, can reduce breast pain (4,
5). A well fitting bra, particularly a sports bra during exercise has been shown to reduce pain during
movement. Analgesics such as naproxen sodium or
ibuprofen alleviate the symptoms. Oral contraceptives also may be helpful with fibrocystic changes.
Nipple discharge
Nipple discharge in the adolescent can be white,
clear, red, yellow, green, or brown and is usually
benign in nature. Nipple discharge often is secondary to local irritation or stimulation, pregnancy,
or use of medications such as antipsychotics, oral
contraceptives, or opiates. Ductal ectasia is a benign
and common finding in the developing breast. It consists of dilation of the mammary ducts, periductal
fibrosis and inflammation. The patient may present
with nipple discharge that may be bloody or dark
brown in nature, or a mass, or both. A bloody nipple
discharge, when associated with a mass, can be seen
in papilloma or papillomatosis and should be evaluated because of the malignant potential of these conditions. Ultrasonography is often used to assist in the
diagnosis and to reassure the patient of her status.
Except in papilloma or papillomatosis, observation
is recommended. As in adults, hyperprolactinemia
can cause galactorrhea in adolescents, thus the
appropriate laboratory and imaging studies should
be ordered in the evaluation process. Treatment is
directed by the results of the history, physical examination, and laboratory studies. As indicated, use of
the offending drugs is stopped, hypothyroidism is
treated, and prolactin tumors are managed medically or surgically. Typically, the patient should be
Breast Masses in the Adolescent Female

Benign
Fibroadenoma
Fibrocystic changes or cysts
Unilateral thelarche
Hemangioma
Intramammary lymph node
Fat necrosis
Abscess
Mastitis
Lipoma
Hematoma
Hamartoma
Micromastia (juvenile hypertrophy)
Galactocele
Intraductal papilloma
Juvenile papillomatosis
Lymphangioma
Malignant
Malignant cystosarcoma phyllodes
Breast carcinoma
Metastatic disease
Lymphoma, neuroblastoma, sarcoma, rhabdomyosarcoma, acute leukemia
Data from Dehner LP, Hill DA, Deschryver K. Pathology
of the breast in children, adolescents, and young adults.
Semin Diagn Pathol 1999;16:23547; Simmons PS.
Diagnostic considerations in breast disorders of children
and adolescents. Obstet Gynecol Clin North Am 1992;
19:91102; and Laufer MR, Goldstein DP. The breast:
examination and lesions. In: Emans SJ, Laufer MR,
Goldstein DP, editors. Pediatric and adolescent gynecology. 5th ed. Philadelphia (PA): Lippincott Williams &
Wilkins; 2005. p. 72959.
32
Breast Hypertrophy
Idiopathic breast hypertrophy occurs in adolescents
and adults. When noted in adolescents, it is referred
to as juvenile or virginal breast hypertrophy.
Juvenile breast hypertrophy involves the uncontrolled overgrowth of breast tissue that occurs in
adolescents whose breasts develop normally during
puberty, but then continue to grow. This rapid
growth can be unilateral or bilateral and usually
occurs shortly after thelarche.
For many adolescents, breast hypertrophy and
persistent significant asymmetry can result in both
psychologic and physical consequences. These adolescents often receive negative attention, experience
difficulties with athletics, and have more socialization problems that may lead to poor self-esteem and
isolation from family and peers (8). These consequences have resulted in the development of eating
disorders in some adolescent females to compensate
for their breast size (9).
Surgical correction by enlarging one breast with
an implant, surgical reduction of the larger breast,
or a bilateral reduction mammoplasty can improve
the quality of life considerably. Studies have demonstrated that the improvement of self-esteem seems to
be the most significant benefit of breast surgery (10,
11). Studies also have demonstrated that breast
reduction in adolescents with large breasts relieves
back, shoulder, and neck pain (10, 12).
Postoperatively, adolescent patients have the
same short- and long-term potential complications as
adult patients, including incisional separation, scarring, sensory loss, and infection. Long-term complications, such as the possible inability to breastfeed,
also have been described in adults undergoing reduction mammoplasty; however, there are numerous surgical techniques, some of which preserve the ability
to breastfeed (8). One study of adolescent patients
who underwent reduction mammoplasty between the
ages of 15 years and 17 years, found that these
patients subsequently breastfed their infants with
complication rates similar to those in the general
population (13). Overall, the most commonly cited
short-term complication is pain; the long-term complications cited are related to scarring (10, 12). The
adolescent patient population reports satisfaction
with reduction mammoplasty exceeding 75%, even
when surveyed several years postoperatively (11, 12).
In one study of adolescent patients who underwent
bilateral breast reduction, 94% would recommend it
to a teenaged friend with a similar condition (10).
There is no definitive guideline for when breast

reduction should be suggested. An assessment of the
adolescents emotional, psychologic, and physical
maturity is recommended to guide this decision.
Breast development is variable, and several recommendations regarding the timing of surgery have
been made, including postponing surgery until
breast maturity is reached, waiting for 6 months with
no change in bra size, or after the age of 18 years.
Surgery can be considered earlier when severe symptoms are encountered (14). The incidence of breast
regrowing after initial reduction during adolescence
is not known, but it has been reported (15). A psychologic evaluation is a reasonable surgical prerequisite because the plastic surgeon needs to fully
understand the motivation, maturity, and psychosocial and emotional attributes of the patient seeking
this surgery. The plastic surgeon should be confident
that the adolescent has realistic goals and fully
understands the risks and benefits, including the limitations of breast surgery (14).
Breast Augmentation
Plastic surgery involving augmentation of adolescent breasts stimulates debate both socially and
medically. Over the past several years, the number of
cosmetic surgical procedures performed in patients
aged 18 years or younger has increased substantially
(16). Breast augmentations were less than 5% of the
total number of cosmetic surgical procedures performed on this age group.
The number of adolescent females seeking
breast augmentation for aesthetic purposes is considerable. This can be attributed to factors such as
media influence and distorted perceptions of an ideal
body type. In response to this trend, the American
Society for Plastic Surgery has adopted guidelines
for the appropriate selection of adolescents for aesthetic breast surgery (17). The guidelines acknowledge that the U.S. Food and Drug Administration
considers the use of breast implants for aesthetic
breast augmentation in patients younger than 18
years to be an off-label use. They state that adolescent candidates for purely aesthetic breast augmentation should be at least 18 years of age and recognize
that aesthetic breast surgery in the adolescent female
encompasses unique mental and physical components. The adolescent and her parent should be
counseled regarding risks, activity restrictions, and
recovery time for the procedure being considered.
COMMITTEE OPINIONS
It is important to understand that for some adolescents, breast augmentation leads to a successful
outcome. A less mature adolescent may have unrealistic expectations and be disappointed by the outcome. For example, self-esteem issues may not
be resolved. An assessment of an adolescents
emotional, psychologic, and physical maturity is,
therefore, a reasonable surgical prerequisite. The
adolescent and her parent should be counseled that
breast implants are not typically associated with
breastfeeding difficulties or an increased risk of
breast cancer. The surgery may, however, make
future mammographic screening more difficult.
Nipple Piercing
Nipple piercing has become increasingly popular
and an emerging concern, particularly for the adolescent. There is a paucity of research in the area of nipple piercing, specifically addressing prevalence and
complications. The most common health risks associated with piercing include infections, pain, bleeding, hematoma, cyst formation, allergic reaction, and
keloid formation (18, 19). Nipple piercing has been
associated with a transmission risk for hepatitis B
and hepatitis C (20) and human immunodeficiency
virus (HIV) (21). There also are a growing number
of case reports of development of a breast abscess
after nipple piercing. A recent review of the literature
reports 10 cases of breast abscess after nipple piercing (22). The average time from piercing to diagnosis is 5 months because of a prolonged incubation
and wound healing time for nipple piercing. The
healing time after nipple piercing is 36 months,
which is longer than piercing of some other sites
(Table 1). In addition, patients may delay seeking
treatment after nipple piercing. Major complications
associated with an abscess after nipple piercing can
include endocarditis, heart valve injury, cardiac prosthesis infection, metal foreign body reaction in
breast tissue, or recurrent infections. Undue anxiety
may be caused by an incorrect initial diagnosis of
breast cancer in the pierced breast. Based on current
data, clinical recommendations for patients with
postpiercing infections should include antibiotic
treatment and removal of the nipple ring; screening
for hepatitis B, hepatitis C, and HIV; and glucose
testing to exclude diabetes mellitus, with its risk of
increased infection rate (22). Given the increasing
popularity of piercing, clinicians should routinely
screen adolescents for intent to undergo a piercing.
For those who intend to undergo a piercing, educa-
33
tion should be provided regarding safer piercing

strategies. Clinicians also should encourage these
individuals to become immunized against hepatitis B
and tetanus before the piercing, if they are not
already immune. Adolescents who have any of the
following factors should be advised to avoid nipple
piercing: alcohol or substance intoxication, metal
allergies (especially to nickel), anticoagulant therapy, a history of chronic or acute infections, steroid
therapy, diabetes, and heart valve defects or any
other causes of immune suppression. For many
adolescents seeking advice regarding nipple piercing, the Internet is often their primary and sole
reference (see Resources). It is common for adolescents to present with piercing complications and
quote or follow the advice provided on these
Internet web sites. Information on many of the
Internet web sites on nipple piercing conflict with
expert medical opinion.
Breast cancer
Primary breast cancer occurs rarely in the adolescent
patient. During the period 19982002, the incidence
of breast cancer in patients younger than 20 years
was 0 per 100,000. During the same period, the incidence of breast cancer in women younger than 24
years of age was 1.3 per 100,000 (23). Malignancies
that occur in the adolescent breast are more likely
metastatic from another primary malignancy (24).
Although primary breast cancer is uncommon, risk
Table 1. Healing Time for Piercing by Body Part
Pierced Body Part
Nipple
Ear lobe
Ear cartilage
Eyebrow
Nostril
Nasal septum
Nasal bridge
Tongue
Lip
Navel
Female genitalia
Male genitalia
Time It Takes to Heal

36 months
68 weeks
4 months to 1 year
68 weeks
24 months
68 months
810 weeks
4 weeks
23 months
4 months to 1 year
410 weeks
4 weeks to 6 months
Center for Young Womens Health, Childrens Hospital Boston. Body

piercing: a guide for teens. Available at: http://www.youngwomenshealth.org/body-piercing.html. Retrieved June 13, 2006. Copyright
2006. All rights reserved. Modified and reprinted with permission.
34
factors for malignancy of the breast should be

assessed. Clinical evidence demonstrates that radiation exposure, such as that seen with the treatment
of childhood cancer, to the prepubertal and pubertal
breast of females between the ages of 10 years and
30 years is associated with the greatest risk of radiation-induced breast cancer later in life (25).
Clinical Management of a Breast

Abnormality
Ultrasonography generally is the best imaging
modality to study the adolescent breast (26, 27).
Mammography is not indicated in adolescents
because it offers poor image quality and is associated with both false-positive and false-negative
results due to the dense nature of the fibroglandular
tissues (28). Mammography also has been associated with unnecessary surgery and the increased risk
of radiation-induced malignant changes (2931).
Although aspiration for relief of pain of cysts can
be useful in the adolescent with a breast mass, fine
needle aspiration for diagnostic purposes has not
been well established in adolescents and should be
discouraged.
Most breast masses diagnosed in adolescents are
fibroadenomas. The majority of longitudinal studies
on fibroadenomas demonstrate that most lesions
decrease in size, and many even completely resolve
and, therefore, should not be excised. Specifically, a
large epidemiologic study of benign breast tumor
cases showed a 13.9% incidence of fibroadenomas
at registration, an increase in fibroadenoma after 5
years, and then a gradual decrease in fibroadenoma
over 8 years (32). Over a 5-year period, one study
examined 25 fibroadenomas and found that 52%
became smaller, 16% remained the same size, and
32% became larger (33). Another study found an
actuarial probability of disappearance of 46% of
lesions at 5 years and 69% at 9 years. It was found
that women 20 years and younger had a higher probability of resolution of a fibroadenoma than women
older than 20 years. Size or multiplicity of lesions
did not affect the probability of resolution (34).
Given the low risk of malignancy, high likelihood
of spontaneous resolution, and risks of deformity in
the growing breast, conservative, nonsurgical management is most often appropriate. Excisional biopsy
and surgery should be reserved for breast masses
that are enlarging or associated with overlying skin
changes, abscesses not responding to medical ther-
apy, or suspicious masses presenting in an adolescent with a history of a previous malignancy.
Family History of Breast Cancer

One area of growing interest to gynecologists is the
management of the adolescent patient with a family
history of breast cancer. It is important to be aware
of the complexities of genetic testing, screening recommendations, and preventive health guidelines.
Currently, a woman living in the United States has a
13.2% lifetime risk of developing breast cancer (35).
A significant risk factor for the development of
breast cancer is a family history of the disease. The
risk in a patient with a first-degree relative affected
by breast cancer increases twofold to threefold (36).
The cumulative risk of breast cancer in women with
BRCA1 or BRCA2 genes ranges from 3.2% at 30
years to 85% at 70 years of age (37). The daughter
of a woman or man who is a BRCA carrier has a 50%
chance of having inherited the gene mutation.
Decisions regarding genetic testing in the adolescent
are complex and should include consideration of the
medical and psychologic implications of genetic
testing for each individual patient and her family.
Referral for genetic counseling by an appropriately
qualified individual is advised for patients considering genetic testing. Current recommendations outlined by the Cancer Genetics Studies Consortium do
not recommend radiographic surveillance for
BRCA1 carriers until 2535 years of age (38). The
National Cancer Institutes most recent summary
(April 2005) concludes that bilateral prophylactic
mastectomy is associated with a reduction in breast
cancer by as much as 90% in adult women with an
increased risk of breast cancer because of strong
family history. However, because of the physical and
psychologic effects of this surgery and its permanence, decisions on this matter are usually deferred
until the individual is at least 35 years of age and has
completed childbearing (39). Therefore, there is no
urgency for testing the adolescent patient. The role
of BRCA1 and BRCA2 testing in adolescents is an
area of much needed research for both evidencebased management and ethical practice (1).
Prevention of Breast Cancer

Effective and accurate counseling for adolescents
and their parents regarding breast cancer prevention
should be a routine component of preventive health
COMMITTEE OPINIONS
services for adolescents. Smoking, alcohol consumption, and exposure to treatment with ionizing radiation during adolescence have all been associated with
an increase in breast cancer in adulthood (40). It is
prudent to advise adolescents to avoid these exposures. Additional preventive health guidance in all
adolescents should include encouraging exercise in
1224-year-old females because physical activity has
been shown to reduce the risk of breast cancer significantly (41). There are no rigorous recent scientific
data to support an association between abortions and
breast cancer. One recent prospective study examined
44,000 women with breast cancer from 53 studies
and 16 countries. This study demonstrated that pregnancies that end in therapeutic abortion do not
increase a womans risk of developing breast cancer
later in life (42). Some parents and patients are
opposed to oral contraceptive use because of a fear of
associated breast cancer. The National Institute of
Child Health evaluated the risk of breast cancer in
more than 4,500 women who were current or past
users of oral contraceptives. The study found no significant increased risk of breast cancer when oral contraceptive users were compared with controls (43).
A casecontrol study found that oral contraceptive use before age 30 years and oral contraceptive
use for more than 5 years were associated with an
increased risk of breast cancer for BRCA1 carriers,
but not in BRCA2 carriers (44). A more recent cohort
study focused on cases of breast cancer diagnosed
before age 40 years and included a substantial number of BRCA1 and BRCA2 mutation carriers (45).
Compared with nonuse of oral contraceptives, use of
current low-dose oral contraceptive formulations did
not increase the risk of breast cancer in carriers of
BRCA1 or BRCA2 mutations. A positive family history of breast cancer, including BRCA1 or BRCA2
mutations, should not be regarded as contraindications to oral contraceptive use (46).
Breast Self-Examination
Historically, experts have recommended teaching
adolescents to perform breast self-examination for a
variety of reasons, including cancer detection, teaching self-detection for future application, and contributing to greater understanding and comfort with
their changing bodies. There are currently no data to
support these rationales. More recently, experts
observe that it might actually be ill advised to encourage breast self-examination in the adolescent
35
because girls who identify a breast mass themselves

may experience multiple physician visits, invasive
testing, and perhaps unwarranted surgery. These
extensive and expensive evaluations usually lead to
benign findings and unnecessary angst (47). The
American College of Obstetricians and Gynecologists states that, despite a lack of definitive data for
or against breast self-examination, breast self-examination may be recommended beginning at age 19
years. Counseling regarding breast self-examination
for those aged 1318 years is not recommended
(48). Some experts have recommended teaching
breast self-examination to adolescent females whose
mothers carry the BRCA1 or BRCA2 gene, beginning at age 1821 years. Early breast self-examination has been recommended in those at high risk for
breast cancer, such as those with a personal history
of malignancy. Women with previous exposure to
therapeutic chest radiation therapy are advised to
begin breast self-examination 10 years after radiation therapy (1, 2, 49).
Conclusion
Breast disorders in the adolescent female can
cause increased anxiety for the patient and her
family and pose a clinical challenge for her
health care provider.
Malignancy is rare in the adolescent breast. A
different emphasis for care in the adolescent
compared with the adult patient is, therefore,
recommended. Conservative, nonsurgical management is most often appropriate.
To increase the likelihood of satisfactory outcomes from breast-reduction or augmentation
surgery, the surgeon should assess the adolescents emotional, psychologic, and physical
maturity.
Given the increasing popularity of piercing,
including nipple piercing, clinicians should routinely screen adolescents for intent to undergo a
piercing. Preventive counseling and relevant
immunizations should be offered to adolescents
interested in piercing. For patients with postpiercing infections, prompt treatment of infections and appropriate screening and testing is
essential.
Further investigation is needed to better counsel
adolescent patients about genetic testing for
breast cancer and the role of breast self-examination.
36
Resources
ACOG Resources
Detecting and treating breast problems. ACOG Patient
Education Pamphlet AP026. Washington, DC: ACOG; 2004.
Fibrocystic breast changes. ACOG Patient Education Pamphlet
Role of the obstetriciangynecologist in the screening and
diagnosis of breast masses. ACOG Committee Opinion No.
Other Resources
The following lists are for informational purposes only.
Referral to these sources and web sites does not imply the
endorsement of ACOG. These lists are not meant to be comprehensive. The exclusion of a source or web site does not reflect
the quality of that source or web site. Please note that web sites
are subject to change without notice.
Association of Professional Piercers
PO Box 1287
Lawrence, KS 66044
Web: www.safepiercing.org
Resources for Your Patients

American Academy of Family Physicians
11400 Tomahawk Creek Parkway
Leawood, KS 66211-2672
Tel: (913) 906-6000
Web: www.aafp.org
American Academy of Pediatrics
NY Chapter 2
420 Lakeville Road, Suite 244
New Hyde Park, NY 11042
Web: www.ny2aap.org/tattoos.html
AWARE Foundation
1015 Chestnut Street
Philadelphia, PA 19107-4302
Tel: (215) 955-9847
Web: www.awarefoundation.org
Center for Young Womens Health
333 Longwood Avenue, 5th floor
Boston, MA 02115
Tel: (617) 355-CYWH (2994)
Web: www.youngwomenshealth.org
Go Ask Alice! (by Columbia University Health
Education Program)
Lerner Hall
2920 Broadway, 7th Floor
MC 2608
New York, NY 10027
Tel: (212) 854-5453
Web: www.goaskalice.columbia.edu
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2. Templeman C, Hertweck SP. Breast disorders in the pediatric and adolescent patient. Obstet Gynecol Clin North
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3. Beach RK. Routine breast exams: a chance to reassure,
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4. Minton JP, Foecking MK, Webster DJ, Matthews RH.
Caffeine, cyclic nucleotides, and breast disease. Surgery
1979;86:1059.
5. Abraham GE. Nutritional factors in the etiology of the
premenstrual tension syndromes. J Reprod Med 1983;
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6. Laufer MR, Goldstein DP. The breast: examination and
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7. Neinstein LS, Atkinson J, Diamant M. Prevalence and
longitudinal study of breast masses in adolescents. J
Adolesc Health 1993;14:27781.
8. Corriveau S, Jacobs JS. Macromastia in adolescence. Clin
Plast Surg 1990;17:15160.
9. Losee JE, Serletti JM, Kreipe RE, Caldwell EH.
Reduction mammoplasty in patients with bulimia nervosa.
Ann Plast Surg 1997;39:4436.
10. McMahan JD, Wolfe JA, Cromer BA, Ruberg RL. Lasting
success in teenage reduction mammoplasty. Ann Plast
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11. McGrath MH, Mukerji S. Plastic surgery and the teenage
patient. J Pediatr Adolesc Gynecol 2000;13:10518.
12. Lee MC, Lehman JA Jr, Tantri MD, Parker MG, Wagner
DS. Bilateral reduction mammoplasty in an adolescent
population: adolescent bilateral reduction mammoplasty.
J Craniofac Surg 2003;14:6915.
13. Aillet S, Watier E, Chevrier S, Pailheret JP, Grall JY.
Breast feeding after reduction mammaplasty performed
during adolescence. Eur J Obstet Gynecol Reprod Biol
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14. McGrath MH, Schooler WG. Elective plastic surgical procedures in adolescence. Adolesc Med Clin 2004;15:
487502.
15. Mayl N, Vasconez LO, Jurkiewicz MJ. Treatment of
macromastia in the actively enlarging breast. Plast
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16. American Society of Plastic Surgeons. National
Clearinghouse of Plastic Surgery Statistics. Procedural
statistics trends 1992-2005. Available at: http://www.plasticsurgery.org/public_education/Statistical-Trends.cfm.
17. American Society of Plastic Surgeons. Plastic surgery for
teenagers. Available at: http://www.plasticsurgery.org/
news_room/loader.cfm?url=/commonspot/security/getfile.cfm&PageID=14990. Retrieved June 12, 2006.
18. Mayers LB, Moriarty BW, Judelson DA, Rundell KW.
Complications of body art. Consultant 2002;42:174452.
19. Braithwaite RL, Stephens T, Sterk C, Braithwaite K.
Risks associated with tattooing and body piercing. J
Public Health Policy 1999;20:45970.
20. Conry-Cantilena C, VanRaden M, Gibble J, Melpolder J,
Shakil AO, Viladomiu L, et al. Routes of infection,
COMMITTEE OPINIONS
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viremia, and liver disease in blood donors found to have

hepatitis C virus infection. N Engl J Med 1996;334:
16916.
Pugatch D, Mileno M, Rich JD. Possible transmission of
human immunodeficiency virus type 1 from body piercing. Clin Infect Dis 1998;26:7678.
Jacobs VR, Golombeck K, Jonat W, Kiechle M. Mastitis
nonpeurperalis after nipple piercing: time to act. Int J
Fertil Womens Med 2003;48:22631.
Ries LA, Eisner MP, Kosary CL, Hankey BF, Miller BA,
Clegg L, et al, editors. SEER cancer statistics review,
19752002. Bethesda (MD): National Cancer Institute;
2005. Available at: http://seer.cancer.gov/csr/1975_2002.
Simmons PS, Wold LE. Surgically treated breast disease
in adolescent females: a retrospective review of 185 cases.
Adolesc Pediatr Gynecol 1989;2:958.
Goss PE, Sierra S. Current perspectives on radiationinduced breast cancer. J Clin Oncol 1998;16(1):33847.
Boothroyd A, Carty H. Breast masses in childhood and
adolescence. A presentation of 17 cases and a review of
the literature. Pediatr Radiol 1994;24:814.
Adler DD. Ultrasound of benign breast conditions. Semin
Ultrasound CT MR1989;10:10618.
Hart BL, Steinbock RT, Mettle FA, Jr, Pathak DR, Bartow
SA. Age and race related changes in mammographic
parenchymal patterns. Cancer 1989;63:25379.
Feig SA. Radiation risk from mammography: is it clinically significant? AJR Am J Roentgenol 1984;143:46975.
Eddy DM, Hasselblad V, McGivney W, Hendee W. The
value of mammography screening in women under age 50
years. JAMA 1988;259:15129.
Brenner DJ, Sawant SG, Hande MP, Miller RC, Elliston
CD, Fu Z, et al. Routine screening mammography: how
important is the radiation-risk side of the benefit-risk
equation? Int J Radiat Biol 2002;78:10657.
Arihiro K. Trends in benign breast tumors in Japanese
women, 19731995: experience of Hiroshima Tumor
Tissue Registry. Jpn J Cancer Res 2002;93:6105.
Carty NJ, Carter C, Rubin C, Ravichandran D, Royle GT,
Taylor I. Management of fibroadenoma of the breast. Ann
R Coll Surg Engl 1995;77:12730.
Cant PJ, Madden MV, Coleman MG, Dent DM. Nonoperative management of breast masses diagnosed as
fibroadenoma. Br J Surg 1995;82:7924.
American Cancer Society. Breast cancer facts & figures
20052006. Atlanta (GA): ACS; 2005. Available at: http://
www.cancer.org/downloads/STT/CAFF2005BrF.pdf.
Ottman R, Pike MC, King MC, Henderson BE. Practical
guide for estimating risk for familial breast cancer. Lancet
1983;2:5568.
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37. Ford E, Easton DF, Bishop DT, Narod SA, Goldgar DE.
Risk of cancer in BRCA1-mutation carriers: Breast
Cancer Linkage Consortium. Lancet 1994;343:6925.
38. NIH consensus conference. Ovarian cancer. Screening,
treatment, and follow-up. NIH Consensus Development
Panel on Ovarian Cancer. JAMA 1995;273:4917.
39. Seeber B, Driscoll DA. Hereditary breast and ovarian cancer syndrome: should we test adolescents? J Pediatr
Adolesc Gynecol 2004;17:1617.
40. Marcus PM, Newman B, Millikan RC, Moorman PG,
Baird DD, Qaqish B. The associations of adolescent
cigarette smoking, alcoholic beverage consumption, environmental tobacco smoke, and ionizing radiation with
subsequent breast cancer risk (United States). Cancer
Causes Control 2000;11:2718.
41. Lagerros YT, Hseih SF, Hsieh CC. Physical activity in
adolescence and young adulthood and breast cancer risk:
a quantitative review. Eur J Cancer Prev 2004;13:512.
42. Beral V, Bull D, Dell R, Peto R, Reeves G. Breast cancer
and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83,000 women with
breast cancer from 16 countries. Collaborative Group on
Hormonal Factors in Breast Cancer. Lancet 2004;363:
100716.
43. Marchbanks PA, McDonald JA, Wilson HG, Folger SG,
Mandel MG, Daling JR, et al. Oral contraceptives and the
risk of breast cancer. N Engl J Med 2002;346:202532.
44. Narod SA, Dube MP, Klijn J, Lubinski J, Lynch HT,
Ghadirian P, et al. Oral contraceptives and the risk of
breast cancer in BRCA1 and BRCA2 mutation carriers. J
Natl Cancer Inst 2002;94:17739.
45. Milne RL, Knight JA, John EM, Dite GS, Balbuena R,
Ziogas A, et al. Oral contraceptive use and risk of earlyonset breast cancer in carriers and noncarriers of BRCA1
and BRCA2 mutations. Cancer Epidemiol Biomarkers
Prev 2005;14:3506.
46. Use of hormonal contraception in women with coexisting
medical conditions. ACOG Practice Bulletin No. 73.
47. Goldbloom RB. Self-examination by adolescents.
48. Primary and preventive care: periodic assessments.
ACOG Committee Opinion No. 292. American College of
102:11724.
49. Burke W, Daly M, Garber J, Botkin J, Kahn MJ, Lynch P,
et al. Recommendations for follow-up care of individuals
with an inherited predisposition to cancer. II. BRCA1 and
BRCA2. Cancer Genetics Studies Consortium. JAMA
1997;277:9971003.
38
ACOG
Committee on
Committee
Opinion

Nichole Zidenberg, MD; Mary
McKenna, PhD; and William H.
Dietz, MD, PhD, for their assistance in the development of this
document.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
The overweight adolescent: prevention, treatment, and obstetricgynecologic implications. ACOG Committee
Opinion No. 351. American College
The Overweight Adolescent:

Prevention, Treatment, and Obstetric
Gynecologic Implications
ABSTRACT: The number of overweight adolescents has grown to epidemic
proportions in the United States. Adolescent females who are overweight
have significant health sequelae. The American College of Obstetricians and
Gynecologists recommends that all adolescents be screened annually for
overweight by determining weight and stature, calculating a body mass index
for age percentile, and asking about body image and eating patterns. Health
care providers should promote healthy eating and physical activity to
adolescent patients and their parents during routine preventive health care
visits. Adolescents with a body mass index greater than or equal to the 95th
percentile for age should have an in-depth dietary and health assessment to
determine psychosocial morbidity and risk for future cardiovascular disease.
Obstetriciangynecologists are strongly encouraged to provide this assessment. Additional research is needed to determine the most appropriate
approach for the successful prevention and treatment of overweight adolescents. Until this research has been completed, it is best to extrapolate an
approach from data and studies pertaining to children and adults, while
remaining cognizant of the special needs that surround adolescent growth
and development. Sound nutritional recommendations and regular physical
activity are essential components of prevention and treatment plans.
The number of overweight adolescents has grown to epidemic proportions in

the United States. The overweight female adolescent faces unique challenges
with her medical, psychologic, and reproductive health. Early intervention is
paramount to prevent associated short- and long-term morbidities. The goal
of this document is to review the most timely and pertinent information
regarding the overweight adolescent, as well as to provide prevention and
treatment strategies to guide the practitioner in providing gynecologic and
obstetric care for such a patient.
COMMITTEE OPINIONS
Definitions of Overweight and Obesity

The discussion of overweight or obesity in adolescents is complicated by the inconsistent use of
definitions in clinical practice, research, and publications. These definitions have been applied to adults
and adolescents. The term obesity is now used less
frequently to avoid the associated negative connotations, especially for children and adolescents. Body
mass index (BMI) is the most widely used tool for
assessment of overweight and obesity. It is calculated
using the following formula: weight in kilograms
divided by height in meters squared (weight [kg] /
height squared [m2]). There are now teen BMI calculators available online. A link to one such calculator
can be found at http://www.acog.org/goto/teens. This
calculator determines the teens BMI for age percentile. Alternatively, Figures 1 and 2 can be used.
The Centers for Disease Control and Prevention
(CDC) defines an adolescent as overweight if she has
a BMI greater than or equal to the 95th percentile for
age. For example, a girl aged 16 years whose height is
60 inches and weight is 155 pounds has a BMI of
30.3, as can be seen in Figure 1. By looking at Figure
2, it can be determined that this girls BMI is above
the 95th percentile; therefore, she is considered to be
overweight. An adolescent whose BMI is equal to or
greater than the 85th percentile for age, but less than
the 95th percentile for age is considered by the CDC
to be at risk for becoming overweight. Adult obesity
is defined by the CDC as a BMI greater than or equal
to 30 and the term overweight is used to describe a
BMI greater than or equal to 25, but less than or equal
to 29.9 (see Table 1) (1). (An adult BMI calculator is
available at http://www.nhlbisupport.com/bmi/.) The
American College of Obstetricians and Gynecologists
(ACOG) uses the CDC definitions.
Prevalence and Trends

According to National Health and Nutrition
Examination Survey 20032004 data, 16% of
females aged 1219 years were considered overweight. Thirty-two percent of adolescent females
were either overweight or at risk of becoming overweight (2). By comparison, only 6% of females aged
1219 years were considered overweight in the
NHANES study conducted in 19711974 (see
Figure 3) (3). There are substantial racial differences
in the prevalence of overweight for adolescents.
Specifically, Latino, Mexican-American, Asian/
39
Pacific Islander, and black populations were more

likely to be overweight or at risk for overweight in
adolescence than the white population (2, 4).
Health Risks of Overweight Adolescents

Overweight status in the adolescent female population has been associated with lower educational
achievement and income, even after controlling for
intelligence and socioeconomic status at baseline (5).
These effects persisted even if the adolescent lost
weight and was no longer considered overweight (6).
Overweight adolescents often experience significant
low self-esteem and depression (79). Overweight
white girls are more likely to develop a negative body
image, and are at greater risk of developing eating
disorders. Overweight adolescent females have
reported experiences with intentional weight-related
teasing, jokes, and derogatory name calling, as well
as less intentional, potentially hurtful comments by
peers, family members, employers, strangers, and
health care providers. Overweight adolescents report
that others often make negative assumptions about
them, including that they are inactive or lazy, do not
have feelings, and are unclean (10).
Among adults who were overweight during
childhood, there is an increased relative risk of 1.5 of
all-cause mortality and 2.0 of cardiovascular disease
mortality (11). Adolescents who are at risk of
becoming overweight or who are overweight have a
significantly higher prevalence of moderate to severe
asthma when compared with a peer group (12).
Hypertension, sleep apnea, dyslipidemia, increased
fasting insulin levels, and sudden death have been
associated with being overweight (1316). More
recently, overweight adolescents have been shown to
be at increased risk of type 2 diabetes (17).
Furthermore, a variety of orthopedic complications
occur in overweight adolescents, such as slipped
capital femoral epiphysis and Blounts disease (a
growth disorder of the shin bone that causes the
lower leg to angle inward) (18). Finally, overweight
adolescents face increased morbidity and mortality
later in their reproductive lives.
Obstetric and Gynecologic Implications

for Overweight Adolescents
Irregular Menses
Overweight adolescents often report amenorrhea,
oligomenorrhea, or menometrorrhagia to their
Fig. 1. Body mass index chart for children and adolescents. (For more information on body mass index for adolescents, visit the Centers for Disease
Control and Prevention web site at www.cdc.gov/nccdphp/dnpa/bmi/childrens_BMI/about_childrens_BMI.htm.)
40
COMMITTEE OPINIONS
41
BMI
BMI
34
34
32
Overweight
(95th percentile and above)
95th
30
32
30
90th
At Risk of
Overweight
(85th94th
percentile)
28
28
85th
26
26
75th
24
24
22
50th
20
25th
22
20
10th
18
5th
16
18
16
Underweight
(5th percentile and below)
14
14
12
12
kg/m2
kg/m2
10 11 12
Age (years)
13
14
15
16
17
18
19
20
Fig. 2. Body mass index for age percentiles: Girls, aged 220 years. (Developed by the National Center for Health
Statistics in collaboration with the National Center for Chronic Disease Prevention and Health Promotion [2000].)
42
Table 1. Definitions
Population
Adolescent
Adult
At Risk for
Becoming Overweight
Body mass index is equal to or
greater than the 85th percentile
for age, but less than the 95th
percentile for age based on growth
charts by the Centers for Disease
Control and Prevention
Term not typically used
Females aged 1219 years

Prevelance of overweight
(percentage of population)
20
15
10
5
0
19711974 19761980 19881994 19992002 20032004
Years of NHANES study
Fig. 3. Overweight adolescent females aged 1219 years.

National Center for Health Statistics. Health, United
States, 2005 with chartbooks on trends in the health of
Americans. Hyattsville (MD): 2005. Ogden CL, Carroll
MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM.
Prevalence of overweight and obesity in the United States,
1999-2004. JAMA 2006;295:154955.
health care providers. Being an overweight adolescent is associated with elevated levels of free estrogens through increased peripheral aromatization of
androgens to estrogens, decreased sex hormone
binding globulin, and increased insulin levels that
can stimulate ovarian stromal tissue production of
androgen. The elevated peripheral estrogen levels are
associated with disruption of normal ovulation and
subsequent irregular menstrual cycles. Higher degrees of overweight have been associated with higher probabilities of menstrual cycle disturbances (19).
Polycystic Ovary Syndrome
Obesity has been reported to occur in one half of
adult patients with polycystic ovary syndrome
(PCOS). Obesity in adult patients with PCOS is
characterized by an increased waist-to-hip ratio or
Overweight
Obesity
Body mass index greater than or

equal to 95th percentile for age
based on growth charts by the
Centers for Disease Control
and Prevention
Term not typically used
Body mass index greater than or

equal to 25, but less than or equal
to 29.9
Body mass index greater

than or equal to 30
android appearance as opposed to truncal obesity.

The presence of obesity compounds clinical risk in
adult patients with PCOS for several reasons.
Obesity is associated with decreased sex hormonebinding globulin, which increases circulating free
testosterone and estradiol in adults (20). Obese
adults have an increased likelihood of dyslipidemia,
raising concern for future cardiovascular events
(21). Finally, obesity is associated with insulin resistance, which may progress to diabetes mellitus in
adult patients with PCOS (22).
Lifestyle modification is recommended as firstline management for overweight female adolescents
with PCOS. Dietary intervention studies have consistently demonstrated the benefit of weight reduction in obese adult females with PCOS to normalize
menstrual cycles and hyperandrogenism and
improve metabolic variables (23).
Oral contraceptives are the standard therapy for
PCOS to provide hormonal suppression of ovarian
androgen production. Metformin has been approved
by the U.S. Food and Drug Administration for use in
patients with type 2 diabetes and is the most common insulin-sensitizing agent used in studies on
PCOS even though the use of metformin in these
patients is currently considered off label. Some
investigators state that based on current data, use of
metformin can be justified in overweight adolescents with PCOS and insulin resistance to improve
metabolic and hormonal alterations and possibly
prevent long-term sequelae (24). The role of insulinreduction therapies in treating PCOS is evolving
and has substantial efficacy in restoring regularity of
menstrual cycles. These therapies usually are associated with initial weight loss, are less effective in the
treatment of hirsutism, and may cause gastrointestinal side effects (25).
COMMITTEE OPINIONS
Hormonal Contraception
Recent studies suggest that women weighing more
than 70.5 kg have an increased risk of unintended
pregnancy while using combination oral contraceptives compared with women who have normal body
mass (relative risk 1.6) (26, 27). Another study
demonstrated that women with BMIs greater than
32.2 had a higher risk of accidental pregnancy while
using combination oral contraceptives than did
women who have normal body mass (27). Several
mechanisms have been proposed to account for the
elevated failure rates in obese adult women. It has
been theorized that obese adult women metabolize
steroids differently than lean women possibly
because of a larger blood volume to transport steroid
hormones and fat cells sequestering steroid hormones (28). In obese adult users of combination oral
contraceptives, the risk of thromboembolism is
increased (29). For overweight adolescents at risk of
pregnancy, it is important to balance the risks and
benefits of combination oral contraceptives, including the risks from pregnancy. Consideration should
be given to progestin-only oral contraceptives and
intrauterine methods when counseling overweight
adolescents regarding contraceptive choices. Women
who weigh more than 90 kg may have a disproportionately higher likelihood of contraceptive failure
with the transdermal contraceptive patch (30).
Serum levonorgestrel levels are lower in obese
adult women compared with nonobese adult women
using a two-rod implant (not yet commercially available). Yet, effective contraception is thought to last 5
years regardless of weight (31). The effectiveness of
the etonogestrel single-rod implant that has been
recently approved by the U.S. Food and Drug
Administration for use in overweight women has not
been adequately studied. However, serum concentrations of the synthetic progestin etonogestrel are
inversely related to body weight and decrease with
time after insertion. It is, therefore, possible that with
time this single-rod implant may be less effective in
overweight women (32). No changes in efficacy have
been shown with the vaginal ring regardless of
patient weight. Although injectable contraception
has not been demonstrated to decrease contraceptive
efficacy based on weight, it has been associated with
weight gain (see Table 2).
Intrauterine Device
The effectiveness of the intrauterine device (IUD) in
obese adult women is similar to that demonstrated in
43
adults of average weight. Insertion of an IUD can be

technically challenging in the obese adult woman
and often requires the use of a larger speculum for
adequate visualization of the cervix. Placing a condom with the tip removed over the speculum blades
can aid in exposure. Ultrasonography also may be a
useful tool both before and during IUD insertion
(33). This information may be applied to the adolescent population until other data are available.
Pregnancy-Related Issues
Maternal obesity (BMI greater than or equal to 30)
is an important obstetric risk factor independent of
maternal age (34). Nearly all complications of pregnancy, except intrauterine growth restriction, are
more frequent in obese adult women (35). In a
recent prospective Danish study, overweight and
obese adult women had increased risks of diabetes,
hypertension, preeclampsia, and cesarean delivery
(36). Obesity is associated with a more than doubled
risk of stillbirth (odds ratio, 2.8; 95% confidence
interval [CI], 1.55.3) and neonatal death (odds
ratio, 2.6; 95% CI, 1.25.8) compared with women
of normal weight. Much of these data are based on
adult women, but may be applied to the pregnant
adolescent population until other data are available.
Most adolescent pregnancies (80%) are unintended (37). This precludes the physician from providing preconception counseling that would address
diet and exercise. The goals of this counseling
include avoiding specific pregnancy complications,
such as macrosomia, operative deliveries, late fetal
deaths, neural tube defects, gestational hypertension, and gestational diabetes. There is a significant
increase in cesarean deliveries in primiparous adolescents with BMIs greater than or equal to 30 compared with those with BMIs less than or equal to 20
(38). Maternal weight also has an effect on the child.
Regardless of maternal age, maternal obesity in the
first trimester of pregnancy is associated with elevated risk of overweight in the child. Specifically, the
relative risk of overweight in the child was 2.0 (95%
CI, 1.72.3) at age 2 years, 2.3 (95% CI, 2.02.6) at
age 3 years, and 2.3 (95% CI, 2.02.6) at age 4 years
(39).
African-American adolescents who are overweight before their first pregnancy become more
overweight; on average, 3.3 years following the
index pregnancy. They also are at increased risk of
retaining gestational weight gain (40). The association between ethnicity, overweight, and obstetric and
44
Table 2. The Effect of Weight on Birth Control Methods

Average Associated
Weight Gain
Does weight affect how well

it prevents pregnancy?
Abstinence
Male condom
Female condom
Emergency contraception
Vaginal spermicide
Diaphragm
None
None
None
None
None
None
Cervical cap
None
Combination oral
contraceptives
None
Progestin-only oral
contraceptives (mini pills)
None
No
No
No
No
No
If gain or loss of 10 pounds or more
occurs, it may need to be refitted
If gain or loss of 10 pounds or more
occurs, it may need to be refitted
If weight is 176 pounds or
more, it may not prevent pregnancy
as well
If weight is 176 pounds or
more, it may not prevent pregnancy
as well
No
No
If weight is 176 pounds or more, it
may not prevent pregnancy as well
No
No
No
Birth Control Method
Contraceptive injection
Vaginal ring
Patch
Copper T intrauterine device
Mirena intrauterine system
Sterilization
5 pounds in first year of use

None
None
None
None
None
Created by the SAFE Study: Computer-Aided Counseling to Prevent Teen Pregnancy/STDs, Principal Investigator:
Melanie A. Gold, D.O., University of Pittsburgh School of Medicine, supported by NICHD grant #HD41058.
Modified and reprinted with permission.
neonatal outcomes needs further exploration in the

adolescent population.
Information regarding pregnancy termination
also is scarce. In second trimester dilation and evacuation abortions, obesity has been linked with technical difficulty, longer operating times, and more
blood loss (41, 42).
Prevention
The American College of Obstetricians and Gynecologists recommends that all adolescents be
screened annually for overweight by determining
weight and stature, calculating a BMI for age, and
asking about body image and eating patterns (43).
The U.S. Preventive Services Task Force concluded
that there is insufficient evidence to recommend for
or against routine screening for overweight in adolescents in primary care settings (44). This is based
on the lack of evidence that screening and therapeutic intervention improve health outcomes for over-
weight adolescents. Although ACOG recognizes the

recent report and the limitations in the data, ACOG
continues to support the screening of adolescents
because screening and interventions may demonstrate benefit if used in combination with several
modalities.
Although the research on prevention of overweight status in adolescents has resulted in few
effective recommendations, some prevention strategies have been generated. Parents play a significant
role. A surgeon general report highlights the probable protective benefit of breastfeeding in preventing
overweight in children and adults (45). Health care
providers should promote healthy eating and physical activity to adolescent patients and their parents
during routine preventive health care visits (43, 45).
Parents can help their children and adolescents to
follow the Dietary Guidelines for Americans at
home and at school. These guidelines include recommendations to decrease consumption of fat,
saturated fat, sodium, and added sugars; increase
COMMITTEE OPINIONS
consumption of fruit, vegetables, whole grains, and

other foods that are rich in fiber; increase the consumption of milk or other foods or beverages that are
good sources of calcium; and participate in at least
60 minutes of physical activity on most, preferably
all, days of the week (45, 46). Adolescents can be
encouraged to increase the amount of regular daily
activity by making small lifestyle changes, such as
climbing the stairs instead of taking an elevator.
They also can be encouraged to choose an activity
that can become a part of their everyday life, such as
bicycling or walking. Leisure activities that are
sedentary, such as television viewing and playing
computer games, should be restricted to less than 2
hours per day. Parents also should be encouraged to
model healthy eating habits and physical activity
and should be informed that food should never be
used as a tool for punishment or reward. Eating
breakfast and regular meals is important to promoting and maintaining a healthy weight. A recent study
funded by the National Institutes of Health monitored nearly 2,400 females aged 919 years for 10
years and found that those who regularly ate breakfast, particularly ones that included cereal, were
slimmer than those who skipped the morning meal
(47). Schools can support healthy behavior by using
several means, including the provision of instruction, the enactment of physical activity and nutrition
policies, and by ensuring that the school environment supports healthy eating and physical activity
(48).
Screening and Treatment

Adolescence can be a difficult time for assessing
weight status because of pubertal changes and differences in individual patterns of growth. A dietary
and health assessment should be conducted on adolescents with BMIs greater than or equal to the 85th
percentile for age, but less than the 95th percentile
for age to determine psychosocial morbidity and risk
for future cardiovascular disease if:
Their BMI has increased by two or more units
during the previous 12 months
They have a family history of premature heart disease, obesity, hypertension, or diabetes mellitus
They express concern about their weight
They have elevated blood pressure or serum
cholesterol levels (43)
45
Adolescents with a BMI greater than or equal to

the 95th percentile for age should have an in-depth
dietary and health assessment to determine psychosocial morbidity and risk for future cardiovascular disease. Obstetriciangynecologists are strongly
encouraged to provide this assessment (43). Early
referral to a nutritional specialist skilled in adolescent care may be warranted. The patient usually is
acutely aware of her weight issue and has likely
attempted many of her own weight loss strategies.
These adolescents need clear and direct support,
guidance, and encouragement. Also they need a better understanding of the widespread nature of the
disease to feel less alone and isolated. Family
involvement in the treatment plan is critical. Any
proposed diet should be consistent with the Dietary
Guidelines for Americans and allow for individualized caloric intake recommendations that support
gradual, not rapid, weight loss.
It is important to note that weight loss is recommended only for adolescents in certain circumstances
(46). For example, older overweight adolescents who
have completed linear growth or those with comorbidities, may require weight loss (18, 49). More
often, the goal is to slow the rate of weight gain
while achieving normal growth and development.
Discussion of portion sizes, snacking, and eating at
restaurants and outside the home is helpful (46).
(See box for examples of healthy snacks.) Wake
Forest University has developed a web site
(http://www1.wfubmc.edu/Nutrition/Count+Your+
Calories/dtd.htm) that provides the nutritional and
caloric information of several of the largest fast food
chains in the United States. This web site may be
useful to adolescent patients and their parents.
There are sufficient adult data indicating that
physical activity contributes to weight loss, both
Healthy Snacks
Providing some examples of healthy snacks may be
useful when discussing the dietary needs of an overweight adolescent female. These examples may include:
A bean burrito
A cheese quesadilla with salsa and lettuce
A yogurt and fruit smoothie with graham crackers
A bowl of whole-grain cereal topped with sliced fruit
and milk
A small salad with sliced deli meat, tuna or beans
Fruit, cheese, and whole-grain crackers
46
alone and when it is combined with dietary therapy.

Efforts to achieve weight loss with physical activity
alone generally produce moderate weight loss. Even
so, increased physical activity is a useful adjunct to
low-calorie diets in promoting weight reduction.
Also, physical activity reduces obesity-associated
comorbidities (1).
The amount of time an adolescent spends performing aerobic versus sedentary activities should
be assessed. As stated previously, it is recommended
that adolescents participate in at least 60 minutes
of physical activity on most, preferably all, days
of the week (46). Increased activity and decreased
television viewing has been shown to reduce an
adolescents weight (50). In children, family-based
programs that encompass diet, physical activity,
reduction of sedentary behavior, and behavioral therapy have been shown to help children lose weight
compared with no treatment. It is important to provide recommendations on diet and physical activity
that are achievable given the patients family environment. It also is important to evaluate the adolescents
psychologic well-being (18). Often, collaboration
with a mental health professional is indicated.
There are limited data to document the efficacy
of prescription medications or over-the-counter
drugs for weight loss in adolescents. The role of surgical intervention for overweight adolescents has yet
to be established, but some recent studies have suggested that surgical weight loss improves the early
mortality experienced by these adolescents (51).
Bariatric surgery currently is recommended for adolescents who have a BMI greater than 40 and have
comorbid conditions. Those who may be candidates
for bariatric surgery should be referred to a multidisciplinary weight management team with expertise in
treating overweight adolescents (52). Long-term
studies are needed to determine the risk and benefits
of bariatric surgery in adolescents. Nationally, a new
paradigm has been proposed with an emphasis on
promoting a healthy lifestyle in overweight patients
instead of focusing solely on weight loss. This idea
of health at any size may encourage patients to
focus on their overall health improvement, rather
than only their weight status (53).
Conclusion
Adolescent females who are overweight have significant health sequelae. There are limited evidence-based
data for the successful prevention and treatment of
overweight adolescents. Because additional research

is needed, our best tool is to extrapolate an approach
from data and studies pertaining to children and
adults, while remaining cognizant of the special
needs that surround adolescent growth and development. Sound nutritional recommendations and regular physical activity are essential components for
overall good health because they convey myriad benefits for growth, brain and cognitive development,
self-esteem, immunity, and disease prevention (54).
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ACOG Resources
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disorders. In: Health care for adolescents. Washington, DC:
ACOG; 2003. p.8194.
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Gynecol 2005;106:8959.
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for teen care. Washington, DC: ACOG; 2003.
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control: eating right and keeping fit. ACOG Patient Education
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Other Resources
We have provided information on the following organizations
and web sites because they have information that may be of
interest to our readers. The American College of Obstetricians
and Gynecologists does not necessarily endorse the views
expressed or the facts presented by these organizations or on
these web sites. Further, ACOG does not endorse any commercial products that may be advertised or available from these
organizations or on these web sites.
11400 Tomahawk Creek Parkway
Leawood, KS 66211-2672
Telephone: 800-274-2237 or 913-906-6000
http://www.aafp.org
141 Northwest Point Boulevard
Elk Grove Village, IL 60007-1098
Telephone: 847-434-4000
http://www.aap.org/obesity
American Alliance for Health, Physical Education,
Recreation, and Dance
1900 Association Drive
Reston, VA 20191-1598
Telephone: 800-213-7193 or 703-476-3400
http://www.aahperd.org
American College of Sports Medicine
401 West Michigan Street
Indianapolis, IN 46202-3233
Telephone: 317-637-9200
http://www.acsm.org
American Dietetic Association
120 South Riverside Plaza, Suite 2000
Chicago, IL 60606-6995
Telephone: 800-877-1600
http://www.eatright.org
American Heart Association
7272 Greenville Avenue
Dallas, TX 75231
Telephone: 800-242-8721
http://www.americanheart.org
American Obesity Association
1250 24th Street NW, Suite 300
Washington, DC 20037
Telephone: 202-776-7711
http://www.obesity.org
COMMITTEE OPINIONS
AWARE Foundation
1015 Chestnut Street, Suite 1225
Philadelphia, PA 19107-4302
Telephone: 215-955-9847
http://www.awarefoundation.org
Division of Adolescent and School Health
Healthy Youth
PO Box 8817
Silver Spring, MD 20907
Telephone: 800-CDC-INFO (800-232-4636)
http://www.cdc.gov/nccdphp/dash
National Center for Chronic Disease Prevention and Health
Promotion
1600 Clifton Rd
Atlanta, GA 30333
Telephone: 404-639-3311 or 800-311-3435 or 800-232-4636
http://www.cdc.gov/nccdphp/dnpa/obesity
http://www.cdc.gov/nccdphp/dnpa/bmi/index.htm
Institute of Medicine
500 Fifth Street NW
Washington DC 20001
Telephone: 202-334-2352
http://www.iom.edu/
National Association for Health & Fitness

The Network of State and Governors Councils
c/o Be Active New York State
65 Niagara Square, Room 607
Buffalo NY 14202
Telephone: 716-583-0521
http://www.physicalfitness.org
National Heart, Lung, and Blood Institute
PO Box 30105
Bethesda, MD 20824-0105
Telephone: 301-592-5873
http://www.nhlbi.nih.gov/index.htm
Society for Adolescent Medicine
1916 NW Copper Oaks Circle
Blue Springs, MO 64015
Telephone: 816-224-8010
http://www.adolescenthealth.org
U.S. Surgeon General
Office of Surgeon General
5600 Fishers LaneRoom 18-66
Rockville MD 20857
301-443-4000
http://www.surgeongeneral.gov/topics/obesity/
calltoaction/fact_adolescents.htm
49
50
ACOG
Committee on
Reaffirmed 2009

The Committee would like to
thank Marc R. Laufer, MD, for
his assistance in the development
of this document.
Copyright December 2006
directed to:
222 Rosewood Drive
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ISSN 1074-861X
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Vaginal agenesis: diagnosis, management, and routine care. ACOG
2006;108:16059.
Committee
Opinion
Number 355, December 2006
(Replaces No. 274, July 2002)
Vaginal Agenesis: Diagnosis,

Management, and Routine Care
ABSTRACT: Vaginal agenesis occurs in 1 of every 4,00010,000 females.
The most common cause of vaginal agenesis is congenital absence of the
uterus and vagina, which also is referred to as mllerian aplasia, mllerian
agenesis, or MayerRokitanskyKsterHauser syndrome. The condition
usually can be successfully managed nonsurgically with the use of successive dilators if it is correctly diagnosed and the patient is sufficiently
motivated. Besides correct diagnosis, effective management also includes
evaluation for associated congenital renal or other anomalies and careful
psychologic preparation of the patient before any treatment or intervention.
If surgery is preferred, a number of approaches are available; the most
common is the AbbeMcIndoe operation. Women who have a history of mllerian agenesis and have created a functional vagina require routine gynecologic care and can be considered in a similar category to that of women
without a cervix and thus annual cytologic screening for cancer may be
considered unnecessary in this population.
Vaginal agenesis is an uncommon, but not rare, condition. Given an incidence ranging from 1 per 4,000 to 1 per 10,000 females (1), vaginal agenesis is a condition that general gynecologists will encounter once or twice
during their professional careers. The most common cause of vaginal agenesis is congenital absence of the uterus and vagina, which also is referred to
as mllerian aplasia, mllerian agenesis, or MayerRokitanskyKster
Hauser syndrome. The term mllerian aplasia will be used to describe this
congenital reproductive anomaly throughout this document. Mllerian aplasia is caused by embryologic growth failure of the mllerian duct, with
resultant anomalies in the mllerian structures. With absence of the vagina,
there is variation on the presence or absence of the uterus. A single midline uterus can be present or uterine horns (with or without an endometrial
cavity) can exist. The ovaries, given their separate embryologic source, are
normal in structure and function.
To manage vaginal agenesis effectively, correct diagnosis of the underlying condition is important. Evaluation for associated congenital, renal, or
other anomalies also is essential. Both diagnosis and evaluation usually can
be completed without surgery. Patient counseling should be provided
COMMITTEE OPINIONS
before any treatment or intervention. Nonsurgical

creation of the neovagina should be the first-line
approach.
Differential Diagnosis
Patients with mllerian aplasia have a normal
46,XX karyotype, normal female phenotype, and
normal ovarian hormonal and oocyte function.
Puberty and development of secondary sexual characteristics progress normally except that menarche
does not occur. Therefore, patients with mllerian
aplasia typically present in adolescence with primary amenorrhea. The practitioner should remember
that it is usually 23 years from the onset of breast
development until the first period. If menarche has
not occurred within 3 years of the onset of breast
development, further evaluation is indicated.
Mllerian aplasia is the second most common cause
of primary amenorrhea, with gonadal dysgenesis
being the most common cause (2).
On physical examination, patients with mllerian aplasia have normal breast development, normal
secondary sexual body proportions, body hair, and
hymenal tissue. A vagina is absent unless it has been
created by sexual encounters. Differential diagnosis
of vaginal agenesis includes congenital absence of
the vagina (with or without uterine structures),
androgen insensitivity (absence or alteration of
androgen-receptor function), 17 -hydroxylase
deficiency, a low transverse vaginal septum, and
imperforate hymen.
In cases of androgen insensitivity, the gonads are
testes, producing normal androgens in karyotypic
46,XY individuals. The lack of androgen tissue
receptors results in sparse or no pubic and axillary
hair. Patients with androgen insensitivity typically
have normal breast development because of peripheral conversion of circulating androgens to estrogens.
They may have a small lower vagina, or a normal
length vagina can occur; however, no uterus or
cervix is present. In pubertal females, the differential diagnosis between androgen insensitivity and
mllerian aplasia is easily made by assessing serum
testosterone levels. A testosterone level in the pubertal male range confirms the diagnosis of androgen
insensitivity.
In postpubertal patients, the presence of functioning ovarian tissue seen on pelvic ultrasound
examinations may serve as a secondary confirmation of the diagnosis of mllerian aplasia, excluding
51
the diagnosis of androgen insensitivity. Chromosomal studies, although more costly than a serum
testosterone level assessment, provide the diagnostic tool to differentiate between mllerian aplasia in
genetic females and disorders of testosterone synthesis in genetic males. Chromosomal analysis also
is helpful in prepubertal children who do not yet
have postpubertal sex steroid production.
In cases of 17 -hydroxylase deficiency, 46XY
individuals will have complete male pseudohermaphroditism with female external genitalia, a blind
short vaginal pouch, no uterus or fallopian tubes,
and intraabdominal testes. Affected males are usually raised as girls, with the underlying disorder
being recognized when the patient is evaluated for
lack of pubertal development (3, 4).
The differential diagnosis of vaginal agenesis
also includes imperforate hymen and low transverse
vaginal septum. Patients with these latter conditions
will have a normal cervix and uterus, both of which
may be palpable on rectal examination. In contrast
to most patients with mllerian aplasia, the patient
with an imperforate hymen will not have the typical
fringe of hymenal tissue. The patient with a low
transverse vaginal septum will have a normal
hymen, like the patient with mllerian aplasia.
Conventional ultrasonography, three-dimensional
ultrasonography, and magnetic resonance imaging
can be used to better define the mllerian structures
and are helpful in definitively defining anatomy.
Correct diagnosis of the underlying condition
affecting the genital anatomy is crucial before any
surgical intervention. If the patient undergoes an
operation because of an incorrect diagnosis (eg, an
incorrect preoperative diagnosis of an imperforate
hymen in cases of vaginal agenesis), it can be
extremely difficult to correct the anomaly because
of scar tissue.
Evaluation of the Patient With

Mllerian Aplasia
Most patients with mllerian aplasia have small
rudimentary mllerian bulbs without any endometrial activity. In 27% of patients with mllerian
aplasia, active endometrium is found in these uterine
structures (1). These patients will present with
cyclic or chronic abdominal pain. Magnetic resonance imaging has been suggested to assess the
reproductive anatomy, although it is rarely needed in
the initial evaluation unless ultrasound evaluation
52
for the presence of functional endometrium in a

mllerian structure is equivocal (5). Although
laparoscopy is not necessary to diagnose mllerian
aplasia, it may be useful in the evaluation of patients
with cyclic abdominal pain to exclude the possibility of endometrial activity in mllerian structures
(6). When obstructed hemi-uteri are identified (uterine horns with the presence of active endometrium
without associated cervix and upper vagina), then
removal of the unilateral or bilateral obstructed uterine structures should be performed. The removal of
the obstructed uterine structures can be accomplished laparoscopically (7, 8).
Patients with mllerian aplasia often have concomitant congenital malformations, especially of
the abdominal wall, urinary tract, and skeleton.
Inguinal hernias occur at an increased incidence in
patients with mllerian aplasia. Ultrasonography
can be used to screen for the more common findings of renal agenesis or a pelvic kidney. This
evaluation can be performed during the study of
ovarian and mllerian structures. The implications
of ureteral duplication in the case of later abdominal or pelvic surgery can be discussed, or intravenous pyelography can be used to exclude this
possibility. Scoliosis is the most common skeletal
abnormality associated with mllerian aplasia. It
also should be noted that there is an increased, but
small, rate of hearing impairment in patients with
mllerian aplasia.
After the diagnosis of mllerian aplasia, the
adolescent should be offered counseling to emphasize that a normal sex life will be possible after a
neovagina has been created. Ultimately, however,
infertility may be a more difficult aspect of this disorder for the patient to accept. Future fertility
options should be addressed with adolescents and
their parent(s) or guardian(s). Discussion of assisted
reproductive techniques and use of a gestational carrier (surrogate) is appropriate. Specifically, it is
important to explain that eggs can be harvested from
patients with mllerian aplasia and used in assisted
reproductive technology; daughters of women with
MayerRokitanskyKsterHauser syndrome conceived by assisted reproductive technology have
been shown to have normal reproductive tracts (9).
This information allows teens to understand their
reproductive potential for becoming a biologic parent and may help them accept the diagnosis and its
implications. Referral to a mental health professional is very worthwhile for some patients. The
best predictor of good emotional outcome after

diagnosis and vaginoplasty is a good relationship
between the patient and her parents or guardians and
the ability to share feelings with family and friends
(7). Contact with a support group or young women
with the same diagnosis may be helpful (6) (see
Resources).
Patients should be given a brief, written medical
summary of their condition, including a summary of
concomitant malformations. This information may
be useful if the patient requires urgent medical care
or emergency surgery from a health care provider
unfamiliar with mllerian aplasia.
Nonsurgical Creation of a Neovagina

Timing for nonsurgical or surgical creation of a neovagina is elective; however, it is best planned when
the patient is emotionally mature. Nonsurgical creation of the vagina is the appropriate first-line
approach in most patients because it is the least morbid procedure. In a recently reported series of
patients with mllerian aplasia, more than 90% were
able to achieve anatomic and functional success by
vaginal dilation (10).
Patients are asked to manually place successive
dilators on the perineal dimple for 30 minutes to 2
hours per day. Another option of sitting on a bicycle
seat stool provides the perineal pressure and allows
the patient to participate in simultaneous productive
activities, such as doing homework or practicing a
musical instrument (11). Many young women find
that sitting on the bicycle seat stool is too uncomfortable or awkward, thus they may have better success using dilators while reclining on a bed after a
relaxing bath. Use of dilators in the management of
vaginal agenesis is appropriate and successful in
most patients. Mature, highly motivated patients
who wish to avoid surgery and are aware that it will
take several months to achieve their goal are likely
to be successful (11, 12). Because the nonoperative
approach is noninvasive and usually successful, it is
strongly recommended as first-line therapy.
Clinicians often use buddies, other patients
with vaginal agenesis who have successfully dilated, as support to the young woman attempting
dilation. Young married patients make excellent
buddies. If fertility issues are a major concern to
the patient or her family, it may be helpful to find
a buddy who has used assisted reproductive techniques to become a mother.
COMMITTEE OPINIONS
Surgical Creation of a Neovagina

Surgery becomes an option for patients who are
unsuccessful with dilators or patients who prefer
surgery after a thorough discussion with the patient
and her parent(s) or guardian(s) of the risks and benefits of the procedure and the available nonsurgical
alternatives. It should be stressed to the young
woman that a surgical vaginoplasty is not a quick
fix and that she will still need to use vaginal dilators postoperatively to maintain her surgically created vagina. The aim of surgery is the creation of a
vaginal canal in the correct axis of adequate size and
secretory capacity to allow intercourse to occur
without the need for continued postoperative dilation. The timing of the surgery depends on the
patient and the type or procedure planned. Surgeries
often are performed in late adolescence (ages 1721
years) when the patient is more mature and better
able to adhere to postoperative dilation or instructions. Surgery usually is scheduled during summer
vacation to allow for an adequate recovery time
without missing school and to reduce questions
from peers (6, 13).
A number of operations are appropriate for the
correction of vaginal agenesis. The approach usually is based on the experience of the operating surgeon. Pediatric surgeons are more likely to use
bowel segments for the creation of a neovagina;
gynecologists are more likely to use a perineal
approach. Whatever technique is chosen, the surgeon must be experienced with the procedure
because the initial surgery is more likely to succeed
than follow-up procedures. Reoperation in these
cases increases the chance of operative injury to surrounding tissues and the possibility of a poor functional outcome. At present, there is no consensus in
the literature regarding the best option for surgical
correction (14).
The most common surgical procedure used by
U.S. gynecologists to create a neovagina is the
AbbeMcIndoe operation. This involves the dissection of a space between the rectum and bladder,
placement of a mold covered with a split-thickness
skin graft into the space, and the diligent use of
vaginal dilation postoperatively. Postoperative dilation must be continued to prevent significant skin
graft contracture. This surgery is inappropriate if the
patient rejects the nonsurgical technique because
she has concerns about or objections to dilation. If
postoperative dilation is not done, the patient will
53
have a nonfunctional vagina. The dilators are used

long-term on a less frequent basis until the woman
is having vaginal intercourse because at that time
the penis will act as a dilator to maintain the length
of the vagina.
Other procedures for the creation of the neovagina are the Vecchietti procedure and laparoscopic modifications of operations previously
performed by laparotomy. The Vecchietti procedure
involves the creation of a neovagina via dilation
with a traction device attached to the abdomen,
sutures placed subperitoneally via laparotomy, and a
plastic olive placed on the vaginal dimple. In the
laparoscopic modification, traction sutures are
placed laparoscopically. The two techniques are
comparable in terms of producing a functional neovagina (15). Davydov developed a three-stage operation involving dissection of the rectovesical space
with abdominal mobilization of the peritoneum,
with creation of the vaginal fornices and attachment
of the peritoneum to the introitus. The newer adaptation involves dissection of the rectovaginal space,
with mobilization of the peritoneum from below and
laparoscopic assistance from above. This is followed by closure of the abdominal end of the neovagina with a laparoscopically placed pursestring
suture (8, 16, 17).
General Gynecologic Care

Women who have a history of mllerian agenesis
and have created a functional vagina do require routine gynecologic care. Annual pelvic examinations
should be performed to examine for vaginal stricture
or stenosis. Women with mllerian agenesis should
be aware that the neovagina has the same risk as a
native vagina for sexually transmitted diseases and
thus they should be appropriately screened. In addition, vaginal speculum examination and inspection
should be performed to look for possible malignancies (in cases of skin graft or bowel vaginas), colitis
or ulceration (in cases of bowel vaginas), or other
problems. No data exists regarding the need or lack
of need for routine Pap testing in women with a neovagina. It is reasonable to consider these women in
the same category as women without a cervix
because of hysterectomy for the treatment of benign
disease. Thus, annual cytologic screening for cancer
can be considered unnecessary, although no data are
available to support or oppose this concept.
54
Conclusion
The most important steps in the effective management of mllerian aplasia are correct diagnosis of
the underlying condition; evaluation for associated
congenital, renal, or other anomalies; and preparation of the patient before any treatment or intervention. If any of these are neglected, the success of the
intervention will be compromised.
Laparoscopy is seldom required to make the
diagnosis but may be appropriate in the patient presenting with pelvic pain. Nonsurgical creation of the
neovagina should be the first-line approach. In cases
in which surgical intervention is required, referrals
to centers with expertise in this area should be considered. Few surgeons have extensive experience in
construction of the neovagina, and the initial surgery
has the greatest chance for success. In addition,
experts at these centers may be more successful in
promoting the nonsurgical approach, given their
experience.
References
1. Evans TN, Poland ML, Boving RL. Vaginal malformations. Am J Obstet Gynecol 1981;141:91020.
2. Reindollar RH, Byrd JR, McDonough PG. Delayed sexual development: a study of 252 patients. Am J Obstet
Gynecol 1981;140:37180.
3. New MI. Male pseudohermaphroditism due to 17 alphahydroxylase deficiency. J Clin Invest 1970;49:193041.
4. Nieman LK, Kovacs WJ. Uncommon causes of congenital adrenal hyperplasia. In: Rose BD, editor. UpToDate.
Waltham (MA); 2006.
5. Fedele L, Dorta M, Brioschi D, Giudici MN, Candiani
GB. Magnetic resonance imaging in Mayer-RokitanskyKuster-Hauser syndrome. Obstet Gynecol 1990;76:
5936.
6. Laufer MR, Goldstein DP, Hendren WH. Structural
abnormalities of the female reproductive tract. In: Emans
SJ, Laufer MR, Goldstein DP, editors. Pediatric and adolescent gynecology. 5th ed. Philadelphia (PA): Lippincott
Williams & Wilkins; 2005. p. 334416.
7. Poland ML, Evans TN. Psychologic aspects of vaginal
agenesis. J Reprod Med 1985;30:3404.
8. Adamyan LV. Laparoscopic management of vaginal aplasia with or without functional noncommunicating rudimentary uterus. In: Arregui ME, Fitzgibbons RJ Jr,
Katkhouda N, McKernan JB, Reich H, editors. Principles
of laparoscopic surgery: basic and advanced techniques.
New York (NY): SpringerVerlag; 1995. p. 64651.
9. Petrozza JC, Gray MR, Davis AJ, Reindollar RH.

Congenital absence of the uterus and vagina is not commonly transmitted as a dominant genetic trait: outcomes
of surrogate pregnancies. Fertil Steril 1997;67:3879.
10. Roberts CP, Haber MJ, Rock JA. Vaginal creation for
mllerian agenesis. Am J Obstet Gynecol 2001;
185:134952; discussion 13523.
11. Williams JK, Lake M, Ingram JM. The bicycle seat stool
in the treatment of vaginal agenesis and stenosis. J Obstet
Gynecol Neonatal Nurs 1985;14:14750.
12. Rock JA, Breech LL. Surgery for anomalies of the
Mllerian ducts. In: Rock JA, Jones HW 3rd, editors. Te
Lindes operative gynecology. 9th ed. Philadelphia (PA):
Lippincott Williams & Wilkins; 2003. p. 70552.
13. Templeman CL, Lam AM, Hertweck SP. Surgical management of vaginal agenesis. Obstet Gynecol Surv
1999;54:58391.
14. Laufer MR. Congenital absence of the vagina: in search
of the perfect solution. When, and by what technique,
should a vagina be created? Curr Opin Obstet Gynecol
2002;14:4414.
15. Borruto F, Chasen ST, Chervenak FA, Fedele L. The
Vecchietti procedure for surgical treatment of vaginal
agenesis: comparison of laparoscopy and laparotomy. Int
J Gynaecol Obstet 1999;64:1538.
16. Davydov SN, Zhvitiashvili OD. Formation of vagina
(colpopoiesis) from peritoneum of Douglas pouch. Acta
Chir Plast 1974;16:3541.
17. Adamyan LV. Therapeutic and endoscopic perspectives.
In: Nichols DH, Clarke-Pearson DL, editors. Gynecologic, obstetric, and related surgery. 2nd ed. St. Louis
(MO): Mosby; 2000. p. 120917.
Resources
MRKH.org, Inc.
PO Box 301494
Jamaica Plain, MA 02130
Web: www.mrkh.org
The Center for Young Womens Health
333 Longwood Avenue, 5th Floor
Boston, MA 02115
(617) 730-0192
Web:www.youngwomenshealth.org
A guide to vaginal agenesis in teens. Available at
www.youngwomenshealth.org/vaginalagenesis.html
MRKH (Mayer Rokitansky Kuster Hauser Syndrome) and
vaginal agenesis: a guide for parents and guardians. Available
at www.youngwomenshealth.org/mrkh_parent.html
COMMITTEE OPINIONS
55
ACOG COMMITTEE OPINION

Number 392 December 2007
Intrauterine Device and Adolescents

Committee on
Adolescent Health
Care
The committee
would like to thank
Nicole Zidenberg, MD,
Nirupama DeSilva, MD,
Melissa Gilliam, MD,
and Eve Espey, MD, for
their contributions to
the development of this
document.
This document reflects
emerging clinical and scientific advances as of the
date issued and is subject
to change. The information should not be construed as dictating an
exclusive course of treatment or procedure to be
followed.
ABSTRACT: The intrauterine device (IUD) is highly effective and widely used by
women throughout the world. Data support the safety of IUDs for most women, including adolescents. This document addresses the major benefits of IUD use in adolescents,
a population at particular risk of unintended pregnancy.
Intrauterine devices (IUDs) are used by

fewer than 3% of reproductive-aged women
in the United States (1). Concerns about
pelvic inflammatory disease (PID), sexually
transmitted diseases (STDs), infertility, and
difficult insertion have limited the use of the
IUD in adolescents. Data support the safety
of IUDs for most women, including adolescents. The World Health Organization supports the use of intrauterine contraception in
women from menarche to age 20 years, stating that the benefits of intrauterine contraception generally outweigh the risks (2).
Importance of Appropriate
Contraception
Approximately 29% of ninth graders and
62% of 12th graders have engaged in intercourse (3). Sexual activity and inconsistent
contraceptive use contribute to the high rate
of adolescent pregnancy in the United States,
which exceeds that of other industrialized
countries (4, 5). Intrauterine devices offer the
long-term, cost-effective, highly reliable, and
effective contraception needed by women,
especially adolescents (6, 7).
Common Misperceptions
The American College

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
The Intrauterine Device Does Not

Increase an Adolescents Risk of
Pelvic Inflammatory Disease and
Sexually Transmitted Diseases
Past experiences with the Dalkon Shield have
perpetuated the myth that IUDs cause pelvic
infections. The studies that showed a causal
relationship between pelvic infection and
IUDs were fraught with methodologic errors.
Confounding factors included inappropriate
comparison groups, overdiagnosis of salpin-
gitis in IUD users, and inability to control for

the effects of sexual behavior, leading to an
exaggeration of risk estimates (8). Ongoing
research continues to demonstrate the safety
of modern types of IUDs.
The risk of PID is increased above baseline only at the time of insertion. Among
22,908 IUD users, within the first 20 days of
use, the risk of PID was 9.7 per 1,000 womanyears; from 21 days to 8 years, the incidence of
PID was 1.4 per 1,000 woman-years, the
same as that in the general population (9).
Other multicenter randomized controlled
trials confirmed these findings (8, 10). The
risk of PID with IUD placement is 02%
when no infection is present at the time of
insertion and 05% when insertion occurred
with a documented infection. The absolute
risk of PID is very small in both groups (10).
Case reports also have shown that women
with positive chlamydia cultures identified at
the time of IUD insertion are unlikely to
develop PID if the infection is treated with
the IUD retained (11, 12).
The levonorgestrel-releasing intrauterine system may lower the risk of PID by
thickening cervical mucus and thinning the
endometrium (13). Studies have demonstrated the reduced risk of PID using the levonorgestrel-releasing intrauterine system as
compared with a copper IUD (14, 15).
Intrauterine Devices Do Not Affect
the Fertility of Adolescents
Compared with other methods, infertility
was not higher after cessation of IUD use versus cessation of other reversible methods of
contraception (8). In a casecontrol study
examining determinants of tubal infertility,
the presence of chlamydial antibodies was
associated with infertility in both users and
56
nonusers of IUDs (16). Fecundity rapidly returns to normal after IUD removal (17, 18).
Discontinuation
Adolescents are more likely than adult women to discontinue a range of contraceptive methods, including pills
and injectable contraception. In women younger than 25
years, discontinuation of the levonorgestrel-releasing
intrauterine system at 12 months was slightly higher
compared with older women (19). Among copper IUD
users, pain and bleeding led to discontinuation (20). The
rate of amenorrhea with the levonorgestrel-releasing
intrauterine system varies from 16.4% to 80% at 1 year
after insertion and may alleviate bleeding concerns (21).
Expulsion
Expulsion contributes to IUD failure with a risk of 1 in 20
(22). Younger age and previous IUD expulsion may confer the greatest risk of failure (23). Prior expulsion should
not be considered a contraindication for a new IUD provided that patients undergo appropriate counseling and
have close follow-up (23).
Contraindications
Contraindications to IUD use include current pregnancy;
PID or puerperal or postabortion sepsis that is current or
within the past 3 months; current STDs; purulent cervicitis; undiagnosed abnormal vaginal bleeding; malignancy
of the genital tract; known uterine anomalies or leiomyomata distorting the uterine cavity in a way incompatible
with IUD insertion; or allergy to any component of the
IUD or Wilsons disease (for copper-containing IUDs)
(24). An asymptomatic patient may use an IUD within
3 months of a treated pelvic infection or septic abortion
(2, 18).
Emergency Contraception and

Menstrual Suppression
The copper IUD may be used for emergency contraception within 5 days of unprotected intercourse (24). The
IUD confers the additional benefit of serving as a longterm contraceptive. One study found that 86% of parous
women and 80% of nulliparous women maintained the
IUD for long-term contraception after use as emergency
contraception (25).
In addition to providing contraception, the levonorgestrel-releasing intrauterine system reduces menstrual blood loss by 75% at 3 months. It offers the most
favorable side effect profile of the progesterone-only
methods. The levonorgestrel-releasing intrauterine system
offers an alternative to birth control pills for cycle control.
Confidentiality, Consent, and

Counseling
Practitioners must be familiar with federal, state, and
institutional guidelines governing consent by adolescents.
In many states, adolescents have the right to receive confidential contraceptive services without parental permission (26). Confidential IUD insertion may be thwarted by
the cost or consent issues. Preinsertion counseling about
the IUD is paramount. Goals of counseling include
awareness of the long-term nature of the contraceptive,
side effects, risks, and benefits. Upon insertion of the
IUD, self-examination to confirm the presence of strings
should be taught, and condom use for STD prevention
should be encouraged. It is important for adolescents
using IUDs to be familiar with their anatomy and comfortable with checking for strings.
Insertion in the Nulliparous Patient

Discomfort with IUD insertion is common. In one study,
86% of adolescents reported mild to severe pain with
insertion (13). Misoprostol may soften a nulliparous
cervix before insertion (27). Studies of use of nonsteroidal antiinflammatory drugs for analgesia yielded
mixed results but they may be used (28). Less studied
methods of analgesia include paracervical blocks or preinsertion narcotics. Little data suggest that IUD insertion
is technically more difficult in adolescents.
Prophylactic antibiotics are not necessary for IUD
insertion (29). Because adolescents have the highest number of reported cases of chlamydia and coinfection with
gonorrhea frequently occurs (30), all adolescents should
be screened for gonorrhea and chlamydia before IUD
insertion (27, 31). Screening at the time of insertion expedites contraceptive use. Patients with positive test results
have no adverse effects if treated promptly (1012).
Conclusion
The IUD is a highly effective method of contraception
that is underused in the United States. Because adolescents contribute disproportionately to the epidemic of
unintended pregnancy in this country, top tier methods
of contraception, including IUDs and implants, should be
considered as first-line choices for both nulliparous and
parous adolescents. After thorough counseling regarding
contraceptive options, health care providers should
strongly encourage young women who are appropriate
candidates to use this method.
References
1. Mosher WD, Martinez GM, Chandra A, Abma JC, Willson
SJ. Use of contraception and use of family planning services
in the United States: 1982-2002. Adv Data 2004;350:136.
2. World Health Organization. Intrauterine devices. In:
Medical eligibility criteria for contraceptive use. 3rd ed.
Geneva: WHO; 2004. p. 117. Available at: http://www.
who.int/reproductive-health/publications/mec/7_iud.pdf.
Retrieved August 16, 2007.
3. Eaton DK, Kann L, Kinchen S, Ross J, Hawkins J, Harris
WA, et al. Youth risk behavior surveillanceUnited States,
2005. MMWR Surveill Summ 2006;55(5):1108.
COMMITTEE OPINIONS
4. Zibners A, Cromer BA, Hayes J. Comparison of continuation rates for hormonal contraception among adolescents.
5. Guttmacher Institute. In brief: facts on American teens sexual and reproductive health. New York (NY): GI; 2006.
Available at: http://guttmacher.org/pubs/fb_ATSRH.html.
6. Trussell J, Vaughan B. Contraceptive failure, method-related discontinuation and resumption of use: results from the
1995 National Survey of Family Growth. Fam Plann
Perspect 1999;31:6472, 93.
7. Chiou CF, Trussell J, Reyes E, Knight K, Wallace J, Udani J,
et al. Economic analysis of contraceptives for women.
Contraception 2003;68:310.
8. Grimes DA. Intrauterine device and upper-genital-tract
infection. Lancet 2000;356:10139.
9. Farley TM, Rosenberg MJ, Rowe PJ, Chen JH, Meirik O.
Intrauterine devices and pelvic inflammatory disease: an
international perspective. Lancet 1992;339:7858.
10. Mohllajee AP, Curtis KM, Peterson HB. Does insertion and
use of an intrauterine device increase the risk of pelvic
inflammatory disease among women with sexually transmitted infection? A systematic review. Contraception
2006;73:14553.
11. Skjeldestad FE, Halvorsen LE, Kahn H, Nordbo SA, Saake K.
IUD users in Norway are at low risk for genital C. trachomatis infection. Contraception 1996;54:20912.
12. Faundes A, Telles E, Cristofoletti ML, Faundes D, Castro S,
Hardy E. The risk of inadvertent intrauterine device insertion in women carriers of endocervical Chlamydia trachomatis. Contraception 1998;58:1059.
13. Suhonen S, Haukkamaa M, Jakobsson T, Rauramo I. Clinical
performance of a levonorgestrel-releasing intrauterine system and oral contraceptives in young nulliparous women: a
comparative study. Contraception 2004;69:40712.
14. Andersson K, Odlind V, Rybo G. Levonorgestrel-releasing
and copper-releasing (Nova T) IUDs during five years of
use: a randomized comparative trial. Contraception 1994;
49:5672.
15. Toivonen J, Luukkainen T, Allonen H. Protective effect of
intrauterine release of levonorgestrel on pelvic infection:
three years comparative experience of levonorgestrel- and
copper-releasing intrauterine devices. Obstet Gynecol
1991;77:2614.
16. Hubacher D, Lara-Ricalde R, Taylor DJ, Guerra-Infante F,
Guzman-Rodriguez R. Use of copper intrauterine devices
and the risk of tubal infertility among nulligravid women.
N Engl J Med 2001;345:5617.
17. Hov GG, Skjeldestad FE, Hilstad T. Use of IUD and subsequent fertilityfollow-up after participation in a randomized clinical trial. Contraception 2007;75:8892.
18. Penney G, Brechin S, de Souza A, Bankowska U, Belfield T,
Gormley M, et al. FFPRHC Guidance (January 2004). The
copper intrauterine device as long-term contraception.
Faculty of Family Planning and Reproductive Health Care
Clinical Effectiveness Unit [published erratum appears in J
Fam Plann Reprod Health Care 2004;30:134]. J Fam Plann
Reprod Health Care 2004;30:2941; quiz 42.
57
19. Luukkainen T, Allonen H, Haukkamaa M, Holma P, Pyorala

T, Terho J, et al. Effective contraception with the levonorgestrel-releasing intrauterine device: 12-month report
of a European multicenter study. Contraception 1987;36:
16979.
20. Rivera R, Chen-Mok M, McMullen S. Analysis of client
characteristics that may affect early discontinuation of the
TCu-380A IUD. Contraception 1999;60:15560.
21. Toma A, Jamieson MA. Revisiting the intrauterine contraceptive device in adolescents. J Pediatr Adolesc Gynecol
2006;19:2916.
22. FFPRHC Guidance (April 2004). The levonorgestrel-releasing intrauterine system (LNG-IUS) in contraception and
reproductive health. Faculty of Family Planning and
Reproductive Health Care Clinical Effectiveness Unit. J Fam
Plann Reprod Health Care 2004;30:99108; quiz 109.
23. Thonneau P, Almont T, de La Rochebrochard E, Maria B.
Risk factors for IUD failure: results of a large multicentre
case-control study. Hum Reprod 2006;21:26126.
24. Intrauterine device. ACOG Practice Bulletin No. 59.
25. Zhou L, Xiao B. Emergency contraception with Multiload
Cu-375 SL IUD: a multicenter clinical trial. Contraception
2001;64:10712.
26. Guttmacher Institute. State policies in brief: minors access
to contraceptive services. New York (NY): GI; 2007.
Available at: http://www.guttmacher.org/statecenter/spibs/
spib_MACS.pdf. Retrieved September 6, 2007.
27. McNaught J. Adolescents and IUCDsNot a contraindication. J Pediatr Adolesc Gynecol 2006;19:3035.
28. Grimes DA, Hubacher D, Lopez LM, Schulz KF. Nonsteroidal anti-inflammatory drugs for heavy bleeding or
pain associated with intrauterine-device use. Cochrane
Database of Systematic Reviews 2006, Issue 4. Art. No.:
CD006034. DOI: 10.1002/14651858.CD006034.pub2.
29. Grimes DA, Schulz FK. Antibiotic prophylaxis for intrauterine contraceptive device insertion. Cochrane Database of
Systematic Reviews 1999, Issue 3. Art. No.: CD001327. DOI:
10.1002/14651858.CD001327.
30. Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2005. Atlanta (GA): CDC; 2006.
Available at: http://www.cdc.gov/std/stats/05pdf/Surv2005. pdf.
31. Lacy J. Clinic opinions regarding IUCD use in adolescents.
Copyright December 2007 by the American College of Obstetricians and Gynecologists, 409 12th Street, SW, PO Box 96920,
Washington, DC 20090-6920. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, posted on
the Internet, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior
written permission from the publisher. Requests for authorization to
make photocopies should be directed to: Copyright Clearance Center,
222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
Intrauterine device and adolescents. ACOG Committee Opinion No.
392. American College of Obstetricians and Gynecologists. Obstet
Gynecol 2007;110:14935.
ISSN 1074-861X
58

Number 415 September 2008
Depot Medroxyprogesterone Acetate and

Bone Effects

followed.
ABSTRACT: Although depot medroxyprogesterone acetate (DMPA) is associated

with bone mineral density (BMD) loss during use, current evidence suggests that partial
or full recovery of BMD occurs at the spine and at least partial recovery occurs at the hip
after discontinuation of DMPA. Given the efficacy of DMPA, particularly for populations
such as adolescents for whom contraceptive adherence can be challenging or for those
who feel they could not comply with a daily contraceptive method or a method that must
be used with each act of intercourse, the possible adverse effects of DMPA must be balanced against the significant personal and public health impact of unintended pregnancy.
Concerns regarding the effect of DMPA on BMD should neither prevent practitioners from
prescribing DMPA nor limit its use to 2 consecutive years. Practitioners should not perform BMD monitoring solely in response to DMPA use because any observed short-term
loss in BMD associated with DMPA use may be recovered and is unlikely to place a
woman at risk of fracture during use or in later years.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Depot medroxyprogesterone acetate (DMPA)

is a highly effective, long-acting contraceptive
injection used by more than two million
women annually in the United States, including approximately 400,000 adolescents (1).
Convenient dose administration and privacy
are appealing to adolescents, and the expanded use of DMPA has been credited for at least
part of the decrease in adolescent pregnancy
rates over the past decade (2, 3). Depot
medroxyprogesterone acetate prevents pregnancy by inhibiting the secretion of pituitary
gonadotropins resulting in anovulation,
amenorrhea, and a decreased production of
serum estrogen. Hypoestrogenism is associated with a decrease in bone mineral density
(BMD). In older women, low BMD consistent with osteopenia or osteoporosis is associated with an increased risk of fracture.
No studies have been conducted to examine
the association between BMD and fractures
in low-risk young women, including those
using DMPA or those experiencing the
physiologic hypoestrogenism of lactation.
Although DMPA is associated with BMD loss
during use, current evidence suggests that
partial or full recovery of BMD occurs at the
spine and at least partial recovery occurs at
Committee on
Adolescent Health
Care
Committee on
Gynecologic
Practice
the hip after discontinuation of DMPA.

Given the efficacy of DMPA, particularly for
populations such as adolescents for whom
contraceptive adherence can be challenging or
for those who feel they could not comply with
a daily contraceptive method or a method that
must be used with each act of intercourse, the
possible adverse effects of DMPA must be balanced against the significant personal and public health impact of unintended pregnancy.
Bone Mineral Density

A number of studies demonstrate the effect
of DMPA on BMD. Cross-sectional and longitudinal studies using dual-energy X-ray
absorptiometry (DXA) technology among
current users of DMPA (ages 1854 years)
demonstrate that DMPA use results in lower
BMD compared with nonusers regardless of
the anatomic site measured (410). Longitudinal studies report BMD losses at the hip
and spine of 0.53.5% after 1 year of DMPA
use (5, 11) and a 5.77.5% loss in BMD after
2 years of use (8, 10).
Although few studies have examined
long-term use of DMPA, it appears that the
greatest BMD loss is experienced during the
first few years of use (7, 10, 11). In one 3-year
COMMITTEE OPINIONS
longitudinal study, mean change in BMD at each

6-month interval decreased as the number of cumulative
months of DMPA use increased (7). Those using DMPA
for 12 months or less lost BMD at a faster rate than those
using DMPA for 13 months or more (7). Another recent
longitudinal study with a 4-year follow-up period
demonstrated that almost 75% of the BMD lost at the hip
and 90% lost at the spine occurred during the first
24 months of use (9). Women who continued DMPA use
beyond 24 months still lost additional bone, but the magnitude of loss was smaller with each subsequent year of
use (9).
A recent prospective study of BMD monitored
DMPA users and nonhormonal contraceptive users
2025 years of age for up to 5 years of use and for up to 2
years after discontinuation. Despite BMD loss during use,
total hip BMD among DMPA users had returned almost
to baseline levels at 2 years after discontinuation (from
-5.16% after 240 weeks of use to -0.2% at 96 weeks after
discontinuation), and BMD values in the lumbar spine
showed partial recovery (from -5.38% after 240 weeks of
use to -1.19% at 96 weeks after discontinuation) (12). As
in prior studies, the rate of BMD loss was greater in the
first year of treatment than in subsequent years.
Bone loss during the reproductive years is not unique
to DMPA use. Studies of adult women show a decrease in
BMD of 28% during pregnancy and 35% during
breastfeeding (13, 14). These losses are temporary; 612
months after birth or cessation of breast-feeding BMD
values increase to near preconception values in most
women (11). Similarly, studies suggest that at least some
of the bone loss experienced as a result of DMPA use is
recovered after discontinuation. However, studies differ in
their assessment of the speed and completeness of this
recovery (7, 9, 10, 12, 1517). Furthermore, the degree of
recovery appears to differ by site. A 3-year longitudinal
study of 1839-year-old DMPA users noted that women
experienced steady gains in BMD after discontinuation,
regardless of duration of DMPA use (7). Lumbar spine
BMD of DMPA users was similar to that of nonusers by
30 months after discontinuation (7). Increases in BMD at
the hip among those discontinuing use of DMPA also
were noted, but the gain in BMD at this location was
lower than that of nonusers 30 months after discontinuation. Similarly, a 4-year study of first-time users of DMPA
1835 years of age demonstrated that the length of time
required for BMD values to return to baseline levels
depended on the site measured and the duration of
DMPA use. Complete recovery occurred at the spine
within 2730 months among those using DMPA up to 24
months. Recovery at the hip was slower; among those
women who used DMPA for 24 months or less, a return
to baseline values was not observed by 30 months after
discontinuation (9).
Bone mineral density normally increases during the
teenaged years. Therefore, a decrease or stabilization in
BMD during this period may be cause for concern. In a
59
study of DMPA users aged 1221 years, BMD decreased

an average of 3.1% (18). In contrast, adolescents who were
not using hormonal contraception gained BMD at an
average rate of 9.5% over 2 years (18). Among new DMPA
users aged 1418 years, a decrease of 5% at the spine
occurred after 24 months compared with an increase of
2.3% in nonusers (16). The decrease in BMD observed in
these studies may be mitigated by the short-term or intermittent nature of DMPA use in many adolescents because
the discontinuation rate is 50% in the first year (19).
Furthermore, increases in BMD of 14% at the hip and
spine 12 months after discontinuation of DMPA have
been shown in adolescents aged 1418 years (16).
At least two cross-sectional studies provide reassuring data that BMD in former adult DMPA users is similar
to that of never users (20, 21). A World Health
Organization study observed this lack of difference in
BMD in an international population of former DMPA
users and nonusers (20). Another study of postmenopausal women in New Zealand indicated similar
BMD in former adult DMPA users compared with that of
never users (21).
Fracture Risk
Although many studies have examined the intermediate
outcome of decreased BMD related to DMPA, few investigations have examined the outcome of critical importance to womens healththat of fracture risk. Two studies
have examined DMPA use and fracture, both in high-risk
populations. A prospective, short-term study of female
military recruits found that, in white women only, history
of DMPA use was one of several factors associated with an
increased risk of stress fractures of the calcaneus (22).
This study was limited to women at high risk of fractures
and is not applicable to the general population. Another
recent study of developmentally delayed women suggests
an increased risk of fractures in those with a history of
DMPA use. This study is limited by its cross-sectional
design and its use of retrospective data (23).
There are no reported studies in which the risk of
osteoporosis or fractures has been examined in a low-risk
population of prior DMPA users. A recent Cochrane
review reveals that not a single randomized controlled
trial of DMPA and fracture risk has been performed (24).
The Black Box Warning

Concerns over the effect of DMPA use on BMD caused
the U.S. Food and Drug Administration to issue a black
box warning in November 2004. This warning stated
that prolonged use of DMPA may result in significant loss
of BMD, that the loss is greater the longer the drug is
used, and that the loss may not be completely reversible
after discontinuation. The warning cautions that use of
DMPA beyond 2 years should be considered only if other
contraceptive methods are inadequate. In a letter to
physicians, a manufacturer of DMPA suggested DXA
monitoring after 2 years of use.
60
The U.S. Food and Drug Administration warning is

based on intermediate effects on BMD, which may or may
not be relevant to increased fracture risk. Because the evidence suggests that the rate of BMD loss may slow with
longer term DMPA use, the rationale for restriction to
2 years of use or DXA monitoring is unclear. Practitioners
should not perform BMD monitoring solely in response
to DMPA use because any observed short-term losses in
BMD may be recovered and are unlikely to place women
at risk of fracture during DMPA use or in later years.
medication and during prolonged use. Practitioners

should not perform BMD monitoring solely in response
to DMPA use because any observed short-term loss in
BMD associated with DMPA use may be recovered and is
unlikely to place a woman at risk of fracture during use or
in later years. Effective long-term contraceptive methods
that have no effect on BMD and have high continuation
rates, such as contraceptive implants and intrauterine
devices, should also be considered as first-line methods
for adolescents.
Risks of Bone Loss Versus the

Benefits of Contraception
References
Most women and adolescents use DMPA to avoid pregnancy. The failure rate in typical users is 23% for DMPA
(25). As a result, DMPA is widely used by women for
whom successful use of a daily or partner-dependent contraceptive method is difficult. Increased use of DMPA in
the past 15 years has been paralleled by a decrease in the
adolescent pregnancy rate (2, 3). Although there are many
factors contributing to the decrease in adolescent pregnancies, DMPA has likely played a role. It is important to
weigh the theoretical risk of future fracture from
decreased BMD in DMPA users against the very real risk
of pregnancy if contraceptive choices are limited (26). For
example, an adolescent who is at high risk for pregnancy
may be best served by the use of DMPA as a contraceptive
option; both pregnancy and DMPA are associated with
loss of BMD. The riskbenefit ratio might differ for a
noncontraceptive indication such as dysmenorrhea (23).
Counseling
Women initiating DMPA should be thoroughly counseled
about the benefits and the potential risks of DMPA. Daily
exercise and age-appropriate calcium and vitamin D
intake should be encouraged. No studies have shown that
these measures will offset loss of BMD during DMPA use,
but these recommendations can benefit general health,
and most adolescents do not ingest sufficient dietary calcium. Although studies of adolescents and adult women
demonstrate that low-dose estrogen supplementation
limits BMD loss in DMPA users (27, 28), estrogen supplementation during DMPA use is not currently recommended. Most importantly, clinicians should provide
counseling regarding the side effects of DMPA, including
irregular bleeding, in order to attempt to reduce the high
rates of discontinuation of this method.
Conclusion
Depot medroxyprogesterone acetate is a safe and effective
means of long-term contraception, which has likely contributed to a decrease in adolescent pregnancy rates over
the past decade. Concerns regarding the effect of DMPA
on BMD should neither prevent practitioners from prescribing DMPA nor limit its use to 2 consecutive years.
Appropriate counseling with a discussion of current medical evidence should occur before the initiation of this
1. Mosher WD, Martinez GM, Chandra A, Abma JC, Willson

SJ. Use of contraception and use of family planning services in the United States: 1982-2002. Adv Data 2004;(350):
136.
2. Santelli JS, Abma J, Ventura S, Lindberg L, Morrow B,
Anderson JE, et al. Can changes in sexual behaviors among
high school students explain the decline in teen pregnancy
rates in the 1990s? J Adolesc Health 2004;35:8090.
3. Santelli JS, Lindberg LD, Finer LB, Singh S. Explaining
recent declines in adolescent pregnancy in the United
States: the contribution of abstinence and improved contraceptive use. Am J Public Health 2007;97:1506.
4. Cundy T, Cornish J, Roberts H, Elder H, Reid IR. Spinal
bone density in women using depot medroxyprogesterone
contraception. Obstet Gynecol 1998;92:56973.
5. Berenson AB, Radecki CM, Grady JJ, Rickert VI, Thomas A.
A prospective, controlled study of the effects of hormonal
contraception on bone mineral density. Obstet Gynecol
2001;98:57682.
6. Wanichsetakul P, Kamudhamas A, Watanaruangkovit P,
Siripakarn Y, Visutakul P. Bone mineral density at various
anatomic bone sites in women receiving combined oral
contraceptives and depot-medroxyprogesterone acetate for
contraception. Contraception 2002;65:40710.
7. Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM.
Injectable hormone contraception and bone density: results
from a prospective study [published erratum appears in
Epidemiology 2002;13:749]. Epidemiology 2002;13:5817.
8. Berenson AB, Breitkopf CR, Grady JJ, Rickert VI, Thomas A.
Effects of hormonal contraception on bone mineral density
after 24 months of use. Obstet Gynecol 2004;103:899906.
9. Clark MK, Sowers M, Levy B, Nichols S. Bone mineral density loss and recovery during 48 months in first-time users
of depot medroxyprogesterone acetate. Fertil Steril 2006;
86:146674.
10. Clark MK, Sowers MR, Nichols S, Levy B. Bone mineral
density changes over two years in first-time users of depot
medroxyprogesterone acetate. Fertil Steril 2004;82:15806.
11. Ulrich CM, Georgiou CC, Snow-Harter CM, Gillis DE.
Bone mineral density in mother-daughter pairs: relations to
lifetime exercise, lifetime milk consumption, and calcium
supplements. Am J Clin Nutr 1996;63:729.
12. Kaunitz AM, Miller PD, Rice VM, Ross D, McClung MR.
Bone mineral density in women aged 25-35 years receiving
depot medroxyprogesterone acetate: recovery following discontinuation. Contraception 2006;74:909.
COMMITTEE OPINIONS
13. Karlsson C, Obrant KJ, Karlsson M. Pregnancy and lactation confer reversible bone loss in humans. Osteoporos Int
2001;12:82834.
14. Sowers M, Corton G, Shapiro B, Jannausch ML, Crutchfield
M, Smith ML, et al. Changes in bone density with lactation.
JAMA 1993;269:31305.
15. Cundy T, Cornish J, Evans MC, Roberts H, Reid IR.
Recovery of bone density in women who stop using
medroxyprogesterone acetate. BMJ 1994;308:2478.
16. Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM.
Change in bone mineral density among adolescent women
using and discontinuing depot medroxyprogesterone
acetate contraception. Arch Pediatr Adolesc Med 2005;
159:13944.
17. Johnson CC, Burkman RT, Gold MA, Brown RT, Harel Z,
Bruner A, et al. Longitudinal study of depot medroxyprogesterone acetate (Depo-Provera) effects on bone health in
adolescents: study design, population characteristics and
baseline bone mineral density. Contraception 2008;77:
23948.
18. Cromer BA, Stager M, Bonny A, Lazebnik R, Rome E,
Ziegler J, et al. Depot medroxyprogesterone acetate, oral
contraceptives and bone mineral density in a cohort of adolescent girls. J Adolesc Health 2004;35:43441.
19. Zibners A, Cromer BA, Hayes J. Comparison of continuation rates for hormonal contraception among adolescents.
20. Petitti DB, Piaggio G, Mehta S, Cravioto MC, Meirik O.
Steroid hormone contraception and bone mineral density:
a cross-sectional study in an international population. The
WHO Study of Hormonal Contraception and Bone Health.
21. Orr-Walker BJ, Evans MC, Ames RW, Clearwater JM,
Cundy T, Reid IR. The effect of past use of the injectable
contraceptive depot medroxyprogesterone acetate on bone
mineral density in normal post-menopausal women. Clin
Endocrinol 1998;49:6158.
22. Lappe JM, Stegman MR, Recker RR. The impact of lifestyle
factors on stress fractures in female Army recruits.
Osteoporos Int 2001;12:3542.
61
23. Watson KC, Lentz MJ, Cain KC. Associations between fracture incidence and use of depot medroxyprogesterone
acetate and anti-epileptic drugs in women with developmental disabilities. Womens Health Issues 2006;16:34652.
24. Lopez LM, Grimes DA, Schulz KF, Curtis KM. Steroidal
contraceptives: effect on bone fractures in women.
Cochrane Database of Systematic Reviews 2006, Issue 4.
Art. No.: CD006033. DOI: 10.1002/14651858.CD006033
25. Trussell J. Contraceptive failure in the United States.
26. Cromer BA, Scholes D, Berenson A, Cundy T, Clark MK,
Kaunitz AM, et al. Depot medroxyprogesterone acetate and
bone mineral density in adolescentsthe Black Box
Warning: a Position Paper of the Society for Adolescent
Medicine. Society for Adolescent Medicine. J Adolesc
Health 2006;39:296301.
27. Cundy T, Ames R, Horne A, Clearwater J, Roberts H,
Gamble G, et al. A randomized controlled trial of estrogen
replacement therapy in long-term users of depot medroxyprogesterone acetate. J Clin Endocrinol Metab 2003;88:
7881.
28. Cromer BA, Lazebnik R, Rome E, Stager M, Bonny A,
Ziegler J, et al. Double-blinded randomized controlled trial
of estrogen supplementation in adolescent girls who receive
depot medroxyprogesterone acetate for contraception. Am
J Obstet Gynecol 2005;192:427.
Copyright September 2008 by the American College of Obstetricians and Gynecologists, 409 12th Street, SW, PO Box 96920,
mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher. Requests for authorization to
Depot medroxyprogesterone acetate and bone effects. ACOG
Committee Opinion No. 415. American College of Obstetricians and
ISSN 1074-861X
62

Addressing Health Risks of Noncoital

Sexual Activity
Committee on
Adolescent Health
Care
Committee on
Gynecologic Practice
should not be construed
as dictating an exclusive
course of treatment or

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Noncoital sexual behaviors, which include mutual masturbation, oral

sex, and anal sex, are common expressions of human sexuality. Couples may engage in
noncoital sexual activity instead of penilevaginal intercourse hoping to reduce the risk of
sexually transmitted diseases and unintended pregnancy. Although these behaviors carry
little or no risk of pregnancy, women engaging in noncoital behaviors may be at risk of
acquiring sexually transmitted diseases. Practitioners can assist by assessing patient risk
and providing risk reduction counseling for those participating in noncoital sexual activities.
Noncoital sexual activities are common in

both adults and adolescents. The 2002
National Survey of Family Growth found
that 88% of females and 90% of males aged
2544 years, and 55% of males and 54% of
females aged 1519 years, have had oral sex
with an opposite-sex partner (1). Anal sex is
less common than oral or vaginal sex and is
commonly initiated at a later age; 35% of
females and 40% of males aged 2544 years
and 11% of male and female adolescents
aged 1519 years reported anal sex with an
opposite-sex partner (1). Comparison of
data on oral sex from the 2002 National
Survey of Family Growth with data from
three national surveys from the early and mid
1990s (the 1991 National Survey of Men, the
1992 National Health and Social Life Survey,
and the 1995 National Survey of Adolescent
Men) provides no evidence for a recent
increase in oral sex prevalence among adolescents and young adults despite concerns
expressed in the popular media (1).
Noncoital behaviors commonly cooccur with coital behaviors. Both oral sex
and anal sex are much more common
among adolescents who have already had
vaginal intercourse as compared with those
who have not (2). Likewise, the prevalence of
oral sex among adolescents jumps dramatically in the first 6 months after initiation of
vaginal intercourse, suggesting that both are
often initiated at the same time and with the
same partner. Initiation of anal sex before
initiation of coitus is rare, and the prevalence of anal sex increases slowly after initiation of coitus.
When engaging in oral sex, most individuals, including adolescents, are unlikely to
use barrier protection for a variety of reasons, including a greater perceived safety of
noncoital sexual activity compared with
vaginal sex (3, 4). In the 2002 National
Survey of Family Growth, only 11% of
females and 15% of males aged 1517 years
who had ever engaged in oral sex reported
using a condom the most recent time that
they had engaged in oral sex (5).
Some sexually transmitted diseases
(STDs) may be transmitted during noncoital
sexual activity. Infections can be spread
through saliva, blood, vaginal secretions,
semen, and fecal material. Preexisting infections, open sores, abrasions, or any compromise of the epithelial tissue can increase the
risk of transmission. Transmission of STDs is
organism specific, with certain infections
commonly infecting the oral or rectal cavity,
and many rarely doing so or causing infection without sequelae.
Human Immunodeficiency
Virus
Human immunodeficiency virus (HIV)
transmission is highly correlated with the
HIV viral load of the infected partner. In
addition, the risk of acquiring HIV varies
dramatically according to the specific sexual
COMMITTEE OPINIONS
behavior, especially whether it is insertive or receptive. The

U.S. Centers for Disease Control and Prevention (CDC)
estimates a 100-fold increase in risk from the safest to the
least safe behavior (Table 1). Human immunodeficiency
virus is most readily transmitted through anal sex.
Receptive anal sex with a partner who is infected with HIV
is the sexual behavior associated with the greatest risk of
HIV transmission. Condom use reduces HIV transmission by approximately 80% in HIV-serodiscordant couples (6). Although saliva appears to have components that
inactivate HIV, there are case reports of HIV acquisition in
men who engaged only in oral sex with other men (7).
Herpes Simplex Virus

Herpes infection is commonly transmitted through kissing and via oral, vaginal, and anal sex. Typically, herpes
simplex virus type 1 (HSV-1) is associated with oral
lesions, whereas herpes simplex virus type 2 (HSV-2) is
associated with genital lesions. However, both HSV-1 and
HSV-2 are capable of infecting oral, anal, and genital sites.
A study of university students seeking treatment for herpes found the percentage of HSV-1 genital herpes infections increased from 31% in 1993 to 78% in 2001 (8).
Therefore, older studies that based their results solely on
the presence of HSV-2 have underestimated the prevalence of genital herpes infections (9, 10).
Human Papillomavirus
Human papillomavirus (HPV) is a very common sexually transmitted virus that causes anogenital and oral cancers as well as the benign genital warts. There are more
than 100 strains of HPV, 40 of which selectively infect the
anogenital and oral areas. More than 90% of the HPV
infections resolve spontaneously without sequelae; however, persistent infection in the anogenital area or oral
cavity may cause cancer. Although the most efficient
means of transmission appear to be penilevaginal sex or
penileanal sex, oral transmission appears to occur as
well. However, data currently suggest that transmission is
Table 1. Risk of Human Immunodeficiency Virus
Transmission According to Sexual Behavior
Sex Act
Insertive fellatio
Receptive fellatio
Insertive vaginal sex
Relative Risk*
1
2
10
Insertive anal sex
13
Receptive vaginal sex
20
Receptive anal sex
100
*Refers to relative risk of acquiring human immunodeficiency virus (HIV) infection

among persons without HIV infection.
Varghese B, Maher JE, Peterman TA, Branson BM, Steketee RW. Reducing the risk
of sexual HIV transmission: quantifying the per-act risk for HIV on the basis of
choice of partner, sex act, and condom use. Sex Transm Dis 2002;29:3843.
63
less efficient to the oral cavity than to the genital area. The
digital spread of HPV is theoretically possible because
genital HPV DNA has been detected on the hand.
However, because this is only detection of DNA, it is not
proved that this DNA is infectious.
Hepatitis Viruses
Hepatitis B virus can be found in semen, saliva, and
feces and is commonly spread through sexual contact.
Hepatitis A is transmitted from fecal contamination of the
oral cavity, thus explaining the higher incidence of infection in homosexual men who engage in oralanal contact.
Sexual transmission of hepatitis C is uncommon but has
been associated with both preexisting hepatitis B and HIV
infection and with oralgenital contact (7).
Nonviral Sexually Transmitted

Diseases
A substantial number of recent primary and secondary
cases of syphilis reported in Chicago were attributable to
oral sex, with 86 of 627 (13.7%) individuals with syphilis
reporting oral sex as the only sexual exposure that could
account for their infection (11).
Most gonorrheal infections are sexually transmitted
and involve the urethra, cervix, rectum, or mouth (12).
Disseminated disease after oralgenital contact has been
documented. Although only 10% of isolated pharyngeal
gonorrheal infections are symptomatic, pharyngitis, with
or without fever or lymphadenopathy, should raise suspicion for gonorrheal infection when all other etiologies
have been ruled out.
Chlamydia has been isolated from throat cultures in
both men and women. In women, pharyngeal infection is
associated with performing oral sex on men (12, 13).
Chancroid, shigellosis, salmonellosis, and other enteric
infections have been linked to oralgenital or oralanal
sex in a few case reports but appear to be relatively
uncommon. The role of noncoital sexual activity in the
transmission of other nonviral infections, such as vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis remains unclear (12).
Patient Counseling
Noncoital sexual activity is not necessarily safe sex.
Because people define sexuality in a variety of ways, it is
important that practitioners ask direct questions regarding sexual activity, including questions about oral or anal
sex and mutual masturbation, and questions about sexual partners, including whether the patient has sex with
men, women, or both men and women.
A positive response to these questions indicates the
need for counseling regarding infection prevention strategies specific to noncoital sexual activity. To individualize counseling, the clinician must consider the womans
infection risk from partner factors (number of sexual partners and her partners sexual behaviors, particularly multiple sexual partnerships) and the community prevalence of
64
STDs. Because most women who engage in noncoital sexual activity also are engaging in penilevaginal intercourse,
the clinician needs to consider whether noncoital behaviors
add any additional risks to those already posed by sexual
intercourse. When a young person engages in only oral or
anal sex, the likelihood of encountering a partner infected
with an STD should be considered. Correct and consistent
condom use should be encouraged, especially for anal sex
and vaginal sex. Practitioners also should consider the
patients history of STDs and patterns of barrier method
use with each partner. In brief, practitioners need to consider the totality of the patients STD risk.
Counseling should focus on reducing STD risk factors
such as multiple partners. This may be more effective than
discouraging oral or anal sex. Risk-reduction strategies may
include engaging in safer behaviors (eg, oral sex often is
safer than vaginal intercourse, anal sex often is riskier than
penilevaginal sex), abstinence, mutual monogamy, limiting the number of partners, STD testing before engaging in
sexual activity with a new partner, and correct and consistent use of condoms, particularly for vaginal and anal sex.
Sex toys should be cleaned between uses. Couples counseling may be helpful for STD-serodiscordant couples.
Routine screening for chlamydia is recommended
annually for all sexually active women aged 25 years or
younger, and routine screening for gonorrhea is recommended for all sexually active adolescents. Although the
2006 CDC STD Treatment Guidelines recommend
behavioral screening for anal and oral sex, they do not
make specific recommendations for routine oral or anal
STD laboratory screening (14). Selected laboratory testing for oral and anal STDs should be based on clinical
symptoms and behavioral risks.
Lesbians and bisexual women should be screened for
STDs based on the same risk factors as other women.
Because most lesbians have been sexually active with men at
some point in their lives and because some STDs also can be
transmitted by sexual activity exclusively among lesbians, it
should not be assumed that STD screening is unnecessary.
Conclusion
Great efforts are needed to educate health care practitioners and the public regarding the potential health risks of
noncoital sexual activities and the importance of risk
reduction and barrier methods of protection. Practitioners
can assist by assessing patient risk and providing risk
reduction counseling for those participating in noncoital
sexual activities. Ultimately, additional research is needed
to determine the full impact of noncoital sexual activity
on the health of patients.
References
1. Mosher WD, Chandra A, Jones J. Sexual behavior and
selected health measures: men and women 1544 years of
age, United States, 2002. Adv Data 2005;(362):155.
2. Lindberg LD, Jones R, Santelli JS. Non-coital sexual activities among adolescents. J Adolesc Health 2008;42(suppl 1):
445.
3. Prinstein MJ, Meade CS, Cohen GL. Adolescent oral sex,
peer popularity, and perceptions of best friends sexual
behavior. J Pediatr Psychol 2003;28:2439.
4. Halpern-Felsher BL, Cornell JL, Kropp RY, Tschann JM.
Oral versus vaginal sex among adolescents: perceptions,
attitudes, and behavior. Pediatrics 2005;115:84551.
5. Terry-Humen E, Manlove J, Cottingham S. Trends and
recent estimates: sexual activity among U.S. teens. Child
Trends Research Brief No. 200608. Washington, DC: Child
Trends; 2006. Available at: http://childtrends.org/files/
sexualactivityrb.pdf. Retrieved April 23, 2008.
6. Weller SC, Davis-Beaty K. Condom effectiveness in reducing heterosexual HIV transmission. Cochrane Database of
10.1002/14651858.CD003255.
7. Edwards S, Carne C. Oral sex and the transmission of viral
STIs. Sex Transm Infect 1998;74:610.
8. Roberts CM, Pfister JR, Spear SJ. Increasing proportion of
herpes simplex virus type 1 as a cause of genital herpes infection in college students. Sex Transm Dis 2003;30:797800.
9. Cherpes TL, Meyn LA, Hillier SL. Cunnilingus and vaginal
intercourse are risk factors for herpes simplex virus type 1
acquisition in women. Sex Transm Dis 2005;32:849.
10. Lafferty WE, Downey L, Celum C, Wald A. Herpes simplex
virus type 1 as a cause of genital herpes: impact on surveillance and prevention. J Infect Dis 2000;181:14547.
11. Centers for Disease Control and Prevention (CDC).
Transmission of primary and secondary syphilis by oral
sexChicago, Illinois, 1998-2002. MMWR Morb Mortal
Wkly Rep 2004;53:9668.
12. Edwards S, Carne C. Oral sex and transmission of non-viral
STIs. Sex Transm Infect 1998;74:95100.
13. Jones RB, Rabinovitch RA, Katz BP, Batteiger BE, Quinn TS,
Terho P, et al. Chlamydia trachomatis in the pharynx and
rectum of heterosexual patients at risk for genital infection.
Ann Intern Med 1985;102:75762.
14. Workowski KA, Berman SM. Sexually transmitted diseases
treatment guidelines, 2006. Centers for Disease Control and
Prevention [published erratum appears in: MMWR Morb
Mortal Wkly Rep 2006;55:997]. MMWR Recomm Rep
2006;55:194.
Addressing health risks of noncoital sexual activity. ACOG Committee
Opinion No. 417. American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;112:7357.
ISSN 1074-861X
COMMITTEE OPINIONS
65

Menstrual Manipulation for Adolescents

With Disabilities
Committee on
Adolescent Health
Care
The Committee would
like to thank Elisabeth
Quint, MD and Ann
Davis, MD for their
assistance in the development of this document.
course of treatment or procedure to be followed.
ABSTRACT: Defining the reasons for intervention and the precise goal of treatment
are the most critical issues regarding use of interventions to alter menstrual flow in
adolescents with disabilities. Reasons for intervention may relate to abnormal uterine
bleeding, hygiene, mood issues, fear of pregnancy, and acute onset of other medical conditions. Goals of treatment may include a decrease in the amount of bleeding, periodic
amenorrhea, or treatment of symptoms, such as mood issues or dysmenorrhea. First-line
treatment options should be safe, minimally invasive, and nonpermanent. Endometrial
ablation has not been studied in adolescents, has not been studied long-term, is considered irreversible and, therefore, is not recommended in teenagers.
For an adolescent with either physical or

developmental disabilities, menstruation can
provide significant challenges for the patient
and her caregivers. The hygiene component
of often irregular early bleeding episodes and
the behavioral concerns that accompany
menstrual periods especially in developmentally delayed teenagers may cause significant
problems. In addition, concerns regarding
sexuality and vulnerability to abuse and pregnancy contribute to the worries of many parents. Requests for amenorrhea or menstrual
manipulation will be presented to obstetriciangynecologists, who then need to offer
information and counseling in this area. This
committee opinion focuses on the concerns,
assessment, and methods used for menstrual
manipulation in adolescents with disabilities.
Communication and Special

Considerations for History
Taking

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Optimal gynecologic health care of adolescents with disabilities is comprehensive;

maintains confidentiality, if possible; does
not treat the patient as infantile, affirms the
patients dignity; maximizes the patients
interests; and avoids harm. When possible,
the patient should have the opportunity to be
interviewed in private (1). Communication
should be directed to the teenager and not
to a family member or personal assistant.

Having knowledge of the teenagers mode of
communication and provider patience in the
process are critical.
Knowledge of puberty, menstruation,
sexual activity, safety, and the ability to consent to any sexual act should be assessed.
Adolescents with disabilities often are thought
to be asexual, but they are as likely as other
teenagers without disabilities to be sexually
active, and are at greater risk for forced sexual encounters (2). When knowledge deficits
are present, developmentally appropriate education on hygiene, contraception, sexually
transmitted infections, and abuse prevention
measures should be provided. Most adolescents who are able to use the toilet without
assistance can learn to use pads or tampons
or both appropriately.
When the obstetriciangynecologist
receives a request for amenorrhea or menstrual manipulation, it is important to assess
the reason(s) for the request, especially if the
request does not directly come from the
patient. If the patient herself requests to have
her menstrual periods eliminated, her reasons can be discussed directly with her. If her
caregiver requests this for the teenager, especially if the teenager has a significant developmental delay, the issues become more
complex. Before determining the next steps,
66
the health care provider needs to ascertain whether the

request is based on convenience for the family or caregivers, vulnerability for abuse and pregnancy, or menses
that truly affect the patients quality of life. If the adolescent with disabilities cannot participate in her usual activities during her menses, this may be due to inadequate
help with her hygiene needs, behavioral issues during
menses, or dysmenorrhea.
Menstrual Concerns
Although all teenagers may have irregular cycles during
the first 25 years after menarche (3), adolescents with disabilities may have additional reasons to experience menstrual irregularities, including thyroid disease in teenagers
with trisomy 21, high prolactin levels due to mood stabilizing medication, and polycystic ovary syndrome in
teenagers with seizure disorders (1020%) (4, 5).
Examination
With the new guidelines regarding cervical cytology
screening (6), a pelvic examination is rarely needed in a
teenager who is not sexually active and is only recommended for specific indications, including abnormal
bleeding, vaginal discharge, suspicion of a vaginal foreign
object, or abuse evaluations, which may require an examination under anesthesia. Sexually transmitted infection
screening can be done by urine and blood testing. The
evaluation for abnormal bleeding is the same for adolescents with disabilities as for other adolescents.
Treatment Options
If after an evaluation, the teenager, her family and health
care provider have decided that menstrual intervention is
warranted, the least invasive, reversible, and least harmful
intervention should be used. It is important to assess if predictable but potentially longer bleeding is easier to manage
than sporadic, irregular bleeding and counsel that total
amenorrhea is difficult to obtain. The following options are
available.
Nonsteroidal Antiinflammatory Drugs
Antiprostaglandin drugs in adequate dosages decrease
ovulatory bleeding by approximately 3040% with less
reduction in anovulatory cycles. Although this will not
stop menses, it may help with pain and bleeding (7).
Estrogen-Containing Methods
Combined Oral Contraceptives

Combined oral contraceptives (OCs) used cyclically
result in less menstrual blood loss in patients. Combined
OCs can be used continuously or for an extended period
to attempt to reduce the total days of menstrual flow.
This, however, increases the incidence of unscheduled
bleeding, especially early in use, but amenorrhea rates
may increase to 50%. There are only sparse data on how
to manage the unscheduled bleeding; however, one study
suggests that use of norethindrone acetate resulted in
more amenorrhea than levonorgestrel (8). There is a

chewable combined OC available to use with G-tubes or
patients who are unable to swallow pills.
Contraceptive Patch
Pharmacologic data indicate that estrogen exposure is
higher with use of the contraceptive patch than with oral
contraceptives or the vaginal ring. It is unclear how this
may affect the risk of deep vein thrombosis (DVT) (9,
10). Caution, therefore, is recommended for use of the
patch in nonmobile women (see following discussion of
DVT). In teenagers with developmental disabilities,
unscheduled removal of the patch may occur. Placement
of the patch on the buttocks or shoulder, where the individual cannot reach it, may remedy this problem.
Contraceptive Ring
Contraceptive rings often are difficult for adolescents
with mobility issues or functional hand limitations to
insert. There are clear intimacy issues with using caregivers to assist with inserting a ring, although some
women may feel comfortable with partner help. The ring
can be used for 3 weeks, with an interval free week, but
rings used for 4 weeks continuously lead to lighter bleeding and more days of amenorrhea (11).
Estrogen Use and Risk of Deep Vein Thrombosis
Immobility is not listed as a contraindication to estrogencontaining contraceptives by the World Health Organization and the American College of Obstetricians and
Gynecologists (12). However, there are minimal data on
the risk of DVT in women who take contraceptives with
or without exogenous estrogen and who use wheelchairs.
Clinicians, therefore, will want to assess patients for
hypercoagulability by obtaining a careful family history
(13) and encourage exercise of extremities in patients
who are physically able. Because there is a possible concern about clotting risk with patches and combined OCs
with third-generation progestins (14), they may not be
the first choice for women who are immobile.
Progestin-Only Methods
Oral Medications
Cyclic progestins reduce blood loss in women with
anovulation, but do not work in this capacity for women
who are ovulatory (15). While taking the progestin only
minipill, patients will have ovulatory cycles approximately 40% of the time, short irregular cycles 40% of
time, or lack of cycles from amenorrhea to irregular
bleeding 20% of the time (16). Oral progestins in higher
doses than the progestin-only birth control pills can be
used daily to achieve amenorrhea. Occasional depressed
mood has been noted by clinicians, although, there is not
substantial data to support this.
Implants
Progestin contraceptive subdermal implants have an incidence of unscheduled bleeding of up to 40% in the first
COMMITTEE OPINIONS
months after insertion (17) and need significant patient

cooperation or sedation for insertion.
Intramuscular Depot Medroxyprogesterone Acetate

Use of depot medroxyprogesterone acetate (DMPA)
results in relatively high rates of amenorrhea by the
fourth dose (approximately as high as 90% per 90-day
cycle in some studies) and has traditionally been used
extensively to suppress menses (18). There are two main
areas of concern for adolescents with disabilities.
1. Bone density: Although a decrease in bone density has
been described with DMPA use in teenagers, there is
evidence showing recovery of bone after DMPA is discontinued (19). However, in teenagers where the suppression may need to be long term or when the risk for
very low bone density may be increased because of
immobility or being under weight or both, DMPA use
may be less advisable. Supplementation with calcium
and vitamin D should be considered. Several studies of
adolescents and women demonstrate that low-dose
estrogen supplementation limits bone mineral density
loss in DMPA users; however, estrogen supplementation during DMPA use is not currently recommended
(19).
2. Weight gain: Weight gain is variable but appears to be
particularly problematic for overweight patients
(20). For adolescents with disabilities who may be
dependent on their own strength or the help of caregivers for transfers in and out of chairs and beds, a
relatively small weight gain may affect their independence and should be closely monitored.
Progesterone-Releasing Intrauterine Contraception

The levonorgestrel intrauterine device (IUD) is utilized
outside of its contraceptive labeling as a method of menstrual suppression (21). Irregular bleeding is common
initially, but amenorrhea rates increase over time and
overall blood loss is significantly decreased. One metaanalysis of levonorgestrel IUD use in the general population indicates a 7080% reduction of blood loss (22).
Ovulation is variable so amelioration of ovulatory symptomatology will vary. Current data on the levonorgestrel
IUD is not specific to adolescents with disabilities. In adolescents with disabilities, IUD insertion may need to be
done under anesthesia because of a higher likelihood of
nulligravid status (23), unpredictable cooperation, a narrow vagina, a small uterus, and significant contractures.
Special Consideration: Antiepileptic Drugs and
Hormone Use
Even though estrogen is a proconvulsant, combined OCs
have not been associated with an increase in seizures.
Irregular bleeding is common and contraceptive effectiveness may be affected by enzyme inducing antiepileptic
drugs (24). Progestins increase seizure threshold and can
play an important role for women with epilepsy (25).
67
Estrogen or progesterone content may need to be

increased or DMPA may be used in 10-week intervals to
decrease irregular bleeding (26).
Surgical Methods
Endometrial Ablation
Endometrial ablation aims to treat heavy bleeding by
selectively destroying the endometrial lining while leaving
the uterus intact. It is generally recommended with concomitant contraception or sterilization, only if reproduction is no longer desired. The use of endometrial ablation
in adolescents with disabilities is not recommended
because of the following issues:
There is no real long-term outcome data (for example, 2040 years) or data on adolescents.
Guardians and patients who request endometrial
ablation in adolescents with disabilities do so in the
hope to obtain amenorrhea, which occurs in approximately 1347% of adults at 12 months (27).
Women younger than 45 years experience a significantly higher failure rate of the procedure than older
women (28).
Although ablation is not considered sterilization by
many, the destruction of the endometrium will render the patient subfertile, if not infertile. In the event
that pregnancy ensues after an ablation, complications are likely (29).
Consent requirements for sterilization in adolescents
with disabilities who cannot give their own consent,
either because of age or developmental delay, should
apply to this procedure as well (1). Although there
are laws in some states protecting minors from sterilization procedures, it is unclear if these laws apply to
ablation.
Hysterectomy
Occasionally, a family may request a hysterectomy for
definitive amenorrhea in adolescents with disabilities.
Issues with hysterectomy in this situation include that this
method is always irreversible and has the highest potential for morbidity and mortality. In situations when
guardians request hysterectomy, it is critical to define
what benefits they desire. Hysterectomy is seen by some as
ideal for pregnancy prevention, and menstrual control
may be a secondary goal. It is critical for guardians to
understand that a hysterectomy will not protect the child
from the hazards of sexual abuse or sexually transmitted
infections. Only very rarely should a hysterectomy be considered for adolescents with disabilities, just as for
teenagers without disabilities, such as when they are done
for extreme situations like cancer. Abnormal bleeding is
almost always managed medically for a teenager without
disabilities. The same should be true for adolescents with
disabilities. Laws regarding minor sterilization, hysterectomy, and consent issues vary from state to state.
68
Guidelines are available from the American College of

Obstetricians and Gynecologists regarding consent (1).
References
1. Sterilization of women, including those with mental disabilities. ACOG Committee Opinion No. 371. American
College of Obstetricians and Gynecologists. Obstet Gynecol
2007;110:21720.
2. Cheng MM, Udry JR. Sexual behaviors of physically disabled adolescents in the United States. J Adolesc Health
2002;31:4858.
3. Menstruation in girls and adolescents: using the menstrual
cycle as a vital sign. ACOG Committee Opinion No. 349.
4. Prasher VP. Down syndrome and thyroid disorders: a review.
Downs Syndr Res Pract 1999;6:2542.
5. Herzog AG, Schachter SC. Valproate and the polycystic
ovarian syndrome: final thoughts. Epilepsia 2001;42:3115.
6. Cervical cytology screening. ACOG Practice Bulletin No.
7. Bonnar J, Sheppard BL. Treatment of menorrhagia during
menstruation: randomised controlled trial of ethamsylate,
mefenamic acid, and tranexamic acid. BMJ 1996;313:
57982.
8. Edelman AB, Koontz SL, Nichols MD, Jensen JT. Continuous
oral contraceptives: are bleeding patterns dependent on the
hormones given? Obstet Gynecol 2006; 107:65765.
9. Use of hormonal contraception in women with coexisting
medical conditions. ACOG Practice Bulletin No. 73.
10. Phelps JY, Kelver ME. Confronting the legal risks of prescribing the contraceptive patch with ongoing litigation.
11. Sulak PJ, Smith V, Coffee A, Witt I, Kuehl AL, Kuehl TJ.
Frequency and management of breakthrough bleeding with
continuous use of the transvaginal contraceptive ring: a
randomized controlled trial. Obstet Gynecol 2008;112:
56371.
12. World Health Organization. Medical eligibility criteria for
contraceptive use. 3rd ed. Geneva: WHO; 2004.
13. Savelli SL, Kerlin BA, Springer MA, Monda KL, Thornton
JD, Blanchong CA. Recommendations for screening for
thrombophilic tendencies in teenage females prior to contraceptive initiation. J Pediatr Adolesc Gynecol 2006;19:3
136.
14. Girolami A, Spiezia L, Rossi F, Zanon E. Oral contraceptives
and venous thromboembolism: which are the safest preparations available? Clin Appl Thromb Hemost 2002;8: 15762.
15. Lethaby A, Irvine GA, Cameron IT. Cyclical progestogens
for heavy menstrual bleeding. Cochrane Database of
10.1002/14651858.CD001016.pub
16. Broome M, Fotherby K. Clinical experience with the
progestogen-only pill. Contraception 1990;42:48995.
17. Funk S, Miller MM, Mishell DR Jr, Archer DF, Poindexter A,
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
Schmidt J, et al. Safety and efficacy of Implanon, a singlerod implantable contraceptive containing etonogestrel.
Implanon US Study Group. Contraception 2005;71:31926.
Speroff L, Fritz MA. Long-acting methods of contraception.
In: Clinical gynecologic endocrinology and infertility. 7th
ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2005.
p. 94969.
Depot Medroxyprogesterone Acetate and Bone Effects.
ACOG Committee Opinion No.415. American College of
112:72730.
Bonny AE, Ziegler J, Harvey R, Debanne SM, Secic M,
Cromer BA. Weight gain in obese and nonobese adolescent
girls initiating depot medroxyprogesterone, oral contraceptive pills, or no hormonal contraceptive method. Arch
Pediatr Adolesc Med 2006;160:405.
Noncontraceptive uses of the levonorgestrel intrauterine
system. ACOG Committee Opinion No. 337. American
2006;107:147982.
Mansour D. Modern management of abnormal uterine
bleeding: the levonorgestrel intra-uterine system. Best Pract
Res Clin Obstet Gynaecol 2007;21:100721.
Suhonen S, Haukkamaa M, Jakobsson T, Rauramo I. Clinical
performance of a levonorgestrel-releasing intrauterine system and oral contraceptives in young nulliparous women:
a comparative study. Contraception 2004;69:40712.
Foldvary-Schaefer N, Falcone T. Catamenial epilepsy:
pathophysiology, diagnosis, and management. Neurology
2003;61:S215.
Foldvary-Schaefer N, Harden C, Herzog A, Falcone T.
Hormones and seizures. Cleve Clin J Med 2004;71 Suppl
2:S118.
Quint EH. Menstrual issues in adolescents with physical
and developmental disabilities. Ann N Y Acad Sci 2008;
1135:2306.
Endometrial ablation. ACOG Practice Bulletin No. 81.
El-Nashar SA, Hopkins MR, Creedon DJ, St Sauver JL,
Weaver AL, McGree ME, et al. Prediction of treatment outcomes after global endometrial ablation. Obstet Gynecol
2009;113:97106.
Hare AA, Olah KS. Pregnancy following endometrial ablation: a review article. J Obstet Gynaecol 2005;25:10814.
Copyright December 2009 by the American College of Obstetricians

and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington,
DC 20090-6920. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the Internet, or
transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording, or otherwise, without prior written permission from the publisher. Requests for authorization to make photocopies should be directed to: Copyright Clearance Center, 222
Rosewood Drive, Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Menstrual manipulation for adolescents with disabilities. ACOG
COMMITTEE OPINIONS
69

Von Willebrand Disease in Women

Committee on
Adolescent Health
Care
Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Approximately 3 million women in the United States have inherited

bleeding disorders. The prevalence of bleeding disorders is particularly high among
women with menorrhagia. Von Willebrand disease is the most common inherited bleeding disorder. Once a diagnosis is made, collaboration with a hematologist is helpful for
long-term management. Women with von Willebrand disease may be at increased risk
for gynecologic and obstetric complications. Many treatments are available for the control of menorrhagia in women with von Willebrand disease, but the first-line therapy
remains combined hormonal contraception.
Background
Approximately 3 million women in the
United States have inherited bleeding disorders (1). Von Willebrand disease is the most
common inherited bleeding disorder, with a
prevalence of 0.61.3% (2, 3). Among women
with menorrhagia, the prevalence is greater,
and ranges from 5% to 15%. In particular,
von Willebrand disease appears to be more
prevalent among Caucasians with menorrhagia (4). One study suggests that 15.9% of
Caucasians were found to have von Willebrand disease, compared with 1.3% of African
Americans (5).
Von Willebrand disease is an autosomally inherited congenital bleeding disorder
involving a qualitative or quantitative deficiency of von Willebrand factor (vWF).
Dominant and recessive patterns of transmission exist. Von Willebrand factor is a protein
that is critical for proper platelet adhesion
and protects against coagulant factor degradation. There are three main types of von
Willebrand disease. Type 1 (deficiency of vWF),
the most common, usually is mild; type 2
(abnormal vWF) is less common; type 3
(complete absence of vWF) and pseudo von
Willebrand forms are rare, and the presentation signs and symptoms are variable (6).
Presenting Symptoms and

Signs
The most commonly reported symptom
among women with a diagnosis of von
Willebrand disease or suspected bleeding dis-
order is menorrhagia, but additional symptoms or signs also may be present (7, 8).
Other presenting symptoms may include
epistaxis, bleeding after dental extraction,
bleeding from minor cuts or abrasions, postoperative bleeding, gingival bleeding, easy
bruising, postpartum hemorrhage, joint
bleeding, and gastrointestinal bleeding (7, 9).
Among women with a diagnosis of von
Willebrand disease, 48% reported easy bruising, 44% reported epistaxis, 51% reported
gingival bleeding, and 84% presented with
menorrhagia (8, 10). In one cross-sectional
study, women with von Willebrand disease
were also more likely than controls to report
other gynecologic conditions, including ovarian cysts (52%), endometriosis (30%), leiomyomas (32%), endometrial hyperplasia
(10%), polyps (8%), and hysterectomy (26%)
in addition to menorrhagia (8).
Up to 20% of women presenting with
menorrhagia at any time in life will have an
underlying bleeding disorder (2, 4, 5). The
onset of heavy menses at menarche is often
the first sign of von Willebrand disease.
Among a cohort of 38 women with type 1
von Willebrand disease, retrospective analysis
of bleeding symptoms revealed that menorrhagia at menarche was the most common
initial bleeding symptom, occurring in 53%
of women (11). The American College of
Obstetricians and Gynecologists recommends that an initial reproductive health
visit occur between the ages of 13 years and
15 years. This gives many clinicians an oppor-
70
tunity to inquire about menstrual history early in reproductive life (12). This also provides an opportunity to discuss the use of a menstrual calendar to aid in patient
recall, which allows for clinicians to better differentiate
menorrhagia from irregular, anovulatory bleeding.
Anovulatory bleeding is more common during early adolescence and generally does not raise suspicion of a bleeding disorder (13, 14). Other screening tools for identifying
women with menorrhagia who should be evaluated for a
bleeding disorder include the pictorial bleeding assessment chart. This tool is useful for women to specifically
record the number of pads or tampons used during their
menstrual periods as well as noting how many times they
may have passed clots or had flooding accidents. This tool
has been validated in adult women and demonstrates
greater than 80% sensitivity and specificity for scores
greater than 100 (15). When the pictorial bleeding assessment chart tool is combined with a set of eight questions
that focus on bleeding history, the sensitivity increases to
95% for diagnosis of any underlying bleeding disorder
and 92% for von Willebrand disease; specificity is 72%
and 8%, respectively (16).
A recent study also highlights the varied presentation
of menorrhagia among women with von Willebrand disease of different age groups (5). One-hundred fifteen
women of all ages with diagnoses of menorrhagia were
evaluated for bleeding conditions. Nearly 50% of these
women were ultimately determined to have platelet dysfunction, von Willebrand disease, or coagulation factor
abnormalities. Importantly, bleeding disorders were
found to be just as prevalent in adolescents as they were
in adult women (5). The evaluation and management of
women presenting with abnormal uterine bleeding have
been addressed in other College publications as well (14).
Nonetheless, inherited and acquired disorders of coagulation and hemostasis should be considered in the differential diagnosis of menorrhagia and abnormal uterine
bleeding regardless of age.
Diagnosis
The first step in the evaluation of women with suspected
bleeding disorders involves careful history and physical
examination (9, 17). Directed questions are useful in assessing risk for inherited bleeding conditions (see Box 1) (9,
17). If red flags exist, then health care providers should
follow the National Heart, Lung, and Blood Institute
guidelines (9, 17). Family history of menorrhagia or other
bleeding problems is helpful in assessing the need for further evaluation, even in the absence of a known bleeding
disorder diagnosis. In one study of 580 women with menorrhagia, 33.9% of women had a family history significant for excessive bleeding, but less than 1% reported
knowing of a specific or known or diagnosed bleeding
condition within their families (5). Other important initial questions include personal history of bleeding problems, liver or kidney disorders, family history of
Box 1. Bleeding Disorder Red Flags

Patient has a relative with an inherited bleeding condition
Prolonged bleeding, lasting more than 15 minutes,
from small injuries or wounds
Heavy prolonged and recurrent bleeding following
surgical procedures
Bruising with minimal or no trauma with palpable lump
under the bruise
Spontaneous nosebleeds
Prolonged bleeding following dental procedures
Blood in the stool or bleeding ulcer that required
urgent medical attention for cessation
History of anemia requiring blood transfusion
Heavy menses resulting in anemia or low iron stores
Passing clots more than 1 inch diameter with menses
or soaking more than one pad or tampon hourly
Heavy bleeding during or following childbirth
Adapted from the National Heart, Lung, and Blood Institute, The
Diagnosis, Evaluation, and Management of von Willebrand
Disease. NIH Pub. No. 08-5832. December, 2007.
hysterectomy at an early age, history of postpartum hemorrhage, or use of anticoagulants. Positive responses to
initial questions should be followed by more probing
questions and physical examination. Physical examination findings suggestive of a bleeding disorder include
petechiae, ecchymoses, skin pallor, or swollen joints,
although absence of these signs does not exclude the possibility of an underlying bleeding condition (7, 18, 19).
In patients with a positive screening history, laboratory testing is indicated (see Fig. 1) (9, 17). Initial tests
should include complete blood count with platelets, prothrombin time, and partial thromboplastin time (fibrinogen or thrombin time are optional); bleeding time is
neither sensitive nor specific, and is not indicated.
Depending on the results of initial tests, or if a patients
history is suggestive of an underlying bleeding condition,
specific tests for von Willebrand disease, including von
Willebrand-Ristocetin cofactor activity, von Willebrand
factor antigen, and factor VIII may be indicated (see
Fig. 1) (9, 17, 1921). These test results may be affected by
several variables such as age, race, family history, blood
type, stress, concurrent heavy bleeding, inflammation,
exogenous or endogenous hormones, pregnancy, time of
the menstrual cycle, sample processing, and quality of the
laboratory (9, 17, 1929). Because existing laboratory
assays have limitations and no single diagnostic test reliably identifies the condition, this testing can be done in
conjunction with a hematologist if necessary (9, 17).
Furthermore, although certain types of von Willebrand
disease may be easily distinguished from other bleeding
COMMITTEE OPINIONS
71
Positive initial screen by history

and physical examination
Initial hemostasis tests

CBC and platelet count
PT and PTT
Fibrinogen or TT (optional)
If bleeding history is strong, consider
performing initial von Willebrand
disease assays in conjunction with
hematologist
Other cause identified, eg, decreased

platelets, isolated abnormal PT, low
fibrinogen, and abnormal TT
Referral to hematologist for other

appropriate evaluation
Isolated prolonged PTT that

corrects on 1:1 mixing study, or no
abnormalities
Referral to hematologist for initial

von Willebrand disease assays
vWF:Ag
vWF:RCo
FVIII
Abbreviations: CBC, complete blood count; FVIII, factor VIII activity;

PT, prothrombin time; PTT, partial thromboplastin time; TT, thrombin
time; vWF:Ag, von Willebrand factor antigen; vWF:RCo, von
Willebrand factor ristocetin cofactor activity.
Fig. 1. Laboratory tests for suspected bleeding disorders *Adapted from the National Heart, Lung, and Blood Institute,
The Diagnosis, Evaluation, and Management of von Willebrand Disease. NIH Pub. No. 08-5832. December, 2007.
conditions on the basis of laboratory testing, not all types

are as straightforward to diagnose. Genetic tests may be
necessary for confirmation of certain von Willebrand disease types (9, 17).
Management
Once a diagnosis has been established, a variety of treatments exist. Treatments include ways to increase endogenous plasma concentration of vWF, replace vWF, or
promote hemostasis without affecting vWF. With mild
von Willebrand disease and menorrhagia, combination
hormonal contraceptives are first-line treatments. In
a study involving women with a diagnosis of von
Willebrand disease, 88% reported improvement in menorrhagia with oral contraceptives alone (7, 18). In addition, the levonorgestrel-releasing intrauterine device has
been proved effective for the reduction of menorrhagia
symptoms in adult women with bleeding disorders (30).
Intrauterine devices containing levonorgestrel have been
used in the adolescent population as well, especially in
cases of traditional hormonal management failure.
Although other contraceptives such as the contraceptive

patch and contraceptive ring have not yet been studied in
this population, theoretically, they would exhibit similar
control of menstrual bleeding. Extended cycle combined
hormonal contraceptives or depot medroxyprogesterone
acetate are other options for consideration to help control
heavy menses, although patients should still be warned
about breakthrough spotting (14).
Newer hemostatic agents include antifibrinolytics,
such as -aminocaproic acid and tranexamic acid (31).
These are agents that inhibit the conversion of plasminogen to plasmin, inhibiting fibrinolysis, and thereby help
stabilize clots. These agents also may be used alone or in
conjunction with hormones to control menstrual bleeding, especially in the event a definitive diagnosis of von
Willebrand disease has not yet been established. Because
tranexamic acid is not yet approved for treatment of menorrhagia, this medication should be used with the guidance of a hematologist (9, 17, 31).
Therapies generally prescribed in conjunction with a
hematologist once a diagnosis of von Willebrand disease-
72
has been established include desmopressin acetate and

Recombinant Factor 8 and vWF complex infusion (9, 17).
Desmopressin acetate is a synthetic derivative of the antidiuretic hormone vasopressin and works by stimulating
the release of vWF from endothelial cells (21). Recombinant factor VIII and vWF complex infusion are a plasma-derived concentrate used to replace vWF and factor
VIII. Patients also should be reminded that products that
prevent platelet adhesion, such as aspirin or nonsteroidal antiinflammatory drugs, should be avoided once
von Willebrand disease is diagnosed (9, 17).
Special Considerations
Gynecologic concerns in women with von Willebrand
disease include ruptured ovarian cysts, menstrual bleeding, endometriosis, and leiomyomas. Patients with heavy
menstrual bleeding or hemorrhagic ovarian cysts may be
easily managed with the introduction of a combined contraceptive regimen, by preventing both heavy menstrual
bleeding or the development of hemorrhagic cysts (10).
For the acute presentation of a ruptured ovarian cyst,
patients with von Willebrand disease may require surgical
intervention for hemostasis. In the presence of menorrhagia, patients with von Willebrand disease may require
hormonal treatment (oral or intravenous) in addition to
a hemostatic agent or desmopressin acetate and vWF
replacement (9, 10, 17).
Obstetric concerns include postpartum hemorrhage,
mode of delivery, operative delivery techniques, spontaneous abortion, and epidural management. Many experts
have advocated that women with von Willebrand disease
may have a vaginal delivery safely, with cesarean delivery
reserved as indicated (9, 17). Because von Willebrand disease is an inherited condition, traumatic vaginal delivery,
such as what may occur with the use of vacuum or rotational forceps, should be avoided because of the potential
risk of traumatic injury to an infant with a possible
hereditary bleeding disorder (32). If surgery is planned,
it is important to coordinate care with a hematologist
because vWF replacement may be necessary. The same
considerations apply to epidural placement because this
may be dependent on severity of disease; therefore, consultation with a hematologist is important. The rate of
spontaneous abortion is similar to that of the general
population. However, because patients may be at risk for
hemorrhage at the time of spontaneous incomplete abortion, the use of vWF and factor VIII to control bleeding
may be required (32). Furthermore, in a recent large epidemiologic study, the risk of postpartum hemorrhage for
women with von Willebrand disease was 50% higher than
for women without a bleeding disorder (29). Von
Willebrand factor and factor VIII concentrates may be
required to control bleeding in this situation as well (9).
Once estrogen levels begin to decrease in the postpartum
period, some individuals with bleeding conditions may
present with delayed hemorrhage. Throughout pregnancy, at the time of delivery, and in the event of postpartum
hemorrhage, vWF and factor VIII levels are important to

assess because some women may require replacement of
vWF and factor VIII for safe range maintenance (10, 32).
Any surgical procedure in a woman with von
Willebrand disease requires consultation with a hematologist because of the potential risk of hemorrhage.
Preprocedure vWF, vWF activity, and factor VIII levels
may be important in determining the need for and timing of infusion treatment preoperatively and postoperatively (21).
It is particularly important to diagnose bleeding disorders early in children and adolescents because accidental trauma is the most common source of morbidity and
mortality in this age group. Early warning signs and family history are critical for the acute treatment in these situations. Ensuring that families have adequate access to
care and encouraging use of medical alert bracelets are
important (9, 32).
Conclusion
Von Willebrand disease is a common cause of menorrhagia
and other bleeding problems. Obstetriciangynecologists
should keep von Willebrand disease and other bleeding
disorders in mind when evaluating patients with menorrhagia, especially at menarche. Once a diagnosis is made,
collaboration with a hematologist is helpful for the longterm management of women with bleeding disorders
such as von Willebrand disease. Von Willebrand disease
affects the reproductive system as well as other body systems, so patients may need access to other health care
providers in addition to gynecologists. Many resources
exist for patients and health care providers through the
National Heart, Lung, and Blood Institute, National
Hemophilia Foundations Project Red Flag, and the
American Society for Hematology (9, 33).
References
1. National Womens Health Information Center. Bleeding
disorders: frequently asked questions. Washington, DC:
NWHIC; 2009. Available at: http://www.womenshealth.
gov/FAQ/bleeding-disorders.cfm. Retrieved August 14,
2009.
2. James AH. More than menorrhagia: a review of the obstetric and gynaecological manifestations of bleeding disorders.
Haemophilia 2005;11:295307.
3. James AH. Von Willebrand disease. Obstet Gynecol Surv
2006;61:13645.
4. Shankar M, Lee CA, Sabin CA, Economides DL, Kadir RA.
von Willebrand disease in women with menorrhagia: a systematic review. BJOG 2004;111:73440.
5. Dilley A, Drews C, Miller C, Lally C, Austin H, Ramaswamy
D, et al. von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia.
6. Pruthi RK. A practical approach to genetic testing for von
Willebrand disease. Mayo Clin Proc 2006;81:67991.
COMMITTEE OPINIONS
7. Valente MJ, Abramson N. Easy bruisability. South Med J

2006;99:36670.
8. Kirtava A, Crudder S, Dilley A, Lally C, Evatt B. Trends in
clinical management of women with von Willebrand disease: a survey of 75 women enrolled in haemophilia treatment centres in the United States. Haemophilia 2004;
10:15861.
9. National Heart, Lung, and Blood Institute. The diagnosis,
evaluation, and management of von Willebrand disease.
NIH Publication No. 08-5832. Bethesda (MD): NHLBI;
2007. Available at: http://www.nhlbi.nih.gov/guidelines/vwd/
vwd.pdf. Retrieved August 14, 2009.
10. James AH, Kouides PA, Abdul-Kadir R, Edlund M, Federici
AB, Halimeh S, et al. Von Willebrand disease and other
bleeding disorders in women: consensus on diagnosis and
management from an international expert panel. Am J
Obstet Gynecol 2009;201:12.e112.e8.
11. Ragni MV, Bontempo FA, Hassett AC. von Willebrand disease and bleeding in women. Haemophilia 1999;5:3137.
12 The initial reproductive health visit. ACOG Committee
13. Philipp CS, Faiz A, Dowling N, Dilley A, Michaels LA, Ayers
C, et al. Age and the prevalence of bleeding disorders in
women with menorrhagia. Obstet Gynecol 2005;105:616.
Management of anovulatory bleeding. ACOG Practice
Bulletin 14. Washington, DC: ACOG; 2000.
15. Lee CA. Women and inherited bleeding disorders: menstrual issues. Semin Hematol 1999;36:217.
16. Philipp CS, Faiz A, Dowling NF, Beckman M, Owens S,
Ayers C, et al. Development of a screening tool for identifying women with menorrhagia for hemostatic evaluation.
Am J Obstet Gynecol 2008;198:163.e1163.e8.
17. James AH, Manco-Johnson MJ, Yawn BP, Dietrich JE,
Nichols WL. Von Willebrand disease: key points from the
2008 National Heart, Lung, and Blood Institute guidelines.
18. Kirtava A, Drews C, Lally C, Dilley A, Evatt B. Medical,
reproductive and psychosocial experiences of women diagnosed with von Willebrands disease receiving care in haemophilia treatment centres: a case-control study. Haemophilia
2003;9:2927.
19. Kouides PA. Current understanding of von Willebrands
disease in women - some answers, more questions. Haemophilia 2006;12(suppl 3):14351.
20. Jennings I, Kitchen S, Woods TA, Preston FE. Laboratory
performance of haemophilia centres in developing countries: 3 years experience of the World Federation of Hemophilia External Quality Assessment Scheme. Haemophilia
1998;4:73946.
21. Foster PA. The reproductive health of women with von
Willebrand Disease unresponsive to DDAVP: results of an
international survey. On behalf of the Subcommittee on
von Willebrand Factor of the Scientific and Standardization
Committee of the ISTH. Thromb Haemost 1995;74:
78490.
73
22. Miller CH, Dilley AB, Drews C, Richardson L, Evatt B.

Changes in von Willebrand factor and factor VIII levels during the menstrual cycle. Thromb Haemost 2002;87: 10823.
23. Miller CH, Haff E, Platt SJ, Rawlins P, Drews CD, Dilley AB,
et al. Measurement of von Willebrand factor activity: relative effects of ABO blood type and race. J Thromb Haemost
2003;1:21917.
24. Miller CH, Dilley A, Richardson L, Hooper WC, Evatt BL.
Population differences in von Willebrand factor levels affect
the diagnosis of von Willebrand disease in AfricanAmerican women. Am J Hematol 2001;67:1259.
25. Keightley AM, Lam YM, Brady JN, Cameron CL, Lillicrap
D. Variation at the von Willebrand factor (vWF) gene locus
is associated with plasma vWF:Ag levels: identification of
three novel single nucleotide polymorphisms in the vWF
gene promoter. Blood 1999;93:427783.
26. Gralnick HR, McKeown LP, Wilson OM, Williams SB, Elin
RJ. von Willebrand factor release induced by endotoxin. J
Lab Clin Med 1989;113:11822.
27. Conlan MG, Folsom AR, Finch A, Davis CE, Sorlie P,
Marcucci G, et al. Associations of factor VIII and von
Willebrand factor with age, race, sex, and risk factors for
atherosclerosis. The Atherosclerosis Risk in Communities
(ARIC) Study. Thromb Haemost 1993;70:3805.
28. Ruggeri ZM, Ware J. von Willebrand factor. FASEB J 1993;
7:30816.
29. James AH, Jamison MG. Bleeding events and other complications during pregnancy and childbirth in women with
von Willebrand disease. J Thromb Haemost 2007;5:11659.
30. Kingman CE, Kadir RA, Lee CA, Economides DL. The use
of levonorgestrel-releasing intrauterine system for treatment of menorrhagia in women with inherited bleeding
disorders. BJOG 2004;111:14258.
31. Fraser IS, Porte RJ, Kouides PA, Lukes AS. A benefit-risk
review of systemic haemostatic agents: part 2: in excessive or
heavy menstrual bleeding. Drug Saf 2008;31:27582.
32. Demers C, Derzko C, David M, Douglas J. Gynaecological
and obstetric management of women with inherited bleeding disorders. Society of Obstetricians and Gynecologists of
Canada. J Obstet Gynaecol Can 2005;27:70732.
33. National Hemophilia Foundation. von Willebrand disease.
Available at: http://www.hemophilia.org/NHFWeb/MainPgs/
MainNHF.aspx?menuid=182&contentid=47&rptname=
bleeding. Retrieved August 14, 2009.

ISSN 1074-861X
Von Willebrand disease in women. ACOG Committee Opinion No.
Gynecol 2009;114:143943.
COMMITTEE OPINIONS
COMMITTEE
ON
NOMENCLATURE
COMMITTEE OPINIONS
COMMITTEE
ON
NOMENCLATURE
ACOG Committee
Committee
on Coding and
Nomenclature
Opinion
Number 205, August 1998
Tubal Ligation with Cesarean

Delivery
This document reflects emerging clinical and scientific advances as of the date issued and
is subject to change. The information should not be construed
as dictating an exclusive course
of treatment or procedure to be
followed. Requests for authorization to make photocopies
should be directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
Copyright August 1998
ISSN 1074-861X
Tubal ligation at the time of cesarean delivery requires significant additional

physician work even though the technical work of the procedure is brief.
Informed consent by the patient requires considerably more counseling by
the physician regarding potential risks and benefits of this procedure than is
necessary with alternative means of sterilization and contraception. Also,
many states require completion of special informed consent documents in
addition to the customary consent forms required by hospitals. These forms
must be completed before scheduling the procedure.
Patients have the right to change their minds. Thus, it is important to
reconfirm the patients decision shortly before the operation.
Tubal ligation with cesarean delivery involves removal of a segment of
fallopian tube, which is sent for histologic confirmation. With most cesarean
deliveries, tissue is not evaluated by a pathologist. Accordingly, it is important for the surgeon to verify the pathology report, which adds an additional
component to post-service work.
The risk of professional liability for operative complications is increased
with this procedure. This risk is low, but real. Furthermore, sterilization failure occurs in about 1 in 100 cases even though the operation was performed
properly. This failure also carries a liability risk.
Because tubal ligation is a discrete extra service, it should be coded
accordingly: 59510 or 59618routine obstetric care including antepartum
care, cesarean delivery, and postpartum careand 58611ligation or transection of fallopian tube(s) done at the time of cesarean delivery or intraabdominal surgery.

409 12th Street, SW
PO Box 96920
77
78
ACOG
Committee on
Coding and
Nomenclature
Reaffirmed 2005
Committee
Opinion
Number 249, January 2001
Coding Responsibility
Physicians are responsible for accurately coding the services they provide
to their patients. Likewise, insurers are obligated to process all legitimate
insurance claims for covered services accurately and in a timely manner.
It is inappropriate for physicians to code or for insurers to process claims
incorrectly in order to enhance or reduce reimbursement. When either
party engages in such a practice intentionally and repetitively, it should
be considered dishonest and may be subject to civil and criminal
penalties.
Copyright January 2001
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
COMMITTEE OPINIONS
ACOG
Committee on
Coding and
Nomenclature
79
Committee
Opinion
Inappropriate Reimbursement
Practices by Third-Party Payers

directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
The American College of Obstetricians and Gynecologists (ACOG)

Committee on Coding and Nomenclature believes that physicians must
code accurately the services they provide and the diagnoses that justify
those services for purposes of appropriate payment. This requirement is
consistent with the rules established by the American Medical Association
(AMA) Current Procedural Terminology Editorial Panel and published as
the Current Procedural Terminology (CPT) and with those established by
the International Classification of Diseases, Ninth Revision, Clinical
Modification (ICD-9-CM), which are published in the American Hospital
Associations ICD-9-CM Coding Clinic. In fairness, payers should be equally obligated to pay physicians based on the CPT standards and accept for
processing all ICD-9-CM codes recorded on the claim. Currently, no such
obligation for payers exists.
Inappropriate Billing Denials

Five frequently encountered billing situations account for most payers inappropriate first-time total or partial denials of correctly coded services. Each
of these situations can inappropriately deny payment to physicians for medically indicated and correctly coded services because of payers payment
policies.
1. Inappropriately bundling correctly coded multiple surgical procedures
Current Procedural Terminology clearly describes surgical procedures that
may be performed to treat various conditions. Each CPT code describes a
specific procedure that was valued under the Resource Based Relative
Value Scale (RBRVS) on the basis of a description of the work it entails.
Many patients, especially those with complex clinical situations, need
more than one surgical procedure to be performed at an operative session.
For instance, a patient may require a vaginal hysterectomy because of
severe irregular bleeding, but also might require repair of a symptomatic
cystocele and rectocele. Because no single CPT code describes this combination of procedures, the physician should apply multiple CPT codes
with appropriate modifiers to the secondary procedures as mandated by
80
CPT rules. Furthermore, the physician should

expect reimbursement for all of the provided services defined by the CPT codes.
Despite the accuracy of the above statement
regarding reimbursement for multiple procedures,
payers often cite the efforts of Medicare to reduce
payments for inappropriately unbundled CPT
codes by physicians as justification for denial of
physician claims for appropriately coded services.
Indeed, the Health Care Financing Administration
has established the Correct Coding Initiative
(CCI), a process for bundling together many services that should not be paid separately. The
process continues to undergo refinement with
input from the AMA and medical specialty societies.
Unfortunately, some commercial software
products that do not adhere to either CPT or CCI
guidelines are being used by third-party payers to
identify CPT codes for services that will not be
reimbursed when coded together. For example,
some of these products incorrectly bundle anterior
and posterior colporrhaphy with enterocele repair
into the code for vaginal hysterectomy, presumably because all of these procedures are performed
through a vaginal approach. The AMA Correct
Coding and Policy Committee, with input from
ACOG staff, has identified many instances of
inappropriate denial of reimbursement with some
of these commercial bundling products. Physicians should appeal such denials (see the box) and
cite the content of this document in requesting
appropriate payment for these services.
2. Ignoring modifiers that explain qualifying circumstancesCurrent Procedural Terminology modifiers provide a coding shorthand that helps explain
situations for which either increased or reduced
payment is justified. There is, at present, no insurance industry standard for recognizing modifiers.
Gynecologists believes that third-party payers
should follow existing CPT guidelines and coding
options, including recognition of all CPT modifiers, to ensure that all circumstances concerning
the service performed are recognized. Payers who
ignore correctly applied CPT modifiers inappropriately underreimburse physicians for the services provided.
3. Denying payment for diagnostic and therapeutic
procedures performed on the same day of
serviceIn certain clinical situations, a diagnostic
surgical procedure is performed to determine
Seven Steps for Appealing Denied Claims

Take these steps when appealing inappropriate reimbursement practices by third-party payers:
1. Keep in mind that this is a negotiation process
that will succeed only if the insurer is convinced that a charge is fair for the patient and
the physician. It is important to use accepted
coding standards when attempting to show
that an insurers policy is wrong. Polite but
direct communication is more likely to achieve
desired results than confrontation.
2. Have your staff contact the claims department
of the insurer and discuss the reason for denial
with the claims processor. These discussions
should be based on clinical facts that rely on
the Current Procedural Terminology (CPT)
code definition of the service and the standard
of care implied by the CPT code as it was valued under the Medicare Resource Based
Relative Value Scale (RBRVS) system.
Document all communication with the insurer
(date, person from office making the call, person spoken with, results).
3. If staff is unsuccessful, contact the medical
director of the payer yourself. Maintain open
lines of communication with the medical director to discuss inappropriate payment policies
and accepted coding standards.
4. Involve the state medical society in disputes
with insurers. Many state societies will become
very involved when patterns of abuse emerge.
5. Contact the American College of Obstetricians
and Gynecologists (ACOG) for assistance in
dealing with inappropriately denied medically
indicated services that are covered by the
patients insurance policy and clearly were correctly reported. Contact ACOGs Department of
Health Economics by fax or mail after downloading a complaint form from ACOGs web
site (www.acog.org), or call (202) 863-2447
for assistance.
6. Send a copy of any correspondence between
the practice and the payer dealing with unresolved problems to the insurance commissioner or equivalent regulatory authority in
your state.
7. Involve your patient when inappropriate billing
problems cannot be resolved in other ways.
Physicians are not responsible for the insurance plan selected by the patient. Many thirdparty payers will revise their payment policies
when they receive a complaint from the patient
or patients employer or union.
COMMITTEE OPINIONS
whether a therapeutic surgical procedure is

required. When this occurs, it often is appropriate
for the two procedures to be done at one time rather
than at two distinct times. For example, if a diagnostic laparoscopy for a suspected benign condition reveals cancer, the physician may decide to
perform a laparotomy to remove the cancer at the
same operative session. In such a situation, many
payers deny payment for the diagnostic laparoscopy even though performance of both the diagnostic and therapeutic procedures at the same time
is medically indicated and requires additional
physician work above that of the therapeutic procedure alone. In accordance with CPT guidelines,
both procedures should be coded and the physician
should be paid for both when the procedures have
been documented appropriately and coded correctly. In the example, proper coding for the diagnostic
service in addition to a therapeutic procedure
would at the present time require the use of modifier 59 to identify the diagnostic procedure as
distinct. In addition, however, the diagnostic procedure must be justified with a specific ICD-9-CM
diagnostic code, which may or may not be the
same as the ICD-9-CM code for the therapeutic
procedure.
The practice by payers of bundling diagnostic
and therapeutic procedures to reduce physicians
payment is inappropriate. Physicians have a legal
obligation to code correctly. Insurers are equally
obligated not to alter coding by physicians that is
in accordance with approved CPT guidelines.
4. Precertifying consultations at a predetermined
levelSome payers require precertification of a
consultation and typically authorize a predetermined level of service based on the diagnostic
information provided by the physician who
requested the consultation. By contrast, the CPT
guidelines state that the correct level of consultation is determined by the extent of the history,
physical examination, and complexity of the medical decision-making process for each patient. This
definition of services was used by Medicare under
RBRVS to assign the relative value for physician
consultation. Each patient who requires a consultation does so with a medical history typically
including co-morbidities that can dramatically alter
the physician work required to provide this service.
Often such co-morbidities will necessitate a more
thorough history and physical examination and
involve more complex medical decision making
than required in their absence. For example, a
81
request for a consultation to assess fetal well-being

in an otherwise healthy patient who has had an
uneventful pregnancy will not resemble a consultation for this same problem when the patient has
preexisting complications of pregnancy, such as
cardiac disease, uncontrolled diabetes mellitus, or
a history of poor obstetric outcomes.
Because it is not possible to determine prospectively the level of service that will be required to
evaluate and recommend treatment based on the
uniqueness of each patients problems, payers
should precertify for an unspecified level of consultation that is paid at the appropriate level once
the service has been provided.
5. Denying diagnostic tests or studies performed at
the same encounter as a distinct evaluation and
management serviceThe CPT manual states:
The actual performance and/or interpretation of diagnostic tests/studies ordered during a patient encounter are not included in
the levels of [evaluation and management
(E/M)] services. Physician performance of
diagnostic tests/studies for which specific
CPT codes are available may be reported
separately, in addition to the appropriate
E/M code.
With this statement, CPT has clarified that diagnostic tests and studies, including colposcopies,
biopsies, diagnostic ultrasound examinations, and
cystometrics, are ordered on the basis of clinical
criteria for each patient and not as a routine service. This definition means that tests performed at
the time of an outpatient or other E/M encounter
are not to be paid as part of the E/M service, but
rather are to be paid separately. The E/M codes in
CPT were valued under the Medicare RBRVS fee
schedule on the basis of the CPT guidelines; these
values do not include any diagnostic tests or studies.
The payer may deny reimbursement of diagnostic tests or studies at the time of an E/M encounter
because the payers payment policies might have
been formulated with a lack of understanding of
CPT coding standards that separate physician
work included with the E/M service from the diagnostic test or study. This lack of understanding
may lead the payer to inappropriately include all
services provided to the patient at the E/M
encounter as part of that service. The payer also
may deny payment because the physician failed to
add a modifier 25 to the billed E/M code to bypass the payers established coding edits to ensure
appropriate payment for both services.
82
Possible Remedies
The physician should ensure that his or her billing
staff are knowledgeable about:
What is normally included and what is excluded
from the service being billed (This information is
provided in the most current edition of ACOGs
OB-GYN Coding Manual: Components of Correct
Procedural Coding.*)
How to link each service billed with one or more
specific ICD-9-CM diagnostic codes that specifically justifies the reason for the service (This information is available in the most current edition of
ACOGs ICD-9-CM: Diagnostic Coding in
Obstetrics and Gynecology.*)
* These resources are available from the American College of
The correct application of CPT modifiers, when

indicated (This information may be found in the
appendixes of the current AMA CPT manual and
in the current edition of ACOGs CPT Coding in
Obstetrics and Gynecology.*)
Billing rules established by individual payers
The billing office should communicate clearly
the indication for performing all coded services on
the same date of service by reporting the most specific ICD-9-CM diagnostic codes. In some encounters,
the justification for all services rendered may be documented by a single ICD-9-CM code. When a patient
has multiple complaints or problems, multiple ICD9-CM codes should be used.
COMMITTEE OPINIONS
COMMITTEE
ON
ETHICS
COMMITTEE OPINIONS
COMMITTEE
ON
ETHICS
ACOG
Committee on
Ethics
Reaffirmed 2009
Committee
Opinion
Nonmedical Use of Obstetric

Ultrasonography
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Nonmedical use of obstetric ultrasonography. ACOG Committee
ABSTRACT: The American College of Obstetricians and Gynecologists

(ACOG) has endorsed the Prudent Use statement from the American
Institute of Ultrasound in Medicine (AIUM) discouraging the use of obstetric
ultrasonography for nonmedical purposes (eg, solely to create keepsake photographs or videos). The ACOG Committee on Ethics provides reasons in
addition to those offered by AIUM for discouraging this practice.
The American College of Obstetricians and Gynecologists (ACOG) has

endorsed the following statement from the American Institute of Ultrasound
in Medicine (AIUM) discouraging the use of obstetric ultrasonography for nonmedical purposes (eg, solely to create keepsake photographs or videos) (1):
The AIUM advocates the responsible use of diagnostic ultrasound. The AIUM
strongly discourages the non-medical use of ultrasound for psychosocial or entertainment purposes. The use of either two-dimensional (2D) or three-dimensional
(3D) ultrasound to only view the fetus, obtain a picture of the fetus or determine the
fetal gender without a medical indication is inappropriate and contrary to responsible medical practice. Although there are no confirmed biological effects on patients
caused by exposures from present diagnostic ultrasound instruments, the possibility exists that such biological effects may be identified in the future. Thus ultrasound
should be used in a prudent manner to provide medical benefit to the patient.
In addition to the concerns noted by AIUM, the ACOG Committee on Ethics

believes that nonmedical use of ultrasonography should be discouraged for
the following reasons:
Nonmedical ultrasonography may falsely reassure women. Even though
centers that perform nonmedical ultrasonography and create keepsake
photographs and videos of the fetus may offer disclaimers about the
limitations of their product, customers may interpret an aesthetically
pleasing image or entertaining video as evidence of fetal health and
appropriate development. Ultrasonography performed for psychosocial
or entertainment purposes may be limited by the extent and duration of
the examination, the training of those acquiring the images, and the quality control in place at the ultrasound facility. Women may incorrectly
believe that the limited scan is, in fact, diagnostic.
85
86
Abnormalities may be detected in settings that

are not prepared to discuss and provide followup for concerning findings. Without the ready
availability of appropriate prenatal health care
professionals, customers at sites for nonmedical
ultrasonography may be left without necessary
support, information, and follow-up for concerning findings. For example, customers may
interpret a minor finding (eg, an echogenic
intracardiac focus) as a major abnormality,
resulting in unnecessary anxiety and concern.
Conversely, in the event of concerning findings
(eg, oligohydramnios), women may not receive

appropriate follow-up. Obstetric ultrasonography is most appropriately obtained as part of an
integrated system for delivering prenatal care.
Reference
1. American Institute of Ultrasound in Medicine. Prudent use.
AIUM Official Statements. Laurel (MD): AIUM; 1999.
Available at http://www.aium.org/provider/statements/
_statementSelected.asp?statement=2. Retrieved May 19, 2004.
COMMITTEE OPINIONS
ACOG
Committee on
Ethics
87
Committee
Opinion
Maternal Decision Making, Ethics,

and the Law

directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Maternal decision making, ethics, and
the law. ACOG Committee Opinion
ABSTRACT: Recent legal actions and policies aimed at protecting the fetus
as an entity separate from the woman have challenged the rights of pregnant
women to make decisions about medical interventions and have criminalized
maternal behavior that is believed to be associated with fetal harm or
adverse perinatal outcomes. This opinion summarizes recent, notable legal
cases; reviews the underlying, established ethical principles relevant to the
highlighted issues; and considers six objections to punitive and coercive
legal approaches to maternal decision making. These approaches 1) fail to
recognize that pregnant women are entitled to informed consent and bodily
integrity, 2) fail to recognize that medical knowledge and predictions of outcomes in obstetrics have limitations, 3) treat addiction and psychiatric illness
as if they were moral failings, 4) threaten to dissuade women from prenatal
care, 5) unjustly single out the most vulnerable women, and 6) create the
potential for criminalization of otherwise legal maternal behavior. Efforts to
use the legal system to protect the fetus by constraining pregnant womens
decision making or punishing them erode a womans basic rights to privacy
and bodily integrity and are not justified. Physicians and policy makers
should promote the health of women and their fetuses through advocacy of
healthy behavior; referral for substance abuse treatment and mental health
services when indicated; and development of safe, available, and efficacious
services for women and families.
Ethical issues that arise in the care of pregnant women are challenging to
physicians, politicians, lawyers, and ethicists alike. One of the fundamental
goals of medicine and society is to optimize the outcome of pregnancy.
Recently, some apparent attempts to foster this goal have been characterized
by legal action and policies aimed at specifically protecting the fetus as an
entity separate from the woman. These actions and policies have challenged
the rights of pregnant women to make decisions about medical interventions
and have criminalized maternal behavior that is believed to be associated
with fetal harm or adverse perinatal outcomes.
Practitioners who care for pregnant women face particularly difficult
dilemmas when their patients reject medical recommendations, use illegal
88
drugs, or engage in a range of other behaviors that

have the potential to cause fetal harm. In such situations, physicians, hospital representatives, and
others have at times resorted to legal actions to
impose their views about what these pregnant
patients ought to do or to effect particular interventions or outcomes. Appellate courts have held, however, that a pregnant womans decisions regarding
medical treatment should take precedence regardless of the presumed fetal consequences of those
decisions. In one notable 1990 decision, a District
of Columbia appellate court vacated a lower courts
decision to compel cesarean delivery in a critically
ill woman at 26 weeks of gestation against her
wishes, stating in its opinion that in virtually all
cases the question of what is to be done is to be
decided by the patientthe pregnant womanon
behalf of herself and the fetus (1). Furthermore,
the court stated that it could think of no extremely
rare and truly exceptional case in which the state
might have an interest sufficiently compelling to
override a pregnant patients wishes (2). Amid often
vigorous debate, most ethicists also agree that a
pregnant womans informed refusal of medical
intervention ought to prevail as long as she has the
ability to make medical decisions (3, 4).
Recent legislation, criminal prosecutions, and
legal cases much discussed in both courtrooms and
newsrooms have challenged these precedents, raising the question of whether there are circumstances
in which a woman who has become pregnant may
have her rights to bodily integrity and informed consent overridden to protect her fetus. In Utah, a
woman who had used cocaine was charged with
homicide for refusing cesarean delivery of a fetus
that was ultimately stillborn. In Pennsylvania, physicians obtained a court order for cesarean delivery in
a patient with suspected fetal macrosomia. Across
the country, pregnant women have been arrested and
prosecuted for being pregnant and using drugs or
alcohol. These cases and the publicity they have
engendered suggest that it is time to revisit the ethical issues involved.
The ethics of caring for pregnant women and an
approach to decision making in the context of the
maternalfetal relationship have been discussed in
previous statements by the American College of
Obstetricians and Gynecologists (ACOG) Committee on Ethics. After briefly reiterating those discussions, this opinion will summarize recent, notable
cases; review the underlying, established ethical
principles relevant to the highlighted issues; consider objections to punitive and coercive legal
approaches to maternal decision making; and summarize recommendations for attending to future
ethical matters that may arise.
Recent Cases
In March 2004, a 28-year-old woman was charged
with first-degree murder for refusing to undergo an
immediate cesarean delivery because of concerns
about fetal well-being and later giving birth to a girl
who tested positive for cocaine and a stillborn boy.
According to press reports, the woman was mentally
ill and intermittently homeless and had been brought
to Utah by a Florida adoption agency to give birth to
the infants and give them up. She ultimately pled
guilty to two counts of child endangerment.
In January 2004, a woman who previously had
given birth vaginally to six infants, some of whom
weighed close to 12 pounds, refused a cesarean delivery that was recommended because of presumed
macrosomia. A Pennsylvania hospital obtained a
court order to perform the cesarean delivery and gain
custody of the fetus before and after delivery, but the
woman and her husband fled to another hospital,
where she reportedly had an uncomplicated vaginal
delivery of a healthy 11-pound infant.
In September 2003, a 22-year-old woman was
prosecuted after her son tested positive for alcohol
when he was born in Glens Falls, New York. A few
days after the birth, the woman was arrested and
charged with two counts of child endangerment for
knowingly feeding her blood, containing alcohol, to
her fetus via the umbilical cord. Several months later,
her lawyers successfully appealed her conviction.
In May 1999, a 22-year-old woman who was
homeless regularly used cocaine while pregnant and
gave birth to a stillborn infant in South Carolina. She
became the first woman in the United States to be
tried and convicted of homicide by child abuse
based on her behavior during pregnancy and was
given a 12-year prison sentence. The conviction was
upheld in the South Carolina Supreme Court, and
the U.S. Supreme Court recently refused to hear her
appeal. At a postconviction relief hearing, expert testimony supported arguments that the woman had
had inadequate representation, but the court held
that there was no ineffective assistance of counsel
and that she is not entitled to a new trial. This decision is being appealed.
COMMITTEE OPINIONS
Ethical Considerations
Framing Ethics in Perinatal Medicine
It is likely that the interventions described in the preceding cases were motivated by a shared concept
that a fetus can and should be treated as separable
and legally, philosophically, and practically independent from the pregnant woman within whom it
resides. This common method of framing ethical
issues in perinatal medicine is not surprising given a
number of developments in the past several decades.
First, since the 1970s, the development of techniques for imaging, testing, and treating fetuses has
led to the widespread endorsement of the notion that
fetuses are independent patients, treatable apart
from the pregnant women upon whom their
existence depends (5). Similarly, some bioethical
models now assert that physicians have moral obligations to fetal patients that are separate from their
obligations to pregnant women (6). Finally, a number of civil laws, discussed later in this section, aim
to create fetal rights separate from a pregnant
womans rights.
Although frameworks that treat the woman and
fetus as separable and independent are meant to simplify and clarify complex issues that arise in obstetrics, many writers have noted that such frameworks
tend to distort, rather than illuminate, ethical and
policy debates (7). In particular, these approaches
have been criticized for their tendency to emphasize
the divergent rather than shared interests of the pregnant woman and fetus. This emphasis results in a
view of the maternalfetal relationship as paradigmatically adversarial, when in fact in the vast majority of cases, the interests of the pregnant woman and
fetus actually converge.
In addition, these approaches tend to ignore the
moral relevance of relationships, including the physically and emotionally intimate relationship between
the woman and her fetus, as well as the relationships
of the pregnant woman within her broader social
and cultural networks. The cultural and policy context, for example, suggests a predominantly childcentered approach to maternal and child health,
which has influenced current perspectives on the
fetus. The prototype for the federal Maternal and
Child Health Bureau dates back to 1912, when the
first organization was called into existence by
reformers such as Florence Kelley, who stated that
the U.S. should have a bureau to look after the child
crop, and Julia Lathrop, who said that the final
89
purpose of the Bureau is to serve all children, to try

to work out standards of care and protection which
shall give to every child his fair chance in the world.
The current home page of the Maternal and Child
Health Bureau web site cites as its vision an equally child-centered goal (8).
At times, in the current clinical and policy contexts, when the woman and fetus are treated as
separate individuals, the woman and her medical
interests, health needs, and rights as moral agent,
patient, and research subject fade from view. Consider, first, womens medical interests as patients.
Researchers performing fetal surgerynovel
interventions to correct fetal anatomic abnormalitieshave been criticized recently not only for their
tendency to exaggerate claims of success with
regard to fetal and neonatal health, but also for their
failure to assess the impact of surgery on pregnant
women, who also undertake the risks of the major
surgical procedures (9). As a result, several centers
performing these techniques now use the term maternalfetal surgery to explicitly recognize the fact
that a womans bodily integrity and health are at
stake whenever interventions directed at her fetus
are performed. Furthermore, a study sponsored by
the National Institute of Child Health and Human
Development comparing maternalfetal surgery
with postnatal repair of myelomeningocele (the
Management of Myelomeningocele Study) is now
assessing maternal as well as fetal outcomes,
including measurement of reproductive and health
outcomes, depression testing, and economic and
family health outcomes in women who participate
in the clinical trial.
Similarly, new civil laws that aim to treat the
fetus as separate and independent have been criticized for their failure both to address the health
needs of the woman within whose body the fetus
resides and to recognize the converging interests of
the woman and fetus. In November 2002, a revision
of the state child health insurance program (sCHIP)
that expanded coverage to individual(s) under the
age of 19 including the period from conception until
birth was signed into law. The program does not
cover pregnant women older than 18 years except
when medical interventions could directly affect the
well-being of their fetuses. For example, under
sCHIP, intrapartum anesthesia is covered, according
to the U.S. Department of Health and Human
Services, only because if a womans pain during a
labor and delivery is not reduced or properly
90
relieved, adverse and sometimes disastrous effects

can occur for the unborn child (10).
Furthermore, for beneficiaries of sCHIP, many
significant womens health issues, even those that
are precipitated by pregnancy (eg, molar gestation,
postpartum depression, or traumatic injury from
intimate partner violence not impacting the fetus),
are not covered as a part of routine antenatal care
(11). This approach has been criticized not only for
its failure to address the health needs of women,
but also for its failure to achieve the narrow goal
of improving child health because it ignores the
fact that maternal and neonatal interests converge.
For instance, postpartum depression is associated
with adverse effects in infants, including impaired
maternalinfant interaction, delayed cognitive and
emotional development, increased anxiety, and decreased self-esteem (12, 13). Thus, the law ignores
the fact that a critical component of ensuring the
health of newborns is the provision of comprehensive care for their mothers.
Likewise, in April 2004, the Unborn Victims of
Violence Act was signed into law, creating a separate
federal offense if, during the commission of certain
federal crimes, an individual causes the death of, or
bodily injury to, a fetus at any stage of pregnancy.
The law, however, does not categorize the death of
or injury to a pregnant woman as a separate federal
offense, or create sentence enhancement for those
who assault or murder a woman while pregnant. The
statutes sponsors explicitly rejected proposals that
had virtually identical criminal penalties but recognized the pregnant woman as the victim, despite the
fact that murder is responsible for more pregnancyassociated deaths in the United States than any other
cause, including hemorrhage and thromboembolic
events (14, 15).
Beyond its impact on maternal and child health,
a failure to recognize the interconnectedness of the
pregnant woman and fetus has important ethical and
legal implications. Because an intervention on a
fetus must be performed through the body of a pregnant woman, an assertion of fetal rights must be reconciled with the ethical and legal obligations toward
pregnant women as women, persons in their own
right. Discussions about rights of the unborn often
have failed to address these obligations. Regardless
of what is believed about fetal personhood, claims
about fetal rights require an assessment of the rights
of pregnant women, whose personhood within the
legal and moral community is indisputable.
Furthermore, many writers have noted a moral

injury that arises from abstracting the fetus from
the pregnant woman, in its failing to recognize the
pregnant woman herself as a patient, person, and
rights-bearer. This approach disregards a fundamental moral principle that persons never be treated
solely as means to an end, but as ends in themselves.
Within the rhetoric of conflict and fetal rights, the
pregnant woman has at times been reduced to a vesseleven a fortress holding the fetus prisoner
(16). As George Annas aptly described, Before birth,
we can obtain access to the fetus only through its
mother, and in the absence of her informed consent,
can do so only by treating her as a fetal container, a
nonperson without rights to bodily integrity (3).
Some writers have argued that at the heart of the
distorting influence of the two-patient model of
the maternalfetal dyad is the fact that, according to
traditional theories that undergird medical ethics, the
very notion of a person or a patient is someone who
is physically separate from others. Pregnancy, however, is marked by a particular and particularly
thoroughgoing kind of intertwinement (17). Thus,
the pregnant woman and fetus fit awkwardly at best
into what the term patient is understood to mean.
They are neither physically separate, as persons are
understood to be, nor indistinguishably fused. A
framework that instead defines the professional ethical obligations with a deep sensitivity to relationships of interdependency may help to avoid the
distorting influence of the two-patient model as traditionally understood (18). Although this opinion
does not specifically articulate a novel comprehensive conceptual model for perinatal ethics, in the discussion that follows, the Committee on Ethics takes
as morally central the essential connection between
the pregnant woman and fetus.
Ethics Committee Opinions and the Maternal
Fetal Relationship
In the context of a framework that recognizes the
interconnectedness of the pregnant woman and fetus
and emphasizes their shared interests, certain opinions previously published by the ACOG Committee
on Ethics are particularly relevant. These include:
Informed Consent (19)
Patient Choice in the MaternalFetal Relationship (20)
At-Risk Drinking and Illicit Drug Use: Ethical
Issues in Obstetric and Gynecologic Practice
(21)
COMMITTEE OPINIONS
One fundamental ethical obligation of health

care professionals is to respect patients autonomous
decision making and to adhere to the requirement
for informed consent for medical intervention. In
January 2004, the Committee on Ethics published a
revised edition of Informed Consent in which the
following points are defended:
Requiring informed consent is an expression of
respect for the patient as a person; it particularly respects a patients moral right to bodily
integrity, to self-determination regarding sexuality and reproductive capacities, and to the
support of the patients freedom within caring
relationships.
The ethical requirement for informed consent
need not conflict with physicians overall ethical
obligation to a principle of beneficence; that is,
every effort should be made to incorporate a
commitment to informed consent within a commitment to provide medical benefit to patients
and thus respect them as whole and embodied
persons.
Pregnancy does not obviate or limit the requirement to obtain informed consent. Intervention on
behalf of the fetus must be undertaken through the
body and within the context of the life of the pregnant woman, and therefore her consent for medical
treatment is required, regardless of the treatment
indication. However, pregnancy presents a special
set of issues. The issues associated with informed
refusal of care by pregnant women are addressed in
the January 2004 opinion Patient Choice in the
MaternalFetal Relationship (20). This opinion
states that in cases of maternal refusal of treatment
for the sake of the fetus, court-ordered intervention
against the wishes of a pregnant woman is rarely if
ever acceptable. The document presents a review of
general ethical considerations applicable to pregnant
women who do not follow the advice of their physicians or do not seem to make decisions in the best
interest of their fetuses. Although the possibility of a
justifiable court-ordered intervention is not completely ruled out, the document presents several recommendations that strongly discourage coercive
measures:
The obstetricians response to a patients
unwillingness to cooperate with medical advice
. . . should be to convey clearly the reasons for
the recommendations to the pregnant woman,
91
examine the barriers to change along with her,

and encourage the development of health-promoting behavior.
[Even if] a womans autonomous decision
[seems] not to promote beneficence-based
obligations (of the woman or the physician) to
the fetus, . . . the obstetrician must respect the
patients autonomy, continue to care for the
pregnant woman, and not intervene against the
patients wishes, regardless of the consequences.
The obstetrician must keep in mind that medical knowledge has limitations and medical
judgment is fallible and should therefore take
great care to present a balanced evaluation of
expected outcomes for both [the woman and the
fetus].
Obstetricians should consider the social and
cultural context in which these decisions are
made and question whether their ethical judgments reinforce gender, class, or racial inequality.
In addition to revisiting questions of how practitioners should address refusal of treatment in the
clinic and delivery room, the four cases outlined previously illustrate punitive and coercive policies
aimed at pregnant women who engage in behaviors
that may adversely affect fetal well-being. The 2004
opinion At-Risk Drinking and Illicit Drug Use:
Ethical Issues in Obstetric and Gynecologic
Practice (21) specifically addresses addiction and
the prosecution of women who use drugs and alcohol during pregnancy and recommends strongly
against punitive policies:
Addiction is not primarily a moral weakness, as
it has been viewed in the past, but a brain disease that should be included in a review of systems just like any other biologic disease
process.
Recommended screening . . . connected with
legally mandated testing or reporting . . . endanger[s] the relationship of trust between physician
and patient, place[s] the obstetrician in an adversarial relationship with the patient, and possibly
conflict[s] with the therapeutic obligation.
Punitive policies are unjust in that they indict
the woman for failing to seek treatment that
actually may not be available to her and in that
they are not applied evenly across sex, race,
and socioeconomic status.
92
Physicians must make a substantial effort to

treat the patient with a substance abuse problem with dignity and respect in order to form a
therapeutic alliance.
Finally, recent legal decisions affirm that physicians have neither an obligation nor a right to perform prenatal testing for alcohol or drug use without
a pregnant womans consent (22, 23). This includes
consent to testing of the woman that could lead to
any form of reporting, both to legal authorities for
purposes of criminal prosecution and to civil child
welfare authorities.
Against Coercive and Punitive Legal Approaches
to the MaternalFetal Relationship
This section addresses specifically the ethical issues
associated with the cases outlined previously and
delineates six reasons why restricting patients liberty and punishing pregnant women for their actions
during pregnancy that may affect their fetuses is neither wise nor justifiable. Each raises important
objections to punishing pregnant women for actions
during pregnancy; together they provide an overwhelming rationale for avoiding such approaches.
1. Coercive and punitive legal approaches to pregnant women who refuse medical advice fail to
recognize that all competent adults are entitled to
informed consent and bodily integrity.
A fundamental tenet of contemporary medical ethics
is the requirement for informed consent, including
the right of competent adults to refuse medical intervention. The Committee on Ethics affirms that
informed consent for medical treatment is an ethical
requirement and is an expression of respect for the
patient as a person with a moral right to bodily
integrity (19).
The crucial difference between pregnant and
nonpregnant individuals, though, is that a fetus is
involved whose health interests could arguably be
served by overriding the pregnant womans wishes.
However, in the United States, even in the case of
two completely separate individuals, constitutional
law and common law have historically recognized
the rights of all adults, pregnant or not, to informed
consent and bodily integrity, regardless of the
impact of that persons decision on others. For
instance, in 1978, a man suffering from aplastic anemia sought a court order to force his cousin, who
was the only compatible donor available, to submit
to bone marrow harvest. The court declined,

explaining in its opinion:
For our law to compel the Defendant to submit to an
intrusion of his body would change every concept
and principle upon which our society is founded. To
do so would defeat the sanctity of the individual and
would impose a rule which would know no limits. . . .
For a society that respects the rights of one individual, to sink its teeth into the jugular vein or neck of
its members and suck from it sustenance for another
member, is revolting to our hard-wrought concepts of
jurisprudence. Forcible extraction of living body tissues causes revulsion to the judicial mind. Such
would raise the specter of the swastika and the
Inquisition, reminiscent of the horrors this portends.
(24)
Justice requires that a pregnant woman, like any

other individual, retain the basic right to refuse medical intervention, even if the intervention is in the
best interest of her fetus. This principle was challenged unsuccessfully in June 1987 with the case of
a 27-year-old woman who was at 25 weeks of gestation when she became critically ill with cancer.
Against the wishes of the woman, her family, and
her physicians, the hospital obtained a court order
for a cesarean delivery, claiming independent rights
of the fetus. Both mother and infant died shortly
after the cesarean delivery was performed. Three
years later, the District of Columbia Court of
Appeals vacated the court-ordered cesarean delivery
and held that the woman had the right to make health
care decisions for herself and her fetus, arguing that
the lower court had erred in subordinating her right
to bodily integrity in favor of the states interest in
potential life (1).
2. Court-ordered interventions in cases of informed
refusal, as well as punishment of pregnant women
for their behavior that may put a fetus at risk,
neglect the fact that medical knowledge and predictions of outcomes in obstetrics have limitations.
Beyond its importance as a means to protect the
right of individuals to bodily integrity, the doctrine
of informed consent recognizes the right of individuals to weigh risks and benefits for themselves.
Women almost always are best situated to understand
the importance of risks and benefits in the context
of their own values, circumstances, and concerns.
Furthermore, medical judgment in obstetrics itself
has limitations in its ability to predict outcomes. In
this document, the Committee on Ethics has argued
that overriding a womans autonomous choice,
whatever its potential consequences, is neither ethi-
COMMITTEE OPINIONS
cally nor legally justified, given her fundamental

rights to bodily integrity. Even those who challenge
these fundamental rights in favor of protecting the
fetus, however, must recognize and communicate
that medical judgments in obstetrics are fallible (25).
And fallibilitypresent to various degrees in all
medical encountersis sufficiently high in obstetric
decision making to warrant wariness in imposing
legal coercion. Levels of certainty underlying medical recommendations to pregnant women are
unlikely to be adequate to justify legal coercion and
the tremendous impact on the lives and civil liberties
of pregnant women that such intervention would
entail (26). Some have argued that court-ordered
intervention might plausibly be justified only when
certainty is especially robust and the stakes are especially high. However, in many cases of courtordered obstetric intervention, the latter criterion has
been met but not the former. Furthermore, evidencebased medicine has revealed limitations in the ability to concretely describe the relationship of maternal
behavior to perinatal outcome. Criminalizing women
in the face of such scientific and clinical uncertainty
is morally dubious. Not only do these approaches fail
to take into account the standards of evidence-based
medical practice, but they are also unjust, and their
application is likely to be informed by bias and opinion rather than objective assessment of risk.
Consider, first, the limitations of medical judgment in predicting birth outcomes based on mode of
childbirth. A study of court-ordered obstetric interventions suggested that in almost one third of cases
in which court orders were sought, the medical judgment was incorrect in retrospect (27). One clear
example of the challenges of predicting outcome is
in the management of risk associated with shoulder
dystocia in the setting of fetal macrosomiawhich
is, and should be, of great concern for all practitioners. When making recommendations to patients,
however, practitioners have an ethical obligation to
recognize and communicate that accurate diagnosis
of macrosomia is imprecise (20). Furthermore,
although macrosomia increases the risk of shoulder
dystocia, it is certainly not absolutely predictive; in
fact, most cases of shoulder dystocia occur unpredictably among infants of normal birthweight. Given
this uncertainty, ACOG makes recommendations
about when cesarean delivery may be considered,
not about when it is absolutely indicated. Because of
the inability to determine with certainty when a situation is harmful to the fetus or pregnant woman and
93
the inability to guarantee that the pregnant woman

will not be harmed by the medical intervention,
great care should be exercised to present a balanced
evaluation of expected outcomes for both parties
(20). The decision about weighing risks and benefits
in the setting of uncertainty should remain the pregnant womans to make in the setting of supportive,
informative medical care.
Medical judgment also has limitations in that
the relationship of maternal behavior to pregnancy
outcome is poorly understood and may be exaggerated in realms often mistaken to be of moral rather
than medical concern, such as drug use. For
instance, recent child development research has not
found the effects of prenatal cocaine exposure that
earlier uncontrolled studies reported (28). It is now
understood that poverty and its concomitantspoor
nutrition and inadequate health carecan account
for many of the effects popularly attributed to
cocaine. Before these data emerged, the criminal
justice approach to drug addiction during pregnancy
was fueled to a great degree by what is now understood to be the distorting image of the crack baby.
Such an image served as a convenient symbol for
an aggressive war on drug users [that] makes it easier to advocate a simplistic punitive response than to
address the complex causes of drug use (29). The
findings questioning the impact of cocaine on perinatal outcome are among many considerations that
bring sharply into question any possible justification
for a criminal justice approach, rather than a public
health approach, to drug use during pregnancy.
Given the incomplete understanding of factors
underlying perinatal outcomes in general and the
contribution of individual behavioral and socioeconomic factors in particular, to identify homeless and
addicted women as personally, morally, and legally
culpable for perinatal outcomes is inaccurate, misleading, and unjust.
3. Coercive and punitive policies treat medical problems such as addiction and psychiatric illness as
if they were moral failings.
Regardless of the strength of the link between an
individuals behaviors and pregnancy outcome,
punitive policies directed at women who use drugs
are not justified, because these policies are, in effect,
punishing women for having a medical problem.
Although once considered a sign of moral weakness,
addiction is now, according to evidence-based medicine, considered a diseasea compulsive disorder
94
requiring medical attention (30). Pregnancy should

not change how clinicians understand the medical
nature of addictive behavior. In fact, studies overwhelmingly show that pregnant drug users are very
concerned about the consequences of their drug
use for their fetuses and are particularly eager to
obtain treatment once they find out they are pregnant (31, 32). Despite evidence-based medical recommendations that support treatment approaches to
drug use and addiction (21), appropriate treatment is
particularly difficult to obtain for pregnant and parenting women and the incarcerated (29). Thus, a
disease process exacerbated by social circumstancenot personal, legal, or moral culpability
is at the heart of substance abuse and pregnancy.
Punitive policies unfairly make pregnant women
scapegoats for medical problems whose cause is
often beyond their control.
In most states, governmental responses to pregnant women who use drugs have upheld medical
characterizations of addiction. Consistent with longstanding U.S. Supreme Court decisions recognizing
that addiction is an illness and that criminalizing it
violates the Constitutions Eighth Amendment prohibitions against cruel and unusual punishment, no state
has adopted a law that specifically creates unique
criminal penalties for pregnant women who use drugs
(33). However, in South Carolina, using drugs or
being addicted to drugs was effectively criminalized
when the state supreme court interpreted the word
child in the states criminal child endangerment
statute to include viable fetuses, making the child
endangerment statute applicable to pregnant women
whose actions risk harm to a viable fetus (23). In all
states, women retain their Fourth Amendment freedom from unreasonable searches, so that pregnant
women may not be subject to nonconsensual drug
testing for the purpose of criminal prosecution.
Partly on the basis of the understanding of addiction as a compulsive disorder requiring medical attention, medical professionals, U.S. state laws, and the
vast majority of courts do not support unique criminal penalties for pregnant women who use drugs.
4. Coercive and punitive policies are potentially
counterproductive in that they are likely to discourage prenatal care and successful treatment,
adversely affect infant mortality rates, and undermine the physicianpatient relationship.
Even if the aforementioned ethical concerns could
be addressed, punitive policies would not be justifi-
able on utilitarian grounds, because they would likely result in more harm than good for maternal and
child health, broadly construed. Various studies have
suggested that attempts to criminalize pregnant
womens behavior discourage women from seeking
prenatal care (34, 35). Furthermore, an increased
infant mortality rate was observed in South Carolina
in the years following the Whitner v State decision
(36), in which the state supreme court concluded
that anything a pregnant woman does that might
endanger a viable fetus (including, but not limited
to, drug use) could result in either charges of child
abuse and a jail sentence of up to 10 years or homicide and a 20-year sentence if a stillbirth coincides
with a positive drug test (23). As documented previously (21), threats and incarceration have been ineffective in reducing the incidence of alcohol and drug
abuse among pregnant women, and removing children from the home of an addicted mother may subject them to worse risks in the foster care system. In
fact, women who have custody of their children
complete substance abuse treatment at a higher rate
(3739).
These data suggest that punishment of pregnant
women might not result in women receiving the
desired message about the dangers of prenatal substance abuse; such measures might instead send an
unintended message about the dangers of prenatal
care. Ultimately, fear surrounding prenatal care
would likely undermine, rather than enhance, maternal and child health. Likewise, court-ordered interventions and other coercive measures may result in
fear about whether ones wishes in the delivery room
will be respected and ultimately could discourage
pregnant patients from seeking care. Encouraging
prenatal care and treatment in a supportive environment will advance maternal and child health most
effectively.
5. Coercive and punitive policies directed toward
pregnant women unjustly single out the most vulnerable women.
Evidence suggests that punitive and coercive policies not only are ethically problematic in and of
themselves, but also unfairly burden the most vulnerable women. In cases of court-ordered cesarean
deliveries, for instance, the vast majority of court
orders have been obtained against poor women of
color (27, 40).
Similarly, decisions about detection and management of substance abuse in pregnancy are fraught
COMMITTEE OPINIONS
with bias, unfairly burdening the most vulnerable

despite the fact that addiction occurs consistently
across race and socioeconomic status (41). In the
landmark case of Ferguson v City of Charleston,
which involved selective screening and arrest of
pregnant women who tested positive for drugs, 29 of
30 women arrested were African American. Studies
suggest that affluent women are less likely to be
tested for use of illicit drugs than poor women of
color, perhaps because of stereotyped but demonstrably inaccurate assumptions about drug use. One
study found that despite similar rates of substance
abuse across racial and socioeconomic status,
African American women were 10 times more likely than white women to be reported to public health
authorities for substance abuse during pregnancy
(42). These data suggest that, as implemented, many
punitive policies centered on maternal behaviors,
including substance use, are deeply unjust in that
they reinforce social and racial inequality.
6. Coercive and punitive policies create the potential
for criminalization of many types of otherwise
legal maternal behavior.
In addition to raising concerns about race and
socioeconomic status, punitive and coercive policies
may have even broader implications for justice for
women. Because many maternal behaviors are associated with adverse pregnancy outcome, these policies could result in a society in which simply being
a woman of reproductive potential could put an individual at risk for criminal prosecution. For instance,
poorly controlled diabetes is associated with numerous congenital malformations and an excessive rate
of fetal death. Periconceptional folic acid deficiency
is associated with an increased risk of neural tube
defects. Obesity has been associated in recent studies with adverse pregnancy outcomes, including
preeclampsia, shoulder dystocia, and antepartum
stillbirth (43, 44). Prenatal exposure to certain
medications that may be essential to maintaining a
pregnant womans health status is associated with
congenital abnormalities. If states were to consistently adopt policies of punishing women whose
behavior (ranging from substance abuse to poor
nutrition to informed decisions about prescription
drugs) has the potential to lead to adverse perinatal
outcomes, at what point would they draw the line?
Punitive policies, therefore, threaten the privacy and
autonomy not only of all pregnant women, but also
of all women of reproductive potential.
95
Recommendations
In light of these six considerations, the Committee
on Ethics strongly opposes the criminal prosecution
of pregnant women whose activities may appear to
cause harm to their fetuses. Efforts to use the legal
system specifically to protect the fetus by constraining womens decision making or punishing them for
their behavior erode a womans basic rights to privacy and bodily integrity and are neither legally nor
morally justified. The ACOG Committee on Ethics
therefore makes the following recommendations:
In caring for pregnant women, practitioners
should recognize that in the majority of cases,
the interests of the pregnant woman and her
fetus converge rather than diverge. Promoting
pregnant womens health through advocacy of
healthy behavior, referral for substance abuse
treatment and mental health services when necessary, and maintenance of a good physician
patient relationship is always in the best interest
of both the woman and her fetus.
Pregnant womens autonomous decisions
should be respected. Concerns about the impact
of maternal decisions on fetal well-being should
be discussed in the context of medical evidence
and understood within the context of each
womans broad social network, cultural beliefs,
and values. In the absence of extraordinary circumstances, circumstances that, in fact, the
Committee on Ethics cannot currently imagine,
judicial authority should not be used to implement treatment regimens aimed at protecting the
fetus, for such actions violate the pregnant
womans autonomy.
Pregnant women should not be punished for
adverse perinatal outcomes. The relationship
between maternal behavior and perinatal outcome is not fully understood, and punitive
approaches threaten to dissuade pregnant
women from seeking health care and ultimately
undermine the health of pregnant women and
their fetuses.
Policy makers, legislators, and physicians
should work together to find constructive and
evidence-based ways to address the needs of
women with alcohol and other substance abuse
problems. This should include the development
of safe, available, and efficacious services for
women and families.
96
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mchb.hrsa.gov/about/default.htm. Retrieved June 17,
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9. Lyerly AD, Gates EA, Cefalo RC, Sugarman J. Toward
the ethical evaluation and use of maternal-fetal surgery.
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prenatal care and other health services for unborn children. Final rule. Centers for Medicare & Medicaid
Services (CMS), HHS. Fed Regist 2002;67:6195574.
11. Steinbock B. Health care coverage for not-yet-born children. Hastings Cent Rep 2003;33(1):49.
12. Murray L, Cooper P. Effects of postnatal depression on
infant development. Arch Dis Child 1997;77:99101.
13. Murray L, Fiori-Cowley A, Hooper R, Cooper P. The
impact of postnatal depression and associated adversity
on early mother-infant interactions and later infant outcome. Child Dev 1996;67:251226.
14. Horon IL, Cheng D. Enhanced surveillance for pregnancy-associated mortalityMaryland, 19931998.
JAMA 2001;285:14559.
15. Frye V. Examining homicides contribution to pregnancyassociated deaths [editorial]. JAMA 2001;285:15101.
16. Phelan JP. The maternal abdominal wall: a fortress against
fetal health care? South Calif Law Rev 1991;65:46190.
17. Little MO. Abortion, intimacy, and the duty to gestate.
Ethical Theory Moral Pract 1999;2:295312.
18. Mattingly SS. The maternal-fetal dyad. Exploring the
two-patient obstetric model. Hastings Cent Rep 1992;22:
138.
19. Informed consent. In: American College of Obstetricians
and Gynecologists. Ethics in obstetrics and gynecology.
2nd ed. Washington, DC: ACOG; 2004. p. 917.
20. Patient choice in the maternalfetal relationship. In:
Ethics in obstetrics and gynecology. 2nd ed. Washington,
DC: ACOG; 2004. p. 346.
21. At-risk drinking and illicit drug use: ethical issues in
obstetric and gynecologic practice. ACOG Committee
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Nelson LJ, Milliken N. Compelled medical treatment of
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Kolder VE, Gallagher J, Parsons MT. Court-ordered
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Murphy S, Rosenbaum M. Pregnant women on drugs:
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42. Chasnoff IJ, Landress HJ, Barrett ME. The prevalence of
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98
ACOG
Committee on
Ethics
Reaffirmed 2008
Committee
Opinion
Number 341, July 2006
Ethical Ways for Physicians

to Market a Practice
Copyright July 2006
stored in a retrieval system, posted on the Internet, or transmitted,
in any form or by any means,
electronic, mechanical, photocopying, recording, or otherwise,
without prior written permission
from the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Ethical ways for physicians to market
a practice. ACOG Committee Opinion
ABSTRACT: It is ethical for physicians to market their practices through any

form of public communication provided that the communication is truthful
and not misleading or deceptive. Communications should not convey discriminatory attitudes involving race, ethnicity, gender, or sexual orientation.
All paid advertising must be clearly identified as such. Producing fair and
accurate advertising of medical practices and services can be challenging. It
often is difficult to include detailed information because of cost and size
restrictions or the limitations of the media form that has been selected. If the
specific advertising form does not lend itself to clear and accurate description, an alternative media format should be selected. Finally, any advertising that seeks to denigrate the competence of other individual professionals
or group practices is always considered unethical.
Traditionally, physicians and medical societies have raised concerns that

advertising commercializes the practice of medicine and does not respect the
dignity of the profession. Physicians have been expected to generate referrals from other physicians and from satisfied patients by providing good care
to their patients. In the past, some state and national professional medical
societies prohibited advertising in their code of ethics. In 1982, the Supreme
Court ruled in favor of the Federal Trade Commission (FTC) in its claim that
the American Medical Association was in restraint of trade because the
American Medical Associations Code of Ethics prohibited advertising (1).
The FTC argued that all businesses and professionals have the right to
inform the public of the services they provide and that all consumers have
the right to make informed choices based on truthful advertising. The purpose of this Committee Opinion is to provide objective criteria to help members of the American College of Obstetricians and Gynecologists determine
whether or not a certain advertisement or method of marketing is ethical. In
considering appropriate marketing practices, physicians should evaluate not
only their own actions but also those undertaken on their behalf by hospitals
or other health care centers that may be marketing their services.
It is ethical for physicians to market their practices through any form of
public communication provided that the communication is truthful and not
misleading or deceptive in any way. In addition, communications should not
COMMITTEE OPINIONS
convey discriminatory attitudes involving race, ethnicity, gender, or sexual orientation.
Appropriate Forms of Communication

According to the FTC guidelines, physicians must
be allowed to make their services known through
advertising to assist the public in obtaining medical
services. A physician or practice should not be
restricted from using any form of public media to
market medical services, such as newspapers, magazines, telephone directories, radio, web pages,
computer billboards, television, and direct mail. All
of these media formats have the potential for both
effective, ethical communication as well as misrepresentation, depending on their form and content.
Advertising in any format may be ethical but still
reflect poorly on the profession and undermine the
public impressions of the profession. For example,
use of a large billboard or television infomercials
to advertise services is not unethical, but still might
be considered by many to be unprofessional.
Physicians should consider not just the intent of the
advertisement but also its impact.
A paid advertisement promoting the activities of
a physician or practice must be clearly identified as
advertising. It is not ethical to compensate the communication media in any way for publicity in a news
item. If a television infomercial is used to inform the
public of services available, it should be very clear at
all times that this is paid advertising and not part of
a news program.
Care should be taken to choose information
appropriate to the form of communication. The complexity of medical terms and treatments may not
always lend itself to the restrictions of a particular
advertisement design or media format. For example,
the brevity of television and radio advertisements
may require omitting so much information that the
advertisement becomes misleading.
The location in which an advertisement is
placed also may contribute to deception. For example, some readers may assume that a physician who
advertises his or her practice under the subheading
Infertility in the telephone directory has received
extensive subspecialty training in that area and regularly treats patients with these problems.
Advertisers should be careful not to imply subspecialty training when none exists.
Actively approaching specific individuals, in
person or by phone, with the purpose of attracting
99
them as patients usually is not considered ethical

because the risk of undue pressure from the solicitor
is too great. Common expectations for a physicianpatient relationship may make the prospective
patient feel obligated to respond affirmatively to the
encounter. Although many physicians view such
active approaches as always being unprofessional,
they may be ethical in rare circumstances if extraordinary care is taken to avoid undue pressure. For
example, it may be appropriate to pass out cards to
potential clients at a community health fair.
Appropriate Content of Advertisements

Advertisements must be truthful and not deceptive
or misleading. Specifically, this means that all information must be accurate and must not create false or
unjustified expectations. The omission of information should not render the advertisement misleading.
Images and graphics can be as deceptive or misleading as text. Finally, the physician or clinic must be
able to substantiate all claims made in the advertisement. Advertisements may include nondeceptive
information, such as address, phone numbers, web
site address, office hours, languages spoken, board
certification, contracted insurance plans, publications by physicians, teaching positions, hospital
affiliations, and methods of payment accepted.
Terms such as top, world-famous, worldclass, or even pioneer, usually are misleading and
designed to attract vulnerable patients. Statements
that rank the competence of physicians or the quality of medical services usually are not factually supportable. If attributions of this type are used, the
advertisement must describe how these rankings
were established. The testimonial of one or two satisfied patients may mislead the public into believing
that all patients, even those with dissimilar histories,
have similar outcomes. The designation Top
Doctor as voted by magazine readers, other doctors, or specific groups may be used in promotional
material since the term is a factual statement of the
results of a survey. However, advertisements must
state if such a designation involved payment by the
physician. Furthermore, any advertising that seeks
to denigrate the competence of other individual professionals or group practices always is considered
unethical.
Care must be taken in advertising procedures
that are experimental or have never been proved to
result in the desired outcome. It is deceptive to give
100
the public the impression that experimental or

unstudied procedures are of proven value or accepted practice.
Claims that a physician or group of physicians
have a unique skill or offer a unique test or treatment
often may be deceptive and rarely should be used. If
a physician has carefully verified that he or she is the
only practitioner to offer a certain treatment in a particular geographic area, then this information may
be dispersed. If the uniqueness results from a restrictive commercial agreement, this fact needs to be disclosed in the advertisement.
Specific outcomes should rarely be advertised
because the definition of a success rate, the selection
of eligible patients for consideration in calculating
rates, and the predictive value of rates are all important in accurately assessing outcomes. Whereas
these should be discussed with an individual patient
in the context of her care, they cannot be interpreted
accurately by someone viewing an advertisement
and may be very confusing or misleading to the
patient trying to determine where to seek care. For
example, a fertility clinics success rate for assisted reproductive technologies is dependent on the
patients age, the clinics patient selection and exclusion policies, and the clinics criteria for cycle cancellation. Success may be stated in many ways,
each of which results in a different rate: as clinical
pregnancies, singleton pregnancies, or live births per
started cycle, per egg retrieval, or per embryo transfer. Comparing hospitals by cesarean delivery rate is
similarly difficult because rates vary with the characteristics of a patient population or the presence of
a neonatal intensive care unit or both. Furthermore,
a new program or site should not present the success
rates of the parent site as its own because its new
facilities are as yet untested. When advertisements
do involve success rates or other outcomes, all
claims must be supported by valid, reproducible
data, must clearly state the method used to calculate
outcomes, and must not lead patients or the public to
believe that outcomes are better than they are.
Fee structures and costs may be advertised, as
long as information is complete and titles for special
programs do not mislead or encourage inaccurate
assumptions. For example, promises of a moneyback guarantee are frequently misleading because
usually they refund only a portion of the patients
money if the desired outcome does not occur.
Shared-risk plans usually do not share risk
between the patient and the clinic, but among a
group of patients. Do one, get one free treatments

may involve extraordinary requirements and expenses for the initial treatment and may not truly save the
patient any money. A free initial consultation
should not contain any hidden costs or routinely
involve recommendations for expensive tests or
treatments. Any advertisements involving such
financial plans should contain enough information
so that the prospective patients are neither misled
nor unduly induced to seek services at that clinic.
Producing fair and accurate advertising of medical practices and services can be challenging, even
with the best intentions. It often is difficult to
include detailed information because of cost and
size restrictions or the limitations of the media form
that has been selected. If the specific advertising
form does not lend itself to clear and accurate
description, an alternative media format should be
selected.
Concerns About Discrimination

Discriminatory attitudes about race, ethnicity, gender, or sexual orientation in advertisements are not
acceptable. A line item stating that a provider speaks
Spanish or Cantonese accurately states the services
provided and would not be considered discriminatory. Similarly, a factual statement that the providers
in a certain clinic are all women is ethical. However,
wording that suggests that health care provided solely by women is superior to health care for women by
men would be considered discriminatory and unethical in the absence of evidence supporting that
claim. If the intent of stating the facts is to imply a
value judgment rather than to offer supportable or
useful information about access, then even a statement of fact may be unethical.
Vulnerable Groups
Certain individuals and groups of individuals may
be more easily misled by some claims made in
advertisements. Special care should be taken when
designing a marketing plan that targets these groups.
Perimenopausal and postmenopausal women, fearful of cancer, may embrace natural therapies, even
when these therapies have not been evaluated adequately for efficacy or risk. Patients with advanced
cancer may be more likely to pursue unapproved
procedures or pharmaceuticals. Patients with infertility or recurrent pregnancy losses, desperate to
COMMITTEE OPINIONS
have a child, often are willing to pursue expensive

new treatments that are completely unproved.
Reference
Summary
Bibliography
Advertising by physicians or groups of physicians is

unethical when it contains material that is false,
unsubstantiated, deceptive, or misleading. Even if
the advertisement follows the guidelines covered in
this statement, the individual professional should be
the one who chooses a marketing plan he or she
believes respects the dignity of the profession.
101
1. American Medical Assoc. v. FTC, 455 U.S. 676 (1982).
American College of Obstetricians and Gynecologists. Code of

professional ethics of the American College of Obstetricians
and Gynecologists. Washington, DC: ACOG; 2004.
Guidelines for advertising by ART programs. Practice
Committee, Society for Assisted Reproductive Technology;
American Society for Reproductive Medicine. Fertil Steril
2004;82:5278.
102
ACOG
Committee on
Ethics
Reaffirmed 2008
Committee
Opinion
Using Preimplantation Embryos

for Research*

photocopying, recording, or
otherwise, without prior written
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Using preimplantation embryos for
research. ACOG Committee Opinion
ABSTRACT: Human embryonic stem cell research promises an increased

understanding of the molecular process underlying cell differentiation.
Transplantation of embryonic stem cells or their derivatives may, in the
future, offer therapies for human diseases. In this Committee Opinion, the
American College of Obstetricians and Gynecologists (ACOG) Committee
on Ethics presents an ethical framework for examining issues surrounding
research using preimplantation embryos and proposes ethical guidelines for
such research. The Committee acknowledges the diversity of opinions among
ACOG members and affirms that no physician who finds embryo research
morally objectionable should be required or expected to participate in such
research. The Committee supports embryo research within 14 days after evidence of fertilization but limits it according to ethical guidelines. The
Committee recommends that cryopreserved embryos be the preferred source
for research but believes that the promise of somatic cell nuclear transfer is
such that research in this area is justified. The Committee opposes reproductive cloning. Intended parents for whom embryos are created should give
informed consent for the disposition of any excess embryos. The donors of
gametes or somatic cells used in the creation of such tissue should give consent for donation of embryos for research. Abandoned embryos should not be
accepted for research. Potential research projects should be described to
potential donors as much as possible. Donation of embryos for stem cell
research requires specific consent. The Committee believes that compensation for egg donors for research is acceptable, consistent with American
Society for Reproductive Medicine guidelines.
The human embryo has long attracted the interest of researchers. Initially,
scientists studying embryos hoped to better understand human pregnancy
and embryonic development. Later, with the emergence of assisted reproductive technologies such as in vitro fertilization (IVF), embryo research
focused on optimizing pregnancy rates and outcomes. Most recently,
research has targeted the stem cells derived from embryos because stem cell
*Update of Preembryo Research in Ethics in Obstetrics and Gynecology,
Second Edition, 2004
Terms defined in the glossary appear in bold type.
COMMITTEE OPINIONS
research promises an increased understanding of the

molecular process underlying cell differentiation
(the process of acquiring characteristics of specific
tissues and organs). Transplantation of embryonic
stem cells or their derivatives may, in the future,
offer therapies for human diseases. These possibilities, coupled with the demonstration in 1998 that
stem cells could be isolated from either the inner
cell mass of blastocysts or fetal germ cell tissue,
have sparked public debate on the ethical foundation
of stem cell work specifically and embryo research
in general. The urgency of these questions makes it
timely both to review the moral issues raised by
human embryo research and to consider appropriate
guidelines for the ethical conduct of these endeavors.
The Committee on Ethics acknowledges the
diversity of opinions regarding these topics among
members of the American College of Obstetricians
and Gynecologists (ACOG), a diversity mirroring
that in society at large. These diverse positions range
from complete rejection of all human embryo
research to approval of the deliberate creation of
human embryos for research. Even among those
who accept embryo research on ethical grounds,
there is disagreement about the conditions under
which it may ethically be conducted.
The purpose of this Committee Opinion is to
present a relevant ethical framework within which to
view contemporary embryo research and to propose
ethical guidelines for such research. The opinion
focuses specifically on issues relating to research
using preimplantation embryos. The Committee
recognizes that the science of this field, especially
the science of stem cell research and therapy, is
changing rapidly and anticipates that future changes
will require revisiting past issues and either modifying previous guidelines or creating new ones in
order to address formerly unimagined possibilities.
Historical Perspective: Policies and

Regulation
Oversight and regulation of research involving
human reproduction, especially that involving fertilized eggs and embryos, have a long and contentious
history linked both to the politics of abortion and to
the introduction of IVF into clinical practice (Fig. 1).
Certainly, clinical progress with assisted reproductive technologies requires research, yet performing
such research raises important questions about how
the needed tissues should be obtained and treated.
103
Several events and issues, including the U.S.

Supreme Courts decision on abortion in Roe v.
Wade and revelations of abuses in human subjects
research, led Congress in 1974 to establish the
National Commission for the Protection of Human
Subjects. On the basis of guidelines proposed by the
National Commission in 1975, the then Department
of Health, Education, and Welfare issued regulations
for federal funding of research involving human
fetuses. These regulations defined the fetus as the
product of conception from the time of implantation
on (1). The regulations also recommended the
appointment of an ethical advisory board to examine
unresolved questions. The Ethics Advisory Board
(EAB) was appointed in 1978, shortly before the
first birth from IVF, with a mandate to review both
IVF research and research using embryos resulting
from IVF.
In its 1979 report, the EAB stated, The human
embryo is entitled to profound respect; but this
respect does not necessarily encompass the full legal
and moral rights attributed to persons (2). The EAB
statement supported the ethical acceptability of
research to study and develop the safety and efficacy of IVF and embryo transfer techniques used for
the treatment of infertility. The EAB also accepted
the use of gametes of informed, married, and consenting donors in such research, provided that developing embryos were not sustained longer than 14
days in vitro, a limit chosen in part because the
primitive streak is formed at this juncture. In its
statement, the EAB did not distinguish between
excess embryos from IVF therapy and embryos
created solely for research. In fact, the EAB
implied that research may require the creation of
embryos that, because of concerns for safety, would
never be intended for transfer.
Because of public and political opposition to
embryo research, however, EAB guidelines were
never implemented, and the boards charter was
allowed to expire in 1980, effectively imposing a
moratorium on federal funding of IVF and embryo
research because existing legislation required the
oversight of an ethical advisory board as a prerequisite. Thus, any embryo research conducted in the
United States at that time had to use private or university funding and often was undertaken in the context of infertility treatment. Recognizing the ethical
and regulatory challenges associated with the conduct of research outside of federal oversight, the
Ethics Committee of the American Fertility Society
American Fertility
Society publishes
ethical guidelines
for embryo
research.
American Fertility
Society publishes
ethical guidelines
for embryo
research.
Clinton administration
determines that the
Dickey Amendment
does not prohibit
federal funding
for research on
established human
stem cell lines.
Referendum in
California approves
state funding for
stem cell research
and establishes the
California Institute
for Regenerative
Medicine.
Stem cell research

funding bill passes
U.S. House of
Representatives
and U.S. Senate,
vetoed by
President Bush.
Human Embryo
Research Panel is
appointed and
approves embryo
research for
specific purposes.
Congress revokes
the requirement of
Ethics Advisory
Board approval and
permits the
National Institutes
of Health to fund
such research.
American Fertility
Society publishes
ethical guidelines
for embryo
research.
Stem cells
isolated
from human
embryonic
and fetal
tissues.
Bill to expand
federal funding for
stem cell research
passes in U.S.
House of
Representatives, is
under consideration
in U.S. Senate.
President
George W. Bush
restricts federal
funding for
embryonic stem
cell research to stem
cell lines existing as
of August 9, 2001.
Fig. 1. Embryo research timeline. The American Fertility Society became the American Society for Reproductive Medicine in 1995.
Ethics Advisory
Board report
supports the
ethical
acceptability of
research on IVF.
National
Commission
recommends that
an ethical advisory
board be appointed
for in vitro fertilization (IVF) research.
1 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06
0
9
8
7
6
5
74
19 197 197 197 197 197 198 198 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 20 20 20 20 20 20 20
U.S. Congress
establishes the
National
Commission for
the Protection Louise Brown,
of Human
the first IVF
Subjects.
baby, is born in
England.
Ethics Advisory
Board charter
expires, effectively
imposing a
moratorium on
federal funding
of IVF and
embryo research.
National Bioethics
Advisory
Commission
Dickey Amendment
supports federal
prohibits federal
funding for stem
funding for any
cell research
research in which
involving embryos
an embryo is
remaining after
destroyed or
infertility treatment.
harmed.
104
COMMITTEE OPINIONS
(now American Society for Reproductive Medicine

[ASRM]) issued specific guidelines for conducting
such work (35). The ASRM committee endorsed
embryo research but, echoing earlier guidelines, recommended that human embryos not be maintained
for research beyond the 14th day after fertilization
(3, 4). The same group noted that because of the
high moral value accorded to preimplantation
embryos, research using these tissues required
strong justification, but later the group also recognized that some studies may require the production
of human [preimplantation embryos] as an integral
part of the analysis (5). In the face of ongoing
debate at a federal level, privately funded research in
the United States has been influenced by these
ASRM recommendations.
Federal funding of embryo research was further
limited in 1995 with passage of the Dickey Amendment, in which Congress prohibited the use of any
federal funds for creation of a human embryo(s) for
research purposes or research in which a human
embryo(s) are destroyed, discarded, or knowingly
subjected to risk of injury or death for research purposes (6). A similar Dickey Amendment has been
attached to the appropriations bill for the Department of Health and Human Services in every year
since. Thus, by the mid-1990s, although the pursuit
of embryo research was not prohibited by the federal government, the ban on federal funding limited its
conduct.
The isolation of stem cells from embryonic and
fetal tissues in 1998 engendered debate about how
existing regulations and guidelines should guide
research with such cells. In 1999, the general counsel
of the Department of Health and Human Services
during the Clinton administration argued that the literal language of the Dickey Amendment permitted
funding of embryonic stem cell research as long as the
stem cell line had been derived through research that
was not federally funded. Under this interpretation,
the use of embryonic stem cells would not constitute
research in which an embryo was destroyed, discarded, or subjected to risk of injury. That same year, the
National Bioethics Advisory Commission, a group
charged with identifying broad principles to govern
the ethical conduct of research, recommended federal support for stem cell research using embryos
remaining after infertility treatments, but opposed
creation of embryos specifically for research (7).
In contrast to these recommendations, in August
2001, the Bush administration announced what re-
105
mains the current federal funding policy for embryonic stem cell research (8). This policy permits
federal funding only for work using stem cell lines
in existence on August 9, 2001; derived from excess
embryos created solely for reproductive purposes;
and made available with the informed consent of the
donors. Although critics note several important limitations that these regulations place on U.S.
researchers (see Are There Alternatives to Using
Preimplantation Embryos for Research?), the regulations remain active and unchanged as of late 2006.
However, funding of stem cell research using fetal
tissues (eg, obtained from abortus materials) is still
permittedalthough perhaps less frequently performedunder the Fetal Tissue Transplantation
Research Act (9) and guidelines established during
the Clinton administration.
Current Clinical Practices

Practices and policies for the care of patients are
likely to inform attitudes and future guidelines
regarding the use of embryos for research. Before
addressing specific questions on stem cell and other
embryo research, established clinical practices
involving gametes and embryos are noted briefly. A
complete review of each area and its moral foundation is, however, beyond the scope of this Committee Opinion.
In Vitro Fertilization
Current IVF techniques often result in the creation
of more embryos than can be transferred safely to a
womans uterus for implantation. Practitioners and
patients should anticipate this possibility by having
patients prospectively consider the matter and detail
their wishes regarding such excess embryos. Many
have advocated, for example, prefreeze agreements in which patients indicate their wishes for
disposition of frozen embryos in the event of lifechanging circumstances such as death or divorce.
Advance discussions and agreements do not, however, preclude the need to continue discussion at the
time final decisions regarding frozen embryos are
made, for researchers have demonstrated the difficulties couples have processing this counseling at
the time of creating embryos for reproductive purpose (10). The ASRM and individual states recognize the right of appropriate individuals to make
such decisions regarding embryos. Such options
include extended freezing, destruction of embryos
106
either by failing to transfer or freeze or later thawing

without transfer, and donation for attempted implantation by another individual or couple. The ACOG
Committee on Ethics recognizes all of these options
as reasonable and appropriate and in so doing
accepts that it is the individual or couple who created the embryos, either with their own or donor
gametes, who are entitled to make these decisions.
This current Committee Opinion outlines ethical
considerations related to the option of using preimplantation embryos for research.
Gamete Donation
Both egg and sperm may be donated either anonymously or by directed donation to specific individuals
or couples. Donated gametes are widely used for
infertility treatment, and sperm and egg obtained in
excess of what is needed for such treatments have,
with appropriate consent, later been used for
research. Gametes also have been donated for
research purposes only, separate from any plans for
infertility treatment and therapy, and the Committee
on Ethics supports such donation. In the past,
research using gametes has included studies designed
to optimize IVF techniques and work examining
gamete cryopreservation. The donation of oocytes for
research purposes is controversial, however, and has
raised what ASRM terms special concern (5)
because of the risk, pain, and side effects involved in
the process of egg donation and because of concerns
about possible exploitation of donors.
Embryo Research: Ethical Questions

What Is the Moral Status of the Embryo?
In debates about the ethics of embryo research, the
central ethical question historically has focused on
the embryos moral status and whether the embryo
is deserving of the same rights and protections as a
child or adult person. This Committee Opinion is
based on the view that although the preimplantation
embryo merits respect, its moral status is not equivalent to that of a human being. Scientific information alone will never resolve questions about the
embryos moral status. However, several distinguishing features of preimplantation embryos
inform the evaluation of the moral status of the
embryo and, hence, the ethical arguments concerning embryo research. Figure 2 outlines the development of pregnancy from gamete to fetus, a path that
highlights the distinguishing characteristics of preimplantation embryos:

1. Early embryonic cells are undifferentiated. Until
the blastocyst stage, each cell is totipotent, having the capacity to differentiate into any of the
cell or tissue types of the fetus or to form placental and other extra-embryonic tissues. Each
of the cells of the inner cell mass of the blastocyst is pluripotent, with the capacity to become
any of the cell or tissue types of the fetus, but at
this stage, these cells form a collection of undifferentiated cells rather than a unified organism.
2. Embryos at early stages lack individuation. This
is evidenced by research demonstrating that, up
to at least the 8-cell stage, one or more blastomeres can be removed from the embryo (eg,
as for preimplantation genetic diagnosis [PGD])
and the remaining blastomeres can still produce
a complete human being. Also, from the initial
stages of cell division until the formation of the
primitive streak, the embryo is capable of dividing into more than one entity (ie, twinning).
Only after this period has differentiation of
embryonic cells advanced to the point that separation can no longer result in two or more individuals (1113).
3. The formation of the primitive streak at day 14
marks the beginning of the differentiation of
cells into the various tissues and organs of
the human body. Before the appearance of the
primitive streak, the cells of the embryo are
undifferentiated and pluripotent. Recognizing
this biologic landmark, many, now including the
ACOG Committee on Ethics, have recommended limiting embryo research to the first 14 days
after fertilization.
4. If the preimplantation embryo is left or maintained outside the uterus, it cannot develop into
a human being. Continuing potential for life
exists if, but only if, the embryo is transferred to
the uterus for implantation (this potential will
have important implications for the conduct of
research and therapy involving embryos). If
never implanted, development ceases. In the
United Kingdom, regulations focus on implantation as a key to distinguishing moral status of
in vitro and cloned embryos from that of an in
vivo pregnancy (14). In the United States, federal regulations on fetal research apply from the
time of implantation on (1).
COMMITTEE OPINIONS
Day
Developmental Stage
Requisite or Resultant
Cells/Structures
Developmental
Morphology
Oocyte
Sperm
Single germ cell

Single germ cell
Fertilization complete
(syngamy) after 24 hours
Zygote
1 cell (male and

female pronuclei)
Cell division begins
Embryo
Process*
0
1
Fertilization begins
Blastomeres
Genomic expression
begins
48 cells
Morula
Blastocyst
5
or
after
Implantation begins
7
or
after
Differentiation begins
2 cells (nuclei)
(totipotential)
816 cells
(compacted)
Multicellular
(inner cell mass
and trophectoderm)
Cell division ends

89
or
after
Implantation complete
Embryonic disc
1416
Embryogenesis begins;
differentiation has passed
point of twinning
Primitive streak
*Both in vivo and in vitro except as noted.
In vivoorganizational structure as a blastocyst is requisite to beginning of implantation and persists after implantation (which may be
complete as early as 89 days after fertilization) until appearance of the primitive streak.
Cell division may end at any time in vivo or in vitro; it has not persisted in vitro beyond 69 days.
In vivo.
Fig. 2. Early in vivo and in vitro human development process.
107
108
Why Pursue Embryo Research?

Most contemporary discussions about embryo
research center entirely on the question of the
embryos intrinsic moral statuswhether or not the
embryo meets specific criteria for moral personhood.
Based on the understanding of the degree to which an
embryo does or does not meet such criteria, these discussions have taken a stand about the permissibility
of options for embryo disposition. Bioethicist Patricia
King has noted that human embryo research policy
should do more than reflect mere abstract assertions
about the moral status of human embryos. Rather, the
moral underpinnings of human embryo research
should be derived from a range of values, including
the facilitation of human procreation, the advancement of applied scientific knowledge, the reduction
of human suffering, and the protection of vulnerable
persons from coercion and exploitation (15).
There can be no compelling argument for
embryo research without the promise of benefit.
Potential benefits of embryo research include an
improved understanding of fertilization, implantation, and early pregnancy biology and, with this
understanding, possibly fewer undesired outcomes,
such as miscarriage. For infertile couples, embryo
research offers the possibility of more effective
therapies: research efforts helped optimize conditions for intracytoplasmic sperm injection, embryo
culture, and cryopreservation, for example. For others at risk for heritable genetic disease who feel
pregnancy termination is undesirable or inappropriate, embryo research has led to the possibility of
early, accurate genetic diagnosis: PGD provides
diagnostic results at a point before implantation, so
pregnancy termination can be avoided. In addition
to these benefits of embryo research in general,
stem cell research promises additional potential
benefits, for such work may lead both to a better
understanding of the processes leading to tissue differentiation and function and to possible therapies
by creating lines that can replace diseased or nonfunctioning tissues. Those who donate gametes or
embryos for research are offered the rewards of
potentially extending scientific knowledge and,
apart from any current or future hope of improving
their own health, the opportunity to help others with
this knowledge. Indeed, in considering the fate of
excess embryos for which destruction is planned,
some have argued that donation for research
accords the embryo more respect than destruction
alone (16, 17).
Are There Alternatives to Using Preimplantation

Embryos for Research?
As with all human research, research on embryos
and embryonic stem cells should be engaged in only
when alternative means of developing knowledge
are inadequate. Whenever possible, animal models
or cell and tissue culture systems should be used to
advance the understanding of human biology.
However, direct extrapolation of results from in vitro
animal embryo studies to humans can be misleading. Unfertilized oocytes also do not offer the same
opportunities for investigating growth processes that
embryos do.
Some have argued that obtaining or using
embryonic stem cells is unnecessary because stem
cells have been or can be isolated from umbilical
cord blood or adult tissues, such as brain and skin.
Yet such adult stem cells, in contrast to embryonic
stem cells, have already progressed along the path of
differentiation and lack the plasticity of embryonic
stem cells. It is unlikely that once differentiated,
these cells can be induced to form the range of tissues that can, by contrast, be produced by less-differentiated embryonic stem cells (18, 19).
Umbilical cord blood stem cells have been
shown in some studies to transdifferentiate to a limited extent into nonhematopoietic cells, including
those of the brain, heart, liver, pancreas, bone, and
cartilage, in experimental culture and animal systems (20, 21). Some have speculated that, on the
basis of these observations, cord blood might serve
as a source of cells to facilitate tissue repair and
regeneration in the distant future. Research is needed to clarify the role, if any, of cord blood in this
field of regenerative medicine.
For those with ethical objections, recent activity
in stem cell research has led to a vigorous search
for alternative sources of stem cells that might
obviate the need to use or destroy fresh or frozen
embryos (22). Suggested techniques include 1) extraction of cells from embryos already dead, 2) nonharmful biopsy of a single blastomere from a living
embryo, 3) extraction of cells from artificially created nonembryonic but embryolike cellular systems
(engineered to lack the essential elements of
embryogenesis but still capable of some cell division
and growth), and 4) dedifferentiation of somatic
cells back to pluripotency. The Committee on Ethics
recognizes that such techniques, if ultimately proved
to be productive, would avoid some but not all of the
arguments and objections that have been raised to
COMMITTEE OPINIONS
embryo and stem cell research. The Committee

believes, however, that until such hypothetical alternatives become realities for human tissues, their
possibility should not stand as a barrier to pursuing
available methods of demonstrated efficacy. Indeed,
technical barriers to these proposed alternatives are
not trivial, and the possibility of reprogramming
adult stem cells to achieve the same potential as
embryonic stem cells has been termed by experts as
exceedingly rare (23). It also is not clear that all
these suggestions are free from ethical concerns or
objections (eg, distinguishing when an embryo is
dead).
In considering embryonic stem cell research, it
is also important to indicate why progress requires
isolation of lines different from those already established. Federal regulations prohibit funding for
investigations of the many new embryonic stem cell
lines created since August 2001, some of which have
been used by both international and U.S. researchers
to advance the field. Yet, advocates of stem cell
research note that in contrast to several of these
newer lines, all lines on the National Institutes of
Health (NIH) registry were cultured in contact with
mouse cells and bovine serum, which limits potential therapeutic applications. Furthermore, the U.S.
federal guidelines prohibit federal funding of
somatic cell nuclear transfer techniques (also
known as SCNT techniques) and research, which
may offer unique opportunities for human therapy
by creating cells tailored to an individuals genotype
and thus, in theory, requiring less need for immunosuppression if therapeutics can one day be created
from such individualized cell lines.
Are There Arguments Against Embryo Research?
Balanced against any potential benefits of embryo
research are known and potential risks. Embryo
research usually will involve destruction of embryos
and, as a result, most human embryo research will
not benefit the embryo that is usedenhancing neither its developmental potential nor its chance of survival. It is this potential harm that has led national
ethics advisory committees and commissions to evaluate the moral status of the embryo and has sharply
separated the two sides of the embryo research and
stem cell debate. Yet, as detailed previously, this document views destruction of in vitro embryos as different from destruction of a human being.
Short of destruction, the manipulation of
embryos that are intended for transfer to the uterus
109
(as with embryo biopsy for PGD) raises concern for

potential manipulation-related damage in ongoing
pregnancies. Some embryo research can be validated scientifically and be beneficial clinically only if
there is a subsequent transfer of the embryo to a
womans uterus in an attempt to achieve pregnancy,
yet until such transfer is accomplished, it remains
unknown whether research interventions will
enhance or reduce the prospects for healthy life.
Women and couples who either participate in
research or donate gametes or embryos for research
also may be at risk. If a couple decides to donate
excess embryos for research, such as stem cell
extraction, they may be at risk for psychologic
harms such as uncertainty, stress, and anxiety. These
potential hazards are not exclusively related to the
option of donation of embryos for research purposes and may accompany all decisions regarding the
disposition of frozen embryos. When research
requires hormonal stimulation and retrieval of
oocytes separate from plans for pregnancy (ie, tissues obtained or created for research alone), the
oocyte donor faces risks similar to those involved in
oocyte donation for reproductive purposes. It is
essential to ensure that a womans or couples choice
is free of coercion and possible exploitation and that
the woman or couple gives informed consent.
Recognizing such risks, some have expressed
concern regarding the potential to exploit women as
oocyte donors. In part to answer such concerns,
some guidelines such as those proposed by the
National Academy of Sciences recommend no compensation for oocyte donation for research other
than for out-of-pocket expenses (24). Such restrictions, however, seem inappropriate to the ACOG
Committee on Ethics and are inconsistent with policy and practice concerning compensation both to
oocyte donors for reproductive purposes and women
participating in other types of research protocols.
Compensation for oocyte donation for reproductive
purposes is supported by ASRM (25) and is customary in the United States, and there is no strong argument for distinguishing this practice from donation
in the research context. The risks to the woman and
the need to protect against potential abuses are similar in the two situations. Payment to an oocyte
donor should be understood to be compensation for
the womans time, effort, risk, and discomfort and
not as payment for the eggs that may be recovered.
The level of compensation should be consistent with
ASRM guidelines intended to preclude payment lev-
110
els that might be construed as exerting undue influence on the donor (25). In providing advice to those
seeking oocyte donors, ASRM guidelines also highlight the importance of protecting vulnerable populations and providing compensation commensurate
with the time and effort involved.
Who Should Give Permission for Embryos to Be
Used for Research?
Individuals will differ in their beliefs about morality
of and appropriate limits for embryo research. This
is true for individuals or couples creating embryos as
part of infertility treatment and later making decisions regarding frozen embryos, as well as for
gamete donors, who may in some cases be different
from the individuals for whom the embryos were
created (26, 27). In considering the question of who
should give consent for research using preimplantation embryos, it is important to recognize that such
research may occur long after gametes have been
donated and embryos created, and in addition, the
details of future research questions and protocols are
unlikely to be known at the time of donation. In
many cases, of course, those supplying the egg and
sperm will be the same as those for whom the
embryo is created, and these circumstances present
the easiest conditions for obtaining appropriate,
informed consent for research. In such cases, couples may indicate at the time the embryos are frozen
that they would be willing to consider future donation for research, but specific permission needs to be
obtained at the later time when custody is transferred to the research team. If details of the research
protocol are known at the time embryos are frozen,
couples should be so informed. Alternatively, some
couples will be willing to donate unused embryos to
an appropriate party (eg, those operating the laboratory or storage facility) for use in future research
projects as yet unformulated at the time of donation.
If such work includes projects in stem cell research,
this should be specifically discussed and the details
of stem cell research (eg, creation of immortal cell
lines) described insofar as they are known at the time
of donation. If both members of the couple have not
previously given consent at the time custody is transferred, embryos should not be used for research.
If gamete donors are different from those for
whom embryos were created, research should proceed only if gamete donors have been made aware of
the option of embryo research and have given their
consent to such research. Given the emotions and
discussion surrounding stem cell research, potential

research projects should be described as much as
possible. However, gamete donors need to recognize
that the details of future research projects are unlikely to be available at the time of gamete donation, and
therefore donors need to be comfortable consenting
to research that is described only in general terms
(28). Abandoned embryos, as defined by the ASRM
Ethics Committee (29, 30), should not be accepted
for research.
When embryo research is conducted in anticipation of transfer (for example, PGD research), the
intended parents and, if different, the gamete donors
must be provided with adequate information regarding the nature of the research, the risks to the embryo,
and the chances for a successful pregnancy resulting
in the birth of a healthy child, and they must provide
their informed consent (31). If research is to be done
on an embryo that is to be transferred eventually to a
third party (a gestational carriers uterus), this individual also should give informed consent for the
research.
Finally, choices should be made in circumstances free of financial or other coercion. Full information should, therefore, include assurance that
consent to donation of embryos for research is not a
condition for receiving services and that fee scales
are not contingent on consent to research. Moreover,
donors of embryos should understand that they will
receive no compensation for their donation of excess
embryos. The consent process also should cover any
possible identifiers that will be maintained with the
tissue to link it back to the donors, access to current
and future health information from donors, willingness of donors to be contacted in the future, ownership, patent rights, and commercial uses of stem cell
lines that may be developed from the embryo. All
providing consent also should understand that they
may withdraw their consent up to the time that the
donated tissues actually are used in research.
In the scenarios of adults donating gametes for
the creation of embryos solely for research and
adults donating somatic cells for somatic cell
nuclear transfer, special considerations must be
taken into account. The information provided to
donors for embryonic stem cell research must
acknowledge that the process of obtaining the
embryonic stem cell line from the inner cell mass of
the blastocyst will result in the destruction of the
embryo and also should indicate that the derived
stem cell lines may be propagated indefinitely. The
COMMITTEE OPINIONS
consent process also should cover the same elements

as consent obtained when unused embryos are
donated for research. A woman wishing to donate
oocytes for research must be informed of possible
risks to her in the process of controlled ovarian
hyperstimulation and retrieving oocytes, and egg
donor programs should set up medical and psychologic screening procedures in order to safeguard
potential donors.
May Embryos Be Created for Research?
Many cryopreserved embryos exist in the United
States. When such embryos are appropriate to the
questions under investigation and appropriate consent can be obtained, the ACOG Committee on
Ethics recommends that these embryos be the preferred resource for research. Not all frozen embryos
are available or appropriate for research, however,
and frozen embryos may not meet all criteria necessary for some therapeutic applications (32). Investigations of specific genetic defects, for example,
may require specific tissues not available in already
frozen embryos, and any future therapies using stem
cells (eg, somatic cell nuclear transfer) by design
may require that embryos and the derived embryonic stem cells have a genetic profile identical to
the intended recipient. The Committee on Ethics
believes that the promise of somatic cell nuclear
transfer as a technique to create important and
unique stem cell lines is such that research in this
area is justified, a finding consistent with the practices of the United Kingdoms Human Fertilisation
and Embryology Authority (33). Furthermore, the
Committee on Ethics can imagine a future day when
the creation of tissues via somatic cell nuclear transfer to be used in the isolation of human stem cell
lines for therapeutic purposes will be possible and
needed; if so, the Committee on Ethics would consider this process to be ethically appropriate.
Although there are no physical differences
between excess embryos from an IVF therapy and
created-for-research embryos, the moral distinction that many make seems to rest on the intent of
the creation of the embryo, whether for procreation
or research, and the special respect given to human
embryos. An embryo originally created for procreation may be seen to be created for its own sake, as
an end in itself, whereas an embryo created for
research may appear to be a mere means to the
ends of others. For some, the respect given to the
human embryo differentiates the embryo from mere
111
human tissues or cells and necessitates greater obligation to justify valid scientific inquiry. Others judge
that the potential benefits of research for societal
health outweigh any limitations conferred by the
respect due to human embryos, whether they are
excess embryos or created for research.
There is a precedent for creation of embryos for
research purposes. The early work in human IVF by
Edwards and colleagues consisted of fertilizing human oocytes for research in order to study the normality of the zygotes thus created before transfer to
a woman was even considered (34). In 1994, the
NIH Human Embryo Research Panel approved the
creation of IVF embryos for research when the very
nature of the research itself required the fertilization
of oocytes and when a research project deemed to be
exceptionally important required a particular type of
embryo for its validity. Currently, there is little need
for the creation of embryos by fertilization for
research purposes, but in the future the supply of
available tissues, research questions, or therapeutic
paradigms may change. If a compelling need arises,
the question of creating embryos by fertilization for
use in research will need to be addressed carefully.
Does Experimental or Other Use of Stem Cells
Lend Support to Reproductive Cloning?
In the processes involved, associated risks, and
intended outcomes, work involving stem cells and
cloning for biomedical research with the intent of
developing future therapies (eg, somatic cell nuclear
transfer) may clearly be distinguished from reproductive cloning. The former areas of research and
practice involve the isolation and manipulation of
cells from embryos that are not allowed to progress
past the 14-day stage and are not transferred to the
uterus. Because reproductive cloning is designed to
produce a human being, it raises a distinct set of
issues and concerns, and these are not the focus of
this Committee Opinion. The support expressed in
this Committee Opinion for embryo research and
cloning for research purposes does not imply
endorsement of reproductive cloning, which the
Committee on Ethics opposes.
Guidelines
The Committee on Ethics takes the position that
human embryo research can be justified under certain conditions. This position is based on an interpretation of the moral status of the embryo as a
112
living entity with a human genetic code, deserving

of some form of respect in itself and not solely for its
usefulness in research. But this position also recognizes the value of the embryo as relative, in the sense
that it does not require the degree of protection and
absolute respect that is accorded human persons. In
other words, the embryo is humannot simply like
other human tissue (for it is genetically unique and
has human potential)but it also is not a human
person.
Risks of harm to the embryo in research can be
justified, but not without limits. Embryos, for example, should not be subjected to trivial or poorly
designed research programs; if the embryos are designated for transfer to a womans uterus, the goals of
successful pregnancy should be given priority; and
the real and symbolic values of the embryo should
not be negated or trivialized. The Committee on
Ethics recommends the following guidelines for
clinical and laboratory research involving human
embryos.
1. Research will be conducted only by scientifically qualified individuals and in settings that
include appropriate and adequate resources and
protections. The design of the research and each
of its procedures should be clearly formulated in
a research protocol that is submitted to a specially appointed independent committee for evaluation, guidance, and approval.
2. The question to be explored must be scientifically valid; must take into account scientific work
to date, including animal studies; and cannot be
answered through research on animal embryos
or on unfertilized gametes.
3. The information sought should offer potential
scientific and clinical benefit in areas such as
embryonic development, human reproduction,
chromosomal and genetic conditions, or, for
embryonic stem cell lines, potential disease
therapies.
4. The research will be conducted using embryos
at the earliest possible developmental stage of
the embryo, not to exceed 14 days after evidence
of fertilization in any case.
5. Any embryo that has undergone research will be
transferred to a uterus only if the original
research was undertaken to prepare the embryo
for selection or placement or to improve its
chances for implantation and only if specific
consent for transfer is obtained.
6. Intended parents for whom embryos are created

(embryo donors) should be provided with the
opportunity to provide informed consent as to
the disposition of any excess embryos, whether
for eventual destruction, donation for attempted
implantation by another individual or couple, or
scientific research. This presupposes an explicit
policy on the part of the researchers and their
sponsoring institutions that facilitates communication of options and provides for informed
donor choice. If gamete donors differ from the
embryo donors, then embryos may be donated
for research only if the gamete donors also have
given explicit consent for donation for research.
7. Those donating excess frozen embryos for
embryonic stem cell research must be adequately informed of the goals, anticipated benefits,
and potential hazards of the particular research.
Each potential donor is informed that she or he
is at liberty to decline participation in the
research and, until such a point when the tissues
are used or cell lines created, to withdraw consent for research.
8. Other information must be included in informed
consent for donation of embryos for stem cell
research:
Acknowledgment that removal of the inner
cell mass will destroy the embryo
Statement that stem cell lines may continue
indefinitely and be shared with other
researchers
Discussion of potential ownership, patent,
and commercial uses of stem cell lines that
may be developed from the embryo
Information regarding whether any identifiers
will be preserved in the stem cell lines derived
9. For research or therapy involving somatic cell
nuclear transfer, oocyte donors and somatic cell
donors must give informed consent for use of
their eggs or somatic cells. In the rare circumstances in which IVF embryos are created for
research, the gamete donors should provide
informed consent for fertilization for research
purposes. In both cases, informed consent
should include points in guideline 8 and clearly
describe the researchers intention to deliberately create a human embryo for research.
10. Special care must be taken to ensure that potential donors of oocytes for research understand
COMMITTEE OPINIONS
the procedure and its risks. To safeguard donors

as much as possible, medical and psychologic
screening should be required. Although compensation for egg donors for research is acceptable, as it is for donors for infertility treatment,
such compensation should be understood to be
compensation for the womans time, effort, risk,
and discomfort and not as payment for the eggs
that may be recovered. The level of compensation should be consistent with ASRM guidelines
to minimize the possibility of exploitation of
egg donors.
11. Techniques and research designed to clone
human beings raise a different set of ethical concerns. The Committee on Ethics opposes reproductive cloning.
3.
4.
5.
6.
7.
8.
9.
10.
Conclusion
The Committee on Ethics has offered a position that
supports embryo research but limits it according to
ethical guidelines. This position advocates treatment
of the embryo with respect but not the same level of
respect that is given to human persons. It is a position that will not be acceptable to those who believe
that full rights should be extended to early-stage
embryos. In arriving at its position, the Committee
on Ethics considered scientific and clinical information relevant to ethical analysis, although it recognizes that such consideration necessarily involves
both scientific and ethical interpretation of what cannot be simply incontrovertible facts.
The Committee on Ethics once again acknowledges that no single position can encompass the
variety of opinions within the membership of
ACOG, and it affirms that no physician should be
required or expected to participate in embryo
research if he or she finds it morally objectionable.
Nonetheless, it is important to public discourse and
to the practice of responsible medicine that physicians become aware of the medical and ethical
issues involved in the complex areas of embryo
research. To advance this discourse, it is helpful for
physicians to reflect on and share the basis of their
own views and to recognize and explore the ethical
perspectives of their patients and colleagues.
References
1. Definitions. 45 CFR 46.202 (2005).
2. U.S. Department of Health, Education, and Welfare. HEW
support of research involving human in vitro fertilization
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and embryo transfer. Washington, DC: U.S. Government

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Ethical considerations of the new reproductive technologies. Ethics Committee of the American Fertility Society.
Fertil Steril 1986;46(suppl 1):1S94S.
Ethical considerations of the new reproductive technologies. Ethics Committee of The American Fertility
Society. Fertil Steril 1990;53(suppl 2):1S104S.
Ethical considerations of assisted reproductive technologies. Ethics Committee of the American Fertility Society.
Fertil Steril 1994;62(suppl 1):1S125S.
The Balanced Budget Downpayment Act, I, Pub. L. No
10499, 128, 110 Stat. 34 (1996).
National Bioethics Advisory Commission. Ethical issues
in human stem cell research. Rockville (MD): NBAC;
1999.
Radio address by the President to the nation. Available at:
http://www.whitehouse.gov/news/releases/2001/08/print/
20010811-1.html. Retrieved March 9, 2006.
42 U.S.C. 289g-1 (2002).
Lyerly AD, Steinhauser K, Namey E, Tulsky JA, CookDeegan R, Sugarman J, et al. Factors that affect infertility
patients decisions about frozen embryos. Fertil Steril
2006;85:162330.
McCormick RA. Who or what is the preembryo?
Kennedy Inst Ethics J 1991;1:115.
Grobstein C. Becoming an individual. In: Science and the
unborn. New York (NY): Basic Books; 1988. p. 2139.
Ford NM. When did I begin? Conception of the human
individual in history, philosophy, and science. New York
(NY): Cambridge University Press; 1988.
Report from the Select Committee on Stem Cell
Research. House of Lords HL 2002;83(i). Available
at: http://www.publications.parliament.uk/pa/ld200102/
ldselect/ldstem/83/8301.htm. Retrieved June 28, 2006.
King PA. Embryo research: the challenge for public policy. J Med Philos 1997;22:44155.
Kukla H. Embryonic stem cell research: an ethical justification. Georgetown Law J 2002;90:50343.
Green RM. Benefiting from evil: an incipient problem
in human stem cell research. Bioethics 2002;16:54456.
Wilcox AJ, Weinberg CR, OConnor JF, Baird DD,
Schlatterer JP, Canfield RE, et al. Incidence of early loss
of pregnancy. N Engl J Med 1988;319:18994.
Weissman IL. Stem cellsscientific, medical, and political issues. N Engl J Med 2002;346:15769.
Porada GA, Porada C, Zanjani ED. The fetal sheep: a
unique model system for assessing the full differentiative
potential of human stem cells. Yonsei Med J 2004;45:
714.
Kogler G, Sensken S, Airey JA, Trapp T, Muschen M,
Feldhahn N, et al. A new human somatic stem cell from
placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 2004;200:12335.
The Presidents Council on Bioethics. Alternative sources
of human pluripotent stem cells. A white paper of the
Presidents Council on Bioethics. Washington, DC: The
Presidents Council on Bioethics; 2005. Available at:
http://www.bioethics.gov/reports/white_paper/
alternative_sources_white_paper.pdf. Retrieved June 28,
2006.
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23. Wagers AJ, Weissman IL. Plasticity of adult stem cells.

Cell 2004;116:63948.
24. National Research Council; Institute of Medicine.
Recruiting donors and banking hES cells. In: Guidelines
for human embryonic stem cell research. Washington,
DC: The Institute; 2005. p. 8196.
25. Financial incentives for oocyte donors. The Ethics
Committee of the American Society for Reproductive
Medicine. Fertil Steril 2000;74:21620.
26. Kalfoglou AL, Geller G. A follow-up study with oocyte
donors exploring their experiences, knowledge, and attitudes about the use of their oocytes and the outcome of
the donation. Fertil Steril 2000;74:6607.
27. Klock SC, Sheinin S, Kazer RR. The disposition of
unused frozen embryos. N Engl J Med 2001;345:6970.
28. Lo B, Chou V, Cedars MI, Gates E, Taylor RN, Wagner
RM, et al. Informed consent in human oocyte, embryo,
and embryonic stem cell research. Fertil Steril 2004;82:
55963.
29. Donating spare embryos for embryonic stem-cell
research. Ethics Committee of the American Society for
30.
31.
32.
33.
34.
Reproductive Medicine. Fertil Steril 2004;82(suppl 1):

S2247.
Ethics Committee of the American Society for Reproductive Medicine. Disposition of abandoned embryos.
Fertil Steril 2004;82(suppl 1):S253.
Wolf SM, Kahn JP. Bioethics matures: the field faces the
future. Hastings Cent Rep 2005;35(4):224.
Hoffman DI, Zellman GL, Fair CC, Mayer JF, Zeitz JG,
Gibbons WE, et al. Cryopreserved embryos in the United
States and their availability for research. Society for
Assisted Reproduction Technology (SART) and RAND.
Fertil Steril 2003;79:10639.
Human Fertilisation & Embryology Authority. HFEA
grants the first therapeutic cloning licence for research.
Press release. London: HFEA; 2004. Available at:
http://www.hfea.gov.uk/PressOffice/Archive/109223388.
Edwards RG, Steptoe PC. A matter of life: the story of a
medical breakthrough. London: Hutchinson; 1980.
Glossary
*Blastocyst: A preimplantation embryo of approximately
150 cells. The blastocyst consists of a sphere made up of an
outer layer of cells (the trophectoderm), a fluid-filled cavity
(the blastocoel), and a cluster of cells on the interior (the
inner cell mass).
Oocyte: An immature female reproductive cell, one that has

not completed the maturing process to form an ovum
(gamete).
Blastomere: The cells derived from the first and subsequent

cell divisions of the zygote.
Preimplantation embryo: In humans, the developing organism from the time of fertilization until implantation in the
uterus or other tissue (eg, ectopic pregnancy).
*Embryo: In humans, the developing organism from the

time of fertilization until the end of the eighth week of gestation, when it becomes known as a fetus. Other ACOG
guidelines address research involving postimplantation
embryos and fetuses (ie, research during pregnancy).
(American College of Obstetricians and Gynecologists.
Research involving women. In: Ethics in obstetrics and
gynecology. 2nd ed. Washington, DC: ACOG; 2004. p.
8691.)
*Embryonic stem cells: Primitive (undifferentiated) cells
from the embryo that have the potential to become a wide
variety of specialized cell types.
Fertilization: The process whereby male and female
gametes unite.
Gametes: Mature reproductive cells, usually having half the
adult chromosome number (ie, sperm or ovum).
Implantation: Attachment of the blastocyst to the endometrial lining of the uterus and subsequent embedding in the
endometrium. Implantation begins approximately 57 days
after fertilization and may be complete as early as 89 days
after fertilization.
*Inner cell mass: The cluster of cells inside the blastocyst.
These cells give rise to the embryonic disk of the later
embryo and, ultimately, the fetus.
Pluripotent: Able to differentiate into multiple cell and tissue types.
Primitive streak: The initial band of cells from which many

tissue systems, including the neural system of the embryo,
begin to develop, located at the caudal end of the embryonic
disc. The primitive streak is present approximately 15 days
after fertilization and marks the axis along which the spinal
cord develops.
Somatic cell nuclear transfer: The transfer of a cell nucleus from a somatic cell into an egg from which the nucleus
has been removed.
Stem cells: Undifferentiated multipotent precursor cells that
are capable of perpetuating themselves indefinitely and of
differentiating into specialized types of cells.
Totipotent: Able to differentiate into every cell and tissue
type; the capacity of a cell or group of cells to produce all of
the products of conception: the extra-embryonic membrane
and tissue, the embryo, and, subsequently, the fetus.
Zygote: The single cell formed by the union of the male and
female haploid gametes at syngamy.
*Definitions marked with an asterisk are adapted from the National
Institutes of Health glossary, available at: http://stemcells.nih.gov.
COMMITTEE OPINIONS
ACOG
Committee on
Ethics
Reaffirmed 2009
115
Committee
Opinion
Innovative Practice: Ethical

Guidelines

photocopying, recording, or
otherwise, without prior written
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ABSTRACT: Innovations in medical practice are critical to the advancement

of medicine. Good clinicians constantly adapt and modify their clinical
approaches in ways they believe will benefit patients. Innovative practice
frequently is approached very differently from formal research, which is governed by distinct ethical and regulatory frameworks. Although opinions
differ on the distinction between research and innovative practice, the production of generalizable knowledge is one defining characteristic of
research. Physicians considering innovative practice must disclose to
patients the purpose, benefits, and risks of the proposed treatment, including
risks not quantified but plausible. They should attempt an innovative procedure only when familiar with and skilled in its basic components. A clinician
should share results, positive or negative, with colleagues and, when feasible, teach successful techniques and procedures to other physicians.
Practitioners should be wary of adopting innovative procedures or diagnostic tests on the basis of promotions and marketing when the value of the
procedures or tests has not been proved. A practitioner should move an innovative practice into formal research if the innovation represents a significant
departure from standard practice, if the innovation carries unknown or
potentially significant risks, or if the practitioners goal is to use data from
the innovation to produce generalizable knowledge. If there is any question
whether innovative practices should be formalized as research, clinicians
should seek advice from the relevant institutional review board.
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Innovative practice: ethical guidelines.
2006;108:158995.
Overview
In 21st-century medicine, the pace at which innovations are introduced into
clinical practice continues to increase. Many innovations differ considerably
from previous practices and may or may not have been subjected to formal
research protocols. In this context, the boundary between innovative practice
and medical research becomes blurred, making it difficult for physicians to
distinguish between them and to recognize the ethical issues that are
involved.
When innovative practices are introduced, they may become widely
accepted based on anecdotal reports of success. As a result, formal research
116
may never be done that might show 1) that the innovative practice carries higher risk than other treatments or 2) that it is no more effective than standard
treatment. An inappropriate introduction of an innovative practice, circumventing the formal study of
the new technique, leaves patients and practitioners
without the necessary data for appropriately assessing an innovations risks and benefits, as well as its
long-term effects on health.
In this Committee Opinion, the Committee on
Ethics will review efforts to distinguish innovative
practice from research, identify ethical concerns
raised by innovative practice, and note current obstacles to the conduct of formal research. Recommendations will focus on two questions: 1) When does
the clinician have an obligation to subject an innovative practice to formal research? 2) In situations
where innovative practice is not regulated as
research, what special ethical obligations might the
clinician haveto patients, to the community of
medical professionals, and to society at large?
Distinguishing Innovative Practice From

Research
In clinical practice, physicians aim to benefit their
patients by providing the best possible procedures
and treatments. The desire to improve currently
available practices has given an important impetus to
the development of new medical knowledge. The
notion of what is best or most appropriate evolves
with time, ongoing research, and changing individual and societal values. Good clinicians constantly
adapt and modify their clinical approaches in ways
they believe will benefit patients. The introduction of
such innovative interventions is guided primarily by
the judgment of the individual physician, although
professional organizations often advise and monitor.
Formal research, however, is highly regulated in
the United States. Research protocols involving
human participants must be described in detail and
submitted to an institutional review board (IRB) for
approval. Federal regulations mandate that IRBs
approve research protocols in order to ensure adequate disclosure to potential participants, informed
consent from participants, appropriate riskbenefit
ratio, protection of participants privacy, and freedom of participants to withdraw from the study at
any time.
Innovative practice has elements in common
with research including, for example, the desire to
learn and to improve treatment. Yet, innovation in

practice frequently is approached very differently
from formal research, which is governed by distinct
ethical and regulatory frameworks. The federal
research regulations as expressed in the Common
Rule draw a sharp distinction between research, which
is regulated, and innovation, which is not, stressing the
production of generalizable knowledgeknowledge
that can be applied beyond the particular individuals
studiedas the defining characteristic of research
(1). However, the distinction is somewhat artificial
and is not always clearly delineated.
An innovative practice may later become the
subject of a formal research protocol, with the
results of this research then applied to guide evidence-based practice. In some cases, however, innovative practice that appears to be safe and effective
may become accepted practice, even if it has never
been subjected to formal research and an evidence
base has never been developed to support efficacy
and safety. When this happens, patients and practitioners are left without the data they need to make
adequately informed decisions.
Background: History and Evolution of

Terminology
It often is difficult to draw a clear line between innovative practice and research. The history of research
regulation illuminates the effort to clarify the distinction.
The National Commission for the Protection of
Human Subjects, established by federal statute in
1975, developed the Belmont Report in 1978 to
identify the basic ethical principles governing
human research (2). In defining research, the
National Commission first distinguished it from
the practice of accepted therapy. However, examples proposed to the National Commission led it to
recognize that much practice is experimental (a term
the American College of Obstetricians and
Gynecologists Committee on Ethics interprets as
congruent with the term innovative), even though it
is not formalized as research. Should all such experimental practice be treated as research and governed
by the ethical and regulatory guidelines for
research? The National Commission decided
against taking this position and adopted a narrower
definition of research, concluding that research
occurs when the clinician or investigator intends the
work to result in generalizable knowledge (2).
COMMITTEE OPINIONS
According to the National Commission,

Research designates an activity designed to test a
hypothesis, permit conclusions to be drawn, and
thereby to contribute to generalizable knowledge
rather than being designed solely to enhance the
well-being of an individual patient or client (2).
The fact that activities designed to enhance patient
well-being may depart significantly from standard
or accepted practice does not of itself make them
research. However, the National Commission
strongly urged that radically new procedures be
tested by formal research at an early stage and that
medical practice committees insist that new techniques and treatments be submitted to formal
hypothesis testing. The National Commission did
not, however, define radically new, leaving its
definition to the judgment of practitioners.
Federal research regulations in effect since 1981
incorporate these concepts to a limited degree, defining research as follows: Research means a systematic investigation, including research development,
testing and evaluation, designed to develop or contribute to generalizable knowledge (3). The preamble to the regulations as finalized in 1981 explicitly
states that the definition is restricted to generalizable knowledge because the regulations were not
intended to encompass innovative therapy (4).
In March 2003, the Lasker Foundation, a charitable trust established to promote advances in medicine, sponsored the invitational Lasker Forum on
Ethical Challenges in Biomedical Research and
Practice. The forum focused on the intersection of
research and practice and questioned the artificial
separation between what is called research and
therefore requires more regulatory oversight, and
what is called care and requires little or none (5).
The report on the Lasker Forum proposed that clinical innovation involving a significant departure from
standard of care imposes particular moral duties on
the practitioner. In the view expressed at the forum,
a practitioner who attempts through innovation to
benefit an individual patient also is morally obligated to facilitate the development of knowledge useful
to other physicians and patients, thus suggesting an
obligation to conduct research on the innovative
practice.
The Lasker Forum report proposed criteria for
identifying the ethical threshold that mandates moving from innovative practice to formal research. In
this view, the most important criterion is the degree
of departure from standard practice, followed by the
117
potential for harm to the patient from the innovative

practice. Other criteria proposed for consideration
are the goal of the clinician investigator, the availability of organizational structures supportive of
research, and the presence of commercial interests
or conflict of interest (5). These considerations will
be discussed more fully after examination of specific ethical concerns related to the introduction of
innovative practices.
Ethical Concerns Regarding Innovative

Practice
A variety of problems may arise when innovative
practices are inappropriately introduced apart from
formal research protocols. These problems often have
ethical implications related to patient safety, patient
autonomy, and the patients right to effective therapy:
Premature adoption of innovative practices
without adequate supporting evidence may promote wide acceptance of therapies that are
ineffective. Examples of procedures that have
been proved ineffective include:
Bed rest or home uterine activity monitoring
for prevention of prematurity (6, 7)
Bone marrow transplant for breast cancer (8)
Diethylstilbestrol or paternal antigen sensitization for the prevention of recurrent miscarriage
From an ethical perspective, recommending
procedures that are not effective for the intended purpose is misleading to patients, incurs
increased unnecessary costs both financial and
personal, and violates the patients autonomybased right to consent to therapy after accurate
disclosure. In addition, an unproven innovative
treatment may carry additional risks or morbidity in comparison with standard treatment, as in
the case of bone marrow transplant for breast
cancer.
Premature adoption of innovative practices
without formal scientific testing may compromise the ability to determine effectiveness,
weigh risk against benefit, compare the practice
with other procedures, or develop alternative
approaches. When results of an innovative practice are publicized without adequate testing, it
may become increasingly difficult to recruit participants for a clinical trial, particularly one that
118
involves randomization. Such may have been

the case when techniques for maternalfetal
surgery, electronic fetal monitoring, and laparoscopic hysterectomy were first introduced as
innovative and only later systematically studied.
When innovative practices are widely adopted
without formal research testing, an incremental
risk over standard practice may not be recognized, and relative effectiveness, safety, and
riskbenefit ratio may never be determined.
Such a situation may make it difficult or impossible for physicians to know if they are fulfilling
their obligation to provide safe and efficacious
treatment to patients (9).
Long-term safety concerns may result when
innovative practices are widely adopted as standard practice without adequate scientific testing.
Examples in which careful, continued study
after a techniques introduction demonstrated
small but potentially important risks include:
Limb reductions associated with early chorionic villus sampling (10, 11)
Sex chromosome abnormalities associated
with intracytoplasmic sperm injection used in
assisted reproductive technology (ART) (12,
13)
Although innovations in obstetrics and ART
offer important benefits to prospective parents,
they also may carry long-term risks that are not
recognized unless formal research is carried out.
Because of their eagerness to become parents,
infertile couples may be willing to overlook risks
involved in the use of ART. It is the responsibility of practitioners to carry out the studies that
are needed to ensure that patients are offered
effective and safe procedures. Appropriately,
many ART centers and practitioners have participated in the ongoing registries and collaborations needed for this research.
Research Barriers to Be Overcome

Medicine cannot advance without innovation.
Recent examples of highly valuable innovations
include new efficient laparoscopic components that
may improve visualization and new laparoscopic
procedures, such as laparoscopic retroperitoneal
lymph node dissection, that may speed or otherwise
facilitate closed surgical procedures. This could
reduce the need for open procedures that may be

associated with longer or more complicated postoperative recovery. At times, it may be appropriate to
introduce an innovative technique apart from a formal research protocol. However, both the National
Commission for the Protection of Human Subjects
and the National Bioethics Advisory Commission
stipulate that innovations in clinical practice should
be studied under a research protocol as soon as it is
appropriate to study them systematically (2, 14).
A number of barriers to the conduct of formal
research exist, with some of them specific to particular subspecialties:
1. Lack of supportive structures. In many clinical
situations, the structures to facilitate research,
such as administrative support and an IRB, may
be lacking. Even if a particular innovation is ripe
for formalization as research, research may be
difficult to accomplish without the necessary
supportive structures. Bureaucratic obstacles
may be cited as an excuse for not conducting
research; however, such obstacles do not provide valid reasons for failure to conduct appropriate research under ethical guidelines. Rather,
clinicians ought to advocate changes in policy
and collaborative efforts that will provide necessary support for research.
2. Absence of financial reimbursement. In addition
to the lack of supportive structures, financial
pressures may inhibit the pursuit of appropriate
research. Insurance coverage may be available
for treatment that is described as innovative
therapy, but not for formal research. This reimbursement situation played a role in the promotion of the untested procedure of bone marrow
transplant for breast cancer, for example (15).
3. Lack of oversight for surgical innovation and
research. The absence of regulations that specifically govern surgical innovation and research
has frequently been noted. Proposals have been
suggested to ensure oversight of surgical innovation when formal research is not planned, for
example, submission of a written plan to the
department head for referral to an ad hoc committee. This committee would provide peer
review of medical and scientific plausibility,
the adequacy of patient safeguards, and the
legitimacy of [the] clinical rationale (16).
4. Prohibition of federal funding for ART and
embryo research. Because of the statutory pro-
COMMITTEE OPINIONS
hibition of federal funding for in vitro fertilization and early embryo research, most research on
ART is privately funded and is conducted within
the practice of clinical infertility treatment.
Hence, it may be difficult to obtain funding for
some types of research on ART, particularly
basic research.
Clinical Decisions on Moving From

Innovation to Research
The field of medicine could neither progress nor be
practiced without innovative therapy. Given the
importance of formal research for evidence-based
medicine, however, the medical community must
determine when an innovative practice should be
subjected to formal research. If there is any question
whether an innovation should be formalized as
research, it is advisable that the protocol be submitted to an IRB for review. From an ethical standpoint,
the following considerations offer guidance and criteria to the clinician for a decision to move from
innovation to formal research (5):
The degree of departure from standard practice.
As recommended by the Lasker Forum, if innovation constitutes a significant departure from
standard practice, the innovative procedure
should quickly be subjected to a formal research
protocol. Significant departure from standard
practice occurs, for example, in most
maternalfetal surgery and many new ART techniques. However, minor modifications, such as a
change in a step during surgery, a different kind
of suture, or a new instrument similar to an old
one, clearly do not require formalization as
research.
The potential for harm to the patient. When an
innovation carries risks that are unknown or that
may be significant in proportion to expected
benefits, its safety should be assessed through a
formal research protocol with the oversight of
an IRB, one of whose primary purposes is to
protect the welfare of participants. In addition,
formal research is essential in order to identify
long-term risks that may affect the safety of
large numbers of patients in the future.
The intent of the physician. The original intent
in an innovation may be solely the welfare of the
individual patient. If the physician intends, however, to eventually use results of a trial of the
119
innovation to produce generalizable knowledge,

the trial should be formalized in a research protocol. Valid generalizable knowledge ordinarily
requires randomized clinical trials rather than
reliance on case series and unplanned observations (17).
Special Ethical Requirements for

Innovative Practice
Duties to Patients
When patients become participants in a formal
research project, they become protected by the federal regulations for research involving human participants. Even when a particular project does not
strictly fall under federal regulations because it does
not involve federal funding or oversight by the U.S.
Food and Drug Administration, most institutions
still comply with federal standards. Also, reputable
journals require compliance with ethical guidelines
as a condition for publication. Access to results of
clinical trials, even trials with negative outcomes, is
protected by the clinical trials registration process
(1820). Many journals now require evidence that
trials were previously registered before accepting
reports for consideration for publication.
The same protections do not hold for a patient
who is offered innovative therapy. Although the
intent of such innovation is to provide the most beneficial treatment possible for the patient, the patient
may not realize that a therapy is new or experimental. The practitioner has the obligation to disclose
information that would be material to the patients
decision, and in many cases, a patient would want to
know that a proposed therapy is innovative. As with
all therapies, the practitioner has the obligation to
disclose the purpose, benefits, and risks of the proposed innovative treatment, including not quantified
but plausible risks. In addition, the practitioner has a
particular obligation to protect the patient from
potential harms that are not proportionate to expected benefits, a role that the IRB assumes with respect
to formal research protocols. To minimize risk,
physicians also need to consider their own knowledge and skill levels and should attempt an innovative procedure only when familiar with and skilled
in its basic components.
Patient protection requires transparent communication. In the words of the Lasker Forum report,
Where innovation is clearly present, the require-
120
ments for disclosure are likely to become more

pressing (5). It may be important to the patient to
know how often this procedure has been done, what
this particular physicians experience with the procedure is, and what is known and unknown about possible adverse events and long-term sequelae. Care
should be taken that a patient is not unduly influenced to consent to an innovative procedure solely
out of deference to her physician. When the advantages and disadvantages of a truly new approach are
explained to the patient, the assistance of an experienced third-party communicator, such as a patient
representative or social worker, may be helpful (5).
Particular care is needed when discussing proposed
treatments with vulnerable or possibly desperate
patients because they may be eager to pursue innovative but unproven procedures or treatments.
Duties to the Profession and to Society
Innovative practice, unlike research, is not directed
specifically toward the production of generalized
knowledge. Yet, it is expected that innovation would
lead to the improvement of practice in general, not
just the practice of an individual physician. This
expectation imposes two duties on the physician: 1)
to structure the process of innovation so as to learn
from it, even if it is not as successful as hoped, and
2) to share what is learned with the medical community as a whole and, where appropriate, with society.
A clinician should share results, positive or negative,
with colleagues and, when feasible, cooperate in
teaching successful techniques and procedures to
other physicians.
Current focus on clinical trials, especially randomized clinical trials, suggests that they ordinarily
provide the best opportunity for unbiased learning
within the practice of medicine. Consequently, innovative practice should move toward clinical trials
whenever possible in order to provide evidencebased knowledge to the medical community for the
welfare of patients.
Practitioners need to be careful not to adopt
innovative procedures or diagnostic tests on the
basis of promotional and marketing campaigns
when the value of such procedures and tests has not
yet been proved. For example, serum-based screening tests for ovarian cancer have been promoted
even though more research is needed to determine
whether they are effective (21, 22). Similar cautions
apply to off-label and unproven uses of pharmaceuticals that may be suggested to physicians. In all
cases, physicians should rely on documented evidence to guide clinical practice.
Summary
The introduction of innovative practices and techniques is essential to medical progress. Ordinarily,
however, innovations should be subjected to systematic formal research as soon as feasible:
In the absence of formal research, innovative
practices may become widely accepted without
adequate data for assessing risks and benefits.
Without an adequate evidence base, practitioners cannot determine whether an innovative
technique is the most safe and effective method
for treating a patient.
Without adequate data on the risks and benefits
of new treatments, patients are unable to provide
a true informed consent.
A practitioner should move an innovative practice into formal research when one of these criteria
is satisfied:
The innovation represents a significant departure from standard practice.
The innovation carries risks that are unknown or
that may be significant in proportion to expected benefits.
The introduction of the innovation is expected
to result in generalizable knowledge, which depends on results of formal clinical trials.
References
1. Protection of human subjects. 45 CFR 46 (2005).
2. National Commission for the Protection of Human
Subjects. Belmont report: ethical principles and guidelines for the protection of human subjects of research. Fed
Regist 1979;44:231927.
3. Definitions. 45 CFR 46.102 (2005).
4. Final regulations amending basic HHS policy for the
protection of human research subjects. U.S. Department
of Health and Human Services. Fed Regist 1981;46:
836691.
5. Lasker Foundation. The Lasker Forum on Ethical
Challenges in Biomedical Research and Practice, May
1416, 2003. New York (NY): Lasker Foundation; 2003.
Available at: http://www.laskerfoundation.org/ethics/ethics_
report.html. Retrieved June 28, 2006.
6. Sosa C, Althabe F, Belizn J, Bergel E. Bed rest in singleton pregnancies for preventing preterm birth. Cochrane
CD003581. DOI: 10.1002/14651858.CD003581.pub2.
COMMITTEE OPINIONS
7. Assessment of risk factors for preterm birth. ACOG

Practice Bulletin No. 31. American College of Obstetricians
8. Farquhar C, Marjoribanks J, Basser R, Lethaby A. High
dose chemotherapy and autologous bone marrow or stem
cell transplantation versus conventional chemotherapy for
women with early poor prognosis breast cancer. Cochrane
CD003139. DOI: 10.1002/14651858.CD003139.pub2.
9. Mayer M. When clinical trials are compromised: a perspective from a patient advocate. PLoS Med 2005;
2(11):e358. Available at: http://medicine.plosjournals.
org/archive/1549-1676/2/11/pdf/10.1371_journal.pmed.
0020358-L.pdf. Retrieved June 28, 2006.
10. World Health Organization Regional Office for Europe
(WHO/EURO). Risk evaluation of chorionic villus sampling (CVS): report on a meeting. Copenhagen: WHO/
EURO; 1992. (WHO/EURO document EUR/ICP/MCH
123).
11. Kuliev AM, Modell B, Jackson L, Simpson JL, Brambati
B, Froster U, et al. Risk evaluation of CVS. Prenat Diagn
1993;13:197209.
12. Rimm AA, Katayama AC, Diaz M, Katayama KP. A metaanalysis of controlled studies comparing major malformation rates in IVF and ICSI infants with naturally conceived
children. J Assisted Reprod Genet 2004;21:43743.
13. Perinatal risks associated with assisted reproductive technology. ACOG Committee Opinion No. 324. American
College of Obstetricians and Gynecologists. Obstet
Gynecol 2005;106:11436.
121
14. National Bioethics Advisory Commission. Ethical and

policy issues in research involving human participants:
report and recommendations of the National Bioethics
Advisory Commission. Bethesda (MD): NBAC; 2001.
15. Mello MM, Brennan TA. The controversy over high-dose
chemotherapy with autologous bone marrow transplant
for breast cancer. Health Aff (Millwood) 2001;20:10117.
16. Jones JW, McCullough LB, Richman BW. The ethics of
innovative surgical approaches for well-established procedures. J Vasc Surg 2004;40:199201.
17. Horton R. Surgical research or comic opera: questions,
but few answers [letter]. Lancet 1996;347:9845.
18. DeAngelis C, Drazen JM, Frizelle FA, Haug C, Horton R,
Kotzin S, et al. Clinical trial registration: a statement from
the International Committee of Medical Journal Editors.
International Committee of Medical Journal Editors [editorial]. Lancet 2004;364:9112.
19. Mayor S. Drug companies agree to make clinical trial
results public [news]. BMJ 2005;330:109.
20. DeAngelis C, Drazen JM, Frizelle FA, Haug C, Hoey J,
Horton R, et al. Is this clinical trial fully registered? A
statement from the International Committee of Medical
Journal Editors. Ann Intern Med 2005;143:1468.
21. American College of Obstetricians and Gynecologists,
Committee on Gynecologic Practice. Position regarding
OvaCheckTM, February 25, 2005.
22. Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro
VA, Steinberg SM, et al. Use of proteomic patterns in
serum to identify ovarian cancer. Lancet 2002;359:5727.
122

Number 358 January 2007
Professional Responsibilities in
ObstetricGynecologic Education*
Committee on Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Physicians must learn new skills in a manner consistent with their ethical obligations to benefit the patient, to do no harm, and to respect a patients right to
make informed decisions. Patients should be given the opportunity to consent to or
refuse treatment by students. Students must hold in confidence any information they
learn about patients. The relationship between teacher and student involves an imbalance
of power and the risk of exploitation of a student for the benefit of the teacher. Students
should not be placed in situations where they must provide care or perform procedures
for which they are not qualified and not adequately supervised. Students have the obligation to be honest, conscientious, and respectful in their relationships with their teachers.
They should act in ways that preserve the dignity of patients and do not undermine relationships between patients and their physicians. If a student observes unethical behavior
or incompetent conduct by a teacher, the appropriate institutional authority should be
informed. Institutions have an obligation to provide a work environment that enhances
professional competence by ensuring that students and residents work reasonable hours,
helping them balance education and patient care responsibilities; providing adequate support services; and, in the case of residents, providing reasonable salaries and benefits.
With increasing numbers of women in education programs, special attention must be
given to the parallel demands of pregnancy and career goals.
Education of health care professionals is

essential to maintain standards of competent
and beneficial practice. Inherent in the education of health professionals is the problem
of disparity in power and authority, including the power of teachers over students and
the power of practitioners over patients (1).
It is therefore important to clarify both the
professional responsibilities to those patients
whose care provides educational opportunities and the responsibilities of teachers and
students toward one another. Students in the
context of this Committee Opinion include

both medical students and residents. However, residents have a dual responsibility as
teacher and student and must be aware of
that in understanding their ethical responsibilities to the students they teach and the
patients they care for.
*Update of ObstetricGynecologic Education, in Ethics

in Obstetrics and Gynecology, Second Edition, 2004.
As commonly categorized by medical schools, residencies, and postgraduate fellowships, the learning and teaching roles of student and teacher represent a hierarchical approach to learning that does not reflect the reality of
lifelong learning and teaching. The line between students
and teachers in medicine is fluid and nonlinear. All clinicians learn from and teach each other at each point in
the development of their profession. In this statement,
the ethical obligations of teachers apply to all of those in
the teaching role, wherever they may be in the educational continuum, and the obligations of students apply
to all of those in the learning role.
Ethical Responsibilities Toward

Patients in Educational Settings
At the turn of the 20th century, some medical
educators were concerned about the needs of
COMMITTEE OPINIONS
patients in teaching hospitals, and they took steps to

ensure that patients rights would be protected. However,
the prevailing opinion was more aptly characterized by a
medical school faculty member: Patients must clearly
understand from the beginning that they are admitted for
teaching purposes and that they are to be willing to submit to this when pronounced physically fit (2). Unfortunately, this sentiment persists as an unstated presumption
in some contemporary education programs. If the power
inherent in the role of medical practitioner is misused in
the educational setting, this misuse is likely to carry over
into attitudes and relationships with future patients as
well.
If health care professionals are to benefit society, they
must be well educated and experienced. Acquisition of
knowledge and skills in the educational process entails
both benefits and risks. The benefits of health care to
society provide the justification for exposure of patients
to risks associated with education in clinical medicine.
Although the benefits generally accrue to society at large,
the burdens fall primarily on individual patients, especially the economically disadvantaged. These burdens are
inherent in situations in which patients interact with students, for example, during medical history taking, physical examinations, and diagnostic and surgical procedures.
Physicians must learn new skills and techniques in a
manner consistent with the ethical obligations to benefit
the patient, to do no harm, and to respect a patients right
to make informed decisions about health matters. These
obligations must not be unjustifiably subordinated to
the need and desire to learn new skills. In consideration
of societys interest in the education of physicians, all
patients should be considered teaching patients. Race or
socioeconomic status should not be the basis for selection
of patients for teaching.
Although patients are given the opportunity to consent to or refuse treatment by students, the obligations of
the profession, the institution, and patients should be
made more uniform and explicit. Professional obligations
include disclosure of the risks and benefits inherent in the
teaching setting and provision of adequate supervision at
all levels of training. The patient should be encouraged to
participate in the teaching process to contribute her fair
share to the development of a new generation of health
care providers. A situation may arise in which a patient
refuses, for whatever reason, to have a student involved in
her health care. Such refusals should initiate discussion
and counseling. Patient choice, however, must be handled
with compassion and respect.
Some procedures, such as pelvic examinations,
require specific consent (3). If any pelvic examination
planned for an anesthetized woman undergoing surgery
offers her no personal benefit and is performed solely for
teaching purposes, it should be performed only with her
specific informed consent, obtained when she has full
decision-making capacity.
123
Participation by anesthetized women in teaching

exercises may be less common today than in the past.
Alternatives to this training method exist that do not raise
the challenges of securing informed consent. Today, many
medical schools employ surrogates for patients to teach
students how to perform pelvic examinations. These surrogates are variously referred to as gynecology teaching
associates, professional patients, patient surrogates, standardized patients, or patient simulators. It is acknowledged, however, that in women preparing for surgery, the
administration of anesthesia results in increased relaxation of the pelvic muscles, which may be beneficial in
some educational contexts. Improvements in technology
continue to allow for increased training in the virtual setting for residents and medical students. Specifically, technology has allowed surgical training using laparoscopic
and hysteroscopic surgery simulation and has improved
resident education in these areas.
Finally, students as well as residents must hold in
confidence any information about patients learned in the
context of a professional relationship. They should discuss specific patient care matters only in appropriate settings, such as teaching conferences or patient care rounds.
Conversations in public places, such as hospital corridors
or elevators, involving comments about patients, their
families, or the care they are receiving are inappropriate
(4). Furthermore, as medical records are increasingly kept
in electronic form, it is important to ensure patient privacy and security of information in accordance with the
Health Insurance Portability and Accountability Act of
1996 (HIPAA) regulations.
Ethical Responsibilities of Teachers

to Students
The relationship between teacher and student in medical
education inevitably involves the problem of imbalance
of power and the risk of exploitation of a student for the
benefit of the teacher (1). The teacherstudent relationship exists at multiple levels among faculty members,
medical students, attending physicians, fellows, and residents. Complex as it may be, there is a fundamental ethical responsibility at all levels for the teacher to impart
wisdom, experience, and skill for the benefit of the student, without expectation of personal service by or
reward from the student. Because so much of medicine
is learned in a preceptorstudent relationship, great care
must be taken that the teacher does not exploit the student. An example is the teacher who expects a student to
spend time that is out of proportion to the educational
value involved on a research project, but gives little or no
credit for such a contribution. In this regard, the behavior
of teachers toward students is a powerful example of
ethics in action. Students are likely to model their behavior on that of their teachers (5).
The relationship of a teacher to a student involves
not only trust and confidence but also power and depen-
124
dency. It is the role of the teacher to foster independence

in the student while nurturing the student in the learning
process. This is a complex relationship, the boundaries of
which can become obscured in the intense setting of a
clinical preceptorship (6). For example, the long hours
spent by teachers and students in relatively arduous and
isolated circumstances may foster amorous relationships.
Regardless of the situation, the power imbalance makes a
romantic or sexual relationship between a teacher and
student ethically suspect. Amorous relationships between
teachers and their current students are never appropriate.
Students should not be placed in situations where
they must provide care or perform procedures for which
they are not qualified and not adequately supervised. To
do otherwise violates an ethical responsibility to the student as well as to the patient. A healthy relationship
between teachers and students allows students to request
assistance or supervision without fear of humiliation or
retribution. Teaching should take place in an atmosphere
that fosters mutual respect.
Conduct and Responsibilities of

Students Toward Their Teachers
Students have the obligation to be honest, conscientious,
and respectful in their relationships with their teachers.
They should act in ways that preserve the dignity of
patients and do not undermine relationships between
patients and their physicians. It is the students responsibility to ask for assistance and supervision when it is
needed. Unfettered communication between student and
teacher is essential in fostering an atmosphere that will
allow, even encourage, students to request help. When
such communication does not occur, both education and
patient care suffer.
Inherent in the teacherstudent relationship is the
vulnerability of the student in dealing with perceived unethical behavior or incompetent conduct of a teacher. If
a student observes such behavior or conduct, the matter
should be brought to the attention of the appropriate institutional authority. Mechanisms that are nonjudgmental
and without penalty should be clearly defined to encourage an open dialogue about these observed behaviors.
Institutional Responsibilities
Institutions have ethical obligations to students, patients,
and teachers, including an obligation to provide a work
environment that enhances professional competence. The
health care system often has exploited students at all levels of education. Students may be viewed as a source of
cheap labor, especially in busy hospitals on a teaching service. Students often provide long hours of service, and the
resultant neglect of the students physical and mental
health must be balanced against the provision of an effective clinical experience. Lack of sleep, heavy workloads,
and increasing amounts of responsibility without commensurate levels of authority are sources of great stress in
medical education, especially during residency (79). The

potentially negative impact of such an educational experience on the students developing attitude toward patients
and the profession should be considered. The obligation
to provide a good work environment includes ensuring
that students and residents work reasonable hours, establishing a balance between medical education and responsibility for patient care, providing adequate ancillary and
administrative support services, and, in the case of residents, providing reasonable salaries and benefits (10).
A source of substantial stress for some students and
residents is the conflict between family responsibilities
and the demands of medical education (11). For many
students, sleep deprivation caused by long work hours
results in fatigue, irritability, and anxiety. The inability to
relate with consideration or affection to a partner or
spouse or to participate in any effective way with child
care or other domestic responsibilities may seriously
impair family relationships. Also, with increasing numbers of women in education programs, special attention
must be given to the parallel demands of pregnancy
(including the postpartum period) and career goals.
Providing ample time for all residents to sustain family
relationships without adversely affecting the educational
experience or imposing excessive burdens on colleagues
is a daunting task, but one that must be confronted.
Shared positions and more flexible timelines for completing educational requirements can be helpful in solving
such problems.
Institutions should maintain a well-established reporting and review process for investigating allegations
of unethical behavior or incompetent conduct. Access
to such a process can facilitate fair and just relationships
between students and teachers in these precarious situations.
As concerns about cost containment increase, education could become a low priority. The process of medical
education may reduce the efficiency of patient care and
increase costs. It is the responsibility of all physicians and
institutions involved in the education of health care professionals to ensure that cost-reduction efforts do not
diminish the opportunities for education in clinical medicine. Institutions have an ethical responsibility to develop policy statements and guidelines for the inclusion of
students in patient care in ways that ensure sound medical education and high-quality medical care.
Summary
The effective education of students, residents, interns, fellows, and other professionals is essential if the health care
professions are to benefit society. The power and authority inherent in relationships between students and
patients as well as between teachers and students are
important ethical concerns. Power and authority should
be exercised responsibly to protect patients dignity and
welfare and to enhance the educational process.
COMMITTEE OPINIONS
Respect for autonomy requires that patients be

informed about the extent to which students at any level
are involved in their care and that patients concerns be
addressed. Students should provide only that level of care
for which they are qualified and adequately supervised.
Working conditions and work schedules should reflect
sensitivity for student welfare in its broadest terms. This
attention to ethics will promote attitudes conducive to the
compassionate and skilled treatment of patients. This
emphasis also should serve as a model for the next generation of teachers.
References
1. Brody H. Medical ethics and power. In: The healers power.
New Haven (CT): Yale University Press; 1992. p. 1225.
2. Ludmerer KM. The rise of the teaching hospital. In:
Learning to heal: the development of American medical
education. New York (NY): Basic Books Inc; 1985. p. 21933.
3. Ubel PA, Jepson C, Silver-Isenstadt A. Dont ask, dont tell:
a change in medical student attitudes after obstetrics/gynecology clerkships toward seeking consent for pelvic examinations on an anesthetized patient. Am J Obstet Gynecol
2003;188:5759.
4. Ubel PA, Zell MM, Miller DJ, Fischer GS, Peters-Stefani D,
Arnold RM. Elevator talk: observational study of inappropriate comments in a public space. Am J Med 1995;99:
1904.
5. Bosk CL. Forgive and remember: managing medical failure.
2nd ed. Chicago (IL): University of Chicago Press; 2003.
6. Plaut SM. Boundary issues in teacher-student relationships. J Sex Marital Ther 1993;19:2109.
7. Butterfield PS. The stress of residency. A review of the literature. Arch Intern Med 1988;148:142835.
125
8. Stress and impairment during residency training: strategies

for reduction, identification, and management. Resident
Services Committee, Association of Program Directors in
Internal Medicine. Ann Intern Med 1988;109:15461.
9. McCall TB. The impact of long working hours on resident
physicians. N Engl J Med 1988;318:7758.
10. Asch DA, Parker RM. The Libby Zion case. One step forward or two steps backward? N Engl J Med 1988;318:
7715.
11. Green MJ. What (if anything) is wrong with residency
overwork? Ann Intern Med 1995;123:5127.
Bibliography
American Medical Association. Medical student involvement in
patient care. In: Code of medical ethics: current opinions with
annotations. Chicago (IL): AMA; 2006. p. 234.
American Medical Association. Resident physicians involvement in patient care. In: Code of medical ethics: current opinions with annotations. Chicago (IL): AMA; 2006. p. 235.
Copyright January 2007 by the American College of Obstetricians

transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission
from the publisher. Requests for authorization to make photocopies
should be directed to: Copyright Clearance Center, 222 Rosewood
Drive, Danvers, MA 01923, (978) 750-8400
Professional responsibilities in obstetricgynecologic education. ACOG
ISSN 1074-861X
126

Commercial Enterprises in Medical Practice*

Committee on Ethics
Reaffirmed 2008

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Increasing numbers of physicians sell and promote both medical and
nonmedical products as part of their practices. Physicians always have rendered advice
and treatment for a fee, and this practice is appropriate. It is unethical under most circumstances, however, for physicians to sell or promote medical or nonmedical products or
services for their financial benefit. The following activities are considered unethical: sale
of prescription drugs to be used at home, sale or promotion of nonprescription medicine,
sale or promotion of presumptively therapeutic agents that generally are not accepted as
part of standard medical practice, sale or promotion of nonhealth-related items, recruitment of patients or other health care professionals into multilevel marketing arrangements, and sale or promotion of any product in whose sale the physician has a significant
financial interest. It is ethical and appropriate, however, to sell products to patients as follows: sale of devices or drugs that require professional administration in the office setting; sale of therapeutic agents, when no other facilities can provide them at reasonable
convenience and at reasonable cost; sale of products that clearly are external to the
patientphysician relationship, when such a sale would be considered appropriate in an
external relationship; and sale of low-cost products for the benefit of community organizations. A rationale is provided for both the prohibited activities and exceptions.
Increasing financial pressures and the pervasiveness of entrepreneurial values in our society have led to an increase in the scope of
activities for which physicians have sought
reimbursement. As a result, increasing numbers of physicians sell and promote both
medical and nonmedical products as part of
their practices.
Physicians always have rendered advice
and treatment for a fee, and this practice is
appropriate; however, the sale and promotion of products for financial benefit is qualitatively different from these traditional
activities. It is unethical under most circumstances for physicians to sell or promote
medical or nonmedical products or services
for their financial benefit. In this Committee
Opinion, the American College of Obste*Update of Commercial Enterprises in Medical
Practice, in Ethics in Obstetrics and Gynecology, Second
Edition, 2004.
tricians and Gynecologists Committee on

Ethics examines the following issues:
The scope of the inappropriate activities
The reasons for their unacceptability
The limited circumstances under which
they may be acceptable
Recommendations
Sale or promotion of products by physicians
to their patients is unethical, with some
exceptions, in either clinical sites or other
places. This is true whether the sale is conducted in person, by telephone, or by written
solicitation. The following activities are considered unethical, subject to the exceptions
outlined later in the discussion:
Sale of prescription drugs to be used at
home (For example, some commercial
drug repackagers prepare these medi-
COMMITTEE OPINIONS
cines in standard doses and provide them to physicians, who then resell them to patients [1].)
Sale or promotion of nonprescription medicine
Sale or promotion of presumptively therapeutic agents
that generally are not accepted as part of standard
medical practice
Sale or promotion of nonhealth-related items, such
as household supplies (2)
Recruitment of patients or other health care professionals into multilevel marketing arrangements
(These are enterprises in which individuals recruit
other individuals to sell products and receive a commission on sales by their recruits. These recruits, in
turn, can recruit a third generation of marketers,
whose commissions are shared with participants of
earlier generations.)
Sale or promotion of any product in whose sale the
physician has a significant financial interest, even if
the sale would otherwise be appropriate (Such financial interest includes, among other things, sale for a
direct profit or sale of a product when the physician
holds a substantial equity interest in the products
manufacturer or wholesaler [3].)
Exceptions
It is ethical and appropriate for physicians to sell products
to patients in the following circumstances:
Sale of devices or drugs that require professional
administration in the office setting (Under these circumstances, the charge for the product should not
exceed the costs, which may include both the direct
cost of the product and the overhead incurred in
obtaining, storing, and administering it.)
Sale of therapeutic agents, when no other facilities
can provide them at reasonable convenience and at
reasonable cost (This circumstance might occur in a
thinly populated area or in a locality in which certain
forms of reproductive control are unpopular. If
physicians sell such products, the price charged
should not exceed the cost of the product, including
both direct and overhead costs.)
Sale of products that clearly are external to the
patientphysician relationship, when such a sale
ordinarily would be considered appropriate in the
context of an external relationship (An example of
such a transaction is a brokered house sale at a fair
market price.)
Sale of low-cost products for the benefit of community organizations (An example of such a product is
Girl Scout cookies. These products must be sold
without pressure, and the physician must not derive
a profit from such sales.)
127
Rationale
There have been arguments given to support the sale in
physicians offices of drugs and other products related to
the treatment of patients (1). One is conveniencea busy
patient need not go to a pharmacy. Another, although not
borne out by empirical studies, is that increasing the
number of dispensers of drugs reduces the cost of drugs
(1). Finally, it is possible that adherence to treatment is
improved if the patient purchases the drug from the
physician.
Under most circumstances, however, the sale of
products by physicians violates several generally accepted
principles of medical ethics. First, and most important,
the practice of physician sales to patients creates a potential conflict of interest with the physicians fiduciary
responsibility to provide a right and good healing action
taken in the interests of a particular patient (4). This
principle of fidelity is defined as the obligation of physicians to put the interests of patients above their own.
Physicians must not engage in actions that violate or
call into question their fiduciary relationship with
patients. The term conflict of interest refers to circumstances in which this commitment to the fiduciary relationship is compromised. Conflict of interest contains two
elements: 1) an individual with an obligation, fiduciary or
otherwise, and 2) the presence of conflicting interests that
may undermine fulfillment of the obligation (5).
The American Medical Association and other professional societies have long opposed practices that result in
conflicts of interest. The associations Council on Ethical
and Judicial Affairs (CEJA) states that as professionals,
physicians are expected to devote their energy, attention
and loyalty fully to the service of their patients (6). Many
statements issued by CEJA and other American Medical
Association bodies have condemned various practices
resulting in conflict of interest. These related improper
commercial practices include fee splitting (payment by or
to a physician solely for the referral of a patient), physician self-referral, physician ownership of pharmacies, and
selling medical products (7). They have condemned
physician ownership of stock in laboratories that pay
physicians in proportion to the amount of work they refer
and have disapproved of rebates from optical or medical
instrumentation companies (5, 8).
Referral by physicians to health care facilities, such as
laboratories, in which they do not engage in professional
activities but in which they have a financial interest is
called self-referral. This practice is analogous to product
sales in that physicians are deriving a profit from goods
(eg, laboratory tests or drugs) that they did not produce.
Both of these practices create a clear conflict of interest
because referring physicians accept money from vendors
to direct patients to use their products or services instead
of alternative products or services (including the option
of no treatment at all). The conflict, therefore, is between
128
the financial advantage that accrues from physicians sales

or referrals and physicians obligation to arrange the best
possible ancillary and consultative services for their
patients. For example, CEJA states that self-referral to
outside facilities is ethical only if there is a demonstrated
need in the community for the facility and alternative
financing is not available (6). In these circumstances, the
practice is considered ethical only if referring physicians
meet certain requirements designed to ensure that they
receive no more financial consideration than would an
ordinary investor and that certain safeguards are taken to
avoid exploitation of patients.
Several other cardinal principles are violated by the
practice of sales by physicians. The principle of truthfulness is violated if a conflict of interest related to the sale
exists and is not communicated to the patient.
The principle of nonmaleficence is violated when
there is a potential for injury to patients, which could
occur in several ways. Physicians may be tempted to sell to
patients items that they do not need. Even if its use is
appropriate, the product in question may not be the most
suitable for given patients. For example, joint ventures in
radiation oncology (ie, those in which referring physicians had a financial interest) were found to provide more
frequent and more intense use of radiation therapy than
did freestanding facilities, without increased benefit (9).
Another principle that may be violated by this practice is that of respect for autonomy. A patient might prefer comparing various alternatives when purchasing
products. If the product is offered by the physician on
whom she depends for advice and treatment, she could
feel constrained to accept the physicians product. She
may feel coercion to comply with treatments with which
she does not agree. If the product is not health related,
patients might feel constrained to purchase goods they do
not want (8).
Finally, this practice violates the principles of professionalism and professional solidarity by weakening public
trust in the profession. As CEJA has stated, The medical
professions ability to preserve autonomy and the nature
of the physicianpatient relationship during periods of
transformation have succeeded in large part due to the
professions lack of tolerance for commercialism in medicine (6).
Conclusion
The sale or promotion of products by physicians to their
patients rarely is ethical. Exceptions have been described
in this Committee Opinion. Practitioners of obstetrics

and gynecology should not engage in commercial
arrangements that result in real, apparent, or potential
conflicts of interest.
References
1. James DN. Selling drugs in the physicians office: a problem
of medical ethics. Bus Prof Ethics J 1992;11:7388.
2. Rice B. Whats a doctor doing selling Amway? Med Econ
1997;74(13):7982, 856, 88.
3. Responsibility of applicants for promoting objectivity in
research for which PHS funding is sought. 42 C.F.R. 50
Subpart F (2005).
4. Pellegrino ED, Thomasma DC. A philosophical reconstruction of medical morality. In: A philosophical basis of
medical practice: toward a philosophy and ethic of the
healing professions. New York (NY): Oxford University
Press; 1981. p. 192220.
5. Rodwin MA. The organized American medical professions
response to financial conflicts of interest: 18901992.
Milbank Q 1992;70:70341.
6. Conflicts of interest. Physician ownership of medical facilities. Council on Ethical and Judicial Affairs, American
Medical Association. JAMA 1992;267:23669.
7. American Medical Association. Sale of health-related products from physicians offices. In: Code of medical ethics of
the American Medical Association: current opinions with
annotations. Chicago (IL): AMA; 2006. p. 2256.
8. Sale of non-health-related goods from physicians offices.
Council on Ethical and Judicial Affairs, American Medical
Association. JAMA 1998;280:563.
9. Mitchell JM, Sunshine JH. Consequences of physicians
ownership of health care facilitiesjoint ventures in radiation therapy. N Engl J Med 1992;327:1497501.

Drive, Danvers, MA 01923, (978) 750-8400
Commercial enterprises in medical practice. ACOG Committee Opinion
No. 359. American College of Obstetricians and Gynecologists. Obstet
Gynecol 2007;109:2435.
ISSN 1074-861X
COMMITTEE OPINIONS
129

Number 360 February 2007
Sex Selection*
Committee on Ethics
Reaffirmed 2008

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: In this Committee Opinion, the American College of Obstetricians and

Gynecologists Committee on Ethics presents various ethical considerations and arguments relevant to both prefertilization and postfertilization techniques for sex selection.
The principal medical indication for sex selection is known or suspected risk of sex-linked
genetic disorders. Other reasons sex selection is requested are personal, social, or cultural in nature. The Committee on Ethics supports the practice of offering patients procedures for the purpose of preventing serious sex-linked genetic diseases. However, the
committee opposes meeting requests for sex selection for personal and family reasons,
including family balancing, because of the concern that such requests may ultimately
support sexist practices. Because a patient is entitled to obtain personal medical information, including information about the sex of her fetus, it will sometimes be impossible for
health care professionals to avoid unwitting participation in sex selection.
Sex selection is the practice of using medical

techniques to choose the sex of offspring.
Patients may request sex selection for a number of reasons. Medical indications include the
prevention of sex-linked genetic disorders. In
addition, there are a variety of social, economic, cultural, and personal reasons for selecting
the sex of children. In cultures in which males
are more highly valued than females, sex selection has been practiced to ensure that offspring will be male. A couple who has one or
more children of one sex may request sex
selection for family balancing, that is, to have
a child of the other sex.
Currently, reliable techniques for selecting sex are limited to postfertilization
methods. Postfertilization methods include
techniques used during pregnancy as well as
techniques used in assisted reproduction
before the transfer of embryos created in
vitro. Attention also has focused on preconception techniques, particularly flow cytometry separation of X-bearing and Y-bearing
spermatozoa before intrauterine insemination or in vitro fertilization (IVF).
*Update of Sex Selection, in Ethics in Obstetrics and
Gynecology, Second Edition, 2004.
In this Committee Opinion, the American College of Obstetricians and Gynecologists Committee on Ethics presents various
ethical considerations and arguments relevant
to both prefertilization and postfertilization
techniques for sex selection. It also provides
recommendations for health care professionals who may be asked to participate in sex
selection.
Indications
The principal medical indication for sex selection is known or suspected risk of sex-linked
genetic disorders. For example, 50% of males
born to women who carry the gene for hemophilia will have this condition. By identifying
the sex of the preimplantation embryo or fetus,
a woman can learn whether or not the 50%
risk of hemophilia applies, and she can receive
appropriate prenatal counseling. To ensure that
surviving offspring will not have this condition, some women at risk for transmitting
hemophilia choose to abort male fetuses or
choose not to transfer male embryos. Where
the marker or gene for a sex-linked genetic disorder is known, selection on the basis of direct
identification of affected embryos or fetuses,
130
rather than on the basis of sex, is possible. Direct identification has the advantage of avoiding the possibility of aborting
an unaffected fetus or deciding not to transfer unaffected
embryos. Despite the increased ability to identify genes and
markers, in certain situations, sex determination is the only
current method of identifying embryos or fetuses potentially
affected with sex-linked disorders.
Inevitably, identification of sex occurs whenever
karyotyping is performed. When medical indications for
genetic karyotyping do not require information about sex
chromosomes, the prospective parent(s) may elect not to
be told the sex of the fetus.
Other reasons sex selection is requested are personal,
social, or cultural in nature. For example, the prospective
parent(s) may prefer that an only or first-born child be of
a certain sex or may desire a balance of sexes in the completed family.
Methods
A variety of techniques are available for sex identification
and selection. These include techniques used before fertilization, after fertilization but before embryo transfer and,
most frequently, after implantation.
Prefertilization
Techniques for sex selection before fertilization include
timing sexual intercourse and using various methods for
separating X-bearing and Y-bearing sperm (15). No current technique for prefertilization sex selection has been
shown to be reliable. Recent attention, however, has
focused on flow cytometry separation of X-bearing and
Y-bearing spermatozoa as a method of enriching sperm
populations for insemination. This technique allows
heavier X-bearing sperm to be separated; therefore, selection of females alone may be achieved with increased
probability (3). More research is needed to determine
whether any of these techniques can be endorsed in terms
of reliability or safety.
Postfertilization and Pretransfer
Assisted reproductive technologies, such as IVF, make
possible biopsy of one or more cells from a developing
embryo at the cleavage or blastocyst stage (6).
Fluorescence in situ hybridization can be used for analysis of chromosomes and sex selection. Embryos of the
undesired sex can be discarded or frozen.
Postimplantation
After implantation of a fertilized egg, karyotyping of fetal
cells will provide information about fetal sex. This presents patients with the option of terminating pregnancies
for the purpose of sex selection.
Ethical Positions of Other Organizations

Many organizations have issued statements concerning
the ethics of health care provider participation in sex
selection. The ethics committee of the American Society

for Reproductive Medicine maintains that the use of preconception sex selection by preimplantation genetic diagnosis for nonmedical reasons is ethically problematic
and should be discouraged (7). However, it issued a
statement in 2001 that if prefertilization techniques, particularly flow cytometry for sperm sorting, were demonstrated to be safe and efficacious, these techniques would
be ethically permissible for family balancing (8). Because
a preimplantation genetic diagnosis is physically more
burdensome and necessarily involves the destruction and
discarding of embryos, it was not considered similarly
permissible for family balancing (9).
The Programme of Action adopted by the United
Nations International Conference on Population and
Development opposed the use of sex selection techniques
for any nonmedical reason (10). The United Nations
urges governments of all nations to take necessary measures to prevent . . . prenatal sex selection.
The International Federation of Gynecology and
Obstetrics rejects sex selection when it is used as a tool for
sex discrimination. It supports preconception sex selection when it is used to avoid sex-linked genetic disorders
(11).
The United Kingdoms Human Fertilisation and
Embryology Authority Code of Practice on preimplantation genetic diagnosis states that centres may not use any
information derived from tests on an embryo, or any
material removed from it or from the gametes that produced it, to select embryos of a particular sex for nonmedical reasons (12).
Discussion
Medical Testing Not Expressly for the Purpose
of Sex Selection
Health care providers may participate unknowingly in sex
selection when information about the sex of a fetus
results from a medical procedure performed for some
other purpose. For example, when a procedure is done to
rule out medical disorders in the fetus, the sex of a fetus
may become known and may be used for sex selection
without the health care providers knowledge.
The American College of Obstetricians and Gynecologists Committee on Ethics maintains that when a
medical procedure is done for a purpose other than
obtaining information about the sex of a fetus but will
reveal the fetuss sex, this information should not be withheld from the pregnant woman who requests it. This is
because this information legally and ethically belongs to
the patient. As a consequence, it might be difficult for
health care providers to avoid the possibility of unwittingly participating in sex selection. To minimize the possibility that they will unknowingly participate in sex
selection, physicians should foster open communication
with patients aimed at clarifying patients goals. Although
COMMITTEE OPINIONS
health care providers may not ethically withhold medical

information from patients who request it, they are not
obligated to perform an abortion, or other medical procedure, to select fetal sex.
Medical Testing Expressly for the Purpose
of Sex Selection
With regard to medical procedures performed for the
express purpose of selecting the sex of a fetus, the following four potential ethical positions are outlined to facilitate discussion:
Position 1: Never participate in sex selection. Health care
providers may never choose to perform medical procedures with the intended purpose of
sex selection.
Position 2: Participate in sex selection when medically
indicated. Health care providers may choose
to perform medical procedures with the
intended purpose of preventing sex-linked
genetic disorders.
Position 3: Participate in sex selection for medical indications and for the purpose of family balancing. Health care providers may choose to
perform medical procedures for sex selection
when the patient has at least one child and
desires a child of the other sex.
Position 4: Participate in sex selection whenever requested. Health care providers may choose to perform medical procedures for the purpose of
sex selection whenever the patient requests
such procedures.
The committee shares the concern expressed by the
United Nations and the International Federation of
Gynecology and Obstetrics that sex selection can be motivated by and reinforce the devaluation of women. The
committee supports the ethical principle of equality
between the sexes.
The committee rejects, as too restrictive, the position
that sex selection techniques are always unethical (position 1). The committee supports, as ethically permissible,
the practice of sex selection to prevent serious sex-linked
genetic disorders (position 2). However, the increasing
availability of testing for specific gene mutations is likely
to make selection based on sex alone unnecessary in many
of these cases. For example, it supports offering patients
using assisted reproductive techniques the option of
preimplantation genetic diagnosis for identification of
male sex chromosomes if patients are at risk for transmitting Duchennes muscular dystrophy. This position is
consistent with the stance of equality between the sexes
because it does not imply that the sex of a child itself
makes that child more or less valuable.
Some argue that sex selection techniques can be ethically justified when used to achieve a balance in a family in which all current children are the same sex and a
131
child of the opposite sex is desired (position 3). To achieve

this goal, couples may request 1) sperm sorting by flow
cytometry to enhance the probability of achieving a pregnancy of a particular sex, although these techniques are
considered experimental; 2) transferring only embryos of
one sex in assisted reproduction after embryo biopsy and
preimplantation genetic diagnosis; 3) reducing, on the
basis of sex, the number of fetuses in a multifetal pregnancy; or 4) aborting fetuses that are not of the desired sex. In
these situations, individual parents may consistently judge
sex selection to be an important personal or family goal
and, at the same time, reject the idea that children of one
sex are inherently more valuable than children of another
sex.
Although this stance is, in principle, consistent with
the principle of equality between the sexes, it nonetheless
raises ethical concerns. First, it often is impossible to
ascertain patients true motives for requesting sex selection procedures. For example, patients who want to abort
female fetuses because they value male offspring more
than female offspring would be unlikely to espouse such
beliefs openly if they thought this would lead physicians
to deny their requests. Second, even when sex selection is
requested for nonsexist reasons, the very idea of preferring a child of a particular sex may be interpreted as condoning sexist values and, hence, create a climate in which
sex discrimination can more easily flourish. Even preconception techniques of sex selection may encourage such a
climate. The use of flow cytometry is experimental, and
preliminary reports indicate that achievement of a female
fetus is not guaranteed. Misconception about the accuracy of this evolving technology coupled with a strong preference for a child of a particular sex may lead couples to
terminate a pregnancy of the undesired sex.
The committee concludes that use of sex selection
techniques for family balancing violates the norm of
equality between the sexes; moreover, this ethical objection arises regardless of the timing of selection (ie, preconception or postconception) or the stage of development
of the embryo or fetus.
The committee rejects the position that sex selection
should be performed on demand (position 4) because this
position may reflect and encourage sex discrimination. In
most societies where sex selection is widely practiced,
families prefer male offspring. Although this preference
sometimes has an economic rationale, such as the financial
support or physical labor male offspring traditionally provide or the financial liability associated with female offspring, it also reflects the belief that males are inherently
more valuable than females. Where systematic preferences
for a particular sex dominate (13, 14), there is a need to
address underlying inequalities between the sexes.
Summary
The committee has sought to assist physicians and other
health care providers facing requests from patients for sex
132
selection by calling attention to relevant ethical considerations, affirming the value of equality between the sexes,
and emphasizing that individual health care providers are
never ethically required to participate in sex selection.
The committee accepts, as ethically permissible, the practice of sex selection to prevent sex-linked genetic disorders. The committee opposes meeting other requests for
sex selection, such as the belief that offspring of a certain
sex are inherently more valuable. The committee opposes
meeting requests for sex selection for personal and family reasons, including family balancing, because of the
concern that such requests may ultimately support sexist
practices.
Medical techniques intended for other purposes have
the potential for being used by patients for sex selection
without the health care providers knowledge or consent.
Because a patient is entitled to obtain personal medical
information, including information about the sex of her
fetus, it will sometimes be impossible for health care
professionals to avoid unwitting participation in sex
selection.
References
1. Gray RH. Natural family planning and sex selection: fact or
fiction? Am J Obstet Gynecol 1991;165:19824.
2. Check JH, Kastoff D. A prospective study to evaluate the
efficacy of modified swim-up preparation for male sex
selection. Hum Reprod 1993;8:2114.
3. Fugger EF, Black SH, Keyvanfar K, Schulman JD. Births of
normal daughters after MicroSort sperm separation and
intrauterine insemination, in-vitro fertilization, or intracytoplasmic sperm injection. Hum Reprod 1998;13:236770.
4. Michelmann HW, Gratz G, Hinney B. X-Y sperm selection: fact or fiction? Hum Reprod Genet Ethics 2000;
6:328.
5. Schulman JD, Karabinus DS. Scientific aspects of preconception gender selection. Reprod Biomed Online 2005;10
(suppl 1):1115.
6. Sermon K, Van Steirteghem A, Liebaers I. Preimplantation
genetic diagnosis. Lancet 2004;363:163341.
7. Sex selection and preimplantation genetic diagnosis. Ethics

Medicine. Fertil Steril 2004;82 (suppl):S2458.
8. Preconception gender selection for nonmedical reasons.
Ethics Committee of the American Society for Reproductive Medicine. Fertil Steril 2004;82(suppl):S2325.
9. Robertson J. Sex selection: final word from the ASRM
Ethics Committee on the use of PGD [news]. Hastings
Cent Rep 2002;32(2):6.
10. United Nations. Gender equality, equity and empowerment of women. In: Population and development: programme of action adopted at the International Conference
on Population and Development, Cairo, 513 September
1994. New York (NY): UN; 1995. p. 1721.
11. Ethical guidelines on sex selection for non-medical purposes. FIGO Committee for the Ethical Aspects of Human
Reproduction and Womens Health. Int J Gynaecol Obstet
2006;92:32930.
12. Human Fertilisation and Embryology Authority. Code of
practice. 6th ed. London: HFEA; 2003.
13. Jha P, Kumar R, Vasa P, Dhingra N, Thiruchelvam D,
Moinedin R. Low female [corrected]-to-male [corrected]
sex ratio of children born in India: national survey of 1.1
million households [published erratum appears in Lancet
2006;367:1730]. Lancet 2006;367:2118.
14. Hesketh T, Lu L, Xing ZW. The effect of Chinas one-child
family policy after 25 years. N Engl J Med 2005;353:11716.
Copyright February 2007 by the American College of Obstetricians

Rosewood Drive, Danvers, MA 01923, (978) 750-8400
Sex selection. ACOG Committee Opinion No. 360. American College
of Obstetricians and Gynecologists. Obstet Gynecol 2007;109:4758.
ISSN 1074-861X
COMMITTEE OPINIONS
133

Number 362 March 2007
Medical Futility*
Committee on Ethics
Reaffirmed 2008

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: The construct of medical futility has been used to justify a physicians
unilateral refusal to provide treatment requested or demanded by a patient or the family
of a patient. It is important that physicians and their institutions develop a process for
dealing with conflict surrounding the construct of medical futility. Prospective policies on
medical futility are preferable to unilateral decision making by individual physicians. When
there is disagreement, patient and family values regarding treatment options and the
default position of maintaining life ordinarily should take priority.
A proliferation in medical technology has

dramatically increased the number of diagnostic and therapeutic options available in
patient care. Health care costs also have
increased as a byproduct of this technologic
expansion. Simultaneously, medical ethics
has undergone a rapid metamorphosis from
a beneficence-focused ethic to one in which
autonomy dominates: that is, from an ethic
in which the physician attempted to determine what was in the patients best interest
and then acted on behalf of the patient to an
ethic in which alternatives are presented to
the patient and the patient makes the ultimate decision. Thus, both the physician and
the patient may face the daunting task of
selecting from among myriad highly technologic and expensive health care choices.
These choices, among other factors,
have created situations in which patients or
families have sometimes demanded care that
physicians may deem futile, or incapable of
producing a desired result. The construct of
medical futility has been used to justify a
physicians unilateral refusal to provide
treatment requested or demanded by a
patient or the family of a patient. Such decisions may be based on the physicians perception of the inability of treatment to
achieve a physiologic goal, to attain other
*Update of Medical Futility, in Ethics in Obstetrics and
goals of the patient or family, or to achieve a

reasonable quality of life.
Although there is general agreement
with the notion that physicians are not obligated to provide futile care (1), there is
vigorous debate and little agreement on the
definition of futile care, the appropriate
determinants of each component of the
definition, and on whose values should
determine the definition of futility. Proposed
definitions of medical futility include one or
more of the following elements:
The patient has a lethal diagnosis or
prognosis of imminent death.
Evidence exists that the suggested therapy cannot achieve its physiologic goal.
Evidence exists that the suggested therapy will not or cannot achieve the
patients or familys stated goals.
Evidence exists that the suggested therapy will not or cannot extend the
patients life span.
Evidence exists that the suggested therapy will not or cannot enhance the
patients quality of life.
The following questions need to be addressed
concerning each of the previously identified
elements:
What is imminent death? Is it death that
is expected within hours or days, or
134
would it include death expected at any time up to

6 months or longer?
At what point can a therapy be defined as unable to
achieve a physiologic goal? Is futility reached when
the goal could never be achieved or when the goal
could be achieved in less than 1% of the cases, in 5%
of the cases, or within some other established limit?
What defines when a therapy can no longer achieve
the patients or familys goals, and who should decide
this?
What constitutes an enhanced life span1 day, 1
week, 1 month?
How is quality of life measured, and who should
determine what constitutes a satisfactory quality of
life for a given patient?
What these definitions have in common is an assessment of whether a particular therapy will be effective (ie,
that it might alter the course of the disease or symptoms
of the patient), whether it offers any benefit to the patient,
and whether it adds to the burdens suffered by the patient
(2). It is important to note that the concept of futility does
not apply exclusively to situations in which a patient has
a terminal illness, but can apply to any clinical situation in
which a proposed treatment offers virtually no chance of
achieving a desired result. For example, futility would be
a sufficient reason to refuse in vitro fertilization treatments to a couple who wishes to use their own gametes
when the female partner is older than 50 years and has a
markedly elevated follicle-stimulating hormone level (3).
Disagreements will sometimes occur between stakeholders in the decision about whether a therapy will be
considered futile or not. These disagreements may concern the definition of futility or whether the conditions to
establish futility have been met. These differences frequently arise because one party places a different value on
one possible outcome of the therapy than the other party.
For example, a patient may judge that even one more
day of life is worth a therapeutic attempt or that living in
a coma is more desirable than death, while a physician
caring for that patient may feel differently. Physicians or
society may be less willing to provide the requested care
as they balance the use of resources and their individual
or collective view of the potential for and degree of benefit. Patients may not include the use of resources in their
equation at all but simply balance negative side effects
and risks against the likelihood and degree of a beneficial
outcome. Society may be more likely to accede to patient
wishes when the use of resources is minimal than when it
is significant, regardless of the likelihood of achieving
physiologic goals, increasing life span, or achieving
patient goals. Reasonableness and equity in the distribution of resources may play a role in determining whether
societal and institutional values should prevail in contested decisions. When resource distribution is an issue, however, the values of the patient and the preservation of life
ordinarily take priority and are ethical default positions.
Ultimately, these are differences of value, with individuals

placing different values on the likelihood of a good outcome, different assessments of what would constitute an
acceptable outcome, and different views about how much
effort and expense can be justified in the pursuit of an
unlikely outcome. Consensus is most likely in situations
where the likelihood of achieving an outcome that anyone
would consider valuable is very low. One suggestion has
been that most physicians could agree that something was
futile if it had not worked in the previous 100 similar
cases (4).
Litigation also has generally resulted in courts supporting the views of patient or family in cases in which
patient and caregiver disagree regarding withholding
care, at least when withholding or withdrawing a medical
treatment would likely result in the death of the patient
(59). Commentators have observed that court decisions
in favor of patient or family wishes appear to be based on
one of the following factors:
Medicines inability to quantify the likelihood of
futility with certainty
The lack of a prospective and clearly stated process
for determining medical futility
The courts current bias toward autonomy
A desire to be consistent in upholding the patients
rights whether the patient is refusing or requesting
treatment
Recognition that withdrawal of life-sustaining care
would likely result in the death of the patient
Need for a Medical Futility Policy

Inability to achieve a physiologic goalstrict physiologic
futilityis an appropriate basis for a physician to refuse
to provide requested therapeutic intervention. However,
the ability to declare strict physiologic futility with certainty exists in only a limited number of clinical situations in which there are conflicts about whether to
continue a therapy.
Other interpretations of medical futility are too subjective to form the basis for unilateral physician decisions.
Therefore, in the absence of strict physiologic futility, the
construct of medical futility should be applied only
according to a prospective organizational policy that provides a process rather than a rule for resolving conflict.
The preferred approach for resolving all disputes
about whether a particular therapy should be offered or
continued should first be communication between the
patient and the physician. This conversation should focus
on reasonable goals of treatment, with emphasis on
whether the therapy in question can, in fact, achieve the
therapeutic goals set by the patient and physician (10).
The discussion should focus on specific clinical problems,
goals, and therapies rather than on whether the family
wants everything done, which represents a meaningless
and misleading request or offer. If resolution cannot be
COMMITTEE OPINIONS
achieved through providerpatient communication, an

ethics consultant or ethics committee should be involved
to assist in the resolution of the dispute.
A policy can be valuable in those situations in which
the probability of reaching a physiologic goal or the
potential for enhancement of lifes duration or quality is
remote and there is disparity in the subjective interpretations by patient (family), physician, institution, and society regarding the cost (economic, physical, emotional)
versus benefit ratio. A medical futility policy should
emphasize communication and negotiation rather than
unilateral physician decision making.
Designing a Medical Futility Policy

A medical futility policy should be built on the following
foundations:
It should be designed to enhance discussion among
the parties.
The responsible physician should be encouraged to
involve all appropriate members of the treatment
team (eg, house staff, nurses, and social workers) to
help reach an agreement between the patient (or surrogate), the physician, and other members of the
health care team.
It should be designed to seek input from other individuals or groups with expertise in the relevant
medical discipline or medical ethics (including
clergy, attorneys, and ethics committees).
It should include some formal institutional mechanism for conflict resolution, such as ethics consultation or an ethics committee that ensures a thorough
review of the institution and provides a fair hearing
for all stakeholders.
It should allow a patient to select another caregiver
whose view is more consistent with her own and
facilitate transfer of care, without prejudice, by the
original physician.
If transfer of care is arranged, all ongoing, life-sustaining treatment and interventions must be continued while the transfer is awaited.
If no conciliation of views or patient transfer occurs,
or if no other caregiver or facility is willing to provide the desired treatment, the caregivers are not
required to provide care that they regard as medically futile.
There must be some process of appeal as the situation comes closer to action by the physician or facility that is still contested by the patient or family.
When caregivers refuse to provide a futile intervention or abrogate a certain aspect of treatment on the
basis of its futility, their obligation to provide care is
undiminished. Providing comfort care and palliative
care and maximizing quality of life at the end of life
remain fundamental obligations of the physician
responsible for a patients care.
135
The policy should require documentation that

includes the following information:
Probable diagnoses
Probable prognosis
Physician-recommended alternatives
Patient-desired pathway
Process of decision making that was followed,
including notes from relevant meetings
An example of a policy that provides a process for
decision making in medical futility is outlined in the
American Medical Association Council on Ethical and
Judicial Affairs report, "Medical Futility in End-of-Life
Care" (1) (see http://jama.ama-assn.org/cgi/reprint/281/
10/937 for a decision tree). Other institutions have published their policies (11), and at least one state (Texas) provides a law that outlines the conditions under which a
treatment team or institution can unilaterally withhold or
withdraw a therapy that has been deemed futile. These
conditions include 1) notifying the patient or the person
responsible for the health care decisions of the patient in
writing about the hospitals policy on ethics consultation,
2) providing the patient or responsible person with 48hour notice of consultation and inviting him or her to participate in the consultation, and 3) providing the patient or
responsible person with a written report of the ethics
review process.
Under Texas law, when the ethics consultation
process fails to resolve the dispute, the hospital must work
with the patient or responsible person to try to arrange
transfer to an institution or physician that will provide
the disputed therapy. If no provider can be found after 10
days, the therapy can be unilaterally withheld or withdrawn. A judicial appeal for an extension beyond 10 days
can be made by the patient or responsible person, but it
can be granted only if the judge determines there is a reasonable likelihood of finding a provider willing to provide
the disputed treatment. When these conditions are met,
the treatment team and institution receive immunity
from civil or criminal prosecution (12).
Summary
It is difficult to define medical futility prospectively and
objectively. Nonetheless, as technology continues to
advance and use more resources, it is important that
physicians and their institutions develop a process for
dealing with conflict surrounding the construct of medical
futility.
Prospective policies on medical futility are preferable
to unilateral decision making by individual physicians.
Such a medical futility policy should provide a systematic
process for dealing with disagreements, for ensuring that
all parties have received a fair hearing, and for reaching a
fair resolution, as outlined previously. When there is disagreement, patient and family values regarding treatment
options and the default position of maintaining life ordi-
136
narily should take priority. However, situations may occur

in which claims of reasonableness and equity in the distribution of resources are so powerful that the views of caregivers, the institution, and society will prevail.
References
1. Medical futility in end-of-life care: report of the Council on
Ethical and Judicial Affairs. JAMA 1999;281:93741.
2. Pellegrino ED. Decisions at the end of lifethe abuse of the
concept of futility. Pract Bioethics 2005;1(3):36.
3. Fertility treatment when the prognosis is very poor or futile.
Ethics Committee of the American Society for
Reproductive Medicine. Fertil Steril 2004;82:80610.
4. Schneiderman LJ, Jecker NS, Jonsen AR. Medical futility: its
meaning and ethical implications. Ann Intern Med
1990;112:94954.
5. Capron AM. In re Helga Wanglie. Hastings Cent Rep 1991;
21(5):268.
6. Capron AM. Abandoning a waning life. Hastings Cent Rep
1995;25(4):246.
7. Angell M. The case of Helga Wanglie. A new kind of right
to die case [editorial]. N Engl J Med 1991;325:5112.
8. Miles SH. Informed demand for non-beneficial medical
treatment. N Engl J Med 1991;325:5125.
9. Diekema DS. What is left of futility? The convergence of
anencephaly and the Emergency Medical Treatment and
Active Labor Act. Arch Pediatr Adolesc Med 1995;
149:11569.
10. Berg JW, Appelbaum PS, Lidz CW, Parker LS. The role of
informed consent in medical decision making. In:
Informed consent: legal theory and clinical practice. 2nd ed.
New York (NY): Oxford University Press; 2001. p. 16787.
11. Singer PA, Barker G, Bowman KW, Harrison C, Kernerman
P, Kopelow J, et al. Hospital policy on appropriate use of
life-sustaining treatment. University of Toronto Joint
Centre for Bioethics/Critical Care Medicine Program Task
Force. Crit Care Med 2001;29:18791.
12. Advance Directives Act. Tex. Health and Safety. 166 (1999).
Available at: www.capitol.state.tx.us/statutes/docs/HS/content/
htm/hs.002.00.000166.00.htm. Retrieved July 28, 2006.
Copyright March 2007 by the American College of Obstetricians

Medical futility. ACOG Committee Opinion No. 362. American College
ISSN 1074-861X
COMMITTEE OPINIONS
137

Number 363 April 2007
Patient Testing: Ethical Issues in Selection

and Counseling*
Committee on Ethics
Reaffirmed 2009

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Recommendations to patients about testing should be based on current medical knowledge, a concern for the patients best interests, and mutual consultation. In addition to establishing a diagnosis, testing provides opportunities to educate,
inform, and advise. The ethical principles of respect for autonomy (patient choice) and
beneficence (concern for the patients best interests) should guide the testing, counseling, and reporting process. Clear and ample communication fosters trust, facilitates
access to services, and improves the quality of medical care.
In the practice of medicine, clinical evaluation is enhanced by a broad range of tests.

Recommendations to patients about testing
should be based on current medical knowledge, a concern for the patients best interests,
and mutual consultation. Patient testing
embodies many scientific and human
ideals. From an ethical perspective, the most
important principles involve a trusting
patientphysician relationship emphasizing
beneficence (the benefits the patient may
derive from testing) and respect for autonomy (an appreciation that patients make
choices about their medical care). Issues of
nonmaleficence (using tests when the consequences of the test are uncertain) and justice
(applying tests to low-risk groups) also may
be important (1).
Rapid technologic development and the
need to consider legal and sociocultural factors as well as medical knowledge have
increased the complexity of the decisionmaking process. The physician often is in
the position of ordering testsfor human
immunodeficiency virus (HIV) or genetic
markers, for examplethat may, unlike a
urinalysis or a hemogram, have a profound
effect on the patient, her partner, her fam*Update of Patient Testing, in Ethics in Obstetrics and
ily, and society in general. This new level of

complexity requires the specification of
both medical and ethical guidelines for
decisions about patient testing. This Committee Opinion provides ethical guidance for
decisions about ordering tests, counseling
patients, and reporting results.
Ordering Tests
The physician and the patient have a
shared responsibility. The quality of medical care improves when there is clear
communication and mutual understanding between physician and patient.
It is the responsibility of the obstetriciangynecologist to communicate effectively and to develop skills that promote
a patientphysician relationship that is
characterized by trust and honesty.
Similarly, it is the responsibility of the
patient to provide accurate information
about her lifestyle, health habits, sexual
practices, and religious and cultural
beliefs when these factors may affect
medical judgment. In decisions about
testing, physicians should be guided by
scientific knowledge. Care must be taken
to avoid subjective assumptions based
on bias that could affect the appropriateness of testing (2).
138
Testing should be performed primarily for the benefit

of the patient. Testing at the request of third parties
partners, health care providers, members of the patients
extended family, employers, or health insurersis
justifiable only when the patient or her valid proxy
understands the potential risks and benefits and gives
consent (3). Examples of this type of testing include
genetic tests to assist family members with reproductive decisions, HIV tests to fulfill conditions for the
purchase of life insurance, and requests for patient
testing after the occupational exposure of health care
workers.
The decision to offer or to withhold a test should not
be made solely on the basis of a physicians assumptions about the patients expected response to test
results (4). Prejudgments about a patients wishes
regarding fetal abnormalities, for example, should
not preclude her being offered prenatal testing. The
patient should join with the physician in deciding the
amount of diagnostic information that is appropriate for making intelligent choices about preventive
care and treatment options. The physician is not,
however, ethically obligated to perform every test a
patient requests, particularly if disease prevalence
and risk factors are low, generating a high false-positive risk.
The patient must be informed prospectively about
policies regarding use of information and legal
requirements. The patient must be told what will be
communicated, to whom, and the potential implications of reporting the information. If, for example, a
patient is concerned about posting HIV test results in
the medical record and who may have access to the
results, she may choose instead to use an anonymous
testing procedure available through another laboratory. In some situations, reporting of results is mandated by law. Physicians should be familiar with the
laws regarding mandatory testing and reporting
requirements in their own jurisdictions.
The physician and patient should discuss concerns
about cost containment and reimbursement. The
mutual goal of physician and patient should be to
avoid both undertesting and overtesting. Contemporary focus on the economics of health care has created worries for both physician and patient about
access to care, limitations to testing, appropriateness
of use, and the impact of financial constraints on
quality of care. Testing done with low probability of
improving patient diagnosis or testing solely for the
sake of professional liability concerns should be
avoided. Open communication about cost concerns
and perceived benefit is the best way to alleviate suspicion and to promote trust.
Pretest and Posttest Counseling

Testing that may have multiple medical or psychosocial consequences requires specific counseling. The
extent of counseling beneficial to each patient will
vary depending on the individual and on the implications inherent in the potential test results. With
simple tests like urinalysis, it is sufficient to provide
information about the nature and purpose of the test
and how the results will guide management. Tests
that may have multiple medical or psychosocial
ramifications require comprehensive explanation of
the process, the goals, and the implications (4).
Counseling can be appropriate for genetic testing
and maternal toxicology assays, for example, because
of the potential for psychologic, social, and economic effects. Tests with low positive predictive value,
such as cervical cytology and mammography, can
generate the need for additional and more extensive
testing. Testing for HIV or inherited breast cancer
mutations may limit future insurance coverage.
In some cases, the potential benefitsincluding societal
benefitsof certain tests may lead some to recommend
alternative schemes for counseling and consent in order
to maximize the rate of testing. The U.S. Centers for
Disease Control and Prevention, ACOG, and the
American Academy of Pediatrics have endorsed an
opt-out protocol with patient notification for
prenatal HIV testing (57). The use of patient notification provides women the opportunity to decline
testing but eliminates the requirement to obtain specific informed consent.
Autonomy of the individual in shared decision making
should always be respected. It is essential in the
informed consent process that subsequent election of
the patient to forgo a recommended intervention
(informed refusal) be carefully documented in the
patients medical record along with the patients reason for refusal. Both pretest and posttest counseling
facilitate womens access to appropriate health care.
Pretest counseling includes both medical considerations and issues such as the availability of emotional
support while waiting for test results. Posttest counseling offers an opportunity to provide access to
resource networks and community-based services.
Referral may be needed for comprehensive counseling.
If time constraints or lack of technical expertise
make it difficult to offer comprehensive counseling
in a particular practice, appropriate options include
either 1) referral to a specialized center for both
counseling and testing, or 2) referral for counseling
only, with return to the original physician for testing
and medical follow-up.
COMMITTEE OPINIONS
Confidentiality and the Reporting

of Test Results
Information ordinarily may not be revealed without
the patients express consent. Physicians have an
obligation to be familiar with federal privacy protection legislation (Health Insurance Portability and
Accountability Act) (8). Guidance is provided here
for the ethical duty to maintain confidentiality.
Maintaining confidentiality is intrinsic to respect for
patient autonomy and permits the free exchange of
information that is relevant to medical decision
making. Situations may arise, however, in which a
physician has competing obligations: protecting the
patients confidentiality or disclosing test results to
prevent harm to a third party. In these situations,
every avenue of communication should be explored
first in discussions with the patient about rights and
responsibilities. Consultation with an institutional
ethics committee or a medical ethics specialist may
be helpful in weighing benefits and harms of disclosure. Legal advice may be prudent.
A violation of confidentiality may be ethically justified
as a last resort. A violation of confidentiality may be
justifiable only when legally required or when all of
the following conditions have been met: 1) there is a
high probability of harm to a third party, 2) the
potential harm is a serious one, 3) the information
communicated can be used to prevent harm, and 4)
greater good will result from breaking confidentiality
than from maintaining it. Case law has not yet been
developed to address the grey area where, on rare
occasions, legal obligations to protect patient confidentiality and ethical and professional obligations to
act for the benefit of the patient may conflict.
Conclusion
In addition to establishing a diagnosis, testing provides
opportunities to educate, inform, and advise. The ethical
principles of respect for autonomy (patient choice) and
beneficence (concern for the patients best interests)
should guide the testing, counseling, and reporting
139
process. Clear and ample communication fosters trust,

facilitates access to services, and improves the quality of
medical care.
References
1. Beauchamp TL, Childress JF. Priniciples of biomedical
ethics. 5th ed. New York (NY): Oxford University Press;
2001.
2. Malm HM. Medical screening and the value of early detection. When unwarranted faith leads to unethical recommendations. Hastings Cent Rep 1999;29:2637.
3. Offit K, Groeger E, Turner S, Wadsworth EA, Weiser MA.
The duty to warn a patients family members about
hereditary disease risks. JAMA 2004;292:146973.
4. McGowan R. Beyond the disorder: one parents reflection
on genetic counselling. J Med Ethics 1999;25:1959.
5. Prenatal and perinatal human immunodeficiency virus
testing: expanded recommendations. ACOG Committee
6. Revised recommendations for HIV screening of pregnant
women. Centers for Disease Control and Prevention.
MMWR Recomm Rep 2001;50(RR-19):6385; quiz CE119a2CE6-19a2.
7. American Academy of Pediatrics, American College of
Obstetricians and Gynecologists. Joint statement on
human immunodeficiency virus screening. ACOG
Statement of Policy 75. Elk Grove Village (IL): AAP; 2005;
HIPAA privacy manual. 2nd ed. Washington, DC: ACOG;
2003.
Copyright April 2007 by the American College of Obstetricians and
Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC
20090-6920. All rights reserved. No part of this publication may be
Drive, Danvers, MA 01923, (978) 750-8400
Patient testing: ethical issues in selection and counseling. ACOG
ISSN 1074-861X
140

Number 364 May 2007
Committees on
Ethics and Genetics
Reaffirmed 2009
emerging scientific advances as of the date issued
and is subject to change.
The information should not
be construed as dictating
an exclusive course of
treatment or procedure to
be followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Patents, Medicine, and the Interests of

Patients*
ABSTRACT: Many basic scientists and clinicians support the right to obtain and
enforce patents on drugs, diagnostic tests, medical devices, and most recently, genes.
Although those who develop useful drugs, diagnostic and screening tests, and medical
technologies have the right to expect a fair return for their efforts and risks, current interpretations of patent law have the potential to impede rather than promote scientific and
medical advances. Policies regarding the patenting of scientific inventions, discoveries,
and improvements must balance the need for the open exchange and use of information
with the need to make the pursuit of such knowledge financially rewarding.
New technologies and the translation of

research discoveries into clinical medicine are
essential for improvements in patient care.
The increasing commercialization of medical
discoveries, however, may hamper the dissemination of new knowledge and the ability
of physicians and patients to benefit from
applications of this knowledge. Many basic
scientists and clinicians support the right to
obtain and enforce patents on drugs, diagnostic tests, medical devices, and most
recently, genes. Some primarily are concerned with recovering the costs they incur in
developing new treatments and technologies.
Others see patents in medicine as a legitimate
means, within a society based on the principle of free enterprise, of protecting and
enhancing intellectual capital.
Such patent protections may be regarded
as necessary incentives for the development
of new tests and treatments. Also, they may
limit the ability of clinicians, patients, and
researchers to obtain the right to use these
discoveries commercially under reasonable
conditions and at an affordable price.
Furthermore, the issue of gene patenting
*Update of Patents, Medicine, and the Interests of
Patients in Ethics in Obstetrics and Gynecology, Second
Edition, 2004.
poses unique challenges to knowledge development and academic collaboration because

a gene sequence, unlike previous technical
advances, is both a tool for pursuing scientific knowledge and the basis for any diagnostic
or therapeutic application.
Patent Protections
The U.S. Patent and Trademark Office (PTO)
is guided by federal statutes, regulations, and
case law in granting patents. Patent protection
is intended to promote research and discovery
and to act as a stimulus to progress in science
and the useful arts. The PTO evaluates an
application for a U.S. patent to determine
whether the claimed invention satisfies the following three conditions: the invention is a 1)
new and 2)useful discovery or improvement that is 3)not obvious to individuals
with ordinary skill in the art (1, 2). In evaluating patent applications, the PTO also assesses
whether the specification adequately describes
the invention and enables the skilled artisan to
make and use it. A patent is granted for an
invention that meets the three conditions and
other requirements, such as being patentable
subject matter. For example, products of
nature can be patented if they are in an isolated form that does not occur in nature.
COMMITTEE OPINIONS
Patents that may affect the practice of medicine fall

into four categories: 1) patents on medical and surgical
procedures, 2) patents on surgical or diagnostic instruments, 3) patents on drugs, and 4) patents on genes and
gene-based diagnostic or predictive tests. All of these
types of patents raise ethical issues and may create conflicts of interest for physicians who contribute to the
development of new products through research. The
commercial potential of medical discoveries may motivate physicians to increase their own incomes in ways that
may jeopardize the care of patients. Academic and
research physicians may be offered incentives by their
institutions to maximize the institutions extramural revenues through patent arrangements that restrict use by
other researchers and, thus, act as barriers to further
research discoveries.
Patenting Medical and Surgical Procedures
Historically, physicians have taught and shared medical
information without regarding this knowledge as trade
secrets to be protected from others. Physicians have a fundamental obligation to provide advice to their patients
about the most appropriate care, without being influenced by any profit they might gain through associated
commercial ventures. Open communication of information gained from research and experience with medical
and surgical procedures is essential if safety and efficacy
are to be validated or refuted by colleagues. It is through
further scientific work by ones peers that diagnostic
methodologies and medical procedures are either validated, refined, and improved or discarded as ineffective or
unhelpful.
Some corporate or individual business arrangementsincluding the patenting and licensing of medical
and surgical procedurescan be adverse to the welfare of
patients. These arrangements present barriers to the
availability of the protected procedures to other physicians and patients. Moreover, they may inhibit new
research that might otherwise be stimulated by open
access to information about the procedures. Investigational use of patented procedures is permitted under the
experimental use doctrine, which allows a patented
invention to be used in a manner that does not interfere
with the economic interests of the patent holder (ie, used
with no commercial intentions).
For these reasons, the enforceability of patents covering medical and surgical procedures has been challenged,
both ethically and legally. The American Medical
Association asserts that it is unethical for physicians to
seek, secure or enforce patents on medical procedures
because such practices may limit the availability of new
procedures to patients (3). In the 1996 case Pallin v Singer,
Dr. Pallin was prohibited from enforcing his patent claims
on a particular type of incision used in cataract surgery
(4). As a result of this case, Congress enacted a 1996
statute making patents of medical or surgical procedures
unenforceable (5). In the United States, medical and sur-
141
gical procedures are still patentable, but patent claims are

not enforceable against a medical practitioner unless the
practitioner uses a patented pharmaceutical, medical
device, or biotechnology process. Thus, the U.S. legal system provides some support for the traditional ethic of
physicians to share their knowledge and the use of
advances in medical and surgical procedures. Other
countries view the patentability of medical procedures
differently than the United States. For instance, the
European Union and Great Britain consider medical procedures to be nonpatentable subject matter.
Patenting Surgical and Diagnostic Instruments
The U.S. patent system also permits medical and surgical
devices to be patented, including surgical and diagnostic
instruments. The U.S. patent protection permits the
patent holder to exclude other individuals or entities from
making, using, or selling the patented invention in the
United States for a period of 20 years, thus providing
market exclusivity to the patent holder. Both ethically and
legally, physicians may obtain patents on surgical or diagnostic instruments that they have invented (6). However,
out of concern for the welfare of patients, the patent holder should make the instrument available at a fair and reasonable cost.
Patenting Drugs
The granting of patents to pharmaceutical companies for
drugs that they have developed may appear to be relatively uncontroversial. Drug makers have successfully argued
the need for patent protection to recoup the cost of their
investment in drug research and to gain a profit before the
makers of generic equivalent drugs are permitted to enter
the market.
However, some techniques used by pharmaceutical
companies to extend the terms of their patents and their
products market exclusivities have recently come under
criticism. For example, companies have paid manufacturers of generic drugs to drop a legal challenge to a patent
or to postpone the manufacture of a generic equivalent,
they have developed minimally altered formulations or
dosages that become eligible for new patents, and they
have lobbied Congress for statutory and legislative patent
extensions on highly profitable drugs. These techniques
may allow the patent holder to continue to charge prices
that are far higher than would be the case in a competitive
market and to extend the government-sanctioned market
exclusivity long beyond when the original patent term
would have expired. As a result, the cost to consumers or
patients may be inflated beyond providing a reasonable
return on research investments and may, in fact, prevent
some patients from using drugs that would be beneficial
to them. As patients bear an increasing share of the cost of
their prescribed drugs, the issue of drug pricing and
extended market exclusivities should be of concern to
physicians. Cost may influence patient compliance with
physician recommendations.
142
The Patenting of Genes

Patent and Trademark Office Guidance
The PTO maintains that genes and gene sequences are
patentable subject matter under existing U.S. federal
statutes and case law. Since 1980, more than 20,000
patents on genes or other gene-related molecules have
been granted, but this total includes gene patents for all
organisms, not only humans. More than 25,000 applications for patents on genes or related molecules are pending (7).
Because of continuing controversy over the granting
of patents on genes and gene sequences, the PTO has
attempted to clarify its standards for granting such
patents in its final guidelines on the written description
and utility requirements of patents. The guidelines were
issued after consideration of public comments on interim
guidelines, and they are pertinent to gene patents. The
PTO guidelines confirm that an isolated and purified
gene (a chemical entity modified from its natural state) is
not a naturally occurring substance. Substances as they
occur in nature in an unisolated form are not patentable.
Under U.S. patent law, the PTO regards a newly isolated gene or modified gene sequence to be a composition of matter. This is subject matter that is eligible for a
product patent as long as the product satisfies all the
statutory conditions for a patent. These conditions
require that the patent specification describe an invention
that is a new discovery or improvement (novel), that is
not obvious to those with ordinary skill in the art (inventive), and that has utility (is useful) (1, 2). Product patents
may be enforced broadly against a variety of uses of the
claimed product. For example, a product patent claiming
an isolated gene sequence can be used to exclude others
from using the sequence for commercial purposes (ie,
both the isolated gene sequence and the methods of using
it in tests and treatments).
If the gene sequence is not new, it may nonetheless be
eligible for a use patent (ie, a patent having claims directed to the products use). The enforcement of a use patent
is narrower, being limited to the patented use. Although a
use patent restricts the right to use a patented method
using a product or composition, it does not restrict access
to the product or composition itself.
A patent claiming an isolated gene covers the isolated gene but does not apply to the gene as it occurs in
nature. Genes as they occur in the body are not patentable
because they do not exist in an isolated and purified form.
Therefore, individuals who possess such genes in their
bodies would not infringe the patent.
In its final guidelines on the utility requirement for
patentability, the PTO requires that the utility be specific, substantial, and credible (8). To satisfy this requirement, the inventor must disclose at least one way in which
the purified gene, isolated from its natural state, may be
used or applied, for example, for diagnostic or predictive
genetic testing. However, if the applicant does not explic-
itly identify a specific utility for the isolated gene

sequence, the guidelines permit the utility requirement to
be satisfied if the examiner believes that an individual
with ordinary skill in the art would recognize that the
gene or sequence has a readily apparent well-established
utility. Some commentators have suggested that this
well-established utility may be simply a comparison with
a structurally analogous gene or sequence that is known
to have utility.
In the view of some commentators, the PTO guidelines do not set a high enough standard for establishing
the usefulness of a gene or gene sequence and, therefore,
may deem a product useful and allow a patent to be issued
covering a gene or gene sequence before the applicant is
able to identify a specific practical application (9).
Allowing patents on genes and sequences to be issued
before their function and purpose are adequately identified could create barriers to other researchers pursuing
such studies or could lessen the incentive for them to do
so. Moreover, researchers warn against relying too heavily
on structural analogues to predict utility because minor
changes in a gene sequence may produce profound
changes in biological activity (10).
Gene Patents and the Interests of Patients
Those who support the granting of broad patents believe
that patent protection encourages rather than impedes
research. It was the intent of Congress that the disclosure
required to secure a patent and the limited exclusivity provided by the patent would stimulate progress in science and
the useful arts. As the PTO notes, a patent application
requires complete public disclosure of the invention, discovery, or improvement and, therefore, may promote dissemination of knowledge rather than secrecy. In the PTOs
view, gene patents foster scientific progress because other
inventors are encouraged to discover new uses beyond the
one specified in the patent application (8). Inventors who
develop new and nonobvious uses for a patented gene may
patent these inventions, according to the PTO, thereby
rewarding researchers who develop the genetic information
to the endpoint of a useful method or product (11, 12).
Opponents of broad gene patenting fear that the welfare of the patient, the traditional role of the physician,
and the public trust are compromised by gene patents.
According to opponents of gene patenting, the patenting
of genes can impinge on the interests of patients in at least
four ways:
1. By retarding the transmission of knowledge (possible
if researchers choose to delay the announcement or
the publication of their findings until after a patent
application is filed)
2. By inhibiting other researchers from pursuing further
investigation on the patented product (developing a
subsequent invention often is difficult, complicated,
or unprofitable because of the need to coordinate
licensing with the original patent holder)
COMMITTEE OPINIONS
3. By establishing a monopoly on all diagnostic and

predictive tests based on a patented gene (such
action would limit the ability of practitioners and
researchers to improve genetic testing by adding new
mutations, devising new testing techniques, and
developing national quality assurance programs
[13])
4. By infringing on the interests of groups of patients
who have provided the original genetic material on
which the discovery of a gene or sequence is based
(they may feel that their concerns are disregarded
because of restrictions on access to tests and treatments made possible by their contribution of biologic material)
European challenges to the patent on the breast cancer gene BRCA1 illustrate problems that arise when a
patent holder claims that a patent on a gene precludes
other researchers or organizations from developing their
own tests for gene mutations. French researchers, supported by the European parliament, argue that such a
monopoly could impede or even prevent the development and use of cheaper and more effective tests for
BRCA1 mutations, such as tests that cover a broader range
of mutations (14, 15).
Similarly, in the clinical setting, experience has
shown that patent holders may in effect deprive patients
and physicians of reasonable access (eg, to a genetic test)
by placing significant hurdles to its use. These hurdles can
include substantial royalties or licensing fees and restrictions on the licensing of clinics or on the number of tests
allowed, such as the conditions placed on prenatal and
carrier testing for some autosomal recessive diseases (16).
Responses to the problem of restricted access to
patented genes have led to several proposed solutions.
One proposed solution is to develop a system similar to
the music licensing system, where gene patent holders
would be required to grant nonexclusive licenses for a
reasonable set fee (17). Another proposed solution is that
genes and genetic sequences should not be granted composition-of-matter patents because the market exclusivity
of their patents extends beyond the use identified by the
patent applicant and covers uses of the substance that may
be discovered later. Instead, a patent would be granted to
an applicant who identifies a specific function of a gene,
but the patent would cover only the use or utility identified, such as a particular genetic test. Then researchers
who later discovered additional applications for the gene
would be able to patent these new discoveries (18).
Response to the issue of access to genetic tests has led
some patient advocacy groups to take a proactive stance at
the time that patients provide tissue samples to researchers. To ensure that any genetic tests that result from
their participation will be inexpensive and widely available, these groups are seeking patents held jointly by the
patient group and the researchers (19). Therefore, rather
than objecting to the patenting of genes and genetic tests,
143
these patients are seeking to use the patent system to protect their own interests.
Recommendations
Practitioners and researchers need to be aware of public
policies that may jeopardize their ability to advance medical knowledge and provide the best tests and treatments
to patients. Although those who develop useful drugs,
diagnostic and screening tests, and medical technologies
have the right to expect a fair return for their efforts and
risks, current interpretations of patent law have the
potential to impede rather than promote scientific and
medical advances. Because the purpose of the patent system is to promote the public welfare, practices that are
inimical to the public good and overly protective of commercial monopolies should be altered (18).
Policies regarding the patenting of scientific inventions, discoveries, and improvements must balance the
need for the open exchange and use of information with
the need to make the pursuit of such knowledge financially rewarding. Therefore, the Committee on Ethics and the
Committee on Genetics of the American College of
Obstetricians and Gynecologists suggest the following
recommendations regarding the patenting of medical and
surgical procedures, medical devices, genes, DNA
sequences, screening and diagnostic tests, and gene-based
therapies:
1. Patents on medical or surgical procedures are ethically unacceptable, and some are legally unenforceable. Physicians may obtain patents on surgical and
diagnostic instruments that they have developed.
However, the patent holders should make these
instruments available at a fair and reasonable cost for
the benefit of patients.
2. Because a patent claiming a gene as a composition of
matter enables a patent holder to control future
applications of the patented gene or sequence, such
patents should not be granted. A patent should be
granted only for the specified use or application of
the gene or sequence (a use patent), thus enabling
others to develop additional applications (18).
Because case law and the PTO interpret a gene as
being a patentable chemical composition of matter,
such a limitation would require congressional intervention. The Committee on Ethics and the
Committee on Genetics support legislation that
would make composition-of-matter patents on genes
unenforceable.
3. If composition-of-matter patents on genes continue
to be enforceable, such patents on genes with clinical
applications should be subject to federal regulation
and oversight to ensure reasonable availability of the
genes and their products for research and clinical
use. Such regulation should include requirements on
licensing arrangements to ensure access for the public good, including both the advancement of knowl-
144
edge and the clinical care of patients. Specifically,

licensing agreements should permit reasonable but
not excessive royalties and should allow unlimited
access to tests by qualified laboratories, precluding
exclusionary arrangements and quotas on the number of tests that may be offered.
14.
15.
16.
References
1. Patentability of inventions, 35 U.S.C. 101103 (2004).
2. Application for patent, 35 U.S.C. 112 (2004).
3. American Medical Association. Patenting of medical procedures. In: Code of medical ethics of the American
Medical Association: current opinions with annotations.
20062007 ed. Chicago (IL): AMA; 2006. p. 2923.
4. Pallin v Singer 1995 U.S. Dist. LEXIS 20824, 36 U.S.P.Q.2d
(BNA) 1050 (D.Vt. May 1 1995).
5. Remedies for infringement of patent and other actions, 35
U.S.C. 281297 (2004).
6. American Medical Association. Patent for surgical or diagnostic instrument. In: Code of medical ethics of the American Medical Association: current opinions with annotations.
20062007 ed. Chicago (IL): AMA; 2006. p. 2912.
7. Doll JJ. Talking gene patents. Sci Am 2001;285:28.
8. Utility examination guidelines. United States Patent and
Trademark Office. Fed Regist 2001;66:10929.
9. United States Patent and Trademark Office. Public comments on the United States Patent and Trademark
Office revised interim utility examination guidelines.
Alexandria (VA): USPTO; 2000. Available at: http://www.
uspto.gov/web/offices/com/sol/comments/utilguide/index.
html. Retrieved January 5, 2007.
10. Spiegel J. Comment 44. In: United States Patent and
Trademark Office. Public comments on the United States
Patent and Trademark Office revised interim utility examination guidelines. Alexandria (VA): USPTO; 2000.
Available at: http://www.uspto.gov/web/offices/com/sol/
comments/utilguide/nih2.pdf. Retrieved January 5, 2007.
11. Doll JJ. The patenting of DNA. Science 1998;280:68990.
12. Wheeler DL. Will DNA patents hinder research? Lawyers
say not to worry. Chron High Educ 1999 July 16; 46:A19.
13. American College of Medical Genetics. Position statement
on gene patents and accessibility of gene testing. Bethesda
17.
18.
19.
(MD):ACMG;1999. Available at http://genetics.faseb.org/

genetics/acmg/pol-34.htm. Retrieved December 13, 2006.
Dorozynski A. France challenges patent for genetic screening of breast cancer. BMJ 2001;323:589.
Watson R. MEPs add their voice to protest at patent for
breast cancer gene. BMJ 2001;323:888.
Marshall E. Genetic testing. Families sue hospital, scientist
for control of Canavan gene. Science 2000;290:1062.
Heller MA, Eisenberg RS. Can patents deter innovation?
The anticommons in biomedical research. Science 1998;
280:698701.
Williamson AR. Gene patents: socially acceptable monopolies or an unnecessary hindrance to research? Trends
Genet 2001;17:6703.
Smaglik P. Tissue donors use their influence in deal over
gene patent terms. Nature 2000;407:821.
Suggested Reading
U.S. Department of Energy Office of Science. Genetics and
patenting. Washington, DC: USDOE; 2002. Available at: http://
www.ornl.gov/hgmis/elsi/patents.html. Retrieved December 13,
2006.
United States Patent and Trademark Office. General information concerning patents. Alexandria (VA): USPTO; 2002.
Available at: http://www.uspto.gov/web/offices/pac/doc/general/
index.html. Retrieved December 13, 2006.
Copyright May 2007 by the American College of Obstetricians and

Patents, medicine, and the interests of patients. ACOG Committee
ISSN 1074-861X
COMMITTEE OPINIONS
145

Number 365 May 2007
Seeking and Giving Consultation*

Committee on
Ethics
ABSTRACT: Consultations usually are sought when practitioners with primary clinical
responsibility recognize conditions or situations that are beyond their level of expertise or
available resources. One way to maximize prompt, effective consultation and collegial relationships is to have a formal consultation protocol. The level of consultation should be
established by the referring practitioner and the consultant. The referring practitioner
should request timely consultation, explain the consultation process to the patient, provide
the consultant with pertinent information, and continue to coordinate overall care for the
patient unless primary clinical responsibility is transferred. The consultant should provide
timely consultation, communicate findings and recommendations to the referring practitioner, and discuss continuing care options with the referring practitioner.
Physicians have a long history of working

together and with other health care professionals to provide efficient and comprehensive care for the patients they serve.
Achieving these goals sometimes requires
that physicians or other care providers seek
consultation from or provide consultation to
their colleagues (1). The basic principles of
consultation for obstetriciangynecologists
are summarized in the Code of Professional
Ethics of the American College of Obstetricians and Gynecologists as follows (2):
The obstetriciangynecologists relationships with other physicians, nurses,
and health care professionals should
reflect fairness, honesty, and integrity,
sharing a mutual respect and concern
for the patient.
The obstetriciangynecologist should
consult, refer, or cooperate with other
physicians, health care professionals, and
institutions to the extent necessary to
serve the best interests of their patients.
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Often, these relationships among clinicians lead to professional dialogue. In professional dialogue, clinicians share their
*Update of Seeking and Giving Consultation in Ethics
opinions and knowledge with the aim of

improving their ability to provide the best
care to their patients. Such dialogue may be
part of a clinicians overall efforts to maintain
current scientific and professional knowledge
or may arise in response to the needs of a particular patient.
In professional dialogue, a second clinician is typically asked a simple question and
he or she does not talk with or examine the
patient. For example, questions might be
asked regarding the significance of an irregular blood antibody or the follow-up interval
for an abnormal cervical cytology result. The
second clinician does not make an entry in
the patients medical record or charge a fee,
and the first clinician should not attribute an
opinion to the second clinician.
Professional dialogue does not constitute a formal consultation or establish a
patientconsultant relationship. Sometimes,
however, professional dialogue does lead to a
formal request for consultation. If, for example, a physician is asked to provide an opinion regarding a patients care and believes an
examination of the patient or her medical
record is necessary to answer the question
appropriately, he or she should ask to see the
patient for a formal consultation.
146
Although consultation usually is requested in an efficient manner that expedites patient care, situations occur
in which the relationship between practitioners or
between institutions and practitioners results in an inefficient, less-than-collegial consultative process that may
not be in the best interest of the patient. For example, a
patient and a consultant may be put at serious disadvantage when consultation is requested late in the process of
care or is not accompanied by sufficient background
information or the reason for consultation is not clearly
stated. Conversely, those seeking consultation may be
denied assistance on arbitrary grounds.
This Committee Opinion outlines the purpose of
consultation and referral, states the underlying ethical
foundations that govern consultation and referral, and
elaborates specifically the responsibilities of those who
seek and those who provide consultation. The Committee
Opinion is directed to physicians but it should be recognized that nonphysician practitioners also may be
involved in consultation.
The Purpose of Consultation and

Referral
Typically, a patient first seeks care from her primary caregiver, who should be aware that the patients needs may
go beyond his or her education, training, or experience
(24). Various levels of consultation may be needed to
make correct diagnoses, provide technical expertise, and
recommend a course of action (see the box). Occasionally, consultation or referral may be indicated when a
patients request for care is in conflict with her primary
caregivers recommendations or preferences. Finally, a
patient may seek consultation with another caregiver to
obtain a second opinion or explore other options for care
(5). In all of these types of consultation, the interests of
the patient should remain paramount (3).
Ethical Foundations
Ethical principles require that the consultative process be
guided by the following concepts (2, 6):
The welfare of the patient should be central to the
consultantpatient relationship (beneficence).
The patient should be fully informed about the need
for consultation and participate in the selection of
the consultant (respect for autonomy).
The patient should have access to adequate consultation regardless of her medical condition, social status, or financial situation (justice).
Practitioners must disclose to patients any pertinent
actual or potential conflict of interest that is involved
in a consultation relationship, including financial
incentives or penalties or restrictive guidelines
(truth-telling).
In addition, both practitioners with primary clinical
responsibility and consultants must respect the rights of
Definitions: Levels of Consultation

Consultation is the act of seeking assistance from another physician(s) or health care professional(s) for diagnostic studies, therapeutic interventions, or other services
that may benefit the patient. There are several levels of
consultation: single-visit consultations, continuing collaborative care, and transfer of primary clinical responsibility. Their descriptions are as follows:
A single-visit consultation involves examination of the
patient or the patients medical record and performance of diagnostic tests or therapeutic procedures.
The findings, procedures, and recommendations of the
consultant are recorded in the patients medical record
or provided to the practitioner with the primary clinical
responsibility for the patient in a written report or letter,
and a fee may be charged. The subsequent care of the
patient continues to be provided by the referring practitioner. Examples of such consultations are confirming
the findings of a pelvic examination, performing a specific urodynamic procedure on a patient with urinary
stress incontinence, and interpreting an electronic
fetal monitoring tracing or imaging studies. In the latter
two cases, the tracing or other output can be transmitted electronically, allowing for the performance of a
single-visit consultation without personal contact
between the patient and consultant.
Continuing collaborative care describes a relationship
in which the consultant provides ongoing care in conjunction with the referring practitioner. Thus, the consultant assumes at least partial responsibility for the
patients care. An example is a high-risk obstetric
patient with a medical complication of pregnancy who
is periodically assessed by the consultant, whereas
the referring practitioner is responsible for the day-today management of the patient.
Transfer of primary clinical responsibility to the consultant may be appropriate for the management of
problems outside the scope of the referring practitioners education, training, and experience or in cases in
which the patient must be transferred to another facility. Examples are the transfer of care of a patient in
preterm labor from a birth center to a consultant in a
perinatal center or referral of a patient with ovarian
cancer to a gynecologic oncologist. In many of these
situations, patients will eventually return to the care of
the referring practitioner when the problem for which
the consultation was sought is resolved.
the patient and also the rights of their respective professional colleagues.
Responsibilities Associated With

Consultation
Seeking Consultation and Requesting Referral
Consultations usually are sought when practitioners with
primary clinical responsibility recognize conditions or
situations that are beyond their level of expertise or avail-
COMMITTEE OPINIONS
able resources. Historically, these practitioners acted as

independent agents who decided when consultation was
appropriate, determined the level of consultation, and
were free to choose particular consultants. More recently,
as a result of recognition of the importance of respect for
patient autonomy, practitioners now inform patients of
the need for consultation and discuss options with them.
The quality of the consultation often is improved by this
collaborative relationship between practitioners and
patients.
Today, this practitionerpatient partnership operates
under new conditions that may affect the process of consultation. Health care guidelines and protocols used by
certain types of managed care arrangements may limit
the freedom of the practitioner to provide complete care
or to request consultation (7). These guidelines may
include instructions about specific situations or medical
conditions in which consultation, second opinion, or
referral is mandated (8). Examples include abnormal
labor that may require operative delivery or chronic uterine bleeding that may require hysterectomy. Other guidelines may require that practitioners seek consultation
when patients develop signs and symptoms of severe
preeclampsia or if ovarian cancer is discovered. Such
arrangements and guidelines may be designed to ensure a
high level of care for patients by requiring that consultants
be involved appropriately in certain clinical problems.
Conversely, practitioners may find themselves in situations that create disincentives to medically appropriate
consultation or that mandate the use of a consultant
panel that is not adequate to support appropriate patient
care. The policies that lead to such situations involve
potential conflicts of interest (9) and may have a negative
effect on the patients medical needs, thus limiting her
autonomy and her right to informed choice. Under all
conditions of practicesolo or group, fee for service, or
managed care contractconsultation and referral should
be carried out in the patients best interest and obtained
with the patients consent after full disclosure of limitations and potential conflicts of interest.
It is in everyones best interestpractitioners with
primary clinical responsibility, consultants, patients, and
health care plansthat the criteria for consultation be
mutually agreed on in advance and stated clearly in writing. Financial incentives or penalties for consultation and
referral that exist either overtly or covertly under many
managed care contracts are sources of serious conflicts of
interest. Practitioners must be free to inform patients of
the best medical practice or options of care, even when
the mandate of directed referrals under contracted care
does not include these alternatives. Ethical responsibility
for patients best interests demands that practitioners disclose any proscriptions to serving as patients advocates.
Practitioners have a responsibility to provide patients
with their best medical judgment and serve as advocates
for patients if recommended care is denied. It then
becomes the patients responsibility to decide whether to
147
abide by insurance plan restrictions, challenge them, or

seek care outside the scope of coverage.
Giving Consultation and Accepting Referral
Physicians generally provide consultations or accept
referred patients in the interest of providing excellent care
for patients and promoting good relationships among
colleagues. Open communication and established professional relationships facilitate effective consultation and
referral. However, at times a consultant may be called on
unexpectedly, inconveniently, and sometimes inappropriately to be involved in or to assume the care of a patient.
In these situations, a physician is only ethically obligated
to provide consultation or assume the care of the patient
if there is a contractual agreement or a preexisting
patientphysician relationship or if there is a severe medical emergency, in which there is no reasonably available
alternative caregiver (10). Hospital or departmental
guidelines for consultation and referral may prevent such
confrontations.
Practical Recommendations
Providing optimal care demands a good working relationship with a number of other physicians and health
care professionals. Consultation may be needed by the
practitioner with primary clinical responsibility regardless of specialty designation or level of training. Ideally,
the referring practitionerconsultant relationship has
been established before the need for consultation or referral arises, and the referring practitionerconsultant relationship should be ongoing.
One way to maximize prompt, effective consultation
and collegial relationships is to have a formal consultation
protocol. This may be especially advantageous for family
physicians who provide obstetric or gynecologic care and
for collaborative practice between obstetriciangynecologists and nurse practitioners, certified nursemidwives,
and other health care professionals. Such protocols create
pathways that anticipate difficult or complex situations.
The level of consultation should be established by a dialogue between the referring practitioner and the consultant that results in mutual agreement (see the box on the
previous page).
Electronic means of communication, such as e-mail,
may be used as long as the consultant and referring physician agree to use such media and have established systems
to confirm receipt and transfer of reports to the medical
chart. Electronic communication must be done in a manner that protects patient confidentiality.
Responsibilities of the Referring Practitioner
The responsibilities of the referring practitioner can be
outlined as follows:
1. The referring practitioner should request consultation in a timely manner, whenever possible before
an emergency arises. A good working relationship
148
2.
3.
4.
5.
6.
between the referring practitioner and the consultant

requires shared concern for the patients needs and a
commitment to timely and clear-cut communication.
The referring practitioner is responsible for preparing the patient with an explanation of the reasons for
consultation, the steps involved, and the names of
qualified consultants.
The referring practitioner should provide a summary of the history, results of the physical examination,
laboratory findings, and any other information that
may facilitate the consultants evaluation and recommendations (11).
Whenever possible, the referring practitioner should
document in the medical record the indications for
the consultation and specific issues to be addressed
by the consultant.
The referring practitioner should discuss the consultants report with the patient and give his or her own
recommendation based on all available data in order
to serve the best interest of the patient.
A complex clinical situation may call for multiple
consultations. Unless authority has been transferred
elsewhere, the responsibility for the patients care
should rest with the referring practitioner (3). This
practitioner should remain in charge of communication with the patient and coordinate the overall care
on the basis of information derived from the consultants. This will ensure a coordinated effort that
remains in the patients best interest.
Responsibilities of the Consultant

The responsibilities of the consultant can be outlined as
follows:
1. Consultants should recognize their individual
boundaries of expertise and provide only those medically accepted services and technical procedures for
which they are qualified by education, training, and
experience.
2. When asked to provide consultation, the consultant
should do so in a timely manner and without regard
to the specialty designation or qualifications of the
referring practitioner.
3. The consultant should effectively communicate findings, procedures performed, and recommendations
to the referring practitioner at the earliest opportunity (12).
4. A summary of the consultation should be included
in the medical record or sent in writing to the referring practitioner.
5. The extent to which the consultant will be involved
in the ongoing care of the patient should be clearly
established by mutual agreement of the consultant,
the referring practitioner, and the patient. At times it
6.
7.
8.
9.
may be appropriate for the consultant to assume primary clinical responsibility for the patient. Even if
this is only a temporary circumstance, the consultant
should obtain the referring practitioners cooperation and assent, whenever possible.
When the consultant does not have primary clinical
responsibility for the patient, he or she should try to
obtain concurrence for major procedures or additional consultants from the referring practitioner.
In all that is done, the consultant must respect the
relationship between the patient and the referring
practitioner, being careful not to diminish inappropriately the patients confidence in her other caregivers (3).
The consultant should be cognizant of the referring
practitioners abilities, and the consultant and referring practitioner should discuss who can best provide the agreed-upon care. Reliance on the referring
practitioners abilities may increase convenience to
the patient, limit transportation needs, and ultimately result in more cost-effective care. In other cases,
however, it may not be possible for the consultants
recommendations to be addressed adequately by the
referring practitioner.
If the consultant believes that the referring practitioner is not qualified to provide an appropriate level
of continuing care, the consultant should recommend to the referring practitioner and, if necessary,
to the patient that the referring practitioner transfer
care of the patient.
References
1. American Medical Association. Referral of patients. In:
Code of medical ethics of the American Medical Association: current opinions with annotations. 20062007 ed.
Chicago (IL): AMA; 2006. p. 1168.
Code of professional ethics of the American College of
Obstetricians and Gynecologists. Washington, DC: ACOG;
2004. Available at: http://www.acog.org/from_home/
acogcode.pdf. Retrieved January 10, 2007.
3. Snyder L, Leffler C. Ethics manual: fifth edition. Ethics and
Human Rights Committee, American College of Physicians.
Physicians working with physicians. In: The assistant:
information for improved risk management. Washington,
DC: ACOG; 2001. p. 1920.
5. American Medical Association. Second opinions. In: Code
of medical ethics of the American Medical Association:
current opinions with annotations. 20062007 ed. Chicago
(IL): AMA; 2006. p. 1989.
6. Beauchamp TL, Childress JF. Principles of biomedical
2001.
COMMITTEE OPINIONS
7. Wallach EE, Fox HE, Gordon T, Faden R. Symposium:

managed care and ethics. Contemp Ob Gyn 1998;43:16276.
8. Chervenak FA, McCullough LB, Chez RA. Responding to
the ethical challenges posed by the business tools of managed care in the practice of obstetrics and gynecology. Am
9. Cain JM, Jonsen AR. Specialists and generalists in obstetrics and gynecology: conflicts of interest in referral and an
ethical alternative. Womens Health Issues 1992;2:13745.
10. American Medical Association. Free choice. In: Code of
medical ethics of the American Medical Association: current opinions with annotations. 20062007 ed. Chicago
(IL): AMA; 2006. p. 2824.
11. Role of the obstetriciangynecologist in the screening and
diagnosis of breast masses. ACOG Committee Opinion
No. 334. American College of Obstetricians and
12. American Medical Association. Consultation. In: Code of
medical ethics of the American Medical Association: current opinions with annotations. 20062007 ed. Chicago
(IL): AMA; 2006. p. 198.
149

Seeking and giving consultation. ACOG Committee Opinion No. 365.
Gynecol 2007;109:12559.
ISSN 1074-861X
150

Number 368 June 2007
Adoption*
Committee on Ethics
ABSTRACT: Obstetriciangynecologists may find themselves at the center of adoption issues because of their expertise in the assessment and management of infertility,
pregnancy, and childbirth. Physicians have a responsibility to provide information about
adoption to all patients with unwanted pregnancies, to all patients with infertility concerns, and to same-sex partners seeking information on parenting. Unless physicians are
truly expert in the field of adoption, they should guard against advocating for a particular
action. Physicians should not serve as brokers in independent adoptions. When authorized by patients to fill out forms for adoption agencies, physicians should do so truthfully, with full disclosure to patients of what they intend to say.
Adoption is a commonly used alternative

strategy for family building. Although adoption is not a medical event per se, obstetriciangynecologists may find themselves at
the center of adoption issues because of their
expertise in the assessment and management
of infertility, pregnancy, and childbirth.
There are several specific roles that the obstetriciangynecologist may be asked to assume
regarding adoption. Physicians commonly
provide information, advice, and counsel,
and they refer birth parents and prospective
adoptive parents to adoption agencies. They
also may be asked to link or match pregnant
women with families desiring adoption.
Frequently, they are asked to provide information about prospective parents to adoption agencies. In each of these roles, it is
important that obstetriciangynecologists
consider the rights, responsibilities, and safety of all concerned parties: the child, the birth
parents, the prospective adoptive parents,
and themselves.
Six principles have historically guided
adoption practices (1):

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
1. Consent of the birth mother was a necessary precondition for adoption, whereas
presumed waiver of consent by absent
birth fathers has been routine.
2. The purpose of adoption was to serve
the childs best interests by placement
with suitable adoptive parents.
*Update of Adoption in Ethics in Obstetrics and
3. Adoption practices were based on the

principle of gratuitous transfer, and
financial transactions suggestive of purchase of a child were prohibited.
4. Relationships with adoptive parents
were expected to substitute entirely for
relationships with biologic parents.
5. Relinquishing birth mothers and adopting parents were assured that their confidentiality and anonymity would be
protected.
6. Adoptive relationships were presumed
to be permanent once they were finalized in court.
These principles currently are undergoing
redefinition and reconsideration. Physicians
should be aware of the following new trends
in adoption practices:
1. There is increased emphasis on the
rights of biologic fathers and reluctance
to use a waiver process to release a child
for adoption when the biologic father
cannot be located.
2. Concepts of suitability of adoptive parents and the best interests of the child
are undergoing reconsideration.
3. The present environment of competition for adoptive infants may lead to
inducements in the form of subsidies for
medical care and other support, making
the gratuitous nature of adoption less
clear and free of financial conflict.
COMMITTEE OPINIONS
4. Proponents of openness in adoption argue that

adoption should include complementary relationships with birth parents. Even in a closed adoption,
proponents argue that the adopted child and adoptive parents need to have access to relevant genetic
and medical information about the biologic parents.
5. It is no longer possible to guarantee absolute confidentiality to either birth or adoptive parents. Many
states have laws that give adopted individuals access
to their birth records.
6. Adoption can no longer be considered to be permanent in every case because situations have arisen in
which adoptive relationships were terminated by
adoptive parents, biologic parents, or adopted children after a final adoption decree had been granted.
The resulting lack of clarity about both ethical issues
and legal consequences may create a potentially hazardous situation for physicians. In the following sections,
the different roles that the obstetriciangynecologist may
be asked to play in adoption are described. Ethical concerns are discussed, and safeguards are proposed.
Education
The physicians role in education is to ensure that adoption is introduced into the description of alternatives for
women with unwanted pregnancies and for potential
adoptive parents. Physicians have a responsibility to provide information about adoption to all patients with
unwanted pregnancies, to all patients with infertility concerns, and to same-sex partners seeking information on
parenting (2, 3). Fact sheets are available to support this
educational role (4). Physicians have an obligation to present alternatives fairly, regardless of personal values and
beliefs. They should not advocate for or against relinquishment or adoption. Nor should they avoid discussing
these issues when they are appropriate to the patients situation. This position is consistent with the right of adults
to the information required to make fully informed decisions. It also is consistent with the ethical obligation to
promote what is good for the patient. These obligations
can be met, for some patients, by placing literature about
adoption in the reception area, thereby validating adoption as a legitimate, respected choice. A lengthy counseling session, in which the risks and benefits of adoption
are weighed against other alternatives, may be indicated
for other patients.
Physicians may have both positive and negative personal biases about adoption for various reasons. For
example, physicians who have chosen the adoption alternative as their own method of family building may present this option either positively or negatively, depending on their individual experiences. Physicians would do
well to disclose their potential sources of bias and take
special care to uphold the principle of respect for patient
autonomy.
151
Physicians also should ensure that financial incentives do not bias the presentation of information about
adoption. For example, physicians must be especially
careful to offer information about adoption to patients
with established infertility because gynecologists have the
potential to benefit financially from the treatment of
infertile patients, and these fees may cease with a decision
to adopt rather than pursue further treatment.
Advice and Counseling

The physicians role in advising and counseling patients is
to assist those for whom adoption may be appropriate in
making a decision that is right for them. Patients often
turn to their physicians and say, Doctor, what do you
think I should do? Women experiencing unwanted pregnancy or infertility are vulnerable, facing confusing and
painful situations. The physician is a caregiver, trained to
solve problems and help patients feel better. The temptation to advocate for a specific position can be great. It may
seem to the physician that the obvious solution for a
young woman who is unemployed is to relinquish her
child or for an infertile couple who are reasonable candidates for in vitro fertilization to pursue that option before
considering adoption.
It is appropriate for physicians to give advice on
medical matters. This is an essential part of the physicianpatient relationship and an expert role for which
physicians are trained. Patients count on the guidance of
physicians for medical decisions. Adoption, however, is
only tangentially a medical matter, and few physicians are
expert in this field. Furthermore, for the physician, the
particular encounter with an individual patient or couple,
no matter how compelling, occurs only during a finite
point in time. The patients will be living with the lifelong
consequences of these decisions. Therefore, physicians
who provide advice and counsel, unless they are truly
expert in the field of adoption, should guard against
advocating for a particular action. The best counsel will
permit the involved parties to explore their options fully
and make a decision that arises out of their own beliefs,
values, needs, and circumstances.
Referrals
The physicians role in referrals is to identify appropriate
resources. Physicians often may best fulfill their obligations to patients through referral to other professionals
who have the appropriate skills and expertise to address
the difficult issues raised by adoption. For example, referral to a mental health professional for short-term counseling provides an opportunity for both birth and
prospective adoptive parents to explore their emotional
reactions and the ways that different alternatives may
affect their lives. Some patients may feel more comfortable having a discussion of this type with someone who is
not involved with their ongoing medical care.
When an obstetriciangynecologist makes a medical
referral, there is an ethical obligation to investigate the
152
skills and credentials of the consultant. The same responsibility for protecting the patients best interests pertains
to psychologic and social referral resources. As a starting
point, there are many sources of information available to
assist physicians in developing their own lists of referral
alternatives (see Resources at the end of this Committee
Opinion). In addition, local hospitals maintain referral
rosters.
Screening
When authorized by patients, the physicians role in
screening is to provide appropriate information to
screening agencies regarding patients qualifications as
prospective parents for an adoptive child. Physicians often
are asked by patients to fill out forms requesting information about their mental, psychologic, and medical suitability as prospective adoptive parents. Physicians are
bound by ethical precepts to be truthful, to act in their
patients best interests, and to protect their patients confidentiality. Adoption agencies, however, give precedence
to the needs and interests of adoptive children.
Difficult situations may arise. A patient may request,
for example, that a physician not reveal to the agency the
extent of her chronic illness and its potential effect on her
life expectancy. Although a physician may wish to advocate for a patient, there is an obligation to be truthful and
to let patients know what can and cannot be said.
Many agency forms request the treating physician to
certify that the individual or couple is fit to parent. If the
physician of record believes that he or she does not have
enough information to make a judgment, the agency may
count that as evidence against the couple. The physician
must be honest and speak accurately to the information
that is available. The best approach is for the physician to
disclose to the patient what will be written in the report,
followed by frank discussion with the patient of the
potential impact of the report.
Limits to the Physicians Role

Physicians should not serve as brokers in independent
adoptions. If asked to do so, they should refer the patient
to an appropriate agency or adoption resource. Among all
the roles that physicians may be asked to play in adoption,
that of a broker is perhaps the most hazardous because of
ethical issues related to undue influence, competing
obligations, and lack of expertise.
Although both birth parents and prospective adoptive parents generally view the adoption agreement as a
binding promise, patients may find themselves unable or
unwilling to fulfill that promise after delivery of the child.
The pregnant woman who agreed to relinquish her child
may have done so in good faith with the best knowledge
available to her at that time. She may not know what that
promise really means or if she can really do what she
agreed to until she has given birth to this child, held it,
and experienced the extent of loss. The couple who
agreed to accept a child may regret that decision and feel
unable to keep their part of the agreement if, for example,

the child is born with serious medical problems. For these
and similar reasons, no adoption agreement is legally
binding before the birth of the child.
If a physician has acted as a broker and the adoption
agreement falls through, he or she will be aware of the loss
experienced by the other party, may feel responsible, and
may be tempted to use the power of the patientphysician
relationship to influence the patient to fulfill the original
promise. The physicians ability to provide current or
future medical care for this patient may be compromised
by these events.
Brokering adoptions is properly the role of an independent authority or agency, which is in a position to protect the interests of all involved partiesthe child, the birth
parents, and the adoptive parents. For these reasons, many
hospitals have bylaws prohibiting staff physicians from
direct involvement as adoption brokers. Physicians should
avoid matching prospective adoptive parents with women
who have unwanted pregnancies and should instead refer
patients to agencies or other adoption resources, when
available. Physicians should receive only the usual compensation for medical and counseling services. Referral fees
and other arrangements for financial gain beyond usual
fees for clinical services are inappropriate.
When physicians also are prospective adoptive parents, there may be a temptation to adopt an infant from
one of their own patients. This arrangement is unethical.
It contravenes principles of fairness to other potential
parents and takes advantage of patients highly vulnerable
situations.
Summary
The adoption field is evolving, and the issues are complex.
Obstetriciangynecologists can play helpful and effective
roles in adoption as educators and advisers. Adoption
should be presented fairly, along with other options, to all
those who might benefit. Physicians can be excellent
sources of information, can assist in weighing risks and
benefits, and can provide emotional support. When
authorized by patients to fill out forms for adoption agencies, physicians should do so truthfully, with full disclosure to patients of what they intend to say.
Physicians should involve themselves in counseling
and screening roles with great care because potential
exists for unintended misuse of the physicianpatient
relationship. Patient confidentiality, patient autonomy,
and the principle of the patients best interest may be
compromised by subtle or blatant conflicts of interest.
Physicians are advised to delegate to an independent
authority all responsibility for matching pregnant women
with prospective adoptive parents.
References
1. Hollinger JH. Adoption law. Future Child 1993;3:4361.
2. Kaunitz AM, Grimes DA, Kaunitz KK. A physicians guide
to adoption. JAMA 1987;258:353741.
COMMITTEE OPINIONS

Special issues in womens health. Washington, DC: ACOG;
2005.
4. American Society for Reproductive Medicine. Patients fact
sheet: adoption. Birmingham (AL): ASRM; 2003. Available
at: http://www.asrm.org/Patients/FactSheets/AdoptionFact.pdf. Retrieved January 10, 2007.
153
Resolve (7910 Woodmont Avenue, Suite 1350, Bethesda, MD

20814; telephone: (301) 652-8585; http://www.resolve.org), the
organization for infertile couples, maintains a directory of
nationally and locally recognized and accredited organizations
and individuals who provide adoption support.
Resources
Arcus D. Adoption. In: Strickland B, editor. The Gale encyclopedia of psychology. 2nd ed. Detroit (MI): Gale Group; 2001. p.
159.
Child Welfare Information Gateway (Childrens Bureau/ACYF,
1250 Maryland Avenue, SW, Eighth Floor, Washington, DC
20024; telephone: (703) 385-7565 or (800) 394-3366; http://
www.childwelfare.gov), a comprehensive resource on all aspects
of adoption, is a service of the U.S. Department of Health and
Human Services.
Perspectives Press (PO Box 90318, Indianapolis, IN 46290; telephone: (317) 872-3055; http://www.perspectivespress.com) concentrates on issues related to adoption.
Copyright June 2007 by the American College of Obstetricians and

Adoption. ACOG Committee Opinion No. 368. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2007;109:150710.
ISSN 1074-861X
154

Multifetal Pregnancy Reduction*

Committee on Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Counseling for treatment of infertility should include a discussion of the

risks of multifetal pregnancy, and multifetal pregnancy reduction should be discussed
with patients before the initiation of any treatment that could increase the risk of multifetal pregnancy. In almost all cases, it is preferable to terminate an ovulation induction
cycle or limit the number of embryos to be transferred to prevent a situation in which
fetal reduction will have to be considered. The best interests of the patient and the future
child or children should be at the center of the riskbenefit equation. Although no physicians need to perform fetal reductions if they believe that such procedures are morally
unacceptable, all obstetricians and gynecologists should be aware of the medical and
ethical issues in these complex situations and be prepared to respond in a professional,
ethical manner.
The ethical issues surrounding the use and

consequences of reproductive technologies
are highly complex, and no one position
reflects the variety of opinions within the
membership of the American College of
Obstetricians and Gynecologists. The purpose of this Committee Opinion is to review
the ethical issues involved in multifetal pregnancy reduction. For the purposes of this
document, multifetal pregnancy reduction is
defined as a first-trimester or early secondtrimester procedure for termination of one
or more fetuses in a multifetal pregnancy,
to increase the chances of survival of the
remaining fetuses and decrease long-term
morbidity for the delivered infants (1).
To many, the ethical issues involved in
multifetal pregnancy reduction are somewhat different from the issues involved in
abortion, as discussed in the Analysis section. Although no physicians need to perform multifetal pregnancy reductions if they
believe that such procedures are morally
unacceptable, all physicians should be aware
of the medical and ethical issues in these
complex situations and be prepared to
respond in a professional, ethical manner to
patient requests for information and procedures.
*Update of Multifetal Pregnancy Reduction in Ethics in
Obstetrics and Gynecology, Second Edition, 2004.
Background
Spontaneous occurrences of multifetal pregnancies always have been a medical problem.
More recently, increased use of potent ovulation-induction drugs and assisted reproductive technology (ART), such as in vitro
fertilization (IVF), have been effective in the
treatment of infertility but subsequently also
have increased the risk of multifetal pregnancy (2). Thousands of patients previously
unable to have children have been assisted to
achieve conception. In a small percentage of
these patients, the resultant pregnancy has
involved more than two fetuses, thereby creating potentially serious problems (26).
There is widespread agreement that the risks
of perinatal morbidity and mortality and
maternal morbidity increase with the number of fetuses. Recent reports have shown
improving outcomes with multifetal pregnancies, but the risks are still significant (6).
Prevention
The first approach to this problem is or
should be prevention. It might be argued that
the problem is best remedied by discontinuing technologic assistance to reproduction.
On the one hand, this approach discounts the
major benefits that ART offers to patients
and suggests an unwarranted coercive
restriction on parental choice and autonomy.
On the other hand, the association of an
COMMITTEE OPINIONS
increased rate of multifetal pregnancies with infertility

treatment deserves serious attention. Some multifetal
pregnancies will inevitably occur despite the best of
intentions, knowledge, skill, and equipment, but it is
essential that those providing infertility treatment exercise a high degree of diligence to minimize the problem.
Both ovulation induction alone and IVF contribute
to high-order multiple births (more than two). In 1977,
43.3% of all births of triplets or greater were the result of
ART (ie, IVF) and 38.2% were the result of the use of ovulation drugs (5). In 1996, the order was reversed; 40.4% of
births of triplets or greater were the result of ovulation
drugs, whereas 38.7% were the result of ART (5).
According to the Centers for Disease Control and Prevention, 3,390 infants were born in triplet or higher-order
multiple deliveries after ART treatment in 2003, accounting for 44% of all infants born in triplet or higher-order
multiple deliveries (7). Similar data are not available for
ovulation induction cycles.
Ovulation induction with gonadotropin cycles in
which ultrasound imaging demonstrates the presence of
many mature follicles, each capable of releasing an ovum,
presents a difficult decision on whether to give human
chorionic gonadotropin (hCG) to induce ovulation. If an
hCG injection is withheld, the patient will have spent
considerable time and emotional and financial resources
for a nonovulatory cycle. Yet, if hCG is given to trigger
ovulation, a high-order multifetal pregnancy may result.
Attempts have been made to develop criteria for withholding hCG (eg, more than six large follicles or estradiol
levels greater than 1,500 pg/mL). However, a large study
showed that the occurrence of high-order multifetal pregnancies after gonadotropin therapy increases with higher
estradiol levels but cannot be reliably predicted by the
number of mature follicles on ultrasound examination
(8). The authors concluded that adherence to criteria for
withholding hCG will not prevent high-order multiple
births and that better criteria cannot easily be established.
They suggest that the use of treatment protocols with lessintensive stimulation of the ovaries may reduce the incidence of high-order multifetal pregnancies, but only to a
limited extent and at the expense of pregnancy rates.
When many follicles are present, alternative approaches
would be conversion of the gonadotropin cycle to an IVF
cycle or selective aspiration of the supernumerary follicles
(9).
In ART, there may be pressure to be successful
because of both prospective parents and programs interests. Direct costs for IVF cycles are many times higher
than those for ovulation induction alone with gonadotropins. Ovulation induction with gonadotropins may be
more likely to be covered by insurance. Patients who
choose to undergo IVF may be paying for treatment out
of pocket, and this may add pressure to achieve pregnancy on the first attempt. In addition, IVF programs face
public scrutiny not faced by programs that offer only ovulation induction. Although success rates for individual
155
IVF programs are public information, published by the

Centers for Disease Control and Prevention, similar
reporting is not done for ovulation induction alone (2).
As the number of embryos transferred increases, program
success rates may increase, but so does the risk of a multifetal pregnancy (2).
The physician who makes decisions about the circumstances for triggering ovulation or guidelines for
embryo transfer must, as in any medical situation, place
the best interests of the patient and the future child or
children at the center of the riskbenefit equation. In
some countries, such as England, where ART is centrally
regulated, limitations are placed on the number of
embryos that can be transferred, and subsequently fewer
multifetal pregnancies result.
In the United States, the decision is left to individual
physicians and programs. In almost all cases, it is preferable to terminate a gonadotropin cycle used for ovulation
induction alone or limit the number of embryos to be
transferred in IVF to prevent a situation in which patients
and physicians will have to consider fetal reduction. The
Practice Committee of the American Society for
Reproductive Medicine (ASRM) has issued a report suggesting prognosis-dependent guidelines for limiting the
number of embryos to be transferred. These guidelines
limit risk while allowing individualization of patient care
for optimal results (10). Multifetal pregnancy reduction
should be viewed as a response to a consequence of ovulation induction that cannot always be avoided; it should
not be a routinely accepted treatment for an iatrogenic
problem.
The ultimate goal in prevention is to significantly
reduce the likelihood that any multifetal pregnancy will
occur, including twins. This will require patients, physicians, and payers to support a culture in which IVF may
replace gonadotropin-only therapy in treatment algorithms. When IVF is performed, the eventual goal in the
future may be to transfer only the embryo with the greatest chance for growth and implantation; currently ASRM
recommends that consideration be given to transferring
only a single embryo for patients with the most favorable
prognosis (10). Nonetheless, data from the Centers for
Disease Control and Prevention indicate that approximately 56% of embryo transfers that used fresh nondonor eggs in 2003 involved the transfer of three or more
embryos (2).
Another strategy under study is transfer of blastocysts instead of cleavage-stage embryos, hoping that
higher pregnancy rates would allow fewer embryos to be
transferred. Yet, although some randomized trials have
found higher pregnancy or live-birth rates with the
transfer of a single blastocyst-stage embryo over a single
cleavage-stage embryo (11, 12), the transfer of blastocyst-stage embryos has not been supported by others
(13). The current position of ASRM is that either blastocyst transfer or cleavage stage-embryo transfer may be
performed (10).
156
Counseling
As with all medical care, counseling for treatment of
infertility should incorporate discussions of risks, benefits, and treatment alternatives, including the option for
no treatment. Counseling should be considered an ongoing process, beginning before treatment decisions are
made and continuing throughout the patients care. The
risks of certain treatments of infertility include, but are
not limited to, the occurrence of multifetal pregnancy,
with its associated risks of spontaneous abortion, preterm
labor and delivery, and neonatal morbidity and mortality.
The informed consent process must include information
about the potential for multifetal pregnancy and associated maternal risks, such as prolonged hospitalization,
antepartum bleeding, postpartum hemorrhage, hypertensive diseases of pregnancy, and an increased rate of
cesarean delivery. Whether patients decide to maintain or
to reduce high-order multiple pregnancies, they should
be assured that they will receive the best available care
(14).
It also is the responsibility of the physician to inform
the patient that fetal reduction as a response to multifetal
pregnancy has inherent medical risks to the remaining
fetuses. Pregnancy loss rates of approximately 46% have
been reported for triplet-to-twin reduction in large samples (1517), but higher rates also have been reported
(18). Reports of lower birth weights for twins reduced
from triplets also are of concern (1920), although more
recent reports have suggested that reduction from triplets
or quadruplets to twins is associated with an outcome as
good as with an unreduced twin gestation (15, 2226).
Nonetheless, patients should not be given the impression
that multifetal pregnancies are without problems because
fetal reduction is available.
Patients struggle with the ethical and emotional
issues of fetal reduction. In a postdelivery informational
survey of couples who had undergone multifetal pregnancy reduction, few of the small sample of respondents
reported that they understood the procedure or its consequences fully at the time of fetal reduction (27). In semistructured interviews of 10 women who had undergone
multifetal pregnancy reduction, one third reported still
feeling guilt 1 year after the procedure (28). Many infertility patients have unrealistic ideas about the outcomes
for high-order multifetal pregnancies that leave them
unprepared for feelings of loss and grief at the time of a
reduction procedure (29, 30). However, in studies that
used standard psychologic tests to assess the emotional
state of patients after multifetal pregnancy reduction,
serious long-term psychologic sequelae were not identified. Among women who underwent multifetal pregnancy reduction and subsequently miscarried the entire
pregnancy, depression scores were similar to scores for a
control group of women who did not undergo fetal
reduction and subsequently miscarried the entire pregnancy (31).
A report that 93% of patients who decided to proceed with fetal reduction would make that decision again
despite their experience of stress and sadness is somewhat
reassuring, but the number of patients studied was quite
small (n = 91) (32). The ethical issues that this option
involves should be discussed with patients before the initiation of any treatment that could increase the risk of
multifetal pregnancy. Although patients should be
encouraged to examine their feelings about these risks
and options at the onset, the counseling process should
encourage them to continue this assessment at appropriate points in the treatment process (33).
Options
In the presence of an already established multifetal pregnancy, the options are inevitably difficult. No choice is
without potential consequences, and the potential benefits must be carefully weighed against the potential harms.
There are three options in multifetal pregnancies:
1. Abort the entire pregnancy (all of the fetuses).
2. Continue the pregnancy (all of the fetuses).
3. Perform multifetal pregnancy reduction on one or
more of the fetuses.
The first option involves aborting the entire multifetal pregnancy. However, for some patients, aborting the
pregnancy is not an acceptable option. For other patients
who may have achieved pregnancy after infertility treatment, this option may be considered the least desirable.
The second option is attempting to carry the multifetal pregnancy to term. However, the risks of perinatal
and maternal morbidity and mortality increase directly
with the number of fetuses (8). These risks include losing
all of the fetuses or having some survive with permanent
impairment as a consequence of extreme preterm birth.
The assessment of what constitutes significant risk
varies among patients and physicians and, therefore, is
not amenable to uniform definition. Physicians should
respect their patients conclusions about which risks are
acceptable and which are too high.
The third option in multifetal pregnancies is multifetal pregnancy reduction. The technique brings about the
demise of one or more fetuses with the intent to allow
continuation of the pregnancy, resulting in the delivery of
fewer infants with lower risks of preterm birth, morbidity, and mortality. Although this procedure is successful in
most cases, it may raise some unsettling ethical concerns.
There is a complex interrelationship between the intention to reduce the morbidity of a smaller number of surviving fetuses and the intentional sacrifice of others that
demands an ethical as well as medical assessment of the
relative benefits and risks of multifetal pregnancy reduction. What follows is an attempt to outline such an assessment, with the understanding that each case ultimately
must be examined on its own merits.
COMMITTEE OPINIONS
Analysis
Many would argue that there are differences between the
ethical analyses involved in multifetal pregnancy reduction and elective abortion because the intent is different.
A woman has an elective abortion because, for many
complex and varied reasons, she does not wish or feels
unable to have a child. In contrast, an infertility patient
who has a multifetal pregnancy undergoes fetal reduction
precisely because she does wish to bear a child. The
patient and her physician may conclude that fetal reduction is the preferred way to continue her pregnancy. For
some individuals, the primary intention justifying fetal
reduction may be the life and well-being of the fetuses
that do survive and continue to develop. For others, it is
unethical to terminate an apparently healthy fetus, even
for the sake of the survival or well-being of other fetuses
in the pregnancy.
Some individuals who believe that abortion is generally unacceptable find multifetal pregnancy reduction to
be justified ethically when the risks of carrying the pregnancy are considerable and could be reduced if the number of fetuses were fewer. Individual patients will evaluate
varying degrees of risk differently. As advances in maternalfetal and neonatal medicine continue, the risk of
extreme preterm birth is expected to decrease. The issues
of patient choice and physician participation and consultation need to be analyzed on a case-by-case basis.
Summary
Although physicians may choose not to participate in
multifetal pregnancy reduction, they should be knowledgeable about this procedure and be prepared to react in
a professional and ethical manner to patient requests for
information or services or both. The first approach to the
problem of multifetal pregnancies should be prevention.
Although fetal reduction will be ethically acceptable to
many as a response to an unforeseen and unavoidable
contingency, in almost all cases, it is preferable to terminate a gonadotropin cycle or limit the number of
embryos to be transferred to prevent a situation in which
the patient and physician need to consider fetal reduction. Counseling for treatment of infertility should
include a discussion of the risks of multifetal pregnancy,
and the ethical issues surrounding fetal reduction should
be discussed with patients before the initiation of any
treatment that could increase the risk of multifetal pregnancy.
References
1. Berkowitz RL, Lynch L. Selective reduction: an unfortunate
misnomer. Obstet Gynecol 1990;75:8734.
2. Centers for Disease Control and Prevention. 2004 Assisted
reproductive technology success rates: national summary
and fertility clinic reports. Atlanta (GA): CDC; 2006.
Available at: http://ftp.cdc.gov/pub/Publications/art/2004
ART508.pdf. Retrieved January 11, 2007.
157
3. Multiple gestation: complicated twin, triplet, and highorder multifetal pregnancy. ACOG Practice Bulletin No. 56.
4. Perinatal risks associated with assisted reproductive technology. ACOG Committee Opinion No. 324. American
2005;106:11436.
5. Contribution of assisted reproductive technology and ovulation-inducing drugs to triplet and higher-order multiple
birthsUnited States, 19801997. Centers for Disease
Control and Prevention (CDC). MMWR Morb Mortal
Wkly Rep 2000;49:5358.
6. Jones HW, Schnorr JA. Multiple pregnancies: a call for
action. Fertil Steril 2001;75:113.
7. Wright VC, Chang J, Jeng G, Macaluso M. Assisted reproductive technology surveillanceUnited States, 2003.
MMWR Surveill Summ 2006;55(SS-4):122.
8. Gleicher N, Oleske DM, Tur-Kaspa I, Vidali A, Karande V.
Reducing the risk of high-order multiple pregnancy after
ovarian stimulation with gonadotropins. N Engl J Med
2000;343:27.
9. Ethical issues related to multiple pregnancies in medically
assisted procreation. ESHRE Task Force on Ethics and Law.
Hum Reprod 2003;18:19769.
10. Guidelines on number of embryos transferred. The Practice
Committee of the Society for Assisted Reproductive
Technology and the Practice Committee of the American
Society for Reproductive Medicine. Fertil Steril 2006;
86(suppl 5):S512.
11. Papanikolaou EG, Camus M, Kolibianakis EM, Van
Landuyt L, Van Steirteghem A, Devroey P. In vitro fertilization with single blastocyst-stage versus single cleavage-stage
embryos. N Engl J Med 2006;354:113946.
12. Gardner DK, Surrey E, Minjarez D, Leitz A, Stevens J,
Schoolcraft WB. Single blastocyst transfer: a prospective
randomized trial. Fertil Steril 2004;81:5515.
13. Blake DA, Proctor M, Johnson NP. The merits of blastocyst
versus cleavage stage embryo transfer: a Cochrane review
[published erratum appears in Hum Reprod 2004;19:2174].
Hum Reprod 2004;19:795807.
14. Ethical recommendations on multiple pregnancy and multifetal reduction. FIGO Committee for the Ethical Aspects
of Human Reproduction and Womens Health. Int J
Gynaecol Obstet 2006;92:3312.
15. Evans MI, Berkowitz RL, Wapner RJ, Carpenter RJ,
Goldberg JD, Ayoub MA, et al. Improvement in outcomes
of multifetal pregnancy reduction with increased experience. Am J Obstet Gynecol 2001;184:97103.
16. Timor-Tritsch IE, Bashiri A, Monteagudo A, Rebarber A,
Arslan AA. Two hundred ninety consecutive cases of multifetal pregnancy reduction: comparison of the transabdominal versus the transvaginal approach. Am J Obstet Gynecol
2004;191:20859.
17. Stone J, Eddleman K, Lynch L, Berkowitz RL. A single center experience with 1000 consecutive cases of multifetal
pregnancy reduction. Am J Obstet Gynecol 2002;187:
11637.
158
18. Antsaklis A, Souka AP, Daskalakis G, Papantoniou N,

Koutra P, Kavalakis Y, et al. Embryo reduction versus expectant management in triplet pregnancies. J Matern Fetal
Neonatal Med 2004;16:21922.
19. Silver RK, Helfand BT, Russell TL, Ragin A, Sholl JS,
MacGregor SN. Multifetal reduction increases the risk of
preterm delivery and fetal growth restriction in twins: a
case-control study. Fertil Steril 1997;67:303.
20. Groutz A, Yovel I, Amit A, Yaron Y, Azem F, Lessing JB.
Pregnancy outcome after multifetal pregnancy reduction to
twins compared with spontaneously conceived twins. Hum
Reprod 1996;11:13346.
21. Depp R, Macones GA, Rosenn MF, Turzo E, Wapner RJ,
Weinblatt VJ. Multifetal pregnancy reduction: evaluation of
fetal growth in the remaining twins. Am J Obstet Gynecol
1996;174:12338; discussion 123840.
22. Papageorghiou AT, Liao AW, Skentou C, Sebire NJ,
Nicolaides KH. Trichorionic triplet pregnancies at 1014
weeks: outcome after embryo reduction compared to
expectant management. J Matern Fetal Neonatal Med
2002;11:30712.
23. Miller VL, Ransom SB, Shalhoub A, Sokol RJ, Evans MI.
Multifetal pregnancy reduction: perinatal and fiscal outcomes. Am J Obstet Gynecol 2000;182:157580.
24. Yaron Y, Bryant-Greenwood PK, Dave N, Moldenhauer JS,
Kramer RL, Johnson MP, et al. Multifetal pregnancy reductions of triplets to twins: comparison with nonreduced
triplets and twins. Am J Obstet Gynecol 1999;180:126871.
25. Torok O, Lapinski R, Salafia CM, Bernasko J, Berkowitz RL.
Multifetal pregnancy reduction is not associated with an
increased risk of intrauterine growth restriction, except for
very-high-order multiples. Am J Obstet Gynecol 1998;
179:2215.
26. Dodd J, Crowther C. Multifetal pregnancy reduction of
triplet and higher-order multiple pregnancies to twins.
27. Vauthier-Brouzes D, Lefebvre G. Selective reduction in multifetal pregnancies: technical and psychological aspects.
28. Garel M, Stark C, Blondel B, Lefebvre G, Vauthier-Brouzes
D, Zorn JR. Psychological reactions after multifetal pregnancy reduction: a 2-year follow-up study. Hum Reprod
1997;12:61722.
29. Goldfarb J, Kinzer DJ, Boyle M, Kurit D. Attitudes of in vitro
fertilization and intrauterine insemination couples toward
multiple gestation pregnancy and multifetal pregnancy
reduction. Fertil Steril 1996;65:81520.
30. Baor L, Blickstein I. En route to an instant family: psychosocial considerations. Obstet Gynecol Clin North Am
2005;32:12739, x.
31. McKinney M, Leary K. Integrating quantitative and qualitative methods to study multifetal pregnancy reduction. J
Womens Health 1999;8:25968.
32. Schreiner-Engel P, Walther VN, Mindes J, Lynch L,
Berkowitz RL. First-trimester multifetal pregnancy reduction: acute and persistent psychologic reactions. Am J
33. Zaner RM, Boehm FH, Hill GA. Selective termination in
multiple pregnancies: ethical considerations. Fertil Steril
1990;54:2035.

Multifetal pregnancy reduction. ACOG Committee Opinion No. 369.
Gynecol 2007;109:15115.
ISSN 1074-861X
COMMITTEE OPINIONS
159

Number 370 July 2007
Institutional Responsibility to Provide

Legal Representation*
Committee on Ethics
Reaffirmed 2009

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Hospitals, academic institutions, professional corporations, and other

health care organizations should have policies and procedures by which alleged violations
of professional behavior can be reported and investigated. These institutions should
adopt policies on legal representation and indemnification to protect those whose
responsibilities in managing such investigations may expose them to potentially costly
legal actions. The American College of Obstetricians and Gynecologists Committee on
Ethics supports the position of the American Association of University Professors regarding institutional responsibility for legal demands on faculty.
The Code of Professional Ethics of the

American College of Obstetricians and
Gynecologists states, The obstetrician
gynecologist should strive to address through
the appropriate procedures the status of
those physicians who demonstrate questionable competence, impairment, or unethical
or illegal behavior. In addition, the obstetriciangynecologist should cooperate with
appropriate authorities to prevent the continuation of such behavior (1). The Code
also identifies those appropriate procedures and appropriate authorities: The
obstetriciangynecologist should respect all
laws, uphold the dignity and honor of the
profession, and accept the professions
self-imposed discipline. The professional
competence and conduct of obstetrician
gynecologists are best examined by professional associations, hospital peer-review
committees, and state medical and licensing
boards. These groups deserve the full cooperation of the obstetriciangynecologist
(1).
Academic institutions, professional corporations, hospitals, and other health care
organizations should have policies and procedures by which alleged violations of professional behavior can be reported and
investigated. Also, it is necessary for these
*Update of Institutional Responsibility to Provide Legal
Representation in Ethics in Obstetrics and Gynecology,
Second Edition, 2004.
institutions to adopt policies on legal representation and indemnification for their

employees or others acting in an official
capacity who, in discharging their obligations
relative to unethical or illegal behavior of
individuals, are exposed to potentially costly
legal actions.
The American College of Obstetricians
and Gynecologists agrees with the position of
the American Association of University
Professors in its 1998 statement,Institutional
Responsibility for Legal Demands on Faculty, that institutions should ensure effective
legal and other necessary representation and
full indemnification in the first instance for
any faculty member named or included in
lawsuits or other extra-institutional legal
proceedings arising from an act or omission
in the discharge of institutional or related
professional duties or in the defense of academic freedom at the institution (2).
Reference
1. American College of Obstetricians and
Gynecologists. Code of professional ethics of
Gynecologists. Washington, DC: ACOG;
2004. Available at: http://www.acog.org/from_
home/acogcode.pdf. Retrieved January 11,
2007.
2. Institutional responsibility for legal demands on faculty. American Association of
University Professors. Academe 1999;85
(1):52.
160
Copyright July 2007 by the American College of Obstetricians and

Institutional responsibility to provide legal representation. ACOG
ISSN 1074-861X
COMMITTEE OPINIONS
161

Sterilization of Women, Including Those

With Mental Disabilities*
Committee on Ethics
Reaffirmed 2009
ABSTRACT: Sterilization, like any other surgical procedure, must be carried out
under the general ethical principles of respect for autonomy, beneficence, and justice.
Women requesting sterilization should be encouraged to discuss their decision and associated issues with their husbands or other appropriate intimate partners. The physician
who objects to a patients request for sterilization solely as a matter of conscience has
the obligation to inform the patient that sterilization services may be available elsewhere
and should refer the patient to another caregiver. The presence of a mental disability does
not, in itself, justify either sterilization or its denial. When a patients mental capacity is
limited and sterilization is considered, the physician must consult with the patients family, agents, and other caregivers in an effort to adopt a plan that protects what the consulted group believes to be the patients best interests while, at the same time,
preserving, to the maximum extent possible, the patients autonomy.
Sterilization, like any other surgical procedure, must be carried out under the general
ethical principles of respect for autonomy,
beneficence, and justice. Special ethical considerations are imposed by the unique attributes of sterilization. The procedure usually is
done not for medical indications but electively for family planning. It may have a significant impact on individuals other than the
patient, especially her partner. It is intended
to be permanent, although techniques are
available to attempt reversal or circumvent
sterility. Finally, sterilization affects procreation and, therefore, may conflict with the
moral beliefs of the patient, her family, or the
physician. When the patient has diminished
mental abilities or chronic mental illness,
even more stringent ethical constraints apply.
General Ethical Principles

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Under the principle of respect for autonomy,

patients have the right to seek, accept, or
refuse care. Respecting the patients autonomy means that the physician cannot impose
treatments. It does not mean that the physician must provide treatment, especially if the
physician considers it inappropriate or harm*Update of Sterilization of Women, Including Those
With Mental Disabilities in Ethics in Obstetrics and
ful (eg, an 18-year-old patient who asks to

undergo sterilization).
Sterilization is for many a social choice
rather than purely a medical issue, but all
patient-related activities engaged in by
physicians are subject to the same ethical
guidelines. Patients sometimes request a
physicians counsel in deciding whether to
request sterilization. Physicians should be
cautious in giving advice and making recommendations that go beyond health-related
issues, even though nonmedical factors might
be the most compelling for the patient. It may
be difficult for the physician to address nonmedical issues without bias. Also, the physician may not have a full understanding of the
patients situation. However, it is entirely
appropriate for the physician to assist the
patient in exploring and articulating the reasons for her decision.
Although a womans request for sterilization may conflict with the physicians medical
judgment or moral beliefs, the patients values and request cannot be dismissed or
ignored. In such cases, the physician has an
obligation to inform the patient of his or her
professional recommendation and the medical reasons for it. The physician remains
responsible for his or her actions and generally is not obligated to act in violation of
162
personal principles of conscience, but the patient should

be informed when personal principles limit action or
treatment. If the patient still desires sterilization, the
physician who objects solely as a matter of conscience has
the obligation to inform her that sterilization services
may be available elsewhere and should refer her to another
caregiver. The physicians values; sense of societal goals;
and racial, ethnic, or socioeconomic issues should not be
the basis of a recommendation to undergo sterilization.
Sterilization requires the patients informed consent
for ethical and medicallegal reasons. The physician performing the procedure has the responsibility of ensuring
that the patient is properly counseled concerning the risks
and benefits of sterilization. The patient should receive
comprehensive and individualized counseling on
reversible alternatives to sterilization (1). The procedures
intended permanence should be stressed, as well as the
possibility of future regret. An estimate of the procedures
failure rate and risk of ectopic pregnancy should be provided. A variety of patient education materials are available to assist in preoperative counseling, but it is essential
for the patient to be given the opportunity to discuss all
relevant issues with her physician and to ask questions.
The physician should be familiar with any laws and
regulations that may constrain sterilization, such as limitations on the patients age and requirements for the consent process. The physician should inform the patient that
insurance coverage for sterilization is variable so that she
can discuss this issue with her insurer.
Specific Ethical Issues

Because sterilization may have important effects on individuals other than the patient, women requesting sterilization should be encouraged to discuss the issues with
their husbands or other appropriate intimate partners. In
many cases, it is preferable for the male partner to be sterilized. It may be helpful for the physician to counsel the
partner directly, with the patients consent.
Hysterectomy solely for the purpose of sterilization is
inappropriate. The risks and cost of the procedure are
disproportionate to the benefit, given the available alternatives. In disabled women with limited functional capability, indications for major surgical procedures remain
the same as in other patients. In all cases, indications for
surgery must meet standard criteria, and the benefits of
the procedure must exceed known procedural risks.
Disabled women with limited functional capacity may
sometimes be physically unable to care for their menstrual hygiene and are profoundly disturbed by their menses.
On occasion, such womens caretakers have sought hysterectomy for these indications. Hysterectomy for the
purpose of cessation of normal menses may be considered only after other reasonable alternatives have been
attempted.
Women may be vulnerable to various forms of coercion in their medical decision making. For example, the
withholding of other medical care by linking it to the
patients consent to undergo sterilization is ethically

unacceptable. Laws, regulations, and reimbursement
restrictions concerning sterilization have been created to
protect vulnerable individuals, including those with mental disabilities, from abuse. However, sterilization should
not be denied to individuals simply because they also may
be vulnerable to coercion. Physicians caring for patients
who request or require procedures that result in sterilization may find themselves in a dilemma when legal and
reimbursement restrictions interfere with a patients
choice of treatment. Rigid timing and age requirements
can restrict access to good health care and result in unnecessary risk (2). Physicians are encouraged to seek legal or
ethical consultation or both whenever necessary in their
efforts to provide care that is most appropriate in individual situations.
At a public policy level, medical professionals have an
opportunity to be a voice of reason and compassion by
pointing out when legislative and regulatory measures
intended to be safeguards interfere with patient choice
and appropriate medical care.
Special Considerations Concerning

Patients With Mental Disabilities
As used in this Committee Opinion, the term women
with mental disabilities refers to individuals whose ability to participate in the informed consent process is, or
might be, limited and whose autonomy is, or might be,
thereby impaired. Such individuals constitute a heterogeneous group, including those with varying degrees of presumably irreversible mental retardation as well as those
with varying types and degrees of chronic mental illness. Some of these illnesses are reversible to varying
degrees and for varying periods. The concept of chronically and variably impaired autonomy has been proposed to describe such situations (3).
Physicians who perform sterilizations must be aware
of widely differing federal, state, and local laws and regulations, which have arisen in reaction to a long and
unhappy history of sterilization of unfit individuals in
the United States and elsewhere. The potential remains
for serious abuses and injustices. Individuals who are
capable of reproducing and parenting without a presumptive risk of child neglect or abuse may be deprived
of their procreative rights simply because they carry a
label, such as mild retardation, that suggests an inherent
unfitness to parent. The implications of this labeling
process for reproductive rights should be examined as
thoroughly and objectively as possible before making a
decision about sterilization.
Conversely, individuals for whom pregnancy is a serious burden or harm may be denied the opportunity for a
full range of contraceptive options. For example, federal
funds may not be used for the sterilization of mentally
incompetent or institutionalized individuals (2).
Physicians always should have the maximum respect for
COMMITTEE OPINIONS
patient autonomy, and the presence of a mental disability

does not, in itself, justify either sterilization or its denial.
Determination of Ability to Give

Informed Consent
Before carrying out any surgical procedure, the physician
has the important responsibility of ascertaining the
patients capacity to provide informed consent. It may be
difficult to be sure that patients with normal intellectual
function understand the complexities of some situations;
when the patient has a mental disability, the task is more
difficult and the responsibility is more challenging.
Evaluating a mentally impaired patients ability to
provide informed consent is seldom straightforward (4).
For example, although degrees of mental retardation have
been defined according to intelligence quotient, there is
no direct relationship between such diagnostic categories
and the capacity to consent. Among the issues that may
need to be considered in the assessment are the patients
language and culture, the quality of information provided (clarity, completeness, and lack of bias), the setting
of counseling (privacy and comfort), and possible fluctuations in the patients comprehension. Such fluctuations
may result from various stressors and medications.
Multiple interviews over an adequate period may be
required. Obtaining the assistance of professionals
trained in communicating with mentally disabled individuals is essential. These professionals may include special educators, psychologists, nurses, attorneys familiar
with disability law, and physicians accustomed to working
with mentally disabled patients.
The process of evaluating a patients ability to give
informed consent may be set forth in laws of the jurisdiction involved, and legal requirements for the determination of competence vary greatly. The concept of legal
competence is quite complex. Standards for the definition
of competence may vary with the specific purpose (eg,
marriage; making a will; consenting to or refusing lifesaving treatment; or, as in the case of sterilization, consenting to elective surgery).
Court approval of sterilization may be required by
law or may be necessary in difficult cases because of disagreement among the patients caregivers and consultants. In most jurisdictions, court action is not required to
carry out a sterilization procedure if there is agreement
among these consultants that a nonminor is capable of
consenting. Certain jurisdictions may not recognize
guardian consent for sterilization of minors with mental
disabilities under any circumstances. Whether or not
recourse to the courts is necessary, every effort should be
made to conduct the determination of competence fairly
and to preserve autonomy.
Ethical Issues When the Patient

Cannot Give Informed Consent
When the patient has been determined to be irreversibly
incapable of participating in all or part of the informed
163
consent process, others must make beneficence-based

decisions regarding medical treatment. Such a determination is relatively uncommon. Even in these situations, it
often is possible and highly desirable to obtain at least the
patients assent. The initial premise should be that nonvoluntary sterilization generally is not ethically acceptable
because of the violation of privacy, bodily integrity, and
reproductive rights that it may represent.
Physicians and other caregivers should avoid paternalistic decisions in all cases in which the individual may
be capable of participating to some degree in decisions
regarding her care. The following recommendations are
based in part on those of McCullough et al (3). They do
not apply to mentally impaired individuals who can participate in the consent process.
For patients with chronically and variably impaired
autonomy, initial efforts should be directed toward
restoring decision-making ability by such means as
adjustment of medication and avoidance of stressors.
This may allow the patient to exercise full autonomy. For
cases in which these efforts fail, the following guidelines
are recommended:
Efforts should be made to conform to the patients
expressed values and beliefs regarding reproduction.
Such information may be available from interviewing the patient, her family, caregivers, and others in
her environment. If possible, alternatives (including
no action) consistent with her beliefs, medical condition, and social situation should be presented to decision makers.
Physicians should be aware of the possibility of
undue pressure from family members whose interests, no matter how legitimate, may not be the same
as the patients. When appropriate, the patient should
have the opportunity to be interviewed without family members present.
Noninvasive modalities designed to assist family
members and other caregivers with setting behavioral
limits should be considered as alternatives to sterilization. These resources may include socialization training, sexual abuse avoidance training, supportive family therapy, and sexuality education.
Consideration should be given to the degree of certainty of various adverse outcomes. For example,
given the patients living circumstances, how likely is
it that she might be sexually exploited? Given available knowledge concerning her reproductive potential (ovulatory status and tubal patency), how likely is
it that she will become pregnant? How likely are
adverse medical or social consequences from a pregnancy? Because it is uncommon for such risks to be
reliably predicted, it may be preferable to recommend a reversible long-term form of contraception,
such as an intrauterine device, long-term injectable
progestin, or long-acting subdermal progestin
implants (if available), instead of sterilization. In
164
most cases, the chosen method of contraception

should be the least restrictive in preserving future
reproductive options. This is especially true when a
major factor in the request for sterilization is concern
about burdens for others. At the same time, risks and
inconveniences of contraception over a long period,
as compared with a single, relatively simple, and
definitive surgical procedure, should not be ignored.
The well-being of a child potentially conceived also
should receive consideration.
Summary
Sterilization is an elective procedure with permanent and
far-reaching consequences. Physicians who perform sterilization have ethical responsibilities of the highest order
to counsel patients fully and without bias. Physicians
must assess thoroughly the capacity of patients with
impaired mental abilities to participate fully in the
informed consent process. When this capacity is limited,
the physician must consult with the patients other caregivers in reaching a decision, which is based on the
patients best interests and preserves her autonomy to the
maximum extent possible. In difficult cases, a hospital
ethics committee may provide useful perspectives.
References
1. Benefits and risks of sterilization. ACOG Practice Bulletin
No. 46. American College of Obstetricians and Gynecologists. Obstet Gynecol 2003;102:64758.
2. Sterilization of persons in federally assisted family planning
projects. 42 C.F.R. 50 Subpart B (2006).
3. McCullough LB, Coverdale J, Bayer T, Chervenak FA.
Ethically justified guidelines for family planning interventions to prevent pregnancy in female patients with chronic
mental illness. Am J Obstet Gynecol 1992;167:1925.
4. Appelbaum PS, Grisso T. Assessing patients capacities to
consent to treatment [published erratum appears in N Engl
J Med 1989;320:748]. N Engl J Med 1988;319:16358.
Sterilization of women, including those with mental disabilities.
ISSN 1074-861X
COMMITTEE OPINIONS
165

Number 373 August 2007
Sexual Misconduct*
Committee on Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: The physicianpatient relationship is damaged when there is either

confusion regarding professional roles and behavior or clear lack of integrity that allows
sexual exploitation and harm. Sexual contact or a romantic relationship between a physician and a current patient is always unethical, and sexual contact or a romantic relationship between a physician and a former patient also may be unethical. The request by
either a patient or a physician to have a chaperone present during a physical examination
should be accommodated regardless of the physicians sex. If a chaperone is present
during the physical examination, the physician should provide a separate opportunity for
private conversation. Physicians aware of instances of sexual misconduct have an obligation to report such situations to appropriate authorities.
The privilege of caring for patients, often

over a long period, can yield considerable
professional satisfaction. The obstetrician
gynecologist may fill many roles for patients,
including primary physician, technology
expert, prevention specialist, counselor, and
confidante. Privy to both birth and death,
obstetriciangynecologists assist women as
they pass through adolescence; grow into
maturity; make choices about sexuality, partnership, and family; experience the sorrows
of reproductive loss, infertility, and illness;
and adapt to the transitions of midlife and
aging. The practice of obstetrics and gynecology includes interaction at times of intense
emotion and vulnerability for the patient and
involves both sensitive physical examinations
and medically necessary disclosure of especially private information about symptoms
and experiences. The relationship between
the physician and patient, therefore, requires
a high level of trust and professional responsibility.
Trust of this sort cannot be maintained
without a basic understanding of the limits
and responsibilities of the professionals role.
Physician sexual misconduct is an example of
abuse of limits and failure of responsibility.
The valued human experience of the physicianpatient relationship is damaged when
there is either confusion regarding profes*Update of Sexual Misconduct in Ethics in Obstetrics
and Gynecology, Second Edition, 2004.
sional roles and behavior or clear lack of

integrity that allows sexual exploitation and
harm.
Sexual misconduct is of particular concern in todays environment of shifting roles
for women and men, greater sexual freedom,
and critical evaluation of power relations in
society (14). Prohibitions against sexual
contact between patient and physician are
not new; they can be found in the earliest
guidelines in western antiquity. From the
beginning, physicians were enjoined to do
no harm and specifically avoid sexual contact with patients (5). In the intervening centuries, as the study of medical ethics has
evolved, attention has been focused on
respect for individual rights, the problem of
unequal power in relationships between professionals and patients, and the potential for
abuse of that power (6).
In this context, the American Medical
Associations Council on Ethical and Judicial
Affairs developed a report, Sexual Misconduct in the Practice of Medicine, condemning sexual relations between physicians and
current patients (7). It raises serious questions about the ethics of romantic relationships with former patients. It is summarized
as follows (8):
Sexual contact that occurs concurrent
with the physicianpatient relationship
constitutes sexual misconduct. Sexual or
romantic interactions between physi-
166
cians and patients detract from the goals of the

physicianpatient relationship, may exploit the vulnerability of the patient, may obscure the physicians
objective judgment concerning the patients health
care, and ultimately may be detrimental to the patients well-being.
If a physician has reason to believe that non-sexual
contact with a patient may be perceived as or may lead
to sexual contact, then he or she should avoid the nonsexual contact. At a minimum, a physicians
ethical duties include terminating the physician
patient relationship before initiating a dating, romantic, or sexual relationship with a patient.
Sexual or romantic relationships between a physician
and a former patient may be unduly influenced by
the previous physicianpatient relationship. Sexual
or romantic relationships with former patients are
unethical if the physician uses or exploits trust, knowledge, emotions, or influence derived from the previous
professional relationship.
The Council provides clear guidelines (7):

Mere mutual consent is rejected as a justification for
sexual relations with patients because the disparity in
power, status, vulnerability, and need make it difficult for a patient to give meaningful consent to sexual contact or sexual relations.
Sexual contact or a romantic relationship concurrent
with the physicianpatient relationship is unethical.
Sexual contact or a romantic relationship with a former patient may be unethical under certain circumstances (9). The relevant standard is the potential
for misuse of physician power and exploitation of
patient emotions derived from the former relationship.
Education on ethical issues involved in sexual misconduct should be included throughout all levels of
medical training (1013).
Physicians have a responsibility to report offending
colleagues to disciplinary boards.
The Society of Obstetricians and Gynaecologists of
Canada has adopted a similar statement that acknowledges and deplores the fact that incidents of physicians
abusing patients do occur and finds that these incidents include sexual impropriety due to poor clinical
skills, chauvinism, or abuse of the power relationship,
and outright systematic sexual abuse (14). The Society
also supports the right to informed, safe, and gendersensitive care and the right of victims of abuse to receive
prompt treatment. Identification, discipline, and,
where possible, rehabilitation of the perpetrators is recommended.
Although much discussion of sexual misconduct by
health care professionals has centered around the particular vulnerability that exists within the relationship a
woman has with her mental health care professional (15,

16), sexual contact between patients and obstetrician
gynecologists also has been documented (3, 4). Physicians
themselves acknowledge that there is a problem, but the
extent of the problem is difficult to determine because
information relies on self-reporting, which carries the
potential for bias in response.
The Committee on Ethics of the American College of
Obstetricians and Gynecologists endorses the ethical
principles expressed by the American Medical Association and the Society of Obstetricians and Gynaecologists
of Canada and affirms the following statements:
Sexual contact or a romantic relationship between a
physician and a current patient is always unethical.
Sexual contact or a romantic relationship between a
physician and a former patient also may be unethical.
Potential risks to both parties should be considered
carefully. Such risks may stem from length of time
and intensity of the previous professional relationship; age differences; the length of time since cessation of the professional relationship; the former
patients residual feelings of dependency, obligation,
or gratitude; the former patients vulnerability to
manipulation as a result of private information disclosed during treatment; or physician vulnerability if
a relationship initiated with a former patient breaks
down.
Physicians should be careful not to mix roles that are
ordinarily in conflict. For example, they should not
perform breast or pelvic examinations on their own
minor children unless an urgent indication exists.
Children and adolescents are particularly vulnerable
to emotional conflict and damage to their developing
sense of identity and sexuality when roles and role
boundaries with trusted adults are confused. It is
essential to ensure the young individuals privacy and
prevent subtly coercive violations from occurring.
The request by either a patient or a physician to have
a chaperone present during a physical examination
should be accommodated regardless of the physicians sex. Local practices and expectations differ
with regard to the use of chaperones, but the presence of a third party in the examination room can
confer benefits for both patient and physician,
regardless of the sex of the chaperone. Chaperones
can provide reassurance to the patient about the
professional context and content of the examination
and the intention of the physician and offer witness
to the actual events taking place should there be any
misunderstanding. The presence of a third party in
the room may, however, cause some embarrassment
to the patient and limit her willingness to talk openly with the physician because of concerns about confidentiality. If a chaperone is present, the physician
should provide a separate opportunity for private
COMMITTEE OPINIONS
conversation. If the chaperone is an employee of

the practice, the physician must establish clear rules
about respect for privacy and confidentiality. In
addition, some patients (especially, but not limited
to, adolescents) may consider the presence of a family member as an intrusion. Family members should
not be used as chaperones unless specifically
requested by the patient and then only in the presence of an additional chaperone who is not a family
member.
Examinations should be performed with only the
necessary amount of physical contact required to
obtain data for diagnosis and treatment. Appropriate
explanation should accompany all examination procedures.
Physicians should avoid sexual innuendo and sexually provocative remarks.
When physicians have questions and concerns about
their sexual feelings and behavior, they should seek
advice from mentors or appropriate professional
organizations (16, 17).
It is important for physicians to self-monitor for any
early indications that the barrier between normal
sexual feelings and inappropriate behavior is not
being maintained (4, 16, 18). These indicators might
include special scheduling, seeing a patient outside
normal office hours or outside the office, driving a
patient home, or making sexually explicit comments
about patients.
Physicians involved in medical education should
actively work to include as part of the basic curriculum information about both physician and patient
vulnerability, avoidance of sexually offensive or denigrating language, risk factors for sexual misconduct,
and procedures for reporting and rehabilitation.
Physicians aware of instances of sexual misconduct
on the part of any health professional have an obligation to report such situations to appropriate
authorities, such as institutional committee chairs,
department chairs, peer review organizations, supervisors, or professional licensing boards.
Physicians with administrative responsibilities in
hospitals, other medical institutions, and licensing
boards should develop clear and public guidelines for
reporting instances of sexual misconduct, prompt
investigation of all complaints, and appropriate disciplinary and remedial action (19).
Sexual misconduct on the part of physicians is an

abuse of professional power and a violation of patient
trust. It jeopardizes the well-being of patients and carries
an immense potential for harm. The ethical prohibition
against physician sexual misconduct is ancient and forceful, and its application to contemporary medical practice
is essential.
167
References
1. Gabbard GO, Nadelson C. Professional boundaries in the
physician-patient relationship [published erratum appears
in JAMA 1995;274:1346]. JAMA 1995;273:14459.
2. Gawande A. Naked. N Engl J Med 2005;353:6458.
3. Dehlendorf CE, Wolfe SM. Physicians disciplined for sexrelated offenses. JAMA 1998;279:18838.
4. Enbom JA, Parshley P, Kollath J. A follow-up evaluation of
sexual misconduct complaints: the Oregon Board of
Medical Examiners, 1998 through 2002. Am J Obstet
Gynecol 2004;190:164250; discussion 16503; 6A.
5. Campbell ML. The Oath: an investigation of the injunction
prohibiting physicianpatient sexual relations. Perspect Biol
Med 1989;32:3008.
2001.
7. Sexual misconduct in the practice of medicine. Council on
Ethical and Judicial Affairs, American Medical Association.
JAMA 1991;266:27415.
8. American Medical Association. Sexual misconduct in the
practice of medicine. In: Code of medical ethics of the
American Medical Association: current opinions with annotations. 20062007 ed. Chicago (IL): AMA; 2006. p. 2558.
9. Hall KH. Sexualization of the doctor-patient relationship: is
it ever ethically permissible? Fam Pract 2001;18:5115.
10. Goldie J, Schwartz L, Morrison J. Sex and the surgery: students attitudes and potential behaviour as they pass
through a modern medical curriculum. J Med Ethics 2004;
30:4806.
11. White GE. Setting and maintaining professional role boundaries: an educational strategy. Med Educ 2004;38: 90310.
12. White GE. Medical students learning needs about setting
and maintaining social and sexual boundaries: a report.
Med Educ 2003;37:10179.
13. Spickard A, Swiggart WH, Manley G, Dodd D. A continuing
education course for physicians who cross sexual boundaries. Sex Addict Compulsivity 2002;9:3342.
14. Sexual abuse by physicians. SOGC Policy Statement No.
134. Society of Obstetricians and Gynaecologists of Canada.
J Obstet Gynaecol Can 2003;25:862.
15. Gabbard GO, editor. Sexual exploitation in professional
relationships. Washington, DC: American Psychiatric Press;
1989.
16. Simon RI. Therapistpatient sex. From boundary violations
to sexual misconduct. Psychiatr Clin North Am 1999;
22:3147.
17. Crausman RS. Sexual boundary violations in the physicianpatient relationship. Med Health R I 2004;87:2556.
18. Searight HR, Campbell DC. Physicianpatient sexual contact: ethical and legal issues and clinical guidelines. J Fam
Pract 1993;36:64753.
19. Federation of State Medical Boards. Addressing sexual
boundaries: guidelines for state medical boards. Dallas
(TX): FSMB; 2006. Available at: http://www.fsmb.org/pdf/
GRPOL _Sexual%20Boundaries.pdf. Retrieved January 23,
2007.
168
Copyright August 2007 by the American College of Obstetricians

Sexual misconduct. ACOG Committee Opinion No. 373. American
College of Obstetricians and Gynecologists. Obstet Gynecol 2007;
110:4414.
ISSN 1074-861X
COMMITTEE OPINIONS
169

Expert Testimony*
Committee on Ethics
ABSTRACT: It is the duty of obstetricians and gynecologists who testify as expert

witnesses on behalf of defendants, the government, or plaintiffs to do so solely in accordance with their judgment on the merits of the case. Obstetriciangynecologists must
limit testimony to their sphere of medical expertise and must be prepared adequately.
They must make a clear distinction between medical malpractice and medical maloccurrence. The acceptance of fees that are greatly disproportionate to those customary for
professional services can be construed as influencing testimony given by the witness,
and it is unethical to accept compensation that is contingent on the outcome of litigation.

Gynecologists (ACOG) recognizes that it is
the duty of obstetricians and gynecologists
who testify as expert witnesses on behalf of
defendants, the government, or plaintiffs to
do so solely in accordance with their judgment on the merits of the case. Furthermore,
ACOG cannot condone the participation of
physicians in legal actions where their testimony will impugn performance that falls
within accepted standards of practice or, conversely, will support obviously deficient practice. Because the experts articulate the
standards in a given case, care must be exercised to ensure that such standards do not
narrowly reflect the experts views to the
exclusion of other choices deemed acceptable
by the profession. The American College of
Obstetricians and Gynecologists considers
unethical any expert testimony that is misleading because the witness does not have
appropriate knowledge of the standard of
care for the particular condition at the relevant time or because the witness knowingly
misrepresents the standard of care relevant to
the case.
The Problem of Professional

LiabilityReality and
Perceptions
of Obstetricians
and Gynecologists
Womens Health Care
Physicians

Gynecologists recognizes its responsibility,
and that of its Fellows, to continue efforts to
*Update of Expert Testimony in Ethics in Obstetrics
advance health care for women through

every available method of quality assessment
and improvement. The American College of
Obstetricians and Gynecologists also recognizes, however, that many claims of professional liability represent the response of a
litigation-oriented society to a technologically advanced form of health care that has fostered unrealistic expectations. As technology
becomes more complex, associated benefits
and risks may increase, making the complication-free practice of medicine less possible.
It therefore becomes important to distinguish between medical maloccurrence
and medical malpractice. Medical maloccurrence is defined as a bad or undesirable
outcome that is unrelated to the quality of
care provided. In some cases, specific medical
or surgical complications may be anticipated
but are felt by the patient and the health care
provider to be offset by the balance of benefits from the planned intervention and,
therefore, represent unavoidable risks of
appropriate medical care. There are other
types of complications that cannot be anticipated and in their unpredictability are similarly unavoidable. Still other complications
occur as a result of decisions that have been
made carefully by patients and physicians
with fully informed consent but appear, in
retrospect, to have been a less optimal choice
among several options. Each of these situations represents a type of maloccurrence,
rather than an example of malpractice, and is
the result of the uncertainty inherent in all of
medicine. Malpractice, in contrast, requires a
170
demonstration of negligence (ie, substandard practice

that causes harm). The potential for personal, professional, and financial rewards from expert testimony may
encourage testimony that undermines the distinction
between unavoidable maloccurrence and actual medical
malpractice. It is unethical to distort or to represent a
maloccurrence as an example of medical malpractice or,
conversely, represent malpractice as a case of maloccurrence.
The American College of Obstetricians and Gynecologists supports the concept of appropriate and prompt
compensation to patients for medically related injuries.
Any such response, however, also should reflect the distinction between medical maloccurrence, for which all of
society should perhaps bear financial responsibility, and
medical malpractice, for which health care providers
should be held responsible.
Responsibility of Individual Physicians

The moral and legal duty of physicians who testify before
a court of law is to do so in accordance with their expertise. This duty implies adherence to the strictest personal
and professional ethics. Truthfulness is essential. Misrepresentation of ones personal clinical opinion as absolute
right or wrong may be harmful to individual parties and
to the profession at large. The obstetriciangynecologist
who is an expert witness must limit testimony to his or
her sphere of medical expertise and must be prepared
adequately. Witnesses who testify as experts must have
knowledge and experience that are relevant to obstetric
and gynecologic practice at the time of the occurrence
and to the specific areas of clinical medicine they are discussing. The acceptance of fees that are greatly disproportionate to those customary for professional services can
be construed as influencing testimony given by the witness. It is unethical for a physician to accept compensation that is contingent on the outcome of litigation (1, 2).
The American College of Obstetricians and Gynecologists encourages the development of policies and standards for expert testimony. Such policies should address
safeguards to promote truth-telling and to encourage
openness of the testimony to peer review. These policies
also would encourage testimony that does not assume an
advocacy or partisan role in the legal proceeding.
The following principles are offered as guidelines for
the physician who assumes the role of an expert witness:
1. The physician must have experience and knowledge
in the areas of clinical medicine that enable him or
her to testify about the standards of care that applied
at the time of the occurrence that is the subject of the
legal action.
2. The physicians review of medical facts must be thorough, fair, and impartial and must not exclude any
relevant information. It must not be biased to create
a view favoring the plaintiff, the government, or the
defendant. The goal of a physician testifying in any
judicial proceeding should be to provide testimony
that is complete, objective, and helpful to a just resolution of the proceeding.
3. The physicians testimony must reflect an evaluation
of performance in light of generally accepted standards, neither condemning performance that falls
within generally accepted practice standards nor
endorsing or condoning performance that falls
below these standards. Experts and their testimony
should recognize that medical decisions often must
be made in the absence of diagnostic and prognostic
certainty.
4. The physician must make a clear distinction between
medical malpractice and medical maloccurrence.
5. The physician must make every effort to assess the
relationship of the alleged substandard practice to
the outcome. Deviation from a practice standard is
not always substandard care or causally related to a
bad outcome.
6. The physician must be prepared to have testimony
given in any judicial proceeding subjected to peer
review by an institution or professional organization
to which he or she belongs.
References
1. American Medical Association. Medical testimony. In: Code
of medical ethics of the American Medical Association: current opinions with annotations. 20062007 ed. Chicago
(IL): AMA; 2006. p. 2869.
2. American Bar Association. Rule 3.4. Fairness to opposing
party and counsel. In: Annotated model rules of professional conduct. 5th ed. Chicago (IL): ABA; 2003. p. 34758.

Expert testimony. ACOG Committee Opinion No. 374. American
110:4456.
ISSN 1074-861X
COMMITTEE OPINIONS
171

Research Involving Women*

Committee on
Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: All women should be presumed to be eligible for participation in clinical studies. The potential for pregnancy should not automatically exclude a woman from
participating in a clinical study, although the use of contraception may be required for participation. Research objectives should not interfere with appropriate clinical management. If a conflict arises between medically appropriate patient care and research
objectives, patient care should prevail. Consent of the pregnant woman alone is sufficient
for most research. Pregnant women considering participation in a research study should
determine the extent to which the father is to be involved in the process of informed consent and the decision.
Attitudes concerning inclusion of women in

research trials have changed dramatically
over the past four decades. In the 1970s and
1980s, women were systematically excluded
from participating in research trials either
because of the fear that unrecognized pregnancy might place an embryo at risk or
because a uniform all-male sample would
simplify analysis of data. In addition, pregnant women were excluded from most
research trials because they were viewed as a
vulnerable population requiring special protection, and there was concern that trial participation would result in harm to the fetus.
Another fear was that participation of pregnant women in research trials would result in
increased liability risk for researchers. In the
1990s, there was a dramatic policy shift
toward wide-scale inclusion of women in
research trials. This policy shift is a direct
result of a conscious effort by government
agencies to expand participation of women
in research in order to obtain valid, evidencebased information about health and disease
in this population (1).
This Committee Opinion is designed to
provide reasonable guidelines for research
involving women. The American College of
Obstetricians and Gynecologists Committee
on Ethics affirms both the need for women to
serve as participants in research and the obligation for researchers, institutional review
*Update of Research Involving Women, in Ethics in
boards (IRBs), and others reviewing clinical

research to evaluate the potential effect of
proposed research on women of childbearing
potential, pregnant women, and the developing fetus.
Rationale for Including Women

in Research
All women should be presumed to be eligible
for participation in clinical studies. The
potential for pregnancy should not automatically exclude a woman from participating in a
clinical study, although the use of contraception may be required for participation.
Inclusion of women in clinical studies is necessary for valid inferences about health and
disease in women. The generalization to
women of results from trials conducted in
men may yield erroneous conclusions that fail
to account for the biologic differences
between men and women.
The rationale for conducting research in
women is to advance knowledge in the following areas:
Medical conditions in women (eg, cardiovascular disease)
Physiology of women
Sex differences in responses to drugs (eg,
antiretroviral agents)
Sex differences in drug toxicities
Sex differences in responses to disease
(eg, mental disorders)
172
Effects of hormonal contraceptives on response to

other therapies (eg, seizure medication)
Variations in response to therapy at different stages
of the menstrual cycle and the life cycle
The rationale for conducting research in pregnant
and postpartum women is to advance knowledge in the
following areas:
Medical conditions (eg, human immunodeficiency
virus [HIV]) in women who become pregnant
Medical conditions unique to pregnancy (eg, preeclampsia)
Conditions that threaten the successful course of
pregnancy (eg, preterm labor)
Prenatal conditions that might threaten the health of
the fetus (eg, diaphragmatic hernia)
Physiologic changes that accompany pregnancy and
lactation
Medical conditions related to pregnancy that might
affect the future health of women (eg, gestational
diabetes)
Safety of medication during pregnancy and breastfeeding
Human experimentation is a necessary and important
part of biomedical research because certain information
can be obtained in no other way. Guidelines for protection
of research participants have been established and are
applicable to women of childbearing potential as well as to
pregnant women (24). Additional protections have been
established for pregnant women (5, 6). Participants in
research should expect full disclosure of the known burdens and benefits of the research study and should understand the potential risks as well as benefits. Investigators
must use research design methods that aim to maximize
safety and minimize risk. A fully informed consent process
and review of study protocols by IRBs help to ensure that
efforts to increase access to and participation of women in
clinical trials will not result in procedural shortcuts that
violate basic ethical standards.
Involvement in research protocols should not
diminish a womans expectation that she will receive
appropriate medical care during the study and in the
future. Health care professionals have a responsibility to
provide the most appropriate clinical management,
whether or not a woman is a participant in research.
Research objectives should not affect clinical management. If a conflict arises between medically appropriate
patient care and research objectives, patient care should
prevail. For example, it is inappropriate to attempt to
delay a medically indicated induction of labor solely to
meet gestational age criteria for participation in a
research project. The welfare of the patient and, in the
case of pregnancy, the patient and her fetus is always the
primary concern.
The Ethical Context

Ethical Requirements for Research
To be considered ethically justified, research on human
participants must satisfy several conditions. These
include a reasonable prospect that the investigation will
produce the knowledge that is being sought, a favorable
balance of benefits over risks, a proven necessity to use
human participants, a system for independent monitoring of outcomes and protection of human participants,
and a fair allocation of the burdens and benefits of the
research among potential groups of participants (7).
These principles should not be weakened by attempts to
increase participation of women in research trials.
Although it is important to try to distinguish ethical
problems involving patient care from ethical issues related to research, a definitive line cannot always be drawn
between the two areas. The dual role that physicians often
assume as research scientists and clinical practitioners
may result in conflict of interest because each role has different goals and priorities. For example, the primary goal
of the investigator is to generate knowledge that has the
potential to benefit patients in the future, whereas clinicians are expected to act in the best interests of their current patients. Researchers need to recognize potential
conflicts, strive to resolve them before beginning specific
research projects, and inform patients about potential
conflicts as they seek consent for research participation.
The potential for role conflict becomes readily apparent when innovative therapies are introduced (8). In the
context of maternalfetal surgery, for example, innovative
surgical procedures have been conducted, but the longterm impact on both the woman and the fetus is unclear.
In this context, it is important to conduct rigorous scientific evaluation of maternalfetal surgery before these
innovative therapies are offered as routine care.
Ethical Principles Supporting the Inclusion of
Women
The recent movement to enroll more women in clinical
research can be justified by ethical principles: beneficence,
nonmaleficence, respect for autonomy, and justice.
Because disease processes may have different characteristics in women and men and because women and men
may respond differently to treatments and interventions,
women need to be included as participants in clinical
research. For women to benefit from the results of
research (beneficence), the research must be designed to
provide a valid analysis as to whether women are affected
differently than men (1). Such differential analysis is necessary not only to benefit women, but also to prevent
harm; if data from studies with men are inappropriately
extrapolated to women, women may actually suffer harm
(nonmaleficence).
Arguments previously advanced to defend the exclusion of women from research often cited the possibility of
harm to women of reproductive potential or to pregnant
COMMITTEE OPINIONS
women and their fetuses, harm that did not apply to men.
However, the risk of such harm can be minimized and, in
itself, does not justify the exclusion of women from
research that is needed to make valid inferences about the
medical treatment of women.
Women have frequently been regarded as a vulnerable population that needs to be protected. Today, however, both civil society and medical ethics recognize the
right and the capacity of women to make decisions
regarding their own lives and their medical care (respect
for autonomy). Similarly, women have the right and the
capacity to weigh the risks and potential benefits of participation in research and to decide for themselves
whether to consent to participate. This autonomy right is
limited, however, by the responsibility of investigators and
IRBs to take precautions to limit the risk for research participants, including pregnant women and their fetuses.
Systematic exclusion of women from research violates the ethical principle of justice, which first requires
that persons be given what is due them. If the medical
treatment of women is invalidly based on studies that
excluded women, then women are not receiving fair treatment. Justice requires that women be included in clinical
studies in sufficient numbers to determine whether their
responses are different from those of men.
In the research setting, justice requires that the benefits of scientific advancement be shared fairly between
men and women. Both women and men should be
encouraged to participate in research. Researchers should
specifically address those obstacles to participation that
are experienced disproportionately by womenfor
example, problems obtaining and paying for adequate
child care during time spent as a research participant.
Because of a history of systematic exclusion of
women from research, in 1993 Congress directed that
women were to be included in all federally funded
research projects (9). Consequently, the National Institutes of Health (NIH) now require that women be included in all NIH-funded clinical research, unless a clear and
compelling rationale establishes that such involvement
would be inappropriate or unsafe (1). Particular focus on
the health needs of women is justifiable at this time in
view of a history of neglect of such studies.
Informed Consent
Appropriate and adequately informed consent by the
potential participant or another authorized person and
an independent review of the risks and benefits of
research by appropriate institutions or agencies (or both)
are fundamental to the formulation of any research protocol (10). The informed consent process should not be
weakened to benefit the researcher. The consent document should be understandable and written in simple
language. In situations in which English is not the primary language of the potential study participant, an interpreter should be used for the consent process to
verify the participants level of understanding of the issues
173
related to risk and benefit. The statement of informed

consent may need to be translated into the participants
native language. Researchers should be familiar with federal and state laws and regulations for informed consent
in settings where pregnant minors and adolescents may
be recruited as participants (11).
The researcher has an obligation to disclose to the
woman and discuss with her all material risks affecting
her; in the case of a pregnant woman, this includes all
material risks to the woman and her fetus (12). Disclosure
should include risks that are likely to affect the patients
decision to participate or not to participate in the
research. Because the process of informed consent cannot
anticipate all conceivable risks, women who develop
unanticipated complications should be instructed to contact the researcher or a representative of the IRB immediately. Pregnant women who enroll in a research trial and
experience a research-related injury should be informed
about their therapeutic options, including those related to
the pregnancy.
The potential participant should be encouraged to
consult her physician independently before deciding to
participate in a research study (13). At the womans
request, the researcher should provide information about
the study to her physician. If relevant, this information
may include the requirements of the study and its possible outcomes and complications.
Both the researcher and the primary caregiver should
guard against inflating the patients perception of the therapeutic benefit expected from participating in the study.
Studies have shown that research participants tend to
believe, despite careful explanation of research protocols,
that they will always benefit from participation or that the
level of actual benefit will be greater than stated in the consent process (14). This risk of therapeutic misconception
may be increased when the patients own physician is
involved in the consent process, especially when one
physician serves as both researcher and clinician.
Consent of the pregnant woman alone is sufficient
for most research. When research has the prospect of
direct benefit to the fetus alone, paternal consent also may
be required (see Table 1). Federal regulations that call for
involvement of the father in the consent process for
research intended to benefit the fetus are controversial
and have generated vigorous debate. Proponents of paternal consent endorse this requirement because they believe
that the requirement is consistent with recognition of and
respect for the rights of the father in protecting the welfare of his unborn child. They believe that this represents
a reasonable compromise between acknowledging paternal rights and reducing barriers to participation in
research by pregnant women.
The Committee on Ethics, however, does not support
recognition of distinct paternal rights before the birth of
a child. Recognition of paternal rights during pregnancy
may infringe on and weaken maternal autonomythe
right of a woman, when pregnant, to independent action
174
Table 1. Selected Federal Regulations on Informed Consent for Participants in Human Research*
Issue
Citation
Regulation
Maternal consent
45 C.F.R. 46.204(d)
If the research holds out the prospect of direct benefit to the pregnant woman,
the prospect of a direct benefit both to the pregnant woman and the fetus, or no
prospect of benefit for the woman nor the fetus when risk to the fetus is not
greater than minimal and the purpose of the research is the development of
important biomedical knowledge that cannot be obtained by any other means, her
consent is obtained in accord with the informed consent provisions of subpart A
of this part;
Paternal consent
45 C.F.R. 46.204(e)
If the research holds out the prospect of direct benefit solely to the fetus then the
consent of the pregnant woman and the father is obtained in accord with the
informed consent provisions of subpart A of this part, except that the fathers
consent need not be obtained if he is unable to consent because of unavailability,
incompetence, or temporary incapacity or the pregnancy resulted from rape or
incest.
*Federal regulations on protection of human research participants are found in the Code of Federal Regulations in Title 45, Part 46. Selected sections of the regulations
dealing with informed consent are reprinted here; the complete, current version may be found at http://www.hhs.gov/ohrp/ humansubjects/guidance/45cfr46.htm.
Basic HHS policy for protection of human research subjects. 45 C.F.R. 46.101124 Subpart A (2006).
in decisions that affect her body and her health. As in clinical situations, the pregnant womans consent should be
sufficient for research interventions that affect her or her
fetus. To further complicate matters, the interpretation as
to whether research is intended for the benefit of the
pregnant woman, the fetus, or both may be subjective.
Two researchers conducting identical studies may reach
different conclusions as to whether benefits of the
research apply to the pregnant woman, the fetus, or both
(eg, maternalfetal surgery for spina bifida).
Informed consent means that women have the right
to choose not to participate in a research protocol and
the right to withdraw from a study at any time. The participation of a woman in a research study is based on the
expectation that she will consider carefully her own
interests. The participation of a pregnant woman in a
research study is based on the expectation that she will
consider carefully her own interests as well as those of
her fetus. Typically, pregnant women are quite willing
to take personal risks for the benefit of their fetuses;
combined with societys expectation that they will do
so, women may find themselves under pressure to participate in research that carries risk to them. Such pressure
actually may interfere with the ability of the pregnant
woman to give fully free consent. In these situations, special care should be taken to ensure that a womans consent
is truly voluntary.
Research Related to Diagnosis and

Therapy
Research that consists of observation and recording without clinical intervention (descriptive research) is of ethical concern primarily to the extent that it requires
informed consent and the preservation of confidentiality.
In research trials where clinical intervention is a compo-
nent, the benefits and burdens of the trial must be clearly

articulated to the participant by the researcher (12). In
research studies conducted in pregnant women, both the
potential benefit to the woman, the fetus, and society as
a whole and the level of risk that may be incurred as a
result of participation in the study should be considered.
The involvement of the participants obstetrician ordinarily is appropriate. All parties concerned need to strive
for clear communication with regard to the following
questions:
Does the research involve intervention or diagnosis
that might affect the womans or the fetuss wellbeing, or is the goal of the study to produce scientific results that will be likely to be useful to future
patients but offer no demonstrable benefit to current
participants?
Can the prospective participant expect any explicit
benefit as a result of participating in the study? If not,
she must be apprised of this fact. Those studies that
search for general information and are not associated
with diagnostic or treatment modalities would be
less likely to create the impression that the research
will result in direct benefit to the participant. The researcher is still obligated to verify that the participant
has understood this aspect of the study correctly.
Is there more than minimal risk to the fetus generated by the research?
According to applicable federal regulations, minimal risk means that the probability and magnitude of
harm or discomfort anticipated in the research are not
greater in and of themselves than those ordinarily
encountered in daily life or during the performance of
routine physical or psychological examinations or tests
(15). It has been questioned whether the daily life used
COMMITTEE OPINIONS
for comparison should be that of the general population

or that of the participant. Using the participants daily life
as the standard might make a higher level of risk acceptable; therefore, the general population standard is advised
(10). Anything beyond minimal risk must be weighed
carefully against the potential benefits to the woman and
the fetus when the advisability of participation is considered. When a pregnancy has been exposed to risk in the
conduct of research, the woman should be strongly
encouraged to participate in follow-up evaluations to
assess the impact on her and her fetus or child.
It is appropriate for investigators and sponsors, with
the approval of the IRB, to require a negative pregnancy
test result as a criterion for participation in research when
the research may pose more than minimal risk to the
fetus. For an adolescent, the process of informed consent
should include a discussion about pregnancy testing and
the management of pregnancy test results, including
whether the results will be shared with her parents or
guardian.
Similarly, it is reasonable for investigators and
research sponsors, with the IRBs approval, to require the
use of effective birth control measures for women of
reproductive capacity as an inclusion criterion for participation in research that may entail more than minimal risk
to the fetus. Consultation with an obstetriciangynecologist or other knowledgeable professional is encouraged if
questions arise about efficacy and risk of contraceptive
measures.
Some study protocols mandate use of a specific contraceptive method, such as oral contraceptives or an
intrauterine device. These mandates are inappropriate
based on the principles of respect for autonomy, beneficence, and justice. A woman should be allowed to choose
a birth control method, including abstinence, according
to her needs and values (16). Requiring birth control use
by women who are not sexually active violates a commitment to respect them as persons. Hormonal contraceptive
methods that could interfere with study results may be
excluded on scientific grounds, but additional restrictions
are inappropriate.
After informed discussion about the research trial,
some women will decline to participate. Researchers
should respect this decision and not allow patient refusal
to affect subsequent clinical care. Reasonable compensation for a womans time, effort, and expense as a participant in a research study is both acceptable and desired,
but researchers should not offer inducements, financial or
otherwise, to influence participation in research beyond
reasonable compensation for the womans time, effort,
and expense.
Recommendations of the Committee

on Ethics
Federal and state laws and regulations governing research
involving women should be observed (2, 5, 11). In addi-
175
tion, the Committee on Ethics makes the following recommendations for research involving women:
1. Women should be presumed to be eligible for participation in all clinical studies except for those addressing health concerns solely relevant to men.
2. Women should be included in research in sufficient
numbers to ensure that inferences from a clinical
trial apply validly to both sexes.
3. All research on women should be conducted in a manner consistent with the following ethical principles:
Research should conform to general scientific standards for valid research.
Research may be conducted only with the informed
consent of the woman.
Researchers should not offer inducements, financial
or otherwise, to influence participation in research
beyond reasonable compensation for the womans
time, effort, and expense.
Conscientious efforts should be made to avoid
any conflicts between appropriate health care and
research objectives. Health care needs of the individual woman should take precedence over research
interests in all situations affecting clinical management.
4. Research involving pregnant women should conform
to the following recommendations:
Research may be conducted only with the informed
consent of the woman. Pregnant women considering participation in a research study should determine the extent to which the father is to be
involved in the process of informed consent and
the decision.
Informed consent of the father must be obtained
when federal regulations require it for research that
has the prospect of direct benefit to the fetus alone.
Research protocols should be evaluated for their
potential impact on both the woman and the fetus,
and that evaluation should be made as part of the
process of informed consent.
In this Committee Opinion, an attempt has been
made to take into account protection of human participants, the eligibility of women to participate in research,
and the benefits that society could derive from participation of women in research. These potential benefits include
reduction in morbidity and mortality from sex-specific
disease processes, as well as reduction in fetal, infant, and
maternal morbidity and mortality.
References
1. National Institutes of Health. NIH policy and guidelines on
the inclusion of women and minorities as subjects in clinical research Amended, October, 2001. Bethesda (MD):
NIH; 2001. Available at http://grants.nih.gov/grants/
funding/women_min/guidelines_amended_10_2001.htm.
176
2. Protection of human subjects. 45 C.F.R. 46 (2006).

3. National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research (US). The
Belmont Report: ethical principles and guidelines for the
protection of human subjects of research. Washington, DC:
U.S. Government Printing Office; 1979. Available at:
http://www.hhs.gov/ohrp/humansubjects/guidance/
belmont.htm. Retrieved May 1, 2007.
4. World Medical Association. Declaration of Helsinki: Ethical
principles for medical research involving human subjects.
Ferney-Voltaire (France): WMA; 2004. Available at: http://
www.wma.net/e/policy/pdf/17c.pdf. Retrieved May 1, 2007.
5. Additional protections for pregnant women, human fetuses and neonates involved in research. 45 C.F.R. 46.201207 Subpart B (2006).
6. Research on transplantation of fetal tissue. Informed consent of donor. 42 U.S.C. 289g-1(b) (2000).
7. Beauchamp TL. The intersection of research and practice.
In: Goldworth A, Silverman W, Stevenson DK, Young EW,
Rivers R. Ethics and perinatology. New York (NY): Oxford
University Press; 1995. p. 23144.
8. Innovative practice: ethical guidelines. ACOG Committee
9. NIH Revitalization Act of 1993, Pub. L. No. 103-43 (1993).
10. National Bioethics Advisory Commission. Ethical and policy issues in research involving human participants.
Bethesda (MD): NBAC; 2001. Available at: http://www.
georgetown.edu/research/nrcbl/nbac/human/overvol1.pdf.
11. Additional protections for children involved as subjects in

research. 45 C.F.R. 46.401409 Subpart D (2006).
12. General requirements for informed consent. 45 CFR
46.116 (2006).
13. Institute of Medicine (US). Women and health research:
ethical and legal issues of including women in clinical studies. Vol. 1. Washington, DC: National Academy Press; 1994.
14. Appelbaum PS, Roth LH, Lidz CW, Benson P, Winslade W.
False hopes and best data: consent to research and the therapeutic misconception. Hastings Cent Rep 1987;17(2):
204.
15. Definitions. 45 C.F.R. 46.102 (2006).
16. Anderson JR, Schonfeld TL, Kelso TK, Prentice ED. Women
in early phase trials: an IRBs deliberations. IRB 2003;25
(4):711.
mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher. Requests for authorization to make
photocopies should be directed to: Copyright Clearance Center, 222
Research involving women. ACOG Committee Opinion No. 377.
American College of Obstetricians and Gynecologists. Obstet Gynecol
2007;110:7316.
ISSN 1074-861X
COMMITTEE OPINIONS
177

Number 385 November 2007
The Limits of Conscientious Refusal in

Reproductive Medicine
Committee on
Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Health care providers occasionally may find that providing indicated,
even standard, care would present for them a personal moral problema conflict of conscienceparticularly in the field of reproductive medicine. Although respect for conscience is important, conscientious refusals should be limited if they constitute an
imposition of religious or moral beliefs on patients, negatively affect a patients health,
are based on scientific misinformation, or create or reinforce racial or socioeconomic
inequalities. Conscientious refusals that conflict with patient well-being should be accommodated only if the primary duty to the patient can be fulfilled. All health care providers
must provide accurate and unbiased information so that patients can make informed decisions. Where conscience implores physicians to deviate from standard practices, they
must provide potential patients with accurate and prior notice of their personal moral commitments. Physicians and other health care providers have the duty to refer patients in a
timely manner to other providers if they do not feel that they can in conscience provide
the standard reproductive services that patients request. In resource-poor areas, access
to safe and legal reproductive services should be maintained. Providers with moral or religious objections should either practice in proximity to individuals who do not share their
views or ensure that referral processes are in place. In an emergency in which referral is
not possible or might negatively have an impact on a patients physical or mental health,
providers have an obligation to provide medically indicated and requested care.
Physicians and other providers may not

always agree with the decisions patients make
about their own health and health care. Such
differences are expectedand, indeed,
underlie the American model of informed
consent and respect for patient autonomy.
Occasionally, however, providers anticipate
that providing indicated, even standard, care
would present for them a personal moral
problema conflict of conscience. In such
cases, some providers claim a right to refuse
to provide certain services, refuse to refer
patients to another provider for these services, or even decline to inform patients of
their existing options (1).
Conscientious refusals have been particularly widespread in the arena of reproductive medicine, in which there are deep
divisions regarding the moral acceptability of
pregnancy termination and contraception. In
Texas, for example, a pharmacist rejected a
rape victims prescription for emergency
contraception, arguing that dispensing the

medication was a violation of morals (2).
In Virginia, a 42-year-old mother of two was
refused a prescription for emergency contraception, became pregnant, and ultimately
underwent an abortion she tried to prevent
by requesting emergency contraception (3).
In California, a physician refused to perform
intrauterine insemination for a lesbian couple, prompted by religious beliefs and disapproval of lesbians having children (4). In
Nebraska, a 19-year-old woman with a lifethreatening pulmonary embolism at 10 weeks
of gestation was refused a first-trimester pregnancy termination when admitted to a religiously affiliated hospital and was ultimately
transferred by ambulance to another facility
to undergo the procedure (5). At the heart of
each of these examples of refusal is a claim of
consciencea claim that to provide certain
services would compromise the moral
integrity of a provider or institution.
178
In this opinion, the American College of Obstetricians and Gynecologists (ACOG) Committee on Ethics
considers the issues raised by conscientious refusals in
reproductive medicine and outlines a framework for
defining the ethically appropriate limits of conscientious
refusal in reproductive health contexts. The committee
begins by offering a definition of conscience and describing what might constitute an authentic claim of conscience. Next, it discusses the limits of conscientious
refusals, describing how claims of conscience should be
weighed in the context of other values critical to the ethical provision of health care. It then outlines options for
public policy regarding conscientious refusals in reproductive medicine. Finally, the committee proposes a series
of recommendations that maximize accommodation of
an individuals religious or moral beliefs while avoiding
imposition of these beliefs on others or interfering with
the safe, timely, and financially feasible access to reproductive health care that all women deserve.
Defining Conscience
In this effort to reconcile the sometimes competing
demands of religious or moral freedom and reproductive
rights, it is important to characterize what is meant by
conscience. Conscience has been defined as the private,
constant, ethically attuned part of the human character. It
operates as an internal sanction that comes into play
through critical reflection about a certain action or inaction (6). An appeal to conscience would express a sentiment such as If I were to do x, I could not live with
myself/I would hate myself/I wouldnt be able to sleep at
night. According to this definition, not to act in accordance with ones conscience is to betray oneselfto risk
personal wholeness or identity. Thus, what is taken seriously and is the specific focus of this document is not simply a broad claim to provider autonomy (7), but rather the
particular claim to a providers right to protect his or her
moral integrityto uphold the soundness, reliability,
wholeness and integration of [ones] moral character (8).
Personal conscience, so conceived, is not merely a
source of potential conflict. Rather, it has a critical and
useful place in the practice of medicine. In many cases, it
can foster thoughtful, effective, and humane care. Ethical
decision making in medicine often touches on individuals deepest identity-conferring beliefs about the nature
and meaning of creating and sustaining life (9). Yet, conscience also may conflict with professional and ethical
standards and result in inefficiency, adverse outcomes,
violation of patients rights, and erosion of trust if, for
example, ones conscience limits the information or care
provided to a patient. Finding a balance between respect
for conscience and other important values is critical to
the ethical practice of medicine.
In some circumstances, respect for conscience must
be weighed against respect for particular social values.
Challenges to a health care professionals integrity may
occur when a practitioner feels that actions required by an
external authority violate the goals of medicine and his or

her fiduciary obligations to the patient. Established clinical norms may come into conflict with guidelines imposed
by law, regulation, or public policy. For example, policies
that mandate physician reporting of undocumented
patients to immigration authorities conflict with norms
such as privacy and confidentiality and the primary principle of nonmaleficence that govern the providerpatient
relationship (10). Such challenges to integrity can result in
considerable moral distress for providers and are best met
through organized advocacy on the part of professional
organizations (11, 12). When threats to patient well-being
and the health care professionals integrity are at issue,
some individual providers find a conscience-based refusal
to comply with policies and acceptance of any associated
professional and personal consequences to be the only
morally tenable course of action (10).
Claims of conscience are not always genuine. They
may mask distaste for certain procedures, discriminatory
attitudes, or other self-interested motives (13). Providers
who decide not to perform abortions primarily because
they find the procedure unpleasant or because they fear
criticism from those in society who advocate against it do
not have a genuine claim of conscience. Nor do providers
who refuse to provide care for individuals because of fear
of disease transmission to themselves or other patients.
Positions that are merely self-protective do not constitute
the basis for a genuine claim of conscience. Furthermore,
the logic of conscience, as a form of self-reflection on and
judgment about whether ones own acts are obligatory or
prohibited, means that it would be odd or absurd to say I
would have a guilty conscience if she did x. Although
some have raised concerns about complicity in the context of referral to another provider for requested medical
care, the logic of conscience entails that to act in accordance with conscience, the provider need not rebuke
other providers or obstruct them from performing an act
(8). Finally, referral to another provider need not be
conceptualized as a repudiation or compromise of ones
own values, but instead can be seen as an acknowledgment of both the widespread and thoughtful disagreement among physicians and society at large and the moral
sincerity of others with whom one disagrees (14).
The authenticity of conscience can be assessed
through inquiry into 1) the extent to which the underlying values asserted constitute a core component of a
providers identity, 2) the depth of the providers reflection on the issue at hand, and 3) the likelihood that the
provider will experience guilt, shame, or loss of selfrespect by performing the act in question (9). It is the
genuine claim of conscience that is considered next, in the
context of the values that guide ethical health care.
Defining Limits for Conscientious

Refusal
Even when appeals to conscience are genuine, when a
providers moral integrity is truly at stake, there are clear-
COMMITTEE OPINIONS
ly limits to the degree to which appeals to conscience may

justifiably guide decision making. Although respect for
conscience is a value, it is only a prima facie value, which
means it can and should be overridden in the interest of
other moral obligations that outweigh it in a given circumstance. Professional ethics requires that health be
delivered in a way that is respectful of patient autonomy,
timely and effective, evidence based, and nondiscriminatory. By virtue of entering the profession of medicine,
physicians accept a set of moral valuesand dutiesthat
are central to medical practice (15). Thus, with professional privileges come professional responsibilities to
patients, which must precede a providers personal interests (16). When conscientious refusals conflict with moral
obligations that are central to the ethical practice of medicine, ethical care requires either that the physician provide care despite reservations or that there be resources in
place to allow the patient to gain access to care in the presence of conscientious refusal. In the following sections,
four criteria are highlighted as important in determining
appropriate limits for conscientious refusal in reproductive health contexts.
1. Potential for Imposition
The first important consideration in defining limits for
conscientious refusal is the degree to which a refusal constitutes an imposition on patients who do not share the
objectors beliefs. One of the guiding principles in the
practice of medicine is respect for patient autonomy,
a principle that holds that persons should be free to
choose and act without controlling constraints imposed
by others. To respect a patients autonomy is to respect her
capacities and perspectives, including her right to hold
certain views, make certain choices, and take certain
actions based on personal values and beliefs (17). Respect
involves acknowledging decision-making rights and acting in a way that enables patients to make choices for
themselves. Respect for autonomy has particular importance in reproductive decision making, which involves
private, personal, often pivotal decisions about sexuality
and childbearing.
It is not uncommon for conscientious refusals to
result in imposition of religious or moral beliefs on a
patient who may not share these beliefs, which may
undermine respect for patient autonomy. Womens
informed requests for contraception or sterilization, for
example, are an important expression of autonomous
choice regarding reproductive decision making. Refusals
to dispense contraception may constitute a failure
to respect womens capacity to decide for themselves
whether and under what circumstances to become
pregnant.
Similar issues arise when patients are unable to
obtain medication that has been prescribed by a physician. Although pharmacist conduct is beyond the scope of
this document, refusals by other professionals can have an
important impact on a physicians efforts to provide
179
appropriate reproductive health care. Providing complete, scientifically accurate information about options
for reproductive health, including contraception, sterilization, and abortion, is fundamental to respect for
patient autonomy and forms the basis of informed decision making in reproductive medicine. Providers refusing
to provide such information on the grounds of moral or
religious objection fail in their fundamental duty to
enable patients to make decisions for themselves. When
the potential for imposition and breach of autonomy is
high due either to controlling constraints on medication
or procedures or to the providers withholding of information critical to reproductive decision making, conscientious refusal cannot be justified.
2. Effect on Patient Health
A second important consideration in evaluating conscientious refusal is the impact such a refusal might have on
well-being as the patient perceives itin particular, the
potential for harm. For the purpose of this discussion,
harm refers to significant bodily harm, such as pain, disability, or death or a patients conception of well-being.
Those who choose the profession of medicine (like those
who choose the profession of law or who are trustees) are
bound by special fiduciary duties, which oblige physicians
to act in good faith to protect patients healthparticularly to the extent that patients health interests conflict
with physicians personal or self-interest (16). Although
conscientious refusals stem in part from the commitment
to first, do no harm, their result can be just the opposite.
For example, religiously based refusals to perform tubal
sterilization at the time of cesarean delivery can place a
woman in harms wayeither by putting her at risk for
an undesired or unsafe pregnancy or by necessitating an
additional, separate sterilization procedure with its attendant and additional risks.
Some experts have argued that in the context of pregnancy, a moral obligation to promote fetal well-being also
should justifiably guide care. But even though views
about the moral status of the fetus and the obligations
that status confers differ widely, support of such moral
pluralism does not justify an erosion of clinicians basic
obligations to protect the safety of women who are, primarily and unarguably, their patients. Indeed, in the vast
majority of cases, the interests of the pregnant woman
and fetus converge. For situations in which their interests
diverge, the pregnant womans autonomous decisions
should be respected (18). Furthermore, in situations in
which maternal competence for medical decision making
is impaired, health care providers should act in the best
interests of the woman first and her fetus second (19).
3. Scientific Integrity
The third criterion for evaluating authentic conscientious
refusal is the scientific integrity of the facts supporting the
objectors claim. Core to the practice of medicine is a
commitment to science and evidence-based practice.
180
Patients rightly expect care guided by best evidence as

well as information based on rigorous science. When conscientious refusals reflect a misunderstanding or mistrust
of science, limits to conscientious refusal should be
defined, in part, by the strength or weakness of the science
on which refusals are based. In other words, claims of
conscientious refusal should be considered invalid when
the rationale for a refusal contradicts the body of scientific evidence.
The broad debate about refusals to dispense emergency contraception, for example, has been complicated
by misinformation and a prevalent belief that emergency
contraception acts primarily by preventing implantation
(20). However, a large body of published evidence supports a different primary mechanism of action, namely
the prevention of fertilization. A review of the literature
indicates that Plan B can interfere with sperm migration
and that preovulatory use of Plan B suppresses the
luteinizing hormone surge, which prevents ovulation or
leads to the release of ova that are resistant to fertilization.
Studies do not support a major postfertilization mechanism of action (21). Although even a slight possibility of
postfertilization events may be relevant to some womens
decisions about whether to use contraception, provider
refusals to dispense emergency contraception based on
unsupported beliefs about its primary mechanism of
action should not be justified.
In the context of the morally difficult and highly contentious debate about pregnancy termination, scientific
integrity is one of several important considerations. For
example, some have argued against providing access to
abortion based on claims that induced abortion is associated with an increase in breast cancer risk; however, a
2003 U.S. National Cancer Institute panel concluded that
there is well-established epidemiologic evidence that
induced abortion and breast cancer are not associated
(22). Refusals to provide abortion should not be justified
on the basis of unsubstantiated health risks to women.
Scientific integrity is particularly important at the
level of public policy, where unsound appeals to science
may have masked an agenda based on religious beliefs.
Delays in granting over-the-counter status for emergency
contraception are one such example. Critics of the U.S.
Food and Drug Administrations delay cited deep flaws in
the science and evidence used to justify the delay, flaws
these critics argued were indicative of unspoken and misplaced value judgments (23). Thus, the scientific integrity
of a claim of refusal is an important metric in determining the acceptability of conscience-based practices or
policies.
manner. One conception of justice, sometimes referred to

as the distributive paradigm, calls for fair allocation of
societys benefits and burdens. Persons intending conscientious refusal should consider the degree to which they
create or reinforce an unfair distribution of the benefits of
reproductive technology. For instance, refusal to dispense
contraception may place a disproportionate burden on
disenfranchised women in resource-poor areas. Whereas
a single, affluent professional might experience such a
refusal as inconvenient and seek out another physician, a
young mother of three depending on public transportation might find such a refusal to be an insurmountable
barrier to medication because other options are not realistically available to her. She thus may experience loss of
control of her reproductive fate and quality of life for herself and her children. Refusals that unduly burden the
most vulnerable of society violate the core commitment
to justice in the distribution of health resources.
Another conception of justice is concerned with
matters of oppression as well as distribution (24). Thus,
the impact of conscientious refusals on oppression of certain groups of people should guide limits for claims of
conscience as well. Consider, for instance, refusals to
provide infertility services to same-sex couples. It is likely
that such couples would be able to obtain infertility services from another provider and would not have their
health jeopardized, per se. Nevertheless, allowing physicians to discriminate on the basis of sexual orientation
would constitute a deeper insult, namely reinforcing the
scientifically unfounded idea that fitness to parent is
based on sexual orientation, and, thus, reinforcing the
oppressed status of same-sex couples. The concept of
oppression raises the implications of all conscientious
refusals for gender justice in general. Legitimizing refusals
in reproductive contexts may reinforce the tendency to
value women primarily with regard to their capacity for
reproduction while ignoring their interests and rights
as people more generally. As the place of conscience
in reproductive medicine is considered, the impact of
permissive policies toward conscientious refusals on the
status of women must be considered seriously as well.
Some might say that it is not the job of a physician to
fix social inequities. However, it is the responsibility,
whenever possible, of physicians as advocates for patients
needs and rights not to create or reinforce racial or socioeconomic inequalities in society. Thus, refusals that create
or reinforce such inequalities should raise significant
caution.
4. Potential for Discrimination

Finally, conscientious refusals should be evaluated on the
basis of their potential for discrimination. Justice is a
complex and important concept that requires medical
professionals and policy makers to treat individuals fairly
and to provide medical services in a nondiscriminatory
Given these limits, individual practitioners may face difficult decisions about adherence to conscience in the context of professional responsibilities. Some have offered,
however, that accepting a collective obligation does not
mean that all members of the profession are forced to violate their own consciences (1). Rather, institutions and
Institutional and Organizational

Responsibilities
COMMITTEE OPINIONS
professional organizations should work to create and

maintain organizational structures that ensure nondiscriminatory access to all professional services and
minimize the need for individual practitioners to act in
opposition to their deeply held beliefs. This requires at the
very least that systems be in place for counseling and
referral, particularly in resource-poor areas where conscientious refusals have significant potential to limit patient
choice, and that individuals and institutions act affirmatively to protect patients from unexpected and disruptive
denials of service (13). Individuals and institutions
should support staffing that does not place practitioners
or facilities in situations in which the harms and thus
conflicts from conscientious refusals are likely to arise.
For example, those who feel it improper to prescribe
emergency contraception should not staff sites, such as
emergency rooms, in which such requests are likely to
arise, and prompt disposition of emergency contraception is required and often integral to professional
practice. Similarly, institutions that uphold doctrinal
objections should not position themselves as primary
providers of emergency care for victims of sexual assault;
when such patients do present for care, they should be
given prophylaxis. Institutions should work toward structures that reduce the impact on patients of professionals
refusals to provide standard reproductive services.
Recommendations
Respect for conscience is one of many values important to
the ethical practice of reproductive medicine. Given this
framework for analysis, the ACOG Committee on Ethics
proposes the following recommendations, which it
believes maximize respect for health care professionals
consciences without compromising the health and wellbeing of the women they serve.
1. In the provision of reproductive services, the
patients well-being must be paramount. Any conscientious refusal that conflicts with a patients wellbeing should be accommodated only if the primary
duty to the patient can be fulfilled.
2. Health care providers must impart accurate and unbiased information so that patients can make informed
decisions about their health care. They must disclose
scientifically accurate and professionally accepted
characterizations of reproductive health services.
3. Where conscience implores physicians to deviate
from standard practices, including abortion, sterilization, and provision of contraceptives, they must
provide potential patients with accurate and prior
notice of their personal moral commitments. In the
process of providing prior notice, physicians should
not use their professional authority to argue or advocate these positions.
4. Physicians and other health care professionals have
the duty to refer patients in a timely manner to other
providers if they do not feel that they can in con-
181
science provide the standard reproductive services

that their patients request.
5. In an emergency in which referral is not possible or
might negatively affect a patients physical or mental
health, providers have an obligation to provide medically indicated and requested care regardless of the
providers personal moral objections.
6. In resource-poor areas, access to safe and legal reproductive services should be maintained. Conscientious refusals that undermine access should raise
significant caution. Providers with moral or religious
objections should either practice in proximity to
individuals who do not share their views or ensure
that referral processes are in place so that patients
have access to the service that the physician does not
wish to provide. Rights to withdraw from caring for
an individual should not be a pretext for interfering
with patients rights to health care services.
7. Lawmakers should advance policies that balance protection of providers consciences with the critical
goal of ensuring timely, effective, evidence-based,
and safe access to all women seeking reproductive
services.
References
1. Charo RA. The celestial fire of consciencerefusing to
deliver medical care. N Engl J Med 2005;352:24713.
2. Denial of rape victims pills raises debate: moral, legal questions surround emergency contraception. New York (NY):
Associated Press; 2004. Available at: http://www.msnbc.
msn.com/id/4359430. Retrieved July 10, 2007.
3. L D. What happens when there is no plan B? Washington
Post; June 4, 2006. p. B1. Available at: http://www.
washingtonpost.com/wp-dyn/content/article/2006/06/02/
AR2006060201405.html. Retrieved July 10, 2007.
4. Weil E. Breeder reaction: does everyone now have a right
to bear children? Mother Jones 2006;31(4):337. Available
at: http://www.motherjones.com/news/feature/2006/07/
breeder_reaction.html. Retrieved July 10, 2007.
5. American Civil Liberties Union. Religious refusals and
reproductive rights: ACLU Reproductive Freedom Project.
New York (NY): ACLU; 2002. Available at: http://www.aclu.
org/FilesPDFs/ACF911.pdf. Retrieved July 10, 2007.
6. Childress JF. Appeals to conscience. Ethics 1979;89:31535.
7. Wicclair MR. Conscientious objection in medicine.
Bioethics 2000;14:20527.
8. Beauchamp TL, Childress JF. Principles of biomedical ethics.
5th ed. New York (NY): Oxford University Press; 2001.
9. Benjamin M. Conscience. In: Reich WT, editor. Encyclopedia of bioethics. New York (NY): Simon & Schuster
Macmillan; 1995. p. 46973.
10. Ziv TA, Lo B. Denial of care to illegal immigrants.
Proposition 187 in California. N Engl J Med 1995;332:
10958.
11. American College of Obstetricians and Gynecologists. Code
of professional ethics of the American College of Obste-
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tricians and Gynecologists. Washington, DC: ACOG; 2004.

Available at: http://www.acog.org/from_home/acogcode.
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American Medical Association. Principles of medical ethics.
In: Code of medical ethics of the American Medical
Association: current opinions with annotations. 20062007
ed. Chicago (IL): AMA; 2006. p. xv.
Dresser R. Professionals, conformity, and conscience.
Hastings Cent Rep 2005;35:910.
Blustein J. Doing what the patient orders: maintaining
integrity in the doctor-patient relationship. Bioethics
1993;7:290314.
Brody H, Miller FG. The internal morality of medicine:
explication and application to managed care. J Med Philos
1998;23:384410.
Dickens BM, Cook RJ. Conflict of interest: legal and ethical
aspects. Int J Gynaecol Obstet 2006;92:1927.
Faden RR, Beauchamp TL. A history and theory of
informed consent. New York (NY): Oxford University
Press; 1986.
Maternal decision making, ethics, and the law. ACOG
Obstetricians and Gynecologists. Obstet Gynecol 2005;106:
112737.
International Federation of Gynecology and Obstetrics.
Ethical guidelines regarding interventions for fetal well
being. In: Ethical issues in obstetrics and gynecology.
London (UK): FIGO; 2006. p. 567. Available at: http://
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www.figo.org/docs/Ethics%20Guidelines.pdf. Retrieved
July 10, 2007.
Cantor J, Baum K. The limits of conscientious objection
may pharmacists refuse to fill prescriptions for emergency
contraception? N Engl J Med 2004;351:200812.
Davidoff F, Trussell J. Plan B and the politics of doubt.
JAMA 2006;296:17758.
Induced abortion and breast cancer risk. ACOG Committee
Grimes DA. Emergency contraception: politics trumps science at the U.S. Food and Drug Administration. Obstet
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The limits of conscientious refusal in reproductive medicine. ACOG
ISSN 1074-861X
COMMITTEE OPINIONS
183

Human Immunodeficiency Virus*

Committee on Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Because human immunodeficiency virus (HIV) infection often is detected

through prenatal and sexually transmitted disease testing, an obstetriciangynecologist
may be the first health professional to provide care for a woman infected with HIV.
Universal testing with patient notification and right of refusal (opt-out testing) is recommended by most national organizations and federal agencies. Although opt-out and optin testing (but not mandatory testing) are both ethically acceptable, the former approach
may identify more women who are eligible for therapy and may have public health advantages. It is unethical for an obstetriciangynecologist to refuse to accept a patient or to
refuse to continue providing health care for a patient solely because she is, or is thought
to be, seropositive for HIV. Health care professionals who are infected with HIV should
adhere to the fundamental professional obligation to avoid harm to patients. Physicians
who believe that they have been at significant risk of being infected should be tested
voluntarily for HIV.
Between 1 million and 1.2 million individuals in the United States are estimated to be
living with human immunodeficiency virus
(HIV) or acquired immunodeficiency syndrome (AIDS) (1). Women represent the
fastest-growing group of individuals with
new HIV infections (2). Many women who
are infected with HIV are not aware of their
serostatus (3).
Human immunodeficiency virus often is
diagnosed in women during prenatal antibody screening or in conjunction with
screening for sexually transmitted diseases
(STDs). Because many women initially identified as infected with HIV are not aware that
they have been exposed to HIV and do not
consider themselves to be at risk, universal
testing with patient notification is more
effective than targeted, risk-based testing in
identifying those who are infected with HIV
(4). The tension between competing goals for
HIV testingtesting broadly in order to treat
the maximum number of women infected
with HIV and, if pregnant, to protect their
newborns, and counseling thoroughly in
order to maximally protect a womans autonomy and right to participate in decision makinghas sparked considerable debate.
*Update of Human Immunodeficiency Virus in Ethics
Because HIV infection often is detected

through prenatal and STD screening, it is
not uncommon for an obstetriciangynecologist to be the first health professional to
provide care for an infected woman. This
Committee Opinion is designed to provide
guidance to obstetriciangynecologists regarding ethical issues associated with HIV
testing, including the use of newly developed
rapid HIV tests and disclosure of positive
test results. It also outlines responsibilities
related to patient care for women who are
infected with HIV, access for affected couples
to assisted reproductive technology, and the
health care professional who is infected
with HIV.
Human Immunodeficiency
Virus Counseling and Testing
The major ethical principles that must be
considered when formulating policies for
HIV counseling and testing include respect
for autonomy, confidentiality, justice, protection of vulnerable individuals, and beneficence to both the woman tested and, if she is
pregnant, to her newborn as well. Individuals
offering testing need to be mindful not only
of the benefits of testing but also its potential
risks because, if a womans test result is positive, she faces the possibility of being ostra-
184
cized by her family, friends, and community or being

subjected to intimate partner violence. In addition,
although the overt stigma of HIV infection has been
reduced over the past 20 years, the potential for job discrimination, loss of health insurance, and loss of housing
still exists.
Over time, three potential strategies for HIV testing
have been considered by public health and public policy
officials: 1) universal testing with patient notification and
right of refusal, also called opt-out testing; 2) voluntary
testing with pretest counseling regarding risks and benefits, also called opt-in testing; and 3) mandatory testing
with no right of refusal. In order to understand their ethical merits, each is considered briefly in the sections that
follow. Increasingly, national organizations and federal
agencies have recommended opt-out testing in preference
to other strategies.
Universal Testing With Patient Notification and
Right of RefusalOpt-Out Testing
Opt-out testing removes the requirement for pretest
counseling and detailed, testing-related informed consent. Under the opt-out strategy, physicians must inform
patients that routine blood work will include HIV testing
and that they have the right to refuse this test. The goal of
this strategy is to make HIV testing less cumbersome and
more likely to be performed by incorporating it into the
routine battery of tests (eg, the first-trimester prenatal
panel or blood counts and cholesterol screening for
annual examinations). In theory, if testing barriers are
reduced, more physicians may offer testing, which may
lead to the identification and treatment of more women
who are infected with HIV and, if pregnant, to the prevention of mother-to-infant transmission of HIV. This
testing strategy aims to balance competing ethical considerations. On the one hand, personal freedom (autonomy) is diminished. On the other hand, there are medical
and social benefits for the woman and, if she is pregnant,
her newborn from identifying HIV infection. Although
many welcome the now widely endorsed opt-out testing
policy for the potential benefits it confers, others have
raised concerns about the possibility that the requirement for notification before testing will be ignored, particularly in todays busy practice environment. Indeed,
the opt-out strategy is an ethically acceptable testing
strategy only if the patient is given the option to refuse
testing. In the absence of that notification, this approach
is merely mandatory testing in disguise. If opt-out testing
is elected as a testing strategy, a clinician must notify the
patient that HIV testing is to be performed. Refusal of
testing should not have an adverse effect on the care the
patient receives or lead to denial of health care. This
guarantee of a right to refuse testing ensures that respect
for a womans autonomy is not completely abridged in
the quest to achieve a difficult-to-reach public health
goal.
Voluntary Testing With Pretest Counseling

Regarding Risks and BenefitsOpt-In Testing
Voluntary testing with counseling is the strategy most
consistent with respect for patient autonomy. Under this
option, physicians provide both pretest and posttest
counseling. Some physicians may perform such counseling themselves, whereas others may prefer to refer the
patient for counseling and testing. (Such specialized HIV
counseling was more widely available in previous years
but has become less available as more health care professionals have become more comfortable treating patients
with HIV and as the opt-out approach to testingan
approach that places less emphasis on pretest counselinghas become more common.) In addition to medical
information, such counseling could include information
regarding potential uses of test information and legal
requirements pertaining to the release of information.
Patients should be told what information will be communicated and to whom and the possible implications of
reporting the information. This approach to testing
maintains HIVs status as being in a class by itself (sui
generis), even as many ethicists have acknowledged the
end to the exceptionalism that marked this disease in the
early years of the epidemic (5).
Mandatory Testing With No Right of Refusal
Mandatory testing strategies are problematic because they
abridge a womans autonomy. In addition, during pregnancy, the public health objective of this strategy, identification of women who are infected with HIV who will benefit from treatment, has been accomplished in certain
populations by other ethically sound testing strategies
noted previously (6). Some see mandatory testing as a
more efficient way of achieving universal testing.
Advocates support this strategy, believing it provides the
greatest good for the greatest number and that the potential benefit to the woman and, if pregnant, her newborn
justifies abridging a womans autonomy. However, because
of the limits it places on autonomy, the Committee on
Ethics believes that mandatory HIV screening without
informing those screened and offering them the option of
refusal is inappropriate. Mandatory prenatal testing is difficult to defend ethically and has few precedents in modern medicine, although HIV testing of newborns is now
required in New York, Connecticut, and Illinois (There are
provisions, however, that permit refusal in a few defined
circumstances.) (7, 8). Importantly, mandatory testing
may compromise the ability to form an effective physicianpatient relationship at the very time when this relationship is critical to the success of treatment.
Selecting a Testing Strategy
Among these three strategies, the opt-out approach is
now recommended by most national organizations and
federal agencies. For prenatal HIV testing, universal testing with patient notification and right of refusal was recommended by the Institute of Medicine to address
COMMITTEE OPINIONS
clinicians concerns that pretest counseling and informed

consent mandates for routine voluntary testing in pregnancy were too time consuming and, thus, reduced the
likelihood of testing being offered (9). The Centers for
Disease Control and Prevention, the American Academy
of Pediatrics, and the American College of Obstetricians
and Gynecologists (ACOG) endorse this approach (10,
11). Evidence suggests that this strategy may be acceptable to many pregnant women (12, 13). To expand the
gains made in diagnosing HIV infection among pregnant
women, the Centers for Disease Control and Prevention
(14) has recently released, and ACOG (15) has adopted,
recommendations to make HIV testing a routine part of
medical care using a similar opt-out approach for all
women at the time of routine health care visits.
In recommending the opt-out approach for prenatal
HIV testing, ACOG encouraged Fellows to include counseling as a routine part of care but not as a prerequisite
for, or barrier to, prenatal HIV testing (11). Similarly, the
American Medical Association, in recommending that
universal HIV testing of all pregnant women with patient
notification of the right of refusal be a routine component of prenatal care, indicated that basic counseling on
HIV prevention and treatment also should be provided
to the patient, consistent with the principles of informed
consent (16). Accordingly, if adopting this option, physicians should be prepared to provide both pretest and
posttest counseling. Broad implementation of an opt-out
strategy, however, will require changing laws in states that
require detailed and specific counseling and consent
before testing. Physicians should be aware of the laws in
their states that affect HIV testing. The National HIV/
AIDS Clinicians Consultation Center at the University of
CaliforniaSan Francisco maintains an online compendium of state HIV testing laws that can be a useful
resource (see http://www.ucsf.edu/hivcntr/).
The benefits of identifying those with HIV infection
will be limited if necessary treatments are unavailable or
not covered by appropriate insurance. Where access to
HIV treatment is limited, Fellows should advocate for
changes in existing policies to broaden access.
Special Issues Involved With Rapid

Testing
Technologies have recently become available that allow
for testing with rapid results (eg, turnaround less than
1 hour). The advantage of these tools is that patients can
be informed of their results at the same visit at which the
testing occurs. In that manner, it is possible to lower the
rate of loss to follow-up associated with the traditional
two-stage testing and notification approach. Nothing
about rapid testing precludes the need for a patient to
opt-in or to be offered the opportunity to opt-out of testing (depending on which strategy is adopted). Rapid testing should not be implemented either as mandatory
185
testing or testing performed without informing the

patient that she will be tested.
In communities with a relatively low prevalence of
HIV, rapid testing can present certain logistic difficulties.
With the traditional approach, testing would occur during an initial visit, and results would be provided during a
follow-up encounter. That would give the health care professional an opportunity to arrange for an individual with
expertise in posttest counseling to be available in a circumstance in which the health care professional knew
that a patient was returning to receive a positive result. A
program of testing and notification at the same visit does
not allow the health care professional the luxury of notifying a counselor before a patient who is infected with
HIV returns for a visit or of steering an individual who is
infected with HIV to a certain session at which the counselor is routinely available. However, the obligation to
make sure that appropriate counseling and support services are available still holds. Health care professionals
should develop links with individuals who can provide
those services on an emergent basis or train their own
staff to handle the initial encounter and thereafter transition infected individuals to professionals who can serve as
ongoing resources to them.

Reporting and Partner Notification
The clinician providing care for a woman who is infected
with HIV has important responsibilities concerning disclosure of the patients serostatus. Clinicians providing
health care should be aware of and respect legal requirements regarding confidentiality and disclosure of HIVrelated clinical information.
In considering disclosure, clinicians may have competing obligations: protecting the patients confidentiality,
on the one hand, and disclosing test results to prevent
substantial harm to a third party, on the other. In some
jurisdictions, a breach of confidentiality may be required
by mandatory reporting regulations. Even absent legal
requirements, in some situations the need to protect
potentially exposed third parties may seem compelling. In
these situations, the clinician first should educate the
patient about her rights and responsibilities and encourage her to inform any third parties involved. If she remains
reluctant to voluntarily share information regarding her
infection, consultation with an institutional ethics committee, a medical ethics specialist, or an attorney may be
helpful in deciding whether to disclose her HIV status. In
general, a breach of confidentiality may be ethically justified for purposes of partner notification when all of the
following four conditions are met:
1. There is a high probability of harm to the partner.
2. The potential harm is serious.
3. The information communicated can be used to prevent harm.
186
4. Greater good will result from breaking confidentiality rather than maintaining it.
Indeed, many if not all of these conditions are likely
met for intimate partners of women and men who are
infected with HIV. Nevertheless, when a breach of confidence is contemplated, practitioners should weigh the
potential harm to the patient and to society at large.
Negative consequences of breaking confidentiality may
include the following situations:
Personal risks to the individual whose confidence is
breached, such as serious implications for the
patients relationship with family and friends, the
threat of discrimination in employment and housing, intimate partner violence, and the impact on
family members
Loss of patient trust, which may reduce the physicians
ability to communicate effectively and provide services
A ripple effect among cohorts of women that may
deter other women at risk from accepting testing and
have a serious negative impact on the educational
efforts that lie at the heart of attempts to reduce the
spread of disease
If, on balance, a breach of confidence is deemed necessary, practitioners should work in advance to anticipate
and manage potentially negative consequences (ie, reactions of intimate partners, family). As well, practitioners
should consider whether the goal of maintaining patient
privacy would be better served by personal communication with the individual placed at risk by the patients
seropositivity or by notification of local public health
authorities. In some areas, anonymous notification of
sexual contacts is possible through local or state departments of health. As a practical matter, because disclosure
is only possible when the index case freely identifies atrisk partners, superseding an individuals refusal to disclose should be a rare occurrence.
Confidentiality should not be breached solely because of perceived risk to health care workers. Health care
workers should rely on strict observance of standard precautions rather than obtaining information about a
patients serostatus to minimize risk. Even in the setting of
an accidental needle-stick or other exposure, the patients
consent for release of serostatus (or for testing) should be
obtained. Efforts to protect patient confidentiality should
not prevent other health care professionals caring for the
patient from learning her serostatus, information they
need to ensure optimal medical management.
Health Care Professionals Obligation

to Provide Care
It is unethical for an obstetriciangynecologist to refuse
to accept a patient or to refuse to continue providing
health care for a patient solely because she is, or is thought
to be, seropositive for HIV. Refusing to provide care to
women who are infected with HIV for fear of contracting

HIV infection or simply as a practice preference is unreasonable, unscientific, and unethical.
Epidemiologic studies have shown that the risk of
HIV transmission from patient to health care professional
is exceedingly low and is related to needle stick or intraoperative injury or to potentially infectious fluid that
comes in contact with a mucous membrane (17). Most
contacts between health care professionals and women
who are infected with HIV occur, however, during routine obstetric and gynecologic care. Health care practitioners should observe standard precautions with all
patients to minimize skin, mucous membrane, and percutaneous exposure to blood and body fluids to protect
against a variety of pathogens, including HIV.
Health care professionals who fail to provide care to
women who are infected with HIV because of personal
practice preferences violate professional ethical standards. The public appropriately expects that health care
practitioners will not discriminate based on diagnosis,
provided that the patients care falls within their scope of
practice. Physicians should demonstrate integrity, compassion, honesty, and empathy. Failure to provide health
care to a woman solely because she is infected with HIV
violates these fundamental characteristics. As with any
other patient, it is acceptable, however, to refer women
who are infected with HIV for care that the physician is
not competent to provide or if care elsewhere would be
more convenient or associated with decreased financial
burden to the patient.
Assisted Reproductive Technology

There is an emerging consensus that indications for
assisted reproductive technology use should not vary
with HIV serostatus; therefore, assisted reproductive
technology should be offered to couples in which one or
both partners are infected with HIV. This approach is
consistent with the principles of respect for autonomy
and beneficence (18, 19). In addition, those who advocate
providing these services cite three clinical arguments to
support their position:
1. Therapeutic improvements in the management of
HIV infection have enhanced both quality and
length of life for individuals who are seropositive for
HIV.
2. Advances in prenatal therapy have substantially
reduced the risk of mother-to-infant HIV transmission.
3. Current assisted reproductive technology methods
may reduce transmission of HIV from an infected
partner to an uninfected partner relative to natural
means of conception.
The Ethics Committee of the American Society for
Reproductive Medicine has said, Health care workers
who are willing to provide reproductive assistance to cou-
COMMITTEE OPINIONS
ples whose offspring are irreducibly at risk for a serious

genetic disease should find it ethically acceptable to treat
HIV-positive individuals or couples who are willing to
take reasonable steps to minimize the risks of transmission. (20).
Those who oppose offering these technologies to
couples who are infected with HIV cite two major objections:
1. Uncertain long-term parental prognosis
2. The continuing risk of mother-to-infant HIV transmission
The ethical underpinning of this opposition is that it
is not felt to be in the best interest of the child to be born
to a parent who may not be available for continued childrearing. In addition, the risk of mother-to-infant transmission places the infant at risk of acquiring a highly debilitating illness. Yet as stated previously, HIV infection currently
is a manageable chronic illness with a life-expectancy
equivalent to that with many other chronic diseases for
which assisted reproductive technology is not routinely
precluded. Further, interventions, such as antiretroviral
therapy or cesarean delivery or both, reduce the absolute
risk of transmission to a level comparable, again, to risks
significantly lower than those tolerated among couples
choosing assisted reproductive technology (eg, parents
who are carriers of autosomal recessive conditions) or risks
often assumed as part of assisted reproductive technology
(eg, risks of prematurity from multiple pregnancies).
Health Care Professionals Who Are

Infected With Human
Immunodeficiency Virus
In making decisions about patient care, health care professionals who are infected with HIV should adhere to the
fundamental professional obligation to avoid harm to
patients. Physicians who have reason to believe that they
have been at significant risk of being infected should be
tested voluntarily for HIV for the protection of their
patients as well as for their own benefit. The physician as
a patient is entitled to the same rights to privacy and confidentiality as any other patient.
Although the risk of clinician-to-patient transmission is extremely low, all infected physicians must make a
decision as to which procedures they can continue to perform safely. This decision primarily will depend on the
particular surgical technique involved and also on the
physicians level of expertise and medical condition,
including mental status. The clinicians decision should
be made in consultation with a personal physician and
may possibly involve such other responsible individuals as
the chief of the department, the hospitals director of
infectious diseases, the chief of the medical staff, or a specialized advisory panel. If physicians avoid procedures
that place patients at risk of harm, they have no obligation
187
to inform the patient of their positive HIV serostatus.

Physicians who are infected with HIV should follow standard precautions, including the appropriate use of handwashing, protective barriers, and care in the use and
disposal of needles and other sharp instruments.
Recommendations
The Committee on Ethics makes the following recommendations:
All women, pregnant or not, should have the opportunity to learn their HIV serostatus.
Women should, at a minimum, be told that they are
being tested and that they may refuse such tests.
Although opt-out and opt-in testing are both ethically acceptable, the former approach may identify
more women who are eligible for therapy and may
have public health advantages.
Rapid testing carries the same ethical responsibilities
as standard testing.
It is unethical for an obstetriciangynecologist to
refuse to accept a patient or to discontinue providing
health care for a patient solely because she is, or is
thought to be, seropositive for HIV.
Seropositivity for HIV per se should not be used as a
reason to refuse to provide assisted reproductive
technology to a family.
References
1. Epidemiology of HIV/AIDSUnited States, 19812005.
MMWR Morb Mortal Wkly Rep 2006;55:58992.
2. Chou R, Smits AK, Huffman LH, Fu R, Korthuis PT.
Prenatal screening for HIV: a review of the evidence for the
U.S. Preventive Services Task Force. U.S. Preventive Services
Task Force. Ann Intern Med 2005;143:3854.
3. Gwinn M, Wortley PM. Epidemiology of HIV infection in
women and newborns. Clin Obstet Gynecol 1996;39:
292304.
4. Revised recommendations for HIV screening of pregnant
women. MMWR Recomm Rep 2001;50(RR19):6385;
quiz CE119a2CE619a2.
5. Bayer R, Fairchild AL. Changing the paradigm for HIV testingthe end of exceptionalism. N Engl J Med 2006;355:
6479.
6. Prenatal discussion of HIV testing and maternal HIV testing14 states, 19961997. MMWR Morb Mortal Wkly Rep
1999;48:4014.
7. HIV testing among pregnant womenUnited States and
Canada, 19982001. MMWR Morb Mortal Wkly Rep 2002;
51:10136.
8. Perinatal HIV Prevention Act. 410 ILCS 335 (2006).
9. Institute of Medicine (US). Reducing the odds: preventing
perinatal transmission of HIV in the United States.
Washington, DC: National Academy Press; 1999.
10. Prenatal and perinatal human immunodeficiency virus
testing: expanded recommendations. ACOG Committee
188

Obstetricians and Gynecologists. Joint statement on human
immunodeficiency virus screening. Elk Grove Village
(IL): AAP; Washington, DC: ACOG; 2006. Available at:
http://www.acog.org/publications/policy_statements/
sop9905.cfm. Retrieved July 10, 2007.
12. Stringer EM, Stringer JS, Cliver SP, Goldenberg RL,
Goepfert AR. Evaluation of a new testing policy for human
immunodeficiency virus to improve screening rates. Obstet
Gynecol 2001;98:11048.
13. Jayaraman GC, Preiksaitis JK, Larke B. Mandatory reporting of HIV infection and opt-out prenatal screening for
HIV infection: effect on testing rates. CMAJ 2003;168:
67982.
14. Branson BM, Handsfield HH, Lampe MA, Janssen RS,
Taylor AW, Lyss SB, et al. Revised recommendations for HIV
testing of adults, adolescents, and pregnant women in
health-care settings. MMWR Recomm Rep 2006;55
(RR14):117; quiz CE14.
15. Primary and preventive care: periodic assessments. ACOG
161522.
16. American Medical Association. Universal, routine screening
of pregnant women for HIV infection. CSA Report I01.
Council on Scientific Affairs. Chicago (IL): AMA; 2001.
Available at: http://www.ama-assn.org/ama/pub/category/

13548.html. Retrieved July 10, 2007.
17. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV
and recommendations for postexposure prophylaxis.
MMWR Recomm Rep 2001;50(RR11):152.
18. Anderson DJ. Assisted reproduction for couples infected
with the human immunodeficiency virus type 1. Fertil
Steril 1999;72:5924.
19. Minkoff H, Santoro N. Ethical considerations in the treatment of infertility in women with human immunodeficiency virus infection. N Engl J Med 2000;342:174850.
20. Human immunodeficiency virus and infertility treatment.
Ethics Committee of the American Society for Reproductive Medicine. Fertil Steril 2002;77:21822.
Human immunodeficiency virus. ACOG Committee Opinion No. 389.
2007;110:14738.
ISSN 1074-861X
COMMITTEE OPINIONS
189

Ethical Decision Making in Obstetrics and

Gynecology*
Committee on Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Physicians vary widely in their familiarity with ethical theories and methods and their sensitivity toward ethical issues. It is important for physicians to improve
their skills in addressing ethical questions. Obstetriciangynecologists who are familiar
with the concepts of medical ethics will be better able to approach complex ethical situations in a clear and structured way. By considering the ethical frameworks involving principles, virtues, care and feminist perspectives, concern for community, and case
precedents, they can enhance their ability to make ethically justifiable clinical decisions.
Guidelines, consisting of several logical steps, are offered to aid the practitioner in analyzing and resolving ethical problems.
The importance of ethics in the practice of

medicine was manifested at least 2,500 years
ago in the Hippocratic tradition, which
emphasized the virtues that were expected to
characterize and guide the behavior of physicians. Over the past 50 years, medical technology expanded exponentially, so that
obstetriciangynecologists have had to face
complex ethical questions regarding assisted
reproductive technologies, prenatal diagnosis
and selective abortion, medical care at the
beginning and end of life, the use of genetic
information, and the like. Medical knowledge
alone is not sufficient to solve these problems. Instead, responsible decisions in these
areas depend on a thoughtful consideration
of the values, interests, goals, rights, and
obligations of those involved. All of these are
the concern of medical ethics. The formal
discipline of biomedical ethics and structured ethical analysis can help physicians
resolve ethical dilemmas.
Physicians vary widely in their familiarity with ethical theories and methods and
their sensitivity toward ethical issues. It is
important for physicians to improve their
skills in addressing ethical questions through
formal undergraduate and graduate medical
education, organized continuing education,
*Update of Ethical Decision Making in Obstetrics and
Gynecology in Ethics in Obstetrics and Gynecology,
Second Edition, 2004.
or personal experience and reading as well as

discussion with others.
Ethical Frameworks and

Perspectives
Principle-Based Ethics
In recent decades, medical ethics has been
dominated by principle-based ethics (13).
In this approach, four principles offer a
systematic and relatively objective way to
identify, analyze, and address ethical issues,
problems, and dilemmas: 1) respect for patient
autonomy, 2) beneficence, 3) nonmaleficence,
and 4) justice. (These four principles will be
discussed in some detail in subsequent sections.) However, critics claim that a principlebased approach cannot adequately resolve or
even helpfully evaluate many difficult clinical
problems. As a result, several other perspectives and frameworks have emerged: virtuebased ethics, an ethic of care, feminist ethics,
communitarian ethics, and case-based reasoning, all of which have merit as well as limitations (28). As this discussion will stress,
these different perspectives and frameworks
are not necessarily mutually exclusive. They
often are complementary because each
emphasizes some important features of
moral reasoning, agents, situations, actions,
or relationships. Perspectives such as an ethic
of care or feminist ethics also may change the
lens through which to view both principles
190
and particular situations in which decisions have to be

made.
Virtue Ethics
A virtue-based approach relies on qualities of character
that dispose health professionals to make choices and decisions that achieve the well-being of patients, respect their
autonomous choices, and the like (8, 9). These qualities of
character include trustworthiness, prudence, fairness,
fortitude, temperance, integrity, self-effacement, and compassion. Virtues need not replace principles as a basis for
ethical decision making or conduct. Indeed, some virtues
correlate with principles and dispose people to act according to those principlesfor instance, the virtue of benevolence disposes agents to act beneficently. Virtues also can
complement and enhance the principles of medical ethics.
Interpreting the principles, applying them in concrete situations, and setting priorities among them require the judgment of morally sensitive professionals with good moral
character and the relevant virtues. Furthermore, in deliberating what to do, a physician may find helpful guidance by
asking, What would a good, that is, morally virtuous,
physician do in these circumstances? Ethical insight may
come from imagining which actions would be compatible
with, for instance, being a compassionate or honest or
trustworthy physician.
Care-Based Ethics
Care-based ethics, also called the ethic of care, directs
attention to dimensions of moral experience often excluded from or neglected by traditional ethical theories (10). It
is concerned primarily with responsibilities that arise from
attachment to others rather than with impartial principles
so emphasized in many ethical theories. The moral foundations of an ethic of care are located not in rights and duties,
but rather in commitment, empathy, compassion, caring,
and love (11). This perspective also pays closer attention to
context and particularity than to abstract principles and
rules. It suggests that good ethical decisions both result
from personal caring in relationships, and should consider
the impact of different possible actions on those relationships. An ethic of care overlaps with a virtue ethic, in
emphasizing the caregivers orientation and qualities. In
this ethical approach, care represents the fundamental orientation of obstetrics and gynecology as well as much of
medicine and health care, and it indicates the direction and
rationale of the relationship between professionals and
those who seek their care. An ethic of care also joins casebased approaches in focusing on particular contexts of
decision making.
Feminist Ethics
Feminist ethics uses the tools of feminist theory to examine ethical issues in at least three distinctive ways (12).
First, it indicates how conceptions of sex often distort peoples view of the world and, more specifically, how gendered conceptions constrain and restrict women. For
instance, feminist theory shows how human society tends

to be androcentric, or male centered, so that man
becomes the generic representative for what it means to
be human, and woman is viewed as different or deviant.
Thus, feminist ethics can expose forms of androcentric
reasoning in ethics of clinical care and public policy, calling into question, for example, the rationale for excluding women from participation in clinical research.
Second, feminist ethics indicates how gendered thinking
has distorted the tools that philosophers and bioethicists
use to examine ethical issues. Historically entrenched
associations between man and reason, woman and emotiondubious in and of themselveshave contributed
to the tendency in moral theory to view emotion as irrelevant or, at worst, distorting. Some, including many feminist thinkers, however, have argued that appropriate
emotion (eg, empathy) is indispensable to moral reasoning in the ethical conduct of medical care. This position,
bolstered further by recent empirical research (13, 14), is
consistent with the perspective represented by the ethic
of care (see previous section). Third, in calling attention
to and attempting to redress the ways that gendered concepts have produced constraints on women, feminism is
concerned with oppression as a pervasive and insidious
moral wrong (15, 16). The tools of feminist ethics can
help to identify and challenge dominance and oppression
not only of women, but also of other groups oppressed
because of race, class, or other characteristics. These tools
also can help to detect more subtle gender and other
biases and assist in addressing significant health disparities. Rather than rejecting such principles as respect for
autonomy and justice, feminist thinkers may interpret
and apply these principles to highlight and redress various kinds of domination, oppression, and bias.
Communitarian Ethics
Communitarian ethics challenges the primacy often
attributed to personal autonomy in contemporary biomedical ethics (17). A communitarian ethic emphasizes a
communitys other shared values, ideals, and goals and
suggests that the needs of the larger community may take
precedence, in some cases, over the rights and desires of
individuals. If proponents of a communitarian ethic
accept the four principles of Beauchamp and Childress
(1), they will tend to interpret those principles through
the lens of community, stressing, for example, benefits
and harms to community and communities as well as the
need to override autonomy in some cases. Major examples arise in the context of public health. However, in
considering the proper framework for communitarian
ethics, questions arise in a pluralistic society about which
community is relevant. For instance, is the relevant
community one embodied in particular traditions (eg,
one religion) or is it the broader, pluralistic society? Even
though there is a broad consensus that communal values
and interests sometimes trump personal autonomy, disputes persist about exactly when it is justifiable to over-
COMMITTEE OPINIONS
ride personal autonomy. To take one example, apart from

laws that specify which diseases are reportable, physicians
may have to balance a patients claims of privacy and confidentiality against risks to others. Different judgments
about the appropriate balance often hinge on an assessment of risks: How probable and serious must the harm
be to justify a breach of privacy and confidentiality?
Case-Based Reasoning
In a final approach, case-based reasoning (sometimes
called casuistry), ethical decision making builds on precedents set in specific cases (18, 19). This is analogous to the
role of case law in jurisprudence in that an accumulated
body of influential cases and their interpretation provide
moral guidance. This approach analyzes current cases
requiring decisions in light of relevantly similar cases that
have already been settled or gained a rough consensus.
Case-based reasoning asserts the priority of practice over
both ethical theory and moral principles. It recognizes the
principles that emerge by a process of generalization from
the analysis of cases but views these principles as always
open to future revision. In considering a particular case,
someone taking this approach would seek to determine
whether there are any relevantly similar cases, either positive or negative, that enjoy an ethical consensus. If, for
example, a new research protocol is relevantly similar to
an earlier and widely condemned one (eg, the Tuskegee
Syphilis Study), that similarity is a reason for moral suspicion of the new protocol. A question for this approach
is how to identify relevant similarities and differences
among cases and whether ethical principles are sometimes useful in this process.
Ethics as Toolbox
An example of how the different ethical frameworks and
perspectives might address a particular case is shown in
the box. From this analysis of different approaches, it is
plausible to derive the following conclusion: enlightened
ethical decision making in clinical medicine cannot rely
exclusively on any single fundamental approach to biomedical ethics. The metaphor of toolbox or toolkit may
provide a useful way to think about these different
approaches to ethical decision making (20). Some ethical
tools may fit some contexts, situations, and cases better
than others, and more than oneor even all of them
usually are valuable.
It is helpful to have access to a variety of ethical tools
because clinical problems often are too complex to be
resolved by using simple rules or by rigidly applying ethical principles. Indeed, virtues such as prudence, fairness,
and trustworthiness enable clinicians to apply ethical
principles sensitively and wisely in situations of conflict.
The specific virtues that are most important may vary
from one circumstance to another, but in womens health
care, there must be particular sensitivity to the needs of
women. Furthermore, in many, perhaps most, difficult
situations requiring ethical insight, tensions exist between
191
the well-being and interests of the individual patient and

the interest of the community, however that is defined.
Finally, current ethical decisions can be improved by
awareness of and guidance from existing precedents.
In short, even though a principle-based approach
may provide a reasonable starting point for ethical decision making, it is not adequate by itself and needs the
valuable contributions and insights of other approaches.
Principles often serve as initial points of reference in ethical decision making in obstetrics and gynecology, however, and the next section examines several ethical principles
in detail.
Ethical Principles
Clinicians and others often make decisions without
appealing to principles for guidance or justification. But
when they experience unclear situations, uncertainties, or
conflicts, principles often can be helpful. The major principles that are commonly invoked as guides to profes-sional action and for resolving conflicting obligations in health
care are respect for autonomy, beneficence and nonmaleficence, and justice (1). Other principles or rules, such as
fidelity, honesty, privacy, and confidentiality, also are
important, whether they are viewed as derived from the
four broad principles or as independent.
Respect for Autonomy
Autonomy, which derives from the Greek autos (self )
and nomos (rule or governance), literally means selfrule. In medical practice, the principle of respect for
autonomy implies personal rule of the self that is free both
from controlling interferences by others and from personal limitations that prevent meaningful choice, such as
inadequate understanding (1). Respect for a patients
autonomy acknowledges an individuals right to hold
views, to make choices, and to take actions based on her
own personal values and beliefs. Respect for autonomy
provides a strong moral foundation for informed consent,
in which a patient, adequately informed about her medical
condition and the available therapies, freely chooses specific treatments or nontreatment. Respect for patient
autonomy, like all ethical principles, cannot be regarded as
absolute. At times it may conflict with other principles or
values and sometimes must yield to them.
Beneficence and Nonmaleficence
The principle of beneficence, which literally means doing
or producing good, expresses the obligation to promote
the well-being of others. It requires a physician to act in a
way that is likely to benefit the patient. Nonmaleficence is
the obligation not to harm or cause injury, and it is best
known in the maxim, primum non nocere (First, do no
harm.). Although there are some subtle distinctions
between nonmaleficence and beneficence, they often are
considered manifestations of a single principle. These two
principles taken together are operative in almost every
treatment decision because every medical or surgical pro-
192
One Case Study: Five Approaches

Although the several approaches to ethical decision making
may all produce the same answer in a situation that requires
a decision, they focus on different, though related, aspects
of the situation and decision. Consider, for instance, how
they might address interventions for fetal well-being if a
pregnant woman rejects medical recommendations or
engages in actions that put the fetus at risk.*
A principle-based approach would seek to identify the
principles and rules pertinent to the case. These might
include beneficencenonmaleficence to both the pregnant
woman and her fetus, justice to both parties, and respect for
the pregnant womans autonomous choices. These principles cannot be applied mechanically. After all, it may be
unclear whether the pregnant woman is making an
autonomous decision, and there may be debates about the
balance of probable benefits and risks of interventions to all
the stakeholders as well as about which principle should
take priority in this conflict. Professional codes and commentaries may offer some guidance about how to resolve
such conflicts.
A virtue-based approach would focus on the courses of
action to which different virtues would and should dispose
the obstetriciangynecologist. For instance, which course
of action would follow from compassion? From respectfulness? And so forth. In addition, the obstetriciangynecologist may find it helpful to ask more broadly: Which course
of action would best express the character of a good
physician?
An ethic of care would concentrate on the implications of
the virtue of caring in the obstetriciangynecologists special relationship with the pregnant women and with the
fetus. In the process of deliberation, individuals using this
approach generally would resist viewing the relationship
between the pregnant woman and her fetus as adversarial,
acknowledging that most of the time women are paradigmatically invested in their fetus well-being and that maternal and fetal interests usually are aligned.* If, however, a
real conflict does exist, the obstetriciangynecologist
should resist feeling the need to take one side or the other.
Instead, he or she should seek a solution in identifying and
balancing his or her duties in these special relationships,
situating these duties in the context of a pregnant womans
cedure has both benefits and risks, which must be balanced

knowledgeably and wisely. Beneficence, the obligation to
promote the patients well-being, may sometimes conflict
with the obligation to respect the patients autonomy. For
example, a patient may desire to deliver a fatally malformed fetus by cesarean because she believes that this procedure will increase the newborns chance of surviving, if
only for a few hours. However, in the physicians best judgment, the theoretical benefit to a nonviable infant may
not justify the risks of the surgical delivery to the woman.
In such a situation, the physicians task is further complicated by the need to consider the patients psychologic,
physical, and spiritual well-being.
values and concerns, instead of specifying and balancing

abstract principles or rights.
To take one example, in considering a case of a pregnant
woman in preterm labor who refuses admission to the hospital for bed rest or tocolytics, Harris combines a care or
relational perspective with a feminist perspective to provide
a much wider gaze than a principle-based approach
might*:
The clinician would focus attention on important
social and family relationships, contexts or constraints that might come to bear on [a] pregnant
[womans] decision making, such as her need to care
for other children at home or to continue working to
support other family members, or whatever life project occupied her, and attempt to provide relief in
those areas.[Often] fetal well-being is achieved
when maternal well-being is achieved.
As this example suggests, a feminist ethics approach
would attend to the social structures and factors that limit
and control the pregnant womans options and decisions in
this situation and would seek to alter any that can be
changed.* It also would consider the implications any intervention might have for further control of womens choices
and actionsfor instance, by reducing a pregnant woman,
in extreme cases, to the status of fetal container or incubator.
Finally, a case-based approach would consider whether
there are any relevantly similar cases that constitute precedents for the current one. For instance, an obstetrician
gynecologist may wonder whether to seek a court order for
a cesarean delivery that he or she believes would increase
the chances of survival for the child-to-be but that the pregnant woman continues to reject. In considering what to do,
the physician may ask, as some courts have asked, whether
there is a helpful precedent in the settled consensus of not
subjecting a nonconsenting person to a surgical procedure
to benefit a third party, for instance, by removing an organ
for transplantation.
*Harris LH. Rethinking maternal-fetal conflict: gender and equality
in perinatal ethics. Obstet Gynecol 2000;96:78691.
In re A.C., 572 A.2d 1235 (D.C. Ct. App. 1990).
Justice
Justice is the principle of rendering to others what is due
to them. It is the most complex of the ethical principles to
be considered because it deals not only with the physicians obligation to render to a patient what is owed but
also with the physicians role in the allocation of limited
medical resources in the broader community. In addition,
various criteria such as need, effort, contribution, and
merit are important in determining what is owed and to
whom it is owed. Justice is the obligation to treat equally
those who are alike or similar according to whatever criteria are selected. Individuals should receive equal treatment unless scientific and clinical evidence establishes
COMMITTEE OPINIONS
that they differ from others in ways that are relevant to the
treatments in question. Determination of the criteria on
which these judgments are based is a highly complex
moral process, as exemplified by the ethical controversies
about providing or withholding renal dialysis and organ
transplantation.
The principle of justice applies at many levels. At the
societal level, it addresses the criteria for allocating scarce
resources, such as organs for transplantation. At a more
local level, it is relevant to questions such as which
patients (and physicians) receive priority for operating
room times. Even at the level of the physicianpatient
relationship, the principle of justice applies to matters
such as the timing of patient discharge. The principle also
governs relationships between physicians and third parties, such as payers and regulators. In the context of the
physicianpatient relationship, the physician should be
the patients advocate when institutional decisions about
allocation of resources must be made.
Balancing the Principles
In order to guide actions, each of these broad principles
needs to be made more concrete. Sometimes the principles
can be addressed in more definite rulesfor instance, rules
of voluntary, informed consent express requirements of the
principle of respect for personal autonomy, and rules of
confidentiality rest on several principles (see Common
Ethical Issues and Problems in Obstetrics and Gynecology). Nevertheless, conflicts may arise among these various principles and rules. In cases of conflict, physicians
have to determine which principle(s) should have priority.
Some ethical theories view all of these principles as prima
facie binding, resist any effort to prioritize them apart from
particular situations, and call for balancing in particular
situations (1). Some other theories attempt to rank principles in advance of actual conflicts (21).
Obstetriciangynecologists, like other physicians,
often face a conflict between principles of beneficence
nonmaleficence in relation to a patient and respect for
that patients personal autonomy. In such cases, the physicians judgment about what is in the patients best interests conflicts with the patients preferences. The physician
then has to decide whether to respect the patients choices or to refuse to act on the patients preferences in order
to achieve what the physician believes to be a better
outcome for the patient. Paternalistic models of physicianpatient relationships have been sharply challenged
and often supplanted by other models. At the other end of
the spectrum, however, the model of following patients
choices, whatever they are, as long as they are informed
choices, also has been criticized for reducing the physician
to a mere technician (22). Other models have been proposed, such as negotiation (23), shared decision making
(24), or a deliberative model, in which the physician integrates information about the patients condition with the
patients values to make a cogent recommendation (22).
Whatever model is selected, a physician may still, in a par-
193
ticular situation, have to decide whether to act on the

patients request that does not appear to accord with the
patients best interests. These dilemmas are considered in
greater detail elsewhere (25).
Common Ethical Issues and Problems

in Obstetrics and Gynecology
Almost everything obstetriciangynecologists do in their
professional lives involves one or more of the ethical principles and personal virtues to a greater or lesser degree.
Nevertheless, several specific areas deserve special attention: the role of the obstetriciangynecologist in the society at large; the process of voluntary, informed consent;
confidentiality; and conflict of interest.
The ObstetricianGynecologists Role in
Society at Large
In addition to their ethical responsibilities in direct
patient care, obstetriciangynecologists have ethical
responsibilities related to their involvement in the organization, administration, and evaluation of health care.
They exercise these broader responsibilities through
membership in professional organizations; consultation
with and advice to community leaders, government officials, and members of the judiciary; expert witness testimony; and education of the public. Justice is both the
operative principle and the defining virtue in decisions
about the distribution of scarce health care resources and
the provision of health care for the medically indigent
and uninsured. Obstetricians and gynecologists should
offer their support for institutions, policies, and practices
that ensure quality of and more equitable access to health
care, particularly, but not exclusively, for women and children. The virtues of truthfulness, fidelity, trustworthiness,
and integrity must guide physicians in their roles as
expert witnesses, as consultants to public officials, as educators of the lay public, and as health advocates (26).
Informed Consent Process
Often, informed consent is confused with the consent
form. In fact, informed consent is the willing acceptance
of a medical intervention by a patient after adequate disclosure by the physician of the nature of the intervention
with its risks and benefits and of the alternatives with their
risks and benefits (27). The consent form only documents the process and the patient decision. The primary
purpose of the consent process is to protect patient autonomy. By encouraging an ongoing and open communication of relevant information (adequate disclosure), the
physician enables the patient to exercise personal choice.
This sort of communication is central to a satisfactory
physicianpatient relationship. Unfortunately, discussions
for the purpose of educating and informing patients
about their health care options are never completely free
of the informants bias. Practitioners should seek to
uncover their own biases and endeavor to maintain objectivity in the face of those biases, while disclosing to the
194
patient any personal biases that could influence the practitioners recommendations (28, 29). A patients right to
make her own decisions about medical issues extends to
the right to refuse recommended medical treatment. The
freedom to accept or refuse recommended medical treatment has legal as well as ethical foundations.
As previously noted, one of the most important elements of informed consent is the patients capacity to
understand the nature of her condition and the benefits
and risks of the treatment that is recommended as well as
those of the alternative treatments (30). A patients capacity to understand depends on her maturity, state of
consciousness, mental acuity, education, cultural background, native language, the opportunity and willingness
to ask questions, and the way in which the information is
presented. Diminished capacity to understand is not
necessarily the same as legal incompetence. Psychiatric
consultation may be helpful in establishing a patients
capacity, or ability to comprehend relevant information.
Critical to the process of informing the patient is the
physicians integrity in choosing the information that is
given to the patient and respectfulness in presenting it in
a comprehensible way. The point is not merely to disclose
information but to ensure patient comprehension of relevant information. Voluntarinessthe patients freedom
to choose among alternativesis also an important element of informed consent, which should be free from
coercion, pressure, or undue influence (31).
Confidentiality
Confidentiality applies when an individual to whom
information is disclosed is obligated not to divulge this
information to a third party. Rules of confidentiality are
among the most ancient and widespread components of
codes of medical ethics. Confidentiality is based on the
principle of respect for patient autonomy, which includes
a patients right to privacy, and on the physicians fidelitybased responsibility to respect a patients privacy. Rules
of confidentiality also are justified by their good effects:
Assurance of confidentiality encourages patients to disclose information that may be essential in making an
accurate diagnosis and planning appropriate treatment.
However, rules of confidentiality are not absolute, either
legally or ethically. Legal exceptions to confidentiality
include the requirements to report certain sexually transmitted diseases or suspected child abuse. Ethically,
breaches of confidentiality also may be justified in rare
cases to protect others from serious harm.
The need for storing and transmitting medical information about patients is a serious threat to confidentiality and privacy, a problem made more complex by the use
of electronic storage and transmission of patient data.
The recent increase in the use of genetic testing and
screening also highlights the need for strong protections
of confidentiality and patient privacy because genetic
information has lifelong implications for patients and
their families.
Obstetriciangynecologists also are confronted with

issues of confidentiality in dealing with adolescents, especially regarding the diagnosis and treatment of sexually
transmitted diseases, contraceptive counseling, and pregnancy (32). The physicians willingness and ability to
protect confidentiality should be discussed with all adolescent patients early in their care. Many state laws protect adolescent confidentiality in certain types of situations, and obstetriciangynecologists should be aware of
the laws in their own states.
Conflict of Interest
It is necessary to distinguish conflicts of interest from
conflicts of obligation. A conflict of obligation exists
when a physician has two or more obligations that sometimes conflictfor example, an obligation to patients
and an obligation to a managed care organization. By
contrast, a conflict of interest exists when a primary
interest (usually the patients well-being) is in conflict
with a physicians secondary interest (such as his or her
financial interest). A conflict of interest is not necessarily
wrong, but it creates the occasion and temptation for the
physician to breach a primary obligation to the patient.
Many kinds of conflicts of interest arise in obstetrics
and gynecology; some are obvious, others more subtle.
Following are a few examples: a managed care guideline
limits coverage for diagnostic tests that physicians consider necessary for patients and penalizes physicians who
order such tests (or rewards physicians who do not order
such tests); a physician recommends products to patients
that are sold for a profit in his or her office (33); a physician refers patients for tests or procedures at an entity in
which the physician has a financial interest; a physician
accepts gifts from a pharmaceutical or medical device
company (34). It is important for physicians to be attentive to the wide range of actual and perceived conflicts of
interest. Even perceived conflicts of interest can threaten
patient and societal trust.
There is ever-increasing intrusion into the patient
physician relationship by government and by the marketplace. Care plans, practice guidelines, and treatment protocols may substantially limit physicians ability to
provide what they consider proper care for patients. If
the conflict is too great, the physician should withdraw
from the organization. In addition to such conflicts of
obligation, a conflict of interest exists if the organizations
incentive plans create inducements to limit care in the
interest of increasing physicians incomes. At one time,
the tension between physicians financial self-interest and
patients interests often encouraged unnecessary testing
and excessive treatment, but the current tension may
provide incentives for too little care. Conflicts of interest
should be avoided whenever possible, and when they are
unavoidable and material to patients decisions, it is the
physicians responsibility to disclose them to patients.
Serious ethical problems arise if organizational rules (socalled gag rules) preclude such disclosures.
COMMITTEE OPINIONS
Guidelines for Ethical Decision

Making
Often, more than one course of action may be morally
justifiable. At times, however, no course of action may
seem acceptable because each may result in significant
harms or compromise important principles or values.
Nevertheless, the clinician must select one of the available
options, justify that decision by ethical reasons, and apply
the same critical thinking faculties that would be applied
to issues of medical evidence. An analysis of the various
factors involved in ethical decisions can aid attempts
to resolve difficult cases. In addition, the involvement of
individuals with a variety of backgrounds and perspectives can be useful in addressing ethical questions.
Informal or formal consultation with those from related
services or with a hospital ethics committee can help
ensure that all stakeholders, viewpoints, and options are
considered as a decision is made.
It is important for the individual physician to find
or develop guidelines for decision making that can be
applied consistently in facing ethical dilemmas. Guidelines consisting of several logical steps can aid the practitioner analyzing and resolving an ethical problem. The
approach that follows incorporates elements of several
proposed schemes (27, 3538).
1. Identify the decision makers. The first step in addressing any problem is to answer the question, Whose
decision is it? Generally, the patient is presumed to
have the authority and capacity to choose among
medically acceptable alternatives or to refuse treatment.
a. Assess the patients ability to make a decision. At
times, this is not clear. An individuals capacity to
make a decision depends on that individuals ability to understand information and appreciate the
implications of that information when making a
personal decision (30). In contrast, competence
and incompetence are legal determinations that
may or may not truly reflect functional capacity.
Assessment of a patients capacity to make decisions must at times be made by professionals
with expertise in making such determinations.
Decisions about competence can be made only in
a court of law.
b. Identify a surrogate decision maker for incompetent patients. If a patient is thought to be incapable of making a decision or has been found
legally incompetent, a surrogate decision maker
must be identified. In the absence of a durable
power of attorney, family members have been
called on to render proxy decisions. In some situations, the court may be called on to appoint a
guardian. A surrogate decision maker should
make the decision that the patient would have
wanted or, if the patients wishes are not known,
that will promote the best interests of the patient.
2.
3.
4.
5.
6.
195
The physician has an obligation to assist the

patients representatives in examining the issues
and reaching a resolution.
c. In the obstetric setting, recognize that a competent pregnant woman is the appropriate decision
maker for the fetus that she is carrying.
Collect data, establish facts.
a. Be aware that perceptions about what may or may
not be relevant or important to a case reflect valueswhether personal, professional, institutional, or societal. Hence, one should strive to be
as objective as possible when collecting the information on which to base a decision.
b. Use consultants as needed to ensure that all available information about the diagnosis, treatment,
and prognosis has been obtained.
Identify all medically appropriate options.
a. Use consultation as necessary.
b. Identify other options raised by the patient or
other concerned parties.
Evaluate options according to the values and principles
involved.
a. Start by gathering information about the values of
the involved parties, the primary stakeholders, and
try to get a sense of the perspective each is bringing to the discussion. The values of the patient
generally will be the most important consideration as decision making proceeds.
b. Determine whether any of the options violates
ethical principles that all agree are important.
Eliminate those options that, after analysis, are
found to be morally unacceptable by all parties.
c. Reexamine the remaining options according to
the interests and values of each party. Some alternatives may be combined successfully.
Identify ethical conflicts and set priorities.
a. Try to define the problem in terms of the ethical
principles involved (eg, beneficence versus respect
for autonomy).
b. Weigh the principles underlying each of the arguments made. Does one of the principles appear
more important than others in this conflict? Does
one proposed course of action seem to have more
merit than the others?
c. Consider respected opinions about similar cases
and decide to what extent they can be useful in
addressing the current problem. Look for morally
relevant differences and similarities between this
and other cases. Usually, physicians find that the
basic dilemma at hand is not a new one and that
points considered by others in resolving past
dilemmas can be useful.
Select the option that can be best justified. Try to arrive
at a rational resolution to the problem, one that can
196
be justified to others in terms of widely recognized

ethical principles.
7. Reevaluate the decision after it is acted on. Repeat the
evaluation of the major options in light of information gained during the implementation of the decision. Was the best possible decision made? What
lessons can be learned from the discussion and resolution of the problem?
Summary
Obstetriciangynecologists who are familiar with the
concepts of medical ethics will be better able to approach
complex ethical situations in a clear and structured way.
By considering the ethical frameworks involving principles, virtues, care and feminist perspectives, concern for
community, and case precedents, they can enhance their
ability to make ethically justifiable clinical decisions. They
also need to attend to the kinds of ethical issues and problems that arise particularly or with special features in
obstetrics and gynecology. Finally, obstetricians and
gynecologists can enhance their decision-making process
by considering when it would be useful to seek a formal
or informal ethics consult as well as which guidelines
would be most helpful to them as they move from case to
case and decision to decision.
References
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4. Steinbock B, Arras JD, London AJ, editors. Ethical issues in
modern medicine. 6th ed. Boston (MA): McGraw-Hill; 2003.
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bioethics. 6th ed. Belmont (CA): Thomson Wadsworth;
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9. Pellegrino ED. Toward a virtue-based normative ethics
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gynecology. 2nd ed. Washington, DC: ACOG; 2004. p. 215.
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COMMITTEE OPINIONS
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Ethical decision making in obstetrics and gynecology. ACOG
ISSN 1074-861X
198

Surgery and Patient Choice*

Committee on Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Acknowledgment of the importance of patient autonomy and increased

patient access to information has prompted more patient-generated requests for surgical
interventions not necessarily recommended by their physicians. Decision making in
obstetrics and gynecology should be guided by the ethical principles of respect for
patient autonomy, beneficence, nonmaleficence, justice, and veracity. Each physician
should exercise judgment when determining whether information presented to the
patient is adequate. When working with a patient to make decisions about surgery, it is
important for obstetricians and gynecologists to take a broad view of the consequences
of surgical treatment and to acknowledge the lack of firm evidence for the benefit of one
approach over another when evidence is limited.
Is it ethical to perform an elective cesarean

delivery for a woman with a normal pregnancy, a prophylactic oophorectomy for a 30year-old patient with no family history of
ovarian cancer, or a tubal ligation for an 18year-old nulligravid woman? How should the
physician respond to a patient who requests a
specific surgical therapy without having an
accepted medical indication? Should health
care options be regarded in the same way as
choice of cereal in the supermarket: the consumer makes a choice based on appearance,
content, and cost, and the grocer takes the
money and bags the cornflakes, without providing any direction? Is choosing a medical
procedure so radically different and complex
that this analogy is inappropriate?
Years ago, patients presented to their
physicians with symptoms, and the physicians
would establish diagnoses then make recommendations for therapy; usually recommendations were accepted by patients without
question. An example of that paternalistic
model was the widespread practice of twilight sleep for labor and delivery. Physicians
administered a narcotic and scopolamine,
and decisions during labor and delivery were
delegated to the medical team. In contrast,
today the first prenatal visit may open with a
discussion of the patients birth plan, including her preferences for anesthesia, episiotomy,
*Update of Surgery and Patient Choice, in Ethics in
forceps use, cesarean delivery, and breastfeeding. The purpose of this Committee Opinion
is to provide the obstetriciangynecologist
with an approach to decision making based
on ethics in an environment of increased
patient information, recognition of patient
autonomy, direct-to-consumer marketing,
often incomplete evidence, and a plethora of
alternative, investigational, or unproven treatments for many conditions.
Ethical Principles
Decision making in obstetrics and gynecology should be guided by the ethical principles
of respect for patient autonomy, beneficence,
nonmaleficence, justice, and veracity and as
set forth throughout this document and in the
Code of Professional Ethics of the American
College of Obstetricians and Gynecologists
(1). Although obligations to the patient are
paramount, in addition, the obstetrician
gynecologist must consider resolution of conflicts of interest, acknowledgment of the professions responsibility to society as a whole,
and the maintenance of the dignity and honor
of the discipline of obstetrics and gynecology
and its standards of care. Issues related to
surgery are addressed in this Committee
Opinion; however, the ethical principles are
the same as for other health care decisions
(eg, diagnostic testing or medical therapy).
Patient autonomy and the concept of
informed consent or refusal are central to
issues regarding patient choice to have or not
COMMITTEE OPINIONS
have a surgical procedure. It is the obligation of the obstetriciangynecologist to fully inform the patient regarding
treatment options and the potential risks and benefits of
those options. In discussing these options, the physician
should take into account the context of the patients decision making, including the potential influences of family
and society (2). Once the physician is satisfied that the
patient fully comprehends the options, her autonomous
decision ordinarily should be respected and supported.
Patients should be encouraged to seek second opinions
when in doubt or in need of reassurance. However, even
though the decision of the patient should be respected,
respect might not include supporting the decision, particularly when doing so is in direct conflict with other guiding ethical principles. At times, these other principles may
take priority over supporting the patients decisions.
The principle of beneficence refers to the ethical
obligation of the physician to promote the health and
welfare of the patient. The complementary principle of
nonmaleficence refers to the physicians obligation to not
harm the patient. When a patient refuses surgery or
another treatment that the obstetriciangynecologist
believes is necessary for her health and welfare, beneficence and nonmaleficence can conflict with respect for
patient autonomy. In almost all situations, the patient has
a right to refuse unwanted treatment. She does not, however, have a parallel right of access to treatment that the
physician believes is unwise or overly risky.
Justice, as an ethical principle, applies to the physician,
the hospital, the payer, and society, as well as to the individual patient. Although there are many theories of justice, in
the medical context, this principle requires that medical
professionals treat individuals fairly. Further, it is important
for the physician to consider the impact on not only the
individual patient but also society. At the level of the physicianpatient relationship, justice implies, for instance, that
physicians consider a patients request for an elective procedure in the context of similar types of requests by other
patients. At the societal level, justice directs physicians to
consider the impact of their decision to perform a procedure in terms of the allocation of scarce resources.
Veracity, or truth telling, is important in surgical
counseling and decision making. When the patient
requests a procedure to which the physician is morally
opposed (such as abortion or permanent sterilization), the
physician may have a limited right to refuse to provide the
service; however, the physician must disclose scientifically
accurate information, convey to the patient that this
refusal is based on moral (not medical) grounds, and refer
the patient in a timely manner (3). The obstetriciangynecologist should not misrepresent his or her experience
with the proposed treatment or knowledge regarding
potential long-term outcomes.
The PhysicianPatient Relationship

Four models of the relationship between the physician and
patient have been described: 1) paternalistic, 2) informative,
199
3) interpretive, and 4) deliberative (4). Depending on

which model is used, different ethical principles emerge as
relevant to ethical decision making. The ideal model for
the physicianpatient relationship has been the subject of
considerable debate. In fact, physicians probably use all
four models, depending on the individual patient, her situation, and the disease process involved (4).
Paternalistic Model
In the paternalistic physicianpatient model (4), the
physician might present only information on risks and
benefits of a procedure that he or she thinks will lead the
patient to make the right decision (ie, in this model, the
physician-supported decision) regarding health care. One
example of the paternalistic model would be the ethically
and professionally problematic practice of recommending amniocentesis for a 35-year-old pregnant patient but
offering no alternatives.
This model is not appropriate when the patient is
competent to make informed decisions, but it may be the
best choice in situations of last resort, such as unconscious patients in the emergency department when no
surrogate decision maker is present. When the patient is
ill and unable to engage, either physically or mentally, in
a discussion of the risks and benefits of a particular surgical intervention and there is neither an advance directive nor an assigned proxy for health care decisions, a
paternalistic physicianpatient relationship may be the
only way to adhere to the ethical principles of beneficence
and nonmaleficence with impaired patient autonomy.
Informative Model
At the opposite end of the spectrum, the informative
model describes a physicianpatient relationship in which
the physician is a provider of objective and technical information regarding the patients medical problem and its
potential therapeutic solutions. The patient has complete
control over surgical decision making, and the physicians
values are not discussed. An example is a physician offering a patient with an abnormal cervical cytology result the
options of watchful waiting, colposcopy, loop electrosurgical excision procedure, laser ablation, cold knife conization, and hysterectomy. The discussion includes a
complete description of advantages, disadvantages, risks,
and complications of each option. The discussion does not
include any statement about the physicians recommendations or prioritization of the options.
A serious drawback of this model is the physicians
abandonment of the role of a caring partner and medical
expert in the decision-making process. This model also
assumes that patients have set values and are able to completely integrate the sometimes complex medical and surgical treatment decisions with those values. However,
when the physicianpatient relationship is necessarily
brief and there are multiple treatment options with comparable risks and benefits, the informative model may be
appropriate. One example is the choice of having a genetic
200
amniocentesis for advanced maternal age versus multiple

marker testing or no testing.
One of the many unfortunate consequences of the
professional liability crisis is the unsubstantiated belief of
some physicians that the informative model reduces the
physicians risk of liability. Such a belief raises concerns
about physicians protecting themselves rather than working in the best interests of their patients.
This model may not be ideal for patient care in most
situations because the physicians professional judgment
generally is of considerable value to patients. In any case,
it probably is impossible for a physician to counsel a
patient with complete objectivity and without introducing some implied preference for one of many options (5).
Interpretive Model
Other models for physicianpatient relationships strike a
middle ground between the extremes of the paternalistic
and informative models. In the interpretive model, the
physician helps the patient clarify and integrate her values
into the decision-making process while acting as an information source regarding the technical aspects of any
given medical procedure. In this model, the physician aids
the patient in self-understanding; the patient comes to
know more clearly who he or she is and how various
medical options bear on his or her identity (4).
Application of this model to an example of cervical
dysplasia might result in the physician noting that the
patient had a history of moderate symptoms associated
with menses, had completed her childbearing, and was
very fearful of cancer. On that basis, the physician recommends hysterectomy over other options, although he or
she describes and discusses other options and their
potential implications for the patient. When implementing this model, the physician must be careful to help the
patient clarify her values while not imposing his or her
own values or beliefs on the patient.
Deliberative Model
In the deliberative model, the physicians role is to guide
the patient in taking the most admirable or moral (based
on her values, needs, and fears) course of treatment or
health-related action (4). It is similar to the interpretive
model in that it includes a discussion of not only the
medical benefits and risks but also the patients individual
priorities, values, and fears. It goes beyond the interpretive model in that the physician must consciously communicate to the patient his or her health values; however,
the physician should not use the moral discussion to dictate to the patient the best course of action (4). Because of
the potential for an unequal balance of power in the
physicianpatient relationship, great care should be taken
in this model to avoid subjecting the patient to undue
pressure.
The case of a patient with a history of tubal ligation
considering her fertility options may illustrate the deliberative model. In this case, the patients understanding of
the moral status of the human embryo might influence

whether tubal anastomosis or in vitro fertilization is pursued. The physician would provide technical information
about the options but might also convey information
about how individuals and organizations have formulated the discussion of the moral status of embryos. This
deliberation then may assist the patient by providing tools
with which the patient might examine her values in support of a treatment decision.
The Process of Decision Making

Each physician should exercise judgment when determining whether information presented to the patient is adequate. The practice of evidence-based medicine involves
understanding the scientific basis of treatment and the
strength of the evidence and applying the results of the
strongest evidence available to medical decision making.
Frequently, both surgical and medical decisions need to
be made in a context in which the scientific evidence supporting one treatment option over another is incomplete,
of poor quality, or totally lacking. There is no ethical
imperative to initiate discussion of treatment options that
are either unproven or not part of accepted medical practice. The physician may, however, want to discuss investigational options so that the patient understands the
unproven nature of these options and can make an
informed decision about them. Surgical and medical
advice or guidance for many obstetric and gynecologic
problems is based in part on science, in part on the experience and values of the physician, and in part on the
physicians understanding of the patients preferences,
values, and desired outcome.
When working with a patient to make decisions
about surgery, it is important for obstetricians and gynecologists to take a broad view of the consequences of surgical treatment and to acknowledge the lack of firm
evidence for the benefit of one approach over another
when evidence is limited. For example, a discussion of
treatment options for menorrhagia associated with
leiomyoma should include the fact that the long-term
risks and benefits of some treatment options have not
been compared directly (6). Recommendation for a particular option is dictated by many factors, including
patient age, leiomyoma size, bleeding severity, and coexisting medical conditions, but in many cases two or more
therapeutic options probably would be regarded as equally
medically sound. Comparing possible long-term complications of hysterectomy, such as bowel obstruction and
loss of vaginal support, with the risks of more conservative surgical approaches, such as the possible need for
future treatment of recurrent leiomyomata, is an important part of informed consent. Helping patients understand potential long- and short-term consequences of any
given decision as well as giving patients an appreciation of
the quality of evidence on which each option is based are
critical parts of informed consent. In addition, the physician must be aware of potential personal conflicts of
COMMITTEE OPINIONS
interest that may be present, such as personal financial

gain related to the provision or nonprovision of surgical
care, and he or she must guard against this as an influence
when giving guidance to patients as they make treatment
choices.
An Example of the Process

Elective cesarean delivery is offered as an example to illustrate an ethical framework physicians may use in responding to patient requests for treatment for which evidence of
benefit is absent or imperfect or which the health care
professional would not usually recommend. In using this
example, the Committee on Ethics does not mean to comment on the clinical appropriateness of or medical evidence supporting elective cesarean delivery, which would
require a review beyond the scope of this document and
the Committee on Ethics and have recently been
addressed by the Committee on Obstetric Practice (7).
In obstetrics, the ethical issues of informed consent
and patient choice are exemplified in the current debate
regarding whether elective cesarean delivery should be
offered as a birth option in normal pregnancy (8). The
wide range of opinion on this issue is reflected in the language that is used, with varying terms reflecting different
views of the physicianpatient relationship. Cesarean
delivery on demand reflects the informative model, in
which the physician simply describes options and provides
the service chosen by the patient. The phrase elective
cesarean delivery is more suggestive of the deliberative
and interpretive models, in which the physician and
patient also discuss concerns, needs, and values.
The ethical evaluation is clouded by the limitations
of data regarding relative short- and long-term risks and
benefits of cesarean delivery versus vaginal delivery (9).
For example, limitations that need to be acknowledged on
both sides of the debate include evidence for long-term
reduction in pelvic floor disorders in women undergoing
elective cesarean delivery and lack of extensive morbidity
and mortality data comparing routine cesarean delivery
with vaginal delivery.
Each of the ethical principles contributes to the decision-making process regarding elective cesarean delivery.
However, none alone is sufficient for making the decision.
If taken in a vacuum, the principle of respect for
patient autonomy would lend support to the permissibility of elective cesarean delivery in a normal pregnancy
(after adequate informed consent). To ensure that the
patients consent is in fact informed, the physician should
explore the patients concerns. For example, a patient may
request elective cesarean delivery because she is afraid of
discomfort during labor (10). In this case, providing her
with information about procedures available for effective
pain relief during labor would actually enhance the
patients capacity for autonomous choice and may result
in an agreement to proceed without surgery (11).
The ethical principle of justice regarding the allocation of medical resources must be considered in the
201
debate over elective cesarean delivery and informed

patient choice. It is not clear whether widespread implementation of elective cesarean delivery would increase or
decrease resources required to provide delivery services.
Comprehensive analysis of costs and benefits for current
and subsequent pregnancies would provide a basis for
application of the principle of justice (12).
Application of the principles of beneficence and nonmaleficence (a physician should offer only treatments that
promote the health and welfare of the patient) is made
problematic by the limitations of the scientific data
described previously. Different interpretations of the risks
and benefits are the basis for reasonable differences among
obstetricians regarding this challenging issue. In addition,
different patients may place considerably different values
on known risks and benefits. How certain is it that elective
cesarean delivery really protects pelvic support 20 years
later? How different is the maternal mortality rate of
elective or repeat cesarean delivery in healthy women
compared with that of women who have had one or two
vaginal deliveries? Are there any desirable or undesirable
psychosocial effects of elective cesarean delivery? The
currently available data do not adequately represent the
comparative populations in question. For instance, data
regarding outcomes of cesarean delivery usually involve
complicated pregnancies or women in whom a trial of
labor has failed. These outcomes are compared with those
involving probably healthier women who were able to give
birth vaginally. As better data accumulate, the principle of
beneficence may result in a shift in clinical practice.
Based on these principles, is it ethical to agree to a
patient request for elective cesarean delivery in the
absence of an accepted medical indication? The response
must begin with the physicians assessment of the current
data regarding the relative benefits and risks of the two
approaches. In the absence of significant data on the risks
and benefits of cesarean delivery, the burden of proof
should fall on those who are advocates for a change in
policy in support of elective cesarean delivery (ie, the
replacement of usual care in labor with a major surgical
procedure). If the physician believes that cesarean delivery promotes the overall health and welfare of the woman
and her fetus more than vaginal delivery, he or she is ethically justified in performing a cesarean delivery.
Similarly, if the physician believes that performing a
cesarean delivery would be detrimental to the overall
health and welfare of the woman and her fetus, he or she
is ethically obliged to refrain from performing the
surgery. In this case, a referral to another health care
provider would be appropriate if the physician and
patient cannot agree on a route of delivery.
Given the lack of data, it currently is not ethically necessary to initiate discussion regarding the relative risks and
benefits of elective cesarean delivery versus vaginal delivery
with every pregnant patient. There is no obligation to initiate discussion about procedures that the physician does
not consider medically acceptable or that are unproven.
202
On the basis of the ethical principles of beneficence

and respect for patient autonomy, an algorithm has been
proposed for deciding between the performance of a
cesarean delivery and making a referral in cases in which
the physicians recommendation is vaginal delivery and
the informed patient makes the autonomous decision to
request a cesarean delivery (13). The Committee on Ethics
addresses other special considerations involving patient
choice in obstetric decision making elsewhere (14).
Summary
Although informed refusal of care by the patient is a
familiar situation for most clinicians in the practice of
both obstetrics and gynecology, acknowledgment of the
importance of patient autonomy and increased patient
access to information, such as information on the
Internet, has prompted more patient-generated requests
for surgical interventions not necessarily recommended
by their physicians. A patient request for elective cesarean
delivery, prompted by a perception of lower risk to the
woman (of pelvic floor and sexual dysfunction) and her
fetus with cesarean delivery, is an obstetric example.
Other examples include requests for prophylactic
oophorectomy to reduce risk of ovarian cancer in otherwise healthy women at low risk.
The response to such requests must begin with the
physician having a good understanding of the scientific
evidence for and against the requested procedure. With
that information, the physician should counsel the patient
within the framework of the ethical principles of respect
for autonomy, beneficence, nonmaleficence, veracity, and
justice. The ethical models described in this document
provide an approach for using these principles. The physician should use the opportunity that this kind of request
presents to explore the patients concerns and values. In
most cases, providing information and careful counseling
will allow patients and their physicians to reach a mutually acceptable decision. If an acceptable balance cannot be
reached by the patient and physician, the patient may
choose to continue care with another provider.
References
of professional ethics of the American College of
acogcode.pdf. Retrieved January 2, 2008.
2. Mackenzie C, Stoljar N. Relational autonomy: feminist perspectives on autonomy, agency, and the social self. New York
(NY): Oxford University Press; 2000.
3. The limits of conscientious refusal in reproductive medicine. ACOG Committee Opinion No. 385. American
2007;110;12038.
4. Emanuel EJ, Emanuel LL. Four models of the physicianpatient relationship. JAMA 1992;267:22216.
5. Mahowald MB. On the treatment of myopia: feminist
standpoint theory and bioethics. In: Wolf S, editor.
Feminism and bioethics: beyond reproduction. New York
(NY): Oxford University Press; 1996. p. 95115.
6. Myers ER, Barber MD, Gustilo-Ashby T, Couchman G,
Matchar DB, McCrory DC. Management of uterine leiomyomata: what do we really know? Obstet Gynecol 2002;100:
817.
7. Cesarean delivery on maternal request. ACOG Committee
8. Minkoff H, Chervenak FA. Elective primary cesarean delivery. N Engl J Med 2003;348:94650.
9. Cesarean delivery on maternal request March 2729, 2006.
National Institutes of Health state-of-the-science conference statement. Obstet Gynecol 2006;107:138697.
10. Bewley S, Cockburn J. Responding to fear of childbirth.
Lancet 2002;359:21289.
11. Saisto T, Salmela-Aro K, Nurmi JE, Kononen T,
Halmesmaki E. A randomized controlled trial of intervention in fear of childbirth. Obstet Gynecol 2001;98:8206.
12. Morrison J, MacKenzie IZ. Cesarean section on demand.
Semin Perinatol 2003;27:2033.
13. Chervenak FA, McCullough LB. An ethically justified algorithm for offering, recommending, and performing cesarean delivery and its application in managed care practice.
14. Maternal decision making, ethics, and the law. ACOG
106:112737.

and Gynecologists, 409 12th Street, SW, PO Box 96920,
Surgery and patient choice. ACOG Committee Opinion No. 395.
2008;111:2437.
ISSN 1074-861X
COMMITTEE OPINIONS
203

Surrogate Motherhood*
Committee on Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Ethical responsibilities are described for obstetriciangynecologists

who choose to participate in surrogacy arrangements by 1) advising couples who are considering surrogacy, 2) counseling potential surrogate mothers, 3) providing obstetric services for pregnant women participating in surrogacy, or 4) offering assisted reproductive
technologies related to surrogacy. Although the obligations of physicians will vary
depending on the type and level of their involvement, in all cases physicians should carefully examine all relevant issues related to surrogacy, including medical, ethical, legal, and
psychologic aspects.
Although the practice of surrogate motherhood has become more common since the
Gynecologists (ACOG) issued its first statement on this subject in 1983, it continues to
be controversial. There are those who believe
that surrogacy should be permitted because
such arrangements can be beneficial to all
parties, and to prohibit them would limit the
autonomy of infertile couples and women
who wish to help them through surrogate
gestation. Others believe that the risks outweigh the benefits or that because of shifting
emotions and attitudes toward the fetus during gestation, it is not possible for a pregnant
woman to give truly informed consent to
relinquish an infant until after birth has
occurred (1).
Many issues related to surrogate motherhood have not been resolved, and considerable disagreement persists within the medical
profession, the medical ethics community,
state legislatures, the courts, and the general
public. Similarly, no one position reflects the
variety of opinions on surrogacy within
ACOGs membership. Although these differences of opinion are recognized, the purpose
of this Committee Opinion is to focus on the
ethical responsibilities of obstetriciangynecologists who choose to participate in surrogacy arrangements on a variety of levels,
including caring for the pregnant woman
and her fetus.
*Update of Surrogate Motherhood in Ethics in
The first part of this Committee Opinion

provides an overview of public policy issues,
descriptions of the types of surrogacy, arguments supporting and opposing surrogacy
arrangements, and particular concerns related to payment and commercialization. The
second part offers ethical recommendations
to physicians and patients who may participate in surrogacy. The ethical obligations of
physicians will vary depending on the type
and level of their involvement in surrogacy
arrangements.
General Issues
Public Policy
In some states, the practice of surrogate
motherhood is not clearly covered under
existing law. There is a split among the states
that have statutes. Some states prohibit surrogacy contracts or make them void and
unenforceable, whereas others permit such
agreements (2, 3).
When a court is asked to decide a dispute regarding parental rights or custody of a
child born as a result of a surrogacy arrangement, existing statutes may not prove adequate given the complexity of the problem.
Courts faced with such decisions have given
preference to different factors: the best interest of the child, the rights of the birth mother (as in adoption situations), the genetic link
between the child and the genetic parents,
and the intent of the couple who entered into
a surrogacy contract to become parents.
Often two or more of these factors conflict
204
with each other, and there is not a consensus in the legal

or ethical communities as to which factor should have
priority (2, 47).
The obstetriciangynecologist who facilitates surrogacy arrangements should be aware of any statutes or
court cases in the state in which he or she practices. In
counseling individuals seeking a child through surrogacy
or a woman who is considering surrogate gestation, the
physician should encourage consideration of the possible
consequences of a surrogacy arrangement, including
potential legal complications.
Types of Surrogacy
Surrogacy can be classified on the basis of the source of
the genetic material. Eggs, sperm, or both may be donated, thereby altering the intended parents biologic relationship to the child.
In one type of surrogacy arrangement, the intended parents are a couple who reach an agreement with a
woman (the surrogate mother) who will be artificially inseminated with sperm provided by the male partner of the couple seeking surrogacy services. Thus, the
genetic and gestational mother of any resultant child is
the surrogate mother, and the genetic father is the
intended father. The intended parents plan to be the
social or rearing parents of the child. Although this
Committee Opinion refers to intended parents as a couple, individual men and women also may seek surrogacy
services.
In another type of surrogacy, in vitro fertilization
and embryo transfer are combined with surrogacy
arrangements. In this case, it is possible for both the
intended father and the intended mother to be the genetic parents of the child, and the surrogate fulfills only the
role of gestational mother. This type of arrangement originally was called surrogate gestational motherhood, and
now the carrying woman is called the gestational carrier
or gestational surrogate.
The different types of relationships that are possiblegenetic (either, both, or neither intended parent),
gestational (the surrogate mother), and social or rearing
(the intended parents)give rise to both conceptual
challenges regarding the nature of parenthood and legal
problems as to who should be considered the parents
responsible for the child.
Major Arguments for and Against Surrogacy
Arrangements
Surrogacy can allow a couple to have a child when they
would otherwise be unable to do so except by adoption
because of an inability to achieve pregnancy or medical
contraindications to pregnancy for the intended mother.
Adoption, however, does not provide a genetic link to the
child, an important consideration for some prospective
parents. Surrogacy is chosen by some prospective parents
because of a desire for genetic linkage or for practical reasons, such as the scarcity of adoptable children.
Arguments based on reproductive liberty also support surrogacy arrangements. In the United States, the
freedom to decide whether and when to conceive or bear
a child is highly valued and protected. Thus, some have
argued that intended parents and surrogate mothers
should be free to cooperate in procreating, at least in cases
of medical need and where care is taken to avoid harming
others, especially the prospective child. Furthermore,
women willing to participate in surrogacy may derive satisfaction from helping the intended parents. Many
women participate in surrogacy primarily for altruistic
reasons and see their services as a gift.
The primary arguments against surrogate motherhood are based on the harms that the practice may be
thought to produceharms to the child that is born,
harms to the surrogate mother herself, harms to her existing children if she has children, and harms to society as a
whole. It is surely harmful to any child to be the object of
a custody dispute. In addition, the rejection of an
infantfor example, rejection of an infant with a disability by both intended parents and surrogate motheris a
significant harm. If an existing relationship is used to
coerce relatives or close friends to become surrogate
mothers, that coercion is a harm resulting from the practice of surrogate motherhood. The existing children of a
surrogate mother may be harmed if her pregnancy and
relinquishment result in high levels of stress for the surrogate mother or her family. These children and society as
a whole may be harmed by the perception that reproduction is trivialized by transactions that translate womens
reproductive capacities and the infants that result into
commodities to be bought and sold. Depersonalization of
a pregnant woman as a vehicle for the genetic perpetuation of other individuals may harm not only surrogate
mothers but also the status of women as a whole. There
also is a concern that redefining concepts of motherhood
may threaten traditional understandings of parenting and
family.
Children are much more vulnerable than adults.
Harms to children who have no choice in a matter are
more serious, from an ethical standpoint, than harms to
adults who make a choice that they later regret. Further, a
distinction should be drawn between harms that
inevitably, or almost invariably, are associated with a
practice and harms that likely could be avoided through
advance planning, appropriate counseling, or oversight
mechanisms.
Few studies provide data about harms and benefits
resulting from surrogacy arrangements. Absent such data,
discussion about possible outcomes does not provide a
solid foundation for ethical conclusions and clinical
guidelines. It is important to know whether these outcomes actually occur and, if so, how frequently. Studies
that will provide more data of this type are needed (8, 9).
In summary, there are strong arguments both for and
against the practice of surrogacy. Physicians will be on
both sides of this debate. If, after careful consideration of
COMMITTEE OPINIONS
the arguments, a physician chooses to facilitate or recommend surrogacy arrangements, then precautions should
be taken to prevent medical, psychologic, and legal harms
to the intended parents, the potential surrogate mother,
and the prospective child.
Payment to the Surrogate Mother
Perhaps no topic related to surrogate motherhood is
more contentious than compensation of the surrogate
mother by the intended parents (10). Payment often is
substantial because of the duration and complexity of
involvement. As noted previously, some states specifically
prohibit surrogacy contracts that involve payment.
Several questions about payment for surrogacy have been
raised:
For what is payment made? Although there is debate on
this point, it is clear that payment must not be made contingent on the delivery of an acceptable producta
live-born, healthy child. Rather, payment should be construed as compensation for the surrogate mothers time
and effort, her initiating and carrying the pregnancy, her
participation in labor and delivery, her acceptance of the
risks of pregnancy and childbirth, and her possible loss of
employment opportunities.
Why is payment offered or requested? In many surrogacy
arrangements among close friends or relatives, there is no
payment for the services of the surrogate mother. Rather,
she may provide her services as an act of altruism, and the
intended parents will be asked to reimburse her only for
out-of-pocket expenses connected with the pregnancy.
However, most women are understandably reluctant to
undertake the burdens and risks of pregnancy on behalf
of strangers without some kind of compensation for their
time, effort, and risk.
Is payment likely to lead to the exploitation of potential surrogate mothers? Surrogacy arrangements often take place
between parties with unequal power, education, and economic status (11). Unless independent legal representation and mental health counseling are mandated, women
serving as surrogate mothers may be particularly vulnerable to being exploited. If a payment offered to a candidate for surrogacy is too low, it may be said to exploit her
by not providing adequate compensation; if the payment
is too high, it may be said to exploit her by being irresistible and coercive. Opponents of surrogate motherhood also have argued that if a fee must be paid to the
surrogate mother, only affluent couples will be able to
seek surrogacy services. This access barrier, however
problematic, exists for most services related to infertility,
for certain other medical procedures, and for adoption
and, thus, is not specific to surrogacy agreements.
Responsibilities of
ObstetricianGynecologists
In this Committee Opinion, the Committee on Ethics
makes ethical recommendations for four categories of
205
physician involvement: 1) advising couples who are considering surrogacy, 2) counseling potential surrogate
mothers, 3) providing obstetric services for pregnant surrogates, and 4) offering assisted reproductive technologies
related to surrogacy. Although the obligations of physicians will vary depending on the type and level of their
involvement, in all cases physicians should carefully
examine all relevant issues related to surrogacy, including
medical, ethical, legal, and psychologic aspects.
Intended parents and surrogate mothers have both
divergent and common interests. Because of these divergent interests, one professional individual (eg, physician,
attorney, or psychologist) or agency should not represent
the interests of both major parties in surrogacy arrangements. The physician who treats the intended parents
should not have the surrogate mother as an obstetric
patient because conflicts of interest may arise that would
not allow the physician to serve all parties properly.
Responsibilities of Physicians to Couples
Considering Surrogacy
When approached by a couple considering surrogacy, the
physician should, as in all other aspects of medical care,
be certain that there will be a full discussion of ethical and
legal issues as well as medical risks, benefits, and alternatives, many of which have been addressed in this statement. An obstetriciangynecologist who is not familiar
with these issues should refer the couple for appropriate
counseling. Additional recommendations for advising
couples considering surrogacy are as follows:
Because of the risks inherent in surrogacy arrangements, such arrangements should be considered only
in the case of infertility or serious health-related
needs, not for convenience alone.
A physician may justifiably decline to participate in
initiating surrogacy arrangements for personal, ethical, or medical reasons.
If a physician decides to become involved in facilitating surrogate motherhood arrangements, the following guidelines should be used:
The physician should be assured that appropriate
procedures are used to screen the intended parents
and the surrogate mother. Such screening should
include appropriate fertility studies, medical
screening, and psychologic assessment.
Mental health counseling should be provided
before initiation of a pregnancy 1) to permit the
potential surrogate mother and the intended parents to explore the range of outcomes and possible
long-term effects and 2) to consider possible psychologic risks to and vulnerabilities of both parties
and the prospective child.
It is preferable that surrogacy arrangements be
overseen by private nonprofit agencies with credentials similar to those of adoption agencies.
However, many existing agencies are entrepre-
206
neurial and for-profit (9). A physician making a

referral to an agency must have assurance that the
agency is medically and ethically reputable and
that it is committed to protecting the interests of
all parties involved.
The physician should receive only usual compensation for medical services. Referral fees and other
arrangements for financial gain beyond usual fees
for medical services are inappropriate.
The physician should not refer patients to surrogacy programs in which the financial arrangements are likely to exploit any of the parties.
The obstetriciangynecologist should urge the
intended parents to discuss preconditions and possible contingencies with the surrogate mother or her
representative and to agree in advance on the
response to them. These issues include, but may not
be limited to, the expected health-related behaviors
of the surrogate mother; the prenatal diagnosis of a
genetic or chromosomal abnormality; the inability
or unwillingness of the surrogate mother to carry the
pregnancy to term; the death of one of the intended
parents or the dissolution of the couples marriage
during the pregnancy; the birth of an infant with a
disability; a decision by the surrogate mother to
abrogate the contract and to contest custody of an
infant conceived with the sperm of the intended
father; or, in the case of gestational surrogacy, the
option of registering the intended parents as the legal
parents.
The obstetriciangynecologist should urge the parties involved to record in writing the preconditions
and contingency plans on which they have agreed to
make explicit the intentions of the parties, to facilitate later recollection of these intentions, and to help
promote the interests of the future child. In the
preparation of this agreement, both parties should be
encouraged to have independent legal representation.
Whatever compensation is provided to the surrogate
mother should be paid solely on the basis of her time
and effort, her initiation and continued gestation of
the pregnancy, her participation in labor and delivery,
her acceptance of the risks of pregnancy and childbirth, and her possible loss of employment opportunities. Compensation must not be contingent on a
successful delivery or on the health of the child.
Where possible, obstetriciangynecologists should
cooperate with and participate in research intended to
provide data on outcomes of surrogacy arrangements.
Responsibilities of Physicians to Potential

Surrogate Mothers
When approached by a patient considering becoming a
surrogate mother, the physician should address ethical
and legal concerns fully along with medical risks and ben-
efits as part of the initial consultation. In particular, the

physician should be sure that preconditions and contingencies, such as those outlined in the previous section,
have been thoroughly considered and that the potential
surrogate mother recognizes the importance of having
explicit written precondition and contingency agreements. In the preparation of this agreement, both the
intended parents and the potential surrogate mother
should be encouraged to have independent legal representation. Additional recommendations for counseling
and providing other services for potential surrogate
mothers are as follows:
To avoid conflict of interest, the physician should not
facilitate a womans becoming a surrogate mother for
a couple whom the physician also is treating.
The physician should ensure that appropriate procedures are used to screen and counsel both the intended parents and the surrogate mother. Referral for
mental health counseling should be provided before
initiation of a pregnancy 1) to permit the potential
surrogate mother to explore the range of outcomes
and possible long-term effects and 2) to evaluate her
psychologic risks and vulnerabilities as well as the
possible effects of surrogacy on her existing relationships and on any existing children.
A physician who provides examinations and performs procedures for an agency that arranges surrogacy contracts should be aware of the policies of the
agency and should decline involvement with any
agency whose policies are not consistent with the ethical recommendations of this Committee Opinion
and those of other professional organizations related
to reproductive medicine, such as the American
Society for Reproductive Medicine (formerly known
as the American Fertility Society) (8, 9, 12).
Whatever compensation is provided to the surrogate
mother should be paid solely on the basis of her time
and effort, her initiation and continued gestation of
the pregnancy, her participation in labor and delivery,
her acceptance of the risks of pregnancy and childbirth, and her possible loss of employment opportunities. Compensation must not be contingent on a
successful delivery or on the health of the child.
The physician should avoid participation in medical
care arising from surrogacy arrangements in which
the financial or other arrangements are likely to
exploit any of the parties. The physician, therefore, is
obliged to become as informed as possible about the
financial and other arrangements between the surrogate mother and intended parents to make ethical
decisions about providing medical care. A physician
who agrees to provide medical care in what he or she
later recognizes as clearly exploitative circumstances
has a responsibility to discuss and, if possible, resolve
problematic arrangements with all parties and may
choose to transfer care when it is possible to do so.
COMMITTEE OPINIONS
Responsibilities of Physicians to Pregnant

Women Participating in Surrogacy
When a woman participating in surrogacy seeks medical
care for an established pregnancy, the obstetrician should
explore with the woman her understanding of her contract with the intended parents and any provisions of it
that may affect her care. If the physician believes that provisions of the contract may conflict with his or her professional judgment, the physician may refuse to accept
the patient under those terms. Once accepted as a patient,
she should be cared for as any other obstetric patient,
regardless of the method of conception, or referred to
an obstetrician who will provide that care. Even if she
has already undergone screening by an agency, a physicianpatient relationship exists between her and the
obstetrician. The obstetrician has the attendant obligations of this relationship. Additional recommendations
regarding the provision of obstetric services in this setting are as follows:
The obstetricians professional obligation is to support the well-being of the pregnant woman and her
fetus, to support the pregnant womans goals for the
pregnancy, and to provide appropriate care regardless of the patients plans to keep or relinquish the
future child. If a physicians discomfort with surrogacy arrangements might interfere with that obligation, the patient should be referred to another
obstetrician.
The pregnant woman should be the sole source of
consent regarding clinical intervention and management of the pregnancy, labor, and delivery.
Agreements the surrogate mother has made with the
intended parents regarding her care and behavior
during pregnancy and delivery should not affect the
physicians care of the patient. The obstetrician must
make recommendations that are in the best interests
of the pregnant woman and her fetus, regardless
of prior agreements between her and the intended
parents.
Confidentiality between the physician and the pregnant patient should be maintained. The intended
parents may have access to the patients medical
information only with the pregnant womans explicit consent.
Obstetriciangynecologists are encouraged to assist
in the development of hospital policies to address
labor, delivery, postpartum, and neonatal care in situations in which surrogacy arrangements exist.
Responsibilities of Infertility Specialists and
Reproductive Endocrinologists to Intended
Parents and Surrogate Mothers
In providing medical services related to surrogate motherhood arrangements, infertility specialists and reproductive endocrinologists should follow the recommendations
207
in the two previous sections. In particular, these specialists should ensure that appropriate procedures are used to
screen the intended parents and the surrogate mother and
that mental health counseling is provided to all parties
before initiation of a pregnancy. Additional recommendations regarding the provision of assisted reproductive
technologies are as follows:
A physician who performs artificial insemination or
in vitro fertilization as a part of surrogacy services
necessarily will be involved with both the intended
parents and the surrogate mother. However, the
intended parents and the surrogate mother should
have independent counseling and independent legal
representation, and the surrogate mother should
obtain obstetric care from a physician who is not
involved with the intended parents.
A physician who provides examinations and performs procedures for an agency that arranges surrogacy contracts should be aware of the policies of the
agency and should decline involvement with any
agency whose policies are not consistent with the
ethical recommendations of this Committee
Opinion and those of other professional organizations related to reproductive medicine (8, 9, 12).
Specialists in infertility and reproductive endocrinology are encouraged to participate in research that is
intended to provide data on the outcomes of surrogacy arrangements.
Summary
The obstetriciangynecologist has an ethical responsibility to review the risks and benefits of surrogacy fully and
fairly with couples who are considering surrogacy
arrangements. The obstetrician who is consulted by a
pregnant woman who is participating in a surrogacy
arrangement owes her the same care as any pregnant
woman and must respect her right to be the sole source of
consent for all matters regarding prenatal care and delivery. The gynecologist or specialist in reproductive
endocrinology who performs procedures required for
surrogacy should be guided by the same ethical principles
aimed at safeguarding the well-being of all participants,
including the future child.
References
1. Lederman RP. Psychosocial adaptation in pregnancy:
assessment of seven dimensions of maternal development.
2nd ed. New York (NY): Springer Publishing Company;
1996.
2. The American Surrogacy Center. Legal: state by state
overview. Kennesaw (GA): TASC; 2005. Available at: http://
www.surrogacy.com/Articles/cate_list.asp?ID=7&n=Legal
%3A++State+by+State+Overview. Retrieved July 10, 2007.
3. National Conference of Commissioners on Uniform State
Laws. Gestational agreement. Article 8. In: Uniform parentage act. Chicago (IL): NCCUSL; 2002. p. 6878.
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4. Andrews LB. Alternative modes of reproduction. In: Cohen

S, Taub N, editors. Reproductive laws for the 1990s. Clifton
(NJ): Humana Press; 1989. p. 361403.
5. Serratelli A. Surrogate motherhood contracts: should the
British or Canadian model fill the U.S. legislative vacuum?
George Washington J Int Law Econ 1993;26:63374.
6. Field M. Reproductive technologies and surrogacy: legal
issues. Creighton Law Rev 1992;25:158998.
7. New York State Task Force on Life and the Law. Assisted
reproductive technologies: analysis and recommendations
for public policy. New York (NY): NYSTF; 1998.
8. Surrogate gestational mothers: women who gestate a genetically unrelated embryo. American Fertility Society. Fertil
Steril 1994;62(suppl 1):67S70S.
9. Surrogate mothers. American Fertility Society. Fertil Steril
1994;62(suppl 1):71S77S.
10. Moody-Adams MM. On surrogacy: morality, markets, and
motherhood. Public Aff Q 1991;5:17590.
11. Harrison M. Financial incentives for surrogacy. Womens

Health Issues 1991;1:1457.
12. Family members as gamete donors and surrogates. Ethics
Committee Report. American Society for Reproductive
Medicine. Fertil Steril 2003;80:112430.

Surrogate motherhood. ACOG Committee Opinion No. 397.
2008;111:46570.
ISSN 1074-861X
COMMITTEE OPINIONS
209

Relationships With Industry*

Committee on Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Although physicians and their professional organizations have routinely

accepted gifts from the health care industry, evidence now indicates that such gifts may
misdirect physicians from their primary responsibility to act in the best interests of their
patients. The American College of Obstetricians and Gynecologists Committee on Ethics
offers revised recommendations for relationships with industry. Physicians should understand the potential for influence when considering accepting gifts, including those of
apparently nominal value. If any gifts are accepted, they should primarily entail benefit to
patients or be related to the physicians work and should not be of substantial value.
Sample drugs (or vouchers) may be dispensed but preferably as a full course of therapy
on the basis of true need. Physicians are obligated to seek the most accurate, up-to-date,
evidence-based, and balanced source of information about products. Neither patient
referral nor industry support of institutions should be contingent on physician use or
advocacy of a product. Physicians should disclose their financial interests to patients and
colleagues. Support from industry for continuing medical education and professional
meetings may be accepted, but subsidies should be disclosed and should not be accepted directly by physicians. Speakers may receive reasonable honoraria. Reimbursement
for research should not exceed reasonable direct and indirect costs, and reasonable compensation for subsequent consulting and lecturing is permissible. Investigators who are
or may become involved in a companys research may not buy or sell its stock until their
involvement ends and the research is published or disseminated.
Industrial development of products is

important to continuing improvement in
health care. Manufacturers of pharmaceutical agents and medical devices assist physicians in the pursuit of their educational goals
and objectives through financial support of
various medical, research, and educational
programs. The goals of corporations, however, may conflict with physicians duties to
their patients. Corporations are primarily
responsible to their stockholders, whereas
physicians are primarily responsible to their
patients.
In the past, physicians and their professional organizations often have uncritically
accepted gifts from the health care industry
in the belief that such gifts did not necessarily create undue influence on medical practice. Evidence has accumulated, however,
about the extent to which gifts from industry
may misdirect physicians from their primary
*Update of Relationships With Industry in Ethics in
Obstetrics and Gynecology, Second Edition, 2004
responsibility, which is to act consistently in

the best interests of their patients. Studies
demonstrate that the prescribing practices of
physicians are commonly influenced by both
subtle and obvious marketing messages and
gifts, even when delivered in an educational
context, and even when the physicians studied did not recognize or admit to any changes
in their practice of medicine (1, 2).
When members of industry interact
with professional societies and their members, corporate activities may generate biases
or obligations unrelated to product merit,
creating the actuality or the appearance of
inappropriate and undue interest on the part
of physicians or organizations. In addition to
selling drugs, medical devices, and tests, corporations are significantly involved in support of medical practice at all levels, leading
to a considerable risk of conflict of interest.
In 2002, pharmaceutical companies spent
$11.5 billion to provide physicians with free
samples (3). Sixty percent of biomedical
210
research is privately funded, of which 70% is directly supported by the pharmaceutical industry. Fifty percent of
continuing medical education (CME) is funded primarily
through educational grants by the pharmaceutical industry (4, 5). Biomedical research expenditures by industry
exceed those of the federal government. In a survey of
more than 3,000 physicians, 78% reported receiving
pharmaceutical samples, 83% received meals, 35%
received reimbursement for CME expenses, and 28%
received payment for consulting or serving on an advisory board or speakers bureau (6). This widespread industry support, funding, and involvement has the strong
potential to affect treatment practices and may lead to
decisions based on factors other than the merit of the
product alone.
The public expects physicians to avoid conflicts of
interest in decisions about patient care, which usually
involve the direct treatment of patients. Conflicts also
may involve physician participation in purchasing decisions by medical organizations, such as hospitals and
group practices. When any product promotion or
research project leads to inappropriate or unbalanced
medical advice to patients, an ethical problem exists.
Sponsorship of medical activities by industrial companies
and by other agencies seeking to influence medical care
patterns must not distort the accuracy, completeness, or
balanced presentation of medical advice to patients.
Disclosure of conflict may not be sufficient to nullify its
effect.
Evidence of the subtle and often unrecognized influence over prescribing behavior is part of an important
ethical argument. Physicians have long been held to a
high moral standard in the patientphysician relationship. This relationship is not egalitarian. Instead, the
physician has control over knowledge of and, often, access
to treatment, creating an obligation of fidelity, the ethical
obligation not to abandon the patient. In this relationship
the patient is given priority, and there is a responsibility to
serve as personal advocate for the patient and to eliminate
impediments to the promotion of patient welfare. The
physician is obligated to ensure that the best medical
advice is transmitted to the patient and is not prejudiced
in any manner by industry incitements of gifts, support,
or advertisement.
Recommendations of Other
Organizations
Several professional and regulatory organizations have
put forth positions related to industrys relationship to
individual physician practices and educational activities
(716). There has been movement within the profession
to further restrict relationships with industry, particularly
in the setting of academic medical centers. The American
Medical Student Association launched the PharmFree
Campaign initiative in 2002 to encourage medical students toward evidence-based prescribing and to avoid all
pharmaceutical advertisements and sponsorships (17). A

growing number of professional leaders have called for
similar restrictions for those in settings other than training programs. They are proposing that, despite the
restrictions put in place by industry, professional societies, and government agencies, conflict of interest is
inherent in all educational ventures promoted by the
health care industry (18). For example, several prominent
teaching institutions have taken the step of banning gifts,
lunches, and educational events sponsored by industry
(19).
In addition, and at least in part in response to this
move toward regulation, the Pharmaceutical Research
and Manufacturers of America (PhRMA) has developed
guidelines for the pharmaceutical industrys relationship
with clinicians (13) and for the conduct of clinical trials
and the communication of clinical trial results (14).
These voluntary guidelines took effect in 2002. Similarly,
in 2004 the Advanced Medical Technology Association
(AdvaMed) adopted a code of ethics to guide its members
(medical technology companies) in interacting with
health care professionals. This code of ethics generally
addresses the same issues as the PhRMA guidelines (15).
Finally, guidance has been issued by the federal government. In 2003, the Office of Inspector General (OIG)
at the U.S. Department of Health and Human Services
issued a notice regarding voluntary compliance programs
for pharmaceutical manufacturers. Among the written
policies and procedures that the OIG suggests be
addressed are 1) a code of conduct and 2) potential risks,
including relationships with purchasers, physicians, and
sales agents (ie, gifts, entertainment, personal compensation, education grants, and research funding). The OIG
guidance references and endorses the voluntary PhRMA
guidelines (16).
Recommendations of the American

College of Obstetricians and
Gynecologists Committee on Ethics
is committed to work toward ensuring that its educational mission is evidence based and free from undue bias
from all outside influence. The following are recommended to address the Colleges and Fellows relationships with industry.
Industryphysician interactions can be divided into
five major types, as characterized in the following sections. Ethical implications specific to each type of interaction are discussed. In providing recommendations, the
Committee on Ethics is mindful both of the effort Fellows
have made to meet past recommendations and the challenges in meeting the ideal behaviors outlined. In presenting these paradigms, the Committee wishes to set goals
that will not only eliminate undue influence on Fellows
practice and behavior but also promote continued confidence in the provider and specialty.
COMMITTEE OPINIONS
Product Promotion to Individual Physicians by

Advertising, Personal Communication, and
Provision of Samples
Physicians have an obligation to go beyond the information provided through advertising or other marketing
strategies in selecting the best product for care of the
patient. Substantial evidence exists that even small gifts
influence prescribing practices and thereby have an impact
on patient care (18). The provision of samples similarly
influences prescribing practice (20). To preclude inappropriate influence, the Committee on Ethics recommends
the following:
Physicians have an obligation to seek the most accurate, up-to-date, evidence-based, and balanced sources
of information about new products that they contemplate using. They should not base decisions solely or
primarily on information provided by the products
marketers. Physicians must recognize that promotional items provided by vendors have been carefully produced or promoted to advocate use of their products.
Although the provision of pharmaceutical samples
offers potential benefits to patients, particularly for
those who are uninsured or for whom purchase of
medications otherwise represents a burden, such samples also may influence prescribing behavior inappropriately. Until a means is found to ensure that all
patients have access to medications, physicians may
choose to provide samples or vouchers but should be
aware of these influences. In particular, physicians
should be mindful of providing samples to cover just
a portion of a course of needed treatment, a practice
that may promote patients ongoing use of a particular medication, when other potential alternatives exist.
When vouchers or samples are dispensed, consideration should be given to providing them preferentially
to those patients with a true need and dispensing a
supply sufficient for a full course of therapy.
Providers should understand that gifts tied to promotional information, even small gifts and meals, are
designed to influence provider behavior. Fellows
should be mindful of such intents and influences
when deciding whether to accept gifts, including gifts
of apparently nominal value. Cash gifts should not be
accepted.
Any gifts accepted by an individual physician should
primarily entail a benefit to patients or be related to
the physicians work and should not be of substantial
value. Accordingly, textbooks, study aids, and similar
gifts may be acceptable only if they serve a genuine
educational function.
Donations, Parties, Trips, Services, and
Opportunities for Investment
The health care industry also has promoted its products
to individual physicians and groups of physicians, such as
211
medical specialty societies, by provision of donations,

parties, trips, services, and opportunities for investment.
Such promotional practices, whether directed toward
professional groups or individual physicians, must be
assumed to have as their purpose the creation of attitudes
or practices favorable to the donor. This may result in a
real or perceived conflict of interest for the individual
recipient or organization. Such ethical conflicts can interfere with patient care and may not be in keeping with the
standards of professional conduct to which physicians are
expected to adhere. In this regard, the Committee on
Ethics recommends the following:
Any individual or group should weigh carefully the
risks of ethical conflicts and adverse public opinion
before accepting donations, parties, trips, and services directly from industry.
When the obstetriciangynecologist has a significant
financial interest in or receives anything of substantial
material value, including royalties, from companies in
the health care industry, such as a manufacturer of
pharmaceuticals and medical devices, this information should be disclosed to patients and colleagues
(21). Physicians should not engage in agreements in
which referral of patients to them is contingent on
their use or advocacy of a product.
Physicians should not engage in agreements in which
companies make substantial donations to a third
party (eg, a hospital or charitable organization) that
is contingent on their use or advocacy of a product.
Support of Educational Activities, Awards, and
Development Contracts
The health care industry has promoted its products to
individual physicians and groups, including specialty
societies, hospitals, and medical schools, through the support of educational activities, awards, and development
contracts. Support of educational programs and the provision of awards, grants, and contracts should follow, in
principle, the guidelines of the American Medical
Association (7, 8) and the Accreditation Council for
Continuing Medical Education (12), which are adapted
by the Committee on Ethics as follows:
Subsidies to underwrite the costs of CME conferences or professional meetings can contribute to the
improvement of patient care and, therefore, are permissible. Payments to defray the costs of a conference
should not be accepted directly from the company by
the physicians who are attending the conference.
Funds from a commercial source should be in the
form of an educational grant made payable to the
accredited provider for the support of programs. The
ultimate decision about funding arrangements for
CME activities must be the responsibility of the
accredited provider. It is most desirable if these funds
are allocated from a central repository.
212
Subsidies from industry should not be accepted

directly to pay for the costs of travel, lodging, or other
personal expenses of the physicians who are attending
the conferences or meetings; subsidies should not be
accepted to compensate physicians for their time.
The gift of special funds to permit medical students,
residents, and fellows to attend carefully selected
educational conferences may be permissible as long
as the selection of the students, residents, or fellows
who will receive the funds is made by the academic
or training institution or by the accredited CME
provider with the full concurrence of the academic
or training institution. These funds should be
deposited at a central office within the training institution that could dispense these funds directly to the
designated trainee.
When companies underwrite medical conferences or
lectures other than under their own labels, the physicians responsible for organizing these activities
should be responsible for and control the selection of
content, faculty, educational methods, and materials.
Subsidies of educational activities, including activities linked to meals, should not include direct
promotion or requisite contact with company representatives.
Accredited CME providers are responsible for the
content, quality, and scientific integrity of all CME
activities and materials certified for credit. Commercially supported social events should be separated clearly from CME programs, and social activities
should not compete with, or take precedence over,
the educational events.
Presentations should give a balanced view of therapeutic options. Use of generic names will contribute
to this impartiality. If trade names are used, those of
several companies should be used rather than only
those of a single company.
When commercial exhibits are part of the overall
program, arrangements for these should not influence the planning or interfere with the presentation
of CME activities. Exhibit placement should not be a
condition of support for a CME activity.
Subsidized professional presentations related to pharmaceutical products should avoid commercial advertisements or biased exposure at the same setting.
All financial support for meetings and educational
activities should be clearly disclosed, but physicians
should be mindful that disclosure in itself may not
eliminate the potential for influence or bias.
Industrial Sponsorship of Research
Companies must conduct clinical testing to obtain
approval for the marketing of new products. This involves
collaboration with physicians and clinical institutions
when conducting such work. The Committee on Ethics
recommends the following guidelines for engaging in

industry-sponsored research:
Research trials should be conducted in accordance
with the federal guidelines for the protection of
human participants (22). Approval by the institutional review board of a medical school or hospital
provides adequate ethical and scientific review. If
the project is to be conducted in a private medical
office, investigators must ascertain the nature of
the ethical and scientific review process by the sponsoring corporation. Submission of the project to the
researchers institution usually is required and helpful. If there is any question about the adequacy or
efficacy of this review, investigators should seek independent consultation for research oversight.
Reimbursement to investigators and their institutions for involvement in research, including recruitment of participants, should not exceed reasonable
direct and indirect costs. Investigators may accept
reasonable compensation for consultation or lecturing that follows participation in research.
Once a clinical investigator becomes involved in a
research project for a company or knows that he or
she might become involved, the investigator, as an
individual, cannot ethically buy or sell the companys
stock until the involvement ends and the results of
the research are published or otherwise disseminated
to the public (23).
The following guidelines should govern control over
information gained from research (24):
All obligations of investigators and sponsors
should be contractually defined.
Scientific freedom of independent investigators
(those not employed by the funding organization)
should be preserved.
Principal investigators should be involved in decisions regarding the publication of data from their
trials. Short delays in the dissemination of data
generated by industry-sponsored research are
acceptable to protect a patent or related proprietary interests. Prolonged delays, or suppression of
information harmful to the sponsors interests, are
unethical.
Investigators should control the use of their names
in promotions.
Project funding should not be contingent on
results.
Investigators should disclose their relationships
with industry funders in publications or lectures
based on the research.
Speakers Bureaus, Consulting Services, and
Ghostwriting
Speakers bureaus are a common marketing strategy to
promote a particular product through the use of recog-
COMMITTEE OPINIONS
nized professional leaders as paid spokespersons.

Speakers bureaus are an efficient way to communicate
information about a specific product but are subject to a
high potential for bias and unbalanced information and
conflict of interest. Audiences may not be able to identify
bias when it occurs (18). Physicians who participate in
industry-sponsored speaking should adhere to the following specific ethical guidelines to reduce the risk of
undue influence:
Speakers should fully disclose the extent of their relationship with the sponsoring entity.
Speakers should ensure that the information in their
presentation is accurate, balanced, evidence based,
and free of undue commercial influence.
Speakers should take responsibility for the material
presented and ensure that the material has not been
regulated by the sponsoring corporation.
Speakers should accept only reasonable honoraria
commensurate with the value of their time and reimbursement for travel, lodging, and expenses derived
from predetermined policies.
Speakers should recognize that they may be influenced through their relationship with the sponsoring
corporation.
Consulting with industry on the development of
new medical devices or pharmaceutical agents can play
an important role in the progress of scientific discovery.
It also is appropriate for consultants who provide genuine services to receive reasonable reimbursement for
travel, lodging, and meal expenses, as well as value of
their time. Token consulting or advisory arrangements
cannot be used to justify the compensation of physicians
for their time or their travel, lodging, and other out-ofpocket expenses. It must be recognized, however, that
industry may use consulting arrangements in order to
influence the consultant.
The practice of ghostwriting or unacknowledged
medical writing that may be sponsored by the pharmaceutical or other industry is unacceptable because it is
inherently deceptive and may bias the presentation of
research results. Authors should write and assume responsibility for the content of all publications for which they
receive authorship credit. Ghostwriting, in which a writer
produces content attributed to another, should be distinguished from acknowledged authorship and peer editing,
which may serve important communication functions.
Summary
Support from the pharmaceutical and device industry
continues to provide substantial and potentially valuable
support for physician education. Obstetriciangynecologists relationships with industry should be structured in
a manner that will enhance, rather than detract from,
their obligations to their patients. The guidelines set forth
in this Committee Opinion will contribute to this goal.
213
References
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gift ever just a gift? JAMA 2000;283:37380.
2. Morgan MA, Dana J, Loewenstein G, Zinberg S, Schulkin J.
Interactions of doctors with the pharmaceutical industry.
J Med Ethics 2006;32:55963.
3. Kumar P, Zaugg AM. IMS review: steady but not stellar.
MM&M May 2003. p. 5063. Available at: http://www.
imshealth.com/vgn/images/portal/cit_40000873/42912029
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4. Studdert DM, Mello MM, Brennan TA. Financial conflicts
of interest in physicians relationships with the pharmaceutical industryself-regulation in the shadow of federal
prosecution. N Engl J Med 2004;351:1891900.
5. Katz D, Caplan AL, Merz JF. All gifts large and small: toward
an understanding of the ethics of pharmaceutical industry
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6. Campbell EG, Gruen RL, Mountford J, Miller LG, Cleary
PD, Blumenthal D. A national survey of physicianindustry
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2006-2007 ed. Chicago (IL): AMA; 2006. p. 2126.
8. American Medical Association. Clarification of opinion
8.061 gifts to physicians from industry. In: Code of medical ethics of the American Medical Association: current
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AMA; 2006. p. 21624.
9. Coyle SL. Physician-industry relations. Part 1: individual
physicians. Ethics and Human Rights Committee,
American College of PhysiciansAmerican Society of
Internal Medicine. Ann Intern Med 2002;136:396402.
10. Coyle SL. Physician-industry relations. Part 2: organizational issues. Ethics and Human Rights Committee, American
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11. Accreditation Council for Graduate Medical Education.
Principles to guide the relationship between graduate medical education and industry. Chicago (IL): ACGME; 2002.
Available at:http://www.acgme.org/acWebsite/position
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12. Accreditation Council for Continuing Medical Education. ACCME standards for commercial support.
Standards to ensure the independence of CME activities. Chicago (IL): ACCME; 2004. Available at: http://
www.accme.org/dir_docs/doc_upload/68b2902a-fb7344d1-872580a1504e520c_uploaddocument.pdf. Retrieved
November 8, 2007.
13. Pharmaceutical Research and Manufacturers of America.
Code on interactions with healthcare professionals.
Washington, DC: PhRMA; 2002. Available at: http://www.
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8, 2007.
14. Pharmaceutical Research and Manufacturers of America.
Principles on conduct of clinical trials and communication
of clinical trial results. Washington, DC: PhRMA; 2002.
Available at: http://www.phrma.org/files/Clinical%20 Trials.
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15. Advanced Medical Technology Association. Code of ethics

on interactions with health care professionals. Washington,
DC: AdvaMed; 2003. Available at: http://www.advamed.
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November 8, 2007.
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Office of Inspector General. Fed Regist 2003;68:2373143.
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Chimonas SC, Cohen JJ, et al. Health industry practices that
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Relationships with industry. ACOG Committee Opinion No. 401.
2008;111:799804.
ISSN 1074-861X
COMMITTEE OPINIONS
215

End-of-Life Decision Making*

Committee on Ethics
ABSTRACT: The purpose of this Committee Opinion is to discuss issues related to

end-of-life care, including terms and definitions, ethical principles, legal constructs, physicianpatient communication, and educational opportunities pertinent for specialists in
obstetrics and gynecology. Assumptions about the objectives of carewhich may be
understood differently by the patient and her caregiversinevitably shape perceptions
about appropriate treatment. Because unarticulated commitments to certain goals may
lead to misunderstanding and conflict, the goals of care should be identified through
shared communication and decision making and should be reexamined periodically. A
good opportunity to initiate the discussion of caregiving goals, including end-of-life care,
is during well-patient care. Physicians must be careful not to impose their own conception of benefit or burden on a patient. End-of-life care is particularly challenging for pregnant women, whose autonomy is limited in many states. Many apparent conflicts will be
averted by recognizing the shared interests of the woman and her fetus. When interests
diverge, however, pregnant womens autonomous decisions should be respected.
Obstetricians and gynecologists, including

those in training, care for women throughout
their life span and not infrequently need to
participate in end-of-life decision making.
Tragic accidents occasionally threaten the life
of a pregnant woman and her fetus, and terminal outcomes occur for some patients with
gynecologic cancer. As a result, physicians are
expected to present options and guide
patients as they make decisions in the face
of such events. Life-threatening situations
are never easy to deal with, even for the well
trained. The purpose of this Committee
Opinion is to discuss issues related to endof-life care, including terms and definitions,
ethical principles, legal constructs, physicianpatient communication, and educational opportunities pertinent for specialists
in obstetrics and gynecology.
The Ethical Basis of Medical

Practice

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
The moral foundation of medicine includes

three values central to the healing relationship. These are patient benefit, patient selfdetermination, and the moral and ethical
integrity of the health care professional (1, 2).
*Update of End-of-Life Decision Making in Ethics in
Obstetrics and Gynecology, Second Edition, 2004
Patient Benefit
The obligation to promote the good of the
patient is a basic presumption of medical
caregiving and a defining feature of the physicians ethical responsibility. The ethical principle of beneficence upholds the physicians
duty to seek to promote the patients good,
providing care in which benefits outweigh
burdens or harms. Providing benefit at the
end of life when further medical intervention
may be deemed futile may at first seem challenging, but further consideration suggests
that the principle of beneficence may be
manifested in many dimensions. In some situations, it may be manifested by providing
treatment to improve health or prolong life.
In other situations, it may be exhibited
through the elimination of false hope, avoidance of unwarranted tests and therapies, and
assistance for patients and their families in
reconciling themselves to the limitations of
available medical options and achieving peace
of mind. Indeed, in considering end-of-life
care, benefits are understood only relative to
the goals that the patient and physician hope
to achieve through medical care. At times,
what is beneficent in the patients eyes may
seem to the physician to cause more suffering
or involve the inappropriate use of medical
216
resources. These complicated issues of futility are

addressed further elsewhere (3).
Patient Self-Determination
The inherent value of individual autonomy or self-determination is one of the fundamental principles of democracy and represents the basis for many individual rights
and protections in the United States. In health care, the
value of individual autonomy is affirmed in the ethical
and legal doctrine of informed consent (4, 5). Under this
doctrine, the patient has a right to control what happens
to her body. This means that in nonemergent situations,
no treatment may be given to the patient without her
consent (or, if she lacks decision-making capacity, the
consent of her valid surrogate). Treatment otherwise
given to the patient without her consent may be judged in
some cases to be assault and battery. A patients right to
informed consent or refusal is not contingent on the presence or absence of terminal illness, on the agreement of
family members, or on the approval of physicians or hospital administrators.
In the medical context, physician respect for patient
self-determination consists of an active inclusion of the
patient in decisions regarding her own care. This involves
frank discussion of diagnoses and prognoses (an essential
part of an informed consent); the relative risks and benefits of alternatives, including the option of refusing all
curative treatments; and, based on these discussions, a
mutual identification of the operative goals of care.
Studies suggest that most patients want to know the reality of their conditions and benefit from an honest communication with the physician (6, 7). It is unethical for a
physician to deny patients important information in
order to avoid physicianpatient interactions that are difficult or uncomfortable. Moreover, appropriate regard for
patient autonomy involves respecting the patients considered choice to change therapeutic modalities to better
meet her current goals of care. The patients choice may
be conveyed through an instructional directive or a surrogate with power of attorney (see box). Advance directives
will be discussed in later sections.
Ethical Integrity of the Health Care Professional
Because physicians, like patients, are autonomous agents,
they usually cannot be compelled to violate personal ethical or religious commitments in service to the patient
(8). If physicians have moral reservations about providing
certain forms of caregiving or about stopping treatment,
they should (if appropriate to the circumstances) make
that known at the outset. Physicians must not stand in the
way of patients desires to seek other caregivers and
should, where possible, help guide the transition.
The profession of medicine is guided by its moral
commitment to avoid subjecting a patient to harms that
are greater than potential benefits (the principle of nonmaleficence). On this basis, physicians have a presumptive
obligation not to provide treatments that are untested,
contraindicated, or useless. For this reason, a patients

demand for care that she deems desirable is not sufficient
to impose on providers an absolute obligation to provide
care that is futile or likely to be harmful without offering
corresponding benefit.
Legal Developments That Bear on

End-of-Life Decision Making
In addition to the emotional and medical challenges that
accompany decisions at the end of life, care in such situations may be shaped by statute and legislation. Laws governing such situations vary from state to state. In the
1990s, there were a number of developments in law that
influence end-of-life decision making.
First, in June 1990, in Cruzan v. Director of the
Missouri Dept. of Health, the United States Supreme
Court affirmed that patients have a constitutionally protected right to refuse unwanted medical treatments (9).
The ruling also affirms the states authority to adopt procedural requirements for the withdrawal and withholding
of life-prolonging medical interventions.
A second legal development was the passage of the
federal Patient Self-Determination Act (PSDA), which
went into effect December 1, 1991 (10). The PSDA requires
Medicaid- and Medicare-participating health care institutions to inform all adult patients of their rights to
make decisions concerning medical care, including the
right to accept or refuse medical or surgical treatment and
the right to formulate an advance directive. Under the
PSDA, institutions that receive Medicare or Medicaid
reimbursement are legally required to provide this
information to patients on admission for care or on
enrollment in a health maintenance organization. The
institution must note in the medical record the existence
of an advance directive and must respect these directives
to the fullest extent under state law. Put simply, the aim of
the PSDA is to empower patients to make decisions
regarding their medical care.
Advance Directives
An advance directive is the formal mechanism by which
a patient may express her values regarding her future
health status. It may take the form of a proxy directive or
an instructional directive or both:
Proxy directives, such as the durable power of attorney for health care, designate a surrogate to make
medical decisions on behalf of the patient who is no
longer competent to express her choices. The terms
health care proxy, health care agent, and surrogate
can be used interchangeably. The term surrogate is
used in this Committee Opinion.
Instructional directives, such as living wills, focus on
the types of life-sustaining treatment that a patient
would or would not choose in various clinical circumstances.
COMMITTEE OPINIONS
A third development is found in legislation and legal

rulings concerning the autonomy of the pregnant woman
to refuse treatment. Although courts at times have intervened to impose treatment on a pregnant woman, currently there is general agreement that a pregnant woman
who has decision-making capacity has the same right to
refuse treatment as a nonpregnant woman (11). When a
pregnant woman does not have decision-making capacity, however, legislation frequently limits her ability to
refuse treatment through an advance directive. As of
2006, 31 states had living will statutes that explicitly forbid the withholding or withdrawal of life support either
from all pregnant patients or from pregnant patients
whose fetuses could become, or currently are, viable (12).
Only four states specifically permit a woman to choose to
refuse life-sustaining treatment if she is pregnant. The
other states either have no living will statute or make no
mention of pregnancy. Similar types of restrictions exist
in some states with respect to a surrogate who is appointed to make decisions on behalf of a pregnant woman
(11). Statutes that prohibit pregnant women from exercising their right to determine or refuse current or future
medical treatment are unethical. (An ethical framework
for addressing end-of-life decisions in pregnant women is
discussed later in this Committee Opinion.)
A final development pertains to euthanasia and
physician-assisted suicide. Euthanasia refers to the
administration of drugs with the intention of ending a
patients life at her request (13). Physician-assisted suicide
refers to supplying a patient with drugs or a prescription
for drugs knowing one is enabling a patient to kill herself.
Oregons 1997 Death With Dignity Act, which permits
physicians to write prescriptions for a lethal dosage of
medication to people with a terminal illness, was upheld
January 2006 by the Supreme Court. No other state in the
United States allows such acts, but other countries that
authorize physician-assisted suicide or euthanasia include
Belgium, The Netherlands, and Australia.
In contrast to the previous decisions and legislation,
some have argued that irrespective of the individuals specific circumstances, support should be offered to maintain life. These arguments were made perhaps most
prominently in debate and legislation surrounding the
care of Terry Schiavo. As discussed in the following section, more than perhaps anything else, this case illustrated the advantage of all individuals providing advance,
written instructions concerning their wishes for end-oflife care.
PhysicianPatient Communication and

the Goals of Care
The practice of obstetrics and gynecology involves many
different types of care. These include but are not limited
to preventive care; periodic examinations; family planning; the provision of prenatal and delivery care; medical
and surgical intervention for conditions that threaten a
patients fertility, life, or quality of life; long-term care for
217
patients with chronic illness; and palliative care for

patients whose illnesses offer no chance of cure or remission. The combination of medical and surgical treatment
approaches, as well as the intimate nature of the specialized care offered by obstetriciangynecologists, allows for
a long-term close relationship with many opportunities
for communication with patients. Questions about the
use of specific therapeutic modalities become meaningful
often only in relation to the goals of management for a
particular patient (14). Goals of care in obstetrics and
gynecology include:
Relief of symptoms, pain, and suffering

Achievement of cure or remission
Achievement or prevention of pregnancy
Optimization of pregnancy outcomes
Prevention of illness in a woman or her fetus or both
Maintenance or restoration of biologic function
Performance of palliative surgery or chemotherapy
Maximization of comfort
Achievement or maintenance of a certain quality
of life
Education of the patient about her medical condition
The ultimate goals of care are properly identified
through a process of shared and ongoing communication
and decision making between the patient and physician
(1517). Skilled, honest communication is key in this
process. Explicit discussion about the goals of care is
important for a number of reasons. First, assumptions
about the objectives of care inevitably shape perceptions
about the appropriate course of treatment. Second, these
objectives may be understood differently by the patient
and her caregivers. Third, unarticulated commitments to
certain goals may lead to misunderstanding and conflict.
Finally, the goals of care are fluid and may evolve and
change in response to clinical or other factors.
A comprehensive and ongoing process of communication not only advances patient self-determination but
also is the basis for preventive ethics; that is, the establishment of a moral common ground that may prevent
ethical conflict and crisis (18). The benefits of engaging in
and becoming skilled at such conversations are many and
include optimizing care, diminishing family burden, diminishing stress among members of the health care team, and
utilizing resources more effectively. Inadequate communication, whether from inappropriate training, personal
provider discomfort with death, or differences in personal
or cultural values, has the potential to impair the process of
informed consent and may result in overtreatment, pain
and suffering, undue burden on the patient and family,
misuse of resources, and loss of the peace of mind that can
result from including interdisciplinary care such as hospice
and palliative care departments.
The well-publicized and discussed case of Terri
Schiavo emphasizes the need to discuss these issues with
218
loved ones and also the need to put them in writing. In

this case, the diagnosis of a permanent vegetative state
and the unwritten wishes of the patient contributed to
painful conflicts between the patients husband and her
parents regarding the effort to keep her alive by tube feedings (19). Even if patients do all they can to make their
wishes known, conflicts may still occur.
Shared Decision Making Regarding

the End of Life
The process of decision making regarding the end of life
may take place under two different circumstances. In the
first, decisions are made in an acute situation of present
health crisis; these are immediate choices that determine
actual end-of-life treatment. In the second, decisions are
made that proactively provide for possible future end-oflife situations; these decisions are expressed through
advance directives. In practice, however, the distinction
may not be drawn sharply, and such decision making
often is more appropriately thought of as an ongoing
process or conversation. Because circumstances may
change, goals also may change over time and will need to
be readdressed with all involved parties on a regular basis.
Communication Regarding Immediate Health
Status
An ongoing process of informed consent requires physicians to communicate information regarding the patients
health status and comparative risks and benefits of treatment (including no treatment) so that she or, if she lacks
decision-making capacity, her surrogate may determine
goals of her care. If the patient decides that the maximization of comfort is her desired goal of care, the practitioners responsibilities will focus on palliative strategies, such
as pain relief, attentive and responsive communication
with the patient about her health status, and the facilitation of communication with the patients involved family
and loved ones. These components of care are essential to
the physicians positive therapeutic role and are often the
most valuable services that can be offered. The expression
nothing more can be done is misleading shorthand that
improperly equates care with cure and, in so doing,
ignores the importance of the physicians role in providing comfort to the dying patient (2022).
If the patient or surrogate and physician finally disagree on the goals that should guide care, a clearly defined
process of discussion and consultation should be followed to resolve the disagreement. Examples of a process
are available (3, 23). In many institutions, such disagreements are first addressed by an ethics consultation service
or an ethics committee. By using consultative services to
clarify the cultural, religious, or personal considerations
that shape decision making, the parties may be able to
resolve apparent conflict. The specific details of this
process may vary by institution and locality.
Results of such a consultation may include the transfer of care to another physician. In other circumstances,
the assistance of a palliative care team to bridge the transition to palliative care may be helpful. Some patients who
are near the end of life and who anticipate ever-increasing
pain and suffering may inquire about the alternative of
physician-assisted suicide. It currently is not legal for
physicians to participate in physician-assisted suicide in
states other than Oregon. When a patient inquires about
physician-assisted suicide as a possible option, the physician should explore with her the nature of her fears and
her expectations and should be prepared to offer reassurances regarding palliative care plans for relieving distress
at the end of life. Physicians should be aware that a
request for physician-assisted suicide may be a marker for
treatable depression or inadequately treated pain.
Communication Regarding Future Health
Status: Advance Directives
In many cases, it is the obstetriciangynecologist who not
only acts as the principal physician for female patients but
also has the most contact with them throughout their
lives. For these reasons, the obstetriciangynecologist is in
an ideal position to discuss with the patient her values
and wishes regarding future care and to encourage her to
formulate an advance directive (see box).
A good opportunity to initiate the discussion of
caregiving goals, including end-of-life care, is during
well-patient care, either at the time of the periodic examination or during pregnancy. Because a patients wishes
regarding care might change over time or under different
conditions of illness, these discussions should include
occasional reexamination of values and goals and, if necessary, updating of her advance directives and other documentation. Decision making should be treated as a
process rather than an event.
To facilitate the initiation of these discussions, the
patient history form could contain questions about a
patients execution of an instructional directive and her
designation of a surrogate or next of kin as her medical
proxy. If the patient has an instructional directive or
durable power of attorney or both, they should become
part of her medical record. If the patient does not have an
advance directive, assistance in executing one might be
provided by the social services or nursing staff of a hospital or clinical practice.
Ideally, these discussions serve an educational purpose for both patient and physician. For the physician,
these discussions establish a basis for future care and provide an opportunity for the candid expression of personal values regarding care. For the patient, the discussions
provide the opportunity to learn about advance directives, to formulate and articulate her values regarding the
goals of care, and to understand the compatibility of these
goals with the values of the health care provider.
Although it is the physicians responsibility to educate patients about possible future health status and
rights regarding medical care, it is the responsibility of the
patient to thoughtfully assess her values and goals and to
COMMITTEE OPINIONS
make them clearly known to those involved in her care.

Again, the explicit discussion and continued reevaluation
of caregiving goals provides an optimal mechanism for
shared decision making.
Potential Physician Influence
In the face of end-of-life decision making, physicians
trained to prize interventionist strategies must be especially careful not to impose their own conception of benefit or burden on a patient or to use coercive means to
establish or achieve goals that are not shared by the
patient. The obstetriciangynecologist should recognize
that the harms associated with prolonged attempts at cure
may not be acceptable to some patients. However, neither
the presence of a do not resuscitate order nor specific
directives regarding limitation of other treatments
remove the responsibility for providing palliative care.
Moreover, the physician should not rely on the presence
or absence of a do-not-resuscitate order to make assumptions about the appropriateness of other treatment but
rather should be guided by the explicitly identified goals
of care.
There is considerable evidence that sociocultural and
gender differences between patients and their physicians
may subtly influence the style and content of
physicianpatient communication and the care that
patients receive (2431). Physicians who are aware of
these potential problems can guard against the influence
of bias in judgments concerning patient choices.
Differences in gender and in ethnic, social, religious, and
economic background between patients and physicians
may complicate communication, but they should not
compromise care.
An additional area of potential conflict is research.
The dual role that physicians often assume as research scientists and clinical practitioners can be challenging
because the goals and priorities of science and clinical
practice may be different (32). For example, one should
not overlook the potential conflict that may arise during
a patients end-of-life transition when the primary physician is also a primary investigator for an oncology trial for
which the patient is eligible. Both the researcher and the
primary caregiver should guard against inflating the
patients perception of the therapeutic benefit expected
from participating in clinical trials. Studies have shown
that research participants tend to believe, despite careful
explanation of research protocols, that they will likely
benefit from participation or that the level of actual benefit will be greater than stated in the consent process (33).
A patients decision to participate in research should be
consistent with her end-of-life goals.
Surrogate Decision Making

If the patient who lacks decision-making capacity has not
designated a surrogate, state law may dictate the order in
which relatives should be asked to serve in this role. The
individual selected should be someone who knows the
219
patients values and wishes and will respect them in his or

her role as surrogate decision maker. If there is conflict
regarding the designation of a surrogate, it may be appropriate to seek the advice of an ethics committee or consultant or, possibly, the courts. The benefit of choosing a surrogate is immeasurable because this individual has the
same authority the patient would if she were able to make
decisions. The surrogate has the legal right to all confidential medical information and ideally would be someone trusted and chosen by the patient herself. Proactively
choosing a surrogate allows the opportunity to discuss
pertinent religious or moral beliefs with that individual.
One additional precaution a patient can take to be sure
her wishes are respected is the execution of a living will.
The surrogate decision maker is ethically obligated to
base decisions on the wishes and values of the patient. If
these wishes and values have been explicitly stated, either
in writing or in oral discussion, the surrogate has to interpret and apply them in the current situation. If wishes and
values have not been explicitly stated beforehand, the surrogate has to attempt to extrapolate them from what is
known about the patient. In some cases (for example, a
never-competent patient), the surrogate will have to
decide entirely on the basis of what is in the best interests
of this particular patient.
Pregnant Patients and End-of-Life

Decisions: Preventing Conflict
For the overwhelming majority of pregnant women, the
welfare of the fetus is of the utmost concern. This concern
motivates women to modify their behaviors for months at
a time and to undergo the discomforts and risks of pregnancy and delivery. This maternal interest in fetal welfare
traditionally has been the basis of the fundamental ethical
commitment of obstetriciangynecologists: that they are
responsible for both the pregnant woman and her fetus
and that they must optimize the benefits to both while
minimizing the risks to each.
In recent years, some have advanced the view of the
fetus as patientan ethics framework that highlights
questions about what should be done in cases in which
the pregnant womans decisions about her own health
seem unlikely to optimize fetal well-being. Many of these
apparent conflicts will be averted by recognizing the
interconnectedness of the pregnant woman and fetus
with an approach that emphasizes their shared interests.
For cases in which their interests do diverge, however,
candid discussion of these matters in advance of a situation, conflict, or crisis is important. Pregnant womens
autonomous decisions should be respected, and concerns
about the impact of those decisions on fetal well-being
should be discussed in the context of medical evidence
and understood within the context of the womens values
and social context (11).
Within the context of obstetric care, situations rarely
arise when a dying pregnant woman must decide between
caregiving goals that emphasize palliative management
220
for her own illness or an interventionist strategy, such as

cesarean delivery, for the sake of her fetus. Likewise, she
might be forced to decide between a curative strategy,
such as chemotherapy, for her metastatic breast cancer
and a course that poses less risk to her fetus but offers her
less anticipated benefit. In either case, it is safe to assume
that having been provided with all of the clinical information necessary to make her decision, she regards the
choice as a difficult, possibly excruciating one and one
that she wishes she did not have to make. The patient with
a life-threatening condition identifies treatment goals by
considering her beliefs and values in the context of obligations and concerns for her family, her fetus, and her own
health and life prospects.
The obstetriciangynecologist, as the womans advocate, should attempt to ensure that the wishes of the pregnant patient are followed. Even if the patient is no longer
able to make her own decisions, her previously expressed
wishes and values (whether expressed as an instructional
directive or through the appointment of a surrogate decision maker) should guide the course of treatment, whenever legally possible. When this is not possible, clinicians
should advocate changes in the law (34, 35).
Clinician Education
The need for effective end-of-life education for physicians
in training is obvious, not only for the benefit of patients
but also for physicians, to avoid burnout and to help them
manage anxiety with issues of mortality. In a survey of six
medical schools, only 2253% of fourth-year medical students felt prepared by the end-of-life education they
received (36). A study of 157 first-year internal medicine
residents (interns) identified very little classroom teaching, clinical observation, or clinical experience with endof-life communication and, perhaps as a consequence,
reported low self-perceived comfort and skill in this area
(37). Finally, in a study of general surgeons, 84% reported receiving no education in palliative care in residency,
and 44% indicated that they had not had sufficient continuing medical education on the topic (38).
One particularly beneficial educational example is
that of the Giving Bad News script (39), but also helpful
are courses such as the Healers Art, designed by Rachael
Naomi Remen (40), and techniques such as Narrative
Medicine (41), designed for physicians to remain selfreflective about issues of humane caring and differences
in their own concerns about life and death.
Conclusion
Effective proactive communication between the patient
and the physician is the cornerstone of the therapeutic
relationship. Explicit identification of the operative goals
of care is important for four reasons:
1. Assumptions about the objectives of care inevitably
shape perceptions about the appropriate course of
treatment.
2. These objectives may be understood differently by

the patient and her caregivers.
3. Unarticulated commitments to certain goals may
lead to misunderstanding and conflict.
4. The goals of care may evolve and change in response
to clinical or other factors.
In the course of providing comprehensive care,
obstetriciangynecologists are in an excellent position to
encourage women to formulate advance directives. The
discussion of the advance directive should be regarded as
integral to the ongoing process of communication to be
initiated by the health care provider. Special attention
should be given to the discussion of treatment wishes
with pregnant women facing end-of-life decisions, especially in view of current state restrictions on the application of advance directives during pregnancy.
Sometimes the maximization of comfort is the chosen therapeutic goal. In this case, the care offered by the
physician can continue to benefit the patient in a number
of important ways by providing humane and supportive
care at the end of life.
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COMMITTEE OPINIONS
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31. Uskul AK, Ahmad F. Physician-patient interaction: a gynecology clinic in Turkey. Soc Sci Med 2003;57:20515.
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2008;111:10217.
ISSN 1074-861X
222

Direct-to-Consumer Marketing of Genetic

Testing
Committee on
Genetics
Committee on Ethics
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Marketing of genetic testing, although similar to direct-to-consumer

advertising of prescription drugs, raises additional concerns and considerations. These
include issues of limited knowledge among patients and health care providers of available genetic tests, difficulty in interpretation of genetic testing results, lack of federal
oversight of companies offering genetic testing, and issues of privacy and confidentiality.
Until all of these considerations are addressed, direct or home genetic testing should be
discouraged because of the potential harm of a misinterpreted or inaccurate result.
With the increase in the number of clinical

genetic tests requested by health care
providers, there has been an increase in
direct-to-consumer advertising and offering
of genetic tests, including at-home tests and
those provided by private companies.
Although similar to direct-to-consumer advertising of prescription drugs, marketing of
genetic testing raises additional concerns and
considerations. These include issues of limited knowledge among patients and health
care providers of available genetic tests, difficulty in interpretation of genetic testing
results, lack of federal oversight of companies
offering genetic testing, and issues of privacy
and confidentiality.
All genetic testing, including at-home
tests, should be considered medical testing
because results might have an impact on
future medical care and clinical decision
making. Although some tests have been
marketed as nonmedical, such as paternity
testing and early fetal sex prediction from
maternal blood, these also should be considered medical tests. Decisions based on these
results regarding a pregnancy may cause a
patient to seek further medical treatment or
intervention.
Despite the clear limitations of direct-toconsumer genetic testing, women still use the
service. Physicians should acknowledge that
one factor that might contribute to this trend
is the belief among some patients that adequate privacy safeguards do not exist when
genetic testing is performed in the office.
Physicians should use mechanisms in their

practice environment that would provide the
reassurance that women seek when being tested for gene mutations associated with disease.
Some companies offering directto-consumer testing promote the increased privacy
of a direct test in their marketing efforts.
However, patients are not made aware that
failure to indicate results of genetic testing in
life insurance or disability applications could
be considered fraud. In addition, many laboratories have not indicated their policies on
what is done with the DNA sample after
analysis. To ensure privacy, DNA samples
should be destroyed after the requested test is
performed. Those overseeing procedures for
testing should continue to work to address
patient privacy concerns.
The U.S. Federal Trade Commission, U.S.
Food and Drug Administration, and the
have issued a public message about at-home
genetic tests. They advise consumers to be
skeptical of the claims of the tests that are
offered. Many tests may be of questionable
value. The agencies also advise talking to a
health care practitioner or genetic counselor
before and after testing to help ensure understanding of what the test offers and what the
results of testing reveal. In addition, they
point out that unlike other home-use medical
tests, the U.S. Food and Drug Administration
has not reviewed any of the at-home genetic
tests. Because of this, the validity and accuracy of many of these tests are unknown.
COMMITTEE OPINIONS
All genetic testing should be provided only after

consultation with a qualified health care professional.
For complex testing, this may involve referral to a genetic counselor or a medical geneticist. Appropriate pretest
and posttest counseling should be provided, including a
discussion of the risks, benefits, and limitations of the
testing. It must be recognized that direct-to-consumer
genetic testing will create downstream needs for counseling, support, and care for those identified as carriers of
genes associated with undesired medical conditions. In
many locales, the current health care system is not sufficient to meet those needs. Although some companies
offer genetic counseling, concerns have been raised
regarding a potential conflict of interest when the company providing the testing employs the genetic counselor
because a company advertising directly to consumers
may receive no compensation for counseling alone and is
compensated only if the test is ordered by the consumer.
Until all of these considerations are addressed, direct
and home genetic testing should be discouraged because
of the potential harm of a misinterpreted or inaccurate
result.
Resources
Bianchi DW. At-home fetal DNA gender testing: caveat emptor.
223
Federal Trade Commission (US). At-home genetic tests: a

healthy dose of skepticism may be the best prescription.
Washington, DC: FTC; 2006. Available at: http://www.ftc.gov/
bcp/edu/pubs/consumer/health/hea02.shtm. Retrieved March
10, 2008.
Gollust SE, Wilfond BS, Hull SC. Direct-to-consumer sales of
genetic services on the Internet. Genet Med 2003;5:3327.
Gollust SE, Hull SC, Wilfond BS. Limitations of direct-to-consumer advertising for clinical genetic testing. JAMA 2002;288:
17627.
Roche PA, Annas GJ. DNA testing, banking, and genetic privacy.
N Engl J Med 2006;355:5456.
Wolfberg AJ. Genes on the Webdirect-to-consumer marketing
of genetic testing. N Engl J Med 2006;355:5435.

Direct-to-consumer marketing of genetic testing. ACOG Committee
224

Ethical Issues in Genetic Testing

Committee on Ethics
Committee on
Genetics
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Genetic testing is poised to play an increasing role in the practice of

obstetrics and gynecology. To assure patients of the highest quality of care, physicians
should become familiar with the currently available array of genetic tests and the tests
limitations. Clinicians should be able to identify patients within their practices who are
candidates for genetic testing. Candidates will include patients who are pregnant or considering pregnancy and are at risk for giving birth to affected children as well as gynecology patients who, for example, may have or be predisposed to certain types of cancer.
The purpose of this Committee Opinion is to review some of the ethical issues related
to genetic testing and provide guidelines for the appropriate use of genetic tests by
obstetriciangynecologists. Expert consultation and referral are likely to be needed when
obstetriciangynecologists are confronted with these issues.
Although ethical questions related to genetic

testing have been recognized for some time,
they have gained a greater urgency because of
the rapid advances in the field as a result of
the success of the Human Genome Project.
That projecta 13-year multibillion-dollar
programwas initiated in 1990 to identify
all the estimated 20,00025,000 genes and to
make them accessible for further study. The
project harnessed Americas scientists in a
quest for rapid completion of a high-priority
mission but left a series of ethical challenges
in its wake. When developing the authorizing
legislation for the federally funded Human
Genome Project, Congress recognized that
ethical conundrums would result from the
projects technical successes and included the
need for the development of federally funded
programs to address ethical, legal, and social
issues. Accordingly, the U.S. Department of
Energy and the National Institutes of Health
earmarked portions of their budgets to
examine the ethical, legal, and social issues
surrounding the availability of genetic information.
The purpose of this Committee Opinion
is to review some of the ethical issues related
to genetic testing and provide guidelines for
the appropriate use of genetic tests by obstetriciangynecologists. It is important to note
at the outset, given the increasing complexity
of this field and the quickness with which it
advances, that expert consultation and referral are likely to be needed when obstetriciangynecologists are confronted with many
of the issues detailed in this Committee
Opinion.
The pace at which new information
about genetic diseases is being developed and
disseminated is astounding. Thus, the ethical
obligations of clinicians start with the need
to maintain competence in the face of this
evolving science. Clinicians should be able to
identify patients within their practices who
are candidates for genetic testing. Candidates
will include patients who are pregnant or
considering pregnancy and are at risk for giving birth to affected children as well as gynecology patients who, for example, may have
or be predisposed to certain types of cancer.
If a patient is being evaluated because of
a diagnosis of cancer in a biologic relative
and is found to have genetic susceptibility to
cancer, she should be offered counseling and
follow-up, with referral as appropriate, to
ensure delivery of care consistent with current standards. In fact, genetic screening for
any clinical purpose should be tied to the
availability of intervention, including prenatal diagnosis, counseling, reproductive decision making, lifestyle changes, and enhanced
phenotype screening.
One of the pillars of professionalism is
social justice, which would oblige physicians
COMMITTEE OPINIONS
to promote justice in the health care system, including

the fair distribution of health care resources (1). In the
context of genetic testing, justice would require clinicians
to press for resources, independent of an individuals ability to pay, when they encounter barriers to health care for
their patients who require care as a consequence of genetic testing and diagnosis (1).
Obstetriciangynecologists also are ideally positioned to educate women. When they, or experts in genetics to whom they refer, counsel on genetics, they should
provide accurate information and, if needed, emotional
support for patients burdened by the results or
consequences of genetic diagnoses, be they related to preconception or prenatal care, cancer risks, or other implications for health. Finally, clinicians should familiarize
their patients with steps that can be taken to mitigate
health risks associated with their genetic circumstance
(eg, having a colonoscopy if there is a predisposition to
colon cancer) (2).
It recently has been suggested that each persons
entire genome may be available for use by physicians for
diagnostic and therapeutic purposes in the not-too-distant future (3). Although that might seem like a medical
panacea, the potential risks associated with wide-scale
genetic testing are substantial. Many incidental findings
will come to light, and yet, although those tested may be
tempted to believe otherwise, genetic findings do not
equate directly with either disease or health: one hundred percent accurate identification of such incidental
pathologies will lead to iatrogenic pathology the belief
that genetics completely determines phenotypic outcome
must be informed by an understanding that most genetic
measurements only shift the probability of an outcome,
which often depends on other environmental triggers and
chance (4).
Informed Consent
Genetic Exceptionalism
Before the appropriate process for obtaining consent for
genetic tests is considered, it is necessary to confront
the broader question of whether the consequences of the
results of those tests are substantively different from
the consequences of other medical tests, for which specific consent is not always obtained. Some ethicists argue
against what has been called the exceptionalism of
genetic tests (5). They maintain that many medical tests
have consequences for patients that are similar to those
of genetic tests. For example, there can be discrimination
by insurance companies against individuals either with a
genetic disease or with a disease that is not linked to
any particular gene. Results of nongenetic tests, as
well as genetic tests, can divulge information about family members (eg, tests for sexually transmitted diseases).
Additionally, both genetic and nongenetic tests can provide information about a persons medical future. As
such, some authors have concluded that many genetic test
results may cause stigmatization, family discord and psy-
225
chological distress. Regardless of whether a test is genetic,

when this combination of characteristics is presenttesting should be performed with particular caution and the
highest standards of informed consent and privacy protection should be applied (6).
However, others argue that genetics should be treated as a unique class and be subject to a more rigorous
process for consent. They base their belief on several factors. Genes, they argue, do not merely inform patients
and their health care providers about the diagnosis of an
extant illness. They also foretell the possibility (or in some
cases the certainty) of a future disease, thus allowing perfectly healthy individuals to be subject to discrimination
based on a predisposing gene. The DNA samplewhich
can be viewed as a coded probabilistic medical record
makes genetic privacy unique and differentiates it from
the privacy of medical records (7). Some believe that this
information is even more sensitive given the uncertainties
attached to genetic results (ie, the reliability of tests, the
penetrance of genes, and the unavailability of efficacious
interventions to reduce the consequences of genetic diseases). Additionally, the consequence of being found to
carry a particular gene has resonance not only for the
individual who is tested but also for family members.
Patients should be informed that genetic testing
could reveal that they have, are at risk for, or are a carrier
of a specific disease. The results of testing might have
important consequences or require difficult choices
regarding their current or future health, insurance coverage, career, marriage, or reproductive options.
Role of the ObstetricianGynecologist
In addition to needing to ensure proper consent, the
obstetriciangynecologist who orders genetic tests should
be aware of when it is appropriate to test, which particular
test to order, and what information the test can provide,
the limitations of the test, how to interpret positive and
negative results in light of the patients medical or family
history, and the medical management options available
(8). The health care provider ordering tests has a responsibility to use and interpret those tests correctly or to refer
to someone with relevant expertise. Because completing
all these tasks is particularly difficult when direct-to-consumer marketing of genetic tests is used, that marketing
approach has significant limitations (9). These enterprises receive compensation only if an individual, after counseling, chooses to undergo a test, bringing the standard of
neutral counseling into question and further rendering
the use of a market-driven approach to testing ethically
problematic (10). In the end, the physician plays an
important role in providing adequate, neutral counseling;
ensuring informed consent; and providing follow-up for
genetic tests. Neutral counseling also may be compromised through the use of patient educational materials or
counselors that are provided by a company that might
profit from a patients decision to undergo testing.
Particular caution should be exercised when obtaining consent for collecting genetic material that may be
226
stored and, therefore, can have future clinical or research

applications. The American College of Medical Genetics
(ACMG) recommends that when samples are obtained
for clinical tests, counseling should address the anticipated use of samples, including whether their use will be
restricted for the purpose for which they were collected
and if and when they will be destroyed (11). When samples will be used for research or the development of
diagnostic tests, the ACMG recommends that consent
should include a description of the work (eg, its purposes, limitations, possible outcomes, and methods for
communicating and maintaining confidentiality of
results). There should be a discussion with the research
participant about whether she wishes to give permission
to use her samples without identifiers for other types of
research, and she should be informed of the institutions
policy regarding recontacting participants in the future.
Current and future use of samples for research should
follow state and federal regulations governing protection of human participants in research (12). Two
authors recently suggested that the best consumer
advice, given current law, is that one should not send a
DNA sample to anyone who does not guarantee to
destroy it on completion of the specified test (7).
Others argue for the creation of a repository of samples
donated by genetic altruists to be used for many different types of research (4).
Genetic Testing in Children and Adolescents
Testing of children presents unique issues in counseling
and consent. Although it is most commonly pediatricians or geneticists who are called on to test children for
genetic diseases, obstetricians may be asked to test
already born children of parents who, through the
process of prenatal testing, have been found to be carriers of genetic diseases. In such cases, the physician
should balance the rights of the parents to have information that can optimize the ongoing health care of
their children against the rights of the children to have
their best interests protected. There will be circumstances in which it can be determined that a child is at
risk for an untoward clinical event in the future, but
there may be no information about interventions that
have the potential to reduce the likelihood of that event
or the magnitude of its effect. In that circumstance, the
benefits of testing a child are not always clear (eg, BRCA
testing in a young child).
The American Society of Human Genetics (ASHG)
and ACMG together have suggested, Counseling and
communication with the child and family about genetic
testing should include the following components: 1)
assessment of the significance of the potential benefits
and harms of the test, 2) determination of the decisionmaking capacity of the child, and 3) advocacy on behalf
of the interests of the child (13). These societies highlighted additional points about benefits and burdens
that should be included in counseling, some of which

follow:
Timely medical benefit to the child should be the primary justification for genetic testing in children and
adolescents. If the medical benefits are uncertain or
will be deferred to a later time, this justification for
testing is less compelling.
If the medical or psychosocial benefits of a genetic
test will not accrue until adulthood, as in the case of
carrier status or adult-onset diseases, genetic testing
generally should be deferred. Further consultation
with other genetic services providers, pediatricians,
psychologists, and ethics committees may be appropriate to evaluate these conditions.
Testing should be discouraged when the health care
provider determines that potential harms of genetic
testing in children and adolescents outweigh the
potential benefits. A health care provider has no
obligation to provide a medical service for a child or
adolescent that is not in the best interest of the child
or adolescent.
The ASHG and ACMG concluded, Providers who
receive requests for genetic testing in children must weigh
the interests of children and those of their parents and
families. The provider and the family both should consider the medical, psychosocial, and reproductive issues that
bear on providing the best care for children (8).
Physicians (obstetricians and pediatricians) also have
a responsibility to provide information to patients regarding newborn screening. The primacy of the childs welfare
should animate these discussions as well. More detail
about this issue can be found elsewhere (14).
Prenatal Genetic Testing

Genetic testing of the fetus offers both opportunities and
ethical challenges. Preconception and prenatal genetic
screening and testing are recommended for a limited
number of severe child-onset diseases because such
screening and testing provides individuals with the
chance to pursue assisted reproductive technology in
order to avoid conception of an affected child, to consider termination of a pregnancy, or to prepare for the birth
of a chronically ill child. With advancing genetic technology, however, physicians may increasingly face requests
for testing of fetuses for less severe child-onset conditions,
adult-onset conditions, or genetically linked traits.
Principles regarding testing of children provide some
guidance for when prenatal testing might be appropriate
but this decision is significantly complicated by the various purposes that prenatal testing can have: to detect a
fetal condition for pregnancy termination, to allow
patients to prepare for the birth and care of a potentially
affected child, or, more rarely, to detect and treat a fetal
condition in utero. Furthermore, many times, a womans
intentions regarding pregnancy termination evolve as
COMMITTEE OPINIONS
genetic information becomes available to her. Therefore,

testing the fetus for adult-onset disorders with no known
therapeutic or preventive treatment (save prevention by
pregnancy termination) should raise caution in a way
similar to the manner in which testing of children can. In
pregnancies likely to be carried to term, consideration
should be given to whether, as in the case of testing children, the decision to test should be reserved for the child
to make upon reaching adulthood. However, consideration also should be given to personal preference, that is,
the interests individuals may have in terminating a pregnancy that may result in a life (such as life that will be
affected by Huntington chorea) that they feel morally
obliged or prefer not to bring into the world. Because
these often are wrenching decisions for parents, referral to
parent support networks (eg, National Down Syndrome
Society, if that is the diagnosis of concern), counselors,
social workers, or clergy may provide additional information and support (15).
Genetic Data and the Family

In a large number of instances, when patients receive the
results of genetic tests, they are party to information that
directly concerns their biologic relatives as well. This
familial quality of genetic information raises ethical
quandaries for physicians, particularly related to their
duty of confidentiality. In these circumstances, some have
posited an ethical tension between obligations the clinician has to protect the confidentiality of the individual
who has consented to a test on the one hand and a physicians duty to protect the health of a different individual
on the other hand. For example, a woman who discovers
that she is a carrier of an X-linked recessive disease during the workup of an affected son might choose not to tell
her pregnant sister about her carrier status because she
does not believe in abortion and fears that her sister
might consider an abortion (16). In another example, a
woman identified as a carrier of a gene predisposing individuals to cancer might not wish to share the information
with relatives, some of whom might even be patients of
the same physician who tested her, because such sharing
would disclose her own status as a carrier.
In both the previously cited cases, information
obtained with the consent of one individual could assist
in the management of another. However, medical ethics
as reflected in American Medical Association (AMA)
policies recognizes a physicians duty to safeguard patient
confidences in such cases (with a few notable exceptions,
often mandated by lawfor example, communicable diseases and gunshot and knife wounds should be reported
as required by applicable statutes or ordinances) (17).
How assiduously that confidentiality needs to be guarded
is the subject of some debate. Some have argued that
genetic information should be subject to stringent safeguards because, even though there may be uncertainty
about the ultimate biologic consequence of a given gene,
the social consequences (discrimination and stigmatiza-
227
tion) can be substantial (18). The AMAs Council on

Ethical and Judicial Affairs has argued that physicians do
indeed have an obligation to pay almost unlimited obeisance to a patients confidentiality save only for certain
circumstances which are ethically and legally justified
because of overriding social considerations (19).
Conversely, there are those who argue against the
withholding of important information from potentially
affected family members (20). Those who subscribe to
this belief feel that when information applies to family as
much as to the proband, an obligation arises that extends
from the physician to those potentially affected family
members but no further. This view is consistent with
court rulings in three states, which have held that a physician owes a duty to the patients potentially affected family members (2124). Two of these rulings addressed the
question of how physicians must fulfill this duty and
reached different conclusions. In one case, the court held
that the physician can discharge the duty by informing
the patient of the risk and is not required to inform the
patients child (22). In another case, the court did not
decide how the physician could satisfy the duty to warn,
other than requiring that reasonable steps be taken to
assure that the information reaches those likely to be
affected or is made available for their benefit (23). As
these alternate decisions illustrate, the legal limits of privacy are evolving, emphasizing the need for patient communication and case-by-case evaluation.
Recommendations of Other Organizations
Organizations that promulgate guidelines for genetic care
and counseling also have proposed different approaches
to the disclosure of genetic information. The ASHG tailors its recommendations to the magnitude and immediacy of risk faced by kindred (25), encouraging voluntary
disclosure by the proband but also articulating circumstances in which the probands refusal to do so should not
preclude disclosure by the health care provider. According
to the ASHG, disclosure is acceptable if the harm is likely to occur, and is serious, immediate and foreseeable. It
adds that the at-risk relative must be identifiable and that
there must be some extant intervention that can have a
salutary effect on the course of the genetic disease. In
summary, the harm from failing to disclose should outweigh the risk from disclosure. Although this suggestion
to disclose seems unequivocal, it also posits circumstances
for its exercise that are highly unlikely at the current time
(ie, very few genetic diagnoses pose an immediate risk, let
alone ones that can be substantively modified with an
intervention [25]).
The Presidents Commission for the Study of Ethical
Problems in Medicine and Biomedical and Behavioral
Research also suggested circumstances in which a health
care provider should disclose information in the absence
of the probands permission to do so (26). The commission indicated that disclosure is required when four conditions are present: 1) efforts to elicit voluntary disclosure
228
by the proband have failed, 2) there is a high probability

that harm will occur if disclosure is not made, and intervention can avert that harm, 3) the harm would be serious, and 4) efforts are made to limit disclosed information to genetic information needed for diagnosis and
treatment. Although the commission did not cite a
requirement for an immediate risk, the requirements for a
high probability of harm and for the availability of an
efficacious intervention make it likely that adherence to
these guidelines rarely will result in cases in which a
patients rights of confidentiality are overridden in order
to inform relatives at risk.
Role of the ObstetricianGynecologist
The best way for the obstetriciangynecologist to avoid
the challenging choice between involuntary disclosure and
being passive in the face of risks to kindred is to anticipate
the issue and raise it at the first genetic counseling session.
At that session, the patient needs to be educated about the
implications of findings for relatives and why voluntary
disclosure would in many circumstances be encouraged
(as well as the possibility that relatives might prefer not to
know the results). Some bioethicists have even suggested
that these sessions should be used as an opportunity for
clinicians to articulate the circumstances under which they
would consider disclosure obligatory, thus allowing
patients to seek care elsewhere if they found the conditions
for testing unacceptable (Macklin has referred to this as
the genetic Miranda warning) (27). Similarly, even if the
health care provider would not disclose without consent
under any circumstance, the initial counseling session
could allow the health care provider to refer the patient
elsewhere if they find they have an irreconcilable difference or have an objection of conscience in expectations
about disclosure. Physicians also should make themselves
available to assist patients at the time of disclosure if that
will help assuage their patients concerns.
A particularly thorny issue related to the ownership
of genetic information might be results that bear on
paternity. It is possible that prenatal assessments and family testing might reveal that the husband, partner, or other
putative father is not the biologic father. In 1994, the
Committee on Assessing Genetic Risks of the Institute of
Medicine recommended that in such situations the health
care provider should inform a woman but should not disclose this information to her partner (28). The Institute of
Medicines reason for withholding such information was
that genetic testing should not be used in ways that disrupt families. Another reason may be that the physicianpatient relationship exists solely with the woman.
Others have disagreed with the Institute of Medicines
recommendation (29). In some cases, it is not merely a
matter of acting to protect families. For example, suppose
a child is born with a disease that is caused by an autosomal recessive gene, and the husband does not carry the
deleterious gene because he is not actually the father. If
the physician were to maintain the charade of paternity,
then the counseling given to both parents (ie, there is one

chance in four that each subsequent child will have the
same disease) would be false and might lead the husband
to argue against more children or for unnecessary amniocenteses in all future pregnancies, or inappropriately lead
to concern for others in his family.
Other circumstances exist in which the interests of a
pregnant woman and family members might diverge. For
example, if the husbands father has Huntington chorea
(an autosomal dominant trait), the pregnant woman
might wish to test the fetus for the gene. If the father did
not want to know his own status, a conflict would arise,
pitting her right to know about her fetus against his right
not to know about himself. Another example of conflict
would be if problems arose during diagnostic linkage
studies for prenatal or preclinical diagnosis in a family
and some family members did not want to participate in
the testing (eg, testing for thalassemia). It might then be
impossible to make a diagnosis in the index case. Both
ethical and legal precedents, however, argue that individuals cannot be forced to have such testing.
Genetic Data and Insurers and

Employers
Concerns about access to health and life insurance in the
face of the discovery of a deleterious or predisposing gene
is one of the most nettlesome issues facing health care
providers who wish to use genetic testing to improve the
health of their patients. In some ways, the importance of
this issue is more pronounced in the United States
because of the manner in which health care coverage is
obtained. In countries with universal health care, individuals with the diagnosis of a predisposing gene need not
fear the loss of access to health insurance.
In recognition of concerns related to genetic testing,
in 1995, the Equal Employment Opportunity Commission issued guidelines stating that individuals who
thought they had been discriminated against by an
employer because of predictive genetic testing had the
right to sue that employer. Additionally, the Health
Insurance Portability and Accountability Act (HIPAA),
enacted in 1996, prevented insurance companies from
denying health care based on predictive testing for individuals transferring from one plan to another (30).
Physicians should advocate for patients ability to obtain
health or life insurance uncompromised by the results of
any genetic tests they might undergo.
Although there is scant evidence of widespread
genetic discrimination, there is clear evidence that fear of
that discrimination can drive patients away from needed
testing or from participation in research and also may
influence physicians uses of genetic tests (31). In commenting on insurance and discrimination and considering needed protections and legislation, ACMG makes the
following points: legislation must not impede the ability
of individuals to maximize use of genetic information in
their health care and employment decision making, and it
COMMITTEE OPINIONS
must not limit the access of health care providers to

genetic information needed to ensure that the care provided is beneficial and specific to the needs of the individual. Furthermore, the privacy of genetic information
must be adequately protected. Protection against unfair
discrimination on the basis of genetic risk for disease is
achieved only by strategies that restrict use of genetic
information in enrollment and rate-setting. Protected
genetic information must include information based on
evaluation, testing, and family histories of individuals and
their family members (32). Finally, as discussed before, it
must be recognized that the confidentiality of these data
has become difficult to guarantee in this era of electronic
medical records.
Genetics and Assisted Reproductive

Technology
There are at least two issues that relate to the intersection
of genetics and assisted reproductive technology (ART).
In the first instance, there is the need to consider whether
all individuals, regardless of genotype, should have access
to ART using their own gametes. In the past, individuals
who were infected with deleterious viruses that have the
potential to be passed to their children (eg, human
immunodeficiency virus) were denied access to ART, in
part because, before the advent of a variety of interventions, as many as one in four of their offspring would
acquire an ultimately fatal infection, a risk similar to that
if both parents are carriers for a serious autosomal recessive disease. Others have argued, however, that procreative liberty should enjoy presumptive primacy when
conflicts about its exercise arise because . . . [it] is central
to personal identity, to dignity and to the meaning of
ones life (33). Such principles would support allowing
prospective parents to be arbiters of the level of risk to
which a child could be exposed.
Second is the question of the extent to which preimplantation genetics should be used in pursuit of the
genetically ideal child. The American College of
Obstetricians and Gynecologists (ACOG) already opposes all forms of sex selection not related to the diagnosis of
sex-linked genetic conditions (34). In the near future,
other potentially controversial genetic manipulations
may be available. Complex genetic systems such as cognition and aging soon may be determinable and may be
constituents of potentially desirable characteristics, such
as intelligence or longevity. They could, therefore, be used
or misused as parameters for prenatal diagnosis (35).
Some have argued for a permissive approach, allowing
parents to choose from a menu of possible children the
one with the chance for the best life. That approach
would allow selection for both disease-related genes (eg,
eliminating carriers of BRCA genes) and nondisease
genes even if this maintains or increases social inequality (36). One author has referred to this as procreative
beneficence, defining it as couples selecting, from the
possible children they could have, the child who is expect-
229
ed to have the best life, or at least as good a life as the

others, based on the relevant, available information (36).
Conversely, in the United Kingdom, strict limits are set on
the use of prenatal genetic diagnosis, and clinics must
apply for a license for every new disease they want to
include in screening. However, even in that country, the
list of allowable preimplantation genetic diagnosis tests
has been expanded recently to include susceptibilities for
certain cancers (37, 38).
Parents requests to select a certain genetic trait may
pose even greater challenges for reproductive endocrinologists and embryologists when parents choices seem to
be antithetical to the best interests of the future child. For
example, deaf parents may prefer to select for an embryo
that will yield a child who will also be deaf. Couples who
have short stature due to skeletal dysplasia might feel they
would prefer to have a child of similar stature. The technical ability to provide these choices is not far from reality, but the ethical roadmap that will offer direction to
physicians is not as clearly laid out.
Conclusions
Genetic testing is poised to play a greater and greater role
in the practice of obstetrics and gynecology. To assure
patients of the highest quality of care, physicians should be
familiar with the currently available array of genetic tests,
as well as with their limitations. They also should be aware
of the untoward consequences their patients might sustain
because of a genetic diagnosis. The physician should work
to minimize those consequences. Genetic information is
unique in being shared by a family. Physicians should
inform their patients of that fact and help them to prepare
for dealing with their results, including considering disclosure to their biologic family. If the genetic information
could potentially benefit family members (eg, allow them
to improve their own prognosis), physicians should guide
their patients toward voluntary disclosure while assiduously guarding their right to confidentiality.
Recommendations
The ACOG Committees on Ethics and Genetics recommend the following guidelines:
1. Clinicians should be able to identify patients within
their practices who are candidates for genetic testing
and should maintain competence in the face of
increasing genetic knowledge.
2. Obstetriciangynecologists should recognize that
geneticists and genetic counselors are an important
part of the health care team and should consult with
them and refer as needed.
3. Discussions with patients about the importance of
genetic information for their kindred, as well as a
recommendation that information be shared with
potentially affected family members as appropriate,
should be a standard part of genetic counseling.
230
4. Obstetriciangynecologists should be aware that

genetic information has the potential to lead to discrimination in the workplace and to affect an individuals insurability adversely. In addition to including
this information in counseling materials, physicians
should recognize that their obligation to professionalism includes a mandate to prevent discrimination.
Steps that physicians can take to fulfill this obligation
could include, among others, advocacy for legislation
to ban genetic discrimination.
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medical ethics of the American Medical Association: current opinions with annotations. 2006-2007 ed. Chicago
(IL): AMA; 2006. p. 13650.
20. Wachbroit R. Rethinking medical confidentiality: the impact
of genetics. Suffolk Univ Law Rev 1993;27:1391410.
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(1996).
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Hum Genet 1998;62:47483.
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Screening and counseling for genetic conditions: a report
on the ethical, social, and legal implications of genetic
screening, counseling, and education programs.
Washington, DC: U.S. Government Printing Office; 1983.
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ethics as guides. New York (NY): Oxford University Press;
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Academy Press; 1994.
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30. Fulda KG, Lykens K. Ethical issues in predictive genetic testing: a public health perspective. J Med Ethics 2006;32:1437.
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unfair discrimination based on genetic disease risk: a position statement of the American College of Medical
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COMMITTEE OPINIONS
34. Sex selection. ACOG Committee Opinion No. 360. American College of Obstetricians and Gynecologists. Obstet
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35. Henn W. Consumerism in prenatal diagnosis: a challenge
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the best children. Bioethics 2001;15:41326.
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decision on the use of PGD for lower penetrance, later onset
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232

(Replaces No. 294, May 2004)
At-Risk Drinking and Illicit Drug Use:

Ethical Issues in Obstetric and Gynecologic
Practice
Committee on Ethics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Drug and alcohol abuse is a major health problem for American women
regardless of their socioeconomic status, race, ethnicity, and age. It is costly to individuals and to society. Obstetriciangynecologists have an ethical obligation to learn and use
a protocol for universal screening questions, brief intervention, and referral to treatment
in order to provide patients and their families with medical care that is state-of-the-art,
comprehensive, and effective. In this Committee Opinion, the American College of
Obstetricians and Gynecologists Committee on Ethics proposes an ethical rationale for
this protocol in both obstetric and gynecologic practice, offers a practical aid for incorporating such care, and provides guidelines for resolving common ethical dilemmas related
to drug and alcohol use that arise in the clinical setting.
Drug and alcohol abuse is a major health

problem for American women regardless of
their socioeconomic status, race, ethnicity,
and age. It is costly to individuals and to society. Among 1825-year-old women, 34%
binge drink and 10% are heavy drinkers.
These rates are lower among women aged 26
years or older (12.8% binge drink and 2.4%
are heavy drinkers), but 6.3% of females aged
12 years or older have been classified as
dependent on alcohol or illegal drugs (1).
Heavy drinking (five or more drinks on one
occasion on five or more days in the last 30
days) carries a higher risk of cardiac and
hepatic complications for women than men.
The alcohol-associated mortality rate is
50100 times higher, and there is an
increased burden of mental and physical disability (2). Among pregnant women aged
1544 years, 11.8% admit to drinking some
alcohol during the previous month (1),
which may put the fetus at risk for fetal alcohol syndrome (FAS), the leading cause of
mental retardation in the United States (3),
and 0.7% reported heavy drinking (1).
Maternal alcoholism is one of the leading
preventable causes of fetal neurodevelopmental disorders (4). The economic costs of
FAS for 2003 are estimated at $5.4 billion.
Each case prevented is predicted to save

$860,000 in lifetime direct and indirect costs
(5). Illicit drug use has major physical and
mental health consequences and is associated
with increased rates of sexually transmitted
infections in women, including hepatitis and
human immunodeficiency virus (HIV), as
well as depression, domestic violence, poverty, and significant prenatal and neonatal
complications (6, 7). Overall, 10% of nonpregnant women and 4% of pregnant
women report illicit drug use, but among
pregnant women aged 1517 years, the rate
of use is 15.5% (8). Drug abuse costs are estimated at more than $180 billion yearly,
including $605 million associated with health
care costs for drug-exposed newborns (9).
As a result of intensive research in addiction over the past decade, evidence-based
recommendations have been consolidated
into a protocol for universal screening questions, brief intervention, and referral to treatment (10). The abstinence rate after drug
abuse treatment (the treatment success rate)
is now comparable to the level of medication
compliance achieved in diabetes, hypertension, or other chronic illnesses (11). Brief
physician advice has been shown unequivocally to be both powerful and feasible in a
COMMITTEE OPINIONS
clinical office setting (10, 12, 13). The American Medical

Association has endorsed universal screening (14), and
health services researchers have determined that treatment saves $7 for every dollar spent (15). For these reasons, the American College of Obstetricians and
Gynecologists (ACOG) collaborated with the Physician
Leadership on National Drug Policy at Brown University
to produce a slidelecture presentation that addresses the
identification and treatment of drug abuse (16). The presentation was distributed to obstetricgynecologic clerkship and residency program directors and is available at
www.acog.org.
Physicians have been slow to implement universal
screening, and rates of detection and referral to treatment
among nonpregnant women remain very low (17).
Studies using simulated patients have demonstrated that
women are less likely than men to be screened or referred
(18, 19). Physicians lack accurate knowledge about physiology (ie, the equivalency of 1.5 oz of distilled spirits, 12 oz
of beer or wine cooler, and 5 oz of wine), risk factors, and
sex differences in problem presentation and treatment
response (20). These knowledge gaps are compounded by
state laws designed to criminalize drug use during pregnancy, by womens fears that they might lose custody of
their children, and by the social stigma experienced by
women who abuse alcohol or use illicit drugs (21, 22). In
one study, for example, the physicians surveyed defined
light drinking as an average of 1.2 drinks per day, an
amount that exceeds the National Institute on Alcohol
Abuse and Alcoholisms (NIAAA) guidelines for at-risk
drinking for women (23). Furthermore, communicating
about difficult issues takes time, requires skills, and is
poorly reimbursed by procedure-oriented insurance coverage. Physicians are concerned about the consequences of
legally mandated reporting, they lack familiarity with
treatment resources, and they do not have the extensive
time required to make an appropriate referral (11). These
are all problems that must be solved in order to provide
medically appropriate and ethically necessary care to
women who engage in at-risk drinking or use illicit drugs.
Many physicians are understandably reluctant to take
on a new responsibility in the context of time constraints
and the already intense demands of practice (24), but
there are practical measures that can be taken to make
screening and brief intervention feasible for many, if not
all, patients. Universal screening can be accomplished by
adding a few questions to a standard intake form (see
box Substance Abuse Screening). In an office practice,
1 in 20 patients will require further intervention (25, 26).
Intervention for these patients can be started effectively in
5 minutes, as demonstrated in a busy academic emergency
department setting (27). Referrals can be provided as a
handout, with a nurse or office assistant available to help
the patient make contact with treatment if desired.
Because more women than men are hidden drinkers, and
many see the obstetrician or gynecologist as their principle source of care, the opportunity to screen and inter-
233
vene, with benefits to women, their children, and society,

are too great to be missed. In recognition of the importance of this activity, Current Procedural Terminology
and Healthcare Common Procedure Coding System
(Medicare) codes have been established for screening,
brief intervention, and referral performed by a physician
or by an educator under the physicians direction. Further,
the Centers for Medicare & Medicaid Services and many
non-Medicare payers provide coverage for these services.
Substance abuse presents complex ethical issues and
challenges. This Committee Opinion proposes an ethical
rationale for universal screening questions, brief intervention, and referral to treatment in both obstetric and
gynecologic practice, offers a practical aid for incorporating such care (see box BNI-ART Institute Intervention
Algorithm), and provides guidelines for resolving common ethical dilemmas that arise in the clinical setting.
The Ethical Rationale for Universal

Screening Questions, Brief
Intervention, and Referral to
Treatment
Support for universal screening questions, brief intervention, and referral to treatment is derived from four basic
principles of ethics. These principles are 1) beneficence,
2) nonmaleficence, 3) justice, and 4) respect for autonomy.
Beneficence
Therapeutic intent, or beneficence, is the foundation of
medical knowledge, training, and practice. Experts at the
NIAAA and the National Institute on Drug Abuse confirm that addiction is not primarily a moral weakness, as
it has been viewed in the past, but a brain disease that
should be included in a review of systems just like any
other biologic disease process (28). A medical diagnosis of
addiction requires medical intervention in the same manner that a diagnosis of diabetes requires nutritional counseling or therapeutic agents or both. Positive behavior
change arises from the trust implicit in the physician
patient relationship, the respect that patients have for
physicians knowledge, and the ability of physicians to
help patients see the links between substance use behaviors and real physical consequences. Brief physician
advice has been shown to be as effective as conventional
treatment for substance abuse and can produce dramatic
reductions in drinking and drug use, improved health status, and decreased costs to society (10, 13, 15, 17, 2931).
The Center for Substance Abuse Prevention has now
implemented more than 147 projects for pregnant and
postpartum women and their children (32), and there are
several different successful models for prevention and
treatment for women and their families: AR-Cares (34),
Choices (35), SafePort (36), Early Start (37), and the Mom/
Kid Trial (38).
Given this capacity for dramatic improvement in
health status, physicians have an obligation to be therapeuticin this case to learn the techniques of screening
234
Substance Abuse Screening

T-ACE
T
Tolerance: How many drinks does it take to make you
feel high? More than 2 drinks is a positive response
score 2 points.
A
Have people Annoyed you by criticizing your drinking?
If Yesscore 1 point.
C
Have you ever felt you ought to Cut down on your drinking? If Yesscore 1 point.
E
Eye opener: Have you ever had a drink first thing in the
morning to steady your nerves or get rid of a hangover?
If Yesscore 1 point.
A total score of 2 or more points indicates a positive screen
for pregnancy risk drinking.
Reprinted from the American Journal of Obstetrics & Gynecology,
Vol 160, Sokol RJ, Martier SS, Ager JW, The T-ACE questions: practical prenatal detection of risk drinking, 8638; discussion 86870,
Copyright 1989, with permission from Elsevier.
TWEAK
T
Tolerance: How many drinks can you hold? If 6 or more
drinks, score 2 points.
W Have close friends or relatives Worried or complained
about your drinking in the past year? If Yes 2 points.
E
Eye opener: Do you sometimes take a drink in the morning when you get up? If Yes 1 point.
A
Amnesia: Has a friend or family member ever told you
about things you said or did while you were drinking
that you could not remember? If Yes 1 point.
K(C) Do you sometimes feel the need to Cut down on your
drinking? If Yes 1 point.
and brief interventionand to inform themselves as they

would if a new test or therapy were developed for any
other recognized disease entity. The practice of universal
screening questions, brief intervention, and referral to
treatment falls well within the purview of the obstetriciangynecologists role as a provider of primary care to
women and has potential for major impact on recognized
obstetric and gynecologic outcomes. Furthermore, if the
topic is raised respectfully, the physicianpatient relationship may be substantially enhanced, even if no substantive changes in lifestyle are achieved immediately.
Therapy is called patient care because both physicians
and patients recognize and value the commitment of the
medical profession to engage in a nurturing relationship
in the course of providing carefully selected therapeutic
modalities. Nurturance of healthy behaviors through universal screening questions, brief intervention, and referral
to treatment is, thus, part of the traditional healing role
and an appropriate focus for the obstetriciangynecologists role as a primary care provider.
The TWEAK is used to screen for pregnant at-risk drinking,

defined here as the consumption of 1 oz or more of alcohol
per day while pregnant. A total score of 2 points or more indicates a positive screen for pregnancy risk drinking.
Adapted from Russell M. New assessment tools for risk drinking
during pregnancy: T-ACE, TWEAK, and others. Alcohol Health Res
World 1994;18:5561.
NIAAA Questionnaire
Do you drink?
Do you use drugs?
On average, how many days per week do you drink alcohol
(beer, wine, liquor)?
On a typical day when you drink, how many drinks do you
have?
Positive score: >14 drinks per week for men and >7 drinks
per week for women
What is the maximum number of drinks you had on any given
occasion during the past month?
Positive score: >4 for men and >3 for women
National Institute on Alcohol Abuse and Alcoholism. Helping
patients who drink too much: a clinicians guide. Updated 2005 ed.
NIH Publication No. 07-3769. Bethesda (MD): NIAAA; 2007. Available
at: http://pubs.niaaa.nih.gov/publications/Practitioner/CliniciansGuide
2005/guide.pdf. Retrieved January 23, 2008.
Nonmaleficence
The obligation to do no harm, or nonmaleficence, also
applies to universal screening questions, brief intervention, and referral to treatment. Medical care can be compromised if physicians are unaware of a patients alcohol
or drug abuse and, thus, miss related diagnoses or medication interactions with alcohol or illegal substances.
If the problem is not identified, major health risks, such
as HIV exposure and depression, also may be missed.
These are examples of harms that may occur as a result
of omission (nondetection of a serious problem). Furthermore, patients may be harmed when substance abuse
is treated by a physician as a moral rather than medical
issue (38). Women who abuse alcohol or use illicit drugs
are more likely than men to be stigmatized and labeled
as hopeless (39). In particular, physicians should avoid
using humiliation as a tool to force change because
such behavior is ethically inappropriate, engenders resistance, and may act as a barrier to successful treatment
and recovery.
COMMITTEE OPINIONS
235
BNI-ART Institute Intervention Algorithm

The BNI-ART Institute (Brief Negotiated Interview and Active Referral to Treatment) is a program of Boston University School
of Public Health and the Youth Alcohol Prevention Center in collaboration with Boston Medical Center. Among its tools is a twosided card that summarizes the process of a brief intervention and referral for treatment.
Front of Card
BNI STEPS
1. Raise subject and ask permission
2. Provide feedback
Review screen
For alcohol
Show NIAAA guidelines & norms
Make connection
(no arguing)
3. Enhance motivation
Explore Pros and Cons
Use reflective listening
Readiness to change
Reinforce positives
Develop discrepancy between ideal and
present self
4. Negotiate & advise
Negotiate goal
Benefits of change
Reinforce resilience/resources
Summarize
Provide handouts
DIALOGUE/PROCEDURES
Would you mind taking a few minutes to talk with me confidentially
about your use of [X]? <<PAUSE and LISTEN>>
Before we start, could you tell me a little about your goals for yourselfWhats important to you?
From what I understand, you are using [insert screening data]
We know that drinking above certain levels, smoking and/or use
of illicit drugs can cause problems, such as [insert medical info].
These are the upper limits of low risk drinking for your age and sex.
By low risk we mean you would be less likely to experience illness
or injury if you stay within the guidelines.
If there is a possible connection between use of [X] and todays
medical problem, ask, What connection (if any) do you see between
your use of [X] and this visit today?
If patient does not see connection: make one using specific
medical information
Ask pros and cons
Help me to understand what you enjoy about [X]? <<PAUSE AND
LISTEN>>
Now tell me what you enjoy less about [X] or regret about your use
of [X] <<PAUSE AND LISTEN>>
On the one hand you said
<<RESTATE PROS>>
On the other hand you said
<<RESTATE CONS>>
So tell me, where does this leave you? [show readiness ruler]
On a scale from 1-10, how ready are you to change any aspect of
your use of [X]?
Ask: Why did you choose that number and not a lower one like a 1
or a 2? Other reasons for change?
Ask: How does this fit with where you see yourself in the future?
Whats the next step?
What do you think you can do to stay healthy and safe?
If you make these changes what do you think might happen?
What have you succeeded in changing in the past? How?
Could you use these methods to help you with the challenges
of changing?
This is what Ive heard you sayHeres an action plan I would
like you to fill out, reinforcing your new goals. This is really an
agreement between you and yourself.
Provide agreement and information sheet
Thank patient for his/her time.
Boston University School of Public Health. BNI-ART Institute intervention algorithm. Available at:
http://www.ed.bmc.org/sbirt/docs/aligo_adult.pdf. Retrieved January 23, 2008.
(continued)
236
BNI-ART Institute Intervention Algorithm (continued)

Back of Card
READINESS RULER
On a scale of 1 to 10, how ready are you to make any changes?

NOT READY
|
1
|
2
VERY READY
|
3
|
4
|
5
|
6
|
7
|
8
|
9
|
10
Source: BNI-ART Institute, Boston University School of Public Health
Justice
The ethical principle of justice governs access to care and
fair distribution of resources. Elimination of health disparities and promotion of quality care for all are at the
top of the list of goals for Healthy People 2010, the nations
health agenda. Injustice may result from a variety of
sources.
Physicians may fail to apply principles of universal
screening. When women are less likely to be screened or
referred for treatment, their burden of disability is
increased and health status decreased. The principle of
justice requires that screening questions related to alcohol
and drug use should be asked equally of men and women,
regardless of race or economic status. It also requires that
women be screened with tests such as TWEAK, T-ACE, or
the NIAAA quantity and frequency questions that are
more accurate in detecting womens patterns of substance
abuse, which differ from those of men (40) (see box
Substance Abuse Screening). Women, for example, are
more likely to be hidden drinkers and frequently underreport alcohol use, especially during pregnancy. Tests to
detect the problem in women must include questions
about tolerance, which are not included in the most commonly used screen, CAGE, which has a sensitivity of only
75% compared with 87% for TWEAK (41).
Pregnant women are more likely to be screened than
nonpregnant women. Although the vulnerability of the
fetus is an important concern, the lives of nonpregnant
women also have compelling value, and there is much
evidence to suggest that women who abuse alcohol or use
illicit drugs have coexisting or preexisting conditions (ie,
mental health disorders, domestic violence, stress, childhood sexual abuse, poverty, and lack of resources) that
put them in a vulnerable status (6, 42, 43). Universal
application of screening questions, brief intervention,
and referral to treatment eliminates these disparities
related to justice.
Additionally, failure to diagnose and treat substance
abuse with the same evidence-based approach applied to
other chronic illnesses reduces patients access to health
services and resources. Justice requires that physicians
counsel patients who have drug or alcohol problems and

refer them to an appropriate treatment resource when
available. No physician would withhold hypertension
therapy because the medication adherence rate is only
60%. Physicians who detect the serious medical condition
of addiction are equally obligated to intervene.
Respect for Autonomy
No person has a right to use illegal drugs, and a pregnant
woman has a moral obligation to avoid the use of both
illicit drugs and alcohol in order to safeguard the welfare
of her fetus. At the same time, effective intervention with
respect to substance abuse by a pregnant or a nonpregnant woman requires that a climate of respect and trust
exist within the physicianpatient relationship. Patients
who begin to disclose behaviors that are stigmatized by
society may be harmed if they feel that their trust is met
with disrespect. Criticism and shaming statements actually increase resistance and impede change. Effective interventions, as summarized in the NIAAA Treatment
Improvement Protocol number 35, are designed to
increase motivation to change by respecting autonomy,
supporting self-efficacy, and offering hope and resources
(10).
Effective intervention also requires that universal
screening questions, brief intervention, and referral to
treatment be conducted with full protection of confidentiality. Patients who fear that acknowledging substance
abuse may lead to disclosure to others will be inhibited
from honest reporting to their physicians (44). A difficult
dilemma is created by state laws that require physicians to
report the nonmedical use of controlled substances by a
pregnant woman or that require toxicology tests after
delivery when there is evidence of possible use of a controlled substance (eg, Minnesota statutes 626.5561 and
626.5562). Although such laws have the goals of referring
the pregnant woman for assessment and chemical
dependency treatment if indicated and of protecting
fetuses and newborns from harm, these laws may unwittingly result in pregnant women not seeking prenatal care
or concealing drug use from their obstetricians. Although
COMMITTEE OPINIONS
it is always appropriate for a physician to negotiate with a

patient about her willingness to accept a medical recommendation, respect for autonomy includes respect for
refusal to be screened.
Special Responsibilities to Pregnant

Patients
Federal warnings about the need to abstain from alcohol
use in pregnancy were first issued in 1984. The American
College of Obstetricians and Gynecologists recommended screening early in pregnancy in its 1977 Standards for
Ambulatory Obstetric Care, and a pamphlet was issued in
1982 entitled Alcohol and Your Unborn Baby. Screening
during pregnancy was subsequently supported in a variety of documents and is recommended in a joint publication issued by ACOG and the American Academy of
Pediatrics (AAP) (45). Although obstetricians report
screening 97% of pregnant women for alcohol use, only
25% used any of the standard screening tools, and only
20% of those surveyed knew that abstinence is the only
known way to avoid all four adverse pregnancy outcomes
(spontaneous abortion, nervous system impairment,
birth defects, and FAS). This is a particularly significant
gap in knowledge because there is no level of alcohol use,
even minimal drinking, that has been determined to be
absolutely safe. More than one half of the respondents
(63%) reported that they lacked adequate information
about referral resources (46). Screening rates for illicit
drugs are lower than for alcohol (89%, according to
unpublished ACOG survey data).
Ethical issues related to beneficence and nonmaleficence and the ethics of care (47) are similar for pregnant
and nonpregnant women and for women who do and do
not have children. In each of these cases, universal screening questions, brief intervention, and referral to treatment enables physicians to collaborate with patients to
improve their own health, reduce the likelihood of
preterm birth and neonatal complications in both current
and future pregnancies, and improve the parenting
capacity of the family unit.
As noted previously, autonomy issues are particularly challenging in pregnancy. In a survey of obstetricians,
pediatricians, and family practice physicians, more than
one half of the respondents believed that pregnant
women have a legal as well as moral responsibility to
ensure that they have healthy newborns (48). Although
61% were concerned that fear of criminal charges would
be a barrier to receiving prenatal care, more than one
half supported a statute that would permit removal of
children from any woman who abused alcohol or drugs
(48). This position is particularly troubling because
these physicians did not state that there needed to be evidence of physical or emotional neglect (adverse effects
on basic needs and safety) for children to be so removed.
Both ethical and legal perspectives require that the best
interests of the child be served, which requires both protecting children and assisting their mothers to be healthy
237
so as to provide an optimal situation for growth and

development.
Physicians concerns about mothers who abuse alcohol or drugs undoubtedly reflect a desire to protect children. However, recommended screening and referral protocols may be perceived as punitive measures when they
are connected with legally mandated testing, or reporting,
or both. Such measures endanger the relationship of trust
between physician and patient, place the obstetrician in
an adversarial relationship with the patient, and possibly
conflict with the therapeutic obligation. If pregnant
women become reluctant to seek medical care because
they fear being reported for alcohol or illegal drug use,
these strategies will actually increase the risks for the
woman and the fetus rather than reduce the consequences of substance abuse. Furthermore, threats and
incarceration have proved to be ineffective in reducing
the incidence of alcohol or drug abuse, and removing
children from the home may only subject them to worse
risks in the foster care system (49). Treatment is both
more effective and less expensive than restrictive policies
(50), and it results in a mean net saving of $4,644 in medical expenses per motherinfant pair (51). Moreover,
women who have custody of their children complete
treatment at a higher rate than those who do not. Putting
women in jail, where drugs may be available but treatment is not, jeopardizes the health of pregnant women
and that of their existing and future children (52).
Referral to treatment, especially if combined with
training in parenting skills, is the clinically appropriate
recommendation, both medically and ethically (37).
Criminal charges against pregnant women on grounds of
child abuse have been struck down in almost all cases
because courts have upheld the right to privacy, which
includes the right to decide whether to have a child, the
right to bodily integrity, and the right to be let alone
(53), and have found that states could better protect fetal
health through education and making available medical
care and drug treatment centers for women (54). The
United States Supreme Court recognized the importance
of privacy to the physicianpatient relationship when it
ruled in 2001 to prohibit a public hospital from performing nonconsensual drug tests on pregnant women without a warrant and providing police with positive results
(55). Despite more than a decade of efforts and the 1992
passage of a federal Alcohol Drug Abuse and Mental
Health Administration Reorganization Act explicitly prohibiting pregnancy discrimination, few treatment programs focus on the needs of pregnant women. In the
absence of appropriate and adequate drug treatment services for pregnant women, criminal charges on grounds
of child abuse are unjust in that they indict women for
failing to seek treatment that actually may not be available
to them.
Justice issues also are problematic in that punitive
measures are not applied evenly across sex, race, and
socioeconomic status. Although several types of legal
238
sanctions against pregnant women who abuse alcohol or

drugs are being tested in the courts, there has been no
attempt to impose similar sanctions for paternal drug
use (56), despite the significant involvement of male
partners in pregnant womens substance abuse (57). In a
landmark study among pregnant women anonymously
tested for drug use, drug prevalence was similar between
African-American women and white women, but
African-American women were 10 times more likely
than white women to be reported as a result of positive
screen results (58). Similar patterns of injustice have
been noted for the types of drugs for which sanctions
exist in the legal system. For example, mandatory incarceration and more severe penalties are applied to crack
cocaine, which is primarily used by African Americans,
than to powder cocaine or heroin, which is primarily
used by whites. In the case of Ferguson v. City of
Charleston, an overwhelming majority of the pregnant
women arrested in the immediate postpartum period
because of cocaine-positive drug screen results were
African American. When the results of similarly drawn
drug screens were positive for methamphetamine or
heroin, which were more commonly used by white
patients, physicians were more likely to refer to social services rather than to the courts (55).
Some physicians are reluctant to record information
related to alcohol or drug abuse in medical records
because of competing obligations. On the one hand, the
physician may be concerned about nonmaleficence.
Because medical records may not be safe from inappropriate disclosure despite federal and state privacy protections, the patient may experience real harmssuch as job
loss unrelated to workplace performance issues, eviction
from public housing, or termination of insuranceif a
diagnosis of dependency is recorded in the medical
record. Although legal redress for harms that result from
inappropriate transfer of information may be possible, it
may not be feasible for a woman in straitened circumstances. On the other hand, the principle of beneficence
often requires disclosure of information needed by the
medical team to provide appropriate medical care.
Without this disclosure, a physician treating the patient
for a problem unrelated to pregnancy or an emergency
department physician seeing the patient for the first time
may miss a major complication related to substance
abuse. Concerns about protection of confidentiality and
nonmaleficence can be addressed most appropriately by
including only medically necessary, accurate information
in the medical record and informing the patient about the
purpose of any disclosure.
Responsibilities to Neonates
The use of illicit drugs and alcohol during pregnancy has
demonstrated adverse effects on the neonate, and these
newborns are subsequently at risk for altered neurodevelopmental outcome and poor health status (59).
Detection and treatment are essential precursors of appro-
priate therapeutic intervention in the immediate setting.

Early recognition of parental substance abuse also may
lead to interventions designed to decrease associated
risks to a childs physical and psychologic health and
safety (3237). Doing so may obviate the necessity for
placement in an already overburdened foster care system
(60). Underrecognition of prenatal alcohol and drug
effects is common, however (61). A toxicology screen and
scoring for craniofacial features suggestive of FAS should
be performed by the neonates physician whenever clinically indicated. According to the AAPs statement on
neonatal drug withdrawal (62), maternal characteristics
that suggest a need for biochemical screening of the
neonate include no prenatal care, previous unexplained
fetal demise, precipitous labor, abruptio placentae,
hypertensive episodes, severe mood swings, cerebrovascular accidents, myocardial infarction, and repeated
spontaneous abortions. Infant characteristics that may
be associated with maternal drug use include preterm
birth, unexplained intrauterine growth restriction, neurobehavioral abnormalities, congenital abnormalities,
atypical vascular incidents, myocardial infarction, and
necrotizing enterocolitis in otherwise healthy term
infants. The legal implications of testing and the need for
maternal consent vary from state to state; therefore,
physicians should be aware of local laws that may influence regional practice.
Biophysical testing, however, has major limitations
(6365). Both urine and meconium screens have a high
rate of false-negative results because of factors related to
the timing and amount of the last maternal drug use (for
urine) and the failure to detect drug metabolites (for
meconium). Hair is associated with a substantial falsepositive rate because of passive exposure to minute quantities of illicit substances in the environment. Physicians
and nurses often fail to recognize the physical manifestations of FAS (66). Maternal self-report of use or consent
to testing, elicited using nonjudgmental, supportive interview techniques within a physicianpatient relationship
of trust, can thus provide the best information for guiding neonatal treatment and the best prognosis for family
intervention. Maternal substance abuse does not by itself
guarantee child neglect or prove inadequate parenting
capacity (67, 68). Parenting skills programs, assistance
with employment and housing issues, and access to substance abuse treatment have been shown to be successful
support mechanisms for families of affected neonates,
and these elements should be part of a comprehensive
approach to substance abuse problems. If there is evidence to suggest the likelihood of neglect or abuse, referral to childrens protective services may be indicated (69).
A childrens protective services referral should never be
undertaken as a punitive measure, but with the aim of
evaluating circumstances, protecting the child, and providing services to maintain or reunify the family unit if at
all possible.
COMMITTEE OPINIONS
Special Issues for Girls and

Young Women
Use of alcohol and illicit drugs among youth is prevalent,
and studies that included both male and female youth
indicate that age of first use is decreasing. Youth who
begin drinking at age 14 years are at least three times
more likely to experience dependence (using criteria
from the Diagnostic and Statistical Manual of Mental
Disorders, 4th Edition) than those who delay drinking to
age 21 years (70). Early onset of drinking increases the
likelihood of alcohol-related unintentional injuries (71),
motor vehicle crash involvement after drinking (72),
unprotected intercourse (73), and getting into fights after
drinking, even after controlling for frequency of heavy
drinking, alcohol dependence, and other factors related
to age of onset (74). A study among a large community
sample of lifetime drinkers showed that those who
reported first drinking at the ages of 1114 years experienced a rapid progression to alcohol-related harm, and
16% developed dependence by age 24 years (75). Among
youth aged 2125 years surveyed in 2006, 27.3% drove
under the influence of alcohol (1). The use of alcohol
and illicit substances by youth and the impact of parental
alcohol and substance use on children have adverse
health outcomes (76, 77). Prevention (universal screening questions, brief intervention, and referral to treatment) has thus been described by leaders in obstetrics
and gynecology and by pediatricians as a moral obligation (78). In 1993, the AAP developed substance abuse
guidelines for clinical practice. These guidelines have
now been refined and developed into competencies that
provide practical direction for clinicians engaged in educating, supporting, and treating patients and families
affected by substance abuse (79).
Confidentiality is as essential to the physician
patient relationship with children as it is with adults.
Many state laws protect the confidentiality of minors
with regard to substance abuse detection and treatment
(79). Autonomy issues are of particular importance in
the detection and treatment of substance abuse for adolescents, who are at a developmental stage in which it is a
normative task to test new identities and engage in risktaking in the process (80). The ACOG Committee on
Adolescent Health Care lists the following key points
concerning informed consent, parental permission, and
assent (81):
Concern about confidentiality is a major obstacle in
the delivery of health care to adolescents. Physicians
should address confidentiality issues with the adolescent patient to build a trusting relationship with her
and to facilitate a candid discussion regarding her
health and health-related behaviors.
Physicians also should discuss confidentiality issues
with the parent(s) or guardian(s) of the adolescent
patient. Physicians should encourage their involve-
239
ment in the patients health and health care decisions

and, when appropriate, facilitate communication
between the two.
The right of a mature minor to obtain selected
medical care has been established in most states.
In a document about testing for drugs of abuse in
children and adolescents, AAP states that the goal of care
is a therapeutic, rather than adversarial, relationship with
the child and, therefore, makes the following recommendations (82):
Screening or testing under any circumstances is
improper if clinicians cannot be reasonably certain
that the laboratory results are valid and that patient
confidentiality is ensured.
Diagnostic testing for the purpose of drug abuse
treatment is within the ethical tradition of health
care, and in the competent patient, it should be conducted noncovertly, confidentially, and with informed
consent in the same context as for other medical
conditions.
Parental permission is not sufficient for involuntary
testing of the adolescent with decisional capacity.
Suspicion that an adolescent is using a psychoactive
drug does not justify involuntary testing, and testing
adolescents requires their consent unless 1) the patient
lacks decision-making capacity or 2) there are strong
medical indications or legal requirements to do so.
Minors should not be immune from the criminal
justice system, but physicians should not initiate or
participate in a criminal investigation, except when
required by law, as in the case of court-ordered drug
testing or child abuse reporting.
Guidance for Physicians

The health care system as it is currently constituted creates
barriers to the practice of universal screening questions,
brief intervention, and referral to treatment for alcohol
and drug abuse. Because of a lack of medical school curricular content about addiction, physicians often are unfamiliar with screening procedures. Many institutions do
not have appropriate protocols in place for intervention
and referral. Time constraints, mandatory reporting laws,
and lack of treatment resources may impede both screening and referral, and some of these problems may be
beyond the ability of the individual physician to modify.
Nevertheless, in fulfillment of the therapeutic obligation,
physicians must make a substantial effort to:
Learn established techniques for rapid, effective
screening, intervention, and referral, and practice
universal screening questions, brief intervention, and
referral to treatment in order to provide benefit and
do no harm. Where possible, create a team approach
to deal with barriers of time limitations, using the
240
skills of social workers, nurses, and peer educators

for universal screening questions, brief intervention,
and referral to treatment. Use external resources (eg,
hospital social worker, health department, addiction
specialist) to develop a list of treatment resources.
Treat the patient with a substance abuse problem
with dignity and respect in order to form a therapeutic alliance.
Protect confidentiality and the integrity of the physicianpatient relationship wherever possible within
the requirements of legal obligations, and communicate honestly and directly with patients about what
information can and cannot be protected. In states
where there are laws requiring disclosure, inform
patients in advance about specific items for which
disclosure is mandated.
Recognize that the most effective safeguard for children is treatment for family members who have a
substance abuse problem.
Balance competing obligations carefully, consulting
with other physicians or an ethicist if troubling situations arise.
Participate, whenever possible, in the policy process
at institutional, state, and national levels as an advocate for the health care needs of patients.
Consider whether elements of personal beliefs and
values may be resulting in biases in medical practice.
Be aware that some physicians minimize the universality and impact of alcohol or prescription drug
abuse to protect against evaluating their own alcohol
or substance abuse problems. A physician who has
questions about his or her own use should seek help.
Conclusion
Substance abuse is a common medical condition that can
have devastating physical and emotional consequences
for women and their children. The traditional role of
healer, the contemporary role of medical expert, and the
newer role of primary care physician all require obstetriciangynecologists to develop an evidence-supported
knowledge base about methods for detection and treatment of substance abuse. The close working relationship
between the physician and the patient that is both a goal
of care and a means to improved health outcomes offers
tremendous potential to influence patients lifestyles positively. Despite this relationship, physicians seldom practice universal screening because of a lack of appreciation
of prevalence, misunderstandings about treatment success rates, unfamiliarity with treatment resources, and
inadequate knowledge about sex differences in presentation and the course of the disease. However, common
barriers to universal screening questions, brief intervention, and referral to treatment can and should be
addressed. Physicians have an ethical obligation to learn
and use techniques for universal screening questions,
brief intervention, and referral to treatment in order to

provide patients and their families with medical care that
is state-of-the-art, comprehensive, and effective.
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ISSN 1074-861X
244

Informed Consent*
Committee on Ethics
ABSTRACT: Obtaining informed consent for medical treatment, for participation in

medical research, and for participation in teaching exercises involving students and
residents is an ethical requirement that is partially reflected in legal doctrines and requirements. As an ethical doctrine, informed consent is a process of communication whereby a patient is enabled to make an informed and voluntary decision about accepting or
declining medical care. In this Committee Opinion, the American College of Obstetricians
and Gynecologists Committee on Ethics describes the history, ethical basis, and purpose
of informed consent and identifies special ethical questions pertinent to the practice of
obstetrics and gynecology. Two major elements in the ethical concept of informed consent, comprehension (or understanding) and free consent, are reviewed. Limits to
informed consent are addressed.
Informed consent is an ethical concept that

has become integral to contemporary medical ethics and medical practice. In recognition of the ethical importance of informed
consent, the Committee on Ethics of the
American College of Obstetricians and Gynecologists (ACOG) affirms the following eight
statements:

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
1. Obtaining informed consent for medical

treatment, for participation in medical
research, and for participation in teaching exercises involving students and residents is an ethical requirement that is
partially reflected in legal doctrines and
requirements.
2. Seeking informed consent expresses
respect for the patient as a person; it particularly respects a patients moral right
to bodily integrity, to self-determination
regarding sexuality and reproductive
capacities, and to support of the patients
freedom to make decisions within caring
relationships.
3. Informed consent not only ensures the
protection of the patient against unwanted medical treatment, but it also makes
possible the patients active involvement
in her medical planning and care.
*Update of Informed Consent in Ethics in Obstetrics
4. Communication is necessary if informed

consent is to be realized, and physicians
can and should help to find ways to facilitate communication not only in individual relations with patients but also in
the structured context of medical care
institutions.
5. Informed consent should be looked on
as a process rather than a signature on a
form. This process includes a mutual
sharing of information over time between
the clinician and the patient to facilitate
the patients autonomy in the process of
making ongoing choices.
6. The ethical requirement to seek informed
consent need not conflict with physicians overall ethical obligation of beneficence; that is, physicians should make
every effort to incorporate a commitment to informed consent within a commitment to provide medical benefit to
patients and, thus, to respect them as
whole and embodied persons.
7. When informed consent by the patient is
impossible, a surrogate decision maker
should be identified to represent the
patients wishes or best interests. In
emergency situations, medical professionals may have to act according to
their perceptions of the best interests of
the patient; in rare instances, they may
COMMITTEE OPINIONS
have to forgo obtaining consent because of some

other overriding ethical obligation, such as protecting the public health.
8. Because ethical requirements and legal requirements
cannot be equated, physicians also should acquaint
themselves with federal and state legal requirements
for informed consent. Physicians also should be aware
of the policies within their own practices because
these may vary from institution to institution.
The application of informed consent to contexts of
obstetric and gynecologic practice invites ongoing clarification of the meaning of these eight statements. What follows is an effort to provide this.
Historical Background
In 1980, the Committee on Ethics developed a statement
on informed consent. This statement, Ethical Considerations Associated with Informed Consent, was subsequently approved and issued in 1980 as a Statement of
Policy by ACOGs Executive Board. The 1980 statement
reflected what is now generally recognized as a paradigm
shift in the understanding of the ethics of the
physicianpatient relationship. During the 1970s, a
marked change took place in the United States from a traditional almost singular focus on the benefit of the
patient as the governing ethical principle of medical care
to a new and dramatic emphasis on a requirement of
informed consent. That is, a central and often sole concern for the medical well-being of the patient was modified to include concern for the patients autonomy in
making medical decisions.
In the 1980s, this national shift was both reinforced
and challenged in medical ethics. Clinical experience as
well as developments in ethical theory generated further
questions about the practice of informed consent and the
legal doctrine that promoted it. If in the 1970s informed
consent was embraced as a corrective to paternalism, in
the 1980s and 1990s shared decision making was increasingly viewed as a necessary corrective to the exaggerated
individualism that patient autonomy had sometimes produced. At the same time, factors such as the proliferation
of medical technologies, the bureaucratic and financial
complexities of health care delivery systems, and the
growing sophistication of the general public regarding
medical limitations and possibilities continued to undergird an appreciation of the importance of patient autonomy and a demand for its promotion in and through
informed consent.
In the early 21st century, there are good reasons for
considering once again the ethical significance and practical application of the requirement to seek informed
consent. This is particularly true in the context of obstetric and gynecologic practice because medical options,
public health problems, legal interventions, and political
agendas have expanded and interconnected with one
245
another in unprecedented ways. The concern of ACOG

for these matters is reflected in its more recent documents on informed consent and on particular ethical
problems that arise in the context of maternalfetal relationships, decisions about relationships, sterilization,
surgical options, and education in the health professions
(17). Although a general doctrine of informed consent
cannot by itself resolve problems like these, it is nonetheless necessary for understanding and responding to
them.
Informed consent for medical treatment and for participation in medical research is both a legal and an ethical matter. In the recent history of informed consent,
statutes and regulations as well as court decisions have
played an important role in the identification and sanctioning of basic duties. Judicial decisions have sometimes
provided insights regarding rights of self-determination
and of privacy in the medical context. Government regulations have rendered operational some of the most general norms formulated in historic ethical codes. Yet,
recent developments in the legal doctrine are few, and the
most serious current questions are ethical ones before
they become issues in the law. As the Presidents Commission reported in 1982, Although the informed consent
doctrine has substantial foundations in law, it is essentially an ethical imperative (8). What above all bears reviewing, then, is the ethical dimension of the meaning, basis,
and application of informed consent.
Although informed consent has both legal and ethical implications, its purpose is primarily ethical in nature.
As an ethical doctrine, informed consent is a process of
communication whereby a patient is enabled to make an
informed and voluntary decision about accepting or
declining medical care. There are important legal aspects
to informed consent that should not be overlooked. It is
critical for physicians to document the contents of this
conversation as part of the permanent medical record. A
signed consent document, however, does not ensure that
the process of informed consent has taken place in a
meaningful way or that the ethical requirements have
been met.
The Ethical Meaning of Informed

Consent
The ethical concept of informed consent contains two
major elements: 1) comprehension (or understanding)
and 2) free consent. Both of these elements together
constitute an important part of a patients self-determination (the taking hold of her own life and action,
determining the meaning and the possibility of what she
The Nuremberg Code in 1948 and the World Medical Associations

Declaration of Helsinki in 1964 identified ethical restrictions for medical
research on human subjects. For a history of the development of such
codes and a general history of the ethical and legal concept of informed
consent, see Faden RR, Beauchamp TL. A history and theory of
informed consent. New York (NY): Oxford University Press; 1986.
246
undergoes as well as what she does). Both of these

elements presuppose a patients capacity to understand
and to consent, a presupposition that will be examined
later.
Comprehension (as an element in informed consent)
includes the patients awareness and understanding of her
situation and possibilities. It implies that she has been
given adequate information about her diagnosis, prognosis, and alternative treatment choices, including the
option of no treatment. Moreover, this information
should be provided in language that is understandable to
the particular patient, who may have linguistic or cognitive limitations. Comprehension in this sense is necessary
for freedom in consenting.
Free consent is an intentional and voluntary choice
that authorizes someone else to act in certain ways. In the
context of medicine, it is an act by which an individual
freely authorizes a medical intervention in her life,
whether in the form of treatment or participation in
research or medical education. Consenting freely is
incompatible with being coerced or unwillingly pressured
by forces beyond oneself. It involves the ability to choose
among options and to select a course other than what
may be recommended. It is important for physicians to be
cognizant of their own beliefs and values during the
informed consent process. Physicians should have insight
into how their opinions may affect the way in which
information is presented to patients and, as a result, influence the patients decision to accept or decline a therapy.
Different models of the physicianpatient relationship
exist, and the degree to which a physician would share his
or her values and professional opinions with patients
varies (5). In many cases, the physicians personal and
professional values and clinical experiences do, to some
degree, influence the presentation and discussion of therapeutic options with patients. Although not considered
frank manipulation or coercion, care should be taken that
the physicians perspectives do not unduly influence a
patients voluntary decision making.
Free consent, of course, admits of degrees, and its
presence is not always verifiable in concrete instances. If
free consent is to be operative at all in the course of medical treatment, it presupposes knowledge about and
understanding of all the available options.
Many thoughtful individuals have different beliefs
about the actual achievement of informed consent and
about human freedom. Many philosophical disputes have
raged about what freedom is and whether it exists. These
differences in underlying philosophical perspectives do
not, however, alter the general agreement about the need
for informed consent and about its basic ethical significance in the context of medical practice and research. It is
still important to try to clarify, however, who and what
informed consent serves and how it may be protected and
fostered. This clarification cannot be achieved without
some consideration of its basis and goals and the concrete
contexts in which it must be realized.
The Ethical Basis and Purpose of

Informed Consent
One of the important arguments for the ethical requirement of informed consent is an argument from utility, or
from the benefit that can come to patients when they
actively participate in decisions about their own medical
care. The involvement of patients in such decisions is
good for their healthnot only because it helps protect
against treatment that patients might consider harmful,
but also because it often contributes positively to their
well-being. There are at least two presuppositions here: 1)
patients know something experientially about their own
medical condition that can be helpful and even necessary
to the sound management of their medical care, and 2)
wherever it is possible, patients active role as primary
guardian of their own health is more conducive to their
well-being than is a passive and submissive sick role.
The positive benefits of patient decision making are obvious, for example, in the treatment of alcohol abuse. But
the benefits of active participation in medical decisions
are multifold for patients, whether they are trying to
maintain their general health, recover from illness, conceive and give birth to healthy newborns, live responsible
sexual lives, or accept the limits of medical technology.
Utility, however, is not the only reason for protecting
and promoting patient decision making. Indeed, the most
commonly accepted foundation for informed consent is
the principle of respect for persons. This principle
expresses an ethical requirement to treat persons as ends
in themselves (that is, not to use them solely as means or
instruments for someone elses purposes and goals). This
requirement is based on the belief that all persons, as persons, have certain features or characteristics that constitute the source of an inherent dignity, a worthiness and
claim to be affirmed in their own right. One of these features has come to be identified as personal autonomya
persons capacity for self-determination (for self-governance and freedom of choice). To be autonomous is to
have the capacity to set ones own agenda. Given this
capacity in persons, it is ordinarily an ethically unacceptable violation of who and what persons are to manipulate
or coerce their actions or to refuse their participation in
important decisions that affect their lives.
An important development in ethical theory in
recent years is the widespread recognition that autonomy
is not the only characteristic of persons that is a basis for
the requirement of respect. Human beings are essentially
social beings, relational in the structure of their personalities, their needs, and their possibilities. As such, then,
the goal of human life and the content of human wellbeing cannot be adequately understood only in terms
of self-determinationespecially if self-determination is
understood individualistically and if it results in human
relationships that are primarily adversarial. A sole or even
central emphasis on narrow conceptions of patient
autonomy that presume a highly individualistic agent in
COMMITTEE OPINIONS
the informed consent process in the medical context risks

replacing paternalism with a distanced and impersonal
relationship of strangers negotiating rights and duties. If
persons are to be respected and their well-being promoted, informed consent must be considered in the context
of individuals various relationships.
Patients approach medical decisions with a history of
relationships, personal and social, familial and institutional. They make decisions in the context of these relationships, shared or not shared, as the situation allows.
One such relationship is between patient and physician
(or often between patient and multiple professional caregivers).
The focus, then, for understanding both the basis
and the content of informed consent must shift to include
the many facets of the physicianpatient relationship.
Informed consent, from this point of view, is not an end,
but a means. It is a means not only to the responsible participation by patients in their own medical care but also
to a relationship between physician (or any medical caregiver) and patient. From this perspective, it is possible to
see the contradictions inherent in an approach to informed
consent that would, for example:
Lead a physician (or anyone else) to say of a patient,
I consented the patient
Assume that informed consent is achieved simply by
the signing of a document
Consider informed consent primarily as a safeguard
for physicians against professional liability
This view of informed consent posits a dialogue
between patient and health care provider in support of
respect for patient autonomy. A major objective of this
view is to prevent the practitioner from imposing treatments. It does not, however, require practitioners to
accede to patient requests for unproven or harmful treatment modalities.
Obstetrics and Gynecology: Special

Ethical Concerns for Informed Consent
The practice of obstetrics and gynecology has always
faced special ethical questions in the implementation of
informed consent. How, for example, can the autonomy
of patients best be respected when serious decisions must
be made in the challenging situations of labor and delivery? What kinds of guidelines can physicians find for
respecting the autonomy of adolescents, when society
acknowledges this autonomy by and large only in the limited spheres of sexuality and reproduction? In the context
of genetic counseling, where being non-directive is the
norm, is it ever appropriate to recommend a specific
course of action? How much information should be given
to patients about controversies surrounding specific
treatments? How are beneficence requirements (regarding the well-being of the patient) to be balanced with
respect for autonomy, especially in a field of medical
247
practice where so many key decisions are irreversible?

These and many other questions continue to be important for fulfilling the ethical requirement to seek informed
consent.
Developments in the ethical doctrine of informed
consent (regarding, for example, the significance that
relationships have for decision making) have helped to
focus some of the concerns that are particularly important in the practice of obstetrics and gynecology (1).
Where womens health care needs are addressed, and
especially where these needs are related to womens sexuality and reproductive capacities, the issues of patient
autonomy and its relational nature come to the forefront.
Perspectives and insights for interpreting these issues are
now being articulated by women out of their experiencethat is, their experience specifically in the medical
setting, but also more generally in relation to their own
bodies, in various patterns of relation with other individuals, and in the larger societal and institutional contexts
in which they live. These perspectives and insights offer
both a help and an ongoing challenge to professional selfunderstanding and practice of obstetricians and gynecologists (whether they themselves are women or men).
New models for the active participation of health
care recipients have been created in obstetrics and gynecology. Some of these developments are the result of arguments that pregnancy and childbirth should not be
thought of as diseases, although they bring women
importantly into relation with medical professionals and,
in some cases, carry a potential for morbidity or mortality. Even when womens medical needs pointedly require
diagnosis and treatment, their concerns to hold together
the values of both autonomy and their relationships have
been influential in shaping not only ethical theory but
also medical practice. Women themselves have questioned, for example, whether autonomy can really be
protected if it is addressed in a vacuum, apart from an
individuals concrete roles and relationships. But women
as well as men also have recognized the ongoing importance of respect for autonomy, although they suggest it
should be reconceptualized as less individualistic and
more relational (9). They call for attention to the complexity of the relationships that are involved, especially
when sexuality and parenting are at issue in medical care,
while upholding the importance of bodily integrity and
self-determination.
The difficulties that beset the full achievement of
informed consent in the practice of obstetrics and gynecology are not limited to individual and interpersonal factors. Both health care providers and recipients of medical
care within this specialty have recognized the influence of
such broad social problems as the historical imbalance of
power in gender relations and in the physicianpatient
relationship, the constraints on individual choice posed
by complex medical technology, and the intersection of
gender bias with race and class bias in the attitudes and
actions of individuals and institutions. None of these
248
problems makes the achievement of informed consent

impossible. But, they point to the need to identify the
conditions and limits, as well as the central requirements,
of the ethical application of this doctrine.
Ethical Applications of Informed

Consent
Insofar as comprehension and voluntariness are the basic
ethical elements in informed consent, its efficacy and adequacy will depend on the fullness of their realization in
patients decisions. There are ways of assessing this and
strategies for achieving informed consent, even though it
involves a process that is not subject to precise measurement.
It is difficult to specify what consent consists of and
requires because it is difficult to describe a free decision in
the abstract. Two things can be said about it in the context
of informed consent to a medical intervention, however,
elaborating on the conceptual elements identified previously in this Committee Opinion. The first is to describe
what consent is not, what it is freedom from. Informed
consent includes freedom from external coercion, manipulation, or infringement of bodily integrity. It is freedom
from being acted on by others when they have not taken
account of and respected the individuals own preference
and choice. This kind of freedom for a patient is not
incompatible with a physicians giving reasons that favor
one option over another. Medical recommendations,
when they are not coercive or deceptive, do not violate the
requirements of informed consent. For example, to try to
convince a patient to take a medication that will improve
her health is not to take away her freedom (assuming that
the methods of persuasion respect and address, rather
than overwhelm, her freedom).
Second, although informed consent to a medical
intervention may be an authorization of someone elses
action toward ones self, it ismore profoundlyan
active participation in decisions about the management
of ones medical care. It is (or can be), therefore, not only
a permitting but a doing. It can include decisions to
make every effort toward a cure of a disease; or when a
cure is no longer a reasonable goal, to maintain functional equilibrium; or, finally, to receive only supportive or
palliative care. The variety of choices that are possible to
a patient ranges, for example, from surgery to medical
therapy, from diagnostic tests to menopausal hormone
therapy, and from one form of contraception to another.
For women in the context of obstetrics and gynecology,
the choices may be positive determination of one kind of
assisted reproduction or another or one kind of preventive medicine or anotherchoices that are best described
as determinations of their own actions rather than passive
receiving of care.
Consent in this sense requires not only external
freedom and freedom from inner compulsion, but also
(as previously noted in this document) freedom from
ignorance. Hence, to be ethically valid, consent must be

informed.
Consent is based on the disclosure of information
and a sharing of interpretations of its meaning by a medical professional. The accuracy of disclosure, insofar as it
is possible, is governed by the ethical requirement of
truth-telling. The adequacy of disclosure has been judged
by various criteria, which may include the following:
1. The common practice of the profession
2. The reasonable needs and expectations of the ordinary individual who might be making a particular
decision
3. The unique needs of an individual patient faced with
a given choice
Although these criteria have been generated in the
rulings of courts, the courts themselves have not provided a unified voice as to which of these criteria should be
determinative. Trends in judicial decisions in most states
were for a time primarily in the direction of the professional practice criterion, requiring only the consistency
of a physicians disclosure with the practice of disclosure
by other physicians. Now the trend in many states is more
clearly toward the reasonable person criterion, holding
the medical profession to the standard of what is judged
to be material to an ordinary individuals decision in the
given medical situation. The criterion of the subjective
needs of the patient in question generally has been too
difficult to implement in the legal arena, but its ethical
force is significant.
Health care providers should engage in some ethical
discernment of their own as to which criteria are most
faithful to the needs and rightful claims of patients for
disclosure. All three criteria offer reminders of ethical
accountability and guidelines for practice. All three can
help to illuminate what needs to be shared in the significant categories for disclosure: diagnosis and description
of the patients medical condition, description of the proposed treatment and its nature and purpose, risks and
possible complications associated with the treatment,
alternative treatments or the relative merits of no treatment at all, and the probability of success of the treatment
in comparison with alternatives.
Listing categories of disclosure does not by itself
include all the elements that are important to adequacy of
disclosure. Among other matters, the obligation to provide adequate information to a patient implies an obligation for physicians to be current in their own knowledge,
for instance, about treatments and disease processes. As
an aid to physicians in communicating information to
patients, ACOG makes available more than 100 patient
education pamphlets on a wide variety of subjects. When
For an overview of legal standards for disclosure and ethical questions

that go beyond legal standards, see Faden RR, Beauchamp TL. A history
and theory of informed consent. New York (NY): Oxford University
Press; 1986.
COMMITTEE OPINIONS
physicians make informed consent possible for patients

by giving them the knowledge they need for choice, it
should be clear to patients that their continued medical
care by a given physician is not contingent on their making the choice that the physician prefers (assuming the
limited justifiable exceptions to this that will be addressed
later).
Those who are most concerned with problems of
informed consent insist that central to its achievement is
communicationcommunication between physician
and patient, communication among the many medical
professionals who are involved in the care of the patient,
and communication (where this is possible and appropriate) with the family of the patient. Documentation in a
formal process of informed consent can be a help to necessary communication (depending on the methods and
manner of its implementation). The completion of a
written consent document, whether required by statute,
regulation, policy, or case law, should never be a substitute
for the communication involved in disclosure, the conversation that leads to an informed and voluntary consent
or refusal (6, 10).
To focus on the importance of communication for the
implementation of an ethical doctrine of informed consent is, then, to underline the fact that informed consent
involves a process. There is a process of communication
that leads to initial consent (or refusal to consent) and that
can make possible appropriate ongoing decision making.
There are, of course, practical difficulties with ensuring the kind of communication necessary for informed
consent. Limitations of time in a clinical context, patterns
of authority uncritically maintained, underdeveloped
professional communication skills, limited English proficiency, language barriers between technical discourse
and ordinarily comprehensible expression, and situations
of stress on all sidesall of these frequently yield less
than ideal circumstances for communication. Yet the ethical requirement to obtain informed consent, no less than
a requirement for good medical care, extends to a requirement for reasonable communication. The conditions for
communication may be enhanced by creating institutional policies and structures that make it more possible and
effective.
Although understanding and voluntariness are basic
elements of informed consent, they admit of degrees.
There will always be varying levels of understanding,
varying degrees of internal freedom. The very matters of
disclosure may be characterized by disagreement among
professionals, uncertainty and fallibility in everyones
judgments, the results not only of scientific analysis but of
medical insight and art. And the capacities of patients for
comprehension and consent are more or less acute, of
greater or lesser power, focused in weak or strong personal integration, and compromised or not by pain, medication, disease, or social circumstance. Some limitations
mitigate the obligation to obtain informed consent, and
some render it impossible. But any compromise or relax-
249
ation of the full ethical obligation to obtain informed

consent requires specific ethical justification.
The Limits of Informed Consent

Because informed consent admits of degrees of implementation, there are limits to its achievement. These are
not only the limits of fallible knowledge or imperfect
communication. They are limitations in the capacity of
patients for comprehension and for choice. Assessment of
patient capacity is itself a complex matter, subject to mistakes and to bias. Hence, a great deal of attention has been
given to criteria for determining individual capacity (and
the legally defined characteristic of competence) and
for just procedures for its evaluation (8). When individuals are entirely incapacitated for informed consent, the
principles of respect for persons and beneficence require
that the patient be protected. In these situations, someone
else must make decisions on behalf of the patient. A surrogate decision maker should be identified to provide a
substituted judgment (a decision based on what the
patient would have wanted, assuming some knowledge of
what the patients wishes would be); if the patients wishes are unknown, the surrogate makes a decision according
to the best interests of the patient. If the patient has previously executed an advance directive, that document
should guide the selection of a surrogate decision maker
or the specific decisions made by the surrogate or both,
depending on the nature of the advance directive.
The judgment that informed consent is impossible in
some circumstances indicates a kind of limit that is different from a partial actualization of consent or consent by
an appropriate surrogate. One way to acknowledge this is
to say that there are limits to the obligation to obtain
informed consent at all. There are several exceptions to
the strict rule of informed consent.
First, impossibility of any achievement of informed
consent suspends or limits the ethical obligation. This is
exemplified in emergency situations in which consent
is unattainable and in other situations when a patient is
not at all competent or capable of giving consent and an
appropriate surrogate decision maker is not available. In
the practice of obstetrics and gynecology, as in any other
specialty practice, there are situations where decisions can
be based only on what is judged to be in the best interest
of the patienta judgment made, if possible, by a designated surrogate, legal guardian, or family members
together with medical professionals. Yet often when a
patient is not able to decide for herself (perhaps, for example, because of the amount of medication needed to control pain), a substituted judgment or a judgment on the
basis of prior informed consent can be made with confidence if care has been taken beforehand to learn the
patients wishes. This signals the importance of early communication so that what a patient would choose in a
developing situation is knownso that, indeed, it remains
possible to respect the self-determination that informed
consent represents.
250
A second way in which the rule of informed consent

may be suspended or limited is by being overridden by
another obligation. A number of other ethical obligations
can, in certain circumstances, override or set limits on
the requirement to obtain informed consent. For example, strong claims for the public good (specifically, public health) may set limits to what a patient can refuse or
choose. That is, although the rights of others not to be
harmed may sometimes take priority over an individuals
right to refuse a medical procedure (as is the case in
exceptional forms of mandatory medical testing and
reporting), scarcity of personnel and equipment may in
some circumstances mean that individual patients cannot
have certain medical procedures just for the choosing.
In rare circumstances, what is known as therapeutic
privilege can override an obligation to disclose information
and hence to obtain informed consent. Therapeutic privilege is the limited privilege of a physician to withhold
information from a patient in the belief that this information about the patients medical condition and options will
seriously harm the patient. Concern for the patients wellbeing (the obligation of beneficence) thus comes into conflict with respect for the patients autonomy (11). This is a
difficult notion to applygreat caution must be taken in
any appeal to itand the rationale for withholding information should be carefully documented. The concept of
therapeutic privilege should not, for example, be used as a
justification for ignoring the needs and rights of adolescents (or adults) to participate in decisions about their sexuality and their reproductive capacities. It is reasonable to
argue that therapeutic privilege is almost never a basis for
permanently overriding the obligation to seek informed
consent. Ordinarily such overriding represents a temporary situation, one that will later allow the kind of communication conducive to the restored freedom of the patient.
Sometimes another exception to the rule of informed
consent is thought to occur in the rare situation when a
patient effectively waives her right to give it. This can take
the form of refusing information necessary for an
informed decision, or simply refusing altogether to make
any decision. However, the following two statements are
reasons for not considering this an exception of the same
type as the other exceptions:
1. A waiver in such instances seems to be itself an exercise of choice, and its acceptance can be part of
respect for the patients autonomy.
2. Implicit in the ethical concept of informed consent is
the goal of maximizing a patients freedoms, which
means that waivers should not be accepted complacently without some concern for the causes of the
patients desire not to participate in the management
of her care.
In any case, it should be noted that in states where
written documentation of informed consent is required,
it may be necessary to meet this requirement in some
legally acceptable way.
Finally, limits intrinsic to the patientphysician relationship keep the requirement of informed consent from
ever being absolute. Physicians also are moral agents and,
as such, retain areas of free choiceas in the freedom in
some circumstances not to provide medical care that
they deem either medically inappropriate or ethically
objectionable. It is unethical to prescribe, provide, or
seek compensation for therapies that are of no benefit to
the patient (12). Interpretations of medical need and
usefulness in some circumstances also may lead a physician to refuse to perform surgery or prescribe medication. The freedom not to provide standard or potentially
beneficial care to which one ethically objects is sometimes called a right to conscientious refusal, although
this right is limited (13). Even in the context of justified
conscientious refusal, physicians must provide the
patient with accurate and unbiased information about
her medical options and make appropriate referrals. In
the mutuality of the patientphysician relationship, each
one is to be respected as a person and supported in her
or his autonomous decisions insofar as those decisions
are not, in particular circumstances, overridden by other
ethical obligations. The existing imbalance of power in
this relationship, however, is a reminder to physicians
of their greater obligation to ensure and facilitate the
informed consent or refusal of each patient. Differences
in knowledge can and should be bridged through efforts
at communication of information; professional responsibilities to be honest and uphold the primacy of patient
welfare should be respected.
Acknowledging the limits of the ethical requirement
to obtain informed consent, then, clarifies but does not
weaken the requirement as such. Hence, the Committee
on Ethics reaffirms the eight statements that were presented at the beginning of this Committee Opinion.
References
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5. Surgery and patient choice. ACOG Committee Opinion
Professional liability and risk management: an essential
COMMITTEE OPINIONS
7.
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13.
guide for obstetriciangynecologists. Washington, DC:

ACOG;2005.
Professional responsibilities in obstetricgynecologic education. ACOG Committee Opinion No. 358. American
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Presidents Commission for the Study of Ethical Problems
in Medicine and Biomedical and Behavioral Research.
Making health care decisions: the ethical and legal implications of informed consent in the patient-practitioner relationship. Washington, DC: U.S. Government Printing
Office; 1982.
Mackenzie C, Stoljar N, editors. Relational autonomy: feminist perspectives on autonomy, agency, and the social self.
New York (NY): Oxford University Press; 2000.
American Medical Association. Medicolegal forms with
legal analysis: documenting issues in the patient-physician
relationship. Chicago (IL): AMA; 1999.
American Medical Association. Withholding information
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at: http://www.ama-assn.org/ad-com/polfind/Hlth-Ethics.
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acogcode.pdf. Retrieved February 3, 2009.
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COMMITTEE OPINIONS
253
COMMITTEE OPINIONS
COMMITTEE
ON
GENETICS
COMMITTEE OPINIONS
COMMITTEE
ON
GENETICS
ACOG
Committee on
Genetics
Reaffirmed 2007
Committee
Opinion
(Replaces No. 162, November 1995)
Screening for TaySachs Disease

of the date issued and is subject to
ABSTRACT: TaySachs disease (TSD) is a severe progressive neurologic disease that causes death in early childhood. Carrier screening should be offered
before pregnancy to individuals and couples at high risk, including those of
Ashkenazi Jewish, FrenchCanadian, or Cajun descent and those with a family history consistent with TSD. If both partners are determined to be carriers
of TSD, genetic counseling and prenatal diagnosis should be offered.

TaySachs disease (TSD) is a lysosomal storage disease in which GM2

gangliosides accumulate throughout the body. The accumulation of these
gangliosides in the central nervous system results in a severe progressive neurologic disease that causes death in early childhood.
The TSD carrier rate in Jewish individuals of Eastern European descent
(Ashkenazi) is approximately 1 in 30; the carrier rate for non-Jewish individuals is estimated to be 1 in 300. It has been determined that individuals of
FrenchCanadian and Cajun descent also have a greater carrier frequency
than the general population.
The enzyme hexosaminidase occurs in two principal forms, Hexosaminidase A and Hexosaminidase B. Hexosaminidase A is composed of one
subunit and one subunit, whereas Hexosaminidase B is composed of two
subunits. TaySachs disease is caused by a deficiency of Hexosaminidase A,
whereas Sandhoff disease is caused by a deficiency of both Hexosaminidase A
and Hexosaminidase B. Both of these diseases are transmitted in an autosomal recessive fashion. Laboratories report Hexosaminidase A levels as a
percentage of total hexosaminidase activity. Hexosaminidase A is almost
completely absent in patients with classical TSD. The percentage of Hexosaminidase A activity in carriers usually is less than 55% of total activity,
whereas Hexosaminidase A activity in noncarriers generally is more than
60% of total activity. TaySachs disease can be diagnosed prenatally by measuring hexosaminidase activity in samples obtained by amniocentesis or by
chorionic villus sampling.
Carrier screening can be performed by molecular analysis, biochemical
analysis, or both. Molecular analyses of the subunit gene for TSD have been
reported in both Jewish and non-Jewish populations. Molecular analysis of
three mutations will detect 94% of carriers in the Ashkenazi Jewish population, compared with biochemical analysis, which will detect 98% of carriers.

directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Screening for TaySachs disease.

Gynecologists. Obstet Gynecol
2005;106:8934.
255
256
Different mutations have been found in other ethnic

groups. Biochemical analysis should be used in lowrisk populations because molecular analysis detects
less than 50% of carriers in these populations.
Test results of biochemical carrier screening
using serum are inaccurate when performed in
women who are pregnant or taking oral contraceptives. If the serum test is used for pregnant women,
many of them will be misclassified as carriers. If
biochemical testing is to be done in women who are
pregnant or taking oral contraceptives, leukocyte
testing must be used. If both partners are determined
to be carriers of TSD, genetic counseling and prenatal diagnosis should be offered.
When the serum test result is inconclusive, biochemical analysis should be performed on leukocytes from peripheral blood. DNA analysis may be
helpful for those individuals whose leukocyte test
results are inconclusive and those individuals whose
test results are positive to rule out a rare pseudodeficiency condition.
Pseudodeficiency refers to a state in which
asymptomatic individuals have a low amount of
Hexosaminidase A activity when tested with conventional artificial substrate. However, these normal
individuals without Hexosaminidase A are able to
catalyze the breakdown of natural substrate GM2
ganglioside. Pseudodeficiency mutations comprise
approximately one third of the mutations identified
in non-Jewish individuals. Because some of these
individuals are compound heterozygotes for a
TaySachs mutation and a pseudodeficiency allele,
the delineation of their precise genotype for reproductive purposes usually requires further biochemical assessment complemented with DNA analysis.
Based on the preceding information, the
Committee on Genetics makes the following recommendations:
1. Screening for TSD should be offered before
pregnancy if both members of a couple are of
Ashkenazi Jewish, FrenchCanadian, or Cajun
descent. Those with a family history consistent
with TSD also should be offered screening.
2. When one member of a couple is at high risk (ie,
of Ashkenazi Jewish, FrenchCanadian, or
Cajun descent or has a family history consistent
with TSD) but the other partner is not, the highrisk partner should be offered screening. This
is particularly important if there is uncertainty
3.
4.
5.
6.
about ancestry or if there is a family history consistent with TSD. If the high-risk partner is
determined to be a carrier, the other partner also
should be offered screening. If the woman is
already pregnant, it may be necessary to offer
screening to both partners simultaneously to
ensure that results are obtained promptly and
that all options are available to the couple.
Biochemical analysis should be used for individuals in low-risk populations.
If TSD biochemical screening is performed in
women who are pregnant or taking oral contraceptives, leukocyte testing must be used.
Ambiguous screening test results or positive
screening test results in individuals should be
confirmed by biochemical and DNA analysis
for the most common mutations. This will detect
patients who carry genes associated with mild
disease or pseudodeficiency states. Referral to a
specialist in genetics may be helpful in these
cases.
If both partners are determined to be carriers of
TSD, genetic counseling and prenatal diagnosis
should be offered.
Bibliography
Prenatal and preconceptional carrier screening for genetic diseases in individuals of Eastern European Jewish descent.
ACOG Committee Opinion 298. American College of
4258.
Kaback M, Lim-Steele J, Dabholkar D, Brown D, Levy N,
Zeiger K. Tay-Sachs diseasecarrier screening, prenatal diagnosis, and the molecular era. An international perspective,
1970 to 1993. The International TSD Data Collection Network.
JAMA 1993;270:230715.
Mules EH, Hayflick S, Dowling CE, Kelly TE, Akerman BR,
Gravel RA, et al. Molecular basis of hexosaminidase A deficiency and pseudodeficiency in the Berks County Pennsylvania
Dutch. Hum Mutat 1992;1:298302.
Prence EM, Natowicz MR, Zalewski I. Unusual thermolability properties of leukocyte beta-hexosaminidase: implications in screening for carriers of Tay-Sachs disease. Clin Chem
1993;39:18114.
Triggs-Raine BL, Feigenbaum AS, Natowicz M, Skomorowski
MA, Schuster SM, Clarke JT, et al. Screening for carriers of
Tay-Sachs disease among Ashkenazi Jews. A comparison of
DNA-based and enzyme-based tests. N Engl J Med 1990;
323:612.
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
Committee on
Committee on
Genetics
Reaffirmed 2007
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Perinatal risks associated with

assisted reproductive technology.
Gynecologists. Obstet Gynecol 2005;
106:11436.
257
Committee
Opinion
Perinatal Risks Associated With

Assisted Reproductive Technology
ABSTRACT: Over the past two decades, the use of assisted reproductive
technology (ART) has increased dramatically worldwide and has made pregnancy possible for many infertile couples. A growing body of evidence suggests an association between pregnancies resulting from ART and perinatal
morbidity (possibly independent of multiple births), although the absolute
risk to children conceived through ART is low. Prospective studies are
needed to further define the risk of ART to offspring. The single most important health effect of ART for the offspring remains iatrogenic multiple fetal
pregnancy. The American College of Obstetricians and Gynecologists supports the effort toward lowering the risk of multiple gestation with ART.
Over the past two decades, the use of assisted reproductive technology
(ART) has increased dramatically worldwide and has made pregnancy possible for many infertile couples. The American Society for Reproductive
Medicine defines ART as treatments and procedures involving the handling
of human oocytes and sperm, or embryos, with the intent of establishing a
pregnancy (1). By this definition, ART includes in vitro fertilization (IVF)
with or without intracytoplasmic sperm injection (ICSI), but it excludes techniques such as artificial insemination and superovulation drug therapy.
Several studies have been conducted to describe and compare the obstetric outcome of pregnancies resulting from ART with those of pregnancies
conceived without treatment. Some retrospective and prospective follow-up
studies suggest that pregnancies achieved by ART are associated with an
increased risk of prematurity, low birth weight, and neonatal encephalopathy
and a higher perinatal mortality rate, even after adjusting for age, parity, and
multiple gestation (2, 3). Even in studies limited to singleton ART pregnancies, the prematurity rate is twice as high, and the proportion of infants with
low birth weight is three times as high as that of the general population
(4, 5). A meta-analysis of 15 studies comprising 12,283 singleton infants
conceived by IVF and 1.9 million spontaneously conceived singleton infants
showed significantly higher odds of perinatal mortality (odds ratio [OR],
2.2), preterm delivery (OR, 2.0), low birth weight (OR, 1.8), very low birth
weight (OR, 2.7), and small for gestational age status (OR, 1.6) in IVF pregnancies, after adjusting for maternal age and parity (6).
258
It is difficult to determine the degree to which

these associations are specifically related to the ART
procedures versus any underlying factors within the
couple, such as coexisting maternal disease, the
cause of infertility, or differences in behavioral risk
(eg, smoking). Many of the adverse obstetric outcomes associated with ART may actually be linked
to infertility rather than the treatment for this disorder. Continued research is needed to examine possible confounding variables for these observations.
Patients undergoing superovulation drug therapy
alone, IVF alone, and IVF with ICSI should be
examined as three distinct risk populations, and control populations should ideally consist of two separate groupsnormal fertile couples and infertile
couples who conceive without treatment.
Assisted reproductive technology has been associated with a 30-fold increase in multiple pregnancies
compared with the rate of spontaneous twin pregnancies (1% in the general white population). The obstetric
and neonatal risks associated with multiple gestation
include preeclampsia, gestational diabetes, preterm
delivery, and operative delivery. Multifetal births
account for 17% of all preterm births (before 37
weeks of gestation), 23% of early preterm births
(before 32 weeks of gestation), 24% of low-birthweight infants (< 2,500 g), and 26% of very-lowbirth-weight infants (< 1,500 g) (710). In a large
population-based cohort study in the United States
from 1996 to 1999, the proportion of multiple births
attributable to ovulation induction or ART was 33%
(11), although the rate of high-order multiple gestations from ART decreased significantly between
1998 and 2001 (12). Methods to limit high-order
multiple pregnancies include monitoring hormone
levels and follicle number during superovulation and
limiting transfer to fewer embryos in IVF cycles
(1214). Transferring two embryos can limit the
occurrence of triplets in younger candidates who
have a good prognosis without significantly decreasing the overall pregnancy rate (15, 16). The American Society for Reproductive Medicine and the
Society for Assisted Reproductive Technology have
developed updated recommendations on the number
of embryos per transfer to reduce the risk of multiple
gestation (1). The multiple gestation risk of ART,
unlike that of superovulation, can be effectively managed by limiting the number of embryos transferred.
When considering how to minimize multiple gestation, ART can be viewed as the safer and more favorable approach compared with superovulation.
Informing couples of the obstetric risks as well

as the socioeconomic consequences of multiple gestations may modify their decisions regarding the
number of embryos to be transferred (17). Patients
undergoing ART procedures should be counseled in
advance regarding the option of multifetal pregnancy reduction to decrease perinatal risks if a highorder multiple pregnancy occurs. Because the
intense motivation for a successful outcome and the
substantial out-of-pocket cost of ART may increase
patients desire for the transfer of an excessive number of embryos, it is critical that couples be aware of
the risk and associated morbidity of high-order multiple gestation.
Most retrospective and prospective follow-up
studies of children born as a result of ART have provided evidence for congenital malformation rates
similar to those reported in the general population
(1820). In contrast, an Australian study of 4,916
women found that the risk of one or more major
birth defects in infants conceived with ART was
twice the expected rate (8.6% for ICSI and 9.0% for
IVF, compared with 4.2% in the general population)
(21). As with other studies, the control group was
not ideal because it did not include couples with
infertility who conceived without ART. Prospective
studies are needed to further define the risk of ART
to offspring.
Male factor infertility is now recognized as an
inherited disorder for some infertile couples. In vitro
fertilization offers the opportunity to achieve pregnancy while increasing the couples awareness of
possible inherited disorders in their offspring.
Genetic conditions can predispose to abnormal
sperm characteristics that may be passed to male
children. In addition, azoospermia is associated with
congenital bilateral absence or atrophy of the vas
deferens in men with gene mutations associated with
cystic fibrosis. Congenital bilateral absence or atrophy of the vas deferens accounts for approximately
2% of all cases of male infertility (22, 23). Therefore, all patients with congenital bilateral absence or
atrophy of the vas deferens and their partners considering IVF by sperm extraction procedure with
ICSI should be offered genetic counseling to discuss
testing for cystic fibrosis.
Approximately 1015% of azoospermic and
severely oligospermic (< 5 million/mL) males have
microdeletions of their Y chromosome that can be
passed on to their male offspring (24, 25). There is
speculation that a deletion could potentially expand
COMMITTEE OPINIONS
in successive generations; however, the reproductive

and nonreproductive health implications of this possibility are unknown (26). Some studies have suggested a 1% increased risk for fetal sex chromosome
abnormalities following ICSI conception (2729),
but others have yielded conflicting results (30).
Subfertile men, with a higher proportion of aneuploid sperm, may have an increased risk of transmitting chromosomal abnormalities to their children
(31). These men should be aware of the possible
reproductive consequences in their male offspring
and the options for prenatal diagnosis.
There is some concern that the micromanipulation of the early embryonic environment in IVF may
result in imprinting errors. Genomic imprinting is an
epigenetic phenomenon in which one of the two
alleles of a subset of genes is expressed differentially according to its parental origin. Imprinting is
established early in gametogenesis and maintained
in embryogenesis. Recent case series have reported
an overrepresentation of two syndromes associated
with abnormal imprinting in IVF offspring
BeckwithWiedemann syndrome and Angelmans
syndrome (32, 33). Both of these conditions may be
associated with severe learning disabilities, mental
retardation, and congenital malformations. Because
these conditions are so rare (1 in 100,0001 in
300,000), large prospective studies of offspring conceived with ART would be necessary to confirm an
increased risk (34). Currently, the risk of imprinting
disorders with offspring conceived with ART is
largely theoretical but warrants further investigation.
A growing body of evidence suggests an association between ART pregnancies and perinatal morbidity (possibly independent of multiple births),
although the absolute risk to children conceived with
IVF is low. There is observational evidence linking
ART and chromosomal abnormalities following
ICSI in severe male factor cases, and concerns have
been raised about a possible relationship to genomic
imprinting modifications. Given the large sample
sizes required to firmly answer these questions, particularly for rare genetic disorders, no causal relationship can be established at this time. It is still
unclear to what extent these associations are related
to the underlying cause(s) of infertility versus the
treatment. It would be prudent to acknowledge these
possibilities and to counsel patients accordingly. The
single most important health effect of ART for the
offspring remains iatrogenic multiple fetal pregnancy. The American College of Obstetricians and
259
Gynecologists supports the effort toward lowering

the risk of multiple gestation with ART.
References
1. Guidelines on the number of embryos transferred. Practice
Committee of the Society for Assisted Reproductive
Technology and the American Society for Reproductive
Medicine. Fertil Steril 2004;82 Suppl 1:S12.
2. Badawi N, Kurinczuk JJ, Keogh JM, Alessandri LM,
OSullivan F, Burton PR, et al. Antepartum risk factors for
newborn encephalopathy: the Western Australian casecontrol study. BMJ 1998;317:154953.
3. Ozturk O, Bhattacharya S, Templeton A. Avoiding multiple pregnancies in ART: evaluation and implementation of
new strategies. Hum Reprod 2001;16:131921.
4. Cetin I, Cozzi V, Antonazzo P. Fetal development after
assisted reproductiona review. Placenta 2003;24 Suppl
B:S10413.
5. Schieve LA, Ferre C, Peterson HB, Macaluso M,
Reynolds MA, Wright VC. Perinatal outcome among singleton infants conceived through assisted reproductive
technology in the United States. Obstet Gynecol 2004;
103:114453.
6. Jackson RA, Gibson KA, Wu YW, Croughan MS.
Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 2004;103:
55163.
7. Donovan EF, Ehrenkranz RA, Shankaran S, Stevenson
DK, Wright LL, Younes N, et al. Outcomes of very low
birth weight twins cared for in the National Institute of
Child Health and Human Development Neonatal
Research Networks intensive care units. Am J Obstet
Gynecol 1998;179:7429.
8. Martin JA, Hamilton BE, Sutton PD, Ventura SJ,
Menacker F, Munson ML. Births: final data for 2002. Natl
Vital Stat Rep 2003;52:1113.
9. Powers WF, Kiely JL. The risks confronting twins: a
national perspective. Am J Obstet Gynecol 1994;170:
45661.
10. Stevenson DK, Wright LL, Lemons JA, Oh W, Korones
SB, Papile LA, et al. Very low birth weight outcomes of
Development Neonatal Research Network, January 1993
through December 1994. Am J Obstet Gynecol 1998;
179:16329.
11. Lynch A, McDuffie R, Murphy J, Faber K, Leff M,
Orleans M. Assisted reproductive interventions and multiple birth. Obstet Gynecol 2001;97:195200.
12. Jain T, Missmer SA, Hornstein MD. Trends in embryotransfer practice and in outcomes of the use of assisted
reproductive technology in the United States. N Engl J
Med 2004;350:163945.
13. Gleicher N, Oleske DM, Tur-Kaspa I, Vidali A, Karande
V. Reducing the risk of high-order multiple pregnancy
after ovarian stimulation with gonadotropins. N Engl J
Med 2000;343:27.
14. Licciardi F, Berkeley AS, Krey L, Grifo J, Noyes N. A
two- versus three-embryo transfer: the oocyte donation
model. Fertil Steril 2001;75:5103.
260
15. Staessen C, Janssenswillen C, Van den Abbeel E, Devroey

P, Van Steirteghem AC. Avoidance of triplet pregnancies
by elective transfer of two good quality embryos. Hum
Reprod 1993;8:16503.
16. Templeton A, Morris JK. Reducing the risk of multiple
births by transfer of two embryos after in vitro fertilization. N Engl J Med 1998;339:5737.
17. Grobman WA, Milad MP, Stout J, Klock SC. Patient perceptions of multiple gestations: an assessment of knowledge and risk aversion. Am J Obstet Gynecol 2001;185:
9204.
18. Bergh T, Ericson A, Hillensjo T, Nygren KG, Wennerholm
UB. Deliveries and children born after in-vitro fertilisation in Sweden 198295: a retrospective cohort study.
Lancet 1999;354:157985.
19. Ericson A, Kallen B. Congenital malformations in infants
born after IVF: a population-based study. Hum Reprod
2001;16:5049.
20. Wennerholm UB, Bergh C, Hamberger L, Lundin K,
Nilsson L, Wikland M. Incidence of congenital malformations in children born after ICSI. Hum Reprod
2000;15:9448.
21. Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of
major birth defects after intracytoplasmic sperm injection
and in vitro fertilization. N Engl J Med 2002;346:72530.
22. Chillon M, Casals T, Mercier B, Bassas L, Lissens W,
Silber S, et al. Mutations in the cystic fibrosis gene in
patients with congenital absence of the vas deferens. N
Engl J Med 1995;332:147580.
23. Dork T, Dworniczak B, Aulehla-Scholz C, Wieczorek D,
Bohm I, Mayerova A, et al. Distinct spectrum of CFTR
gene mutations in congenital absence of vas deferens.
Hum Genet 1997;100:36577.
24. Dohle GR, Halley DJ, Van Hemel JO, van den Ouwel AM,
Pieters MH, Weber RF, et al. Genetic risk factors in infertile men with severe oligozoospermia and azoospermia.
Hum Reprod 2002;17:136.
25. Feng HL. Molecular biology of male infertility. Arch

Androl 2003;49:1927.
26. Tournaye H. ICSI: a technique too far? Int J Androl 2003;
26:639.
27. Bonduelle M, Aytoz A, Van Assche E, Devroey P,
Liebaers I, Van Steirteghem A. Incidence of chromosomal
aberrations in children born after assisted reproduction
through intracytoplasmic sperm injection. Hum Reprod
1998;13:7812.
28. Bonduelle M, Ponjaert I, Van Steirteghem A, Derde MP,
Devroey P, Liebaers I. Developmental outcome at 2 years
of age for children born after ICSI compared with children born after IVF. Hum Reprod 2003;18:34250.
29. Int Veld P, Brandenburg H, Verhoeff A, Dhont M, Los F.
Sex chromosomal abnormalities and intracytoplasmic
sperm injection. Lancet 1995;346:773.
30. Loft A, Petersen K, Erb K, Mikkelsen AL, Grinsted J,
Hald F, et al. A Danish national cohort of 730 infants born
after intracytoplasmic sperm injection (ICSI) 19941997.
Hum Reprod 1999;14:21438.
31. Calogero AE, Burrello N, De Palma A, Barone N,
DAgata R, Vicari E. Sperm aneuploidy in infertile men.
Reprod Biomed Online 2003;6:3107.
32. Cox GF, Burger J, Lip V, Mau UA, Sperling K, Wu BL,
et al. Intracytoplasmic sperm injection may increase the
risk of imprinting defects. Am J Hum Genet 2002;71:
1624.
33. DeBaun MR, Niemitz EL, Feinberg AP. Association of in
vitro fertilization with BeckwithWiedemann syndrome
and epigenetic alterations of L1T1 and H19. Am J Hum
Genet 2003;72:15660.
34. Niemitz EL, Feinberg AP. Epigenetics and assisted reproductive technology: a call for investigation. Am J Hum
Genet 2004;74:599609.
COMMITTEE OPINIONS
ACOG
Committee
on Genetics
Reaffirmed 2007
261
Committee
Opinion

stored in a retrieval system, posted
on the Internet, or transmitted,
from the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Update on carrier screening for cystic

fibrosis. ACOG Committee Opinion
Update on Carrier Screening for

Cystic Fibrosis
ABSTRACT: In 2001, the American College of Obstetricians and Gynecologists and the American College of Medical Genetics introduced guidelines
for prenatal and preconception carrier screening for cystic fibrosis. The
American College of Obstetricians and Gynecologists has updated current
guidelines for cystic fibrosis screening practices among obstetrician
gynecologists.
Prenatal and preconception carrier screening for cystic fibrosis was introduced into routine obstetric practice in 2001. Preconception and Prenatal
Carrier Screening for Cystic Fibrosis: Clinical and Laboratory Guidelines
(1), developed by the American College of Obstetricians and Gynecologists
(ACOG) and the American College of Medical Genetics (ACMG), was sent
to all ACOG members in practice. According to a survey of ACOG members
2 years later, most obstetricians are offering cystic fibrosis carrier screening
to their pregnant patients (2). As recommended in the guidelines, most obstetricians ask their patients if there is a family history of cystic fibrosis and provide the pregnant patients with information on cystic fibrosis. In contrast,
significantly fewer obstetriciangynecologists offer nonpregnant patients
cystic fibrosis carrier screening unless a patient requests the information or
has a family history. After cystic fibrosis carrier screening was implemented,
the ACMG convened a work group to review the prevalence of mutations in
the general population and to evaluate the cystic fibrosis carrier screening
program in the United States. The purpose of this document is to provide an
update on cystic fibrosis carrier screening.
The goal of cystic fibrosis carrier screening is to identify couples at risk
for having a child with classic cystic fibrosis. The ACOG/ACMG guidelines
recommended that cystic fibrosis carrier screening be offered to Caucasian
couples (including Ashkenazi Jews) who are planning a pregnancy or seeking
prenatal care and be made available to all patients. This recommendation
took into account differences in cystic fibrosis prevalence and test sensitivity.
Cystic fibrosis is more common (ie, has higher carrier rate) in Caucasians
(including Ashkenazi Jews) than in other populations, and the screening test
detects a higher percentage of carriers in this population than in other popu-
262
lations (Table 1). In practice, two thirds of obstetricians offer cystic fibrosis carrier screening to all
pregnant patients rather than using the selective criteria. Because it is becoming increasingly difficult to
assign a single ethnicity, it is reasonable to offer cystic fibrosis carrier screening to all pregnant patients,
provided that women are aware of their carrier risk
and of the test limitations. The sensitivity of the
screening test and the carrier risk vary among different ethnic groups. The results often are reported with
a table of the residual carrier risk for each ethnic
group, and it is the physicians responsibility to
interpret the results based on the patients ethnicity.
A negative carrier screening test result can reduce
but not eliminate the risk of being a cystic fibrosis
carrier.
Generally, it is more cost-effective and practical
to perform initial carrier screening for the patient. If
the patient is a cystic fibrosis carrier then her partner
should be tested. Concurrent screening of the patient
and her partner is preferred if there are time constraints for decisions regarding prenatal diagnostic
testing or termination of the affected pregnancy. If a
woman is a carrier of a cystic fibrosis mutation and
her partner is unavailable for testing, genetic counseling to review the risk of having an affected child
and prenatal testing options and limitations in this
situation may be helpful.
Preconception carrier screening allows carrier
couples to consider the fullest range of reproductive
options. A significant proportion of obstetrician
gynecologists are not offering screening to their
nonpregnant patients unless there is a family history
or the patient specifically requests screening.
Knowledge of the risk for having an affected child
may influence a carrier couples decision to conceive, to use donor gametes, and to consider preimplantation or prenatal genetic testing.
The initial guidelines recommended that laboratories screen a panel of 25 pan-ethnic mutations that
were present in at least 0.1% of patients with cystic
fibrosis. Based on a review of the first 2 years of laboratory data from screening the general population,
the ACMG Cystic Fibrosis Carrier Screening Work
Group recommended that two mutations (I148T and
1078delT) be removed from the panel because they
do not cause classic cystic fibrosis or occur less frequently than 0.1%. The work group did not recommend additions to the panel at this time because they
would not substantially increase the test sensitivity
but acknowledged that some laboratories may
choose to add mutations to the standard panel to
increase the sensitivity of testing for specific ethnic
groups.
Cystic fibrosis screening may identify a 5T/7T/9T
variant, located in a noncoding region of the gene for
cystic fibrosis, the cystic fibrosis transmembrane regulator (CFTR) gene. During the first 2 years of carrier testing, some laboratories reported this variant
indiscriminately, resulting in some confusion in the
interpretation of test results. Testing for the variant as
a reflex test is appropriate only when the R117H
mutation is detected. Classic cystic fibrosis occurs
when 5T is on the same chromosome with R117H
and there is a CFTR mutation of the other chromosome. Other combinations of the 5T variant with a
CFTR mutation on the opposite chromosome are not
known to have a clinical significance in females.
Males with this genotype are at increased risk for
congenital bilateral absence of the vas deferens and
atypical cystic fibrosis. Couples with the R117H
mutation will benefit from genetic counseling.
Complete analysis of the CFTR gene by DNA
sequencing is not appropriate for routine carrier
screening. This type of testing generally is reserved
for patients with cystic fibrosis, a family history of
Table 1. Cystic Fibrosis Detection and Carrier Rates Before and After Testing
Racial or
Ethnic Group
Ashkenazi Jewish
Non-Hispanic Caucasian
Hispanic American
African American
Asian American
Detection
Rate
Carrier Rate
Before Testing
Carrier Risk After

Negative Test Result
94%
88%
72%
65%
49%
1/24
1/25
1/46
1/65
1/94
Approximately 1/400
Approximately 1/208
Approximately 1/164
Approximately 1/186
Approximately 1/184
COMMITTEE OPINIONS
cystic fibrosis, infertile males with congenital bilateral absence of the vas deferens, or a positive newborn screening test result when mutation testing
using an expanded panel of mutations has a negative
result.
The decision to have cystic fibrosis carrier
screening should be by informed choice. Patients
should receive information about cystic fibrosis and
its inheritance pattern. Educational brochures are
available from ACOG (sales.acog.org) and a brief
description is included in this document. It is important for patients and their partners to recognize the
sensitivity and limitations of testing as well as their
reproductive options. Molecular testing does not
identify all carriers. The ability to identify carriers
differs based on ethnic origin, ranging from less than
50% in Asian Americans to up to 94% in the
Ashkenazi Jewish population (Table 1). Therefore, a
negative carrier screening test result will reduce but
not eliminate the risk of being a cystic fibrosis carrier.
When both parents are carriers of CFTR mutations
that cause the disease, prenatal diagnosis by chorionic villus sampling or amniocentesis can be
accomplished using DNA analysis.
Based on the preceding information, the Committee on Genetics provides the following recommendations:
1. Information about cystic fibrosis screening
should be made available to all couples. It is reasonable to offer cystic fibrosis carrier screening
to all couples regardless of race or ethnicity as
an alternative to selective screening.
2. Cystic fibrosis carrier screening should be
offered before conception or early in pregnancy
when both partners are of Caucasian, European,
or Ashkenazi Jewish ethnicity. Patients may
elect to use either sequential or concurrent carrier screening; the latter option may be preferred
if there are time constraints for decisions regarding prenatal diagnostic testing or termination of
the affected pregnancy.
3. For individuals with a family history of cystic
fibrosis, medical records indicating the CFTR
mutation in the affected family member should
be obtained whenever possible. If the mutation
has not been identified, screening with an
expanded panel of mutations or, in some cases,
complete analysis of the CFTR gene by
sequencing may be indicated. Genetic counseling in this situation usually is beneficial.
263
4. Individuals who have a reproductive partner with

cystic fibrosis or congenital bilateral absence of
the vas deferens may benefit from screening with
an expanded panel of mutations or, in some
cases, a complete analysis of the CFTR gene by
sequencing.
5. When both partners are cystic fibrosis carriers,
genetic counseling is recommended to review
prenatal testing and reproductive options.
Prenatal diagnosis by chorionic villus sampling
or amniocentesis, using DNA-based testing of
the fetal cells, should be offered. If the partner is
unavailable for testing, genetic counseling may
be helpful.
6. Cystic fibrosis carrier screening may identify
individuals with two cystic fibrosis mutations
who have not previously received a diagnosis of
cystic fibrosis. These individuals may have a
milder form of cystic fibrosis and should be
referred to a specialist in cystic fibrosis for further evaluation. Genetic counseling also is beneficial.
Information on Cystic Fibrosis to Share

With Your Patients
Cystic fibrosis is a progressive, multisystem disease
that primarily affects the pulmonary, pancreatic, gastrointestinal, biliary, and reproductive systems.
Individuals with cystic fibrosis typically present
with cough, wheezing, failure to thrive, loose stools,
abdominal pain, and, in males, infertility secondary
to congenital bilateral absence of the vas deferens.
Treatment involves pancreatic enzymes, proper
nutrition, and respiratory therapy with aggressive
treatment of infection. The current median survival
is approximately 30 years, and the cause of death
usually is respiratory failure. Approximately 15% of
individuals with cystic fibrosis are pancreatic sufficient and have a milder disease course and a median
survival of 56 years.
Cystic fibrosis is an autosomal recessive genetic
condition. Therefore, when a patient and her partner
are both carriers of a mutation in the cystic fibrosis
gene, they have a one-in-four chance of having a
child with cystic fibrosis. More than 1,300 mutations
have been identified in the gene for cystic fibrosis,
but screening for 23 common mutations is available
and can reduce a couples risk for having a child with
cystic fibrosis. The risk of being a carrier depends on
an individuals ethnicity and family history.
264
References
American College of Medical Genetics. Preconception
and prenatal carrier screening for cystic fibrosis: clinical
and laboratory guidelines. Washington, DC: ACOG;
Bethesda (MD): ACMG; 2001.
2. Morgan MA, Driscoll DA, Mennuti MT, Schulkin J.
Practice patterns of obstetriciangynecologists regarding
preconception and prenatal screening for cystic fibrosis.
Genet Med 2004;6:4505.
Bibliography
Cystic fibrosis mutation database. Available at: http://www.
genet. sickkids.on.ca/cftr/. Retrieved March 18, 2005.
Grosse SD, Boyle CA, Botkin JR, Comeau AM, Kharrazi M,
Rosenfeld M, et al. Newborn screening for cystic fibrosis: eval-
uation of benefits and risks and recommendations for state

newborn screening programs. MMWR Recomm Rep 2004;
53(RR-13):136.
Morgan MA, Driscoll DA, Zinberg S, Schulkin J, Mennuti MT.
Impact of self-reported familiarity with guidelines for cystic
fibrosis carrier screening. Obstet Gynecol 2005;105:135561.
Muller F, Simon-Bouy B, Girodon E, Monnier N, Malinge
MC, Serre JL. Predicting the risk of cystic fibrosis with abnormal ultrasound signs of fetal bowel: results of a French molecular collaborative study based on 641 prospective cases. French
Collaborative Group. Am J Med Genet 2002;110:10915.
Watson MS, Cutting GR, Desnick RJ, Driscoll DA, Klinger K,
Mennuti M, et al. Cystic fibrosis population carrier screening:
2004 revision of American College of Medical Genetics mutation panel [published errata appear in Genet Med 2004;6:548;
Genet Med 2005;7:286]. Genet Med 2004;6:38791.
COMMITTEE OPINIONS
ACOG
Committee on
Genetics
Committee
Opinion
Number 338, June 2006

Copyright June 2006
from the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Screening for fragile X syndrome.

2006;107:14835.
265
(Replaces No. 161, October 1995)
Screening for Fragile X Syndrome

ABSTRACT: Fragile X syndrome is the most common inherited form of mental retardation, affecting approximately 1 in 4,000 males and 1 in 8,000
females. DNA-based molecular analysis is the preferred method of diagnosis
for fragile X syndrome and its premutations. Prenatal testing for fragile X
syndrome should be offered to known carriers of the premutation or mutation. Testing for fragile X syndrome should be considered for any child with
developmental delay of uncertain etiology, autism, or autistic behavior or for
any individual with mental retardation of uncertain etiology. Women with
ovarian failure or an elevated follicle-stimulating hormone level before 40
years of age without a known cause should be screened to determine whether
they have the fragile X premutation.
Fragile X syndrome is the most common inherited form of mental retardation, affecting approximately 1 in 4,000 males and 1 in 8,000 females from
a variety of ethnic backgrounds. Mental retardation ranges from borderline
to severe, although most patients have moderate degrees of mental retardation. Other associated phenotypic abnormalities include autistic behaviors,
macroorchidism in adult males, characteristic narrow face with a large jaw,
and speech and language problems. The abnormal facial features are subtle
and become more noticeable with age, making phenotypic diagnosis difficult, especially in the newborn. Affected females may have a more subtle
phenotype and it is sometimes hard to establish the diagnosis.
Fragile X syndrome is transmitted in a classic X-linked recessive fashion. However, the molecular genetics of the syndrome are complex. The
disorder is caused by expansion of a repeated trinucleotide segment of
DNA (cytosineguanineguanine) that leads to altered transcription of the
fragile X mental retardation 1 (FMR1) gene. The number of repeats varies
among individuals and has been classified into four groups depending on
repeat size: unaffected, intermediate, premutation, and full mutation (see
Table 1). A person with 61200 repeats usually is phenotypically normal
and is said to have a premutation. When more than 200 repeats are present,
an individual has a full mutation that results in the full expression of fragile X syndrome in males and variable expression in females secondary to X
inactivation. This condition occurs because the large number of repeats
causes the FMR1 gene to become methylated and inactivated in these
patients. The number of repeats and the status of gene methylation are
266
Table 1. Mutation in the Fragile X Mental Retardation 1

Gene
Status of Individual
Unaffected
Intermediate
(also called grey zone)
Premutation
Full mutation
Number of Triplet Repeats

(CytosineGuanineGuanine)
Less than 40
4160
61200
More than 200
determined by use of DNA-based molecular tests

(eg, Southern blot analysis and polymerase chain
reaction). Chorionic villus sampling (CVS),
although reliable for determinating the number of
triplet repeats, may not be reliable for diagnosis
because of gestational age differences in ultimate
methylation patterns in the trophoblast and may not
adequately determine the methylation status of the
FMR1 gene. DNA methylation is a process that
controls tissue specific gene expression. Methylation turns off the regulatory region of a gene,
thereby preventing DNA transcription. Rarely, the
size of the triplet repeat and the methylation status
do not correlate, making prediction of the clinical
phenotype difficult.
Transmission of a disease-producing mutation to
a fetus depends on the sex of the parent and the number of cytosineguanineguanine repeats present in
the parental gene. Parents at risk for transmission of
the disease are those who have the premutation or the
full DNA mutation. When a female carries the premutation and the length of the repeat exceeds 90,
premutation genes are much more likely to expand
and result in the birth of an affected child. Women
with an intermediate number of triplet repeats
(4160) rarely transmit a full mutation to their offspring, although there may be some continued
expansion through the generations. Genetic counseling for intermediate results may be useful. Males
may transmit the unexpanded premutation gene to
their children, but expansion to a full mutation is
extremely rare in the offspring of a male having the
premutation gene. Typically, the children of a male
premutation carrier receive the premutation
unchanged; in children of female carriers, however,
the premutation may expand during meiosis.
Empirically determined risks are available for the
purposes of genetic counseling.
Males and, to a lesser extent, females carrying a
premutation are at increased risk for a late-onset
neurodegenerative disorder characterized by tremor

and ataxia. However, additional research is needed
to define the relative risk. In addition, women carrying a premutation are at increased risk (2030%) for
premature ovarian failure. If a woman has ovarian
failure or an elevated follicle-stimulating hormone
level before the age 40 years without a known cause,
fragile X carrier screening should be considered to
determine whether she has a premutation. Recent
studies also have demonstrated an increased frequency of autism or autisticlike behavior in children
with a premutation.
The Committee on Genetics recommendations
regarding testing for fragile X syndrome are listed as
follows:
1. DNA-based molecular analysis (eg, Southern blot
analysis and polymerase chain reaction) is the
preferred method of diagnosis for fragile X syndrome and its premutations. In rare cases where
there is discordancy between the triplet repeat
number and the methylation status, the patient
should be referred to a genetic specialist.
2. Patients with a family history of mental retardation or a history of fragile X mental retardation
should receive genetic counseling and should be
offered genetic testing to assess their risk for having an affected child.
3. Prenatal testing for fragile X syndrome by
amniocentesis or CVS should be offered to
known carriers of the fragile X premutation or
mutation. Although it is reliable for determining
the number of triplet repeats, CVS may not adequately determine the methylation status of the
FMR1 gene.
4. Testing for fragile X syndrome should be considered in any child with developmental delay of
uncertain etiology, autism, or autisticlike behavior
or any individual with mental retardation of
uncertain etiology.
5. If a woman has ovarian failure or an elevated follicle-stimulating hormone level before the age 40
years without a known cause, fragile X carrier
screening should be considered to determine
whether she has a premutation.
Bibliography
Warren ST, Sherman SL. The fragile x syndrome. In: Scriver
CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and
molecular bases of inherited disease. 8th ed. New York (NY):
McGraw-Hill; 2001. p. 125789.
COMMITTEE OPINIONS
Hagerman RJ, Hagerman PJ, editors. Fragile X syndrome:

diagnosis, treatment, and research. 3rd ed. Baltimore (MD):
Johns Hopkins University Press; 2002.
Hagerman PJ, Hagerman RJ. The fragile-X premutation: a
maturing perspective [published erratum appears in Am J Hum
genet 2004;75:352]. Am J Hum Genet 2004;74:80516.
267
Sherman S, Pletcher BA, Driscoll DA. Fragile X syndrome:

diagnostic and carrier testing. Genet Med 2005;78:5847.
268

Newborn Screening
Committee on
Genetics
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Newborn screening tests are designed to detect infants with specific
conditions whose families also would benefit from early diagnosis and treatment. These
conditions include disorders of metabolism, endocrinopathies, hemoglobinopathies,
hearing loss, and cystic fibrosis. Each state program must have a system in place for notification, timely follow-up, and evaluation of any infant with a positive screening result.
Newborn screening programs have enormous public health benefits and have been
effective in identifying newborns that can benefit from early treatment.
Obstetricians need to be aware of the status

of newborn screening in their states and
should be prepared to address questions or
refer their patients to appropriate sources for
additional information. Newborn screening
tests are designed to detect infants with specific conditions whose families also would
benefit from early diagnosis and treatment.
These conditions include disorders of metabolism, endocrinopathies, hemoglobinopathies, hearing loss, and cystic fibrosis. These
screening tests secondarily may identify couples who are carriers of inherited conditions.
Currently, state public health agencies fund
and implement newborn screening programs
for their own residents, leading to variations
in practice nationwide.
Technologic advances in combination
with new genetic information have led to a
re-examination of the implementation and
standardization of newborn screening practices across the United States. These efforts
are lead by the Health and Human Resources
Services Administration Maternal Child and
Health Bureau. As providers of obstetric services, obstetriciangynecologists are advocates for women and play an expanded role
in newborn screening (14). A recent report
by the American Academy of Pediatrics
highlights the need for a more uniform
national policy for the selection of newborn
screening tests. In response, the American
College of Medical Genetics was commissioned by the Health and Human Resources
Services Administration Maternal Child and
Health Bureau to determine a uniform panel
of core conditions appropriate for newborn
screening. Each of the 29 conditions in the

core panel (Table 1) has a screening test that
can be performed within 2448 hours after
birth, can be treated, and has a known natural history. It is intended that this core panel
remain flexible and criteria yet to be established will be used to expand this panel in the
future. Secondary targets (supplemental conditions) are conditions that can be detected
using the same technology as in the detection
of core conditions (Table 1). Although secondary targets are clinically important, they
may lack known treatments or their natural
histories may not be well understood.
Most states require newborn screening
for the core panel, and a number of states
require newborn screening for some conditions on the secondary panel. However, the
list of conditions screened for in each state
can be expected to change over time; a listing
of the most current panel of conditions
screened for by states can be viewed at the
web site of the National Newborn Screening
and Genetics Resource Center (http://genesr-us.uthscsa. edu).
Collection of newborn heel stickderived blood onto filter paper specimens
remains the method of sample collection.
Technologic advances have enabled newborn
screening to rely less on single platform tests
and more on multiplex technology, such as
tandem mass spectrometry (MS/MS),
immunoassay, and spectrophotometry.
Newborn screening may now include 1)
screening for genetic conditions that relies on
polymerase chain reaction and immunoassay
(eg, cystic fibrosis), 2) screening for hemo-
COMMITTEE OPINIONS
269
Table 1. Newborn Screening Panel: Core Panel and Secondary Targets

Tandem Mass Spectrometry
Acylcarnitines
Conditions of
Organic Acid
Metabolism
Amino Acids
Conditions of
Fatty Acid
Metabolism
Conditions of
Amino Acid
Metabolism
Hemoglobinopathies
Others
CORE PANEL
Glutaric acidemia type 1
Medium-chain acyl-CoA
dehydrogenase deficiency
3-hydroxy 3-methyl glutaric

aciduria
Very long-chain acyl-CoA

Multiple carboxylase deficiency
Long-chain 3-OH acyl-CoA

Isovaleric acidemia
Methylmalonic acidemia
(mutase)
3-Methylcrotonyl-CoA
carboxylase deficiency
Phenylketonuria
Maple syrup (urine)
disease
Homocystinuria
Hb SS disease (sickle
cell anemia)
Congenital hypothyroidism
Hb S/-thalassemia
Biotinidase deficiency
Hb S/C disease
Congenital adrenal
hyperplasia
Citrullinemia
Trifunctional protein deficiency

Carnitine uptake defect
Argininosuccinic
acidemia
Classic galactosemia
Tyrosinemia type I
Cystic fibrosis
Hearing loss
(Cbl A, B)
Propionic acidemia
-Ketothiolase deficiency
SECONDARY TARGETS
(Cbl C, D)
Short-chain acyl-CoA dehydrogenase deficiency
Benign hyperphenylalaninemia
Malonic aciduria
Isobutyryl-CoA dehydrogenase
deficiency
Glutaric acidemia type II
Tyrosinemia type II
Medium/short-chain 3-OH
acyl-CoA DH deficiency
Defects of biopterin
cofactor biosynthesis
2-Methyl 3-hydroxy butyric

aciduria
Medium chain ketoacyl-CoA

thiolase deficiency
Argininemia
2-Methylbutyryl-CoA carboxylase
deficiency
Carnitine palmitoyltransferase II deficiency
Defects of biopterin
cofactor regeneration
3-Methylglutaconic aciduria
Carnitine/acylcarnitine
translocase deficiency
Hypermethioninemia
Carnitine palmitoyltransferase Ia deficiency (L)
Other variant hemoglobinopathies

(including Hb E)
Galactokinase deficiency
Galactose epimerase
deficiency
Tyrosinemia type III
Citrullinemia type II
Dienoyl-CoA reductase
deficiency
Abbreviations: Cbl indicates cobalamin; Hb, hemoglobin.
Maternal and Child Health Bureau. Newborn screening: toward a uniform screening panel and system. Executive summary. Rockville (MD): MCHB; 2005. Available at:
http://mchb.hrsa.gov/screening/summary.htm. Retrieved September 10, 2007.
globinopathies that uses isoelectric focusing, high-performance liquid chromatography, or electrophoresis, 3)

screening for hearing loss that incorporates either otoacoustic emissions or auditory brainstem response, and 4)
screening for infectious diseases (eg, human immunodeficiency virus [HIV] and toxoplasmosis) using immuno-
assays for disease specific immunoglobulin G and

immunoglobulin M antibodies.
Newborn screening programs are expected to operate with maximal sensitivity and specificity within a public health model that must account for population-based
challenges that are distinct from the more familiar chal-
270
lenges of a single-patient diagnosis. There are at least

eight different testing platforms used in screening for the
29 conditions listed in Table 1 (eg, MS/MS screens for 22
of the listed conditions). Although patients may inquire
regarding the detection rate (sensitivity) and the positive
predictive value, these data are not readily available for
the aggregate of tests. Performance data for specific
screening tests or platforms require discussions with the
state screening laboratory. State-specific contact information for newborn screening programs can be found at the
web site of the National Newborn Screening and Genetics
Resource Center (http://genes-r-us.uthscsa.edu).
Statistical uncertainty is driven in large part by the
addition of MS/MS technology used to screen for rare
metabolic conditions (Table 1). With any technology, the
rate of false-positive results are reduced as experience
grows (5). Defining detection rates using MS/MS is complicated by incomplete data reporting, variation in testing procedures, variation in definition of false-positive
results, variation in case definition, and nonuniform
screening thresholds. Calculating detection rates is made
difficult by the nature of the disorders being screened for
and the inability to determine prevalence with confidence. For example, it is not uncommon for children
with rare metabolic disorders to succumb before a diagnosis can be made. These aspects are compounded by the
problems commonly encountered in clinical laboratory
settings, including inadequate clinical information and
mislabeled samples. Performance goals for newborn
screening using MS/MS have been suggested (6). On
average, the number of neonates that must be tested to
detect one affected patient should be approximately
3,000. A performance goal is used to ensure that at least
one fifth of patients (20%) with a positive screening
result will, after follow-up testing, be determined to be
affected (positive predictive value). Finally, by addressing
causes of false-positive rates, these may be reduced to
approximately 3 per 1,000 results. These screening test
performance goals compare with first-trimester screening for aneuploidy as follows: 1) at least 67 individuals
per 3,000 screened individuals are affected, 2) the positive predictive value for patients aged 35 years is approximately 45%, 3) the false-positive rate for first trimester
screening is approximately 5% for women younger than
35 years at the time of delivery (79).
Each state program must have a system in place for
notification, timely follow-up, and evaluation of any
infant with a positive screening result. Furthermore, the
system should incorporate protocols for more evaluation,
treatment, and long-term follow-up for any infant whose
positive screening result suggests a likely risk of the condition. Positive newborn screening results typically are
reported to the newborns primary care provider and,
subsequently, the custodial parent(s).
Patients typically are not billed for their participation
in newborn screening programs. Newborn screening is
mandated by state statute or regulation, and, in most states,
parents are informed that testing will be done as part of

standard care unless they specifically decline (opt out
consent process); Maryland, the District of Columbia, and
Wyoming currently require written consent (opt in).
Many states allow parents to refuse testing based on religious or personal grounds. Hospitals and newborn
nurseries usually provide written materials to parents
immediately postpartum to inform them of the newborn
screening their children will undergo. Survey data suggest
that patients are underinformed regarding newborn
screening (10) and desire information during the prenatal period. Prenatal education about newborn screening
not only provides parents with the reasons for obtaining
their newborns blood specimen, but also informs them
that an initial positive test result does not necessarily
mean that their child has the condition for which the
screening result was positive. Materials are available on
the web site of the American College of Obstetricians and
Gynecologists (http://www.acog.org/from_home/misc/
dept_pubs.cfm).
Newborn screening programs have enormous public
health benefits and have been effective in identifying newborns that can benefit from early treatment. In addition,
many couples have been made aware of their carrier status because of diagnoses in their newborns. There are
many important issues surrounding the debate on universal screening, including financial resources, level of
screening, continuity of care, and informed consent. To
date, policy on newborn screening has been fragmented,
but efforts are underway to ensure uniformity and equity
for all newborns. Obstetriciangynecologists are encouraged to make written or video materials or electronic
information available to parents regarding the availability
of newborn screening tests.
References
1. Newborn screening: toward a uniform screening panel and
systemexecutive summary. American College of Medical
Genetics Newborn Screening Expert Group. Pediatrics
2006;117:S296307.
2. Lloyd-Puryear MA, Tonniges T, van Dyck PC, Mann MY,
Brin A, Johnson K, et al. American Academy of Pediatrics
Newborn Screening Task Force recommendations: how far
have we come? Pediatrics 2006;117(suppl):S194211.
3. Larsson A, Therrell BL. Newborn screening: the role of the
obstetrician. Clin Obstet Gynecol 2002;45:697710; discussion 7302.
4. Campbell ED, Ross LF. Incorporating newborn screening
into prenatal care. Am J Obstet Gynecol 2004;190:8767.
5. Feuchtbaum L, Faulkner L, Verghese S. Tandem mass spectrometry program implementation challenges for state
newborn screening programs: national survey of barriers
and issues. Pediatrics 2006;117(suppl):S25360.
6. Rinaldo P, Zafari S, Tortorelli S, Matern D. Making the case
for objective performance metrics in newborn screening by
tandem mass spectrometry. Ment Retard Dev Disabil Res
Rev 2006;12:25561.
COMMITTEE OPINIONS
7. Screening for fetal chromosomal abnormalities. ACOG

8. Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH,
Bukowski R, et al. First-trimester or second-trimester
screening, or both, for Downs syndrome. First- and
Second-Trimester Evaluation of Risk (FASTER) Research
Consortium. N Engl J Med 2005;353:200111.
9. Gardner RJ, Sutherland GR. Parental age counseling and
screening for fetal trisomy. In: Chromosome abnormalities
and genetic counseling. 3rd ed. New York (NY): Oxford
10. Davis TC, Humiston SG, Arnold CL, Bocchini JA Jr, Bass PF
3rd, Kennen EM, et al. Recommendations for effective newborn screening communication: results of focus groups
271
with parents, providers, and experts. Pediatrics 2006;117

(suppl): S32640.
Newborn screening. ACOG Committee Opinion No. 393. American
2007;110:1497500.
ISSN 1074-861X
272

(Replaces No. 183, April 1997)
Umbilical Cord Blood Banking

Committee on
Obstetric Practice
Committee on
Genetics
followed.
ABSTRACT: Two types of banks have emerged for the collection and storage of
umbilical cord bloodpublic banks and private banks. Public banks promote allogenic
(related or unrelated) donation, analogous to the current collection of whole blood units
in the United States. Private banks were initially developed to store stem cells from
umbilical cord blood for autologous use (taken from an individual for subsequent use by
the same individual) by a child if the child develops disease later in life. If a patient
requests information on umbilical cord blood banking, balanced and accurate information
regarding the advantages and disadvantages of public versus private banking should be
provided. The remote chance of an autologous unit of umbilical cord blood being used for
a child or a family member (approximately 1 in 2,700 individuals) should be disclosed. The
collection should not alter routine practice for the timing of umbilical cord clamping.
Physicians or other professionals who recruit pregnant women and their families for forprofit umbilical cord blood banking should disclose any financial interests or other potential conflicts of interest.
Introduction

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Once considered a waste product that was

discarded with the placenta, umbilical cord
blood is now known to contain potentially
life-saving hematopoietic stem cells. When
used in hematopoietic stem cell transplantation, umbilical cord blood offers several distinct advantages over bone marrow or
peripheral stem cells. Biologically, a greater
degree of human leukocyte antigen mismatch is tolerated by the recipient and the
incidence of acute graft-versus-host reaction
is decreased when umbilical cord blood is
used (1, 2). The predominant disadvantage of
umbilical cord blood use is related to the low
number of stem cells acquired per unit.
However, the use of combined units of
umbilical cord blood allows for the expansion of umbilical cord blood volume (and
increased number of stem cells) to be used
for adult hematopoietic transplants. Studies
are currently underway evaluating the feasibility of ex vivo expansion of the units (3, 4).
Since the first successful umbilical cord blood
transplant in 1988, it has been estimated
that more than 7,000 transplants have been
performed in children and adults for the correction of inborn errors of metabolism,
hematopoietic malignancies, and genetic disorders of the blood and immune system (5).
Two types of banks have emerged for the
collection and storage of umbilical cord
bloodpublic banks and private banks. The
first public bank was established at the New
York Blood Center in 1991 and other public
banks have since been established in various
regions of the country. In 1999, the National
Bone Marrow Donor Program established a
network of these banks listing their units on
the National Bone Marrow Donor Program
Registry and established the Center for Cord
Blood in 2005 (6). As part of this effort, specific subcommittees have been established to
address issues related to umbilical cord blood
banking, such as standards, quality improvement, donor recruitment, collection, testing,
and processing methodology. In December
2005, federal legislation was enacted that
provides funding for continued growth of a
national umbilical cord blood registry in the
United States through the C.W. Bill Young
Cell Transplantation Act. Some states have
passed legislation requiring physicians to
inform their patients about umbilical cord
blood banking options. Clinicians should
consult their state medical associations for
more information regarding state laws.
COMMITTEE OPINIONS
Public banks promote allogenic (related or unrelated) donation, analogous to the current collection of whole
blood units in the United States. These banks typically are
associated with a local network of obstetric hospitals that
send their units of blood to a central processing facility. A
minority of public banks will accept units from any provider through shipment by an overnight express courier
(7). Units of umbilical cord blood collected for public
banks must meet rigorous standards of donor screening
and infectious disease testing as outlined by the U.S. Food
and Drug Administration. Initial human leukocyte antigen typing of these units allows them to be entered into
computerized registries so that when the need arises, a
specific unit can be rapidly located for a patient.
Private banks were initially developed to store stem
cells from umbilical cord blood for autologous use (taken
from an individual for subsequent use by the same individual) by a child if the child develops disease later in life.
There is a cost associated with the initial specimen processing and an annual storage fee for for-profit umbilical
cord blood banks (8).
The utility of long-term storage of autologous
umbilical cord blood has been questioned. There is no
accurate estimate of an individuals likelihood of using an
autologous unit of umbilical cord blood. One estimate is
approximately 1 in 2,700 individuals, whereas others
argue that the rate would be even lower (9). Stem cells
obtained from banked umbilical cord blood cannot currently be used to treat inborn errors of metabolism or
other genetic diseases in the same individual from whom
they were collected because the genetic mutation would
already be present in the stem cells. Autologous umbilical
cord blood is not used as a source of stem cells to treat
childhood leukemia because chromosomal translocations
in fetal blood have been detected in some children who
ultimately develop leukemia (10, 11). In addition, the use
of autologous stem cells would negate the beneficial graftversus-leukemic effect that occurs with allogenic stem cell
transplants (9).
Recommendations and Conclusions

If a patient requests information on umbilical cord
banking, balanced and accurate information regarding the advantages and disadvantages of public versus private umbilical cord blood banking should be
provided. The remote chance of an autologous unit
being used for a child or a family member (approximately 1 in 2,700 individuals) should be disclosed.
Discussion may include information regarding
maternal infectious disease and genetic testing, the
ultimate outcome of use of poor quality units of
umbilical cord blood, and a disclosure that demographic data will be maintained on the patient.
Some states have passed legislation requiring physicians to inform their patients about umbilical cord
blood banking options. Clinicians should consult
273
their state medical associations for more information

regarding state laws.
Directed donation of umbilical cord blood should be
considered when there is a specific diagnosis of a disease known to be treatable by hematopoietic transplant for an immediate family member.
Obstetric providers are not obligated to obtain consent for private umbilical cord blood banking.
The collection should not alter routine practice for
the timing of umbilical cord clamping.
Physicians or other professionals who recruit pregnant women and their families for for-profit umbilical cord blood banking should disclose any financial
interests or other potential conflicts of interest.
References
1. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ,
Champlin RE, et al. Outcomes after transplantation of cord
blood or bone marrow from unrelated donors in adults
with leukemia. N Engl J Med 2004;351:226575.
2. Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R,
Bosi A, et al. Transplants of umbilical-cord blood or bone
marrow from unrelated donors in adults with acute
leukemia. Acute Leukemia Working Party of European
Blood and Marrow Transplant Group; Eurocord-Netcord
Registry. N Engl J Med 2004;351:227685.
3. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB,
Miller JS, et al. Transplantation of 2 partially HLA-matched
umbilical cord blood units to enhance engraftment in
adults with hematologic malignancy. Blood 2005;105:
13437.
4. Jaroscak J, Goltry K, Smith A, Waters-Pick B, Martin PL,
Driscoll TA, et al. Augmentation of umbilical cord blood
(UCB) transplantation with ex vivo-expanded UCB cells:
results of a phase 1 trial using the AastromReplicell System.
Blood 2003;101:50617.
5. Moise KJ Jr. Umbilical cord stem cells. Obstet Gynecol
2005;106:1393407.
6. National Marrow Donor Program. Where to donate cord
blood. Minneapolis (MN): NMDP; 2007. Available at:
http://www.marrow.org/HELP/Donate_Cord_Blood_Share
_Life/How_to_Donate_Cord_Blood/CB_Participating_Hos
pitals/nmdp_cord_blood_hospitals.pl. Retrieved August 22,
2007.
7. Parents Guide to Cord Blood. Public cord blood banks in
the USA. Available at: http://parentsguidecordblood.org/
content/usa/banklists/publicbanks_new.shtml?navid=9.
8. Parents Guide to Cord Blood. Family cord blood banks in
the USA. Available at: http://parentsguidecordblood.org/
content/usa/banklists/listusa.shtml?navid=11. Retrieved
August 22, 2007.
9. Johnson FL. Placental blood transplantation and autologous bankingcaveat emptor. J Pediatr Hematol Oncol
1997;19:1836.
10. Rowley JD. Backtracking leukemia to birth. Nat Med
1998;4:1501.
274
11. Greaves MF, Wiemels J. Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer 2003;3:
63949.
Additional Resources
National Marrow Donor Program
3001 Broadway Street, NE
Minneapolis, MN 55413
612-627-5000 or 1-800-627-7692
http://www.marrow.org
Parents Guide to Cord Blood Banks
http://parentsguidecordblood.org
141 Northwest Point Boulevard.
Elk Grove Village, IL 60007
847-434-4000
http://www.aap.org
American Association of Blood Banks
8101 Glenbrook Road
Bethesda, MD 20814
301-907-6977
http://www.aabb.org

Umbilical cord blood banking. ACOG Committee Opinion No. 399.
Gynecol 2008;111:4757.
ISSN 1074-861X
COMMITTEE OPINIONS
275

Preimplantation Genetic Screening for

Aneuploidy
Committee on
Genetics
followed.
ABSTRACT: Preimplantation genetic screening differs from preimplantation genetic

diagnosis for single gene disorders and was introduced for the detection of chromosomal aneuploidy. Current data does not support a recommendation for preimplantation
genetic screening for aneuploidy using fluorescence in situ hybridization solely because
of maternal age. Also, preimplantation genetic screening for aneuploidy does not improve
in vitro fertilization success rates and may be detrimental. At this time there are no data
to support preimplantation genetic screening for recurrent unexplained miscarriage and
recurrent implantation failures; its use for these indications should be restricted to
research studies with appropriate informed consent.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Preimplantation genetic screening differs

from preimplantation genetic diagnosis
(PGD) for single gene disorders. In order to
perform genetic testing for single gene disorders, PGD was introduced in 1990 as a component of in vitro fertilization programs. Such
testing allows the identification and transfer
of embryos unaffected by the disorder in
question and may avoid the need for pregnancy termination (1). Assessment of polar bodies as well as single blastomeres from cleavage
stage embryos has been reported, although
the latter is the approach most widely practiced. Preimplantation genetic diagnosis has
become a standard method of testing for single gene disorders, and there have been no
reports to suggest adverse postnatal effects of
the technology. Preimplantation genetic diagnosis has been used for diagnosis of translocations and single-gene disorders, such as cystic
fibrosis, X-linked recessive conditions, and
inherited mutations, which increase ones risk
of developing cancer.
In contrast, in the latter half of the 1990s,
preimplantation genetic screening was introduced for the detection of chromosomal aneuploidy (24). Aneuploidy leads to increased
pregnancy loss with increasing maternal age
and also was thought to be a major cause of
recurrent pregnancy loss in patients using
assisted reproductive technologies. However,
when compared with the molecular diagnos-
tics available for PGD of single gene disorders, the current technologies available for
preimplantation genetic screening for aneuploidy are more limited. Preimplantation
genetic screening using fluorescence in situ
hybridization is constrained by the technical
limitations of assessing the numerical status
of each chromosome. Typically assessed are
the chromosome abnormalities associated
with common aneuploidies found in spontaneous abortion material, and because of this,
and other limitations noted in this Committee
Opinion, a significant false-negative rate exists.
Therefore, this form of testing should be considered a screening test, and not a diagnostic
test, as is the case for PGD for single gene disorders.
Because preimplantation chromosome
assessment tests a single cell, there are certain
limitations:
Testing a single cell prohibits confirmation of results.
There is a limit to the number of tests
that can be done with a single cell.
Embryo mosaicism of normal and aneuploid cell lines may not be clinically significant.
Guidelines for counseling on limitations
of this screening have been developed by the
American Society for Reproductive Medicine
(5).
276
Nonrandomized studies of preimplantation genetic

screening in women with advanced maternal age suggested
improved implantation rates and decreased spontaneous
abortion rates but did not document an improvement in
live birth rates (36). A study of women with recurrent
miscarriages found no evidence of benefit of preimplantation genetic screening in women of any age (7). There
have now been two randomized trials for women older
than 35 years comparing in vitro fertilization with and
without preimplantation genetic screening for aneuploidy
(89). Neither study provides support for preimplantation
genetic screening in women older than 35 years, and one
study suggests lowered live birth rates, possibly due to the
impact of the biopsy on the embryos ability to implant
(8).
Recommendations
Current data does not support a recommendation
for preimplantation genetic screening for aneuploidy
using fluorescence in situ hybridization solely
because of maternal age.
Preimplantation genetic screening for aneuploidy
does not improve in vitro fertilization success rates
and may be detrimental.
At this time there are no data to support preimplantation genetic screening for recurrent unexplained
miscarriage and recurrent implantation failures; its
use for these indications should be restricted to
research studies with appropriate informed consent.
4.
5.
6.
7.
8.
9.
aneuploidy in human embryos. Hum Reprod 1999;14:

21919.
Gianaroli L, Magli MC, Ferraretti AP, Munne S.
Preimplantation diagnosis for aneuploidies in patients
undergoing in vitro fertilization with a poor prognosis:
identification of the categories for which it should be proposed. Fertil Steril 1999;72:83744.
Preimplantation genetic testing: a Practice Committee
opinion. Practice Committee of the Society for Assisted
Reproductive Technology; Practice Committee of the
American Society for Reproductive Medicine. Fertil Steril
2007;88:1497504.
Munne S, Chen S, Fischer J, Colls P, Zheng X, Stevens J, et al.
Preimplantation genetic diagnosis reduces pregnancy loss
in women aged 35 years and older with a history of recurrent miscarriages. Fertil Steril 2005;84:3315.
Munne S, Fischer J, Warner A, Chen S, Zouves C, Cohen J.
Preimplantation genetic diagnosis significantly reduces
pregnancy loss in infertile couples: a multicenter study.
Referring Centers PGD Group. Fertil Steril 2006;85:32632.
Platteau P, Staessen C, Michiels A, Van Steirteghem A,
Liebaers I, Devroey P. Preimplantation genetic diagnosis for
aneuploidy screening in patients with unexplained recurrent miscarriages. Fertil Steril 2005;83:393,7; quiz 5256.
Staessen C, Platteau P, Van Assche E, Michiels A, Tournaye
H, Camus M, et al. Comparison of blastocyst transfer with
or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a
prospective randomized controlled trial. Hum Reprod
2004;19:284958.
References
1. Handyside AH, Kontogianni EH, Hardy K, Winston RM.
Pregnancies from biopsied human preimplantation
embryos sexed by Y-specific DNA amplification. Nature
1990;344:76870.
2. Gianaroli L, Magli MC, Ferraretti AP, Fiorentino A, Garrisi
J, Munne S. Preimplantation genetic diagnosis increases the
implantation rate in human in vitro fertilization by avoiding the transfer of chromosomally abnormal embryos.
3. Munne S, Magli C, Cohen J, Morton P, Sadowy S, Gianaroli
L, et al. Positive outcome after preimplantation diagnosis of
Copyright March 2009 by the American College of Obstetricians and

ISSN 1074-861X
Preimplantation genetic screening for aneuploidy. ACOG Committee
COMMITTEE OPINIONS
277

Number 432 May 2009
Spinal Muscular Atrophy

Committee on
Genetics
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that results from degeneration of spinal cord motor neurons leading to
atrophy of skeletal muscle and overall weakness. In current practice, patients with a
family history of SMA are being offered carrier screening for the survival motor neuron
gene (SMN1) deletion mutations. Recent marketing and public awareness campaigns by
laboratories and advocacy organizations are promoting widespread population-based
carrier screening for SMA in the prenatal or preconception setting, regardless of family
history. However, the American College of Obstetricians and Gynecologists Committee
on Genetics agrees that preconception and prenatal screening for SMA is not recommended in the general population at this time.
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that

results from degeneration of spinal cord
motor neurons leading to atrophy of skeletal
muscle and overall weakness. The disorder is
caused by a mutation in the gene known as
the survival motor neuron gene (SMN1),
which is responsible for the production of a
protein essential to motor neurons. There has
been recent interest, by both private and professional organizations, in carrier screening
for SMA in the general prenatal population
(1). This interest has been prompted both by
the severity of the disease and relatively high
carrier frequency, as well as the advent of
improved DNA diagnostic assays for mutations in the disease causing gene (SMN1).
The genetics of SMA is complex, and because
of limitations in the molecular diagnostic
assays available, accurate prediction of the
phenotype in affected fetuses may be not be
possible.
The incidence of SMA is approximately
1 in 10,000 live births and it is reported to be
the leading genetic cause of infant death.
Carrier frequencies are estimated at 1 in 40 to
1 in 60. There is no effective treatment for the
disease. The most severe form, type I
(WernigHoffman), has symptomatic onset
of the disease before 6 months of age and
death from respiratory failure within the first
2 years of life. Type II, the most common
form of SMA disease, is of intermediate
severity, with typical onset before 2 years

of age. Affected children are able to sit but
few are able to stand or walk unaided.
Respiratory insufficiency is a frequent cause
of death during adolescence; however, the
lifespan of patients with SMA type II varies
from 2 years to the third decade of life. A
milder form, type III (KugelbergWelander),
has typical symptomatic onset after 18
months of age. However, the symptom profile of affected children is quite variable. They
typically reach all major motor milestones,
but function ranges from requiring wheelchair assistance in childhood to completely
unaided ambulation into adulthood with
minor muscular weakness. Many patients
have normal life expectancies. There are other
forms of SMA-like disorders with similar
symptoms as those described previously, but
they are linked to genes other than SMN1.
Molecular Genetics
There are two nearly identical survival motor
neuron genes present in humans, known as
SMN1 and SMN2. SMN1 is considered the
active gene for survival motor neuron protein production and more than 98% of
patients with SMA have an abnormality in
both SMN1 genes, which can be caused by a
deletion (95%), or other mutation. There is
generally one, but occasionally two, copies
of SMN1 per chromosome and a variable
number of SMN2 gene copies (ranging from
278
zero to three). The SMN2 gene does not produce much

in the way of functional survival motor neuron protein.
However, the primary genetic feature, which determines
the severity of SMA, appears to be the number of gene
copies of SMN2 in a given individual. Studies have
shown that a higher number of SMN2 copies correlates
with generally milder clinical phenotypes. The modulation of clinical severity due to variable copy numbers of
SMN2 is the result of a small amount of full-length survival motor neuron transcripts and the protein generated
by SMN2. This protein product can partially compensate for the complete absence of protein from the SMN1
alleles. However, accurate prediction of the SMA phenotype based on SMN2 copy number is not possible.
Although most of the population has one to three copies
of SMN2, approximately 15% of normal individuals have
no SMN2 gene.
DNA Assay
For diagnosis of SMA, it is sufficient to simply detect the
classic SMN1 deletion using DNA analysis in both SMN1
alleles. This is approximately 95% sensitive (100% specific) for patients with clinical features suspicious for
SMA. However, this approach is not sufficient to identify
patients who are heterozygous, or carriers, for the SMN1
deletion. Carrier testing requires a quantitative polymerase chain reaction assay that provides a measure of
SMN1 copy number. Detection of a single normal copy of
SMN1 would indicate the carrier state.
There are limitations, however, to the use of this
assay to determine carrier status. Approximately 34% of
the general population, having two SMN1 copies on one
chromosome and no copies on the other, will be incorrectly identified as being negative, or not carriers of SMA.
These individuals are carriers because one of their chromosomes is missing the SMN1 allele. Another 2% of the
general population has SMN1 mutations that are not
detectable by the polymerase chain reaction method of
SMN1 dosage analysis. Therefore, the counseling of
patients who are tested for carrier status must account for
the residual risk present when carrier screening assay
results are negative, particularly in patients from SMA
affected families.
Carrier Screening
In current practice, patients with a family history of SMA
are being offered carrier screening for the SMN1 deletion
mutations. Recent marketing and public awareness campaigns by laboratories and advocacy organizations are
promoting widespread population-based carrier screening for SMA in the prenatal or preconception setting,
regardless of family history. The American College of
Medical Genetics has recently recommended offering carrier testing to all couples regardless of race or ethnicity
(1). However, to date, no pilot studies have been completed in the United States that would determine best practices for pretest and posttest education and counseling
with specific regard to SMA screening. In addition, there

have been no studies to date to determine patient preferences and utility measures that would allow the completion of an analysis of the cost-effectiveness of widespread
carrier screening for SMA.
From a public policy perspective, there are generally
accepted criteria that a candidate disease should meet
before widespread screening is instituted. Briefly, these
criteria are: 1) the disease significantly impairs health in
the affected offspring; 2) there is a high frequency of carriers in the population to be screened; 3) technically and
clinically valid screening methods are available to the
population, and screening is cost-effective; 4) testing is
voluntary, and informed consent and pretest and posttest
counseling are available and effective; 5) fetal testing is
available for couples whose screening results are positive
and reproductive options are readily available in a timesensitive manner. In addition to these well-accepted criteria, it is imperative that any screening program be carried
out in a manner by which a patients privacy is protected
so that risks of discrimination and stigmatization in the
community are minimized. Nevertheless, public awareness campaigns regarding the disease and carrier screening availability will enhance knowledge of SMA and SMA
testing in the prenatal population. This may lead to
patients requesting SMA carrier testing.
Although SMA does meet some of the criteria cited
previously for population-based carrier screening, there
are specific areas that have not yet been addressed. In general terms, the question of what threshold for carrier frequency any disease must meet to be considered for widespread screening has never been formally addressed by
genetics and public policy professionals. In the case of
SMA, carrier frequencies in the general population (1 in
40 to 1 in 60) may be in the range of those found in diseases such as TaySachs (1 in 31), where screening programs are already in place in specific ethnic populations.
However, offering SMA carrier screening to the entire
prenatal population raises logistic, educational, and
counseling issues on a much different scale compared
with those screening programs aimed at a small subset of
the population. Successful programs for carrier screening
in the Eastern European Jewish community that came
about with the previously mentioned criteria met and
involved a well-informed patient population. In contrast,
the well-documented failures of the early sickle cell carrier screening programs highlight the need for appropriate
pretest and posttest counseling and for greater attention
to the social and clinical needs of the at-risk community.
Before panethnic prenatal screening for SMA can be recommended there should be a variety of issues addressed
which include, but may not be limited to, critical assessment of pilot screening programs, cost effectiveness
analysis, development of appropriate educational materials for both patients and primary obstetriciangynecologists, and the development of laboratory assay standards
and result reporting.
COMMITTEE OPINIONS
Recommendations
1. Preconception and prenatal screening for SMA is not
recommended in the general population at this time.
2. Genetic counseling and SMA carrier screening should
be offered to the following patients or couples:
a. Those with a family history SMA or SMA-like
disease
b. Those who request SMA carrier screening and
have completed genetic counseling that included
discussion of the sensitivity, specificity, and limitations of screening.
3. All identified carriers for SMA should be referred for
follow-up genetic counseling for a discussion of risk
to the fetus and future pregnancies. Prenatal and
preimplantation diagnosis should be discussed,
including gamete donations (egg and sperm donors).
4. Patients requesting fetal testing for SMA should be
referred to an appropriate provider of prenatal
genetic counseling and testing services. If needed,
referral for medical and genetic counseling should be
made for patients with a fetus found to be affected
with SMA.
5. Physicians and counselors involved in carrier screening should make every effort to provide reassurance
to patients that the results of screening and diagnostic testing will be held confidentially and that their
right to privacy, as with all genetic information, will
be respected.
Resources
Lunn MR, Wang CH. Spinal muscular atrophy. Lancet.
2008;371:212033.
Markowitz JA, Tinkle MB, Fischbeck KH. Spinal muscular atrophy in the neonate. J Obstet Gynecol Neonatal
Nurs 2004;33:1220.
279
National Human Genome Research Institute. Summary

of population-based carrier screening for single gene disorders: lessons learned and new opportunities. Bethesda
(MD): NHGRI; 2008. Available at: http://www.genome.
gov/27026048. Retrieved January 16, 2009.
National Institute of Neurological Disorders and Stroke:
Spinal muscular atrophy fact sheet. Bethesda (MD):
NINDS;2008. Available at: http://www.ninds. nih.gov/
disorders/sma/detail_sma.htm. Retrieved January 16,
2009.
Ogino S, Leonard DG, Rennert H, Ewens WJ, Wilson
RB. Genetic risk assessment in carrier testing for spinal
muscular atrophy. Am J Med Genet 2002;110:30107.
Pearn J. Classification of spinal muscular atrophies.
Lancet 1980;1:91922.
Russman BS. Spinal muscular atrophy: clinical classification and disease heterogeneity. J Child Neurol 2007;
22:94651.
Reference
1. Prior TW. Carrier screening for spinal muscular atrophy.
Professional Practice and Guidelines Committee. Genet
Med 2008;10:8402.

ISSN 1074-861X
Spinal muscular atrophy. ACOG Committee Opinion No. 432.
2009;113:11946.
280

Number 442 October 2009
(Replaces No. 298, August 2004)
Preconception and Prenatal Carrier

Screening for Genetic Diseases in
Individuals of Eastern European
Jewish Descent
Committee on
Genetics
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Certain autosomal recessive disease conditions are more prevalent in

individuals of Eastern European Jewish (Ashkenazi) descent. Previously, the American
College of Obstetricians and Gynecologists recommended that individuals of Eastern
European Jewish ancestry be offered carrier screening for TaySachs disease, Canavan
disease, and cystic fibrosis as part of routine obstetric care. Based on the criteria used to
justify offering carrier screening for TaySachs disease, Canavan disease, and cystic fibrosis, the American College of Obstetricians and Gynecologists Committee on Genetics
recommends that couples of Ashkenazi Jewish ancestry also should be offered carrier
screening for familial dysautonomia. Individuals of Ashkenazi Jewish descent may inquire
about the availability of carrier screening for other disorders. Carrier screening is available
for mucolipidosis IV, Niemann-Pick disease type A, Fanconi anemia group C, Bloom syndrome, and Gaucher disease.
Carrier screening for specific genetic conditions often is determined by an individuals

ancestry. Certain autosomal recessive disease
conditions are more prevalent in individuals
of Eastern European Jewish (Ashkenazi)
descent. Most individuals of Jewish ancestry
in North America are descended from
Ashkenazi Jewish communities and, thus, are
at increased risk for having offspring with
one of these conditions. Many of these disorders are lethal in childhood or are associated
with significant morbidity.
Screening options continue to evolve.
The American College of Medical Genetics
has recently recommended additional carrier
screening for the Ashkenazi Jewish population. The basis for these recommendations
seems to be the high detection rate (Table 1).
The Committee on Genetics reaffirms support for screening for Tay-Sachs disease,
Canavan disease, cystic fibrosis, and familial
dysautonomia.
TaySachs disease (TSD) was one of the
first disorders available for carrier screening.
As a result of carrier screening programs
established in the 1970s, the incidence of

TSD in the North American Ashkenazi
Jewish population has decreased by more
than 90%. Carrier screening also is recommended for individuals of French Canadian
and Cajun descent. Initially, carrier screening
was based on the measurement of hexosaminidase A levels (the enzyme deficient in
TSD) in serum or leukocytes. As the genes for
TSD and other diseases more prevalent in
Ashkenazi Jews were identified, DNA carrier
tests were developed. Because each of these
disorders is caused by a small number of
common mutations, the carrier tests are very
sensitive (9499% detection rates). Previously,
Gynecologists recommended that individuals
of Eastern European Jewish ancestry be
offered carrier screening for TSD, Canavan
disease, and cystic fibrosis as part of routine
obstetric care. Because of recent advances in
genetics, additional carrier tests are now
available (Table 1).
In 2001, the gene for familial dysautonomia was identified. At least 2 mutations in the
COMMITTEE OPINIONS
281
Table 1. Recessive Genetic Diseases Frequent Among Individuals of Eastern European Jewish Descent Amenable to Carrier
Screening
Disorder
TaySachs disease
Canavan disease
Disease Incidence
Carrier Frequency*
Detection Rate*
1/3,000
1/30
98% by hexosaminidase A test,

94% by DNA-based test
1/6,400
1/40
98%
1/2,5003,000
1/29
97%
Familial dysautonomia
1/3,600
1/32
99%
Fanconi anemia group C
1/32,000
1/89
99%
Cystic fibrosis
Niemann-Pick disease type A
1/32,000
1/90
95%
Mucolipidosis IV
1/62,500
1/127
95%
Bloom syndrome
1/40,000
1/100
9597%
Gaucher disease
1/900
1/15
95%
*Non-Jewish carrier frequency and detection rates are unknown except for TaySachs disease and cystic fibrosis. Carrier frequency for TaySachs disease is 1 in 30 if French
Canadian or Cajun ancestry and 1 in 300 for others with a 98% carrier detection rate by hexosaminidase A test.
Modified from March of Dimes. Genetic screening pocket facts. White Plains (NY): MOD; 2001.
familial dysautonomia gene, IKBKAP, have been identified in patients with familial dysautonomia of Ashkenazi
Jewish descent. One of the mutations (IVS20 +6TC) is
found in more than 99% of patients with familial dysautonomia. It occurs almost exclusively in individuals of
Ashkenazi Jewish descent; the carrier rate (1 in 32) is similar to TSD and cystic fibrosis. Familial dysautonomia, a
disorder of the sensory and autonomic nervous system, is
associated with significant morbidity. Clinical features
include abnormal suck and feeding difficulties, episodic
vomiting, abnormal sweating, pain and temperature
insensitivity, labile blood pressure levels, absent tearing,
and scoliosis. Treatment is available, which can improve
the length and quality of life, but there currently is no
cure. Based on the criteria used to justify offering carrier
screening for TSD, Canavan disease, and cystic fibrosis,
the ACOG Committee on Genetics recommends that
couples of Ashkenazi Jewish ancestry also should be
offered carrier screening for familial dysautonomia.
Carrier screening tests are available for several diseases that are less common (carrier rates 1 in 89 to 1 in
127), including Fanconi anemia group C, Niemann-Pick
disease type A, Bloom syndrome, and mucolipidosis IV.
These conditions are associated with significant neurologic or medical problems and very limited treatment
options (see Box 1). Carrier screening also is available for
Gaucher disease, the most common disorder in Eastern
European Jews. Although Gaucher disease affects 1 in 900
individuals, the age of onset (from a few months to 90
years) and severity are variable (see Box 1). Gaucher disease can be very mild, and treatment is available.
All of these tests have a high sensitivity in the Jewish
population. The prevalence of these disorders in nonJewish populations, except for TSD and cystic fibrosis, is
unknown. The sensitivity of these carrier tests in nonJewish populations has not been established. The muta-
tions may be different and more diverse. Consequently,

when only one partner is Jewish, it is difficult to assess the
risk of having an affected offspring. Therefore, carrier
screening of the non-Jewish partner is of limited value.
Based on these developments, the ACOG Committee
on Genetics makes the following seven recommendations:
1. The family history of individuals considering pregnancy, or who are already pregnant, should determine whether either member of the couple is of
Eastern European (Ashkenazi) Jewish ancestry or has
a relative with one or more of the genetic conditions
listed in Table 1.
2. Carrier screening for TSD, Canavan disease, cystic
fibrosis, and familial dysautonomia should be offered
to Ashkenazi Jewish individuals before conception or
during early pregnancy so that a couple has an
opportunity to consider prenatal diagnostic testing
options. If the woman is already pregnant, it may be
necessary to screen both partners simultaneously so
that the results are obtained in a timely fashion to
ensure that prenatal diagnostic testing is an option.
3. Individuals of Ashkenazi Jewish descent may inquire
about the availability of carrier screening for other disorders. Carrier screening is available for mucolipidosis
IV, Niemann-Pick disease type A, Fanconi anemia
group C, Bloom syndrome, and Gaucher disease.
Patient education materials can be made available so
that interested patients can make an informed decision
about having additional screening tests . Some patients
may benefit from genetic counseling.
4. When only one partner is of Ashkenazi Jewish
descent, that individual should be screened first. If it
is determined that this individual is a carrier, the
other partner should be offered screening. However,
the couple should be informed that the carrier fre-
282
quency and the detection rate in non-Jewish individuals is unknown for all of these disorders, except for
TSD and cystic fibrosis. Therefore, it is difficult to
accurately predict the couples risk of having a child
with the disorder.
5. Individuals with a positive family history of one of
these disorders should be offered carrier screening
for the specific disorder and may benefit from genetic
counseling.
6. When both partners are carriers of one of these disorders, they should be referred for genetic counseling
and offered prenatal diagnosis. Carrier couples
should be informed of the disease manifestations,
range of severity, and available treatment options.
Prenatal diagnosis by DNA-based testing can be performed on cells obtained by chorionic villus sampling and amniocentesis.
7. When an individual is found to be a carrier, his or her

relatives are at risk for carrying the same mutation.
The patient should be encouraged to inform his or
her relatives of the risk and the availability of carrier
screening. The provider does not need to contact
these relatives because there is no providerpatient
relationship with the relatives, and confidentiality
must be maintained.
Carrier screening is voluntary. Informed consent and
assurance of confidentiality are required. For all of these
disorders, a negative screening test result for one or both
partners significantly reduces the possibility of an affected
offspring. However, it does not exclude the possibility
because the test sensitivity is less than 100% so not all carriers can be identified.
The number and choice of genetic tests available to
patients is likely to increase as a result of the Human
Box 1. Clinical Features of Autosomal Recessive Genetic Diseases Frequent Among Individuals
of Eastern European Jewish Descent
Bloom syndrome is a genetic condition associated with
increased chromosome breakage, a predisposition to infections and malignancies, prenatal and postnatal growth
deficiency, skin findings (such as facial telangiectasias or
abnormal pigmentation), and in some cases learning difficulties and mental retardation. The mean age of death is 27
years and usually is related to cancer. No effective treatment
currently is available.
Canavan disease is a disorder of the central nervous system
characterized by developmental delay, hypotonia, large
head, seizures, blindness, and gastrointestinal reflux. Most
children die within the first several years of life. Canavan disease is caused by a deficiency of the aspartoacylase
enzyme. No treatment currently is available.
Familial dysautonomia is a neurologic disorder characterized by abnormal suck and feeding difficulties, episodic vomiting, abnormal sweating, pain and temperature insensitivity,
labile blood pressure levels, absent tearing, and scoliosis.
There currently is no cure for familial dysautonomia, but
some treatments are available that can improve the length
and quality of a patients life.
Fanconi anemia group C usually presents with severe anemia that progresses to pancytopenia, developmental delay,
and failure to thrive. Congenital anomalies are not uncommon, including limb, cardiac, and genitalurinary defects.
Microcephaly and mental retardation may be present.
Children are at increased risk for leukemia. Some children
have been successfully treated with bone marrow transplantation. Life expectancy is 812 years.
Gaucher disease is a genetic disorder that mainly affects the
spleen, liver, and bones; it occasionally affects the lungs, kidneys, and brain. It may develop at any age. Some individuals
are chronically ill, some are moderately affected, and others

are so mildly affected that they may not know that they have
Gaucher disease. The most common symptom is chronic
fatigue caused by anemia. Patients may experience easy
bruising, nosebleeds, bleeding gums, and prolonged and
heavy bleeding with their menses and after childbirth. Other
symptoms include an enlarged liver and spleen, osteoporosis, and bone and joint pain. Gaucher disease is caused by
the deficiency of the -glucosidase enzyme. Treatment is
available through enzyme therapy, which results in a vastly
improved quality of life.
Mucolipidosis IV is a neurodegenerative lysosomal storage
disorder characterized by growth and psychomotor retardation, corneal clouding, progressive retinal degeneration, and
strabismus. Most affected infants never speak, walk, or
develop beyond the level of a 12 year old. Life expectancy
may be normal, and there currently is no effective treatment.
Niemann-Pick disease type A is a lysosomal storage disorder typically diagnosed in infancy and marked by a rapid
neurodegenerative course similar to TaySachs disease.
Affected children die by age 35 years. Niemann-Pick disease type A is caused by a deficiency of the sphingomyelinase enzyme. There currently is no treatment.
TaySachs disease (TSD) is a severe, progressive disorder of
the central nervous system leading to death within the first few
years of life. Infants with TSD appear normal at birth but by age
56 months develop poor muscle tone, delayed development,
loss of developmental milestones, and mental retardation.
Children with TSD lose their eyesight at age 1218 months.
This condition usually is fatal by age 6 years. TaySachs disease is caused by a deficiency of the hexosaminidase A
enzyme. No effective treatment currently is available.
COMMITTEE OPINIONS
Genome Project and advances in technology. For some

patients, it can be difficult to decide whether to have a
specific test. There are many factors patients may consider,
including the prevalence of the disease, the carrier risk,
the disease severity and treatment options, cost, and
reproductive choices. Counseling by a genetic counselor,
geneticist, or physician with expertise in these diseases
may assist patients in making an informed decision about
carrier testing.
Bibliography
Screening for Tay-Sachs disease. ACOG Committee Opinion
No. 318. American College of Obstetricians and Gynecologists.
Dong J, Edelmann L, Bajwa AM, Kornreich R, Desnick RJ.
Familial dysautonomia: detection of the IKBKAP IVS20
(+6T > C) and R696P mutations and frequencies among
Ashkenazi Jews. Am J Med Genet 2002;110:2537.
283
Eng CM, Desnick RJ. Experiences in molecular-based prenatal

screening for Ashkenazi Jewish genetic diseases. Adv Genet
2001;44:27596.
Zlotogora J, Bach G, Munnich A. Molecular basis of mendelian
disorders among Jews. Mol Genet Metab 2000;69:16980.
Copyright October 2009 by the American College of Obstetricians
ISSN 1074-861X
Preconception and prenatal carrier screening for genetic diseases in
individuals of Eastern European Jewish descent. ACOG Committee
284

Array Comparative Genomic Hybridization

in Prenatal Diagnosis
Committee on
Genetics

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: The widespread use of array comparative genomic hybridization (CGH)

for the diagnosis of genomic rearrangements in children with idiopathic mental retardation, developmental delay, and multiple congenital anomalies has spurred interest in
applying array CGH technology to prenatal diagnosis. The use of array CGH technology
in prenatal diagnosis is currently limited by several factors, including the inability to detect
balanced chromosomal rearrangements, the detection of copy number variations of
uncertain clinical significance, and significantly higher costs than conventional karyotype
analysis. Although array CGH has distinct advantages over classic cytogenetics in certain
applications, the technology is not currently a replacement for classic cytogenetics in prenatal diagnosis.
Completion of the Human Genome Project

stimulated development of ancillary technologies that continue to revolutionize medical
sciences and diagnostic techniques. Current
conventional cytogenetic analysis (G-banded
karyotype) can detect unbalanced structural
rearrangements and numeric abnormalities,
as well as apparently balanced rearrangements within the limits of resolution of the
technique. The resolution of the current conventional cytogenetic analyses lies in the
range of 310 Mb (1 Mb = 1 million base
pairs) and requires dividing cells. Therefore,
chromosomal microdeletions or microduplications (those smaller than 3 Mb) will go
undetected with conventional cytogenetic
analyses. These submicroscopic rearrangements may account for a sizable portion of
the human genetic disease burden, with some
estimates as high as 15% (1). Fluorescence in
situ hybridization technology can be used to
detect chromosomal abnormalities smaller
than 3 Mb (DiGeorge syndrome for example), but because of technical limitations, it
can only screen for a limited number of chromosomal abnormalities at one time.
Genomic microarray-based technologies can theoretically detect human genomic
DNA variation at virtually any site in the
human genome. Genomic microarrays can
detect both duplications and deletions, also
referred to in the literature as genomic copy

number variants. Genomic copy number
variants are defined as deletions and duplications of DNA segments larger than 1,000
bases and up to several megabases in size.
Genomic microarrays can be used to perform karyotyping, which often is referred to
as array comparative genomic hybridization
or array CGH. Array CGH improves resolution over conventional G-banded karyotype
in detecting chromosomal abnormalities
smaller than 3 Mb. Array CGH has been
reported to be useful in detecting causative
genomic imbalances in as many as 10% of
patients with unexplained mental retardation and previously normal conventional
karyotype (2). In addition, array CGH has
been a useful tool in discovering underlying
genetic mutations in known, but genetically
undefined, human genetic syndromes (3).
The potential advantages of array CGH
over conventional karyotyping in prenatal
diagnosis include higher resolution, avoidance of culturing amniocytes or chorionic villi,
automation, and faster turnaround times. In
addition, array CGH does not require dividing cells, which is useful in the case of fetal
demise where the ability to successfully culture cells may be compromised (4). The disadvantages of array CGH include the inability
to detect balanced inversions or translocations
COMMITTEE OPINIONS
as well as certain forms of triploidy, and array CGH costs

significantly more than conventional karyotype analysis.
The technique detects a large number of either benign
copy number variants or copy number variants of uncertain clinical significance and is unlikely to detect mosaicism below 20% (5).
The two types of arrays currently available are targeted and genome-wide arrays. Targeted arrays are currently
preferred in clinical genetic practice because they can
detect chromosomal abnormalities for known genetic
syndromes. This allows genetic counseling with more
certainty regarding phenotype and long-term prognosis.
Targeted arrays, however, can miss novel pathologic copy
number variants, which may explain a constellation of
congenital anomalies that do not fit any particular known
syndrome. In approximately 1215% of samples, copy
number variants of uncertain clinical significance will be
detected among currently used targeted arrays (6). In
such cases, DNA from the biological mother and father
must also be analyzed by microarray to distinguish copy
number variants that were inherited from the parents
(inherited copy number variants) versus copy number
variants that are absent in the parents and arose spontaneously in the child (de novo copy number variants).
Inherited copy number variants are relatively common
and represent benign polymorphisms in most cases.
However, a recent report has indicated that inherited copy
number variants from seemingly normal parents can
cause major pathology in the offspring (7). De novo copy
number variants are more likely to be the cause of congenital and developmental abnormalities compared with
inherited copy number variants, but interpretation of
copy number variant results can be clinically complex. A
genetics professional should be involved in the interpretation of both inherited and de novo copy number variants.
Genome-wide arrays, however, are designed to cover
a greater portion of the human genome than targeted
arrays. Genome-wide arrays have been particularly useful
in research efforts to discover new submicroscopic syndromes (8, 9). However, at this point in time, genomewide arrays will detect many more copy number variants
of unknown clinical significance. Growing clinical experience with genome-wide arrays and the development of
copy number variant databases of both healthy and
affected individuals will reduce the number of copy number variants of unknown clinical significance and will
make genome-wide arrays more useful in clinical practice.
Several reports have now shown the potential utility
of array CGH in prenatal diagnosis (10, 11). In a relatively large series of fetuses with ultrasound abnormalities
and normal conventional karyotype, array CGH detected
chromosomal abnormalities in 5% of fetuses and up to
10% in those with three or more anatomic abnormalities.
In addition, array CGH was found to detect two genetic
syndromes among 300 amniocentesis or chorionic villus
samples that otherwise would not have been detected by
conventional karyotype or aneuploidy fluorescence in
285
situ hybridization (11). Data from this and other studies

have generated increasing interest in the utilization of
array CGH as an additional assay for fetal abnormalities,
beyond conventional cytogenetic analysis. However,
many of the known genomic disorders that can be detected on current targeted arrays do not show readily
detectable fetal abnormalities on prenatal ultrasound
examinations. Therefore, ordering array CGH only in the
presence of ultrasound abnormalities may limit the diagnostic potential of this assay (11).
The usefulness of array CGH as a first-line tool in
detecting chromosomal abnormalities in all amniocentesis or chorionic villus samples is still unknown. The additional detection rate of chromosomal abnormalities using
array CGH, as compared with conventional karyotype,
for routine fetal chromosomal analysis, awaits a larger
population-based study, which is currently underway in
the United States. The answers to these and other questions are required before the routine clinical use of array
CGH in prenatal diagnosis can be recommended.
Recommendations
Conventional karyotyping remains the principal cytogenetic tool in prenatal diagnosis.
Targeted array CGH, in concert with genetic counseling, can be offered as an adjunct tool in prenatal
cases with abnormal anatomic findings and a normal
conventional karyotype, as well as in cases of fetal
demise with congenital anomalies and the inability
to obtain a conventional karyotype.
Couples choosing targeted array CGH should receive
both pretest and posttest genetic counseling. Followup genetic counseling is required for interpretation
of array CGH results. Couples should understand that
array CGH will not detect all genetic pathologies and
that array CGH results may be difficult to interpret.
Targeted array CGH may be useful as a screening
tool; however, further studies are necessary to fully
determine its utility and its limitations.
References
1. Vissers LE, Veltman JA, van Kessel AG, Brunner HG.
Identification of disease genes by whole genome CGH
arrays. Hum Mol Genet 2005;14(spec no. 2):R21523.
2. de Vries BB, Pfundt R, Leisink M, Koolen DA, Vissers LE,
Janssen IM, et al. Diagnostic genome profiling in mental
retardation. Am J Hum Genet 2005;77:60616.
3. Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de
Vries BB, Janssen IM, et al. Mutations in a new member of
the chromodomain gene family cause CHARGE syndrome.
Nat Genet 2004;36:9557.
4. Schaeffer AJ, Chung J, Heretis K, Wong A, Ledbetter DH,
Lese Martin C. Comparative genomic hybridization-array
analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages. Am J
Hum Genet 2004;74:116874.
286
5. Stankiewicz P, Beaudet AL. Use of array CGH in the evaluation of dysmorphology, malformations, developmental
delay, and idiopathic mental retardation. Curr Opin Genet
Dev 2007;17:18292.
6. Sahoo T, Cheung SW, Ward P, Darilek S, Patel A, del Gaudio
D, et al. Prenatal diagnosis of chromosomal abnormalities
using array-based comparative genomic hybridization.
Genet Med 2006;8:71927.
7. Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K,
et al. Recurrent rearrangements of chromosome 1q21.1 and
variable pediatric phenotypes. N Engl J Med 2008;359:
168599.
8. Slavotinek AM. Novel microdeletion syndromes detected
by chromosome microarrays. Hum Genet 2008;124:117.
9. Koolen DA, Vissers LE, Pfundt R, de Leeuw N, Knight SJ,
Regan R, et al. A new chromosome 17q21.31 microdeletion
syndrome associated with a common inversion polymorphism. Nat Genet 2006;38:9991001.
10. Le Caignec C, Boceno M, Saugier-Veber P, Jacquemont S,
Joubert M, David A, et al. Detection of genomic imbalances
by array based comparative genomic hybridisation in fetuses
with multiple malformations. J Med Genet 2005;42:1218.
11. Van den Veyver IB, Patel A, Shaw CA, Pursley AN, Kang SH,
Simovich MJ, et al. Clinical use of array comparative genomic hybridization (aCGH) for prenatal diagnosis in 300
cases. Prenat Diagn 2009;29:2939.
Copyright November 2009 by the American College of Obstetricians

ISSN 1074-861X
Array comparative genomic hybridization in prenatal diagnosis. ACOG
Gynecologists. Obstet Gynecol 2009;114:11613 .
COMMITTEE OPINIONS
287

(Replaces No. 230, January 2000)
Maternal Phenylketonuria
Committee on
Genetics
followed.
ABSTRACT: Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) metabolism characterized by a deficiency of the hepatic enzyme, phenylalanine hydroxylase, an enzyme responsible for the conversion of phenylalanine to tyrosine,
and elevated levels of Phe and Phe metabolite. All women with PKU or hyperphenylalaninemia should be strongly encouraged to receive family planning and preconception
counseling. Women with PKU or hyperphenylalaninemia should begin appropriate, medically directed dietary phenylalanine restriction before conception.
Phenylketonuria is an autosomal recessive

disorder of phenylalanine (Phe) metabolism
characterized by a deficiency of the hepatic
enzyme, phenylalanine hydroxylase (PAH),
an enzyme responsible for the conversion of
phenylalanine to tyrosine, and elevated levels
of Phe and Phe metabolite. More than 400
mutations of the PAH gene have been
described, and the severity of the disorder is
dependent on the type of mutation present.
A deficiency of the PAH enzyme results in
increased blood phenylalanine levels, which
are toxic. If untreated, phenylketonuria (PKU)
can result in fetal growth failure, microcephaly, seizures, and mental retardation. Two
aspects of this metabolic disorder are particularly relevant to the obstetriciangynecologistthe prevention of fetal embryopathy
associated with maternal hyperphenylalaninemia and the risk of genetic transmission
of PKU.
Prevention of Fetal Embryopathy Associated With Maternal

Hyperphenylalaninemia

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
In the United States, approximately 3,000

women of reproductive age are affected with
PKU. Although evidence suggests that women
with PKU will benefit from remaining on a
phenylalanine-free diet throughout their
lives, many are not adherent to such a diet
because of the unpalatable nature of many
phenylalanine-free products. The failure of
young women with PKU to adhere to dietary
modification represents a significant public
health challenge because of the significant

fetal consequences of maternal hyperphenylalaninemia. Importantly, phenylalanine
crosses the placenta by an active transport
process that results in a fetal-to-maternal
plasma phenylalanine ratio of 1.5. Therefore,
higher levels of phenylalanine exist in fetal
blood than would be expected based on the
maternal blood level. The developing brain
and heart are particularly vulnerable to high
concentrations of blood phenylalanine. Children born to women with PKU on unrestricted diets have a 92% risk for mental
retardation, a 73% risk for microcephaly, and
a 12% risk for congenital heart defects (1).
If phenylalanine levels are normalized (Phe
levels between 120360 micromole/L) before
conception or by 8 weeks of gestation, there
is evidence to suggest a reduction in the
fetal sequelae of hyperphenylalaninemia (2).
Reduction of the maternal blood phenylalanine level to 600 micromole/L or less,
reduced the incidence of microcephaly from
73% to 8% (3). The challenge of identifying
and educating women about dietary restriction before conception is highlighted by a
study that found 64% of women failed to
achieve blood phenylalanine control by 8
weeks of gestation (4). The crucial role played
by dietary restriction should be stressed in
the patient with PKU, preferably 3 months
before conception, to normalize the blood
phenylalanine level and optimize neural and
cardiac developmental outcomes for the
fetus.
288
Risk of Genetic Transmission of

Phenylketonuria
Children of women with PKU will carry at least one
abnormal gene, which is inherited from their homozygous-affected mother. The carrier frequency for PKU is
approximately 1 in 60. Given an affected mother, approximately 1 in 120 children will inherit an abnormal PAH
gene from both parents and will be affected with PKU.
Children of women with PKU are carriers and should
receive genetic counseling in the future. If the mutations
are known, further consultation and screening with a
genetics professional to discuss reproductive options
should be recommended. Universal neonatal PKU
screening in the United States has facilitated early detection of these newborns.
Conclusions and Recommendations

All women with PKU or hyperphenylalaninemia
should be strongly encouraged to receive family
planning and preconception counseling.
Women with PKU or hyperphenylalaninemia should
begin appropriate, medically directed dietary phenylalanine restriction before conception (5).
Ideally, pregnant women with PKU or hyperphenylalaninemia should be managed in consultation with
practitioners from experienced PKU centers.
Resource
Maternal phenylketonuria. American Academy of Pediatrics. Pediatrics 2008;122:4459.
References
1. Lenke RR, Levy HL. Maternal phenylketonuria and hyperphenylalaninemia. An international survey of the outcome
of untreated and treated pregnancies. N Engl J Med 1980;
303:12028.
2. Widaman KF, Azen C. Relation of prenatal phenylalanine
exposure to infant and childhood cognitive outcomes:
results from the International Maternal PKU Collaborative
Study. Pediatrics 2003;112:153743.
3. Matalon KM, Acosta PB, Azen C. Role of nutrition in pregnancy with phenylketonuria and birth defects. Pediatrics
2003;112:15346.
4. Brown AS, Fernhoff PM, Waisbren SE, Frazier DM, Singh R,
Rohr F, et al. Barriers to successful dietary control among
pregnant women with phenylketonuria. Genet Med 2002;
4:849.
5. Levy HL, Waisbren SE, Lobbregt D, Allred E, Schuler A,
Trefz FK, et al. Maternal mild hyperphenylalaninaemia: an
international survey of offspring outcome. Lancet 1994;
344:158994.
ISSN 1074-861X
Maternal phenylketonuria. ACOG Committee Opinion No. 449.
2009;114:14323.
COMMITTEE OPINIONS
289
ACOG
TECHNOLOGY ASSESSMENT
I N O B S T E T R I C S A N D G Y N E CO LO G Y
NUMBER 1, J ULY 2002
This Technology Assessment

was developed by the ACOG
Committee on Genetics with the
assistance of Deborah A. Driscoll,
MD, FACOG; Katherine D.
Wenstrom, MD, FACOG, and
John Williams III, MD, FACOG.
clinical and scientific advances
as of the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of
treatment or procedure to be
followed. Variations in practice
may be warranted based on the
needs of the individual patient,
resources, and limitations unique
to the institution or type of
practice.
Reaffirmed 2006
T H E A M E R I C A N CO L L E G E
OF OBSTETRICIANS
A N D G Y N E CO LO G I S T S
WOM E N S H E A LT H C A R E P H YS I C I A N S
Genetics and Molecular

Diagnostic Testing
Knowledge of human genetics has increased dramatically in the past few
decades. The genetic basis of disease and the response to therapy is rapidly
being elucidated and may soon become a part of routine medical practice. A
draft of the human genome was published in 2001 (1). This project produced
a detailed map of the genes, markers, and other landmarks along each chromosome. It is hoped that these maps will facilitate the development of genetic screening and diagnostic tests, as well as novel therapies, technologies, and
strategies for prevention. Obstetricians and gynecologists, who deal with
inheritance and the genetic transmission of traits and disease on a daily basis,
will be called on to incorporate genetics and recent developments in genetic
testing into their medical practice. This document reviews the basics of genetic transmission and genetic technologies in current use. (See the Glossary
for definitions of terms for genetics and molecular diagnostic testing.)
ORGANIZATION OF THE GENOME

There are 2 meters of DNA, including approximately 30,000 genes, in each
human nucleus. The DNA is wrapped very compactly around basic proteins
called histones to form nucleosomes, which are then organized into solenoid
structures and looped around a nonhistone protein scaffold to form chromatin. As the cell enters prophase, the chromatin begins to condense until it
assumes the familiar structure of metaphase chromosomes. Each chromosome is composed of densely packed nontranscribed DNA near the centromeres, called heterochromatin, and less densely packed transcribed DNA
called euchromatin.
Seventy-five percent of the genome is unique, single copy DNA, and the
remainder consists of various classes of repetitive DNA. Surprisingly, virtually all of the repetitive DNA and a large portion of the single copy DNA
have no apparent or recognized function. Less than 10% of the genome
encodes genes. The single copy DNA contains all of the genes necessary to
make and sustain the organism, while the repetitive DNA contains unique
markers that identify each individual and can be used to study genetic variation between individuals.
290
Genes
A gene is a unique series of four purine and pyrimidine bases that ultimately specifies an amino acid
sequence for a polypeptide chain of a protein. The
basic gene contains one or more exons, which are
DNA sequences that will be transcribed into messenger RNA (mRNA), and introns (or intervening
sequences), which are noncoding or nontranscribed
regions that separate exons (Fig. 1). The regions
upstream and downstream to the exons are called
the 5 untranslated region and the 3 untranslated
region, respectively. These regions are transcribed,
but not translated (as the name implies), and they are
important in gene regulation.
The processes of transcription and translation
are more complex than previously recognized. The
transcription of DNA to mRNA requires transcription factors. Enhancers and silencer DNA sequences
located upstream or downstream of a gene can
increase and decrease transcriptional activity of the
gene, respectively. Transcription is initiated when
the enzyme RNA polymerase II binds to the promot-
er, a DNA sequence upstream of a gene. RNA polymerase moves along a single strand of DNA and
forms a complementary strand of mRNA. Once the
mRNA is formed, a cap or chemically modified guanine nucleotide is added to the 5 end to prevent
the mRNA from being degraded, and a chain of
100200 adenine bases (poly-A tail) is added to the
3 end. Before the mRNA leaves the nucleus, the
introns are excised by a process called gene splicing.
The mature mRNA then moves to the ribosomes for
translation. The protein product usually is created in
a precursor form, and undergoes cleavage into a
smaller active protein or combines with other
polypeptides to form a larger functional protein. The
protein may be further modified in the Golgi apparatus of the cell by glycosylation. Some genes contain more than one promoter in different parts of the
gene or have alternative splice sites, which allows
the same gene to encode different protein products.
Gene expression also is controlled by methylation of the regulatory region, which prevents gene
transcription and effectively turns the gene off.
Other specific promoter

elements (eg, CACCC
in -globin)
Cap site
TAA, TGA, or TAG

stop codon
transcription
start site
TissueEnhancer specific
elements
CCAAT box
ATG
initiation codon
GT
AG
TATA
box
AATAAA
polyadenylation signal
GT
Site for addition

of (A)n
AG
Gene
5
untranslated
region
5
mRNA precursor
Intron 1
GU
Intron 2
Transcription
AG
GU
3
untranslated
region
3
AAAAA
AG
Cap
Splicing
Mature mRNA Cap
AAAAA
Fig. 1. Structure of a typical gene. In this example, the gene has three exons (solid dark regions) and two introns
(white regions), a 5 untranslated region and 3 untranslated region. The intron splice donor site (GT) and the splice
acceptor site (AG) identify where introns are removed in mRNA production. The upstream region (5) contains an
enhancer, tissue specific elements, and promoter elements, such as the CCAAT box and TATA box, which regulate
expression. Typical locations for the translation initiation site (ATG), translation stop codons (TAA, TAG, TGA), and the
polyadenylation signal (AATAAA) are shown. (Gelehrter TD, Ginsburg D, Collins FS. Principles of medical genetics. 2nd
ed. Baltimore: Williams and Wilkins, 1997)
COMMITTEE OPINIONS
Methylation serves the important function of controlling tissue-specific gene activation. The expression of genes that are not essential for each specific
tissue type is prevented by methylation, while necessary genes remain active. For example, the globin
genes are methylated in all nonerythroid tissues
but are not methylated in reticulocytes, ensuring
that only red blood cells produce hemoglobin.
Methylation also allows the temporal control of gene
expression. Parental alleles may demonstrate different patterns of methylation that are not tissue specific (see section on Imprinting).
Many genes exist in several alternate forms
called alleles. These are normal variants within the
population. For example, there are several normal
alleles for the genes that determine blood type and
Rh status. In contrast, a mutation is an alteration in
the DNA sequence that results in a change in protein structure or function, which may have adverse
effects. Mutations can occur in the germline (eg,
gametes) and can be transmitted from one generation to the next, or can occur only in the somatic
cells and can be associated with cancer. There are
many types of mutations, such as single purine or
pyrimidine base substitutions (missense, nonsense),
deletions and insertions of one or more bases, and
visible chromosome deletions and duplications.
Mutations occur infrequently in the population. The
distinction between an allele and a mutation can be
blurred; many normal alleles probably result from
ancient mutations that either did not affect survival
or conferred some selective advantage.
The vast majority (99.8%) of DNA is identical
in all humans. However, minor differences that distinguish one person from another do exist. These
differences, called polymorphisms, generally consist of a single nucleotide change and occur every
200 to 500 base pairs. Polymorphisms, in general,
do not produce deleterious effects. Some polymorphisms may modify gene function (eg, splice
variant or thymidine tract in intron 8 of the cystic
fibrosis [CF] gene can influence the amount of
mRNA produced). In most cases, polymorphisms
are normal variants, which often are used to track
the transmission of disease genes (see sections on
Restriction Fragment Length Polymorphism
Analysis and Linkage Analysis).
When newly discovered genes are analyzed, it
can be difficult to distinguish a normal allele from a
polymorphism or a mutation. For example, more
than 100 variations of the BRCA1 gene, one of the
major genes associated with familial breast and
ovarian cancers, have been identified. It is not cur-
291
rently known whether all of these variations are

actually mutations associated with disease, or if
some could be polymorphisms or allelic variants.
The ability to distinguish alleles from mutations
is essential for molecular diagnosis and screening
programs.
SINGLE GENE (MENDELIAN)

DISORDERS
A mendelian trait or disease is determined by a single gene. Diseases caused solely by abnormalities in
a single gene are relatively rare. The phenotype of
many single gene disorders is influenced by modifying genes, or by the independent actions of a combination of additional genes, often with environmental
influences.
Autosomal Dominant
All genes come in pairs; one copy of the gene is present on each of a pair of chromosomes. The influence of each gene in determining the phenotype is
described as either dominant or recessive. If one of
the genes in a pair specifies the phenotype in preference to the other gene, that gene and the trait or disease it specifies are considered to be dominant. The
carrier of a gene causing an autosomal dominant disease has a 50% chance of passing on the affected
gene with each conception.
The phenotype of an individual carrying a dominant gene is determined by several factors. One factor is penetrance. Penetrance indicates whether or
not the mutant gene is expressed. If a dominant gene
produces some kind of recognizable phenotypic
expression in all individuals who carry it, it is said to
have complete penetrance. A gene that is not
expressed in all individuals who carry it has incomplete penetrance. For individuals, penetrance is an
all-or-nothing phenomenon, but penetrance in a population can be quantitated. For example, a phenotype
that is expressed in 80% of individuals who carry the
gene has 80% penetrance.
Incomplete penetrance may account for some
autosomal dominant diseases that appear to skip
generations. Alternatively, the individual carrying
the dominant gene may have very mild phenotypic
abnormalities that have been overlooked, the disease
may have a late onset, the gene carrier is either too
young or died before the genes effects were manifest, or phenotypic expression of the dominant gene
could require the presence of a second mutated gene
or certain epigenetic phenomena. An example of
such a disease is retinoblastoma.
292
The degree to which a penetrant gene is

expressed (the range of phenotypic features) is
called expressivity. If all individuals carrying the
affected gene do not have identical phenotypes, the
gene has variable expressivity. Such a gene can produce a range of phenotypic features from mild to
severe. An example of a disease with variable
expressivity is neurofibromatosis.
Autosomal Recessive
Autosomal recessive traits or diseases occur only
when both copies of the gene in question are the
same. Individuals who have only one abnormal gene
(heterozygotes or carriers) may have some phenotypic alteration recognized at the biochemical or cellular level, but only individuals who have two copies
of the affected gene (homozygotes) have the disease.
Many enzyme deficiency diseases are autosomal
recessive. The enzyme level in the carrier of an
abnormal recessive gene will be approximately 50%
of normal, but because enzymes are made in great
excess, this reduction usually is not enough to cause
disease. However, the reduced enzyme level can be
used for genetic screening purposes. For example, to
identify carriers of TaySachs disease, hexosaminidase A levels are measured. Carriers of recessive
conditions that do not produce any physical or quantitative biochemical change in the heterozygote can
be identified only by molecular methods (eg,
Canavan disease).
The carrier of a gene causing an autosomal
recessive disease usually is recognized after the birth
of an affected child, after the diagnosis of an affected family member, or as the result of a genetic
screening program. A couple whose child has an
autosomal recessive disease has a 25% recurrence
risk with each conception. The likelihood that a normal sibling of an affected child is a carrier of the
gene is 2 out of 3 (one fourth of all offspring will be
homozygous normal, two fourths will be heterozygote carriers, and one fourth will be homozygous
abnormal; thus, 3 of 4 children will be phenotypically normal and 2 of these 3 will be carriers). Carrier
children will not have affected children unless their
partners are gene carriers or are affected. Because
genes leading to rare autosomal recessive conditions
have a low prevalence in the general population, the
chance that the partner will be a gene carrier is low
unless the couple is related (consanguineous). When
individuals inherit two different mutated alleles that
result in abnormal phenotypes, they are called compound heterozygotes. For example, an individual
who inherits a F508 and W1282X mutation in the
CF gene has CF without expressing two identical

alleles.
Co-Dominant
If the genes in a gene pair are different from each
other, but both are expressed in the phenotype, they
are considered to be co-dominant. For example, the
genes responsible for the hemoglobinopathies are codominant. The individual with one hemoglobin gene
directing the production of sickle hemoglobin, and
the other directing the production of hemoglobin C,
will produce both S and C hemoglobins. Likewise,
the genes that determine blood type are co-dominant,
because an individual is capable of expressing both A
and B red cell antigens simultaneously.
X-Linked
X-linked diseases usually are recessive, and primarily affect men because men have only one copy of
the X chromosome. Examples of X-linked recessive
disorders are color blindness, hemophilia A (classical hemophilia or factor VIII deficiency), and
Duchenne muscular dystrophy. Women carrying an
X-linked recessive gene generally are unaffected
unless unfavorable lyonization (the inactivation of
one X chromosome in every cell) results in the X
chromosome carrying the abnormal gene being
active in the majority of cells.
When a woman carries a gene causing an Xlinked recessive condition, there is a 50% chance of
passing on the gene with each conception; each of
her sons has a 50% chance of being affected and
each of her daughters has a 50% chance of being a
carrier. When a man has an X-linked disease, all of
his sons will be unaffected (because they receive the
Y chromosome from their father) and all of his
daughters will be carriers (because they receive the
affected X chromosome from their father). X-linked
dominant disorders have been described, and affect
females predominantly because they tend to be
lethal in male offspring. An example of this is Xlinked hypophosphatemia.
DUPLICATION AND DELETION

SYNDROMES
A deletion refers to a region of a chromosome that is
missing, while a duplication is the presence of an
extra copy of a region of a chromosome. The carrier
of a deletion is effectively monosomic for the genes
in the missing segment, while the carrier of a duplication is trisomic for the duplicated genes. Deletions
and duplications usually are described by their loca-
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tion (eg, duplication 4p) or by the two chromosomal

break points defining the missing or extra segment
(4p15.216.1). If the deletion is a common one, it
may be defined by an eponym (eg, del 1q32-q41
also is called Van der Woudes syndrome). Terminal
deletions and duplications are caused simply by
chromosome breakage with loss or gain of the terminal chromosome segment. Interstitial deletions and
duplications occur during prophase of meiosis when
homologous chromosomes align and cross-overs
occur. If the chromosomes are misaligned during
this process, the unaligned loop containing the mismatched segment could be deleted. Alternatively,
misalignment could lead to unequal crossing over,
so that one chromosome has a deletion and the other
a duplication. A similar problem with meiosis can
produce deletions and duplications in the offspring
of individuals who are carriers of chromosome
inversions. Deletions and duplications also occur as
a result of malsegregation during meiosis in carriers
of balanced translocations.
When a deletion or duplication is identified in a
fetus or child, the parents should be tested to see if it
arose de novo in their offspring or if either parent is
a carrier or has a translocation. Deletions and duplications may be identified by routine or high resolution cytogenetic analysis. Microdeletions and
duplications, which are too small to be detected by
traditional cytogenetic techniques, can now be recognized with molecular techniques, such as fluorescence in situ hybridization (FISH) (see section on
Fluorescence In Situ Hybridization).
Chromosome deletions and duplications can
result in a constellation of phenotypic abnormalities
with widely varying pathophysiology or pathogenesis because the genes that are in close proximity to
one another on a chromosome may have completely
unrelated functions and control independent traits.
Deletion syndromes usually cause more serious phenotypic and functional abnormalities than duplication syndromes. Monosomy generally has more
severe consequences than trisomy.
Syndromes caused by a microdeletion involving
genes physically located together in a chromosome
segment are called contiguous gene deletion syndromes, and their study has yielded a great deal of
information about gene location and function.
Although deletions can occur in any area of any
chromosome, some deletions occur more frequently
than would be expected by chance alone. Several
common chromosome deletion syndromes have
been recognized, such as DiGeorge syndrome,
which most often results from a microdeletion of the
293
long arm of chromosome 22 (del 22q11.2). Affected

individuals typically have conotruncal cardiac
defects; thymus and parathyroid gland hypoplasia or
aplasia; atypical facies, including short palpebral fissures, micrognathia with a short philtrum, and ear
anomalies; and learning and speech difficulties.
Deletions of the terminal portions of the short arms
of chromosomes 4 (4 p- or Wolf-Hirschhorn syndrome) and 5 (5 p- or cri du chat syndrome) also
occur more frequently than would be expected by
chance alone.
NONMENDELIAN PATTERNS OF
INHERITANCE
Hereditary Unstable DNA
Mendels first law states that genes are passed
unchanged from parent to progeny. Barring the
occurrence of new mutations, this law still applies to
many genes or traits. However, it is now known that
certain genes are inherently unstable, and their size
and, consequently, their function may be altered as
they are transmitted from parent to child. These
genes generally contain a region of triplet repeats,
such as (CGG)n. The number of triplet repeats in
gametes can increase as meiosis is completed prior
to fertilization. If the number of triplet repeats reaches a critical level, the gene containing the triplets
becomes methylated and is turned off, resulting in
phenotypic abnormalities. Some triplet regions
expand only during female meiosis, while others can
expand when transmitted by either parent. Some
triplet regions have been passed from parent to child
for many generations without expansion, for unknown reasons.
An example of a genetic disease caused by such
triplet repeats is fragile X syndrome. Fragile X syndrome is the most common form of all familial
mental retardation, accounting for 48% of all individuals with mental retardation in all ethnic and
racial groups. Affected individuals have mild to
severe mental retardation, autistic behavior, attention deficit hyperactivity disorder, speech and language problems, a narrow face with a large jaw, long
prominent ears, and macro-orchidism (in postpubertal males). Some children also have seizures. The
incidence of the full fragile X syndrome generally is
quoted as 1 per 1,500 males and 1 per 2,500 females.
Until recently, fragile X syndrome was diagnosed using a cytogenetic technique. Cells were cultured in a folate deficient medium, which resulted in
fragile sites identified cytogenetically as nonstaining
294
gaps or constrictions on the long arm of the X chromosome (Xq27-28). This technique was unreliable
for carrier testing, and less than half the cells from
affected males manifested the fragile site. Fortunately, the fragile X gene can now be directly examined using molecular techniques (see section on
Trinucleotide Repeat Analysis).
The fragile X mutation is now known to be a
region of unstable DNA in the X chromosome.
The region is best described as a series of CGG
(cytosineguanineguanine) repeats at Xq27. The
number of repeats and the degree of methylation
determines whether or not an individual is affected.
Individuals carrying 249 repeats are phenotypically normal. Individuals carrying 50199 repeats are
phenotypically normal but have a premutation,
which can expand as it is passed on to their offspring, who would then be affected. Those with
more than 200 repeats have the full mutation and, if
methylation occurs, usually are affected. However,
not all individuals carrying the full mutation are
mentally retarded. Phenotypic variability results
from lyonization (in females) and mosaicism for the
size of the expansion, the degree of methylation, or
both during mitosis in the zygote. Therefore, the
phenotype cannot be predicted by analysis of either
the parental gene or fetal cells.
The number of repeats usually remains stable
when the gene is transmitted by a male. However,
when the gene passes through female meiosis, it can
expand. The risk of expansion generally correlates
with the number of repeats in the premutation.
Premutations with 100 or more repeats expand on
transmission 100% of the time. The risk of expansion
of mutations with 5099 repeats increases proportionally with expansion size. If a female carries a premutation, which then increases in size as she transmits it to her offspring, it is possible for her to have a
child with fragile X syndrome even though she is
unaffected and has no family history of mental retardation.
The number of CGG repeats and the methylation
status of the gene can be determined using restriction
endonuclease digestion and Southern blot analysis
(see section on Trinucleotide Repeat Analysis). It
is now apparent that triplet repeat expansion is
responsible for a number of primarily neurologic diseases, such as myotonic dystrophy, Huntingtons
chorea, and Friedreichs ataxia. The expansion of
triplet repeats is an important mechanism of genetic
disease, and is likely to play an important part in diseases for which preconceptional counseling and prenatal diagnosis may be considered.
Imprinting
Another tenet of mendelian genetics is that gene
function is not influenced by the sex of the parent
transmitting the gene. In contrast to this rule, it is
now apparent that the function of certain genes is
altered by the sex of the parent from whom they
were inherited, by a process known as imprinting.
Imprinting is a mechanism for epigenetic control of
gene expression; that is, it changes the phenotype
without permanently altering the genotype. An
imprinted gene is inherited in an inactivated (transcriptionally silent) state, as the result of methylation of the promoter region. The extent of the
imprinting, and thus the degree of inactivation, is
determined by the sex of the transmitting parent.
When a gene is inherited in an imprinted or
inactivated state, gene function is necessarily directed entirely by the active co-gene inherited from the
other parent. It appears that imprinting exerts an
effect in part by controlling the dosage of specific
genes. Certain important genes appear to be monoallelic; that is, under normal circumstances only one
member of the gene pair is functional (as opposed to
most of the genes in the genome, which are biallelic). Only a fraction of human genes are imprinted.
With imprinted genes, however, normal development occurs only when both a paternally derived and
a maternally derived copy of the gene is present.
Imprinting was first recognized in association
with genetic disease. Two very distinct genetic diseases with dissimilar phenotypes were discovered to
be associated with the same chromosomal deletion,
at 15q11-13. One of the diseases is Prader-Willi syndrome, which is characterized by obesity; hyperphagia; short stature; small hands, feet, and external
genitalia; and mild mental retardation. The other
disorder is Angelmans syndrome, which includes
normal stature and weight, severe mental retardation,
absent speech, seizure disorder, ataxia and jerky arm
movements, and paroxysms of inappropriate laughter. Cytogenetic analysis has confirmed that both diseases are associated with the same deletion. If the
maternally derived chromosome 15 is deleted, the
result is Angelmans syndrome; if the paternally
derived chromosome 15 is deleted, the result is
Prader-Willi syndrome. Furthermore, a deletion is
not required to produce the phenotype. If an individual has two normal intact copies of chromosome 15,
but both came from the man (see section on
Uniparental Disomy), the phenotype is consistent
with Angelmans syndrome, because the maternal
contribution is missing. Likewise, two complete
copies of chromosome 15 of maternal origin pro-
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duces Prader-Willi syndrome. Studies of the methylation patterns in individuals with the 15q11-13 deletion have shown that differential methylation
(imprinting) is responsible for these observed phenotypic differences.
Several clinical examples from obstetrics illustrate the developmental importance of imprinting.
Complete hydatidiform mole, which has an exclusively paternally derived diploid chromosome complement, is characterized by the abundant growth of
placental tissue, but no fetal structures. Conversely,
ovarian teratoma, which has a maternally derived
diploid chromosome complement, is characterized
by the growth of various fetal tissues, but no placental structures. Triploidy, characterized by a conceptus with three complete haploid chromosome
complements (69 chromosomes), has two distinct
phenotypes. If the extra haploid chromosome complement comes from the man, the embryo will be
lost early in gestation and the placenta will be large
and cystic, and severe early onset preeclampsia is
likely to develop; if the extra chromosome complement comes from the woman, the fetus will be
anomalous and the placenta will be extremely small.
These observations confirm that both the paternally
derived and maternally derived imprinted genes
must be present for normal fetal development to
occur.
Uniparental Disomy
Uniparental disomy is a situation in which both
members of one pair of chromosomes are inherited
from one parent. Every gene on each of the chromosomes in question will have come from one parent.
This usually occurs as the result of correction of a
trisomic zygote by loss of a chromosome. When a
conceptus with three copies of a chromosome loses
one chromosome and retains the two chromosomes
transmitted by the other parent, this results in heterodisomy (inheritance of two different homologous
chromosomes from one parent). Less frequently,
rescue of a monosomic conceptus with only one
chromosome from one parent may occur by duplication of the chromosome during mitosis producing a
cell with two copies of the same chromosome or
uniparental isodisomy. For some chromosomes, uniparental disomy can result in functional or developmental fetal abnormalities, particularly if imprinting
of the genes on that chromosome exists. Recent
studies have demonstrated clinically significant
uniparental disomy for chromosomes 6, 7, 11, 14,
and 15. Uniparental disomy has no effect on the
majority of chromosomes.
295
Mitochondrial Inheritance
Every human cell contains hundreds of mitochondria. Because each mitochondrian contains its own
genome and associated replication systems, each
behaves as a virtually autonomous organism. The
human oocyte contains approximately 100,000 mitochondria in the cytoplasm and mitochondrial DNAs.
In contrast, a sperm contains only 100 mitochondria,
which are selectively eliminated during fertilization.
Therefore, mitochondria are inherited exclusively
from the woman. Because mitochondria contain
genetic information, mitochondrial inheritance
allows the transmission of genes directly from the
woman to her offspring without the possibility of
recombination.
If a mutation occurs in the mitochondrial DNA,
it may segregate into a daughter cell during cell division and thus be propagated. Over time, the percentage of mutant mitochondrial DNAs in different cell
lines can drift towards either normal or pure mutant.
If an oocyte containing largely mutant mitochondrial DNAs is fertilized, the offspring might have a
mitochondrial disease. Several mitochondrial genetic diseases have been described. These include
myoclonic epilepsy with ragged red fibers
(MERRF), Lebers hereditary optic neuropathy,
KearnsSayre syndrome, Leigh syndrome (ataxia,
hypotonia, spasticity, and optic abnormalities), and
pigmentary retinopathy.
Germline Mosaicism
Some cytogenetically normal individuals have
mosaicism (the presence of two or more populations
of cells with different characteristics within one tissue or organ) confined to their gonads. Gonadal or
germline mosaicism can arise as the result of a mitotic error occurring in the zygote; if the error occurs in
cells destined to become the gonad, a portion of the
germ cells may be abnormal. Because spermatogonia and oogonia continue to divide throughout fetal
development, gonadal mosaicism also could occur as
the result of a meiotic error in the dividing germ cells
of the embryo. Germline mosaicism may explain the
occurrence of a new (not previously occurring in a
family) autosomal dominant mutation causing a disease, such as achondroplasia or osteogenesis imperfecta, or a new X-linked disease, such as Duchenne
muscular dystrophy. It also explains the recurrence
of such diseases in more than one offspring in a previously unaffected family. Because of the potential
for germline mosaicism, the recurrence risk after the
birth of a child with a disease caused by a new mutation is approximately 6%.
296
Multifactorial and Polygenic Inheritance

Polygenic traits are determined by the combined
effects of many genes; multifactorial traits are determined by multiple genes and environmental factors.
It is now believed that the majority of inherited traits
are multifactorial or polygenic. Traits determined by
single genes and transmitted by strict mendelian
inheritance, without the contribution of modifier
genes, are probably relatively rare. Birth defects
caused by multifactorial or polygenic inheritance are
recognized by their tendency to recur in families, but
not according to a mendelian inheritance pattern.
Other characteristics that distinguish multifactorial
traits from those with other inheritance patterns are
listed in the box. When counseling couples regarding their offsprings risk of a familial multifactorial
trait, it is important to consider the affected relatives
degree of relatedness to the fetus, not the parents.
The empiric recurrence risk for first-degree relatives
(the fetuss parents or siblings) usually is quoted as
23%, but the risk declines exponentially with successively more distant relationships. Multifactorial
traits generally fall into one of the three following
categories: 1) continuously variable, 2) threshold, or
3) complex disorders.
Continuously variable traits have a normal distribution in the general population. By convention,
abnormality is defined as a trait or measurement
greater than two standard deviations above or below
the population mean. These are typically measurable
or quantitative traits like height or head size, and are
believed to result from the individually small effects
of many genes combined with environmental
factors. Such traits tend to be less extreme in the offspring of affected individuals, because of the statistical principle of regression to the mean.
Multifactorial Inheritance
1. The disorder is familial, but there is no apparent pattern
of inheritance.
2. The risk to first-degree relatives is the square root of
the population risk.
3. The risk is sharply lower for second-degree relatives.
4. The recurrence risk is higher if more than one family
member is affected.
5. The risk is higher if the defect is more severe (ie, the
recurrence risk for bilateral cleft lip is higher than for
unilateral cleft lip).
6. If the defect is more common in one sex, the recurrence risk is higher if the affected individual is of the
less commonly affected sex.
Threshold traits do not appear until a certain

threshold of liability is exceeded. Factors creating
liability to the malformation are assumed to be continuously distributed in the population; only individuals who are at the extreme of this distribution
exceed the threshold and have the trait or defect. The
phenotypic abnormality is thus an all or none phenomenon. Individuals in high-risk families have
enough abnormal genes or environmental influences
that their liability is close to the threshold; for
unknown reasons, some factor or factors increases
the liability for certain family members still further
and the threshold is crossed, resulting in the defect.
Cleft lip and palate and pyloric stenosis are examples of threshold traits.
Certain threshold traits have a predilection for
one gender, indicating that males and females have a
different liability threshold. When a family includes
an affected member who is the less frequently
affected sex, this indicates that even more abnormal
genes or environmental influences are present, and
the affected individual (and possibly the family) has
a more extreme position in the normal distribution of
predisposing factors. The affected persons firstdegree relatives (eg, their siblings) have a higher liability for that particular trait. For example, pyloric
stenosis is more common in males. If a girl is born
with pyloric stenosis, this indicates that she or her
parents have even more abnormal genes or predisposing factors than usually are necessary to produce
pyloric stenosis. After the birth of a girl with pyloric
stenosis, the recurrence risk for her siblings or for
her future children will be higher than expected;
male siblings or offspring will have the highest liability because they are the most susceptible sex and
they will inherit more than the usual number of predisposing genes.
The recurrence risk for threshold traits also is
higher if the defect is severe, again indicating the
presence of more abnormal genes or influences. For
example, the recurrence risk after the birth of a child
with bilateral cleft lip and palate is 8%, compared
with only 4% after unilateral cleft lip without cleft
palate.
Complex disorders of adult life are traits in
which many genes determine an individuals susceptibility to environmental factors, with disease resulting from the most unfavorable combination of both.
This category includes common diseases, such as
heart disease and hypertension. These disorders usually are familial and behave as threshold traits but
with a very strong environmental influence. The
genetic mechanisms of many common adult dis-
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eases have not yet been elucidated, although several

associated genes have been identified. In some
cases, the identity of the associated gene provides a
clue to the pathogenesis of the disease; in others, the
related gene may simply be used as a disease marker. Premature cardiovascular diseases, for example,
are associated with the gene for apolipoprotein E, a
gene that likely influences the pathology of the disease. In contrast, the association of type 1 diabetes
with HLA-DR3/4 is less clear.
MOLECULAR DIAGNOSTIC TESTING

Advances in our understanding of the molecular
basis of inherited disorders have led to the development of DNA-based tests, which may be used for the
confirmation of a diagnosis, prenatal diagnosis, and
carrier testing. Molecular diagnostic testing is now
widely available for a number of single gene disorders, such as TaySachs disease, Canavan disease,
sickle cell disease, CF, muscular dystrophies, and
fragile X syndrome. Molecular-cytogenetic testing
has been developed for the detection of chromosomal abnormalities, including aneuploidy and submicroscopic deletions and duplications.
DNA can be obtained from many sources,
including blood lymphocytes, skin, hair, cheek cells,
and paraffin tissue blocks. Most diagnostic laboratories prefer either blood samples or buccal swabs for
DNA testing. Cultured amniocytes, chorionic villi,
and fetal blood are used for prenatal DNA testing of
the fetus.
MUTATION DETECTION
Once a gene has been cloned and mutations have
been identified, direct testing for the mutation
is possible. This is the most accurate diagnostic method. Direct mutation tests usually are
performed by commercial and hospital-based laboratories for common mutations, which are well
characterized and account for the majority of cases.
In some cases, the mutations are unique to a specific ethnicity. For example, two specific mutations in
the aspartoacylase gene account for 97% of the
mutations that cause Canavan disease in the
Ashkenazi Jewish population. For some genetic
disorders, the mutations are unique or specific to an
individual family; therefore, mutation testing may
not be routinely provided by a commercial laboratory. In these cases, there may be only one or two
academic or hospital laboratories in the country that
offer the testing. (This information is provided by
297
GeneTests, a genetic testing resource web site at

www.genetests.org.) In general, initial screening of
a gene for mutations usually takes place in research
laboratories under approved protocols and is not
practical for diagnostic testing. Once a mutation
has been identified, it may be possible to offer diagnostic or carrier testing to individuals at risk.
There are a variety of methods available for
detecting mutations. The methodology usually is
determined by the nature of the specific mutation.
Allele specific oligonucleotide hybridization and
restriction fragment length polymorphisms analysis
frequently are used to detect point mutations.
Southern blot analysis and polymerase chain reaction (PCR) often are used to detect gene deletions
associated with disorders such as Duchenne muscular dystrophy and spinal muscular atrophy. A combination of PCR and Southern blot analysis are used to
determine the number of trinucleotide repeats for
disorders such as fragile X syndrome and myotonic
dystrophy.
Southern Blot Analysis

Southern blot analysis provides a basis for studying
genetic disorders at the DNA level. This procedure,
named after its inventor E. M. Southern, separates
DNA fragments according to size and allows the
identification of specific DNA fragments using
radiolabeled DNA probes.
The steps to prepare a Southern blot are shown
in Figure 2. First, DNA is extracted from nucleated
cells (leukocytes, trophoblasts, or amniocytes) or tissue, and digested into small pieces with a restriction
enzyme. Then, the DNA is loaded into an agarose
gel, an electric current is applied, and DNA fragments migrate down the gel according to size (smaller fragments move faster). The DNA contained
within the agarose gel is still double stranded and
must be denatured by alkali treatment into singlestranded pieces and then transferred to a nitrocellulose or nylon membrane. The membrane contains
many thousands of fixed DNA fragments. Specific
DNA fragments can be detected using a DNA probe
labeled with a radionuclide, such as 32P, although
nonradioactive substances such as biotinavidin
may be used. The probes may be complementary
DNA (cDNA), genomic DNA (exons, introns, or
regulatory regions), or short pieces of single-stranded DNA called oligonucleotides, which usually
range in size from 20 to 50 base pairs. The DNA
probe will hybridize only with DNA fragments on
the blot that are complementary. To visualize the
DNA fragment, the blot is exposed to X-ray film at
298
Isolate genomic DNA

Digest DNA with
restriction
enzymes
Separate DNA
fragments by
electrophoresis
Transfer DNA
to membrane
Hybridize with
labeled probe
xxxxxxxxxx
Autoradiogram
Specific hybridizing
DNA band
Fig. 2. Southern blot analysis. (Jameson JL. Principles of

molecular medicine. Totowa, NJ: Humana Press, 1998:16)
-70C, a process called autoradiography. The film is

developed, and the presence or absence of DNA
bands or fragments can be determined.
Polymerase Chain Reaction

The development of the PCR has greatly simplified
DNA analysis and shortened laboratory time.
Polymerase chain reaction allows the exponential
amplification of the targeted gene or DNA sequence.
Only minute quantities of DNA, typically 0.11 g,
are necessary for PCR. DNA can be amplified from
a single cell. One important prerequisite of PCR,
which is not required for Southern blot analysis, is
that the sequence of the gene, or at least the borders
of the region of DNA to be amplified, must be
known.
The PCR procedure has three steps (Fig. 3).
First, DNA is denatured by heating to render it single stranded. Second, the PCR primers (primer A
and B), which are short pieces of DNA (oligonucleotides) 2030 base pairs in length exactly com-
plementary to the ends of each piece of the doublestranded DNA to be amplified, anneal to their complementary regions of the DNA. Third, synthesis of
the complementary strand of DNA occurs in the
presence of the enzyme Taq polymerase and
nucleotides triphosphates (dATP, dCTP, dGTP, and
dTTP). The reaction cycle of denaturation, annealing, and extension is repeated 2530 times to produce millions of copies of DNA.
Typically, fragments several kilobases (kb) in
size can be amplified, but sequences up to 10 kb
have been successfully amplified. The exact cycling
parameters and conditions for PCR must be determined empirically for each set of primers. Polymerase chain reaction is very sensitive; therefore,
extreme care must be taken to avoid amplification of
contaminant DNA from aerosolized secretions or
sloughed skin cells. These precautions are particularly important when DNA from a single cell is
being amplified.
Restriction Fragment Length

Polymorphism Analysis
Restriction fragment length polymorphism analysis
can be used when a mutation either creates or
destroys a restriction endonuclease site. To detect
the mutation, DNA around the site of the mutation is
amplified by the PCR, incubated with the appropriate restriction enzyme, and analyzed by agarose gel
electrophoresis. When a mutation creates a new
restriction site, two DNA fragments will be detected
if the mutation is present (Fig. 4A). An individual
without the mutation will demonstrate a single fragment. This method frequently is used for the prenatal genetic diagnosis of sickle cell disease. Sickle
cell disease is caused by a single base pair substitution (adenine to thymidine) in codon 6 of the -subunit of hemoglobin, which results in the loss of the
MstII restriction site. Individuals with sickle cell disease are homozygous for this mutation.
Allele Specific Oligonucleotide

Hybridization (Dot Blot)
Allele specific oligonucleotide hybridization (dot
blot) frequently is used to detect point mutations. A
segment of DNA surrounding the mutation is amplified by PCR and then an aliquot is spotted onto a filter membrane. The membrane is hybridized with an
oligonucleotide probe specific for the normal
sequence and one specific for the mutation. A positive hybridization signal is detected only when the
sequence of the PCR product on the membrane is
COMMITTEE OPINIONS
5
3
Taq polymerase
DNA template
Primer A
299
Restriction-enzyme recognition site

created by mutation
PCR primer
3
5
Primer B
Agarose gel
94C
Denature
3
3
Anneal primers
5068C
5
3
5
Repeat for
2530 cycles
1
Site of mutation
72C
5
PCR primer
Polymerize
3
5
Wild-type
oligonucleotide
Cycle
Mutant
oligonucleotide
Fig. 3. Polymerase chain reaction. (Jameson JL.
Principles of molecular medicine. Totowa, NJ: Humana

Press, 1998:15)
complementary to the sequence of the oligonucleotide. For example, testing an individual who is
heterozygous for the mutant allele will reveal a positive hybridization signal with both the normal
sequence and the mutant oligonucleotide probe.
DNA from individuals homozygous for the mutation
will only hybridize to the mutant oligonucleotide
(Fig. 4B). This technique is used for the detection of
point mutations for many single gene disorders,
including CF, TaySachs disease, Gauchers disease,
Canavan disease, and sickle cell disease.
Deletion Analysis
Intragenic deletions can be detected by PCR or
Southern blot analysis or both. Polymerase chain
reaction can be used to determine the absence or
presence of exons within a gene. A sample of DNA
is amplified by PCR and then the PCR products are
WT
HET
MUT
Fig. 4. Mutation detection. (A) Restriction fragment

length polymorphism (RFLP) analysis. The region of
DNA surrounding the mutation is amplified by specific
PCR primers, digested with a restriction enzyme, and
analyzed by agarose-gel electrophoresis. In this example, the mutation creates a new restriction site. Individuals homozygous for the mutation have two DNA
fragments (Lane 2) while an individual with two normal
copies has one single fragment (Lane 1). A heterozygous individual has one normal uncut fragment and two
cut fragments (Lane 3). (B) Allele specific oligonucleotide (ASO) hybridization. The amplified DNA from
an individual homozygous for the mutation only
hybridizes to the mutant oligonucleotide (MUT) whereas
a heterozygous individual (HET) hybridizes to both the
normal (wild-type) and the mutant. A normal individual
will only hybridize to the normal oligonucleotide (WT).
(Korf B. Molecular diagnosis. N Engl J Med 1995;332:
1500. Copyright 1995 Massachusetts Medical
Society. All rights reserved.)
300
analyzed by gel electrophoresis, stained with ethidium bromide to detect the absence or presence of
DNA fragments (Fig. 5). The absence of a DNA
fragment indicates the presence of a deletion. This
method is used routinely for diagnostic and prenatal
testing for Duchenne muscular dystrophy, an Xlinked disorder. Approximately 60% of patients with
Duchenne muscular dystrophy have intragenic deletions in the dystrophin gene and the majority of
these can be detected by PCR. Most laboratories use
a multiplex strategy to examine multiple exons in
one PCR. However, PCR is not useful to determine
carrier status in the mothers of affected males. This
requires Southern blot analysis with cDNA probes
from the dystrophin gene and scanning densitometry
to assess gene dosage. Testing of females at risk to
be carriers based on their family history is less reliable when an affected relative is not available for
DNA testing. Dosage analysis also can be used to
test male patients with Duchenne muscular dystrophy with a negative result by multiplex PCR to
detect duplications within the dystrophin gene,
which occur in approximately 6% of patients with
Duchenne muscular dystrophy.
Linkage Analysis
When the location of a gene is known but the gene
has not yet been characterized, or when the mutations have not been identified, linkage analysis may
be performed to predict the likelihood that a relative
or fetus has inherited a disease-causing gene within
an at-risk family. Linkage analysis requires that 1) at
least two generations of family members, including
affected individuals, are available and willing to be
tested, and 2) highly polymorphic markers such as
restriction fragment length polymorphisms, or short
tandem repeat polymorphisms close to or within the
gene are available. These polymorphic markers
result from normal genetic variation and are not disease causing but may be used to track the inheritance
of genetic diseases within families. The closer a
marker is to a gene, the higher the likelihood that the
marker and gene are transmitted or inherited together (linkage). The accuracy of linkage analysis
depends on the correct diagnosis, the informativeness of the markers within the family, and the distance between the marker and the disease-causing
gene. Markers closest to or within a gene are less
likely to undergo recombination and will provide the
Multiplex PCR analysis of gene deletions
D
1
Fig. 5. Multiplex gene deletion analysis. Exons AD are simultaneously amplified with 4 sets of PCR primers. When an exon is deleted, the DNA fragment
is absent. In lane 2 exon A is absent, in lane 3 exons B and C, and in lane 4
exon C. Lane 1 shows no evidence of a deletion; all 4 DNA products are present. (Korf B. Molecular diagnosis. N Engl J Med 1995; 332:1219. Copyright
1995 Massachusetts Medical Society. All rights reserved.)
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most accurate prediction. Although linkage analysis

is less accurate than direct mutation detection, under
the specified circumstances it may provide families
with helpful information.
TRINUCLEOTIDE REPEAT ANALYSIS

The detection of trinucleotide repeat expansions,
associated with diseases such as fragile X syndrome,
myotonic dystrophy, and Huntingtons disease, often
requires a combination of PCR and Southern blot
analysis (Fig. 6). The size of normal alleles, premutation alleles, and, in some cases, full mutations
can be determined by using PCR. However, full
mutations associated with a large expansion (eg,
>200 repeats in fragile X syndrome) may need to be
detected using Southern blot analysis. It also is used
to assess the methylation status in fragile X patients
and pregnancies with the full mutation. The repeat
region not only expands to more than 200 repeats but
also becomes hypermethylated in affected individu-
301
als. DNA is digested with restriction enzymes including a methylation-sensitive enzyme such as BsshII,
gel electrophoresed, and hybridized with a DNA
probe from the repeat region of the fragile X gene
(FMR-1).
FLUORESCENCE IN SITU HYBRIDIZATION

Fluorescence in situ hybridization (FISH) is performed on either metaphase chromosome preparations from cultured lymphocytes, amniocytes, or
villi, or interphase nuclei from blood, tissue, chorionic villi, or amniotic fluid. After the chromosomes or
nuclei are fixed on a microscope slide, they are
hybridized with a fluorochrome-labeled DNA probe
specific for a particular region of a chromosome. The
probe will hybridize to complementary DNA
sequences that can be visualized using a fluorescence
microscope. Fluorescence in situ hybridization is
used as an adjunct to routine cytogenetic analysis
for the detection of submicroscopic chromosome
CGG repeat region
Coding sequence
Wild type
Premutation
Full mutation
Restriction-enzyme recognition sites
Probe
PCR primers
Wild
type
Asymptomatic
carrier
Southern blot
Full
mutation
Wild
type
Asymptomatic
carrier
Full
mutation
PCR
Fig. 6. Trinucleotide repeat analysis by PCR and Southern blot. A region of DNA containing the CGG repeat is amplified
and the product is analyzed on an agarose gel. The DNA fragment from a carrier with a premutation is larger because
of the expanded number of repeats. Sometimes the expansion is so large that the DNA fails to amplify and the number
of repeats cannot be detected using PCR. In this case, a Southern blot is performed (left panel) and the DNA from an
individual with a full mutation appears as a much larger band. (Korf B. Molecular diagnosis. N Engl J Med 1995;332:
1501. Copyright 1995 Massachusetts Medical Society. All rights reserved.)
302
deletions and duplications. These deletions and

duplications often are several 1,000 base pairs but
are too small to be detected by conventional cytogenetics. DNA probes have been developed for the
common deletion and duplication syndromes (Table
1). It also may be used to identify or confirm the
presence of a subtle chromosomal rearrangement
(eg, translocation) or characterize a marker chromosome. Fluorescence in situ hybridization of interphase nuclei is used prenatally for the rapid
detection of common aneuploidies, such as trisomy
21. However, this is generally reserved for cases
where confirmation of a chromosomal abnormality
may influence a couples reproductive options or
obstetric management.
COMPARATIVE GENOMIC
HYBRIDIZATION
Comparative genomic hybridization is a relatively
new DNA-based cytogenetic technique to identify
subtle chromosome deletions and duplications that
have not been detected using traditional cytogenetic
methods. To accomplish this, DNA from a patient is
labeled with a green fluorochrome and normal control DNA is labeled with a red fluorochrome, which
can be visualized with a fluorescence microscope.
The DNA is hybridized to normal metaphase chromosomes. Wherever a chromosome region is duplicated, the metaphase chromosome will hybridize
with the excess green-labeled DNA and appear
green. Conversely, deletions will appear red.
Clinically, comparative genomic hybridization is
primarily used to detect cytogenetic changes in
tumors but, it also has been used to identify subtle
unbalanced translocations, the origin of marker or
supernumerary chromosomes, and intrachromosomal duplications.
MICROARRAY TECHNOLOGY
DNA chip technology is a high throughput method
used primarily to study gene expression. Miniature
arrays of cDNA clones are spotted onto a glass slide
and hybridized with labeled cDNA prepared from
the tissue of interest. If a gene is strongly expressed
in the tissue, the hybridization signal will be intense.
This technique can analyze the gene expression of
thousands of genes at one time. In the future,
oligonucleotide arrays also may be used to search
for gene mutations and polymorphisms. Chips containing gene specific oligonucleotides matching normal and single nucleotides substitution sequences
Table 1. Microdeletion Syndromes

Syndrome
Aniridia/Wilms tumor
Angelmans
DiGeorge/velocardiofacial
Langer-Giedion
Miller-Dieker
Prader-Willi
Smith-Magenis
Williams
Chromosome Deletion
11p13
15q11-13
22q11.2
8q24
17p13.3
15q11-13
17p11.2
7q11.23
are hybridized with fluorescent-labeled DNA.

Improvements in chip technology will enable whole
genome expression screening as well as improved
mutation detection in the future.
INDICATIONS FOR MOLECULAR

TESTING
A variety of molecular diagnostic tests are available
to determine whether an individual or fetus has
inherited a disease-causing gene mutation. In general, testing is offered to individuals or couples
identified as being at risk for a genetic disorder
based on their family history, medical history, or
ethnicity. Determination of an individuals carrier
status for a genetic disorder provides a more accurate estimate of their risk of having an affected
offspring and allows an individual or couple to consider prenatal testing options. This information also
may assist couples with their reproductive decisions. Furthermore, it can identify other family
members or relatives at risk for the disorder or at
risk for being a carrier.
Molecular testing also may be used in clinical
and prenatal situations to confirm a diagnosis. For
example, screening for CF mutations may determine
whether an infertile male with congenital bilateral
absence of the vas deferens is a CF carrier. Prenatal
molecular testing for some genetic disorders may be
offered when a congenital anomaly is identified
antenatally. For example, FISH for the 22q11.2 deletion may establish a cause when a conotruncal
cardiac defect is detected by ultrasonography.
Establishing an etiology enables clinicians to provide couples with accurate genetic risk assessments,
prognostic information, and recommendations for
obstetric and neonatal management.
Prior to diagnostic and carrier testing for genetic disorders, patients should be informed of the nat-
COMMITTEE OPINIONS
ural history of the disorder and current therapy, the

inheritance and their risk of inheriting or transmitting the gene, benefits and limitations of testing, and
the implications of negative and positive results.
Preconceptional and prenatal testing also should
include a discussion of reproductive options including prenatal testing, adoption, donor programs, and
termination of pregnancy. Written informed consent
should be obtained from all individuals undergoing
genetic screening. Patients should understand that
molecular testing is voluntary and that every effort
will be made to ensure confidentiality of their medical records and test results.
ACCURACY AND LIMITATIONS OF

MOLECULAR TESTING
Direct detection of a point mutation, deletion, or
duplication is the most accurate test. However, the
accuracy of molecular diagnosis also is dependent
on an accurate diagnosis. If an affected relative is
not available to identify the presence of a mutation
or if medical records are not available to confirm the
diagnosis, this may decrease the accuracy of testing
for a specific mutation and for the suspected genetic disorder.
One of the limitations of molecular diagnostic
testing is test sensitivity. There are a number of
factors that determine the ability to detect mutations. Many genetic disorders result from a variety
of genetic alterations. For example, more than
800 mutations have been reported in patients with
CF. The mutation detection rates for many genetic
disorders, including neurofibromatosis, CF, and
hemophilia, are less than 100%. Therefore, the
absence of a mutation does not exclude the possibility that an individual may be a carrier. Furthermore,
there may be ethnic differences in the detection
rates; 97% of CF mutations have been identified in
the Ashkenazi Jewish population while only 30% in
Asian Americans. The incidence and carrier risk for
some genetic disorders also is dependent on ethnicity and has led to the current recommendations for
carrier screening for specific genetic disorders.
Differences in test sensitivity and the prevalence of
mutations must be considered for each individual
genetic disorder and discussed with the patient prior
to testing. Disease prevalence and test sensitivity
should be taken into account in future recommendations for molecular-based carrier testing.
Another limitation to molecular testing is genetic heterogeneity. In some cases, there may be more
than one gene or chromosomal locus responsible for
303
a genetic disorder. For example, at least two genes

have been identified that cause tuberous sclerosis, an
autosomal dominant disorder. Conversely, mutations
in a single gene can cause different phenotypes. For
example, mutations in fibroblast growth factor receptor 3 (FGFR3) are associated with several types of
skeletal disorders, including achondroplasia, hypochondroplasia, thanatophoric dysplasia, and with
craniosynostosis (eg, Crouzons disease, coronal
synostosis).
In some diseases, the identification of a genetic
mutation cannot precisely predict the phenotype
because of reduced penetrance or phenotypic variability or both. For example, 85% of women with a
BRCA1 mutation develop breast cancer during their
lifetime; therefore, the finding of a BRCA1 mutation
indicates a strong predisposition to breast cancer but
it does not indicate which women with the mutation
will develop a malignancy. Some genetic disorders
are highly variable even within families with the
same mutation. Therefore, it may only be possible to
provide patients with a description of the natural history of the disorder and an estimate of the frequency
of specific features in patients with similar mutations. The lack of genotype phenotype correlation
for some genetic disorders, such as CF, also can
limit the ability to accurately predict the course of
the disease. Therefore, when molecular testing indicates that a patient or fetus has inherited a mutation,
it is helpful to consult a geneticist or someone with
expertise in the specific disorder to provide current
information regarding the prognosis, as well as, the
limitations and accuracy of testing.
APPLICATIONS IN OBSTETRICS AND

GYNECOLOGY
Genetics is taking an increasingly prominent role in
the practice of obstetrics and gynecology. Gene
identification, characterization of disease-causing
mutations, and advances in genetic technology have
led to an increased number of available genetic tests,
which may be used for the diagnosis of genetic
disorders, carrier detection, and prenatal or preimplantation genetic diagnosis. Testing for a specific
genetic disorder most often occurs in an obstetric
setting based on either the family history or the couples ethnicity. Genetic counseling should be offered
to couples at risk so they can review the nature of the
disorder, the inheritance pattern, their specific risk
for being a carrier and for having a child with the
disorder, the current availability of prenatal and
postnatal testing as well the accuracy and limitations
304
of testing, and their reproductive options. Most molecular genetic testing for disorders, such as
Duchenne muscular dystrophy, fragile X syndrome,
neurofibromatosis, and hemophilia, is performed
when a couple is at high risk based on their family
history. Initially, testing is performed to determine
whether the parent is a carrier. If the parent is a carrier, prenatal testing by amniocentesis or chorionic
villus sampling is possible. Some couples may consider preimplantation genetic diagnosis. Single gene
disorders and chromosomal abnormalities, such as
deletions and translocations, may be identified in an
embryo conceived through in vitro fertilization by
testing a single blastomere. Genetic testing for disorders prevalent in specific ethnic populations such
as CF for Caucasians and TaySachs and Canavan
disease for individuals of Eastern European Jewish
ancestry, is used to determine if an individual is a
carrier. Prenatal molecular diagnostic testing is
available for couples who are both carriers of sickle
cell disease and thalassemia determined by hemoglobin electrophoresis. The genetic testing options
in pregnancy are rapidly growing with the completion of the human genome project; however, a thorough family history is essential to identify a couple
at risk.
Genetic testing during pregnancy may establish
a diagnosis that may influence obstetric management. For example, PCR of amniotic fluid is used to
determine the Rh status of the fetus to determine if
the fetus is at risk for hemolytic disease of the newborn when the woman is Rh sensitized and the man
is a heterozygous carrier of antigen D. The fetus at
risk will need close surveillance during the pregnancy. A specific molecular diagnostic test may be
considered when the finding of a fetal malformation
by ultrasonography raises the suspicion of a genetic
disorder. For example, mutation testing for CF in a
fetus with echogenic bowel, fibroblast growth factor
receptor 2 (FGFR2) for suspected Aperts syndrome
(craniosynostosis), and 22q11.2 deletion testing
when a conotruncal cardiac defect is detected.
Identification of an etiology provides the physician
and couple with a better understanding of the prognosis that influences not only the obstetric and
neonatal care of the infant but also a couples reproductive decisions. Furthermore, it establishes an
accurate assessment of the recurrence risk for this
family and their relatives.
Some of the genes responsible for the inherited
forms of some types of cancer (such as breast, ovarian, and colon) have been identified. Risk assess-
ment for relatives in these families may include

genetic testing in addition to evaluating other risk
factors, such as family history. In some families,
breast and ovarian cancer is attributed to an inherited genetic mutation, BRCA1 or BRCA2. The genes
responsible for hereditary nonpolyposis colorectal
cancer, juvenile polyposis, and familial adenomatosis polyposis, have been identified. It is likely that
other genes that contribute to cancer will be identified in the future, which may be useful for cancer
risk assessment and management.
Genetic screening and testing should be considered a component of an infertility evaluation.
Preconceptional genetic screening and counseling
can identify couples at risk for having offspring with
a genetic disorder and provide them with information that enables them to make informed decisions
regarding their reproductive options. Genetic causes
of severe oligospermia and azoospermia include
balanced translocations, Klinefelters syndrome
(47,XXY), and Y chromosome abnormalities and
microdeletions. Cytogenetic studies and PCR-based
Y chromosome deletion testing should be considered. Approximately two thirds of males with congenital bilateral absence of the vas deferens have at
least one CF mutation. Men with congenital bilateral absence of the vas deferens should be offered CF
carrier testing. Partners of carriers and individuals
with CF should be tested to assess their risk for having a child with CF. This information may be useful
for an infertile couple considering their reproductive
options, such as testicular aspiration and biopsy with
intracytoplasmic sperm injection, preimplantation
genetic diagnosis with in vitro fertilization, donor
gamete, adoption, and prenatal testing.
SUMMARY
Human genetics and molecular testing is playing an
increasingly important role in obstetric and gynecologic practice. It is essential that obstetricians and
gynecologists are aware of the advances in our
understanding of genetic disease and the fundamental principles of molecular testing and genetic
screening as genetics is integrated into routine
medical practice. In the future, elucidation of the
genetic basis for reproductive disorders, common
diseases, and cancer with improved high throughput
technology for genetic testing will expand testing
opportunities and influence treatment options and
prevention strategies.
COMMITTEE OPINIONS
REFERENCE
1. The human genome. Science 2001;291:11451434
305

www.cdc.gov/genetics
Gene Clinics
www.geneclinics.org
RESOURCES
Bell J. The new genetics in clinical practice. BMJ 1998;316:
618620
Blackwood MA, Weber BL. BRCA1 and BRCA2: from molecular genetics to clinical medicine. J Clin Oncol 1998;16:
19691977
Brown PO, Botstein D. Exploring the new world of the genome
with DNA microassays. Nat Genet 1999;21(suppl):3337
Caskey CT. Medical genetics. JAMA 1997;277:18691870
Collins FS. Genetics: an explosion of knowledge is transforming clinical practice. Geriatrics 1999;54:4147;quiz 48
Cooper DN, Schmidtke J. Diagnosis of human genetic disease
using recombinant DNA. 4th ed. Hum Genet 1993;92:211236
Davis JG. Predictive genetic tests: problems and pitfalls. Ann
N Y Acad Sci 1997;833:4246
Jameson JL. Principles of molecular medicine. Totowa, New
Jersey: Humana Press, 1998
Korf B. Molecular diagnosis (1). N Engl J Med 1995;332:
12181220
Korf B. Molecular diagnosis (2). N Engl J Med 1995;332:
14991502
Makowski DR. The Human Genome Project and the clinician.
J Fla Med Assoc 1996;83:307314
Mark HF, Jenkins R, Miller WA. Current applications of molecular cytogenetic technologies. Ann Clin Lab Sci 1997;27:
4756
Pyeritz RE. Family history and genetic risk factors: forward to
the future. JAMA 1997;278:12841285
SOURCES OF ONLINE INFORMATION

Tutorial in Genetics (HHMI)
www.hhmi.org/GeneticTrail/
Online Mendelian Inheritance in Man
www3.ncbi.nlm.nih.gov/Omim/
MEDLINE
www.ncbi.nlm.nih.gov/PubMed/
GeneTests
www.genetests.org
Genome Database
www.gob.org
Biochemical testing information
biochemgen.ucsd.edu/wbgtests/dz.tst.htm
Alliance of Genetic Support Groups
medhlp.netusa.net/www/agsg.htm
National Human Genome Research
www.nhgri.nih.gov
GLOSSARY
Allele: One of two or more alternate forms of a gene.
Allele specific oligonucleotides: Synthetic oligonucleotide
designed to hybridize to a specific sequence, and under the
right conditions, to fail to hybridize to a related sequence.
Allele specific oligonucleotides also are used as PCR primers
in several methods similarly designed to distinguish between
closely related alleles.
Autosomal Dominant: An allele located on an autosome (nonsex chromosome) that expresses itself phenotypically in the
presence of the same or a different allele (ie, in a homozygous
or heterozygous condition).
Autosomal Recessive: An allele located on an autosome that
does not express itself phenotypically in the presence of a dominant allele (ie, in a heterozygous condition). It is only phenotypically expressed in a homozygous condition.
Chimera: An organism with tissues composed of two or more
genetically distinct cell types.
Chromatin: An intranuclear and intrachromosomal complex
made up of DNA, and histone and nonhistone proteins.
Co-Dominant: Alleles that are different from each other, but
both are expressed in the phenotype.
Codon: A section of DNA (three nucleotide pairs in length)
that codes for a single amino acid.
Comparative Genomic Hybridization: A cytogenetic method
based on a combination of fluorescence microscopy and digital image analysis. Differentially labeled test DNA and normal
reference DNA are hybridized simultaneously to normal chromosome spreads. Hybridization is detected with two different
fluorochromes. Deletions, duplications, or amplifications are
seen as changes in the ratio of the intensities of the two fluorochromes along the target chromosomes.
Complementary DNA (cDNA) Probe: A DNA sequence that
is exactly complementary to mRNA, lacking introns and regulatory regions.
Contiguous Gene Deletion Syndrome: A syndrome caused
by a deletion involving genes that are physically located
together in a chromosome segment.
Constitutive Heterochromatin: Condensed genetically inactive chromatin located in the same regions of both homologous
chromosomes.
DNA: A double-helical structure composed of two coils of
nucleotide chains connected by nitrogen bases.
DNA Hybridization: A process whereby labeled nucleic acid
molecules (oligonucleotide probe) bind to a DNA sequence on
a target (Southern blot, metaphase chromosomes, or interphase
nuclei) that is complementary to its own.
306
DNA Methylation: A process for control of tissue specific

gene expression. Methylation turns off the regulatory region
of a gene, thereby preventing DNA transcription.
Mutation: An alteration of DNA sequencing in a gene that

results in a heritable change in protein structure or function that
frequently has adverse effects.
Epigenetic: NonDNA/RNA related process that affects genotype and phenotype (ie, methalization).
Deletion: A mutation that is generated by removal of a

sequence of DNA, with the regions on either side being
joined together.
Exon: A region of a gene made up of DNA sequences that will

be transcribed into mRNA.
Expressivity: The degree to which a genotype is expressed in
the phenotype (range of phenotypic features).
Fluorescence in situ Hybridization (FISH): A procedure for
detecting specific nucleic acid sequences in morphologically
preserved chromosomes, cells, and tissue sections using fluorescent labeled oligonucleotide probes.
Expansion (see Hereditary Unstable DNA)

Frame-shift: A mutation caused by deletions or insertions
that are not a multiple of three base pairs. Results in a
change in the reading frame in which triplet codons are
translated into protein.
Insertion: A mutation caused by the presence of an additional sequence of nucleotide pairs in DNA.
Gene: A unit of heredity responsible for the inheritance of a

specific trait that occupies a fixed chromosomal site and corresponds to a sequence of nucleotides along a DNA molecule.
Inversion: A mutation involving the removal of a DNA

sequence, its rotation through 180 degrees, and its reinsertion in the same location.
Genome: The entire complement of genetic material in a chromosome set.
Missense: A mutation that alters a codon so that it encodes

a different amino acid.
Genomic Imprinting: The existence of parent-of-origin differences in the expression of certain genes.
Northern Blot: A technique for transferring RNA from an

electrophoresis gel to a nitrocellulose filter on which it can be
hybridized to a complementary DNA (cDNA) probe.
Germline Mosaicism: Mosaicism that is confined to the gonad.

Hereditary Unstable DNA (Triplet Repeat Expansion):
Gene containing a region of triplet codon repeats such as
(CGC)n. The number of triplet repeats can increase during
meiosis. If the expansion of repeats reaches a critical number,
the gene becomes methylated and is turned off, resulting in
phenotypic abnormalities.
Heterochromatin: Chromatin that remains condensed
throughout interphase. It contains DNA that is genetically inactive and replicates late in the S phase of the cell cycle. There
are two types of heterochromatin: constitutive and facultative.
Hybridization (Dot Blot): A semiquantitative technique for
evaluating the relative abundance of nucleic acid sequences in
a mixture or the extent of similarity between homologous
sequences.
Imprinting: The imposition of a stable behavior pattern in a
young animal by exposure, during a particular period in its
development, to one of a restricted set of stimuli.
Intron: A region of a gene, made up of noncoding DNA
sequences that lies between exons.
Karyotype: The chromosome constitution of an individual.
Linkage: The association of genes on the same chromosome.
Nucleotide: A component of a DNA or RNA molecule composed of a nitrogenous base, one deoxyribose or ribose sugar,
and one phosphate group. In DNA, adenine specifically joins to
thymine and guanine joins to cytosine. In RNA, uracil replaces
thymine.
Oligonucleotide Primer: A short sequence of nucleotides that
is necessary to hybridize to a DNA or RNA strand using the
enzymes DNA polymerase or reverse transcriptase.
Penetrance: The ability of a mutant gene to be expressed in an
individual who carries the gene.
Phenotype: Observable physical characteristics of an organism resulting from the expression of the genotype and its interaction with the environment.
Polygenic Inheritance: Inheritance of traits that are determined by the combined effects of many genes.
Polymerase Chain Reaction (PCR): A method for enzymatically amplifying a short sequence of DNA through repeated
cycles of denaturation, binding with an oligonucleotide primer
and extension of the primers by a DNA polymerase.
Polymorphisms: Minor differences that distinguish one individual from another.
Methylation: (see DNA Methylation)
Recombinant DNA: A new DNA sequence formed by the

combination of two nonhomologous DNA molecules.
Mitochondrial Inheritance: Mitochondria are inherited

exclusively from women. Because they contain DNA, mitochondrial inheritance allows transmission of genes directly
from the woman to her offspring.
Restriction Endonuclease: An enzyme that recognizes and

cleaves a specific DNA sequence (usually 410 nucleotide
bases long).
Mosaicism: The presence of two or more populations of cells

with different characteristics within one tissue or organ.
Restriction Fragment Length Polymorphism: A polymorphic difference in DNA sequence between individuals that can
be recognized by restriction endonucleases.
Multifactorial Inheritance: Inheritance of traits that are

determined by a combination of genetic and environmental
factors.
Southern Blot: A technique used to detect specific DNA

sequences by separating restriction enzyme digested DNA
fragments on an electrophoresis gel, transferring (blotting)
COMMITTEE OPINIONS
these fragments from the gel onto a membrane or nitrocellulose

filter, followed by hybridization with a labeled probe to a specific DNA sequence.
Spectral Karyotype: A molecular cytogenetic method in
which all of the chromosomes in a metaphase spread are visualized in different colors (multicolor FISH).
Uniparental Disomy: Inheritance of two copies of part or all
of a chromosome from one parent and no copy from the other
parent.
Uniparental Heterodisomy: Inheritance of two homologous
chromosomes from one parent.
Uniparental Isodisomy: Inheritance of two identical chromosomes from one parent.
Threshold Traits: Traits that are not manifested until a certain
threshold of liability is exceeded.
Transcription: The process of RNA synthesis from a DNA
template that is directed by RNA polymerase.
Triplet Repeat Expansion (see Hereditary Unstable DNA)
Trinucleotide Repeat Analysis (Repeats): Unstable DNA
sequences found in several human genes. Normally the triplets
are repeated in tandem 550 times. When the number rises
above the normal range, mutant disease syndromes appear.
X-inactivation: A process by which one of the X chromosomes in each somatic cell of females is rendered inactive. This
results in a balance in gene expression between the X chromosomal and autosomal genes, which is necessary because males
have only one X chromosome.
X-linked: An allele for a trait or disorder that is located on the
X chromosome, and may be either dominant or recessive.
Western Blot: A technique, conceptually related to the
Southern and Northern blot that is used to detect specific
proteins.
307
Copyright July 2002 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system, or
transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be
directed to Copyright Clearance Center, 222 Rosewood Drive,
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409 12th Street, SW
PO Box 96920
Genetics and molecular diagnostic testing. ACOG Technology
Assessment in Obstetrics and Gynecology No. 1. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2002;100:193211
COMMITTEE OPINIONS
309
COMMITTEE OPINIONS
COMMITTEE
ON
GYNECOLOGIC PRACTICE
COMMITTEE OPINIONS
COMMITTEE
ON
GYNECOLOGIC PRACTICE
ACOG
Committee on
Committee on
Obstetric Practice
Reaffirmed 2008
Committee
Opinion
Statement on Surgical Assistants
followed.
the publisher.
Competent surgical assistants should be available for all major obstetric and
gynecologic operations. In many cases, the complexity of the surgery or the
patients condition will require the assistance of one or more physicians to
provide safe, quality care. Often, the complexity of a given surgical procedure
cannot be determined prospectively. Procedures including, but not limited to,
operative laparoscopy, major abdominal and vaginal surgery, and cesarean
delivery may warrant the assistance of another physician to optimize safe surgical care.
The primary surgeons judgment and prerogative in determining the
number and qualifications of surgical assistants should not be overruled by
public or private third-party payers. Surgical assistants should be appropriately compensated.

directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
311
312
ACOG
Committee on
Reaffirmed 2008
Committee
Opinion
Number 253, March 2001
(Replaces Statement of Policy on

Liposuction, January 1988)
Nongynecologic Procedures
followed.
Copyright March 2001
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Cosmetic procedures (such as laser hair removal, body piercing, tattoo

removal, and liposuction) are not considered gynecologic procedures and,
therefore, generally are not taught in approved obstetric and gynecologic
residencies. Because these are not considered gynecologic procedures, it is
inappropriate for the College to establish guidelines for training. As with
other surgical procedures, credentialing for cosmetic procedures should be
based on education, training, experience, and demonstrated competence.
COMMITTEE OPINIONS
ACOG
Committee on
Reaffirmed 2009
313
Committee
Opinion
followed.
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Avoiding inappropriate clinical decisions based on false-positive human

chorionic gonadotropin test results.
2002;100:1057-9.
Avoiding Inappropriate Clinical

Decisions Based on False-Positive
Human Chorionic Gonadotropin
Test Results
ABSTRACT: Clinically significant false-positive human chorionic gonadotropin (hCG) test results are rare. However, some individuals have circulating
factors in their serum (eg, heterophilic antibodies or nonactive forms of hCG)
that interact with the hCG antibody and cause unusual or unexpected test
results. False-positive and false-negative test results can occur with any specimen, and caution should be exercised when clinical findings and laboratory
results are discordant. Methods to rule out the presence of interfering substances include using a urine test, rerunning the assay with serial dilutions of
serum, preabsorbing serum, and using another assay. Physicians must decide
whether the risks of waiting for confirmation of results outweigh the risks of
failing to take immediate medical action. Patients should be notified if they
are at risk for recurrent false-positive hCG test results, and this information
should be included in the patients medical record.
Clinical management of many gynecologic conditions has improved dramatically over recent decades through the development of very sensitive and
highly specific assays for hormones, particularly human chorionic
gonadotropin (hCG). These assays have revolutionized the management of
ectopic pregnancy and gestational trophoblastic disease, which now have a
substantially lower mortality rate as a result of the ability to quantitate circulating (serum) and urinary hCG.
With the technologic improvements, hCG assays are now capable of
detecting the presence of a pregnancy before a missed menstrual period. It is
vital to remember that, despite technical advances, the ability of laboratory
measurements to guide the clinician appropriately in every circumstance is
limited (13). The purpose of this Committee Opinion is to offer recommendations to better manage situations in which hCG assays may provide falsepositive results.
Some individuals have circulating factors in their serum that interact
with the hCG antibody. The most common are heterophilic antibodies.
These are human antibodies directed against animal-derived antigens used
314
in immunoassays (1, 49). Individuals who have

worked as animal laboratory technicians or in
veterinary facilities or who were reared on farms are
more likely to develop heterophilic antibodies.
Immunoassays of all kinds use animal antibodies.
People with heterophilic antibodies might have
unusual results in a number of different kinds of
assays. However, because the animal antibodies are
used in different amounts and with other reagents
in each assay system, a person with heterophilic
antibodies will not always have an unusual or unexpected result. Results can differ depending on the
particular assay used.
Clinically significant false-positive results are
rare. One report noted that 5 of 162 women studied
had evidence of assay interference sufficient to provide misleading results (10). If results are misleading, they usually are seen with values below 1,000
mIU/mL. To rule out the presence of heterophilic
antibodies or other interfering substances, several
methods can be used:
A urine test (either quantitative or qualitative) for
hCG can be performed. Because heterophilic
antibodies are not present in urine, if the urine test
result is negative and the serum test result is persistently positive, interference in the serum
immunoassay is confirmed if the serum value is
50 mIU/mL (3).
The assay can be rerun with serial dilutions of the
serum. Because heterophilic antibodies are
directed to reagents in the immunoassay and not
hCG, their interaction with the hCG curve will
not be linear. Lack of linearity confirms assay
interference.
Some laboratories can preabsorb serum to
remove heterophilic antibodies before performing
the assay. If the result becomes negative after
removal of the heterophilic antibody, interference
can be confirmed (11).
There are other ways in which the amount of
true hCG can be measured differently or even
incorrectly by immunoassays. The size of the hCG
molecule circulating in the blood of individuals may
vary as a result of differences in the protein and carbohydrate structure of hCG. This type of variation is
called microheterogeneity of hCG, and it sometimes
can account for differences in measurements reported by different assays. Additionally, some individuals may produce aberrant forms of hCG that are
not biologically activeor are other hormones
entirelythat will cross-react with the hCG assays.

Still others may partly break down circulating
hCG into nonbiologically active forms that react
differently with the various assay systems. In these
circumstances, substances other than native, biologically active hCG may be recognized by the assay
system. Repeating the hCG measurement in a different assay system can best detect this problem.
Wide variations between repeat runs of the same
assay could result from serum factors interfering
with the assay. Serial dilution of the specimen will
be helpful in documenting nonlinearity and confirming the presence of interference.
Finally, inherent assay factors can result in falsepositive hCG results. Repeat testing using a different
assay system may confirm that the result was falsely positive if the result is now negative.
Patients with evidence of hCG assay interference should be notified that they are at risk for recurrent false-positive hCG assay results. These patients
should be instructed to inform all future health care
practitioners of this problem, and the information
should be included in the patients medical record.
In summary, modern assay methods have almost
eliminated laboratory error. However, false-positive
and false-negative test results can occur with any
specimen. Caution should be exercised whenever
clinical findings and laboratory results are discordant. Although false-positive serum hCG results are
rare, if unrecognized, they may lead to unwarranted
clinical interventions for conditions such as persistent trophoblastic disease. The physician must judge
whether the risks of waiting for confirmation of
results outweigh the risks of failing to take immediate action.
References
1. Cole LA, Kardana A. Discordant results in human chorionic gonadotropin assays. Clin Chem 1992;38:26370.
2. Cole LA, Rinne KM, Shahabi S, Omrani A. False-positive
hCG assay results leading to unnecessary surgery and
chemotherapy and needless occurrences of diabetes and
coma. Clin Chem 1999;45:3134.
3. Rotmensch S, Cole LA. False diagnosis and needless therapy of presumed malignant disease in women with falsepositive human chorionic gonadotropin concentrations.
Lancet 2000;355:7125.
4. Boscato LM, Stuart MC. Incidence and specificity of
interference in two-site immunoassays. Clin Chem 1986;
32:14915.
5. Boscato LM, Stuart MC. Heterophilic antibodies: a problem for all immunoassays. Clin Chem 1988;34:2733.
COMMITTEE OPINIONS
6. Check JH, Nowroozi K, Chase JS, Lauer C, Elkins B, Wu

CH. False-positive human chorionic gonadotropin levels
caused by a heterophile antibody with the immunoradiometric assay. Am J Obstet Gynecol 1988;158:99100.
7. Weber TH, Kapyaho KI, Tanner P. Endogenous interference in immunoassays in clinical chemistry. A review.
Scand J Clin Lab Invest Suppl 1990;201:7782.
8. Berglund L, Holmberg NG. Heterophilic antibodies
against rabbit serum causing falsely elevated gonadotropin
levels. Acta Obstet Gynecol Scand 1989;68:3778.
315
9. King IR, Doody MC. False-positive hCG by enzyme

immunoassay resulting in repeated chemotherapy. Obstet
Gynecol 1995;86:6823.
10. Rzasa PJ, Caride VJ, Prokop EK. Discordant inter-kit
results in the radioimmunoassay for choriogonadotropin
in serum. Clin Chem 1984;30:12403.
11. Cole LA. Phantom hCG and phantom choriocarcinoma.
Gynecol Oncol 1998;71:3259.
316
ACOG Committee
Committee on
Reaffirmed 2005
Society of
Gynecologic
Oncologists
The Committee and Society wish
to thank William T. Creasman,
MD, FACOG, for his assistance in
the development of this opinion.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
The role of the generalist obstetrician
gynecologist in the early detection of
ovarian cancer. ACOG Committee
Opinion No. 280. American College of
Opinion
The Role of the Generalist

ObstetricianGynecologist in the
Early Detection of Ovarian Cancer
ABSTRACT: The purpose of this Committee Opinion is to define the role of the
generalist obstetriciangynecologist in the early detection of ovarian cancer.
Currently, it appears that the best way to detect early ovarian cancer is for
both the patient and her clinician to have a high index of suspicion of the diagnosis in the symptomatic woman. In evaluating symptoms, physicians should
perform a physical examination, including a pelvic examination. In premenopausal women with symptoms, a CA 125 measurement has not been
shown to be useful in most circumstances. In postmenopausal women with a
pelvic mass, a CA 125 measurement may be helpful in predicting a higher
likelihood of a malignant tumor than a benign tumor, which may be useful in
making consultation or referral decisions or both. A woman with a suspicious
or persistent complex adnexal mass requires surgical evaluation by a physician trained to appropriately stage and debulk ovarian cancer. Data suggest
that currently available screening tests do not appear to be beneficial for
screening low-risk, asymptomatic women. An annual gynecologic examination
with an annual pelvic examination is recommended for preventive health care.
Although ovarian cancer is the second most common female reproductive

cancer, preceded by cancer of the uterine corpus, more women die from ovarian cancer than from cervical and uterine cancer combined. In the United
States, it is estimated that ovarian cancer will be diagnosed in 23,300 women,
and 13,900 women will die from this malignancy in 2002. The principal reason for these poor outcomes is the advanced stage of disease at diagnosis in
7075% of cases and an overall 5-year survival of only 2030%. However,
women with a diagnosis of stage I disease achieve a 9095% probability of
cure. The purpose of this Committee Opinion is to define the role of the generalist obstetriciangynecologist in the early detection of ovarian cancer.
The poor prognosis of ovarian cancer often is attributed to the fact that it
is a silent cancer, with symptoms appearing only late in the disease process.
This is a misconception, in that studies have shown that women with ovarian
cancers are symptomatic often several months before the diagnosis, even with
early-stage disease. In a survey of 1,725 women with ovarian cancer, 70%
recalled having symptoms for 3 months or longer before the diagnosis, and
COMMITTEE OPINIONS
35% recalled having symptoms for at least 6 months

(1). About three fourths of these women had abdominal symptoms and half had pain or constitutional
symptoms. Overall, only 5% were asymptomatic,
including only 11% of those with stage I and stage
II disease. Pelvic examinations and tests to evaluate
symptoms in these women were done more frequently by obstetriciangynecologists than by other
primary care physicians, resulting in earlier disease
diagnosis.
Currently, it appears that the best way to detect
early ovarian cancer is for both the patient and her
clinician to have a high index of suspicion of the
diagnosis in the symptomatic woman. This requires
education of both as to the symptoms commonly
associated with ovarian cancer. Persistent symptoms
such as an increase in abdominal size, abdominal
bloating, fatigue, abdominal pain, indigestion,
inability to eat normally, urinary frequency, pelvic
pain, constipation, back pain, urinary incontinence
of recent onset, or unexplained weight loss should
be evaluated with ovarian cancer being included in
the differential diagnosis. Because ovarian cancer
occurs most frequently in the postmenopausal
woman (median age, approximately 60 years), these
symptoms should not be ignored in these women.
Unfortunately, many women and clinicians are
quick to attribute such symptoms to menopause,
aging, dietary changes, stress, or functional bowel
problems. As a result, delays of weeks or months
often occur before medical advice is sought or diagnostic studies are performed.
In evaluating these symptoms, physicians
should perform a physical examination, including a
pelvic examination. Imaging studies (including
vaginal ultrasonography) may be helpful before
making the diagnosis of irritable bowel syndrome,
depression, stress, or other diagnoses. In premenopausal women with symptoms, a CA 125 measurement has not been shown to be useful in most
circumstances because elevated levels of CA 125
are associated with a variety of common benign
conditions, including uterine leiomyomata, pelvic
inflammatory disease, endometriosis, adenomyosis, pregnancy, and even menstruation. In postmenopausal women with a pelvic mass, a CA 125
measurement may be helpful in predicting a higher
likelihood of a malignant tumor than a benign
tumor, which may be useful in making consultation
or referral decisions or both; however, a normal CA
125 measurement alone does not rule out ovarian
cancer because up to 50% of early-stage cancers and
2025% of advanced cancers are associated with
normal values. The longer the delay in evaluating
317
symptoms or suspicious findings by either the

patient or the clinician, the more likely advanced
disease will be found.
Diagnostic criteria based on physical examination and imaging techniques that should be used to
consider referral to or consultation with a gynecologic oncologist are as follows:
Postmenopausal women who have a pelvic mass
that is suspicious for a malignant ovarian neoplasm, as suggested by at least one of the following indicators: elevated CA 125 level; ascites; a
nodular or fixed pelvic mass; evidence of abdominal or distant metastasis; a family history of one
or more first-degree relatives with ovarian or
breast cancer
Premenopausal women who have a pelvic mass
that is suspicious for a malignant ovarian neoplasm, as suggested by at least one of the following indicators: very elevated CA 125 level (eg,
>200 U/mL); ascites; evidence of abdominal or
distant metastasis; a family history of one or more
first-degree relatives with ovarian or breast cancer
A woman with a suspicious or persistent complex adnexal mass requires surgical evaluation. In
these circumstances, a physician trained to appropriately stage and debulk ovarian cancer, such as a
gynecologic oncologist, should perform the operation. This should be done in a hospital facility that
has the necessary support and consultative services
(eg, pathology) to optimize the patients outcome.
When a malignant ovarian tumor is discovered and
the appropriate operation cannot be properly performed, a gynecologic oncologist should be consulted.
Of particular concern is the observation that
many women with early-stage disease do not undergo appropriate surgical staging. Patients whose
comprehensive surgical staging confirms early-stage
disease have a much better prognosis than those
patients who were thought to have early-stage disease but did not undergo comprehensive surgical
staging, presumably because occult disease was
missed. In the absence of clinically apparent malignant disease, intraoperative pathology consultation
should be obtained if cancer remains a concern. If an
apparent early-stage malignancy is present, comprehensive surgical staging should be performed,
preferably during the same operation. At the time of
surgery for a pelvic mass, samples for peritoneal
cytology should be obtained when the abdomen is
entered. The mass should be removed intact through
an incision that permits thorough staging and surgical management of the primary tumor and possible
318
sites of metastasis. After the liver, spleen, and all

peritoneal surfaces, including both hemidiaphragms,
are inspected and palpated, a bilateral pelvic and
paraaortic lymphadenectomy is performed along
with an omentectomy, peritoneal biopsies, removal
of the uterus and adnexa, and biopsies or removal of
any suspicious lesions. When the cancer appears to
be confined to one ovary, especially if it is low
grade, it may be appropriate to modify the staging
procedure by leaving the uterus and the uninvolved
ovary in place for younger women who wish to preserve their fertility.
Unfortunately, there is no screening test for
ovarian cancer that has proved effective in screening
low-risk asymptomatic women. Measurement of
CA 125 levels and completion of pelvic ultrasonography (both abdominal and transvaginal) have been
the two tests most thoroughly evaluated. One group
of researchers evaluated 22,000 women with
CA 125 screening, followed by pelvic ultrasonography if an elevated tumor marker was present (2, 3).
More than 98% of women had normal CA 125 values. Of the remaining group, 41 (0.1%) had both
increased CA 125 values and abnormal ultrasonograms and underwent surgical assessment. Only 11
women (0.05% of women screened) had ovarian
cancer, which was stage III in 7 women. The falsepositive rate among those undergoing surgery was
73%. Another group of researchers evaluated 14,469
asymptomatic women with transvaginal ultrasonography, performing 57,214 scans over a period of several years (4). During the period of evaluation, only
11 of 180 women who had surgery for abnormal
adnexal masses (6% of operations and 0.07% of
women screened) had primary epithelial ovarian
cancers, 6 of whom had cancers beyond stage I.
Unfortunately, 4 additional women developed primary epithelial ovarian cancers (stage II and stage
III) within 12 months of a normal scan. In a mass
screening study of 51,500 women conducted over
several years using transvaginal ultrasonography,
324 women were identified with abnormalities
requiring surgery (5). Only 17 of these women (5%
of operations and 0.03% of women screened) were
found to have primary epithelial ovarian cancers.
Data suggest that currently available tests do not
appear to be beneficial for screening low-risk,
asymptomatic women because their sensitivity,
specificity, positive predictive value, and negative
predictive value have all been modest at best. Because of the low incidence of disease, reported to be
approximately one case per 2,500 women per year,
it has been estimated that a test with even 100% sensitivity and 99% specificity would have a positive
predictive value of only 4.8%, meaning 20 of 21

women undergoing surgery would not have primary
ovarian cancer. Unfortunately, no test available
approaches this level of sensitivity or specificity.
Hereditary ovarian cancer is estimated to represent only 510% of all ovarian cancers. Based on
current data, a woman with a germline mutation of
BRCA1 or BRCA2 has a lifetime risk of 1545% of
developing ovarian cancer. There are no data
demonstrating that screening improves early detection of ovarian cancer in this population. These
women should be offered genetic counseling to
address issues that relate to their high risk of breast
and ovarian cancer and the potential impact of these
genetic mutations on their offspring. Even if this
group were screened for ovarian cancer on a regular
basis, more than 90% of all potential ovarian cancer
patients would remain unscreened.
Despite varying recommendations regarding the
frequency of cervical cytology screening, the
Committee on Gynecologic Practice and the Society
of Gynecologic Oncologists still believe that an
annual gynecologic examination with an annual
pelvic examination is recommended for preventive
health care. Although newer tumor markers and proteomics are undergoing investigation and appear
promising for screening, it is unclear whether they
will help identify high-risk women or facilitate the
early diagnosis of more women with ovarian cancer.
Currently, there are no techniques that have proved
to be effective in the routine screening of asymptomatic low-risk women for ovarian cancer.
References
1. Goff BA, Mandel L, Muntz HG, Melancon CH. Ovarian
carcinoma diagnosis. Cancer 2000;89:206875.
2. Jacobs IJ, Skates SJ, MacDonald N, Menon U, Rosenthal
AN, Davies AP, et al. Screening for ovarian cancer: a pilot
randomized controlled trial. Lancet 1999;353:120710.
3. Jacobs I, Davies AP, Bridges J, Stabile I, Fay T, Lower A,
et al. Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography. BMJ 1993;306:10304.
4. van Nagell JR Jr, DePriest PD, Reedy MB, Gallion HH,
Ueland FR, Pavlik EJ, et al. The efficacy of transvaginal
sonographic screening in asymptomatic women at risk for
ovarian cancer. Gynecol Oncol 2000;77:3506.
5. Sato S, Yokoyama Y, Sakamoto T, Futagami M, Saito Y.
Usefulness of mass screening for ovarian carcinoma using
transvaginal ultrasonography. Cancer 2000;89:5828.
COMMITTEE OPINIONS
ACOG
Committee on
Reaffirmed 2009

clinical and scientific advances as of
the date issued and is subject to
change. The information should not
be construed as dictating an exclusive course of treatment or procedure
to be followed.
The Committee wishes to thank the
ACOG Preconception Care Work
Group co-chairs, Michele G. Curtis,
MD, and Paula J. Adams Hillard,
MD, and members, Hani K. Atrash,
MD, MPH; Alfred Brann Jr, MD;
Siobhan M. Dolan, MD, MPH; Ann
Lang Dunlop, MD; Ann Weathersby,
CNM, MSN; and Gerald Zelinger,
MD, for their assistance in the development of this opinion.
Copyright September 2005 by the
and Gynecologists. All rights
reserved. No part of this publication
may be reproduced, stored in a
retrieval system, or transmitted, in any
form or by any means, electronic,
mechanical, photocopying, recording,
or otherwise, without prior written
Requests for authorization to make
photocopies should be
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
The importance of preconception

care in the continuum of womens
health care. ACOG Committee
Obstet Gynecol 2005;106:6656
319
Committee
Opinion
The Importance of Preconception

Care in the Continuum of Womens
Health Care
ABSTRACT: The goal of preconception care is to reduce the risk of adverse
health effects for the woman, fetus, or neonate by optimizing the womans health
and knowledge before planning and conceiving a pregnancy. Because reproductive capacity spans almost four decades for most women, optimizing womens
health before and between pregnancies is an ongoing process that requires
access to and the full participation of all segments of the health care system.
Although most pregnancies result in good maternal and fetal outcomes, some
pregnancies may result in adverse health effects for the woman, fetus, or
neonate. Although some of these outcomes cannot be prevented, optimizing
a womans health and knowledge before planning and conceiving a pregnancyalso referred to as preconception care or prepregnancy caremay
eliminate or reduce the risk. For example, initiation of folic acid supplementation at least 1 month before pregnancy reduces the incidence of neural tube
defects such as spina bifida and anencephaly (13). Similarly, adequate glucose control in a woman with diabetes before conception and throughout pregnancy can decrease maternal morbidity, spontaneous abortion, fetal
malformation, fetal macrosomia, intrauterine fetal death, and neonatal morbidity (4).
Nearly half of all pregnancies in the United States are unintended (5).
Therefore, the challenge of preconception care lies not only in addressing
pregnancy planning for women who seek medical care and consultation
specifically in anticipation of a planned pregnancy but also in educating and
screening all reproductively capable women on an ongoing basis to identify
potential maternal and fetal risks and hazards to pregnancy before and
between pregnancies.
This Committee Opinion reinforces the importance of preconception
care, provides resources for the womans health care clinician, and proposes that every reproductively capable woman create a reproductive health
plan. The specific clinical content of preconception care is outlined elsewhere (68).
Several national and international medical organizations and advocacy
groups have focused on the optimization of health before conception, result-
320
ing in the development of clinical recommendations

and educational materials (see Resources). Core preconception care considerations addressed by all
include the following factors:
Undiagnosed, untreated, or poorly controlled
medical conditions
Immunization history
Medication and radiation exposure in early
pregnancy
Nutritional issues
Family history and genetic risk
Tobacco and substance use and other high-risk
behaviors
Occupational and environmental exposures
Social issues
Mental health issues
As medical care rapidly advances, the list of issues
to consider when planning a pregnancy continues to
grow.
Clinicians should encourage women to formulate a reproductive health plan and should discuss it
in a nondirective way at each visit. Such a plan would
address the individuals or couples desire for a child
or children (or desire not to have children); the optimal number, spacing, and timing of children in the
family; and age-related changes in fertility. Because
many womens plans change over time, creating a
reproductive health plan requires an ongoing conscientious assessment of the desirability of a future
pregnancy, determination of steps that need to be
taken either to prevent or to plan for and optimize a
pregnancy, and evaluation of current health status and
other issues relevant to the health of a pregnancy.
A question such as Are you considering pregnancy, or could you possibly become pregnant? can
initiate several preconception care interventions,
including those listed as follows:
A dialogue regarding the patients readiness for
pregnancy
An evaluation of her overall health and opportunities for improving her health
Education about the significant impact that
social, environmental, occupational, behavioral,
and genetic factors have in pregnancy
Identification of women at high risk for an
adverse pregnancy outcome
If pregnancy is not desired, current contraceptive use
and options should be discussed to assist the patient
in identifying the most appropriate and effective
method for her.
Preconception and interpregnancy care are components of a larger health care goaloptimizing the
health of every woman (9). Because reproductive
capacity spans almost four decades for most women,
optimizing womens health before and between
pregnancies is an ongoing process that requires
access to and the full participation of all segments of
the health care system.
References
1. Czeizel AE, Dudas I. Prevention of the first occurrence of
neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327:18325.
2. Prevention of neural tube defects: results of the Medical
Research Council Vitamin Study. MRC Vitamin Study
Research Group. Lancet 1991;338:1317.
3. Botto LD, Moore CA, Khoury MJ, Erickson JD. Neuraltube defects. N Engl J Med 1999;341:150919.
4. Pregestational diabetes mellitus. ACOG Practice Bulletin
5. Henshaw SK. Unintended pregnancy in the United States.
Fam Plann Perspect 1998;30:249, 46.
care. 5th ed. Elk Grove Village (IL): AAP; Washington,
DC: ACOG; 2002.
Guidelines for womens health care. 2nd ed. Washington,
DC: ACOG; 2002.
American College of Medical Genetics. Preconception
and prenatal carrier screening for cystic fibrosis. Clinical
and laboratory guidelines. Washington, DC: ACOG; 2001.
Access to womens health care. ACOG Statement of
Policy. Washington, DC: ACOG; 2003.
Resources
www.acog.org
www.aafp.org
www.aap.org
American College of Nurse-Midwives
www.acnm.org
www.asrm.org
Association of Womens Health, Obstetric and Neonatal
Nurses
www.awhonn.org
Centers for Disease Control and Prevention National Center
on Birth Defects and Developmental Disabilities
www.cdc.gov/ncbddd
March of Dimes
www.marchofdimes.com
COMMITTEE OPINIONS
ACOG
Committee on
321
Committee
Opinion

directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
The role of the obstetriciangynecologist in the assessment and management of obesity. ACOG Committee
The Role of the Obstetrician

Gynecologist in the Assessment and
Management of Obesity
ABSTRACT: Approximately one third of all women in the United States are
obese. Obstetriciangynecologists should evaluate all women for obesity by
calculating a body mass index (BMI) measurement and should offer appropriate interventions or referrals to promote a healthy weight and lifestyle.
The purpose of this Committee Opinion is to address the role of the obstetriciangynecologist in the assessment and management of obesity in nonpregnant adult women. Definitions of overweight and obesity will be reviewed,
the importance of calculating the body mass index (BMI) will be outlined,
and resources for counseling and referral will be provided. The impact of
obesity on pregnancy and the assessment of overweight and obesity in adolescents are addressed elsewhere (1, 2).
Background
Obesity, defined as a BMI of 30 or greater, is the fastest-growing health
problem in the United States, and its prevalence has increased sharply over
the past 20 years (3). Approximately one third of all U.S. women are
obese (3). Obesity is more prevalent in lower-income and minority women;
49% of AfricanAmerican women and 38% of MexicanAmerican women
are obese, compared with 31% of white women (3). Obesity has been associated with increased morbidity, including type 2 diabetes, hypertension,
infertility, heart disease, gallbladder disease, osteoarthritis, and a variety of
cancers, including breast, uterine, and colon cancers (47). Endometrial
cancer is the most common gynecologic malignancy, and obese women are
almost five times more likely than nonobese women (BMI 2022.9) to
develop endometrial cancer (8). Obesity and overweight are associated with
an increased risk for heart disease, the leading cause of death of American
women (4, 5, 9). An estimated 112,000 individuals die annually of obesityassociated causes (10).
322
Assessment
Central adiposity, defined as a waist circumference greater than 35 inches (>88 cm) in women,
may further identify women at risk for obesityrelated morbidity (11). Waist circumference is measured at the end of a normal expiration of breath by
placing a measuring tape around the abdomen at the
level of the iliac crest.
The patients medical, social, and family history

should be reviewed for weight-related conditions. To
determine if the patient is overweight or obese, the
BMI should be calculated. If the patients BMI is 30
or greater, the severity of obesity (Class I, II, or III)
should be noted (Table 1).
Table 1. Body Mass Index Calculation, Chart, and Categories
The Body Mass Index (BMI) is an indirect measure of body fat and is used to determine obesity. The BMI is calculated as weight in
kilograms (kg) divided by the square of height in meters (m2).
BMI =
weight (kg)
height squared (m2)
Using a BMI chart is an easy and rapid way of identifying the BMI for all adult patients.
Body Mass Index Table
Overweight
Normal
BMI
19
20
21
22
23
24
25
26
27
28
Obese
29
30
31
32
33
Height
(inches)
Extreme Obesity
Extreme Obesity
Obese
34
35
36
37
38
39
40
41
42 43
44
45
46
47
48
49
50
51
52
53
54
Body Weight (pounds)
58
91
96 100 105 110 115 119 124 129 134 138 143 148 153 158 162 167 172 177 181 186 191 196 201 205 210 215 220 224 229 234 239 244 248 253 258
59
94
99 104 109 114 119 124 128 133 138 143 148 153 158 163 168 173 178 183 188 193 198 203 208 212 217 222 227 232 237 242 247 252 257 262 267
60
97 102 107 112 118 123 128 133 138 143 148 153 158 163 168 174 179 184 189 194 199 204 209 215 220 225 230 235 240 245 250 255 261 266 271 276
61
100 106 111 116 122 127 132 137 143 148 153 158 164 169 174 180 185 190 195 201 206 211 217 222 227 232 238 243 248 254 259 264 269 275 280 285
62
104 109 115 120 126 131 136 142 147 153 158 164 169 175 180 186 191 196 202 207 213 218 224 229 235 240 246 251 256 262 267 273 278 284 289 295
63
107 113 118 124 130 135 141 146 152 158 163 169 175 180 186 191 197 203 208 214 220 225 231 237 242 248 254 259 265 270 278 282 287 293 299 304
64
110 116 122 128 134 140 145 151 157 163 169 174 180 186 192 197 204 209 215 221 227 232 238 244 250 256 262 267 273 279 285 291 296 302 308 314
65
114 120 126 132 138 144 150 156 162 168 174 180 186 192 198 204 210 216 222 228 234 240 246 252 258 264 270 276 282 288 294 300 306 312 318 324
66
118 124 130 136 142 148 155 161 167 173 179 186 192 198 204 210 216 223 229 235 241 247 253 260 266 272 278 284 291 297 303 309 315 322 328 334
67
121 127 134 140 146 153 159 166 172 178 185 191 198 204 211 217 223 230 236 242 249 255 261 268 274 280 287 293 299 306 312 319 325 331 338 344
68
125 131 138 144 151 158 164 171 177 184 190 197 203 210 216 223 230 236 243 249 256 262 269 276 282 289 295 302 308 315 322 328 335 341 348 354
69
128 135 142 149 155 162 169 176 182 189 196 203 209 216 223 230 236 243 250 257 263 270 277 284 291 297 304 311 318 324 331 338 345 351 358 365
70
132 139 146 153 160 167 174 181 188 195 202 209 216 222 229 236 243 250 257 264 271 278 285 292 299 306 313 320 327 334 341 348 355 362 369 376
71
136 143 150 157 165 172 179 186 193 200 208 215 222 229 236 243 250 257 265 272 279 286 293 301 308 315 322 329 338 343 351 358 365 372 379 386
72
140 147 154 162 169 177 184 191 199 206 213 221 228 235 242 250 258 265 272 279 287 294 302 309 316 324 331 338 346 353 361 368 375 383 390 397
73
144 151 159 166 174 182 189 197 204 212 219 227 235 242 250 257 265 272 280 288 295 302 310 318 325 333 340 348 355 363 371 378 386 393 401 408
74
148 155 163 171 179 186 194 202 210 218 225 233 241 249 256 264 272 280 287 295 303 311 319 326 334 342 350 358 365 373 381 389 396 404 412 420
75
152 160 168 176 184 192 200 208 216 224 232 240 248 256 264 272 279 287 295 303 311 319 327 335 343 351 359 367 375 383 391 399 407 415 423 431
76
156 164 172 180 189 197 205 213 221 230 238 246 254 263 271 279 287 295 304 312 320 328 336 344 353 361 369 377 385 394 402 410 418 426 435 443
Weight category
Underweight
Normal weight
BMI
<18.5
18.524.9
Overweight
2529.9
Obesity (Class I)
3034.9
Obesity (Class II)
3539.9
Extreme Obesity (Class III)
40
The practical guide: identification, evaluation, and treatment of

overweight and obesity in adults. National Heart, Lung, and Blood
Institute and North American Association for the Study of
Obesity. Bethesda (MD): National Institutes of Health; 2000.
COMMITTEE OPINIONS
Blood pressure measurements, fasting lipid panels, and fasting blood glucose measurements may be
appropriate for identifying comorbidities. However,
no single laboratory test or diagnostic evaluation is
indicated for all patients with obesity, and the tests
and evaluations performed should be based on
the patients symptoms and risk factors and the
clinicians index of suspicion for specific comorbidities (12).
make behavioral changes should be the initial

approach. The clinician should inform the patient in
a sensitive manner that her weight is a health concern and assist her in developing a weight loss and
exercise plan. Asking the patient if she is concerned
about her weight and has ever tried to lose weight
will help the clinician determine if she is interested
in weight management. Applying the stages of
change model, as adapted for overweight and obesity, may help determine patient motivation and
interest in weight loss (Table 3). Educational handouts for the patient to read at home can be discussed
at a follow-up visit. Setting an initial goal of losing
510% of total body weight over a 6-month period
is realistic and achievable and can decrease the
severity of obesity-associated risk factors (14).
Contact information for community resources, support groups, and weight loss programs may be
provided (see Patient Resources). Evaluation by a
nutritionist may be of benefit, in addition to followup visits with a clinician to monitor progress and
provide support. Patients can be informed that some
insurance carriers may provide coverage for weight
loss interventions.
Orlistat and sibutramine hydrochloride monohydrate have been approved by the U.S. Food and
Drug Administration for patients with a BMI of 30
or greater and for those with a BMI of 27 or greater
and other risk factors (eg, hypertension, diabetes, or
dyslipidemia) when used in combination with
lifestyle changes (see Table 2). These agents are the
two most studied pharmacologic treatments for obesity, although efficacy and safety beyond 12 months
have not been investigated in randomized, controlled trials (15, 16). Orlistat is a gastrointestinal
lipase inhibitor that limits fat absorption. Side
Management
Weight management is a challenge for patients and
their physicians. For many women, achieving and
maintaining a healthy weight is a difficult and lifelong process. Improved health through weight loss
and appropriate increased physical activity should
be the goal. Counseling to support improvements in
diet and physical activity are considered first-line
interventions, although pharmacotherapy and
surgery may be appropriate for some women (Table
2). The U.S. Preventive Services Task Force found
the most successful nonsurgical approaches to be
intensive, weight-focused counseling (more than
one session per month) or multicomponent, intensive interventions that combine nutrition and exercise counseling with supportive, skill-building
behavioral interventions (13). If available, referral
for further evaluation and treatment should be considered whenever the resources of the clinician are
insufficient to meet the patients current needs, for
women with a BMI of 40 or greater, and for women
with a BMI of 35 or greater with comorbidities or
who have failed appropriate prior intervention(s).
Reinforcing the importance of weight loss and
exercise and assessing the patients readiness to
Table 2. Guide to Selecting Treatment

Body Mass Index Category
Treatment
Diet, physical activity,
and behavior therapy
Pharmacotherapy
Surgery
323
2526.9
2729.9
3034.9
3539.9
40
With
comorbidities
With
comorbidities
With
comorbidities
With
comorbidities
With
comorbidities
With
comorbidities
The + represents the use of indicated treatment regardless of comorbidities.

The practical guide: identification, evaluation, and treatment of overweight and obesity in adults. National Heart, Lung, and
Blood Institute and North American Association for the Study of Obesity. Bethesda (MD): National Institutes of Health; 2000.
324
Table 3. Stages of Change Model to Assess Readiness for Weight Loss

Stage
Appropriate
Intervention
Characteristic
Patient Verbal Cue
Sample Dialogue
Precontemplation
Unaware of problem,
no interest in change
Im not really interested

in weight loss. Its not
a problem.
Provide information
about health risks and
benefits of weight loss
Would you like to read

some information about the
health aspects of obesity?
Contemplation
Aware of problem,
beginning to think of
changing
I know I need to lose

weight, but with all thats
going on in my life right
now, Im not sure I can.
Help resolve ambivalence;

discuss barriers
Lets look at the benefits

of weight loss, as well as
what you may need to
change.
Preparation
Realizes benefits of
making changes and
thinking about how
to change
I have to lose weight, and

Im planning to do that.
Teach behavior
modification;
provide education
Lets take a closer look at

how you can reduce some
of the calories you eat and
how to increase your
activity during the day.
Action
Actively taking steps

toward change
Im doing my best. This is

harder than I thought.
Provide support and

guidance, with a focus
on the long term
Its terrific that youre

working so hard. What
problems have you had so
far? How have you solved
them?
Maintenance
Initial treatment goals

reached
Ive learned a lot through

this process.
Relapse control
What situations continue

to tempt you to overeat?
What can be helpful for the
next time you face such a
situation?
Assessment and management of adult obesity: a primer for physicians, assessing readiness and making treatment decisions. American Medical
Association and the Robert Wood Johnson Foundation, Copyright 2003.
effects are common and include fecal urgency, flatulence, and oily rectal discharge. A recent literature
review found six trials that demonstrated significant
weight loss (2.84.5 kg in 612.5 months) by
patients who took orlistat (120 mg, taken 3 times
daily before meals) compared with patients who
took a placebo (17). In three trials reporting
response rates, 1438% of patients treated with orlistat lost 10% of their body weight. This degree of
weight loss was 919% more common in patients
who received orlistat than patients who received a
placebo (17). Sibutramine is a dopamine, norepinephrine, and serotonin reuptake inhibitor for which
the method of action for weight loss is unknown.
Side effects include increases in blood pressure and
heart rate. Six clinical trials of sibutramine (1020
mg daily) versus placebo have shown at 612
months of treatment that patients taking sibutramine
have a weight loss of 2.87.8 kg more than patients
taking a placebo (17). Loss of 10% of body weight
occurred in 634% of patients who took sibu-
tramine; this degree of weight loss was 527% more

common in patients who took sibutramine than in
patients who received a placebo (17). Unfortunately,
discontinuation of pharmacotherapy may lead to
rapid weight regain.
In some patients with severe obesity (BMI > 40)
or patients with a BMI of 35 or greater with comorbid conditions, surgical intervention may be an
option if nonsurgical methods of weight loss have
failed (4). Surgical options can promote substantial,
long-term weight loss (17). These patients should be
evaluated by a comprehensive bariatric treatment
team.
Conclusion
Obstetriciangynecologists should evaluate all
women for obesity by calculating BMI. Clinicians should offer patients appropriate interventions or referrals to promote a healthy weight and
lifestyle.
COMMITTEE OPINIONS
References
1. Obesity in pregnancy. ACOG Committee Opinion 315.
3. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin
LR, Flegal KM. Prevalence of overweight and obesity
among U.S. children, adolescents, and adults, 19992002.
JAMA 2004;291:284750.
4. Clinical guidelines on the identification, evaluation, and
treatment of overweight and obesity in adultsthe evidence report. National Institutes of Health [published
erratum appears in Obes Res 1998;6:464]. Obes Res
1998;6 Suppl 2:51S209S.
5. Office of the Surgeon General. The Surgeon Generals
call to action to prevent and decrease overweight and obesity 2001. Rockville (MD): U.S. Department of Health
and Human Services, Public Health Service, Office of the
Surgeon General; 2001.
6. World Health Organization. Obesity: preventing and managing the global epidemic. WHO Technical Report Series
894. Geneva, Switzerland: World Health Organization;
2000.
7. Azziz R. Reproductive endocrinologic alterations in
female asymptomatic obesity. Fertil Steril 1989;52:
70325.
8. Schouten LJ, Goldbohm RA, van den Brandt PA.
Anthropometry, physical activity, and endometrial cancer
risk: results from the Netherlands Cohort Study. J Natl
Cancer Inst 2004;96:16358.
9. Mosca L, Appel LJ, Benjamin EJ, Berra K, ChandraStrobos N, Fabunmi RP, et al. Evidence-based guidelines
for cardiovascular disease prevention in women.
American Heart Association. Circulation 2004;109:
67293.
10. Flegal KM, Graubard BI, Williamson DF, Gail MH.
Excess deaths associated with underweight, overweight,
and obesity. JAMA 2005;293:18617.
11. Janssen I, Katzmarzyk PT, Ross R. Body mass index,
waist circumference, and health risk: evidence in support
of current National Institutes of Health guidelines. Arch
Intern Med 2002;162:20749.
12. Kushner RF, Weinsier RL. Evaluation of the obese
patient. Practical considerations. Med Clin North Am
2000;84:38799, vi.
13. Screening for obesity in adults: recommendations and
rationale. U.S. Preventive Services Task Force. Ann Intern
Med 2003;139:9302.
14. Goldstein DJ. Beneficial health effects of modest weight
loss. Int J Obes Relat Metab Disord 1992;16:397415.
15. Li Z, Maglione M, Tu W, Mojica W, Arterburn D,
Shugarman LR, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005;142:53246.
325
16. Snow V, Barry P, Fitterman N, Qaseem A, Weiss K.

Pharmacologic and surgical management of obesity in
primary care: a clinical practice guideline from the
American College of Physicians. Clinical Efficacy
Assessment Subcommittee of the American College of
Physicians. Ann Intern Med 2005;142:52531.
17. McTigue KM, Harris R, Hemphill B, Lux L, Sutton S,
Bunton AJ, et al. Screening and interventions for obesity
in adults: summary of the evidence for the U.S. Preventive
Services Task Force. Ann Intern Med 2003;139:93349.
Physician Resources
American Medical AssociationRoadmaps for Clinical
Practice series: Assessment and management of adult obesity
www.ama-assn.org/ama/pub/category/10931.html
American Society for Bariatric Surgery
www.asbs.org
ACOG Clinical Updates in Womens Health CareWeight
control: assessment and management
www.clinicalupdates.org
National Heart, Lung, and Blood InstituteClinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults
www.nhlbi.nih.gov/guidelines/obesity/ob_home.htm
The Surgeon Generals call to action to prevent and decrease
overweight and obesity
www.surgeongeneral.gov/topics/obesity
U.S. Preventive Services Task ForceScreening for obesity
in adults
www.ahrq.gov/clinic/uspstf/uspsobes.htm
Patient Resources
American Obesity Association
www.obesity.org
American Society of Bariatric Physicians
www.asbp.org
MedlinePlus: Weight Loss and Dieting
www.nlm.nih.gov/medlineplus/weightlossanddieting.html
National Heart, Lung, and Blood Institute Obesity Education
Initiative
www.nhlbi.nih.gov/about/oei/index.htm
Overeaters Anonymous
www.overeatersanonymous.org
TOPSTake Off Pounds Sensibly
www.tops.org
Weight-control Information Network
www.win.niddk.nih.gov
326
ACOG
Committee on
Reaffirmed 2007
Committee
Opinion
Compounded Bioidentical Hormones

directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400

409 12th Street, SW
PO Box 96920
Compounded bioidentical hormones.

106:113940.
ABSTRACT: Compounded bioidentical hormones are plant-derived hormones that are prepared, mixed, assembled, packaged, or labeled as a drug
by a pharmacist and can be custom made for a patient according to a
physicians specifications. Most compounded products have not undergone
rigorous clinical testing for safety or efficacy, and issues regarding purity,
potency, and quality are a concern. Compounded hormone products have the
same safety issues as those associated with hormone therapy agents that are
approved by the U.S. Food and Drug Administration and may have additional risks intrinsic to compounding. There is no scientific evidence to support
claims of increased efficacy or safety for individualized estrogen or progesterone regimens.
Compounded drugs are agents that are prepared, mixed, assembled, packaged, or labeled as a drug by a pharmacist. Unlike drugs that are approved
by the U.S. Food and Drug Administration (FDA) to be manufactured and
sold in standardized dosages, compounded medications often are custom
made for a patient according to a physicians specifications. One category of
compounded products is referred to as bioidentical hormones; however,
there is confusion over what this term implies. Bioidentical hormones are
plant-derived hormones that are biochemically similar or identical to those
produced by the ovary or body.
The steroid hormones most commonly compounded include dehydroepiandrosterone, pregnenolone, testosterone, progesterone, estrone,
estradiol, and estriol (1). Bioidentical hormones made by a compounding
pharmacist from a health care providers prescription are available in various
routes of administration, including oral, sublingual, and percutaneous or as
implants, injectables, and suppositories. Examples of compounded hormones include Biest and Triest preparations. The name Biest (biestrogen)
commonly refers to an estrogen preparation based on a ratio of 20% estradiol and 80% estriol on a milligram-per-milligram basis. A similar preparation, Triest (triestrogen), usually contains a ratio of 10% estradiol, 10%
estrone, and 80% estriol. It is important to note that these ratios are not based
on each agents estrogenic potency but on the milligram quantity of the
different agents added together (2). Purchases of compounded hormones are
not typically reimbursed by insurance companies.
COMMITTEE OPINIONS
Most compounded products have not undergone

any rigorous clinical testing for either safety or efficacy, and issues of quality assurance regarding the purity, potency, and quality of compounded products are
a concern. From June 2001 to December 2001, the
FDA analyzed 29 product samples from 12 compounding pharmacies (3). The types of products varied, but examples include oral, injectable, pellet
implants, and inhalation compounds such as hormonal products, steroids, and antibiotics. Although none
of the compounded products failed identity testing, 10
of the 29 products (34%) failed one or more standard
quality tests performed. Nine of the 10 failing products failed assay or potency tests, with all products
failing potency testing demonstrating subpotent
results; that is, the products analyzed contained less of
the active ingredient than expected. In comparison
with these results, the analytical testing failure rate for
drug therapies approved by the FDA is less than 2%.
Although many advocates and compounders of
bioidentical hormones recommend the use of salivary hormone level testing as a means of offering
individualized therapy, hormone therapy does not
belong to a class of drugs with an indication for individualized dosing. Individualized dosing is indicated when a narrow therapeutic window exists for a
drug or a drug class. Such drugs include those with
nonlinear pharmacokinetics, those that are renally
eliminated as the active drug, some that are not
metabolized during first pass through the liver,
and those with clearly defined therapeutic and toxic
concentrations based on large population pharmacokinetic studies of serum concentrations. Steroid hormones such as estrogen and progesterone do not
meet these criteria and, thus, do not require individualized dosing.
There is no evidence that hormonal levels in saliva are biologically meaningful. Whereas saliva is an
ultrafiltrate of the blood and in theory should be
amenable to testing for free (unbound) concentrations of hormones, this has not proved to be the case
(4). The problem with salivary testing and monitoring
of free hormone levels is twofold: 1) there is no biologically meaningful relationship between salivary
sex steroidal hormone concentrations and free serum
hormone concentrations and 2) there is large withinpatient variability in salivary hormone concentrations
(59). Salivary hormone levels vary depending on
diet, time of day of testing, the specific hormone
being tested, and other variables (6, 7, 1012).
Currently, the FDA requires manufacturers of
products approved by the FDA that contain estrogen
and progestogen to use class labeling (the black box
warning) reflective of the findings of the Womens
327
Health Initiative. However, because compounded

products are not approved by the FDA and have no
official labeling (ie, a package insert), they are exempt
from including the contraindications and warnings
required by the FDA in class labeling for hormone
therapy. Given the lack of well-designed and wellconducted clinical trials of these alternative therapies,
compounded hormone products should be considered
to have the same safety issues as those associated with
hormone therapy agents that are approved by the
FDA. They also may have additional risks intrinsic to
compounding. There is no scientific evidence to support claims of increased efficacy or safety for individualized estrogen or progesterone regimens.
References
1. Drisko JA. Natural isomolecular hormone replacement:
an evidence-based medicine approach. Int J Pharmaceut
Compounding 2000;4:41420.
2. Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause 2004;11:35667.
3. Food and Drug Administration, Center for Drug Evaluation
and Research. Report: limited FDA survey of compounded drug products. Available at: http://www.fda.gov/
cder/pharmcomp/survey.htm. Retrieved June 15, 2005.
4. Marder MZ, Joshi U, Mandel ID. Estrogen concentration
in human parotid and submaxillary saliva. J Dent Res
1979;58:2370.
5. Hardiman P, Thomas M, Osgood V, Vlassopoulou V,
Ginsburg J. Are estrogen assays essential for monitoring
gonadotropin stimulant therapy? Gynecol Endocrinol
1990;4;2619.
6. Klee GG, Heser DW. Techniques to measure testosterone
in the elderly. Mayo Clin Proc 2000;75 Suppl:S1925.
7. Lewis JG, McGill H, Patton VM, Elder PA. Caution on the
use of saliva measurements to monitor absorption of progesterone form transdermal creams in postmenopausal
women. Maturitas 2002;41:16.
8. Meulenberg PM, Ross HA, Swinkels LM, Benraad TJ.
The effect of oral contraceptives on plasma-free and salivary cortisol and cortisone. Clin Chim Acta 1987;165:
37985.
9. Wren BG, McFarland K, Edwards L, OShea P, Sufi S,
Gross B, et al. Effect of sequential transdermal progesterone cream on endometrium, bleeding pattern, and plasma progesterone and salivary progesterone levels in postmenopausal women. Climacteric 2000;3:15560.
10. Bolaji II, Tallon DF, ODwyer E, Fottrell PF. Assessment
of bioavailability of oral micronized progesterone using a
salivary progesterone enzymeimmunoassay. Gynecol
Endocrinol 1993;7:10110.
11. Raff H, Raff JL, Duthie EH, Wilson CR, Sasse EA,
Rudman I, et al. Elevated salivary cortisol in the evening
in healthy elderly men and women: correlation with bone
mineral density. J Gerentol A Biol Sci Med Sci 1999;
54:M47983.
12. Zava DT, Dollbaum CM, Blen M. Estrogen and progestin
bioactivity of foods, herbs, and spices. Proc Soc Exp Biol
Med 1998;217:36978.
328
ACOG
Committee on
Reaffirmed 2009
Committee
Opinion

directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400

409 12th Street, SW
PO Box 96920
Elective coincidental appendectomy.

2005;106:11412.
(Replaces No. 164, December 1995)
Elective Coincidental Appendectomy

ABSTRACT: Because of a lack of evidence from randomized trials, it remains
unclear whether the benefits of routine elective coincidental appendectomy
outweigh the cost and risk of morbidity associated with this prophylactic procedure. Because the riskbenefit analysis varies according to patient age and
history, the decision to perform an elective coincidental appendectomy at the
time of an unrelated gynecologic surgical procedure should be based on individual clinical scenarios and patient characteristics and preferences.
Elective coincidental appendectomy is defined as the removal of the appendix at the time of another surgical procedure unrelated to appreciable appendiceal pathology. Cases in which appendectomy may be indicated on the
basis of appendiceal pathology are not addressed in this document.
The possible benefits of performing elective coincidental appendectomy
include preventing a future emergency appendectomy and excluding appendicitis in patients with complicated differential diagnoses, such as those who
have chronic pelvic pain or endometriosis. Other groups that may benefit
from elective coincidental appendectomy include women in whom pelvic or
abdominal radiation or chemotherapy is anticipated, women undergoing
extensive pelvic or abdominal surgery in which major adhesions are
anticipated postoperatively, and patients in whom making the diagnosis of
appendicitis may be difficult because of diminished ability to perceive or
communicate symptoms (eg, the developmentally disabled).
Most studies suggest that there is little, if any, increased morbidity associated with elective coincidental appendectomy at the time of gynecologic
surgery, whether performed during an open surgical procedure (13) or during laparoscopy (4, 5). However, most of these studies are affected by
methodological limitations such as retrospective design, small sample size,
and lack of an appropriate control group. One large retrospective study using
discharge data from all general hospitals in Ontario during a 10-year period
highlights some of the challenges of addressing this issue with data from
nonrandomized studies (6). This study compared in-hospital fatality rates,
complication rates, and lengths of hospital stay between patients undergoing
open primary cholecystectomy with and without incidental appendectomy.
Initial results indicated a paradoxical reduction in morbidity and mortality
COMMITTEE OPINIONS
after cholecystectomy when incidental appendectomy was performed. This most likely was because
healthier, lower-risk patients are more likely to
undergo an elective coincidental appendectomy.
However, once multivariate adjustments were made
to address these differences in patient characteristics, differences in complication rates were reduced
or eliminated. Furthermore, when the study excluded high-risk subgroups, a consistently significant increase in complication rates among low-risk
patients who underwent incidental appendectomy
was found. These findings suggest that unmeasured
or uncontrolled confounding or both make the interpretation of most nonrandomized studies of this
topic difficult, but there is probably a small
increased risk of nonfatal complications associated
with elective coincidental appendectomy.
Given this presumed small but increased risk of
complications, the primary debate surrounding elective coincidental appendectomy is whether the additional cost and morbidity incurred at the time of this
prophylactic procedure outweigh the cost and risk of
morbidity from developing appendicitis in the
future. Because the estimated lifetime risk of appendicitis among women is less than 7% (7), a number
of elective appendectomies will be required to prevent one case of acute appendicitis. Depending on
hospital costs and physician reimbursement rates,
the cost-effectiveness of this procedure will vary
according to the clinical setting.
Although the incidence of acute appendicitis is
greatest between the ages of 10 and 19 years and
decreases with age (7), the risks associated with
acute appendicitis increase with age. Therefore, the
riskbenefit analysis changes according to patient
age. A study involving open coincidental appendectomies in otherwise healthy women undergoing
gynecologic procedures concluded that the greatest
benefit was in patients younger than 35 years (8).
The study also concluded that patients between 35
years and 50 years of age might benefit from elective coincidental appendectomy based on specific
clinical circumstances. The data, however, did not
support elective coincidental appendectomy for
patients older than 50 years.
329
The benefit of elective coincidental appendectomy remains controversial and is still open to
debate. It appears, from limited data, that women
35 years of age and younger benefit most from elective coincidental appendectomy. The decision to perform elective coincidental appendectomy at the time
of gynecologic procedures should be based on individual clinical scenarios after a discussion of risks
and benefits with the patient. In light of the low risk
of morbidity based on current limited data, a
patients concern about developing future appendicitis may be considered. If there is a reasonable probability that the benefits outweigh the risks, based on
age or history, elective coincidental appendectomy
during a primary gynecologic procedure may be
appropriate. Because there are clinical situations in
which the benefits of an elective coincidental appendectomy may outweigh the risks, insurance companies should be encouraged to pay for this procedure
in select cases.
Reference
1. Salom EM, Schey D, Penalver M, Gomez-Marin O,
Lambrou N, Almeida Z, et al. The safety of incidental
appendectomy at the time of abdominal hysterectomy. Am
J Obstet Gynecol 2003;189:15637; discussion 15678.
2. Tranmer BI, Graham AM, Sterns EE. Incidental appendectomy?Yes. Can J Surg 1981;24:1912.
3. Voitk AJ, Lowry JB. Is incidental appendectomy a safe
practice? Can J Surg 1988;31:44851.
4. Chiarugi M, Buccianti P, Decanini L, Balestri R,
Lorenzetti L, Franceschi M, et al. What you see is not
what you get. A plea to remove a normal appendix during diagnostic laparoscopy. Acta Chir Belg 2001;101:
2435.
5. Nezhat C, Nezhat F. Incidental appendectomy during
videolaseroscopy. Am J Obstet Gynecol 1991;165:
55964.
6. Wen SW, Hernandez R, Naylor CD. Pitfalls in nonrandomized outcomes studies. The case of incidental appendectomy with open cholecystectomy. JAMA 1995;274:
168791.
7. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the
United States. Am J Epidemiol 1990;132:91025.
8. Snyder TE, Selanders JR. Incidental appendectomyyes
or no? A retrospective case study and review of the literature. Infect Dis Obstet Gynecol 1998;6:307.
330
ACOG
Committee on
Reaffirmed 2009
Committee
Opinion
Number 332, May 2006

Copyright May 2006
from the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Hepatitis B and hepatitis C virus

infections in obstetriciangynecologists. ACOG Committee Opinion No.
Gynecol 2006;107:12078.
Hepatitis B and Hepatitis C

Virus Infections in
ObstetricianGynecologists
ABSTRACT: Hepatitis B and hepatitis C may be transmitted from patients to
health care workers and from health care workers to patients. To reduce the
risk, all obstetriciangynecologists who provide clinical care should receive
hepatitis B virus vaccine. Obstetriciangynecologists who are hepatitis B
surface antigen positive and e antigen positive should not perform exposureprone procedures until they have sought counsel from an expert review panel.
Because the risk of hepatitis C virus transmission is lower than that of hepatitis B virus transmission, routine testing of health care workers is not recommended, and hepatitis C virus-positive health care workers are not required
to restrict professional activities.
In health care settings, bloodborne pathogens, such as hepatitis B virus

(HBV) and hepatitis C virus (HCV) may be transmitted from infected
patients to health care workers as well as from infected health care workers
to patients. To prevent transmission of bloodborne pathogens, such as hepatitis in the health care setting, it is critical that health care workers adhere to
standard precautions, follow fundamental infection control principles, and
use appropriate procedural techniques.
All obstetriciangynecologists who provide clinical care should receive
HBV vaccine. Postvaccination testing for the hepatitis B surface antigen
(HBsAg) antibody (anti-HBs) 12 months after completing the vaccine
series is recommended by the Centers for Disease Control and Prevention (1). Individuals who do not respond to the primary vaccine series (antiHBs titers of less than 10 mIU/mL) should complete a second three-dose
series or be evaluated to determine if they are HBsAg positive. Revaccinated
persons should be retested at the completion of the second vaccine series (2).
Obstetriciangynecologists who are HBsAg positive also should know
their hepatitis B e antigen status, which indicates the presence of high viral
concentrations. Because high viral load concentrations have been associated
with an increased risk of transmission, obstetriciangynecologists who are
e antigen positive should not perform exposure-prone procedures until they
COMMITTEE OPINIONS
have sought counsel from an expert review panel

and have been advised under what circumstances, if
any, they may continue to perform these procedures
(3). The Centers for Disease Control and Prevention
recommends that the expert review panel be a locally convened panel of experts representing a variety
of perspectives and may include the following: 1)
the obstetriciangynecologists personal physician,
2) an infectious disease specialist with expertise in
hepatitis transmission, 3) a health care professional
with expertise in the procedures performed by the
obstetriciangynecologist, 4) state or local public
health official(s), and 5) a hospital epidemiologist or
other member of the infection-control committee of
the hospital. Exposure-prone procedures refer to certain procedures that have been implicated in hepatitis transmission despite adherence to the principles
of standard precautions. Examples of exposureprone procedures in obstetrics and gynecology that
have been implicated in hepatitis transmission
include deep pelvic surgery, particularly when sharp
instruments are guided by the surgeons fingers, and
simultaneous presence of the surgeons fingers and a
needle or sharp instrument or object in a poorly visualized or highly confined anatomic site (4, 5).
Referral to a specialist may be necessary in
cases involving persons who do not respond serologically after completing a second series of HBV vaccination and practicing obstetriciangynecologists
who are HBsAg positive but are e antigen negative.
However, specific evidence-based guidance is lacking in these areas.
Although there is currently no immunization
available to prevent infection with HCV, the risk of
acquiring HCV infection appears lower than the risk
of acquiring HBV (an average of 1.8% after a percutaneous exposure to an HCV-positive source patient
compared with 2060% for an HBV-positive source
331
patient who is e antigen positive) (2). Routine HCV

testing is not recommended for health care workers,
and there are currently no recommendations in the
United States to restrict the professional activities of
health care workers with HCV infection (6). After
an occupational exposure, such as a needle stick, the
exposed health care worker, as well as the source
patient, should be tested for the antibody to HCV.
Postexposure prophylaxis is not effective and not
recommended. However, early antiviral therapy may
be effective in reducing the risk of progression to
chronic HCV infection (7).
References
1. Immunization of health-care workers: recommendations
of the Advisory Committee on Immunization Practices
(ACIP) and the Hospital Infection Control Practices
Advisory Committee (HICPAC). MMWR Recomm Rep
1997;46(RR-18):142.
2. Updated U.S. Public Health Service Guidelines for the
Management of Occupational Exposures to HBV, HCV,
and HIV and Recommendations for Postexposure Prophylaxis. U.S. Public Health Service. MMWR Recomm Rep
2001;50(RR-11):152.
3. Recommendations for preventing transmission of human
immunodeficiency virus and hepatitis B virus to patients
during exposure-prone invasive procedures. MMWR
Recomm Rep 1991;40(RR-8):19.
4. Welch, J, Webster M, Tilzey AJ, Noah ND, Banatvala JE.
Hepatitis B infections after gynaecological surgery.
Lancet 1989;1:2057.
5. Carl M, Blakey DL, Francis DP, Maynard JE. Interruption
of hepatitis B transmission by modification of a gynaecologists surgical technique. Lancet 1982;1:7313.
6. Recommendations for prevention and control of hepatitis
C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention.
MMWR Recomm Rep 1998;47(RR-19):139.
7. Recommendations for follow-up of health-care workers
after occupational exposure to hepatitis C virus. Centers
for Disease Control and Prevention. MMWR Morb
Mortal Wkly Rep 1997;46:6036.
332
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Reaffirmed 2008
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Role of the obstetriciangynecologist

in the screening and diagnosis of
breast masses. ACOG Committee
Opinion 334. American College of
(Replaces No. 186, September 1997)
Role of the Obstetrician

Gynecologist in the Screening and
Diagnosis of Breast Masses
ABSTRACT: Obstetriciangynecologists are in a favorable position to diagnose breast disease in their patients. Obstetriciangynecologists are more
likely to encounter a patient with breast cancer than a patient with any gynecologic cancer. The American College of Obstetricians and Gynecologists
(ACOG) has adopted the goals of assisting in educating obstetriciangynecologists in the diagnosis and treatment of breast cancer and in reducing
mortality from breast cancer. To help meet these goals, ACOG has developed
recommendations for the early diagnosis of breast disease.
Obstetriciangynecologists are in a favorable position to diagnose breast disease in their patients. Because more than 200,000 new cases of breast cancer
are diagnosed each year, compared with fewer than 80,000 gynecologic cancers, obstetriciangynecologists are more likely to encounter a patient with
breast cancer than a patient with any gynecologic cancer. The American
College of Obstetricians and Gynecologists (ACOG) has adopted the goals
of assisting in educating obstetriciangynecologists in the diagnosis and
treatment of breast cancer and in reducing mortality from breast cancer. As
an initial step toward these goals, ACOG has developed the following guidelines for the early diagnosis of breast disease:
1. There are factors that increase the risk for breast carcinoma in women.
Information regarding risk factors for breast cancer should be elicited in
the medical and family history.
2. Breast examination by visual inspection and palpation should be an integral part of initial obstetric and all complete gynecologic examinations.
A clinical breast examination lacks the sensitivity to function as a
comprehensive screening tool on its own; however, it may identify
abnormalities that may go undetected by other techniques and can assist
in directing further investigation.
3. Patients may be instructed in the technique of periodic self-examination
of the breast. Although available randomized controlled trials do not
confirm a reduction in overall breast cancer mortality in women per-
COMMITTEE OPINIONS
4.
5.
6.
7.
forming breast self-examination, awareness of

normal breast findings and changes from these
findings may lead to early detection for some
women.
Patients should be encouraged to undergo screening by mammography in accordance with ACOG
guidelines. Women who undergo mammography
may be counseled that high false-positive rates
(10% per screening in postmenopausal women
and as high as 20% per screening in obese or
premenopausal women) may result in further
testing.
Obstetriciangynecologists may perform diagnostic procedures when indicated or should
make referrals to physicians who specialize in
the diagnosis and treatment of breast disease.
Institutions that grant physicians privileges to
perform breast surgery should apply the same
criteria for privileging to obstetriciangynecologists as to other physicians.
A persistent palpable breast mass requires evaluation. A normal diagnostic mammography
alone is not always sufficient to rule out malignant pathology in a patient with a palpable
breast mass.
When a patient is referred to another physician
for diagnostic testing or consultation, the obstetriciangynecologist should ensure that the
patient is provided with the following:
An explanation that she needs further care
The names of qualified physicians from
whom the patient can receive care
333
An opportunity to have her questions

answered
A summary of the history, physical examination, and diagnostic tests performed
Information for the consultant if diagnostic
imaging is required for a reason of clinical
concern and not just routine screening
Documentation of these steps and a description of
the clinical findings should be included in the medical record.
Bibliography
Breast cancer screening. ACOG Practice Bulletin No. 42.
Gynecol 2003;101:82131.
Elmore JG, Carney PA, Abraham LA, Barlow WE, Egger JR,
Fosse JS, et al. The association between obesity and screening
mammography accuracy. Arch Intern Med 2004;164:11407.
Elmore JG, Barton MB, Moceri VM, Polk S, Arena PJ,
Fletcher SW. Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med
1998;338:108996.
Humphrey LL, Helfand M, Chan BK, Woolf SH. Breast cancer
screening: a summary of the evidence for the U.S. Preventive
Services Task Force. Ann Intern Med 2002;137:34760.
Kosters JP, Gotzsche PC. Regular self-examination or clinical
examination for early detection of breast cancer. The Cochrane
CD003373. DOI: 10.1002/14651858.CD003373.
Olsen O, Gotzsche PC. Screening for breast cancer with mammography. The Cochrane Database of Systematic Reviews
2001, Issue 4. Art. No.: CD001877. DOI: 10.1002/14651858.
CD001877.
334
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Committee on
Reaffirmed 2008
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directed to:
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Tamoxifen and uterine cancer.

2006;107:14758.
Tamoxifen and Uterine Cancer

ABSTRACT: Tamoxifen may be associated with endometrial proliferation,
hyperplasia, polyp formation, invasive carcinoma, and uterine sarcoma. Any
symptoms of endometrial hyperplasia or cancer reported by a postmenopausal woman taking tamoxifen should be evaluated. Premenopausal women
treated with tamoxifen have no known increased risk of uterine cancer and as
such require no additional monitoring beyond routine gynecologic care. If
atypical endometrial hyperplasia develops, appropriate gynecologic management should be instituted, and the use of tamoxifen should be reassessed.
Tamoxifen, a nonsteroidal antiestrogen agent, is used widely as adjunctive

therapy for women with breast cancer. It has been approved by the U.S. Food
and Drug Administration for the following indications:
Adjuvant treatment of breast cancer
Metastatic breast cancer
Reduction in breast cancer incidence in high-risk women
Because obstetriciangynecologists frequently treat women with breast
cancer and women at risk for the disease, they may be consulted for advice
on the proper follow-up of women receiving tamoxifen. The purpose of this
Committee Opinion is to review the risk and to recommend care to prevent
and detect uterine cancer in women receiving tamoxifen.
Tamoxifen is one of a class of agents known as selective estrogen receptor modulators (SERMs). Although the primary therapeutic effect of tamoxifen is derived from its antiestrogenic properties, this agent also has modest
estrogenic activity. In standard dosages, tamoxifen may be associated with
endometrial proliferation, hyperplasia, polyp formation, invasive carcinoma,
and uterine sarcoma.
Most studies have found that the increased relative risk of developing
endometrial cancer for women taking tamoxifen is two to three times higher than that of an age-matched population (13). The level of risk of endometrial cancer in women treated with tamoxifen is dose and time dependent.
Studies suggest that the stage, grade, histology, and biology of tumors that
develop in individuals treated with tamoxifen (20 mg/d) are no different
from those that arise in the general population (3, 4). However, some reports
have indicated that women treated with a higher dosage of tamoxifen
COMMITTEE OPINIONS
(40 mg/d) are more prone to develop more biologically aggressive tumors (5).
In one early study of the National Surgical
Adjuvant Breast and Bowel Project (NSABP), the
rate of endometrial cancer occurrence among tamoxifen users who were administered 20 mg/d was 1.6
per 1,000 patient years, compared with 0.2 per 1,000
patient years among control patients taking a placebo (3). In this study, the 5-year disease-free survival
rate from breast cancer was 38% higher in the
tamoxifen group than in the placebo group, suggesting that the small risk of developing endometrial
cancer is outweighed by the significant survival benefit provided by tamoxifen therapy for women with
breast cancer (3). The survival advantage with 5
years of tamoxifen therapy continued with long-term
follow-up, but extending the duration of tamoxifen
use to 10 years failed to improve the survival benefit
gained from 5 years of tamoxifen use (6). In a more
recent update of all NSABP trials of patients with
breast cancer, the rate of endometrial cancer was
1.26 per 1,000 patient years in women treated with
tamoxifen versus 0.58 per 1,000 patient years in the
placebo group (7).
Uterine sarcomas consisting of malignant mixed
mllerian tumors, leiomyosarcoma, and stroma cell
sarcomas are a rare form of uterine malignancy
occurring in 25% of all patients with uterine malignancies (8). In a review of all NSABP breast cancer
treatment trials, the rate of sarcoma in women treated with tamoxifen was 17 per 100,000 patient years
versus none in the placebo group (7). Similarly, in a
separate trial of high-risk women without breast cancer taking tamoxifen as part of a breast cancer prevention trial with a median follow-up of 6.9 years,
there were four sarcomas (17 per 100,000 patient
years) in the tamoxifen group versus none in the
placebo group (7). This is compared with the incidence of one to two per 100,000 patient years in the
general population (9).
The NSABP prevention trial (P-1) data suggest
that the risk for both invasive and noninvasive breast
cancer is reduced markedly with tamoxifen prophylaxis. In this trial, however, the risk ratio for developing endometrial cancer was 2.53 in women using
tamoxifen compared with women receiving a placebo (10). In addition, the ability of tamoxifen to
induce endometrial malignancy as well as other
histopathologic conditions appears to differ between
premenopausal and postmenopausal women. In the
prevention trial of high-risk women, there was no
335
statistically significant difference in endometrial

cancer rates between women treated with tamoxifen
and those in the placebo group in the women aged
49 years and younger; however, in women aged 50
years and older, the risk ratio was 4.01 (95% confidence interval, 1.7010.90) for those treated with
tamoxifen versus those receiving placebo. The
annual rate was 3.05 malignancies per 1,000 women
treated with tamoxifen versus 0.76 malignancies per
1,000 women receiving placebo (10). Another study
of women with breast cancer found that premenopausal women, treated or untreated, had no differences in endometrial thickness on ultrasound
examination, uterine volume, or histopathologic findings, whereas postmenopausal women treated with
tamoxifen had significantly more abnormalities (11).
Several approaches have been explored for
screening asymptomatic women using tamoxifen for
abnormal endometrial proliferation or endometrial
cancer. Correlation is poor between ultrasonographic measurements of endometrial thickness and
abnormal pathology in asymptomatic tamoxifen
users because of tamoxifen-induced subepithelial
stromal hypertrophy (12). In asymptomatic women
using tamoxifen, screening for endometrial cancer
with routine transvaginal ultrasonography, endometrial biopsy, or both has not been shown to be
effective (1315). Although asymptomatic postmenopausal tamoxifen-treated women should not
have routine testing to diagnose endometrial pathology, sonohysterography has improved the accuracy
of ultrasonography in excluding or detecting
anatomical changes, when necessary (16).
Other data suggest that low- and high-risk
groups of postmenopausal patients may be identified
before the initiation of tamoxifen therapy for breast
cancer (1719). Pretreatment screening identified 85
asymptomatic patients with benign polyps in 510
postmenopausal patients with newly diagnosed
breast cancer (16.7%). All polyps were removed. At
the time of polypectomy, two patients had atypical
hyperplasias and subsequently underwent hysterectomies. The rest were treated with tamoxifen, 20
mg/d, for up to 5 years. The incidence of atypical
hyperplasia was 11.7% in the group with initial
lesions versus 0.7% in the group without lesions
(P <.0001), an 18-fold increase in risk. In addition,
polyps developed in 17.6% of the group with initial
lesions versus 12.9% in the group without.
Although the concurrent use of progestin reduces
the risk of endometrial hyperplasia and cancer in
336
patients receiving unopposed estrogen, the effect of

progestin on the course of breast cancer and on the
endometrium of women receiving tamoxifen is not
known. Therefore, such use cannot be advocated as a
means of lowering risk in women taking tamoxifen.
On the basis of these data, the committee recommends the following:
Postmenopausal women taking tamoxifen
should be monitored closely for symptoms of
endometrial hyperplasia or cancer.
Premenopausal women treated with tamoxifen
have no known increased risk of uterine cancer
and as such require no additional monitoring
beyond routine gynecologic care.
Women taking tamoxifen should be informed
about the risks of endometrial proliferation,
endometrial hyperplasia, endometrial cancer,
and uterine sarcomas. Women should be encouraged to promptly report any abnormal vaginal
symptoms, including bloody discharge, spotting, staining, or leukorrhea.
Any abnormal vaginal bleeding, bloody vaginal
discharge, staining, or spotting should be investigated.
Emerging evidence suggests the presence of
high- and low-risk groups for development of
atypical hyperplasias with tamoxifen treatment
in postmenopausal women based on the presence or absence of benign endometrial polyps
before therapy. Thus there may be a role for pretreatment screening of postmenopausal women
with transvaginal ultrasonography, and sonohysterography when needed, or office hysteroscopy
before initiation of tamoxifen therapy.
Unless the patient has been identified to be at
high risk for endometrial cancer, routine
endometrial surveillance has not been effective
in increasing the early detection of endometrial
cancer in women using tamoxifen. Such surveillance may lead to more invasive and costly
diagnostic procedures and, therefore, is not recommended.
Tamoxifen use should be limited to 5 years
duration because a benefit beyond this time has
not been documented.
If atypical endometrial hyperplasia develops,
appropriate gynecologic management should be
instituted, and the use of tamoxifen should be
reassessed. If tamoxifen therapy must be contin-
ued, hysterectomy should be considered in

women with atypical endometrial hyperplasia.
Tamoxifen use may be reinstituted following
hysterectomy for endometrial carcinoma in consultation with the physician responsible for the
womans breast care.
References
1. Sismondi P, Biglia N, Volpi E, Giai M, de Grandis T.
Tamoxifen and endometrial cancer. Ann N Y Acad Sci
1994;734:31021.
2. Bissett D, Davis JA, George WD. Gynaecological monitoring during tamoxifen therapy. Lancet 1994;344:1244.
3. Fisher B, Costantino JP, Redmond CK, Fisher ER,
Wickerham DL, Cronin WM. Endometrial cancer in
tamoxifen-treated breast cancer patients: findings from
the National Surgical Adjuvant Breast and Bowel Project
(NSABP) B-14. J Natl Cancer Inst 1994;86:52737.
4. Barakat RR, Wong G, Curtin JP, Vlamis V, Hoskins WJ.
Tamoxifen use in breast cancer patients who subsequently develop corpus cancer is not associated with a higher
incidence of adverse histologic features. Gynecol Oncol
1994;55:1648.
5. Magriples U, Naftolin F, Schwartz PE, Carcangiu ML.
High-grade endometrial carcinoma in tamoxifen-treated
breast cancer patients. J Clin Oncol 1993;11:48590.
6. Fisher B, Dignam J, Bryant J, DeCillis A, Wickerham DL,
Wolmark N, et al. Five versus more than five years of
tamoxifen therapy for breast cancer patients with negative
lymph nodes and estrogen receptor-positive tumors. J Natl
Cancer Inst 1996;88:152942.
7. Wickerham DL, Fisher B, Wolmark N, Bryant J,
Costantino J, Bernstein L, et al. Association of tamoxifen
and uterine sarcoma. J Clin Oncol 2002;20:275860.
8. Averette HE, Nguyen H. Gynecologic cancer. In: Murphy
GP, Lawrence W Jr, Lenhard RE Jr, editors. American
Cancer Society textbook of clinical oncology. 2nd ed.
Atlanta (GA): American Cancer Society; 1995. p. 55279.
9. Mouridsen H, Palshof T, Patterson J, Battersby L.
Tamoxifen in advanced breast cancer. Cancer Treat Rev
1978;5:13141.
10. Fisher B, Costantino JP, Wickerham DL, Redmond CK,
Kavanah M, Cronin WM, et al. Tamoxifen for prevention
of breast cancer: report of the National Surgical Adjuvant
Breast and Bowel Project P-1 Study. J Natl Cancer Inst
1998;90:137188.
11. Cheng WF, Lin HH, Torng PL, Huang SC. Comparison of
endometrial changes among symptomatic tamoxifentreated and nontreated premenopausal and postmenopausal breast cancer patients. Gynecol Oncol
1997;66:2337.
12. Achiron R, Lipitz S, Sivan E, Goldenberg M, Horovitz A,
Frenkel Y, et al. Changes mimicking endometrial neoplasia in postmenopausal, tamoxifen-treated women with
breast cancer: a transvaginal Doppler study. Ultrasound
13. Bertelli G, Venturini M, Del Mastro L, Garrone O, Cosso
M, Gustavino C, et al. Tamoxifen and the endometrium:
COMMITTEE OPINIONS
findings of pelvic ultrasound examination and endometrial biopsy in asymptomatic breast cancer patients. Breast
Cancer Res Treat 1998;47:416.
14. Fung MF, Reid A, Faught W, Le T, Chenier C, Verma S, et
al. Prospective longitudinal study of ultrasound screening
for endometrial abnormalities in women with breast cancer receiving tamoxifen. Gynecol Oncol 2003;91:1549.
15. Love CD, Muir BB, Scrimgeour JB, Leonard RC, Dillon
P, Dixon JM. Investigation of endometrial abnormalities
in asymptomatic women treated with tamoxifen and an
evaluation of the role of endometrial screening. J Clin
Oncol 1999;17:20504.
16. Markovitch O, Tepper R, Aviram R, Fishman A, Shapira
J, Cohen I. The value of sonohysterography in the predic-
337
tion of endometrial pathologies in asymptomatic postmenopausal breast cancer tamoxifen-treated patients.

17. Berliere M, Charles A, Galant C, Donnez J. Uterine side
effects of tamoxifen: a need for systematic pretreatment
screening. Obstet Gynecol 1998;91:404.
18. Berliere M, Radikov G, Galant C, Piette P, Marbaix E,
Donnez J. Identification of women at high risk of developing endometrial cancer on tamoxifen. Eur J Cancer
2000;36(suppl 4):S356.
19. Vosse M, Renard F, Coibion M, Neven P, Nogaret JM,
Hertens D. Endometrial disorders in 406 breast cancer
patients on tamoxifen: the case for less intensive monitoring. Eur J Obstet Gynecol Reprod Biol 2002;101:5863.
338
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Committee on
Reaffirmed 2008
Committee
Opinion

Copyright June 2006
from the publisher.
directed to:
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ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Noncontraceptive uses of the levonorgestrel intrauterine system.

2006;107:147982.
Noncontraceptive Uses of the

Levonorgestrel Intrauterine System
ABSTRACT: The levonorgestrel intrauterine system, approved for contraceptive use for up to 5 years, also has noncontraceptive uses. It appears to
reduce menstrual bleeding significantly in women with idiopathic menorrhagia. Current studies suggest that menopausal hormone therapy regimens
combining the levonorgestrel intrauterine system with estradiol are effective
in reducing climacteric symptoms and in inducing amenorrhea in most
women after 1 year. Further studies are required before this device can be
recommended as a treatment for endometriosis-associated pelvic pain,
hyperplasia, or endometrial adenocarcinoma, or as adjuvant therapy with
tamoxifen.
In 2000, the U.S. Food and Drug Administration (FDA) approved the levonorgestrel-releasing intrauterine system for intrauterine contraception for
up to 5 years. The purpose of this Committee Opinion is to address noncontraceptive uses of the levonorgestrel intrauterine system.
The system consists of a 32-mm T-shaped polyethylene frame with a
steroid reservoir containing a mixture of 52 mg of levonorgestrel and silicone covered by a silicone membrane. After insertion, the initial release of
levonorgestrel into the uterine cavity is 20 mcg/d. A stable plasma concentration of 150200 pg/mL is achieved after the first few weeks (1). Although
some degradation of concentration is seen over timeby 2 years of use, levels are closer to 100 pg/mL (2, 3)the concentration is maintained for at
least 5 years (1) and the typical histologic changes in the endometrium
induced by the levonorgestrel intrauterine system have been observed for up
to 7 years (4). The plasma concentration of levonorgestrel in patients using
the levonorgestrel intrauterine system is less than 25% of that seen with 150
mcg of oral levonorgestrel (5).
Menorrhagia
In women with idiopathic menorrhagia (generally defined as excessively
heavy, regular menses in the absence of intracavitary pathology or coagulopathy), the levonorgestrel intrauterine system appears to reduce menstrual
blood loss significantly. Reductions of up to 86% after 3 months and up to
COMMITTEE OPINIONS
97% after 12 months of use have been reported

(69). At 12 months after insertion of the levonorgestrel intrauterine system, reported rates of
amenorrhea vary between 20% and 80% (1012).
Several randomized controlled trials have evaluated use of the levonorgestrel intrauterine system
and other treatment modalities for menorrhagia (6,
11, 1315). Most studies have been in Scandinavian
populations. A Cochrane Collaboration review concluded that the levonorgestrel intrauterine system is
significantly more effective than oral cyclical
norethindrone as a treatment for heavy menstrual
bleeding (16). Although the levonorgestrel intrauterine system results in a smaller mean reduction of
menstrual blood loss at 1 year than does transcervical resection of the endometrium, the rates of patient
satisfaction at 1 year are similar in both groups (6).
Another trial reported a blood loss reduction of 79%
in the group using the levonorgestrel intrauterine
system versus 89% in the group undergoing transcervical resection of the endometrium (11). In terms
of quality of life and cost-effectiveness, the levonorgestrel intrauterine system appears to be a costeffective alternative to hysterectomy during the first
5 years of use (17, 18).
The most common side effects resulting in discontinuation of levonorgestrel intrauterine system
therapy include irregular bleeding and hormonal
side effects such as breast tenderness, mood
changes, and acne (6). Other potential drawbacks
include abdominal pain, infection, and difficult
insertions requiring cervical dilation (6).
Hormone Therapy
A number of trials have evaluated use of the levonorgestrel intrauterine system as an alternative
delivery system for the progestin component of
combined hormone therapy (HT) (5, 1923).
Current studies suggest that HT regimens combining
the levonorgestrel intrauterine system with estradiol
delivered by various methods (vaginal ring, gel, oral,
transdermal) are effective in reducing climacteric
symptoms and in inducing amenorrhea in 5983%
of women after 1 year (24, 25). The long-term health
effects of the levonorgestrel intrauterine system as a
means of hormone therapy during menopause are
unknown. Although most studies suggest that the
levonorgestrel intrauterine system often is associated with irregular bleeding in the first 13 months
of use, amenorrhea may occur with long-term use
339
(19). Women with persistent bleeding should be

evaluated in the typical manner, regardless of the
presence of the levonorgestrel intrauterine system.
Endometrial biopsies after 1 and 5 years of levonorgestrel intrauterine system use as a component
of HT have consistently shown atrophy, suggesting
that the levonorgestrel intrauterine system protects
the endometrium from hyperplasia (12, 22, 26).
Furthermore, no cases of endometrial hyperplasia
have been reported during treatment with a levonorgestrel intrauterine system combined with
estrogen therapy (4, 12, 27, 28). The aforementioned studies used the FDA-approved levonorgestrel intrauterine system, which delivers 20 mcg/d;
a smaller version of the product that may be more
suitable for the postmenopausal uterus also has been
studied (29, 30).
Treatment of Endometrial Hyperplasia

and Early Endometrial Cancer
The use of oral progestin therapy is a recognized
treatment option in selected patients with atypical
endometrial hyperplasia. Thus far, only one study of
a series of 12 women with endometrial hyperplasia
with or without atypia treated with a frameless
levonorgestrel intrauterine system (releasing only
14 mcg/d of levonorgestrel) has been published,
showing effective suppression of the endometrium
(31). Two additional studies of small series (one of
12 women, one of four women) have assessed the
feasibility of using a progestin-containing intrauterine system to treat grade 1, stage I endometrioid
uterine adenocarcinoma in women who are poor operative candidates (32, 33). These preliminary results
were consistent with other progestational agents.
Adjuvant Therapy With Tamoxifen

Tamoxifen stimulates the endometrium and increases the risk of endometrial hyperplasia and malignancy (34). A randomized controlled trial of women
with previous breast cancer using tamoxifen for
more than 1 year suggested that the levonorgestrel
intrauterine system may prevent tamoxifen-induced
endometrial changes (35). However, this must be
balanced against potential breakthrough bleeding
associated with levonorgestrel intrauterine system
use and the unproven safety of administering progestational agents to women with a history of breast
cancer. Before the levonorgestrel intrauterine sys-
340
tem can be recommended as an adjuvant therapy

with tamoxifen in women with a history of breast
cancer, long-term randomized trials are needed.
Endometriosis and Pelvic Pain

Small pilot studies suggest that the levonorgestrel
intrauterine system improves endometriosis-associated pelvic pain for up to 3 years (3640). Although
further studies are needed before the levonorgestrel
intrauterine system can be recommended as a treatment for endometriosis-associated pelvic pain, it is
reasonable to consider its use by women with endometriosis desiring effective, long-term contraception.
Conclusion
There is sufficient evidence to support the use of the
levonorgestrel intrauterine system as a treatment
option for idiopathic menorrhagia. There also is sufficient evidence that the levonorgestrel intrauterine
system protects against endometrial hyperplasia in
women using menopausal estrogen therapy.
Additional studies are required before this device
can be recommended as a treatment for endometriosis-associated pelvic pain, hyperplasia, or endometrial adenocarcinoma, or as adjuvant therapy with
tamoxifen.
References
1. Mirena. In: Physicians desk reference: PDR. 60th ed.
Montvale (NJ): Thomson PDR; 2006. p. 8105.
2. Nilsson CG, Lahteenmaki P, Luukkainen T. Levonorgestrel plasma concentrations and hormone profiles after
insertion and after one year of treatment with a levonorgestrel-IUD. Contraception 1980;21:22533.
3. Xiao BL, Zhou LY, Zhang XL, Jia MC, Luukainen T,
Allonen H. Pharmacokinetic and pharmacodynamic studies of levonorgestrel-releasing intrauterine device.
4. Silverberg SG, Haukkamaa M, Arko H, Nilsson CG,
Luukkainen T. Endometrial morphology during long-term
use of levonorgestrel-releasing intrauterine devices. Int J
Gynecol Pathol 1986;5:23541.
5. Suhonen S, Allonen H, Lahteenmaki P. Sustained-release
estradiol implants and a levonorgestrel-releasing intrauterine device in hormone replacement therapy. Am J
6. Istre O, Trolle B. Treatment of menorrhagia with the levonorgestrel intrauterine system versus endometrial resection. Fertil Steril 2001;76:3049.
7. Barrington JW, Bowen-Simpkins P. The levonorgestrel
intrauterine system in the management of menorrhagia.
Br J Obstet Gynaecol 1997;104:6146.
8. Tang GW, Lo SS. Levonorgestrel intrauterine device in

the treatment of menorrhagia in Chinese women: efficacy
versus acceptability. Contraception 1995;51:2315.
9. Andersson JK, Rybo G. Levonorgestrel-releasing intrauterine device in the treatment of menorrhagia. Br J
Obstet Gynaecol 1990;97:6904.
10. Ronnerdag M, Odlind V. Health effects of long-term use
of the intrauterine levonorgestrel-releasing system. A follow-up study over 12 years of continuous use. Acta Obstet
Gynecol Scand 1999;78:71621.
11. Crosignani PG, Vercellini P, Mosconi P, Oldani S, Cortesi
I, De Giorgi O. Levonorgestrel-releasing intrauterine
device versus hysteroscopic endometrial resection in
treatment of dysfunctional uterine bleeding. Obstet
Gynecol 1997;90:25763.
12. Varila E, Wahlstrom T, Rauramo I. A 5-year follow-up
study on the use of a levonorgestrel intrauterine system in
women receiving hormone replacement therapy. Fertil
Steril 2001;76:96973.
13. Lahteenmaki P, Haukkamaa M, Puolakka J, Riikonen U,
Sainio S, Suvisaari J, et al. Open randomised study of use
of levonorgestrel releasing intrauterine system as alternative to hysterectomy. BMJ 1998;316:11226.
14. Irvine GA, Campbell-Brown MB, Lumsden MA, Heikkila
A, Walker JJ, Cameron IT. Randomized comparative trial
of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia. Br J
Obstet Gynaecol 1998;105:5928.
15. Kittelsen N, Istre O. A randomized study comparing levonorgestrel intrauterine system (LNS IUS) and transcervical resection of the endometrium (TCRE) in the treatment
of menorrhagia: preliminary results. Gynaecol Endosc
1998;7:615.
16. Lethaby AE, Cooke I, Rees M. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual
bleeding. The Cochrane Database of Systematic Reviews
2005, Issue 4. Art. No.: CD002126. DOI: 10.1002/
14651858.CD002126.pub2.
17. Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman
S, Kivela A, et al. Quality of life and cost-effectiveness of
levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised
trial. Lancet 2001;357:2737.
18. Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman
S, Kivela A, et al. Clinical outcomes and costs with the
levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia: randomized trial 5-year
follow up. JAMA 2004;291:145663.
19. Suvanto-Luukkonen E, Sundstrom H, Penttinen J, Laara
E, Pramila S, Kauppila A. Percutaneous estradiol gel with
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progesterone in hormone replacement therapy. Maturitas
1997;26:2117.
20. Andersson K, Mattsson LA, Rybo G, Stadberg E.
Intrauterine release of levonorgestrela new way of
adding progestogen in hormone replacement therapy.
21. Raudaskoski TH, Lahti EI, Kauppila AJ, Apaja-Sarkkinen
MA, Laatikainen TJ. Transdermal estrogen with a levonorgestrel-releasing intrauterine device for climacteric
complaints: clinical and endometrial responses. Am J
COMMITTEE OPINIONS
22. Kalogirou D, Antoniou G, Karakitsos P, Kalogirou O,

Antoniou D, Giannikos L. A comparative study of the
effects of an estradiol-releasing vaginal ring combined
with an oral gestagen versus transdermal estrogen combined with a levonorgestrel-releasing IUD: clinical findings and endometrial response. Int J Fertil Menopausal
Stud 1996;41:5227.
23. Sturdee DW, Rantala ML, Colau JC, Zahradnik HP,
Riphagen FE. The acceptability of a small intrauterine
progestogen-releasing system for continuous combined hormone therapy in early postmenopausal women. Multicenter
MLS Investigators. Climacteric 2004;7:40411.
24. Riphagen FE. Intrauterine application of progestins in
hormone replacement therapy: a review. Climacteric
2000;3:199211.
25. Boon J, Scholten PC, Oldenhave A, Heintz PA. Continuous intrauterine compared with cyclic oral progestin
administration in perimenopausal HRT. Maturitas
2003;46:6977.
26. Suvanto-Luukkonen E, Kauppila A. The levonorgestrel
intrauterine system in menopausal hormone replacement
therapy: five-year experience. Fertil Steril 1999;72:1613.
27. Suhonen S, Holmstrom T, Allonen H, Lahteenmaki P.
Intrauterine and subdermal progestin administration in
postmenopausal hormone replacement therapy. Fertil
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28. Suhonen S, Holmstrom T, Lahteenmaki P. Three-year follow-up of the use of a levonorgestrel-releasing intrauterine system in hormone replacement therapy. Acta Obstet
Gynecol Scand 1997;76:14550.
29. Raudaskoski T, Tapanainen J, Tomas E, Luotola H,
Pekonen F, Ronni-Sivula H, et al. Intrauterine 10 microg
and 20 microg levonorgestrel systems in postmenopausal
women receiving oral oestrogen replacement therapy:
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30. Wildemeersch D, Schacht E, Wildemeersch P.
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342
ACOG
Committee on
Reaffirmed 2008
American Society
for Colposcopy and
Cervical Pathology
The Committee and Society wish
to thank Hope K. Haefner, MD,
and Mark Spitzer, MD, for their
assistance in the development of
this document.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Vulvodynia. ACOG Committee
Committee
Opinion
Vulvodynia
ABSTRACT: Vulvodynia is a complex disorder that can be difficult to treat.
It is described by most patients as burning, stinging, irritation, or rawness.
Many treatment options have been used, including vulvar care measures,
medication, biofeedback training, physical therapy, dietary modifications,
sexual counseling, and surgery. A cotton swab test is used to distinguish generalized disease from localized disease. No one treatment is effective for all
patients. A number of measures can be taken to prevent irritation, and several medications can be used to treat the condition.
Vulvodynia is a complex disorder that can be difficult to treat. This

Committee Opinion provides an introduction to the diagnosis and treatment
of vulvodynia for the generalist obstetriciangynecologist. It is adapted with
permission from the 2005 American Society for Colposcopy and Cervical
Pathology publication, The Vulvodynia Guideline (1).
Terminology and Classification

Many women experience vulvar pain and discomfort that affects the quality
of their lives. Vulvodynia is described by most patients as burning, stinging,
irritation, or rawness. It is a condition in which pain is present although the
vulva appears normal (other than erythema).
The most recent terminology and classification of vulvar pain by the
International Society for the Study of Vulvovaginal Disease defines vulvodynia as vulvar discomfort, most often described as burning pain, occurring in
the absence of relevant visible findings or a specific, clinically identifiable,
neurologic disorder (2). It is not caused by commonly identified infection
(eg, candidiasis, human papillomavirus, herpes), inflammation (eg, lichen
planus, immunobullous disorder), neoplasia (eg, Pagets disease, squamous
cell carcinoma), or a neurologic disorder (eg, herpes neuralgia, spinal nerve
compression). The classification of vulvodynia is based on the site of the
pain, whether it is generalized or localized, and whether it is provoked,
unprovoked, or mixed. Although the term vulvar dysesthesia has been used
in the past, there is now consensus to use the term vulvodynia and subcategorize it as localized or generalized.
Several causes have been proposed for vulvodynia, including embryologic abnormalities, increased urinary oxalates, genetic or immune factors,
COMMITTEE OPINIONS
hormonal factors, inflammation, infection, and neuropathic changes. Most likely, there is not a single
cause.
Because the etiology of vulvodynia is unknown,
it is difficult to say whether localized vulvodynia
(previously referred to as vestibulitis) and generalized vulvodynia are different manifestations of the
same disease process. Distinguishing localized disease from generalized disease is fairly straightforward and is done with the cotton swab test as
described in the following section. Early classification to localized or generalized vulvodynia can facilitate more timely and appropriate treatment.
Diagnosis and Evaluation

Vulvodynia is a diagnosis of exclusion, a pain syndrome with no other identified cause. A thorough
history should identify the patients duration of pain,
previous treatments, allergies, medical and surgical
history, and sexual history.
Cotton swab testing (Fig. 1) is used to identify
areas of localized pain and to classify the areas
where there is mild, moderate, or severe pain. A diagram of pain locations may be helpful in assessing
the pain over time. The vagina should be examined,
and tests, including wet mount, vaginal pH, fungal
culture, and Gram stain, should be performed as

indicated. Fungal culture may identify resistant
strains, but sensitivity testing usually is not required.
Testing for human papillomavirus infection is
unnecessary.
Treatment
Most of the available evidence for treatment of vulvodynia is based on clinical experience, descriptive
studies, or reports of expert committees. There are
few randomized trials of vulvodynia treatments.
Outlined here are treatments used by clinicians with
an interest in vulvodynia. Multiple treatments have
been used (Fig. 2), including vulvar care measures;
topical, oral, and injectable medications; biofeedback
training; physical therapy; dietary modifications;
cognitive behavioral therapy; sexual counseling; and
surgery. Newer treatments being used include
acupuncture, hypnotherapy, nitroglycerin, and botulinum toxin.
Gentle care of the vulva is advised. The following vulvar care measures can minimize vulvar
irritation:
Figure 1. Cotton swab testing for vestibulodynia. The

vestibule is tested at the 2-, 4-, 6-, 8-, and 10-oclock
positions. When pain is present, the patient is asked to
quantify it as mild, moderate, or severe. (Haefner HK.
Critique of new gynecologic surgical procedures: surgery for vulvar vestibulitis. Clin Obstet Gynecol 2000;
43:689700.)
343
Wearing 100% cotton underwear (no underwear

at night)
Avoiding vulvar irritants (perfumes, dyes, shampoos, detergents) and douching
Using mild soaps for bathing, with none applied
to the vulva
Cleaning the vulva with water only
Avoiding the use of hair dryers on the vulvar
area
Patting the area dry after bathing, and applying
a preservative-free emollient (such as vegetable
oil or plain petrolatum) topically to hold moisture in the skin and improve the barrier function
Switching to 100% cotton menstrual pads (if
regular pads are irritating)
Using adequate lubrication for intercourse
Applying cool gel packs to the vulvar area
Rinsing and patting dry the vulva after urination
Different medications have been tried as treatments for vulvar pain. These include topical, oral,
and intralesional medications, as well as pudendal
nerve blocks. Many of these medications are known
to interact with other drugs, and many patients with
vulvodynia may be taking multiple medications.
Clinicians should check for any potential drug inter-
344
Physical examination
Cutaneous or mucosal surface disease present
Yes
No
Cotton swab test
Not tender, no area of vulva

touched described as area
of burning
Treat abnormal visible condition present (infections,

dermatoses, premalignant or malignant conditions)
Tender, or patient describes

area touched as area of
burning
Yeast culture
Alternative diagnosis (incorrect belief
that vulvodynia is
present)
Positive
Negative
Antifungal
therapy
Inadequate
relief
Adequate relief
Good relief
Treatment Options
1. Vulvar care measures
2. Topical medications
3. Oral medications
4. Injections
5. Biofeedback/physical therapy
6. Dietary modifications
7. Cognitive behavioral therapy
8. Sexual counseling
Inadequate relief
and pain localized
to vestibule
Inadequate relief and

pain generalized
No additional treatment;
stop treatment when indicated
Surgery
(Vestibulectomy)
High-dose and
multiple
medications for
neuropathic pain;
consider referral
to pain specialist;
consider
neuromodulation
Figure 2. Vulvodynia treatment algorithm. (Adapted from Haefner HK, Collins ME, Davis GD, Edwards L, Foster DC,
Hartmann EH, et al. The vulvodynia guideline. J Low Genit Tract Dis 2005;9:4051.)
actions before prescribing a new medication. Before

prescribing a new course of therapy, clinicians may
stop use of all topical medication.
Commonly prescribed topical medications
include a variety of local anesthetics (which can be
applied immediately before intercourse or in extended use), estrogen cream, and tricyclic antidepressants compounded into topical form. Although
topical steroids generally do not help patients with
vulvodynia, trigger-point injections of a combination of steroid and bupivacaine have been successful
for some patients with localized vulvodynia (3).
Tricyclic antidepressants and anticonvulsants
can be used for vulvodynia pain control. When first
prescribing drugs, clinicians should avoid polypharmacy. One drug should be prescribed at a time.
Before prescribing antidepressants or anticonvulsants for a patient of reproductive age, the clinician
COMMITTEE OPINIONS
should emphasize the need for contraception.

Antidepressants have been found to have a 60%
response rate for various pain conditions; however,
no randomized, controlled studies have been published regarding the use of antidepressants for
vulvodynia. Both tricyclic antidepressants and anticonvulsants take time to achieve adequate pain control, which may take up to 3 weeks. Patients usually
develop tolerance to the side effects of these medications (particularly sedation, dry mouth, and dizziness).
Biofeedback and physical therapy also are used
in the treatment of both localized and generalized
vulvodynia (4). Physical therapy techniques include
internal (vaginal and rectal) and external soft tissue
mobilization and myofascial release; trigger-point
pressure; visceral, urogenital, and joint manipulation; electrical stimulation; therapeutic exercises;
active pelvic floor retraining; biofeedback; bladder
and bowel retraining; instruction in dietary revisions; therapeutic ultrasonography; and home vaginal dilation.
Vestibulectomy has been helpful for many
patients with localized pain that has not responded
to previous treatments (5). Patients should be evaluated for vaginismus and, if present, treated before a
vestibulectomy is performed. For generalized vulvar
burning unresponsive to previous behavioral and
medical treatments, referral to a pain specialist may
be helpful.
Conclusion
Vulvodynia is a complex disorder that frequently is
frustrating to both clinician and patient. It can be difficult to treat, and rapid resolution is unusual, even
with appropriate therapy. Decreases in pain may
take weeks to months and may not be complete. No
single treatment is successful in all women.
345
Expectations for improvement need to be realistically addressed with the patient. Emotional and psychologic support is important for many patients, and
sex therapy and counseling may be beneficial.
Resources
Haefner HK, Collins ME, Davis GD, Edwards L,
Foster DC, Hartman ED, et al. The vulvodynia guideline. J Low Genit Tract Dis 2005;9:4051. Available at: http://www.jlgtd.com/pt/re/jlgtd/pdfhandler.
00128360-200501000-00009.pdf. Retrieved March
15, 2006.
National Vulvodynia Association
http://www.nva.org
PO Box 4491
Silver Spring, MD 20914-4491
301-299-0775
References
1. Haefner HK, Collins ME, Davis GD, Edwards L, Foster
DC, Hartmann EH, et al. The vulvodynia guideline. J Low
Genit Tract Dis 2005;9:4051.
2. Moyal-Barracco M, Lynch PJ. 2003 ISSVD terminology
and classification of vulvodynia: a historical perspective.
J Reprod Med 2004;49:7727.
3. Segal D, Tifheret H, Lazer S. Submucous infiltration of
betamethasone and lidocaine in the treatment of vulvar
vestibulitis. Eur J Obstet Gynecol Reprod Biol 2003;
107:1056.
4. Bergeron S, Binik YM, Khalife S, Pagidas K, Glazer HI,
Meana M, et al. A randomized comparison of group cognitive-behavioral therapy, surface electromyographic
biofeedback, and vestibulectomy in the treatment of dyspareunia resulting from vulvar vestibulitis. Pain 2001;
91:297306.
5. Haefner HK. Critique of new gynecologic surgical procedures: surgery for vulvar vestibulitis. Clin Obstet Gynecol
2000;43:689700.
346

The Role of Cystourethroscopy in the

Generalist ObstetricianGynecologist
Practice
Committee on
Gynecologic
Practice
followed.
ABSTRACT: Cystourethroscopy can be performed for diagnostic and a few operative indications by obstetriciangynecologists to help improve patient care. Perhaps the
most important indications for cystourethroscopy are to rule out cystotomy and intravesical or intraurethral suture or mesh placement and to verify bilateral ureteral patency
during or after certain gynecologic surgical procedures. The granting of privileges for cystourethroscopy and other urogynecologic procedures should be based on training, experience, and demonstrated competence. Postgraduate education, including residency
training programs in obstetrics and gynecology and continuing medical education, should
include education in the instrumentation, technique, and evaluation of findings of cystourethroscopy, and in the pathophysiology of diseases of the lower urinary tract.
Although many of the pioneers of cystourethroscopy, most notably Howard Kelly,

were gynecologists, for decades the procedure has been performed mainly by urologists. However, cystourethroscopy can be
performed for diagnostic and a few operative
indications by obstetriciangynecologists to
help improve patient care. This document
reviews the definition and indications for
cystourethroscopy and discusses the evidence
and recommendations for its use in the generalist obstetriciangynecologist practice.
Cystoscopy
Cystoscopy is a surgical procedure in which a
rigid or flexible fiberoptic endoscope is used
to examine the lumen of the bladder.
Urethroscopy, in which the urethral lumen is
examined for urethral diseases or abnormalities, is a related procedure. For cystoscopy,
the endoscope is introduced through the urethra, allowing the surgeon to visualize both
the bladder and urethra, thus the term cystourethroscopy.
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Operative Technique
When performing cystourethroscopy for
diagnostic indications, the surgeon should
follow a technical routine in which the entire
lumen of the urethra and bladder are exam-
ined systematically. The instrumentation,

surgical technique, and typical findings (normal and abnormal) have been reviewed in
most textbooks on urogynecology and
female urology. Briefly, diagnostic cystourethroscopy is performed using sterile techniques, usually with local anesthesia, while
the patient is awake and in the supine lithotomy position. It also can be performed during or after gynecologic surgery with the
patient under general or regional anesthesia.
The urine should be free of infection before
the procedure. After sterile preparation of the
urethral meatus and surrounding vulvar
vestibule, 2% lidocaine jelly can be introduced into the urethra and then used as
lubrication for the endoscope. Sterile water
or saline is used to fill the bladder by gravity
during the procedure. If electrocautery is to
be performed, a nonconducting solution,
such as glycine, should be used.
Depending on the indication for the cystourethroscopy, the surgeon generally starts
with a 30-degree endoscope and, with the
solution running, introduces it through the
urethra under direct vision with or without
video assistance. After partial distention of
the bladder, the trigone is examined for
mucosal abnormalities, lesions, or foreign
bodies, as indicated. The interureteric ridge
COMMITTEE OPINIONS
is noted above the trigone, and both ureteral orifices are

visualized. If the goal is to examine for ureteral patency,
5 mL of indigo carmine can be given intravenously 1015
minutes before the cystoscopy, followed by observation of
blue-stained urine from the ureteral orifices. An inout
technique is used to circumferentially examine sections of
the bladder surface, usually starting at the trigone at the
6-oclock position, progressing clockwise around the right
bladder surface to the dome at the 12-oclock position,
and then back to the trigone on the left side of the bladder
(1). After the entire bladder examination is accomplished,
the urethra is reexamined with removal of the endoscope.
If the specific goal is to examine for lesions or for suture
or mesh material in the lateral edges of the bladder, a 70degree rigid or flexible endoscope can be reintroduced to
reexamine the bladder. If the specific goal is to examine
the urethra, a 0-degree or 25-degree endoscope can be
used. The findings should be documented carefully, noting the systematic nature of the procedure.
Shortly before the procedure, a single dose of prophylactic antibiotics is recommended to prevent urinary
tract infection or septicemia for patients at moderate or
high risk of endocarditis, those who are neutropenic, and
those with preoperative bacteriuria or an indwelling
catheter (2, 3).
Indications and Complications

The indications for cystourethroscopy, like hysteroscopy,
are both diagnostic and operative and are for symptoms
and diseases related to the lower urinary tract. Diagnostic
cystourethroscopy can be performed as part of an evaluation of abnormal symptoms, signs, or laboratory
findings; intraoperatively during gynecologic or urogynecologic surgery to rule out bladder, urethral, or
ureteral trauma; and as part of staging or surgery for
gynecologic malignancy. A list of possible indications for
diagnostic cystourethroscopy during gynecologic surgery
is shown in the box. Operative cystoscopy usually involves
the introduction of additional instruments, such as biopsy forceps or scissors, through an operating channel in the
Possible Indications for

Diagnostic Cystourethroscopy
During Gynecologic Surgery
During or after surgery for pelvic organ prolapse or
stress urinary incontinence to rule out cystotomy and
intravesical or intraurethral suture or mesh placement
Verification of bilateral ureteral flow during or after
obstetric, gynecologic, urogynecologic, or gynecologic oncologic surgery
Evaluation of suspected urine leak during or after
laparotomy, laparoscopy, or vaginal surgery
Verification of suprapubic catheter placement, if desired
347
cystoscope to perform procedures or interventions. It also

can be done as part of a reparative procedure to the bladder or urethra, such as vesicovaginal fistula or urethral
diverticulum repair. Operative procedures generally are
performed by urologists and selectively by urogynecologists and gynecologic oncologists. However, generalist
obstetriciangynecologists with special expertise and
experience may perform minor operative procedures
such as passage of ureteral stents and injection of urethral
bulking agents.
Complications after cystourethroscopy are few.
These generally involve minor pain related to the procedure and the small risk of postoperative urinary tract
infection. These risks usually are negligible with use of
local anesthesia and single-dose prophylactic antibiotics
in patients at moderate or high risk for endocarditis.
Other rare complications include perforation of the urethra or bladder or ureteral perforation if instruments or
stents are placed into the ureter.
There is a small risk that the surgeon will not recognize abnormalities that are present, such as bladder
lesions or mesh or sutures in the bladder. For example, in
one study, urologists had less than perfect agreement
between cystoscopic and histologic diagnoses when biopsies were performed for suspicious bladder lesions (4).
Because routine intraoperative cystourethroscopy examines only the bladder and urethral mucosal surfaces and
ureteral orifices, it does not guarantee recognition of all
lower urinary tract injuries (5). Nonobstructive, partially
obstructive, or late ureteral injuries may not be recognized or prevented (68). When cystourethroscopy is performed, there are minimal additional costs and time
spent in the operating room.
Recommendations for the Generalist

ObstetricianGynecologist
Few studies have been conducted that provide evidencebased recommendations for the use of cystourethroscopy
in a general obstetric and gynecologic practice. Typically,
recommendations for the use of cystourethroscopy in
general obstetric and gynecologic practice imply that the
physician has knowledge and competency in the instrumentation and surgical technique; can recognize normal
and abnormal bladder and urethral findings; and has
knowledge of pathology, diagnosis, and treatment of specific diseases of the female lower urinary tract. Specialists
in female pelvic medicine and reconstructive surgery and
gynecologic oncology have an expanded use of cystourethroscopy based on their additional training and
resulting greater level of expertise and experience.
The granting of privileges for cystourethroscopy and
other urogynecologic procedures should be based on
training, experience, and demonstrated competence.
Obstetriciangynecologists who are appropriately trained
in a technique, have sufficient experience performing it,
and have demonstrated current clinical competence
should be granted privileges accordingly.
348
In 1996, the Agency for Healthcare Research and

Quality (then known as the Agency for Healthcare Policy
and Research) provided recommendations for cystoscopy
(regardless of specialty), but none of the recommendations were supported by scientific evidence from properly designed and implemented controlled trials and are no
longer considered current (9). In that document, cystoscopy was recommended for the evaluation of patients
who have sterile hematuria or pyuria; new-onset irritative
voiding symptoms such as frequency, urgency, and urge
incontinence in the absence of any reversible causes; bladder pain; recurrent cystitis; suspected presence of a foreign body; or when urodynamic testing failed to duplicate
symptoms of urinary incontinence. Cystoscopy was not
recommended in the basic evaluation of urinary incontinence. Likewise, routine cystoscopy in women with urinary incontinence to exclude neoplasia was not indicated
because the risk of bladder lesions is less than 2% (9, 10).
Cystourethroscopy is indicated during or after some
surgical procedures performed 1) to treat stress urinary
incontinence and anterior vaginal prolapse, such as Burch
colposuspension, paravaginal defect repair, pubovaginal
sling procedure, and tension-free vaginal tape procedure;
2) to rule out intravesical placement of sutures or mesh;
and 3) to verify ureteral patency. Tension-free vaginal tape
and related mid-urethral sling procedures that pass
through the retropubic space especially require routine
cystourethroscopy to detect intraoperative bladder perforation, which occurs in 39% of cases (11, 12). As noted
earlier, certain other surgical procedures usually performed by specialists, such as repair of vesicovaginal
fistula or urethral diverticulum, routinely require cystourethroscopy to aid the surgical repair.
The issue of whether cystourethroscopy should be
performed during and after gynecologic surgery to evaluate for bladder integrity and for ureteral patency remains
unresolved. Intraoperative cystotomies usually are noted
at the time of the injury, especially if retrograde bladder
filling is used to aid recognition. However, sutures or
mesh placed in the bladder or urethral lumen during surgical procedures usually are not recognized unless cystourethroscopy is performed.
Ureteral injuries are of particular concern to practicing obstetriciangynecologists. Although the incidence of
bladder and ureteral injury during common gynecologic
procedures is low, wide ranges have been reported in the
literature making estimation of risk difficult for individual surgical procedures. A recent systematic review of
urinary tract injuries during gynecologic surgery with
routine intraoperative cystourethroscopy for benign disease reported crude ureteral injury rates for laparoscopic
hysterectomy with bilateral salpingo-oophorectomy of
17.3 per 1,000 procedures (95% confidence interval [CI],
0.366.3); for other gynecologic and urogynecologic surgical procedures, including other types of hysterectomy,
the overall ureteral injury rate was 8.8 per 1,000 proce-
dures (95% CI, 2.312.6) (13). The overall bladder injury

rate per 1,000 laparoscopic hysterectomies with bilateral
salpingo-oophorectomy was 29.2 (95% CI, 7.5148.0);
after other gynecologic and urogynecologic surgical procedures, the rate was 16.3 (95% CI, 4.326.6) (13).
Factors that should be considered when deciding
when to perform diagnostic cystourethroscopy include
complication rates associated with the procedure and the
difficulty of the individual surgical case. Cystourethroscopy is indicated during or after tension-free vaginal tape
procedure, Burch colposuspension, and high uterosacral
ligament vaginal vault suspension. Surgical procedures
such as McCall culdoplasty, colpocleisis, and perhaps
certain advanced and difficult vaginal and laparoscopic
procedures and hysterectomies may be indications for
intraoperative diagnostic cystourethroscopy.
Conclusions
Cystourethroscopy is a low-risk operative procedure used
to examine the lumen of the bladder and urethra. Perhaps
the most important indications for cystourethroscopy are
to rule out cystotomy and intravesical or intraurethral
suture or mesh placement and to verify bilateral ureteral
patency during or after certain gynecologic surgical procedures. The procedures that have a relatively high risk
for these complications (at least 12%) may benefit from
cystourethroscopy to help avoid additional surgery,
permanent loss of renal function, fistulas, and other
abnormalities. Because intraoperative cystourethroscopy
examines only the bladder and urethral mucosal surfaces
and ureteral orifices, it does not guarantee recognition of
all lower urinary tract injuries. Nonobstructive, partially
obstructive, or late ureteral or bladder injuries may not be
recognized or prevented. Whether the routine use of
intraoperative cystourethroscopy during hysterectomy
and other gynecologic surgical procedures with a lower
risk of urinary tract injury is advisable requires further
study.
Postgraduate education, including residency training
programs in obstetrics and gynecology and continuing
medical education, should include education in the
instrumentation, technique, and evaluation of findings of
cystourethroscopy, and in the pathophysiology of diseases
of the lower urinary tract.
References
1. Cundiff GW, Bent AE. Endoscopic evaluation of the lower
urinary tract. In: Walters MD, Karram MM, editors.
Urogynecology and reconstructive pelvic surgery. 3rd ed.
Philadelphia (PA): Mosby Elsevier; 2007. p. 11423.
2. Dajani AS, Taubert KA, Wilson W, Bolger AF, Bayer A,
Ferrieri P, et al. Prevention of bacterial endocarditis.
Recommendations by the American Heart Association.
JAMA 1997;277:1794801.
3. Olson ES, Cookson BD. Do antimicrobials have a role in
preventing septicemia following instrumentation of the
urinary tract? J Hosp Infect 2000;45:8597.
COMMITTEE OPINIONS
4. Mitropoulos D, Kiroudi-Voulgari A, Nikolopoulos P,

Manousakas T, Zervas A. Accuracy of cystoscopy in predicting histologic features of bladder lesions. J Endourol
2005;19:8614.
5. Dwyer PL, Carey MP, Rosamilia A. Suture injury to the
urinary tract in urethral suspension procedures for stress
incontinence. Int Urogynecol J Pelvic Floor Dysfunct
1999;10:1521.
6. Councell RB, Thorp JM Jr, Sandridge DA, Hill ST.
Assessments of laparoscopic-assisted vaginal hysterectomy.
J Am Assoc Gynecol Laparosc 1994;2:4956.
7. Dandolu V, Mathai E, Chatwani A, Harmanli O, Pontari M,
Hernandez E. Accuracy of cystoscopy in the diagnosis of
ureteral injury in benign gynecologic surgery. Int
Urogynecol J Pelvic Floor Dysfunct 2003;14:42731.
8. Gustilo-Ashby AM, Jelovsek JE, Barber MD, Yoo EH,
Paraiso MF, Walters MD. The incidence of ureteral obstruction and the value of intraoperative cystoscopy during vaginal surgery for pelvic organ prolapse. Am J Obstet Gynecol
2006;194:147885.
9. Agency for Health Care Policy and Research. Urinary
incontinence in adults: acute and chronic management.
Clinical Practice Guideline, No. 2, 1996 update. AHCPR
Publication No. 96-0682. Rockville (MD): AHCPR; 1996.
10. Ouslander J, Leach G, Staskin D, Abelson S, Blaustein J,
Morishita L, et al. Prospective evaluation of an assessment
strategy for geriatric urinary incontinence. J Am Geriatr Soc
1989;37:71524.
349
11. Ward K, Hilton P. Prospective multicentre randomised trial

of tension-free vaginal tape and colposuspension as primary treatment for stress incontinence. United Kingdom and
Ireland Tension-Free Vaginal Tape Trial Group. BMJ
2002;325:6770.
12. Tamussino KF, Hanzal E, Kolle D, Ralph G, Riss PA.
Tension-free vaginal tape operation: results of the Austrian
registry. Austrian Urogynecology Working Group. Obstet
Gynecol 2001;98:7326.
13. Gilmour DT, Das S, Flowerdew G. Rates of urinary tract
injury from gynecologic surgery and the role of intraoperative cystoscopy. Obstet Gynecol 2006;107:136672.

20090-6920. All rights reserved. No part of this publication may
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The role of cystourethroscopy in the generalist obstetriciangynecologist practice. ACOG Committee Opinion No. 372. American College of
ISSN 1074-861X
350

Brand Versus Generic Oral Contraceptives

Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: The U.S. Food and Drug Administration considers generic and brand
name oral contraceptive (OC) products clinically equivalent and interchangeable. The
American College of Obstetricians and Gynecologists supports patient or clinician
requests for branded OCs or continuation of the same generic or branded OCs if the
request is based on clinical experience or concerns regarding packaging or compliance,
or if the branded product is considered a better choice for that individual patient.
To control pharmaceutical costs and standardize national practice, the U.S. Food and Drug
Administration (FDA) was given the authority
to approve generic versions of branded pharmaceutical products by the Drug Price
Competition and Patent Term Restoration
Act. Before 1984, manufacturers of generic
products had to submit clinical safety and efficacy data for their products just as the innovator drug manufacturer had to do for initial
approval. Since 1984, generic products, including generic oral contraceptive (OC)
products, must demonstrate pharmaceutical
equivalence, meaning that this new generic
product contains the same active ingredients,
identical in strength and dosage, as the
branded product. This generic product also
must be bioequivalent, meaning that blood
levels obtained in clinical trials demonstrate
a rate and extent of absorption not substantially different from the branded product (1).
Studies demonstrating bioequivalence of
generic OC products are submitted by the
generic pharmaceutical company after a
crossover study of adequate power (usually
of 2024 women) with pharmacokinetic calculations of serial blood levels of the progestin or its active metabolite and ethinyl
estradiol, plasma concentration time curves
(AUC), peak concentration, and the time to
peak concentration. The average blood level
deviation from the brand must be in the
range of 80125%. If these criteria are met,
the FDA Office of Generic Drugs does not
request or recommend clinical efficacy or
safety studies for the generic product before
granting marketing approval, and it considers the generic product to be interchangeable
with the branded product. No clinical trial is

needed given that the safety and efficacy of
the generic product is expected to be that of
the clinically tested and FDA-approved
branded product. Brand name and generic
drug facilities are required to meet the same
standards of good manufacturing practices.
Patients and clinicians have questioned
whether generic and brand name OC
products are clinically equivalent and interchangeable, as effective in preventing pregnancy, and have similar occurrences of side
effects, such as breakthrough bleeding. The
FDA considers generic and brand name OC
products clinically equivalent and interchangeable; however, others imply that this
may not be true (2). The statistical methods
used by the FDA to determine bioequivalence
have been challenged. The FDA Center for
Drug Evaluation and Research has taken a
firm stand upholding the therapeutic equivalence and interchangeability of generic and
branded products (3).
Oral contraceptive pills are the most
commonly used form of reversible contraception in the United States. Overall, the FDA
lists more than 90 combination hormonal
contraceptives containing ethinyl estradiol.
Most OCs are no longer patent protected and
are available for the development of generic
pharmaceutical copies. The 2007 27th edition of Approved Drug Products With Therapeutic Equivalence Evaluations, the so-called
Orange Book, lists only seven combination
OCs that do not have a generic alternative (4).
Although new OC formulations are protected
by patent for 20 years from initial patent filing, in practice there is a much shorter inter-
COMMITTEE OPINIONS
val from final approval and marketing to loss of patent

protection.
Although considered clinically equivalent by the
FDA, branded and generic OCs may differ in shape, packaging, color, flavor, and shelf life. In addition, nonactive
ingredients such as preservatives and labeling and storage
requirements also may differ. Products are considered
bioequivalent if they fall within the required parameters;
the mean bioequivalence cannot be more than 20% lower
or 25% higher, with 95% certainty. In practice, the reported ranges of generics are much narrower. Given the range
of acceptable generic bioequivalence, switching between
generic OCs or from branded to generic OCs might be
associated with increased side effects or other problems,
but similar problems theoretically might occur when
switching between two batches made by the same manufacturer. Additionally, some firms package their own
branded drugs and sell them under a generic or other
brand label.
When taken correctly and consistently, combination
OCs and other hormonal contraceptives have failure rates
of less than one pregnancy per 100 couples over 1 year.
Published studies report different failure rates for various
brands, but few head-to-head studies have been performed, and there is no evidence that with perfect use different combination products have different failure rates
(5).
Although there are no clinical data on any difference
in compliance between different branded OCs or between
generic and branded OCs, patients and clinicians anecdotally report problems when switching occurs. It is possible
that side effects or pregnancy occur as a result of poor
compliance because patients are confused by new packaging, they fear that they received the wrong pill, or they
lack confidence in generics. Although this likely affects
compliance and effectiveness, there are no evidence-based
data addressing these issues. Even though some patients
may perceive generic products to be less effective, there
are no clinical data on how this perception affects continuation rates.
Given an individuals variations in metabolism, it is
probably impossible to improve our knowledge of OCs by
completing larger studies; effectiveness and side effects will
tend to be overwhelmed by other nonpharmaceutical
effects. Breakthrough bleeding, which is a common cause
of OC discontinuation, is related to missed pills, smoking,
infection, and possibly drug interactions, which will tend
to overwhelm subtle variations between already confirmed
bioequivalent and pharmaceutically equivalent products.
As the FDA has pointed out, patients may be more likely to
be aware of symptoms when substitutions occur or if they
have been told they are taking a generic brand.
Oral contraceptive pills are obtained by patients in a
variety of settings and with different reimbursement
plans, and cost clearly influences access and use. For a
patient whose insurance will pay only for a generic product on formulary or in cases where a patient is paying
351
out of pocket, the difference in price can be as much as

70% less for a generic, especially when multiple generic
choices for a specific branded product are available.
Often, the difference is much less. Cost has been shown to
be among the most important factors in OC continuation, and less expensive generic OCs may have better continuation rates than more expensive alternatives (6).
Generic OCs approved by the FDA have been shown
to be bioequivalent and pharmaceutically equivalent to
the branded product and are interchangeable. There are
no evidence-based data to challenge this conclusion.
However, because of possible effects on patient compliance, the American College of Obstetricians and Gynecologists supports patient or clinician requests for
branded OCs or continuation of the same generic or
branded OC if the request is based on clinical experience
or concerns regarding packaging or compliance, or if the
branded product is considered a better choice for that
individual patient. Women should be informed when a
different OC is substituted for a previously prescribed OC.
References
1. Welage LS, Kirking DM, Ascione FJ, Gaither CA.
Understanding the scientific issues embedded in the generic drug approval process. J Am Pharm Assoc 2001;41:
85667.
2. Bioequivalence between brand-name and generic OCs.
Contracept Rep 2002;13(2):69.
3. U.S. Food and Drug Administration. Therapeutic equivalence of generic drugs. Letter to health practitioners.
Rockville (MD): FDA; 1998. Available at: http://www.fda.
gov/cder/news/nightgenlett.htm. Retrieved April 3, 2007.
4. U.S. Food and Drug Administration. Approved drug products with therapeutic equivalence evaluations. 27th ed.
Rockville (MD): FDA; 2007. Available at: http://www.fda.
gov/cder/ob. Retrieved April 3, 2007.
5. Rosenberg MJ, Waugh MS. Oral contraceptive discontinuation: a prospective evaluation of frequency and reasons.
6. Shrank WH, Hoang T, Ettner SL, Glassman PA, Nair K,
DeLapp D, et al. The implications of choice: prescribing
generic or preferred pharmaceuticals improves medication
adherence for chronic conditions. Arch Intern Med 2006;
166:3327.

Brand versus generic oral contraceptives. ACOG Committee Opinion
ISSN 1074-861X
352

Vaginal Rejuvenation and Cosmetic

Vaginal Procedures
Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: So-called vaginal rejuvenation, designer vaginoplasty, revirgination,

and G-spot amplification are vaginal surgical procedures being offered by some practitioners. These procedures are not medically indicated, and the safety and effectiveness
of these procedures have not been documented. Clinicians who receive requests from
patients for such procedures should discuss with the patient the reason for her request
and perform an evaluation for any physical signs or symptoms that may indicate the need
for surgical intervention. Women should be informed about the lack of data supporting
the efficacy of these procedures and their potential complications, including infection,
altered sensation, dyspareunia, adhesions, and scarring.
There have been an increasing number of

practitioners offering various types of vaginal surgeries marketed as ways to enhance
appearance or sexual gratification. Among
the types of procedures being promoted are
so-called vaginal rejuvenation, designer
vaginoplasty, revirgination, and G-spot
amplification. Often the exact procedure
performed is not clear because standard
medical nomenclature is not used. Some procedures, such as vaginal rejuvenation, appear
to be modifications of traditional vaginal
surgical procedures. Other procedures are
performed to alter the size or shape of the
labia majora or labia minora. Revirgination
involves hymenal repair in an attempt to
approximate the virginal state. G-spot amplification involves the injection of collagen
into the anterior wall of the vagina.
Medically indicated surgical procedures
may include reversal or repair of female genital cutting and treatment for labial hypertrophy or asymmetrical labial growth secondary
to congenital conditions, chronic irritation,
or excessive androgenic hormones. Other
procedures, including vaginal rejuvenation,
designer vaginoplasty, revirgination, and
G-spot amplification, are not medically indicated, and the safety and effectiveness of these
procedures have not been documented. No
adequate studies have been published assessing the long-term satisfaction, safety, and
complication rates for these procedures.
Also of concern are ethical issues associated with the marketing of these procedures
and the national franchising in this field.
Such a business model that controls the dissemination of scientific knowledge is troubling.
Clinicians who receive requests from
patients for such procedures should discuss
with the patient the reason for her request
and perform an evaluation for any physical
signs or symptoms that may indicate the
need for surgical intervention. A patients
concern regarding the appearance of her genitalia may be alleviated by a frank discussion
of the wide range of normal genitalia and
reassurance that the appearance of the external genitalia varies significantly from woman
to woman (1). Concerns regarding sexual
gratification may be addressed by careful
evaluation for any sexual dysfunction and an
exploration of nonsurgical interventions,
including counseling.
It is deceptive to give the impression that
vaginal rejuvenation, designer vaginoplasty,
revirgination, G-spot amplification, or any
such procedures are accepted and routine
surgical practices. Absence of data supporting the safety and efficacy of these procedures
makes their recommendation untenable.
Patients who are anxious or insecure about
their genital appearance or sexual function
may be further traumatized by undergoing
an unproven surgical procedure with obvi-
COMMITTEE OPINIONS
ous risks. Women should be informed about the lack of

data supporting the efficacy of these procedures and their
potential complications, including infection, altered sensation, dyspareunia, adhesions, and scarring.
Reference
1. Lloyd J, Crouch NS, Minto CL, Liao LM, Creighton SM.
Female genital appearance: normality unfolds. BJOG
2005;112:6436.
353
Vaginal rejuvenation and cosmetic vaginal procedures. ACOG
ISSN 1074-861X
354

Colonoscopy and Colorectal Cancer

Screening and Prevention
Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Most colorectal cancer can be detected by screening modalities and

treated at a preinvasive or early invasive stage, before it has developed to a fully invasive
and potentially fatal disease. Obstetriciangynecologists should counsel all patients aged
50 years and older about the benefits of colorectal cancer screening and should encourage colonoscopy as the preferred method of screening for women at either average risk
or high risk. The advantages and limitations of other appropriate colorectal cancer screening methods also should be discussed so that women may choose to be tested by
whichever method they are most likely to accept and complete.
More than 74,000 women develop colorectal

cancer in the United States each year, almost
as many as the number of women who
receive diagnoses of gynecologic cancers.
Each year more than 26,000 women die from
colorectal cancer, making it the third leading
cause of cancer death in women, after lung
cancer and breast cancer (1). Most colorectal
cancer can be detected by screening modalities and treated at a preinvasive or early invasive stage, before it has developed to a fully
invasive and potentially fatal disease. The
purpose of this document is to review
colonoscopy and the other available screening methods to enable the obstetriciangynecologist to appropriately and adequately
counsel patients about the indications for
and benefits of colorectal cancer screening.
Screening for colorectal cancer, using
one of the methods listed in the box, is indicated for all women aged 50 years or older
who are at average risk. It is important to
note that digital rectal examination and inoffice stool sample collection for fecal occult
blood testing are not recommended screening methods for the detection of colorectal
cancer. For women at increased risk, screening and surveillance guidelines also have
been published (Table 1). Although the
guidelines for women at increased risk primarily will be used by physicians who perform colonoscopy, it may be useful for the
obstetriciangynecologist to be aware that
there are specific guidelines for women who
are not considered to be at average risk.
Colorectal Cancer Screening for

Women at Average Risk
Starting at Age 50 Years*
Preferred method
Colonoscopy every 10 years
Other appropriate methods
Fecal occult blood testing or fecal
immunochemical testing every year
Flexible sigmoidoscopy every 5 years
Fecal occult blood testing or fecal
immunochemical testing every year plus
flexible sigmoidoscopy every 5 years
Double contrast barium enema every 5
years
*American College of Gastroenterology recommends that African Americans begin screening
at age 45 years with colonoscopy because of
increased incidence and earlier age of onset of
colorectal cancer. (Agrawal S, Bhupinderjit A,
Bhutani MS, Boardman L, Nguyen C, Romero Y,
et al. Colorectal cancer in African Americans.
Committee of Minority Affairs and Cultural
Diversity, American College of Gastroenterology
[published erratum appears in Am J Gastroenterol 2005;100:1432]. Am J Gastroenterol 2005;
100:51523; discussion 514.)
Both fecal occult blood testing and fecal

immunochemical testing require two or three
samples of stool collected by the patient at home
and returned for analysis. A single stool sample
for fecal occult blood testing or fecal immunochemical testing obtained by digital rectal examination is not adequate for the detection of colorectal cancer.
COMMITTEE OPINIONS
355
Table 1. American Cancer Society Guidelines for Colorectal Cancer Screening and Surveillance for Women at Increased Risk or
High Risk
Risk Category
Age to Begin
Recommendation
Comment
Increased Risk
Women with a single, small
(less than 1 cm) adenoma
At 36 years after the initial

polypectomy
Colonoscopy*
If the examination result is normal, the

patient can thereafter be screened as
per average risk guidelines.
Women with a large (1 cm or Within 3 years after the initial

larger) adenoma, multiple
polypectomy
adenomas, or adenomas with
high-grade dysplasia or villous
change
Colonoscopy*
If normal, repeat examination in 3 years;

if normal then, the patient can thereafter be screened as per average risk
guidelines.
Personal history of curativeintent resection of colorectal

cancer
Within 1 year after cancer

resection
Colonoscopy*
If normal, repeat examination in 3 years;

if normal then, repeat examination
every 5 years.
Either colorectal cancer or

adenomatous polyps in any
first-degree relative before
age 60 years or in two or
more first-degree relatives at
any age (if not a hereditary
syndrome)
Age 40 years or 10 years before

the youngest case in the
immediate family
Colonoscopy*
Every 510 years. Colorectal cancer in

relatives more distant than first degree
does not increase risk substantially
above the average risk group.
Puberty
Early surveillance with

endoscopy and counseling to
consider genetic testing
If the genetic test result is positive,

colectomy is indicated. These patients
are best referred to a center with
experience in the management of
familial adenomatous polyposis.
Family history of hereditary

nonpolyposis colon cancer
Age 21 years
Colonoscopy and counseling to If the genetic test result is positive or if

consider genetic testing
the patient has not had genetic testing,
colonoscopy every 12 years until age
40 and then annually. These patients
are best referred to a center with experience in the management of hereditary
nonpolyposis colon cancer.
Inflammatory bowel disease,

chronic ulcerative colitis, or
Crohns disease
Cancer risk begins to be significant Colonoscopy with biopsies for

8 years after the onset of
dysplasia
pancolitis or 1215 years after
the onset of left-sided colitis
High Risk
Family history of familial
adenomatous polyposis
Every 12 years. These patients are

best referred to a center with experience
in the surveillance and management of
inflammatory bowel disease.
*If colonoscopy is unavailable, not feasible, or not desired by the patient, double contrast barium enema alone or the combination of flexible sigmoidoscopy and double contrast barium enema are acceptable alternatives. Adding flexible sigmoidoscopy to double contrast barium enema may provide a more comprehensive diagnostic evaluation
than double contrast barium enema alone in finding considerable lesions. A supplementary double contrast barium enema may be needed if a colonoscopic examination
fails to reach the cecum, and a supplementary colonoscopy may be needed if a double contrast barium enema identifies a possible lesion or does not adequately visualize
the entire colorectum.
Smith R, von Eschenbach A, Wender R, Levin B, Byers T, Rothenberger D, et al. American Cancer Society guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers. CA Cancer J Clin 2001;51:3875.
Understanding the advantages and limitations of

each screening method is necessary to adequately counsel
women. Because superiority of any one method with
regard to risks, benefits, or cost-effectiveness has not been
clearly documented (2), all methods are acceptable
options for screening. However, many experts prefer
colonoscopy.
For women at either average risk or high risk,

colonoscopy is the preferred method for colorectal cancer
screening. Colonoscopy offers direct visualization of all
colonic surfaces and the ability to remove any precancerous lesions that are detected (3). Colonoscopy gives access
to right-sided lesions, which comprise a considerable proportion (65%) of advanced colorectal neoplasia in
356
women that would be missed by other screening methods

(4). In one study, it was shown that the incidence of colorectal cancer was reduced by 7690% among individuals
undergoing colonoscopy with polypectomy compared
with individuals in a general population registry (5).
Abnormalities found with any of the other screening
methods necessitate referral for diagnostic colonoscopy.
Limitations of colonoscopy include cost, inconvenience
of the preparation required of the patient, and the risk of
complications. In the United States, the capacity for
colonoscopy is limited by an inadequate number of
trained endoscopists to perform the estimated 41 million
colonoscopies required to reach the currently unscreened
population at average risk (6).
Flexible sigmoidoscopy is technically easier, requires
less preparation, and has a lower risk of complications
than colonoscopy but is limited to examining the most
distal portion of the colon and will miss a significant
number of right-sided colonic lesions, particularly in
women (4). Because of these limitations, the combination
of yearly fecal occult blood testing or fecal immunochemical testing with flexible sigmoidoscopy every 5 years may
be preferable to either method alone (7).
Fecal occult blood testing and fecal immunochemical
testing detect occult blood in the stool from a polyp or
cancer disrupting the mucosal barrier. Fecal immunochemical testing specifically detects lower-tract bleeding;
thus, fecal immunochemical testing does not require
changes in diet or medications before testing (8).
Although fecal occult blood testing and fecal immunochemical testing are the least invasive colorectal cancer
screening methods, both of these methods require samples obtained by the patient at home using a kit that must
be returned for analysis.
Both fecal occult blood testing and fecal immunochemical testing require two to three samples of stool. In
a recent study, the sensitivity of a single stool sample for
fecal occult blood testing obtained during an office visit
by digital rectal examination was 4.9%, compared with
23.9% for the recommended at-home fecal occult blood
testing series (9). Therefore, fecal occult blood testing of a
single stool sample from a rectal examination performed
during an office visit is not adequate for the detection of
colorectal cancer and is not recommended.
Noninvasive methods of colorectal cancer screening
currently being evaluated include computed tomography
colonography or virtual colonoscopy and fecal DNA
testing. Virtual colonoscopy requires bowel preparation
similar to colonoscopy. In randomized trials, virtual
colonoscopy has shown 39% sensitivity and 90.5% specificity in detecting lesions of at least 6 mm, significantly
lower than the 99% sensitivity and 100% specificity of
colonoscopy (10). Fecal DNA testing for genetic mutations associated with colorectal cancer requires only a single stool sample. In a recent prospective randomized trial,
the DNA test was found to be more sensitive than fecal
occult blood testing in detecting both precancerous and
cancerous colonic lesions in persons at average risk for

developing colorectal cancer (11). However, neither computed tomography colonography nor fecal DNA testing
have been recommended for use in routine screening for
colorectal cancer. Pending further data supporting their
effectiveness, neither should be recommended as a
screening modality for women at average risk outside of a
research setting.
Colorectal cancer accounts for a considerable number of preventable cancer deaths of women in the United
States each year. Despite consensus among health care
organizations about the value of screening for colorectal
cancer, less than 50% of U.S. women older than 50 years
are screened by any of the recommended methods (12).
As providers of longitudinal care, obstetriciangynecologists have a unique opportunity to increase colorectal
cancer screening rates among their patients and thus
decrease the rate of colorectal cancer mortality in women.
Obstetriciangynecologists should counsel all patients
aged 50 years and older about the benefits of colorectal
cancer screening and should encourage the use of
colonoscopy as the preferred method of screening for
women at either average risk or high risk. The advantages
and limitations of other appropriate colorectal cancer
screening methods also should be discussed so that
women may choose to be tested by whichever method
they are most likely to accept and complete.
References
1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer
statistics, 2007. CA Cancer J Clin 2007;57:4366.
2. Screening for colorectal cancer: recommendation and rationale. U.S. Preventive Services Task Force. Ann Intern Med
2002;137:12931.
3. Smith RA, von Eschenbach AC, Wender R, Levin B, Byers T,
Rothenberger D, et al. American Cancer Society guidelines
for the early detection of cancer: update of early detection
guidelines for prostate, colorectal, and endometrial cancers.
Also: update 2001testing for early lung cancer detection.
ACS Prostate Cancer Advisory Committee, ACS Colorectal
Cancer Advisory Committee, ACS Endometrial Cancer
Advisory Committee [published erratum appears in CA
Cancer J Clin 2001;51:150]. CA Cancer J Clin 2001;51:
3875; quiz 7780.
4. Schoenfeld P, Cash B, Flood A, Dobhan R, Eastone J, Coyle
W, et al. Colonoscopic screening of average-risk women for
colorectal neoplasia. CONCeRN Study Investigators.
N Engl J Med 2005;352:20618.
5. Winawer SJ, Zauber AG, Ho MN, OBrien MJ, Gottlieb LS,
Sternberg SS, et al. Prevention of colorectal cancer by
colonoscopic polypectomy. The National Polyp Study
Workgroup. N Engl J Med 1993;329:197781.
6. Seeff LC, Manninen DL, Dong FB, Chattopadhyay SK,
Nadel MR, Tangka FK, et al. Is there endoscopic capacity to
provide colorectal cancer screening to the unscreened population in the United States? Gastroenterology 2004;127:
16619.
COMMITTEE OPINIONS
7. Smith RA, Cokkinides V, Eyre HJ. American Cancer Society

guidelines for the early detection of cancer, 2006. CA
Cancer J Clin 2006;56:1125; quiz 4950.
8. Allison JE. Colon Cancer Screening Guidelines 2005: the
fecal occult blood test option has become a better FIT.
Gastroenterology 2005;129:7458.
9. Collins JF, Lieberman DA, Durbin TE, Weiss DG. Accuracy
of screening for fecal occult blood on a single stool sample
obtained by digital rectal examination: a comparison with
recommended sampling practice. Veterans Affairs
Cooperative Study #380 Group. Ann Intern Med 2005;142:
815.
10. Cotton PB, Durkalski VL, Pineau BC, Palesch YY, Mauldin
PD, Hoffman B, et al. Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with
standard colonoscopy for detection of colorectal neoplasia.
JAMA 2004;291:17139.
11. Imperiale TF, Ransohoff DF, Itzkowitz SH, Turnbull BA,
Ross ME. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population.
357
Colorectal Cancer Study Group. N Engl J Med 2004;351:

270414.
12. Meissner HI, Breen N, Klabunde CN, Vernon SW. Patterns
of colorectal cancer screening uptake among men and
women in the United States. Cancer Epidemiol Biomarkers
Prev 2006;15:38994.
Colonoscopy and colorectal cancer screening and prevention. ACOG
ISSN 1074-861X
358

Pharmaceutical Compounding
Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Compounding is the preparation of an individualized drug product in

response to a physicians prescription to create a medication tailored to the specialized
needs of an individual patient. There are currently no specific prohibitions by the U.S.
Food and Drug Administration on what constitutes a legitimate claim for compounded
drug products, even if there is no efficacy, risk, or safety evidence to support an advertised claim. Physicians and patients should exercise caution in prescribing and using
products that are largely untested for safety and efficacy.
An increase in the marketing and media coverage of compounded pharmaceutical products has resulted in questions from many
Fellows of the American College of Obstetricians and Gynecologists and their patients
regarding the preparation, regulation, efficacy,
and safety of compounded drug products.
Compounding is the preparation of an individualized drug product in response to a physicians prescription to create a medication
tailored to the specialized needs of an individual patient. Compounded drug products may
fill gaps in the commercially available armamentarium. For example, a compounded
drug may be prepared for the pediatric
patient who is not able to swallow solid oral
dosage forms, yet for whom no liquid preparation is commercially available or for the
patient who may be allergic to an inactive
ingredient in a commercially available product. The use of 17-hydroxyprogesterone to
reduce preterm birth is another example
where compounding may be necessary.
Despite evidence that 17-hydroxyprogesterone may be useful in preventing preterm
birth in a select high-risk population, the formulation of this drug used in research currently is not commercially available (1). Far
removed from these traditional uses of compounding are products that simply blend
commercially available drug products in
proportions tailored to individual patient
information. Many compounded bioidentical
hormone products fall into this category (2).
Although technically all compounded
prescription drug products could be considered unapproved new drugs, the U.S. Food
and Drug Administration has adopted a policy of enforcement discretion, allowing

legitimate preparation of compounded formulations as regulated by state boards of
pharmacy, with a provision of stepping in
when dangerous practices must be addressed
and when drug manufacturing occurs under
the guise of compounding. In general, states
regard compounding to be part of the practice of pharmacy. In addition, there normally
is a provision in individual states pharmacy
acts to permit other licensed practitioners
(eg, physicians, nurse practitioners, and others with prescriptive authority) to engage in
the practice of pharmacy compounding
for their own patients. According to the
American Pharmacists Association, the
essence of pharmaceutical compounding is
the triangular relationship between the
individual health practitioner, his or her
patient, and the compounding pharmacy. It
is this individual prescriberindividual
patientcompounder triad that distinguishes
compounding from manufacturing, which
involves the mass production of medication
with no connection between the producer
of the medication and the ultimate user (3).
Thus, the key in distinguishing compounding from manufacturing is whether the product is created in response to an individual
patients need.
There are currently no specific prohibitions by the U.S. Food and Drug Administration on what constitutes a legitimate
claim for compounded drug products, even
if there is no efficacy, risk, or safety evidence
to support an advertised claim. Significant
COMMITTEE OPINIONS
quality concerns may exist for compounded agents, particularly when sterility is important (eg, injectable or
inhalational agents), and questions about the safety of
certain compounded drug products have been raised (4).
Although it is required that manufactured drugs be consistent from batch to batch, there are no similar quality
control measures for compounded drugs to ensure that
the bioavailability of active ingredients is consistent.
Therefore, although interest in and requests for compounded pharmaceutical products appear to be increasing, physicians and patients should exercise caution in
prescribing and using products that are largely untested
for safety and efficacy.
References
1. Use of progesterone to reduce preterm birth.
ACOG Committee Opinion No. 291. American College
of Obstetricians and Gynecologists. Obstet Gynecol
2003;102:11156.
2. Compounded bioidentical hormones. ACOG Committee
3. American Pharmacists Association. Testimony of the
American Pharmacists Association on federal and state role
in pharmacy compounding and reconstitution: exploring
the right mix to protect patients. Before the Committee on
Health, Education, Labor and Pensions, United States
Senate, October 23, 2003. Washington (DC): APA; 2003.
359
Available at: http://www.aphanet.org/AM/Template.cfm?

Section=Federal_Government_Affairs&CONTENTID
=2932&TEMPLATE=/CM/ContentDisplay.cfm. Retrieved
July 20, 2007.
4. Food and Drug Administration (US). Report: limited FDA
survey of compounded drug products. Rockville (MD):
FDA; 2003. Available at: http://www.fda.gov/cder/pharmcomp/survey.htm. Retrieved July 20, 2007.
Resources
Compounded bioidentical hormones. ACOG Committee
Food and Drug Administration (US). The practice of pharmacy
compounding. Rockville (MD): FDA; 2005. Available at:
http://www.fda.gov/cder/pharmcomp. Retrieved July 20, 2007.
Pharmaceutical compounding. ACOG Committee Opinion No. 387.
Gynecol 2007;110:12134.
ISSN 1074-861X
360

Supracervical Hysterectomy
Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Women with known or suspected gynecologic cancer, current or recent

cervical dysplasia, or endometrial hyperplasia are not candidates for a supracervical procedure. Patients electing supracervical hysterectomy should be carefully screened preoperatively to exclude cervical or uterine neoplasm and should be counseled about the need for
long-term follow-up, the possibility of future trachelectomy, and the lack of data demonstrating clear benefits over total hysterectomy. The supracervical approach should not be
recommended by the surgeon as a superior technique for hysterectomy for benign disease.
Hysterectomy remains one of the most commonly performed surgical procedures in the
United States, with the most frequent indications being abnormal uterine bleeding and
symptomatic uterine leiomyomata. Variations
in surgical technique have been described in
an attempt to reduce operative morbidity
and reduce the effects of hysterectomy on
urinary and sexual function. Supracervical
hysterectomy is one such technique in which
there has been renewed interest among
patients and some gynecologic surgeons.
Historically, the supracervical hysterectomy
was abandoned in favor of total hysterectomy
because of problems related to the retained
cervix. The purpose of this document is to
review the scientific data for elective supracervical hysterectomy in which it is the preference of the patient or physician to preserve
the cervix at the time of hysterectomy unrelated to the indications for surgery.
Techniques for supracervical hysterectomy, defined as removal of the uterine corpus with preservation of the cervix, are well
described for both the abdominal and
laparoscopic approaches (1, 2). Features
common to both the laparoscopic and open
techniques of supracervical hysterectomy are
removal of the corpus at or below the level of
the internal os and attempted ablation of the
endocervical canal after removal of the corpus (1). In laparoscopic supracervical hysterectomy, morcellation of the uterine fundus is performed to facilitate its removal
through the port site incisions (1).
Women with known or suspected gynecologic cancer, current or recent cervical dys-
plasia, or endometrial hyperplasia are not

candidates for a supracervical procedure
(35). Candidates for elective supracervical
hysterectomy must have normal results from
a recent cytologic cervical examination and
normal gross appearance of the cervix documented before surgery (35). Clinicians also
should consider testing for high-risk human
papillomavirus to identify patients who
could be at risk for future cervical neoplasia.
Amputation of the uterine corpus in the
abdominal approach and morcellation of the
corpus in the laparoscopic approach require
adequate preoperative assessment of the
endometrial cavity to exclude neoplasm
(35).
Possible benefits of supracervical hysterectomy with regard to perioperative morbidity are not supported by recent evidence.
In three prospective randomized controlled
trials that did not include laparoscopic procedures, no difference in complications,
including infection; blood loss requiring
transfusion; or urinary tract, bowel, or vascular injury, was seen between women randomized to total abdominal hysterectomy (TAH)
and supracervical abdominal hysterectomy
(35). Length of hospital stay (5.2 versus 6
days, P = .04) and duration of surgical procedure (59.5 versus 71.1 minutes P <.001) were
significantly shorter for women randomized
to supracervical hysterectomy in European
studies, but no significant difference was seen
in any outcome measured in the only
prospective randomized trial of TAH versus
supracervical hysterectomy conducted in the
United States (35). Reported rates of post-
COMMITTEE OPINIONS
operative cyclical vaginal bleeding in women randomized

to supracervical hysterectomy were 520% in these three
prospective trials. Of the two trials that reported reoperation rates, 1.5% of the participants had a second operation to remove the cervix less than 3 months from the
time of hysterectomy.
Choosing to preserve the cervix to reduce adverse
effects of hysterectomy on sexual and urinary function
also is not supported by data from prospective randomized trials. Differences in preoperative and postoperative
stress or urge incontinence, urinary frequency, and
incomplete bladder emptying were not statistically significant between women randomized to supracervical hysterectomy or TAH in either the U.S. or British trials (3, 4).
The Danish Hysterectomy Group found a higher incidence of urinary incontinence in women randomized to
supracervical hysterectomy (P = .043) (5). Sexual satisfaction was reported with similar frequency preoperatively
and 1 year postoperatively by women in the Danish study,
irrespective of type of hysterectomy performed (5).
Frequency of intercourse, frequency of orgasm, and rating of sexual relationship with a partner measured preoperatively and postoperatively were similar for the supracervical hysterectomy and TAH groups in the British study
(4). In the U.S. study, there were no differences between
the supracervical hysterectomy and the TAH groups in
sexual functioning and measure of health-related quality
of life, including sexual desire, orgasm frequency and
quality, and body image, measured 2 years after surgery
(6).
Because there have been no randomized, controlled
trials of laparoscopic supracervical hysterectomy compared with either TAH or laparoscopically assisted vaginal
hysterectomy (LAVH), evidence regarding the potential
benefits of this technique is limited to retrospective series.
In a retrospective comparison of laparoscopic supracervical hysterectomy with LAVH, less blood loss, shorter
operating time, and fewer complications were found in
the patients who had supracervical hysterectomy (7). In
contrast, the recent experience of a large managed care
organization was documented, indicating longer operating time for laparoscopic supracervical hysterectomy
compared with TAH but less blood loss, shorter hospital
stay, and fewer major complications for laparoscopic
supracervical hysterectomy compared with TAH (8).
Although only reported in series with small numbers of
patients, the long-term complications of laparoscopic
supracervical hysterectomy include cyclical vaginal bleeding in 1117% of cases and the need for trachelectomy
because of symptoms in 23% of cases at a mean of 14
months from the time of hysterectomy (9, 10). The
potential risks as well as benefits of laparoscopic supracervical hysterectomy should be carefully considered by
the individual surgeon and patient until data from
prospective randomized controlled trials comparing this
technique with LAVH or TAH are available.
361
An additional risk of supracervical hysterectomy

relates to the development of benign or neoplastic conditions that require future removal of the cervical stump.
Complications of trachelectomy reported in the largest
published series (310 cases) include a 9% incidence of
infection and perioperative bleeding and a 2% incidence
of intraoperative bowel injury. Fewer complications were
seen with vaginal trachelectomy than with abdominal trachelectomy (11).
Although data from uncontrolled series may suggest
a benefit from preserving the cervix, review of recently
published Level I evidence reveals no advantage to the
supracervical abdominal technique with regard to surgical complications, urinary symptoms, or sexual function
in women undergoing hysterectomy for symptomatic
uterine leiomyomata or abnormal uterine bleeding (35).
Despite the potential advantages of shorter hospital stay
and less blood loss afforded by the laparoscopic supracervical approach, there are no prospective data comparing
laparoscopic supracervical hysterectomy with either
LAVH or TAH.
Patients electing supracervical hysterectomy should
be carefully screened preoperatively to exclude cervical or
uterine neoplasm and should be counseled about the
need for long-term follow-up, the possibility of future
trachelectomy, and the lack of data demonstrating clear
benefits over total hysterectomy. The supracervical
approach should not be recommended by the surgeon as
a superior technique for hysterectomy for benign disease.
References
1 Jenkins TR. Laparoscopic supracervical hysterectomy. Am J
2. Parker WH. Total laparoscopic hysterectomy and laparoscopic supracervical hysterectomy. Obstet Gynecol Clin
North Am 2004;31:52337, viii.
3. Learman LA, Summitt RL Jr, Varner RE, McNeeley SG,
Goodman-Gruen D, Richter HE, et al. A randomized comparison of total or supracervical hysterectomy: surgical
complications and clinical outcomes. Total or Supracervical
Hysterectomy (TOSH) Research Group. Obstet Gynecol
2003;102:45362.
4. Thakar R, Ayers S, Clarkson P, Stanton S, Manyonda I.
Outcomes after total versus subtotal abdominal hysterectomy. N Engl J Med 2002;347:131825.
5. Gimbel H, Zobbe V, Andersen BM, Filtenborg T, Gluud C,
Tabor A. Randomised controlled trial of total compared
with subtotal hysterectomy with one-year follow up results.
BJOG 2003;110:108898.
6. Kuppermann M, Summitt RL Jr, Varner RE, McNeeley SG,
Goodman-Gruen D, Learman LA, et al. Sexual functioning
after total compared with supracervical hysterectomy: a
randomized trial. Total or Supracervical Hysterectomy
Research Group. Obstet Gynecol 2005;105:130918.
7. El-Mowafi D, Madkour W, Lall C, Wenger JM. Laparoscopic
supracervical hysterectomy versus laparoscopic-assisted
vaginal hysterectomy. J Am Assoc Gynecol Laparosc 2004;
11:17580.
362
8. Hoffman CP, Kennedy J, Borschel L, Burchette R, Kidd A.

Laparoscopic hysterectomy: the Kaiser Permanente San
Diego experience. J Minim Invasive Gynecol 2005;12:1624.
9. Okaro EO, Jones KD, Sutton C. Long term outcome following laparoscopic supracervical hysterectomy. BJOG 2001;
108:101720.
10. Ghomi A, Hantes J, Lotze EC. Incidence of cyclical bleeding
after laparoscopic supracervical hysterectomy. J Minim
Invasive Gynecol 2005;12:2015.
11. Hilger WS, Pizarro AR, Magrina JF. Removal of the retained
cervical stump. Am J Obstet Gynecol 2005;193:211721.
Supracervical hysterectomy. ACOG Committee Opinion No. 388.
Gynecol 2007;110:12157.
ISSN 1074-861X
COMMITTEE OPINIONS
363

Intraperitoneal Chemotherapy
for Ovarian Cancer
Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Postoperative intravenous (IV) chemotherapy for advanced stage ovarian cancer has been the standard treatment. Recent studies have found significant survival advantages with the use of adjuvant intraperitoneal (IP) chemotherapy. Combination
IV/IP chemotherapy may be an option for well counseled, carefully selected patients with
optimally debulked stage III ovarian cancer. However, IV/IP treatment also has increased
rates of pain, fatigue, and hematologic, gastrointestinal, metabolic, and neurologic toxicities. Given the balance of efficacy, quality of life, and toxicity, the decision to use IP
chemotherapy must be individualized.
Epithelial ovarian cancer is the second most

common gynecologic malignancy, but is the
leading cause of death from gynecologic cancer in the United States. In 2007, an estimated 22,430 new cases of ovarian cancer and
15,280 deaths from ovarian cancer will occur
in the United States (1). Most patients with
ovarian cancer present with either stage III or
stage IV disease.
Patients with early stage disease need to
have comprehensive surgical staging to
assess risks and to direct adjuvant chemotherapy. In addition, for advanced ovarian
cancer, primary surgical cytoreduction plays
an important role. The goal of cytoreductive
surgery is to achieve optimal tumor reduction, ideally with individual aggregates of
residual disease less than 1 cm. Postoperative
intravenous (IV) chemotherapy in advanced
stage ovarian cancer has been the standard
treatment. Recent trials have suggested that
patients with optimally debulked stage III
ovarian cancer may be candidates to receive
part of their chemotherapy intraperitoneally.
Patients with newly diagnosed ovarian cancer may solicit input from their generalist
obstetriciangynecologist regarding treatment options. The purpose of this
Committee Opinion is to provide the generalist obstetriciangynecologist with information regarding the use of intraperitoneal
(IP) chemotherapy in the treatment of ovarian cancer and a summary of recent trial
results.
Intraperitoneal chemotherapy as a therapeutic strategy for patients with ovarian

cancer was based on pharmacologic modeling studies performed in the late 1970s (2).
The rationale was based on the findings of
high intraperitoneal concentration of drugs
and longer half-life of the drug in the peritoneal cavity, which resulted in a prolonged
exposure of the chemotherapy agents. One of
the concerns of the use of IP chemotherapy
has been uniform distribution of the drug,
which may not occur because of adhesions
that result from surgery.
To study these concerns, randomized
clinical trials of IV chemotherapy versus IP
chemotherapy began approximately 20 years
ago. The results of Gynecologic Oncology
Group (GOG) Protocol 172 were published
in early 2006 (3). This trial compared IV
chemotherapy with an experimental regimen
containing both IV and IP chemotherapy in
women with optimally debulked stage III
ovarian cancer. The treatment regimen was
administered every 3 weeks for six cycles (see
box). The results of this trial are summarized
in Table 1.
The survival advantage of approximately
16 months in GOG Protocol 172 was considered to be a significant advance. The results
of this trial and six other randomized trials
prompted the National Cancer Institute
(NCI) to issue a Clinical Announcement pertaining to IP chemotherapy for epithelial
ovarian cancer (4). Seven randomized trials
364
Gynecologic Oncology Group

Protocol 172 Treatment Schedules
Standard Therapy
Experimental Arm
IV administration of
paclitaxel, 135 mg/m2
over 24 h
over 24 h
plus
plus
cisplatin, 75 mg mg/m2
every 3 wk 6
IP administration of
cisplatin, 100 mg/m2
plus
IP administration of
on d 8 every 3 wk 6
Table 1. Gynecologic Oncology Group Protocol 172 Results

Therapy
Standard
Experimental
P Value
Progression-free survival
18.3 mos
23.8 mo
.05
Survival
49.7 mos
65.8 mo
.03
found that women who received adjuvant IP chemotherapy had greater overall survival rates than women who
did not receive such treatment.
However, in GOG Protocol 172, the complication
rate of the experimental IV/IP regimen was significantly
greater than the complication rate of IV therapy alone.
The IV/IP chemotherapy group had more severe toxicities, which included pain and fatigue and hematologic,
gastrointestinal, metabolic, and neurologic toxicities.
Quality of life was lower in the IV/IP chemotherapy
group during the first year after initial treatment. In addition, only 42% of the patients randomized to IV/IP
chemotherapy completed the recommended six cycles.
The most common reason for discontinuation of IP therapy was catheter-related problems (34%) (5). Nine percent of patients refused additional IP treatment.
There has not been widespread acceptance of IV/IP
therapy because of toxicities, catheter problems, and a
complicated treatment regimen. Acceptance of the IV/IP
regimen is further complicated because the IV-only regimen used in GOG Protocol 172 was not the current preferred treatment of IV administration of paclitaxel, 175
mg/m2 over 3 hours, and IV administration of carboplatin (area under the curve, 7.5). Intravenous administration of paclitaxel, 175 mg/m2 over 3 hours, and IV
administration of carboplatin (area under the curve, 7.5)
was one of the treatments compared with 24-hour IV
administration of paclitaxel and cisplatin in GOG
Protocol 158. The paclitaxel (given over 3 hours) and car-
boplatin treatment arm of GOG Protocol 158 demonstrated improved survival compared with 24-hour IV
administration of paclitaxel and cisplatin, which was the
IV-only regimen used in GOG Protocol 172 (6). Women
in GOG Protocol 172 and GOG Protocol 158 had optimally debulked stage III ovarian cancer. Robust
exploratory cross-trial comparisons of IV administration
of carboplatin and IV administration of paclitaxel compared with IV/IP regimens suggest similar efficacy (7). A
recent international consensus conference recommended
IV administration of carboplatin and paclitaxel as the
standard regimen against which new treatments should
be compared (8).
Patients with optimally debulked stage III epithelial
ovarian cancer who would be potential candidates for IP
chemotherapy should be well counseled regarding the
risks and benefits of IV plus IP chemotherapy versus IV
chemotherapy alone. Clinically, many patients are being
treated with IP chemotherapy, but probably are not using
the GOG Protocol 172 dosing regimen. Consequently,
women may be treated with IV/IP chemotherapy regimens that have no scientific evidence of better outcomes.
The NCI Clinical Announcement summary stated that
despite the positive findings of the trials, the ideal combination of drugs for IV/IP therapy had not been identified.
The NCI Clinical Announcement suggested consideration
of IP cisplatin therapy, 100 mg/m2, and IV-only taxane
administration or by IV plus IP administration. The
Gynecology Oncology Group is currently evaluating other
IV/IP chemotherapy regimens to identify a less toxic,
more tolerable, and less complicated treatment regimen.
In summary, combination IV/IP chemotherapy may
be an option for well counseled, carefully selected patients
with optimally debulked stage III ovarian cancer when
provided by a physician with the requisite training
and experience in administering this treatment. However, given the balance of efficacy, quality of life, and
toxicity, the decision to use IP chemotherapy must be
individualized.
References
Atlanta (GA): ACS; 2007. Available at: http://www.cancer.
org/downloads/STT/CAFF2007PWSecured.pdf. Retrieved
August 22, 2007.
2. Dedrick RL, Myers CE, Bungay PM, DeVita VT Jr.
Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep
1978;62:111.
3. Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R,
Lele S, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. Gynecologic Oncology Group. N Engl J Med
2006;354:3443.
4. National Cancer Institute. Clinical announcement on
intraperitoneal chemotherapy in ovarian cancer. Cancer
Therapy Evaluation Program. Bethesda (MD): NCI; 2006.
Available at: http://ctep.cancer.gov/highlights/clin_annc_
010506.pdf. Retrieved September 28, 2007.
COMMITTEE OPINIONS
5. Walker JL, Armstrong DK, Huang HQ, Fowler J, Webster K,

Burger RA, et al. Intraperitoneal catheter outcomes in a
phase III trial of intravenous versus intraperitoneal
chemotherapy in optimal stage III ovarian and primary
peritoneal cancer: a Gynecologic Oncology Group Study.
6. Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson
D, Burger RA, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with
optimally resected stage III ovarian cancer: a Gynecologic
Oncology Group study. Gynecologic Oncology Group. J
Clin Oncol 2003;21:3194200.
7. Ozols RF, Bookman MA, du Bois A, Pfisterer J, Reuss A,
Young RC. Intraperitoneal cisplatin therapy in ovarian cancer: comparison with standard intravenous carboplatin and
paclitaxel. Gynecol Oncol 2006;103:16.
8. du Bois A, Quinn M, Thigpen T, Vermorken J, AvallLundqvist E, Bookman M, et al. 2004 consensus statements
on the management of ovarian cancer: final document of the
3rd International Gynecologic Cancer Intergroup Ovarian
365
Cancer Consensus Conference (GCIG OCCC 2004).

Gynecologic Cancer Intergroup; AGO-OVAR; ANZGOG;
EORTC; GEICO; GINECO; GOG; JGOG; MRC/NCRI;
NCIC-CTG; NCI-US; NSGO; RTOG; SGCTG; IGCS;
Organizational team of the two prior International OCCC.
Ann Oncol 2005;16(suppl 8):viii7viii12.

Intraperitoneal chemotherapy for ovarian cancer. ACOG Committee
ISSN 1074-861X
366

Number 405 May 2008
Ovarian Tissue and Oocyte Cryopreservation

Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: As more young women are cured of cancer with chemotherapy and
radiotherapy, which can be gonadotoxic, interest is growing in treatments that may preserve fertility. In vitro fertilization with cryopreservation of embryos is currently the best
option for fertility preservation when treatment for cancer is anticipated. Ovarian tissue
cryopreservation and oocyte cryopreservation are two options with the potential to preserve fertility. Although these methods are developing rapidly, their use as a means to
have a child after cancer treatment must be considered investigational and offered only
with appropriate informed consent in a research setting and under the auspices of an
institutional review board.
The number of oocytes in the ovaries

declines naturally and progressively through
the process of atresia. Chemotherapy and
radiotherapy have the potential to accelerate
this process, placing women who require
these treatments at risk of premature ovarian
failure.
A number of techniques have been used
to protect the ovaries and preserve fertility in
women at risk of losing ovarian function prematurely as a consequence of cancer therapy.
For women who would otherwise lose function from radiation treatment, ovarian transposition (moving the ovary as far as possible
outside the field of radiation while maintaining the blood supply) may be useful (1).
Treatment with oral contraceptives and
gonadotropin-releasing hormone agonists
to preserve ovarian function has been advocated but does not have proven efficacy.
In vitro fertilization (IVF) with cryopreservation of embryos is a proven method
and is the most successful approach. In all
reported procedures (not just those for
women with cancer), this technique affords
a live-birth rate of 15.931.7% with the
transfer of two or three cryopreserved
embryos (2) and may offer the opportunity
to carry out several attempts at embryo
transfer from a single oocyte retrieval.
Oocyte retrieval and IVF require several
weeks of preparation and the availability of
sperm. Elevated estrogen levels have the
potential to be detrimental to women with
some cancers, and consultation with a repro-
ductive medicine specialist and the oncologist is recommended.

Two investigational methods, oocyte
cryopreservation for future IVF and ovarian
tissue cryopreservation, have garnered increased interest for preserving fertility in the
patient with cancer (3). Clinical pregnancy
rates with oocyte cryopreservation and subsequent IVF are significantly lower than rates
with embryo cryopreservation. In oocytes,
the rate of survival and subsequent fertilization depends on the maturational stage and
method of cryopreservation. The mature
metaphase-II oocyte is extremely fragile
because of its large size, water content, and
chromosomal arrangement along the meiotic
spindle. This spindle apparatus is damaged
easily by intracellular ice formation during
the freezing and thawing process. Oocytes
frozen at an early germinal vesicle stage have
a lower rate of cryopreservation-induced
abnormalities of the spindle apparatus, but
they must undergo the relatively new process
of in vitro maturation. Vitrification, a cryopreservation method that limits the formation of ice crystals, has been shown to
improve survival and fertilization rates after
thawing. To date, the number of live births
reported from oocyte cryopreservation is
limited, with one report calculating a livebirth rate per thawed oocyte of only 4% (4).
Current data are insufficient to allow any
valid estimate of the likelihood of success for
an individual woman. Similar to the cryopreservation of embryos, in order to cryopre-
COMMITTEE OPINIONS
serve oocytes, the ovaries must be stimulated, and this

process will lead to increased estrogen levels and may
delay the initiation of treatment.
Orthotopic transplantation (autograft placed near
the infundibulopelvic ligament or residual ovarian tissue)
and heterotopic transplantation (autograft placed above
the fascia in the forearm) of previously cryopreserved
ovarian tissue are other investigational options that have
been shown to restore ovarian function at least temporarily. Human live births have been reported after orthotopic
transplantation of cryopreserved ovarian tissue (5) and
the transplantation of ovarian cortical tissue between
monozygotic twins (6). Potential risks of the transplantation of cryopreserved tissue in the patient with cancer
include reseeding of tumor cells in cancer types such as
leukemia, malignant transformation of the transplanted
tissue, and recurrence of the malignancy during pregnancy (7). Further research defining patient suitability,
methods of tissue collection, cryopreservation protocols,
and methods of processing human ovarian tissue after
thawing will determine whether fertility can be restored
reliably with ovarian tissue transplantation.
In conclusion, ovarian tissue and oocyte cryopreservation hold promise for fertility preservation. However,
cryopreservation of ovarian tissue and oocytes is investigational. At this time, these procedures may be offered
only with appropriate informed consent in a research setting and under the auspices of an institutional review
board. Further research is necessary to determine patient
selection, methods of tissue collection, and optimal cryopreservation protocols.
References
1. Morice P, Castaigne D, Haie-Meder C, Pautier P, El Hassan
J, Duvillard P, et al. Laparoscopic ovarian transposition for
pelvic malignancies: indications and functional outcomes.
367
2. Centers for Disease Control and Prevention. Assisted reproductive technology (ART) report: 2005 preliminary national summary. Atlanta (GA): CDC; 2007. Available at:
http://apps.nccd.cdc.gov/ART2005/nation05.asp. Retrieved
November 20, 2007.
3. Borini A, Bonu MA, Coticchio G, Bianchi V, Cattoli M,
Flamigni C. Pregnancies and births after oocyte cryopreservation. Fertil Steril 2004;82:6015.
4. Porcu E, Venturoli S. Progress with oocyte cryopreservation.
Curr Opin Obstet Gynecol 2006;18:2739.
5. Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C,
Squifflet J, et al. Livebirth after orthotopic transplantation
of cryopreserved ovarian tissue [published erratum appears
in Lancet 2004;364:2020]. Lancet 2004;364:140510.
6. Silber SJ, Lenahan KM, Levine DJ, Pineda JA, Gorman KS,
Friez MJ, et al. Ovarian transplantation between monozygotic twins discordant for premature ovarian failure. N Engl
J Med 2005;353:5863.
7. Ovarian tissue and oocyte cryopreservation. Practice
Medicine; Practice Committee of the Society for Assisted
Reproductive Technology. Fertil Steril 2006;86(suppl):
S1427.

Ovarian tissue and oocyte cryopreservation. ACOG Committee
368

Number 407 May 2008
Low Bone Mass (Osteopenia)

and Fracture Risk
Committee on
Gynecologic
Practice
followed.
ABSTRACT: Diagnosis of low bone mass or osteopenia, defined by measures of

bone mineral density (BMD), has generated much confusion. Because BMD alone is not
sufficient to describe risk of fracture, clinicians face challenges in interpreting BMD and
clinical risk factors, counseling patients on absolute risk of fracture, and determining the
need for pharmacologic intervention. For fracture risk assessment, the most valuable risk
factors appear to be BMD, age, prior fracture history, and risk of falling. Until better models of fracture risk exist, postmenopausal women in their 50s with T scores in the
osteopenia range and without risk factors may well benefit from counseling on calcium
and vitamin D intake and risk factor reduction to delay the initiation of pharmacologic
intervention.
Diagnosis of low bone mass or osteopenia

has generated much confusion related to
counseling, follow-up, and the need for
pharmacologic intervention. An estimated
26 million American women have osteopenia, defined as bone mineral density (BMD)
T scores between 1 and 2.5 (Table 1).
Although the risk of fracture is higher in
women with osteoporosis, the total number
of fractures is greater in postmenopausal
women with osteopenia because of the
Table 1. World Health Organization Definition
of Osteoporosis Based on Bone Mineral Density
of Total Hip*
Bone Classification

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
T Score
Normal
Greater than or equal to 1
Osteopenia
(low bone mass)
1 to 2.5
Osteoporosis
Less than or equal to 2.5
*These definitions were used to describe a Caucasian cohort of

women to define risk. This classification was not intended to be
applicable to non-Caucasians and men or to peripheral bone density screening devices. The use of the World Health Organization
guidelines and definitions nonetheless has become generalized.
Standard deviations from the average value of the mean peak

bone mineral density of a normal, young adult population
Data from Assessment of fracture risk and its application to
screening for postmenopausal osteoporosis. Report of a WHO
Study Group. World Health Organ Tech Rep Ser 1994;843:1129.
greater numbers of these women (1). Given

that women with T scores between 1 and
2.5 account for the majority of fractures,
women with low bone mass represent the
greatest opportunity to reduce fractures.
After menopause, bone density values
decline and the incidence of most fractures
increases. Large prospective studies have
demonstrated that bone density is an important predictor of fracture risk in untreated
populations (2, 3). However, treatment currently is not recommended uniformly for
women with osteopenia. Mechanisms to
stratify fracture risk within this group are
needed to determine appropriate intervention. Reliance on BMD measurements alone
to determine fracture risk has been described
as analogous to the relationship between
blood pressure and cardiovascular disease
risk. For example, although cardiovascular
disease risk is increased with hypertension,
many patients with hypertension will never
experience a heart attack or stroke, and some
with normal blood pressure will (4). Osteopenia may be considered similar to prehypertension, defining an intermediate risk group
that should be offered preventive therapy.
Clearly, there are risk factors other than
hypertension in the development of cardiovascular disease. Similarly, many factors
other than BMD affect fracture risk.
COMMITTEE OPINIONS
Bone mineral density is only one component of bone

integrity, and it is a reflection of bone quantity but not
quality. Bone quality is determined by trabecular architecture, bone turnover, degree of matrix mineralization,
and other physiologic, molecular, and material processes.
This partly explains the loose correlation between fracture risk reduction (significant) and BMD increases
(often minimal) after pharmacologic intervention. Not
observing an increase in BMD after pharmacologic intervention is not evidence of treatment failure. Loss of bone
mass is a continuum, and cutoffs used to define normal
versus low bone mass are arbitrary.
The diagnostic category of osteopenia is problematic. The range for normally distributed measures usually
is defined as the values within two standard deviations of
the mean (T scores 2 and +2). Approximately 16% of
young healthy adults have T score values lower than 1
and are most commonly smaller women (5). In interpreting T scores in younger women, it is important to realize
that original World Health Organization (WHO) definitions of osteoporosis and osteopenia were based on
T scores in postmenopausal Caucasian women. Although
relative risk of fracture may increase with decreasing
BMD in younger women, absolute risk of fracture may
still remain minimal. Relative risk describes risk in a comparative way between two populations, usually expressed
as a ratio (eg, twice as likely = relative risk of 2), whereas absolute risk describes the probability of a given event
occurring over a specific interval of time and usually is
expressed as a percentage or a ratio (eg, 5% per year).
Differentiating between relative risk and absolute risk is
critical when contemplating pharmacologic intervention
for osteopenia. For example, given the same BMD T score
of 2, the 10-year risk of hip fracture has been estimated
to vary from 3% (at age 50 years) to 9% (at age 75 years)
(6). Put another way, a 50-year-old patient with a T score
of 3 has the same absolute fracture risk as an 80-year-old
patient with a T score of 1. Age is clearly a factor that
must be considered when interpreting BMD. Overestimating fracture risk in younger, osteopenic women is
likely when BMD is used alone because age increases
absolute fracture risk.
Various models that incorporate BMD and other
clinical factors have been suggested to help the clinician
predict both short-term and long-term fracture risks (7).
For fracture risk assessment, the most valuable risk factors appear to be BMD, age, prior fracture, and risk of
falling (5). The World Health Organization and other
organizations are developing tools that incorporate BMD
and clinical risk factors to calculate 5- or 10-year absolute
risks of fracture. The WHO fracture model may well
become the standard because it is reportedly applicable to
both sexes, uses a broad age range, includes those exposed
to glucocorticoids, and provides absolute fracture risks
that have been developed and tested (8, 9). If absolute risk
could be calculated easily in an office setting, clinicians
369
and patients could better understand the cost versus the

benefit of pharmacologic intervention.
Listed as follows are recommendations of the
(ACOG) for BMD testing (10):
Bone mineral density testing should be recommended to all postmenopausal women aged 65 years or
older regardless of risk factors.
Bone mineral density testing may be recommended
for postmenopausal women younger than 65 years
who have one or more risk factors for osteoporosis
(see box). According to these risk factors, all Caucasian postmenopausal women younger than 65 years
would be candidates for BMD testing.
Bone mineral density testing should be performed
on all postmenopausal women with fractures to confirm the diagnosis of osteoporosis and determine
disease severity.
However, because BMD alone is not sufficient to
describe risk of fracture, clinicians face challenges in
interpreting BMD, incorporating clinical risk factors, and
counseling patients on absolute risk of fracture. This is
particularly challenging in the large category of low bone
mass or osteopenia, in which patients with various levels
Risk Factors for Osteoporotic Fracture

in Postmenopausal Women
History of prior fracture
Family history of osteoporosis
Caucasian race
Dementia
Poor nutrition
Smoking
Low weight and body mass index
Estrogen deficiency*
Early menopause (age younger than 45 years) or
bilateral oophorectomy
Prolonged premenopausal amenorrhea (>1 year)
Long-term low calcium intake
Alcoholism
Impaired eyesight despite adequate correction
History of falls
Inadequate physical activity
*A patients current use of hormone therapy does not preclude
estrogen deficiency.
Data from Osteoporosis prevention, diagnosis, and therapy.
NIH Consens Statement 2000;17(1):145. Available at: http://
consensus.nih.gov/2000/2000Osteoporosis111PDF.pdf. Retrieved
November 28, 2007.
370
of risk can be found. Current recommendations advise all

individuals to obtain an adequate intake of dietary calcium and vitamin D and encourage lifestyle practices that
reduce the risk of bone loss and osteoporotic fractures,
including regular weight-bearing and muscle-strengthening exercise, smoking cessation, moderation of alcohol
intake, and fall prevention strategies.
Pharmacotherapy is recommended by ACOG (10)
for the following women:
Postmenopausal women who have experienced a
fragility or low-impact fracture
Postmenopausal women with no risk factors who
have a BMD T score determined by central dual
energy X-ray absorptiometry of less than 2
Postmenopausal women with risk factors for fracture
(see box) who have a BMD T score by central dual
energy X-ray absorptiometry of less than 1.5
For now, the recommendation to treat postmenopausal women with T scores lower than 2 appears to be
reasonable, assuming age is strongly considered. T scores
between 1.5 and 2.0 require interpretation with existing risk factors, understanding that absolute risk may still
be low. Clinicians must be careful because the diagnosis
of osteopenia often is interpreted as indicating a pathologic skeletal condition or significant bone loss, neither of
which is necessarily true. Until better models of absolute
fracture risk exist, postmenopausal women in their 50s
with T scores in the osteopenia range and without risk
factors may well benefit from counseling on calcium and
vitamin D intake and risk factor reduction to delay initiation of pharmacologic intervention.
References
1. Siris ES, Miller PD, Barrett-Connor E, Faulkner KG,
Wehren LE, Abbott TA, et al. Identification and fracture
outcomes of undiagnosed low bone mineral density in
postmenopausal women: results from the National
Osteoporosis Risk Assessment. JAMA 2001;286:281522.
2. Johnell O, Gullberg B, Kanis JA, Allander E, Elffors L,
Dequeker J, et al. Risk factors for hip fracture in European
3.
4.
5.
6.
7.
8.
9.
10.
women: the MEDOS Study. Mediterranean Osteoporosis

Study. J Bone Miner Res 1995;10:180215.
Cummings SR, Black DM, Nevitt MC, Browner W, Cauley
J, Ensrud K, et al. Bone density at various sites for prediction
of hip fractures. The Study of Osteoporotic Fractures
Research Group. Lancet 1993;341:725.
Goldstein SR. Osteopenia: sorting out the confusion.
Menopause Manage 2006;15(1):107.
McClung MR. The relationship between bone mineral density and fracture risk. Curr Osteoporos Rep 2005;3:5763.
Kanis JA, Johnell O, Oden A, Dawson A, De Laet C, Jonsson
B. Ten year probabilities of osteoporotic fractures according
to BMD and diagnostic thresholds. Osteoporos Int 2001;
12:98995.
Ettinger B, Hillier TA, Pressman A, Che M, Hanley DA.
Simple computer model for calculating and reporting
5-year osteoporotic fracture risk in postmenopausal women.
J Womens Health 2005;14:15971.
Ettinger B. Making the most of managed care dollars spent
for postmenopausal osteoporosis. Manag Care Interface
2005;18(12):559.
FRAX WHO fracture risk assessment tool. Sheffield (UK):
World Health Organization Collaborating Centre for
Metabolic Bone Diseases. University of Sheffield; 2008. Available at: http://www.shef.ac.uk/FRAX/index.htm. Retrieved
March 6, 2008.
Osteoporosis. ACOG Practice Bulletin No. 50. American
2004;103:20316.

Low bone mass (osteopenia) and fracture risk. ACOG Committee
COMMITTEE OPINIONS
371

Professional Liability and Gynecology-Only

Practice
Committee on
Gynecologic
Practice
Committee on
Obstetric Practice
ABSTRACT: Fellows of the American College of Obstetricians and Gynecologists

may choose to limit the scope of their practices to gynecology. The College considers
early pregnancy care (often up to 1214 weeks of gestation) to be within the scope of
gynecology and gynecologic practice. Liability insurers who provide coverage for gynecology-only practices should provide coverage for clinical practice activities that involve
the management of early pregnancy and its complications.
Committee on
Professional Liability
Fellows of the American College of Obstetricians and Gynecologists may choose to limit the
scope of their practices to gynecology and, accordingly, may choose not to request professional liability coverage for obstetrics. However, the College considers early pregnancy care (often
up to 1214 weeks of gestation) to be within the scope of gynecology and gynecologic practice. Management of conditions such as ectopic pregnancy as well as spontaneous and elective
abortion, including early midtrimester abortion, may be properly undertaken in such practices. Liability insurers who provide coverage for gynecology-only practices should provide
coverage for clinical practice activities that involve the management of early pregnancy and its
complications.
Copyright June 2008 by the American College of Obstetricians and Gynecologists, 409 12th Street, SW, PO
Box 96920, Washington, DC 20090-6920. All rights reserved. No part of this publication may be reproduced,
stored in a retrieval system, posted on the Internet, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher.
Requests for authorization to make photocopies should be directed to: Copyright Clearance Center, 222
Professional liability and gynecology-only practice. ACOG Committee Opinion No. 408. American College of

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
372

Routine Human Immunodeficiency

Virus Screening
Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: The American College of Obstetricians and Gynecologists recommends routine human immunodeficiency virus (HIV) screening for women aged 1964
years and targeted screening for women with risk factors outside of that age range.
Ideally, opt-out HIV screening should be performed, in which the patient is notified that
HIV testing will be performed as a routine part of gynecologic and obstetric care, unless
the patient declines testing (1). The American College of Obstetricians and Gynecologists
recommends that obstetriciangynecologists annually review patients risk factors for
HIV and assess the need for retesting.
An estimated one quarter of all individuals

infected with the human immunodeficiency
virus (HIV) in the United States are unaware
of their HIV status. In order to identify individuals with undiagnosed HIV infection,
the U.S. Centers for Disease Control and
Prevention (CDC) recommends HIV screening for all patients aged 1364 years in health
care settings (1). Because obstetriciangynecologists provide primary and preventive
care for women, they are ideally suited to
play an important role in promoting HIV
screening for their patients. Although most
obstet-riciangynecologists are familiar with
routine HIV testing of their pregnant
patients, physicians should incorporate routine HIV testing into their gynecologic practices as well.
There are a number of reasons why it
is critical that women, who represent an
increasing proportion of overall HIV and
acquired immunodeficiency syndrome (AIDS)
cases, know their HIV status. Early diagnosis
and treatment of HIV can improve survival
and reduce morbidity (2). In addition,
women who are infected with HIV can take
steps to avoid unintended pregnancy, protect
their sexual partners, and reduce the likelihood of mother-to-child transmission
should pregnancy occur (3). Therefore, the
Gynecologists (ACOG) recommends routine
HIV screening for women aged 1964 years
and targeted screening for women with risk

factors outside of that age range, for example,
sexually active adolescents younger than 19
years.
Ideally, opt-out HIV screening should be
performed, in which the patient is notified
that HIV testing will be performed as a routine part of gynecologic and obstetric care,
unless the patient declines testing (1). In optout screening, neither specific signed consent
nor prevention counseling is required. However, women should be provided with oral or
written information about HIV and the
meaning of positive and negative test results
and given the opportunity to ask questions
and decline testing. If a patient declines HIV
testing, this should be documented in the
medical record and should not affect access to
care (4). Although ACOG recommends optout screening where legally possible, state and
local laws may have specific requirements for
HIV testing that are not consistent with such
an approach. Therefore, obstetriciangynecologists should be aware of and comply with
legal requirements regarding HIV testing in
their jurisdictions. Legal requirements for
HIV testing may be verified by contacting
state or local health departments. The
National HIV/AIDS Clinicians Consultation
Center at the University of California San
Francisco maintains an online compendium
of state HIV testing laws that can be a useful
resource (www. nccc.ucsf.edu).
COMMITTEE OPINIONS
The use of rapid HIV tests may provide test results to

women in a more timely manner and may reduce the
resources necessary to follow-up with patients regarding
their test results. Although a positive rapid test result is
preliminary and must be confirmed with additional testing, a negative rapid test result does not require any
additional testing. Therefore, rapid testing may be a feasible and acceptable approach for an HIV screening program in an obstetricgynecologic practice (5). To code for
rapid testing, the modifier 92 is added to the basic
HIV testing Current Procedural Terminology* (CPT) codes
(8670186703).
Although CDC and ACOG both recommend that
reproductive-aged women be tested at least once in their
lifetime, there is no consensus regarding how often
women should be retested. The American College of
Obstetricians and Gynecologist recommends that
obstetriciangynecologists annually review patients risk
factors for HIV and assess the need for retesting. Repeat
HIV testing should be offered at least annually to women
who:
Are injection drug users
Have sex partners who are injection drug users or are
infected with HIV
Exchange sex for drugs or money
Have received a diagnosis of another sexually transmitted disease in the past year
Have had more than one sex partner since their most
recent HIV test
Obstetriciangynecologists also should encourage
women and their prospective sex partners to be tested
before initiating a new sexual relationship. In addition,
periodic retesting could be considered even in the absence
of risk factors depending on clinical judgment and the
patients wishes because patients may be concerned about
their status but not know about or want to disclose risktaking behavior to their physicians.
Although HIV-negative test results may be conveyed
without direct personal contact, HIV-positive test results
should be communicated confidentially and in person by
a physician, nurse, or other skilled staff member. Women
who are infected with HIV should receive or be referred
for appropriate clinical and supportive care.
Rapid test results usually will be available during the
same clinical visit that the specimen (eg, blood or oral
swab sample) is collected. Obstetriciangynecologists who
use these tests must be prepared to provide counseling to
women who receive positive rapid test results the same
day that the specimen is collected (ie, women with posi*Current Procedural Terminology (CPT) is copyright 2008 by American
Medical Association. All rights reserved. No fee schedules, basic units,
relative values, or related listings are included in CPT . The AMA
assumes no liability for the data contained herein. CPT is a trademark
of the American Medical Association.
373
tive rapid test results should be counseled regarding the

meaning of these preliminarily positive test results and
the need for confirmatory testing) (4). Obstetrician
gynecologists should develop links with individuals who
can provide these counseling services on an emergent
basis or train their own staff to handle the initial
encounter and, thereafter, transition infected individuals
to professionals who can serve as ongoing resources to
them. Women whose confirmatory testing yields positive
results and, therefore, are infected with HIV should
receive or be referred to appropriate clinical and supportive care.
Resources
409 12th Street SW, PO Box 96920
202-638-5577
ACOG HIV resources: www.acog.org/goto/HIV
National HIV/AIDS Clinicians Consultation Center
UCSF Department of Family and Community Medicine at
San Francisco General Hospital
1001 Potrero Ave., Bldg. 20, Ward 22
San Francisco, CA 94110
415-206-8700
National HIV Telephone Consultation Service:
1-800-933-3413 (MF, 8 AM8 PM [EST])
www.nccc.ucsf.edu
American Academy of HIV Medicine, American Medical
Association. Coding guidelines for routine HIV testing in
health care settings. Washington, DC: AAHIVM; Chicago (IL):
AMA; 2008. Available at: http://aahivm.org/images/stories/
pdfs/brochure_reimburse_guide_routinehivtest.pdf. Retrieved
May 6, 2008.
References
health-care settings. Centers for Disease Control and
Prevention (CDC). MMWR Recomm Rep 2006;55(RR14):117; quiz CE14.
2. Palella FJ Jr, Deloria-Knoll M, Chmiel JS, Moorman AC,
Wood KC, Greenberg AE, et al. Survival benefit of initiating
antiretroviral therapy in HIV-infected persons in different
CD4+ cell strata. HIV Outpatient Study Investigators. Ann
Intern Med 2003;138:6206.
3. U.S. Public Health Service Task Force. Recommendations
for use of antiretroviral drugs in pregnant HIV-infected
women for maternal health and interventions to reduce
perinatal HIV transmission in the United States. Rockville
(MD): USPHSTF; 2007. Available at: http://www.aidsinfo.
nih.gov/contentfiles/PerinatalGL.pdf. Retrieved March 7,
2008.
374
5. Jamieson DJ, Cohen MH, Maupin R, Nesheim S, Danner

SP, Lampe MA, et al. Rapid human immunodeficiency
virus-1 testing on labor and delivery in 17 US hospitals: the
MIRIAD experience. Am J Obstet Gynecol 2007;197(suppl
1):S72S82.

Routine human immunodeficiency virus screening. ACOG Committee
ISSN 1074-861X
COMMITTEE OPINIONS
375

Aromatase Inhibitors in Gynecologic

Practice
Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Aromatase inhibitors appear to be effective as an adjuvant treatment

for early-stage and late-stage breast cancer. Their role in chemoprevention of breast cancer in high-risk patients remains to be defined. Side effects of aromatase inhibitors in
postmenopausal women are due to estrogen-lowering action at the target tissues and
include hot flushes, vaginal dryness, arthralgias, and decreased bone mineral density. In
reproductive-aged women, aromatase inhibitors stimulate gonadotropin secretion and
increase ovarian follicular activity. The role of aromatase inhibitors in the treatment of
endometriosis and in ovulation induction is still being investigated.
The pharmacologic manipulation of hormone levels has been very successful in the
treatment of estrogen-dependent disease
processes such as breast cancer, endometriosis, and uterine leiomyomas. As part of this
approach, aromatase inhibitors have been
introduced for the treatment of breast cancer
and, more recently, endometriosis. Aromatase
inhibitors also have been used as ovulation
induction agents.
The aromatase enzyme is a cytochrome
P-450 complex encoded by a single gene, and
it is widely expressed in tissues, such as brain,
breast, placenta, ovary, testes, endometrium,
skin, bone, and fat. Within these tissues, aromatase mediates the conversion of androstenedione to estrone and testosterone to
estradiol in situ. Thus, for tissues that express
this enzyme, conversion of circulating androgens from an adrenal or ovarian source will
significantly increase the in situ estrogen
concentrations and provide these tissues with
a proliferative advantage.
Three aromatase inhibitors are currently
available in the United States. Exemestane is a
steroid-derived aromatase inhibitor that
binds irreversibly to aromatase and permanently inactivates the available enzyme.
Letrozole and anastrozole are reversible
inhibitors of aromatase that compete with
androgens for aromatase binding sites. All
three aromatase inhibitors appear to have
similar clinical efficacy despite these differences in pharmacologic properties.

In postmenopausal women, aromatase
inhibitors were first introduced for the treatment of advanced breast cancer. Although
these compounds did not increase overall
survival, they appeared to be similar or better
than megestrol when objective responses
were the endpoint (1). The early success of
these studies led to clinical trials of aromatase
inhibitors in breast cancer patients with
resectable, estrogen receptor-positive tumors.
The largest of these trials compared anastrozole with tamoxifen, alone or in combination, as adjuvant treatment in women with
early breast cancer following surgical resection. The study results demonstrated a small
but significantly improved 3-year diseasefree survival in postmenopausal women with
invasive, operable breast cancer who received
anastrazole alone compared with tamoxifen
(89.4% versus 87.4%, hazard ratio 0.83 [95%
confidence interval, 0.710.96]) (2). Subsequent trials have been initiated to examine
the effectiveness of aromatase inhibitors in
other breast cancer clinical scenarios, including the use of aromatase inhibitors as a
sequential therapy following tamoxifen, aromatase inhibitors for the treatment of ductal
carcinoma in situ, and aromatase inhibitors
for the prevention of breast cancer in highrisk patients (3). Although data from these
376
trials are not complete, it appears that aromatase

inhibitors will play a significant role in therapy for estrogen receptor-positive breast cancer.
The short-term and long-term adverse effects of aromatase inhibitors in postmenopausal women are related
to lack of estrogen action at aromatase-targeted tissue
sites. These side effects include hot flushes, vaginal dryness, arthralgias, decreased bone mineral density, and an
increased fracture rate (4). The American Society of
Clinical Oncologists recommends that bone mineral
density screening be repeated annually in all patients
receiving aromatase inhibitor adjuvant therapy, and
bisphosphonate therapy should be initiated when T
scores are 2.5 or lower (5). To reduce the risk of osteoporosis in high-risk patients, bisphosphonates may be coadministered to patients during long-term treatment
with aromatase inhibitors.
In contrast to tamoxifen, aromatase inhibitors are
associated with a reduced incidence of thrombosis (6)
and endometrial cancer (7), and a reduction in vaginal
bleeding. Although the results of early studies suggest that
aromatase inhibitors have adverse effects on the cardiovascular system and lipid profiles compared with tamoxifen, these effects are milder or have not been seen when
comparing aromatase inhibitors with placebo. This suggests that aromatase inhibitors lack the protective effects
found with tamoxifen rather than exhibit true toxicity
(8). Increased cardiovascular morbidity or mortality
through poor lipid profiles or other mechanisms has not
been clearly established in patients treated with aromatase inhibitors compared with tamoxifen or placebo
(9). More rigorous study is required in this area because
most of the trials were not designed to address cardiac
disease.
Aromatase inhibitors also have been used as treatment for premenopausal women with early breast cancer
who have chemotherapy-induced amenorrhea. This offlabel use should be prescribed with caution because case
series have described the resumption of ovarian function
following initiation of an aromatase inhibitor regimen
(10, 11). Serial monitoring of estradiol and gonadotropin
levels to identify women who experience a return of ovarian function may be indicated (10).
In premenopausal women, aromatase inhibitors
reduce hypothalamicpituitary estrogen feedback that
leads to increased gonadotropin-releasing hormone
(GnRH) secretion, concomitant elevations in luteinizing hormone and follicle-stimulating hormone, and
increased ovarian follicular development. The gonadotropin-stimulating action of letrozole has been used
off-label in the treatment of patients with ovulatory
dysfunction, such as polycystic ovary syndrome, and for
increasing the number of ovarian follicles recruited for
ovulation in women who are already ovulatory (12, 13).
In a meta-analysis of four published trials, including 662
women with polycystic ovary syndrome, pregnancy rates
were similar between women treated with clomiphene
and women treated with letrozole (relative risk, 1.02; 95%

confidence interval, 0.831.26) (14). Some have raised
concerns about this off-label use because letrozole may
disrupt the normal aromatase activity in tissues during
early fetal development and can be potentially teratogenic
if administered inadvertently during early pregnancy.
However, a large study of 911 newborns conceived using
letrozole for ovulation induction showed no difference in
rates of congenital malformations (15). In addition, the
half-life of letrozole (approximately 3060 hours) is
shorter than that of clomiphene citrate (57 days) and,
thus, should be effectively cleared from the body by the
time of embryo implantation, likely preventing a teratogenic effect when used in ovulation induction (14).
Possible advantages of letrozole over clomiphene citrate
include reduced multiple pregnancies, lower estradiol levels, and an absence of antiestrogenic adverse effects on the
endometrium. However, there is no evidence that letrozole is more effective than clomiphene for ovulation
induction. Letrozole may have a role in the treatment of
clomiphene-resistant patients (16).
The recent demonstration that aromatase is
expressed at higher levels in endometriosis implants than
in normal endometrium has led to pilot studies using
anastrozole co-administered with progestins in patients
with endometriosis resistant to conventional medical and
surgical therapies (17). These small studies suggest that
aromatase inhibitors could reduce endometriosis-associated pelvic pain, whereas the progestin could effectively
suppress gonadotropins and reduce ovarian activity.
Results of subsequent trials have shown similar efficacy
for relief of pelvic pain when aromatase inhibitors were
combined with combination oral contraceptives (18), or
when aromatase inhibitors were given concomitantly
with a GnRH agonist (19). There are no randomized controlled trials comparing aromatase inhibitors with traditional medical treatment for endometriosis. Side effect
profiles of aromatase inhibitor regimens (including a
progestin or oral contraceptive as add-back therapy) are
favorable compared with regimens containing GnRH
agonists or danazol. These aromatase inhibitor regimens
with add-back progestin or oral contraceptives do not
appear to be associated with significant bone loss after 6
months of treatment and may be suitable for long-term
use (20). Randomized controlled trials are needed to
establish the efficacy and side effects of these regimens.
Aromatase inhibitors appear to be effective as an
adjuvant treatment for early-stage and late-stage breast
cancer. Their role in chemoprevention of breast cancer in
high-risk patients remains to be defined. Side effects of
aromatase inhibitors in postmenopausal women are due
to estrogen-lowering action at the target tissues and
include hot flushes, vaginal dryness, arthralgias, and
decreased bone mineral density. Although there are no
long-term data with regard to side effects and complications associated with the use of aromatase inhibitors in
breast cancer patients, the overall safety profile of aro-
COMMITTEE OPINIONS
377
matase inhibitors is good, with less endometrial and

thromboembolic toxicity than tamoxifen. In reproductive-aged women, aromatase inhibitors stimulate
gonadotropin secretion and increase ovarian follicular
activity. The role of aromatase inhibitors in the treatment
of endometriosis and in ovulation induction is still being
investigated.
11. Burstein HJ, Mayer E, Patridge AH, OKane H, Litsas G,

Come SE, et al. Inadvertent use of aromatase inhibitors in
patients with breast cancer with residual ovarian function:
cases and lessons. Clin Breast Cancer 2006;7:15861.
References
13. Bedaiwy MA, Forman R, Mousa NA, Al Inany HG, Casper

RF. Cost-effectiveness of aromatase inhibitor co-treatment
for controlled ovarian stimulation. Hum Reprod 2006;
21:283844.
1. Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP,

Vogel CL, et al. Anastrozole versus megestrol acetate in the
treatment of postmenopausal women with advanced breast
carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials.
Arimidex Study Group. Cancer 1998;83:114252.
2. Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH,
Klijn JG, et al. Anastrozole alone or in combination with
tamoxifen versus tamoxifen alone for adjuvant treatment of
postmenopausal women with early breast cancer: first
results of the ATAC randomised trial. Lancet 2002;359:
21319.
3. Bickenbach KA, Jaskowiak N. Aromatase inhibitors: an
overview for surgeons. J Am Coll Surg 2006;203:37689.
4. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes
JF, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone
or in Combination) trial after completion of 5 years adjuvant treatment for breast cancer. Lancet 2005;365:602.
5. Hillner BE, Ingle JN, Chlebowski RT, Gralow J, Yee GC,
Janjan NA, et al. American Society of Clinical Oncology 2003
update on the role of bisphosphonates and bone health
issues in women with breast cancer. J Clin Oncol 2003;21:
404257.
6. Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J,
Delozier T, et al. A randomized trial of exemestane after two
to three years of tamoxifen therapy in postmenopausal
women with primary breast cancer. N Engl J Med 2004;
350:108192.
7. Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch
C, et al. Switching of postmenopausal women with
endocrine-responsive early breast cancer to anastrozole
after 2 years adjuvant tamoxifen: combined results of
ABCSG trial 8 and ARNO 95 trial. Lancet 2005;366:45562.
8. Conte P, Frassoldati A. Aromatase inhibitors in the adjuvant
treatment of postmenopausal women with early breast cancer: Putting safety issues into perspective. Breast J 2007;
13:2835.
9. Gandhi S, Verma S. Aromatase inhibitors and cardiac toxicity: getting to the heart of the matter. Breast Cancer Res
Treat 2007;106:19.
10. Smith IE, Dowsett M, Yap YS, Walsh G, Lonning PE, Santen
RJ, et al. Adjuvant aromatase inhibitors for early breast cancer after chemotherapy-induced amenorrhoea: caution and
suggested guidelines. J Clin Oncol 2006;24:24447.
12. Fisher SA, Reid RL, Van Vugt DA, Casper RF. A randomized
double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory
function in normal women. Fertil Steril 2002;78:2805.
14. Casper RF. Letrozole versus clomiphene citrate: which is

better for ovulation induction? Fertil Steril 2007 June 21.
DOI: 10.1016/j.fertnstert.2007.03.094.
15. Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari
J, et al. Congenital malformations among 911 newborns
conceived after infertility treatment with letrozole or
clomiphene citrate. Fertil Steril 2006;85:17615.
16. Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or
letrozole for ovulation induction in women with polycystic
ovarian syndrome: a prospective randomized trial. Fertil
Steril 2007 Jun 18. DOI: 10.1016/j.fertnstert.2007.02.062.
17. Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE.
Treatment of endometriosis and chronic pelvic pain with
letrozole and norethindrone acetate: a pilot study. Fertil
Steril 2004;81:2906.
18. Amsterdam LL, Gentry W, Jobanputra S, Wolf M, Rubin
SD, Bulun SE. Anastrazole and oral contraceptives: a novel
treatment for endometriosis. Fertil Steril 2005;84:3004.
19. Soysal S, Soysal ME, Ozer S, Gul N, Gezgin T. The effects of
post-surgical administration of goserelin plus anastrozole
compared to goserelin alone in patients with severe
endometriosis: a prospective randomized trial. Hum
Reprod 2004;19:1607.
20. Attar E, Bulun SE. Aromatase inhibitors: the next generation of therapeutics for endometriosis? Fertil Steril 2006;85:
130718.

Aromatase inhibitors in gynecologic practice. ACOG Committee
ISSN 1074-861X
378

Age-Related Fertility Decline

Committee on
Gynecologic
Practice
followed.
American Society for

Reproductive
Medicine

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Age is a significant factor influencing a womans ability to conceive.

Social trends have led to deferred childbearing, and an increasing number of women are
experiencing age-related infertility and pregnancy loss. Women older than 35 years
should receive expedited evaluation and treatment after 6 months of failed attempts to
conceive, or earlier if clinically indicated.
The number of oocytes in the ovaries

declines naturally and progressively through
the process of atresia. The maximum complement of oocytes is 67 million and exists
at 20 weeks of gestation in the female fetus.
The number of oocytes decreases to approximately 12 million oocytes at birth;
300,000500,000 at puberty; 25,000 at age
37 years; and 1,000 at age 51 years, the average age of menopause in the United States
(13). Fecundity declines gradually but significantly beginning approximately at age 32
years, and decreases more rapidly after age 37
years, reflecting primarily a decrease in egg
quality in association with a gradual increase
in the circulating level of follicle-stimulating
hormone (3). The mechanisms involved are
poorly understood, but appear to include
multiple factors encoded by genes on both
the X chromosome and the autosomes (4).
Age alone has an impact on fertility.
Historical data suggest that among populations that do not use contraception, fertility
rates decrease with increasing age of women
(Fig. 1). Because sexual activity also declines
with age, it is difficult to separate out the
effects of sexual behavior from age. However,
a classic French study was able to separate
behavioral and age effects by studying normal women with azoospermic husbands
undergoing donor insemination. The study
found that pregnancy rates decreased progressively with increasing age of the recipient
female (5). The cumulative pregnancy rate
observed across up to 12 insemination cycles
was 74% for women younger than 31 years
and decreased to 62% for women aged 3135
years and to 54% for women older than 35
years (5). A similar trend has been observed

in analyses of data derived from in vitro fertilization (IVF) embryo transfer programs in
the United States. For the year 2006, the percentage of embryo transfers resulting in live
births decreased progressively from 44.9% in
women younger than 35 years to 37.3% for
women aged 3537 years, 26.6% for women
aged 3840 years, 15.2% for women aged 41
42 years, and 6.7% for women aged 4344
years (6). By contrast, in cycles using eggs
obtained from healthy, young donors, 54% of
transfers resulted in a live birth, regardless of
the age of the recipient (6). As age increases,
the risks of other disorders that may adversely
affect fertility, such as fibroids, tubal disease,
and endometriosis, also increase. Women
with a history of prior ovarian surgery,
chemotherapy, radiation therapy, severe
endometriosis, smoking, pelvic infection, or
a strong family history of early menopause
may be at increased risk for having a premature decline in the size of their follicular pool
and their fertility.
The age-related decline in fertility is
accompanied by a significant increase in the
rates of aneuploidy and spontaneous abortion (7). Autosomal trisomy is the most frequent finding and is related, at least in part,
to changes in the meiotic spindle (8) that
predispose to nondisjunction (9). Even for
morphologically normal embryos selected
for transfer in IVF cycles, the prevalence of
aneuploidy is high in women of advanced
maternal age (10). The fetal loss rate also is
significantly higher, even after fetal heart rate
motion is detected by transvaginal ultrasonography (11). Whereas 9.9% of women
COMMITTEE OPINIONS
379
600
500
Rate per 1,000 wives
400
300
200
100
0
20
25
30
35
Age of wife
40
45
50
Fig.1. Marital fertility rates by 5-year age groups. The ten populations (in descending order at
age 2024 years) are Hutterites, marriages from 192130 (); Geneva bourgeoisie, husbands
born in 160049 (); Canada, marriages 170030 (); Normandy, marriages 176090 ( );
Hutterites, marriages before 1921 ( ); Tunis, marriages of Europeans 184059 ( );
Normandy, marriages 16741742 (); Norway, marriages 187476 ( ); Iran, village marriages, 194050 (); Geneva bourgeoisie, husbands born before 1600 ( ). From Menken J,
Trussel J, Larsen U. Age and infertility. Science 1986;233:138994. Reprinted with permission
from AAAS.
younger than 33 years who conceive during IVF with a

fresh embryo transfer experience a pregnancy loss after
fetal heart activity is observed, the rate of miscarriage
progressively increases to 11.4% for women aged 3334
years, 13.7% for women aged 3537 years, 19.8% for
women aged 3840 years, 29.9% for women aged 4142
years, and 36.6% for women older than age 42 years (11).
Therefore, given the anticipated age-related decline in fertility, the increased incidence of disorders that impair fertility, and the higher risk of pregnancy loss, women older
than 35 years should receive expedited evaluation and
treatment after 6 months of failed attempts to conceive,
or earlier if clinically indicated.
In conclusion, fertility in women is closely related to
reproductive age and becomes significantly compromised
before the onset of perimenopausal menstrual irregularity. Education and enhanced awareness of the impact of
age on fertility is essential in counseling the patient who
desires pregnancy. Women older than 35 years should
receive expedited evaluation and treatment after 6
months of failed attempts to conceive, or earlier if clinically indicated.
References
1. Baker TG. A quantitative and cytological study of germ cells
in human ovaries. Proc R Soc Lond B Biol Sci 1963;158:
41733.
2. Block E. Quantitative morphological investigations of the
follicular system in women; variations at different ages. Acta
Anat (Basel) 1952;14:10823.
3. Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson
JF. Accelerated disappearance of ovarian follicles in midlife: implications for forecasting menopause. Hum Reprod
1992;7:13426.
4. Simpson JL. Genetic programming in ovarian development
and oogenesis. In: Lobo RA, Kelsey J, Marcus R, editors.
Menopause: biology and pathobiology. San Diego (CA):
Academic Press; 2000. p. 7794.
5. Schwartz D, Mayaux MJ. Female fecundity as a function of
age: results of artificial insemination in 2193 nulliparous
women with azoospermic husbands. Federation CECOS.
N Engl J Med 1982;306:4046.
6. Society for Assisted Reproductive Technology. Clinic summary report: all SART member clinics. Birmingham (AL):
SART; 2007. Available at: https://www.sartcorsonline.com/
rptCSR_PublicMultYear.aspx?ClinicPKID=0. Retrieved
March 18, 2008.
380
7. Newcomb WW, Rodriguez M, Johnson JW. Reproduction

in the older gravida. A literature review. J Reprod Med
1991;36:83945.
8. Battaglia DE, Goodwin P, Klein NA, Soules MR. Influence
of maternal age on meiotic spindle assembly in oocytes
from naturally cycling women. Hum Reprod 1996;11:
221722.
9. Pellestor F, Andreo B, Arnal F, Humeau C, Demaille J.
Maternal aging and chromosomal abnormalities: new data
drawn from in vitro unfertilized human oocytes. Hum
Genet 2003;112:195203.
10. Munne S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo
morphology, developmental rates, and maternal age are
correlated with chromosome abnormalities. Fertil Steril
1995;64:38291.
11. Farr SL, Schieve LA, Jamieson DJ. Pregnancy loss among
pregnancies conceived through assisted reproductive technology, United States, 1999-2002. Am J Epidemiol 2007;165:
13808.

Age-related fertility decline. ACOG Committee Opinion No. 413.
Gynecol 2008;112:40911.
ISSN 1074-861X
COMMITTEE OPINIONS
381

Hormone Therapy and Heart Disease

Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: The effect of menopausal hormone therapy on coronary heart disease

has been the subject of much concern. The Heart and Estrogen/Progestin Replacement
Study (HERS) and Womens Health Initiative studies found an increased risk of cardiovascular events with conjugated equine estrogen and medroxyprogesterone acetate use.
However, recent evidence suggests that women in early menopause who are in good
cardiovascular health are at low risk of adverse cardiovascular outcomes and as such
should be considered candidates for the use of conjugated equine estrogen or conjugated equine estrogen and medroxyprogesterone acetate for relief of menopausal vasomotor symptoms. Hormone therapy use should be limited to the treatment of menopausal
symptoms at the lowest effective dosage over the shortest duration possible, and continued use should be reevaluated on a periodic basis.
More than two decades of accumulated evidence suggested that women taking estrogen
plus progesterone hormone therapy (HT)
and estrogen therapy (ET) alone gained protection against coronary heart disease
(CHD). Notably criticized, these largely
observational studies were confounded by
superior cardiovascular health profiles
among participants electing to use HT or ET.
To assess fully the role of HT and ET for
CHD protection among menopausal
women, large-scale randomized, controlled
clinical trials were begun. Recent evidence
suggesting cardioprotective effects of HT
and ET has sparked debate regarding the
possibility of a timing hypothesis (ie,
women who recently experienced menopause may be more likely to benefit from HT
than women who have been menopausal for
a longer period) (1, 2).
Among menopausal women with
known CHD, the Heart and Estrogen/Progestin Replacement Study (HERS) examined
whether conjugated equine estrogen and
medroxyprogesterone acetate altered CHD
risk (3). After 4 years of follow-up, the study
did not demonstrate an overall reduction
in CHD risk. Those receiving conjugated
equine estrogen and medroxyprogesterone
acetate exhibited a 52% increase in CHD and
a 34-fold increase in venous thromboem-
bolic events during the first and second years

of use.
In 2002, the Womens Health Initiative
(WHI), a CHD prevention trial among predominantly healthy menopausal women,
published its initial results after 5.2 years of
follow-up (4). The study was prematurely terminated because of reports of adverse cardiovascular effects and a worsened global index.
Not only did conjugated equine estrogen and
medroxyprogesterone acetate not provide
protection against CHD, but its use also
imparted a 29% increase in CHD-related
events (37 versus 30 per 10,000 woman-years)
that developed soon after randomization.
Notably, most CHD events attributed to conjugated equine estrogen and medroxyprogesterone acetate use were nonfatal myocardial
infarctions, and there were no significant differences in overall CHD deaths (hazard ratio
(HR): 1.18; 95% CI, 0.701.97). Unlike prior
randomized studies (5, 6), WHI associated
conjugated equine estrogen and medroxyprogesterone acetate use with a 41%
increased stroke risk, mostly nonfatal events
(29 versus 21 per 10,000 woman-years) that
became apparent between the first and second year of use. Consistent with the HERS
trial, WHI provided further evidence that
conjugated equine estrogen and medroxyprogesterone acetate increased venous throm-
382
boembolism and pulmonary embolism risks twofold

(venous thromboembolism: 34 versus 16 per 10,000
woman-years; pulmonary embolism: 16 versus 8 per
10,000 woman-years). Time-trend analyses suggested that
the risk of CHD and pulmonary embolism began to
occur immediately following the initiation of HT. Similar
to HERS, the conjugated equine estrogen and medroxyprogesterone acetate arm of the WHI indicated that there
was a 26% increase in invasive breast cancer (38 versus 30
per 10,000 woman-years). Benefits associated with conjugated equine estrogen and medroxyprogesterone acetate
use in the WHI trial included a 37% reduction in colorectal carcinoma rates (10 versus 16 per 10,000 womanyears) and reduced incidence of hip (10 versus 15 per
10,000 woman-years) and vertebral fractures (9 versus 15
per 10,000 woman-years).
Nearly 2 years later, the conjugated equine estrogen
alone study of the WHI was published after a mean of 6.8
years of follow-up, in advance of its designed observation
period because of a lack of improvement in CHD risk
(the primary outcome) and an increased rate of stroke
(7). This conjugated equine estrogen alone trial revealed
several notable differences from the initial WHI study
publications. No differences in CHD incidence were
observed among those receiving conjugated equine estrogen compared with placebo. Although not statistically significant, another notable finding was that invasive breast
cancer occurred 23% less frequently in the conjugated
equine estrogen alone group compared with the control
group (HR=0.77; 95% CI, 0.591.01; P=.06). Moreover,
no differences were seen in colorectal carcinoma rates. In
line with the conjugated equine estrogen and medroxyprogesterone acetate arm of the WHI trial, conjugated
equine estrogen alone increased stroke rates by 39% and
reduced both hip and vertebral fractures. Although deep
vein thrombosis risk was increased (21 versus 15 per
10,000 woman-years), increases in venous thromboembolism and pulmonary embolism risk failed to reach statistical significance. Time-trend analyses demonstrated
an increased stroke risk immediately after randomization,
but no risk differences could be elucidated for pulmonary
embolism or CHD.
Subsequent to the aforementioned studies, the WHI
investigators have published several follow-up studies.
Consistent with previous reports, analysis directed at
extricating the HT effect on CHD risk found superior
lipid, insulin, and glucose profiles with conjugated equine
estrogen and medroxyprogesterone acetate (8). Subsequent data from the conjugated equine estrogen alone
arm suggested an attenuation of venous thromboembolism risk by the exclusion of progestin, yet venous
thromboembolism risks were increased with HT use in
both the conjugated equine estrogen and conjugated
equine estrogen and medroxyprogesterone acetate arms
of the study after a longer mean follow-up period (conjugated equine estrogen: 7.1 years; conjugated equine estrogen and medroxyprogesterone acetate: 5.6 years) (9, 10).
Likewise, HT increased the risk of ischemic stroke in both

the conjugated equine estrogen and conjugated equine
estrogen and medroxyprogesterone acetate arms (11, 12).
Overall, the risks associated with long-term primary preventive therapy appeared to outweigh the beneficial
effects.
The mean participant age of the WHI trial exceeded
60 years and it has been suggested that the results may not
apply to women who recently experienced menopause
and for whom treatment would likely be initiated. In an
attempt to delineate the impact of age on CHD risk with
HT use, WHI data was stratified according to participant
age and duration of menopause (13). This study found
that the effects of either conjugated equine estrogen or
conjugated equine estrogen and medroxyprogesterone
acetate on CHD risk might depend, in part, on age at the
start of treatment. When analyzed according to treatment
type, a trend toward reduced total mortality with conjugated equine estrogen or conjugated equine estrogen and
medroxyprogesterone acetate use was noted among those
women aged 5059 years (see Table 1). When individual
treatment type data were pooled, total mortality decreased
by 30% with conjugated equine estrogen or conjugated
equine estrogen and medroxyprogesterone acetate use
(95% CI, 0.510.96). Whether conjugated equine estrogen
or conjugated equine estrogen and medroxyprogesterone
acetate administration improves the cardiovascular health
of women who recently experienced menopause remains
to be determined. Presently, there is insufficient evidence
to suggest that long-term conjugated equine estrogen or
conjugated equine estrogen and medroxyprogesterone
acetate use improves cardiovascular outcomes (1).
Nevertheless, recent evidence suggests that women in
early menopause who are in good cardiovascular health
are at low risk of adverse cardiovascular outcomes and as
such should be considered candidates for the use of conjugated equine estrogen or conjugated equine estrogen
and medroxyprogesterone acetate for relief of
menopausal vasomotor symptoms (2). Ongoing studies,
including the Kronos Early Estrogen Prevention Study
(KEEPS) are evaluating alterations in surrogate CHD risk
markers, including carotid intimal thickness and the
accrual of coronary calcium deposition induced by HT, in
this case conjugated equine estrogen or transdermal
estradiol patches combined with cyclic oral, micronized
progesterone.
The WHI Coronary-Artery Calcium Study (WHICACS) recently evaluated 1,064 women aged 5059 years
who were previously enrolled in the conjugated equine
estrogen arm of WHI (14). Because coronary atherosclerotic plaques have been associated with future CHD risk,
the investigators used computed tomography heart imaging to determine the degree of coronary-artery calcium
burden. The study results indicated that the overall distribution of coronary-artery calcification scores were lower
among those receiving conjugated equine estrogen compared with those receiving placebo (P=.03). Furthermore,
COMMITTEE OPINIONS
383
Table 1. Cardiovascular and Global Index Events by Age at Baseline
Abbreviations: CEE, conjugated equine estrogens; CHD, coronary heart disease; CI, confidence interval; HR, hazard ratio; MPA, medroxyprogesterone acetate.
*Cox regression models stratified according to prior cardiovascular disease and randomization status in the Dietary Modification Trial.
Test for trend (interaction) using age as continuous (linear) form of categorical coded values. Cox regression models stratified according to active vs placebo and trial,
including terms for age and the interaction between trials and age.
Defined as CHD death, nonfatal myocardial infarction, or definite silent myocardial infarction (Novacode 5.1 or 5.2).
Defined as CHD, stroke, pulmonary embolism, breast cancer, colorectal cancer, endometrial cancer for CEE plus MPA trial only, hip fracture, or death from other causes.
Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since
menopause. JAMA 2007;297:146577. April 4. Copyright 2007 American Medical Association. All rights reserved.
for those who adhered to the study medication regimen

(80% medication adherence for 5 or more years), conjugated equine estrogen use was associated with a significant reduction in the coronary-artery calcification
(OR=0.64; 95% CI, 0.46-0.91; P=.01). This preliminary
evidence, using surrogate outcome markers, needs confirmation of its clinical significance and correlation with
clinical outcomes. Nevertheless, it suggests that conjugated equine estrogen therapy may reduce CHD risk factors
and may provide cardiovascular protection for select
populations of women who experienced menopause
recently.
Conclusion
Menopausal HT should not be used for the primary or
secondary prevention of CHD at the present. Recent
analyses suggest that HT may not increase CHD risk for
select populations of women who have experienced
menopause recently. Hormone therapy use should be
limited to the treatment of menopausal symptoms at the
lowest effective dosage over the shortest duration possible
and continued use should be reevaluated on a periodic
basis. Some women may require extended therapy
because of persistent symptoms.
384
References
1. Barrett-Connor E. Hormones and heart disease in women:
the timing hypothesis. Am J Epidemiol 2007;166:50610.
2. Manson JE, Bassuk SS. Invited commentary: hormone therapy and risk of coronary heart disease why renew the focus
on the early years of menopause? Am J Epidemiol
2007;166:5117.
3. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs
B, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin
Replacement Study (HERS) Research Group. JAMA 1998;
280(7):60513.
4. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ,
Kooperberg C, Stefanick ML, et al. Risks and benefits of
estrogen plus progestin in healthy postmenopausal women:
principal results From the Womens Health Initiative randomized controlled trial. Writing Group for Womens
Health Initiative Investigators. JAMA 2002;288(3):32133.
5. Simon JA, Hsia J, Cauley JA, Richards C, Harris F, Fong J,
et al. Postmenopausal hormone therapy and risk of stroke:
The Heart and Estrogen-progestin Replacement Study
(HERS). Circulation 2001;103:63842.
6. Grady D, Herrington D, Bittner V, Blumenthal R, Davidson
M, Hlatky M, et al. Cardiovascular disease outcomes during
6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). HERS
Research Group. JAMA 2002;288:4957.
7. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford
SA, Black H, et al. Effects of conjugated equine estrogen in
postmenopausal women with hysterectomy: the Womens
Health Initiative randomized controlled trial. Womens
Health Initiative Steering Committee. JAMA 2004;291:
170112.
8. Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR,
Lasser NL, et al. Estrogen plus progestin and the risk of
coronary heart disease. Womens Health Initiative
Investigators. N Engl J Med 2003;349:52334.
9. Curb JD, Prentice RL, Bray PF, Langer RD, Van Horn L,
Barnabei VM, et al. Venous thrombosis and conjugated
equine estrogen in women without a uterus. Arch Intern
Med 2006;166:77280.
10. Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty
BM, Stafford RS, et al. Estrogen plus progestin and risk of
venous thrombosis. Womens Health Initiative Investigators. JAMA 2004;292:157380.
11. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G,
Kooperberg C, Baird A, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: the Womens
Health Initiative: a randomized trial. WHI Investigators.
JAMA 2003 May;289:267384.
12. Hendrix SL, Wassertheil-Smoller S, Johnson KC, Howard
BV, Kooperberg C, Rossouw JE, et al. Effects of conjugated
equine estrogen on stroke in the Womens Health Initiative.
WHI Investigators. Circulation 2006;113:242534.
13. Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D,
Barnabei VM, et al. Postmenopausal hormone therapy and
risk of cardiovascular disease by age and years since
menopause. JAMA 2007;297:146577.
14. Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD,
Hsia J, et al. Estrogen therapy and coronary-artery calcification. WHI and WHI-CACS Investigators. N Engl J Med
2007;356:2591602.

Hormone therapy and heart disease. ACOG Committee Opinion No.
Gynecol 2008;112:118992.
ISSN 1074-861X
COMMITTEE OPINIONS
385

Induced Abortion and Breast Cancer Risk

Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Abstract: The relationship between induced abortion and the subsequent development of breast cancer has been the subject of a substantial amount of epidemiologic
study. Early studies of the relationship between prior induced abortion and breast cancer
risk were methodologically flawed. More rigorous recent studies demonstrate no causal
relationship between induced abortion and a subsequent increase in breast cancer risk.
The relationship between induced abortion

and the subsequent development of breast
cancer has been the subject of a substantial
amount of epidemiologic study. Early case
control studies that reported an association
between induced abortion and subsequent
development of breast cancer had significant
methodological problems, most notably
reliance on retrospective reporting of abortion history. A key methodological consideration in interpreting the evidence for any
relationship between abortion and breast
cancer risk is the sensitive nature of abortion,
which could affect the accuracy in retrospective studies that rely on participant reports of
having had an abortion.
In contrast to retrospective studies,
prospective studies conclude there is no association between induced abortion and breast
cancer. A world-wide meta-analysis of 83,000
women examined the relationship between
induced abortion and breast cancer and
found a significant difference between the
overall estimate of relative risk (RR) from
studies that had recorded information on
induced abortion prospectively (RR, 0.93;
95% confidence interval, 0.890.96) and the
overall estimate of RR from studies that had
recorded such information retrospectively
(RR, 1.11; 95% confidence interval, 1.091.14),
suggesting that reporting bias was probably
present in studies using retrospective reporting of abortion history (1).
In 2003, the National Cancer Institute
convened the Early Reproductive Events and
Breast Cancer Workshop to evaluate the current strength of evidence of epidemiologic,
clinical, and animal studies addressing the
association between reproductive events and

the risk of breast cancer (2). The workshop
participants concluded that induced abortion is not associated with an increase in
breast cancer risk. Studies published since
2003 continue to support this conclusion
(37).
Early studies of the relationship between
prior induced abortion and breast cancer risk
were methodologically flawed. More rigorous
recent studies demonstrate no causal relationship between induced abortion and a
subsequent increase in breast cancer risk.
References
1. Beral V, Bull D, Doll R, Peto R, Reeves G.
Breast cancer and abortion: collaborative
reanalysis of data from 53 epidemiological
studies, including 83,000 women with breast
cancer from 16 countries. Collaborative
Group on Hormonal Factors in Breast Cancer.
Lancet 2004;363:100716.
2. National Cancer Institute. Summary report:
early reproductive events and breast cancer
workshop. Bethesda (MD): NCI; 2003. Available at: http://www.cancer.gov/cancertopics/
ere-workshop-report. Retrieved November 6,
2008.
3. Rosenblatt KA, Gao DL, Ray RM, Rowland
MR, Nelson ZC, Wernli KJ, et al. Induced
abortions and the risk of all cancers combined and site-specific cancers in Shanghai.
Cancer Causes Control 2006;17:127580.
4. Reeves GK, Kan SW, Key T, Tjonneland A,
Olsen A, Overvad K, et al. Breast cancer risk in
relation to abortion: results from the EPIC
study. Int J Cancer 2006;119:17415.
5. Michels KB, Xue F, Colditz GA, Willett WC.
Induced and spontaneous abortion and inci-
386
dence of breast cancer among young women: a prospective

cohort study. Arch Intern Med 2007;167:81420.
6. Lash TL, Fink AK. Null association between pregnancy termination and breast cancer in a registry-based study of
parous women. Int J Cancer 2004;110:4438.
7. Henderson KD, Sullivan-Halley J, Reynolds P, Horn-Ross
PL, Clarke CA, Chang ET, et al. Incomplete pregnancy is not
associated with breast cancer risk: the California Teachers
Study. Contraception 2008;77:3916.

ISSN 1074-861X
Induced abortion and breast cancer risk. ACOG Committee Opinion
Gynecol 2009;113:14178.
COMMITTEE OPINIONS
387

The Role of Transvaginal Ultrasonography in

the Evaluation of Postmenopausal Bleeding
Committee on
Gynecologic
Practice
followed.
ABSTRACT: The clinical approach to postmenopausal bleeding requires prompt and

efficient evaluation to exclude or diagnose carcinoma. Women with postmenopausal
bleeding may be assessed initially with either endometrial biopsy or transvaginal ultrasonography; this initial evaluation does not require performance of both tests.
Transvaginal ultrasonography can be useful in the triage of patients in whom endometrial sampling was performed but tissue was insufficient for diagnosis. When transvaginal ultrasonography is performed for patients with postmenopausal bleeding and an
endometrial thickness of less than or equal to 4 mm is found, endometrial sampling is
not required. Meaningful assessment of the endometrium by ultrasonography is not possible in all patients. In such cases, alternative assessment should be completed. When
bleeding persists despite negative initial evaluations, additional assessment usually is
indicated.
Cancer of the endometrium is the most common type of gynecologic cancer in the
United States. In 2008, an estimated 40,100
cases of cancer of the endometrium will
occur and an estimated 7,470 deaths (1).
Vaginal bleeding is the presenting sign in
more than 90% of postmenopausal patients
with endometrial carcinoma (2). The majority of patients with postmenopausal vaginal
bleeding experience bleeding secondary to
atrophic changes of the vagina or endometrium. However, depending on age and risk factors, 114% will have endometrial cancer
(36). Thus, the clinical approach to postmenopausal bleeding requires prompt and
efficient evaluation to exclude or diagnose
carcinoma.
Transvaginal Ultrasonography

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Transvaginal ultrasonography has been

explored as an alternative technique to indirectly visualize the endometrium. Endometrial thickness is measured as the maximum
anteriorposterior thickness of the endometrial echo on a long-axis transvaginal view of
the uterus. The earliest reports comparing
transvaginal ultrasonography with endometrial sampling consistently found that an
endometrial thickness of less than or equal to

45 mm in patients with postmenopausal
bleeding reliably excluded endometrial cancer
(79). Since that time, a number of confirmatory multicenter trials have been completed
(see Table 1). Because transvaginal ultrasonography in postmenopausal patients with
bleeding has an extremely high negative predictive value, it is a reasonable first approach.
An endometrial thickness of greater than
4 mm is not diagnostic of any particular
pathology and cannot be relied on to exclude
disease.
Biopsy Findings of Tissue

Insufficient for Diagnosis
Endometrial tissue sampling resulting in
findings insufficient for diagnosis is common. In a study of 97 consecutive patients
with postmenopausal bleeding evaluated by
transvaginal ultrasonography and endometrial biopsy, in only 82% of the patients with
an endometrial thickness of less than 5 mm
(n=45) was a Pipelle biopsy able to be performed (10). Of these patients, a sample adequate for diagnosis was obtained in only
27%. There was no correlation with parity or
cavity length. In other studies of patients
388
Table 1. Endometrial Thickness and Cancer Findings in Postmenopausal Women With Bleeding
Reference
Karlsson 1995
Ferrazzi 1996
Gull 2000
Epstein 2001||
Gull 2003
Endometrial
Thickness*
Number of
Women
Number of
Cases of Cancer
Negative
Predictive Value
4 mm
4 mm
5 mm
4 mm
5 mm
4 mm
1,168
930
0
2
4
1
0
0
100%
99.8%
99.6%
99.4%
100%
100%
163
97
394
*Determined by transvaginal ultrasonography
Karlsson B, Granberg S, Wikland M, Ylostalo P, Torvid K, Marsal K, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleedinga Nordic multicenter study. Am J Obstet Gynecol 1995;172:148894.
Ferrazzi E, Torri V, Trio D, Zannoni E, Filiberto S, Dordoni D. Sonographic endometrial thickness: a useful test to predict atrophy in patients with postmenopausal bleeding. An Italian multicenter study. Ultrasound Obstet Gynecol 1996;7:31521.
Gull B, Carlsson S, Karlsson B, Ylostalo P, Milsom I, Granberg S. Transvaginal ultrasonography of the endometrium in women with postmenopausal
bleeding: is it always necessary to perform an endometrial biopsy? Am J Obstet Gynecol 2000;182:50915.
||
Epstein E, Valentin L. Rebleeding and endometrial growth in women with postmenopausal bleeding and endometrial thickness < 5 mm managed by
dilatation and curettage or ultrasound follow-up: a randomized controlled study. Ultrasound Obstet Gynecol 2001;18:499504.
Gull B, Karlsson B, Milsom I, Granberg S. Can ultrasound replace dilation and curettage? A longitudinal evaluation of postmenopausal bleeding and
transvaginal sonographic measurement of the endometrium as predictors of endometrial cancer. Am J Obstet Gynecol 2003;188:4018.
with postmenopausal bleeding, the range of sampling

failure (ie, inadequate sample or inability to perform the
biopsy) with Pipelle biopsy was 054% (11).
Transvaginal ultrasonography can be useful in the
triage of patients in whom endometrial sampling was
performed but tissue was insufficient for diagnosis (12).
No further evaluation is necessary following an insufficient endometrial biopsy if subsequent transvaginal
ultrasonography demonstrates an endometrial thickness
of less than or equal to 4 mm in a woman with postmenopausal bleeding because the incidence of malignancy is rare in these cases (Table 1). However, if
bleeding recurs or persists, additional evaluation usually
is indicated.
Postmenopausal Patients Without

Bleeding
Whereas several studies have evaluated transvaginal ultrasonography in postmenopausal women with bleeding,
there are fewer data on transvaginal ultrasonography
endometrial findings in patients without bleeding. In
1,750 postmenopausal women without bleeding being
screened for a selective estrogen receptor modulator study,
an endometrial thickness of less than or equal to 6 mm
had a negative predictive value of 99.94% for excluding
malignancy (only 1 case of cancer in 1,750 women) and a
99.77% negative predictive value for complex hyperplasia
(only 4 cases in 1,750 women) (13). Among 42 patients
with endometrial thickness of greater than 6 mm, there
was 1 case of adenocarcinoma and no cases of hyperplasia
(positive predictive value = 2.4%).
In another study, 82 asymptomatic postmenopausal

women had an incidental ultrasonographic finding suspected to be an intrauterine polyp (14). All underwent operative
hysteroscopy. Of these patients, a benign polyp was found in
68, submucosal myoma in 7, atrophic endometrium in 6,
and proliferative endometrium in 1. One polyp contained
simple hyperplasia. There were no cases of endometrial carcinoma or complex hyperplasia. The total complication rate
was 3.6% (two perforations, one difficult intubation).
The significance of an endometrial measurement
greater than 4 mm incidentally discovered in a postmenopausal patient without bleeding has not been established. This finding need not routinely trigger evaluation,
although an individualized assessment based on patient
characteristics and risk factors is appropriate. Transvaginal ultrasonography is not an appropriate screening tool
for cancer in postmenopausal women without bleeding.
Limitations
It is not possible to complete a meaningful transvaginal
ultrasound examination with a reliable measurement of
endometrial thickness in all patients (15). An axial uterus,
marked obesity, coexisting myomas, or previous uterine
surgery all can contribute to difficulty in obtaining reliable transvaginal ultrasound assessment of endometrial
thickness and texture. Failure to adequately identify a
thin, distinct endometrial thickness in a postmenopausal
patient with bleeding should trigger some alternative
method of evaluation. In addition, when endometrial
fluid is present, it should not be included in measuring
endometrial thickness.
COMMITTEE OPINIONS
Recommendations
Any vaginal bleeding in a postmenopausal woman
requires assessment to exclude malignancy.
Women with postmenopausal uterine bleeding may
be assessed initially with either endometrial biopsy
or transvaginal ultrasonography; this initial evaluation does not require performance of both tests.
When endometrial biopsy is performed and tissue is
reported as insufficient for diagnosis, some further
investigation is necessary and transvaginal ultrasonography may be performed.
When transvaginal ultrasonography is performed for
patients with postmenopausal bleeding and an
endometrial thickness of less than or equal to 4 mm
is found, endometrial sampling is not required.
Endometrial thickness of greater than 4 mm in a
patient with postmenopausal bleeding should trigger
alternative evaluation (such as sonohysterography,
office hysteroscopy, or endometrial biopsy), as
should an inability to adequately visualize thickness.
Meaningful assessment of the endometrium by
ultrasonography is not possible in all patients. In such
cases, alternative assessment should be completed.
When bleeding persists despite negative initial evaluations, additional assessment usually is indicated.
The significance of an endometrial thickness of
greater than 4 mm in an asymptomatic, postmenopausal patient has not been established, and this
finding need not routinely trigger evaluation.
References
Atlanta (GA): ACS; 2008. Available at: http://www.cancer.
org/downloads/STT/2008CAFFfinalsecured.pdf. Retrieved
June 20, 2008.
2. Goldstein RB, Bree RL, Benson CB, Benacerraf BR, Bloss JD,
Carlos R, et al. Evaluation of the woman with postmenopausal bleeding: Society of Radiologists in UltrasoundSponsored Consensus Conference statement. J Ultrasound
Med 2001;20:102536.
3. Smith-Bindman R, Kerlikowske K, Feldstein VA, Subak L,
Scheidler J, Segal M, et al. Endovaginal ultrasound to
exclude endometrial cancer and other endometrial abnormalities. JAMA 1998;280:15107.
4. Tabor A, Watt HC, Wald NJ. Endometrial thickness as a test
for endometrial cancer in women with postmenopausal
vaginal bleeding. Obstet Gynecol 2002;99:66370.
5. Gupta JK, Chien PF, Voit D, Clark TJ, Khan KS.
Ultrasonographic endometrial thickness for diagnosing
endometrial pathology in women with postmenopausal
bleeding: a meta-analysis. Acta Obstet Gynecol Scand 2002;
81:799816.
389
6. Smith-Bindman R, Weiss E, Feldstein V. How thick is too

thick? When endometrial thickness should prompt biopsy
in postmenopausal women without vaginal bleeding.
Ultrasound Obstet Gynecol 2004;24:55865.
7. Goldstein SR, Nachtigall M, Snyder JR, Nachtigall L.
Endometrial assessment by vaginal ultrasonography before
endometrial sampling in patients with postmenopausal
bleeding. Am J Obstet Gynecol 1990;163:11923.
8. Varner RE, Sparks JM, Cameron CD, Roberts LL, Soong SJ.
Transvaginal sonography of the endometrium in postmenopausal women. Obstet Gynecol 1991;78:1959.
9. Granberg S, Wikland M, Karlsson B, Norstrom A, Friberg
LG. Endometrial thickness as measured by endovaginal
ultrasonography for identifying endometrial abnormality.
10. Elsandabesee D, Greenwood P. The performance of Pipelle
endometrial sampling in a dedicated postmenopausal
bleeding clinic. J Obstet Gynaecol 2005;25:324.
11. Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. The
accuracy of endometrial sampling in the diagnosis of
patients with endometrial carcinoma and hyperplasia: a
meta-analysis. Cancer 2000;89:176572.
12. Bakour SH, Khan KS, Gupta JK. Controlled analysis of factors associated with insufficient sample on outpatient
endometrial biopsy. BJOG 2000;107:13124.
13. Fleischer AC, Wheeler JE, Lindsay I, Hendrix SL, Grabill S,
Kravitz B, et al. An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms. Am J Obstet
Gynecol 2001;184:705.
14. Lev-Sagie A, Hamani Y, Imbar T, Hurwitz A, Lavy Y. The significance of intrauterine lesions detected by ultrasound in
asymptomatic postmenopausal patients. BJOG 2005;112:
37981.
15. Sit AS, Modugno F, Hill LM, Martin J, Weissfeld JL.
Transvaginal ultrasound measurement of endometrial
thickness as a biomarker for estrogen exposure. Cancer
Epidemiol Biomarkers Prev 2004;13:145965.

ISSN 1074-861X
The role of transvaginal ultrasonography in the evaluation of postmenopausal bleeding. ACOG Committee Opinion No. 440. American
114:40911.
390

Choosing the Route of Hysterectomy for

Benign Disease
Committee on
Gynecologic
Practice
followed.
Abstract: Hysterectomies are performed vaginally, abdominally, or with laparoscopic

or robotic assistance. When choosing the route and method of hysterectomy, the physician should take into consideration how the procedure may be performed most safely
and cost-effectively to fulfill the medical needs of the patient. Evidence demonstrates
that, in general, vaginal hysterectomy is associated with better outcomes and fewer
complications than laparoscopic or abdominal hysterectomy. When it is not feasible to
perform a vaginal hysterectomy, the surgeon must choose between laparoscopic hysterectomy, robot-assisted hysterectomy, or abdominal hysterectomy. Experience with
robot-assisted hysterectomy is limited at this time; more data are necessary to determine
its role in the performance of hysterectomy. The decision to electively perform a salpingoophorectomy should not be influenced by the chosen route of hysterectomy and is not
a contraindication to performing a vaginal hysterectomy.
Hysterectomy is one of the most frequently

performed surgical procedures in the United
States. During 20002004, approximately
3.1 million hysterectomies were performed
(approximately 600,000 per year). The most
common indications for hysterectomy are
symptomatic uterine leiomyomas (40.7%),
endometriosis (17.7%), and prolapse (14.5%)
(1).
Hysterectomies are performed vaginally,
abdominally, or with laparoscopic or robotic
assistance. When choosing the route and
method of hysterectomy, the physician should
take into consideration how the procedure
may be performed most safely and cost-effectively to fulfill the medical needs of the
patient. Most literature supports the opinion
that, when feasible, vaginal hysterectomy is the
safest and most cost-effective route by which
to remove the uterus (2). However, analysis of
U.S. surgical data shows that abdominal
hysterectomy is performed in 66% of cases,
vaginal hysterectomy in 22% of cases, and
laparoscopic hysterectomy in 12% of cases (3).
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Factors That Influence the

Route of Hysterectomy
Factors that may influence the route of hysterectomy for benign causes include the size
and shape of the vagina and uterus; accessibility to the uterus; extent of extrauterine disease; the need for concurrent procedures;
surgeon training and experience; available
hospital technology, devices, and support;
emergency or scheduled cases; and preference of the informed patient.
A narrow pubic arch (less than 90
degrees), a narrow vagina, an undescended
immobile uterus, nulliparity, prior cesarean
delivery, and enlarged uterus have been proposed by some authors as contraindications
for vaginal hysterectomy. However, many
nulliparous women and women who have
not given birth vaginally have adequate vaginal caliber to allow successful completion of
the vaginal hysterectomy (4). If the vagina
will allow access to divide the uterosacral and
cardinal ligaments, uterine mobility usually is
improved enough to allow vaginal hysterectomy, even in cases where there is minimal
uterine descent (5). When the uterus is
enlarged, vaginal hysterectomy often can be
accomplished safely by using uterine size
reduction techniques such as wedge morcellation, uterine bisection, and intramyometrial
coring.
Guidelines incorporating uterine size,
mobility, accessibility, and pathology con-
COMMITTEE OPINIONS
fined to the uterus (no adnexal pathology or known or

suspected adhesions) have been proposed as selection criteria for vaginal hysterectomy (6). In a randomized trial,
when residents followed specific guidelines for selection
and performance of hysterectomy, the percentage of vaginal hysterectomies for benign conditions was more than
90%. Uterine morcellation and other uterine size reduction techniques were only necessary in 11% of cases (7).
Extrauterine disease such as adnexal pathology,
severe endometriosis, or adhesions may preclude vaginal
hysterectomy. However, in these cases, it may be prudent
to visualize the pelvis with a laparoscope before deciding
on the route of hysterectomy.
The decision to electively perform a salpingoophorectomy should not be influenced by the chosen
route of hysterectomy and is not a contraindication to
performing a vaginal hysterectomy. The success of removing the ovaries vaginally varies greatly and is reported to
range from 6597.5% (810). In a randomized trial that
compared vaginal hysterectomy with bilateral salpingoophorectomy to laparoscopically assisted vaginal hysterectomy with bilateral salpingoophorectomy, there were
more complications and increased operating time with
the laparoscopic approach (11).
391
Box 1. Comparison of Different

Approaches to Hysterectomy
Vaginal Hysterectomy Compared With Abdominal
Hysterectomy
Shorter duration of hospital stay
Faster return to normal activity
Fewer febrile episodes or unspecified infections
Vaginal Hysterectomy Compared With Laparoscopic
Hysterectomy
Shorter operating time
Laparoscopic Hysterectomy Compared With Abdominal
Hysterectomy
Faster return to normal activity

Shorter duration of hospital stay
Smaller drop in hemoglobin
Lower intraoperative blood loss
Fewer wound or abdominal wall infections
Longer operating time
Higher rate of lower urinary tract (bladder and ureter)
injuries
Outcomes and Complication Rates

Evidence demonstrates that, in general, vaginal hysterectomy is associated with better outcomes and fewer complications. A Cochrane review of 34 randomized trials of
abdominal hysterectomy, laparoscopic hysterectomy, and
vaginal hysterectomy, including 4,495 patients, concluded
that vaginal hysterectomy has the best outcomes of these
three routes. The review also found that when a vaginal
hysterectomy is not possible, laparoscopic hysterectomy
has advantages (including faster return to normal activity, shorter duration of hospital stays, lower intraoperative
blood loss, and fewer wound infections) over abdominal
hysterectomy; however, laparoscopic surgery also is associated with longer operating time and higher rates of urinary tract injury (2) (see Box 1).
The authors of one study compared vaginal and
abdominal hysterectomy and found that abdominal hysterectomy was associated with 1.7 times more complications, 1.9 times more febrile morbidity, and 2.1 times
more blood transfusions than vaginal hysterectomy (12).
In another study, when women with enlarged uteri (200
1,300 gm) were randomly assigned surgery by the vaginal or abdominal route, the vaginal procedure resulted in
decreased operative time, less febrile morbidity, reduced
postoperative narcotic use, and shorter hospital stay (13).
When it is not feasible to perform a vaginal hysterectomy, the surgeon must choose between laparoscopic hysterectomy, robot-assisted hysterectomy, or abdominal
hysterectomy. Experience with robot-assisted hysterectomy
for benign conditions is currently limited (14). Abdominal hysterectomy is also an important surgical procedure,
especially when the vaginal or laparoscopic approach is
Data from Nieboer TE, Johnson N, Lethaby A, Tavender E, Curr E,

Garry R, et al. Surgical approach to hysterectomy for benign
gynaecological disease. Cochrane Database of Systematic
Reviews 2009, Issue 3. Art. No.: CD003677. DOI: 10.1002/14651858.
CD003677.pub4.
not appropriate to manage the patients clinical situation

or when facilities cannot support a specific procedure.
Other Considerations
Cost analysis has consistently demonstrated that vaginal
hysterectomy is the most cost-effective route (15, 16).
Patient preference may influence the route by which the
hysterectomy is performed (17). For example, despite the
evidence that there is no significant difference in outcome
between a supracervical hysterectomy and a total hysterectomy (18), some patients may choose a supracervical
hysterectomy. In these cases, a laparoscopic or open
abdominal approach is most appropriate.
Conclusions
Listed as follows are the conclusions of the ACOG Committee on Gynecologic Practice:
Vaginal hysterectomy is the approach of choice
whenever feasible, based on its well-documented
advantages and lower complication rates.
The choice of when to perform prophylactic oophorectomy at the time of hysterectomy is based on the
patients age, risk factors, and informed wishes, but
not on the route of hysterectomy.
392
Laparoscopic hysterectomy is an alternative to abdominal hysterectomy for those patients in whom a vaginal hysterectomy is not indicated or feasible.
Experience with robot-assisted hysterectomy is limited
at this time; more data are necessary to determine its
role in the performance of hysterectomy.
References
1. Whiteman MK, Hillis SD, Jamieson DJ, Morrow B,
Podgornik MN, Brett KM, et al. Inpatient hysterectomy
surveillance in the United States, 2000-2004. Am J Obstet
Gynecol 2008;198:34.e134.e7.
2. Nieboer TE, Johnson N, Lethaby A, Tavender E, Curr E,
Garry R, et al. Surgical approach to hysterectomy for benign
gynaecological disease. Cochrane Database of Systematic
14651858.CD003677.pub4.
3. Wu JM, Wechter ME, Geller EJ, Nguyen TV, Visco AG.
Hysterectomy rates in the United States, 2003. Obstet
Gynecol 2007;110:10915.
4. Tohic AL, Dhainaut C, Yazbeck C, Hallais C, Levin I,
Madelenat P. Hysterectomy for benign uterine pathology
among women without previous vaginal delivery. Obstet
Gynecol 2008;111:82937.
5. Doucette RC, Sharp HT, Alder SC. Challenging generally
accepted contraindications to vaginal hysterectomy.
Am J Obstet Gynecol 2001;184:13869; discussion 13901.
6. Kovac SR. Decision-directed hysterectomy: a possible
approach to improve medical and economic outcomes. Int
7. Kovac SR, Barhan S, Lister M, Tucker L, Bishop M, Das A.
Guidelines for the selection of the route of hysterectomy:
application in a resident clinic population. Am J Obstet
Gynecol 2002;187:15217.
8. Ballard LA, Walters MD. Transvaginal mobilization and
removal of ovaries and fallopian tubes after vaginal hysterectomy. Obstet Gynecol 1996;87:359.
9. Davies A, OConnor H, Magos AL. A prospective study to
evaluate oophorectomy at the time of vaginal hysterectomy.
Br J Obstet Gynaecol 1996;103:91520.
10. Sheth SS. The place of oophorectomy at vaginal hysterectomy. Br J Obstet Gynaecol 1991;98:6626.
11. Agostini A, Vejux N, Bretelle F, Collette E, De Lapparent T,

Cravello L, et al. Value of laparoscopic assistance for vaginal
hysterectomy with prophylactic bilateral oophorectomy.
12. Dicker RC, Greenspan JR, Strauss LT, Cowart MR, Scally MJ,
Peterson HB, et al. Complications of abdominal and vaginal
hysterectomy among women of reproductive age in the
United States. The Collaborative Review of Sterilization.
13. Benassi L, Rossi T, Kaihura CT, Ricci L, Bedocchi L, Galanti B,
et al. Abdominal or vaginal hysterectomy for enlarged uteri:
a randomized clinical trial. Am J Obstet Gynecol 2002;187:
15615.
14. ACOG Technology Assessment: Robot-Assisted Surgery (in
publication for November 2009)
15. Dorsey JH, Holtz PM, Griffiths RI, McGrath MM, Steinberg EP.
Costs and charges associated with three alternative techniques of hysterectomy. N Engl J Med 1996;335:47682.
16. Sculpher M, Manca A, Abbott J, Fountain J, Mason S, Garry R.
Cost effectiveness analysis of laparoscopic hysterectomy
compared with standard hysterectomy: results from a randomised trial. BMJ 2004;328:134.
17. Surgery and patient choice. ACOG Committee Opinion
18. Supracervical hysterectomy. ACOG Committee Opinion

ISSN 1074-861X
Choosing the route of hysterectomy for benign disease. ACOG
COMMITTEE OPINIONS
393

Increasing Use of Contraceptive Implants

and Intrauterine Devices To Reduce
Unintended Pregnancy
Committee on
Gynecologic
Practice
Long-Acting
Reversible
Contraception
Working Group
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: High unintended pregnancy rates in the United States may in part be
the result of relatively low use of long-acting reversible contraceptive (LARC) methods,
specifically the contraceptive implant and intrauterine devices. Top-tier reversible methods share the characteristic of requiring a single act of motivation for long-term use, eliminating adherence and user-dependence from the effectiveness equation. According to
the World Health Organizations evidence-based Medical Eligibility Criteria for contraceptive use, LARC methods have few contraindications, and almost all women are eligible
for implants and intrauterine devices. Because of these advantages and the potential to
reduce unintended pregnancy rates, LARC methods should be offered as first-line contraceptive methods and encouraged as options for most women. To increase use of
LARC methods, barriers such as lack of health care provider knowledge or skills, low
patient awareness, and high upfront costs must be addressed.
Unintended pregnancy persists as a major

public health problem in the United States.
Over the past 20 years, overall rates in the
United States have not changed and remain
unacceptably high at approximately 50% of
all pregnancies (1). Although the rate for
unintended pregnancy has decreased somewhat for higher income women, rates have
increased for lower income women (1).
Unwanted births to women aged 1524 years
nearly doubled between 1995 and 2002 (2).
Many factors, including contraceptive
method choice and continuation patterns,
contribute to the lack of progress in reducing
unintended pregnancies. Combined oral contraceptives and condoms, the predominant
reversible contraceptive methods used in the
United States, are user dependent, have relatively low continuation rates, and have relatively high failure rates with typical use patterns (3). Interventions such as enhanced
counseling and same day start have not consistently improved contraceptive use patterns, continuation rates, or unintended
pregnancy rates (46). Further, the predicted
effect of emergency contraception to reduce
unintended pregnancy has not been achieved
(7). The United States has higher unintended

pregnancy rates than other countries (8).
Long-Acting Reversible
Contraception and
In part, high-unintended pregnancy rates in
the United States may be the result of relatively low use of long-acting reversible contraceptive (LARC) methods, specifically the contraceptive implant and intrauterine devices
(IUDs). Use of LARC methods is much less
common in the United States than in countries such as France, where unintended pregnancy rates are much lower (7). According to
the most recent cycle of the National Survey of
Family Growth, fewer than 5% of women in
the United States reported ever using
intrauterine contraception or an implant (9).
Increasing use of LARC methods in the
United States could lower unintended pregnancy rates (7), and expanding access to
LARC for young women has been declared a
national priority (10).
Emerging evidence indicates that increasing the use of contraceptive implants and IUDs
394
also could reduce repeat pregnancy among adolescent

mothers and repeat abortions among women seeking
induced abortion. In a U.S. study of adolescent mothers,
the factor most strongly associated with repeat pregnancy
prevention in the first 2 postpartum years was initiation
of the six-rod contraceptive implant (11). Other studies
have concluded that immediate postabortion initiation of
LARC methods is associated with reduced repeat abortion rates. In a retrospective cohort study conducted in
the United States, women who received immediate
postabortion IUDs for contraception had a significantly
lower rate of repeat abortions than women who chose
other non-IUD postabortion contraception (34.6 versus
91.3 abortions per 1,000 woman-years of follow-up) (12).
Similarly, in a prospective cohort study from Northern
Europe, 1,269 women undergoing early medical abortion
were monitored for 49 months. Women who chose
immediate IUD insertion had the lowest repeat abortion
risk, as compared with those who chose other methods or
postponed starting a contraceptive method (13).
Long-Acting Reversible Contraceptive

Methods
The World Health Organization family planning counseling guide lists all methods in tiers of effectiveness (see
Fig. 1). The top-tier reversible methods all share the characteristic of requiring a single act of motivation for
long-term use, essentially eliminating adherence and userdependence from the effectiveness equation. These toptier methods also share the highest continuation rates of
all contraceptive methods, one of the most important factors in contraceptive success (3).
Currently, three LARC methods are available in the
United States. The single-rod etonogestrel implant was
approved by the U.S. Food and Drug Administration in
July 2007 for use up to 3 years. Two IUDs are available, the
Copper T380A for use up to 10 years, and the levonorgestrel intrauterine system for use up to 5 years. According to the World Health Organizations evidence-based
Medical Eligibility Criteria for contraceptive use, LARC
methods have few contraindications, and almost all women
are eligible for implants and IUDs (14, 15).
Despite high up-front costs and the need for office
visits for insertion and removal, LARC methods share the
following advantages over other methods:
Are independent from coitus and user motivation
and adherence
Have the highest effectiveness, continuation rates,
and user satisfaction
Do not require frequent visits for resupply
Require no additional funding for consistent use
once they have been placed
Are highly cost-effective
Are reversible, with a rapid return to fertility after
removal
Because of these advantages and the potential to reduce

unintended pregnancy rates, LARC methods should be
offered as first-line contraceptive methods and encouraged as options for most women.
Barriers to Long-Acting Reversible

Contraception
To increase use of LARC methods, barriers such as lack of
health care provider knowledge or skills, low patient
awareness, and high upfront costs should be addressed.
Increasing familiarity with changes in practice guidelines and improvements associated with the newer LARC
devices may address some health care provider reluctance
to encourage LARC use. Although health care providers
generally have favorable attitudes about IUDs, they may
use overly restrictive criteria to identify IUD candidates
(16). For example, IUDs may be safely used by nulliparous women and by adolescents (17, 18). Although there is
a slight increased risk of infection in the first 20 days after
IUD insertion, evidence indicates there is no increased
risk of pelvic inflammatory disease or infertility in IUD
users (18).
Immediate postpartum and postabortal insertion of
an IUD is safe and effective (19, 20). Although expulsion
rates may be higher, the convenience of postpartum or
postabortal placement may outweigh this disadvantage and
increase access and use of effective contraception (19, 20).
The single-rod contraceptive implant is relatively new
and many physicians may be unaware of its advantages,
including its ease of removal as compared with the older
six-rod system. In one study, mean removal time for the single-rod implant was 3.5 minutes (21). In order to procure
the single-rod contraceptive implant, health care providers
are required by the U.S. Food and Drug Administration to
participate in manufacturer-sponsored training.
Lack of experience or comfort with implant or IUD
insertion may result in physician reluctance to recommend LARC methods, and overly cumbersome insertion
protocols, multiple visits, and unnecessary testing could
discourage patient use. The American College of Obstetricians and Gynecologists supports efforts to increase
educational and hands-on training opportunities for clinicians in implant and IUD insertion.
Patient barriers include a general lack of awareness of
LARC methods and their safety and effectiveness. Women
describe the ideal contraceptive as reversible and not
needing frequent thought (22). Yet, two recent surveys
found that most young women had not heard of the IUD
(23, 24). However, young women were likely to report a
positive attitude about intrauterine contraception after a
brief, 3-minute educational intervention (23).
Cost may present a barrier to LARC method use for
many women. Implants and IUDs have high up-front
costs that often are not fully covered by insurance.
Instead, less effective but initially less expensive methods
such as oral contraceptives are more often covered.
However, both the implant and IUDs are highly cost-
COMMITTEE OPINIONS
395
Fig. 1. Abbreviations: IUD, intrauterine device; LAM, lactational amenorrhea method.
effective even with relatively short-term (1224 months)

use (2527).
Recommendations
Although lowering unintended pregnancy rates requires
multiple approaches, individual obstetriciangynecologists may contribute by increasing access to LARC methods for their patients. The following strategies can reduce
barriers and increase use of implants and IUDs:
Provide counseling on all contraceptive options,
including implants and IUDs, even if the patient initially states a preference for a specific contraceptive
method.
Encourage implants and IUDs for all appropriate candidates, including nulliparous women and adolescents.
Adopt same-day insertion protocols. Screening for

chlamydia, gonorrhea, and cervical cancer should not
be required before implant or IUD insertion but may
be obtained on the day of insertion, if indicated.
Avoid unnecessary delays, such as waiting to initiate
a method until after a postabortion or miscarriage
follow-up visit or to time insertion with menses.
Support efforts to lower the up-front costs of LARC
methods.
Advocate for coverage of all contraceptive methods
by all insurance plans, both private and public.
Become familiar with and support local, state, federal (including Medicaid), and private programs that
improve affordability of all contraceptive methods,
including implants and IUDs.
396
Resources
Long-Acting Reversible Contraception Program
409 12th Street, SW, PO Box 96920
800-673-8444 or 202-638-5577
http://www.acog.org/goto/larc
Patient Education Pamphlet AP014 (2007)
The intrauterine device
Available at: http://www.acog.org/publications/patient_
education/bp014.cfm
Spanish language version (pamphlet SP014) available at:
http://www.acog.org/publications/patient_education/
sp014.cfm
Patient Education Pamphlet AP159 (2007)
Hormonal contraceptionInjections, implants, rings,
and patches.
Available at: http://www.acog.org/publications/patient_
education/bp159.cfm
Spanish language version (pamphlet SP159) available at:
http://www.acog.org/publications/patient_education/
sp159.cfm
World Health Organization
Promoting family planning
Available at: http://www.who.int/reproductivehealth/
topics/family_planning/en/index.html
References
1. Finer LB, Henshaw SK. Disparities in rates of unintended
pregnancy In the United States, 1994 and 2001. Perspect Sex
Reprod Health 2006;38(2):906.
2. Kissin DM, Anderson JE, Kraft JM, Warner L, Jamieson DJ.
Is there a trend of increased unwanted childbearing among
young women in the United States? J Adolesc Health 2008;
43:36471.
3. Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F,
Kowal D, editors. Contraceptive technology. 19th rev. ed.
New York (NY): Ardent Media, Inc.; 2007.
4. Halpern V, Grimes DA, Lopez LM, Gallo MF. Strategies to
improve adherence and acceptability of hormonal methods
of contraception. Cochrane Database of Systematic Reviews
2006, Issue 1. Art. No.: CD004317. DOI: 10.1002/14651858.
CD004317.pub2.
5. Moos MK, Bartholomew NE, Lohr KN. Counseling in the
clinical setting to prevent unintended pregnancy: an evidence-based research agenda. Contraception 2003;67:
11532.
6. Lopez LM, Newmann SJ, Grimes DA, Nanda K, Schulz KF.
Immediate start of hormonal contraceptives for contraception. Cochrane Database of Systematic Reviews 2008, Issue
2. Art. No.: CD006260. DOI: 10.1002/14651858.CD006260.
pub2.
7. Trussell J, Schwarz EB, Guthrie K, Raymond E. No such
thing as an easy (or EC) fix. Contraception 2008;78:3514.
8. Trussell J, Wynn LL. Reducing unintended pregnancy in the

United States. Contraception 2008;77:15.
9. Chandra A, Martinez GM, Mosher WD, Abma JC, Jones J.
Fertility, family planning, and reproductive health of U.S.
women: data from the 2002 National Survey of Family
Growth. Vital Health Stat 23 2005;(25):1160.
10. Institute of Medicine (US). Initial national priorities for
comparative effectiveness research. Washington, DC:
National Academies Press; 2009.
11. Stevens-Simon C, Kelly L, Kulick R. A village would be nice
but...it takes a long-acting contraceptive to prevent repeat
adolescent pregnancies. Am J Prev Med 2001;21:605.
12. Goodman S, Hendlish SK, Reeves MF, Foster-Rosales A.
Impact of immediate postabortal insertion of intrauterine
contraception on repeat abortion. Contraception 2008;78:
1438.
13. Heikinheimo O, Gissler M, Suhonen S. Age, parity, history
of abortion and contraceptive choices affect the risk of
repeat abortion. Contraception 2008;78:14954.
contraceptive use. 3rd ed. Geneva: WHO; 2004. Available at:
http://whqlibdoc.who.int/publications/2004/9241562668.p
df. Retrieved August 13, 2009.
contraceptive use: 2008 update. Geneva: WHO; 2008.
Available at: http://whqlibdoc.who.int/hq/2008/WHO_
RHR_08.19_eng.pdf. Retrieved August 13, 2009.
16. Harper CC, Blum M, de Bocanegra HT, Darney PD, Speidel
JJ, Policar M, et al. Challenges in translating evidence to
practice: the provision of intrauterine contraception. Obstet
Gynecol 2008;111:135969.
17. Intrauterine device and adolescents. ACOG Committee
18. Intrauterine device. ACOG Practice Bulletin No. 59.
19. Grimes DA, Lopez LM, Schulz KF, Stanwood NL.
Immediate postabortal insertion of intrauterine devices.
Art. No.: CD001777. DOI: 10.1002/14651858.CD001777.
pub2.
20. Grimes DA, Schulz KF, Van Vliet HH, Stanwood NL, Lopez
LM. Immediate post-partum insertion of intrauterine
devices. Cochrane Database of Systematic Reviews 2001,
CD003036.
21. Funk S, Miller MM, Mishell DR Jr, Archer DF, Poindexter A,
Schmidt J, et al. Safety and efficacy of Implanon, a singlerod implantable contraceptive containing etonogestrel. The
Implanon US Study Group. Contraception 2005;71:31926.
22. Cwiak C, Gellasch T, Zieman M. Peripartum contraceptive
attitudes and practices. Contraception 2004;70:3836.
23. Whitaker AK, Johnson LM, Harwood B, Chiappetta L,
Creinin MD, Gold MA. Adolescent and young adult
womens knowledge of and attitudes toward the intrauterine device. Contraception 2008;78:2117.
COMMITTEE OPINIONS
24. Stanwood NL, Bradley KA. Young pregnant womens

knowledge of modern intrauterine devices. Obstet Gynecol
2006;108:141722.
25. Trussell J, Lalla AM, Doan QV, Reyes E, Pinto L, Gricar J.
Cost effectiveness of contraceptives in the United States.
26. Foster DG, Rostovtseva DP, Brindis CD, Biggs MA, Hulett
D, Darney PD. Cost savings from the provision of specific
methods of contraception in a publicly funded program.
Am J Public Health 2009;99:44651.
27. Chiou CF, Trussell J, Reyes E, Knight K, Wallace J, Udani J,
et al. Economic analysis of contraceptives for women.
397

ISSN 1074-861X
Increasing use of contraceptive implants and intrauterine devices to
reduce unintended pregnancy. ACOG Committee Opinion No. 450.
2009;114:1434 8.
398

Primary and Preventive Care: Periodic

Assessments
Committee on
Gynecologic
Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Periodic assessments offer an excellent opportunity

and gynecologists to provide preventive screening, evaluation, and
American College of Obstetricians and Gynecologists Committee
Practice recommends routine assessments in primary and preventive
based on age and risk factors.
The following charts are updated versions of

those previously published by the American
(ACOG) in Committee Opinion No. 357 and
Guidelines for Womens Health Care, Third
Edition. This version replaces the previous
versions. The policies and recommendations
of ACOG committees regarding specific
aspects of the health care of women have
been incorporated; they may differ from the
recommendations of other groups.
and Gynecologists recommends that the first
visit to the obstetriciangynecologist for
screening and the provision of preventive
health care services and guidance take place
between the ages 13 years and 15 years. This
visit will provide health guidance, screening,
and preventive health care services and provide an excellent opportunity for the obstetriciangynecologist to start a physicianpatient
relationship. This visit does not necessarily
include an internal pelvic examination.
Periodic assessments provide an excellent
opportunity to counsel patients about preventive care. These assessments, yearly or as
appropriate, should include screening, evaluation and counseling, and immunizations
based on age and risk factors. Personal behavioral characteristics are important aspects of a
womans health. Positive behaviors, such as
for obstetricians
counseling. The
on Gynecologic
care for women
exercise, should be reinforced, and negative

ones, such as smoking, should be discouraged.
The following guidelines indicate routine
assessments for nonpregnant women based on
age groups and risk factors (see Table 1) and
list leading causes of death for each age group.
Gynecologists generally adopts the immunization recommendations of the Centers for
Disease Control and Prevention. The current
adolescent and adult immunization schedules
are available atwww.cdc.gov/vaccines/recs/
schedules.
The recommendations included in this
document serve as a framework for care,
which may be provided by a single physician
or a team of health care professionals. The
scope of services provided by obstetrician
gynecologists in the ambulatory setting will
vary from practice to practice. The list should
serve as a guide for the obstetriciangynecologist and others providing health care for
women and should be adapted as necessary
to meet patients needs. For example, certain
risk factors may influence additional assessments and interventions. Physicians should
be alert to high-risk factors (indicated by an
asterisk and further elucidated in Table 1).
During evaluation, the patient should be
made aware of high-risk conditions that
require targeted screening or treatment.
COMMITTEE OPINIONS
Periodic Assessment
Periodic Assessment
Ages
1318 Years
Ages 1318 Years
Screening
History
Reason for visit
Health status: medical, menstrual,
surgical, family
Dietary/nutrition assessment
Physical activity
Use of complementary and alternative
medicine
Tobacco, alcohol, other drug use
Abuse/neglect
Sexual practices
Physical Examination
Height
Weight
Body mass index (BMI)
Blood pressure
Secondary sexual characteristics
(Tanner staging)
Pelvic examination (when indicated by
the medical history)
Skin*
Laboratory Testing
Periodic
Chlamydia and gonorrhea testing
(if sexually active)
Human immunodeficiency virus
(HIV) testing (if sexually active)
High-Risk Groups*
Colorectal cancer screening
Fasting glucose testing
Genetic testing/counseling
Hemoglobin level assessment
Hepatitis C virus testing
Lipid profile assessment
Rubella titer assessment
Sexually transmitted disease
testing
Tuberculosis skin testing
Evaluation and Counseling

Sexuality
Development
High-risk behaviors
Preventing unwanted/unintended
pregnancy
Postponing sexual involvement
Contraceptive options, including
emergency contraception
Sexually transmitted diseases
Partner selection
Barrier protection
Fitness and Nutrition
Exercise: discussion of program
(including eating disorders)
Folic acid supplementation
Calcium intake
Psychosocial Evaluation
Suicide: depressive symptoms
Interpersonal/family relationships
Sexual orientation and gender identity
Personal goal development
Behavioral/learning disorders
Abuse/neglect
Satisfactory school experience
Peer relationships
Date rape prevention
Cardiovascular Risk Factors
Family history
Hypertension
Dyslipidemia
Obesity
Diabetes mellitus
Health/Risk Behaviors
Hygiene (including dental), fluoride
supplementation*
Injury prevention
Exercise and sports involvement
Firearms
Hearing
Occupational hazards
Recreational hazards
Safe driving practices
Helmet use
Skin exposure to ultraviolet rays

Immunizations
Periodic
Diphtheria and reduced tetanus
toxoids and acellular pertussis
vaccine booster (once between
ages 1118 years) ||
Hepatitis B vaccine (one series for
those not previously immunized)
Human papillomavirus vaccine
(one series for those not previously
immunized, ages 926 years)
Influenza vaccine (annually)
Measlesmumpsrubella vaccine
(for those not previously
immunized)
Meningococcal conjugate vaccine
(before entry into high school for
those not previously immunized)
Varicella vaccine (one series for
those without evidence of
immunity)
High-Risk Groups*
Hepatitis A vaccine
Pneumococcal vaccine
Leading Causes of Death

1. Accidents (unintentional injuries)
2. Malignant neoplasms
3. Intentional self harm (suicide)
4. Assault (homicide)
5. Diseases of the heart
6. Congenital malformations,
deformations, and chromosomal
abnormalities
7. Chronic lower respiratory
diseases
8. Cerebrovascular diseases
9. Influenza and pneumonia
10. In situ neoplasms, benign
neoplasms, and neoplasms of
uncertain or unknown behavior
*See Table 1.
Urine-based sexually transmitted disease screening is an efficient means for accomplishing such screening without a speculum examination.
Physicians should be aware of and follow their states HIV screening requirements. For a more detailed discussion of HIV screening, see Branson BM, Handsfield HH, Lampe
MA, Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. Centers for Disease
Control and Prevention (CDC). MMWR Recomm Rep 2006;55(RR-14):117; quiz CE14. See also Routine human immunodeficiency virus screening. ACOG Committee Opinion
Only for those with a family history of familial adenomatous polyposis or 8 years after the start of pancolitis. For a more detailed discussion of colorectal cancer screening,
see Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous
polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. American
Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee. CA Cancer J Clin 2008;58:13060.
||For more information on the use of Td and Tdap, see Broder KR, Cortese MM, Iskander JK, Kretsinger K, Slade BA, Brown KH, et al. Preventing tetanus, diphtheria, and
pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization
Practices (ACIP). Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55(RR-3):134.
Leading causes of mortality are provided by the Mortality Statistics Branch at the National Center for Health Statistics. Data are from 2004, the most recent year for which
final data are available. The causes are ranked.
399
400
Periodic Assessment
Periodic Assessment
Ages
1939 Years
Ages 1939 Years
Screening
History
Reason for visit
Health status: medical, surgical, family
Physical activity
medicine
Abuse/neglect
Sexual practices
Urinary and fecal incontinence
Height
Weight
Blood pressure
Neck: adenopathy, thyroid
Breasts
Abdomen
Pelvic examination: for ages 1920 years,
when indicated by the medical history;
age 21 or older, periodic pelvic
examination
Skin*
Laboratory Testing
Periodic
Cervical cytology:
Age 21 years: screen every 2 years
Age 30 years or older:
Option 1: may screen every 3 years
after three consecutive negative
test results with no history of
cervical intraepithelial neoplasia
2 or 3, immunosuppression, human
immunodeficiency virus (HIV)
infection, or diethylstilbestrol
exposure in utero; or
Option 2: screen every 3 years after
negative human papillomavirus
DNA test and negative cervical
cytology
Chlamydia and gonorrhea testing (if
aged 25 years or younger and sexually
active)
testing
High-Risk Groups*
Bone mineral density screening

Mammography
Sexually transmitted disease testing
Thyroid-stimulating hormone testing
Sexuality and Reproductive
Planning
Contraceptive options for prevention of
unwanted pregnancy, including
Discussion of a reproductive health plan
High-risk behaviors
Preconception and genetic counseling
Sexual function
Partner selection
Barrier protection
Calcium intake
Interpersonal/family relationships
Intimate partner violence
Date rape prevention
Work satisfaction
Lifestyle/stress
Sleep disorders
Family history
Hypertension
Dyslipidemia
Obesity
Diabetes mellitus
Lifestyle
Breast self-examination||
Chemoprophylaxis for breast cancer (for
high-risk women aged 35 years or older)
Hygiene (including dental)

Injury prevention
Firearms
Hearing
Safety belts and helmets
Immunizations
Periodic
toxoids and acellular pertussis vaccine
(substitute one-time dose of Tdap for
Td booster; then boost with Td every
10 years) #
Human papillomavirus vaccine (one
series for those aged 26 years or less
and not previously immunized)
Varicella vaccine (one series for those
without evidence of immunity)
High-Risk Groups*
Hepatitis A vaccine (consider
combination vaccine for those at risk
for hepatitis A and B)
Hepatitis B vaccine (consider
Influenza vaccine
Meningococcal vaccine
Leading Causes of Death**

5. Human immunodeficiency virus
(HIV) disease
6. Assault (homicide)
8. Diabetes mellitus
9. Chronic liver diseases and cirrhosis
10. Chronic lower respiratory diseases
*See Table 1.
For a more detailed discussion of cervical cytology screening, including the use of human papillomavirus DNA testing and screening after hysterectomy, see Cervical cytology
screening. ACOG Practice Bulletin No. 109. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009:114;140920.
Physicians should be aware of and follow their states HIV screening requirements. For a more detailed discussion of HIV screening, see Branson BM, Handsfield HH, Lampe
MA, Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. Centers for Disease
Control and Prevention (CDC). MMWR Recomm Rep 2006;55(RR-14):117; quiz CE14. See also Routine human immunodeficiency virus screening. ACOG Committee Opinion
For a more detailed discussion of the reproductive health plan, see The importance of preconception care in the continuum of womens health care. ACOG Committee Opinion
||
Despite a lack of definitive data for or against breast self-examination, breast self-examination has the potential to detect palpable breast cancer and can be recommended.
For a more detailed discussion of risk assessment and chemoprevention therapy, see Selective estrogen receptor modulators. ACOG Practice Bulletin No. 39. American College
# For more information on the use of Td and Tdap, see Kretsinger K, Broder KR, Cortese MM, Joyce MP, Ortega-Sanchez I, Lee GM, et al. Preventing tetanus, diphtheria, and
pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices
(ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. Centers
for Disease Control and Prevention; Advisory Committee on Immunization Practices; Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep
2006;55(RR-17):137.
**Leading causes of mortality are provided by the Mortality Statistics Branch at the National Center for Health Statistics. Data are from 2004, the most recent year for which
final data are available. The causes are ranked.
COMMITTEE OPINIONS
Periodic Assessment
Periodic
Assessment
Ages
4064
Years
Ages 40 64 Years
Screening
History
Reason for visit
Physical activity
medicine
Pelvic prolapse
Menopausal symptoms
Abuse/neglect
Sexual practices
Height
Weight
Blood pressure
Oral cavity
Breasts, axillae
Abdomen
Pelvic examination
Skin*
Laboratory Testing
Periodic
Cervical cytology (may screen every
3 years after three consecutive negative
test results if no history of cervical intraepithelial neoplasia 2 or 3, immunosuppression, human immunodeficiency
virus infection (HIV), or diethylstilbestrol exposure in utero, or every 3 years
after negative human papillomavirus
DNA test and negative cervical cytology)
Colorectal cancer screening (beginning
at age 50 years: colonoscopy every 10
years [preferred])
Fasting glucose testing (every 3 years
after age 45 years)
testing
Lipid profile assessment (every 5 years
beginning at age 45 years)
Mammography (every 12 years
beginning at age 40 years, yearly
(every 5 years beginning at age 50 years)
High-Risk Groups*
Bone mineral density screening
Sexuality ||
High-risk behaviors
Contraceptive options for prevention of
unwanted pregnancy, including
Sexual function
Partner selection
Barrier protection
Calcium intake
Family relationships
Intimate partner violence
Work satisfaction
Retirement planning
Lifestyle/stress
Sleep disorders
Family history
Hypertension
Dyslipidemia
Obesity
Diabetes mellitus
Lifestyle
Aspirin prophylaxis to reduce the risk
of stroke (ages 5579 years)
Breast self-examination #
Chemoprophylaxis for breast cancer
(for high-risk women)**
Hormone therapy
Injury prevention
Firearms
Hearing
Immunizations
Periodic
toxoids and acellular pertussis vaccine
booster (substitute one-time dose of
Tdap for Td booster; then boost with
Td every 10 years)
Herpes zoster (single dose in adults
aged 60 years or older)
Influenza vaccine (annually
Varicella vaccine (one series for
those without evidence of
immunity)
High-Risk Groups*
combination vaccine for those at
risk for hepatitis A and B)
combination vaccine for those at
risk for hepatitis A and B)
Influenza vaccine
Leading Causes of Death

7. Chronic liver disease and cirrhosis
8. Septicemia
10. Human immunodeficiency virus
(HIV) disease
*See Table 1.
For a more detailed discussion of cervical cytology screening, including the use of human papillomavirus DNA testing and screening after hysterectomy, see Cervical cytology
screening. ACOG Practice Bulletin No. 109. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009:114;140920.
Other methods include: 1) fecal occult blood testing or fecal immunochemical test, annual patient-collected (fecal occult blood testing and fecal immunochemical testing require
two or three samples of stool collected by the patient at home and returned for analysis. A single stool sample obtained by digital rectal examination is not adequate for the
detection of colorectal cancer.); 2) flexible sigmoidoscopy every 5 years; 3) double contrast barium enema every 5 years; 4) computed tomography colonography every 5 years; and
5) stool DNA. The American College of Gastroenterology recommends that African Americans begin screening at age 45 years with colonoscopy because of increased incidence
and earlier age of onset of colorectal cancer. (Agrawal S, Bhupinderjit A, Bhutani MS, Boardman L, Nguyen C, Romero Y, et al. Colorectal cancer in African Americans. Committee
of Minority Affairs and Cultural Diversity, American College of Gastroenterology [published erratum appears in Am J Gastroenterol 2005;100:1432]. Am J Gastroenterol
2005;100:515,523; discussion 514.)
Physicians should be aware of and follow their states HIV screening requirements. For a more detailed discussion of HIV screening, see Branson BM, Handsfield HH, Lampe MA,
Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. Centers for Disease Control
and Prevention (CDC). MMWR Recomm Rep 2006;55(RR-14):117; quiz CE14. See also Routine human immunodeficiency virus screening. ACOG Committee Opinion No. 411.
American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;112:4013.
||
Preconception and genetic counseling is appropriate for certain women in this age group.
The recommendation for aspirin prophylaxis must weigh the benefits of stroke prevention against the harm of gastrointestinal bleeding. See Aspirin for the prevention of
cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. U.S. Preventive Services Task Force. Ann Intern Med 2009;150:396404.
#
Despite a lack of definitive data for or against breast self-examination, breast self-examination has the potential to detect palpable breast cancer and can be recommended.
**For a more detailed discussion of risk assessment and chemoprevention therapy, see Selective estrogen receptor modulators. ACOG Practice Bulletin No. 39. American College
If Tdap not previously given, give one time, then Td every 10 years thereafter. If Tdap previously given, give Td every 10 years. For more information on the use of Td and Tdap,
see Kretsinger K, Broder KR, Cortese MM, Joyce MP, Ortega-Sanchez I, Lee GM, et al. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced
diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the
Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. Centers for Disease Control and Prevention; Advisory Committee
on Immunization Practices; Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep 2006;55(RR-17):137.
Leading causes of mortality are provided by the Mortality Statistics Branch at the National Center for Health Statistics. Data are from 2004, the most recent year for which final
data are available. The causes are ranked.
401
402
Periodic Assessment
Periodic
Assessment
Ages 65
Years
and Older
Ages 65 Years and Older
Screening
History
Reason for visit
Physical activity
Pelvic prolapse
Menopausal symptoms
medicine
Tobacco, alcohol, other drug use, and
concurrent medication use
Abuse/neglect
Sexual practices
Height
Weight
Blood pressure
Oral cavity
Breasts, axillae
Abdomen
Pelvic examination*
Skin
Laboratory Testing
Periodic
Bone mineral density screening (In the
absence of new risk factors, screen no
more frequently than every 2 years.)
Cervical cytology: consider discontinuing
at age 65 years or 70 years if patient
has had three or more normal results in
a row, no abnormal results in 10 years,
no history of cervical cancer, no history
of diethylstilbestrol exposure in utero, is
human immunodeficiency virus (HIV)
negative, is not immunosuppressed; if
cervical cytology has been discontinued,
annual review of risk factors to evaluate
need for reinitiation of screening. If
cervical cytology is needed: may screen
every 3 years after three consecutive
negative test results if no history of
cervical intraepithelial neoplasia 2 or 3,
immunosuppression, HIV infection, or
diethylstilbestrol exposure in utero or
every 3 years after negative human
papillomavirus DNA test and negative
cervical cytology.
Colorectal cancer screening:

colonoscopy every 10 years (preferred)
Fasting glucose testing (every 3 years)
Lipid profile assessment (every 5
years)
Mammography
(every 5 years)
Urinalysis
High-Risk Groups
testing
Sexuality
Sexual function
Sexual behaviors
Partner selection
Barrier protection
Calcium intake
Neglect/abuse
Lifestyle/stress
Depression/sleep disorders
Family relationships
Work/retirement satisfaction
Hypertension
Dyslipidemia
Obesity
Diabetes mellitus
Sedentary lifestyle
Aspirin prophylaxis (for women aged
79 years or younger) ||
Breast self-examination
Chemoprophylaxis for breast cancer
(for high-risk women) #
Hearing
Hormone therapy
Injury prevention
Firearms
Prevention of falls
Visual acuity/glaucoma
Immunizations
Periodic
Herpes zoster (single dose, if not
previously immunized)
Influenza vaccine (annually)
Pneumococcal vaccine (once)
Tetanusdiphtheria booster (every
10 years)
Varicella vaccine (one series for those
without evidence of immunity)
High-Risk Groups
Leading Causes of Death**

5. Alzheimers disease
6. Influenza and pneumonia
8. Nephritis, nephrotic syndrome, and
nephrosis
10. Septicemia
*When a womans age or other health issues are such that she would not choose to intervene on conditions detected during the routine examination, it is
reasonable to discontinue pelvic exams.
See Table 1.
For a more detailed discussion of cervical cytology screening, including the use of human papillomavirus DNA testing and screening after hysterectomy,
see Cervical cytology screening. ACOG Practice Bulletin No. 109. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009:114;140920.
Other methods include: 1) fecal occult blood testing or fecal immunochemical test, annual patient-collected (fecal occult blood testing and fecal
immunochemical testing require two or three samples of stool collected by the patient at home and returned for analysis. A single stool sample obtained
by digital rectal examination is not adequate for the detection of colorectal cancer.); 2) flexible sigmoidoscopy every 5 years; 3) double contrast barium
enema every 5 years; 4) computed tomography colonography every 5 years; and 5) stool DNA. More frequent testing is recommended for those with other
risk factors.
||
The recommendation for aspirin prophylaxis must weigh the benefits of stroke prevention against the harm of gastrointestinal bleeding. See Aspirin for the
prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. U.S. Preventive Services Task Force. Ann Intern Med
2009;150:396404.
Despite a lack of definitive data for or against breast self-examination, breast self-examination has the potential to detect palpable breast cancer and can
be recommended.
#
For a more detailed discussion of risk assessment and chemoprevention therapy, see Selective estrogen receptor modulators. ACOG Practice Bulletin No. 39.
**Leading causes of mortality are provided by the Mortality Statistics Branch at the National Center for Health Statistics. Data are from 2004, the most
recent year for which final data are available. The causes are ranked.
COMMITTEE OPINIONS
403
Table 1. High-Risk Factors

Intervention
High-Risk Factors
Bone mineral density screening* Postmenopausal women younger than age 65 years: history of prior fracture as an adult; family history of
osteoporosis; Caucasian; dementia; poor nutrition; smoking; low weight and BMI; estrogen deficiency
caused by early (age younger than 45 years) menopause, bilateral oophorectomy, or prolonged (longer than
1 year) premenopausal amenorrhea; low lifelong calcium intake; alcoholism; impaired eyesight despite adequate correction; history of falls; inadequate physical activity
All women: certain diseases or medical conditions and certain drugs associated with an increased risk of
osteoporosis
Colorectal cancer or adenomatous polyps in first-degree relative younger than age 60 years or in two or
more first-degree relatives of any ages; family history of familial adenomatous polyposis or hereditary nonpolyposis colon cancer; history of colorectal cancer, adenomatous polyps, inflammatory bowel disease,
chronic ulcerative colitis, or Crohns disease

toxoids and acellular pertussis
vaccine
Adults who have or who anticipate having close contact with an infant aged less than 12 months and
health care providers. When possible, women should receive Tdap before becoming pregnant.
Overweight (BMI greater than or equal to 25); first-degree relative with diabetes mellitus; habitual physical
inactivity; high-risk race or ethnicity (eg, African American, Latina, Native American, Asian American,
Pacific Islander); have given birth to a newborn weighing more than 9 lb or have a history of gestational
diabetes mellitus; hypertension; high-density lipoprotein cholesterol level less than 35 mg/dL; triglyceride
level greater than 250 mg/dL; history of impaired glucose tolerance or impaired fasting glucose; polycystic
ovary syndrome; history of vascular disease; other clinical conditions associated with insulin resistance
Fluoride supplementation
Live in area with inadequate water fluoridation (less than 0.7 ppm)
Considering pregnancy and: patient, partner, or family member with history of genetic disorder or birth
defect; exposure to teratogens; or African, Cajun, Caucasian, European, Eastern European (Ashkenazi)
Jewish, French Canadian, Mediterranean, or Southeast Asian ancestry
Caribbean, Latin American, Asian, Mediterranean, or African ancestry; history of excessive menstrual flow
HAV vaccination
Chronic liver disease, clotting factor disorders, illegal drug user, individuals who work with HAV-infected
nonhuman primates or with HAV in a research laboratory setting, individuals traveling to or working in
countries that have high or intermediate endemicity of hepatitis A
HBV vaccination
Hemodialysis patients; patients who receive clotting factor concentrates; health care workers and public safety
workers who have exposure to blood in the workplace; individuals in training in schools of medicine, dentistry,
nursing, laboratory technology, and other allied health professions; injecting drug users; individuals with more
than one sexual partner in the previous 6 months; individuals with a recently acquired STD; all clients in STD
clinics; household contacts and sexual partners of individuals with chronic HBV infection; clients and staff of
institutions for the developmentally disabled; international travelers who will be in countries with high or
intermediate prevalence of chronic HBV infection for more than 6 months; inmates of correctional facilities
HCV testing
History of injecting illegal drugs, recipients of clotting factor concentrates before 1987, chronic (long-term)
hemodialysis, persistently abnormal alanine aminotransferase levels, recipients of blood from donors who
later tested positive for HCV infection, recipients of blood or blood-component transfusion or organ transplant before July 1992, occupational percutaneous or mucosal exposure to HCV-positive blood
HIV testing
More than one sexual partner since most recent HIV test or a sexual partner with more than one sexual
partner since most recent HIV test, have received a diagnosis of another STD in the past year, drug use by
injection, history of prostitution, past or present sexual partner who is HIV positive or injects drugs, longterm residence or birth in an area with high prevalence of HIV infection, history of transfusion from 1978 to
1985, invasive cervical cancer, sexually active adolescent younger than age 19 years, adolescent entering
detention facilities. Recommend to women seeking preconception evaluation.
(continued)
404
Table 1. High-Risk Factors (continued)

Intervention
High-Risk Factors
Influenza vaccination
Anyone who wishes to reduce the chance of becoming ill with influenza; anyone who wants to reduce the
risk of transmitting it to others; chronic cardiovascular or pulmonary disorders, except hypertension, including asthma; chronic metabolic diseases, including diabetes mellitus, renal dysfunction, hemoglobinopathies,
and immunosuppression (including immunosuppression caused by medications or by HIV); hepatic disorders;
residents and employees of nursing homes and other long-term care facilities; individuals likely to transmit
influenza to high-risk individuals (eg, household members and caregivers of the elderly, children aged from
birth to 59 months, and adults with high-risk conditions); those with any condition (eg, cognitive dysfunction, spinal cord injury, seizure or other neuromuscular disorder) that compromises respiratory function or
the handling of respiratory secretions, or that increases the risk of aspiration; health care workers; pregnancy during the influenza season; adults older than age 50 years; adolescents who are receiving longterm aspirin therapy who therefore might be at risk for experiencing Reye syndrome after influenza virus
infection
Family history suggestive of familial hyperlipidemia; family history of premature cardiovascular disease (age
younger than 50 years for men, age younger than 60 years for women); previous personal history of coronary heart disease or noncoronary atherosclerosis (eg, abdominal aortic aneurysm, peripheral artery disease, carotid artery stenosis); obesity (BMI greater than 30); personal and/or family history of peripheral
vascular disease; diabetes mellitus; multiple coronary heart disease risk factors (eg, tobacco use, hyper-tension)
Mammography
Women who have had breast cancer or who have a first-degree relative (ie, mother, sister, or daughter) or
multiple other relatives who have a history of premenopausal breast or breast and ovarian cancers
Meningococcal vaccination
Adults with anatomic or functional asplenia or terminal complement component deficiencies, first-year
college students living in dormitories, microbiologists routinely exposed to Neisseria meningitides isolates,
military recruits, travel to hyperendemic or epidemic areas
MMR vaccination
Adults born in 1957 or later should be offered vaccination (one dose of MMR) if there is no proof of immunity or documentation of a dose given after first birthday; individuals vaccinated in 19631967 should be
offered revaccination (two doses); health care workers, students entering college, international travelers,
and rubella-negative postpartum patients should be offered a second dose.
Pneumococcal vaccination
Chronic illness, such as cardiovascular disease, pulmonary disease, diabetes mellitus, alcoholism, chronic
liver disease, cerebrospinal fluid leaks, Hodgkin disease, lymphoma, leukemia, kidney failure, multiple
myeloma, nephrotic syndrome, functional asplenia (eg, sickle cell disease) or splenectomy; exposure to
an environment where pneumococcal outbreaks have occurred; immunocompromised patients (eg, HIV
infection, hematologic or solid malignancies, chemotherapy, steroid therapy); Alaskan Natives and certain
Native American populations. Revaccination after 5 years may be appropriate for certain high-risk groups.
Childbearing age and no evidence of immunity
STD testing
History of multiple sexual partners or a sexual partner with multiple contacts; sexual contact with individuals
with culture-proven STD; history of repeated episodes of STDs; attendance at clinics for STDs; women with
developmental disabilities; annual screening for chlamydial infection for all sexually active women aged
25 years or younger; other asymptomatic women at high risk for infection and women older than age 25 years
with risk factors (new sexual partner or multiple sexual partners); annual screening for gonorrheal infection
for all sexually active adolescents and other asymptomatic women at high risk for infection; testing for
syphilis for sexually active adolescents who exchange sex for drugs or money, use intravenous drugs, are
entering a detention facility, or live in a high prevalence area
Skin examination
Increased recreational or occupational exposure to sunlight; family or personal history of skin cancer;
clinical evidence of precursor lesions; fair skin, freckling; light hair; immune suppression; age; xeroderma
pigmentosum
COMMITTEE OPINIONS
405
Table 1. High-Risk Factors (continued)

Intervention
High-Risk Factors
Thyroid-stimulating hormone
testing
Strong family history of thyroid disease; autoimmune disease (evidence of subclinical hypothyroidism may
be related to unfavorable lipid profiles)
HIV infection; close contact with individuals known or suspected to have tuberculosis; medical risk factors
known to increase risk of disease if infected; born in country with high tuberculosis prevalence; medically
underserved; low income; alcoholism; intravenous drug use; resident of long-term care facility (eg, correctional institutions, mental institutions, nursing homes and facilities); health professional working in highrisk health care facilities; recent tuberculin skin test converter (individuals with baseline testing results who
have an increase of 10 mm or more in the size of the tuberculin skin test reaction within a 2-year period);
radiographic evidence of prior healed tuberculosis
Varicella vaccination
Adults and adolescents aged 13 years or older; all adolescents and adults without evidence of immunity;
students in all grade levels, and persons attending college or other postsecondary educational institutions;
susceptible persons who have close contact with persons at high risk for serious complications, including
health care workers; household contacts of immunocompromised individuals; teachers; daycare workers;
residents and staff of institutional settings, colleges, prisons, or military installations; adolescents and
adults living in households with children; international travelers; nonpregnant women of childbearing age
Abbreviations: BMI, body mass index; HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; MMR, measlesmumps
rubella; STD, sexually transmitted disease; Tdap, diptheria and reduced tetanus toxoids and acellular pertussis vaccine.
*For a more detailed discussion of bone mineral density screening, see Osteoporosis. ACOG Practice Bulletin No. 50. American College of Obstetricians and Gynecologists.
For a more detailed discussion of colorectal cancer screening, see Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance
for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal
Cancer, and the American College of Radiology. American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology
Colon Cancer Committee. CA Cancer J Clin 2008;58:13060.
For more information, see Broder KR, Cortese MM, Iskander JK, Kretsinger K, Slade BA, Brown KH, et al. Preventing tetanus, diphtheria, and pertussis among adolescents:
use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). Advisory
Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55(RR-3):134.; Kretsinger K, Broder KR, Cortese MM, Joyce MP, Ortega-Sanchez I, Lee GM, et al.
Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory
Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of
Tdap among health-care personnel. Centers for Disease Control and Prevention; Advisory Committee on Immunization Practices; Healthcare Infection Control Practices
Advisory Committee. MMWR Recomm Rep 2006;55(RR-17):137.
For more information, see Postpartum screening for abnormal glucose tolerance in women who had gestational diabetes mellitus. ACOG Committee Opinion No. 435.
Copyright December 2009 by the American College of Obstetricians and Gynecologists, 409 12th Street, SW, PO Box 96920, Washington, DC
20090-6920. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, posted on the Internet, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher. Requests for authorization to make photocopies should be directed to: Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA
01923, (978) 750-8400.
ISSN 1074-861X
Primary and preventive care: periodic assessments. ACOG Committee Opinion No. 452. American College of Obstetricians and Gynecologists.
406
ACOG
NUMBER 4, AUGUST 2005
This Technology Assessment was

developed by the ACOG Committee on Gynecologic Practice.
clinical and scientific advances
as of the date issued and is subject to change. The information
treatment or procedure to be followed. Variations in practice
practice.
Reaffirmed 2007
Hysteroscopy
ABSTRACT: Hysteroscopy is an effective, minimally invasive procedure for
the diagnosis and treatment of intrauterine pathology. Selection of a distending medium requires consideration of the advantages, disadvantages,
and risks associated with various media as well as their compatibility with
electrosurgical or laser energy. Preoperative discussions with patients
should address risks and benefits of the procedure, comorbidities, analgesia
or anesthesia, and possible preoperative cervical dilation. Pregnancy, genital tract infection, and uterine carcinoma are contraindications to hysteroscopy. Possible complications include hemorrhage, fluid overload, perforation, visceral injury, infection, and embolization.
Hysteroscopy is performed to view and treat pathology within the uterine

cavity. Diagnostic hysteroscopy allows visualization of the endocervical
canal, endometrial cavity, and fallopian tube ostia. Common abnormal findings include polyps, leiomyomata, intrauterine adhesions, and mllerian
anomalies. Operative hysteroscopy incorporates the use of mechanical,
electrosurgical, or laser instruments to treat intracavitary disease.
INSTRUMENTATION
THE AMERICAN COLLEGE

OF OBSTETRICIANS
AND GYNECOLOGISTS
Hysteroscopes are available in both flexible and rigid models, all of which
contain a telescope consisting of light bundles. Flexible hysteroscopes range
in diameter from 2.7 mm to 5 mm and have a bendable tip that can be
deflected in two directions ranging from 120 degrees to 160 degrees. Most
also contain an operating channel for tubal catheterization or endometrial
biopsy. Rigid hysteroscopes may consist of two or three pieces and range
from 1 mm to 5 mm in diameter. Their tips have varying viewing angles (0,
12, 15, 30, and 70 degrees). An outer sheath fits over the telescope to allow
inflow of a distending medium into the intrauterine cavity. This system
allows fluid to return on the outside of the outer sheath passively from the
intrauterine cavity through the cervix.
Continuous flow hysteroscopes consist of two channels to allow fluid to
flow into the intrauterine cavity while debris and cloudy intrauterine fluid
exit through perforations in the outer sheath to the outflow port. Fluid exiting the outflow port can be collected through tubing and returned to a device
for the accurate measurement of fluid volume.
COMMITTEE OPINIONS
Operative hysteroscopes typically range from 8

mm to 10 mm in diameter and contain a working
element. These hysteroscopes contain a retractable
hand piece wherein electrosurgical tips (eg, rollerballs, loops, and vaporizing tips), lasers, or mechanical instruments (eg, scissors) can be attached.
DISTENDING MEDIA
The uterine cavity requires distension for adequate
visualization. Several distending media are available, and each has inherent advantages and disadvantages. It is critically important to understand
which media are compatible with electrosurgical
and laser energy. Furthermore, the risks associated
with various media should be understood.
Carbon Dioxide Gas

Carbon dioxide (CO2), a colorless gas, is used in
outpatient settings for diagnostic purposes. The
advantages include the ease of cleaning and maintaining equipment and a clear view of the cavity in
the absence of active bleeding or bubbles. To minimize the risk of gas embolization, the flow of CO2
should be limited to 100 mL/min with intrauterine
pressures less than 100 mm Hg. Insufflators
designed for use in laparoscopy must not be used for
hysteroscopy.
407
may cause hyponatremia but not decreased serum

osmolality (1).
Low-Viscosity Electrolyte Fluid. Normal saline
and lactated Ringers solution are electrolyte fluids.
The use of these fluids is advantageous because they
are readily available and are isotonic. These solutions are the distending media of choice during diagnostic hysteroscopy and in operative cases where
mechanical, laser, or bipolar energy is used.
Although the risk of hyponatremia and decreased
serum osmolality can be reduced by using these
media, pulmonary edema can still occur, and careful
attention should be paid to fluid input and output.
High-Viscosity Fluid. Dextran 70 is a colorless, viscous, polysaccharide liquid. The advantage of using
this liquid is that it is immiscible with blood and,
therefore, provides excellent visibility, especially in
the presence of blood in the endometrial cavity. The
major disadvantage of using dextran 70 is that it is
sticky and, when dry, tends to harden and crystallize
onto the equipment. It also can be a powerful plasma expander, and the volume usually is limited to
300 mL and must not exceed 500 mL. For every 100
mL absorbed, the plasma volume may expand by
an additional 860 mL (2). Other concerns include
anaphylaxis and disseminated intravascular coagulation. Beet sugar allergy is an absolute contraindication.
Fluid Media
Fluid media have historically been divided into electrolyte and nonelectrolyte media, based on compatibility with electrosurgical procedures. However, it is
now possible to use electrolyte media with bipolar
electrosurgical systems. It also is important to understand which media are hypoosmolar. Media also are
categorized by viscosity.
Low-Viscosity, Electrolyte-Poor Fluid. Low-viscosity, electrolyte-poor fluids include glycine, 1.5%,
sorbitol, 3%, and mannitol, 5%. These fluids have
been widely used for operative hysteroscopy. They
are compatible with radiofrequency energy, which
cuts, desiccates, and fulgurates intrauterine tissue.
Monopolar devices require electrolyte-poor fluids. If
electrolyte-containing fluid is used, the electrical
current will dissipate away from the electrode, rendering it ineffective. Glycine, 1.5%, and sorbitol,
3%, are hypoosmolar. The use of these fluids can
cause hyponatremia and decreased serum osmolality, with the potential for cerebral edema and death.
Some clinicians have recommended mannitol, 5%,
which is isoosmolar and acts as its own diuretic. It
PREOPERATIVE CONSIDERATIONS
A preoperative consultation allows the patient and
physician to discuss the hysteroscopic procedure,
weigh its inherent risks and benefits, and review the
patients medical history for any comorbid conditions. Appropriate analgesia or anesthesia should
also be considered depending on the venue (ie,
office versus operating room). Preoperative placement of laminar or osmotic dilators or pretreatment
with misoprostol for cervical ripening may facilitate
cervical dilation and decrease operative time (3).
CONTRAINDICATIONS
Known viable pregnancy, known genital tract infections, and known uterine carcinomas are contraindications to hysteroscopy. Theoretically, hysteroscopy
may cause reflux of neoplastic cells into the peritoneal cavity, although it is unclear if this adversely
affects the prognosis (4, 5). However, hysteroscopy
is acceptable as part of the evaluation of abnormal
uterine bleeding.
408
PREVENTION AND MANAGEMENT OF

COMPLICATIONS
The most common perioperative complications
associated with operative hysteroscopy are hemorrhage (2.4%), fluid overload (1.5%) (6), and cervical
laceration (111%) (7). Other complications include
uterine perforation, visceral injury, infection, CO2
and air embolism, and, rarely, death. Late complications may include intrauterine adhesions and
infertility.
Hemorrhage
Hemorrhage may occur during hysteroscopic resection of the endometrium, myomata, uterine septa, or
synechia. For cases in which there is continued
bleeding, electrosurgical coagulation can be used
(8). Alternative strategies such as injection of vasopressin at the bleeding site, Foley catheter balloon
tamponade (9), or irrigation of the uterine cavity
with epsilon aminocaproic acid can be attempted. In
extreme cases, uterine artery embolization or hysterectomy may be necessary.
Fluid Overload
Complications from fluid overload may best be
avoided by limiting excess fluid absorption, recognizing and treating fluid overload promptly, and
selecting a distending medium that minimizes risk.
The best way to limit excess fluid intravasation
is to monitor the fluid deficit closely and frequently
throughout the procedure. Newer methods of fluid
monitoring based on measurement of fluid weight
have made this more accurate; however, some of
these systems can be expensive and may not be
available in all settings. One difficulty in estimating
fluid input and output is that commercially purchased 3-liter bags may be overfilled by up to
150300 mL (10). Dilutional hyponatremia can be
rapidly evaluated by serum sodium analysis.
Guidelines for fluid monitoring and the limits
of fluid excess have been published (1) and adapted
by the American College of Obstetricians and
Gynecologists Committee on Gynecologic Practice
as follows:
Hydration of patients undergoing hysteroscopy
should be closely monitored preoperatively and
intraoperatively.
With low-viscosity, electrolyte-poor fluids, a
deficit of 750 mL implies excessive intravasation,
and the fluid deficit should be monitored at an
extremely close interval. In elderly patients,
patients with comorbid conditions, and patients

with cardiovascular compromise, consideration
should be given to terminating the procedure
immediately.
Depending on patient size and other factors, if
fluid deficit reaches 1,0001,500 mL of a nonelectrolyte solution or 2,500 mL of an electrolyte
solution, further infusion should be stopped and
the procedure should be promptly concluded.
Electrolytes should be assessed, administration of
diuretics considered, and further diagnostic and
therapeutic intervention begun as indicated.
In an outpatient setting with limited acute care
and laboratory services, consideration should be
given to discontinuing procedures at a lower fluid
deficit threshold.
An automated fluid monitoring system facilitates
early recognition of excessive deficit in real-time
totals.
In the absence of automated monitoring, an individual should be designated to frequently measure intake and outflow and report the deficit to
the operative team.
The treatment of fluid overload from hypotonic

agents may require consultation and possibly transfer to an acute care facility. Whereas most women
recover, seizures, permanent brain damage, and
death have been reported with serum sodium levels
of 116 2 mmol/L (11). Although the rate at which
severe hyponatremia should be corrected is controversial, most authors agree that if acute hyponatremia has existed for less than 24 hours, there are few
long-term complications from rapid correction.
Therapy is most often provided in the form of hypertonic saline in conjunction with loop-acting diuretics. Serum sodium levels should be increased by 12
mEq/L/h but by no more than 12 mEq/L in the first
24 hours (12). When patients present with hyponatremia of greater than 48 hours postoperatively,
rapid correction should not be undertaken because it
can lead to neurologic compromise, seizures, and
death. Consultation is strongly encouraged in these
situations and often requires slower correction in an
intensive care setting.
Perforation
Prior to performing hysteroscopy, a pelvic examination should be performed to determine uterine position. If resistance is encountered during insertion of
the hysteroscope, the cervix may need further dilation. Midline uterine perforation rarely leads to significant morbidity unless a laser or electrosurgical
COMMITTEE OPINIONS
device is used. Lateral uterine or cervical perforations can result in significant bleeding. Laparoscopy
may be useful to determine the extent of damage,
including the existence of bowel or bladder injury.
5.
Embolization
Air and CO2 emboli are rare complications of hysteroscopy and may result in circulatory collapse. For
such emboli to occur, there must be both vascular
access and a pressure gradient between the site of
access and the right side of the heart. In the conscious patient, chest pain and dyspnea may be noted.
Other findings can include decreased oxygen saturation, the presence of a mill wheel heart murmur,
hypotension, bradycardia, or tachycardia. In the
anesthetized patient, cardiopulmonary status shows
signs of collapse with sudden hypotension, decrease
in oxygenation and/or in end-tidal CO2, or cardiac
dysrhythmias (13).
Management of this emergency consists of placing the patient in a left lateral decubitus position
with the head tilted downward 5 degrees. This
maneuver favors the movement of air in the right
ventricle and right ventricular outflow tract toward
the apex of the right ventricle (14). The air may be
aspirated by passing a catheter down the jugular vein
into the right ventricle, or possibly by performing
cardiocentesis.
SUMMARY
Hysteroscopy is an effective procedure for the diagnosis and treatment of intrauterine pathology. It is
minimally invasive and can be used with a high
degree of safety. Knowledge of potential dangers
relating to distending media and intraoperative complications will enhance its safety.
REFERENCES
1. Loffer FD, Bradley LD, Brill AI, Brooks PG, Cooper JM.
Hysteroscopic fluid monitoring guidelines. The ad hoc
committee on hysteroscopic training guidelines of the
American Association of Gynecologic Laparoscopists. J
Am Assoc Gyn Laparosc 2000;7:1678.
2. Lukacsko P. Noncardiogenic pulmonary edema secondary
to intrauterine instillation of 32% dextran 70. Fertil Steril
1985;44:5601.
3. Thomas JA, Leyland N, Durand N, Windrim RC. The use
of oral misoprostol as a cervical ripening agent in operative
hysteroscopy: a double-blind, placebo-controlled trial. Am
4. Obermair A, Geramou M, Gucer F, Denison U, Graf AH,
Kapshammer E, et al. Does hysteroscopy facilitate tumor
6.
7.
8.
9.
10.
11.
12.
13.
14.
409
cell dissemination? Incidence of peritoneal cytology from

patients with early stage endometrial carcinoma following
dilatation and curettage (D&C) versus hysteroscopy and
D&C. Cancer 2000;88:13943.
Arikan G, Reich O, Weiss U, Hahn T, Reinisch S,
Tamussino K, et al. Are endometrial carcinoma cells disseminated at hysteroscopy functionally viable? Gynecol
Oncol 2001;83:2216.
Overton C, Hargreaves J, Maresh M. A national survey of
the complications of endometrial destruction for menstrual disorders: the MISTLETOE study. Minimally
Invasive Surgical TechniquesLaser, EndoThermal or
Endoresection. Br J Obstet Gynaecol 1997;104:13519.
Preutthipan S, Herabutya Y. Vaginal misoprostol for cervical priming before operative hysteroscopy: a randomized
control trial. Obstet Gynecol 2000;96:8904.
Loffer FD. Complications of hysteroscopytheir cause,
prevention, and correction. J Am Assoc Gynecol Laparosc
1995;3:1126.
Goldrath MH. Uterine tamponade for the control of acute
uterine bleeding. Am J Obstet Gynecol 1983;147:86972.
Vulgaropulos SP, Haley LC, Hulka JF. Intrauterine pressure and fluid absorption during continuous flow hysteroscopy. Am J Obstet Gynecol 1992;167:386390; discussion 3901.
Arieff AI. Management of hyponatraemia. BMJ 1993;
307:3058.
Witz CA, Silverberg CM, Burns WN, Schenken RS, Olive
DL. Complications associated with the absorption of hysteroscopic fluid media. Fertil Steril 1993;60:74556.
Stoloff DR, Isenberg RA, Brill AI. Venous air and gas
emboli in operative hysteroscopy. J Am Assoc Gynecol
Laparosc 2001;8:18192.
deWet C, Harrison L, Jacobsohn E. Air embolism. In: Atlee
JL, editor. Complications in anesthesia. Philadelphia
(PA):WB Saunders;1999. p. 3235.
Copyright August 2005 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
Danvers, MA 01923, (978) 750-8400.
409 12th Street, SW
PO Box 96920
Hysteroscopy. ACOG Technology Assessment in Obstetrics

and Gynecology No. 4. American College of Obstetricians and
410
ACOG
NUMBER 5, D ECEMBER 2008
(Replaces Technology Assessment No. 3, September 2003)
This Technology Assessment was
developed by the ACOG Committee on Gynecologic Practice
with the assistance of
Daniel
Breitkopf, MD, John W. Seeds,

MD, and Steven R. Goldstein,
MD. This document reflects
emerging clinical and scientific
advances as of the date issued and
is subject to change. The information should not be construed as
dictating an exclusive course of
treatment or procedure to be
followed. Variations in practice
practice.
THE AMERICAN COLLEGE

OF OBSTETRICIANS
AND GYNECOLOGISTS
Sonohysterography
ABSTRACT: The goal of sonohysterography is to visualize the endometrial
cavity in more detail than is possible with routine transvaginal ultrasound.
The procedure consists of the manual injection of sterile fluid under
real-time ultrasonographic imaging. The most common indication for sonohysterography is abnormal uterine bleeding. The procedure should not be
performed in a woman who is pregnant or who could be pregnant, or who
has a pelvic infection or unexplained pelvic tenderness. Physicians who perform or supervise diagnostic sonohysterography should be skilled in vaginal ultrasonography and transcervical placement of catheters; should have
training, experience, and demonstrated competence in gynecologic ultrasonography and sonohysterography; and should keep careful records.
Portions of this document were developed jointly with the American College
of Radiology and the American Institute of Ultrasound in Medicine.
Sonohysterography can provide information about the uterus and endometrial cavity. Additional studies may be necessary for a complete diagnosis.
Adherence to the following recommendations serves to maximize the diagnostic benefits and safety of sonohysterography.
The clinical aspects of this document include sections addressing indications and contraindications, specifications of the examination, and equipment specifications that were developed collaboratively by the American
College of Radiology, the American Institute of Ultrasound in Medicine,
and the American College of Obstetricians and Gynecologists and adapted
by the American College of Obstetricians and Gynecologists Committee on
Gynecologic Practice. Sections of the document addressing physician qualifications and responsibilities, documentation, quality control, performance
improvement, safety, infection control, and patient education are recommendations of the American College of Obstetricians and Gynecologists
Committee on Gynecologic Practice.
Most clinical experience and medical literature to date have focused on
the ultrasonographic imaging of the uterus, and specifically the endometrial cavity, using the transcervical injection of sterile fluid. Thus, terms such
as saline infusion sonohysterography or simply sonohysterography have
been used to describe this technique. The goal of sonohysterography is to
visualize the endometrial cavity in more detail than is possible with routine
transvaginal ultrasound.
Studies are underway to evaluate fluids other than saline for use in
sonohysterography to determine tubal patency, but their use is currently
COMMITTEE OPINIONS
investigational because this application of sonohysterography has not yet been validated.
INDICATIONS AND CONTRAINDICATIONS

The indications for sonohysterography include, but
are not limited to, evaluation of
abnormal uterine bleeding in premenopausal and
postmenopausal women
infertility and habitual abortion
congenital abnormalities of the uterine cavity
suspected uterine myomas, polyps, and synechiae
abnormalities detected on transvaginal ultrasonography, including focal or diffuse endometrial
or intracavitary abnormalities
suboptimally imaged endometrium by transvaginal ultrasonography
The most common indication for sonohysterography is as an adjunct to transvaginal ultrasound in
the evaluation of abnormal uterine bleeding in both
premenopausal and postmenopausal women.
Sonohysterography should not be performed in
a woman who is pregnant or who could be pregnant.
This usually is avoided by scheduling the examination in the follicular phase of the menstrual cycle,
after the menstrual flow has essentially ceased, but
before the patient has ovulated. In a patient with regular menstrual cycles, sonohysterography should, in
most cases, be performed by the 10th day of the
menstrual cycle. Sonohysterography should not be
performed in patients with a pelvic infection or
unexplained pelvic tenderness, which could be due
to pelvic inflammatory disease. Active vaginal
bleeding is not an absolute contraindication to the
procedure but may make the interpretation more
challenging.
PHYSICIAN QUALIFICATIONS AND

RESPONSIBILITIES
Physicians who perform or supervise diagnostic
sonohysterography should be skilled in vaginal
ultrasonography and transcervical placement of
catheters. They should understand the indications,
limitations, and possible complications of the procedure. Physicians should have training, experience,
and demonstrated competence in gynecologic ultrasonography and sonohysterography. Physicians are
responsible for the documentation of the examination, quality control, and patient safety.
411
SPECIFICATIONS OF THE EXAMINATION

Patient Preparation
The sonohysterography procedure should be fully
explained to the patient in advance. Transvaginal
ultrasonography is a specialized form of a pelvic
examination. Therefore, policies applied locally
regarding chaperone or patient privacy issues during a
pelvic examination also should be applied during a
transvaginal ultrasound examination. Pelvic organ
tenderness should be assessed during a preliminary
transvaginal ultrasound examination. If adnexal tenderness or pain suspicious for active pelvic infection is
found prior to fluid infusion, the examination should
be deferred until after an appropriate course of treatment. Although routine use of antibiotic prophylaxis is
not recommended, consideration should be given to
administering antibiotics based on individual risk factors (eg, in the presence of nontender hydrosalpinges).
A pregnancy test is advised when clinically indicated.
Procedure
Preliminary routine transvaginal ultrasonography
with measurements of the endometrium and evaluation of the uterus and ovaries should be performed
before sonohysterography. A speculum is used to
allow visualization of the cervix. The presence of
unusual pain, lesions, or purulent vaginal or cervical
discharge may require rescheduling the procedure
pending further evaluation. After the external os is
cleansed, a catheter should be inserted into the cervical canal or uterine cavity or both using aseptic technique. Appropriate sterile fluid should be instilled
slowly by means of manual injection under real-time
ultrasonographic imaging. Imaging should include
real-time scanning of the endometrium and cervical
canal.
Images
Appropriate images, in at least two planes, using a
high-frequency transvaginal ultrasound probe should
be produced and recorded to demonstrate normal and
abnormal findings. Precatheterization images should
be obtained, including the thickest bilayer endometrial measurement on a sagittal image.
Once the uterine cavity is filled with fluid, representative images with a complete survey of the
uterine cavity are obtained as necessary for diagnostic evaluation. If a balloon catheter is used for the
examination, images should be obtained at the end
of the procedure with the balloon deflated to fully
evaluate the endometrial cavity, particularly the cervical canal and lower uterine segment.
412
Documentation
Appropriate documentation of a sonohysterography
examination is essential for clinical care and quality
assessment and improvement. An adequate written
report should include patient identification, procedural technique, measurements, morphologic
descriptions, and interpretation. Images of key findings and written reports from ultrasound examinations are considered part of the medical record and
should be documented and stored appropriately. (In
Current Procedural Terminology [CPT], sonohysterography is referred to as hysterosonography.)
Equipment Specifications
Sonohysterography usually is conducted with a
transvaginal transducer. If a patient has an enlarged
uterus, additional transabdominal images during
infusion may be required to fully evaluate the
endometrium. The transducer should be adjusted to
operate at the highest clinically appropriate frequency under the ALARA (as low as reasonably
achievable) principle.
Quality and Infection Control

Quality control is accomplished through careful
record keeping, reliable archiving of reports and
images, and clinical correlation with outcomes. Transvaginal transducers always should be covered with a
single-use disposable latex or nonlatex cover. However, because no such disposable protective cover is
without risk of rupture or defect, transvaginal transducers should undergo appropriate antimicrobial and
antiviral reprocessing between patient use.
BIBLIOGRAPHY
Becker E Jr, Lev-Toaff AS, Kaufman EP, Halpern EJ, Edelweiss MI, Kurtz AB. The added value of transvaginal sonohysterography over transvaginal sonography alone in women with
known or suspected leiomyoma. J Ultrasound Med 2002;
21:23747.
Benacerraf BR, Shipp TD, Bromley B. Improving the efficiency of gynecologic sonography with 3-dimensional volumes: a
pilot study. J Ultrasound Med 2006;25:16571.
Dubinsky TJ, Stroehlein K, Abu-Ghazzeh Y, Parvey HR, Maklad N. Prediction of benign and malignant endometrial disease:
hysterosonographic-pathologic correlation. Radiology 1999;
210:3937.
Goldstein RB, Bree RL, Benson CB, Benacerraf BR, Bloss JD,
Carlos R, et al. Evaluation of the woman with postmenopausal
bleeding: Society of Radiologists in Ultrasound-Sponsored
Consensus Conference statement. J Ultrasound Med 2001;20:
102536.
Goldstein SR. Use of ultrasonohysterography for triage of perimenopausal patients with unexplained uterine bleeding. Am J
Hann LE, Gretz EM, Bach AM, Francis SM. Sonohysterography for evaluation of the endometrium in women treated with
tamoxifen. AJR Am J Roentgenol 2001;177:33742.
Laifer-Narin S, Ragavendra N, Parmenter EK, Grant EG.
False-normal appearance of the endometrium on conventional
transvaginal sonography: comparison with saline hysterosonography. AJR Am J Roentgenol 2002;178:12933.
Laifer-Narin SL, Ragavendra N, Lu DS, Sayre J, Perrella RR,
Grant EG. Transvaginal saline hysterosonography: characteristics distinguishing malignant and various benign conditions.
AJR Am J Roentgenol 1999;172:151320.
Lev-Toaff AS, Toaff ME, Liu JB, Merton DA, Goldberg BB.
Value of sonohysterography in the diagnosis and management
of abnormal uterine bleeding. Radiology 1996;201:17984.
Lindheim SR, Sprague C, Winter TC 3rd. Hysterosalpingography and sonohysterography: lessons in technique. AJR Am J
Roentgenol 2006;186:249.
Mihm LM, Quick VA, Brumfield JA, Connors AF Jr, Finnerty
JJ. The accuracy of endometrial biopsy and saline sonohysterography in the determination of the cause of abnormal uterine bleeding. Am J Obstet Gynecol 2002;186:85860.
Parsons AK, Lense JJ. Sonohysterography for endometrial
abnormalities: preliminary results. J Clin Ultrasound 1993;
21:8795.
Schwartz LB, Snyder J, Horan C, Porges RF, Nachtigall LE,
Goldstein SR. The use of transvaginal ultrasound and saline
infusion sonohysterography for the evaluation of asymptomatic
postmenopausal breast cancer patients on tamoxifen. Ultrasound Obstet Gynecol 1998;11:4853.
Copyright December 2008 by the American College of
Obstetricians and Gynecologists. All rights reserved. No part
of this publication may be reproduced, stored in a retrieval
system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without
prior written permission from the publisher.
Bree RL, Bowerman RA, Bohm-Velez M, Benson CB,

Doubilet PM, DeDreu S, et al. US evaluation of the uterus in
patients with postmenopausal bleeding: a positive effect on
diagnostic decision making. Radiology 2000;216:2604.

Danvers, MA 01923, (978) 750-8400.
Breitkopf DM, Frederickson RA, Snyder RR. Detection of

benign endometrial masses by endometrial stripe measurement
in premenopausal women. Obstet Gynecol 2004;104:1205.

Doubilet PM. Society of Radiologists in Ultrasound Consensus

Conference statement on postmenopausal bleeding. J Ultrasound Med 2001;20:103742.
Sonohysterography. ACOG Technology Assessment No. 5.

Gynecol 2008;112:14679.
COMMITTEE OPINIONS
413
ACOG
NUMBER 6, N OVEMBER 2009
This Technology Assessment
was developed by the ACOG
Committee on Gynecologic
Practice. This document reflects
emerging clinical and scientific
advances as of the date issued
and is subject to change. The
information should not be construed as dictating an exclusive
course of treatment or procedure to be followed. Variations
in practice may be warranted
based on the needs of the individual patient, resources, and
limitations unique to the institution or type of practice.
Robot-Assisted Surgery
ABSTRACT: The field of robotic surgery is developing rapidly, but experience with this technology is currently limited. In response to increasing
interest in robotics technology, the Committee on Gynecologic Practices
Technology Assessment was developed to describe the robotic surgical system, potential advantages and disadvantages, gynecologic applications, and
the current state of the evidence. Randomized trials comparing robot-assisted
surgery with traditional laparoscopic, vaginal, or abdominal surgery are
needed to evaluate long-term clinical outcomes and cost-effectiveness, as
well as to identify the best applications of this technology.
Robot-assisted surgery evolved from the on-site needs of battlefield medicine and
from the technical limitations of traditional laparoscopy (1). Although a number
of precursors existed, the da Vinci Surgical System, introduced in 1999, is the only
commercially available system approved by the U.S. Food and Drug
Administration (FDA) for gynecologic surgery. Initial applications included radical retropubic prostatectomy and cardiac surgery. Use in gynecologic surgery was
approved by the FDA in 2005. In response to increasing interest in robotics technology, the Committee on Gynecologic Practices Technology Assessment was
developed to describe the robotic surgical system, potential advantages and disadvantages, gynecologic applications, and the current state of the evidence.
DESCRIPTION OF ROBOTIC INSTRUMENTATION
T H E A M E R I C A N CO L L E G E
OF OBSTETRICIANS
A N D G Y N E CO LO G I S T S
The current robotic surgical system consists of four components: 1) a console

where the surgeon sits, views the screen, and controls the robotic instruments and
camera via finger graspers and foot pedals; 2) a robotic cart with three or four
interactive arms that hold instruments through trocars attached to the patient; 3) a
camera and vision system that allows for a three-dimensional image of the pelvis
using image synchronizers and illuminators; and 4) wristed instruments with computer interfaces that translate the mechanical movements of the surgeons hands
into computer algorithms directing the instrument use within the patient (2).
During robotic surgery, the primary surgeon sits unscrubbed at the console, and at
some distance from the patient, with fingers through graspers controlling the
instruments. Foot pedals and a clutch are used for camera control, activation of
energy sources, focusing, and robotic arm switching. Three or four robotic arms
are docked to trocars inserted through the patients abdomen. A 12-mm, threedimensional endoscope is placed at the midline and two or three instruments are
414
passed through the lateral ports. Assistant surgical team

members pass robotic instruments and sutures through
these ports for use by the primary surgeon and also provide suction, irrigation, and countertraction. Instruments
for suturing, clamping, endosurgery, and tissue manipulation are used with the robotic arms.
POTENTIAL ADVANTAGES AND

DISADVANTAGES
Potential advantages over traditional laparoscopic
surgery include 1) three-dimensional visualization with
improved depth perception, 2) improved dexterity and
instrument articulation secondary to increased freedom
of movement and elimination of tremor and counterintuitive motions, and 3) the potential for use in telesurgery.
The improved visualization and dexterity may offer
some advantages over conventional laparoscopy for
complex procedures such as those required for gynecologic malignancy or invasive endometriosis (3, 4). Shorter
hospital stays and decreased blood loss also may be
advantages over laparotomy (5, 6).
Disadvantages of robotic surgery include 1) the high
costs associated with the technology (more than $1 million
for the initial system, with additional costs of yearly service contracts and disposable instrumentation), 2) the
increased operating time associated with equipment
setup and docking, 3) the lack of tactile feedback and sensation (haptics), 4) the inability to reposition the patient
once the robotic arms are attached, and 5) the bulkiness
of the current robotic system making it difficult for assistants to maneuver around it (eg, when applying uterine
manipulation for hysterectomy).
Robotic surgery has the potential to be a useful educational tool in resident and physician training. A current
concern is that its use may adversely affect surgical
training by decreasing residents overall surgical experience because only one surgeon can sit at the console.
Newer models that allow two surgeons to operate with
dual consoles are now available.
GYNECOLOGIC APPLICATIONS
The field of robotic surgery is developing rapidly, but
experience with the technology is limited at this time.
Limited data, mostly from heterogeneous small retrospective case series and a few small nonrandomized,
mostly retrospective comparative studies (2, 3, 511)
have shown the safety and feasibility of robot-assisted
surgery for numerous procedures, including tubal
reanastomosis, hysterectomy, nodal sampling, and prolapse suspension procedures. However, the comparative
studies frequently use historical controls, with different

surgeons, patient selection criteria, or settings (8). Large
prospective comparative studies evaluating long-term
clinical outcomes and costs are lacking. Few data exist on
how surgeon experience relates to overall complication
rates, operative time, or costs. Similarly, data are insufficient to demonstrate the specific patients or indications
where robot-assisted procedures might be advantageous
over vaginal surgery, laparotomy, or conventional laparoscopy. Although randomized controlled trials comparing
robotic-assisted surgery to conventional approaches are
ongoing (7), results are currently unavailable. Additional
information on ongoing clinical trials is available at
ClinicalTrials.gov.
CREDENTIALING
When surgeons adopt a new surgical technique, they
should be supervised or assisted by a more experienced
colleague, whenever feasible, until satisfactory competency has been demonstrated (12). Credentialing for
robotic-assisted surgery within and across specialties is
based on training, experience, and documented current
competency.
CONCLUSION
The field of robotic surgery is developing rapidly, but
experience with this technology is currently limited.
Randomized trials comparing robot-assisted surgery with
traditional laparoscopic, vaginal, or abdominal surgery are
needed to evaluate long-term clinical outcomes and costeffectiveness, as well as to identify the best applications of
this technology.
REFERENCES
1. Falcone T, Goldberg JM. Robotics in gynecology. Surg
Clin North Am 2003;83:14839, xii.
2. Visco AG, Advincula AP. Robotic gynecologic surgery.
3. Veljovich DS, Paley PJ, Drescher CW, Everett EN, Shah C,
Peters WA 3rd. Robotic surgery in gynecologic oncology:
program initiation and outcomes after the first year with
comparison with laparotomy for endometrial cancer staging. Am J Obstet Gynecol 2008;198:679.e19; discussion
679.e910.
4. Advincula AP, Reynolds RK. The use of robot-assisted
laparoscopic hysterectomy in the patient with a scarred or
obliterated anterior cul-de-sac. JSLS 2005;9:28791.
5. Geller EJ, Siddiqui NY, Wu JM, Visco AG. Short-term outcomes of robotic sacrocolpopexy compared with abdominal sacrocolpopexy. Obstet Gynecol 2008;112:12016.
6. Magrina JF, Kho RM, Weaver AL, Montero RP, Magtibay PM.
Robotic radical hysterectomy: comparison with lap-
COMMITTEE OPINIONS
7.
8.
9.
10.
11.
aroscopy and laparotomy. Gynecol Oncol 2008;109:86

91.
Obermair A, Gebski V, Frumovitz M, Soliman PT,
Schmeler KM, Levenback C, et al. A phase III randomized
clinical trial comparing laparoscopic or robotic radical hysterectomy with abdominal radical hysterectomy in patients
with early stage cervical cancer. J Minim Invasive Gynecol
2008;15:5848.
Belgian Health Care Knowledge Center (KCE). Robotassisted surgery: health technology assessment. KCE reports
104C. Brussels: KCE; 2009. Available at: http://www.kce.
fgov.be/Download.aspx?ID=1462. Retrieved June 29, 2009.
Persson J, Reynisson P, Borgfeldt C, Kannisto P, Lindahl B,
Bossmar T. Robot assisted laparoscopic radical hysterectomy
and pelvic lymphadenectomy with short and long term
morbidity data. Gynecol Oncol 2009;113:18590.
Seamon LG, Cohn DE, Henretta MS, Kim KH, Carlson MJ,
Phillips GS, et al. Minimally invasive comprehensive surgical staging for endometrial cancer: robotics or
laparoscopy? Gynecol Oncol 2009;113:3641.
Dharia Patel SP, Steinkampf MP, Whitten SJ, Malizia BA.
Robotic tubal anastomosis: surgical technique and cost
effectiveness. Fertil Steril 2008;90:11759.
415
12. Patient safety in the surgical environment. ACOG

Obstetricians and Gynecologists. Obstet Gynecol
2006;107:42933.
Copyright November 2009 by the American College of

of this publication may be reproduced, stored in a retrieval
system, or transmitted, in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise, without
Danvers, MA 01923, (978) 750-8400.
Robot-assisted surgery. ACOG Technology Assessment in
Obstetrics and Gynecology No. 6. American College of
11535.
COMMITTEE OPINIONS
COMMITTEE OPINIONS
COMMITTEE ON HEALTH CARE FOR
UNDERSERVED WOMEN
417
COMMITTEE OPINIONS
COMMITTEE ON HEALTH CARE
UNDERSERVED WOMEN
FOR
ACOG
Committee on
Health Care for
Underserved Women
Reaffirmed 2008
Committee
Opinion
The information should not be

Kurt Barnhart, MD, MSCE;
Jeffrey Ecker, MD; and Carol
Tauer, PhD; for their assistance in
the development of this document.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Partner consent for participation in

womens reproductive health research.
104:14679.
Partner Consent for Participation in

Womens Reproductive Health
Research
ABSTRACT: Recent advances in reproductive medicine include treatment of
subfertility as well as investigation of agents that may serve as both contraceptives and potential prophylaxis against sexually transmitted diseases,
including potential protection from human immunodeficiency virus (HIV).
Although there is no doubt regarding the need for informed consent by women
participating in trials evaluating the safety and effectiveness of these novel
agents and treatments, there has been some debate regarding the necessity
and propriety of requiring consent from the partners of women involved in
certain types of clinical trials involving reproductive health. Issues of partner
consent are unique to research surrounding womens reproductive health as
opposed to research pertaining to womens health, in general. This is due, in
part, to a valid concern about a potential effect of the research on the partner. There are, therefore, legitimate reasons to obtain partner consent for a
womans participation in a clinical trial. In the absence of such reason, partner consent should not be mandated.
Background
A large number of clinical trials are currently being conducted in nearly every
therapeutic area, including womens health. Women may be motivated to participate in clinical trials by altruism to further the care of women, by the ability to receive novel and state-of-the-art medical care, or by the benefits of
highly supervised medical monitoring of treatment. Often women without
health insurance choose to participate in these trials because such trials may
provide enhanced access to care, the care provided is often rendered without
cost, and there is reimbursement for time and travel. The American College
of Obstetricians and Gynecologists supports the development of new devices
and medications to advance womens health and reproductive options. The
American College of Obstetricians and Gynecologists also endorses the highest ethical and moral conduct of clinical research. All women, regardless of
socioeconomic status and race, should have access to enrollment in clinical
trials. The decision to enter a clinical trial should be autonomous, without
419
420
coercion, and after informed consent. Informed consent is the ability to understand the risks and benefits
of ones participation in a research activity and to
authorize ones participation in this activity freely (1).
A research subject is defined as An individual
who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control.
(2). In research on womens reproductive health,
sometimes both the woman and her partner will be
the subjects. For example, in a study designed to
identify any risk or harm to a partner of a new contraceptive method, both the woman and her partner
may be research subjects. If a partner is a subject in
the research, informed consent for both participants
is required. This Committee Opinion primarily
addresses the need for partner consent in research
for which the woman, and not a partner, is the
research subject. The respect for the autonomy of
research subjects to consent to participation is one of
the pillars of The Belmont Report, promulgated by
The National Commission for the Protection of
Human Subjects of Biomedical and Behavioral
Research in 1979 (3). The decision to reproduce or
use contraceptives should remain autonomous for a
woman even when enrolled in a clinical trial.
It also is important to note that the discussion
and recommendations that follow do not pertain to
research involving pregnant women. There are specific regulations that apply to federally funded
research involving this population (4).
Partner Consent Requirement

Inconsistencies
Recent advances in reproductive medicine include
treatment of subfertility as well as investigation of
agents that may serve as both contraceptives and
potential prophylaxis against sexually transmitted
diseases, including potential protection from human
immunodeficiency virus (HIV). Although there is no
doubt regarding the need for informed consent by
women participating in trials evaluating the safety
and effectiveness of these novel agents and treatments, there has been some debate regarding the
necessity and propriety of requiring consent from the
partners of women involved in certain types of clinical
trials involving reproductive health. Some local institutional review boards (IRB) have requested consent
of a womans partner and at other times a trial sponsor or an individual investigator has made the deci-
sion unilaterally. Because of the lack of guidance on

this issue, there is great inconsistency regarding
requirements for partner consent and the manner in
which partner consent is obtained (see box
Methods of Obtaining Partner Consent).
When Is Partner Consent Needed?

Issues of partner consent are unique to research surrounding womens reproductive health as opposed
to research pertaining to womens health, in general.
This is partly due to a valid concern about a potential impact of the research on the partner. Therefore,
there are legitimate reasons to obtain partner consent
for a womans participation in a clinical trial. In the
absence of such reason, partner consent should not
be mandated. Partner consent should be obtained if:
A sexual partner is a subject in the same clinical
trial as the woman.
A partner will be exposed to a novel agent and
there is a potential for more than minimal risks*
of exposure to the investigational agent.
Data will be collected regarding a partners
acceptance of the investigational agent, or the
impact of partners acceptance of the agent on
the female participant.
Inclusion or exclusion criteria directly relate to
a partner, for example, if testing of a partner is
required for a woman to enroll in the trial (eg,
semen analysis or testing for a sexually transmitted disease).
If, after careful consideration, it is determined that
none of the previous conditions apply, partner consent is not warranted because it should not needlessly:
Impose a barrier to participation for a woman
Interfere with a womans choice of reproductive options
Interfere with a womans right to make independent decisions about her reproductive health
care due to an IRBs or regulatory agencys
paternalistic reasons for partner consent
*According to applicable federal regulations, Minimal risk
means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during
the performance of routine physical or psychological examinations or tests. (45 C.F.R 46.102[I]).
COMMITTEE OPINIONS
Methods of Obtaining Partner Consent

Several methods exist that may be used to obtain partner
consent regarding a womans participation in a clinical
trial. The suitability of these methods depends on the
particular research study. Some ways of obtaining partner consent include:
Having a partner attend the screening visit and sign
the consent at that time
Giving a copy of the consent to the participant and
having a partner come in for a separate visit to consent
Mailing the consent and having it mailed back
Performing the informed consent process over the
telephone
Obtaining a single informed consent that is signed by
the woman and partner
Recommendations
Recognizing the complexities of the conduct and
consent requirements for trials in womens reproductive health, the following recommendations are
made:
The partner consent requirements of each clinical trial need to be individually evaluated and
based on the best available scientific and medical evidence and ethical principles.
When partner consent is required, efforts
should be undertaken to decrease the likelihood
that receipt of such consent will be a barrier for
participation of a woman interested in enrolling
in such a trial. The addition of consent adds
complexity to all trials, often resulting in additional visits for the participant and partner.
This can result in fewer women enrolling and a
decrease in compliance.
Whenever possible, the choice of a woman to
enroll in a clinical trial regarding her reproductive function and health should be hers alone
when it does not also include a partner as a
research subject. In these instances, the woman,
not the IRB or the researcher(s), considering
the research study should determine the extent
to which a partner is to be involved in the
process of informed consent and the decision to
participate. For example:
In the case of the study of a microbicide or
barrier contraception efficacy, the risk to a
421
partner is likely negligible (compared with

the female partner) because of minimal contact time. If potential irritation to a male partner is suspected, it should be ruled out in the
early stages of clinical investigation.
In contraceptive research where the participant may face an unintended pregnancy, a
partner may be a potential father with the
resultant legal and moral responsibilities for
the child. However, the principle of autonomy, allowing a woman to make a choice to
enter a trial regarding her reproductive
rights, should take precedence (5). The
Gynecologists does not support recognition
of distinct paternal rights before the birth of a
child (6).
Regardless of the requirement for partner consent, communication with a partner about
reproductive health and contraception use
should be encouraged.
References
2nd ed. Washington (DC): ACOG; 2004. p. 917.
2. International Conference On Harmonisation. Guideline for
good clinical practice. ICH Harmonised Tripartite Guideline
E6. London: ICH; 1997. Available at: http://www.proclinica.fr/
GCPICH.pdf. Retrieved August 26, 2004.
3. The National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research. The
Belmont report: ethical principles and guidelines for the
protection of human subjects of research. Washington,
DC: U.S Department of Health and Human Services;
1979. Available at: http://www.hhs.gov/ohrp/humansub
jects/guidance/belmont.htm. Retrieved August 26, 2004.
4. Protection of human subjects. 45 C.F.R 46 (2003). Available
at: http://www.access.gpo.gov/nara/cfr/waisidx_03/45cfr46
_03.html. Retrieved August 27, 2004.
5. Holder AR. Contraceptive research: do sex partners have
rights? IRB 1982;4(2):67.
Research involving women. In: Ethics in obstetrics and
gynecology. 2nd ed. Washington (DC): ACOG; 2004.
p. 8691.
422
ACOG
ACOG Committee on
Health Care for
Underserved Women

Gene Burkett, MD; Ronald Chez,
MD; and Eve Espey, MD, for
their assistance in the development of this document.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Health Care for Homeless Women.

2005;106:42934.
Committee
Opinion
Health Care for Homeless Women

Abstract: Homelessness is a considerable social and health problem in the
United States with far-reaching effects on the health of homeless women.
Homeless women are at higher risk for injury and illness and are less likely
to obtain needed health care than women who are not homeless. It is critical
to undertake efforts to prevent homelessness. Until this can be accomplished,
community-based services targeted specifically to this population that provide both health care and support services are essential. Health care
providers can help address the needs of the homeless by identifying their own
patients who may be homeless, treating their health problems, offering preventive care, and working with the community to improve the full range of
resources available to these individuals.
Approximately 3.5 million Americans are currently homeless (1), and as

many as 14% of the U.S. population have been homeless at some time (2)
(see box Definition of Homelessness). Women make up nearly one third of
the homeless population and are one of the fastest growing groups (3). In the
population of homeless individuals in families, 84% are women (4). Sixty
percent of homeless women have children younger than 18 years, but many
do not have custody of their children. There also are children who are homeless in their own right. This group includes runaways (5). Many homeless
adolescents left home because of conflicts with parents over their sexual orientation (6). Most homeless adolescents are white and come from suburban
and rural areas. They are more likely than other populations to experience
depression and substance abuse, to have previously attempted suicide, and to
have a history of sexual and physical abuse (7).
Extreme poverty is a universal characteristic of homeless individuals, but
not all impoverished individuals become homeless. The shortage of lowincome housing is a major precipitating factor to homelessness. It can render
homeless even individuals who are not extremely poor. Unemployment or job
loss, personal or family crisis, an increase in rent disproportionate to income,
or reduction in public health benefits increase the likelihood of loss of a home
among those at risk (4). For women, an additional risk factor is early motherhood (8).
Many homeless individuals lack education and money. Thirty-eight percent of homeless individuals did not graduate from high school and another
34% finished only high school. Slightly more than one quarter of homeless
individuals have any education beyond high school. The average monthly
COMMITTEE OPINIONS
Definition of Homelessness
An individual is considered homeless if he or she lacks a
fixed, regular, and adequate nighttime residence, or an
individual who has a primary nighttime residence that is:
a) a supervised publicly or privately operated shelter
designed to provide temporary living accommodations (including welfare hotels, congregate shelters, and transitional housing for the mentally ill);
b) a public or private place that provides a temporary
residence for individuals intended to be institutionalized; or
c) a public or private place not designed for, or ordinarily used as, regular sleeping accommodations
for human beings.
Interagency Council on the Homeless. Homelessness: programs
and the people they serve. Findings of the National Survey of
Homeless Assistance Providers and Clients. Washington, DC:
U.S. Department of Housing and Urban Development, Office of
Policy Development and Research; 1999.
income for a homeless family is $475 (46% of the

federal poverty level for a family of three at the time
of the study), and for a single homeless individual is
$348 (51% of the federal poverty level for one person) (4). Other risk factors include lack of job skills,
inadequate social support, problems with alcohol or
illicit drugs, mental illness, experiences of violence
and victimization, and previous incarceration.
423
personal security when living outdoors or in a shelter. Twenty-two percent report having been physically
assaulted or beaten up at least once while homeless (4). One study reported that 13% of homeless
women, particularly those with mental illness, were
sexually assaulted or raped in the past year, compared with 2.7% of the general population (13).
Twenty-two percent of homeless adolescents report
prior child abuse and 13% report sexual abuse (1, 4).
Gynecologic Health
Among homeless women interviewed in Los
Angeles, 66% used no method of contraception even
though most had intercourse at least once per week.
Fewer than 10% of homeless women report regular
condom use although they are at high risk for sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV) infection (14, 15), which
are especially problematic in the homeless adolescent population (11). Pelvic inflammatory disease
occurred in approximately 28% of homeless women, and 60% had a history of a least one STD (1).
Obstetric Health
Pregnancy and recent birth are highly correlated with
becoming homeless in the newly homeless population. At the time they requested emergency shelter,
35% of homeless women were pregnant and 26%
Impact of Homelessness on Women

Homelessness may be difficult to recognize. However, certain circumstances, many of which affect
the individuals health, are seen more frequently in
this population (see box Common Characteristics
of Homelessness). Being homeless creates an increased risk for illness and injury resulting in high
levels of morbidity and mortality (9). Homeless adolescent and adult women often participate in survival
sex, which refers to the selling of sex to meet subsistence needs (10, 11). Approximately 26% of young
homeless females reported having participated in
survival sex (10). More than two thirds of homeless
mothers have a diagnosis of mental illness. Cases of
posttraumatic stress disorder, substance abuse disorders, and major depression are disproportionately higher
among homeless women compared with other populations (12).
Violence
Violence is common among homeless populations.
Homeless individuals are at risk because they lack
Common Characteristics of Homelessness

Appearance: unkempt, disheveled, dirty, aggressive,
hostile
Chronic recurrent diseases, including respiratory
infections, hepatitis, asthma, arthritis, or tuberculosis
Multiple STDs or HIV
Substance abuse (alcohol and other substances)
Chronic mental illness with or without comorbidity,
suicide attempts, posttraumatic stress disorders,
stresses associated with sexual identity and
orientation
Repetitive, nonspecific complaints for which a diagnosis cannot be found
Underweight with history of subnutrition or poor
nutritional state
Domestic violence, including sexual abuse and
victimization
No fixed address or multiple addresses in a short
period
Lack of adherence with physician directives and
orders
424
had given birth in the past year. Only 6% of women

in the study who were not homeless were pregnant
and only 11% had given birth in the past year (8).
Homeless women often have little choice in the timing, the place, the partner, and the circumstances
surrounding conception. Factors associated with unintended pregnancy were victimization, survival sex,
lack of contraception, uncertain fertility status, desire
for intimacy, and lack of hope for the future (16).
Women younger than 21 years living on the streets
are at much greater risk of having ever been pregnant
than are young women living in households (5).
Adverse birth outcomes are substantially higher
in homeless women than in the general population
(17). In a study conducted in 1997, 17% of babies
born to homeless women were low birth weight
compared with 11% among those residing in lowincome housing (17). The rate of low birth weight at
the time of that study was 7.5% for all women (18).
Similarly, 19% of births in the homeless population
were preterm compared with 11% nationally (17,
18). Homeless women are less likely to receive prenatal care (19, 20). The more severe the homelessness (defined by whether or not the woman was
homeless during the first trimester of her pregnancy,
the number of times she had been homeless, and the
percentage of her life during which she had been
homeless), the less likely a woman is to receive prenatal care and the more likely an adverse pregnancy
outcome will occur. Older homeless women and
those who abuse drugs also are less likely to receive
prenatal care. Other predictors of adverse pregnancy
outcomes among homeless women include history
of preterm birth, antenatal complications, and birth
complications; STDs; low income; nulliparity; and
being African American (17).
Adverse birth outcomes are higher in AfricanAmerican homeless women than in homeless
women of other races. In the homeless population,
22% of infants born to African-American women
were low birth weight, whereas only 16% of
Hispanic infants and 5% of non-Hispanic white
infants were low birth weight. African-American
homeless women are more likely to experience
preterm birth. Homeless Native American women
also appear to have a large proportion of preterm
births and babies with low birth weight (17).
Homeless women may forgo meals in favor of
alcohol and other drugs (20). Day-to-day survival
stresses are superimposed on emotional distress,
which may lead to new or increased substance abuse
(20). Homeless pregnant women are prone to urinary tract infections and vaginal infections (20).
Children of homeless women are more likely to

be separated from their mothers by social service
providers. Forty-four percent of homeless mothers,
compared with 8% of mothers receiving public
assistance who are not homeless, were separated
from their children. Homelessness was the major
risk factor in such separation, although substance
abuse, domestic violence, and maternal institutionalization also were risk factors. A substantial minority of these children are placed in foster care. (21).
This separation from children may lead to emotional strain, anxiety, loss of control, instability,
guilt, and insecurity among homeless mothers.
Preventive Health
Homeless women receive breast examinations,
mammograms, and Pap tests at lower rates than the
general population (2224). Although no studies
have specifically examined cervical dysplasia and
cancer in this population, homeless women have
many risk factors for inadequate diagnosis, incomplete follow-up, and incomplete treatment because
of the competing survival needs.
Use of Health Care

Most homeless people seek care in hospital emergency rooms; only 27% go to an established ambulatory care provider. The younger homeless population
is even more likely to receive care in the emergency
room. Nearly three quarters of homeless individuals
who are hospitalized have conditions that were preventable and could have been treated before admission compared with 41% of low-income individuals
who are not homeless (25). Recurrent admission for
the same diagnosis is common and occurs in approximately 40% of homeless adults, which imposes a
financial burden on hospitals (1).
Barriers to Health Care

Approximately 57% of homeless individuals lack a
regular source of care compared with 24% of the
poor and 19% of the general population (26). Nearly
25% of homeless individuals who reported a need
for medical attention in the previous year were
unable to obtain care. The following factors contribute to this situation (1, 4, 27, 28):
Cost and lack of health insurance (55% of
homeless individuals report that they have no
medical insurance) and inability to purchase or
acquire medications
COMMITTEE OPINIONS
Lack of transportation to and from medical

facilities
Competing needs for survival (food, clothing,
shelter)
Mental illness and substance abuse
Unstable lifestyle interfering with continuity of
care and adherence with treatment
Because an exhibition of toughness is necessary
to survive on the streets, homeless individuals
may at times deny that they have health problems. They also may have a fear of authority figures, including medical providers.
Lack of availability of shelters and treatment
facilities for the homeless
Medical providers, including physicians, may
prefer not to care for homeless individuals in
their offices
Inadequate inpatient discharge planning and follow-up care because of failure to recognize
homelessness
Lack of health care professionals knowledge
and information on services available within the
community for homeless individuals
Recommendations to Improve the Health

of Homeless Women
Health care services for a homeless woman should
be a part of a multifaceted approach tailored to her
needs, perspectives, and values. Acceptance of the
individual is critical to the provision of services.
Accomplishing these goals is a major challenge to
the obstetriciangynecologist or any other health
care provider. Often the resources required, including the necessary professionals and support services,
are either not available in the community or difficult
for the private provider to obtain. Even though individual obstetriciangynecologists can and do provide services to homeless patients in their practices,
it may be more beneficial for communities to develop organized services targeted specifically to this
population that can better provide both health care
and support services. Organized services can better
implement both the preventive care and the obstetric
and gynecologic care recommended in the guidelines of the American College of Obstetricians and
Gynecologists (30). Prenatal care that coordinates
with social services, rehabilitation programs, and
housing programs to shelter homeless women during pregnancy should be the goal.
425
Health care professionals also can contribute to

improved health care for homeless women by participating in the following activities:
Care for homeless women in individual practices without bias.
Volunteer or form volunteer groups to provide
health care services at homeless shelters and
soup kitchens. Adherence to treatment is enhanced when medical care is coupled with services to meet the survival needs of patients. Care
should not be withheld because of concerns
about lack of adherence.
Seek donations of medications from pharmaceutical companies for use in homeless clinics
and shelters.
Implement health care programs for the homeless with local hospitals and clinics (see box
J.C. Lewis Health Center: An Example of
Success).
J.C. Lewis Health Center: An Example of Success

An example of a successful health care program for
homeless women is the J.C. Lewis Health Center. This
center is a 32-bed primary and respite care clinic in
Savannah, Georgia, that has saved area hospitals $10.3
million in uncompensated care for the homeless. The
center allows homeless individuals to gain access to primary care providers who manage acute and episodic
health needs and diagnose, control, and monitor chronic
health problems such as HIV, hypertension, and diabetes. The operation includes the staffing of four shelterbased primary care clinics across the city where health
promotion and primary care divert homeless people
from emergency rooms. Wellness care for the homeless
includes physical examinations, screening for disease,
and patient education. Respite care allows the hospital
to release patients too sick to stay in shelters, but not
sick enough to stay in the hospital. These individuals
would otherwise have remained hospitalized. The health
center also coordinates its services with housing and
social services to help the individuals obtain permanent
housing. Ninety-five percent of the respite care patients
ended their homelessness after leaving the program.
Program funding is provided by hospitals (each contribute $250,000 to the program), public support
through government grants ($244,000), philanthropic
organizations ($164,000), and private citizens ($19,000).
In addition, volunteers from the community, including
doctors, nurses, and educators, donate their time to the
health center, and the center receives in-kind contributions of pharmaceuticals and supplies.
The J.C. Lewis Health Center. Available at:
http://www.unionmission.org. Retrieved June 6, 2005.
426
Work with medical schools and residency programs to encourage modification of the educational curriculum to increase awareness of the
problems associated with homelessness and to
involve medical students and residents in care
for homeless individuals as part of their training.
Assess current community programs for homeless individuals and advocate for improved coordination of services between these programs and
other special programs such as prenatal care,
immunization, tuberculosis treatment, STD clinics, mental health care, and housing and legal aid.
Advocate for professional liability protections
for physicians who volunteer their services to
the homeless.
Encourage federal, state, and local governments
to provide adequate funding for the provision of
comprehensive health care services, including
mental health treatment for all homeless individuals. (See box Health Care for the Homeless Federal Program.)
Health Care for the Homeless Federal Program

The Health Care for the Homeless program is the only
federal program with the sole responsibility of addressing the primary health care needs of homeless individuals. The Health Care for the Homeless program provides primary health care and substance abuse services
at locations accessible to individuals who are homeless,
emergency care with referrals to hospitals for inpatient
care services or other needed services, outreach services to assist difficult-to-reach homeless individuals in
gaining access to care, and assistance in establishing eligibility for entitlement programs and housing.
To increase access to services and resources for people who are homeless, the grantees of the Health Care
for the Homeless program are encouraged to develop,
or actively participate in, local coalitions of health care
providers and social service agencies. These collaborations help ensure the adequate and appropriate delivery
of services to the clients of the Health Care for the
Homeless program. Each individual program determines
which service delivery system or combination of systems is appropriate for the people it serves. Programs
provide services in a variety of different settings, including traditional clinic sites, shelter-based clinics, and
mobile units. In addition, they take health care services
to locations where homeless individuals are found, such
as streets, parks, and soup kitchens.
Bureau of Primary Health Care. Health Care for the Homeless
Information Resource Center. 2004-2005 Health Care for the
Homeless Grantee profiles. Available at:
http://www.bphc.hrsa.gov/hchirc/directory/text_directory.htm.
The Prevention of Homelessness

Although it is critical to undertake efforts to improve
the health of homeless women, it is even more
important to undertake efforts to prevent homelessness. Increased federal, state, and local government support and provision of adequate funding for
comprehensive programs for the prevention of
homelessness, including increased availability of
affordable, usually subsidized, housing are essential
to this goal. Numerous studies indicate that affordable housing prevents homelessness more effectively than anything else. This applies to all groups of
poor people, including those with persistent and
severe mental illness or those with substance abuse
problems (29). Additional research is needed to determine other efforts that would be effective at reducing
this problem and thereby improve womens health
and the overall health of society.
References
1. Gelberg L, Arangua L. Homeless persons. In: Anderson
RM, Rice TH, Kominski GF, editors. Changing the U.S.
health care system: key issues in health services, policy,
and management. San Francisco (CA): Jossey-Bass;
2001. p.33286.
2. Link BG, Susser E, Stueve A, Phelan J, Moore RE,
Struening E. Lifetime and five-year prevalence of homelessness in the United States. Am J Public Health 1994;
84:190712.
3. Hodnicki DR, Horner SD, Boyle JS. Womens perspectives
on homelessness. Public Health Nurs 1992;9:25762.
4. Interagency Council on the Homeless. Homelessness:
programs and the people they serve. Findings of the
National Survey of Homeless Assistance Providers and
Clients. Washington, DC: U.S. Department of Housing
and Urban Development, Office of Policy Development
and Research; 1999.
5. Greene JM, Ringwalt CL. Pregnancy among three national samples of runaway and homeless youth. J Adolesc
Health 1998;23:370 7.
6. Farrow JA, Deisher RW, Brown R, Kulig JW, Kipke MD.
Health and health needs of homeless and runaway youth.
A position paper of the Society for Adolescent Medicine.
J Adolesc Health 1992;13:71726.
7. Pennbridge J, Mackenzie RG, Swofford A. Risk profile of
homeless pregnant adolescents and youth. J Adolesc
Health 1991;12:5348.
8. Weitzman BC. Pregnancy and childbirth: risk factors for
homelessness? Fam Plann Perspect 1989;21:1758.
9. Hwang SW. Is homelessness hazardous to your health?
Obstacles to the demonstration of a causal relationship.
Can J Public Health 2002;93:40710.
10. Greene JM, Ennett ST, Ringwalt CL. Prevalence and correlates of survival sex among runaway and homeless
youth. Am J Public Health 1999;89:14069.
11. Bailey SL, Camlin CS, Ennett ST. Substance use and risky
sexual behavior among homeless and runaway youth.
J Adolesc Health 1998;23:37888.
COMMITTEE OPINIONS
12. Bassuk EL, Buckner JC, Perloff JN, Bassuk SS.

Prevalence of mental health and substance use disorders
among homeless and low-income housed mothers. Am J
Psychiatry 1998;155:15614.
13. Wenzel SL, Leake BD, Gelberg L. Health of homeless
women with recent experience of rape. J Gen Intern Med
2000;15:2658.
14. Shuler PA, Gelberg L, Davis JE. Characteristics associated with the risk of unintended pregnancy among urban
homeless women: use of the Shuler Nurse Practitioner
Practice Model in research. J Am Acad Nurse Pract
1995;7:1322.
15. Gelberg L, Leake BD, Lu MC, Andersen RM, Wenzel SL,
Morgenstern H, et al. Use of contraceptive methods
among homeless women for protection against unwanted
pregnancies and sexually transmitted diseases: prior use
and willingness to use in the future. Contraception 2001;
63:27781.
16. Killion CM. Poverty and procreation among women. An
anthropologic study with implications for health care
providers. J Nurse Midwifery 1998;43:2739.
17. Stein JA, Lu MC, Gelberg L. Severity of homelessness
and adverse birth outcomes. Health Psychol 2000;19:
524 34.
18. Ventura SJ, Martin JA, Curtin SC, Mathews TJ. Births:
final data for 1997. Natl Vital Stat Rep 1999;47(18):196.
19. Chavkin W, Kristal A, Seabron C, Guigli PE. The reproductive experience of women living in hotels for the
homeless in New York City. NY State J Med 1987; 87:
10 3.
20. Killion CM. Special health care needs of homeless pregnant women. ANS Adv Nurs Sci 1995;18:44 56.
21. Cowal K, Shinn M, Weitzman BC, Stojanovic D, Labay L.
Mother-child separations among homeless and housed
families receiving public assistance in New York City. Am
J Community Psychol 2002;30:71130.
427
22. Chau S, Chin M, Chang J, Luecha A, Cheng E,

Schlesinger J, et al. Cancer risk behaviors and screening
rates among homeless adults in Los Angeles County.
Cancer Epidemiol Biomarkers Prev 2002;11:4318.
23. Long HL, Tulsky JP, Chambers DB, Alpers LS, Robertson
MJ, Moss AR, et al. Cancer screening in homeless
women: attitudes and behaviors. J Health Care Poor
Underserved 1998;9:27692.
24. Weinreb L, Goldberg R, Perloff J. Health characteristics
and medical service use patterns of sheltered homeless
and low-income housed mothers. J Gen Intern Med 1998;
13:38997.
25. Salit SA, Kuhn EM, Hartz AJ, Vu JM, Mosso AL.
Hospitalization costs associated with homelessness in
New York City. N Engl J Med 1998;338:173440.
26. Gallagher TC, Andersen RM, Koegel P, Gelberg L.
Determinants of regular source of care among homeless
adults in Los Angeles. Med Care 1997;35:81430.
27. Lim YW, Andersen R, Leake B, Cunningham W, Gelberg
L. How accessible is medical care for homeless women?
Med Care 2002;40:51020.
28. Kushel MB, Vittinghoff E, Haas JS. Factors associated
with the health care utilization of homeless persons.
JAMA 2001;285:2006.
29. U.S. Department of Housing and Urban Development,
U.S. Department of Health and Human Services. Practical
lessons: the 1998 National Symposium on Homelessness
Research. Available at: http://aspe.hhs.gov/progsys/home
less/symposium/toc.htm. Retrieved April 12, 2005.
102:111724.
428
ACOG
Committee on
Health Care for
Underserved Women
Committee on
Obstetric Practice
The Committees would like to
thank Kelli Mudd Miller, MD,
and Kirsten Smith, MD, for their
this bulletin.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Smoking cessation during pregnancy.
2005;106:8838.
Committee
Opinion
(Replaces Educational Bulletin 260,

September 2000)
Smoking Cessation During Pregnancy

ABSTRACT: Smoking is one of the most important modifiable causes of poor
pregnancy outcomes in the United States. An office-based protocol that systematically identifies pregnant women who smoke and offers treatment has
been proved to increase quit rates. For pregnant women who are light to moderate smokers, a short counseling session with pregnancy-specific educational materials often is an effective intervention for smoking cessation. The
5 As is an office-based intervention developed for use by trained practitioners. Techniques for smoking reduction, pharmacotherapy, and health
care support systems can help smokers quit.
Epidemiology
Increased public education measures and public health campaigns in the
United States have led to a decline in smoking during pregnancy (1).
Pregnancy appears to motivate women to make lifestyle changes; approximately 46% of prepregnancy smokers quit during pregnancy (1). From 1990
to 2003, the rate of smoking reported by pregnant women decreased from
18.4% (2) to 11% (3). The smoking rate during pregnancy in 2002 for
women ages 18 and 19 years was 18%, higher than that for pregnant women
of any other age (4).
Consequences of Maternal Smoking

The biologic evidence that maternal smoking has a detrimental effect on the
fetus includes fetal hypoxia from increased carboxyhemoglobin; reduced
blood flow to the uterus, placenta, and fetus; and direct effects of nicotine
and other compounds in tobacco smoke on the placenta and fetus (5). Health
risks associated with smoking during pregnancy include intrauterine growth
restriction, placenta previa, and abruptio placentae (5). Adverse pregnancy
outcomes include premature rupture of membranes (6, 7), low birth weight,
and perinatal mortality (5). Evidence also suggests that smoking is associated with an increase in ectopic pregnancies (5). It is estimated that eliminating smoking during pregnancy would reduce infant deaths by 5% (8) and
reduce the incidence of singleton low-birth-weight infants by 10.4% (9).
COMMITTEE OPINIONS
There is a strong association between smoking during pregnancy and sudden infant death syndrome
(SIDS) (5). Children born to mothers who smoke
during pregnancy are at increased risk for asthma
(10), infantile colic (11), and childhood obesity (12).
Successful smoking cessation before the third
trimester eliminates much of the reduced birth
weight caused by maternal smoking (5). Women
who continue to smoke during pregnancy must
achieve very low levels of tobacco use to see
improvements in infant birth weight, and they must
quit entirely if their infants are to have birth weights
similar to those of women who do not smoke (13).
Intervention
Both cessation of tobacco use and prevention of
relapse to smoking are key clinical intervention
strategies during pregnancy. Techniques for helping
patients to stop smoking have included counseling,
cognitive and behavioral therapy, hypnosis, acupuncture, and pharmacologic therapy. A 515-minute
counseling session performed by appropriately
trained health care providers is most effective with
pregnant women who smoke fewer than 20 cigarettes
per day (14). This intervention, known as the 5 As, is
appropriate for use during routine prenatal office visits and includes the following five steps: Ask, Advise,
Assess, Assist, and Arrange. The intervention is
adapted from the U.S. Public Health Service clinical
practice guideline, Treating Tobacco Use and
Dependence (14). Its effectiveness can be enhanced
for those who smoke any amount by referring the
patient to a pregnancy-specific smokers quitline.
The approach described in the box and outlined as
follows guides the provider through the interaction
and in documentation of the treatment (14).
1. Ask about smoking status. Providers should ask
the patient at the first prenatal visit to choose a
statement that best describes her smoking status
from a list of statements on smoking behavior
(see the box). Using this multiple-choice method
is more likely to elicit an accurate response than
asking a question that elicits a simple yes or
no answer. A smoking cessation chart, a tobacco use sticker, or a vital signs stamp that
includes smoking status may be useful in the
medical record to remind providers to ask
patients about smoking status at follow-up visits
(see resource box).
429
2. Advise patients who smoke to stop by providing

clear, strong advice to quit with personalized
messages about the benefits of quitting and the
impact of continued smoking on the woman,
fetus, and newborn. Congratulate patients who
report having stopped smoking and affirm their
efforts with a statement about the benefits of
quitting.
3. Assess the patients willingness to attempt to
quit smoking within the next 30 days. One
approach to this assessment is to say, Quitting
smoking is one of the most important things you
can do for your health and your babys health. If
we can give you some help, are you willing to
try? If the patient is willing, the provider can
move to the next step. If the patient is unwilling
to try, providers may consider having a brief discussion with the patient to educate and reassure
her about quitting (14). Quitting advice, assessment, and assistance should be offered at subsequent prenatal care visits.
4. Assist patients who are interested in quitting by
providing pregnancy-specific, self-help smoking cessation materials (see resource box).
Enhance the patients problem-solving skills by
asking when and where she typically smokes
and suggesting how she might avoid these situations that trigger the desire to smoke. Offer
support on the importance of 1) having a smokefree space at home, 2) seeking out a quitting
buddy such as a former smoker or nonsmoker
both at work and at home, and 3) understanding
nicotine withdrawal, such as irritability and
cravings. Communicate caring and concern and
encourage the patient to talk about the process
of quitting.
The provider also may refer the patient to a
smokers quitline. Telephone quitlines offer
information, direct support, and ongoing counseling and have been very successful in helping
pregnant smokers quit and remain smoke free
(15). Great Start (1-866-66-START) is a national pregnancy-specific smokers quitline operated
by the American Legacy Foundation. Some
states also have proactive direct fax referral
capability for providers to connect pregnant
smokers directly to their state quitline. By dialing the national quitline network (1-800-QUIT
NOW), callers are routed immediately to their
state smokers quitline.
430
5. Arrange follow-up visits to track the progress of

the patients attempt to quit smoking. For current
and former smokers, smoking status should be
monitored throughout pregnancy, providing
opportunities to congratulate and support success, reinforce steps taken toward quitting, and
advise those still considering a cessation attempt.
Although counseling and pregnancy-specific
materials are effective cessation aids for many pregnant women, some women continue to smoke.
These women often are heavily addicted to nicotine
and should be Asked and Advised and Assessed
about smoking at follow-up visits. Women who continue to smoke may benefit from screening for alcohol use and other drug use (16). If the alcohol or
drug use screen result is positive, information about
the risks associated with alcohol and drug use during pregnancy should be added to the Advise step,
and specific strategies for abstaining from alcohol
and drugs should be discussed in the Assist step.
Clinicians also may consider referring patients for
additional psychosocial treatment (14).
Although quitting smoking early in pregnancy
yields the greatest benefits for the pregnant woman
and fetus, quitting at any point can be beneficial
(14). The benefits of cutting down are difficult to
measure or verify. The effort of women who cut
down should be reinforced, but these women also
should be reminded that quitting entirely brings the
best results for their health, the health of the fetus,
and that of their babies (17).
Approximately 6080% of women who quit
smoking during pregnancy return to smoking within
a year postpartum (1). Former smokers should be
counseled in the third trimester and at the postpartum visit and subsequent gynecology visits concerning relapse to smoking (18).
Pharmacotherapy
The use of nicotine replacement products or other
pharmaceuticals for smoking cessation aids during
pregnancy and lactation have not been sufficiently
evaluated to determine their efficacy or safety.
Nicotine gum, lozenges, patches, inhalers, and special-dose antidepressants that reduce withdrawal
symptoms, such as bupropion, should be considered for use during pregnancy and lactation only
when nonpharmacologic treatments (eg, counseling) have failed. If the increased likelihood of
Smoking Cessation Intervention

for Pregnant Patients
Ask1 minute
Ask the patient to choose the statement that best
describes her smoking status:
A. I have NEVER smoked or have smoked FEWER
THAN 100 cigarettes in my lifetime.
B. I stopped smoking BEFORE I found out I was pregnant, and I am not smoking now.
C. I stopped smoking AFTER I found out I was pregnant, and I am not smoking now.
D. I smoke some now, but I have cut down on the
number of cigarettes I smoke SINCE I found out I
was pregnant.
E. I smoke regularly now, about the same as BEFORE I
found out I was pregnant.
If the patient stopped smoking before or after she found
out she was pregnant (B or C), reinforce her decision to
quit, congratulate her on success in quitting, and encourage her to stay smoke free throughout pregnancy and
postpartum.
If the patient is still smoking (D or E), document smoking status in her medical record, and proceed to Advise,
Assess, Assist, and Arrange.
Advise1 minute
Provide clear, strong advice to quit with personalized
messages about the benefits of quitting and the
impact of smoking and quitting on the woman, fetus,
and newborn.
Assess1 minute
Assess the willingness of the patient to attempt to quit
within 30 days.
If the patient is ready to quit, proceed to Assist.
If the patient is not ready, provide information to motivate the patient to quit and proceed to Arrange.
Assist3 minutes
Suggest and encourage the use of problem-solving
methods and skills for smoking cessation (eg, identify
situations that trigger the desire to smoke).
Provide social support as part of the treatment (eg,
We can help you quit).
Arrange social support in the smokers environment
(eg, identify a quit buddy and smoke-free space).
Provide pregnancy-specific, self-help smoking cessation materials.
Arrange1 minute or more
Assess smoking status at subsequent prenatal visits
and, if patient continues to smoke, encourage cessation.
Adapted from Melvin CL, Dolan-Mullen P, Windsor RA Jr,
Whiteside HP, Goldenberg RL. Recommended cessation counselling for pregnant women who smoke: a review of the evidence. Tob Control 2000;9(suppl 3):III804. Reproduced with
permission from the BMJ Publishing Group.
COMMITTEE OPINIONS
431
Resources for Smoking Cessation

Gynecologists Resources for the Clinician
Smoking cessation during pregnancy: a clinicians guide
to helping pregnant women quit smoking. Washington,
DC: ACOG; 2002. Contains guidelines, a tool kit for the
clinician, lecture guide, and CD-ROM. Request a copy by
e-mail to: smoking@acog.org. Lecture guide is available
online. Go to www.acog.org/goto/smoking.
Treating tobacco use and dependence: clinicians packet.

A how-to guide for implementing the Public Health Service
Clinical Practice Guidelines. Washington, DC: U.S. Public
Health Service; 2003. Available at: www.surgeongeneral.
gov/tobacco/clincpack.html. Retrieved June 22, 2005.
Dartmouth Medical School. Smoking cessation for pregnancy and beyond: learn proven strategies to help your patients
quit. Hanover (NH): Dartmouth Medical School; 2004.
Available for purchase from the ACOG Distribution Center
(800-762-2264, sales.acog.org): Item No. AA423; price: $25.
The American Heart Association

www.americanheart.org

Smoking and womens health. In: Special issues in womens
health. Washington, DC: ACOG; 2005. p. 15167. Available
for purchase from the ACOG Distribution Center (800-7622264, sales.acog.org): Item No. AA451; price: $59; ACOG
members: $45. Available online to members. Go to
www.acog.org/goto/underserved.
American College of Obstetricians and Gynecologists Ask
about tobacco use chart stickers. Washington, DC: ACOG.
(800-762-2264, sales.acog.org): Item No. AA268; price:
$19/260 stickers; ACOG members: $15/260 stickers.
Other Resources for the Clinician
The following resources are for information purposes only.
Referral to these sources and web sites does not imply the
endorsement of ACOG. This list is not meant to be comprehensive. The exclusion of a source or web site does not
reflect the quality of that source or web site. Please note
that web sites are subject to change without notice.
Many states offer free or low-cost smoking cessation
counseling services consisting of telephone quitlines,
group or individual counseling programs, and materials to
help the smoker quit and prevent relapse. Check with the
state or local public health office or tobacco control program to access these resources.
Helping pregnant women quit smoking: progress and future
directions. Nicotine Tob Res 2004; 6(suppl 2): S95277.
National Partnership to Help Pregnant Smokers Quit: has
tools on helping patients quit, assessing smokers quitlines, and obtaining Medicaid reimbursement for smoking
cessation services. Posters are also available.
Web: www.helppregnantsmokersquit.org.
E-mail: info@helppregnantsmokersquit.org.
British Medical Association. Smoking and reproductive life:
the impact of smoking on sexual, reproductive and child
health. London (UK): BMA; 2004. Available at:
www.bma.org.uk/ap.nsf/Content/smokingreproductivelife/
$file/smoking.pdf. Retrieved June 22, 2005.
Web Sites
American Cancer Society
www.cancer.org
The Centers for Disease Control and Prevention: Tobacco

Information and Prevention Source (TIPS).
www.cdc.gov/tobacco
TIPS contains documents for health providers to implement
tobacco control programs
The National Cancer Institute
www.cancer.gov
National Partnership to Help Pregnant Smokers Quit
www.helppregnantsmokersquit.org/quit/toll_free.asp
The partnership has a listing of states with pregnancyspecific quitlines.
Smoke-Free Families
www.smokefreefamilies.org
Smokefree.gov
www.smokefree.gov
Web site has multiple cessation strategies and information
for smokers.
Resources for Patients
American College of Obstetricians and Gynecologists, SmokeFree Families. Need help putting out that cigarette?
Washington, DC: ACOG; Chapel Hill (NC): Smoke-Free
Families; 2001. Available in English and Spanish for purchase
from the ACOG Distribution Center (800-762-2264,
sales.acog.org): Item Nos. AA424 and AA4245; price:
$10/10 booklets.
You can quit smoking: support and advice from your prenatal
care provider. Available at: www.surgeongeneral.gov/tobacco/
prenatal.pdf. Retrieved June 22, 2005. Available for multiple
orders from AHRQ (PO Box 8547, Silver Spring MD 209078547, 800-358-9295): Item No. AHRQ 00-0052.
Recomendaciones y apoyo de su mdico de cuidados, Spanish
language. Available at: www.surgeongeneral.gov/tobacco/
prenatalsp.pdf. Retrieved June 22, 2005. Available for multiple
orders from AHRQ (PO Box 8547, Silver Spring MD 209078547, 800-358-9295): Item No. AHRQ 00-0065.
American Legacy Foundation. Great start quitline. Available at:
www.americanlegacy.org/greatstart/html/quitline.html.
Retrieved: June 22, 2005. 866-66-START for toll free help
MondayFriday 8:00 AM8:00 PM (Eastern Time) and Saturday
9:00 AM4:00 PM. Counseling in English or Spanish.
432
smoking cessation, with its potential benefits, outweighs the unknown risk of nicotine replacement
and potential concomitant smoking, nicotine
replacement products or other pharmaceuticals may
be considered (14). Because potential benefits seem
to outweigh potential risks, research to determine
the safety and efficacy of pharmacotherapy is
underway. Some tobacco control experts have
reported that if nicotine replacement therapy is
used during pregnancy, products with intermittent
dosages, such as the gum or inhaler, should be tried
first (19). If the nicotine patch is used, it can be
removed at night to reduce fetal nicotine exposure
(20). Nicotine replacement therapy also may be
considered during lactation. Optimally, smokers
can be treated with these pharmacotherapies before
conception.
Support Systems
The Agency for Healthcare Research and Quality
has recommended systems changes to help health
care providers identify and treat tobacco users (14).
These changes require the partnership of health care
administrators and insurers, and include the following strategies: 1) provide education, resources, and
feedback to promote provider involvement in smoking cessation; 2) promote hospital policies that support and provide smoking cessation services; 3)
include effective smoking cessation treatments as
paid or covered services in all health benefits packages; and 4) reimburse clinicians and specialists for
delivery of effective tobacco dependence treatments
and include these interventions among the defined
duties of the clinicians (14).
Coding
Office visits specifically addressing smoking cessation may be coded using International Classification
of Diseases, Ninth Revision, Clinical Modification
(ICD-9-CM) code 305.1 (tobacco use disorder,
tobacco dependence from the Mental Health section) with Current Procedural Terminology* (CPT )
code 99401 or 99211:
* Current Procedural Terminology (CPT) is copyright 2004
American Medical Association. All rights reserved. No fee
schedules, basic units, relative values or related listings are
included in CPT. The AMA assumes no liability for the data
contained herein. CPT is a trademark of the American
Medical Association.
CPT code 99401 (preventive medicine counseling lasting approximately 15 minutes): If counseling is done by the physician at the time of a
regular antepartum visit, use modifier 25 on
code 99401. If counseling is done by the physician at another encounter, separate from the
antepartum visit, no modifier is needed with
code 99401.
CPT code 99211: If a nurse counsels the patient,
and if nurses are recognized by the insurance
company as qualified providers of the service,
code 99211 would be used instead of code
99401. If the nurse is not recognized as a caregiver, the services will not be covered unless
provided by the physician.
Note that not all payers reimburse for counseling
outside of the global package and some do not cover
preventive services at all.
Many private and public insurers are changing
policy to provide coverage for smoking cessation
counseling for pregnant women. Although coverage
for such counseling may have been denied previously, it may be prudent for the clinician to continue to
submit for reimbursement for these services.
References
1. Colman GJ, Joyce T. Trends in smoking before, during,
and after pregnancy in ten states. Am J Prev Med
2003;24:2935.
2. Smoking during pregnancyUnited States19902002.
Centers for Disease Control and Prevention. MMWR
Morb Mortal Wkly Rep 2004;53:9115.
3. Hamilton BE, Martin JA, Sutton PD. Births: preliminary
data for 2003. Centers for Disease Control and Prevention,
National Center for Health Statistics. Natl Vital Stat Rep
2004;53(a):117.
States, 2004: with chartbook on trends in the health of
Americans. Hyattsville (MD): NCHS; 2004. Available at:
http://www.cdc.gov/nchs/data/hus/hus04.pdf. Retrieved June
20, 2005.
5. U.S. Department of Health and Human Services. The
health consequences of smoking: a report of the Surgeon
General. Washington, DC: HHS; 2004. Available at: www.
cdc.gov/tobacco/sgr/sgr_2004/chapters.htm. Retrieved
June 20, 2005.
6. Castles A, Adams EK, Melvin CL, Kelsch C, Boulton
ML. Effects of smoking during pregnancy. Five metaanalyses. Am J Prev Med 1999;16:20815.
7. Spinillo A, Nicola S, Piazzi G, Ghazal K, Colonna L,
Baltaro F. Epidemiological correlates of preterm premature rupture of membranes. Int J Gynaecol Obstet 1994;
47:715.
COMMITTEE OPINIONS
8. Salihu HM, Aliyu MH, Pierre-Louis BJ, Alexander GR.

Levels of excess infant deaths attributable to maternal
smoking during pregnancy in the United States. Matern
Child Health J 2003;7:21927.
9. Ventura SJ, Hamilton BE, Mathews TJ, Chandra A.
Trends and variations in smoking during pregnancy and
low birth weight: evidence from the birth certificate,
1990-2000. Pediatrics 2003;111:117680.
10. Li YF, Langholz B, Salam MT, Gilliland FD. Maternal
and grandmaternal smoking patterns are associated with
early childhood asthma. Chest 2005;127:123241.
11. Sondergaard C, Henriksen TB, Obel C, Wisborg K.
Smoking during pregnancy and infantile colic. Pediatrics
2001;108:3426.
12. von Kries R, Toschke AM, Koletzko B, Slikker W Jr.
Maternal smoking during pregnancy and childhood obesity. Am J Epidemiol 2002;156:95461.
13. England LJ, Kendrick JS, Wilson HG, Merritt RK,
Gargiullo PM, Zahniser SC. Effects of smoking reduction
during pregnancy on the birth weight of term infants. Am
J Epidemiol 2001;154:694701.
14. Fiore MC, Bailey WC, Cohen SJ, Dorfman SF, Goldstein
MG, Gritz ER. Treating tobacco use and dependence.
Clinical practice guideline. Rockville (MD): U.S. Department of Health and Human Services, Public Health Service; 2000.
433
15. Tomson T, Helgason AR, Gilljam H. Quitline in smoking

cessation: a cost-effectiveness analysis. Int J Technol
Assess Health Care 2004;20:46974.
16. Ockene J, Ma Y, Zapka J, Pbert L, Valentine Goins K,
Stoddard A. Spontaneous cessation to smoking and alcohol use among low-income pregnant women. Am J Prev
Med 2002;23:1509.
17. Melvin CL, Dolan-Mullen P, Windsor RA, Whiteside HP
Jr, Goldenberg RL. Recommended cessation counselling
for pregnant women who smoke: a review of the evidence.
Tob Control 2000;9(suppl 3):III804.
18. Dolan Mullen P. How can more smoking suspension during pregnancy become lifelong abstinence? Lessons
learned about predictors, interventions, and gaps in our
accumulated knowledge. Nicotine Tob Res 2004;6(suppl
2):S21738.
19. Benowitz N, Dempsey D. Pharmacotherapy for smoking
cessation during pregnancy. Nicotine Tob Res 2004;6
(suppl 2):S189202.
20. Windsor R, Oncken C, Henningfield J, Hartmann K,
Edwards N. Behavioral and pharmacological treatment
methods for pregnant smokers: issues for clinical practice.
J Am Med Womens Assoc 2000;55:30410.
434
ACOG
Committee on
Health Care for
Underserved Women
Committee
Opinion

to be followed.
The Committee on Health Care
for Underserved Women wishes
to thank Raymond L. Cox, MD,
MBA, for his invaluable assistance in the development of this
document.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Racial and ethnic disparities in

womens health. ACOG Committee
Racial and Ethnic Disparities in

Womens Health
ABSTRACT: Significant racial and ethnic disparities exist in womens health.
These health disparities largely result from differences in socioeconomic
status and insurance status. Although many disparities diminish after taking
these factors into account, some remain because of health care system-level,
patient-level, and provider-level factors. The American College of Obstetricians and Gynecologists strongly supports the elimination of racial and
ethnic disparities in the health and the health care of women. Health professionals are encouraged to engage in activities to help achieve this goal.
Health disparities can be defined as differences in the incidence, prevalence,

mortality, and burden of diseases and other adverse health conditions that
exist among specific population groups in the United States (1). These differences can be assessed according to a variety of factors including gender,
race or ethnicity, education, income, disability, geographic location, or sexual orientation (2). Although significant health disparities occur between men
and women and among certain groups of women based on the factors mentioned previously, disparities are most likely to be experienced by women
who are members of racial and ethnic minority groups. For example, disease
and premature death occur disproportionately in minority women compared
with non-Hispanic white women (3).
Approximately 44 million women in the United States, nearly one third
of all women in this country, are members of racial and ethnic minority
groups. African-American women and women of Hispanic origin together
comprise roughly one quarter of the total population of U.S. women (4). The
Hispanic population accounted for 22% of the 4 million births in the United
States in 2003 (5). The largest segment of the immigrant population in the
United States is from Latin America (6).
It is important to note that race and ethnicity are primarily social characteristics much more than they are biologic categories. However, race and ethnicity can provide useful information to womens health care providers about
environmental, cultural, behavioral, and medical factors that may affect their
patients health. Also, the frequency of certain genetic variations may differ
between racial or ethnic groups. For instance, there is an increased frequency
COMMITTEE OPINIONS
of mutations for certain genetic diseases, such as

Tay-Sachs disease, in individuals of Ashkenzic
Jewish descent. These differences in the frequency
of genetic variations generally are related to a common ancestral lineage (founder effect).
Genetic polymorphisms associated with increased susceptibility to disease also may vary in
frequency in different racial and ethnic groups (7).
Another consideration is the issue of gene-environment interaction. Genetic variations, even those that
do not vary in frequency among racial or ethnic
groups, may enhance susceptibility to an environmental exposure that occurs more frequently in a
particular racial or ethnic group. Thus, although race
and ethnicity are primarily social constructs, the
impact of common ancestral lineage on the segregation and frequency of genetic variations in combination with the influence of cultural factors on
environmental exposures cannot be ignored. All of
these factors should be considered when trying to elucidate the multifactorial causes of health disparities.
Examples of Racial and Ethnic Health

Disparities Among Women
During 19911995, heart disease death rates
remained the highest for African-American
women, followed by white, American Indian/
Alaskan Native, and Asian/Pacific Islander
women, with more than a twofold difference
between the lowest and highest rates (8).
Asian/Pacific Islander women, especially those
who are Vietnamese; black women; and
Hispanic white women have higher incidence
rates of invasive cervical cancer than nonHispanic white women (9, 10). Cervical cancer
mortality rates are higher among American
Indian/Alaskan Natives than among all racial
and ethnic populations (3.7 per 100,000 population and 2.6 per 100,000 population, respectively) despite lower incidence (11).
When compared with white women, black
women have a higher mortality rate (34.7 per
100,000 compared with 25.9 per 100,000) for
breast cancer despite a lower breast cancer incidence rate (10).
Seventy-eight percent of the female population
with acquired immunodeficiency syndrome
(AIDS) is African American or Hispanic.
Although American Indian/Alaskan Native
435
women have a lower annual rate of new AIDS

cases (4.8 per 100,000) than non-Hispanic black
(50.2 per 100,000) and Hispanic (12.4 per
100,000) women, the rate is still more than twice
the rate for non-Hispanic white women (2.0 per
100,000) (12).
Non-Hispanic black and some Hispanic populations have preterm births at rates 60% and 27%
higher, respectively, than the rate for nonHispanic white women (13).
African-American women have higher infant,
fetal, and perinatal mortality rates than white
women (14) (see Table 1).
Although maternal mortality ratios for all ethnic
groups have declined over the past half century,
racial and ethnic disparities in maternal mortality have actually increased (15, 16). AfricanAmerican women are three to six times more
likely to have a pregnancy-related death than
white women (16).
Understanding the Causes of Health

Disparities
Many health disparities are directly related to
inequities in income, housing, safety, education, and
job opportunities; they largely result from differences in socioeconomic status and insurance status.
Although many disparities diminish after taking
these factors into account, some remain because of
health care system-level, patient-level, and providerlevel factors (17).
The current U.S. health care financing paradigm
inadvertently may contribute to disparities in health
outcomes. The United States is the only developed
country that does not extend health care as a right of
citizenship. In the United States, health care is
Table 1. Infant, Fetal, and Perinatal Mortality by Race
of Mother
Race of
Mother
White
Black or
Africian
American
Infant
Mortality Rate
Fetal
Mortality Rate
Perinatal
Mortality Rate
5.8
5.5
5.9
14.4
11.9
12.8
National Center for Health Statistics. Health, United States, 2004: with
chartbook on trends in the health of Americans. Hyattsville (MD):
NCHS; 2004. Available at: http://www.cdc.gov/nchs/data/hus/hus04.pdf.
436
driven by market forces; the ultimate goal of the

health care business is to maximize profit. For these
reasons, this health care system contributes to a lack
of access for citizens who are either uninsured or
underinsured. The varying geographic availability of
health care institutions also may contribute to racial
and ethnic disparities in health care.
Access to health insurance coverage and care
and utilization of care is significantly different for
minority women. The following examples illustrate
this point:
Hispanic and African-American women are
more likely to be uninsured than white women.
In 2001, 16% of white women, 20% of AfricanAmerican women, and 37% of Hispanic women
1864 years of age were uninsured (18).
Asian-American and Hispanic women are most
likely to have not received preventive care in the
past year. In 1998, 29% of Asian-American
women and 21% of Hispanic women received
no preventive services in the previous year compared with 16% of white women and 7% of
African-American women. (19).
The proportion of Asian-American women
obtaining Pap tests was considerably lower than
that for white women. Only approximately one
half (49%) of Asian-American women reported
receiving a Pap test in the previous year compared with 64% of white women (19).
Non-Hispanic black, Hispanic, and American
Indian women are more than twice as likely as
non-Hispanic white women to begin prenatal
care in the third trimester or not at all (5).
Evidence suggests that factors such as stereotyping and prejudice on the part of health care
providers may contribute to racial and ethnic disparities in health (17). Additionally, cultural differences
between the health care provider and patient can
cause communication problems between the patient
and the provider and can lead to an inaccurate
understanding of the patients symptoms. Ambiguities between health care providers and patients
understanding and interpretation of information
may contribute to disparities in care (17). For example, language and literacy barriers interfere with
physicianpatient communication and can contribute to culturally derived mistrust of the health
care system and to reduced adherence to health care
provider recommendations. Use of traditional or
folk remedies can interfere with science-based treatments. There also are lifestyle risk factors, such as
unhealthy diets, low levels of physical activity, and
alcohol and tobacco use, which contribute to morbidity and mortality and are more prevalent among
certain populations (3).
ACOG Recommendations
Gynecologists strongly supports the elimination of
racial and ethnic disparities in womens health and
health care as well as gender disparities in health
and health care. The elimination of disparities in
womens health and health care requires a comprehensive, multilevel strategy that involves all members of society. Our goal as health care providers
and leaders must be to optimize individuals health
status and the quality of health care. We encourage
health professionals to engage in the following
activities:
1. Advocate for universal access to basic affordable health care (20).
2. Improve cultural competency in the physician
patient relationship and engage in cross-cultural
educational activities to improve communication and language skills (21).
3. Use national best practice guidelines to reduce
unintended variation in health care outcomes by
gender, race, and ethnicity.
4. Provide high quality, compassionate, and ethically sound health care services to all. Engage
in dialogue with patients to determine their care
expectations, and counsel patients regarding the
benefits of preventive health care and early
screening, intervention, and treatment.
5. Advocate for increased public awareness of the
benefits of preventive health care and early
screening and intervention.
6. Encourage and become active in recruiting
minorities to the health professions.
7. Advocate for improved access to programs that
develop fluency in English among non-English
speaking populations.
8. Acquire team-building skills to help attract and
retain qualified nurses and other health professionals for provision of quality services to
underserved women.
COMMITTEE OPINIONS
9. Conduct research to determine causes of health

disparities and develop and evaluate interventions to address these causes.
10. Advocate for the continued collection of racebased data which is important in understanding
disparities. Advocate for increased funding for
this research.
11. Increase training of health care providers about
racial, ethnic, and gender disparities in health
and health care.
12. Support safety net providers, including public
health systems, urban academic centers, and
other health care delivery systems that are more
likely to provide health care to minority populations.
References
1.
2.
3.
4.
5.
6.
7.
8.
Fauci AS. Slideshow: The NIH Strategic Plan to Address

Health Disparities. Bethesda (MD): National Institutes of
Allergy and Infectious Diseases; 2000. Available at:
http://www.niaid.nih.gov/director/healthdis.htm.
U.S. Department of Health and Human Services. Healthy
people 2010: understanding and improving health. 2nd ed.
Available at: http://www.healthypeople.gov/Document/
pdf/uih/2010uih.pdf. Retrieved June 23, 2005.
Clark A, Fong C, Romans M. Health disparities among
U.S. women of color: an overview. Washington, DC: The
Jacobs Institute of Womens Health; 2002.
U.S. Bureau of the Census. Population by age, sex, race,
and Hispanic or Latino origin for the United States:
2000(PHC-T-9). Washington, DC: The Bureau;
2001. Available at: http://www.census.gov/population/
www/cen2000/phc-t9.html. Retrieved June 23, 2005.
Hamilton BE, Martin JA, Sutton PD. Births: preliminary
data for 2003. Natl Vital Stat Rep 2004;53(9):117.
Larsen LJ. The foreign-born population in the United States:
2003: population characteristics. Current Population
Reports, P20-539. Washington, DC: US Census Bureau;
2004. Available at: http://www.census.gov/prod/2004
pubs/p20551.pdf. Retrieved June 23, 2005.
Romero R, Kuivaniemi H, Tromp G, Olson J. The design,
execution, and interpretation of genetic association studies to decipher complex diseases. Am J Obstet Gynecol
2002;187:1299312.
Casper ML, Barnett E, Halverson JA, Elmes GA, Braham
VE, Majeed ZA, et al. Racial and ethnic disparities in
heart disease among women. In: Women and heart disease: an atlas of racial and ethnic disparities in mortality.
2nd ed. Atlanta (GA): Centers for Disease Control and
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
437
Prevention; Morgantown (WV): West Virginia University,

Office for Social Environment and Health Research;
2000. Available at: ftp://ftp.cdc.gov/pub/Publications/
womens_atlas/00-atlas-all.pdf. Retrieved June 22, 2005.
p. 1924.
Satcher D. American women and health disparities [editorial]. J Am Med Womens Assoc 2001;56:1312, 160.
Ries LA, Eisner MP, Kosary CL, Hankey BF, Miller BA,
Clegg L, et al., editors. SEER cancer statistics review,
19752002. Bethesda (MD): National Cancer Institute;
2005. Available at: http://seer.cancer.gov/csr/1975_2002.
Cancer mortality among American Indians and Alaska
NativesUnited States, 19941998. Centers for Disease
Control and Prevention. MMWR Morb Mortal Wkly Rep
2003;52:7047.
Centers for Disease Control and Prevention. HIV/AIDS
Surveillance Report, 2003;15:146. Available at:
http://www.cdc.gov/hiv/stats/2003SurveillanceReport.pdf.
Martin JA, Hamilton BE, Sutton PD, Ventura SJ,
Vital Stat Rep 2003;52(10):1113.
National Center for Health Statistics. Health, United
http://www.cdc.gov/nchs/data/hus/hus04.pdf. Retrieved
June 23, 2005.
Differences in maternal mortality among black and white
womenUnited States, 1990. MMWR Morb Mortal
Wkly Rep 1995;44:67, 134.
State-specific maternal mortality among black and white
womenUnited States, 19871996. MMWR Morb Mortal
Wkly Rep 1999;48:4926.
Institute of Medicine (US). Unequal treatment: confronting racial and ethnic disparities in healthcare.
Washington, DC: The Institutes 2002.
Kaiser Family Foundation. Racial and ethnic disparities
in womens health coverage and access to care: findings
from the 2001 Kaiser Womens Health Survey. Menlo
Park (CA): KFF; 2004. Available at: http://www.kff.org/
womenshealth/loader.cfm?url=/commonspot/security/get
file.cfm&PageID=33087. Retrieved June 23, 2005.
Collins KS, Schoen C, Joseph S, Duchon L, Simantov E,
Yellowitz M. Health concerns across a womans lifespan:
The Commonwealth Fund 1998 Survey of Womens
Health. New York (NY): The Commonwealth Fund;
1999.
The uninsured. ACOG Committee Opinion No. 308.
Cultural competency, sensitivity and awareness in the
delivery of health care. In: Special issues in womens
health. Washington, DC: ACOG; 2005. p. 1120.
438
ACOG
Committee on
Health Care for
Underserved Women

to be followed.
The Committee on Health Care
for Underserved Women wishes
to thank Deborah Smith, MD, and
Maureen Phipps, MD, for their
this document.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Psychosocial risk factors: perinatal

screening and intervention. ACOG
2006;108:46977.
Committee
Opinion
(Replaces Educational Bulletin 255,

November 1999)
Psychosocial Risk Factors: Perinatal

Screening and Intervention
ABSTRACT: The American College of Obstetricians and Gynecologists
advocates assessing for psychosocial risk factors and helping women manage psychosocial stressors as part of comprehensive care for women.
Psychosocial screening of all women seeking pregnancy evaluation or prenatal care should be performed regardless of social status, educational level,
or race and ethnicity. Because problems may arise during the pregnancy that
were not present at the initial visit, it is best to perform psychosocial screening at least once each trimester to increase the likelihood of identifying
important issues and reducing poor birth outcomes. When screening is completed, every effort should be made to identify areas of concern, validate
major issues with the patient, provide information, and, if indicated, make
suggestions for possible changes. When necessary, the health care provider
should refer the patient for further evaluation or intervention. Psychosocial
risk factors also should be considered in discharge planning after delivery.
Many of the psychosocial issues that increase the risk for poor pregnancy
outcome also can affect the health and welfare of the newborn. Screening
should include assessment of barriers to care, unstable housing, unintended
pregnancy, communication barriers, nutrition, tobacco use, substance use,
depression, safety, intimate partner violence, and stress.
The American College of Obstetricians and Gynecologists (ACOG) advocates addressing psychosocial issues faced by women and their families during the childbearing years. In general, psychosocial issues are nonbiomedical
factors that affect mental and physical well-being. Screening for psychosocial
risk factors may help predict a womans attentiveness to personal health matters, her use of prenatal services, and the health status of her offspring (1).
Most women undergo psychologic adaptation to pregnancy and develop coping mechanisms to deal with the routine as well as unanticipated
changes that pregnancy brings. This pregnancy-specific adaptation is greatly affected by a womans beliefs, desires, and culture. Physicians should
engage women in dialogue about these important influences. All women,
including multiparous women, must receive help in the preparation for
childbirth and parenting. Past obstetric events and infant outcomes, medical
considerations in a current pregnancy, beliefs about and experience with
COMMITTEE OPINIONS
breastfeeding, and family circumstances are some

of the factors that influence the experience of labor,
delivery, and early neonatal and postpartum adjustment. Additionally, some women experience social,
economic, and personal difficulties in pregnancy.
Some of these issues represent preexisting problems; others arise during the course of pregnancy
and may be a result of the pregnancy itself. These
are the challenges and issues commonly thought of
as risk factors for adverse maternal, fetal, and infant
outcomes.
An emerging body of evidence indicates that
women place high value on attention to psychosocial issues and report greater satisfaction with physician visits when there is more psychosocial talk
and less biomedical talk (2). Discussing and
screening for psychosocial factors, including social
support, intimate partner violence, lack of insurance
coverage, unstable housing, adapting to parenting,
and substance abuse, are beneficial.
Addressing Psychosocial Factors

in Pregnancy
Classically, prenatal protocols were intended to
establish the diagnosis of pregnancy; monitor for the
onset of complications, such as hypertensive disorders associated with pregnancy and preterm labor;
identify feto-pelvic disproportion; and prevent sudden fetal death from certain conditions, such as
maternal diabetes. During the two decades between
1970 and 1990, an appreciation of the significance
of psychosocial issues during pregnancy emerged.
Pivotal publications in the late 1980s formally recommended that preconception counseling and
enhanced prenatal education and counseling be
added to clinical practice (3, 4). One example is the
explicit detection and management of behavioral
risks, such as smoking, associated with low birth
weight as an integral part of prenatal care.
Biomedical risks, such as complications of pregnancy, concomitant maternal disease, infection,
nutritional deficiencies, and exposure to teratogens,
are estimated to account for approximately one half
of the incidence of low-birth-weight infants and of
prematurity and their postnatal sequelae (5). An
important portion of the remaining cases of these
adverse pregnancy outcomes may be attributable to
psychosocial stress even after controlling for the
effects of recognized sociodemographic, obstetric,
and behavioral risk factors (6, 7).
439
The analysis and commentary on the content of

prenatal care also have begun to include assessment
of quality of care, cultural appropriateness, and
patient responsibility and satisfaction. The American College of Obstetricians and Gynecologists
advocates assessing for psychosocial risk factors
and helping women manage psychosocial stressors
as part of comprehensive care for women (8, 9).
Screening for Psychosocial Risk

Psychosocial screening of all women seeking pregnancy evaluation or prenatal care should be performed regardless of social status, educational level,
or race and ethnicity. Given the sensitive nature of
psychosocial assessment, every effort should be
made to screen patients in private, especially when
inquiring about intimate partner or domestic violence. Even then, patients may not be comfortable
discussing problems with physicians until a trusting
relationship has been formed.
During pregnancy, problems may arise that
were not present at the initial visit; therefore, it is
best to perform psychosocial screening at least once
each trimester to increase the likelihood of identifying important issues and reducing poor birth outcomes. There is evidence that women who are
screened for psychosocial issues once each trimester
are half as likely as women who are not screened
to have a low-birth-weight or preterm baby (10).
Although psychosocial issues may be complex,
there is a reasonable degree of specificity and sensitivity to single-item (one question per topic) screening instruments. The Healthy Start Program of the
Florida Department of Health has designed a wellregarded screening system, which has been used
widely and refined. The Healthy Start tool provides
a concise and simple means of collecting psychosocial data that can be used for self-reporting or interview-style information retrieval (see the box). The
questions from this tool are now included in the
ACOG Obstetric Medical History form. Although
many of the topics identified in this tool are discussed more fully in various ACOG documents (see
Resources), consolidated information on these
topics has been provided in this document for quick
reference.
When screening is completed, every effort
should be made to identify areas of concern, validate
major issues with the patient, provide information,
and, if indicated, make suggestions for possible
440
Psychosocial Screening Tool

1. Yes
No
Do you have any problems (job, transportation, etc.) that prevent you from
keeping your health care appointments?
2. Yes
No
Do you feel unsafe where you live?
3. Yes
No
In the past 2 months, have you used

any form of tobacco?
4. Yes
No
In the past 2 months, have you used

drugs or alcohol (including beer, wine,
or mixed drinks)?
5. Yes
No
In the past year, have you been

threatened, hit, slapped, or kicked by
anyone you know?
6. Yes
No
Has anyone forced you to perform any

sexual act that you did not want to do?
7. On a 1-to-5 scale, how do you rate your current

stress level?
1
2
3
4
5
Low
High
8. How many times have you moved in the past 12
months? __________
9. If you could change the timing of this pregnancy,
would you want it
earlier
later
not at all
no change
Modified and reprinted with permission from Floridas Healthy
Start Prenatal Risk Screening Instrument. Tallahassee (FL):
Florida Department of Health; 1997. DH 3134.
changes. Screening positive for a condition often

necessitates a referral to resources outside the practice for further evaluation or intervention (3).
Therefore, having a well-developed referral network
is important to provide care successfully for a broad
range of medical and psychosocial issues. Constructing a resource list can help health care
providers develop this network and is as straightforward as contacting local hospital social services
departments and community centers. If additional
assistance is needed with locating appropriate referral sites, local or state health officials may be helpful. Using previously collected information about
community-based resources can help save time.
Examples of commonly used resources include
smoking cessation programs, weight loss programs,
womens shelters, and medical assistance programs.
Office practice staff can compile this information
and be assigned to keeping it up-to-date. It is also

important to obtain feedback from patients and staff
on their experiences with the various resources.
Psychosocial risk factors also should be considered in discharge planning after delivery. Many of
the psychosocial issues that increase the risk for
poor pregnancy outcome also can affect the health
and welfare of the newborn. In the absence of complications, a 48-hour hospital stay after a normal
vaginal delivery or a 96-hour stay after a cesarean
delivery is recommended (9). When outpatient follow-up may not be reliable, it is essential that
women with significant psychosocial problems stay
in the hospital after delivery as long as necessary to
assess adequately the health of the mother and the
newborn and educate the mother regarding postpartum issues and infant care. Documentation should
include the nature of any problems identified, the
chosen interventions, and plans for follow-up.
Identification of Contributing Factors

Barriers to Care
Inadequate insurance coverage, inability to pay for
health care services, and not knowing where to go
for care are a few of the most common barriers to
health care. Others include lack of transportation,
family support, and child care (11). These barriers
are especially problematic for adolescents. For individuals faced with these barriers, referral to an
appropriate social service agency may be useful.
These agencies can sometimes help women navigate
the health care system. In particular, they can help
women enroll in Medicaid, which covers the costs of
medical care and transportation to and from medical
and social service appointments and also subsidizes
or provides free day care. They also can help women
enroll in Early Head Start programs, which provide
services to pregnant women and their families
through a childs first 3 years of life. By flexible
scheduling of appointments, inquiring about difficulties a patient may have with keeping appointments, and assisting with solutions, the health care
provider increases the likelihood of adherence to
prenatal care recommendations.
Unstable Housing
Frequent moves can indicate a variety of problems.
For example, the patient may be having difficulty
finding acceptable affordable housing. If this is the
case, the patient can be referred to the appropriate
COMMITTEE OPINIONS
social service agency for assistance. These local

agencies also can provide information about other
resources in the area, including health services,
social support groups, and child care resources.
In addition, frequent moves may reflect violence
in the home or may indicate legal problems.
Inadequate housing also may be a source of environmental contamination and toxic exposure. Inquiring
about the patients feelings of isolation is important.
If this is a problem, referral to any available neighborhood support groups or a counselor can be helpful.
Approximately 49% of all pregnancies are unintended at the time of conception (12). This percentage is
considerably higher among adolescents. An unintended pregnancy is defined as a pregnancy that was
mistimed or unwanted at the time of conception.
Research has shown that having an unintended pregnancy is a predictor of insufficient prenatal care,
resulting in an increased risk of a poor birth outcome. Women with unintended pregnancies are
more likely to smoke, drink alcohol, or abuse substances and have a greater likelihood of giving birth
to a low-birth-weight infant. Their infants are more
likely to die within the first year of life (13). In addition, the incidence of unintended pregnancy is higher among women who have been battered (14), and
battering is more common during an unplanned
pregnancy (15).
Unintended pregnancies often become accepted
pregnancies that produce loved and wanted children.
However, women with pregnancies that remain
unwanted should be counseled about the full range of
reproductive options, including abortion and adoption. Women must be allowed to make independent
decisions about their own pregnancies. This choice
remains a womans right and must be respected.
It is important to reassess those factors that may
have resulted in an unintended pregnancy during the
pregnancy. Poor access to family planning services
or lack of education and information should be
addressed with discussion and counseling during the
course of prenatal care or in the postpartum or
postabortal period.
Communication Barriers
Barriers to care are magnified when the patient does
not speak English. Federal and state laws mandate
the provision of interpreter and translation services
441
to patients with limited English proficiency.

Innovative new technologies can make language
access easier and more effective. One new method is
the use of wireless headsets like those used during
international meetings, which allow the physician to
speak and hear in one language and the patient in
another language. Another method is videoconferencing, linking a patient and physician at one location to an interpreter at another location through the
use of computers with video cameras and microphones. If these services are not available, health
care providers can ask the patient to identify a family member or friend who can act as a translator.
This should be done as a last resort, however,
because under these circumstances, information
may be intentionally or unintentionally translated
incorrectly. For example, in cases of intimate partner
violence, if the abusive spouse is translating, he
might omit a question about safety in the home, misrepresent the patients response, or retaliate, and the
patient may choose to conceal the abuse. Another
partial solution is to provide written materials in
appropriate languages for patients who do not speak
English. If communication is not adequate, possibilities such as whether the patient should remain in the
practice or be referred to a facility with better access
to translators should be considered.
The Americans with Disabilities Act requires
that health care providers have an adequate system of
communication in place for interaction with women
who are deaf or hard of hearing. This may include
using a qualified interpreter for these women. For
these women as well as those who are blind or have
low vision, the appointment time length may be
increased in order to obtain a complete medical history and physical database; conduct psychosocial
screening; plan continued care; arrange communication systems, such as telephone relays; and obtain
education resources, such as large-print materials.
Nutrition
Problems with nutrition can occur in women of any
socioeconomic status. These problems range from
an inability to acquire and prepare food to an eating disorder. If a woman cannot afford a sufficient
supply of food, she should be referred to food
pantries and other resources in her area. All lowincome women should receive information about the
Special Supplemental Nutrition Program for
Women, Infants, and Children (WIC) and food stamp
programs. Referrals to the appropriate social ser-
442
vice agency or other available services can be helpful (9).

Women of low socioeconomic status often live
in environments that do not allow for the adequate
storage, refrigeration, or preparation of food. Many
nutritionists are trained in alternative methods of
food storage and preparation and would, therefore,
be able to assist the patient upon referral. The nutritionist also could assess the patients diet and suggest healthy foods that are inexpensive.
Questions should be asked, especially of adolescents and young women, about eating habits such as
fasting or skipping meals, which may be indicative
of anorexia and bulimia. If it is determined that the
patient has an eating disorder, referrals to a mental
health provider who specializes in this issue and a
nutritionist for counseling about food management
are essential (9). All WIC programs have nutritionists who are required to counsel patients on these
matters. Hospitalization may be required for patients
with eating disorders. Poor weight gain also may
reflect substance abuse, intimate partner violence, or
depression.
Women who are obese at the outset of pregnancy also may have altered body image and weight
gain concerns. They may require specialized instruction regarding suggested weight gain during pregnancy to optimize nutritional status and reduce risk
of future health problems (9, 16).
Tobacco Use
Smoking tobacco is associated with increased perinatal mortality, ectopic pregnancy, and bleeding
complications of pregnancy and a higher incidence
of small-for-gestational-age babies, low-birthweight babies, and preterm delivery. It is estimated
that a 5% reduction in fetal and infant deaths and a
10.4% reduction in the incidence of singleton lowbirth-weight infants (17) would be achieved if pregnant women stopped smoking (18). There is a strong
association between smoking during pregnancy and
sudden infant death syndrome (17). Children born to
mothers who smoke during pregnancy are at
increased risk for asthma (19), infantile colic (20),
and childhood obesity (21). Therefore, it is essential
that patients be screened for tobacco use and provided information on smoking cessation and why it is
necessary to stop smoking during pregnancy (22,
23). Interventions by clinicians that are as brief as
515 minutes have been shown to be effective at
improving smoking cessation rates (24).
Substance Use
The use of mind-altering substances, including illegally obtained drugs, alcohol, or the recreational use
of prescription or nonprescription drugs, puts the
pregnant woman at an increased risk for preterm
delivery and her fetus at increased risk for growth
restriction, fetal alcohol syndrome, death, or longterm neurobehavioral effects. These pregnant
women also are at increased risk for sexually transmitted diseases, including human immunodeficiency
virus (HIV). Women who use or abuse these substances often obtain prenatal care late in the pregnancy, achieve poor weight gain, and frequently
miss appointments, all of which can have negative
effects on the health of the woman and her fetus.
Substance abuse, by either the woman or her partner,
also is associated with intimate partner violence.
Asking patients about substances used at the time of
the first prenatal visit is essential bearing in mind
that often multiple substances are used; questions
about a womans partners use of substances also
may be helpful. If either inquiry indicates an area of
concern, additional assessment is required (25).
Depression
Mood disorders, especially depression, are among
the leading causes of disease-related disability in
women of childbearing age (26). Perinatal depression includes major and minor depression that
occurs during pregnancy or within the 12-month
period following birth (27). The prevalence of major
depression is estimated to be as high as 11% at different times during pregnancy and is not appreciably
different from rates among women who are not
pregnant (27). However, depression has an impact
on the development and management of pregnancyrelated complications. Untreated depression has
been associated with unfavorable health behaviors in
pregnancy and subsequent fetal growth restriction,
preterm delivery, placental abruption, or newborn
irritability (28). Recent evidence-based reviews do
not appear to distinguish between the different
screening instruments for depression. Using the following two questions to screen for depression may
be as effective as more lengthy tools. A positive
response to both questions suggests the need for further evaluation.
1. Over the past 2 weeks, have you ever felt down,
depressed, or hopeless?
2. Over the past 2 weeks, have you felt little interest or pleasure in doing things? (29)
COMMITTEE OPINIONS
Postpartum depression is defined as intense

feelings of sadness, anxiety, or despair after childbirth that interfere with a mothers ability to function
and that do not resolve. In such circumstances, there
is an increased risk of serious harm to the mother or
the infant. It is to be distinguished from the baby
blues, a period of mild depressive mood and lability that typically has its onset within 23 days postpartum and lasts up to 2 weeks. Women who lack
psychosocial support, have a history of postpartum
depression or other psychiatric illnesses, or have
experienced a recent stressful life event are at greater
risk for postpartum depression. Screening for these
risk factors is, therefore, important. Other risk factors include child care stress, low self-esteem, and
low socioeconomic status (30). Clinical practices
that screen for depression should have systems in
place to ensure that positive screening results are
followed by accurate diagnosis, implementation of
treatment, and follow-up either within the practice
or through referral (31).
Safety
Safety concerns can pertain to safety in the home or
the immediate neighborhood. A patient may be
unable to gain access to needed services and support
because of fear. If there is immediate danger to the
patient, alternative housing should be discussed. If
there are children who are not safe in the household,
a referral to the states child protection agency may
be required. The state agency can be contacted for
specific reporting requirements. If the safety concern relates specifically to the house, such as structural defects, rat or insect infestation, or sanitation
issues, further inquiry can determine the appropriate
local health department referral or intervention.
There also should be an inquiry about the presence
of guns and other weapons in the home. If present,
the patient should be counseled to remove the
weapons or to carefully secure them and the ammunition separately (32).
Intimate Partner Violence
The incidence of abuse during pregnancy ranges
from 1% to 20% of all pregnant women (33). Many
studies report that violence often begins in pregnancy; if already present, it may escalate (34). Research
also suggests that violence may increase during the
postpartum period (35). Given these findings, ACOG
recommends screening every pregnant woman for
intimate partner violence at the first prenatal visit, at
443
least once in each trimester, and at the postpartum

visit (36). There are characteristics that may serve as
markers for abuse. Women who are abused are more
likely to receive inadequate prenatal care. In particular, abused pregnant women seek prenatal care later
in pregnancy (37), miss more appointments, and are
more likely to cancel appointments on short notice
than nonabused pregnant women (38).
If the woman believes that her safety is endangered if she returns to her home, shelter should be
offered by contacting or referring her to social services, homeless shelters, or community services for
battered women. If the patient is afraid for her safety
and shelter space is not immediately available, sometimes special arrangements can be made to admit the
patient into a hospital until other arrangements can
be made. If the patient is not in need of immediate
shelter, she should be provided with information on
community resources and referred for continued
assistance and support (36). Health care providers
need to be aware that the patient is the best judge of
her own safety. She, therefore, may choose to return
home despite receiving advice to the contrary. Health
care providers should honor such decisions.
Stress
Not all women with high levels of psychosocial
stress have adverse pregnancy outcomes. But there
is a growing body of evidence indicating that individual psychosocial stress, strenuous physical activity, and fasting are independent risk factors for
preterm birth and low-birth-weight neonates
(3943). Vulnerability to stress in pregnancy may
vary according to the nature of the stressful experience, the timing with respect to gestational period,
and the presence of other maternal risk factors combined with stress (39). Stress may be a factor that
interacts with some of the other factors described
previously. Community-level circumstances and
conditions can affect health outcomes, and there is a
well-established social class gradient in health and
health care. Several clinical studies have found that
women who are anxious during pregnancy tend to
have smaller babies. Additionally, women with high
levels of stress hormones such as corticotropinreleasing hormone are more likely to give birth
preterm (4446). A relationship also has been shown
between stressful experiences, some forms of work
stress, and depression and anxiety in pregnancy with
preeclampsia, preterm birth and low birth weight,
and reduced head circumference (6, 47).
444
Practitioners should identify patients under

stress. The stress associated with pregnancy itself,
concerns about labor and delivery, and projected
fears about parenting often can be reduced by providing counseling, information, and social support
during the course of prenatal care. Some patients
may require evaluation and treatment by mental
health practitioners to help identify and resolve distress. Lack of social support has been associated with
morbidity and mortality (48, 49). Social support has
been defined as resources and aid derived from ones
social relationships. Social support may influence
health by one of two mechanisms: a direct positive
effect or a buffering effect. These effects are not
mutually exclusive. A direct effect may be neuroendocrine or neuroimmune in origin. Buffering may be
a result of either an increase in health-promoting
behaviors or a decrease in risk behaviors or both.
Intervention studies in evaluating direct effects in
pregnant women have had mixed results but effects
on behaviors have been demonstrated (49).
American College of Obstetricians and Gynecologists. Ask

about tobacco use chart stickers. Washington, DC: ACOG.
(800-762-2264, sales.acog.org): Item No. AA268; Price:
$19/260 stickers; ACOG members: $15/260 stickers.
Summary

Substance use: obstetric and gynecologic implications. In:
Special issues in womens health. Washington, DC: ACOG;
2005. p. 10550.
Addressing the broad range of psychosocial issues

with which pregnant women are confronted is an
essential step toward improving womens health and
birth outcomes. An effective system of referrals
will be helpful in augmenting the screening and
brief intervention that can be carried out in an office
setting. To increase the likelihood of successful
interventions, psychosocial screening should be performed on a regular basis and documented in the
patients prenatal record. Screening should include
assessment of barriers to care, unstable housing,
unintended pregnancy, communication barriers,
nutrition, tobacco use, substance use, depression,
safety, intimate partner violence, and stress.
Resources
Resources for Practitioners
American Academy of Pediatrics, American College of
Obstetricians and Gynecologists. Guidelines for perinatal care.
5th ed. Elk Grove Village (IL): AAP; Washington, DC: ACOG;
2002.
American College of Obstetricians and Gynecologists. A clinicians guide to helping pregnant women quit smoking. A lecture guide. Washington, DC; ACOG; 2002. Available at:
www.acog.org/from_home/departments/smoking/smoking
slides.ppt. Retrieved March 24, 2006.

disorders. In: Health care for adolescents. Washington, DC:
ACOG; 2003. p. 8194.
Intimate partner violence and domestic violence. In: Special
issues in womens health. Washington, DC: ACOG; 2005. p.
16988.
Intimate partner violence and domestic violence. A slide lecture presentation. Washington, DC: ACOG; 2005.
Obstetric medical history. Washington, DC: ACOG; 2002.
Smoking and womens health. In: Special issues in womens
Smoking cessation during pregnancy: a clinicians guide to
helping pregnant women quit smoking. Washington, DC:
ACOG; 2002.
Dartmouth Medical School. Smoking cessation for pregnancy

and beyond: learn proven strategies to help your patients quit.
Hanover (NH): Trustees of Dartmouth College; 2004.
Available for purchase through the ACOG Distribution Center
(800-762-2264, sales.acog.org).
Obesity in pregnancy. ACOG Committee Opinion No. 315.
Gynecol 2005;106:6715.
Smoking cessation during pregnancy. ACOG Committee
Resources for Patients

American College of Obstetricians and Gynecologists. Alcohol
and women. ACOG Patient Education Pamphlet AP068.
Depression. ACOG Patient Education Pamphlet AP106.
Domestic violence. ACOG Patient Education Pamphlet
American College of Obstetricians and Gynecologists. Its time
to quit smoking. ACOG Patient Education Pamphlet AP065.
COMMITTEE OPINIONS
American College of Obstetricians and Gynecologists, Smokefree families. Need help putting out that cigarette? Washington,
DC: ACOG; Chapel Hill (NC): Smoke-Free Families; 2001.
American College of Obstetricians and Gynecologists,
Violencia domestica. ACOG Patient Education Pamphlet
SP083. Washington, DC: ACOG; 2002.
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Wadhwa PD, Sandman CA, Porto M, Dunkel-Schetter C,
Garite TJ. The association between prenatal stress and
infant birth weight and gestational age at birth: a prospective investigation. Am J Obstet Gynecol 1993;169:85865.
Paarlberg KM, Vingerhoets AJ, Passchier J, Dekker GA,
Van Geijn HP. Psychosocial factors and pregnancy outcome: a review with emphasis on methodological issues.
J Psychosom Res 1995;39:56395.
Teixeira JM, Fisk NM, Glover V. Association between
maternal anxiety in pregnancy and increased uterine
artery resistance index: cohort based study. BMJ 1999;
318:1537.
Wadhwa PD, Porto M, Garite TJ, Chicz-DeMet A,
Sandman CA. Maternal corticotropin-releasing hormone
levels in the early third trimester predict length of gestation in human pregnancy. Am J Obstet Gynecol 1998;
179:107985.
Hobel CJ, Dunkel-Schetter C, Roesch SC, Castro LC,
Arora CP. Maternal plasma corticotropin-releasing hormone associated with stress at 20 weeks gestation in
pregnancies ending in preterm delivery. Am J Obstet
Gynecol 1999;180:S25763.
Copper RL, Goldenberg RL, Das A, Elder N, Swain M,
Norman G, et al. The preterm prediction study: maternal
stress is associated with spontaneous preterm birth at less
than thirty-five weeks gestation. National Institute of
Child Health and Human Development Maternal-Fetal
Medicine Units Network. Am J Obstet Gynecol 1996;
175:128692.
Cohen S. Psychosocial models of the role of social support in the etiology of physical disease. Health Psychol
1988;7:26997.
Orr ST. Social support and pregnancy outcome: a review
of the literature. Clin Obstet Gynecol 2004;47:84255;
discussion 8812.
COMMITTEE OPINIONS
447

Breastfeeding: Maternal and Infant

Aspects
Committee on
Health Care for
Underserved
Women
Committee on
Obstetric Practice
The Committees
would like to thank
Sharon Mass, MD, for
her contributions to
the development of
this document.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Evidence continues to mount regarding the value of breastfeeding for

both women and their infants. The American College of Obstetricians and Gynecologists
strongly supports breastfeeding and calls on its Fellows, other health care professionals
caring for women and their infants, hospitals, and employers to support women in choosing to breastfeed their infants. Obstetriciangynecologists and other health care professionals caring for pregnant women should provide accurate information about
breastfeeding to expectant mothers and be prepared to support them should any problems arise while breastfeeding.
Research in the United States and throughout

the world indicates that breastfeeding and
human milk provide benefits to infants,
women, families, and society. In 1971, only
24.7% of mothers left the hospital breastfeeding. Since then, breastfeeding initiation
rates have been increasing because of a growing awareness of the advantages of breast
milk over formula, but they have not yet
reached the goal set by the U.S. Public Health
Service for Healthy People 2010 (1). In 2005,
72.9% of new U.S. mothers initiated breastfeeding (2). Although this is close to the target rate of 75% in the early postpartum
period, there is still a long way to go to
achieve target breastfeeding rates of 50% at
6 months and 25% at 12 months (1).
Improvement in breastfeeding initiation
rates has been uneven as women attempt to
overcome practical obstacles. Women and
infants who could benefit most from breastfeeding are often within population groups
(geographic, racial, economic, and educational) with low rates of breastfeeding.
Education and support services can improve
rates among these as well as other women.
Breastfeeding education and support are an
economical investment for health plans and
employers because there are lower rates of illness among infants who are breastfed.
Breastfeeding is the preferred method of

feeding for newborns and infants. Nearly
every woman can breastfeed her child.
Exceptions are few and include those women
who take street drugs or do not control alcohol use, have an infant with galactosemia, are
infected with human immunodeficiency
virus (HIV) or human T-cell lymphotropic
virus type I or type II, and have active
untreated tuberculosis or varicella or active
herpes simplex virus with breast lesions (3,
4).
and Gynecologists strongly supports breastfeeding and calls upon its Fellows, other
health care professionals caring for women
and their infants, hospitals, and employers to
support women in choosing to breastfeed
their infants. All should work to facilitate the
continuation of breastfeeding in the workplace and public facilities. Health care professionals have a wide range of opportunities to
serve as a primary resource to the public and
their patients regarding the benefits of
breastfeeding and the knowledge, skills, and
support needed for successful breastfeeding
(5). In addition to providing supportive clinical care for their own patients, obstetriciangynecologists should be in the forefront
of fostering changes in the public environ-
448
ment that will support breastfeeding, whether through

change in hospital practices, through community efforts,
or through supportive legislation.
The advice and encouragement of the obstetriciangynecologist during preconception, prenatal, postpartum, and interconception care are critical in making
the decision to breastfeed. Good hospital practices surrounding childbirth are significant factors in enabling
women to breastfeed. Health care providers should be
aware that the giving of gift packs with formula to breastfeeding women is commonly a deterrent to continuation
of breastfeeding (4). A professional recommendation of
the care and feeding products in the gift pack is implied.
For this reason, physicians may conclude that noncommercial educational alternatives or gift packs without
health-related items are preferable. After discharge, the
obstetriciangynecologists office should be a resource for
24-hour assistance, or provide links to other resources in
the community. Breastfeeding problems, including breast
and nipple pain, should be evaluated and treated promptly. Clinical breast examinations are recommended for
breastfeeding women. If any mass or abnormality is
detected, it should be fully evaluated.
Contraception is an important topic for early discussion and follow-up for breastfeeding women. Women
should be encouraged to consider their future plans for
contraception and childbearing during prenatal care and
be given information and services that will help them
meet their goals. Options that should be explained in
detail include nonhormonal methods, hormonal methods, and the lactational amenorrhea method.
Women should be supported in integrating breastfeeding into their daily lives in the community and in the
workplace to enable them to continue breastfeeding as
long as possible. Maintaining milk supply depends largely on frequency and adequacy of maternal stimulation
through breastfeeding and through pumping when
mother and baby are separated. The American College of
Obstetricians and Gynecologists recommends that exclusive breastfeeding be continued until the infant is approximately 6 months old. A longer breastfeeding experience
is, of course, beneficial. The professional objectives are to
encourage and enable as many women as possible to
breastfeed and to help them continue as long as possible
(3, 4). Physicians offices can set the example in encourag-
ing and welcoming breastfeeding through staff training,

office environment, awareness and educational materials,
and supportive policies (3, 4).
More detailed information on breastfeeding and
practical strategies for support can be found in the
ACOG Clinical Review Special Report From ACOG,
Breastfeeding: Maternal and Infant Aspects and in the
American Academy of Pediatrics and ACOG resource,
Breastfeeding Handbook for Physicians (3, 4).
References
1. U.S. Department of Health and Human Services. Increase
in the proportion of mothers who breastfeed their babies.
In: Healthy people 2010: objectives for improving health.
2nd ed. Washington, DC: U.S. Government Printing Office;
2000. p. 1646.
2. Centers for Disease Control and Prevention. Breastfeeding:
data and statistics: breastfeeding practicesresults from
the 2005 National Immunization Survey. Atlanta (GA):
CDC. Available at: http://www.cdc.gov/breastfeeding/
data/NIS_data/data_2005.htm. Retrieved November 14,
2006.
Obstetricians and Gynecologists. Breastfeeding handbook
for physicians. Elk Grove Village (IL): AAP; Washington,
DC: ACOG; 2006.
Breastfeeding: maternal and infant aspects. Special report
from ACOG. ACOG Clin Rev 2007;12(suppl):1S16S.
Breastfeeding. ACOG Executive Board Statement.
Washington, DC; ACOG: 2003. Available at: http://www.
acog.org/departments/underserved/breastfeedingStatement.
pdf. Retrieved November 1, 2006.
Breastfeeding: maternal and infant aspects. ACOG Committee
ISSN 1074-861X
COMMITTEE OPINIONS
449

Health Literacy
Committee on
Health Care for
Underserved
Women
The Committee would
like to thank Maureen
Phipps, MD and Eve
Espey, MD for their
assistance in the development of this document.
This information should
not be construed as dictating an exclusive course
of treatment or procedure
to be followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: According to the U.S. Department of Health and Human Services,

health literacy is the degree to which individuals have the capacity to obtain, process, and
understand basic health information and services needed to make appropriate health
decisions. The American College of Obstetricians and Gynecologists (ACOG) is committed to the promotion of health literacy for all. The purpose of this committee opinion is
to outline the complex issues surrounding health literacy and offer strategies for increasing health literacy in clinical practice.
Each day, patients encounter the challenges

of interpreting health information presented
by health care providers and making decisions based on their understanding of that
information. Engaging patients in difficult
health care decisions requires that patients
listen, understand, read, and analyze information about their health; in essence, we
expect patients to be health literate. Health
literacy relates to the individuals capacity to
obtain, interpret, and understand health
information and health care services, and to
use such information and services in ways
that are health enhancing (1). Because situations regarding an individuals health are
often complex and the language used to
explain them is often specialized, years of
education or reading ability do not necessarily translate into adequate health literacy.
Health care professionals often use technical
language specific to their areas of expertise
with the expectation that people who are not
familiar with the professional jargon will
understand the meaning of complex ideas
and terms. Even individuals highly trained
in other fields may have difficulty understanding health information and instructions
about their care.
The problem of limited health literacy is
widespread. Whereas approximately 10% of
Americans have low general literacy (skills
necessary to perform simple and everyday literacy activities) (2), 50% of adults are estimated to have marginal to low health literacy
skills (3). Multiple studies have demonstrated
the seriousness of the problem. Adults with
low health literacy are at increased risk for
hospitalization (4), encounter more barriers

to receiving necessary health care services
(5), and are less likely to understand medical
advice that can affect their disease progression (6, 7). Given the scope of the problem,
the U.S. Department of Health and Human
Services identified several target areas in the
Healthy People 2010 objectives to improve
health communication, which incorporated
goals related to health literacy and cultural
competency (8).
Our current health care delivery system
assumes a high level of health literacy.
Individuals are expected to understand and
apply verbal information, including diagnosis, medical advice, and treatment; have
access to and use a computer and the
Internet; calculate and interpret numerical
data; and interpret graphs and visual information. Patients are expected to be articulate
and accurate about their conditions and
symptoms, as well as to have sophisticated
decision-making skills. Often those individuals with the greatest health care needs have
limited skills to synthesize and interpret
health information (9).
Patients with specific educational or linguistic challenges also may have limited
health literacy. Nonadherence to therapeutic and medication recommendations, often
pejoratively labeled noncompliance, can
lead to poor outcomes and may be more
related to limited health literacy than to
patients indifference toward their health. It
may be that nonadherent patients are not following recommendations because they do
not understand what is expected of them.
450
This is often the case with older patients and those with
limited English proficiency or no English proficiency. In
the United States, people aged 65 years and older consume 30% of prescriptions and 40% of over-the-counter
drugs (10). Senior citizens often have low literacy skills
and, therefore, poor comprehension of information on
medication labels (2, 11). Low health literacy also may be
a problem for immigrant populations for whom English
is a second language (12). According to a recent ACOG
project focusing on language access solutions in
California, 25% of ACOG Fellows reported that one quarter of their patients have limited English proficiency and
38% reported an increase in patients with limited English
proficiency during the past 5 years (13).
When the concept of health literacy is taken into consideration, all facets of the medical encounter, including
patient education, are important to improving the
patients and the publics health. Patient health literacy
includes the ability to understand instructions on prescription drug bottles, appointment slips, patient education brochures, and consent forms, as well as the ability to
negotiate complex health care systems.
Multiple factors affect a patients understanding of
health information, including the physicians health
knowledge and communication skills, the demands of the
situation in which the health information is being conveyed, and time constraints for delivering the information.
Other factors include the patients ability to communicate
effectively with the health care team, to manage and commit to his or her own health care, and to comprehend
complex concepts such as probability and risk. Understanding the unique capabilities of the individual patient
will make the information provided by the health care
team more accessible for both the patient and his or her
family members. When patients can obtain, process, and
understand basic health information, they are more likely
to make the most appropriate health decisions.
Responsibility for recognizing and addressing the
problem of limited health literacy lies with all entities in
the health care profession, from the primary health care
team to public health care systems. Making information
understandable and accessible to all patients involves a
systematic approach toward health literacy in physicians
offices, hospitals, clinics, national organizations, local
health organizations, advocacy organizations, medical
and allied health professional schools, residency training
programs, and continuing medical education programs.
Community-based partnerships to help understand and
address the needs of the local community and consumer
health information organizations to focus on the issue of
health literacy are needed in the effort to improve health
literacy.
Gynecologists supports the following guidelines (adapted
from the U.S. Department of Health and Human Services
Office of Disease Prevention and Health Promotion
Guide to Health Literacy) (14):
1. Tailor speaking and listening skills to individual

patients.
Ask open-ended questions using the words what
or how to start the sentence. (For example:
What questions do you have for me? rather than
Do you have any questions?)
Use medically trained interpreters.
Check for comprehension by asking patients to
restate the health information given in their own
words. (For example: Tell me how you are going
to take this medication.)
Encourage staff and colleagues to obtain training
in patient communication and use of plain language along with cultural competency (15). (For
more information, please refer to the corresponding chapters in the ACOG publication Special
Issues in Womens Health.)
2. Tailor health information to the intended user.
When developing health information, make sure
it reflects the target groups age, social and cultural diversity, language, and literacy skills.
When developing information and services,
include the target group in the development
(pretest) and implementation (posttest) phases to
ensure the program is effective.
In preparing health information, consider cultural factors and the influence of culture on health,
including race, ethnicity, language, nationality,
religion, age, gender, sexual orientation, income
level, and occupation.
3. Develop written materials.
Keep the messages simple.
Limit the number of messages (general guideline is
four main messages).
Focus on action. Give specific recommendations
based on behavior rather than the medical principle. (For example, Take a warm water bath two
times a day instead of Sitz baths may help
healing.)
Use the active instead of the passive voice. (For
example, These pills can make you sick to your
stomach instead of Nausea may be caused by this
medication.)
Use familiar language and avoid jargon. (For
example, Your may have itching instead of You
may experience pruritus on your genitalia.)
Use visual aids such as drawings or models for key
points. Make sure the visual messages are culturally relevant.
Use at least 12-point font to make the messages
easy to read.
Leave plenty of white space around margins and
between sections.
COMMITTEE OPINIONS
Resources
The following online resources may be helpful to physicians in finding resources for patients:
www.acog.org/goto/patients
www.familydoctor.org
National Center for Farmworker Health, Inc.
www.ncfh.org/00_nc_rc_pateduc.php
Oregon Health and Science University
www.ohsu.edu/library/patiented/links.shtml#lowlit
U.S. Department of Health and Human Services
www.womenshealth.gov/espanol
University of Washington, Harborview Medical Center
www.ethnomed.org
The resources listed here are for information purposes
only. Referral to these web sites does not imply the
endorsement of ACOG. Further, ACOG does not endorse
any commercial products that may be advertised or available from these organizations or on these web sites. This
list is not meant to be comprehensive. The exclusion of a
source or web site does not reflect the quality of that
source or web site. Please note that web sites and URLs are
subject to change without notice.
7.
8.
9.
10.
11.
12.
13.
References
1. Joint Committee on National Health Education Standards. National health education standards: achieving
health literacy. Atlanta (GA): American Cancer Society;
1995. Available at: http://eric.ed.gov/ERICDocs/data/eric
docs2sql/content_ storage_01/0000019b/80/14/24/30.pdf.
Retrieved September 7, 2007.
2. National Center for Education Statistics. National
Assessment of Adult Literacy (NAAL): a first look at the literacy of Americas adults in the 21st century. Washington,
DC:U.S. Department of Education: 2005. Available at:
http://nces.ed.gov/NAAL/PDF/2006470.PDF. Retrieved
July 27,2007.
3. Paasche-Orlow MK, Parker RM, Gazmararian JA, NielsenBohlman LT, Rudd RR. The prevalence of limited health literacy. J Gen Intern Med 2005;20:17584.
4. Baker DW, Parker RM, Williams MV, Clark WS. Health literacy and the risk of hospital admission. J Gen Intern Med
1998;13:7918.
5. Williams MV, Parker RM, Baker DW, Parikh NS, Pitkin K,
Coates WC, et al. Inadequate functional health literacy
among patients at two public hospitals. JAMA 1995;274:
167782.
6. Williams MV, Baker DW, Parker RM, Nurss JR.
Relationship of functional health literacy to patients
14.
15.
451
knowledge of their chronic disease. A study of patients with

hypertension and diabetes. Arch Intern Med 1998;158:
16672.
Gazmararian JA, Baker DW, Williams MV, Parker RM, Scott
TL, Green DC, et al. Health literacy among Medicare
enrollees in a managed care organization. JAMA 1999;281:
54551.
U.S. Department of Health and Human Services. Health
communication. In: Healthy people 2010: objectives for
improving health (part A). 2nd ed. Washington, DC: HHS,
2000. p. 11-111-25. Available at: http://www.healthypeo
ple.gov/Document/pdf/Volume1/11HealthCom.pdf.
Parker RM, Gazmararian JA, Health literacy: essential for
health communication. J Health Commun. 2003;8(suppl
1):1168.
Salom IL, Davis K. Prescribing for older patients: how to
avoid toxic drug reactions. Geriatrics 1995;50:3740, 43;
discussion 445.
Morell RW, Park DC, Poon LW. Effects of labeling techniques on memory and comprehension of prescription
information in young and old adults. J Gerontol 1990;
45:16672.
Guerra C, Krumholz M, Shea J. Literacy and knowledge,
attitudes and behavior about mammography in Latinas. J of
Health Care of the Poor and Underserved 2005;16:15266.
Strengthening communication capacity: Californias
OB/GYNs enhance language access for limited English proficient patients. Sacramento (CA): ACOG District IX;2006.
Available at: http://www.acog.org/acog_districts/dist9
/2006LanguageAccessSolutionsReport.pdf. Retrieved July
27, 2007.
U.S. Department of Health and Human Services. Quick
guide to health literacy. Washington, DC: HHS; 2006.
Available at: http://www.health.gov/communication/litera
cy/quickguide/Quickguide.pdf. Retrieved July 27, 2007.
Special issues in womens health. Washington DC: ACOG;
2005.
Health literacy. ACOG Committee Opinion No. 391. American College
of Obstetricians and Gynecologists. Obstet Gynecol 2007;110:
148991.
ISSN 1074-861X
452

Human Immunodeficiency Virus and

Acquired Immunodeficiency Syndrome
and Women of Color
Committee on
Health Care for
Underserved Women
The Committee would
like to thank Diana
Contreras, MD;
Maureen Phipps, MD;
and Heather Watts, MD;
for their assistance in
document.
not be construed as dictating an exclusive course of
be followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: In the United States, women of color (primarily African-American and

Hispanic women) comprise most new cases of human immunodeficiency virus (HIV)
infection and acquired immunodeficiency syndrome (AIDS) among women. Most
women of color acquire the disease from heterosexual contact, often from a partner who
has undisclosed risk factors for HIV infection. Safe-sex practices, especially consistent
condom use, must be emphasized for all women, particularly for women of color. A combination of testing, education, and brief behavioral interventions can help reduce the rate
of HIV infection and its complications among women of color.
Impact on Women
Early in the epidemic, human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) were rarely
diagnosed in women of all ages, including
adolescents. They now account for a growing
proportion of new HIV and AIDS diagnoses.
In 1985, women represented 8% of HIV/
AIDS cases but by 2005 accounted for 27% of
the estimated 45,669 new diagnoses of
HIV/AIDS (1). (According to this Centers for
Disease Control and Prevention report and
others cited in this document, HIV/AIDS is
defined as infection with or without AIDS.)
Heterosexual contact was the source of 80%
of these new infections (2). Many women are
unaware of their male partners risk factors
for HIV infection (such as unprotected sex
with multiple partners, sex with men, or
injection drug use).
Of great concern is the number of young
women with HIV infection and AIDS. In
2005, 36% of HIV/AIDS cases in the 1319
year-old age group were in girls, and 28% of
HIV/AIDS cases were in women in the 2024
year-old age group (3). Of women with
AIDS, 71% received the diagnosis between
the ages of 25 years and 44 years, suggesting
that many were infected as adolescents (2).
Older women also represent an increasing
proportion of HIV diagnoses. Between 1999
and 2004, the number of women with newly

diagnosed HIV infections from heterosexual
activity increased by 4.8% per year among
women aged 4049 years, 6.8% per year
among women aged 5059 years, and 4.1%
per year among women older than 60 years (4).
There are many reasons why women
infected with HIV may have difficulty obtaining health care, including lack of financial
resources and health insurance, lack of transportation, and the added responsibility of
caring for others, especially children. Lack of
access to effective therapy has been associated
with an increase in the mortality rate (5).
Women of Color
Women of color comprise most new cases of
HIV infection among women in the United
States, accounting for more than 80% of
new diagnoses in women (2). The rate of
AIDS diagnosis for African-American and
Hispanic women is disproportionate to the
population. Data from the 2005 census show
that African-American and Hispanic women
represent 24% of all U.S. women; however,
both groups accounted for 82% of the estimated total of AIDS diagnoses for women
(6). Among African-American women, the
rate of AIDS diagnosis is 23 times the rate
for white women and four times the rate for
Hispanic women (6).
COMMITTEE OPINIONS
Mortality rates in these groups remain very high. In

2004, HIV infection was the leading cause of death for
African-American women aged 2534 years and the third
leading cause of death for African-American women aged
3544 years (7). HIV was the fourth leading cause of
death for Hispanic women aged 3544 years (7). The
death rate from HIV infection among African-American
women was higher than for all other groups, both male
and female, except for African-American men.
The reasons for the increased risk of HIV infection
among women of color are multifactorial. Among
African-American and Hispanic women living with
HIV/AIDS, the most common exposures were high-risk
heterosexual contact and injection drug use (6, 8). The
higher prevalence of HIV infection in the AfricanAmerican community makes women more likely to be
exposed to HIV. African-American men who have sex
with men have the highest incidence and prevalence of
HIV among any ethnic or behavioral risk group in the
United States (9). Among men who have sex with men,
African-American men are more likely than EuropeanAmerican men to also have sex with women and less
likely to disclose their behavior to friends and partners,
putting women unknowingly at risk (10). Poverty and
economic uncertainty may make it more difficult for
women to feel empowered to negotiate condom use and
other safe-sex practices (11). In addition, among AfricanAmerican women, increased rates of other genital infections, including bacterial vaginosis and trichomoniasis
vaginalis, may increase susceptibility to HIV infection
(12, 13). Racially associated differences in allele frequencies of genes that influence both susceptibility to and progression of HIV infection may increase the risk of HIV
infection in African-American women (14).
Many Hispanic women are hesitant to discuss condom use with their partners because they fear emotional
or physical abuse or the abandonment of financial support (15). In addition, traditional gender roles hinder
open communication of safe-sex practices with male
partners (8). Hispanic men and women both are disproportionately likely to face serious socioeconomic barriers,
including lack of education, unemployment, inadequate
health insurance, and limited access to health care that
can increase the risk of HIV infection (8). Language also
can be a barrier for this population, thus, culturally and
linguistically focused interventions are warranted (8).
Community-Based Interventions for

Women of Color
Among women of color, adolescent girls are at high risk
of HIV infection. In a recent Centers for Disease Control
and Prevention report, among African-American adolescents across 33 states aged 1324 years in whom
HIV/AIDS is diagnosed, approximately 41% are female
(16). In a randomized controlled trial that evaluated efficacy of an HIV prevention intervention among sexually
experienced African-American adolescent girls, it was
453
found that a gender-tailored and culturally appropriate

intervention can enhance HIV-preventive behavior and
skills, such as condom use, and psychosocial mediators,
such as knowledge, attitudes, and partner communication (17). In another randomized controlled trial it was
found that skill-based HIV and sexually transmitted disease (STD) interventions can reduce sexual risk-taking
behavior and rates of STDs among African-American and
Latino adolescent girls in clinic settings (18). In other
studies, similar findings also have been found in which
preventive interventions among adolescents that take a
cultural approach and take place in groups with ethnic
similarity are effective (19, 20). Despite these findings,
more intensive interventions and research designed
specifically for African-American and Latino adolescents
that demonstrate efficacy in reducing behavior associated
with HIV risk are necessary (17).
Behavioral interventions targeting adult women of
color also are crucial to decrease rates of morbidity and
mortality from HIV and AIDS. In a randomized controlled trial testing the efficacy of HIV and STD riskreduction interventions for African-American women in
primary care settings it was found that brief single-session, one-on-one, or group skill-building interventions
may reduce behavior associated with HIV and STD risk,
such as unprotected sex, and also may reduce rates of STD
morbidity (21). In another randomized controlled trial it
was found that three small-group sessions decreased rates
of chlamydial and gonorrheal infection among MexicanAmerican and African-American women at high risk of
STDs (22). In multiple studies, it has been shown that
brief behavioral interventions, including personalized
risk assessment, training in negotiation skills, and identification of specific targets for behavioral change, can
increase rates of condom use and decrease rates of acquisition of sexually transmitted infections compared with
education alone among women of color (21, 2325).
Many interventions range in duration from 132 hours,
using individual or small-group counseling (26). These
findings suggest that targeted and focused programs can
be effective among women of color.
Recommendations
Human immunodeficiency virus infection and AIDS can
affect all women, but women of color are acquiring the
disease at higher rates than other groups. Most of these
women are acquiring the disease from heterosexual contact, often from a partner who has undisclosed risk factors for HIV infection. Prevention and early recognition
are critical, but women of color are not benefiting maximally from these two interventions. Several approaches
can reduce the rate of HIV infection in women and optimize health:
The American College of Obstetricians and Gynecologists (ACOG) recommends routine HIV screening
for women aged 1964 years and targeted screening
454
for women with risk factors outside of that age range,

for example, sexually active adolescents younger than
19 years. Ideally, opt-out HIV screening should be
performed, in which the patient is notified that HIV
testing will be performed as a routine part of gynecologic and obstetric care, unless the patient declines
testing (27). (Please refer to ACOGs Committee
Opinion No. 411 Routine Human Immunodeficiency Virus Screening for more information.)
Obstetriciangynecologists should be aware of and
comply with legal requirements regarding HIV testing in their jurisdictions (28). The National
HIV/AIDS Clinicians Consultation Center at the
University of California-San Francisco maintains an
online compendium of state HIV testing laws that
can be a useful resource (www.nccc.ucsf.edu/).
Women whose confirmatory testing yields positive
results and, therefore, are infected with HIV should
receive or be referred for appropriate clinical and
supportive care. Early recognition allows initiation of
optimal care and medication, when indicated, as well
as education to prevent transmission.
Safe-sex practices, especially consistent condom use,
must be emphasized for all women, particularly for
women of color. Multiple studies have shown that
behavioral interventions can increase rates of condom use, reduce risk-taking behavior, and decrease
rates of acquisition of sexually transmitted infections. Most interventions are designed to be provided
by nurses or peer educators and often are available
through local health departments or community
organizations.
More intensive interventions and research designed
specifically for women of color that demonstrate efficacy in reducing behavior associated with HIV risk
are necessary.
Health care providers are urged to identify resources
in their community for training of office staff in risk
reduction interventions for women of color or for
referral of women to these programs.
A combination of testing, education and brief behavioral interventions can help reduce the rate of HIV infection and its complications among women of color.
References
1. Epidemiology of HIV/AIDSUnited States, 1981-2005.
Centers for Disease Control and Prevention (CDC).
2. Centers for Disease Control and Prevention. HIV/AIDS
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Human immunodeficiency virus and acquired immunodeficiency
syndrome and women of color. ACOG Committee Opinion No. 414.
Gynecol 2008;112:4136.
ISSN 1074-861X
456

The Uninsured
Committee on Health
Care for Underserved
Women
The Committee on
Health Care for
Underserved Women
would like to thank
Kerry M. Lewis, MD,
and Virginia C. Leslie,
MD, for their assistance
in the development of
this document.
be followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: The United States is one of the few industrialized nations in the world
that do not guarantee health care for their populations. Access to health care for all
women is of paramount concern to obstetriciangynecologists and the American College
of Obstetricians and Gynecologists. Pregnant women and infants are among the most
vulnerable populations in the United States and the American College of Obstetricians
and Gynecologists believes that providing them with full insurance coverage and access
to health care must be a primary step in the process of providing coverage for all individuals within the U.S. borders. Health care professionals can play a pivotal role in improving access to needed health care by helping society and our political representatives
understand the importance of broadening health insurance coverage.
The United States is one of the few industrialized nations in the world that do not guarantee health insurance for their populations.
Of the 30 countries in the Organization of
Economic Cooperation and Development,
only Mexico and Turkey have a higher uninsured rate than the United States (1). There
are more than 17 million uninsured women
(aged 1864 years) in the United States. This
number has increased by 1.2 million since
2004, with one half of this growth occurring
among low-income women (2). The number
of women in the United States who are uninsured grew three times faster than the number of men without health insurance during
the late 1990s and early 2000s (3). In 2006,
one in five women of childbearing age
totaling 12.6 million womenwas uninsured, showing no improvement from 2005
and accounting for 27% of all uninsured
Americans (4). Nearly eight out of ten uninsured women (79%) are in families with at
least one part-time or full-time worker (2).
Most uninsured women do not qualify for
Medicaid, do not have access to employersponsored plans, and cannot afford individual policies. Access to health care also is
affected by other barriers, including health
literacy and cultural differences along with
proximity to health care facilities and lack of
transportation. Women who are young and
low-income are particularly at risk of being
uninsured, as are women of color, especially
Latina women (2). Most low income uninsured women are not eligible for public programs but cannot afford private coverage (5).
This is a problem for both U.S and non-U.S.
citizens.
Effect of Lack of Insurance on

Womens Reproductive Health
and Health Care
Having health insurance does not guarantee
good health, but not having insurance is
guaranteed to put Americans at higher risk
for poor health outcomes and economic
hardship. Acquiring health insurance reduces
mortality rates for the uninsured by 1015%
(6). The uninsured receive less preventive
care, receive diagnoses at more advanced disease stages, and, once diseases are diagnosed,
tend to receive less therapeutic care (7). Lack
of health insurance may affect womens
health in the following ways:
Uninsured pregnant women receive
fewer prenatal care services than their
insured counterparts (1) (a total of 18%
of uninsured pregnant women reported
that they did not receive some needed
medical care versus 7.6% of privately
insured and 8.1% of Medicaid-enrolled
pregnant women [8]).
Uninsured pregnant women are more
likely to experience an adverse maternal
outcome (1).
COMMITTEE OPINIONS
Uninsured newborns are more likely to experience

adverse health outcomes and are more likely to die
than insured newborns (1).
Uninsured women with breast cancer have a 3050%
higher risk of dying than insured women with breast
cancer (1).
Uninsured womens options for contraception are
limited (9).
Uninsured women aged 1864 years are three times
less likely to have had a needed Pap test in the past
3 years (10). This contributes to a 60% greater risk
of late-stage diagnosis of cervical cancer among
uninsured women compared with insured women
(11).
Uninsured Non-U.S. Citizens

As efforts to expand coverage are pursued, assessing the
coverage needs of low-income non-citizen adults, who
have a high uninsured rate caused by limited access to
both private and public coverage, will be an important
consideration (12). Following the 1996 welfare reform
law, almost all legal immigrants became ineligible for federally matched Medicaid coverage during their first 5
years of residence in the United States. Undocumented
immigrants and temporary immigrants generally are
ineligible for Medicaid regardless of their length of residence in the country, a restriction that has been in place
before welfare reform.
The Capacity of the Health Care

System to Serve the Uninsured
The cost of uncompensated care is staggering; in 2004, it
was estimated to be $40.7 billion. Most uncompensated
care expenses are incurred by hospitals, where services are
the most costly. In 2001, hospitals spent 63% of total costs
in uncompensated care. Office-based physicians and direct
care programs or clinics accounted for 18% and 19% of
uncompensated costs, respectively (13). A 2001 Commonwealth Fund study found that the value of care provided by
academic health centers to those who were unable to pay
for their services increased as a percentage of gross patient
revenues by more than 40% in the past decade (14). The
number of patients treated at hospitals who are unable to
pay is increasing as the number of uninsured individuals
grows, threatening the financial viability of some institutions.
The proportion of private physicians providing care
to the uninsured is decreasing and those who provide
such care are spending less time doing so (15).
Specifically, the number of physicians providing any care
to individuals unable to pay decreased from 71.5% in
2001 to 68.2% in 2005 (15). A combination of higher
office expenses, including professional liability insurance,
and stagnant insurance payments reduces the ability of
physicians to provide uncompensated care.
457
Covering the Uninsured

In recent years, there has been bipartisan interest in
broadening access to health coverage to the nearly 47 million uninsured Americans. Although there has been relatively little activity at the federal level, a handful of states
have recently adopted or are considering adopting proposals to expand coverage. States are using a combination
of strategies, such as expanding public programs to cover
most children in a state, mandating employers to cover all
workers or contribute to a public financing pool, and
requiring all individuals to carry health insurance with
subsidies for those with lower incomes.
Massachusetts and Vermont passed laws in 2006 to
achieve nearly universal coverage as well as address cost
and quality. On April 12, 2006, Massachusetts enacted legislation requiring that individuals have health insurance
and that the government provide subsidies to ensure
affordability (16). Vermonts law, which includes access to
subsidized or low-cost insurance, relies on voluntary participation. Approximately 21 states introduced universal
coverage bills in 2007 (17).
Conclusion
Access to health care for all women is a paramount concern of the American College of Obstetricians and
Gynecologists (see box). Pregnant women and infants are
among the most vulnerable populations in the United
States and the American College of Obstetricians and
Gynecologists believes that providing them with full
insurance coverage and access to care must be a priority.
Lack of health care coverage creates access issues that
affect women, practitioners, and the health care system as
a whole. A change in our currently fragmented health care
system is warranted to expand coverage to the millions of
uninsured individuals within the U.S. borders. Health
Principles for Reform of the

U.S. Health Care System
January 2007
PREAMBLE: Health care coverage for all is needed to
facilitate access to quality health care, which will in turn
improve the individual and collective health of society.
1. Health care coverage for all is needed to ensure
quality of care and to improve the health status of
Americans.
2. The health care system in the U.S. must provide
appropriate health care to all people within the U.S.
borders, without unreasonable financial barriers to
care.
3. Individuals and families must have catastrophic health
coverage to provide protection from financial ruin.
4. Improvement of health care quality and safety must
be the goal of all health interventions, so that we can
assure optimal outcomes for the resources expended.
(continued)
458
Principles for Reform of the

U.S. Health Care System
January 2007 (continued)
5. In reforming the health care system, we as a society
must respect the ethical imperative of providing
health care to individuals, responsible stewardship
of community resources, and the importance of personal health responsibility.
6. Access to and financing for appropriate health services must be a shared public/private cooperative
effort, with a system which will allow individuals/
employers to purchase additional services or
insurance.
7. Cost management by all stakeholders, consistent
with achieving quality health care, is critical to
attaining a workable, affordable and sustainable
health care system.
8. Less complicated administrative systems are essential to reduce costs, and increase efficiency.
9. Sufficient funds must be available for research (basic,
clinical, translational, and health services), medical
education, and comprehensive health information
technology infrastructure and implementation.
10. Sufficient funds must be available for public health
and other essential medical services to include, but
not be limited to, preventive services, trauma care
and mental health services.
11. Comprehensive medical liability reform is essential
to ensure access to quality health care.
American Academy of Family Physicians, American Academy of
Orthopaedic Surgeons, American College of Cardiology,
American College of Emergency Physicians, American College
of Obstetricians and Gynecologists, American College of
Osteopathic Family Physicians, American College of Physicians,
American College of Surgeons, American Medical Association,
American Osteopathic Association. Principles for reform of the
U.S. health care system. Leawood (KS): AAFP; Rosemont (IL):
AAOS; Washington, DC: ACC; Irving (TX): ACEP; Washington,
DC: ACOG; Arlington Heights (IL): ACOFP; Philadelphia (PA):
ACP; Chicago (IL): ACS; Chicago (IL): AMA; Chicago (IL): AOA;
2007. Available at: http://www.acponline.org/pressroom/health_
reform.pdf. Retrieved June 10, 2008.
professionals can play a pivotal role in improving access

to needed health care by helping society understand the
importance of universal health care access. For a listing
of resources on the topic of the uninsured, go to
www.acog.org/goto/underserved.
References
1. Institute of Medicine. Insuring Americas health: principles
and recommendations. Washington, DC: National Academies Press; 2004.
2. Henry J. Kaiser Family Foundation.Womens health insurance coverage: December 2007. Menlo Park (CA): KFF;
2007. Available at: http://www.kff.org/womenshealth/upload/
6000 _06.pdf. Retrieved June 10, 2008.
3. Lambrew JM. Diagnosing disparities in health insurance for

women: a prescription for change. New York (NY): The
Commonwealth Fund; 2001. Available at: http://www.
commonwealthfund.org/usr_doc/lambrew_disparities_
493.pdf?section=4039. Retrieved June 10, 2008.
4. March of Dimes. Census data on uninsured women and children. Washington (DC): MOD; 2007. Available at: http://
www.marchofdimes.com/Census.pdf. Retrieved June 10,
2008.
5. Henry J. Kaiser Family Foundation. Characteristics of the
uninsured: who is eligible for public coverage and who
needs help affording coverage? Kaiser Commission on
Medicaid and the Uninsured. Washington, DC: KFF; 2007.
Available at: http://www.kff.org/uninsured/upload/7613.pdf.
6. Henry J. Kaiser Family Foundation. Sicker and poorer: the
consequences of being uninsured. A review of the research
on the relationship between health insurance, health, work,
income, and education. Kaiser Commission on Medicaid
and the Uninsured. Washington, DC: KFF; 2002. Available
at: http://www.kff.org/uninsured/upload/Full-Report.pdf.
7. American College of PhysiciansAmerican Society of
Internal Medicine. No health insurance? Its enough to
make you sick. Philadelphia (PA): ACP-ASIM; 1999.
8. Bernstein AB. Insurance status and use of health services
by pregnant women. Washington, DC: Alpha Center;
1999. Available at: http://www.marchofdimes.com/files/
bernstein_paper.pdf. Retrieved June 10, 2008.
9. Sonfield A, Gold RB. New study documents major strides in
drive for contraceptive coverage. Guttmacher Rep Public
Policy 2004;7(2):45, 14.
10. Ayanian JZ, Weissman JS, Schneider EC, Ginsburg JA,
Zaslavsky AM. Unmet health needs of uninsured adults in
the United States. JAMA 2000;284:20619.
11. Ferrante JM, Gonzalez EC, Roetzheim RG, Pal N, Woodard
L. Clinical and demographic predictors of late-stage cervical cancer. Arch Fam Med 2000;9:43945.
12. Henry J. Kaiser Family Foundation. Health insurance coverage and access to care for low-income non-citizen adults.
Kaiser Commission on Medicaid and the Uninsured.
Washington, DC: KFF; 2007. Available at: http://www.kff.
org/uninsured/upload/7651.pdf. Retrieved June 10, 2008.
13. Henry J. Kaiser Family Foundation. The cost of care for the
uninsured: what do we spend, who pays, and what would
full coverage add to medical spending? Issue update. Kaiser
Commission on Medicaid and the Uninsured. Washington,
DC: KFF; 2004. Available at: http://www.kff.org/uninsured/
upload/The-Cost-of-Care-for-the-Uninsured-What-DoWe-Spend-Who-Pays-and-What-Would-Full-CoverageAdd-to-Medical-Spending.pdf. Retrieved June 10, 2008.
14. The Commonwealth Fund. A shared responsibility: academic health centers and the provision of care to the poor and
uninsured. A report of The Commonwealth Fund Task
Force on Academic Health Centers. New York (NY):
Commonwealth Fund; 2001. Available at: http://www.
commonwealthfund.org/usr_doc/AHC_indigentcare_
443.pdf?section=4039. Retrieved June 10, 2008.
15. Center for Studying Health System Change. A growing hole
in the safety net: physician charity care declines again.
COMMITTEE OPINIONS
Tracking Report No. 13. Washington, DC: HSC; 2006.

Available at: http://www.hschange.com/CONTENT/826/
826. pdf. Retrieved June 10, 2008.
16. Henry J. Kaiser Family Foundation. Massachusetts health
care reform plan: an update. Kaiser Commission on
Available at: http://www.kff.org/uninsured/upload/749402.pdf. Retrieved June 10, 2008.
17. National Conference of State Legislatures. Health reform
bills. Denver (CO): NCSL; 2007. Available at: http://www.
ncsl.org/programs/health/universalhealth2007.htm.
459
The uninsured. ACOG Committee Opinion No. 416. American College
7314.
ISSN 1074-861X
460

Motivational Interviewing: A Tool for

Behavior Change
Committee on
Health Care for
Underserved Women
The Committee on
Health Care for
Underserved Women
would like to thank
Ann Honebrink, MD,
for her assistance in the
development of this
document.
be followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Abstract: Applying the principles of motivational interviewing to everyday patient

interactions has been proved effective in eliciting behavior change that contributes to
positive health outcomes and improved patientphysician communication. Current
Procedural Terminology codes are available to aid in obtaining reimbursement for time
spent engaging patients in motivational interviewing for some conditions.
Many common diseases affecting womens

health can be moderated or controlled by
behavior change. However, promoting
changes in a patients dietary habits, alcohol
use, or sexual practices usually is daunting
to the obstetriciangynecologist. The practice of motivational interviewing is emerging as an effective and efficient catalyst for
behavior change. Motivational interviewing
tactics have been successfully used within
the clinical setting to promote weight reduction, dietary modification, exercise, and
smoking cessation, thus having a potential
profound impact on heart disease, hypertension, and diabetes mellitus. Prompting
patients to use safe sex practices and to use
contraception more consistently also has
been achieved through motivational interviewing techniques (1).
Communication with patients that indicates sensitivity and empathy is an approach
used successfully by obstetriciangynecologists (2). Whereas the traditional manner by
which physicians give advice often is enough
to motivate some patients to adopt more
healthy behaviors, advice alone has little
impact for those engaged in risky health
behaviors (3). This resistance to change may
be associated with the patients misunderstanding of the connection between the activity and the health risk. The resistance also may
be associated with minimizing the risk, valuing a social connection associated with the
behavior, or even addiction. Evidence suggests
that motivational interviewing is one technique that can be used to break through this
resistance and achieve behavior change within

the constraints of an active clinical practice
(4). The American College of Obstetricians
and Gynecologists (ACOG) encourages the
use of motivational interviewing as one effective approach to elicit behavior change.
Definition of Motivational
Interviewing
Motivational interviewing is defined as, a
directive, client-centered counseling style for
eliciting behavior change by helping clients
explore and resolve ambivalence (5).
Initially, it was used to motivate patients who
abused alcohol to modify their drinking
behaviors. The goal of motivational interviewing is to help patients identify and
change behaviors that place them at risk of
developing health problems or that may be
preventing optimal management of a chronic
condition (6). Recognizing the dynamics of
an individual patients readiness to change
behavior is integral to this approach (7). The
goal of using motivational interviewing is to
help patients move through the stages of
readiness for change in dealing with risky or
unhealthy behavior (see the box).
CPT copyright 2008 American Medical Association
(AMA). All rights reserved. Fee schedules, relative value
units, conversion factors and/or related components are
not assigned by the AMA, are not part of CPT, and the
AMA is not recommending their use. The AMA does not
directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for the data
contained or not contained herein. CPT is a registered
trademark of the AMA.
COMMITTEE OPINIONS
Stages of Readiness for Change

PrecontemplationThe patient does not believe a problem exists. (I wont get pregnant!)
ContemplationThe patient recognizes a problem
exists and is considering treatment or behavior
change. (Maybe I could get pregnant and there are
things I could do to prevent this.)
ActionThe patient begins treatment or behavior
change. (Ill take that prescription for birth control
pills.)
MaintenanceThe patient incorporates new behavior
into daily life. (Im taking the pill every day.)
RelapseThe patient returns to the undesired behavior. (The pill makes me sick, I think Ill stop.)
461
ior and her goals. For example, consider stating, You

have told me that you would like to feel better and
cut down on your medication. I think you know that
losing weight would help with this. Why do you
think it is hard for you to find more time to exercise?
Roll with resistance and provide personalized feedback. When patients express reasons for not achieving goals, the physician can help them find ways to
succeed. For example, consider stating, I know you
are tired when you get home from work, but do you
think you could try walking up the stairs at work
instead of taking the elevator?
Support self-efficacy, elicit self-motivationFor
example, the physician can state, Lets talk about
what you can do to be more physically active.
Effectiveness
In motivational interviewing, the traditional
approach of advice giving gives way to one of reflective
listening. Although a physician may give sound and logical advice, the patient, often concurrently, experiences
resistance to that advice. Motivational interviewing
reframes the patientphysician interaction but does not
necessarily add time to the patient visit. Studies show that
when a patient is allowed to talk and the physician is
actively listening and reflecting back to the patient what
he or she has heard, no more than 3 minutes are added to
the encounter (8). Use of the reflective listening approach
helps to better define patient concerns and decreases
late-arising concerns at the end of the patients visit (9).
Principles and Practice of

Motivational Interviewing
Motivational interviewing helps the patient identify the
thoughts and feelings that cause her to continue
unhealthy behaviors and help her to develop new thought
patterns to aid in behavior change. This technique is implemented most effectively after the physician has established
a trusting rapport with the patient. Once the desired outcome (eg, weight loss, better compliance with contraception, smoking cessation) is set, the health care provider then
uses the following principles during the interview:
Express empathy and avoid argumentsFor example, as part of a discussion about weight loss in a
patient with diabetes mellitus, the physician can
state, I understand that is has been difficult for you
to exercise and lose weight in the past. Many of my
patients find this to be difficult. I think it is still
important for us to try to find ways for you to work
on this. What do you think you can do to exercise
more and eat less?
Develop discrepanciesThe physician can help the
patient understand the difference between her behavCPT only 2008 American Medical Association. All Rights Reserved.
Motivational interviewing techniques have been evaluated and found to be effective in randomized clinical trials. These trials have examined the impact of the use of
motivational interviewing to elicit behavior modification
such as smoking cessation, human immunodeficiency
virus (HIV) risk reduction, and increased diet and exercise (4, 10). In a meta-analysis of 72 randomized clinical
trials on the effectiveness of motivational interviewing in
eliciting behavior change such as smoking cessation,
weight loss, decreased alcohol use, and cholesterol level
control, it was found that motivational interviewing had
a significant and clinically relevant effect in modifying
behaviors in approximately 75% of the studies, with an
approximate equal effect on those with physiologic and
psychologic diseases (11). More than one encounter
ensured greater effectiveness with the patient. Discussion
of behavior change to improve health outcomes is not
associated with diminished patient satisfaction. In fact,
tobacco use assessment and counseling by the physician
are associated with greater satisfaction (12).
Applications for the

ObstetricianGynecologist
The use of motivational interviewing has been shown to
help reduce alcohol consumption in heavy drinkers during pregnancy and help drinkers who do not want to
become pregnant use contraception more effectively (13).
Other studies suggest that the use of motivational interviewing may increase the duration of breast-feeding and
improve smoking cessation efforts. Some studies support
the use of motivational interviewing to reduce risky
behaviors in individuals with HIV infection as well as
improve adherence with medication regimens. The use of
motivational interviewing has been successful in such
diverse areas as reducing the fear of childbirth, and thus
decreasing the rate of cesarean delivery (14), and in
lifestyle intervention for women with polycystic ovary
syndrome. Studies have shown the effective application of
the use of motivational interviewing in changing risk
462
behavior in adolescents (15, 16). The use of motivational

interviewing also has been used in the general population
to aid in counseling for effective contraception use and to
reduce the risk of sexually transmitted diseases. Specific
Current Procedural Terminology (CPT) codes are available
for billing for the counseling of patients regarding smoking cessation and other substance abuse. In addition, evaluation and management codes can be selected, using the
time component, when working with patients to modify
specific behaviors related to a medical diagnosis. The use
of motivational interviewing is one of the strategies for
structured brief intervention mentioned within the coding requirements.
Training
Traditional medical training has not included the principles of motivational interviewing, but curricula have been
developed and evaluated for both postgraduate and medical student training (11). Several approaches, known by
their acronyms, have been developed for use in training.
One such approach is FRAMES (17):
F FeedbackCompare the patients risk behavior with
nonrisk behavior patterns. She may not be aware that
what she considers normal is risky.
R ResponsibilityStress that it is her responsibility to
make the change.
A AdviceGive direct advice (not insistence) to
change the behavior.
M MenuIdentify risk situations and offer options
for coping.
E EmpathyUse a style of interaction that is understanding and involved.
S Self-efficacyElicit and reinforce self-motivating
statements such as I am confident that I can stop
drinking. Help the patient to develop strategies,
implement them, and commit to change.
An example of an intervention, using the FRAMES
approach, with a nonpregnant woman is listed as follows:
Your drinking is in the range that we call risky drinking
because it can cause health risks for you. These risks
includeIt is important to reduce your drinking to no
more than seven drinks per week and no more than three
drinks on one occasion. The health care provider should
ask for a response to this advice to ensure that the patient
understands the need to take action: What do you think
about what I just said? How do you feel about reducing
your drinking below risky levels? What about using effective birth control? If the patient agrees, consider establishing goals and creating a change plan to reinforce her
behavior change.
Other successful motivational interviewing approaches
can be found within the ACOG Drinking and Reproductive Health Tool Kit (17).
Training courses in motivational interviewing can be

brief. In one clinical trial, it was noted that obstetric care
clinicians who viewed a 20-minute motivational interviewing training video showed greater empathy, minimized patient defensiveness, and supported womens
beliefs in their ability to change (18). Presentation of techniques used for motivational interviewing and case examples are suitable for Grand Rounds or other continuing
medical education activities.
Coding
As of 2008, new CPT codes have been developed for
patient counseling using motivational interviewing and
other structured counseling techniques for smoking
cessation and for screening and intervention in cases of
alcohol and substance abuse. Smoking cessation coding
information is available on the ACOG web site at
www.acog.org/departments/dept_web.cfm?recno=13.
For patients with positive screening results for substance use or alcohol abuse, a motivational discussion by
the physician or a qualified staff member that is focused
on increasing the patients understanding of the impact of
substance use and motivating behavior change can be
coded for reimbursement. Evaluation and Management
(E/M) service codes are listed as follows (both assessment
and intervention components must be documented):
99408Alcohol and/or substance (other than tobacco) abuse structured assessment and brief intervention services 1530 minutes
99409Screening and brief intervention services
greater than 30 minutes
These E/M services are separate from other E/M services
that are performed during the same clinical visit. Modifier
25, indicating an additional separate and distinct E/M service, may be coded for some health plans.
G0396Alcohol and/or substance (other than
tobacco) abuse structured assessment and brief
intervention services 1530 minutes
G0397Screening and brief intervention services
greater than 30 minutes
Conclusion
Applying principles of motivational interviewing to
everyday patient interactions has the potential to elicit
behavior change that contributes to positive health outcomes. These changes could have an important impact on
the management of major diseases in women. In addition,
the principle of effective listening improves physician
patient communication and patient satisfaction during all
types of physicianpatient encounters. Motivational interviewing principles should be incorporated into physician
and medical student training. Although the groundwork
CPT only 2008 American Medical Association. All Rights Reserved.
COMMITTEE OPINIONS
for eliciting behavior change can be set during a brief

encounter, follow-up is helpful and often necessary to
aid in the achievement of long term, often incremental, results. Current Procedural Terminology codes are
available to aid in obtaining reimbursement for time
spent engaging patients in motivational interviewing. Incorporation of motivational interviewing tools
into everyday clinical encounters enhances the obstetriciangynecologists ability to serve patients.
Resources
Books
Miller WR, Rollnick S. Motivational interviewing:
preparing people for change. 2nd ed. New York (NY):
Guilford Press; 2002
Rollnick S, Miller WR, Butler C. Motivational interviewing in health care: helping patients change
behavior. New York (NY): Guilford Press; 2008.
Videos
Miller WR. Motivational interviewing. Albuquerque
(NM): University of New Mexico; 1989. Available
from the author at the Department of Psychology,
University of New Mexico, Albuquerque, NM 87131,
(505) 277-4121.
Hester RK, Handmaker NS. Motivating pregnant
women to stop drinking. Albuquerque (NM):
Behavior Therapy Associates; 1997. Available from
Behavior Therapy Associates, 9426 Indian School
Road NE, Suite 1, Albuquerque, NM 87112, (505)
345-6100.
Additional video training materials available at:
www.motivationalinterview.org/training/videos.html
References
1. Golin CE, Patel S, Tiller K, Quinlivan EB, Grodensky CA,
Boland M. Start talking about risks: development of a motivational interviewing-based safer sex program for people
living with HIV. AIDS Behav 2007;11(suppl):S7283.
Patient communication. In: Special issues in womens
3. Steinbrook R. Imposing personal responsibility for health.
N Engl J Med 2006;355:7536.
4. Dunn C, Deroo L, Rivara FP. The use of brief interventions
adapted from motivational interviewing across behavioral
domains: a systematic review. Addiction 2001;96:172542.
5. Hettema J, Steele J, Miller WR. Motivational interviewing.
Annu Rev Clin Psychol 2005;1:91111.
6. Bundy C. Changing behaviour: using motivational interviewing techniques. J R Soc Med 2004;97(suppl 44):437.
CPT only 2008 American Medical Association. All Rights Reserved.
463
7. Prochaska JO, DiClemente CC, Norcross JC. In search of

how people change. Applications to addictive behaviors.
Am Psychol 1992;47:110214.
8. Beckman HB, Frankel RM. The effect of physician behavior
on the collection of data. Ann Intern Med 1984;101:6926.
9. Marvel MK, Epstein RM, Flowers K, Beckman HB.
Soliciting the patients agenda: have we improved? JAMA
1999;281:2837.
10. Burke BL, Arkowitz H, Menchola M. The efficacy of motivational interviewing: a meta-analysis of controlled clinical
trials. J Consult Clin Psychol 2003;71:84361.
11. Rubak S, Sandbaek A, Lauritzen T, Christensen B.
Motivational interviewing: a systematic review and metaanalysis. Br J Gen Pract 2005;55:30512.
12. Barzilai DA, Goodwin MA, Zyzanski SJ, Stange KC. Does
health habit counseling affect patient satisfaction? Prev Med
2001;33:5959.
13. Floyd RL, Sobell M, Velasquez MM, Ingersoll K, Nettleman
M, Sobell L, et al. Preventing alcohol-exposed pregnancies:
a randomized controlled trial. Project CHOICES Efficacy
Study Group [published erratum appears in Am J Prev Med
2007;32:360]. Am J Prev Med 2007;32:110.
14. Saisto T, Salmela-Aro K, Nurmi JE, Kononen T, Halmesmaki
E. A randomized controlled trial of intervention in fear of
childbirth. Obstet Gynecol 2001;98:8206.
15. Knight JR, Sherritt L, Van Hook S, Gates EC, Levy S, Chang
G. Motivational interviewing for adolescent substance use:
a pilot study. J Adolesc Health 2005;37:1679.
16. Erickson SJ, Gerstle M, Feldstein SW. Brief interventions
and motivational interviewing with children, adolescents,
and their parents in pediatric health care settings: a review.
Arch Pediatr Adolesc Med 2005;159:117380.
Drinking and reproductive health: a fetal alcohol spectrum
disorders prevention tool kit. Washington, DC: ACOG;
2006. Available at: http://www.acog.org/departments/health
issues/FASDToolKit.pdf. Retrieved September 19, 2008.
18. Handmaker NS, Hester RK, Delaney HD. Videotaped training in alcohol counseling for obstetric care practitioners: a
randomized controlled trial. Obstet Gynecol 1999;93:2138.

ISSN 1074-861X
Motivational interviewing: a tool for behavior change. ACOG Committee Opinion No. 423. American College of Obstetricians and
464

Abortion Access and Training

Committee on Health
Women
The Committee on
Health Care for Underserved Women would like
to thank Eve Espey, MD,
for her assistance in the
development of this
document.
This information should not
be followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Despite a decrease in abortion rates over the past decade, numerous
political, social, and provider barriers limit access to abortion services. Barriers include
state restrictions and mandates limiting access, lack of public funding for abortion services, and the decrease in abortion providers. Abortion education and training are limited
in medical schools and in residency programs. The American College of Obstetricians and
Gynecologists supports education in family planning and abortion for both medical students and residents and abortion training among residents. In addition, the American
College of Obstetricians and Gynecologists supports availability of reproductive health
services for all women, including strategies to reduce unintended pregnancy and to
improve access to safe abortion services.
Abortion is one of the most common health

services performed in the United States and
is an integral component of womens reproductive health services. In 2005, 1.2 million
abortions were performed (1). Approximately 50% of women in the United States
will experience an unintended pregnancy by
age 45 years, and based on current abortion
rates, nearly one in three women will have an
abortion by age 45 years (2). Since 1973 when
the U.S. Supreme Court recognized the
constitutional right to abortion in Roe v.
Wade, morbidity and mortality from the
performance of unsafe abortion have
decreased dramatically. Abortion-related
deaths decreased from 40 per million live
births in 1970 to eight per million live births
in 1976 (3). Although the majority of terminations are performed with aspiration, medication abortion has provided an alternative
for women seeking first trimester termination (up to 63 days) of pregnancy since 2000,
when the U.S. Food and Drug Administration
approved mifepristone and misoprostol (4).
In 2005, early medication abortion accounted for 13% of abortions.
Public health efforts have focused on
reducing the frequency of unintended pregnancy, but the demand for abortion continues. The availability of abortion services is in
jeopardy because of restricted access to the
procedure and to limited training of physicians during residency.
Reducing the Need for

Abortion
Reducing unintended pregnancy is the best
way to reduce abortion. Abortion rates have
decreased over the past decade. Obtaining
accurate statistics about abortion prevalence
is difficult given underreporting of abortion
and lack of a national requirement for reporting abortion. Some states require reporting
and others voluntarily report to the Centers
for Disease Control and Prevention. Statistics
from the Centers for Disease Control and
Prevention indicate that the number of abortions in the United States has decreased during the 1990s and was at its lowest level in
2005 since 1974, at 19.4 abortions per 1,000
reproductive-aged women (1). The decrease
in abortions directly reflects the decrease in
unintended pregnancy over the same period
(1). Three quarters of the decrease in unintended pregnancy is attributable to higher
contraceptive prevalence and use of more
effective contraceptive methods in reproductive-aged women (5). Strategies that may contribute to higher contraceptive prevalence
include comprehensive sexuality education
and improved access to contraceptive methods and emergency contraception.
Reduced Access to Abortion

Numerous barriers limit access to abortion.
Federal funds may not be used for abortion
COMMITTEE OPINIONS
except when the womans life is endangered or in the case

of rape or incest. Only 17 states allow state Medicaid
funds to be used for medically necessary abortions (6).
Private insurance varies in its coverage of abortion. Some
states specifically prohibit private insurance from covering abortion except in cases where the womans life
would be endangered if she carried the pregnancy to
term (7). Lack of health insurance and other financial
concerns constitute a further barrier to access for the economically disadvantaged women who require abortion
services.
State mandated restrictions on abortion reduce
access. Thirty five states require some parental notification or consent or both for a minor seeking abortion (8).
A minor can be exempted from a states parental notification or consent requirement or both through a judicial
bypass, by which a court grants approval instead of a parent. However, some evidence suggests that these procedures are frequently inadequate as well as medically and
psychologically harmful to adolescents (9, 10). Twentyfour states require delays of up to 24 hours before an
abortion may be performed as well as requiring the provision of information about abortion that may be misleading and sometimes not based on scientific evidence
(11). Parental notification and consent laws and mandatory delays create obstacles for women, including family
problems, increased expense, and travel difficulties. These
restrictions may disproportionately affect low-income
women, particularly those in rural settings.
The number of abortion providers has decreased
over the past 2 decades. From 1996 to 2000, the number
of abortion providers decreased from 2,042 to 1,819, a
decrease of 11% (1). From 2000 to 2005, that number
decreased from 1,819 to 1,787, a further decrease of 2%
(1). Nearly 35% of women across 87% of U.S. counties
had no abortion provider in 2005 (1). The lack of providers and the lack of integration of the procedure into
routine practice may single out abortion as a reproductive
health service that is much less accessible than others.
One third of women live in counties without an abortion
provider and more than 20% of women undergoing
abortion in 2000 traveled more than 50 miles to obtain
the procedure (12).
Abortion may take place in an atmosphere of controversy, harassment, and sometimes violence (13). The highly charged emotional and political debate stigmatizes the
women who undergo abortion and the providers who
offer abortion. In addition to creating a barrier for seeking
care, this negative atmosphere may be a deterrent to training providers and offering reproductive health services.
Abortion Training
Despite the high demand for abortion procedures, education and training in abortion care are limited. Education
in medical school about abortion is limited. In a recent
survey of abortion education in medical school curriculum, 17% of educators reported no formal education
465
about abortion either in the preclinical or clinical years

for medical students (14). Only 32% of schools have at
least one lecture specifically about abortion during the
clinical years (14). Although 45% of schools offer a clinical experience in abortion care, participation is low (14).
Unlike most clinical experiences that are integrated into
the clerkship, clinical experience in abortion is often opt
instudents must discuss their interest with the clerkship director and help arrange the clinical experience.
Approximately one half of the schools offered a fourthyear elective in family planning and abortion, but few students participated (14).
Obstetrics and gynecology residency training in
abortion care is similarly limited. Concerns about the lack
of abortion training led the Accreditation Council for
Graduate Medical Education (ACGME) to issue program
requirements in 1996 that were specific to abortion training (15). These standards, supported by the American
College of Obstetricians and Gynecologists, required that
experience with induced abortion must be part of residency training. Although residency programs may opt
out of providing in-house training, they must provide
their residents the opportunity for abortion training at an
outside facility. Similarly, residents with religious or
moral objections may opt out of receiving abortion training. However, residents must receive training in management of abortion complications.
Despite the institution of these standards, a survey
performed by the National Abortion Federation in 1998
of the 261 accredited obstetrics and gynecology residencies revealed that although 81% of programs reported
that they offered first-trimester abortion training, only
46% offered it routinely. In 34% of programs, abortion
training was offered as an elective, outside the standard
curriculum (16). The nature of elective or opt in training
places the burden to create a clinical experience on the
residents, and prior data show that the majority of residents participate in training when it is integrated whereas a minority of residents participate when it is elective
(17). Forty percent of programs responded that fewer
than one half of their residents received training and 14%
responded that no residents were trained. In a follow-up
survey, conducted in 2004, 51% of responding obstetrics
and gynecology residency program directors reported
their programs offered routine abortion training, 39%
offered elective training, and 10% did not offer training at
all (18). Residents who attended programs where abortion training was integrated into the curriculum were
more likely to undergo training in all abortion modalities
and received more training.
A recent study supports high satisfaction with abortion training (19). Obstetrics and gynecology residents at
the University of California at San Francisco were asked
to evaluate their rotations and, specifically, to compare
the value of their family planning rotation, which
includes abortion training, with others. The family planning rotation received the highest rating of the third-year
466
resident rotations and was comparable to a high volume

surgical rotation. Training in abortion offers many skills
which are applicable for the obstetrics and gynecology
practice, including early gestational sizing through the
use of examination and ultrasonography, pain management, and the use of manual vacuum aspiration for
incomplete and missed abortions. Furthermore, evidence
suggests that residents who receive more extensive abortion training are more likely to provide abortions after
residency (20). Information on family planning and abortion training opportunities is listed in the box.
ACOG supports the availability of comprehensive
reproductive health services for all women (21) and
specifically supports:
1. Strategies that may reduce unintended pregnancy,
such as comprehensive sexuality education and
improved access to effective contraceptive methods
and emergency contraception for all women wishing
to avoid pregnancy.
2. Availability of safe, legal, and accessible abortion
services.
3. Education about family planning and abortion for all
medical students as an integral part of reproductive
health education.
4. Education about family planning and abortion as an
integrated component of the obstetrics and gynecology residency training.
Family Planning and Abortion Training

Opportunities
The Fellowship in Family PlanningThe objective of the
program is to develop specialists focused on research,
teaching, and clinical practice in contraception and abortion by receiving training in clinical and epidemiologic
research, developing clinical and teaching skills, working
internationally, and connecting to a rapidly expanding
network of family planning experts. For more information,
go to: http://familyplanningfellowship.org/whatis.html.
The Kenneth J. Ryan Residency Training Program in
Abortion and Family PlanningA national program with
the goal of formally integrating and enhancing family
planning training for residents in obstetrics and gynecology. It strives to create academic settings for didactic
education, clinical training, and research. For more information, go to: http://bixbycenter.ucsf.edu/training/training/ kenneth_j_ryan_training.html.
For additional information, please go to www.acog.org/
goto/underserved. Please note the American College of
Obstetricians and Gynecologists (ACOG) does not necessarily endorse the views expressed or the facts presented on these web sites. Further, ACOG does not endorse
any commercial products that may be advertised or available on these web sites.
References
1. Jones RK, Zolna MR, Henshaw SK, Finer LB. Abortion in
the United States: incidence and access to services, 2005.
Perspect Sex Reprod Health 2008;40:616.
2. Guttmacher Institute. In brief: facts on induced abortion in
the United States. New York (NY): GI; 2008. Available at:
http://www.guttmacher.org/pubs/fb_induced_abortion.ht
ml. Retrieved July 17, 2008.
3. Cates W Jr, Grimes DA, Schulz KF. The public health impact
of legal abortion: 30 years later. Perspect Sex Reprod Health
2003;35:258.
4. Medical management of abortion. ACOG practice bulletin
5. Santelli JS, Lindberg LD, Finer LB, Singh S. Explaining
recent declines in adolescent pregnancy in the United
States: the contribution of abstinence and improved contraceptive use. Am J Public Health 2007;97:1506.
6. Guttmacher Institute. State funding of abortion under
Medicaid. State Policies in Brief. New York (NY): GI; 2008.
spib_SFAM.pdf. Retrieved December 19, 2007.
7. Guttmacher Institute. Restricting insurance coverage of
abortion. State Policies in Brief. New York (NY): GI; 2008.
spib_RICA.pdf. Retrieved July 22, 2008.
8. Guttmacher Institute. Parental involvement in minors
abortions. State Policies in Brief. New York (NY): GI; 2008.
spib_PIMA.pdf. Retrieved July 22, 2008.
9. The adolescents right to confidential care when considering
abortion. American Academy of Pediatrics. Pediatrics 1996;
97:74651.
10. Dailard C, Richard CT. Teenagers access to confidential
reproductive health services. Guttmacher Rep Public Policy
2005;8(4):611.
11. Guttmacher Institute. Counseling and waiting periods for
abortion. State Policies in Brief. New York (NY): GI; 2008.
spib_MWPA.pdf. Retrieved July 16, 2008.
12. Henshaw SK, Finer LB. The accessibility of abortion services in the United States, 2001. Perspect Sex Reprod Health
2003;35:1624.
13. Harper CC, Henderson JT, Darney PD. Abortion in the
United States. Annu Rev Public Health 2005;26:50112.
14. Espey E, Ogburn T, Chavez A, Qualls C, Leyba M. Abortion
education in medical schools: a national survey. Am J
15. Accreditation Council for Graduate Medical Education.
ACGME program requirements for graduate medical education in obstetrics and gynecology. Chicago (IL): ACGME;
2007. Available at: http://www.acgme.org/acWebsite/downloads/RRC_progReq/220obstetr icsandg ynecology07012007.pdf. Retrieved December 19, 2007.
16. Almeling R, Tews L, Dudley S. Abortion training in U.S.
obstetrics and gynecology residency programs, 1998. Fam
Plann Perspect 2000;32:26871, 320.
COMMITTEE OPINIONS
17. MacKay HT, MacKay AP. Abortion training in obstetrics

and gynecology residency programs in the United States,
1991-1992. Fam Plann Perspect 1995;27:1125.
18. Eastwood KL, Kacmar JE, Steinauer J, Weitzen S, Boardman
LA. Abortion training in United States obstetrics and gynecology residency programs. Obstet Gynecol 2006;108:
3038.
19. Steinauer J, Drey EA, Lewis R, Landy U, Learman LA.
Obstetrics and gynecology resident satisfaction with an
integrated, comprehensive abortion rotation. Obstet
Gynecol 2005;105:133540.
20. Steinauer JE, Landy U, Jackson RA, Darney PD. The effect
of training on the provision of elective abortion: a survey of
five residency programs. Am J Obstet Gynecol 2003;
188:11613.
Abortion policy. ACOG Statement of Policy. Washington,
DC: ACOG; 2007.
467

ISSN 1074-861X
Abortion access and training. ACOG Committee Opinion No. 424.
Gynecol 2009;113:24750.
468

Health Care for Undocumented

Immigrants
Committee on Health
Women
The Committee would
like to thank Alan
Waxman, MD, MPH,
and Raymond Cox, MD,
MBA, for their assistance
in the development of
this document.
be followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Abstract: Undocumented immigrants are less likely than other residents of the
United States to have health insurance. Their access to publicly funded health programs
has become increasingly limited since the passage of welfare reform in 1996 and varies
from state to state. This is reflected in less preventive health care, including prenatal
care, and poorer health outcomes, including those associated with childbirth. The U.S.born children of undocumented immigrant women are U.S. citizens, and the nations public health is enhanced by assuring that all who reside in the United States, including
undocumented immigrants, have access to quality health care.
Scope of the Problem

The United States has been called a nation of
immigrants. Approximately 11% of the U.S.
population, more than 30 million people, were
born outside the United States (1). Two thirds
of these immigrant residents are not U.S. citizens (1). Approximately 29% of these immigrant residents are undocumented (i.e. they
either entered the country illegally or have
expired visas) (2, 3). Over the past 30 years, the
proportion of recent immigrants in the
United States without documentation has
increased almost 10-fold (4). A majority of
undocumented immigrants (57%) come from
Mexico, and almost one quarter (24%) are
from elsewhere in Latin America. The remainder come from Asia (9%), Europe and Canada
(6%), or Africa and other locales (4%) (2, 3).
The undocumented immigrant population is spread throughout the United States,
with about one half concentrated in
California, Texas, Florida, and New York (2).
Thirty five percent of undocumented immigrants are women and 15% are children.
Because children born in the United States
are granted citizenship by the 14th amendment to the U.S. Constitution, many children
living in families headed by undocumented
immigrants are U.S. citizens (3, 5).
Undocumented immigrants frequently
remain in the United States for many years. A
survey by the Kaiser Family Foundation of
undocumented Latinos in Fresno County
and Los Angeles County, found that 60% and

65%, respectively, of adult undocumented
Latinos have resided in the United States
for more than 5 years (6). Most undocumented immigrants live in poverty and have
low rates of health insurance coverage (5, 7,
8). Prenatal care coverage may be an exception. A recent study examining prenatal coverage among undocumented Hispanic
women who gave birth in three U.S. cities,
found that 7999% had some coverage,
mostly from public sources (9).
Immigrants do not appear to use an
excess of health care resources. In Los
Angeles County, undocumented immigrants
comprise 12% of the population, but the cost
of their medical care represents only 6% of
medical expenditures in the county (4). In a
1998 study, immigrants (documented and
undocumented) used 55% fewer dollars than
their U.S.-born counterparts on medical care
and prescription drugs (10). Undocumented
Latino immigrants are less likely to visit a
physician in an outpatient setting than the
general U.S. population, although their rate
of childbirth-related hospitalization is significantly higher (5).
Health Status of
Undocumented Immigrant
Women
Studies in several areas of the country have
found that undocumented immigrant women
COMMITTEE OPINIONS
begin prenatal care later and have fewer prenatal visits

compared with the general population (9, 11). Use of
prenatal care varies, however, with the availability of publicly funded prenatal programs (9). Looking at maternal
outcomes, a Colorado study found significantly lower
rates of primary cesarean deliveries and increased rates
of operative vaginal deliveries and vaginal birth after
cesarean in undocumented women when compared with
the general state population (11). Birth complications
were more common among the undocumented women,
including meconium staining, excessive bleeding, precipitous labor, malpresentation, cord prolapse, and fetal
distress. Neonatal morbidity, including fetal alcohol syndrome, respiratory distress syndrome and seizures, also
was more common (11). Few studies of perinatal morbidity distinguish undocumented from legal immigrant
women.
Some investigators have found that Hispanic immigrants have lower rates of prematurity and low birth
weight infants than the general U.S. population (1113).
These outcomes have been attributed to a healthy
migrant effect resulting from a bias toward younger and
healthier individuals coming to the United States. This
tendency toward better birth outcomes particularly in
Latina immigrants appears to last only one generation.
Some evidence indicates that immigrants have less
access to preventive services. For example, although the
incidence and mortality from cervical cancer is on the
decline among women born in the United States, it is
actually increasing among immigrant women (14, 15). A
1998 survey showed that U.S. and foreign-born Latinas
were less likely than whites to have had a recent mammogram and more likely to have never had a mammogram
or Pap test (16). A retrospective study of patients with
cervical cancer in Chicago found recent immigrant status
to be a risk factor for never having had a Pap test (17).
Lack of health insurance was the strongest predictor of no
recent mammogram, clinical breast examination, or Pap
test (16).
Health Programs and Undocumented

Immigrants
Although some health care services are available to uninsured immigrants, the complexity of accessing care in the
face of ever-changing and conflicting laws, coupled with a
fear of harassment by immigration officials, inhibit many
legal and undocumented immigrants from seeking care.
The Personal Responsibility and Work Opportunity
Reconciliation Act, popularly known as the 1996 Welfare
Reform Act, widened the gap in health insurance coverage
between low-income U.S. citizens and immigrants (18).
The Act eliminated Medicaid and other federal health
program eligibility for indigent undocumented immigrants, and restricted eligibility for legal immigrants,
allowing exceptions for emergency medical conditions,
immunization, and treatment for symptoms of communicable diseases.
469
Welfare reform also made undocumented immigrants ineligible for many similar benefits previously provided by state and local governments unless new state
legislation was enacted (19). A number of states have
passed legislation to continue use of state funds to provide care, especially prenatal care, to undocumented
immigrants based on residence and financial need (9, 20).
A number of federally funded public health programs are
still available to undocumented immigrants, including
those administered under Title V of the Social Security
Act (Maternal and Child Health Services Block Grant)
and Title X of the Public Health Service Act (Family
Planning). In addition, Federally Qualified Health
Centers, Healthcare for the Homeless, and Migrant
Health Clinics provide comprehensive primary care,
including prenatal care, without regard to income, insurance, or immigration status.
State grantees in the National Breast and Cervical
Cancer Early Detection Program may elect to offer
screening without regard to immigration status. If cancer
or premalignant conditions are diagnosed via this program, however, undocumented patients may not receive
care through its companion law, the Breast and Cervical
Cancer Prevention and Treatment Act (21). The Act
allows Medicaid eligibility for those who receive diagnoses through the program; as stated earlier, undocumented immigrants cannot receive Medicaid benefits.
The State Childrens Health Insurance Program,
which provides health coverage for children in families
with incomes too high for Medicaid but too low to afford
private coverage, contains similar restrictions on care for
immigrant children. In 2002, the Centers for Medicare
and Medicaid Services permitted states to use the State
Childrens Health Insurance Program funds to provide
coverage for fetuses. Some states have used this option as
a way to finance coverage for legal and undocumented
pregnant women. This can be done because, although the
pregnant woman is ineligible, her child will be a U.S. citizen and qualifies for the program. However, conferring
eligibility on the fetus, rather than the pregnant woman
herself, may lead to the exclusion of essential perinatal
services, including postpartum care.
Undocumented immigrants, who meet Medicaid
financial and categorical eligibility requirements but are
not eligible for Medicaid because of their immigration
status, can receive Emergency Medicaid to cover emergency care, including labor and delivery (18). In addition,
federal law requires provision of emergency care to any
individual regardless of insurance or ability to pay,
citizenship, or immigration status (22). Under the
Emergency Medical Treatment and Active Labor Act,
passed in 1986, hospital emergency departments must
provide an appropriate medical screening examination to
any patient who comes to an emergency department
requesting examination or treatment for a medical condition. If the emergency department determines that
the patient is experiencing an emergency medical condi-
470
tion, the hospital must provide treatment until the

patient is stabilized (23). The Emergency Medical
Treatment and Active Labor Act was enacted to ensure
that indigent and uninsured patients receive necessary
emergency medical care, and the law specifically addresses emergency medical conditions for pregnant women.
A pregnant woman in true labor who seeks care may not
be transferred to another facility if there is not adequate
time to effect a safe transfer and if the transfer would
pose a threat to the health or safety of the mother or the
fetus.
The Emergency Medical Treatment and Active Labor
Act requires hospitals to provide necessary treatment, but
does not require the federal government to reimburse
hospitals for the cost of this care. Funding was addressed
for the first time when Congress passed Section 1011 of
the Medicare Prescription Drug, Improvement, and
Modernization Act of 2003 (Pub. L. 108-173), which provides $250 million each year for fiscal years 20052008 to
reimburse hospitals, physicians, and ambulance companies for emergency care provided to undocumented
immigrants under the Emergency Medical Treatment and
Active Labor Act (22). Health care providers can send
payment requests until March 30, 2009, when the programs fiscal year ends. Funds will remain available until
expended or otherwise revised. Updated information can
be found at: http://www. cms.hhs.gov/undocAliens/.
Recommendations
supports a basic health care package for all women. The
College has long promoted the elimination of the disparities in health status and health care access among women
and includes recent and undocumented immigrants in its
advocacy efforts. Immigrant women living within our
borders should have the same access to basic preventive
health care as U.S. citizens without regard to their country of origin or documentation of their status. The
College can help to achieve this by promoting universal
access to health insurance for all individuals in the United
States and eliminating barriers to existing federal programs, such as Medicaid (24).
Health professionals can play a pivotal role in
improving access to needed health care for undocumented immigrants by:
Helping the larger society understand the importance of universal health care access
Being advocates for the goal of securing quality,
affordable coverage for every woman with active support of proposed local, state, and national legislation
Continuing to support the safety net system and provision of care in the community and office setting for
the uninsured
Providing a comfortable office atmosphere with translators and materials available in languages appropriate for the patient population
Becoming informed and involved in the American

College of Obstetricians and Gynecologists government relations outreach activities. (For more information go to: http://www.acog.org/departments/dept_
web.cfm?recno=11.)
References
1. Gold RB. Immigrants and Medicaid after welfare reform.
Guttmacher Rep Public Policy 2003;6(2):69.
2. Pew Hispanic Center. Unauthorized migrants: numbers
and characteristics. Washington, DC: PHC; 2005. Available
at: http://pewhispanic.org/files/reports/46.pdf. Retrieved
January 31, 2008.
3. Pew Hispanic Center. The size and characteristics of the
unauthorized migrant population in the U.S. estimates
based on the March 2005 Current Population Survey.
Washington, DC; PHC; 2006. Available at: http://pewhispanic.org/files/reports/61.pdf. Retrieved January 31, 2008.
4. Goldman DP, Smith JP, Sood N. Immigrants and the cost of
medical care. Health Aff 2006;25:170011.
5. Berk ML, Shur CL, Chavez LR, Frankel M. Health care use
among undocumented Latino immigrants. Health Aff 2000;
19:5164.
6. Henry J. Kaiser Family Foundation. Californias undocumented Latino immigrants: a report on access to health
care services. Menlo Park (CA): KFF; 1999. Available at:
http://www.kff.org/statepolicy/upload/California-sUndocumented-Latino-Immigrants-A-Report-on-Accessto-Health-Care-Services-Report.pdf. Retrieved January 31,
2008.
7. Prentice JC, Pebley AR, Sastry N. Immigration status and
health insurance coverage: who gains? Who loses? Am J
Public Health 2005;95:10916.
8. Goldman DP, Smith JP, Sood N. Legal status and health
insurance among immigrants. Health Aff 2005;24:164053.
9. Fuentes-Afflick E, Hessol NA, Bauer T, OSullivan MJ,
Gomez-Lobo V, Holman S, et al. Use of prenatal care by
Hispanic women after welfare reform. Obstet Gynecol 2006;
107:15160.
10. Mohanty SA, Woolhandler S, Himmelstein DU, Pati S,
Carrasquillo O, Bor DH. Health care expenditures of immigrants in the United States: a nationally representative
analysis. Am J Public Health 2005;95:14318.
11. Reed MM, Westfall JM, Bublitz C, Battaglia C, Fickenscher
A. Birth outcomes in Colorados undocumented immigrant
population. BMC Public Health 2005;5:100.
12. Kelaher M, Jessop DJ. Differences in low-birthweight
among documented and undocumented foreign-born and
US-born Latinas. Soc Sci Med 2002;55:21715.
13. Leslie JC, Diehl SJ, Galvin SL. A comparison of birth outcomes among US-born and non-US-born Hispanic women
in North Carolina. Matern Child Health J 2006;10:338.
14. Schleicher E. Immigrant women and cervical cancer prevention in the United States. Baltimore (MD): Womens and
Childrens Health Policy Center, Johns Hopkins Bloomberg
School of Public Health; 2007. Available at: http://www.
jhsph.edu/wchpc/publications/ImmigrantWomenCer
CancerPrevUS.pdf. Retrieved July 28, 2008.
COMMITTEE OPINIONS
15. Seeff LC, McKenna MT. Cervical cancer mortality among

foreign-born women living in the United States, 1985 to
1996. Cancer Detect Prev 2003;27:2038.
16. Rodriguez MA, Ward LM, Perez-Stable EJ. Breast and cervical cancer screening: impact of health insurance status,
ethnicity, and nativity of Latinas. Ann Fam Med 2005;
3:23541.
17. Behbakht K, Lynch A, Teal S, Degeest K, Massad S. Social
and cultural barriers to Papanicolaou test screening in an
urban population. Obstet Gynecol 2004;104:135561.
18. Henry J. Kaiser Family Foundation. Key facts: Medicaid and
SCHIP eligibility for immigrants. Kaiser Commission on
Available at: http://www.kff.org/medicaid/upload/7492.pdf.
19. Kullgren JT. Restrictions on undocumented immigrants
access to health services: the public health implications of
welfare reform. Am J Public Health 2003;93:16303.
20. Henry J. Kaiser Family Foundation. Deficit Reduction Act
of 2005: implications for Medicaid. Kaiser Commission on
Available at: http://www.kff.org/medicaid/upload/7465.pdf.
21. Centers for Disease Control and Prevention. National breast
and cervical cancer early detection program. Available at:
http://www.cdc.gov/cancer/nbccedp. Retrieved July 28, 2008.
22. Centers for Medicare and Medicaid Services. Emergency
health services for undocumented aliens: Section 1011 of
471
the Medicare Modernization Act. Baltimore (MD): CMS;

2005. Available at: http://www.cms.hhs.gov/apps/media/
press/release.asp?Counter=1452. Retrieved January 31,
2008.
23. Kaiser Commission on Medicaid and the Uninsured.
Covering new Americans: a review of federal and state policies related to immigrants eligibility and access to publicly
funded health insurance. Washington, DC: KCMU; 2004.
Available at: http://www.kff.org/medicaid/upload/CoveringNew-Americans-A-Review-of-Federal-and-State-PoliciesRelated-to-Immigrants-Eligibility-and-Access-to-PubliclyFunded-Health-Insurance-Report.pdf. Retrieved October
1, 2008.
24. The Uninsured. ACOG Committee Opinion No. 416.
Copyright January 2009 by the American College of Obstet-ricians
Health care for undocumented immigrants. ACOG Committee Opinion

Gynecol 2009;113:2514.
472

Legal Status: Health Impact for

Lesbian Couples
Committee on Health
Women
The Committee on
Health Care for
Underserved Women
would like to thank
Kirsten Smith, MD, and
Virginia Leslie, MD, for
their assistance in the
development of this
document.
The information should
be followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Women in same-sex relationships encounter barriers to health care that

include concerns about confidentiality and disclosure, discriminatory attitudes and treatment, limited access to health care and health insurance, and often a limited understanding as to what their health risks may be. Lesbians and their families also are adversely
affected by the lack of legal recognition of their relationships. Tangible harm comes from
the lack of financial and health care protections that are granted to legal spouses, and children are harmed by the lack of protections afforded married families. The American
College of Obstetricians and Gynecologists endorses equitable treatment for lesbians and
their families, not only for direct health care needs but also for indirect health care issues;
this should include the same legal protections afforded married couples.
Background
In the United States, civil marriage is a legal
status established through a license issued by
a state government that grants both legal
rights and obligations to two individuals (1).
Civil marriage currently is available to
same-sex couples only in Connecticut (as of
2008) and Massachusetts (as of 2004) (2).
Civil marriage, as recognized by the federal
government, must be between a man and a
woman (3). Civil marriage grants rights under
1,138 federal statutory provisions as well as
additional state protections, benefits, and
responsibilities designed to support and protect family life (4).
Religious marriage is a sacrament or rite
that provides recognition by a specific religious group. These religious organizations
have rules and requirements that are separate
from those established for civil marriage by a
state (1). In the United States, judges and
other public officials have the authority to
establish civil marriages. However, clergy also
have been given the authority to endorse a
civil marriage, leading to significant confusion between the civil and religious aspects of
marriage. The legality of civil marriage
comes from the state not the religious group.
A civil union has a more limited legal
scope than civil marriage. A civil union is a
legal status designed to confer to a same-sex

couple state-based benefits, protections, and
responsibilities similar to civil marriage. In
the United States, Vermont, New Jersey, and
New Hampshire have established civil
unions. Connecticut established civil unions
in 2005. This law remains in place along with
the newest civil marriage ruling in that state
in 2008. (2). These legal arrangements are
not reciprocally recognized in most states,
and are not recognized by the federal government.
A domestic partnership is a legally recognized partnership between two individuals, who may or may not be of the same sex.
Domestic partnership does not provide the
same rights, benefits, and protections as civil
union and civil marriage and what is provided varies by jurisdiction (1). Statewide
domestic partner laws that provide the equivalent of state-level spousal rights to same-sex
couples within the state have been implemented in California, Oregon, and the
District of Columbia. Statewide laws providing some statewide spousal rights to same-sex
couples within the state have been implemented in Hawaii, Maine, and Washington
(2). These legal relationships also are not recognized by the federal government or most
other jurisdictions.
COMMITTEE OPINIONS
In 44 states, laws have been passed prohibiting same

sex marriage or prohibiting recognition of such a marriage from another state. Twenty-nine states have passed
constitutional amendments prohibiting civil marriages
between persons of the same sex (5).
In almost all states, same sex couples are currently
vulnerable and are left to piece together a patchwork of
legal and financial documents to protect themselves and
their families.
Health Considerations Related to

Legal Status
Even with legal documents such as a medical power
of attorney, discriminatory practices can result in a
woman in a same-sex relationship being excluded
from seeing her partner in the hospital (1, 68).
Individuals in same-sex relationships can be prevented from providing consent for medical care or authorizing emergency treatment and health care decisions
for nonbiological or not-jointly adopted children
(1).
In many jurisdictions, even if a woman in a same-sex
relationship does have access to health insurance
through her employer and that employer offers
spouse and family coverage, she is not able to obtain
coverage for her partner (1, 9).
Unless she is defined as a spouse or parent under
state law, a woman in a same-sex relationships does
not have access to the federal Family Medical Leave
Act, which allows those eligible to take up to 12
weeks of unpaid leave each year to care for immediate family members (spouse, child, or parent) (1, 10).
Same-sex couples who are not defined as legal spouses will not have protections and compensation for
families of crime victims in state and federal programs (1, 11).
Even with prior legal arrangements for individuals in
same-sex relationships, the surviving partner may
not be able to sign for the release of the body from
the hospital for funeral/disposition arrangements
(12, 13).
Financial Considerations Related to

Legal Status
A multitude of financial protections are granted to legal
spouses but not to same-sex partners. These financial
protections include differences in taxation eligibility for
Social Security benefits and rights to shared property.
Financial security is intimately tied to access to health
care and the health and well being of women and their
families. Although these examples also apply to unmarried heterosexual partners, they can overcome them by
becoming married. Same-sex partners do not have that
option. Even in states where civil marriage is available to
same-sex couples, the marriage is not recognized by the
473
federal government and does not grant the same protections provided to heterosexual married couples.
When same-sex partners are able to arrange for
domestic partner benefits to cover health insurance,
the value of the benefit is considered taxable income
to the employee under federal law. The only exception is when a domestic partner qualifies as a dependent of the employee under Internal Revenue Service
definitions. Because this amount is also considered
income, the employer must also pay payroll taxes,
such as Social Security on the amount. Additionally,
employees cannot use pretax dollars to pay for a
domestic partners coverage (9).
Same-sex couples cannot file joint tax returns and
are not eligible for additional federal tax benefits and
claims (11).
Same-sex couples are not eligible for the Social
Security and veterans survivor benefits of the
deceased partner (11). A surviving partner may not
have access to spousal benefits under workers compensation. She cannot roll a deceased partners 401K
funds into an IRA without paying income tax and, in
many states, inheritance taxes on those funds. In
many states the surviving partner will be required to
pay inheritance taxes on the partners portion of any
shared assets (14, 15).
For same-sex couples, if a house is titled in one name
only, upon that partners death, the house ownership
passes as designated in the will of the deceased or if
there is no will, to the legal next-of-kin.
In only a few states, those with marriage and some
domestic partnership laws, can a same sex partner
sue for wrongful death of a deceased spouse (16).
Individuals who are U.S. citizens in a same-sex couple cannot sponsor their partner or family members
for immigration and citizenship (1, 17, 18).
Positions of Health Organizations

on Legal Protections for Same-Sex
Couples
The American Psychiatric Association, the American
Psychological Association, and the American Psychoanalytic Association have issued policy statements supporting civil marriage for same-sex partners (1921). The
American Medical Womens Association issued a position
statement on lesbian health in 1993 encouraging national, state, and local legislation to end discrimination based
on sexual orientation in housing, employment, marriage,
tax, and child custody and adoption laws (22). The
American Academy of Pediatrics recognizes the advantages for children of having two legally recognized parents
and in 2002 published their technical report in support of
coparent/second parent adoption by same-sex parents
(23, 24). The American College of Obstetricians and
474
Gynecologists has previously recognized that lesbians

should have equal access to coparenting and second parent adoption rights (25).
Conclusion
is dedicated to the advancement of womens health
through education, practice, research, and advocacy. The
advocates for the health and well-being of all women and
believes that no woman should suffer discrimination (26).
This includes women in same-sex relationships. The
health and well-being of women in same-sex relationships
and their families are harmed by lack of legal recognition
(1, 27, 28). The American College of Obstetricians and
Gynecologists endorses equitable treatment for lesbians
and their families, not only for direct health care needs but
also for indirect health care issues, which includes the
same legal protections afforded married couples.
References
1. Pawelski JG, Perrin EC, Foy JM, Allen CE, Crawford JE, Del
Monte M, et al. The effects of marriage, civil union, and
domestic partnership laws on the health and well-being of
children. Pediatrics 2006;118:34964.
2. Human Rights Campaign. Relationship recognition in the
U.S. Washington DC: HRC; 2008. Available at:
http://www.hrc.org/documents/Relationship_Recognition
_Laws_Map.pdf. Retrieved November 17, 2008.
3. Defense of Marriage Act, Pub L No. 104-199, 110 Stat 2419.
4. General Accounting Office (US). Defense of Marriage Act:
update to prior report. Washington, DC: GAO; 2004.
Available at: http://www.gao.gov/new.items/d04353r.pdf.
5. Human Rights Campaign. Statewide marriage prohibitions.
Washington, DC: HRC; 2008. Available at: http://www.
hrc.org/documents/marriage_prohibitions.pdf. Retrieved
November 17, 2008.
6. Human Rights Campaign. Healthcare laws: state by state.
Available at: http://www.hrc.org/issues/7935.htm. Retrieved
October 28, 2008.
7. Human Rights Campaign. Health care proxy. Available at:
http://www.hrc.org/issues/2725.htm. Retrieved October 28,
2008.
8. Gay and Lesbian Medical Association. Same-sex marriage
and health. Gay and Lesbian Medical Association Marriage
Equality Initiative. San Francisco (CA): GLMA; 2008.
Available at: http://glma.org/document/docWindow.cfm?
fuseaction=document.viewDocument&documentid
=146&documentFormatId=236. Retrieved October 28,
2008.
9. Center for American Progress, The Williams Institute.
Unequal taxes on equal benefits: the taxation of domestic
partner benefits. Washington, DC: CAP; Los Angeles (CA):
WI; 2007. Available at: http://www.americanprogress.
org/issues/2007/12/pdf/domestic_partners.pdf. Retrieved
September 30, 2008.
10. What do spouse,parent, and son or daughter mean for

purposes of an employee qualifying to take FMLA leave? 29
C.F.R. 825.113 (2007).
11. Government Accounting Office. Defense of Marriage Act.
GAO/OGC-97-16. Washington, DC: GAO; 1997. Available
at: http://www.gao.gov/archive/1997/og97016.pdf. Retrieved
October 14, 2008.
12. Equality Maryland. Marriage inequality in the state of
Maryland. Silver Spring (MD): EM; 2006.
13. Human Rights Campaign. To have and to hold? Maybe not.
True stories from same-sex couples denied the protections
of marriage in life and death. Washington (DC): HRC;
2005. Available at: http://www.hrc.org/documents/tohaveandhold.pdf. Retrieved October 29, 2008.
14. Human Rights Campaign. How do I cut the inheritance
taxes for my partner? Washington (DC): HRC; 2000.
Available at: http://www.hrc.org/issues/4670.htm. Retrieved
October 28, 2008.
15. American Civil Liberties Union. Protect your relationship.
New York, NY: ACLU. Available at: http://www.aclu.org/
getequal/rela/protect.html. Retrieved October 20, 2008.
16. Lambda Legal. Relationship recognition for same-sex couples across the United States. Available at: http://data.lambdalegal.org/pdf/690.pdf. Retrieved October 28, 2008.
17. Immigration Equality, Lambda Legal. Sexual orientation
and immigration: the basics. Available at: http://www.
immigrationequality.org/uploadedfiles/Sexual_Orientation_
and_Immigration_Lambda_Booklet.pdf. Retrieved October
29, 2008.
18. Human Rights Campaign. Rights and protections denied
same-sex partners. Available at: http://www.hrc.org/issues/
5478.htm. Retrieved October 28, 2008.
19. American Psychiatric Association. Support of legal recognition of same-sex civil marriage: position statement.
Arlington (VA): APA; 2005. Available at: http://archive.
psych.org/edu/other_res/lib_archives/archives/200502.pdf.
20. American Psychoanalytic Association. Marriage resolution.
New York (NY): APsaA; 2008. Available at: http://
www.apsa.org/ABOUTAPSAA/POSITIONSTATEMENTS/MARRIAGERESOLUTION/tabid/470/Default.as
px. Retrieved September 30, 2008.
21. American Psychological Association. Resolution on sexual
orientation and marriage. Washington, DC: APA; 2004.
Available at: http://www.apa.org/pi/lgbc/policy/marriage.
pdf. Retrieved September 30, 2008.
22. Position paper on lesbian health. American Medical
Womens Association. J Am Med Womens Assoc 1994;49:
86.
23. Coparent or second-parent adoption by same-sex parents.
American Academy of Pediatrics. Pediatrics 2002;109:
33940.
24. Technical report: coparent or second-parent adoption by
same-sex parents. American Academy of Pediatrics.
Primary care of lesbians and bisexual women in obstetric
COMMITTEE OPINIONS
and gynecologic practice. In: Special issues in womens

Access to womens health care. ACOG Statement of Policy.
27. Hammond CB. Time to change. Obstet Gynecol 2006;107:
549.
28. OHanlan KA. Health policy considerations for our sexual
minority patients. Obstet Gynecol 2006;107:70914.
475

ISSN 1074-861X
Legal status: health impact for lesbian couples. ACOG Committee
Gynecologists. Obstet Gynecol;113:46972
476

Health Disparities for Rural Women

Committee on
Health Care for
Underserved Women
The Committee
would like to thank
Ann M. Koontz, DrPH,
and Eliza Buyers, MD,
for their assistance in
document.
The information should
be followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Significant health disparities exist for rural women in all categories of
womens health, including obstetric and gynecologic outcomes and access to care.
Minority women living in rural areas may face even greater risks based on their combined
characteristics. Many rural areas have limited numbers of health care providers, particularly those who provide obstetric and gynecologic care. Generalizations regarding rural
America are difficult because of the heterogeneity of rural areas within the United States
and even within the borders of a single state. Health professionals are encouraged to
engage in activities to diminish health disparities for rural women.
Significant health disparities exist between

women living in rural and urban areas. For
most people, the term rural implies regions
that are less populated and geographically
distant compared with urban areas. Multiple
agencies, policy makers, and researchers have
included aspects of these notions in the many
definitions used to study and report population data, and to determine eligibility and
reimbursement levels for numerous federal
and state programs. Two commonly used
definitions are those generated by the Office
of Management and Budget and the U.S.
Census Bureau, which characterize territories
or populations as metropolitan/nonmetropolitan and urban/rural respectively (13).*
In this document, because of definitional
complexities, the term rural will be used
interchangeably with nonmetropolitan and
the term urban will be used interchangeably with metropolitan.
Rural America represents 80% of the
national landmass and is home to 17% of
U.S. females aged 15 years and older and
approximately 18% of all live births per year
(47). Rural communities are extremely heterogeneous, with substantial regional differences in ethnic and racial composition (8).
*Both definitions identify populations of 50,000 or
greater as urbanized areas but differ in their geopolitical
unit of focus, county for metropolitan/nonmetropolitan
area and census block for urban/rural area. In addition,
some mid-range population areas are classified as metropolitan by one scheme and rural by the other.
Whereas 82% of nonmetropolitan residents

are non-Hispanic white, Hispanics and
Asians are now the fastest growing rural subgroups (4). Well-documented racial and ethnic health disparities (9) may be amplified by
additional barriers to care in rural areas.
Rural Health Disparities

Although national data on womens health
and outcomes according to residence are relatively sparse, disparities for rural women are
apparent. Rates of rural womens health disparities presented as follows reflect comparisons with their urban counterparts unless
otherwise noted. General health conditions
and behaviors for which U.S. rural women
experience higher rates include unintentional injury and motor vehicle related deaths,
suicide, cigarette smoking, obesity, limitation
of activities caused by chronic health conditions (8), and incidence of cervical cancer
(10). Other comparisons show that the
ischemic heart disease death rate in rural
women exceeds that for all U.S. women, and
in some regions of the country, there are
higher rates of heavy alcohol consumption
for women in nonmetropolitan areas (8).
Proportionately fewer rural women receive
such recommended preventive services as a
recent mammogram, Pap test, or colorectal
screening; however, when income and other
sociodemographic variables are controlled,
only the difference for obtaining a mammogram is significant (11).
COMMITTEE OPINIONS
Other examples of less favorable outcomes for U.S.

rural women and their infants related to obstetric and
gynecologic practice include lower likelihood of receiving
at least one family planning service within the past year
(5); highest adolescent birth rates in the nation for rural
teenagers in the South (8); increased risk of inadequate
prenatal care (including late or no prenatal care) that is
especially apparent in rural counties nonadjacent to metropolitan counties (6); higher overall adjusted risk of lowbirth weight that is significantly greater for residents of
rural counties with at least 20% of their population living
in poverty for three decades compared with residents of
all other rural counties (6); and a 17.4% higher risk of
neonatal mortality and a 19.3% higher risk of postneonatal mortality for rural infants after adjusting for maternal
age, parity, race, marital status, education, and inadequate
prenatal care (6). In rural hospitals, African-American
Medicaid beneficiaries are at greater risk of potentially
avoidable maternity complications than non-Hispanic
white Medicaid beneficiaries, despite lower potentially
avoidable maternity complications rates for all Medicaid
deliveries in rural hospitals compared with urban
hospitals (12).
Data in the 2001 Nationwide Inpatient Sample reveal
differences in rates of cesarean delivery in rural hospitals.
Although the total rate in rural hospitals was identical to
that in urban nonteaching hospitals, small rural hospitals
with an average daily census of less than 10, 2549, or
100249 had significantly higher cesarean delivery rates
than comparable urban hospitals (13).
Health Services Access and

Availability
Access to health care for rural residents is complicated by
patient factors as well as those related to the delivery of
care. Rural residents are more likely to be poor, lack health
insurance, or rely substantially on Medicaid and
Medicare; they also travel longer distances to receive care
or to access a range of medical, dental, and mental health
specialty services (1). Increasing closures of hospitalbased obstetric services and decreasing percentages of all
physicians doing deliveries, exacerbated by reluctance to
select rural practice, is disquieting. In 2002, only 56% of
women living in nonmetropolitan counties and 21% of
women in counties with no population made up of 2,500
or more individuals per square mile had access to obstetric care in a local hospital. Reasons cited by hospital
administrators for closing obstetric units include low volumes of deliveries, financial vulnerability because of
Medicaid patients, malpractice burden, and difficulty
finding staff for the obstetric unit (eg, obstetricians, anesthesiologists, family physicians) (14). Counties without
an obstetriciangynecologist affect 5.8 million (29%)
rural women (7). In some rural areas, family physicians
provide 100% of obstetric care. Data show that an
increasing proportion of women are entering obstetrics
and family practice; however, substantially fewer females
477
compared with males in both specialties choose to practice in rural areas (1517). This could contribute to a
potential decrease in the rural workforce.
Obstetric and gynecologic health services along with
family planning options are limited in some nonmetropolitan areas. Counties without publicly funded family
planning clinics are typically the least populated (18).
Data in the 2001 Nationwide Inpatient Sample reveal that
the rate of vaginal birth after cesarean delivery in rural
hospitals (17.8%) was statistically lower than that for
urban nonteaching hospitals (20%) and for urban teaching hospitals (25.5%) (13). Local availability of abortion
services is restricted. Ninety-seven percent of nonmetropolitan counties have no abortion provider. Nonhospital
abortion providers estimate that 19% of their patients
travel 50100 miles, and 8% travel more than 100 miles
(19). There also is concern about availability of emergency contraception. Data on current over-the-counter
availability of emergency contraception in rural pharmacies are lacking.
Current Initiatives to Improve Services

for Rural Women
Regional organization of perinatal services is an important strategy to improve outcomes for underserved
women and their infants in rural communities, although
implementation can be a challenge in these areas. One
indicator used to measure how the system is functioning
is the percentage of very low birth weight (less than 1,500
grams) deliveries that take place in subspecialty hospitals.
Twelve of the 15 states ranked the lowest in the country
on this indicator have relatively high proportions of rural
populations (20, 21). Some studies examining very low
birth weight deliveries suggest that residing in more distant areas from a subspecialty facility, as well as inadequate prenatal care, increases the likelihood of delivery in
a lower level facility (22, 23).
A variety of initiatives have been established to
address the difficulties in providing care to rural women.
There are multiple sources of funding, such as a range of
state programs (eg, Medicaid) and medical school department budgets. Examples of recent or current approaches
are listed as follows:
Oregon enacted legislation to offer financial incentives such as a state income tax credit for rural practitioners and assistance with medical liability insurance
for obstetricians practicing in rural areas (24).
The University of Missouri-Columbia Family
Practice Residency Program incorporated a rural
obstetric rotation to increase the practice of obstetrics among family physicians (25).
Wyoming, a state with no tertiary care centers for
pregnant women or infants and few pediatric specialists, approves out-of-state providers and facilities
as state Medicaid providers. This allows the state to
reimburse transport to and care and delivery in an
478
out-of-state subspecialty hospital when medically

necessary (26).
The Department of Obstetrics and Gynecology at the
University of Texas Medical Branch in Galveston
developed its Regional Maternal & Child Health
Program to serve geographically underserved women
in 37 off-site clinics. The program addresses culturally
relevant services and transportation needs, and uses
an electronic medical record to facilitate continuity
of care. It also provides free housing in its Regional
Perinatal Residence for high-risk women (and family members) living in distant locations to facilitate
their access to regional center care when hospitalization is not necessary (27).
The Arkansas Medicaid Program and the University
of Arkansas for Medical Sciences are collaborating
with the states medical community to enhance primary obstetric care in rural Arkansas and increase
risk-appropriate referrals to maternalfetal medicine
subspecialists. Their system uses telemedicine and
clinic networks to facilitate access to maternalfetal
medicine consultation services, and to provide continuing education for practitioners (28).
Recommendations
Obstetricians and gynecologists in every region of the
United States can work to reduce rural health disparities.
The diversity of rural communities necessitates local
solutions to local problems. Suggestions are listed as
follows:
Collaborate with maternal-child and rural health
agencies in your state to identify the health needs of
rural women and barriers to care. Share your professional expertise as a member of an advisory committee or task force focused on improving the health of
rural women.
Partner with family physicians and other womens
primary care providers to ensure that appropriate
consultation and training are available for practitioners in rural areas.
Promote state initiatives offering financial incentives
to rural practitioners and providers of rural obstetric
care and reproductive health services.
Reinvigorate the implementation of regionalized
perinatal care in underserved, rural areas. Share and
network resources as well as clinical expertise.
Encourage and participate in efforts to utilize effective telemedicine technologies to expand and
improve services for rural women.
For more information see, American Academy of Family Physicians,

American College of Obstetricians and Gynecologists. AAFP-ACOG
joint statement on cooperative practice and hospital privileges. ACOG
Statement of Policy 73. Leawood (KS): AAFP; Washington, DC: ACOG;
1998.
Advocate for comprehensive professional liability

reform to facilitate the practice of providers in rural
areas.
Conduct further research to understand acceptable
conditions for performance of vaginal birth after
cesarean delivery in rural areas and to study the effect
of vaginal birth after cesarean delivery policies on
access to care for rural women.
Advocate for increased access to contraceptive methods and emergency contraception.
Advocate for availability of safe, legal, and accessible
abortion services.
Include place of residence in the collection of data for
health-related databases and their analyses to ensure
improved understanding of ruralurban health disparities among women.
Rural health disparities are only partially due to lack
of health care services. Rural communities have disparities in education, employment, and poverty that
also should be addressed.
References
1. Hart LG, Larson EH, Lishner DM. Rural definitions for
health policy and research. Am J Public Health 2005;
95:114955.
2. Rural Policy Research Institute. Choosing rural definitions:
implications for health policy. Rural Policy Research
Institute Health Panel Issue Brief No. 2. Columbia (MO):
RUPRI; 2007. Available at: http://www.rupri.org/Forms/
RuralDefinitionsBrief.pdf. Retrieved August 25, 2008.
3. Rural Assistance Center. What is rural? Grand Forks (ND):
RAC; 2008. Available at: http://www.raconline.org/info_
guides/ruraldef. Retrieved August 25, 2008.
4. United States Department of Agriculture Economic
Resource Service. Rural population and migration.
Washington, DC: USDA; 2007. Available at: http://ers.
usda.gov/briefing/population. Retrieved August 25, 2008.
5. Chandra A, Martinez GM, Mosher WD, Abma JC, Jones J.
Fertility, family planning, and reproductive health of U.S.
women: data from the 2002 National Survey of Family
Growth. Vital Health Stat 23 2005;(25):1160.
6. University of Washington Rural Health Research Center.
Poor birth outcome in the rural United States: 1985-1987 to
1995-1997. Final Report No. 119. Seattle (WA): UWRHRC;
2008. Available at: http://depts.washington.edu/uwrhrc/
uploads/RHRC_FR119_Larson.pdf. Retrieved August 25,
2008.
7. National Center for Health Statistics. Health, United States,
2007: with chartbook on trends in the health of Americans.
Hyattsville (MD): NCHS; 2007. Available at: http://www.
cdc.gov/nchs/data/hus/hus07.pdf. Retrieved August 25,
2008.
8. National Center for Health Statistics. Health, United States,
2001: with urban and rural health chartbook. Hyattsville
(MD): NCHS; 2001. Available at: http://www.cdc.gov/nchs/
data/hus/hus01.pdf. Retrieved August 25, 2008.
COMMITTEE OPINIONS
9. Racial and ethnic disparities in womens health. ACOG

Committee Opinion No. 317. Obstet Gynecol 2005;
106:88992.
10. Benard VB, Coughlin SS, Thompson T, Richardson LC.
Cervical cancer incidence in the United States by area of
residence, 1998 2001. Obstet Gynecol 2007;110:6816.
11. Larson S, Correa-de-Araujo R. Preventive health examinations: a comparison along the rural-urban continuum.
Womens Health Issues 2006;16:808.
12. Laditka SB, Laditka JN, Bennett KJ, Probst JC. Delivery
complications associated with prenatal care access for
Medicaid-insured mothers in rural and urban hospitals. J
Rural Health 2005;21:15866.
13. Greene SB, Holmes GM, Slifkin R, Freeman V, Howard HA.
Cesarean section rates in rural hospitals. Findings Brief.
Chapel Hill (NC): North Carolina Rural Health Research
and Policy Analysis Center, Cecil G. Sheps Center for Health
Services Research; 2005. Available at: http://www.sheps
center.unc.edu/research_programs/rural_program/FB79.p
df. Retrieved August 25, 2008.
14. Zhao L. Why are fewer hospitals in the delivery business?
NORC Walsh Center for Rural Health Analysis Working
Paper #2007-04. Rockville (MD): Office of Rural Health
Policy; 2007.
Profile of ob-gyn practice. Washington, DC: ACOG; 2004.
Available at: http: //www.acog.com/from_home/depart
ments/practice/ProfileofOb-gynPractice1991-2003.pdf.
16. Emmons SL, Nichols M, Schulkin J, James KE, Cain JM. The
influence of physician gender on practice satisfaction
among obstetrician gynecologists. Am J Obstet Gynecol
2006;194:172838; discussion 1739.
17. Colwill JM, Cultice JM. The future supply of family physicians: implications for rural America. Health Aff
2003;22:1908.
18. Frost JJ, Frohwirth L, Purcell A. The availability and use
of publicly funded family planning clinics: U.S. trends,
19942001. Perspect Sex Reprod Health 2004;36:20615.
19. Jones RK, Zolna MR, Henshaw SK, Finer LB. Abortion in
the United States: incidence and access to services, 2005.
Perspect Sex Reprod Health 2008;40:616.
20. Maternal and Child Health Bureau. Search TVIS national
performance measures: most recent year available. Available
at: https://perfdata.hrsa.gov/mchb/mchreports/Search/core/
corsch01p.asp. Retrieved September 2, 2008.
479
21. U.S. Census Bureau. Table A-2. States population by residence. In: State and metropolitan area data book: 2006.
Washington (DC): Census; 2006. p. 4. Available at:
http://www.census.gov/prod/2006pubs/smadb/smadb06tablea.pdf. Retrieved September 2, 2008.
22. Samuelson JL, Buehler JW, Norris D, Sadek R. Maternal
characteristics associated with place of delivery and neonatal mortality rates among very-low-birthweight infants,
Georgia. Paediatr Perinat Epidemiol 2002;16:30513.
23. Gould JB, Sarnoff R, Liu H, Bell DR, Chavez G. Very low
birth weight births at non-NICU hospitals: the role of
sociodemographic, perinatal, and geographic factors. J
Perinatol 1999;19:197205.
24. Oregon Office of Rural Health. Providers. Available at:
http://www.ohsu.edu/ohsuedu/outreach/oregonrural
health/providers/index.cfm. Retrieved September 2, 2008.
25. Delzell JE Jr, Ringdahl EN. The University of Missouri Rural
Obstetric Network: creating rural obstetric training sites for
a university-based residency program. Fam Med 2003;
35:2435.
26. Maternal and Child Health Bureau. State narrative for
Wyoming: application for 2008 annual report for 2006.
Maternal and Child Health Services Title V Block Grant.
Rockville (MD): MCHB; 2007. Available at: https://perfdata.
hrsa.gov/mchb/mchreports/documents/2008/Narrative/W
Y-Narratives.pdf. Retrieved October 1, 2008.
27. Anderson GD, Nelson-Becker C, Hannigan EV, Berenson
AB, Hankins GD. A patient-centered health care delivery
system by a university obstetrics and gynecology department. Obstet Gynecol 2005;105:20510.
28. Lowery C, Bronstein J, McGhee J, Ott R, Reece EA, Mays GP.
ANGELS and University of Arkansas for Medical Sciences
paradigm for distant obstetrical care delivery. Am J Obstet
Gynecol 2007;196:534.e1534.e9.
Copyright March 2009 by the American College of Obstetricians and
ISSN 1074-861X
Health disparities for rural women. ACOG Committee Opinion No.
Gynecol 2009;113:7625.
480

Community Involvement and Volunteerism

Committee on
Health Care for
Underserved Women
The Committee
would like to thank
Maureen G. Phipps,
MD, MPH, for her assistance with the development of this document.
be followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Abstract: As professional and community leaders, obstetriciangynecologists have

unlimited opportunities to become involved in and have a positive impact on local,
national, and international communities and organizations. Volunteering outside of daily
work routines often revitalizes a commitment to medicine while serving as a much needed resource to the community.
As practitioners, obstetriciangynecologists
affect the lives of hundreds of women every
year. As community members, physicians
have the potential to influence thousands,
even millions, of lives. Although some physicians may be reluctant to get involved in
community organizations because of the
perceived time commitment, others ask
themselves how they could make a difference
beyond their practice in the local community,
the national community, and globally. Most
obstetriciangynecologists pursued their
profession because of a commitment and
passion for improving the lives of women,
children, and families. As community leaders,
obstetriciangynecologists have the ability
to inspire other people to be involved in supporting worthy causes and to truly make a
positive difference in the community. The
demands of training, clinical practice, and
home life may make it difficult to know how
to get involved in the community.
Volunteerism generally has been defined
as time and effort devoted to helping others
without regard for compensation (1) for charitable, educational, social, or other worthwhile purposes. In the United States between
the years 2005 and 2007, the average volunteer rate was 27.2% per year. To put this in
perspective, in 2007, approximately 61 million people dedicated 8 billion hours of volunteer service (2).
Using skills as an obstetriciangynecologist, volunteerism opportunities for ACOG
members are unlimited and some examples
include: participating in hospital or university
committees; participating in local, state, or
regional public health committees; teaching in
the community; serving on an advisory board

for a local health agency; serving on a board of
directors for a nonprofit health organization;
providing care at a free clinic; providing guidance to students who want to pursue medicine as a career; assisting in the design and
implementation of research projects; mentoring; working to promote better state and local
health care services; providing expertise for
the development of a new school-based clinic
or sex education curriculum; and providing
expertise at a community health fair.
Great rewards can come to obstetrician
gynecologists who volunteer at the hospital
where they deliver patients and operate.
Undertaking efforts to participate in hospital
committees that seek to improve the quality
of care for patients and streamline services to
improve efficiency can be beneficial. Improving care requires thoughtful input from
knowledgeable clinicians who are willing to
consider ways to enhance and change clinical
practice in the best interests of patient care.
Realizing the importance of participating in
hospital quality committees or executive
committees may increase the level of physician engagement and satisfaction.
Involvement in the community may
extend to nonmedical areas. Improving safe
walking paths; building safe housing; donating food, clothing, and shelter; or participating in other safety initiatives to help families
are ways to volunteer and make a significant
impact on the local community. All of these
efforts directly or indirectly improve womens
health.
Another form of volunteerism is philanthropy. Contributing to organizations that
COMMITTEE OPINIONS
affect womens health, such as a womens shelter, may

come in the form of a financial contribution or in the
form of helping to organize or solicit donations.
Being involved in local chapters of national professional organizations may lead to opportunities for leadership at the regional and national level. For example, there
are numerous ways to participate in activities of the
(ACOG). Volunteering at the section and district level
may include seeking nomination to become an officer,
mentoring, or serving as a community liaison. At the
national level, opportunities exist for serving on an
ACOG committee or working on a specific project or
program such as the National Fetal and Infant Mortality
Review Program (www.nfimr.org).
Volunteering for international organizations also can
include donating time and expertise or needed supplies,
finances, and resources. Opportunities for volunteering
internationally are diverse. The ACOG web site (http://
www.acog.org/goto/international) and other international
volunteer web sites provide many resources on volunteer
opportunities.
The positive influence one could have in the community and nationally is a strong motivation for volunteering. The contributions of obstetriciangynecologists to
promote womens health or serve womens health causes
are essential to the growth and development of many
organizations. Sharing medical knowledge will increase
their capacity to provide accurate information, thereby
increasing the credibility of the organization. In addition,
getting involved in nonprofit organizations often helps
physicians realize their value in the community and the
impact they can have on specific causes.
Making the commitment to get involved often is the
most difficult aspect initially because it seems impossible
to fit more into already overloaded schedules. However,
being involved in an organization that contributes to the
health of a community outside of daily professional activities can help recharge the volunteer as much as it helps
the community. Working with committed volunteers and
staff helps keep the energy and enthusiasm of volunteering vital.
481
It is important for obstetriciangynecologists to consider the type of impact they would like to have on their
communities and likewise the type of organizations or
programs that might fit these goals. The next step is to
contact either the organizations executive director or
program director to express interest in volunteering, such
as staffing an event, giving a lecture on a relevant topic, or
leading a discussion about a specific issue. These initial
encounters will lead to an understanding of the organizations mission and direction.
Volunteering outside of daily work routines often
revitalizes a commitment to medicine while serving as a
much needed resource to the community. The skills and
training of obstetriciangynecologists extend well beyond
direct patient care. Obstetriciangynecologists have the
potential to make a significant positive impact on womens
health in local communities, professional organizations,
as well as the international community.
References
1. Sloan Work and Family Research Network. Community
as a context for the work-family interface. Boston (MA):
Boston College; 2002. Available at: http://wfnetwork. bc.
edu/encyclopedia_entry.php?id=223&area=academics.
2. Volunteering in America. How we volunteer. Available at:
http://www.volunteeringinamerica.gov/index.cfm.

ISSN 1074-861X
Community involvement and volunteerism. ACOG Committee Opinion
Obstet Gynecol 2009:114:2034.
COMMITTEE OPINIONS
COMMITTEE
ON INTERNATIONAL
AFFAIRS
COMMITTEE OPINIONS
COMMITTEE
ON INTERNATIONAL
AFFAIRS

Misoprostol for Postabortion Care

Committee on
International Affairs
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: The World Health Organization estimates that 67,000 women, mostly
in developing countries, die each year from untreated or inadequately treated abortion
complications. Postabortion care, a term commonly used by the international reproductive health community, refers to a specific set of services for women experiencing problems from all types of spontaneous or induced abortion. There is increasing evidence that
misoprostol is a safe, effective, and acceptable method to achieve uterine evacuation for
women needing postabortion care. To reduce maternal mortality, availability of postabortion care services must be increased. Misoprostol must be readily available especially for
women who do not otherwise have access to postabortion care. Nurses and midwives
can safely provide first-line postabortion care services, including in outpatient settings,
provided they receive appropriate training and support. Access to contraception and safe
abortion services prevents complications from unsafe abortion and decreases the need
for postabortion care. It is much less expensive and far better for womens health to
prevent the problem of unsafe abortion rather than to treat resulting complications.
Complications arising from spontaneous and

unsafely induced abortion are recognized
worldwide as a major public health concern
and are one of the leading reasons women
seek emergency care. The World Health
Organization estimates that 67,000 women,
mostly in developing countries, die each year
from untreated or inadequately treated abortion complications (1). This represents 13%
of all pregnancy-related deaths, and is especially prevalent in low-resource settings,
wherever abortion laws are restrictive, or
when access to safe abortion services is difficult. Many women survive with chronic pain,
pelvic inflammatory disease, and infertility.
Most deaths and morbidities resulting from
such complications are preventable through
access to contraception and safe abortion services.
Postabortion care, a term commonly
used by the international reproductive health
community, refers to a specific set of services
for women experiencing problems from all
types of spontaneous or induced abortions.
In the United States the comparable concept
involves management of incomplete abortion, and complications include retained tissue, hemorrhage, and infection. Treatment
for women experiencing these problems
includes evacuation of the uterus (traditionally by manual or electrical vacuum aspiration, and now with the use of misoprostol as
well), pain management, and treatment for
suspected infection or other issues. Contraceptive education and method provision are
considered integral parts of postabortion
care. Additionally, community and service
provider partnerships help prevent unwanted
pregnancies and unsafe abortion and mobilize resources to help women receive appropriate and timely care for complications of
abortion.
Both expectant management and surgical evacuation of the uterus have been used
for women requiring postabortion care. In
addition, there is increasing evidence that
misoprostol is a safe, effective, and acceptable
method to achieve uterine evacuation for
women needing postabortion care. Misoprostol reduces the cost of postabortion care
services because it does not require the
immediate availability of sterilized equipment, operating theatres, or skilled personnel
(2). It is inexpensive, does not require refrigeration, and may be administered by several
different routes (3). Misoprostol thus holds
the potential to extend first-line postabortion
care services beyond urban areas and hospi485
486
tals to settings where physicians and surgical services are

not available.
Efficacy
A review of the recent literature on misoprostol shows
that it successfully completes expulsion in approximately
6699% of women who receive it for incomplete,
inevitable, and missed abortion in the first trimester
(412). Specifically, one extensive review found median
success was 80% or higher for missed abortion and 92%
for incomplete abortion treated with misoprostol (15).
Misoprostol may be more successful at treating women
experiencing an incomplete abortion compared with a
missed abortion (12, 14). Although studies show a range
of efficacy, higher success has been achieved when clinicians wait for 12 weeks after misoprostol treatment
before judging success or failure (11, 13, 15). Efficacy rates
usually are higher in studies where outcome is determined by clinical parameters such as uterine size and cervical exam rather than ultrasound criteria.
Indications
Misoprostol may be used to treat women with an incomplete and missed abortion. Incomplete abortion usually is
diagnosed when a pregnant woman has an open cervix
and has passed some, but not all of the products of conception (16). Missed abortion usually is diagnosed when
a pregnant woman has a closed cervix and a uterus that
does not increase in size over time or an ultrasound
examination that shows either an anembryonic pregnancy or embryonic demise.
No published studies have investigated the use of
misoprostol to treat women with septic abortion.
Contraindications
Women with suspected ectopic pregnancy, hemodynamic instability or allergies to misoprostol should not
be treated with misoprostol (13).
Protocols
The protocols listed as follows apply to women whose
uterine size is less than 12 weeks of gestation (13). The
optimal protocol has not yet been defined (15). However,
there is ample evidence in the literature to make a few key
recommendations:
Incomplete abortion: misoprostol, 600 mcg orally (4,
5, 9, 11, 13, 15, 17). Misoprostol, 400 mcg sublingually, is a promising alternative but supporting
published research is currently limited (13).
Missed abortion: misoprostol, 800 mcg vaginally (10,
12) or 600 mcg sublingually; may be repeated every 3
hours for two additional doses (18, 19). The impact
of repeat doses is not clear. Moistening the tablets
before vaginal application in this circumstance does
not appear to improve efficacy (20).
Side Effects
Women treated with misoprostol for an incomplete or
missed abortion will experience vaginal bleeding. Usually
the bleeding is not clinically significant and does not
require intervention (7, 15). Typically, women experience
bleeding heavier than a menses for approximately 3 or 4
days, and then it lightens to spotting. In one prospective,
randomized study of 652 women undergoing treatment
for early pregnancy failure, women receiving misoprostol
experienced larger decreases in hemoglobin compared
with women treated with curettagealthough actual levels of hemoglobin decrease were small (7). In this study,
median duration of bleeding was 12 days.
Other side effects include nausea, vomiting, fever,
and chills, most of which occur only a minority of women
(6). Diarrhea is more common following sublingual compared with vaginal misoprostol (21). Misoprostol appears
to be highly acceptable for women requiring treatment
for an incomplete or missed abortion; 7899% stated that
it was either satisfactory, very satisfactory, or would use it
again and recommend it to a friend (46, 11, 12).
Serious complications are rare; in one prospective
randomized trial hospitalization for endometritis or
hemorrhage occurred in less than 1% of patients (12). In
situations where safe conditions for surgery cannot be
assured, misoprostol may be the preferred method of
treatment (15).
Pain Management
Women receiving postabortion care should be offered
pain management options according to what is locally
available and clinically appropriate; ideally, both nonsteroidal antiinflammatory agents such as ibuprofen as
well as narcotic analgesics should be offered.
Infection Prevention
Universal precautions should be used when contact with
blood or body fluids is anticipated (22). Appropriate
hygiene and infection prevention behaviors are recommended to prevent the spread of infection. For example,
hand washing should be done after coming into contact
with any blood or tissue, and proper infectious waste disposal should be utilized. No evidence exists delineating
whether or not antibiotics prevent infection when used in
conjunction with postabortion care regardless of the
method of uterine evacuation used. However, antibiotics
have been shown to decrease infection in women undergoing vacuum aspiration during abortion (23). Lack of
antibiotics should not serve as an obstacle to receiving
care.
Contraception
Women should be counseled about and offered contraception when receiving postabortion care. Contraceptive
acceptance and continuation rates are higher when
offered at the site of initial treatment (2427). All women
COMMITTEE OPINIONS
need to know that fertility returns within just a few weeks

after abortion and, thus, they need to protect themselves
from unintended pregnancy. Many women and their
partners have questions about side effects and risks of
modern contraceptive methods. These concerns should
be addressed in the counseling session. Regular supplies
of contraceptive commodities should be ensured.
Follow-up
Women should be evaluated 12 weeks after misoprostol
administration in order to ensure complete abortion.
This can be done through obtaining a history and clinical
examination (4, 11). If the process is not yet finished and
as long as the woman is clinically stable, she may be
offered a choice between expectant management or a
repeat dose of misoprostol at the follow-up visit (18). The
follow-up visit is also a good time to reiterate key contraceptive messages and to involve the male partner.
Recommendations
Increase availability of postabortion care services in
order to reduce maternal mortality. In many countries, postabortion care is difficult to obtain and
women often have to travel considerable distances to
reach services. The complete postabortion care
model should be expanded beyond hospital settings
to community health centers. Involvement of men in
promoting community support for access to postabortion care and contraceptive services should be
encouraged. Advocacy to increase awareness of the
need for timely treatment of abortion complications
also will improve access.
Misoprostol must be readily available, especially for
women who do not otherwise have access to postabortion care. Barriers to a sustainable misoprostol
supply must be eliminated in order to ensure that
underserved women receive treatment.
Postabortion care services need not be dependent
on the availability of obstetriciangynecologists or
surgeons. Nurses and midwives can safely provide
first-line postabortion care services, including in
outpatient settings, provided they receive appropriate training and support (28).
Access to contraception and safe abortion services
prevents complications from unsafe abortion and
decreases the need for postabortion care (29, 30). It is
much less expensive and far better for womens
health to prevent the problem of unsafe abortion
rather than to treat resulting complications.
References
1. World Health Organization. Unsafe abortion: global and
regional estimates of the incidence of unsafe abortion and
associated mortality in 2003. 5th ed. Geneva: WHO; 2007.
Available at: http://www.who.int/reproductive-health/pub-
487
lications/unsafeabortion_2003/ua_estimates03.pdf.
Retrieved October 28, 2008.
2. You JH, Chung TK. Expectant, medical or surgical treatment for spontaneous abortion in first trimester of pregnancy: a cost analysis. Hum Reprod 2005;20:28738.
3. World Health Organization. Safe abortion: technical and
policy guidance for health systems. Geneva: WHO;
2003. Available at: http://www.who.int/reproductivehealth/
publications/safe_abortion/safe_abortion.pdf. Retrieved
October 28, 2008.
4. Shwekerela B, Kalumuna R, Kipingili R, Mashaka N,
Westheimer E, Clark W, et al. Misoprostol for treatment of
incomplete abortion at the regional hospital level: results
from Tanzania. BJOG 2007;114:13637.
5. Dao B, Blum J, Thieba B, Raghavan S, Ouedraego M,
Lankoande J, et al. Is misoprostol a safe, effective and
acceptable alternative to manual vacuum aspiration for
postabortion care? Results from a randomised trial in
Burkina Faso, West Africa. BJOG 2007;114:136875.
6. Bique C, Usta M, Debora B, Chong E, Westheimer E,
Winikoff B. Comparison of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion. Int
7. Davis AR, Hendlish SK, Westhoff C, Frederick MM, Zhang
J, Gilles JM, et al. Bleeding patterns after misoprostol vs surgical treatment of early pregnancy failure: results from a
randomized trial. Am J Obstet Gynecol 2007;196:31.
e131.e7.
8. Graziosi GC, Mol BW, Ankum WM, Bruinse HW. Management of early pregnancy loss. Int J Gynaecol Obstet 2004;86:
33746.
9. Blanchard K, Taneepanichskul S, Kiriwat O, Sirimai K,
Svirirojana N, Mavimbela N, et al. Two regimens of misoprostol for treatment of incomplete abortion. Obstet
Gynecol 2004;103:8605.
10. Ngoc NT, Blum J, Westheimer E, Quan TT, Winikoff B.
Medical treatment of missed abortion using misoprostol.
Int J Gynaecol Obstet 2004;87:13842.
11. Weeks A, Alia G, Blum J, Winikoff B, Ekwaru P, Durocher J,
et al. A randomized trial of misoprostol compared with
manual vacuum aspiration for incomplete abortion. Obstet
Gynecol 2005;106:5407.
12. Zhang J, Gilles JM, Barnhart K, Creinin MD, Westhoff C,
Frederick MM, et al. A comparison of medical management
with misoprostol and surgical management for early pregnancy failure. National Institute of Child Health Human
Development (NICHD) Management of Early Pregnancy
Failure Trial. N Engl J Med 2005;353:7619.
13. Blum J, Winikoff B, Gemzell-Danielsson K, Ho PC,
Schiavon R, Weeks A. Treatment of incomplete abortion
and miscarriage with misoprostol. Int J Gynaecol Obstet
2007;99(suppl 2):S1869.
14. Tang OS, Ho PC. The use of misoprostol for early pregnancy failure. Curr Opin Obstet Gynecol 2006;18:5816.
15. Clark W, Shannon C, Winikoff B. Misoprostol for uterine
evacuation in induced abortion and pregnancy failure.
Expert Rev Obstet Gynecol 2007;2:67108.
488
16. Castleman LD, Blumenthal PD. Spontaneous and induced

abortion. In: Ryden J, Blumenthal PD, editors. Practical
gynecology: a guide for the primary care physician.
Philadelphia (PA): American College of Physicians; 2009. p.
13757.
17. Phupong V, Taneepanichskul S, Kriengsinyot R, Sriyirojana
N, Blanchard K, Winikoff B. Comparative study between
single dose 600 microg and repeated dose of oral misoprostol for treatment of incomplete abortion. Contraception
2004;70:30711.
18. Gemzell-Danielsson K, Ho PC, Gomez Ponce de Leon R,
Weeks A, Winikoff B. Misoprostol to treat missed abortion
in the first trimester. Int J Gynaecol Obstet 2007;99(suppl
2):S1825.
19. Tang OS, Lau WN, Ng EH, Lee SW, Ho PC. A prospective
randomized study to compare the use of repeated doses of
vaginal with sublingual misoprostol in the management of
first trimester silent miscarriages. Hum Reprod 2003;18:
17681.
20. Gilles JM, Creinin MD, Barnhart K, Westhoff C, Frederick
MM, Zhang J, et al. A randomized trial of saline solutionmoistened misoprostol versus dry misoprostol for firsttrimester pregnancy failure. Am J Obstet Gynecol 2004; 190:
38994.
21. Neilson JP, Hickey M, Vazquez J. Medical treatment for early
fetal death (less than 24 weeks). Cochrane Database of
10.1002/14651858.CD002253.pub3.
22. Herrick J, Turner K, McInerney T, Castleman L. Infection
prevention. In: Woman-centered postabortion care: reference manual. Chapel Hill (NC): Ipas; 2004. p.3140.
Available at:http://www.ipas.org/Publications/asset_upload
_file975_2148.pdf. Retrieved October 28, 2008.
23. Sawaya GF, Grady D, Kerlikowske K, Grimes DA. Antibiotics
at the time of induced abortion: the case for universal prophylaxis based on a meta-analysis. Obstet Gynecol 1996;87:
88490.
24. Solo J, Billings DL, Aloo-Obunga C, Ominde A, Makumi M.

Creating linkages between incomplete abortion treatment
and family planning services in Kenya. Stud Fam Plann
1999;30:1727.
25. Johnson BR, Ndhlovu S, Farr SL, Chipato T. Reducing
unplanned pregnancy and abortion in Zimbabwe through
postabortion contraception. Stud Fam Plann 2002;33:
195202.
26. Savelieva I, Pile JM, Sacci I, Loganathan R. Postabortion
family planning operations research study in Perm, Russia.
Washington, DC: FRONTIERS; 2003. Available at: http://
www.popcouncil.org/pdfs/frontiers/FR_FinalReports/Russi
a_PAC.pdf. Retrieved October 28, 2008.
27. Rasch V, Massawe S, Yambesi F, Bergstrom S. Acceptance of
contraceptives among women who had an unsafe abortion
in Dar es Salaam. Trop Med Int Health 2004;9:399405.
28. Corbett MR, Turner KL. Essential elements of postabortion
care: origins, evolution and future directions. Int Fam Plan
Perspect 2003;29:10611.
29. World Health Organization. Complications of abortion:
technical and managerial guidelines for prevention and
treatment. Geneva: World Health Organization; 1995.
30. Grimes DA, Benson J, Singh S, Romero M, Ganatra B,
Okonofua FE, et al. Unsafe abortion: the preventable pandemic. Lancet 2006;368:190819.

ISSN 1074-861X
Misoprostol for postabortion care. ACOG Committee Opinion No.
Gynecol 2009;113:4658.
COMMITTEE OPINIONS
COMMITTEE
ON
OBSTETRIC PRACTICE
COMMITTEE OPINIONS
COMMITTEE
ON
OBSTETRIC PRACTICE
Committee on Obstetrics: Maternal and Fetal Medicine
Number 125July 1993

(Replaces #102, December 1991)
Placental Pathology
Recently, there has been heightened interest in clinicalpathologic correlation between placental abnormalities and adverse pregnancy outcome. When
a skilled and systematic examination of the umbilical cord, membranes, and placenta is performed on
properly prepared specimens, insight into antepartum pathophysiology may be gained under certain
circumstances.
In most of these instances, such as chorioamnionitis, the diagnosis already will have been
made on clinical grounds, with the placental examination providing confirmation. In other cases of
poor outcome, a disorder that was not suspected
clinically may be revealed by placental pathology.
Examples of pathologic findings and the disorders
they suggest include the microabscesses of listeriosis and amnion nodosum suggesting long-standing
oligohydramnios. The underlying pathophysiology
of these lesions has been confirmed by laboratory
testing or consistent and specific clinical associations.
The significance of other findings, such as villous
edema, hemorrhagic endovasculitis, and chronic
villitis, has not been as well delineated. These lesions, among others, have been variously reported
to correlate with poor short-term and long-term
neonatal outcome. The paucity of properly designed studies of adequate size with appropriate
outcome parameters has prevented universal
agreement as to positive predictive values, underlying pathophysiology, or even the consistency of
clinical correlations with these findings.
Furthermore, the distribution of pathologists with
the expertise to interpret more subtle placental
findings is uneven from region to region. Although
a protocol for obtaining routine placental pathologic examination under certain obstetric and neonatal
conditions has been recommended (1), there are
few data to support the clinical utility of this
approach.
In addition to the issue of positive and
negative predictive values of the spectrum of pla-
cental findings, there are practical concerns regarding examination of the placenta. In some instances,
a neonatal problem may not be ascertained until
days or weeks after birth, when the placenta is no
longer available. Different approaches have been
recommended to address this problem, including
routinely examining all placentas, securing a small
section from each placenta in a fixed state for an indefinite period, and saving all placentas unfixed at
4C for 1 week before discarding. However, routine
determinations of placental pathology are not feasible on either a cost or manpower basis, and a small
portion of placenta obtained at random would be
unlikely to provide useful information. The practice
of saving all placentas for 1 week after delivery
would permit ascertaining most neonatal problems
in which pathologic examination of the placenta
may be appropriate, but the effectiveness of this
approach has not been proven.
In conclusion, an examination of the umbilical
cord, membranes, and placenta may assist the obstetric care provider in clinicalpathologic correlation when there is an adverse perinatal outcome.
However, the scientific basis for clinical correlation
with placental pathology is still evolving, and the
benefit of securing specimens on a routine basis is
as yet unproven. Continued research and education
in this field should be encouraged. Research should
be designed with the goal of defining clinical indications for placental examination. In contrast,
pathologic examination of the stillborn fetus and
placenta is always potentially informative.
Obstetric providers should be persistent in seeking
consent from parents for autopsy examinations.
REFERENCE
1. College of American Pathologists Conference XIX.
The examination of the placenta: patient care and risk
management. Arch Pathol Lab Med 1991;115: 641732
Copyright July 1993

Reaffirmed 2006
is subject to change. The information should not be construed as dictating an exclusive
409 12th Street, SW Washington, DC 20024-2188
491
492
ACOG
Committee on
Obstetric Practice
Reaffirmed 2008
Committee
Opinion
followed.
Copyright May 2000 by the
American College of
the publisher.
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PO Box 96920
Scheduled Cesarean Delivery and the

Prevention of Vertical Transmission of
HIV Infection
Prevention of transmission of the human immunodeficiency virus (HIV) from
mother to fetus or newborn (vertical transmission) is a major goal in the care
of pregnant women infected with HIV. An important advance in this regard
was the demonstration that treatment of the mother with zidovudine (ZDV)
during pregnancy and labor and of the neonate for the first 6 weeks after birth
could reduce the transmission rate from 25% to 8% (1).
Continuing research into vertical transmission of HIV suggests that a
substantial number of cases occur as the result of fetal exposure to the virus
during labor and delivery; the precise mechanisms are not known. Transmission could occur by transplacental maternalfetal microtransfusion of
blood contaminated with the virus during uterine contractions or by exposure
to the virus in maternal cervicovaginal secretions and blood at delivery. Data
also indicate that the risk of vertical transmission is proportional to the concentration of virus in maternal plasma (viral load). At very low concentrations
of virus in maternal plasma (viral load less than 1,000 copies per milliliter),
the observed incidence of vertical transmission among 141 motherinfant
pairs was 0 with a 95% upper confidence bound of about 2% (2, 3).
In theory, the risk of vertical transmission in mothers with high viral
loads could be reduced by performing cesarean deliveries before the onset of
labor and before rupture of membranes (termed scheduled cesarean delivery
in this document). Early studies of the relationship between the mode of
delivery and the risk of vertical transmission yielded inconsistent results.
Data from two prospective cohort studies (4, 5), an international randomized
trial (6), and a meta-analysis of individual patient data from 15 prospective
cohort studies, including more than 7,800 motherchild pairs (7), indicate
that there is a significant relationship between the mode of delivery and vertical transmission of HIV. This body of evidence, accumulated mostly before
the use of highly active antiretroviral therapy (HAART) and without any data
regarding maternal viral load, indicates that scheduled cesarean delivery
reduces the likelihood of vertical transmission of HIV compared with either
unscheduled cesarean delivery or vaginal delivery. This finding holds true
whether or not the patient is receiving ZDV therapy. Whether cesarean deliv-
COMMITTEE OPINIONS
ery offers any benefit to women on HAART or to

women with low or undetectable maternal viral loads
is unknown. Data are insufficient to address the question of how long after the onset of labor or rupture of
membranes the benefit is lost. It is clear that maternal
morbidity is greater with cesarean delivery than with
vaginal delivery, as is true for women not infected
with HIV (810). Increases in postpartum morbidity
seem to be greatest among women infected with HIV
who have low CD4 cell counts (9).
Although many issues remain unresolved
because of insufficient data, there is consensus that
the following should be recommended:
Patients should be counseled that in the absence of
antiretroviral therapy, the risk of vertical transmission is approximately 25%. With ZDV therapy, the
risk is reduced to 58%. When care includes both
ZDV therapy and scheduled cesarean delivery, the
risk is approximately 2%. A similar risk of 2% or
less is seen among women with viral loads of less
than 1,000 copies per milliliter, even without the systematic use of scheduled cesarean delivery. No combination of therapies can guarantee that a newborn
will not become infected (a 0% transmission rate).
Women infected with HIV, whose viral loads are
greater than 1,000 copies per milliliter, should be
counseled regarding the potential benefit of scheduled cesarean delivery to further reduce the risk of
vertical transmission of HIV beyond that achievable with antiretroviral therapy alone.
Neonates of women at highest risk for vertical
transmission, with relatively high plasma viral
loads, are most likely to benefit from scheduled
cesarean delivery. Data are insufficient to demonstrate a benefit for neonates of women with plasma
viral loads of less than 1,000 copies per milliliter.
The available data indicate no reduction in the
transmission rate if cesarean delivery is performed
after the onset of labor or rupture of membranes.
The decision regarding the route of delivery must
be individualized in these circumstances.
The patients autonomy in making the decision
regarding route of delivery must be respected. A
patients informed decision to undergo vaginal
delivery must be honored, with cesarean delivery
performed only for other accepted indications and
with patient consent.
Patients should receive antiretroviral chemotherapy during pregnancy according to currently accepted guidelines for adults (11). This should not be
interrupted around the time of cesarean delivery.
For those patients receiving ZDV, adequate levels
493
of the drug in the blood should be achieved if

the infusion is begun 3 hours preoperatively (1),
according to the dosing schedule recommended by
the Centers for Disease Control and Prevention
(www.cdc.gov/hiv/treatment).
Because morbidity is increased in HIV-infected
women undergoing cesarean delivery, physicians
should consider using prophylactic antibiotics during all such cesarean deliveries.
Gynecologists generally recommends that scheduled cesarean deliveries not be performed before
39 completed weeks of gestation. In women with
HIV infection, however, delivery at 38 completed
weeks of gestation is recommended to reduce the
likelihood of onset of labor or rupture of membranes before delivery.
Best clinical estimates of gestational age should be
used for planning cesarean delivery. Amniocentesis to determine fetal lung maturity in pregnant
women infected with HIV should be avoided
whenever possible.
Current recommendations for adults indicate that
plasma viral load should be determined at baseline
and then every 3 months or following changes in
therapy (11). Plasma viral load should be monitored,
according to these guidelines, during pregnancy as
well. The patients most recently determined viral
load should be used to direct counseling regarding
mode of delivery.
Preoperative maternal health status affects the
degree of risk of maternal morbidity associated
with cesarean delivery. All women should be clearly informed of the risks associated with cesarean
delivery. Ultimately, the decision to perform a
cesarean delivery must be individualized in each
case according to circumstances.
A skin-penetrating injury (eg, needlestick or

scalpel laceration) is a risk to care providers during
all deliveries, vaginal or cesarean. This risk is not
greater during cesarean delivery, although there
generally are more health care personnel present
and, thus, at risk during a cesarean delivery than
during a vaginal delivery (12). Appropriate care and
precautions against such injuries always should be
taken, but these concerns should not affect decisions
regarding route of delivery (13).
In summary, cesarean delivery performed before
the onset of labor and before rupture of membranes
effectively reduces the risk of vertical transmission of
HIV infection. Scheduled cesarean delivery should be
discussed and recommended for women with viral
494
loads greater than 1,000 copies per milliliter whether

or not they are taking antiretroviral therapy. As with
all complex clinical decisions, the choice of delivery
must be individualized. Discussion of the option of
scheduled cesarean delivery should begin as early as
possible in pregnancy with every pregnant woman
with HIV infection to give her an adequate opportunity to consider the choice and plan for the procedure.
The risks, which are greater for the mother, must be
balanced with the benefits expected for the neonate.
The patients autonomy must be respected when making the decision to perform a cesarean delivery,
because the potential for maternal morbidity is significant.
6.
7.
8.
9.
10.
References
1. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G,
OSullivan MJ, et al. Reduction of maternal-infant
transmission of human immunodeficiency virus type 1
with zidovudine treatment. Pediatric AIDS Clinical
Trials Group Protocol 076 Study Group. N Engl J Med
1994;331:11731180
2. Mofenson LM, Lambert JS, Stiehm ER, Bethel J, Meyer
WA 3rd, Whitehouse J, et al. Risk factors for perinatal
transmission of human immunodeficiency virus type 1
in women treated with zidovudine. Pediatric AIDS
Clinical Trials Group Study 185 Team. N Engl J Med
1999;341:385393
3. Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn T,
Burchett SK, et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal
transmission. Women and Infants Transmission Study
Group. N Engl J Med 1999;341:394402
4. Kind C, Rudin C, Siegrist CA, Wyler CA, Biedermann K,
Lauper U, et al. Prevention of vertical HIV transmission:
additive protective effect of elective cesarean section and
zidovudine prophylaxis. AIDS 1998;12:205210
5. Mandelbrot L, Le Chenadec J, Berrebi A, Bongain A,
Benifla JL, Delfraissy JF, et al. Perinatal HIV-1 transmis-
11.
12.
13.
sion: interaction between zidovudine prophylaxis and mode

of delivery in the French Perinatal Cohort. JAMA
1998;280:5560
The European Mode of Delivery Collaboration. Elective
caesarean-section versus vaginal delivery in prevention of
vertical HIV-1 transmission: a randomized clinical trial.
Lancet 1999;353:10351039
The International Perinatal HIV Group. The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1: a meta-analysis of 15 prospective
cohort studies. N Engl J Med 1999;340:977987
Nielsen TF, Hakegaard KH. Postoperative cesarean section
morbidity: a prospective study. Am J Obstet Gynecol 1983;
146:911915
Semprini AE, Castagna C, Ravizza M, Fiore S, Savasi V,
Muggiasca ML, et al. The incidence of complications after
cesarean section in 156 HIV-positive women. AIDS 1996;
9:913917
Bulterys M, Chao A, Dushimimana A, Saah A. Fatal complications after cesarean section in HIV-infected women.
AIDS 1996;10:923924
Centers for Disease Control and Prevention. Report of the
NIH Panel to define principles of therapy of HIV infection
and guidelines for the use of antiretroviral agents in HIVinfected adults and adolescents. MMWR Morb Mortal
Wkly Rep 1998;47(RR-5):182
Duff P, Robertson AW, Read JA. Single-dose cefazolin versus cefonicid for antibiotic prophylaxis in cesarean delivery. Obstet Gynecol 1987;70:718721
Centers for Disease Control. Update: universal precautions
for prevention of transmission of human immunodeficiency
virus, hepatitis B virus, and other bloodborne pathogens in
health-care settings. MMWR Morb Mortal Wkly Rep
1988;37:377382;387388
Bibliography
Rodman JH, Robbins BL, Flynn PM, Fridland A. A systematic
and cellular model for zidovudine plasma concentrations and
intracellular phosphorylation in patients. J Infect Dis 1996;174:
490499
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
Reaffirmed 2009
495
Committee
Opinion
followed.
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
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ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Circumcision. ACOG Committee

Obstet Gynecol 2001;98:707-708
Circumcision
ABSTRACT: The American College of Obstetricians and Gynecologists supports the current position of the American Academy of Pediatrics that finds
the existing evidence insufficient to recommend routine neonatal circumcision. Given this circumstance, parents should be given accurate and impartial information to help them make an informed decision. There is ample
evidence that newborns circumcised without analgesia experience pain and
stress. If circumcision is performed, analgesia should be provided.
Some studies have shown potential medical benefits to newborn male circumcision; however, these benefits are modest. The exact incidence of complications after circumcision is not known, but data indicate that the rate is low,
and the most common complications are local infection and bleeding. The
current position of the American Academy of Pediatrics is that the existing
evidence is insufficient to recommend routine neonatal circumcision. The
American College of Obstetricians and Gynecologists Committee on
Obstetric Practice supports this position. Given this circumstance, parents
should be given accurate and impartial information to help them make an
informed decision. It is reasonable for parents to take cultural, religious, and
ethnic traditions, as well as medical factors, into consideration when making
this decision. Circumcision of newborns should be performed only on healthy
and stable infants.
There is ample evidence that newborns circumcised without analgesia
experience pain and stress. Analgesia has been found to be safe and effective
in reducing the pain associated with circumcision. Therefore, if circumcision
is performed, analgesia should be provided. Swaddling, sucrose by mouth,
and acetaminophen administration may reduce the stress response but are not
sufficient for the operative pain and cannot be recommended as the sole
method of analgesia. EMLA cream, dorsal penile nerve block, and subcutaneous ring block are all reasonable options, although the subcutaneous ring
block may provide the most effective analgesia.
496
References
1. Circumcision policy statement. Task Force on Circumcision. American Academy of Pediatrics. Pediatrics
1999;103:686693
2. Prevention and management of pain and stress in the
neonate. American Academy of Pediatrics. Committee on
Fetus and Newborn. Committee on Drugs. Section on

Anesthesiology. Section on Surgery. Canadian Paediatric
Society. Fetus and Newborn Committee. Pediatrics
2000;105:454461
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
Reaffirmed 2009
497
Committee
Opinion
followed.
Copyright January 2002 by
the American College of
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Exercise during pregnancy and the

postpartum period. ACOG Committee
Exercise During Pregnancy and the

Postpartum Period
ABSTRACT: The physiologic and morphologic changes of pregnancy may
interfere with the ability to engage safely in some forms of physical activity.
A womans overall health, including obstetric and medical risks, should be
evaluated before prescribing an exercise program. Generally, participation in
a wide range of recreational activities appears to be safe during pregnancy;
however, each sport should be reviewed individually for its potential risk, and
activities with a high risk of falling or those with a high risk of abdominal
trauma should be avoided during pregnancy. Scuba diving also should be
avoided throughout pregnancy because the fetus is at an increased risk for
decompression sickness during this activity. In the absence of either medical
or obstetric complications, 30 minutes or more of moderate exercise a day on
most, if not all, days of the week is recommended for pregnant women.
The current Centers for Disease Control and Prevention and American
College of Sports Medicine recommendation for exercise, aimed at improving the health and well-being of nonpregnant individuals, suggests that an
accumulation of 30 minutes or more of moderate exercise a day should occur
on most, if not all, days of the week (1). In the absence of either medical or
obstetric complications, pregnant women also can adopt this recommendation.
Given the potential risks, albeit rare, thorough clinical evaluation of each
pregnant woman should be conducted before recommending an exercise
program. In the absence of contraindications (see boxes), pregnant women
should be encouraged to engage in regular, moderate intensity physical activity to continue to derive the same associated health benefits during their
pregnancies as they did prior to pregnancy.
Epidemiologic data suggest that exercise may be beneficial in the primary prevention of gestational diabetes, particularly in morbidly obese women
(BMI >33) (2). The American Diabetes Association has endorsed exercise
as a helpful adjunctive therapy for gestational diabetes mellitus when
euglycemia is not achieved by diet alone (3, 4).
The cardiovascular changes associated with pregnancy are an important
consideration for pregnant women both at rest and during exercise. After the
498
Absolute Contraindications to Aerobic Exercise

During Pregnancy
Hemodynamically significant heart disease

Restrictive lung disease
Incompetent cervix/cerclage
Multiple gestation at risk for premature labor
Persistent second- or third-trimester bleeding
Placenta previa after 26 weeks of gestation
Premature labor during the current pregnancy
Ruptured membranes
Preeclampsia/pregnancy-induced hypertension
Relative Contraindications to Aerobic Exercise

During Pregnancy
Severe anemia
Unevaluated maternal cardiac arrhythmia
Chronic bronchitis
Poorly controlled type 1 diabetes
Extreme morbid obesity
Extreme underweight (BMI <12)
History of extremely sedentary lifestyle
Intrauterine growth restriction in current pregnancy
Poorly controlled hypertension
Orthopedic limitations
Poorly controlled seizure disorder
Poorly controlled hyperthyroidism
Heavy smoker
first trimester, the supine position results in relative

obstruction of venous return and, therefore,
decreased cardiac output and orthostatic hypotension. For this reason, pregnant women should avoid
supine positions during exercise as much as possible. Motionless standing also is associated with a
significant decrease in cardiac output so this position
should be avoided as much as possible (5).
Epidemiologic studies have long suggested that
a link exists between strenuous physical activities,
deficient diets, and the development of intrauterine
growth restriction. This is particularly true for pregnant women engaged in physical work. It has been
reported that pregnant women whose occupations
require standing or repetitive, strenuous, physical
work (eg, lifting) have a tendency to deliver earlier
and have small-for-gestational-age infants (6).

However, other reports have failed to confirm these
associations suggesting that several factors or conditions have to be present for strenuous activities to
affect fetal growth or outcome (7, 8).
In general, participation in a wide range of recreational activities appears to be safe. The safety of
each sport is determined largely by the specific
movements required by that sport. Participation in
recreational sports with a high potential for contact,
such as ice hockey, soccer, and basketball, could
result in trauma to both the woman and fetus.
Similarly, recreational activities with an increased
risk of falling, such as gymnastics, horseback riding,
downhill skiing, and vigorous racquet sports, have an
inherently high risk for trauma in pregnant and nonpregnant women. Those activities with a high risk of
falling or for abdominal trauma should be avoided
during pregnancy (9). Scuba diving should be avoided throughout pregnancy because during this activity the fetus is at increased risk for decompression
sickness secondary to the inability of the fetal pulmonary circulation to filter bubble formation (10).
Exertion at altitudes of up to 6,000 feet appears
to be safe; however, engaging in physical activities
at higher altitudes carries various risks (11). All
women who are recreationally active should be
made aware of signs of altitude sickness for which
they should stop the exercise, descend from the altitude, and seek medical attention.
Data regarding the effects of exercise on core
temperature during pregnancy are limited (12, 13,
14). There have been no reports that hyperthermia
associated with exercise is teratogenic.
Warning Signs to Terminate Exercise

While Pregnant
Vaginal bleeding
Dyspnea prior to exertion
Dizziness
Headache
Chest pain
Muscle weakness
Calf pain or swelling (need to rule out thrombophlebitis)
Preterm labor
Decreased fetal movement
Amniotic fluid leakage
COMMITTEE OPINIONS
Competitive athletes are likely to encounter the

same physiologic limitations during pregnancy faced
by recreational athletes during pregnancy. The competitors tend to maintain a more strenuous training
schedule throughout pregnancy and resume high
intensity postpartum training sooner. The concerns of
the pregnant, competitive athlete fall into two general categories: 1) the effects of pregnancy on competitive ability, and 2) the effects of strenuous training
and competition on pregnancy and the fetus. Such
athletes may require close obstetric supervision.
Many of the physiologic and morphologic
changes of pregnancy persist 46 weeks postpartum.
Thus, prepregnancy exercise routines may be
resumed gradually as soon as it is physically and
medically safe. This will vary from one individual to
another with some women able to resume an exercise routine within days of delivery. There are no
published studies to indicate that, in the absence of
medical complications, rapid resumption of activities will result in adverse effects. Having undergone
detraining, resumption of activities should be gradual. No known maternal complications are associated with resumption of training (15). Moderate
weight reduction while nursing is safe and does not
compromise neonatal weight gain (16). Finally, a
return to physical activity after pregnancy has been
associated with decreased incidence of postpartum
depression, but only if the exercise is stress relieving
and not stress provoking (17).
Conclusions and Recommendations

Recreational and competitive athletes with
uncomplicated pregnancies can remain active
during pregnancy and should modify their usual
exercise routines as medically indicated. The
information on strenuous exercise is scarce; however, women who engage in such activities
require close medical supervision.
Previously inactive women and those with medical or obstetric complications should be evaluated before recommendations for physical activity
during pregnancy are made. Exercise during
pregnancy may provide additional health benefits
to women with gestational diabetes.
A physically active woman with a history of or
risk for preterm labor or fetal growth restriction
should be advised to reduce her activity in the
second and third trimesters.
499
References
1. American College of Sports Medicine. ACSMs guidelines for exercise testing and prescription. 6th ed.
Philadelphia: Lippincott, Williams and Wilkins, 2000
2. Dye TD, Knox KL, Artal R, Aubry RH, Wojtowycz MA.
Physical activity, obesity, and diabetes in pregnancy. Am
J Epidemiol 1997;146:961965
3. Jovanovic-Peterson L, Peterson CM. Exercise and the
nutritional management of diabetes during pregnancy.
Obstet Gynecol Clin North Am 1996;23:7586
4. Bung P, Artal R. Gestational diabetes and exercise: a survey. Semin Perinatol 1996;20:328333
5. Clark SL, Cotton DB, Pivarnik JM, Lee W, Hankins GD,
Benedetti TJ, et al. Position change and central hemodynamic profile during normal third-trimester pregnancy
and post partum. Am J Obstet Gynecol 1991;164:883887
[erratum in Am J Obstet Gynecol 1991;165:241]
6. Launer LJ, Villar J, Kestler E, deOnis M. The effect of
maternal work on fetal growth and duration of pregnancy:
a prospective study. Br J Obstet Gynaecol 1990:97;6270
7. Saurel-Cubizolles MJ, Kaminski M. Pregnant womens
working conditions and their changes during pregnancy: a
national study in France. Br J Ind Med 1987;44:236243
8. Ahlborg G Jr, Bodin L, Hogstedt C. Heavy lifting during
pregnancya hazard to the fetus? A prospective study. Int
J Epidemiol 1990;19:9097
9. Artal R, Sherman C. Exercise during pregnancy: safe and
beneficial for most. Phys Sports Med 1999;27:5152, 54,
5758
10. Camporesi EM. Diving and pregnancy. Semin Perinatol
1996;20:292302
11. Artal R, Fortunato V, Welton A, Constantino N,
Khodiguian N, Villalobos L, et al. A comparison of cardiopulmonary adaptations to exercise in pregnancy at sea
level and altitude. Am J Obstet Gynecol 1995;172:
11701180
12. Clapp JF 3rd, Capeless EL. Neonatal morphometrics after
endurance exercise during pregnancy. Am J Obstet
Gynecol 1990;163:18051811
13. Artal R, Wiswell RA, Drinkwater BL, eds. Exercise in
Pregnancy. 2nd ed. Baltimore: Williams and Wilkins, 1991
14. Soultanakis HN, Artal R, Wiswell RA. Prolonged exercise
in pregnancy: glucose homeostasis, ventilatory and cardiovascular responses. Semin Perinatol 1996;20:315327
15. Hale RW, Milne L. The elite athlete and exercise in pregnancy. Semin Perinatol 1996;20:277284
16. McCrory MA, Nommsen-Rivers LA, Mole PA, Lonnerdal
B, Dewey KG. Randomized trial of the short-term effects
of dieting compared with dieting plus aerobic exercise on
lactation performance. Am J Clin Nutr 1999;69:959967
17. Koltyn KF, Schultes SS. Psychological effects of an aerobic exercise session and a rest session following pregnancy. J Sports Med Phys Fitness 1997;37:287291
500
ACOG
Committee on
Obstetric Practice
Reaffirmed 2009
Committee
Opinion
Number 268, February 2002
followed.
Copyright February 2002
the publisher.
directed to:
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Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
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Management of asymptomatic pregnant or lactating women exposed to

anthrax. ACOG Committee Opinion
Management of Asymptomatic
Pregnant or Lactating Women
Exposed to Anthrax
ABSTRACT: Anthrax infections are diagnosed by isolating Bacillus anthracis
from body fluids or by measuring specific antibodies in the blood of persons
suspected to have the disease. It is recommended that asymptomatic pregnant
and lactating women who have been exposed to a confirmed environmental
contamination or a high-risk source as determined by the local Department
of Health (not the womens health care provider) receive prophylactic treatment. A variety of antimicrobial regimens are available. Although some of
these drugs may present risks to the developing fetus, these risks are clearly
outweighed by the potential morbidity and mortality from anthrax. Guidelines
for prophylactic treatment of anthrax and treatment of suspected active cases
of anthrax are changing continually, and the Centers for Disease Control and
Prevention web site should be consulted for the latest recommendations.
Anthrax is an infection caused by Bacillus anthracis, an aerobic, grampositive, spore-forming, nonmotile bacillus species. There are three primary clinical manifestations of the disease: 1) cutaneous, 2) inhalational, and
3) gastrointestinal.
Cutaneous: This is the most common presentation, accounting for 95% of
naturally occurring infections. The organisms portal of entry is a cut or
abrasion on the skin. The areas of greatest exposure are the hands, arms,
face or neck. Potential sources of the organism include wool, hides, and
leather and hair products of infected animals, particularly goats. Exposure
also may result from a bioterrorist act (eg, a contaminated letter). Incubation
periods may be as long as 12 days. Skin infection begins as a raised pruritic papule, resembling an insect bite. Within 12 days a vesicle develops, followed by a painless ulcer 13 cm in diameter with a characteristic black
necrotic eschar in the center. Localized lymphangitis and painful lymphadenopathy may occur. Although antibiotic therapy does not appear to
change the course of eschar formation and healing, it does decrease the risk
of systemic disease. Mortality rates are 20% if untreated, but less than 1%
with antibiotic therapy.
COMMITTEE OPINIONS
Inhalational: This is the most serious presentation,

resulting from deposition of spore-bearing particles
of 15 m into the alveolar spaces. Macrophages
ingest the spores that are then transported to the pulmonary lymphatics where they germinate. The
asymptomatic incubation period usually is 17 days
after exposure, but spores may germinate in the mediastinal lymphatics for up to 60 days. Once germination occurs, replicating bacteria release toxins leading
to hemorrhage, edema, and necrosis. Initial symptoms resemble a flulike illness with fever, cough, and
headache, but without rhinitis, followed by progressive dyspnea that rapidly progresses to respiratory
failure and death within hours. Case-fatality estimates
are extremely high, even with supportive care and
appropriate antibiotics.
Gastrointestinal: The relatively rare intestinal form of
anthrax follows ingestion, deposition, and subsequent
germination of spores in the upper or lower gastrointestinal tract. The former leads to the oral-pharyngeal
form of the disease marked by oral-esophageal ulcers
and regional lymphadenopathy. The latter results in
acute inflammation of the intestinal tract with symptoms that include anorexia, malaise, nausea, vomiting, and fever. Subsequently patients infected with
gastrointestinal anthrax develop abdominal pain;
hematemesis; severe, bloody diarrhea; and sepsis.
Intestinal anthrax may be fatal in 2560% of cases;
the effect of early antibiotic therapy is unknown.
Evaluation and Management of Possible

Anthrax Exposure Caused by
Bioterrorist Acts
The risk of anthrax exposure is remote for people not
in direct contact with the contaminated object or site
and is greatest for those present in the immediate
vicinity of contamination. The disease is not spread
by casual contact or by coughing and sneezing.
Active Infection
Anthrax infections are diagnosed by isolating B
anthracis from the blood, cerebrospinal fluid, skin
lesions, or respiratory secretions or by measuring
specific antibodies in the blood of persons suspected
to have the disease. Rapid diagnostic immunoassays
and polymerase chain reaction are available at
national reference laboratories. Strategies of antimicrobial treatment of active anthrax infection are
501
evolving. For the latest recommendations consult

the Centers for Disease Control and Prevention
(CDC) web site at www.cdc.gov/mmwr and
www.bt.cdc.gov.
Exposure
For asymptomatic individuals with low-risk exposure, antimicrobials are not warranted until there is
an evident risk of actual exposure based on microbiologically documented anthrax as determined by
law enforcement and public health authorities. The
womans health care provider is not the party to validate a threat.
In the current crisis, when screening for exposure is deemed necessary, it is conducted by nasal
swab. The resultant secretions can be examined by
Gram stain and culture. However, given the lack of
reliability of nasal swab screening, postexposure
prophylaxis is indicated only after confirmed or
high-risk suspected exposure. In the latter cases,
treatment can be stopped if anthrax is not documented.
For adult postexposure prophylaxis against
anthrax infections, the CDC currently recommends
500 mg of ciprofloxacin orally every 12 hours for 60
days or 100 mg of doxycycline orally every 12 hours
for 60 days.
Management of Exposed Asymptomatic

Pregnant or Lactating Women
At this time, the Committee on Obstetric Practice
recommends that prophylaxis of asymptomatic
pregnant and lactating women be limited to those
women who have had exposure to a confirmed environmental contamination or who are exposed to a
high-risk source as determined by the local
Department of Health. Prophylaxis for asymptomatic pregnant or lactating women is 500 mg of
ciprofloxacin orally every 12 hours for 60 days (6).
Ciprofloxacin and other fluoroquinolones generally are not used during pregnancy and lactation
because of suggested irreversible drug-induced
arthropathy associated with such treatment in a variety of species of adolescent animals (15). However,
no clear evidence of teratogenicity has been demonstrated in humans (15). Despite these concerns, the
potential morbidity and mortality from anthrax
clearly outweighs these risks. Thus, if the bacteria
are shown to be sensitive to penicillin, the treatment
502
should be switched to 500 mg of amoxicillin orally

three times a day for 60 days (6).
If a woman has been prescribed ciprofloxacin
and is found to be pregnant, she should continue her
course of antibiotics for the full 60 days (6) unless
the bacteria are shown to be penicillin-sensitive. She
should then be switched to amoxicillin. A 1999
expert review of published data on experiences with
ciprofloxacin concluded that therapeutic doses during pregnancy are unlikely to pose substantial teratogenic risk, but the data are insufficient to state
that there is no risk (1). In the case of penicillin- and
ciprofloxacin-allergic patients, treatment should
consist of doxycycline or penicillin desensitization
should be considered if the organism is proved sensitive (6). In this situation, the risks of anthrax
would far outweigh the risks of doxycycline to the
fetus (ie, dental staining of the primary teeth and
possible depressed bone growth and defective dental enamel).
The guidelines for prophylactic treatment of
anthrax and treatment of suspected active cases of
anthrax are continually evolving. Please refer to
www.bt.cdc.gov and www.cdc.gov/mmwr for any
updates in CDC treatment guidelines.
References
1. Friedman JM, Polifka JE. Ciprofloxacin. In: Teratogenic
effects of drugs: a resource for clinicians (TERIS). 2nd ed.
Baltimore: The Johns Hopkins University Press, 2000:
149150
2. Friedman JM, Polifka JE. Doxycyclicne. In: Teratogenic

effects of drugs: a resource for clinicians (TERIS). 2nd ed.
Baltimore: The Johns Hopkins University Press, 2000:
238239
3. Center for Drug Evaluation and Research. U.S. Food and
Drug Administration. CIPRO (Ciprofloxacin) use by
pregnant and lactating women. Available at http://www.
fda.gov/cder/drug/infopage/cipro/cipropreg.htm.
Retrieved November 2, 2001
Drug Administration. Drug preparedness and response to
bioterrorism. Available at http://www.fda.gov/cder/drug
prepare/default.htm. Retrieved November 2, 2001
Drug Administration. Doxycycline (Vibramycin,
Monodox, Doryx, Doxy, Atridox, Periodox, Vibra-Tabs)
use by pregnant and lactating women. Available at
http://www.fda.gov/cder/drug/infopage/penG_doxy/doxy
preg.htm. Retrieved November 2, 2001
6. Updated recommendations for antimicrobial prophylaxis
among asymptomatic pregnant women after exposure to
bacillus anthracis. MMWR Morb Mortal Wkly Rep 2001;
50:960
Resources
Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E,
Friedlander AM, et al. Anthrax as a biological weapon: medical
and public health management. Working Group on Civilian
Biodefense. JAMA 1999;281:17351745[erratum JAMA
2000;283:1963]
Update: investigation of anthrax associated with intentional
exposure and interim public health guidelines, October 2001.
MMWR Morb Mortal Wkly Rep 2001;50:889893
Use of anthrax vaccine in the United States. MMWR Morb
Mortal Wkly Rep 2000;49(RR-15):120
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
Reaffirmed 2005
Committee
Opinion
followed.
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Obstetric management of patients

with spinal cord injuries. ACOG
2002;100:6257.
503
Obstetric Management of Patients

with Spinal Cord Injuries
ABSTRACT: Effective rehabilitation and modern reproductive technology
may increase the number of women considering pregnancy who have spinal cord injuries (SCIs). It is important that obstetricians caring for these
patients are aware of the specific problems related to SCIs. Autonomic dysreflexia is the most significant medical complication seen in women with SCIs,
and precautions should be taken to avoid stimuli that can lead to this potentially fatal syndrome. Women with SCIs may give birth vaginally, but when
cesarean delivery is indicated, adequate anesthesia (spinal or epidural if possible) is needed.
Approximately 11,000 new spinal cord injuries (SCIs) are reported per year
in the United States. More than 50% occur in persons between the ages of 16
and 30 years, with women constituting approximately 18% of these cases.
Effective rehabilitation and modern reproductive technology may increase
the number of these patients considering pregnancy.
Ideally, women with SCIs who are considering pregnancy should have a
preconceptional evaluation. Chronic medical conditions and the womans
adaptation to her disability must be evaluated. Baseline pulmonary function
and renal studies may be appropriate. Also, it should be recognized that fertility in these patients usually is not affected, and family planning should be
discussed.
It is important that obstetricians caring for such patients acquaint themselves with the problems related to SCIs that may occur throughout pregnancy. Common complications affecting women with SCIs include urinary
tract infections, decubital ulcers, impaired pulmonary function, and autonomic dysreflexia. Additional potential complications include anemia, deep vein
thrombosis, pulmonary emboli, and unattended delivery.
Common Complications
Urinary Tract Infections
Asymptomatic bacteruria occurs in a majority of patients with SCIs during
pregnancy. The incidence of lower urinary tract infections and pyelonephritis
504
also is increased. Incomplete bladder emptying, neurogenic bladder, urinary diversions, and indwelling
catheters contribute to this risk. Frequent urine cultures or antibiotic suppression are indicated.
Decubital Ulcers
Decubital ulcers are a frequently preventable complication in women with SCIs. During pregnancy,
women with SCIs should have routine skin examinations, frequent position changes, adequate padding,
and appropriately sized medical equipment (eg,
wheelchairs). Weight gain and edema also may contribute to decubital ulceration.
Pulmonary Function
Impaired pulmonary function may be present in
women with high thoracic or cervical spine lesions.
For patients with borderline function, ventilatory
support and meticulous attention to pulmonary care
is necessary during pregnancy and delivery. Supine
positioning may further impair pulmonary function.
Serial assessments of vital capacity will help assess
the need for ventilatory assistance.
Autonomic Dysreflexia
Autonomic dysreflexia is the most significant medical complication occurring in women with SCIs
(85% of patients with lesions above T5 through T6
level). This condition is attributed to a loss of hypothalamic control of sympathetic spinal reflexes and
occurs in patients with viable spinal cord segments
distal to the level of injury. It can occur in patients
with incomplete transections. In susceptible
patients, afferent stimuli from a hollow viscus (eg,
the bladder, bowel, or uterus) and from the skin
below the level of the lesion or of the genital areas
ascend in the spinothalamic tracts and posterior
columns, which causes reflex sympathetic activation
unmodified by the supraspinal centers. The resultant
catecholamine release and vasoconstriction lead to
hypertension associated with headache, bradycardia,
tachycardia, cardiac arrhythmia, sweating, flushing,
tingling, nasal congestion, piloerection, and, occasionally, respiratory distress. Uteroplacental vasoconstriction may result in fetal hypoxemia.
It is important to avoid stimuli that can lead to
autonomic dysreflexia, such as distension or manipulation of the vagina, bladder, urethra, or bowel.
During labor, the symptoms of autonomic dysreflexia are commonly synchronous with uterine contractions. The severity of the syndrome during labor
ranges from unpleasant symptoms to hypertensive

encephalopathy, cerebrovascular accidents, intraventricular and retinal hemorrhages, and death.
Therefore, continual hemodynamic monitoring during labor is mandatory in all at-risk patients.
Although patients with SCIs may perceive no
pain during labor, anesthesia should be used to prevent autonomic dysreflexia. Spinal or epidural anesthesia extending to the T10 level is the most reliable
method of preventing autonomic dysreflexia by
blocking stimuli that arise from pelvic organs.
Therefore, antepartum consultation with an anesthesiologist and the establishment of a plan for induction of epidural or spinal anesthesia at the onset of
labor is imperative. If autonomic dysreflexia occurs
before a regional anesthetic is available or occurs
despite regional anesthesia, hypertension may be
treated with antihypertensive agents that have a
rapid onset and short duration of action (eg, sodium
nitroprusside or nitroglycerin), ganglionic blocking
agents (eg, trimethaphan), adrenergic blocking
agents (eg, guanethidine), or a direct vasodilator (eg,
hydralazine).
If there is evidence of autonomic dysreflexia
during the second stage of labor, delivery can be
expedited by forceps or vacuum assisted delivery
with adequate anesthesia. If autonomic dysreflexia
during labor cannot be controlled by any means,
cesarean delivery may be necessary. Adequate anesthesia, spinal or epidural if possible, is needed for
cesarean deliveries in all patients with SCIs.
Ascertainment of Labor
Women with SCIs may give birth vaginally. Women
with spinal cord transection above the T10 segment
may have painless labor. In a patient with total transection at a lower thoracic level, labor pain may be
so reduced that the patient is unaware of uterine contractions, especially during sleep. However, symptoms under the control of the sympathetic nervous
system (eg, abdominal or leg spasms, shortness of
breath, increased spasticity) concurrent with uterine
contractions may make patients aware of labor.
Patients should be instructed in uterine palpation
techniques to detect contractions at home.
General Support
Excess weight gain may increase the difficulty of
moving and transporting pregnant women with
SCIs. Muscle-strengthening exercises may be rec-
COMMITTEE OPINIONS
ommended for the upper extremities of nonquadriplegic patients. For all patients, elevation of the legs
and range-of-motion exercises may be implemented
as pregnancy advances. The possibility of an
increased need for social support services also
should be addressed.
Bibliography
American Society of Anesthesiologists. Standards for basic
anesthetic monitoring. In: ASA standards, guidelines and statements. Park Ridge (IL): ASA; 2000. p. 56.
Atterbury JL, Groome LJ. Pregnancy in women with spinal
cord injuries. Nurs Clin North Am 1998;33:60313.
505
Baker EB, Cardenas DD. Pregnancy in spinal cord injured

women. Arch Phys Med Rehabil 1996;77:5017.
Baker EB, Cardena DD, Benedetti TJ. Risks associated with
pregnancy in spinal cord-injured women. Obstet Gynecol
1992;80:4258.
Hambly PR, Martin B. Anaesthesia for chronic spinal cord
lesions. Anaesthesia 1998;53:27389.
Nobunaga AI, Go BK, Karunas RB. Recent demographic and
injury trends in people served by the Model Spinal Cord Injury
Care Systems. Arch Phys Med Rehabil 1999;80:137282.
Paonessa K, Fernand R. Spinal cord injury and pregnancy.
Spine 1991;16:5968.
Verduyn WH. Spinal cord injured women, pregnancy and
delivery. Paraplegia 1986;24:23140.
506
ACOG
Committee on
Obstetric Practice
Reaffirmed 2008
Committee
Opinion
followed.
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Safety of Lovenox in pregnancy.

2002;100:8456.
Safety of Lovenox in Pregnancy

ABSTRACT: Lovenox (enoxaparin sodium) therapy appears to be safe and
efficacious for pregnant women who are candidates for either prophylactic or
therapeutic heparin. However, the use of enoxaparin and other low-molecular-weight heparins for therapeutic anticoagulation is not recommended
for pregnant women with prosthetic heart valves. Additionally, enoxaparin
should be used with caution or discontinued before administration of epidural for pain relief during labor.
Aventis Pharmaceuticals has issued a letter to health professionals describing

the addition of warnings and precautions to their Lovenox Injection (enoxaparin sodium) prescribing information. The Warnings section notes that
Lovenox Injection is not recommended for thromboprophylaxis in patients
with prosthetic heart valves because of reports of valvular thrombosis in
patients who were apparently adequately anticoagulated. The cases reported
by the manufacturer and in the literature suggest a relatively frequent occurrence of valvular thromboses in pregnant women treated with low-molecularweight heparin, possibly caused by the hypercoagulability of pregnancy (1,
2). The American College of Obstetricians and Gynecologists (ACOG)
Committee on Obstetric Practice concurs that low-molecular-weight heparins
should not be used for anticoagulation in pregnant women with prosthetic
heart valves.
The Precautions section now includes a paragraph in the Pregnancy
subsection that reports the occurrence of congenital anomalies in infants of
women treated with Lovenox Injection during pregnancy, but it notes that a
cause and effect relationship has not been established nor has the incidence
been shown to be higher than in the general population. The Committee on
Obstetric Practice does not believe that Lovenox Injection presents a teratogenic risk for the following three reasons: 1) the agent does not cross the placenta, providing no biologic plausibility for such a risk (3); 2) a large study
by Lepercq and associates described pregnancy outcomes in 604 women
treated with enoxaparin during 624 pregnancies and observed a congenital
anomaly rate of 2.5%, which is consistent with the rate in the general population (4); and 3) the variety of anomalies reported by Aventis Pharmaceuticals, and their rare occurrence, suggests no specific pathogenic pattern or
increased frequency.
COMMITTEE OPINIONS
Aventis Pharmaceuticals also states that there

have been post-marketing reports of fetal death
when pregnant women received Lovenox
Injection and warns of the risk of hemorrhage in
women receiving enoxaparin during pregnancy.
However, a review by the Committee on Obstetric
Practice of the reported events actually suggests the
occurrence of both fetal deaths and hemorrhage is
rare despite the high-risk nature of this population.
This is borne out in the survey of enoxaparin users
by Lepercq and associates who observed a 1.1%
fetal death rate and noted that none of the fetal or
neonatal adverse events was related to enoxaparin
(4). This study noted enoxaparin-related hemorrhage occurred in 1 of 624 pregnancies, and the
occurrence of recurrent maternal venous thrombotic
events in this high-risk population was 1.3%.
Enoxaparin therapy appears to be safe and efficacious when used in pregnant women. The Committee
on Obstetric Practice reiterates the recommendations made by ACOG that Patients who are candidates for either prophylactic or therapeutic heparin
may be given enoxaparin or dalteparin during pregnancy (5). In addition, the Committee on Obstetric
Practice recommends against the use of enoxaparin
and other low-molecular-weight heparins for therapeutic anticoagulation in pregnant women with pros-
507
thetic heart valves. Enoxaparin should not be used

1824 hours before administration of epidural for
pain relief during labor (6).
References
1. Rowan JA, McCowan LM, Raudkivi PJ, North RA.
Enoxaparin treatment in women with mechanical heart
valves during pregnancy. Am J Obstet Gynecol 2001;
185:6337.
2. Lev-Ran O, Kramer A, Gurevitch J, Shapira I, Mohr R.
Low-molecular-weight heparin for prosthetic heart valves:
treatment failure. Ann Thorac Surg 2000;69:2645; discussion 2656.
3. Dimitrakakis C, Papageorgiou P, Papageorgiou I,
Antzaklis A, Sakarelou N, Michalas S. Absence of
transplacental passage of the low molecular weight heparin
enoxaparin. Haemostasis 2000;30:2438.
4. Lepercq J, Conard J, Borel-Derlon A, Damon JY,
Boudignat O, Francoual C, et al. Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies. BJOG 2001;108:113440.
Thromboembolism in pregnancy. ACOG Practice Bulletin
19. Washington DC: ACOG; 2000.
6. Horlocker TT, Wedel DJ. Neuraxial block and low-molecular-weight heparin: balancing perioperative analgesia and
thromboprophylaxis. Reg Anesth Pain Med 1998;23(suppl
2):16477.
508
ACOG
Committee on
Obstetric Practice
Reaffirmed 2009
Committee
Opinion
followed.
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Prevention of early-onset group B

streptococcal disease in newborns.
2002;100:140512.
(Replaces No. 173, June 1996)
Prevention of Early-Onset Group B

Streptococcal Disease in Newborns
ABSTRACT: During the past two decades, group B streptococci (GBS), or
Streptococcus agalactiae, has emerged as an important cause of perinatal
morbidity and mortality. Intrapartum administration of antibiotics to the
woman (during labor or after rupture of membranes, but before delivery) has
been demonstrated to reduce early-onset neonatal GBS disease. In 1996, the
federal Centers for Disease Control and Prevention (CDC), the American
College of Obstetricians and Gynecologists, and the American Academy of
Pediatrics recommended that obstetric providers adopt either a culture-based
or a risk-based approach for the prevention of early-onset GBS. A recent multistate retrospective cohort study of live births in 1998 and 1999 of residents
from eight areas of the Active Bacterial Core Surveillance/Emerging
Infections Program network suggests that the culture-based approach is
superior to the risk-based approach. The Committee on Obstetric Practice
supports the new CDC recommendations that obstetric providers adopt a culture-based strategy for the prevention of early-onset GBS disease in the newborn. It is important to acknowledge that complete implementation of this
complex strategy will not eliminate all cases of early-onset GBS.
During the past two decades, group B streptococci (GBS), or Streptococcus

agalactiae, has emerged as an important cause of perinatal morbidity and
mortality (1, 2). The gram-positive organism can colonize the lower gastrointestinal tract, and secondary spread to the genitourinary tract is common.
Between 10% and 30% of pregnant women are colonized with GBS in the
vagina or rectum (36). The organism may cause urinary tract infection,
amnionitis, endometritis, sepsis, or, rarely, meningitis (712).
Vertical transmission of GBS during labor or delivery may result in invasive infection in the newborn during the first week of life. This is known as
early-onset GBS infection, resulting in approximately 1,600 cases and 80
deaths annually (13). Late-onset GBS disease in the newborn may be the
result of vertical transmission or of nosocomial or community-acquired infection. Invasive GBS disease in the newborn is characterized primarily by sepsis, pneumonia, or meningitis. The incidence of invasive GBS infections
among pregnant women in the United States decreased by 21% from 1993 to
1998 to an incidence of 0.23 per 1,000 live births (1). Morbidity caused by
COMMITTEE OPINIONS
overwhelming sepsis and neurologic sequelae of

meningitis also is clinically important but more difficult to estimate.
Factors Associated with Early-Onset

Disease
A number of obstetric factors have been associated
with an increased likelihood of early-onset GBS disease in the newborn (14). These include maternal
colonization of the vagina and rectum with GBS,
premature births, prolonged rupture of membranes,
or intrapartum fever. The incidence of GBS disease
also is higher among infants born to AfricanAmerican women (15, 16), to Hispanic women, and
to women younger than 20 years (16, 17). Neonates
born to women with a prior GBS-infected infant
(1820) or women with heavy colonization such as
that seen with GBS bacteriuria equal to or greater
than 104 colony-forming units (CFU) (2125) or low
levels of anti-GBS capsular antibody, also are more
likely to be infected (26).
Intrapartum administration of antibiotics to the
women (during labor or after rupture of membranes,
but before delivery) has been demonstrated to reduce
early-onset neonatal GBS disease. Coinciding with
active prevention efforts in the 1990s, the incidence
of early-onset disease decreased by 70% to 0.5 cases
per 1,000 live births in 1999. Projections derived
from 1999 active surveillance data from the Active
Bacterial Core Surveillance/Emerging Infections
Program Network (27) estimate that intrapartum
antibiotics prevented nearly 4,500 early-onset
cases and 225 deaths that year (1, 2). Other countries that have adopted perinatal GBS prevention
guidelines similar to the United States guidelines
have seen comparable decreases in early-onset disease incidence (2830). Recent estimates of earlyonset disease incidence in the United States suggest
a slight increase in incidence from 1999 to 2000,
consistent with a plateau in the impact of prevention efforts.
Strategies for Intrapartum Antibiotic

Prophylaxis
In 1996, the federal Centers for Disease Control
and Prevention (CDC) (31), the American College
of Obstetricians and Gynecologists (ACOG), and
the American Academy of Pediatrics (AAP) recommended that obstetric providers adopt either a
509
culture-based or a risk-based approach for the prevention of early-onset GBS. Using the risk-based
approach, women with preterm labor (<37 weeks of
gestation), preterm premature rupture of membranes
(preterm PROM) (<37 weeks of gestation), rupture
of membranes greater than or equal to 18 hours, or
maternal fever during labor (38C or 100.4F)
receive intrapartum antibiotic prophylaxis. With
both culture-based and risk-based approaches,
women with GBS bacteriuria during their current
pregnancy or women who previously gave birth to
an infant with early-onset GBS disease were candidates for intrapartum antibiotic prophylaxis. The
culture-based approach requires obtaining a single
swab from the lower vagina (introitus) and perianal
area, placing the swab in transport media, and using
selective broth media. Use of prenatal cultures
remote from term to identify women who are colonized with GBS at delivery may not be accurate, and
since 1996, the CDC, ACOG, and AAP have recommended obtaining rectovaginal cultures at 3537
weeks of gestation with the culture-based approach.
All women who are GBS culture positive should be
treated with intrapartum antibiotic prophylaxis in
labor. Still, intrapartum antibiotic prophylaxis
should be administered to women with preterm
labor or preterm PROM who are in labor.
A recent multistate retrospective cohort study of
live births in 1998 and 1999 of residents from eight
areas of the Active Bacterial Core Surveillance/
Emerging Infections Program network suggests that
the culture-based approach is superior to the riskbased approach (32). All cases of early-onset GBS
identified by population-based surveillance in these
areas were identified. The providers intended strategy was unknown; thus, women without documented prenatal GBS screening were considered to have
been managed by the risk-based approach. The
study used data abstracted from records of 5,144
births, including 312 early-onset GBS cases.
Univariate analysis showed that intrapartum fever
equal to or greater than 38C or a previous infant
with GBS disease was associated with the highest
risks of early-onset GBS disease with a relative risk
(RR) of 5.99 (95% confidence interval [CI],
4.288.38) and RR of 3.79 (95% CI, 1.311.11),
respectively. In addition, all risk factors (ie, preterm
delivery, prolonged rupture of membranes 18
hours, inadequate prenatal care, black race, Hispanic
ethnicity, and maternal age <20 years) except GBS
bacteriuria were significantly associated with earlyonset GBS. The risk of having an infant with early-
510
onset GBS was significantly lower in the culture

cohort relative to the risk cohort with an adjusted RR
of 0.46 (95% CI, 0.370.60). Moreover, of the 312
infants with early-onset GBS, 63% of the mothers
had no risk factors. Even when the women who had
no strategy applied were excluded (n=207, including
30 early-onset GBS cases), the culture approach
remained protective with an adjusted RR of 0.48
(95% CI, 0.370.63).
In addition, a number of small studies have evaluated compliance of hospitals with GBS guideline
recommendations and found that a greater proportion of GBS-positive women receive intrapartum
prophylaxis under the culture-based approach than
with the risk-based approach (28, 3239). Data from
a large cohort of term infants with early-onset GBS
infections found that more than one half of the term
infants with culture-proven infection were born to
women with no obstetric risk factors (40). Based on
CDC surveillance data, the risk-based approach fails
to identify approximately 50% of infants with GBS
sepsis (41).
Commentary
The Committee on Obstetric Practice recognizes
that some of these recent studies have methodologic
flaws. Still, they represent the best available comparison of the risk-based and culture-based strategies to
date. Larger studies or randomized studies are not
likely to be conducted; therefore, the Committee
supports the new CDC recommendation that obstetric providers adopt a culture-based strategy for the
prevention of early-onset GBS disease in the newborn (see Fig. 1). The Committee agrees with the
CDC that the risk-based approach is no longer an
acceptable alternative except for circumstances
where culture results are not available before delivery. Laboratories must process GBS cultures correctly using the recommended selective broth media
for results to be accurate. Culture specimens should
be collected by swabbing the lower vagina and rectum (ie, through the anal sphincter), not by speculum examination, to maximize the likelihood of
GBS recovery (see box). Laboratories also must
Vaginal and rectal group B streptococci (GBS) screening cultures at 3537 weeks of gestation for ALL pregnant women
(unless patient had GBS bacteriuria during the current pregnancy or a previous infant with invasive GBS disease)
Intrapartum prophylaxis indicated

Previous infant with invasive GBS disease
GBS bacteriuria during current pregnancy
Positive GBS screening culture during current pregnancy
(unless a planned cesarean delivery, in the absence of
labor or amniotic membrane rupture, is performed)
Unknown GBS status (culture not done, incomplete, or
results unknown) and any of the following:
Delivery at < 37 weeks of gestation*
Amniotic membrane rupture 18 hours
Intrapartum prophylaxis not indicated

Previous pregnancy with a positive GBS
screening culture (unless a culture was also
positive during the current pregnancy)
Planned cesarean delivery performed in the
absence of labor or membrane rupture
(regardless of maternal GBS culture status)
Negative vaginal and rectal GBS screening
culture in late gestation during the current
pregnancy, regardless of intrapartum risk
factors
Intrapartum temperature 100.4F (38.0C)

*If onset of labor or rupture of amniotic membranes occurs at <37 weeks of gestation and there is a significant risk for preterm delivery (as
assessed by the clinician), follow the suggested algorithm for GBS prophylaxis as indicated by the CDC.
If amnionitis is suspected, broad-spectrum antibiotic therapy that includes an agent known to be active against GBS should replace GBS prophylaxis.
Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR
Recomm Rep 2002;51(RR-11):122.
Fig. 1. Indications for intrapartum antibiotic prophylaxis to prevent perinatal group B streptococcal disease under a
universal prenatal screening strategy based on combined vaginal and rectal cultures collected at 3537 weeks of
gestation from all pregnant women.
COMMITTEE OPINIONS
Procedures for collecting and processing clinical specimens for group B streptococcal culture
and performing susceptibility testing to clindamycin and erythromycin
Procedure for collecting clinical specimens for culture
of group B streptococcus at 3537 weeks of gestation
Swab the lower vagina (vaginal introitus), followed by
the rectum (ie, insert swab through the anal sphincter)
using the same swab or two different swabs. Cultures
should be collected in the outpatient setting by the
health care provider or the patient herself, with appropriate instruction. Cervical cultures are not recommended and a speculum should not be used for culture
collection.
Place the swab(s) into a nonnutritive transport medium. Appropriate transport systems (eg, Amies or
Stuart without charcoal) are commercially available. If
vaginal and rectal swabs were collected separately,
both swabs can be placed into the same container of
medium. Transport media will maintain GBS viability
for up to 4 days at room temperature or under refrigeration.
Specimen labels should clearly identify that specimens
are for group B streptococcal culture. If susceptibility
testing is ordered for penicillin-allergic women, specimen labels should also identify the patient as penicillin
allergic and should specify that susceptibility testing for
clindamycin and erythromycin should be performed if
GBS is isolated.
Procedure for processing clinical specimens for culture
of group B streptococcus
Remove swab(s) from transport medium.* Inoculate
swab(s) into a recommended selective broth medium,
such as Todd-Hewitt broth supplemented with either
gentamicin (8 g/mL) and nalidixic acid (15 g/mL), or
with colistin (10 g/mL) and nalidixic acid (15 g/mL).
Examples of appropriate commercially available options
include Trans-Vag broth supplemented with 5% defibrinated sheep blood or LIM broth.
Incubate inoculated selective broth for 1824 hours at
3537C in ambient air of 5% CO2. Subculture the
broth to a sheep blood agar plate (eg, tryptic soy agar
with 5% defibrinated sheep blood).
Inspect and identify organisms suggestive of GBS (ie,

narrow zone of beta hemolysis, gram-positive cocci,
catalase negative). Note that hemolysis may be difficult
to observe, so typical colonies without hemolysis
should also be further tested. If GBS is not identified
after incubation for 1824 hours, reincubate and
inspect at 48 hours to identify suspected organisms.
Various streptococcus grouping latex agglutination
tests or other tests for GBS antigen detection (eg,
genetic probe) may be used for specific identification,
or the cAMP test may be employed for presumptive
identification.
Procedure for clindamycin and erythromycin disk susceptibility testing of isolates, when ordered for penicillin-allergic patients
Use a cotton swab to make a suspension from an
1824-hour growth of the organism in saline or
Mueller-Hinton broth to match a 0.5 McFarland turbidity standard.
Within 15 minutes of adjusting the turbidity, dip a sterile cotton swab into the adjusted suspension. The swab
should be rotated several times and pressed firmly on
the inside wall of the tube above the fluid level. Use the
swab to inoculate the entire surface of a Mueller-Hinton
sheep blood agar plate. After the plate is dry, use sterile
forceps to place a clindamycin (2-g) disk onto half of
the plate and an erythromycin (15-g) disk onto the
other half.
Incubate at 35C in 5% CO2 for 2024 hours.
Measure the diameter of the zone of inhibition using a
ruler or calipers. Interpret according to NCCLS guidelines for Streptococcus species other than S pneumoniae (2002 breakpoints: clindamycin: 19 mm = susceptible, 1618 = intermediate, 15 = resistant; erythromycin: 21 mm = susceptible, 1620 = intermediate, 15 = resistant).
cAMP, cyclic adenosine monophosphate; CNA, Columbia colistinnalidixic acid; LIM broth, Todd-Hewitt with CNA.
*Before inoculation step, some laboratories may choose to roll swab(s) on a single sheep blood agar plate or CNA sheep blood agar plate.
This should be done only in addition to, and not instead of, inoculation into selective broth. The plate should be streaked for isolation, incubated at 3537C in ambient air or 5% CO2 for 1824 hours and inspected for organisms suggestive of GBS as described above. If suspected colonies are confirmed as GBS, the broth can be discarded, thus shortening the time to obtain culture results.
Source: Fenton, LJ, Harper MH. Evaluation of colistin and nalidixic acid in Todd-Hewitt broth for selective isolation of group B streptococci. J
Clin Microbiol 1979;9:1679. Although Trans-Vag medium is often available without sheep blood, direct comparison of medium with and
without sheep blood has shown higher yield when blood is added. LIM broth also may benefit from the addition of sheep blood, although the
improvement in yield is smaller and sufficient data are not yet available to support a recommendation.
Source: NCCLS. Performance standard for antimicrobial susceptibility testing. M100-S12, Table 2H, Wayne Pa.: NCCLS, 2002. NCCLS recommends disk diffusion (M-2) or broth microdilution testing (M-7) for susceptibility testing of GBS. Commercial systems that have been cleared
or approved for testing of streptococci other than S pneumoniae may also be used. Penicillin susceptibility testing is not routinely recommended for GBS because penicillin-resistant isolates have not been confirmed to date.
Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR
Recomm Rep 2002;51(RR-11):122.
511
512
communicate culture results to the obstetric

provider, the anticipated site of delivery if possible,
and the patient so that intrapartum antibiotic prophylaxis can be given to all GBS-positive women. For
women who have GBS bacteriuria in any concentration during the current pregnancy or who have previously given birth to an infant with early-onset
GBS disease, GBS cultures are not required. Those
women should automatically receive intrapartum
prophylaxis. Urine specimens should be labeled to
indicate they were obtained from a pregnant woman
so laboratories can report any presence of GBS bacteriuria in specimens obtained from pregnant
women. If, at anytime during pregnancy, GBS is present in urine in concentrations equal to or greater
than 10 5, antibiotics for asymptomatic bacteriuria or
a symptomatic urinary tract infection should be
administered, as it would be for any other organism
in significant concentration (42, 43). Women who
had GBS colonization during a previous pregnancy
may no longer be colonized during subsequent pregnancies and require GBS culture evaluation with
each pregnancy.
Penicillin remains the agent of choice for intrapartum prophylaxis. Ampicillin is an acceptable
alternative, but penicillin is preferred. However, data
also show that GBS isolates are increasingly resistant to second-line therapies. Up to 15% of GBS
isolates are resistant to clindamycin and 725% of
isolates are resistant to erythromycin (44). This pattern of resistance has led to a change in the recommendations for second-line therapies (see Table 1).
Intravenous administration is the only route recommended for intrapartum GBS prophylaxis because
of the higher intraamniotic concentrations achieved
with this route. Of note, erythromycin does not cross
the placenta.
The benefit of GBS prevention must be weighed
against the risk to the woman and her fetus of maternal allergic reactions to antibiotics during labor.
Although the risk of fatal anaphylaxis has been estimated at 1 per 100,000 (45, 46), the risk of less
severe anaphylactic or allergic reactions is important. In the recent CDC surveillance project of more
than 5,000 live births, there was a single, nonfatal
anaphylactic reaction (13, 47). The Committee
agrees with the CDC that local health agencies
should establish surveillance systems to monitor the
incidence of early-onset neonatal GBS disease, the
emergence of infection in women and their newborns that is caused by resistant organisms, and
other complications of widespread maternal antibiotic administration such as severe allergic reactions.
The Committee believes that when culture

results are not available, intrapartum prophylaxis
should be offered only on the basis of the presence
Table 1. Recommended Regimens for Intrapartum

Antimicrobial Prophylaxis for Perinatal Group B
Streptococcal Disease Prevention*
Regimens
Recommended
Alternative
If penicillin allergic
Patients not at high
risk for anaphylaxis
Antimicrobial
Penicillin G, 5 million units IV
initial dose, then 2.5 million
units IV every 4 hours until
delivery
Ampicillin, 2 g IV initial dose,
then 1 g IV every 4 hours until
delivery
Cefazolin, 2 g IV initial dose,
then 1 g IV every 8 hours until
delivery
Patients at high risk

for anaphylaxis
GBS susceptible
to clindamycin
and erythromycin
Clindamycin, 900 mg IV
every 8 hours until delivery
OR
GBS resistant to
clindamycin or
erythromycin or
susceptibility
unknown
Erythromycin, 500 mg IV every

6 hours until delivery
Vancomycin,|| 1 g IV every
12 hours until delivery
GBS, group B streptococci; IV, intravenously.

*Broader-spectrum agents, including an agent active against GBS, may
be necessary for treatment of chorioamnionitis.
History of penicillin allergy should be assessed to determine whether

a high risk for anaphylaxis is present. Penicillin-allergic patients at
high risk for anaphylaxis are those who have experienced immediate
hypersensitivity to penicillin including a history of penicillin-related
anaphylaxis; other high-risk patients are those with asthma or other
diseases that would make anaphylaxis more dangerous or difficult to
treat, such as persons being treated with beta-adrenergicblocking
agents.
If laboratory facilities are adequate, clindamycin and erythromycin

susceptibility testing should be performed on prenatal GBS isolates
from penicillin-allergic women at high risk for anaphylaxis.
Resistance to erythromycin often but not always is associated with

clindamycin resistance. If a strain is resistant to erythromycin but
appears susceptible to clindamycin, it may still have inducible resistance to clindamycin.
||
Cefazolin is preferred over vancomycin for women with a history of
penicillin allergy other than immediate hypersensitivity reactions, and
pharmacologic data suggest it achieves effective intraamniotic concentrations. Vancomycin should be reserved for penicillin-allergic
women at high risk for anaphylaxis.
Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal
group B streptococcal disease. Revised guidelines from CDC. MMWR
Recomm Rep 2002;51(RR-11):122.
COMMITTEE OPINIONS
of intrapartum risk factors for early-onset GBS disease (see previous description and Fig. 1). The
Committee strongly discourages using a hybrid of
both strategies (eg, administering intrapartum antibiotics to a woman with rupture of membranes 18
hours despite a negative GBS culture at 3537
weeks of gestation).
The Committee has insufficient data to suggest
a specific course of management for women with
threatened preterm labor or preterm PROM when
delivery is postponed successfully. Determining the
timing of intrapartum prophylaxis in these women is
challenging. Management of preterm PROM and
threatened preterm labor should be guided by clinical considerations. The Committee supports CDCs
potential management scheme (see Fig. 2).
The Committee concurs with the CDC that

intrapartum prophylaxis is not recommended for
women undergoing a planned cesarean delivery in
the absence of labor or rupture of membranes,
regardless of the GBS colonization status. A retrospective study at a single institution (48) and a
review of CDC surveillance data showed that the
risk of transmission of GBS from a colonized
woman to her infant during a prelabor cesarean
delivery with intact membranes is low. Patients
expected to undergo planned cesarean deliveries
should nonetheless undergo culture screening at
3537 weeks of gestation because onset of labor or
rupture of membranes may occur before the planned
cesarean delivery. If intrapartum prophylaxis is
administered before a planned cesarean delivery,
Onset of labor or* rupture of membranes at <37 weeks of gestation

with significant risk for imminent preterm delivery
No GBS culture
Obtain vaginal
and rectal GBS
culture and
initiate IV penicillin
No growth
at 48 hrs
GBS+
513
GBS+
GBS
Penicillin IV
for 48 hrs
(during tocolysis)
No GBS
prophylaxis
IAP|| at delivery
Stop penicillin
*If a hospital chooses to give antibiotics to prolong the latent period, a GBS culture should be obtained before initiating therapy and the
results used to guide intrapartum management.
Penicillin should be continued for a total of at least 48 hours, unless delivery occurs sooner. At the physicians discretion, antibiotic prophylaxis may be continued beyond 48 hours in a GBS culture-positive woman if delivery has not yet occurred. For women who are GBS culture
positive, antibiotic prophylaxis should be reinitiated when labor likely to proceed to delivery occurs or recurs.
If antibiotics are used to prolong the latent period, GBS cultures should be obtained prior to initiating therapy and the results used to guide
intrapartum management.
If delivery has not occurred within 4 weeks, a vaginal and rectal GBS screening culture should be repeated and the patient should be managed as described, based on the result of the repeat culture.
||
Intrapartum antibiotic prophylaxis.
Adapted from Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from
CDC. MMWR Recomm Rep 2002;51(RR-11):122.
Fig. 2. Sample algorithm for group B streptococci (GBS) prophylaxis for women with threatened preterm delivery.
This algorithm is not an exclusive course of management. Variations that incorporate individual circumstances or
institutional preferences may be appropriate.
514
the timing of administration of antibiotics and the

timing of incision should be individualized (49).
The Committee has insufficient data to support
or discourage the use of scalp electrodes or fetal
scalp/blood pH determinations in women known to
be GBS colonized. Furthermore, the risks of membrane stripping in GBS-colonized women have not
been investigated in well-designed prospective studies. Therefore, data are insufficient to encourage or
discourage this practice in women known to be GBS
colonized.
Current rapid tests for the detection of GBS
colonization at the time of labor or rupture of
membranes do not have sufficient sensitivity and
specificity to eliminate the need for culture-based
prenatal screening (50, 51).
The Committee on Obstetric Practice recognizes that compliance with the culture-based
approach will require the implementation of
several steps. Patient and professional materials are
available from ACOG (sales.acog.org and
www.acog.org) and the CDC (www.cdc.gov.ncidod/dbmd/gbs). Success of the culture-based
approach will require the following:
Obtaining accurate culture data
Appropriate processing of the culture by laboratories
Timely reporting of results to obstetric providers
Administering intrapartum prophylaxis to culture-positive women
It is important to acknowledge that complete implementation of this complex strategy still will not
eliminate all cases of early-onset GBS.
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Selective intrapartum chemoprophylaxis of neonatal
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10. Yancey MK, Duff P, Clark P, Kurtzer T, Frentzen BH,
Kubilis P. Peripartum infection associated with vaginal
group B streptococcal colonization. Obstet Gynecol
1994;84:8169.
11. Fox BC. Delayed-onset postpartum meningitis due to
group B streptococcus. Clin Infect Dis 1994;19:350.
12. Aharoni A, Potasman I, Levitan Z, Golan D, Sharf M.
Postpartum maternal group B streptococcal meningitis.
Rev Infect Dis 1990;12:2736.
13. Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A.
Prevention of perinatal group B streptococcal disease.
Revised guidelines from CDC. MMWR Recomm Rep
2002;51(RR-11):122.
14. Boyer KM, Gotoff SP. Strategies for chemoprophylaxis of
GBS early-onset infections. Antibiot Chemother 1985;
35:26780.
15. Zangwill KM, Schuchat A, Wenger JD. Group B streptococcal disease in the United States, 1990: report from a
multistate active surveillance system. Mor Mortal Wkly
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16. Schuchat A, Oxtoby M, Cochi S, Sikes RK, Hightower A,
Plikaytis B, et al. Population-based risk factors for neonatal group B streptococcal disease: results of a cohort study
in metropolitan Atlanta. J Infect Dis 1990;162:6727.
17. Schuchat A, Deaver-Robinson K, Plikaytis BD, Zangwill
KM, Mohle-Boetani J, Wenger JD. Multistate case-control study of maternal risk factors for neonatal group B
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18. Carstensen H, Christensen KK, Grennert L, Persson K,
Polberger S. Early-onset neonatal group B streptococcal
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19. Faxelius G, Bremme K, Kvist-Christensen K, Christensen
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20. Christensen KK, Dahlander K, Linden V, Svenningsen N,
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21. Pass MA, Gray BM, Khare S, Dillon HC Jr. Prospective
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23. Moller M, Thomsen AC, Borch K, Dinesen K, Zdravkovic
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Persson K, Christensen KK, Christensen P, Forsgren A,
Jorgensen C, Persson PH. Asymptomatic bacteriuria during pregnancy with special reference to group B streptococci. Scand J Infect Dis 1985;17:1959.
Baker CJ, Kasper DL. Correlation of maternal antibody
deficiency with susceptibility to neonatal group B streptococcal infection. N Engl J Med 1976;294:7536.
Schuchat A, Hilger T, Zell E, Farley M, Reingold A,
Harrison L, et al. Active bacterial core surveillance of the
emerging infections program network. Emerging Infect
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Jeffery HE, Moses Lahra M. Eight-year outcome of universal screening and intrapartum antibiotics for maternal
group B streptococcal carriers. Pediatrics 1998;101:E2.
Isaacs D, Royle JA. Intrapartum antibiotics and early
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Davies HD, Adair CE, Schuchat A, Low DE, Sauve RS,
McGeer A. Physicians prevention practices and incidence
of neonatal group B streptococcal disease in 2 Canadian
regions. CMAJ 2001;164:47985.
Prevention of perinatal group B streptococcal disease: a
public health perspective. Centers for Disease Control and
Prevention. MMWR Recomm Rep1996;45:124.
Schrag SJ, Zell ER, Lynfield R, Roome A, Arnold KE,
Craig AS, et al. A population-based comparison of strategies to prevent early-onset group B streptococcal disease
in neonates. N Engl J Med 2002;347:2339.
Hafner E, Sterniste W, Rosen A, Schuchter K, Plattner M,
Asboth F, et al. Group B streptococci during pregnancy: a
comparison of two screening and treatment protocols. Am
Lieu TA, Mohle-Boetani JC, Ray GT, Ackerson LM,
Walton DL. Neonatal group B streptococcal infection in a
managed care population. Perinatal Group B Streptococcal Infection Study Group. Obstet Gynecol 1998;92:
217.
Factor SH, Levine OS, Nasser A, Potter J, Fajardo A,
OSullivan MJ, et al. Impact of a risk-based prevention
policy on neonatal group B streptococcal disease. Am J
Cheon-Lee E, Amstey MS. Compliance with the Centers
for Disease Control and Prevention antenatal culture protocol for preventing group B streptococcal neonatal sepsis. Am J Obstet Gynecol 1998;179:779.
Katz VL, Moos MK, Cefalo RC, Thorp JM Jr, Bowes WA
Jr, Wells SD. Group B streptococci: results of a protocol
of antepartum screening and intrapartum treatment. Am J
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38. Gilson GJ, Christensen F, Romero H, Bekes K, Silva L,

Qualls CR. Prevention of group B streptococcus earlyonset neonatal sepsis: comparison of the Center for
Disease Control and Prevention screening-based protocol
to a risk-based protocol in infants at greater than 37
weeks gestation. J Perinatol 2000;20:4915.
39. Brozanski BS, Jones JG, Krohn MA, Sweet RL. Effect of
a screening-based prevention policy on prevalence of
early-onset group B streptococcal sepsis. Obstet Gynecol
2000;95:496501.
40. Bromberger P, Lawrence JM, Braun D, Saunders B,
Contreras R, Petitti DB. The influence of intrapartum
antibiotics on the clinical spectrum of early-onset group B
streptococcal infection in term infants. Pediatrics 2000;
106:24450.
41. Rosenstein NE, Schuchat A. Opportunities for prevention
of perinatal group B streptococcal disease: a multistate
surveillance analysis. The Neonatal Group B Streptococcal Disease Study Group. Obstet Gynecol 1997;90:
9016.
42. Persson K, Bjerre B, Elfstrom L, Polberger S, Forsgren A.
Group B streptococci at delivery: high count in urine
increases risk for neonatal colonization. Scand J Infect
Dis 1986;18:52531.
43. Persson K, Bjerre B, Elfstrom L, Forsgren A. Longitudinal study of group B streptococcal carriage during late
pregnancy. Scand J Infect Dis 1987;19:3259.
44. Pearlman MD, Pierson CL, Faix RG. Frequent resistance
of clinical group B streptococci isolates to clindamycin
and erythromycin. Obstet Gynecol 1998;92:25861.
45. Schwartz B, Schuchat A, Oxtoby MJ, Cochi SL,
Hightower A, Broome CV. Invasive group B streptococcal
disease in adults. A population-based study in metropolitan Atlanta. JAMA 1991;266:11124.
46. Hardman JG, Limbird LE, Molinoff PB, Ruddon RW,
Gilman AG, editors. Goodman and Gilmans the pharmacological basis of therapeutics. 9th ed. New York:
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47. Dunn AB, Blomquist J, Khouzami V. Anaphylaxis in labor
secondary to prophylaxis against group B Streptococcus:
a case report. J Reprod Med 1999;44:3814.
48. Ramus RM, McIntire DD, Wendel GD Jr. Antibiotic
chemoprophylaxis for group B strep is not necessary with
elective cesarean section at term [abstract]. Am J Obstet
Gynecol 1999;180:S85.
49. Hager WD, Schuchat A, Gibbs R, Sweet R, Mead P,
Larsen JW. Prevention of perinatal group B streptococcal
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50. Yancey MK, Armer T, Clark P, Duff P. Assessment of
rapid identification tests for genital carriage of group B
streptococci. Obstet Gynecol 1992;80:103847.
51. Walker CK, Crombleholme WR, Ohm-Smith MJ, Sweet
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516
ACOG
Committee on
Obstetric Practice
Reaffirmed 2008
Committee
Opinion
followed.
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
Rubella Vaccination
ABSTRACT: The incidence of rubella decreased from 0.45 per 100,000 in
1990 to 0.1 per 100,000 in 1999. Although there is a nationwide shortage of
rubella vaccine, women who are rubella susceptible during pregnancy should
receive MMR (measlesmumpsrubella) vaccination postpartum. In October
2001, the federal Centers for Disease Control and Prevention changed the
recommendations concerning the pregnancy interval after receiving rubella
vaccine. This interval has been reduced from 3 months to 1 month.
The incidence of rubella decreased from 0.45 per 100,000 in 1990 to 0.1 per
100,000 in 1999 (1). There have been cluster outbreaks, especially among
persons born outside of the United States. Although there is a nationwide
shortage of rubella vaccine, women who are rubella susceptible during
pregnancy should receive MMR (measlesmumpsrubella) vaccination postpartum. The appropriate test for assessing rubella immunity is the
immunoglobulin G serology. There is no contraindication to giving MMR
vaccination while breastfeeding. Receipt of rubella vaccination in a new
mother does not pose a risk of transmission of the virus to the newborn or to
other children in her household. Receipt of rubella vaccination during pregnancy is not an indication for interruption of that pregnancy.
In October 2001, the federal Centers for Disease Control and Prevention
changed the recommendations concerning the pregnancy interval after receiving rubella vaccine. This interval has been reduced from 3 months to 1 month
(2). The safe interval for measles and mumps vaccination was already 1
month.
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Rubella vaccination. ACOG

2002;100:1417.
References
1. Reef SE, Frey TK, Theall K, Abernathy E, Burnett CL, Icenogle J, et al. The changing
epidemiology of rubella in the 1990s: on the verge of elimination and new challenges
for control and prevention. JAMA 2002;287:464-72.
2. Revised ACIP recommendation for avoiding pregnancy after receiving a rubella-containing vaccine. MMWR Morb Mortal Wkly Rep 2001;50:1117.
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
Reaffirmed 2006
517
Committee
Opinion
followed.
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Nonobstetric surgery in pregnancy.

2003;102:431.
Nonobstetric Surgery in Pregnancy

ABSTRACT: Although there are no data to support specific recommendations
regarding nonobstetric surgery and anesthesia in pregnancy, it is important
for nonobstetric physicians to obtain obstetric consultation before performing nonobstetric surgery. The decision to use fetal monitoring should be individualized, and each case warrants a team approach for optimal safety of the
woman and her baby.
The American College of Obstetricians and Gynecologists Committee on

Obstetric Practice acknowledges that the issue of nonobstetric surgery and
anesthesia in pregnancy is an important concern for physicians who care for
women; however, there are no data to allow us to make specific recommendations. It is important for physicians to obtain obstetric consultation before
performing nonobstetric surgery because obstetricians are uniquely qualified
to discuss aspects of maternal physiology and anatomy that may affect
intraoperative maternalfetal well-being. The decision to use fetal monitoring
should be individualized, and, if used, may be based on gestational age, type
of surgery, and facilities available. Ultimately, each case warrants a team
approach (anesthesia, obstetrics, surgery) for optimal safety of the woman
and her baby.
518
ACOG
Committee on
Obstetric Practice
Reaffirmed 2008
American Society of
Anesthesiologists
followed.
Copyright July 2004
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Pain relief during labor. ACOG

2004;104:213.
Committee
Opinion
(Replaces No. 231, February 2000)
Pain Relief During Labor

ABSTRACT: Pain management should be provided whenever medically indicated. The American Society of Anesthesiologists (ASA) and the American
College of Obstetricians and Gynecologists (ACOG) believe that women
requesting epidural analgesia during labor should not be deprived of this service based on their insurance or inadequate nursing participation in the management of regional analgesic modalities. Furthermore, in an effort to allow
the maximum number of patients to benefit from neuraxial analgesia, ASA
and ACOG believe that labor nurses should not be restricted from participating in the management of pain relief during labor.
Labor causes severe pain for many women. There is no other circumstance
where it is considered acceptable for an individual to experience untreated
severe pain, amenable to safe intervention, while under a physicians care. In
the absence of a medical contraindication, maternal request is a sufficient
medical indication for pain relief during labor. Pain management should be
provided whenever medically indicated.
Of the various pharmacologic methods used for pain relief during labor
and delivery, neuraxial analgesia techniques (epidural, spinal, and combined
spinalepidural) are the most flexible, effective, and least depressing to the
central nervous system, allowing for an alert participating woman and an alert
neonate. The American Society of Anesthesiologists (ASA) and the American
College of Obstetricians and Gynecologists (ACOG) believe that women
requesting epidural analgesia during labor should not be deprived of this service based on their insurance or inadequate nursing participation in the management of regional analgesic modalities. In addition, third-party payers who
provide reimbursement for obstetric services should not deny reimbursement
for labor analgesia because of an absence of other medical indications.
Although the availability of various methods of labor analgesia will vary from
hospital to hospital, within an institution the methods available should not be
based on a patients ability to pay. Furthermore, in an effort to allow the maximum number of patients to benefit from neuraxial analgesia, ASA and
ACOG believe that labor nurses should not be restricted from participating in
the management of pain relief during labor. Under appropriate physician
supervision, labor and delivery nursing personnel who have been properly
educated and have demonstrated current competence should be able to participate in the management of epidural infusions, including adjusting dosage
and discontinuing infusions.
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
Reaffirmed 2009
Committee
Opinion
followed.
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Guidelines for diagnostic imaging

during pregnancy. ACOG Committee
519
(Replaces No. 158, September 1995)
Guidelines for Diagnostic Imaging

During Pregnancy
ABSTRACT: Undergoing a single diagnostic X-ray procedure does not result
in radiation exposure adequate to threaten the well-being of the developing
preembryo, embryo, or fetus and is not an indication for therapeutic abortion.
When multiple diagnostic X-rays are anticipated during pregnancy, imaging
procedures not associated with ionizing radiation, such as ultrasonography
and magnetic resonance imaging, should be considered. Additionally, it may
be helpful to consult an expert in dosimetry calculation to determine estimated fetal dose. The use of radioactive isotopes of iodine is contraindicated for
therapeutic use during pregnancy. Other radiopaque and paramagnetic contrast agents have not been studied in humans, but animal studies suggest that
these agents are unlikely to cause harm to the developing human fetus.
Although imaging techniques requiring these agents may be diagnostically
beneficial, these techniques should be used during pregnancy only if potential
benefits justify potential risks to the fetus.
Various imaging modalities are available for diagnostic use during pregnancy. These include X-ray, ultrasonography, magnetic resonance imaging
(MRI), and nuclear medicine studies. Of these, diagnostic X-ray is the most
frequent cause of anxiety for obstetricians and patients. Much of this anxiety
is secondary to a general belief that any radiation exposure is harmful and
will result in an anomalous fetus. This anxiety could lead to inappropriate
therapeutic abortion and litigation. Actually, most diagnostic radiologic procedures are associated with little, if any, known significant fetal risks.
Moreover, according to the American College of Radiology, no single diagnostic X-ray procedure results in radiation exposure to a degree that would
threaten the well-being of the developing preembryo, embryo, or fetus (1).
Thus, exposure to a single X-ray during pregnancy is not an indication for
therapeutic abortion (2, 3).
Some women are exposed to X-rays before the diagnosis of pregnancy.
Occasionally, X-ray procedures will be indicated during pregnancy for significant medical problems or trauma. To enable physicians to counsel patients
appropriately, the following information is provided about the potential risks
and measures that can reduce diagnostic X-ray exposure.
520
X-Ray Exposure
Ionizing radiation can result in the following 3 harmful effects: 1) cell death and teratogenic effects, 2)
carcinogenesis, and 3) genetic effects or mutations
in germ cells (2, 3). There is little or no information
to estimate either the frequency or magnitude of
adverse genetic effects on future generations.
Units traditionally used to measure the effects of
X-ray include the rad and roentgen equivalents man
(rem). Modern units include the gray (Gy) and sievert (Sv). The definitions of these units of measure
are summarized in Table 1.
The estimated fetal exposure from some common radiologic procedures is summarized in Table
2. A plain X-ray generally exposes the fetus to very
small amounts of radiation. Commonly during pregnancy, the uterus is shielded for nonpelvic procedures. With the exception of barium enema or small
bowel series, most fluoroscopic examinations result
in fetal exposure of millirads. Radiation exposure
from computed tomography (CT) varies depending
on the number and spacing of adjacent image sections. Although CT pelvimetry can result in fetal
exposures as high as 1.5 rad, exposure can be
reduced to approximately 250 mrad (including fetal
gonad exposure) by using a low-exposure technique
(4).
Spiral (or helical) CT allows continuous scanning of the patient as the couch is moved through the
scanner, providing superior speed and image quality.
Radiation exposure is affected by slice thickness, the
number of cuts obtained, and the pitch, a ratio
defined as the distance the couch travels during one
360-degree rotation divided by the section thickness.
The patient dose is proportional to 1 per pitch.
Under typical use with a pitch of 1 or greater, the
radiation exposure to the fetus from spiral CT is
comparable to conventional CT (5).
Cell Death and Teratogenic Effects

Data from an animal study suggest that exposure to
high-dose ionizing radiation (ie, much greater than
that used in diagnostic procedures) before implantation will most likely be lethal to the embryo (2). In
other words, cell death is most likely an all or
none phenomenon in early embryonic development.
Myriad teratogenic effects have developed in
animals exposed to large doses of radiation (ie,
100200 rad). However, in humans, growth restriction, microcephaly, and mental retardation are the
most common adverse effects from high-dose radiation (3, 6, 7). Based on data from atomic bomb survivors, it appears that the risk of central nervous
system effects is greatest with exposure at 815
weeks of gestation, with no proven risk at less than
8 weeks of gestation or at greater than 25 weeks of
gestation (3, 8). Thus, at 815 weeks of gestation,
the fetus is at greatest risk for radiation-induced
mental retardation, and the risk appears to be a nonthreshold linear function of dose at doses of at least
20 rad (3, 6, 8, 9). For example, the risk of severe
mental retardation in fetuses exposed to ionizing
radiation is approximately 40% at 100 rad of exposure and as high as 60% at 150 rad of exposure (3,
8). It has been suggested that a threshold for this
adverse effect may exist in the range of 2040 rad
(7, 8). Even multiple diagnostic X-ray procedures
rarely result in ionizing radiation exposure to this
degree. Fetal risks of anomalies, growth restriction,
or abortions are not increased with radiation exposure of less than 5 rad, a level above the range of
exposure for diagnostic procedures (2).
Carcinogenesis
The risk of carcinogenesis as a result of in utero
exposure to ionizing radiation is unclear but is prob-
Table 1. Some Measures of Ionizing Radiation

Measure
Definition
Unit
Exposure
Dose
Number of ions produced by X-rays per kilogram of air

Amount of energy deposited per kilogram of tissue
Roentgen (R)
Rad (rad)*
Relative
effective
dose
Amount of energy deposited per kilogram of tissue

normalized for biological effectiveness
Roentgen
equivalents
man (rem)*
Unit
Roentgen (R)
Gray (Gy)
1 Gy = 100 rad
Sievert (Sv)
1 Sv = 100 rem
*For diagnostic X-rays, 1 rad = 1 rem

Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC 3rd, Hauth JC, Wenstrom KD. General considerations and maternal evaluation. In: Williams obstetrics. 21st ed. New York (NY): McGraw-Hill; 2001. p. 114358. Reproduced with permission of The McGraw-Hill Companies.
COMMITTEE OPINIONS
Table 2. Estimated Fetal Exposure From Some Common

Radiologic Procedures
Procedure
Fetal Exposure
Chest X-ray (2 views)

Abdominal film (single view)
Intravenous pyelography
Hip film (single view)
Mammography
Barium enema or small bowel series
CT scan of head or chest
CT scan of abdomen and lumbar spine
CT pelvimetry
0.020.07 mrad
100 mrad
1 rad*
200 mrad
720 mrad
24 rad
<1 rad
3.5 rad
250 mrad
*Exposure depends on the number of films
Abbreviation: CT, computed tomography

Data from Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC 3rd, Hauth
JC, Wenstrom KD. General considerations and maternal evaluation. In:
Williams obstetrics. 21st ed. New York (NY): McGraw-Hill; 2001.
p. 114358.
ably very small. It is estimated that a 12 rad fetal

exposure may increase the risk of leukemia by a factor of 1.52.0 over natural incidence and that an
estimated 1 in 2,000 children exposed to ionizing
radiation in utero will develop childhood leukemia.
This is increased from a background rate of approximately 1 in 3,000 (2, 10). If elective abortion were
chosen in every instance of fetal exposure to radiation, 1,999 exposed, normal fetuses would be aborted
for each case of leukemia prevented (2, 11). It has
been estimated that the risk of radiation-induced carcinogenesis may indeed be higher in children compared with adults, but such risks are not likely to
exceed 1 in 1,000 children per rad (12). Thus, abortion should not be recommended solely on the basis
of exposure to diagnostic radiation.
Ultrasonography
Ultrasonography involves the use of sound waves and
is not a form of ionizing radiation. There have been no
reports of documented adverse fetal effects for diagnostic ultrasound procedures, including duplex
Doppler imaging. Energy exposure from ultrasonography has been arbitrarily limited to 94 mW/cm2 by
the U.S. Food and Drug Administration. There are no
contraindications to ultrasound procedures during
pregnancy, and this modality has largely replaced Xray as the primary method of fetal imaging during
pregnancy.
521
Magnetic Resonance Imaging

With MRI, magnets that alter the energy state of
hydrogen protons are used instead of ionizing radiation (13). This technique could prove especially
useful for diagnosis and evaluation of fetal central
nervous system anomalies and placental abnormalities (eg, accreta, previa).
Nuclear Medicine
Nuclear studies such as pulmonary ventilationperfusion, thyroid, bone, and renal scans are performed
by tagging a chemical agent with a radioisotope.
The fetal exposure depends on the physical and biochemical properties of the radioisotope (6).
Technetium Tc 99m is one of the most commonly used isotopes and is used for brain, bone, renal,
and cardiovascular scans. In general, these latter
procedures result in a uterus, embryo, or fetal exposure of less than 0.5 rad (6, 12).
One of the more common nuclear medicine
studies performed during pregnancy is the ventilationperfusion scan for suspected pulmonary
embolism. Macroaggregated albumin labeled with
Technetium Tc 99m is used for the perfusion portion, and inhaled xenon gas (127Xe or 133Xe) is used
for the ventilation portion. The amount of radiation
to which the fetus is exposed is extremely small
(approximately 50 mrad) (14).
In a 2002 study, investigators calculated the
mean fetal radiation exposure resulting from helical (spiral) CT in healthy pregnant women and
compared it with reported fetal radiation doses
for ventilationperfusion lung scanning (approximately 100370 Gy) (15). Although the exposure
from ventilationperfusion is relatively low, the
study found that the mean fetal doses associated
with helical CT were lower. Although exposure
varied with gestational age (3.320.2 Gy for
the first trimester, 7.976.7 Gy for the second
trimester, and 51.3130.8 Gy for the third
trimester), 20 of 23 study patients exhibited a
mean fetal dose of less than 60 Gy for all 3
trimesters.
Radioactive iodine readily crosses the placenta
and can adversely affect the fetal thyroid, especially
if used after 1012 weeks of gestation. Radioactive
isotopes of iodine used for treatment of hyperthyroidism are contraindicated during pregnancy, and
such therapy should be delayed until after delivery.
If a diagnostic scan of the thyroid is essential,
522
123
I or Technetium Tc 99m should be used in place

of 131I (14).
3.
Contrast Agents
A variety of oral and intravascular contrast agents
are used with X-ray and magnetic imaging procedures. Most radiopaque agents used with CT and
conventional radiography contain derivatives of
iodine and have not been studied in humans; however iohexol, iopamidol, iothalamate, ioversol,
ioxaglate, and metrizamide have been studied in animals and do not appear to be teratogenic (16).
Neonatal hypothyroidism has been associated with
some iodinated agents taken during pregnancy (17).
For this reason, these compounds generally are
avoided unless essential for correct diagnosis.
Studies requiring views before and after the administration of contrast agents will necessarily have
greater radiation exposure. Although some
radiopaque agents pass into the breast milk, they
have not been associated with problems in nursing
babies (16).
Paramagnetic contrast agents used during MRI
have not been studied in pregnant women. Animal
studies have demonstrated increased rates of spontaneous abortion, skeletal abnormalities, and visceral
abnormalities when given at 27 times the recommended human dose (18, 19). It is not known if these
compounds are excreted into human milk. Generally,
these agents should be used during pregnancy only if
the potential benefit justifies the potential risk to the
fetus as demonstrated in animal studies.
Guidelines
The following guidelines for X-ray examination or
exposure during pregnancy are suggested:
1. Women should be counseled that X-ray exposure from a single diagnostic procedure does not
result in harmful fetal effects. Specifically,
exposure to less than 5 rad has not been associated with an increase in fetal anomalies or pregnancy loss.
2. Concern about possible effects of high-dose ionizing radiation exposure should not prevent
medically indicated diagnostic X-ray procedures from being performed on a pregnant
woman. During pregnancy, other imaging procedures not associated with ionizing radiation
4.
5.
6.
(eg, ultrasonography, MRI) should be considered instead of X-rays when appropriate.

Ultrasonography and MRI are not associated
with known adverse fetal effects.
Consultation with an expert in dosimetry calculation may be helpful in calculating estimated
fetal dose when multiple diagnostic X-rays are
performed on a pregnant patient.
The use of radioactive isotopes of iodine is contraindicated for therapeutic use during pregnancy.
Radiopaque and paramagnetic contrast agents
are unlikely to cause harm and may be of diagnostic benefit, but these agents should be used
during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
References
1. Gray JE. Safety (risk) of diagnostic radiology exposures.
In: American College of Radiology. Radiation risk: a
primer. Reston (VA): ACR; 1996. p. 157.
2. Brent RL. The effect of embryonic and fetal exposure to
x-ray, microwaves, and ultrasound: counseling the pregnant and nonpregnant patient about these risks. Semin
Oncol 1989;16:34768.
3. Hall EJ. Scientific view of low-level radiation risks.
Radiographics 1991;11:50918.
4. Moore MM, Shearer DR. Fetal dose estimates for CT
pelvimetry. Radiology 1989;171:2657.
5. Parry RA, Glaze SA, Archer BR. The AAPM/RSNA
physics tutorial for residents. Typical patient radiation
doses in diagnostic radiology. Radiographics 1999;19:
1289302.
6. Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC 3rd,
Hauth JC, Wenstrom KD. General considerations and
maternal evaluation. In: Williams obstetrics. 21st ed. New
York (NY): McGraw-Hill; 2001. p. 114358.
7. Otake M, Yoshimaru H, Schull WJ. Severe mental retardation among prenatally exposed survivors of the atomic
bombing of Hiroshima and Nagasaki: a comparison of
the T65DR and DS86 dosimetry systems. Technical
report; RERF TR 87-16. Hiroshima: Radiation Effects
Research Foundation; 1988.
8. National Research Council. Other somatic and fetal
effects. In: Health effects of exposure to low levels of ionizing radiation: BEIR V. Washington, DC: National
Academy Press; 1990:35270.
9. Schull WJ, Otake M. Neurological deficit among survivors exposed to the atomic bombing of Hiroshima and
Nagasaki: a reassessment and new directions. In: Kriegel
H, Schmahl W, Gerber GB, Stieve FE, editors. Radiation
risks to the developing nervous system. Neuherberg, June
18-29, 1985, Munich. Stuttgart: G Fischer Verlag; 1986.
p. 399419.
COMMITTEE OPINIONS
10. Miller RW. Epidemiological conclusions from radiation

toxicity studies. In: Fry RJ, Grahn D, Griem ML, Rust JH,
editors. Late effects of radiation: proceedings of the colloquium held at the Center for Continuing Education, the
University of Chicago, Illinois, May 1969. New York
(NY): Van Nostrand Reinhold; 1970. p. 24556.
11. Early diagnosis of pregnancy: a symposium. J Reprod
Med 1981;26(suppl 4):14978.
12. Mettler FA Jr, Guiberteau MJ. Essentials of nuclear medicine imaging. 4th ed. Philadelphia (PA): WB Saunders;
1998.
13. Curry TS 3rd, Dowdey JE, Murry RC Jr, editors.
Christensens physics of diagnostic radiology. 4th ed.
Philadelphia (PA): Lea & Febiger; 1990.
14. Ginsberg JS, Hirsh J, Rainbow AJ, Coates G. Risks to the
fetus of radiologic procedures used in the diagnosis of
maternal venous thromboembolic disease. Thromb
Haemost 1989;61:18996.
15. Winer-Muram HT, Boone JM, Brown HL, Jennings SG,
Mabie WC, Lombardo GT. Pulmonary embolism in
16.
17.
18.
19.
523
pregnant patients: fetal radiation dose with helical CT.

Radiology 2002;224:48792.
Radiopaque agents (diagnostic). MedlinePlus drug information. Available at: http://www.nlm.nih.gov/medlineplus/
druginfo/uspdi/202997.html. Retrieved June 17, 2004.
Mehta PS, Metha SJ, Vorherr H. Congenital iodide goiter
and hypothyroidism: a review. Obstet Gynecol Surv
1983;38:23747.
Gadodiamide (systemic). In: USP DI: drug information
for the health care professional. 24th ed. Greenwood
Village (CO): Microdemex; 2004. Available at http://uspdi.
micromedex.com/v1/excluded/Gadodiamide(Systemic).
Gadoteridol (systemic). In: USP DI: drug information for
the health care professional. 24th ed. Greenwood Village
(CO): Microdemex; 2004. Available at: http://uspdi.
micromedex.com/v1/excluded/Gadoteridol(Systemic).pdf.
524
ACOG
Committee on
Obstetric Practice
Reaffirmed 2006
Committee
Opinion
followed.
the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Influenza vaccination and treatment

during pregnancy. ACOG Committee
Influenza Vaccination and Treatment

During Pregnancy
ABSTRACT: Influenza vaccination is an essential element of prenatal care.
Obstetric Practice supports the Centers for Disease Control and Preventions
expanded recommendation that women who will be pregnant during the
influenza season (October through mid May) should be vaccinated. The ideal
time to administer the vaccine is October and November; however, it is appropriate to vaccinate patients throughout the influenza season as long as the
vaccine supply lasts. This intramuscular, inactivated vaccine may be used in
all 3 trimesters. Because of the unknown effects of influenza antiviral drugs
on pregnant women and their fetuses, the Committee on Obstetric Practice
recommends that these antiviral agents should be used during pregnancy only
if the potential benefits justify the potential risks.
Influenza vaccination is an essential element of prenatal care. The risks of

serious illness associated with influenza are increased in young children and
pregnant women. The influenza epidemic in 2003 resulted in numerous hospitalizations for cardiopulmonary complications among pregnant women and
some deaths among young children (1).
Obstetric Practice supports the Centers for Disease Control and Preventions
expanded recommendation that women who will be pregnant during the
influenza season (October through mid May) should be vaccinated (1). The
ideal time to administer the vaccine is October and November; however, it is
appropriate to vaccinate patients throughout the influenza season as long as
the vaccine supply lasts. This intramuscular, inactivated vaccine may be used
in all 3 trimesters. One study of influenza vaccination of more than 2,000
pregnant women demonstrated no adverse fetal effects associated with
influenza vaccination (2). Any theoretical risk of the vaccination is outweighed by its benefits. Likewise, the benefits of the vaccine outweigh any
unproven potential concerns about traces of thimerosal preservative, which
exist only in the multidose vials (see http://www.cdc.gov/mmwr/preview/
mmwrhtml/rr53e430a1.htm). It should be noted that the intranasal vaccine
spray contains a live, attenuated virus and should not be used during
pregnancy.
COMMITTEE OPINIONS
Immunizing pregnant women also confers protection to their infants; this is an important consideration because infants aged 06 months do not
respond to the influenza vaccine. Breastfeeding is
not a contraindication for vaccination.
If influenza A develops, amantadine and rimantadine may reduce the duration of illness when given
within 2 days of illness onset whereas zanamivir and
oseltamivir may reduce the duration of uncomplicated influenza A and B (1). However, no clinical studies have been conducted regarding their safety or
efficacy during pregnancy. Therefore, because of the
unknown effects of influenza antiviral drugs on
pregnant women and their fetuses, the Committee on
Obstetric Practice recommends that these antiviral
agents should be used during pregnancy only if the
525
potential benefits justify the potential risks. Antiviral

agents should not be used as a substitute for influenza vaccination.
References
1. Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges CB.
Prevention and control of influenza: recommendations of
the Advisory Committee on Immunization Practices
(ACIP). Centers for Disease Control and Prevention (CDC)
Advisory Committee on Immunization Practices (ACIP).
MMWR Recomm Rep 2004;53(RR-6):140. Available at:
http://www.cdc.gov/mmwr/PDF/rr/rr5306.pdf. Retrieved
August 6, 2004.
2. Heinonen OP, Shapiro S, Monson RR, Hartz SC,
Rosenberg L, Slone D. Immunization during pregnancy
against poliomyelitis and influenza in relation to childhood malignancy. Int J Epidemiol 1973;2:22935.
526
ACOG
Committee on
Obstetric Practice
Reaffirmed 2008
Committee
Opinion
Obesity in Pregnancy
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Obesity in pregnancy. ACOG Committee Opinion No. 315. American

2005;106:6715.
ABSTRACT: One third of adult women in the United States are obese. During
pregnancy, obese women are at increased risk for several adverse perinatal
outcomes, including anesthetic, perioperative, and other maternal and fetal
complications. Obstetricians should provide preconception counseling and
education about the possible complications and should encourage obese
patients to undertake a weight reduction program before attempting pregnancy. Obstetricians also should address prenatal and peripartum care considerations that may be especially relevant for obese patients, including those
who have undergone bariatric surgery.
The prevalence of obesity in the United States has increased dramatically

over the past 20 years. The World Health Organization and the National
Institutes of Health define normal weight as a body mass index (BMI) of
18.524.9, overweight as a BMI of 2529.9, and obesity as a BMI of 30 or
greater. Obesity is further categorized by BMI into Class I (3034.9), Class
II (3539.9), and Class III or extreme obesity (40) (1, 2). (For online BMI
calculator, see www.nhlbisupport.com/bmi.) The most recent National Health
and Nutrition Examination Survey (NHANES) for 19992002 found that
approximately one third of adult women are obese (3). This problem is greatest among non-Hispanic black women (49%) compared with MexicanAmerican women (38%) and non-Hispanic white women (31%) (3).
Obese women are at increased risk for several pregnancy complications;
therefore, preconception assessment and counseling are strongly encouraged.
Obstetricians should provide education about the possible complications and
should encourage obese patients to undertake a weight reduction program,
including diet, exercise, and behavior modification, before attempting pregnancy. Specific medical clearance may be indicated for some patients.
At least three cohort studies suggest that obesity is an independent risk
factor for spontaneous abortion among women who undergo infertility treatment (46). Given this association, obese women should be encouraged to
lose weight before beginning infertility therapy. Data also link obesity with
spontaneous abortion among women after natural conception (7).
In a prospective multicenter study of more than 16,000 patients, Class I
(BMI 3034.9) and Class II (BMI 3539.9) obesity was associated with an
increased risk of gestational hypertension (odds ratio [OR] = 2.5 and 3.2,
respectively), preeclampsia (OR = 1.6 and 3.3), gestational diabetes (OR =
2.6 and 4.0), and fetal macrosomia (OR = 1.7 and 1.9), when compared with
COMMITTEE OPINIONS
a BMI of less than 30 (8). In this same study, the

cesarean delivery rate was 20.7% for women with a
BMI of 29.9 or less, 33.8% for women with a BMI
of 3034.9, and 47.4% for women with a BMI of
3539.9. Several other studies consistently report
higher rates of preeclampsia, gestational diabetes,
and cesarean delivery, particularly for failure to
progress, in obese women than in nonobese women
(912). Operative and postoperative complications
include increased rates of excessive blood loss, operative time greater than 2 hours, wound infection, and
endometritis (1315). Surgery in obese women
poses anesthetic challenges, such as difficult epidural and spinal placement requiring multiple attempts
and intraoperative respiratory events from failed or
difficult intubation (16). Sleep apnea occurring in
this group of women may further complicate anesthetic management and postoperative care (17).
Height and weight should be recorded for all
women at the initial prenatal visit to allow calculation of the BMI. Recommendations for prenatal
weight gain should be made based on the Institute of
Medicine (IOM) guidelines, which suggest a gain of
2535 lb for women of normal weight, 1525 lb for
overweight women, and 15 lb for obese women (18).
Nutrition consultation should be offered to all obese
women, and they should be encouraged to follow an
exercise program. This consultation should continue
postpartum and before attempting another pregnancy. Consideration should be given to screening
for gestational diabetes upon presentation or during
the first trimester and repeating it later in pregnancy
if the initial screening result is negative. Because
these patients are at increased risk for emergent cesarean delivery and anesthetic complications, anesthesiology consultation before delivery is encouraged (19).
It is important to discuss potential intrapartum
complications, such as difficulty estimating fetal
weight (even with ultrasonography), inability to
obtain interpretable external fetal heart rate and uterine contraction patterns, and difficulty performing
an emergent cesarean delivery. If an anesthesiology
consultation was not obtained antepartum, it should
be conducted early in labor to allow adequate time
for development of an anesthetic plan.
If obese patients require cesarean delivery, they
should receive antibiotic prophylaxis even if surgery
is elective (14). Obese women who require cesarean
delivery are more likely to have an increased incidence of wound breakdowns and infections (20).
Attempts to decrease these postoperative complications have included closure of the subcutaneous layers and the placement of subcutaneous drains.
527
Investigators have demonstrated that suture closure

of the subcutaneous layer after cesarean delivery in
obese patients may lead to a significant reduction in
the incidence of postoperative wound disruption (21,
22). Postoperative placement of subcutaneous draining systems, however, have not consistently been
shown to be of value in reducing postcesarean delivery morbidity (23, 24).
It has been recommended that graduated compression stockings, hydration, and early mobilization be used during and after cesarean delivery in
obese patients. Postpartum heparin therapy has been
recommended for patients thought to be at high risk
for venous thromboembolism (25, 26); however,
data are insufficient to determine whether the benefits of heparin prophylaxis in this group of patients
outweigh the risks (27, 28).
Women with a BMI of 35 or greater who have
preexisting medical conditions, such as hypertension
or diabetes, may benefit from a cardiac evaluation
(29). Because of the increased likelihood of complicated and emergent cesarean delivery, extremely
obese women may require specific resources such as
additional blood products, a large operating table,
and extra personnel in the delivery room. Particular
attention to the type and placement of the surgical
incision is needed (ie, placing the incision above the
panniculus adiposus) (20, 30). The success rate of
attempted vaginal birth after cesarean delivery is
very low in extremely obese women (31). There are
additional logistical challenges to monitoring labor
and performing an emergent cesarean delivery in the
extremely obese patient. Therefore, these patients
should be counseled about these possible complications of an emergent cesarean delivery.
The number of obese women of childbearing
age considering bariatric surgery is increasing,
resulting in questions about pregnancy after these
types of surgeries. Early case reports and series described various pregnancy complications after bariatric surgery such as gastrointestinal bleeding (32),
anemia (33), intrauterine growth restriction (34), and
neural tube defects (35, 36). However, recent studies
suggest that previous bariatric surgery is not associated with adverse perinatal outcomes (37, 38).
Researchers have determined that pregnancies after
bariatric surgery are less likely to be complicated by
gestational diabetes, hypertension, macrosomia, and
cesarean delivery than are pregnancies of obese
women who have not had the surgery (3840).
Bariatric surgical procedures are categorized into
two main types: malabsorptive procedures (jejunoileal bypass and biliopancreatic diversion) and re-
528
strictive procedures (gastric banding and vertical

banded gastroplasty). Both types of procedures can
result in deficiencies in iron, vitamin B12, folate, and
calcium. Women who have undergone bariatric
surgery require the following counseling before and
during pregnancy:
Patients with adjustable gastric banding should
be advised that they are at risk of becoming
pregnant unexpectedly after weight loss following surgery (39).
All patients are advised to delay pregnancy for
1218 months after surgery to avoid pregnancy
during the rapid weight loss phase (39).
Women with a gastric band should be monitored
by their general surgeons during pregnancy
because adjustment of the band may be necessary (41).
Patients should be evaluated for nutritional deficiencies and vitamin supplementation where
indicated.
In counseling all obese women about potential
pregnancy complications, it is important to inform
them of the fetal risks (eg, prematurity, stillbirth,
neural tube defect, and macrosomia). Some studies
have reported a greater rate of premature delivery for
obese women than for women of normal weight (9,
42). However, in a study of more than 2,900 obese
women, prepregnancy obesity was associated with a
lower rate of spontaneous preterm birth (43). A large
Swedish cohort study reported a greater risk of
antepartum stillbirth among obese patients than
among women who had a BMI of less than 20 (42).
Data establish that the risk of neural tube defects
among obese women is double that among women
of normal weight, after correcting for diabetes as a
potential confounding factor (4446). The benefit of
folic acid doses higher than 400 g has not been
studied in nondiabetic obese women. Multiple studies have shown that maternal obesity and excessive
weight gain during pregnancy are associated with
macrosomic and large-for-gestational-age infants
(10, 19, 47, 48). Furthermore, these large-for-gestational-age infants are at increased risk for childhood
obesity (11, 49). The decision to perform a primary
cesarean delivery for these obese women is based on
the previously recommended maternal and fetal
indications. A cesarean delivery should be considered for those patients who have a fetus with a fetal
weight estimated to be greater than 5,000 g if the
patient does not have diabetes (50) or greater than
4,500 g if the patient has diabetes (51).
Recommendations for obese women who are

pregnant or planning a pregnancy include the following:
Preconception counseling
Provision of specific information concerning
the maternal and fetal risks of obesity in pregnancy
Consideration of screening for gestational diabetes upon presentation or in the first trimester,
and repeated screening later in pregnancy if
results are initially negative
Assessment and possible supplementation of
vitamin B12, folate, iron, and calcium for
women who have undergone bariatric surgery
Possible use of graduated compression stockings, hydration, and early mobilization during
and after cesarean delivery
Anesthesiology consultation
Continuation of nutrition counseling and exercise program after delivery, and consultation
with weight loss specialists before attempting
another pregnancy
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1. World Health Organization. Obesity: preventing and managing the global epidemic. Geneva, Switzerland: World
Health Organization; 2000. WHO technical report series
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National Institute for Diabetes and Digestive and Kidney
Diseases (NIDDK). Clinical guidelines on the identification, evaluation and treatment of overweight and obesity
in adults. The evidence report. Obes Res 1998;6(suppl
2):51S210S.
among US children, adolescents, and adults, 1999-2002.
JAMA 2004;291:284750.
4. Bellver J, Rossal LP, Bosch E, Zuniga A, Corona JT,
Melendez F, et al. Obesity and the risk of spontaneous
abortion after oocyte donation. Fertil Steril 2003;79:
113640.
5. Fedorcsak P, Storeng R, Dale PO, Tanbo T, Abyholm T.
Obesity is a risk factor for early pregnancy loss after IVF
or ICSI. Acta Obstet Gynecol Scand 2000;79:438.
6. Wang JX, Davies MJ, Norman RJ. Obesity increases the
risk of spontaneous abortion during infertility treatment.
Obes Res 2002;10:5514.
7. Lashen H, Fear K, Sturdee DW. Obesity is associated
with increased risk of first trimester and recurrent miscarriage: matched case-control study. Hum Reprod
2004;19:16446.
8. Weiss JL, Malone FD, Emig D, Ball RH, Nyberg DA,
Comstock CH, et al. Obesity, obstetric complications and
cesarean delivery ratea population-based screening
COMMITTEE OPINIONS
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
study. FASTER Research Consortium. Am J Obstet

Gynecol 2004;190:10917.
Baeten JM, Bukusi EA, Lambe M. Pregnancy complications and outcomes among overweight and obese nulliparous women. Am J Public Health 2001:91:43640.
Cedergren MI. Maternal morbid obesity and the risk of
adverse pregnancy outcome. Obstet Gynecol 2004;103:
21924.
Sebire NJ, Jolly M, Harris JP, Wadsworth J, Joffe M,
Beard RW, et al. Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London. Int J
Obes Relat Metab Disord 2001;25:117582.
Young TK, Woodmansee B. Factors that are associated
with cesarean delivery in a large private practice: the
importance of prepregnancy body mass index and weight
gain. Am J Obstet Gynecol 2002;187:3128; discussion
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Kabiru W, Raynor BD. Obstetric outcomes associated
with increase in BMI category during pregnancy. Am J
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Myles TD, Gooch J, Santolaya J. Obesity as an independent risk factor for infectious morbidity in patients who
undergo cesarean delivery. Obstet Gynecol 2002;100:
95964.
Perlow JH, Morgan MA. Massive maternal obesity and
perioperative cesarean morbidity. Am J Obstet Gynecol
1994;170:5605.
Hood DD, Dewan DM. Anesthetic and obstetric outcome
in morbidly obese parturients. Anesthesiology 1993;79:
1210 8.
Maasilta P, Bachour A, Teramo K, Polo O, Laitinen LA.
Sleep-related disordered breathing during pregnancy in
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Institute of Medicine (US). Nutritional status and weight
gain. In: Nutrition during pregnancy. Washington, DC:
National Academy Press; 1990. p. 27233.
Rode L, Nilas L, Wojdemann K, Tabor A. Obesity-related
complications in Danish single cephalic term pregnancies.
Wall PD, Deucy EE, Glantz JC, Pressman EK. Vertical
skin incisions and wound complications in the obese parturient. Obstet Gynecol 2003;102(5 pt):9526.
Cetin A, Cetin M. Superficial wound disruption after
cesarean section: effect of the depth and closure of subcutaneous tissue. Int J Gynaecol Obstet 1997;57:1721.
Chelmow D, Rodriguez EJ, Sabatini MM. Suture closure
of subcutaneous fat and wound disruption after cesarean
section: a meta-analysis. Obstet Gynecol 2004;103:
97480.
Al-Inany H, Youssef G, Abd ElMaguid A, Abdel Hamid
M, Naguib A. Value of subcutaneous drainage system in
obese females undergoing cesarean section using
Pfannenstiel incision. Gynecol Obstet Invest 2002;53:
758.
Magann EF, Chauhan SP, Rodts-Palenik S, Bufkin L,
Martin JN Jr, Morrison JC. Subcutaneous stitch closure
versus subcutaneous drain to prevent wound disruption
after cesarean delivery: a randomized clinical trial. Am J
Bates SM, Greer IA, Hirsh J, Ginsberg JS. Use of
antithrombotic agents during pregnancy: the Seventh
ACCP Conference on Antithrombotic and Thrombolytic
Therapy. Chest 2004;126:627S44S.
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26. Royal College of Obstetricians and Gynaecologists.

Report of the RCOG working party on prophylaxis
against thromboembolism in gynaecology and obstetrics.
London: RCOG; 1995.
27. Gates S, Brocklehurst P, Davis LJ. Prophylaxis for venous
thromboembolic disease in pregnancy and the early postnatal period. The Cochrane Database of Systematic
Reviews 2002, Issue 2. Art. No.: CD001689. DOI: 10.
1002/14651858.CD001689.
28. Hague WM, North RA, Gallus AS, Walters BN,
Orlikowski C, Burrows RF, et al. Anticoagulation in pregnancy and the puerperium. Working Group on behalf of
the Obstetric Medicine Group of Australasia. Med J Aust
2001;175:25863.
29. Tomoda S, Tamura T, Sudo Y, Ogita S. Effects of obesity
on pregnant women: maternal hemodynamic change. Am
J Perinatol 1996;13:738.
30. Houston MC, Raynor BD. Postoperative morbidity in the
morbidly obese parturient woman: supraumbilical and
low transverse abdominal approaches. Am J Obstet
Gynecol 2000;182:10335.
31. Chauhan SP, Magann EF, Carroll CS, Barrilleaux PS,
Scardo JA, Martin JN Jr. Mode of delivery for the morbidly obese with prior cesarean delivery: vaginal versus
repeat cesarean section. Am J Obstet Gynecol 2001;
185:34954.
32. Ramirez MM, Turrentine MA. Gastrointestinal hemorrhage during pregnancy in a patient with a history of vertical-banded gastroplasty. Am J Obstet Gynecol 1995;
173:16301.
33. Gurewitsch ED, Smith-Levitin M, Mack J. Pregnancy following gastric bypass surgery for morbid obesity. Obstet
Gynecol 1996;88:65861.
34. Granstrom L, Granstrom L, Backman L. Fetal growth
retardation after gastric banding. Acta Obstet Gynecol
Scand 1990;69:5336.
35. Haddow JE, Hill LE, Kloza EM, Thanhauser D. Neural
tube defects after gastric bypass. Lancet 1986;1:1330.
36. Martin L, Chavez GF, Adams MJ Jr, Mason EE, Hanson
JW, Haddow JE, et al. Gastric bypass surgery as maternal
risk factor for neural tube defects. Lancet 1988;1:6401.
37. Marceau P, Kaufman D, Biron S, Hould FS, Lebel S,
Marceau S, et al. Outcome of pregnancies after biliopancreatic diversion. Obes Surg 2004;14:31824.
38. Sheiner E, Levy A, Silverberg D, Menes TS, Levy I, Katz
M, et al. Pregnancy after bariatric surgery is not associated with adverse perinatal outcome. Am J Obstet Gynecol
2004;190:133540.
39. Martin LF, Finigan KM, Nolan TE. Pregnancy after
adjustable gastric banding. Obstet Gynecol 2000;95:
92730.
40. Wittgrove AC, Jester L, Wittgrove P, Clark GW. Pregnancy following gastric bypass for morbid obesity. Obes
Surg 1998;8:4614; discussion 4656.
41. Weiss HG, Nehoda H, Labeck B, Hourmont K, Marth C,
Aigner F. Pregnancies after adjustable gastric banding.
Obes Surg 2001;11:3036.
outcomes. N Engl J Med 1998;338:14752.
43. Hendler I, Blackwell SC, Treadwell MC, Bujold E, Sokol
RJ, Sorokin Y. Does advanced ultrasound equipment
improve the adequacy of ultrasound visualization of fetal
530
44.
45.
46.
47.
cardiac structures in the obese gravid woman? Am J

Obstet Gynecol 2004;190;16169; discussion 161920.
Shaw GM, Velie EM, Schaffer D. Risk of neural tube
defect-affected pregnancies among obese women. JAMA
1996;275:10936.
Waller DK, Mills JL, Simpson JL, Cunningham GC,
Conley MR, Lassman MR, et al. Are obese women at
higher risk for producing malformed offspring? Am J
Werler MM, Louick C, Shapiro S, Mitchell AA.
Prepregnancy weight in relation to risk of neural tube
defects. JAMA 1996;275:108992.
Stephansson O, Dickman PW, Johansson A, Cnattingius
S. Maternal weight, pregnancy weight gain, and the risk
of antepartum stillbirth. Am J Obstet Gynecol 2001;
184:4639.
48. Watkins ML, Rasmussen SA, Honein MA, Botto LD,

Moore CA. Maternal obesity and risk for birth defects.
Pediatrics 2003;111:11528.
49. Hediger ML, Overpeck MD, McGlynn A, Kuczmarski RJ,
Maurer KR, Davis WW. Growth and fatness at three to six
years of age of children born small- or large-for-gestational age. Pediatrics 1999;104:e33.
50. Spellacy WN, Miller S, Winegar A, Peterson PQ.
Macrosomiamaternal characteristics and infant complications. Obstet Gynecol 1985;66:15861.
51. Lipscomb KR, Gregory K, Shaw K. The outcome of
macrosomic infants weighing at least 4500 grams: Los
Angeles County + University of Southern California
experience. Obstet Gynecol 1995;85:55864.
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
531
Committee
Opinion

from the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Inappropriate use of the terms fetal

distress and birth asphyxia. ACOG
Committee Opinion No. 326. American
College of Obstetricians and Gynecologists. Obstet Gynecol 2005;106:
146970.
Inappropriate Use of the Terms Fetal

Distress and Birth Asphyxia
ABSTRACT: The Committee on Obstetric Practice is concerned about the
continued use of the term fetal distress as an antepartum or intrapartum
diagnosis and the term birth asphyxia as a neonatal diagnosis. The
Committee reaffirms that the term fetal distress is imprecise and nonspecific.
The communication between clinicians caring for the woman and those caring for her neonate is best served by replacing the term fetal distress with
nonreassuring fetal status, followed by a further description of findings
(eg, repetitive variable decelerations, fetal tachycardia or bradycardia, late
decelerations, or low biophysical profile). Also, the term birth asphyxia is a
nonspecific diagnosis and should not be used.
The Committee on Obstetric Practice is concerned about the continued use

of the term fetal distress as an antepartum or intrapartum diagnosis and the
term birth asphyxia as a neonatal diagnosis. The Committee reaffirms that
the term fetal distress is imprecise and nonspecific. The term has a low positive predictive value even in high-risk populations and often is associated
with an infant who is in good condition at birth as determined by the Apgar
score or umbilical cord blood gas analysis or both. The communication
between clinicians caring for the woman and those caring for her neonate is
best served by replacing the term fetal distress with nonreassuring fetal status, followed by a further description of findings (eg, repetitive variable
decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile). Whereas in the past, the term fetal distress generally
referred to an ill fetus, nonreassuring fetal status describes the clinicians
interpretation of data regarding fetal status (ie, the clinician is not reassured
by the findings). This term acknowledges the imprecision inherent in the
interpretation of the data. Therefore, the diagnosis of nonreassuring fetal status can be consistent with the delivery of a vigorous neonate.
Because of the implications of the term fetal distress, its use may result
in inappropriate actions, such as an unnecessarily urgent delivery under general anesthesia. Fetal heart rate patterns or auscultatory findings should be
considered when the degree of urgency, mode of delivery, and type of anesthesia to be given are determined. Performing a cesarean delivery for a non-
532
reassuring fetal heart rate pattern does not necessarily preclude the use of regional anesthesia.
Since October 1, 1998, all inclusion terms
except metabolic acidemia have been removed
from the International Classification of Diseases
code for fetal distress. The Committee believes that
there should be uniformity in wording. The
International Classification of Diseases, Ninth
Revision, Clinical Modification code for fetal distress is based on fetal metabolic acidemia and
excludes abnormal fetal acidbase balance, abnormality in fetal heart rate or rhythm, fetal bradycardia, fetal tachycardia, and meconium in liquor.
The term birth asphyxia is a nonspecific diagnosis and should not be used. The Committee strongly
supports the criteria required to define an acute
intrapartum hypoxic event sufficient to cause cerebral palsy, as modified by the ACOG Task Force on
Neonatal Encephalopathy and Cerebral Palsy from
the template provided by the International Cerebral
Palsy Task Force (1) (Box 1).
Criteria to Define an Acute Intrapartum Hypoxic

Event as Sufficient to Cause Cerebral Palsy
1.1: Essential criteria (must meet all four)
1. Evidence of a metabolic acidosis in fetal umbilical
cord arterial blood obtained at delivery (pH <7 and
base deficit 12 mmol/L)
2. Early onset of severe or moderate neonatal
encephalopathy in infants born at 34 or more
weeks of gestation
3. Cerebral palsy of the spastic quadriplegic or dyskinetic type*
4. Exclusion of other identifiable etiologies, such as
trauma, coagulation disorders, infectious conditions, or genetic disorders
1.2: Criteria that collectively suggest an intrapartum
timing (within close proximity to labor and delivery, eg,
048 hours) but are nonspecific to asphyxial insults
1. A sentinel (signal) hypoxic event occurring immediately before or during labor
2. A sudden and sustained fetal bradycardia or the
absence of fetal heart rate variability in the presence of persistent, late, or variable decelerations,
usually after a hypoxic sentinel event when the
pattern was previously normal
3. Apgar scores of 03 beyond 5 minutes
4. Onset of multisystem involvement within 72 hours
of birth
5. Early imaging study showing evidence of acute
nonfocal cerebral abnormality
*Spastic quadriplegia and, less commonly, dyskinetic cerebral
palsy are the only types of cerebral palsy associated with acute
hypoxic intrapartum events. Spastic quadriplegia is not specific
to intrapartum hypoxia. Hemiparetic cerebral palsy, hemiplegic
cerebral palsy, spastic diplegia, and ataxia are unlikely to result
from acute intrapartum hypoxia (Nelson KB, Grether JK.
Potentially asphyxiating conditions and spastic cerebral palsy
in infants of normal birth weight. Am J Obstet Gynecol
1998;179:50713.).
Modified from MacLennan A. A template for defining a causal
relation between acute intrapartum events and cerebral palsy:
international consensus statement. BMJ 1999;319:10549.
References
1. American College of Obstetricians and Gynecologists and
American Academy of Pediatrics. Neonatal encephalopathy and cerebral palsy: defining the pathogenesis and
pathophysiology. Washington, DC: American College of
Obstetricians and Gynecologists; 2003.
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
American Academy
of Pediatrics
533
Committee
Opinion
DEDICATED TO THE HEALTH OF ALL CHILDREN
Committee on
Fetus and Newborn
Reaffirmed 2008
This document reflects clinical
and scientific advances as of the
date issued and is subject to
Copyright May 2006 by the
and the American College of
from the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
The Apgar score. ACOG Committee
Opinion No. 333. American Academy
of Pediatrics; American College of
The Apgar Score

ABSTRACT. The Apgar score provides a convenient shorthand for reporting
the status of the newborn infant and the response to resuscitation. The Apgar
score has been used inappropriately to predict specific neurologic outcome
in the term infant. There are no consistent data on the significance of the
Apgar score in preterm infants. The Apgar score has limitations, and it is
inappropriate to use it alone to establish the diagnosis of asphyxia. An Apgar
score assigned during resuscitation is not equivalent to a score assigned to
a spontaneously breathing infant. An expanded Apgar score reporting form
will account for concurrent resuscitative interventions and provide information to improve systems of perinatal and neonatal care.
Introduction
In 1952, Dr. Virginia Apgar devised a scoring system that was a rapid method
of assessing the clinical status of the newborn infant at 1 minute of age and
the need for prompt intervention to establish breathing (1). A second report
evaluating a larger number of patients was published in 1958 (2). This scoring system provided a standardized assessment for infants after delivery. The
Apgar score comprises 5 components: heart rate, respiratory effort, muscle
tone, reflex irritability, and color, each of which is given a score of 0, 1, or
2. The score is now reported at 1 and 5 minutes after birth. The Apgar score
continues to provide a convenient shorthand for reporting the status of the
newborn infant and the response to resuscitation. The Apgar score has been
used inappropriately in term infants to predict specific neurologic outcome.
Because there are no consistent data on the significance of the Apgar score
in preterm infants, in this population the score should not be used for any
purpose other than ongoing assessment in the delivery room. The purpose of
this statement is to place the Apgar score in its proper perspective.
The neonatal resuscitation program (NRP) guidelines state that Apgar
scores should not be used to dictate appropriate resuscitative actions, nor
should interventions for depressed infants be delayed until the 1-minute
assessment (3). However, an Apgar score that remains 0 beyond 10 minutes
of age may be useful in determining whether additional resuscitative efforts
are indicated (4). The current NRP guidelines state that if there is no heart
534
rate after 10 minutes of complete and adequate resuscitation efforts, and there is no evidence of other
causes of newborn compromise, discontinuation of
resuscitation efforts may be appropriate. Current data
indicate that, after 10 minutes of asystole, newborns
are very unlikely to survive, or the rare survivor is
likely to survive with severe disability (3).
Previously, an Apgar score of 3 or less at 5 minutes was considered an essential requirement for the
diagnosis of perinatal asphyxia. Neonatal Encephalopathy and Cerebral Palsy: Defining the Pathogenesis and Pathophysiology, produced in 2003 by
the American College of Obstetricians and Gynecologists in collaboration with the American
Academy of Pediatrics, lists an Apgar score of 0
to 3 beyond 5 minutes as one suggestive criterion
for an intrapartum asphyxial insult (5). However,
a persistently low Apgar score alone is not a specific
indicator for intrapartum compromise. Further,
although the score is used widely in outcome studies, its inappropriate use has led to an erroneous
definition of asphyxia. Intrapartum asphyxia implies
fetal hypercarbia and hypoxemia, which, if prolonged, will result in metabolic acidemia. Because
the intrapartum disruption of uterine or fetal blood
flow is rarely, if ever, absolute, asphyxia is an imprecise, general term. Descriptions such as hypercarbia,
hypoxia, and metabolic, respiratory, or lactic acidemia are more precise for immediate assessment of
the newborn infant and retrospective assessment of
intrapartum management.
Limitations of the Apgar Score

It is important to recognize the limitations of the
Apgar score. The Apgar score is an expression of the
infants physiologic condition, has a limited time
frame, and includes subjective components. In addition, the biochemical disturbance must be significant
before the score is affected. Elements of the score
such as tone, color, and reflex irritability partially
depend on the physiologic maturity of the infant.
The healthy preterm infant with no evidence of
asphyxia may receive a low score only because of
immaturity (6). A number of factors may influence
an Apgar score, including but not limited to drugs,
trauma, congenital anomalies, infections, hypoxia,
hypovolemia, and preterm birth (7). The incidence
of low Apgar scores is inversely related to birth
weight, and a low score is limited in predicting morbidity or mortality (8). Accordingly, it is inappropri-
ate to use an Apgar score alone to establish the diagnosis of asphyxia.
Apgar Score and Resuscitation

The 5-minute Apgar score, and particularly a change
in the score between 1 and 5 minutes, is a useful
index of the response to resuscitation. If the Apgar
score is less than 7 at 5 minutes, the NRP guidelines
state that the assessment should be repeated every
5 minutes up to 20 minutes (3). However, an Apgar
score assigned during a resuscitation is not equivalent to a score assigned to a spontaneously breathing
infant (9). There is no accepted standard for reporting an Apgar score in infants undergoing resuscitation after birth, because many of the elements
contributing to the score are altered by resuscitation.
The concept of an assisted score that accounts for
resuscitative interventions has been suggested, but
the predictive reliability has not been studied. To
describe such infants correctly and provide accurate
documentation and data collection, an expanded
Apgar score report form is proposed (Fig. 1).
Prediction of Outcome
A low 1-minute Apgar score alone does not correlate
with the infants future outcome. A retrospective
analysis concluded that the 5-minute Apgar score
remained a valid predictor of neonatal mortality, but
using it to predict long-term outcome was inappropriate (10). On the other hand, another study stated
that low Apgar scores at 5 minutes are associated
with death or cerebral palsy, and this association
increased if both 1- and 5-minute scores were low
(11).
An Apgar score at 5 minutes in term infants correlates poorly with future neurologic outcomes. For
example, a score of 0 to 3 at 5 minutes was associated with a slightly increased risk of cerebral palsy
compared with higher scores (12). Conversely, 75%
of children with cerebral palsy had normal scores at
5 minutes (12). In addition, a low 5-minute score in
combination with other markers of asphyxia may
identify infants at risk of developing seizures (odds
ratio: 39; 95% confidence interval: 3.9392.5) (13).
The risk of poor neurologic outcomes increases
when the Apgar score is 3 or less at 10, 15, and 20
minutes (7).
A 5-minute Apgar score of 7 to 10 is considered
normal. Scores of 4, 5, and 6 are intermediate and
COMMITTEE OPINIONS
Apgar Score
Sign
Color
Heart rate
Gestational age_______________weeks
0
Blue or Pale
Acrocyanotic
Completely
Pink
Absent
<100 minute
>100 minute
No Response
Grimace
Cry or Active
Withdrawal
Muscle tone
Limp
Some Flexion
Active Motion
Respiration
Absent
Weak Cry;
Hypoventilation
Good, Crying
Reflex irritability
535
1 minute
5 minute
10 minute
15 minute
20 minute
15
20
Total
Comments:
Minutes
Resuscitation
10
Oxygen
PPV/NCPAP
ETT
Chest Compressions
Epinephrine
Fig. 1. Expanded Apgar score form. Record the score in the appropriate place at specific time intervals.
The additional resuscitative measures (if appropriate) are recorded at the same time that the score is reported using a
check mark in the appropriate box. Use the comment box to list other factors including maternal medications and/or
the response to resuscitation between the recorded times of scoring. PPV/NCPAP indicates positive-pressure ventilation/nasal continuous positive airway pressure; ETT, endotracheal tube.
are not markers of increased risk of neurologic

dysfunction. Such scores may be the result of physiologic immaturity, maternal medications, the presence of congenital malformations, and other factors.
Because of these other conditions, the Apgar score
alone cannot be considered evidence of or a consequence of asphyxia. Other factors including nonreassuring fetal heart rate monitoring patterns and
abnormalities in umbilical arterial blood gases, clinical cerebral function, neuroimaging studies, neonatal electroencephalography, placental pathology,
hematologic studies, and multisystem organ dysfunction need to be considered when defining an
intrapartum hypoxicischemic event as a cause of
cerebral palsy (5).
Other Applications
Monitoring of low Apgar scores from a delivery service can be useful. Individual case reviews can identify needs for focused educational programs and
improvement in systems of perinatal care. Analyzing
trends allows assessment of the impact of quality

improvement interventions.
Conclusion
The Apgar score describes the condition of the newborn infant immediately after birth (14), and when
properly applied, is a tool for standardized assessment. It also provides a mechanism to record fetalto-neonatal transition. An Apgar score of 0 to 3 at 5
minutes may correlate with neonatal mortality but
alone does not predict later neurologic dysfunction.
The Apgar score is affected by gestational age,
maternal medications, resuscitation, and cardiorespiratory and neurologic conditions. Low 1- and
5-minute Apgar scores alone are not conclusive
markers of an acute intrapartum hypoxic event.
Resuscitative interventions modify the components
of the Apgar score. There is a need for perinatal
health care professionals to be consistent in assigning an Apgar score during a resuscitation. The
American Academy of Pediatrics and the American
536
College of Obstetricians and Gynecologists propose

use of an expanded Apgar score reporting form that
accounts for concurrent resuscitative interventions.
References
1. Apgar V. A proposal for a new method of evaluation of the
newborn infant. Curr Res Anesth Analg 1953;32:2607.
2. Apgar V, Holaday DA, James LS, Weisbrot IM, Berrien C.
Evaluation of the newborn infant; second report. JAMA
1958;168:19858.
3. American Academy of Pediatrics, American Heart
Association. Textbook of neonatal resuscitation. 4th ed.
Elk Grove Village (IL): American Academy of Pediatrics;
Dallas (TX): American Heart Association; 2000.
4. Jain L, Ferre C, Vidyasagar D, Nath S, Sheftel D. Cardiopulmonary resuscitation of apparently stillborn infants:
survival and long-term outcome. J Pediatr 1991;118:77882.
Obstetricians and Gynecologists. Neonatal encephalopathy and cerebral palsy: defining the pathogenesis and
pathophysiology. Elk Grove Village (IL): AAP; Washington, DC: ACOG; 2003.
6. Catlin EA, Carpenter MW, Brann BS 4th, Mayfield SR,
Shaul PW, Goldstein M, et al. The Apgar score revisited:
influence of gestational age. J Pediatr 1986;109:8658.
7. Freeman JM, Nelson KB. Intrapartum asphyxia and cerebral palsy. Pediatrics 1988;82:2409.
8. Hegyi T, Carbone T, Anwar M, Ostfeld B, Hiatt M, Koons
A, et al. The Apgar score and its components in the
preterm infant. Pediatrics 1998;101:7781.
9. Lopriore E, van Burk GF, Walther FJ, de Beaufort AJ.
Correct use of the Apgar score for resuscitated and intubated newborn babies: questionnaire study. BMJ 2004;
329:1434.
10. Casey BM, McIntire DD, Leveno KJ. The continuing
value of the Apgar score for the assessment of newborn
infants. N Engl J Med 2001;344:46771.
11. Moster D, Lie RT, Irgens LM, Bjerkedal T, Markestad T.
The association of Apgar score with subsequent death and
cerebral palsy: a population-based study in term infants. J
Pediatr 2001;138:798803.
12. Nelson KB, Ellenberg JH. Apgar scores as predictors of
chronic neurologic disability. Pediatrics 1981;68:3644.
13. Perlman JM, Risser R. Can asphyxiated infants at risk for
neonatal seizures be rapidly identified by current highrisk markers? Pediatrics 1996;97:45662.
14. Papile LA. The Apgar score in the 21st century. N Engl J
Med 2001;344:51920.
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
Reaffirmed 2008
Committee
Opinion

Copyright June 2006
from the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Analgesia and cesarean delivery rates.

2006;107:14878.
537
Analgesia and Cesarean

Delivery Rates
ABSTRACT: Neuraxial analgesia techniques are the most effective and least
depressant treatments for labor pain. The American College of Obstetricians
and Gynecologists previously recommended that practitioners delay initiating epidural analgesia in nulliparous women until the cervical dilatation
reached 45 cm. However, more recent studies have shown that epidural
analgesia does not increase the risks of cesarean delivery. The choice of
analgesic technique, agent, and dosage is based on many factors, including
patient preference, medical status, and contraindications. The fear of unnecessary cesarean delivery should not influence the method of pain relief that
women can choose during labor.
Neuraxial analgesia techniques (epidural, spinal, and combined spinalepidural) are the most effective and least depressant treatments for labor pain (1, 2).
Early studies generated concern that the benefits of neuraxial analgesia may
be offset by an associated increase in the risk of cesarean delivery (3, 4).
Recent studies, however, have determined that when compared with intravenous systemic opioid analgesia, the initiation of early neuraxial analgesia
does not increase the risk of cesarean delivery (57).
In 2000, the American College of Obstetricians and Gynecologists
(ACOG) Task Force on Cesarean Delivery recommended that when feasible, obstetric practitioners should delay the administration of epidural anesthesia in nulliparous women until the cervical dilatation reaches at least 45
cm (8). This recommendation was based on earlier studies, which suggested that epidural analgesia increased the risk of cesarean delivery by as much
as 12-fold (3, 4, 9, 10). Furthermore, certain studies demonstrated an even
greater association between epidural analgesia and cesarean delivery in
women who received their epidurals before reaching cervical dilatation of
5 cm (3, 9). In 2002, an evaluation of cesarean delivery sponsored by ACOG
concluded, there is considerable evidence suggesting that there is in fact an
association between the use of epidural analgesia for pain relief during labor
and the risk of cesarean delivery (8).
Since the last Committee Opinion on analgesia and cesarean delivery,
additional studies have addressed the issue of neuraxial analgesia and its
association with cesarean delivery. Three recent meta-analyses systematical-
538
ly and independently reviewed the previous literature, and all concluded that epidural analgesia does
not increase the rates of cesarean delivery (odds ratio
1.001.04; 95% confidence interval, 0.711.48)
(1113). In addition, three recent randomized controlled trials clearly demonstrated no difference in
rate of cesarean deliveries between women who had
received epidurals and women who had received
only intravenous analgesia (57). Furthermore, a
randomized trial comparing epidurals done early in
labor versus epidurals done later in labor demonstrated no difference in the incidence of cesarean delivery
(17.8% versus 20.7%) (5). The use of intrathecal
analgesia and the concentration of the local anesthetic used in an epidural also have no impact on the rate
of cesarean delivery (5, 1315).
Therefore, ACOG reaffirms the opinion it published jointly with the American Society of
Anesthesiologists, in which the following statement
was articulated: Labor causes severe pain for many
women. There is no other circumstance where it is
considered acceptable for an individual to experience untreated severe pain, amenable to safe intervention, while under a physicians care. In the
absence of a medical contraindication, maternal
request is a sufficient medical indication for pain
relief during labor (16). The fear of unnecessary
cesarean delivery should not influence the method of
pain relief that women can choose during labor.
Gynecologists recognizes that many techniques are
available for analgesia in laboring patients. None of
the techniques appears to be associated with an
increased risk of cesarean delivery. The choice of
technique, agent, and dosage is based on many factors, including patient preference, medical status,
and contraindications. Decisions regarding analgesia should be closely coordinated among the obstetrician, the anesthesiologist, the patient, and skilled
support personnel.
References
1. Gibbs CP, Krischer J, Peckham BM, Sharp H,
Kirschbaum TH. Obstetric anesthesia: a national survey.
Anesthesiology 1986;65:298306.
2. Hawkins JL, Gibbs CP, Orleans M, Martin-Salvaj G,
Beaty B. Obstetric anesthesia work force survey, 1981
versus 1992. Anesthesiology 1997;87:135 43.
3. Thorp JA, Hu DH, Albin RM, McNitt J, Meyer BA,

Cohen GR, et al. The effect of intrapartum epidural analgesia on nulliparous labor: a randomized, controlled,
prospective trial. Am J Obstet Gynecol 1993;169:8518.
4. Ramin SM, Gambling DR, Lucas MJ, Sharma SK, Sidawi
JE, Leveno KJ. Randomized trial of epidural versus intravenous analgesia during labor. Obstet Gynecol 1995;
86:7839.
5. Wong CA, Scavone BM, Peaceman AM, McCarthy RJ,
Sullivan JT, Diaz NT, et al. The risk of cesarean delivery
with neuraxial analgesia given early versus late in labor.
N Engl J Med. 2005;352:65565.
6. Sharma SK, Alexander JM, Messick G, Bloom SL,
McIntire DD, Wiley J, et al. Cesarean delivery: a randomized trial of epidural analgesia versus intravenous meperidine analgesia during labor in nulliparous women.
Anesthesiology 2002;96:54651.
7. Halpern SH, Muir H, Breen TW, Campbell DC, Barrett J,
Liston R, et al. A multicenter randomized controlled trial
comparing patient-controlled epidural with intravenous
analgesia for pain relief in labor. Anesth Analg 2004;
99:15328.
Evaluation of cesarean delivery. Washington, DC: ACOG;
2000.
9. Lieberman E, Lang JM, Cohen A, DAgostino R Jr, Datta
S, Frigoletto FD Jr. Association of epidural analgesia with
cesarean delivery in nulliparas. Obstet Gynecol 1996;
88:9931000.
10. Howell C, Chalmers I. A review of prospectively controlled comparisons of epidural with non-epidural forms
of pain relief during labour. Int J Obstet Anesth
1992;1:93110.
11. Leighton BL, Halpern SH. The effects of epidural analgesia on labor, maternal, and neonatal outcomes: a systemic
review. Am J Obstet Gynecol 2002;186:S6977.
12. Liu EH, Sia AT. Rates of caesarean section and instrumental vaginal delivery in nulliparous women after low
concentration epidural infusion or opiod analgesia: systemic review. BMJ 2004;328:1410.
13. Sharma SK, McIntire DD, Wiley J, Leveno KJ. Labor
analgesia and cesarean delivery: an individual patient
meta-analysis of nulliparous women. Anesthesiology
2004;100:1428.
14. Effect of low-dose mobile versus traditional epidural
techniques on mode of delivery: a randomised controlled
trial. Comparative Obstetric Mobile Epidural Trial
(COMET) Study Group UK. Lancet 2001;358:1923.
15. Chestnut DH, McGrath JM, Vincent RD Jr, Penning DH,
Choi WW, Bates JN, et al. Does early administration of
epidural analgesia affect obstetric outcome in nulliparous
women who are in spontaneous labor? Anesthesiology
1994;80:12018.
16. Pain relief during labor. ACOG Committee Opinion
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
Reaffirmed 2008
Committee
Opinion

Copyright July 2006
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Mode of term singleton breech

delivery. ACOG Committee Opinion
539
Mode of Term Singleton Breech

Delivery
ABSTRACT: In light of recent studies that further clarify the long-term risks
of vaginal breech delivery, the American College of Obstetricians and
Gynecologists recommends that the decision regarding mode of delivery
should depend on the experience of the health care provider. Cesarean delivery will be the preferred mode for most physicians because of the diminishing expertise in vaginal breech delivery. Planned vaginal delivery of a term
singleton breech fetus may be reasonable under hospital-specific protocol
guidelines for both eligibility and labor management. Before a vaginal
breech delivery is planned, women should be informed that the risk of perinatal or neonatal mortality or short-term serious neonatal morbidity may be
higher than if a cesarean delivery is planned, and the patients informed consent should be documented.
During the past decade, there has been an increasing trend in the United
States to perform cesarean delivery for term singleton fetuses in a breech
presentation. In 2002, the rate of cesarean deliveries for women in labor with
breech presentation was 86.9% (1). The number of practitioners with the
skills and experience to perform vaginal breech delivery has decreased. Even
in academic medical centers where faculty support for teaching vaginal
breech delivery to residents remains high, there may be insufficient volume
of vaginal breech deliveries to adequately teach this procedure (2).
In 2000, researchers conducted a large, international multicenter randomized clinical trial comparing a policy of planned cesarean delivery with
planned vaginal delivery (Term Breech Trial) (3). These investigators noted
that perinatal mortality, neonatal mortality, and serious neonatal morbidity
were significantly lower among the planned cesarean delivery group compared with the planned vaginal delivery group (17/1,039 [1.6%] versus
52/1,039 [5%]), although there was no difference in maternal morbidity or
mortality observed between the groups (3). The benefits of planned cesarean delivery remained for all subgroups identified by the baseline variables
(eg, older and younger women, nulliparous and multiparous women, frank
and complete type of breech presentation). They found that the reduction in
risk attributable to planned cesarean delivery was greatest among centers in
industrialized nations with low overall perinatal mortality rates (0.4% versus
540
5.7%). In countries with low perinatal mortality

rates, the reduction in risk was driven primarily by
the pooled rates of perinatal or neonatal mortality
and serious neonatal morbidity, rather than by the
rates of mortality alone (0% versus 0.6%). Given the
results of this exceptionally large and well-controlled clinical trial, the American College of
Obstetricians and Gynecologists Committee on
Obstetric Practice in 2001 recommended that
planned vaginal delivery of a term singleton breech
was no longer appropriate.
Since that time, there have been additional publications that modify the original conclusions of the
2000 Term Breech Trial. The same researchers have
published three follow-up studies examining maternal outcomes at 3 months postpartum, as well as outcomes for mothers and children 2 years after the
births (46). At 3 months postpartum, the risk of urinary incontinence was lower for women in the
planned cesarean delivery group; however, there was
no difference at 2 years. At 2 years postpartum,
maternal morbidity, which was assessed via questionnaire in 917 of 1,159 (79.1%), was not different
for most maternal parameters, including breastfeeding, pain, depression, menstrual problems, fatigue,
and distressing memories of the birth experience (5).
The follow-up study to address outcomes of the
children at 2 years involved 85 centers (with both
high and low perinatal mortality rates) that were chosen at the start of the original trial. Most children, 923
of 1,159 (79.6%), were assessed first by a screening
questionnaire (Ages and Stages) that was completed
by their parents (4). All abnormal results were further
evaluated with a clinical neurodevelopment assessment. The risk of death or neurodevelopmental delay
was no different in the planned cesarean delivery
group compared with the planned vaginal delivery
group (14 children [3.1%] versus 13 children [2.8%];
relative risk, 1.09; 95% CI, 0.522.30; P = 0.85).
There are several explanations for this seemingly
contradictory finding. The follow-up study was
underpowered to show a clinically important benefit
from cesarean delivery if this were true. Only 6 of the
16 infants who died in the neonatal period were from
centers participating in the follow-up to 2 years (one
in the planned cesarean delivery group, five in the
planned vaginal delivery group), and most of the
children with serious neonatal morbidity after birth
survived and developed normally. In this cohort, 17
out of 18 children with serious morbidity in the original study were normal at this 24-month follow-up.
Another explanation is that the use of pooled mortality and morbidity data at the time of birth overstated
the true long-term risks of vaginal delivery (7).
A recent retrospective observational report
reviewed neonatal outcome in the Netherlands
before and after the publication of the Term Breech
Trial (8). Between 1998 and 2002, 35,453 term
infants were delivered. The cesarean delivery rate
for breech presentation increased from 50% to 80%
within 2 months of the trials publication and
remained elevated. The combined neonatal mortality rate decreased from 0.35% to 0.18%, and the
incidence of reported birth trauma decreased from
0.29% to 0.08%. Of interest, a decrease in mortality
also was seen in the emergency cesarean delivery
group and the vaginal delivery group, a finding that
the authors attribute to better selection of candidates
for vaginal breech delivery.
There are many retrospective reports of vaginal
breech delivery that follow very specific protocols
and note excellent neonatal outcomes. One report
noted 298 women in a vaginal breech trial with no
perinatal morbidity and mortality (9). Another
report noted similar outcomes in 481 women with
planned vaginal delivery (10). Although they are not
randomized trials, these reports detail the outcomes
of specific management protocols and document the
potential safety of a vaginal delivery in the properly
selected patient. The initial criteria used in these
reports were similar: gestational age greater than 37
weeks, frank or complete breech presentation, no
fetal anomalies on ultrasound examination, adequate maternal pelvis, and estimated fetal weight
between 2,500 g and 4,000 g. In addition, the protocol presented by one report required documentation
of fetal head flexion and adequate amniotic fluid
volume, defined as a 3-cm vertical pocket (9).
Oxytocin induction or augmentation was not
offered, and strict criteria were established for normal labor progress.
In light of the recent publications that further
clarify the long-term risks of vaginal breech delivery, the American College of Obstetricians and
Gynecologists Committee on Obstetric Practice
issues the following recommendations:
The decision regarding the mode of delivery
should depend on the experience of the health
care provider. Cesarean delivery will be the preferred mode of delivery for most physicians
because of the diminishing expertise in vaginal
breech delivery.
COMMITTEE OPINIONS
Obstetricians should offer and perform external

cephalic version whenever possible.
Planned vaginal delivery of a term singleton
breech fetus may be reasonable under hospitalspecific protocol guidelines for both eligibility
and labor management.
In those instances in which breech vaginal deliveries are pursued, great caution should be exercised, and detailed patient informed consent
should be documented.
Before embarking on a plan for a vaginal breech
delivery, women should be informed that the
risk of perinatal or neonatal mortality or shortterm serious neonatal morbidity may be higher
than if a cesarean delivery is planned.
There are no recent data to support the recommendation of cesarean delivery to patients
whose second twin is in a nonvertex presentation, although a large multicenter randomized
controlled trial is in progress (www.utoronto.ca/
miru/tbs).
4.
5.
6.
7.
8.
References
Vital Stat Rep 2003;52(10):1113.
2. Lavin JP Jr, Eaton J, Hopkins M. Teaching vaginal breech
delivery and external cephalic version. A survey of faculty attitudes. J Reprod Med 2000;45:80812.
3. Hannah ME, Hannah WJ, Hewson SA, Hodnett ED,
Saigal S, Willan AR. Planned caesarean section versus
9.
10.
541
planned vaginal birth for breech presentation at term:

a randomised multicentre trial. Term Breech Trial
Collaborative Group. Lancet 2000;356:137583.
Whyte H, Hannah ME, Saigal S, Hannah WJ, Hewson S,
Amankwah K, et al. Outcomes of children at 2 years after
planned cesarean birth versus planned vaginal birth for
breech presentation at term: the International Randomized
Term Breech Trial. Term Breech Trial Collaborative
Group. Am J Obstet Gynecol 2004;191:86471.
Hannah ME, Whyte H, Hannah WJ, Hewson S, Amankwah
K, Cheng M, et al. Maternal outcomes at 2 years after
planned cesarean section versus planned vaginal birth for
breech presentation at term: the international randomized
Term Breech Trial. Term Breech Trial Collaborative Group.
Su M, Hannah WJ, Willan A, Ross S, Hannah ME.
Planned caesarean section decreases the risk of adverse
perinatal outcome due to both labour and delivery complications in the Term Breech Trial. Term Breech Trial
Collaborative Group. BJOG 2004;111:106574.
Kotaska A. Inappropiate use of randomised trials to evaluate complex phenomena: case study of vaginal breech
delivery [published erratum appears in BMJ 2004;329:
1385]. BMJ 2004;329:103942.
Rietberg CC, Elferink-Stinkens PM, Visser GH. The
effect of the Term Breech Trial on medical intervention
behaviour and neonatal outcome in The Netherlands: an
analysis of 35,453 term breech infants. BJOG 2005;
112:2059.
Alarab M, Regan C, OConnell MP, Keane DP, OHerlihy
C, Foley ME. Singleton vaginal breech delivery at term:
still a safe option. Obstet Gynecol 2004;103:40712.
Guiliani A, Scholl WM, Basver A, Tamussino KF. Mode
of delivery and outcome of 699 term singleton breech
deliveries at a single center. Am J Obstet Gynecol 2002;
187:16948.
542
ACOG
Committee on
Obstetric Practice
Committee
Opinion

directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Induction of labor for vaginal birth

after cesarean delivery. ACOG
2006;108:46567.
Induction of Labor for Vaginal Birth

After Cesarean Delivery
ABSTRACT: Induction of labor in women who have had cesarean deliveries
may be necessary because of fetal or maternal indications. The potentially
increased risk of uterine rupture should be discussed with the patient and
documented in the medical record. Selecting women most likely to give birth
vaginally and avoiding the sequential use of prostaglandins and oxytocin
appear to offer the lowest risks. Misoprostol should not be used in patients
who have had cesarean deliveries or major uterine surgery.
An ongoing controversy surrounds whether induction of labor with or without prostaglandins (specifically, the prostaglandin E2 series) significantly
increases the baseline risk of uterine rupture during labor. Induction with
misoprostol (prostaglandin E1) in women who have had cesarean deliveries
has been shown, in a randomized trial, to be associated with a significant risk
of uterine rupture, with two cases of uterine rupture out of 17 women treated with 25-mcg doses of misoprostol (1). This trial was stopped because of
the increased rupture rate, and the Committee on Obstetric Practice continues to recommend that misoprostol not be used for induction of labor in
women who have had cesarean deliveries or major uterine surgery (24).
Since the last Committee on Obstetric Practice Opinion on induction of labor
for vaginal birth after cesarean delivery was published, additional studies
have addressed the issue of induction of labor with or without prostaglandins
in women who have had cesarean deliveries.
Several studies noted an increased risk of uterine rupture from induction
of labor in women who have had cesarean deliveries (57). A populationbased, retrospective cohort study of the relationship of uterine rupture to
vaginal birth after cesarean delivery using vital records and abstracted hospital discharge International Classification of Diseases, 9th Revision,
Clinical Modification (ICD-9-CM) code diagnoses reviewed 20,095 women
with histories of cesarean deliveries for their first delivery (5). The risk of
uterine rupture was compared between patients who had repeat cesarean
deliveries, patients giving birth after spontaneous onset of labor, and patients
who had labor induced with or without the use of prostaglandins. There were
91 cases of uterine rupture with rates of 1.6 per 1,000 (0.16%) for repeat
COMMITTEE OPINIONS
cesarean delivery, 5.2 per 1,000 (0.52%) for spontaneous labor, 7.7 per 1,000 (0.77%) for labor induced
without prostaglandins, and 24.5 per 1,000 (2.4%)
for prostaglandin-induced labor. Compared with
women who gave birth by elective repeat cesarean
delivery, the relative risk (RR) of uterine rupture was
significantly higher among women who had spontaneous labor (RR, 3.3; 95% confidence interval [CI],
1.86), induction of labor without prostaglandins
(RR, 4.9; 95% CI, 2.49.7), and induction of labor
with prostaglandins (RR, 15.6; 95% CI, 8.130).
There was no difference in the risks of uterine rupture between spontaneous labor and labor induced
without prostaglandins. The authors acknowledged
that they did not confirm the diagnoses of uterine
rupture by examining medical records. Furthermore,
their use of ICD-9-CM codes may have resulted in
an overstatement of the actual incidence of uterine
rupture because a single code is used for both uterine incision extension and uterine rupture (5). In
another study, only 40% of ICD-9-CM-coded uterine ruptures were actually found to be uterine ruptures when the charts were reviewed, which raises a
concern about the reliability of these findings (8).
In a larger, more recent, prospective, multicenter
study, 33,699 women who had cesarean deliveries
(17,898 and 15,801 with trial of labor or elective
repeat cesarean deliveries, respectively) were studied (9). Charts were reviewed to document uterine
rupture. There was no difference in the incidence of
hysterectomy, thromboembolic disease, or maternal
death between these two groups. Augmentation or
induction of labor was associated with an increased
risk of uterine rupture compared with spontaneous
labor. There were 124 cases of uterine rupture, and
the rate of uterine rupture in the trial of labor group
was 0.4% for spontaneous labor, 0.9% for augmentation of labor, and 1% for induction of labor. In
the group of women in whom labor was induced,
the rate of uterine rupture was 1.1% when only oxytocin was used and 1.4% when any prostaglandins
were used in combination with oxytocin; this result
was not significantly different. There were no cases
of uterine rupture in the group of women in whom
labor was induced who received only prostaglandins. The prostaglandins used in this group included
misoprostol, dinoprostone, and prostaglandin E2 gel.
This absence of uterine rupture likely represents
women who went into labor easily, requiring no
oxytocin after prostaglandin administration. In
543
another large study evaluating 25,005 women,

induction or augmentation of labor was associated
with an increased risk of uterine rupture (10). There
was no significantly increased association between
oxytocin or prostaglandins not used in combination
with uterine rupture compared with women who
went into spontaneous labor (10). The risk of uterine
rupture was significantly increased with sequential
use of prostaglandins and oxytocin (odds ratio, 4.54;
95% CI, 1.6612.42) (10). Uterine rupture was confirmed with chart reviews in this study.
The rate of uterine rupture was significantly
higher in women who had failed trials of labor
(2.3%) compared with successful trials of labor
(0.1%) (9). These results are similar to a study that
reported nearly identical rates of uterine rupture (2%
versus 0.1% in failed versus successful trials of
labor) (11). Together, these studies (5, 911) suggest
that rates of uterine rupture are likely increased by
induction of labor more than by spontaneous labor,
but the magnitude of risk is still low (12.4%).
Additionally, sequential use of prostaglandins and
oxytocin may further increase risk. Consistently, the
highest rates of uterine rupture are associated with
failed trials of labor (22.3% versus 0.1% for successful trials of labor). These more recent data do
not confirm a specific increase in uterine rupture
with the use of prostaglandins alone. The three
largest studies vary in the quality of data, and data
quality should be incorporated into any decision to
use these data. Two of the three studies were
prospective and confirmed uterine rupture with chart
reviews (910). These two studies reported lower
rates of uterine rupture with induction and prostaglandin induction of labor (11.4%). The third study
was smaller, retrospective, and did not confirm uterine rupture with chart reviews, and it reported the
highest rate of uterine rupture with the use of
prostaglandins (2.4%) (5).
Induction of labor may be necessary for women
who have had cesarean deliveries, for a maternal or
fetal indication. Induction of labor remains a reasonable option, but the potentially increased risk of
uterine rupture associated with any induction should
be discussed with the patient and documented in the
medical record. Selecting women most likely to
give birth vaginally and avoiding sequential use of
prostaglandins and oxytocin appear to offer the lowest risks of uterine rupture. Misoprostol should not
be used in patients who have had cesarean deliveries
or major uterine surgery.
544
References
1. Wing DA, Lovett K, Paul RH. Disruption of prior uterine
incision following misoprostol for labor induction in
women with previous cesarean delivery. Obstet Gynecol
1998;91:82830.
Response to Searles drug warning on misoprostol. ACOG
Committee Opinion 248. Washington, DC: ACOG; 2000.
Induction of labor with misoprostol. ACOG Committee
Opinion 228. Washington, DC: ACOG; 1999.
Induction of labor. ACOG Practice Bulletin 10.
5. Lydon-Rochelle M, Holt VL, Easterling TR, Martin DP.
Risk of uterine rupture during labor among women with a
prior cesarean delivery. N Engl J Med 2001;345:38.
6. Ravasia DJ, Wood SL, Pollard JK. Uterine rupture during
induced trial of labor among women with previous cesarean delivery. Am J Obstet Gynecol 2000;183:11769.
7. Zelop CM, Shipp TD, Repke JT, Cohen A, Caughey AB,
Lieberman E. Uterine rupture during induced or aug-
8.
9.
10.
11.
mented labor in gravid women with one prior cesarean

delivery. Am J Obstet Gynecol 1999;181:8826.
Use of hospital discharge data to monitor uterine ruptureMassachusetts, 19901997. Centers for Disease
Wkly Rep 2000;49:2458.
Landon MB, Hauth JC, Leveno KJ, Spong CY,
Leindecker S, Varner MW, et al. Maternal and perinatal
outcomes associated with a trial of labor after prior
cesarean delivery. National Institute of Child Health and
Human Development MaternalFetal Medicine Units
Network. N Engl J Med 2004;351:25819.
Macones GA, Peipert J, Nelson DB, Odibo A, Stevens EJ,
Stamilio DM, et al. Maternal complications with vaginal
birth after cesarean delivery: a multicenter study. Am J
Wen SW, Rusen ID, Walker M, Liston R, Kramer MS,
Baskett T, et al. Comparison of maternal mortality and
morbidity between trial of labor and elective cesarean section among women with previous cesarean delivery.
Maternal Health Study Group, Canadian Perinatal
Surveillance System. Am J Obstet Gynecol 2004;191:
12639.
COMMITTEE OPINIONS
ACOG
Committee on
Obstetric Practice
Reaffirmed 2008
545
Committee
Opinion

from the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Amnioinfusion does not prevent

meconium aspiration syndrome.
2006;108:10535.
Amnioinfusion Does Not Prevent

Meconium Aspiration Syndrome
ABSTRACT: Amnioinfusion has been advocated as a technique to reduce the
incidence of meconium aspiration and to improve neonatal outcome.
However, a large proportion of women with meconium-stained amniotic fluid
have infants who have taken in meconium within the trachea or bronchioles
before meconium passage has been noted and before amnioinfusion can be
performed by the obstetrician; meconium passage may predate labor. Based
on current literature, routine prophylactic amnioinfusion for the dilution of
meconium-stained amniotic fluid is not recommended. Prophylactic use of
amnioinfusion for meconium-stained amniotic fluid should be done only in
the setting of additional clinical trials. However, amnioinfusion remains a
reasonable approach in the treatment of repetitive variable decelerations,
regardless of amniotic fluid meconium status.
Meconium-stained amniotic fluid is a common obstetric situation, occurring

in 1222% of women in labor (1, 2). Meconium aspiration syndrome is a
major complication in the neonate. This syndrome occurs in up to 10% of
infants who have been exposed to meconium-stained amniotic fluid, with significant morbidity and mortality.
Amnioinfusion has been advocated as a technique to reduce the incidence
of meconium aspiration and to improve neonatal outcome. Although generally
considered safe, reported complications associated with amnioinfusion include
uterine hypertonus, uterine rupture, placental abruption, chorioamnionitis, nonreassuring fetal heart rate tracing, maternal pulmonary embolus, and maternal
death (3). The purported benefit of amnioinfusion for the dilution of meconium-stained amniotic fluid is dilution of thick clumps of meconium. However,
a large proportion of women with meconium-stained amniotic fluid have
infants who have taken in meconium within the trachea or bronchioles before
meconium passage has been noted and before amnioinfusion can be performed
by the obstetrician. Furthermore, meconium aspiration syndrome is hypothesized to predate labor in many cases (4). Studies were performed to evaluate
whether prophylactic amnioinfusion for meconium-stained amniotic fluid
would be beneficial and if it would decrease the incidence of meconium aspiration syndrome (518).
546
The initial trials of amnioinfusion generally

consisted of small studies that randomized women
with moderate to thick meconium-stained amniotic
fluid to receive prophylactic amnioinfusion or no
amnioinfusion. These studies suggested that women
receiving amnioinfusion had fewer operative deliveries and fetuses with significantly less distress and
less meconium below the vocal cords (511). Two
meta-analyses also found that amnioinfusion significantly reduced the frequency of meconium aspiration syndrome and the incidence of meconium
below the vocal cords in fetuses of pregnant women
with meconium-stained amniotic fluid treated with
amnioinfusion (12, 13).
A randomized trial in women with meconiumstained amniotic fluid evaluated prophylactic
amnioinfusion versus therapeutic amnioinfusion for
variable decelerations occurring after enrollment
(14). The authors found no differences in operative
deliveries, fetal distress, Apgar scores, the incidence
of meconium below the fetal vocal cords, or umbilical artery blood pH values between the groups. There
were four cases of meconium aspiration syndrome;
three occurred in the prophylactic amnioinfusion
group. Of the women receiving standard care, only
16% required therapeutic amnioinfusion for repetitive severe variable decelerations. These findings are
consistent with studies evaluating institutional protocols of routine prophylactic amnioinfusion for thick
meconium that found that meconium aspiration syndrome continued to occur at the same rate, with no
improvement in neonatal outcome (1517).
A large, international, multicenter trial randomized 1,998 women in labor at 36 weeks of gestation
or later with thick meconium-stained amniotic fluid
to amnioinfusion or no amnioinfusion, after stratification according to the presence or absence of variable decelerations (18). The number of women
enrolled in this well-conducted study was greater
than in all other prior studies combined. The authors
found that amnioinfusion did not reduce perinatal
death (0.5 % in both groups) or moderate or severe
meconium aspiration (4.4 % versus 3.1 % in controls), nor was there a significant reduction in
cesarean delivery (31.8 % versus 29.0 % in controls). Although the absence of benefit from
amnioinfusion occurred whether or not there were
variable decelerations, the study did not have adequate power to definitively determine if amnioinfusion was efficacious in the subgroup of women with
decelerations.
Based on current literature, routine prophylactic

amnioinfusion for meconium-stained amniotic fluid
is not recommended. Prophylactic use of amnioinfusion for meconium-stained amniotic fluid should be
done only in the setting of additional clinical trials.
Data are not available on whether amnioinfusion for
fetal heart rate decelerations in the presence of
meconium-stained amniotic fluid decreases meconium aspiration syndrome or other meconium-related
morbidities. However, amnioinfusion remains a reasonable approach in the treatment of repetitive variable decelerations, regardless of amniotic fluid
meconium status (19).
References
1. Katz VL, Bowes WA Jr. Meconium aspiration syndrome:
reflections on a murky subject. Am J Obstet Gynecol
1992;166:17183.
2. Nathan L, Leveno KJ, Carmody TJ 3rd, Kelly AM,
Sherman ML. Meconium: a 1990s perspective on an old
obstetric hazard. Obstet Gynecol 1994;83:32932.
3. Wenstrom K, Andrews WW, Maher JE. Amnioinfusion
survey: prevalence, protocols, and complications. Obstet
Gynecol 1995;86:5726.
4. Ghidini A, Spong CY. Severe meconium aspiration syndrome is not caused by aspiration of meconium. Am J
5. Wenstrom KD, Parsons MT. The prevention of meconium
aspiration in labor using amnioinfusion. Obstet Gynecol
1989;73:64751.
6. Sadovsky Y, Amon E, Bade ME, Petrie RH. Prophylactic
amnioinfusion during labor complicated by meconium: a
preliminary report. Am J Obstet Gynecol 1989;161:
6137.
7. Macri CJ, Schrimmer DB, Leung A, Greenspoon JS, Paul
RH. Prophylactic amnioinfusion improves outcome of
pregnancy complicated by thick meconium and oligohydramnios. Am J Obstet Gynecol 1992;167:11721.
8. Cialone PR, Sherer DM, Ryan RM, Sinkin RA,
Abramowicz JS. Amnioinfusion during labor complicated
by particulate meconium-stained amniotic fluid decreases
neonatal morbidity. Am J Obstet Gynecol 1994;170:
8429.
9. Eriksen NL, Hostetter M, Parisi VM. Prophylactic
amnioinfusion in pregnancies complicated by thick meconium. Am J Obstet Gynecol 1994;171:102630.
10. Puertas A, Paz Carrillo MP, Molto L, Alvarez M, Sedeno
S, Miranda JA. Meconium-stained amniotic fluid in labor:
a randomized trial of prophylactic amnioinfusion. Eur J
Obstet Gynecol Reprod Biol 2001;99:337.
11. Rathor AM, Singh R, Ramji S, Tripathi R. Randomised
trial of amnioinfusion during labour with meconium
stained amniotic fluid. BJOG 2002;109:1720.
12. Pierce J, Gaudier FL, Sanchez-Ramos L. Intrapartum
amnioinfusion for meconium-stained fluid: meta-analysis
of prospective clinical trials. Obstet Gynecol 2000;95:
10516.
COMMITTEE OPINIONS
13. Hofmeyr GJ. Amnioinfusion for meconium-stained liquor

in labour. The Cochrane Database of Systematic Reviews
14651858.CD000014.
14. Spong CY, Ogundipe OA, Ross MG. Prophylactic
amnioinfusion for meconium-stained amniotic fluid. Am
15. De Meeus JB, DHalluin G, Bascou V, Ellia F, Magnin G.
Prophylactic intrapartum amnioinfusion: a controlled retrospective study of 135 cases. Eur J Obstet Gynecol
Reprod Biol 1997;72:1418.
16. Rogers MS, Lau TK, Wang CC, Yu KM. Amnioinfusion
for the prevention of meconium aspiration during labour.
Aust N Z J Obstet Gynaecol 1996;36:40710.
547
17. Usta IM, Mercer BM, Aswad NK, Sibai BM. The impact
of a policy of amnioinfusion for meconium-stained amniotic fluid. Obstet Gynecol 1995;85:23741.
18. Fraser WD, Hofmeyr J, Lede R, Faron G, Alexander S,
Goffinet F, et al. Amnioinfusion for the prevention of the
meconium aspiration syndrome. Amnioinfusion Trial
Group. N Engl J Med 2005;353:90917.
19. Miyazaki FS, Nevarez F. Saline amnioinfusion for relief
of repetitive variable decelerations: a prospective randomized study. Am J Obstet Gynecol 1985;153:3016.
548
ACOG
Committee on
Obstetric Practice
Reaffirmed 2009
Committee
Opinion

directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Umbilical cord blood gas and acidbase analysis. ACOG Committee
Umbilical Cord Blood Gas and

Acid-Base Analysis
ABSTRACT: Umbilical cord blood gas and acid-base assessment are the
most objective determinations of the fetal metabolic condition at the moment
of birth. Moderate and severe newborn encephalopathy, respiratory complications, and composite complication scores increase with an umbilical
arterial base deficit of 1216 mmol/L. Moderate or severe newborn complications occur in 10% of neonates who have this level of acidemia and the
rate increases to 40% in neonates who have an umbilical arterial base deficit
greater than 16 mmol/L at birth. Immediately after the delivery of the neonate,
a segment of umbilical cord should be double-clamped, divided, and placed
on the delivery table. Physicians should attempt to obtain venous and arterial cord blood samples in circumstances of cesarean delivery for fetal compromise, low 5-minute Apgar score, severe growth restriction, abnormal fetal
heart rate tracing, maternal thyroid disease, intrapartum fever, or multifetal
gestation.
Laboratory research demonstrates a complex relationship between fetal

(antepartum and intrapartum) asphyxia, newborn asphyxia, and possible
resulting brain damage. The degree, duration, and nature of the asphyxic
insult are modulated by the quality of the cardiovascular compensatory
response. A task force set up by the World Federation of Neurology Group
defined asphyxia as a condition of impaired blood gas exchange, leading, if
it persists, to progressive hypoxemia and hypercapnia (1). This is a precise
definition of asphyxia as it may affect the fetus and neonate. In the American
College of Obstetricians and Gynecologists Task Force on Neonatal
Encephalopathy and Cerebral Palsy report, asphyxia is defined as:
. . . [a] clinical situation of damaging acidemia, hypoxia, and metabolic acidosis.
This definition, although traditional, is not specific to cause. A more complete definition of birth asphyxia includes a requirement for a recognizable sentinel event
capable of interrupting oxygen supply to the fetus or infant. This definition fails to
include conditions that are not readily recognized clinically, such as occult abruption, but is probably correct in a majority of cases. (2)
Asphyxia may occur in a transient fashion that, although of physiologic

interest, has no pathologic sequelae. Significant fetal exposure to asphyxia
COMMITTEE OPINIONS
leads to tissue oxygen debt, accumulation of fixed

acids, and a metabolic acidosis. Thus, for intrapartum fetal asphyxia the following addition is proposed for this definition:
Fetal asphyxia is a condition of impaired blood gas
exchange leading to progressive hypoxemia and
hypercapnia with a significant metabolic acidosis.
The diagnosis of intrapartum fetal asphyxia requires
a blood gas and acid-base assessment. The important
question for the clinician is what is the threshold of
metabolic acidosis beyond which fetal morbidity or
mortality may occur?
Low and associates have proposed a scoring

system for predicting the likelihood of neonatal
encephalopathy (3). They defined umbilical arterial
base deficits at birth as mild at 48 mmol/L, moderate at 812 mmol/L, and severe at greater than 12
mmol/L. Newborn complications in the central nervous system, respiratory system, cardiovascular system, and kidney during the 5 days after delivery
were documented. Assessment of the central nervous system included clinical evidence of newborn
encephalopathy defined as minor with irritability or
jitteriness, moderate with profound lethargy or
abnormal tone, and severe with coma or abnormal
tone and seizures. Cardiovascular complications
were classified as minor with bradycardia (100 beats
per minute or less) or tachycardia (170 beats per
minute or more), moderate with hypotension or
hypertension (defined by the 95% confidence limits
for blood pressure in term neonates), and severe with
abnormal electrocardiographic or echocardiographic
findings. Respiratory complications were classified
as minor if requiring supplementary oxygen, moderate if requiring continuous positive airway pressure
or ventilation less than 24 hours, and severe if
requiring mechanical ventilation more than 24
hours. Abnormalities of renal function were classified as minor if hematuria was observed, moderate
with an elevation of serum creatinine level (greater
than 100 mmol/L)*, and severe with anuria or oliguria (less than 1 mL/kg/h). A scoring system
expressed the magnitude of the complications in each
neonate. The score for each complication was 1 for
minor, 2 for moderate, and 4 for severe. The
maximum complication score was 16. Moderate
and severe newborn encephalopathy, respiratory
complications, and composite complication scores
*In the United States, creatinine level is expressed in mg/dL. To
convert creatinine in mmol/L to mg/dL, the value should be
divided by 88.4. In this case, 100 mmol/L is 1.14. mg/dL.
549
were increased with an umbilical arterial base deficit

of 1216 mmol/L. Moderate or severe newborn complications occurred in 10% of neonates with this level
of acidemia, increasing to 40% in neonates with an
umbilical arterial base deficit greater than 16 mmol/L
at birth. Low and associates concluded that the
threshold of fetal metabolic acidosis at delivery associated with moderate or severe newborn complications was an umbilical arterial base deficit of 12
mmol/L and that increasing levels of metabolic acidosis were associated with a progression of the severity of newborn complications (3). At the mild base
deficit range, there is no association with abnormal
newborn outcome. A similar threshold for neonatal
neurologic complications has been reported by other
investigators (4, 5). Importantly, and in contrast to
moderate or severe levels of acidemia, term neonates
exposed to mild antepartum fetal asphyxia were not
at an increased risk of minor motor or cognitive
defects at the age of 48 years compared with controls with no evidence of asphyxia (6).
Term Infants
The prevalence of fetal asphyxia, ranging from mild
to severe at delivery, in the term infant is reported at
25 per 1,000 live births; of these, 15% are either
moderate or severe (3.75 per 1,000) (7). Even at
these levels of acidemia, it must be appreciated that
most fetuses will not be injured, yielding a final
overall incidence of neonatal encephalopathy attributable to intrapartum hypoxia, in the absence of any
other preconception or antepartum abnormalities, of
approximately 1.6 per 10,000 (8, 9). Similar observations have been reported from Japan, where
among a series of 10,030 infants there were nine
cases of cerebral palsy at age 1 year or older diagnosed by pediatric neurologists. Analysis of these
cases reveals that preexisting asphyxia existed
before the initiation of fetal monitoring in six cases;
two of the cases involved cytomegalovirus infections and one case involved a maternal amniotic
fluid embolism (10). These investigators concluded
that in low-risk pregnancies, cerebral palsy caused
by intrapartum asphyxia was restricted to unavoidable intrapartum accidents.
Preterm Infants
Low and colleagues reported that the prevalence of
asphyxia in preterm infants was 73 per 1,000 live
550
births (7). Of these, 50% were at the moderate to

severe level of asphyxia. The authors caution that it
remains to be determined how often the asphyxia
recognized at delivery may have been present before
the onset of labor. This point is particularly germane
in the preterm infant, inasmuch as medical or obstetric complications or both often are the preceding
event necessitating the preterm delivery. Examples
include significant degrees of intrauterine growth
restriction, placental abruption, chorioamnionitis
with funisitis, and severe preeclampsia, each of
which has been shown to be a significant independent risk factor for moderate or severe neonatal
encephalopathy (8, 9).
Acidemia and Cerebral Palsy

Both the International Cerebral Palsy Task Force and
Gynecologists Task Force on Neonatal Encephalopathy and Cerebral Palsy have published criteria
to define an acute intrapartum event as sufficient
to cause cerebral palsy (2, 11). Among the essential
criteria cited by both task forces is evidence of metabolic acidosis in fetal umbilical cord arterial blood
obtained at delivery (pH less than 7 and base deficit
greater than or equal to 12 mmol/L) (see box).
Additionally, the National Collaborating Center for
Womens and Childrens Health, commissioned by
the National Institute for Clinical Excellence, has
recommended that umbilical artery pH be performed
after all cesarean deliveries for suspected fetal compromise, to allow review of fetal well-being and to
guide ongoing care of the infant (12).
Technique for Obtaining Cord Blood

Samples
Immediately after the delivery of the neonate, a segment of umbilical cord should be double-clamped,
divided, and placed on the delivery table pending
assignment of the 5-minute Apgar score. Values from
the umbilical cord artery provide the most accurate
information regarding fetal and newborn acid-base
status. A clamped segment of cord is stable for pH
and blood gas assessment for at least 60 minutes, and
a cord blood sample in a syringe flushed with heparin
is stable for up to 60 minutes (13, 14). If the 5-minute
Apgar score is satisfactory and the infant appears stable and vigorous, the segment of umbilical cord can
be discarded. If a serious abnormality that arose in
the delivery process or a problem with the neonates

condition or both persist at or beyond the first 5 minutes, blood can be drawn from the cord segment and
sent to the laboratory for blood gas analysis. Analysis
of paired arterial and venous specimens should prevent debate over whether a true arterial specimen was
obtained. Therefore, the Committee on Obstetric
Practice recommends obtaining an arterial umbilical
cord blood sample, but, where possible, obtaining
both venous and arterial samples (paired specimen).
It is important to label the sample as either venous or
arterial. Similarly, in known high-risk circumstances,
such as severe growth restriction, an abnormal fetal
heart rate tracing, maternal thyroid disease, intrapartum fever, or multifetal gestations, it is prudent to
obtain blood gas and acid-base assessments (2). It
should be noted that it occasionally may be difficult
to obtain an adequate cord arterial blood sample. If
the practitioner encounters difficulty in obtaining
arterial blood from the umbilical cord (ie, in a very
preterm infant), a sample obtained from an artery on
Criteria to Define an Acute Intrapartum Hypoxic

Event as Sufficient to Cause Cerebral Palsy
Essential criteria (must meet all four):
1. Evidence of a metabolic acidosis in fetal umbilical
cord arterial blood obtained at delivery (pH <7 and
base deficit 12 mmol/L)
2. Early onset of severe or moderate neonatal
encephalopathy in infants born at 34 or more
weeks of gestation
3. Cerebral palsy of the spastic quadriplegic or dyskinetic type*
4. Exclusion of other identifiable etiologies, such as
trauma, coagulation disorders, infectious conditions, or genetic disorders
*Spastic quadriplegia and, less commonly, dyskinetic cerebral
palsy are the only types of cerebral palsy associated with acute
hypoxic intrapartum events. Spastic quadriplegia is not specific
to intrapartum hypoxia. Hemiparetic cerebral palsy, hemiplegic
cerebral palsy, spastic diplegia, and ataxia are unlikely to result
from acute intrapartum hypoxia (Nelson KB, Grether JK. Potentially asphyxiating conditions and spastic cerebral palsy in
infants of normal birth weight. Am J Obstet Gynecol 1998;179:
50713.).
Excerpted from American Academy of Pediatrics, American
College of Obstetricians and Gynecologists. Neonatal
encephalopathy and cerebral palsy: defining the pathogenesis
and pathophysiology. Elk Grove Village (IL): AAP; Washington,
DC: ACOG; 2003. Modified from MacLennan A. A template for
defining a causal relation between acute intrapartum events and
cerebral palsy: international consensus statement. BMJ
1999;319:10549.
COMMITTEE OPINIONS
the chorionic surface of the placenta will provide

accurate results (15). These arteries are relatively
easy to identify because they cross over the veins.
Conclusion
Umbilical cord arterial blood acid-base and gas
assessment remains the most objective determination of the fetal metabolic condition at the moment
of birth. Thresholds have been established below
which it is unlikely that an intrapartum asphyxial
insult will have resulted in neurologic injury to the
infant. Additionally, most infants born with umbilical arterial metabolic acidemia at a level consistent
with causing a neurologic injury will, in fact, develop normally.
Physicians should attempt to obtain venous and
arterial cord blood samples in the following situations:
Cesarean delivery for fetal compromise

Low 5-minute Apgar score
Severe growth restriction
Abnormal fetal heart rate tracing
Maternal thyroid disease
Intrapartum fever
Multifetal gestations
References
1. Bax M, Nelson KB. Birth asphyxia: a statement. World
Federation of Neurology Group. Dev Med Child Neurol
1993;35:10224.
Obstetricians and Gynecologists. Neonatal encephalopathy and cerebral palsy: defining the pathogenesis and
pathophysiology. Elk Grove Village (IL): AAP;
551
3. Low JA, Lindsay BG, Derrick EJ. Threshold of metabolic

acidosis associated with newborn complications. Am J
4. Winkler CL, Hauth JC, Tucker JM, Owen J, Brumfield
CG. Neonatal complications at term as related to the
degree of umbilical artery acidemia. Am J Obstet Gynecol
1991;164:63741.
5. Goldaber KG, Gilstrap LC, 3rd, Leveno KJ, Dax JS,
McIntire DD. Pathologic fetal acidemia. Obstet Gynecol
1991;78:11037.
6. Handley-Derry M, Low JA, Burke SO, Waurick M, Killen
H, Derrick EJ. Intrapartum fetal asphyxia and the occurrence of minor deficits in 4- to 8-year-old children. Dev
Med Child Neurol 1997;39:50814.
7. Low JA. Determining the contribution of asphyxia to
brain damage in the neonate. J Obstet Gynaecol Res
2004;30:27686.
OSullivan F, Burton PR, et al. Intrapartum risk factors for
10. Sameshima H, Ikenoue T, Ikeda T, Kamitomo M, Ibara S.
Unselected low-risk pregnancies and the effect of continuous intrapartum fetal heart rate monitoring on umbilical
blood gases and cerebral palsy. Am J Obstet Gynecol
2004;190:11823.
11. MacLennan A. A template for defining a causal relation
between acute intrapartum events and cerebral palsy:
international consensus statement. BMJ 1999;319:
10549.
12. National Collaborating Centre for Womens and Childrens
Health. Caesarean section. London (UK): RCOG Press;
2004.
13. Duerbeck NB, Chaffin DG, Seeds JW. A practical
approach to umbilical artery pH and blood gas determinations. Obstet Gynecol 1992;79:95962.
14. Strickland DM, Gilstrap LC 3rd, Hauth JC, Widmer K.
Umbilical cord pH and PCO2: effect of interval from
delivery to determination. Am J Obstet Gynecol 1984;
148:1914.
15. Riley RJ, Johnson JW. Collecting and analyzing cord
blood gases. Clin Obstet Gynecol 1993;36:1323.
552

Nalbuphine Hydrochloride Use for

Intrapartum Analgesia
Committee on
Obstetric Practice
followed.
ABSTRACT: Safety concerns have been raised regarding the use of nalbuphine
hydrochloride during labor. The American College of Obstetricians and Gynecologists finds
data are insufficient to recommend any changes in nalbuphine hydrochloride administration at this time.
Nalbuphine hydrochloride (formerly marketed as Nubain) is a synthetic opioid agonist

antagonist analgesic commonly used for intrapartum analgesia. Concerns for fetal safety
have been raised by one pharmaceutical company that no longer manufactures this agent
(www.fda.gov/medwatch/safety/2005/aug_PI/Nubain_PI.pdf). To date there are insufficient
data to support these concerns or to recommend any change in the administration of this
medication for analgesia in labor.
Copyright August 2007 by the American College of Obstetricians and Gynecologists, 409 12th Street, SW, PO
Box 96920, Washington, DC 20090-6920. All rights reserved. No part of this publication may be reproduced,
Nalbuphine hydrochloride use for intrapartum analgesia. ACOG Committee Opinion No. 376. American College
ISSN 1074-861X

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
COMMITTEE OPINIONS
553

Committee on
Obstetric Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Management of Delivery of a Newborn

With Meconium-Stained Amniotic Fluid
ABSTRACT: In accordance with the new guidelines from the American Academy of
Pediatrics and the American Heart Association, all infants with meconium-stained amniotic fluid should no longer routinely receive intrapartum suctioning. If meconium is present and the newborn is depressed, the clinician should intubate the trachea and suction
meconium and other aspirated material from beneath the glottis.
In 2006, the American Academy of Pediatrics

and the American Heart Association published new guidelines on neonatal resuscitation (1). The most significant impact these
new guidelines have on obstetricians relates
to the management of delivery of a newborn
with meconium-stained amniotic fluid.
Previously, management of a newborn with
meconium-stained amniotic fluid included
suctioning of the oropharynx and nasopharynx on the perineum after the delivery of the
head but before the delivery of the shoulders
(intrapartum suctioning). Current evidence
does not support this practice because routine intrapartum suctioning does not prevent
or alter the course of meconium aspiration
syndrome (1).
The Committee on Obstetric Practice
agrees with the recommendation of the
American Academy of Pediatrics and the
American Heart Association that all infants
with meconium-stained amniotic fluid should
no longer routinely receive intrapartum suctioning. If meconium is present and the
newborn is depressed, the clinician should
intubate the trachea and suction meconium
or other aspirated material from beneath the
glottis. If the newborn is vigorous, defined as
having strong respiratory efforts, good muscle
tone, and a heart rate greater than 100 beats

per minute, there is no evidence that tracheal
suctioning is necessary. Injury to the vocal
cords is more likely to occur when attempting to intubate a vigorous newborn.
Reference
1. 2005 American Heart Association (AHA)
guidelines for cardiopulmonary resuscitation
(CPR) and emergency cardiovascular care
(ECC) of pediatric and neonatal patients:
pediatric basic life support. American Heart
Association. Pediatrics 2006;117:e9891004.
Copyright September 2007 by the American College

of Obstetricians and Gynecologists, 409 12th Street,
SW, PO Box 96920, Washington, DC 20090-6920. All
rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the
Internet, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the
publisher. Requests for authorization to make photocopies should be directed to: Copyright Clearance
Center, 222 Rosewood Drive, Danvers, MA 01923,
(978) 750-8400.
Management of delivery of a newborn with meconium-stained amniotic fluid. ACOG Committee Opinion
ISSN 1074-861X
554

Subclinical Hypothyroidism in Pregnancy

Committee on
Obstetric Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Subclinical hypothyroidism is diagnosed in asymptomatic women when

the thyroid-stimulating hormone level is elevated and the free thyroxine level is within the
reference range. Thyroid hormones, specifically thyroxine, are essential for normal fetal
brain development. However, data indicating fetal benefit from thyroxine supplementation in pregnant women with subclinical hypothyroidism currently are not available.
Based on current literature, thyroid testing in pregnancy should be performed on symptomatic women and those with a personal history of thyroid disease or other medical
conditions associated with thyroid disease (eg, diabetes mellitus). Without evidence that
identification and treatment of pregnant women with subclinical hypothyroidism
improves maternal or infant outcomes, routine screening for subclinical hypothyroidism
currently is not recommended.
Subclinical hypothyroidism is diagnosed in

asymptomatic women when the thyroidstimulating hormone (TSH) level is elevated
and the free thyroxine (T4) level is within the
reference range. During pregnancy, the diagnosis of thyroid abnormalities is confused by
significant but reversible changes in maternal
thyroid physiology that lead to alterations in
thyroid function tests during gestation. These
changes are related to estrogen-mediated
increases in maternal thyroid-binding protein, structural homology between TSH and
human chorionic gonadotropin, and a relative decrease in availability of iodide during
pregnancy (1). There are gestational age-specific normograms and thresholds for evaluating thyroid status during pregnancy (24).
Thyroid hormones, specifically T4, are
essential for normal fetal brain development
(5). Before 12 weeks of gestation, a time
when the fetal thyroid begins to concentrate
iodine and synthesize T4, the fetus is entirely
dependent on maternal transfer of thyroid
hormones. Brain development begins during
this period of fetal dependency in the first
trimester and continues throughout pregnancy and on into infancy. In the case of
pregnant women who are iodine-deficient, in
which thyroxine production in both mother
and fetus is insufficient throughout pregnancy,
the impact on neurodevelopment of offspring can be dramatic (6). In women with
overt hypothyroidism (elevated TSH and low
free T4 levels), T4 supplementation during

pregnancy also has been associated with
improved pregnancy outcomes. However,
data indicating fetal benefit from T4 supplementation in pregnant women with subclinical hypothyroidism are not currently
available.
Interest in thyroid disease in pregnancy,
especially subclinical hypothyroidism, has
escalated in part because of reports suggesting that variously defined thyroid deficiency
(including both overt and subclinical disease) during pregnancy results in impaired
neurodevelopment in offspring (7, 8).
Further, other reports have associated subclinical hypothyroidism with preterm delivery (3, 9). These findings have led some
national societies as well as public interest
groups to recommend routine thyroid
screening during pregnancy (10). The rationale for routine screening of pregnant
women is tied both to the prevalence of subclinical hypothyroidism and the potential
benefits of treatment during pregnancy. The
prevalence of subclinical hypothyroidism
could be anticipated to be between 2% and
5% of women screened, depending on the
TSH and free T4 level thresholds applied, and
this represents most women who would be
identified with thyroid deficiency through
routine screening (3). According to criteria
established by The U.S. Preventive Services
Task Force, before recommending screening
COMMITTEE OPINIONS
of asymptomatic individuals, there must be demonstrated improvement in important health outcomes of those
individuals identified through screening (11, 12). As
stated previously, benefit of treatment to either mother or
fetus has not yet been demonstrated in pregnant women
with subclinical hypothyroidism.
Based on current literature, thyroid testing in pregnancy should be performed on symptomatic women and
those with a personal history of thyroid disease or other
medical conditions associated with thyroid disease (eg,
diabetes mellitus). In these women, it is most appropriate
to assess TSH levels first and then evaluate other thyroid
functions if the TSH level is abnormal. Women with
established overt thyroid disease (hyperthyroidism or
hypothyroidism) should be appropriately treated to
maintain a euthyroid state throughout pregnancy and
during the postpartum period. Without evidence that
identification and treatment of pregnant women with
subclinical hypothyroidism improves maternal or infant
outcomes, routine screening for subclinical hypothyroidism is not currently recommended.
References
1. Glinoer D, de Nayer P, Bourdoux P, Lemone M, Robyn C,
van Steirteghem A, et al. Regulation of maternal thyroid
during pregnancy. J Clin Endocrinol Metab 1990;71:
27687.
2. Dashe JS, Casey BM, Wells CE, McIntire DD, Byrd EW,
Leveno KJ, et al. Thyroid-stimulating hormone in singleton
and twin pregnancy: importance of gestational age-specific
reference ranges. Obstet Gynecol 2005;106:7537.
3. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W,
Leveno KJ, et al. Subclinical hypothyroidism and pregnancy
outcomes. Obstet Gynecol 2005;105:23945.
4. Casey BM, Dashe JS, Spong CY, McIntire DD, Leveno KJ,
Cunningham GF. Perinatal significance of isolated maternal
hypothyroxinemia identified in the first half of pregnancy.
5. Morreale de Escobar G, Obregon MJ, Escobar del Rey F. Is
neuropsychological development related to maternal
hypothyroidism or to maternal hypothyroxinemia? J Clin
Endocrinol Metab 2000;85:397587.
555
6. Glinoer D. Pregnancy and iodine. Thyroid 2001;11:47181.

7. Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight
GJ, Gagnon J, et al. Maternal thyroid deficiency during
pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999;341:54955.
8. Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM,
de Vijlder JJ, et al. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired
psychomotor development in infancy. Clin Endocrinol
1999;50:14955.
9. Stagnaro-Green A, Chen X, Bogden JD, Davies TF, Scholl
TO. The thyroid and pregnancy: a novel risk factor for very
preterm delivery. Thyroid 2005;15:3517.
10. Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA,
McDermott MT. Subclinical thyroid dysfunction: a joint
statement on management from the American Association
of Clinical Endocrinologists, the American Thyroid Association, and The Endocrine Society. Consensus Statement
#1. American Association of Clinical Endocrinologists;
American Thyroid Association; The Endocrine Society.
Thyroid 2005;15:248; response 323.
11. Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD,
Teutsch SM, et al. Current methods of the US Preventive
Services Task Force: a review of the process. Methods Work
Group, Third US Preventive Services Task Force. Am J Prev
Med 2001;20(suppl):2135.
12. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin
RH, et al. Subclinical thyroid disease: scientific review and
guidelines for diagnosis and management. JAMA 2004;
291:22838.

Subclinical hypothyroidism in pregnancy. ACOG Committee Opinion
ISSN 1074-861X
556

Fetal Monitoring Prior to Scheduled

Cesarean Delivery
Committee on
Obstetric Practice
followed.
ABSTRACT: There are insufficient data to determine the value of fetal monitoring
prior to scheduled cesarean delivery in patients without risk factors.
With the increasing rate of scheduled cesarean deliveries in the United States, clinicians and
hospitals must decide whether there is need to determine fetal status prior to scheduled
cesarean delivery. At the present time there are insufficient data to determine the value of fetal
monitoring, either by electronic fetal heart rate monitoring or by ultrasound, prior to scheduled cesarean delivery in patients without risk factors. The decision to monitor the fetus prior
to scheduled cesarean delivery should be individualized. Presence of fetal heart tones prior to
surgery should be documented.
Copyright October 2007 by the American College of Obstetricians and Gynecologists, 409 12th Street, SW,
PO Box 96920, Washington, DC 20090-6920. All rights reserved. No part of this publication may be reproduced,
Fetal monitoring prior to scheduled cesarean delivery. ACOG Committee Opinion No. 382. American College of
ISSN 1074-861X

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
COMMITTEE OPINIONS
557

Cesarean Delivery on Maternal Request

Committee on
Obstetric Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Cesarean delivery on maternal request is defined as a primary cesarean delivery at maternal request in the absence of any medical or obstetric indication. A
potential benefit of cesarean delivery on maternal request is a decreased risk of hemorrhage for the mother. Potential risks of cesarean delivery on maternal request include a
longer maternal hospital stay, an increased risk of respiratory problems for the baby, and
greater complications in subsequent pregnancies, including uterine rupture and placental implantation problems. Cesarean delivery on maternal request should not be per-
formed before gestational age of 39 weeks has been accurately determined unless
there is documentation of lung maturity. Cesarean delivery on maternal request should
not be motivated by the unavailability of effective pain management. Cesarean delivery
on maternal request is not recommended for women desiring several children, given
that the risks of placenta previa, placenta accreta, and the need for gravid hysterectomy
increase with each cesarean delivery.
Cesarean delivery on maternal request is

defined as a primary cesarean delivery at
maternal request in the absence of any
medical or obstetric indication. Cesarean
delivery rates in the United States are at the
highest levels ever, with more than 1.2 million cesarean deliveries (30.2% of live births)
performed in 2005 (1). The incidence of
cesarean delivery on maternal request and
its contribution to the overall increase in the
cesarean delivery rate are not known, but it
is estimated that 2.5% of all births in the
United States are cesarean delivery on maternal request (2).
Cesarean delivery on maternal request is
not a well-recognized clinical entity, and
there are no accurate means of reporting it
for research studies, coding, or reimbursement. There are few studies that directly
compare the intended mode of delivery (ie,
cesarean delivery on maternal request or
planned vaginal delivery). Most of the current knowledge is based on indirect analyses
that compare elective cesarean deliveries
without labor (instead of cesarean delivery
on maternal request) with the combination
of vaginal deliveries and unplanned and
emergency cesarean deliveries (instead of
planned vaginal deliveries) or outcomes of
actual modes of delivery.
At the National Institutes of Health
State-of-the-Science Conference on Cesarean
Delivery on Maternal Request in 2006, a

panel of experts was charged with reviewing
the available literature and expert opinions
on the subject (2). A systematic literature
review of 1,406 recent articles was conducted to evaluate the relevance of existing studies on cesarean delivery on maternal request
and the quality of evidence. The panel concluded that the available information comparing the risks and benefits of cesarean
delivery on maternal request and planned
vaginal delivery does not provide the basis
for a recommendation for either mode of
delivery. The panel identified the best information available on the short-term and
long-term risks and benefits of cesarean
delivery on maternal request and planned
vaginal delivery for both the mother and her
baby.
Benefits and Risks of Cesarean

Delivery on Maternal Request
Compared With Planned
Vaginal Delivery
Maternal Outcomes
Potential short-term maternal benefits of
planned vaginal delivery included a shorter
maternal length of hospital stay, lower infection rates, fewer anesthetic complications,
and higher breastfeeding initiation rates.
However, at 3 months and 24 months after
558
delivery, breastfeeding rates did not differ by mode of

delivery (3, 4).
Potential short-term maternal benefits of planned
cesarean delivery include a decreased risk of postpartum
hemorrhage and transfusion, fewer surgical complications, and a decrease in urinary incontinence during
the first year after delivery. Analysis of stress urinary
incontinence at 2 years (3) and 5 years after delivery (5)
showed no difference by mode of delivery. The benefit
of a planned cesarean delivery may be eliminated by
advanced maternal age and increased body mass index
(5).
Maternal outcomes that favored neither delivery
route include postpartum pain, pelvic pain, postpartum
depression, fistula, anorectal function, sexual function,
pelvic organ prolapse, subsequent stillbirth, and maternal mortality. Evidence for thromboembolism was conflicting. Potential risks of cesarean delivery on maternal
request include greater complications in subsequent
pregnancies, such as uterine rupture, placenta previa,
placenta accreta, bladder and bowel injuries, uterine rupture, and the need for hysterectomy. A recent Canadian
study of primiparous women with singleton pregnancies
showed an increased risk of postpartum cardiac arrest,
wound hematoma, hysterectomy, major puerperal infection, anesthetic complications, venous thromboembolism, and hemorrhage requiring hysterectomy in
patients who had a planned primary cesarean delivery
(6). These are also factors that may be influenced by parity and planned family size. Uterine scars put women at
increased risk for uterine rupture in subsequent pregnancies. Although there is no difference between planned
cesarean delivery or planned vaginal delivery in risk of
peripartum hysterectomy in a womans first delivery,
there is a significant increased risk of placenta previa,
placenta accreta, placenta previa with accreta, and the
need for gravid hysterectomy after a womans second
cesarean delivery (Table 1). This emphasizes the need to
consider the mothers total number of planned or
expected pregnancies if cesarean delivery on maternal
request is discussed during her first pregnancy, realizing

that many pregnancies are unplanned.
Neonatal Outcomes
Potential neonatal benefits of planned vaginal delivery
include a lower risk of respiratory problems, fewer problems with iatrogenic prematurity, and shorter length of
hospital stay. There are limited studies on cesarean delivery on maternal request and neonatal outcomes, so literature on elective cesarean delivery without labor has been
evaluated. The risk of respiratory morbidity, including
transient tachypnea of the newborn, respiratory distress
syndrome, and persistent pulmonary hypertension, is
higher for elective cesarean delivery compared with vaginal delivery when delivery is earlier than 3940 weeks of
gestation (7, 8). The literature on elective cesarean delivery without labor also shows an increased rate of complications related to prematurity, including respiratory
symptoms, other neonatal adaptation problems such as
hypothermia and hypoglycemia, and neonatal intensive
care unit admissions, for infants delivered by cesarean
delivery before 39 weeks of gestation (2). Because of these
potential complications, cesarean delivery on maternal
request should not be performed before gestational age of
39 weeks has been accurately determined unless there is
documentation of lung maturity.
Potential neonatal benefits of planned cesarean
delivery include lower fetal mortality; lower newborn
infection rate; reduced risk of intracranial hemorrhage
diagnosis, neonatal asphyxia, and encephalopathy; and
fewer birth injuries. In epidemiologic models, cesarean
delivery on maternal request by 40 weeks of gestation
would reduce fetal mortality because planned vaginal
delivery could occur at up to 42 weeks of gestation, and
there is a finite risk of stillbirth between 40 and 42 weeks
of gestation. Rates of intracranial hemorrhage are similar
for spontaneous vaginal deliveries and cesarean deliveries
without labor but are higher in operative vaginal deliveries and cesarean deliveries with labor (2).
Table 1. Risk of Placenta Accreta and Hysterectomy by Number of Cesarean Deliveries Compared
With the First Cesarean Delivery
Cesarean
Delivery
Accreta
[n (%)]
Odds Ratio
(95% CI)
Hysterectomy
[n (%)]
Odds Ratio
(95% CI)
First
15 (0.2)
40 (0.7)
Second
49 (0.3)
1.3 (.72.3)
67 (0.4)
0.7 (0.40.97)
Third
36 (0.6)
2.4 (1.34.3)
57 (0.9)
1.4 (0.91.2)
Fourth
31 (2.1)
9.0 (4.816.7)
35 (2.4)
3.8 (2.46.0)
Fifth
6 (2.3)
9.8 (3.825.5)
9 (3.5)
5.6 (2.711.6)
Six or more
6 (6.7)
29.8 (11.378.7)
8 (9.0)
15.2 (6.933.5)
CI, confidence interval.

Silver RM, Landon MB, Rouse DJ, Leveno KJ, Spong CY, Thom EA, et al. Maternal morbidity associated with multiple repeat cesarean
deliveries. National Institute of Child Health and Human Development MaternalFetal Medicine Units Network. Obstet Gynecol
2006;107:122632.
COMMITTEE OPINIONS
There is also weak quality evidence of a lower risk of

neonatal encephalopathy and asphyxia with elective
cesarean delivery without labor compared with the combined risks of spontaneous vaginal delivery, operative
vaginal delivery, emergency cesarean delivery, and cesarean delivery with labor (9, 10). The incidence of brachial
plexus injury is significantly lower for cesarean delivery
than vaginal delivery, with the highest incidence for
assisted vaginal delivery. The incidence of fetal laceration
at the time of cesarean delivery is lower for elective cesarean delivery without labor (0.8%) than unscheduled
cesarean delivery (1.41.5%) (11). Studies on neonatal
mortality and long-term neonatal outcomes lacked statistical power and quality data to assess the effect of the
planned delivery route.
Summary of Data
In summary, only five outcome variables have moderate
quality evidence regarding delivery route: 1) maternal
hemorrhage, 2) maternal length of stay, 3) neonatal respiratory morbidity, 4) subsequent placenta previa or accreta, and 5) subsequent uterine rupture. The remaining
outcome assessments are based on weak evidence, which
limits the reliability of the results. A potential benefit of
cesarean delivery on maternal request as compared with
planned vaginal delivery is a decreased risk of hemorrhage for the mother. Potential risks of cesarean delivery
on maternal request include a longer maternal hospital
stay, an increased risk of respiratory problems for the
baby, and greater complications in subsequent pregnancies, including uterine rupture and placental implantation problems.
Other Factors
When a woman desires a cesarean delivery on maternal
request, her health care provider should consider her specific risk factors, such as age, body mass index, accuracy of
estimated gestational age, reproductive plans, personal
values, and cultural context. Critical life experiences (eg,
trauma, violence, poor obstetric outcomes) and anxiety
about the birth process may prompt her request. If her
main concern is a fear of pain in childbirth, then prenatal
childbirth education, emotional support in labor, and
anesthesia for childbirth should be offered.
Further research is needed to get direct evidence for
better counseling in the future. This includes surveys on
cesarean delivery on maternal request, modification of
birth certificates and Current Procedural Terminology
coding to facilitate tracking, prospective cohort studies,
database studies, and studies of modifiable risk factors for
cesarean delivery on maternal request versus planned
vaginal delivery. Short-term and long-term maternal and
neonatal outcomes as well as cost need further study.
Conclusions
The available data on cesarean delivery on maternal
request compared with planned vaginal delivery is mini-
559
mal and mostly based on indirect comparisons. Most of

the studies of proxy outcomes do not adequately adjust
for confounding factors and, thus, must be interpreted
cautiously.
Recommendations
Cesarean delivery on maternal request should not be
performed before gestational age of 39 weeks has
been accurately determined unless there is documentation of lung maturity.
Cesarean delivery on maternal request should not be
motivated by the unavailability of effective pain
management.
Cesarean delivery on maternal request is not recommended for women desiring several children, given
that the risks of placenta previa, placenta accreta, and
gravid hysterectomy increase with each cesarean
delivery.
References
1. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary
2. National Institutes of Health. NIH State-of-the-Science
Conference statement on cesarean delivery on maternal
request. NIH Consensus and State-of-the-Science Statements. Bethesda (MD): NIH; 2006. Available at: http://
consensus.nih.gov/2006/CesareanStatement_Final053106.p
df. Retrieved July 20, 2007.
3. Hannah ME, Whyte H, Hannah WJ, Hewson S, Amankwah
K, Cheng M, et al. Maternal outcomes at 2 years after
planned cesarean section versus planned vaginal birth for
breech presentation at term: the international randomized
Term Breech Trial. Term Breech Trial Collaborative Group.
4. Hannah ME, Hannah WJ, Hodnett ED, Chalmers B, Kung
R, Willan A, et al. Outcomes at 3 months after planned
cesarean vs planned vaginal delivery for breech presentation
at term: the international randomized Term Breech Trial.
Term Breech Trial 3-Month Follow-up Collaborative
Group. JAMA 2002;287:182231.
5. Rortveit G, Daltveit AK, Hannestad YS, Hunskaar S. Urinary
incontinence after vaginal delivery or cesarean section.
Norwegian EPINCONT Study. N Engl J Med 2003;348: 9007.
6. Liu S, Liston RM, Joseph KS, Heaman M, Sauve R, Kramer
MS. Maternal mortality and severe morbidity associated
with low-risk planned cesarean delivery versus planned
vaginal delivery at term. Maternal Health Study Group of
the Canadian Perinatal Surveillance System. CMAJ 2007;
176:45560.
7. Zanardo V, Simbi AK, Franzoi M, Solda G, Salvadori A,
Trevisanuto D. Neonatal respiratory morbidity risk and
mode of delivery at term: influence of timing of elective
caesarean delivery. Acta Paediatr 2004;93:6437.
8. Morrison JJ, Rennie JM, Milton PJ. Neonatal respiratory
morbidity and mode of delivery at term: influence of timing of elective caesarean section. Br J Obstet Gynaecol
1995;102:1016.
560

OSullivan F, Burton PR, et al. Intrapartum risk factors for
newborn encephalopathy: the Western Australian case-control study. BMJ 1998;317:15548.
10. Towner D, Castro MA, Eby-Wilkens E, Gilbert WM. Effect
of mode of delivery in nulliparous women on neonatal
intracranial injury. N Engl J Med 1999;341:170914.
11. van Ham MA, van Dongen PW, Mulder J. Maternal consequences of caesarean section. A retrospective study of intraoperative and postoperative maternal complications of caesarean section during a 10-year period. Eur J Obstet
Gynecol Reprod Biol 1997;74:16.
Cesarean delivery on maternal request. ACOG Committee Opinion
ISSN 1074-861X
COMMITTEE OPINIONS
561

Antenatal Corticosteroid Therapy for Fetal

Maturation
Committee on
Obstetric Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: A single course of corticosteroids is recommended for all pregnant

women between 24 and 34 weeks of gestation who are at risk of preterm delivery within 7 days. A single course of antenatal corticosteroids should be administered to women
with premature rupture of membranes (PROM) before 32 weeks of gestation to reduce
the risks of respiratory distress syndrome, perinatal mortality, and other morbidities. The
efficacy of corticosteroid use at 3233 completed weeks of gestation for preterm PROM
is unclear based on available evidence, but treatment may be beneficial, particularly if pulmonary immaturity is documented. No data exist on the efficacy of corticosteroid use
before viability, and such use is not recommended at this time. Because of insufficient
scientific evidence, repeat corticosteroid courses, including so-called rescue therapy,
should not be used routinely but should be reserved for women enrolled in clinical trials.
In August 2000, the National Institute of

Child Health and Human Development
and the Office of Medical Applications of
Research of the National Institutes of
Health reconvened a consensus conference
on antenatal steroids, entitled Consensus
Development Conference on Antenatal Corticosteroids Revisited: Repeat Courses, to
address the issue of repeated courses of corticosteroids for fetal maturation. The consensus panel from this conference reaffirmed the
1994 consensus panels recommendation of
giving a single course of corticosteroids to all
pregnant women between 24 and 34 weeks of
gestation who are at risk of preterm delivery
within 7 days (1). Because of insufficient
scientific evidence, the panel also recommended that repeat corticosteroid courses,
including so-called rescue therapy, should
not be routinely used but should be reserved
for women enrolled in clinical trials. The
American College of Obstetricians and Gynecologists Committee on Obstetric Practice
supports the conclusions of the consensus
conferences.
There is no convincing scientific evidence that antenatal corticosteroid therapy
increases the risk of neonatal infection,
although multiple courses have been associated with fetal adrenal suppression (2).
Follow-up studies of children aged 14 years
who were exposed to at least one course of

corticosteroid treatment indicate there is no
apparent risk of adverse neurodevelopmental
outcome associated with antenatal corticosteroids (3). In a randomized trial of single
versus multiple courses of antenatal corticosteroids, a reduction in birth weight and an
increase in the number of infants who were
small for gestational age was found, especially after four courses of corticosteroids (4).
Although not consistent, six studies found
decreased birth weight and head circumference with repeat courses (49) and three
studies did not (1012). Recently it has been
shown that repeat doses of antenatal corticosteroids are associated with smaller placentas, but treatment does not appear to have an
influence on significant histologic placental
findings related to placental maturation,
infarction, abruptio placentae, necrosis, or
fetal hypoxia (13). The 2000 consensus panel
concluded that studies regarding the possible
benefits and risks of repeat courses of antenatal corticosteroids are limited because of
their study design and methodologic inconsistencies. The 2000 consensus panel noted
that, although there is a suggestion of possible benefit from repeated doses (especially in
the reduction and severity of respiratory distress), there also are animal and human data
that suggest deleterious effects on the fetus
562
regarding cerebral myelination, lung growth, and function of the hypothalamicpituitaryadrenal axis. Followup of children at 2 years of age exposed to repeat courses
of antenatal corticosteroids showed no significant difference in physical or neurocognitive measures (14, 15).
Although not statistically significant, the relative risk of
cerebral palsy in infants exposed to multiple courses of
antenatal corticosteroids (relative risk = 5.7) is of concern
and warrants further study (14). Maternal effects include
increased infection and suppression of the hypothalamic
pituitaryadrenal axis (6, 16).
Betamethasone and dexamethasone are the most
widely studied corticosteroids and have generally been
preferred for antenatal treatment to accelerate fetal organ
maturation. Both cross the placenta in their active form
and have nearly identical biologic activity. Both lack mineralocorticoid activity and have relatively weak immunosuppressive activity with short-term use. Although
betamethasone and dexamethasone differ only by a single
methyl group, betamethasone has a longer half-life
because of its decreased clearance and larger volume of
distribution (17). Meta-analyses of randomized trials have
shown that, although both agents decrease the frequency
of respiratory distress syndrome, only betamethasone
decreases neonatal mortality (18). A recent large, uncontrolled retrospective study suggested that betamethasone
also may have significant benefit in decreasing the rate of
newborn cystic periventricular leukomalacia by approximately 50% in treated women compared with untreated
and dexamethasone-treated women (19). The offspring of
pregnant mice who were given betamethasone performed
neurobehavioral developmental tasks better than the offspring of pregnant mice given dexamethasone (20).
Furthermore, betamethasone requires fewer intramuscular
injections. Betamethasone use, however, has been associated with a significant transient decrease in fetal movements
and heart rate variability (21, 22). In a recent randomized
trial of 299 women, investigators found that although
both betamethasone and dexamethasone were comparable in reducing neonatal morbidities and mortality, dexamethasone was more effective in reducing the rate of
intraventricular hemorrhage (23).
The 2000 consensus panel reviewed all available
reports on the safety and efficacy of betamethasone and
dexamethasone. It did not find significant scientific evidence to support a recommendation that betamethasone
should be used preferentially instead of dexamethasone.
Thus, based on this information, the Committee on
Obstetric Practice recommends either of the following
corticosteroid regimens:
Two 12-mg doses of betamethasone given intramuscularly 24 hours apart
Dexamethasone (6 mg) given intramuscularly every
12 hours for four doses
A single course of corticosteroids is recommended
for all pregnant women between 24 and 34 weeks of ges-
tation who are at risk of preterm delivery within 7 days

(24). A single course of antenatal corticosteroids should
be administered to women with premature rupture of
membranes (PROM) before 32 weeks of gestation to
reduce the risks of respiratory distress syndrome, perinatal mortality, and other morbidities. The efficacy of corticosteroid use at 3233 completed weeks of gestation for
preterm PROM is unclear based on available evidence,
but treatment may be beneficial, particularly if pulmonary
immaturity is documented. There are no data regarding
the efficacy of corticosteroid use before viability, and it is
not recommended at this time. Because of insufficient
scientific evidence, repeat corticosteroid courses, including so-called rescue therapy, should not be used
routinely but should be reserved for women enrolled in
clinical trials.
References
1. Antenatal corticosteroids revisited: repeat courses. NIH
Consens Statement 2000;17(2):118.
2. Kairalla AB. Hypothalamic-pituitary-adrenal axis function
in premature neonates after extensive prenatal treatment
with betamethasone: a case history. Am J Perinatol 1992;9:
42830.
3. Doyle LW, Ford GW, Rickards AL, Kelly EA, Davis NM,
Callanan C, et al. Antenatal corticosteroids and outcome at
14 years of age in children with birth weight less than 1501
grams. Pediatrics 2000;106:E2.
4. Wapner RJ, Sorokin Y, Thom EA, Johnson F, Dudley DJ,
Spong CY, et al. Single versus weekly courses of antenatal
corticosteroids: evaluation of safety and efficacy. National
Institute of Child Health and Human Development
Maternal Fetal Medicine Units Network. Am J Obstet
Gynecol 2006;195:63342.
5. French NP, Hagan R, Evans SF, Godfrey M, Newnham JP.
Repeated antenatal corticosteroids: size at birth and subsequent development. Am J Obstet Gynecol 1999;180:11421.
6. Abbasi S, Hirsch D, Davis J, Tolosa J, Stouffer N, Debbs R, et
al. Effect of single versus multiple courses of antenatal corticosteroids on maternal and neonatal outcome. Am J
7. Banks BA, Cnaan A, Morgan MA, Parer JT, Merrill JD,
Ballard PL, et al. Multiple courses of antenatal corticosteroids and outcome of premature neonates. North
American Thyrotropin-Releasing Hormone Study Group.
8. Bloom SL, Sheffield JS, McIntire DD, Leveno KJ. Antenatal
dexamethasone and decreased birth weight. Obstet Gynecol
2001;97:48590.
9. Thorp JA, Jones PG, Knox E, Clark RH. Does antenatal corticosteroid therapy affect birth weight and head circumference? Obstet Gynecol 2002;99:1018.
10. Guinn DA, Atkinson MW, Sullivan L, Lee M, MacGregor S,
Parilla BV, et al. Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: a randomized controlled trial. JAMA 2001;286:1581-7.
COMMITTEE OPINIONS
11. Pratt L, Waschbusch L, Ladd W, Gangnon R, Hendricks SK.

Multiple vs. single betamethasone therapy. Neonatal and
maternal effects. J Reprod Med 1999;44:25764.
12. Shelton SD, Boggess KA, Murtha AP, Groff AO, Herbert
WN. Repeated fetal betamethasone treatment and birth
weight and head circumference. Obstet Gynecol 2001;97:
3014.
13. Sawady J, Mercer BM, Wapner RJ, Zhao Y, Sorokin Y,
Johnson F, et al. The National Institute of Child Health and
Human Development Maternal-Fetal Medicine Units
Network Beneficial Effects of Antenatal Repeated Steroids
study: impact of repeated doses of antenatal corticosteroids
on placental growth and histologic findings. National
Maternal Fetal Medicine Units Network. Am J Obstet
Gynecol 2007;197:281.e18.
14. Wapner RJ, Sorokin Y, Mele L, Johnson F, Dudley DJ, Spong
CY, et al. Long-term outcomes after repeat doses of antenatal corticosteroids. National Institute of Child Health and
Network. N Engl J Med 2007;357:11908.
15. Crowther CA, Doyle LW, Haslam RR, Hiller JE, Harding JE,
Robinson JS. Outcomes at 2 years of age after repeat doses
of antenatal corticosteroids. ACTORDS Study Group. N
Engl J Med 2007;357:117989.
16. McKenna DS, Wittber GM, Nagaraja HN, Samuels P. The
effects of repeat doses of antenatal corticosteroids on
maternal adrenal function. Am J Obstet Gynecol 2000;
183:66973.
17. Fanaroff AA, Hack M. Periventricular leukomalacia
prospects for prevention. N Engl J Med 1999;341:122931.
18. Ballard PL, Ballard RA. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am J Obstet
Gynecol 1995;173:25462.
19. Baud O, Foix-LHelias L, Kaminski M, Audibert F, Jarreau
PH, Papiernik E, et al. Antenatal glucocorticoid treatment
20.
21.
22.
23.
24.
563
and cystic periventricular leukomalacia in very premature

infants. N Engl J Med 1999;341:11906.
Rayburn WF, Christensen HD, Gonzalez CL. A placebocontrolled comparison between betamethasone and
dexamethasone for fetal maturation: differences in
neurobehavioral development of mice offspring. Am J
Obstet Gynecol 1997;176:84250; discussion 8501.
Mulder EJ, Derks JB, Visser GH. Antenatal corticosteroid
therapy and fetal behaviour: a randomised study of the
effects of betamethasone and dexamethasone. Br J Obstet
Gynaecol 1997;104:123947.
Senat MV, Minoui S, Multon O, Fernandez H, Frydman R,
Ville Y. Effect of dexamethasone and betamethasone on
fetal heart rate variability in preterm labour: a randomised
study. Br J Obstet Gynaecol 1998;105:74955.
Elimian A, Garry D, Figueroa R, Spitzer A, Wiencek V, Quirk
JG. Antenatal betamethasone compared with dexamethasone (betacode trial): a randomized controlled trial. Obstet
Gynecol 2007;110:2630.
Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm
birth. Cochrane Database of Systematic Reviews 2006, Issue
3. Art. No.: CD004454. DOI: 10.1002/14651858.CD004454.
pub2.

Antenatal corticosteroid therapy for fetal maturation. ACOG
ISSN 1074-861X
564

Late-Preterm Infants
Committee on
Obstetric Practice
This Committee Opinion
was developed with the
assistance of William A.
Engle, MD, Kay M.
Tomashek, MD, Carol
Wallman, MSN, and the
American Academy of
Pediatrics Committee on
Fetus and Newborn.
followed.
ABSTRACT: Late-preterm infants (defined as infants born between 3407 weeks and
3667 weeks of gestation) often are mistakenly believed to be as physiologically and metabolically mature as term infants. However, compared with term infants, late-preterm
infants are at higher risk than term infants of developing medical complications, resulting
in higher rates of infant mortality, higher rates of morbidity before initial hospital discharge, and higher rates of hospital readmission in the first months of life. Preterm delivery should occur only when an accepted maternal or fetal indication for delivery exists.
Collaborative counseling by both obstetric and neonatal clinicians about the outcomes of
late-preterm births is warranted unless precluded by emergent conditions.
During the past decade, the proportion of all

U.S. births that were late-preterm births
(defined as birth between 3407 weeks and 3667
weeks of gestation) increased 16% (1). The
rate of all preterm births (defined as birth at
less than 37 weeks of gestation) in the United
States increased from 10.9% in 1990 to
12.7% in 2005 (2), an increase of 16.5%.
This increase largely was caused by the increase in late-preterm births. Late-preterm
infants often are mistakenly believed to be as
physiologically and metabolically mature as
term infants. However, compared with term
infants, late-preterm infants are at higher
risk of developing medical complications resulting in higher rates of infant mortality,
higher rates of morbidity before initial hospital discharge (35), and higher rates of
hospital readmission in the first months of
life (46).
Infant Implications

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Late-preterm births make up 71% of all

preterm births (1). It is important to limit
late-preterm deliveries to those with a clear
maternal or fetal indication for delivery. As
the number of late-preterm births increases, it
is important to understand the unique problems that this growing population of infants
may experience.
The American Academy of Pediatrics has
published guidelines for the care of latepreterm infants (7). The following sections
contain extracts taken from these guidelines.
Summary
During the initial birth hospitalization,
late-preterm infants are 4 times more
likely than term infants to have at least
1 medical condition diagnosed and 3.5
times more likely to have 2 or more
conditions diagnosed (6). Late-preterm
infants are more likely than term
infants to be diagnosed during the birth
hospitalization with temperature instability (6), hypoglycemia (6), respiratory
distress (6, 811), apnea (12, 13), jaundice (6), and feeding difficulties (6).
During the first month after birth, latepreterm infants are also more likely
than term infants to develop hyperbilirubinemia (1417) and to be readmitted for hyperbilirubinemia (1820)
and nonjaundice-related diagnoses
such as feeding difficulties and ruleout sepsis (18).
In 2002, the neonatal mortality
rate (deaths among infants 027 days
chronologic age) for late-preterm
infants was 4.6 times higher than the
rate for term infants (4.1 vs 0.9 per
1000 live births, respectively). This difference in neonatal mortality has
widened slightly since 1995, when
there was a fourfold difference in rates
between late-preterm and term infants
(4.8 vs 1.2 per 1000 live births, respectively). The infant mortality rate was
also higher among late-preterm infants
COMMITTEE OPINIONS
than term infants in 2002 (7.7 vs 2.5 per 1000 live

births, respectively). This threefold difference has
remained relatively constant since 1995, at which
time the infant mortality rate was 9.3 per 1000 live
births among late-preterm infants and 3.1 per 1000
live births among term infants.
Pulmonary Function
After birth, infants with fetal lung structure
and immature functional capacity are at greatest
risk of respiratory distress, need for oxygen and
positive-pressure ventilation, and admission for
intensive care (6, 9, 21, 22). From 3407 through
3667 weeks gestation, terminal respiratory units of
the lung evolve from alveolar saccules lined with
both cuboidal type II and flat type I epithelial cells
(terminal sac period) to mature alveoli lined primarily with extremely thin type I epithelial cells
(alveolar period) (23, 24). During the alveolar period, pulmonary capillaries also begin to bulge into
the space of each terminal sac, and adult pool
sizes of surfactant are attained (25). Functionally,
this immature lung structure may be associated
with delayed intrapulmonary fluid absorption, surfactant insufficiency, and inefficient gas exchange
(8, 26).
Apnea occurs more frequently among latepreterm infants than term infants. The incidence of
apnea in late-preterm infants is reported to be
between 4% and 7% (12, 21, 27, 28) compared with
less than 1% to 2% at term (12, 29). The predisposition to apnea in late-preterm infants is associated
with several underlying factors including increased
susceptibility to hypoxic respiratory depression,
decreased central chemosensitivity to carbon dioxide, immature pulmonary irritant receptors,
increased respiratory inhibition sensitivity to laryngeal stimulation, and decreased upper airway dilator muscle tone (12, 13, 21, 30, 31).
Cardiac Function
It is generally believed that structural and functional
immaturity restricts the amount of cardiovascular reserve that is available during times of stress
(32, 33). Immature cardiovascular function also
may complicate recovery of the late-preterm infant
with respiratory distress because of delayed ductus
arteriosus closure and persistent pulmonary hypertension (34).
Cold Response
Late-preterm infants have less white adipose tissue
for insulation, and they cannot generate heat from
brown adipose tissue as effectively as infants born
at term. In addition, late-preterm infants are likely
to lose heat more readily than term infants, because
they have a larger ratio of surface area to weight and
are smaller in size.
565
Hypoglycemia
The incidence of hypoglycemia is inversely proportional to gestational age. Preterm infants are at
increased risk of developing hypoglycemia after
birth, because they have immature hepatic glycogenolysis and adipose tissue lipolysis, hormonal dysregulation, and deficient hepatic gluconeogenesis
and ketogenesis. Blood glucose concentrations
among preterm infants typically decrease to a
nadir 1 to 2 hours after birth and remain low until
metabolic pathways can compensate or exogenous
sources of glucose are provided (35, 36). Immature
glucose regulation likely occurs in late-preterm
infants, because hypoglycemia that requires glucose infusion during the initial birth hospitalization occurs more frequently than in term infants
(6).
Jaundice
Jaundice and hyperbilirubinemia occur more commonly and are more prolonged among latepreterm infants than term infants, because
late-preterm infants have delayed maturation and a
lower concentration of uridine diphosphoglucuronate glucuronosyltransferase (14, 37). Latepreterm infants are 2 times more likely than term
infants to have significantly elevated bilirubin concentrations and higher concentrations 5 and 7 days
after birth (14). Late-preterm infants also have
immature gastrointestinal function (38, 39) and
feeding difficulties that predispose them to an
increase in enterohepatic circulation, decreased
stool frequency, dehydration, and hyperbilirubinemia (15, 19, 20, 4046). Feeding during the birth
hospitalization may be transiently successful but
not sustained after discharge. Feeding difficulties in
late-preterm infants that are associated with relatively low oromotor tone, function, and neural
maturation also predispose these infants to dehydration and hyperbilirubinemia (4548).
Obstetric Implications
Because of the aforementioned increase in rates of morbidity and mortality of late-preterm infants, preterm
delivery should only occur when an accepted maternal or
fetal indication for delivery exists. Examples may include
nonreassuring fetal status or a maternal condition that is
likely to be improved by delivery. Collaborative counseling by both obstetric and neonatal clinicians about the
outcomes of late-preterm births is warranted unless precluded by emergent conditions.
References
1. Davidoff MJ, Dias T, Damus K, Russell R, Bettegowda R,
Dolans, et al. Changes in the gestational age distribution
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566
2. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary

3. Kramer MS, Demissie K, Yang H, Platt RW, Sauve R, Liston
R. The contribution of mild and moderate preterm birth to
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Barfield W, Weiss J, Evans S. Risk factors for neonatal morbidity and mortality among healthy, late preterm newborns. Semin Perinatol 2006;30:5460.
5. Tomashek KM, Shapiro-Mendoza CK, Weiss J, Kotelchuck
M, Barfield W, Evans S, et al. Early discharge among late
preterm and term newborns and risk of neonatal morbidity. Semin Perinatol 2006;30:618.
6. Wang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics 2004;114:3726.
7. Engle WA, Tomashek KM, Wallman C. Late preterm
infants: a population at risk. Committee on Fetus and Newborn. Pediatrics 2007;120:13901401.
8. Escobar GJ, Clark RH, Greene JD. Short-term outcomes of
infants born at 35 and 36 weeks gestation: we need to ask
more questions. Semin Perinatol 2006;30:2833.
9. Rubaltelli FF, Bonafe L, Tangucci M, Spagnolo A, Dani C.
Epidemiology of neonatal acute respiratory disorders. A
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acute respiratory disorders according to gestational age,
maternal age, pregnancy complications and type of delivery. Italian Group of Neonatal Pneumology. Biol Neonate
1998;74:715.
10. Gilbert WM, Nesbitt TS, Danielsen B. The cost of prematurity: quantification by gestational age and birth weight.
11. Dani C, Reali MF, Bertini G, Wiechmann L, Spagnolo A,
Tangucci M, et al. Risk factors for the development of respiratory distress syndrome and transient tachypnoea in newborn infants. Italian Group of Neonatal Pneumology. Eur
Respir J 1999;14:1559.
12. Henderson-Smart DJ. The effect of gestational age on the
incidence and duration of recurrent apnoea in newborn
babies. Aust Paediatr J 1981;17:2736.
13. Merchant JR, Worwa C, Porter S, Coleman JM, deRegnier
RA. Respiratory instability of term and near-term healthy
newborn infants in car safety seats. Pediatrics 2001;108:
64752.
14. Sarici SU, Serdar MA, Korkmaz A, Erdem G, Oran O,
Tekinalp G, et al. Incidence, course, and prediction of
hyperbilirubinemia in near-term and term newborns.
Pediatrics 2004;113:77580.
15. Newman TB, Escobar GJ, Gonzales VM, Armstrong MA,
Gardner MN, Folck BF. Frequency of neonatal bilirubin
testing and hyperbilirubinemia in a large health maintenance organization [published erratum appears in
Pediatrics 2001;1:126]. Pediatrics 1999;104:1198203.
16. Newman TB, Liljestrand P, Escobar GJ. Infants with bilirubin levels of 30 mg/dL or more in a large managed care
organization. Pediatrics 2003;111:130311.
17. Chou SC, Palmer RH, Ezhuthachan S, Newman C, PradellBoyd B, Maisels MJ, et al. Management of hyperbilirubinemia in newborns: measuring performance by using a
benchmarking model. Pediatrics 2003;112:126473.
18. Escobar GJ, Greene JD, Hulac P, Kincannon E, Bischoff K,
Gardner MN, at al. Rehospitalisation after birth hospitalisation: patterns among infants of all gestations. Arch Dis
Child 2005;90:12531.
19. Bhutani VK, Johnson LH, Maisels MJ, Newman TB, Phibbs
C, Stark AR, et al. Kernicterus: epidemiological strategies for
its prevention through systems-based approaches.
J Perinatol 2004;24:65062.
20. Brown AK, Damus K, Kim MH, King K, Harper R,
Campbell D, et al. Factors relating to readmission of term
and near-term neonates in the first two weeks of life. Early
Discharge Survey Group of the Health Professional
Advisory Board of the Greater New York Chapter of the
March of Dimes. J Perinat Med 1999;27:26375.
21. Arnon S, Dolfin T, Litmanovitz I, Regev R, Bauer S, Fejgin
M. Preterm labour at 3436 weeks of gestation: should it be
arrested? Paediatr Perinat Epidemiol 2001;15:2526.
22. Avery ME, Mead J. Surface properties in relation to atelectasis and hyaline membrane disease. AMA J Dis Child 1959;
97:51723.
23. Jobe AH. The respiratory system. Part 1: lung development
and maturation. In: Martin RJ, Fanaroff AA, Walsh MC,
editors. Fanaroff and Martins neonatal-perinatal medicine:
diseases of the fetus and infant. 8th ed. Philadelphia (PA):
Mosby Elsevier; 2006. p. 10691194.
24. Post M. Lung development: pulmonary structure and function. In: Gluckman PD, Heymann MA, editors. Pediatrics
and perinatology: the scientific basis. 2nd ed. New York
(NY): Oxford University Press; 1996. p. 797800.
25. Hawgood S. Alveolar region: pulmonary structure and
function. In: Gluckman PD, Heymann MA, editors.
Pediatrics and perinatology: the scientific basis. 2nd ed.
New York (NY): Oxford University Press; 1996. p. 8149.
26. Jain L, Eaton DC. Physiology of fetal lung fluid clearance
and the effect of labor. Semin Perinatol 2006;30:3443.
27. Hunt CE. Ontogeny of autonomic regulation in late preterm infants born at 3437 weeks postmenstrual age. Semin
Perinatol 2006;30:7376.
28. Henderson-Smart DJ, Pettigrew AG, Campbell DJ. Clinical
apnea and brain-stem neural function in preterm infants.
N Engl J Med 1983;308:3537.
29. Ramanathan R, Corwin MJ, Hunt CE, Lister G, Tinsley LR,
Baird T, et al. Cardiorespiratory events recorded on home
monitors: comparison of healthy infants with those at
increased risk for SIDS. Collaborative Home Infant
Monitoring Evaluation (CHIME) Study Group. JAMA
2001;285:2199207.
30. Curzi-Dascalova L, Christova-Gueorguieva E. Respiratory
pauses in normal prematurely born infants. A comparison
with full-term newborns. Biol Neonate 1983;44:32532.
31. Miller MJ, Fanaroff AA, Martin RJ. The respiratory system.
Part 5: respiratory disorders in preterm and term infants. In:
Martin RJ, Fanaroff AA, Walsh MC, editors. Fanaroff and
Martins neonatal-perinatal medicine: diseases of the fetus
COMMITTEE OPINIONS
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Lee LA, Kimball TR, Daniels SR, Khoury P, Meyer RA. Left
ventricular mechanics in the preterm infant and their effect
on the measurement of cardiac performance. J Pediatr
1992;120:11419.
Zahka KG. The cardiovascular system. Part 4: principles of
neonatal cardiovascular hemodynamics. In: Martin RJ,
Fanaroff AA, Walsh MC, editors. Fanaroff and Martins
neonatal-perinatal medicine: diseases of the fetus and
infant. 8th ed. Philadelphia (PA): Mosby Elsevier; 2006.
p. 121115.
Randala M, Eronen M, Andersson S, Pohjavuori M,
Pesonen E. Pulmonary artery pressure in term and preterm
neonates. Acta Paediatr 1996;85:134447.
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Averys disease of the newborn. 8th ed. Philadelphia (PA):
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Kalhan SC, Parimi PS. Metabolic and endocrine disorders.
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RJ, Fanaroff AA, Walsh MC, editors. Fanaroff and Martins
neonatal-perinatal medicine: diseases of the fetus and
infant. 8th ed. Philadelphia (PA): Mosby Elsevier; 2006.
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bilirubin and the effect of premature birth on this activity
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Al Tawil Y, Berseth CL. Gestational and postnatal maturation of duodenal motor responses to intragastric feeding.
J Pediatr 1996;129:37481.
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infants in the first 2 weeks of life. J Perinatol 2000;20:
4327.
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43. Soskolne EI, Schumacher R, Fyock C, Young ML, Schork A.
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Carpenter DM. Rehospitalization in the first two weeks
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ISSN 1074-861X
568

Prenatal and Perinatal Human

Immunodeficiency Virus Testing: Expanded
Recommendations
Committee on
Obstetric Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Early identification and treatment of all pregnant women with human
immunodeficiency virus (HIV) is the best way to prevent neonatal disease and improve
the womans health. Human immunodeficiency virus screening is recommended for all
pregnant women after they are notified that they will be tested for HIV infection as part
of the routine panel of prenatal blood tests unless they decline the test (ie, opt-out
screening). Repeat testing in the third trimester, or rapid HIV testing at labor and delivery
as indicated or both also are recommended as additional strategies to further reduce
the rate of perinatal HIV transmission. The American College of Obstetricians and
Gynecologists makes the following recommendations: obstetriciangynecologists should
follow opt-out prenatal HIV screening where legally possible; repeat conventional or rapid
HIV testing in the third trimester is recommended for women in areas with high HIV
prevalence, women known to be at high risk for acquiring HIV infection, and women who
declined testing earlier in pregnancy; rapid HIV testing should be used in labor for women
with undocumented HIV status following opt-out screening; and if a rapid HIV test result
in labor is positive, immediate initiation of antiretroviral prophylaxis should be recommended without waiting for the results of the confirmatory test.
The Centers for Disease Control and Prevention (CDC) estimates that 40,000 new cases
of human immunodeficiency virus (HIV)
infection still occur in the United States each
year (1). This figure includes approximately
138 infants infected via mother-to-child
(vertical) transmission (2). Antiretroviral
medications given to women with HIV perinatally and to their newborns in the first
weeks of life reduce the vertical transmission
rate from 25% to 2% or less (36). Even instituting maternal prophylaxis during labor and
delivery, or neonatal prophylaxis within
2448 hours of delivery, or both can substantially decrease rates of infection in infants
(4). A retrospective review of HIV-exposed
infants in New York State showed a transmission rate of approximately 10% when
zidovudine prophylaxis was begun intrapartum or if given to newborns within 48
hours of life. There is no significant reduction of neonatal transmission if therapy is
started after 3 days of life (4). Early identification and treatment of pregnant women
and prophylactic treatment of newborns in
the first hours of life are essential to prevent
neonatal disease.
Prenatal Human
Immunodeficiency Virus
Testing
All pregnant women should be screened for
HIV infection as early as possible during each
pregnancy after they are notified that HIV
screening is recommended for all pregnant
patients and that they will receive an HIV test
as part of the routine panel of prenatal tests
unless they decline (opt-out screening). No
woman should be tested without her knowledge; however, no additional process or written documentation of informed consent
beyond what is required for other routine
prenatal tests is required for HIV testing.
Pregnant women should be provided with
COMMITTEE OPINIONS
oral or written information about HIV (1, 7) that

includes an explanation of HIV infection, a description of
interventions that can reduce HIV transmission from
mother to infant, the meanings of positive and negative
test results, and the opportunity to ask questions and
decline testing (1). If a patient declines HIV testing,
this should be documented in the medical record and
should not affect access to care. Women who decline an
HIV test because they have had a previous negative test
result should be informed of the importance of retesting
during each pregnancy (1). The American College of
Obstetricians and Gynecologists, the American Academy
of Pediatrics (7), and the CDC (1, 8) recommend opt-out
HIV screening for pregnant women. Since the release of
CDC recommendations in September 2006 (1), some
states have changed their state laws and regulations to
opt-out screening. Obstetriciangynecologists should be
aware of and comply with their states legal requirements
for perinatal HIV screening. Legal requirements for perinatal HIV testing may be verified by contacting state or
local public health departments. The National HIV/AIDS
Clinicians Consultation Center at the University of
CaliforniaSan Francisco maintains an online compendium of state HIV testing laws that can be a useful resource
(see Resources). The Centers for Disease Control and
Prevention recommend that jurisdictions with barriers to
routine prenatal screening using opt-out screening consider addressing them (9).
Perinatal Human Immunodeficiency

Virus Testing
The conventional HIV testing algorithm, which may take
up to 2 weeks to complete if a result is positive, begins
with a screening test, the enzyme-linked immunosorbent
assay (ELISA) that detects antibodies to HIV; if the results
are positive, it is followed by a confirmatory test, either a
Western blot or an immunofluorescence assay (IFA). A
positive ELISA test result is not diagnostic of HIV infection unless confirmed by the Western blot or IFA. The
sensitivity and specificity of ELISA with a confirmatory
Western blot test are greater than 99%. The false-positive
rate for ELISA with a confirmatory Western blot test is 1
in 59,000 tests. If the ELISA test result is positive and the
Western blot or IFA test result is negative, the patient is
not infected and repeat testing is not indicated.
If the ELISA test result is repeatedly positive and the
Western blot result contains some but not all of the viral
bands required to make a definitive diagnosis, the test
result is labeled indeterminate. Most patients with indeterminate test results are not infected with HIV. However,
consultation with a health care provider well versed in
HIV infection is recommended. This specialist may suggest viral load testing or repeat testing later in pregnancy
to rule out the possibility of recent infection.
If the screening (eg, ELISA) and confirmatory test
(eg, Western blot or IFA) results are both positive, the
patient should be given her results in person. The impli-
569
cations of HIV infection and vertical transmission should

be discussed with the patient. Additional laboratory evaluation, including CD4 count, HIV viral load, resistance
testing, hepatitis C virus antibody, hepatitis B surface
antigen, complete blood count with platelet count, and
baseline chemistries with liver function tests, will be useful before prescribing antiretroviral prophylaxis.
A rapid HIV test is an HIV screening test with results
available within hours. Obstetriciangynecologists may
use rapid testing as their standard outpatient test and
should also use rapid testing in labor and delivery (see
details as follows regarding labor and delivery). A negative
rapid test result is definitive. A positive rapid test result is
not definitive and must be confirmed with a supplemental
test, such as a Western blot or IFA test. Rapid test results
usually will be available during the same clinical visit that
the specimen (eg blood, or oral swab) is collected. Health
care providers who use these tests must be prepared to
provide counseling to pregnant women who receive positive rapid test results the same day that the specimen is collected. Pregnant women with positive rapid test results
should be counseled regarding the meaning of these preliminary positive test results and the need for confirmatory testing. As with conventional HIV testing, consultation
with a health care provider well versed in HIV infection is
recommended. To code for rapid testing, the modifier 92
is added to the basic HIV testing Current Procedural
Terminology (CPT )* code 86701-86703) (10). If the
results of the rapid test and the confirmatory test are discrepant, both tests should be repeated and consultation
with an infectious disease specialist is recommended.
Any woman who arrives at a labor and delivery facility with undocumented HIV status should be screened
with a rapid HIV test unless she declines (opt-out screening) in order to provide an opportunity to begin prophylaxis of previously undiagnosed infection before delivery
(1). Data from several studies indicate that 4085% of
infants infected with HIV are born to women whose HIV
infection is unknown to their obstetric provider before
delivery (1114). If a rapid test is used in labor and HIV
antibodies are detected, immediate initiation of antiretroviral prophylaxis should be recommended without waiting for the results of the confirmatory test to further
reduce possible transmission to the infant. All antiretroviral prophylaxis should be discontinued if the confirmatory test result is negative (11). Recommendations for the
use of antiretroviral medications in pregnant women
infected with HIV are available at www.aidsinfo.nih.gov
and are updated frequently.
The rapid HIV antibody screening tests, which are
approved by the U.S. Food and Drug Administration, all
have sensitivity and specificity equal to or greater than
*Current Procedural Terminology (CPT) is copyright 2008 by
American Medical Association. All rights reserved. No fee schedules,
basic units, relative values, or related listings are included in CPT. The
AMA assumes no liability for the data contained herein. CPT is a
trademark of the American Medical Association.
570
99% (15). As with all screening tests, the likelihood of a

false-positive result is higher in populations with low HIV
prevalence when compared with populations with high
HIV prevalence. Additionally, at present it is not known
how the false-positive rate for rapid testing will compare
with the false-positive rate for conventional testing.
If the rapid HIV test result at labor and delivery is positive, the obstetric provider should take the following steps:
1. Tell the woman she may have HIV infection and that
her neonate also may be exposed
2. Explain that the rapid test result is preliminary and
that false-positive results are possible
3. Assure the woman that a second test is being done
right away to confirm the positive rapid test result
4. Immediate initiation of antiretroviral prophylaxis
should be recommended without waiting for the
results of the confirmatory test to reduce the risk of
transmission to the infant
5. Once the woman gives birth, discontinue maternal
antiretroviral therapy pending receipt of confirmatory test results
6. Tell the woman that she should postpone breast-feeding until the confirmatory result is available because
she should not breast-feed if she is infected with HIV
7. Inform pediatric care providers (depending on state
requirements) of positive maternal test results so
that they may institute the appropriate neonatal
prophylaxis
Repeat Human Immunodeficiency

Virus Testing in the Third Trimester
Repeat testing in the third trimester should be considered
in jurisdictions with elevated HIV or AIDS incidence and
in health care facilities in which prenatal screening identifies at least one HIV-infected pregnant woman per 1,000
women screened (1). Additionally, although physicians
need to be aware of and follow their states perinatal HIV
screening requirements, repeat testing in the third
trimester, preferably before 36 weeks of gestation, is recommended for pregnant women at high risk for acquiring HIV. Criteria for repeat testing can include (1):
Have been diagnosed with another sexually transmitted disease in the last year
Injection drug use or the exchange of sex for money
or drugs
A new or more than one sex partner during this
pregnancy or a sex partner(s) known to be HIV-positive or at high risk
Women who are candidates for third-trimester testing, including those who declined testing earlier in pregnancy, should be given a conventional or rapid HIV test
rather than waiting to receive a rapid test at labor and
delivery (as allowed by state laws and regulations).
Recommendations
Given the enormous advances in the prevention of perinatal transmission of HIV, it is clear that early identification and treatment of all pregnant women with HIV is the
best way to prevent neonatal disease and also may
improve the womens health. Therefore, the American
College of Obstetricians and Gynecologists makes the following recommendations:
Screen all pregnant women for HIV as early as possible during each pregnancy following opt-out prenatal HIV screening where legally possible
Repeat HIV testing in the third trimester is recommended for women in areas with high HIV prevalence, women known to be at high risk for acquiring
HIV infection, and women who declined testing earlier in pregnancy
Use conventional or rapid HIV testing for women
who are candidates for third-trimester testing
Use rapid HIV testing in labor for women with undocumented HIV status following opt-out screening
If a rapid HIV test result in labor is positive, immediate initiation of antiretroviral prophylaxis should be
recommended without waiting for the results of the
confirmatory test
Resources
AIDSinfo
PO Box 6303
Rockville, MD 20849-6303
1-800-448-0440
www.aidsinfo.nih.gov
409 12th Street SW, PO Box 96920
800-673-8444 or (202) 638-5577
www.acog.org
Perinatal HIV page: www.acog.org/goto/HIV
ACOG Bookstore: www.acog.org/bookstore
1600 Clifton Road NE
Atlanta, GA 30333
(404) 639-3311 or 800-232-4636
www.cdc.gov
HIV/AIDS page: www.cdc.gov/hiv
National AIDS Hotline: 800-342-AIDS (2437) (English);
800-344-7432 (Spanish); 800-243-7889 (TTY, deaf access)
www.cdc.gov/hiv
National HIV/AIDS Clinicians Consultation Center
UCSF Department of Family and Community Medicine at
San Francisco General Hospital
1001 Potrero Ave., Bldg. 20, Ward 22
(415) 206-8700
Perinatal HIV Hotline: 1-888-448-8765
www.nccc.ucsf.edu
COMMITTEE OPINIONS
References
health-care settings. MMWR Recomm Rep 2006;55(RR14):117; quiz CE1-4.
2. McKenna MT, Hu X. Recent trends in the incidence and
morbidity that are associated with perinatal human
immunodeficiency virus infection in the United States. Am
J Obstet Gynecol 2007;197(suppl):S106.
3. Recommendations of the U.S. Public Health Service Task
Force on the use of zidovudine to reduce perinatal transmission of human immunodeficiency virus. MMWR
Recomm Rep 1994;43(RR-11):120.
4. Wade NA, Birkhead GS, Warren BL, Charbonneau TT,
French PT, Wang L, et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human
immunodeficiency virus. N Engl J Med 1998;339:140914.
5. Mofenson LM, Lambert JS, Stiehm ER, Bethel J, Meyer WA
3rd, Whitehouse J, et al. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women
treated with zidovudine. Pediatric AIDS Clinical Trials
Group Study 185 Team. N Engl J Med 1999;341:38593.
6. Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC,
Burchett SK, et al. Maternal levels of plasma human
immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study
Group. N Engl J Med 1999;341:394402.
Obstetricians and Gynecologists. Joint statement on human
immunodeficiency virus screening. Elk Grove Village (IL):
AAP; Washington (DC): ACOG; 1999; Reaffirmed 2006.
8. Advancing HIV prevention: new strategies for a changing
epidemicUnited States, 2003. Centers for Disease Control
and Prevention (CDC). MMWR Morb Mortal Wkly Rep
2003;52:32932.
9. Gerberding JL, Jaffe HW. Routine prenatal testing the optout approach. Atlanta (GA): Centers for Disease Control
and Prevention; 2003. Available at: http://www.cdc.gov/
10.
11.
12.
13.
14.
15.
571
hiv/topics/perinatal/resources/other/dear_colleague2003.htm. Retrieved June 10, 2008.

American Medical Association. Current procedural terminology: CPT 2008. Standard ed. Chicago (IL): AMA; 2007.
Centers for Disease Control and Prevention. Rapid HIV-1
Antibody Testing during Labor and Delivery for Women of
Unknown HIV Status: A Practical Guide and Model
Protocol. Atlanta (GA): CDC; 2004. Available at: http://
www.cdc.gov/hiv/topics/testing/resources/guidelines/
rt-labor&delivery.htm. Retrieved June 10, 2008.
Peters V, Liu KL, Dominguez K, Frederick T, Melville S, Hsu
HW, et al. Missed opportunities for perinatal HIV prevention among HIV-exposed infants born 1996-2000, pediatric
spectrum of HIV disease cohort. Pediatrics 2003;111:
118691.
Gross E, Burr CK. HIV counseling and testing in pregnancy. N J Med 2003;100:216; quiz 678.
Paul SM, Grimes-Dennis J, Burr CK, DiFerdinando GT.
Rapid diagnostic testing for HIV. Clinical implications. N J
Med 2002;99:204; quiz 246.
Centers for Disease Control and Prevention. FDA-approved
rapid HIV antibody screening tests. Atlanta (GA): CDC;
2008. Available at: http://www.cdc.gov/hiv/topics/testing/
rapid/rt-comparison.htm. Retrieved June 10, 2008.
Prenatal and perinatal human immunodeficiency virus testing:
expanded recommendations. ACOG Committee Opinion No. 418.
Gynecol 2008;112:73942.
ISSN 1074-861X
572

Use of Progesterone to Reduce

Preterm Birth
Committee on
Obstetric Practice
followed.
The Society for

Maternal Fetal Medicine
Publications Committee

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Preterm birth affects 12% of all births in the United States. Recent
studies support the hypothesis that progesterone supplementation reduces preterm
birth in a select group of women. Despite the apparent benefits of progesterone, the
ideal progesterone formulation is unknown. The American College of Obstetricians and
Gynecologists Committee on Obstetric Practice and the Society for Maternal Fetal
Medicine believe that further studies are needed to evaluate the optimal preparation,
dosage, route of administration, and other indications for the use of progesterone for
the prevention of preterm delivery. Based on current knowledge, it is important to offer
progesterone for pregnancy prolongation to only women with a documented history of a
previous spontaneous birth at less than 37 weeks of gestation.
Preterm birth affects 12% of all births in the

United States. This statistic has led multiple
investigators to identify those women at
greatest risk (eg, those with prior preterm
delivery, multiple gestation, short cervical
length, maternal weight less than 50 kg,
bleeding, and those of African American
race). Recent randomized trials comparing
progesterone with placebo have been conducted using several groups at high risk and
low risk for preterm delivery. The purpose of
this Committee Opinion is to review these
results.
A large randomized placebo-controlled
trial investigating the use of 17-hydroxyprogesterone caproate (17P) therapy (250
mg administered intramuscularly) for the
prevention of preterm birth in a select, highrisk group of women (with a documented
history of a previous spontaneous singleton
preterm birth at less than 37 weeks of gestation) was conducted for the National
Institute of Child Health and Human
Development (NICHD) Maternal-Fetal Medicine Units Network (1). A total of 459
women with a history of previous spontaneous singleton births at less than 37 weeks
of gestation were enrolled between 16 weeks
and 20 weeks of gestation. Of note, the mean
gestational age of their previous preterm
deliveries was 30.7 weeks. They were ran-
domly assigned to receive weekly intramuscular injections of 17-hydroxyprogesterone

caproate (n = 306) or placebo (n = 153) from
enrollment to 37 weeks of gestation or delivery. The study was stopped early when results
showed a significant protection against
recurrent preterm birth for all races of
women who received 17-hydroxyprogesterone caproate. This study demonstrated
significant reductions in preterm and early
preterm birth, low birth-weight, as well as
significant reductions in infant complications (intraventricular hemorrhage, necrotizing enterocolitis, neonatal intensive care unit
admissions, and the need for supplemental
oxygen therapy) with progesterone therapy
(Table 1). Four-year follow-up found no
adverse health outcomes of surviving children (2).
In a randomized placebo-controlled trial
of supplemental vaginal progesterone (100
mg daily) in 142 women at high risk for
preterm birth (more than 90% of whom had
a previous spontaneous singleton preterm
birth) the authors found that for delivery at
less than 34 weeks of gestation, the preterm
birth rate was significantly lower among
women receiving progesterone than among
those receiving placebo (2.7% versus 18.6%)
(3). The results of this study and the NICHD
trial support the hypothesis that proges-
COMMITTEE OPINIONS
573
Table 1. Rates of Preterm Labor With Progesterone Therapy or Placebo

Placebo Group
(n = 153)
Progesterone
Group (n = 306)
Relative
Risk
Confidence
Interval
Less than 37 weeks
54.9%
36.3%
0.66
0.540.81
.001
Less than 35 weeks
30.7%
20.6%
0.67
0.480.93
.0165
Less than 32 weeks
19.6%
11.4%
0.58
0.370.91
.0180
Gestation
Data from Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.
N Engl J Med 2003;348:237985.
terone supplementation reduces preterm birth in women

at risk for preterm birth, with a prior preterm birth.
The effectiveness of progesterone supplementation
has been evaluated in several other high-risk groups for
preterm delivery, with conflicting results. A randomized
trial of 17-hydroxyprogesterone caproate in 661 women
with twin gestations found no benefit of progesterone
supplementation for the prevention of preterm delivery
(4). A randomized trial of 659 women with a history of
spontaneous preterm delivery randomized and treated
between 18 weeks and 23 weeks of gestation with 90 mg
of natural progesterone vaginal gel or placebo found no
improvement in preterm birth at less than 37 weeks, less
than 35 weeks or less than 32 weeks of gestation. (5).
Another randomized trial evaluated asymptomatic
women with a short cervix and singleton and twin gestations. Of 24,620 women screened with endovaginal ultrasonography between 20 weeks and 25 weeks of gestation,
413 women had a cervical length less than 15 mm (1.5%)
and of those women, 250 were randomized (1:1) to daily
vaginal progesterone (200 mg micronized progesterone
capsules) or placebo from 24 weeks to 34 weeks of gestation. Of note, 15% of the study population had a history
of a prior preterm delivery and 10% of the study population had a twin gestation. Overall, progesterone therapy
significantly reduced the rate of spontaneous preterm
birth at less than 34 weeks of gestation (19.2% versus
34.3%) [6].
Despite the apparent benefits of progesterone in
some situations, the ideal formulation is unknown. The
17-hydroxyprogesterone caproate used in the NICHD
trial was specially formulated for the trial and is not currently commercially available. Although the initial trial
(3) used 100 mg vaginal suppositories and demonstrated
pregnancy prolongation with treatment, vaginal progesterone gel was not beneficial in reducing preterm birth in
women with a history of spontaneous preterm delivery
randomized and treated between 18 weeks and 23 weeks
of gestation (5). Micronized progesterone capsules (200
mg vaginally daily) were used in the trial of progesterone
for asymptomatic women with a very short cervix (less
than 15 mm), and appeared to be effective for this indication (6). Whether the differences seen in efficacy of the
recently studied vaginal preparations reflects differences
in dosages (100 mg versus 200 mg), variation in absorp-
tion and bioavailability with different preparations (gel

versus capsule versus suppository), or differences in study
populations remain to be elucidated. Progesterone has not
been studied as a supplemental treatment to cervical cerclage for suspected cervical insufficiency, as a preventive
agent for asymptomatic women with a positive cervicovaginal fetal fibronectin screen result, as a tocolytic agent,
or as a therapeutic agent after tocolysis, and it should not
be used at this time for these indications alone.
Progesterone supplementation for the prevention of
recurrent preterm birth should be offered to women with
a singleton pregnancy and a prior spontaneous preterm
birth due to spontaneous preterm labor or premature
rupture of membranes. Current evidence does not support the routine use of progesterone in women with multiple gestations. Progesterone supplementation for
asymptomatic women with an incidentally identified very
short cervical length (less than 15 mm) may be considered; however, routine cervical length screening is not
recommended. The American College of Obstetricians
and Gynecologists Committee on Obstetric Practice and
the Society for Maternal Fetal Medicine believe that further studies are needed to determine if there are other
indications for progesterone therapy for the prevention of
preterm delivery.
References
1. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B,
Moawad AH, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. National
Maternal-Fetal Medicine Units Network [published erratum appears in N Engl J Med 2003;349:1299]. N Engl J
Med 2003;348:237985.
2. Northen AT, Norman GS, Anderson K, Moseley L, Divito M,
Cotroneo M, et al. Follow-up of children exposed in utero
to 17 alpha-hydroxyprogesterone caproate compared with
placebo. National Institute of Child Health and Human
Development (NICHD) Maternal-Fetal Medicine Units
(MFMU) Network. Obstet Gynecol 2007;110: 86572.
3. da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M.
Prophylactic administration of progesterone by vaginal
suppository to reduce the incidence of spontaneous
preterm birth in women at increased risk: a randomized
placebo-controlled double-blind study. Am J Obstet
Gynecol 2003;188:41924.
574
4. Rouse DJ, Caritis SN, Peaceman AM, Sciscione A, Thom

EA, Spong CY, et al. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. National
Maternal-Fetal Medicine Units Network. N Engl J Med
2007;357:45461.
5. OBrien JM, Adair CD, Lewis DF, Hall DR, Defranco EA,
Fusey S, et al. Progesterone vaginal gel for the reduction of
recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound
6. da Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH.
Progesterone and the risk of preterm birth among women
with a short cervix. N Engl J Med 2007;357:4629.

Use of progesterone to reduce preterm birth. ACOG Committee
ISSN 1074-861X
COMMITTEE OPINIONS
575

(Replaces Practice Bulletin No. 47, October 2003)
Antibiotic Prophylaxis for Infective

Endocarditis
Committee on
Obstetric Practice
followed.
ABSTRACT: The recommendations for endocarditis prophylaxis from the American

Heart Association have changed for three main reasons: 1) most cases of endocarditis
are not attributable to an invasive procedure but rather are the result of randomly occurring bacteremia from routine daily activities; 2) prophylaxis may only prevent a small number of cases of infective endocarditis in women undergoing genitourinary procedures;
and 3) the risk of antibiotic associated adverse events exceeds the benefit, if any, from
prophylactic antibiotic therapy. The specific changes pertinent to the obstetriciangynecologist are discussed.
The recommendations for endocarditis prophylaxis from the American Heart Association have changed for three main reasons:
1) most cases of endocarditis are not
attributable to an invasive procedure but
rather are the result of randomly occurring
bacteremia from routine daily activities;
2) prophylaxis may only prevent a small
number of cases of infective endocarditis in
women undergoing genitourinary procedures; and 3) the risk of antibiotic associated
adverse events exceeds the benefit, if any,
from prophylactic antibiotic therapy (1). The
specific changes pertinent to the obstetriciangynecologist are discussed as follows.
Delivery
Infective endocarditis prophylaxis is no longer
recommended for vaginal or cesarean delivery
in the absence of infection, regardless of the
type of maternal cardiac lesion. Mitral valve
prolapse is no longer considered a lesion that
ever needs infective endocarditis prophylaxis.
Only cardiac conditions associated with the
highest risk of adverse outcome from endocarditis are appropriate for any infective
endocarditis prophylaxis (see box). In patients
of Obstetricians
and Gynecologists
Womens Health Care
Physicians
with one of these conditions and who have an

established infection that could cause bacteremia, such as chorioamnionitis or pyelonephritis, the underlying infection should be
treated in the usual fashion and the treatment
should include a regimen effective for infective endocarditis prophylaxis (Table 1).
Prophylaxis should be given intravenously.
Dental Procedures
The American Heart Association recommends that only those women with the cardiac conditions associated with the highest
risk of adverse outcome from endocarditis
(see box) receive infective endocarditis prophylaxis for certain dental procedures.
Specifically, prophylaxis should be provided
for all dental procedures that include manipulation of the gingival tissue or periapical
region of the teeth or oral mucosa.
Prophylaxis is not required in the following
circumstances: injecting anesthetic into noninfected tissue, general dental cleaning, cavity
filling, performing radiography, placing or
adjusting orthodontic appliances, or when
there is bleeding from trauma to lips and oral
mucosa.
576
Table 1. Antibiotic Prophylaxis Appropriate for Infective Endocarditis

Treatment
Regimen (preferably
3060 min before procedure)
Antibiotic
Intravenous therapy
Ampicillin or
Cefazolin or ceftriaxone
2 g intravenously
1 g intravenously
Allergic to penicillin or ampicillin*
Cefazolin or ceftriaxone
or clindamycin
1 g intravenously
600 mg intravenously
Oral
Amoxicillin
2g
*Cephalosporins should not be used in patients with a significant sensitivity to penicillins.
This regimen does not cover enterococcus. Vancomycin can be used if enterococcus is of concern.
Reference
Cardiac Conditions for Which
Prophylaxis for Deliveries Associated
with Infection, or Certain Dental
Procedures, is Reasonable
Prosthetic cardiac valve or prosthetic material used
for cardiac valve repair
Previous infective endocarditis
Congenital heart disease (CHD)*
Unrepaired cyanotic CHD, including palliative
shunts and conduits
Completely repaired CHD with prosthetic material
or device whether placed by surgery or catheter
intervention, during the first 6 months after procedure
Repaired CHD with residual defects at the site or
adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)
*Except for the conditions listed, antibiotic prophylaxis is no
longer recommended for any other form of CHD.
Prophylaxis is reasonable because endothelialization of prosthetic material occurs within 6 months after the procedure.
1. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour

LM, Levison M, et al. Prevention of infective endocarditis:
guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever,
Endocarditis, and Kawasaki Disease Committee, Council
on Cardiovascular Disease in the Young, and the Council on
Clinical Cardiology, Council on Cardiovascular Surgery
and Anesthesia, and the Quality of Care and Outcomes
Research Interdisciplinary Working Group [published erratum appears in Circulation 2007;116:e376-7]. Circulation
2007;116:173654.

Antibiotic prophylaxis for infective endocarditis. ACOG Committee
ISSN 1074-861X
COMMITTEE OPINIONS
577

Number 433 May 2009
Optimal Goals for Anesthesia Care in

Obstetrics
Committee on
Obstetric Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
409 12th Street, SW
PO Box 96920
ABSTRACT: A joint statement from the American Society of Anesthesiologists and

the American College of Obstetricians and Gynecologists was developed to address
issues of concern to both specialties. Good obstetric care requires the availability of qualified personnel and equipment to administer general or regional anesthesia both electively and emergently. The extent and degree to which anesthesia services are available
varies widely among hospitals. However, for hospitals providing obstetric care, certain
optimal anesthesia goals should be sought.
This joint statement from the American

Society of Anesthesiologists and the American
has been designed to address issues of concern to both specialties. Good obstetric care
requires the availability of qualified personnel and equipment to administer general or
regional anesthesia both electively and emergently. The extent and degree to which anesthesia services are available varies widely
among hospitals. However, for any hospital
providing obstetric care, certain optimal
anesthesia goals should be sought as follows:
I. Availability of a licensed practitioner who
is credentialed to administer an appropriate anesthetic whenever necessary.
For many women, regional anesthesia
(epidural, spinal, or combined spinal
epidural) will be the most appropriate
anesthetic.
II. Availability of a licensed practitioner
who is credentialed to maintain support
of vital functions in any obstetric emergency.
III. Availability of anesthesia and surgical
personnel to permit the start of a cesarean delivery within 30 minutes of the
decision to perform the procedure.
IV. Immediate availability of appropriate
facilities and personnel, including obstetric anesthesia, nursing personnel, and a
physician capable of monitoring labor
and performing cesarean delivery, in-
cluding an emergency cesarean delivery

in cases of vaginal birth after cesarean
delivery (1). The definition of immediately available personnel and facilities
remains a local decision based on each
institutions available resources and geographic location.
V. Appointment of a qualified anesthesiologist to be responsible for all anesthetics
administered. There are many obstetric
units where obstetricians or obstetriciansupervised nurse anesthetists administer
labor anesthetics. The administration of
general or regional anesthesia requires
both medical judgment and technical
skills. Thus, a physician with privileges
in anesthesiology should be readily
available.
Persons administering or supervising
obstetric anesthesia should be qualified to
manage the infrequent but occasional lifethreatening complications of major regional
anesthesia such as respiratory and cardiovascular failure, toxic local anesthetic convulsions, or vomiting and aspiration. Mastering
and retaining the skills and knowledge
necessary to manage these complications
require adequate training and frequent application.
To ensure the safest and most effective
anesthesia for obstetric patients, the director
of anesthesia services, with the approval of
the medical staff, should develop and enforce
578
written policies regarding provision of obstetric anesthesia as follows:

I. A qualified physician with obstetric privileges to perform operative vaginal or cesarean delivery should be
readily available during administration of anesthesia.
Readily available should be defined by each institution within the context of its resources and geographic location. Regional or general anesthesia or
both should not be administered until the patient has
been examined and the fetal status and progress of
labor evaluated by a qualified individual. A physician
with obstetric privileges who concurs with the
patients management and has knowledge of the
maternal and fetal status and the progress of labor
should be readily available to handle any obstetric
complications that may arise. A physician with
obstetric privileges should be responsible for midwifery back up in hospital settings that utilize certified nursemidwives and certified midwives as
obstetric providers.
II. Availability of equipment, facilities, and support personnel equal to that provided in the surgical suite.
This should include the availability of a properly
equipped and staffed recovery room capable of
receiving and caring for all patients recovering from
major regional or general anesthesia. Birthing facilities, when used for analgesia or anesthesia, must be
appropriately equipped to provide safe anesthetic
care during labor and delivery or postanesthesia
recovery care.
III. Personnel other than the surgical team should be
immediately available to assume responsibility for
resuscitation of the depressed newborn. The surgeon
and anesthesiologist are responsible for the mother
and may not be able to leave her to care for the newborn even when a regional anesthetic is functioning
adequately. Individuals qualified to perform neonatal
resuscitation should demonstrate:
A. Proficiency in rapid and accurate evaluation of the
newborn condition, including Apgar scoring
B. Knowledge of the pathogenesis of a depressed
newborn (acidosis, drugs, hypovolemia, trauma,
anomalies, and infection), as well as specific indications for resuscitation
C. Proficiency in newborn airway management,
laryngoscopy, endotracheal intubations, suctioning of airways, artificial ventilation, cardiac massage, and maintenance of thermal stability
In larger maternity units and those functioning as
high-risk centers, 24-hour in-house anesthesia, obstetric,
and neonatal specialists usually are necessary. Preferably,
the obstetric anesthesia services should be directed by an
anesthesiologist with special training or experience in
obstetric anesthesia. These units also will frequently
require the availability of more sophisticated monitoring

equipment and specially trained nursing personnel.
A survey jointly sponsored by the American Society
of Anesthesiologists and The American College of
Obstetricians and Gynecologists found that many hospitals in the United States have not yet achieved the goals
mentioned previously. Deficiencies were most evident in
smaller delivery units. Some small delivery units are necessary because of geographic considerations. Currently,
approximately 34% of hospitals providing obstetric care
have fewer than 500 deliveries per year (2). Providing
comprehensive care for obstetric patients in these small
units is extremely inefficient, not cost-effective, and frequently impossible. Thus, the following recommendations are made:
1. Whenever possible, small units should consolidate.
2. When geographic factors require the existence of
smaller units, these units should be part of a wellestablished regional perinatal system.
The availability of the appropriate personnel to assist
in the management of a variety of obstetric problems is a
necessary feature of good obstetric care. The presence of
a pediatrician or other trained physician at a high-risk
cesarean delivery to care for the newborn, or the availability of an anesthesiologist during active labor and
delivery when vaginal birth after cesarean delivery is
attempted and at a breech or multifetal delivery are
examples. Frequently, these physicians spend a considerable amount of time standing by for the possibility that
their services may be needed emergently but may ultimately not be required to perform the tasks for which
they are present. Reasonable compensation for these
standby services is justifiable and necessary.
A variety of other mechanisms have been suggested to
increase the availability and quality of anesthesia services in obstetrics. Improved hospital design, which places
labor and delivery suites closer to the operating rooms,
would allow for more efficient supervision of nurseanesthetists. Anesthesia equipment in the labor and delivery
area must be comparable to that in the operating room.
Finally, good interpersonal relations between obstetricians and anesthesiologists are important. Joint meetings between the two departments should be encouraged.
Anesthesiologists should recognize the special needs and
concerns of obstetricians and obstetricians should recognize anesthesiologists as consultants in the management
of pain and life-support measures. Both should recognize
the need to provide high-quality care for all patients.
References
1. Vaginal birth after previous cesarean delivery. ACOG
2. Bucklin BA, Hawkins JL, Anderson JR, Ullrich FA. Obstetric
anesthesia workforce survey: twenty-year update. Anesthesiology 2005;103:64553.
COMMITTEE OPINIONS

Gynecologists and the American Society of Anesthesiologists.
All rights reserved. No part of this publication may be reproduced,
stored in a retrieval system, posted on the Internet, or transmitted, in
any form or by any means, electronic, mechanical, photocopying,
recording, or otherwise, without prior written permission from the
publisher. Requests for authorization to make photocopies should be
directed to: Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1074-861X
Optimal goals for anesthesia care in obstetrics. ACOG Committee
Opinion No. 433. American College of Obstetricians and Gynecologists and American Society of Anesthesiologists. Obstet Gynecol
2009;113:11979.
579
580

Postpartum Screening for Abnormal

Glucose Tolerance in Women Who Had
Gestational Diabetes Mellitus
Committee on
Obstetric Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Establishing the diagnosis of gestational diabetes mellitus offers an

opportunity not only to improve pregnancy outcome, but also to decrease risk factors
associated with the subsequent development of type 2 diabetes. The American College
of Obstetricians and Gynecologists Committee on Obstetric Practice recommends that
all women with gestational diabetes mellitus be screened at 612 weeks postpartum and
managed appropriately.
Gestational diabetes mellitus (GDM),

defined as carbohydrate intolerance leading
to hyperglycemia with onset or first recognition during pregnancy, affects 210% of
pregnancies in the United States depending
on the characteristics of the population studied (1). Gestational diabetes mellitus is characterized by insulin resistance that is specific
to pregnancy. This Committee Opinion augments ACOG Practice Bulletin No. 30:
Gestational Diabetes (2) by highlighting
recent thinking about the risk for diabetes
mellitus among women whose pregnancies
were affected by GDM, and presents recommendations for screening and management
for these women.
Although the carbohydrate intolerance
of GDM frequently resolves after delivery (3,
4), up to one third of affected women will
have diabetes or impaired glucose metabolism at postpartum screening, and it has been
estimated that 1550% will develop diabetes
in the decades following the affected pregnancy (512). The original cutoff points for
performing an abnormal glucose tolerance
test in pregnancy were chosen for their ability to predict the subsequent onset of type 2
diabetes mellitus (13). Postpartum screening
at 612 weeks has been recommended for
women who had GDM to identify women
with diabetes mellitus, or impaired fasting
glucose level, or impaired glucose tolerance
(14, 19). The latter two may respond to life-
style modification and pharmacologic interventions to decrease incident diabetes.

However, there is marked variability in the
proportion of women with GDM who are
screened postpartum as well as in the type of
screening used (67, 9, 1520).
Either a fasting plasma glucose test or
the 75-g, 2-hour oral glucose tolerance test
are appropriate for diagnosing diabetes. Although the fasting plasma glucose test is
easier to perform, it lacks sensitivity for detecting other forms of abnormal glucose metabolism; results of the oral glucose tolerance test
can confirm an impaired fasting glucose level
and impaired glucose tolerance (see Table 1).
In light of this, the Fifth International Workshop on GDM recommended that women
with GDM undergo a 75-g oral glucose tolerance test 612 weeks postpartum (21).
Establishing the diagnosis of GDM offers
an opportunity not only to improve pregnancy outcome, but also to affect risk factors
associated with the subsequent development
of type 2 diabetes. The American College of
Obstetricians and Gynecologists Committee
on Obstetric Practice recommends that all
women with GDM be screened at 612 weeks
postpartum and managed appropriately (see
Fig. 1). The American Diabetes Association
recommends repeat testing at least every 3
years for women who had a pregnancy affected by GDM and normal results of postpartum screening (14). For women who may
COMMITTEE OPINIONS
581
Table 1. Diagnostic criteria for diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance.
Diabetes
Impaired Fasting
Glucose
Fasting plasma
glucose
Fasting plasma glucose is

greater than or equal to 126
Fasting plasma glucose

is 100125
75-g 2 hr oral glucose

tolerance test
Fasting plasma glucose is

or
Fasting plasma glucose

is 100125
Test
Impaired Glucose
Tolerance
NA
2-hr plasma glucose is
140199
2-hr plasma glucose is

Gestational diabetes
FPG or 75-g 2 hr OGTT at 612 weeks postpartum
Diabetes mellitus
Refer for diabetes management
Impaired fasting glucose or IGT or both
Consider referral for management

Weight loss and physical activity
counseling as needed
Consider metformin if combined
impaired fasting glucose and IGT
Medical nutrition therapy
Yearly assessment of glycemic status
Normal
Assess glycemic status every

3 years
Weight loss and physical activity
counseling as needed
Fig. 1. Management of postpartum screening results. Abbreviations: FPG, fasting plasma glucose; OGTT, oral glucose
tolerance test; IGT, impaired glucose tolerance.
have subsequent pregnancies, screening more frequently

has the advantage of detecting abnormal glucose metabolism before pregnancy and provides an opportunity to
ensure preconception glucose control (21). Women
should be encouraged to discuss their GDM history and
need for screening with all of their health care providers.
References
1. Hunt KJ, Schuller KL. The increasing prevalence of diabetes
in pregnancy. Obstet Gynecol Clin North Am 2007;
34:17399, vii.
2. Gestational diabetes. ACOG Practice Bulletin No. 30.
3. Kaaja RJ, Greer IA. Manifestations of chronic disease during
pregnancy. JAMA 2005;294:27517.
4. Buchanan TA, Xiang AH. Gestational diabetes mellitus.

J Clin Invest 2005;115:48591.
5. Russell MA, Phipps MG, Olson CL, Welch HG, Carpenter
MW. Rates of postpartum glucose testing after gestational
diabetes mellitus. Obstet Gynecol 2006;108:145662.
6. Kim C, Tabaei BP, Burke R, McEwen LN, Lash RW, Johnson
SL, et al. Missed opportunities for type 2 diabetes mellitus
screening among women with a history of gestational diabetes mellitus. Am J Public Health 2006;96:16438.
7. Smirnakis KV, Chasan-Taber L, Wolf M, Markenson G,
Ecker JL, Thadhani R. Postpartum diabetes screening in
women with a history of gestational diabetes. Obstet
Gynecol 2005;106:1297303.
8. Schaefer-Graf UM, Buchanan TA, Xiang AH, Peters RK,
Kjos SL. Clinical predictors for a high risk for the development of diabetes mellitus in the early puerperium in
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10.
11.
12.
13.
14.
15.
16.
17.
women with recent gestational diabetes mellitus. Am J

Conway DL, Langer O. Effects of new criteria for type 2 diabetes on the rate of postpartum glucose intolerance in
women with gestational diabetes. Am J Obstet Gynecol
1999;181:6104.
Albareda M, Caballero A, Badell G, Piquer S, Ortiz A, de
Leiva A, et al. Diabetes and abnormal glucose tolerance in
women with previous gestational diabetes. Diabetes Care
2003;26:1199205.
Lee AJ, Hiscock RJ, Wein P, Walker SP, Permezel M.
Gestational diabetes mellitus: clinical predictors and longterm risk of developing type 2 diabetes: a retrospective
cohort study using survival analysis. Diabetes Care 2007;30:
87883.
Kim C, Newton KM, Knopp RH. Gestational diabetes and
the incidence of type 2 diabetes: a systematic review.
Diabetes Care 2002;25:18628.
OSullivan JB, Mahan CM. Criteria for the oral glucose tolerance test in pregnancy. Diabetes 1964;13:27885.
American Diabetes Association. Standards of medical care
in diabetes2008. Diabetes Care 2008;31(suppl 1):S1254.
Gabbe SG, Gregory RP, Power ML, Williams SB, Schulkin J.
Management of diabetes mellitus by obstetrician-gynecologists. Obstet Gynecol 2004;103:122934.
Dacus JV, Meyer NL, Muram D, Stilson R, Phipps P, Sibai
BM. Gestational diabetes: postpartum glucose tolerance
testing. Am J Obstet Gynecol 1994;171:92731.
Almario CV, Ecker T, Moroz LA, Bucovetsky L, Berghella V,
Baxter JK. Obstetricians seldom provide postpartum diabetes screening for women with gestational diabetes. Am J
18. Hunt KJ, Conway DL. Who returns for postpartum glucose
screening following gestational diabetes mellitus? Am J
19. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF,
Lachin JM, Walker EA, et al. Reduction in the incidence of
type 2 diabetes with lifestyle intervention or metformin.
Diabetes Prevention Program Research Group. N Engl J
Med 2002;346:393403.
20. Dietz PM, Vesco KK, Callaghan WM, Bachman DJ, Bruce
FC, Berg CJ, et al. Postpartum screening for diabetes after a
gestational diabetes mellitus-affected pregnancy. Obstet
Gynecol 2008;112:86874.
21. Metzger BE, Buchanan TA, Coustan DR, de Leiva A, Dunger
DB, Hadden DR, et al. Summary and recommendations of
the Fifth International Workshop-Conference on Gestational Diabetes Mellitus [published erratum appears in
Diabetes Care 2007;30:3154]. Diabetes Care 2007;30 (suppl
2):S25160.

ISSN 1074-861X
Postpartum screening for abnormal glucose tolerance in women who
had gestational diabetes mellitus. ACOG Committee Opinion No.
Gynecol 2009;113:141921.
COMMITTEE OPINIONS
583

(Replaces No. 282, January 2003)
Update on Immunization and Pregnancy:

Tetanus, Diphtheria, and Pertussis
Vaccination
Committee on
Obstetric Practice
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: To provide optimal protection for the pregnant woman and her neonate,
preconception immunization is preferred to vaccination during pregnancy. However,
when indicated, the benefits of immunization to the pregnant woman and her neonate
usually outweigh the theoretic risks of adverse effects. To add protection against pertussis or for pregnant women who need tetanus or diphtheria protection during pregnancy,
immunization with the diphtheria and reduced tetanus toxoids and acellular pertussis
vaccine (Tdap) instead of the tetanus and diphtheria toxoids (Td) vaccine may be considered in the second or third trimester. Pregnant women (including women who are breastfeeding) who have not received a dose of Tdap previously, should receive it after delivery and before discharge from the hospital if 2 years or more have elapsed since the
most recent Td vaccination. Current information on the safety of vaccines given during
pregnancy is frequently updated and may be verified from the Centers for Disease
Control and Prevention web site at www.cdc.gov/vaccines.
Ideally, vaccinations should be administered

before conception in order to avoid unnecessary exposure to the fetus. Prenatal care offers
the opportunity to review immunization status. The American College of Obstetricians
and Gynecologists recommends routine
assessment of each pregnant womans immunization status and appropriate immunization if indicated. There is no evidence of risk
from vaccinating pregnant women with an
inactivated virus or bacterial vaccines or toxoids, and these should be administered if
indicated. However, live vaccines do pose a
theoretic risk to the fetus and generally
should be avoided during pregnancy. The
benefits of vaccines outweigh any unproven
potential concerns about traces of thimerosal
preservative (16). When deciding whether to
immunize a pregnant woman with a vaccine
not routinely recommended in pregnancy,
the risk of exposure to disease as well as the
benefits of vaccination for reducing the deleterious effects on the woman and the fetus
must be balanced against unknown risks of
the vaccine. All vaccines administered should
be fully documented in the patients permanent medical record (7).

Immunization guidelines are subject to
change. The most current recommendations
specifically for the immunization of pregnant
women are available at www.cdc.gov/vaccines/
pubs/preg-guide.htm (8). Tables in PDF format are available at www.cdc.gov/vaccines/
pubsflyers-brochures.htm#preg. Extensive
information for health care providers and
consumers about all vaccines can be obtained
at www.cdc.gov/vaccines. The Advisory Committee on Immunization Practices (ACIP) of
the Centers for Disease Control and Prevention issues recommendations on immunization of pregnant women that are updated
regularly and are available at www.cdc.gov/
vaccines/pubs/ACIP-list.htm
The ACIP recommendations for pertussis, tetanus and diphtheria vaccination
have been revised to include routine postpartum Tdap administration if the woman
has not had Tdap in the past (see Box) (9).
The Committee on Obstetric Practice supports these recommendations, which are
584
available at: http://www.cdc.gov/mmwr/pdf/rr/ rr57e0514.

pdf.
Health care providers who administer Tdap to pregnant women should inform the women of the potential
benefits and risks of immunization. The benefits of Tdap
are the reduced risk of contracting or transmitting tetanus,
diphtheria, and pertussis. There are few data on safety,
immunogenicity, and pregnancy outcomes. Whether

Tdap affects active immunization of the infant after birth
is unknown. Health care providers are encouraged to
report Tdap administration regardless of trimester to the
appropriate manufacturers pregnancy registry (Sanofi
Pasteur 1-800-822-2463, GlaxoSmithKline Biologicals
1-888-825-5249).
Advisory Committee on Immunization Practices

Recommendations for Prevention of Pertussis,
Tetanus, and Diphtheria Among Pregnant and
Postpartum Women and Their Infants
Listed as follows are recommendations and conclusions reported by the Advisory
Committee on Immunization Practices:
Pertussis is still endemic in the United States.
Infants less than 12 months of age suffer the majority of the morbidity and mortality
of pertussis.
Tdap was licensed in 2005 for use in persons 1164 years of age.
Tdap is a combination vaccine with tetanus toxoid, reduced diphtheria toxoid and
acellular pertussis and is given only once during a lifetime.
Immunization with Tdap should be recommended before conception if the woman
has not received Tdap, and if at least 2 years have passed since her last Td booster.
Pregnant women (including women who are breastfeeding) who have not received a
dose of Tdap previously should receive Tdap after delivery and before discharge
from the hospital if 2 years or more have elapsed since the most recent Td administration. However, Td booster vaccination should be given during pregnancy if 10
years or more have elapsed since a previous Td booster or if booster protection
against diphtheria is needed.
To add protection against pertussis, Td vaccination during pregnancy can be
deferred and Tdap vaccination given before postpartum discharge from the hospital
in women who are likely to have sufficient tetanus and diphtheria protection until
delivery, who have not previously received Tdap and in whom it has been 2 years or
more since the most recent Td. Having standing orders at the hospital can help facilitate this. If Tdap cannot be administered at or before discharge, the woman should
receive the dose as soon as possible thereafter.
To add protection against pertussis or for pregnant women who need tetanus or
diphtheria protection during pregnancy, vaccination with Tdap instead of Td may be
considered in the second or third trimester unless earlier protection is needed
urgently, such as during a community pertussis outbreak
Health care providers and all household and child care provider contacts of infants
aged 12 months or younger should be vaccinated with Tdap.
Advisory Committee on Immunization Practices describes contraindications and precautions for individuals with a history of adverse reaction after previous doses of
vaccines containing tetanus and diphtheria toxoids.
Tdap is not the same as pediatric vaccines DTP or DTaP (diphtheria and tetanus
toxoids and acellular pertussis antigens).
Murphy TV, Slade BA, Broder KR, Kretsinger K, Tiwari T, Joyce PM, et al. Prevention of pertussis,
tetanus, and diphtheria among pregnant and postpartum women and their infants. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Advisory Committee on
Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC) [published erratum
appears in MMWR Morb Mortal Wkly Rep 2008;57:723]. MMWR Recomm Rep 2008;57:151.
COMMITTEE OPINIONS
Resources
Centers for Disease Control and Prevention. Vaccines
and immunizations. Available at: http://www.cdc.gov/
vaccines. Retrieved April 28, 2009.
Centers for Disease Control and Prevention. Flyers and
brochures: immunization and pregnancy. Available at:
http://www.cdc.gov/vaccines/pubs/flyers-brochures.
htm#preg. Retrieved April 28, 2009.
References
1. Thompson WW, Price C, Goodson B, Shay DK, Benson P,
Hinrichsen VL, et al. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. Vaccine Safety
Datalink Team. N Engl J Med 2007;357:128192.
2. Centers for Disease Control and Prevention. Mercury and
vaccines (thimerosal). Available at: http://www.cdc.gov/
vaccinesafety/concerns/thimerosal.htm. Retrieved April 28,
2009.
3. Food and Drug Administration (US). Thimerosal in vaccines.
Available at: http://www.fda.gov/cber/vaccine/ thimerosal.
htm. Retrieved April 28, 2009.
4. Joint statement of the American Academy of Pediatrics
(AAP) and the United States Public Health Service (USPHS).
5. Thimerosal in vaccinesAn interim report to clinicians.
American Academy of Pediatrics. Committee on Infectious
Diseases and Committee on Environmental Health.
6. Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, Wilson
E, et al. Effectiveness of maternal influenza immunization
in mothers and infants [published erratum appears in N
Engl J Med 2009;360:648]. N Engl J Med 2008;359:155564.
585
7. Centers for Disease Control and Prevention. Epidemiology

and prevention of vaccine-preventable diseases. 10th ed.
Atlanta (GA): CDC; 2008. Available at: http://www. cdc.
gov/vaccines/pubs/pinkbook/default.htm. Retrieved April 28,
2009.
8. Centers for Disease Control and Prevention. Guidelines for
vaccinating pregnant women. Atlanta (GA): CDC; 2007.
Available at: http://www.cdc.gov/vaccines/pubs/downloads/
b_preg_guide.pdf. Retrieved April 28, 2009.
9. Murphy TV, Slade BA, Broder KR, Kretsinger K, Tiwari T,
Joyce PM, et al. Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their
infants. Recommendations of the Advisory Committee on
Immunization Practices (ACIP). Advisory Committee on
Immunization Practices (ACIP), Centers for Disease
Control and Prevention (CDC) [published erratum appears
in MMWR Morb Mortal Wkly Rep 2008;57:723]. MMWR
Recomm Rep 2008;57:151.

ISSN 1074-861X
Update on immunization and pregnancy: tetanus, diphtheria, and pertussis vaccination. ACOG Committee Opinion No. 438. American
114:398400.
586

Oral Intake During Labor

Committee on
Obstetric Practice

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: There is insufficient evidence to address the safety of any particular

fasting period for solids in obstetric patients. Expert opinion supports that patients undergoing either elective cesarean delivery or elective postpartum tubal ligation should undergo a fasting period of 68 hours. Adherence to a predetermined fasting period before
nonelective surgical procedures (ie, cesarean delivery) is not possible. Therefore, solid
foods should be avoided in laboring patients.
Over the past 60 years, the incidence of

maternal death because of aspiration has
decreased dramatically. Contributing to this
decrease have been hospital policies and
strategies to reduce maternal gastric volume
and increase gastric pH and improvements in
obstetric anesthesia practice. This has led to
questions about the utility of very restrictive
oral intake policies in laboring patients and
calls to liberalize these policies in low-risk
patients.
There is insufficient evidence to draw
conclusions about the relationship between
fasting times for clear liquids and the risk of
emesis or reflux or both or pulmonary aspiration during labor. Although there is some
disagreement, most experts agree that oral
intake of clear liquids during labor does not
increase maternal complications.
The oral intake of modest amounts of
clear liquids may be allowed for patients with
uncomplicated labor. The patient without
complications undergoing elective cesarean
delivery may have modest amounts of clear
liquids up to 2 hours before induction of
anesthesia. Examples of clear liquids include,
but are not limited to, water, fruit juices without pulp, carbonated beverages, clear tea,
black coffee, and sports drinks. Particulate
containing fluids should be avoided. Patients
with risk factors for aspiration (eg, morbid
obesity, diabetes, and difficult airway), or
patients at increased risk for operative delivery may require further restrictions of oral
intake, determined on a case-by-case basis.
There is insufficient evidence to address

the safety of any particular fasting period for
solids in obstetric patients. Expert opinion
supports that patients undergoing either
elective cesarean delivery or elective postpartum tubal ligation should undergo a fasting
period of 68 hours. Adherence to a predetermined fasting period before nonelective
surgical procedures (ie, cesarean delivery) is
not possible. Therefore, solid foods should be
avoided in laboring patients.
Resource
Practice guidelines for obstetric anesthesia: an
updated report by the American Society of
Anesthesiologists Task Force on Obstetric
Anesthesia. American Society of Anesthesiologists Task Force on Obstetric Anesthesia.
Anesthesiology 2007;106:84363. Available at:
http://www.asahq.org/publicationsAndSer
vices/OBguide.pdf. Retrieved June 11, 2009.
Copyright September 2009 by the American College
of Obstetricians and Gynecologists, 409 12th Street,
SW, PO Box 96920, Washington, DC 20090-6920. All
rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, posted on the
Internet, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher. Requests for authorization to make photocopies
should be directed to: Copyright Clearance Center, 222
ISSN 1074-861X
Oral intake during labor. ACOG Committee Opinion No.
441. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;114:714.
COMMITTEE OPINIONS
587

Air Travel During Pregnancy

Committee on
Obstetric Practice
course of treatment or

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: In the absence of obstetric or medical complications, pregnant women

can observe the same precautions for air travel as the general population and can fly safely.
Pregnant women should be instructed to continuously use their seat belts while seated,
as should all air travelers. Pregnant air travelers may take precautions to ease in-flight
discomfort and, although no hard evidence exists, preventive measures can be used to
minimize risks of venous thrombosis. For most air travelers, the risks to the fetus from
exposure to cosmic radiation are negligible. For pregnant aircrew members and other frequent flyers, this exposure may be higher. Information is available from the FAA to estimate this exposure.
Occasional air travel during pregnancy is

generally safe. Recent cohort studies suggest
no increase in adverse pregnancy outcomes
for occasional air travelers (1, 2). Most commercial airlines allow pregnant women to fly
up to 36 weeks of gestation. Some restrict
pregnant women from international flights
earlier in gestation and some require documentation of gestational age. For specific airline requirements, women should check with
the individual carrier. Civilian and military
aircrew members who become pregnant
should check with their specific agencies for
regulations or restrictions to their flying
duties.
Air travel is not recommended at any
time during pregnancy for women who have
medical or obstetric conditions that may be
exacerbated by flight or that could require
emergency care. The duration of the flight
also should be considered when planning
travel. Pregnant women should be informed
that the most common obstetric emergencies
occur in the first and third trimesters.
In-craft environmental conditions, such
as changes in cabin pressure and low humidity, coupled with the physiologic changes of
pregnancy, do result in adaptations, including increased heart rate and blood pressure,
and a significant decrease in aerobic capacity
(3, 4). The risks associated with long hours of
air travel immobilization and low cabin
humidity, such as lower extremity edema and
venous thrombotic events, recently have been
the focus of attention for all air travelers.

Despite the lack of evidence of such events
during pregnancy, certain preventive measures can be used to minimize these risks, eg,
use of support stockings and periodic movement of the lower extremities, avoidance of
restrictive clothing, occasional ambulation,
and maintenance of adequate hydration.
Because severe air turbulence cannot be
predicted and the subsequent risk for trauma
is significant should this occur, pregnant
women should be instructed to use their
seatbelts continuously while seated. The seatbelt should be belted low on the hipbones,
between the protuberant abdomen and pelvis.
Several precautions may ease discomfort for
pregnant air travelers. For example, gas-producing foods or drinks should be avoided
before scheduled flights because entrapped
gases expand at altitude (5). Preventive antiemetic medication should be considered for
women with increased nausea.
Available information suggests that noise,
vibration, and cosmic radiation present a negligible risk for the occasional pregnant air
traveler (6, 7). Both the National Council on
Radiation Protection and Measurements and
the International Commission on Radiological
Protection recommend a maximum annual
radiation exposure limit of 1 millisievert
(mSv) (100 rem) for members of the general
public and 1 mSv over the course of a
40-week pregnancy (7). Even the longest
available intercontinental flights will expose
588
passengers to no more than 15% of this limit (7); therefore, it is unlikely that the occasional traveler will exceed
current exposure limits during pregnancy. However,
aircrew or frequent flyers may exceed these limits. The
Federal Aviation Administration and the International
Commission on Radiological Protection consider aircrew
to be occupationally exposed to ionizing radiation and
recommend that they be informed about radiation exposure and health risks (8, 9). A tool to estimate an individual exposure to cosmic radiation from a specific flight is
available from the Federal Aviation Administration on its
web site (http://jag.cami.jccbi.gov/cariprofile.asp).
In the absence of a reasonable expectation for obstetric or medical complications, occasional air travel is safe
for pregnant women. Women should check with specific
carriers for airline requirements.
5.
6.
7.
8.
9.
tations to exercise in pregnancy at sea level and altitude.

Am J Obstet Gynecol 1995;172:11708; discussion 1178 80.
Bia FJ. Medical considerations for the pregnant traveler.
Infect Dis Clin North Am 1992;6:37188.
Morrell S, Taylor R, Lyle D. A review of health effects of aircraft noise. Aust N Z J Public Health 1997;21:22136.
Barish RJ. In-flight radiation exposure during pregnancy.
Federal Aviation Administration. In-flight radiation exposure. Advisory Circular No. 120-61A Washington, DC: FAA;
2006.
The 2007 recommendations of the International Commission on Radiological Protection. International Commission
on Radiological Protection. IRCP Publication 103. Ann
IRCP 2007;37:(24);1332.
References
1. Chibber R, Al-Sibai MH, Qahtani N. Adverse outcome of
pregnancy following air travel: a myth or a concern? Aust N
Z J Obstet Gynaecol 2006;46:248.
2. Freeman M, Ghidini A, Spong CY, Tchabo N, Bannon PZ,
Pezzullo JC. Does air travel affect pregnancy outcome? Arch
Gynecol Obstet 2004;269:2747.
3. Huch R, Baumann H, Fallenstein F, Schneider KT, Holdener F,
Huch A. Physiologic changes in pregnant women and their
fetuses during jet air travel. Am J Obstet Gynecol 1986;
154:9961000.
4. Artal R, Fortunato V, Welton A, Constantino N, Khodiguian N,
Villalobos L, et al. A comparison of cardiopulmonary adap-

DC 20090-6920. All rights reserved. No part of this publication may
be reproduced, stored in a retrieval system, posted on the Internet,
or transmitted, in any form or by any means, electronic, mechanical,
ISSN 1074-861X
Air travel during pregnancy. ACOG Committee Opinion No. 443.
2009;114:9545.
COMMITTEE OPINIONS
589

Antibiotics for Preterm Labor

Committee on
Obstetric Practice
followed.
The Society for

Maternal Fetal Medicine

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: The utility of antibiotics to prolong pregnancy and reduce neonatal morbidities in women with preterm labor and intact membranes has been evaluated in
numerous randomized clinical trials. Antibiotic use intended only for pregnancy prolongation in women with preterm labor with intact membranes does not have short-term
neonatal benefits and may be associated with long-term harm. Thus, antibiotics should
not be used for this indication in women with preterm labor and intact membranes.
The utility of antibiotics to prolong pregnancy and reduce neonatal morbidities in

women with preterm labor and intact membranes has been evaluated in numerous randomized clinical trials. Improved neonatal
outcomes have not been demonstrated with
such treatment, although some trials have
suggested pregnancy prolongation (1). Longterm follow-up childhood data from these
studies have not been available until recently.
A recent multicenter, randomized, double-masked clinical trial provided a 7-year
follow-up of a large group of patients receiving antibiotics (placebo versus oral erythromycin, amoxicillinclavulanate or both)
for preterm labor with intact membranes.
From this trial, 3,196 children (71% of those
enrolled) had outcome information available
(2). Despite being comparable in acute morbidities and mortality, the study groups were
significantly different on long-term followup. Infants exposed prenatally to erythromycin, had more functional impairment
(42.3% versus 38.3%) and mild functional
impairment (23.9% versus 21.3%) compared
with those who did not receive erythromycin.
Additionally, death or any functional
impairment (31.3% versus 28.3%) and
death or cerebral palsy (5.9% versus 4.3%)
were more common with exposure to erythromycin. Cerebral palsy was more common
with exposure to erythromycin (3.3% versus
1.7%) and amoxicillinclavulanic acid (3.2%
versus 1.9%) relative to those not exposed to

these agents. All of these findings were statistically significant.
Of importance, infant outcomes were
ascertained based on parental reports rather
than on individual infant assessments by
medical personnel. Of note, 64% of infants
in whom preterm labor was initially diagnosed were delivered at term. Further, the
previously mentioned adverse findings were
not evident in a similar follow-up evaluation
of women treated with the same antibiotics
after preterm premature rupture of the
membranes (3).
Antibiotic use intended only for pregnancy prolongation in women with preterm
labor with intact membranes does not have
short-term neonatal benefits and may be
associated with long-term harm. Thus,
antibiotics should not be used for this indication in women with preterm labor and
intact membranes. This recommendation is
distinct from recommendations for antibiotic use for preterm premature rupture of
membranes (4) and group B streptococcus
carrier status (5) (see Box 1). Given inconsistent childhood data regarding potential
long-term risks of erythromycin and amoxicillinclavulanate, these agents continue to
be considered appropriate for treatment of
acute infections during pregnancy and they
should not be withheld when otherwise
indicated.
590
References
Box 1. Recommendations for Use of
Antibiotics in Women With Preterm
Premature Rupture of Membranes and
Preterm Labor
For patients with preterm labor with intact membranes:
Use intrapartum antibiotics to prevent group B streptococcal perinatal infection.
Do not use antibiotics to prolong pregnancy.
For patients with acute infections requiring antibiotic
treatment during pregnancy:
Erythromycin or amoxicillinclavulanate or both may
be given if appropriate based on known or anticipated
bacterial sensitivities to these agents.
For patients with preterm premature rupture of
membranes:
Use antibiotics to prevent group B streptococcal
perinatal infection.
Use broad-spectrum antibiotics during conservative
management to prolong pregnancy and decrease
short-term neonatal complications for preterm premature rupture of membranes remote from term.
1. King JF, Flenady V, Murray L. Prophylactic antibiotics for

inhibiting preterm labour with intact membranes.
Art. No.: CD000246. DOI: 10.1002/14651858.CD000246.
2. Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N, Salt
A, et al. Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour:
7-year follow-up of the ORACLE II trial. Lancet
2008;372:131927.
3. Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N, Salt
A, et al. Childhood outcomes after prescription of antibiotics to pregnant women with preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial. Lancet
2008;372:13108.
4. Premature rupture of membranes. ACOG Practice Bulletin
5. Prevention of early-onset group B streptococcal disease in
newborns. ACOG Committee Opinion No. 279. American
2002;100:140512.

ISSN 1074-861X
Antibiotics for preterm labor. Committee Opinion No. 445. American
2009;114:115960.
COMMITTEE OPINIONS
COMMITTEE
ON
PROFESSIONAL LIABILITY
COMMITTEE OPINIONS
COMMITTEE
ON
PROFESSIONAL LIABILITY

Disclosure and Discussion of

Adverse Events
Committee on
Patient Safety and
Quality Improvement
Committee on
emerging concepts on
patient safety and is subject to change. The information should not be construed as dictating an exclusive course of treatment or
Obstetricians and Gynecologists, 409 12th Street, SW,
PO Box 96920, Washington, DC 20090-6920. All
rights reserved. No part of
this publication may be
reproduced, stored in a
retrieval system, posted on
the Internet, or transmitted,
in any form or by any
means, electronic, mechanical, photocopying, recording, or otherwise, without
prior written permission
from the publisher. Requests for authorization to
make photocopies should
be directed to: Copyright
Clearance Center, 222
Rosewood Drive, Danvers,
MA 01923, (978) 750-8400.
Disclosure and discussion
of adverse events. ACOG
Committee Opinion No.
380. American College of
2007;110:9578
ISSN 1074-861X

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Disclosure and discussion of adverse events in health care is desired

by patients and championed by safety experts and policy makers. Improving the disclosure process through policies, programmatic training, and accessible resources will
enhance patient satisfaction, strengthen the physicianpatient relationship, and most
importantly, promote a higher quality of health care.
Adverse outcomes, preventable or otherwise,

are an uncomfortable reality of medical
care. The Institute of Medicine proposes a
multifaceted approach toward reducing and
managing adverse events, including the
establishment of a national focus on patient
safety, the creation of a mandatory reporting
system, raising standards and expectations
for safety improvements at the national level,
and creating safety systems in health care
organizations (1). Despite continuing efforts
to prevent their occurrence, adverse events
may happen even in the absence of medical
error. Thus, there is a need for health care
providers and institutions to understand how
to best disclose and discuss these adverse
events with patients and their families. The
Gynecologists (ACOG) supports these efforts
and seeks to assist members in understanding the value of disclosure and discussion in
the face of preventable and nonpreventable
adverse events and to provide guidance for
such conversations.
The call for health care organizations to
develop processes for disclosure is broadbased. Patient advocacy groups, patient safety
experts, ethicists, policy makers, accrediting
organizations, and physician groups all advocate the adoption of policies related to the
disclosure and discussion of unanticipated
adverse events. When adverse events occur,
providers should engage the patient and family in discussions about the event(s), including expressions of sympathy.
The Joint Commission requires that
accredited hospitals tell patients of unantic-
ipated adverse events. According to the Joint

Commission Standard RI.2.90, patients
and, when appropriate, their families are
informed about the events of care, treatment, and services that have been provided.
Further, the responsible licensed independent practitioner or his or her designee
informs the patient (and when appropriate,
the family) about those unanticipated outcomes of care, treatment, and services (2).
Similar statements are in the ethics code of
the American Medical Association, which
states that in cases in which a patient suffers significant medical complications that
may have resulted from a physicians mistake . . . the physician is ethically required
to inform the patient of the facts necessary to ensure understanding of what has
occurred(3).
It is important to remember the difference between expressions of sympathy
(acknowledgement of suffering) and apology
(accountability for suffering). Expressions of
sympathy are always appropriate. The appropriateness of an apology, however, will vary
from case to case. When considering whether
an apology is appropriate, the physician may
wish to seek advice from the hospitals risk
manager and the physicians liability carrier.
It is also important to be knowledgeable
about the states laws on apology and disclosure because these laws vary and may have an
effect on the way in which the disclosure is
conducted.
Physicians have an ethical obligation to
communicate honestly with patients. Disclosing information about unanticipated
593
594
adverse events likely has benefits for both parties through

a strengthened physicianpatient relationship and a promotion of trust. Studies show that in the event of an
adverse outcome, patients expect and want full disclosure
of the event(s), an acknowledgement of responsibility, an
understanding of what happened, expressions of sympathy, and discussion of what is being done to prevent recurrence(s) (4, 5). Additionally, disclosure of adverse events
can be important for the physicians personal healing.
Barriers to full disclosure are many, including shame,
lack of training in how to disclose, and fear of lawsuits (6,
7, 8). Based on surveys, it appears that patients want and
expect timely and honest disclosure of adverse events and
that patients are more likely to sue if they perceive that
such disclosure was absent (9, 10). In studies of patients
who sued their health care providers for adverse perinatal
events, 43% were driven by a suspicion of a cover-up or
by the desire for revenge (11).
Several organizations have reported on the success of
their disclosure programs. One of the oldest programs
advocating full disclosure of medical errors, the Veterans
Affairs Medical Center in Lexington, Kentucky, reported
that their facilitys liability payments were moderate and
comparable to similar institutions despite a proactive disclosure policy that might be anticipated to increase litigation (12). The University of Michigan Health System
reported a 50% reduction in legal fees and actions since
implementing a policy encouraging disclosure and apology in 2001 (13, 14).
A number of health care organizations, insurance
carriers, and states have developed programs to educate
physicians about disclosure. Examples include the
University of Michigan Hospitals and Health Centers
Guidelines on How to Disclose Errors and When
Things Go Wrong: Responding to Adverse Events, a consensus statement of the Harvard Hospitals (15). These
can provide valuable guidance and education about the
specifics of disclosure and apology. COPIC, a professional liability carrier for academic and community physicians in Colorado, provides its physicians with a training
program and ongoing support in error disclosure entitled
The 3Rs Program for Recognize, Respond, and Resolve
unanticipated medical events (16).
Health care institutions should have written policies
that address the timing, content, communication, and
documentation of disclosure. Once policies are developed, health care organizations should educate their
providers on the policies and consider the need for additional resources and training such as disclosure coaching,
mediation, and emotional support for health care workers involved in harmful medical errors (7, 17). Individual
physicians and physician practice groups may contact
their local hospitals, liability carriers, specialty organizations, or medical societies for disclosure assistance training and resources available to them.
REFERENCES
1. Institute of Medicine. To err is human: building a safer
health system. Washington, DC: National Academy Press;
2000.
2. Joint Commission on Accreditation of Healthcare
Organizations. Comprehensive accreditation manual for
hospitals: CAMH. Oakbrook Terrace (IL): JCAHO; 2006.
3. American Medical Association. Code of medical ethics of
the American Medical Association: current opinions with
annotations. 20062007 ed. Chicago (IL): AMA; 2006.
4. Gallagher TH, Waterman AD, Ebers AG, Fraser VJ,
Levinson W. Patients and physicians attitudes regarding
the disclosure of medical errors. JAMA 2003;289:10017.
5. Mazor KM, Simon SR, Yood RA, Martinson BC, Gunter MJ,
Reed GW, et al. Health plan members views about disclosure of medical errors. Ann Intern Med 2004;140:40918.
6. Finkelstein D, Wu AW, Holtzman NA, Smith MK. When a
physician harms a patient by a medical error: ethical, legal,
and risk-management considerations. J Clin Ethics
1997;8:330.
7. Goldberg RM, Kuhn G, Andrew LB, Thomas HA Jr. Coping
with medical mistakes and errors in judgment. Ann Emerg
Med 2002;39:28792.
8. Mello MM, Studdert DM, DesRoches CM, Peugh J, Zapert
K, Brennan TA, et al. Caring for patients in a malpractice
crisis: physician satisfaction and quality of care. Health Aff
(Millwood) 2004;23(4):4253.
9. Vincent C, Young M, Phillips A. Why do people sue doctors?
A study of patients and relatives taking legal action. Lancet
1994;343:160913.
10. Beckman HB, Markakis KM, Suchman AL, Frankel RM.
The doctorpatient relationship and malpractice. Lessons
from plaintiff depositions. Arch Intern Med 1994;154:
136570.
11. Hickson GB, Clayton EW, Githens PB, Sloan FA. Factors
that prompted families to file medical malpractice claims
following perinatal injuries. JAMA 1992;267:135963.
12. Kraman SS, Hamm G. Risk management: extreme honesty
may be the best policy. Ann Intern Med 1999;131:9637.
13. Gallagher TH, Levinson W. Disclosing harmful medical
errors to patients: a time for professional action. Arch
Intern Med 2005;165:181924.
14. Orlovsky C. Proposed legislation encourages hospital disclosure initiatives. Glen Carbon (IL): The Sorry Works!
Coalition; 2005. Available at: http://www.sorryworks.
net/media40.phtml. Retrieved March 5, 2007.
15. Massachusetts Coalition for the Prevention of Medical
Errors. When things go wrong: responding to adverse
events: a consensus statement of the Harvard Hospitals.
Burlington (MA): MAC; 2006. Available at: http://www.
macoalition.org/documents/respondingToAdverseEvents.
pdf. Retrieved March 5, 2007.
16. 3Rs program. Denver (CO): Copic Companies. Available at:
http://www.callcopic.com/home/what-we-offer/coveages/
medical-professional-liability-insurance-co/physiciansmedical-practices/special-programs/3rs-program.
17. Liebman CB, Hyman CS. A mediation skills model to manage disclosure of errors and adverse events to patients.
Health Aff (Millwood) 2004;23(4):2232.
COMMITTEE OPINIONS
595

Number 406 May 2008
Coping With the Stress of Medical

Professional Liability Litigation
Committee on
This document provides
risk management information that is current as of
the date issued and is subject to change. This document does not define a
standard of care nor should
it be interpreted as legal
advice.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Obstetriciangynecologists should recognize that being a defendant in

a medical professional liability lawsuit can be one of lifes most stressful experiences.
Coping with the stress of medical professional liability litigation is an ongoing, complex
process in which physicians often must struggle to regain a sense of personal identity
and professional mastery, as well as control of their clinical practices. Open communication
with family members will assist in reducing emotional isolation and self-blame; however,
legal and clinical aspects of a case must be kept confidential. Peer support and individual
professional counseling can be of great benefit. Rapid intervention facilitates healthier
coping strategies and can restore a sense of equilibrium and self-esteem during an unpredictable time.

Gynecologists (ACOG) has long been concerned about the psychologic and emotional
impact of medical professional liability litigation on physicians, especially because 89.2%
of ACOG Fellows have been sued at least
once in their careers (1). Defendant physicians may experience a wide range of distressing emotions and increased stress, which
can disrupt their personal lives and the lives
of their families, their relationships with
patients, and their medical practices. Because
a medical professional liability case in obstetrics and gynecology usually takes several
years to resolve, this stressful period can seem
interminable for all involved.
Common responses to medical liability
litigation include feelings of shock, outrage,
denial, anxiety, guilt, shame, and despair.
Coping with medical professional liability litigation is an ongoing, complex process in
which physicians often must struggle to
regain a sense of personal identity and professional mastery as well as control of their
clinical practices.
Claims managers and defense attorneys
often advise physicians not to speak to anyone regarding any aspect of the medical liability case. Nevertheless, physicians often
need to express their emotional responses to
being sued. Literal adherence to the advice
to speak to no one can result in isolation,

increased stress, and dysfunctional behavior.
Guidance on interventions for impaired
or dysfunctional physician behavior is
addressed elsewhere (2). Such behavior may
jeopardize family relationships and also may
affect the physicians ability to function professionally and to represent himself or herself
appropriately and effectively during a trial.
Therefore, the physician is encouraged to
inform family members of the lawsuit, the
allegations, the potential for publicity, and
any expected testimony, while maintaining
confidentiality. Children should be told
about the lawsuit and their questions honestly answered, commensurate with their age
and ability to understand the information.
Open communication with family members
will assist in reducing emotional isolation
and self-blame (3).
Certainly, legal and clinical aspects of a
case must be kept confidential. An exception to this rule, however, might be made in
the context of professional counseling. Any
clinical aspects of a medical professional liability case that are discussed in counseling
should be disclosed within the confines of a
formal counselorpatient relationship to
ensure the confidentiality privilege. State laws
determine whether confidentiality can be
maintained if the counselor is other than a
596
physician or member of the clergy. Moreover, confidentiality may be lost if third parties are present.
Obstetriciangynecologists should recognize that
being a defendant in a medical professional liability lawsuit can be one of lifes most stressful experiences.
Although negative emotions in response to a lawsuit are
normal, physicians may need help from professionals or
peers to cope with this stress. Residents, as young physicians in training, may be particularly vulnerable to the
psychologic and emotional upheaval that often occurs
when named in a medical liability claim. State or local
medical societies and medical liability insurance carriers
often sponsor support groups for defendant physicians
and their families. Support mechanisms for residents also
may be available through residency program directors,
department chairs, departments of risk management, or
mentors. In the absence of such services, individual professional counseling can be of great benefit. Rapid intervention facilitates healthier coping strategies and can
restore a sense of equilibrium and self-esteem during an
unpredictable time.
References
1. Wilson N, Strunk AL. Overview of the 2006 ACOG Survey
on Professional Liability. ACOG Clin Rev 2007;12(2):1,
1316.
Guidelines for womens health care: a resource manual. 3rd
ed. Washington, DC: ACOG; 2007.
3. Charles SC, Frish PR. Adverse events, stress, and litigation:
a physicians guide. New York (NY): Oxford University
Press; 2005.
Bibliography
Brazeau CM. Coping with the stress of being sued. Fam Pract
Manag 2001;8(5):414.
Charles SC. How to handle the stress of litigation. Clin Plast
Surg 1999;26:6977, vii.
Charles SC. Medical liability litigation as a disruptive life event.
Bull Am Coll Surg 2005;90(12):1723.
Hutchison JR, Hutchison S. The toughest part of being sued.
Med Econ 1995;72(23):367, 414, 48, passim.
Page L. On the defensive. A physicians confidence can shatter
in the wake of a lawsuit. Mod Healthc 2004;34:51, 54.
Physician Litigation Stress Resource Center. St. Joseph (MI):
PLSRC; 2007. Available at: http://www.physicianlitigationstress.
org. Retrieved November 14, 2007.
Settel KM. The impact of malpractice litigation on physicians.
Forum 1998;19(4):135.
Weiss GG. Youve been sued. Theres help. Med Econ 2003;
80(3):56, 5960.

Coping with the stress of medical professional liability litigation.
ACOG Committee Opinion No. 406. American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;111:12578.
COMMITTEE OPINIONS
COMMITTEE OPINIONS
COMMITTEE
PATIENT SAFETY AND

QUALITY IMPROVEMENT
ON
597
598
COMMITTEE OPINIONS
COMMITTEE ON PATIENT SAFETY
QUALITY IMPROVEMENT
AND
ACOG
Committee on
Quality Improvement
and Patient Safety
Reaffirmed 2007
Committee
Opinion

concepts on patient safety and is
subject to change. The information should not be construed as
dictating an exclusive course
followed.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400

409 12th Street, SW
PO Box 96920
Partnering with patients to improve

safety. ACOG Committee Opinion
Partnering With Patients to Improve

Safety
ABSTRACT: Actively involving patients in their care will lead to increased
patient satisfaction, increased diagnostic accuracy, enhanced adherence to
therapeutic recommendations, and ultimately, improved health quality.
Partnering with patients in the office setting by sharing information and
enhancing communication can lead to improved patient health care and
satisfaction.
The foundation for a positive physicianpatient interaction is formed by

establishing a partnership and creating a meaningful dialogue. Accomplishing this in a brief office visit may be challenging, but with adequate
planning these encounters can be structured in a positive way. Improving
communication with patients, listening to their concerns, and facilitating
active partnerships should be central to any patient safety strategy (1).
Involving patients in planning and delivering health services also is recommended as a means of improving the quality of services (2). Additionally,
several studies indicate that physicianpatient communication problems may
account for an increase in medical professional liability actions (3, 4).
Information Sharing
Patients are responsible for providing their physicians with the information
that is necessary to reach an accurate diagnosis or treatment plan. To facilitate this process, patients should be encouraged to discuss the reasons for
their visits and ask questions such as, What is my primary problem? What
do I need to do? and Why is it important for me to do this?(5). In
response, physicians should actively listen to engage their patients.
Physicians also can solicit the patients concerns and opinions by asking
open-ended questions and asking patients to share key information such as
their medical history (including illnesses, immunizations, and hospitalizations), medication history (including over-the-counter [OTC] medications,
and dietary supplements), and any allergies, reactions, or sensitivities experienced after taking medication.
599
600
Health Literacy
According to an Institute of Medicine report,nearly
half of all American adults90 million people
have difficulty understanding and acting upon health
information (6). The Institute of Medicine defines
health literacy as the degree to which individuals
have the capacity to obtain, process, and understand
basic health information and services needed to
make appropriate health decisions (6). Cultural barriers also can impede physicianpatient communication. Consequently, it is important for clinicians to
use proven strategies to facilitate communication
with patients. Listed as follows are examples of useful methods:
Speaking slowly and using plain, nonmedical
language
Limiting the amount of information provided
and repeating the information
Using teach-back or show-me techniques (asking the patient to repeat any instructions given)
to confirm that the patient understands
Making patients feel comfortable to ask questions (7)
Providing written materials to reinforce oral
explanations
per day, the patient should be told what time of day

the medication should be taken, whether it should be
taken with food or without food, how much should
be taken at one time, how long the medication
should be continued, possible interactions with other
medications the patient is taking, and whether any
medications (including OTC medications), foods, or
alcohol are contraindicated while taking this medication. Physicians should encourage their patients
to maintain a list of all the medications, including
herbal supplements and OTC medications, they are
taking and share the list with any other physicians
they may be seeing. Medication forms to facilitate
this process have been developed by some groups
(see Resources).
Follow-up
Physicians should develop a system to track test
results and communicate those results to patients.
Tracking strategies in the office may include log
books or computer prompts. Clinicians should
inform their patients that no news is not necessarily
good news. Patients should be given a reasonable
time frame within which they should expect to hear
about their test results, and they should be encouraged to call if they have not heard from the office at
the end of that period.
Informed Consent
Informed consent is a process, not a form. At the end
of this process, the patient should understand her
diagnosis, recommended treatment, potential complications, and treatment options. This discussion
should be documented in the medical record. It often
is helpful to invite the patient to bring a relative or a
close friend to this discussion. There are many commercially available videotapes and printed materials,
including those produced by ACOG, that can reinforcebut not replacethis process.
Medications
Medication errors are the largest source of preventable adverse events. It is important for patients to provide their physicians with a list of the prescription
and nonprescription medications they take. Whenever new prescriptions are given, patients should be
told why the medication is being prescribed and
given instructions for taking the medication. For
example, if a medication is to be taken three times
Conclusion
Partnering with patients to improve communication
results in increased patient satisfaction, increased
diagnostic accuracy, enhanced adherence to therapeutic recommendations, and improved health quality. In addition to the physician, other staff, such as
nurses and physician assistants, may play an important role in ensuring appropriate communication.
More time may be required during the patient
encounter, but overall, these measures will save
time, improve patient safety and satisfaction, and
will be worth the additional effort.
References
1. Vincent CA, Coulter A. Patient safety: what about the
patient? Qual Saf Health Care 2002;11:7680.
2. Crawford MJ, Rutter D, Manley C, Weaver T, Bhui K,
Fulop N, et al. Systematic review of involving patients in
the planning and development of health care. BMJ 2002;
325:1263.
COMMITTEE OPINIONS
3. Hickson GB, Clayton EW, Githens PB, Sloan FA. Factors

that prompted families to file medical malpractice claims
following perinatal injuries. JAMA 1992;267:135963.
4. Hickson GB, Clayton EW, Entman SS, Miller CS,
Githens PB, Whetten-Goldstein K, et al. Obstetricians
prior malpractice experience and patients satisfaction
with care. JAMA 1994;272:15837.
5. Partnership for Clear Health Communication. Ask me 3:
good questions for your good health. Available at:
http://www.askme3.org/pdfs/Patient_Eng.pdf. Retrieved
July 29, 2005.
6. Institute of Medicine (US). Health literacy. A prescription
to end confusion. Washington, DC: National Academies
Press; 2004.
7. Weiss BD. Health literacy: a manual for clinicians.
Chicago (IL): American Medical Association; 2003.
Resources
National Patient Safety Foundation
www.npsf.org
Institute for Safe Medical Practice
www.ismp.org
601
602
ACOG
Committee on
Quality Improvement
and Patient Safety
Reaffirmed 2007
Committee
Opinion

subject to change. The information
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Do not use abbreviations. ACOG

Committee Opinion No. 327. American
2134
Do Not Use Abbreviations

ABSTRACT: There are numerous abbreviations used in health care that have
several different meanings. Some of these abbreviations may be mistaken for
other abbreviations, numbers, or symbols, and these mistakes can have serious consequences. Therefore, the Joint Commission on Accreditation of
Healthcare Organizations has established an Official Do Not Use List of
abbreviations as part of its accreditation standards. It is important for obstetriciangynecologists to consider this list when using these and other abbreviations in their practice settings.
In 2004, as part of its National Patient Safety Goals, the Joint Commission
on Accreditation of Healthcare Organizations (Joint Commission) added a
list of do not use abbreviations as part of Goal 2B, standardize a list of
abbreviations, acronyms and symbols that are not to be used throughout the
organization. This list has subsequently been reaffirmed by the Joint
Commission (Table 1).
The list is used for accreditation purposes in all clinical settings. The
scope of this list should apply to all orders, not just medication orders, and
all medication documentation, either handwritten or preprinted. The use of
abbreviations on this list remains one of the most frequent noncompliance
findings of Joint Commission surveys.
There are several other items that may possibly be added to the list,
although they are currently not considered for accreditation purposes:
The symbols > and <

All abbreviations for drug names
Apothecary units (eg, drams or grains)
The symbol @
The abbreviation cc
The abbreviation g
Because of the potential for ambiguity that might result in a medication error
and subsequent patient harm, using fewer or perhaps no abbreviations is
suggested.
COMMITTEE OPINIONS
Table 1. Official Do Not Use List*

Do Not Use
Potential Problem
Use Instead
U (unit)
Mistaken for 0 (zero),

the number 4 (four), or cc
Mistaken for IV (intravenous)
or the number 10 (ten)
Mistaken for each other
Period after the Q mistaken
for I and the O mistaken
for I
Decimal point is missed
Write unit
IU (International Unit)
Q.D., QD, q.d., qd (daily)
Q.O.D., QOD, q.o.d., qod
(every other day)
Trailing zero (X.0 mg)
Lack of leading zero (.X mg)
MS
MSO4 and MgSO4
Can mean morphine sulfate

or magnesium sulfate
Confused for one another
Write International Unit

Write daily
Write every other day
Write X mg
Write 0.X mg
Write morphine sulfate
Write magnesium sulfate
*Applies to all orders and all medication-related documentation that is handwritten (including free-text
computer entry) or on preprinted forms.
A trailing zero may be used only where required to demonstrate the level of precision of the value
being reported, such as for laboratory results, imaging studies that report size of lesions, or catheter/tube
sizes. It may not be used in medication orders or other medication-related documentation.
Joint Commission on Accreditation of Healthcare Organizations. Official do not use list. Available at:
http://www.jcaho.org/accredited+organizations/laboratory+services/npsg/06_dnu_list.pdf. Retrieved
September 8, 2005.
Bibliography
Joint Commission on Accreditation of Healthcare Organizations. Facts about the official do not use list. Available at:
http://www.jcaho.org/accredited+organizations/patient+
safety/dnu_facts.htm. Retrieved September 8, 2005.
603
604
ACOG
Committee on
Quality Improvement
and Patient Safety
Reaffirmed 2007
Committee
Opinion
Number 328, February 2006

treatment or procedure to be followed.
Copyright February 2006
from the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Patient safety in the surgical environment. ACOG Committee Opinion No.

328. American College of
Patient Safety in the Surgical

Environment
ABSTRACT: Ensuring patient safety in the operating room begins before the
patient enters the operative suite and includes attention to all applicable
types of preventable medical errors (including, for example, medication
errors), but surgical errors are unique to this environment. Steps to prevent
wrong-site, wrong-person, or wrong-procedure errors have been recommended. Prevention of surgical errors requires the attention of all personnel
involved in the patients care.
Potentially preventable surgical errors have received increasing attention in

recent years, although they appear to occur relatively infrequently compared
with other classes of medical errors. The Joint Commission on Accreditation
of Healthcare Organizations (JCAHO) has published two Sentinel Event
Alerts addressing wrong-site surgery, the latest in 2001. Sentinel Event Alert
24 reported 150 cases of wrong-site, wrong-person, or wrong-procedure
surgery, of which 126 had root cause analysis information (1). Wrong-site
surgery was most common during orthopedic or podiatric procedures (41%).
Although no obstetric or gynecologic cases were reported in the JCAHO
series, no surgical specialty is immune from surgical errors.
Terminology
The term wrong-site surgery often is used to refer to any surgical procedure
performed on the wrong patient, wrong body part, wrong side of the body,
or at the wrong level of the correctly identified anatomic site. The following
terms can be used to describe the various specific errors:
Wrong-side surgery indicates a surgical procedure performed on the
wrong extremity or side of the patients body (eg, the left ovary rather
than the right ovary).
Wrong-patient surgery describes a surgical procedure performed on a
different person than the one intended to receive the operation.
Wrong-level surgery and wrong-part surgery are used to indicate surgical procedures that are performed at the correct operative site, but at the
wrong level or part of the operative field or patients anatomy.
COMMITTEE OPINIONS
605
Systems Approach
The Universal Protocol
Particularly because of the potential for serious harm

from surgical errors, vigorous efforts are required to
eliminate or reduce their frequency. Preventing this
type of error appears to be amenable to a systems
approach involving a team effort by all individuals
participating in the surgical process. Although all
members of the surgical team share in this responsibility, the primary surgeon should oversee these
efforts. The Joint Commission on Accreditation of
Healthcare Organizations has identified the following factors that may contribute to an increased risk
of wrong-site surgery:
In 2003, JCAHO published Universal Protocol for

Preventing Wrong Site, Wrong Procedure, and
Wrong Person Surgery (2). The universal protocol
is based on three levels of activity before initiation
of any surgical procedure:
Multiple surgeons involved in the case

Multiple procedures during a single surgical
visit
Unusual time pressures to start or complete the
procedure
Unusual physical characteristics, including morbid obesity or physical deformity
A common theme in cases of wrong-site surgery
involves failed communication between the surgeon
or surgeons, the other members of the health care
team, and the patient. Communication is crucial
throughout the surgical process, particularly during
the preoperative assessment of the patient and the
procedures used to verify the operative site. Effective
preoperative patient assessment includes a review of
the medical record or imaging studies immediately
before starting surgery. To facilitate this step, all relevant information sources, verified by a predetermined checklist, should be available in the operating
room and rechecked by the entire surgical team
before the operation begins. Whenever possible, the
patient (or the patients designee) should be involved
in the process of identifying the correct surgical site,
both during the informed consent process and in the
physical act of marking the intended surgical site in
the preoperative area. A formal procedure for final
confirmation of the correct patient and surgical site
(a time out) that requires the participation of all
members of the surgical team may be helpful. It is
inappropriate to place total reliance on the surgeon to
identify the correct surgical site or to assume that the
surgeon should never be questioned. The risk of error
may be reduced by involving the entire surgical team
in the site verification process and encouraging any
member of that team to point out a possible error
without fear of ridicule or reprimand.
1. Preoperative verification process

The health care team ensures that all relevant
documents and studies are available before the
procedure starts and that the documents have
been reviewed and are consistent with each
other, with the patients expectations, and with
the teams understanding of the intended
patient, procedure, site, and, as applicable, any
implants. The team must address missing information or discrepancies before starting the
procedure.
2. Marking of the operative site
The health care team, including the patient (if
possible), identifies unambiguously the intended site of incision or insertion by marking all
operative sites involving laterality, multiple
structures, or multiple levels.
3. Time out before starting the procedure
The operative team conducts a final verification
of the correct patient, procedure, site, and, as
applicable, implants.
A relatively new but essential element of this
overall process is the formal enlistment of active
involvement by the patient to avert errors in the
operative arena. Involving the patient in this manner
requires personal effort by the surgeon to educate
the patient during the preoperative evaluation
process. The patient, who has the greatest stake in
avoiding errors, thus becomes integrally involved in
helping ensure that errors are avoided.
Granting Privileges for New Procedures

New techniques and new equipment are important
components for developing and delivering the best
quality care in the operating room, but they also represent sources of potential surgical error. Prudence
demands that, whenever possible, a surgeon who is
incorporating a new surgical technique should be
assisted or supervised by a colleague more experienced in the technique until competency has been
satisfactorily demonstrated. In some circumstances,
606
however, a technique may be so innovative that no

other surgeon at that locale has more experience. In
such situations, it may be wise to arrange for extra
support staff or surgical backup to be available
should difficulties arise. The surgeon involved
should have already documented skills and experience in the related surgical arena and should have
solicited and received the advice and support of
other experienced surgeons.
When new equipment is introduced, all members of the surgical team must be trained on and
practice with the new equipment as appropriate for
the extent of their involvement, and all personnel
involved must be aware of all safety features, warnings, and alarms of the device. Whenever possible,
the institutions medical engineering department
should inspect the equipment and verify that it is
functioning properly before the equipment is put
into clinical use. Any informational material (eg,
users manuals, operating instructions) provided by
the manufacturer of the equipment should be carefully reviewed by the principal users and should be
familiar to anyone using the equipment. Stickers
attached to the device or plastic cards summarizing
instructions for proper use may be helpful until
everyone involved is comfortable with the new
equipment. All necessary adaptors, attachments, and
supplies should be in the room or readily available
before beginning surgery using the new equipment.
Any recommended protective devices, such as eye
shields or special draping material, should be used
for the safety of all concerned. The lead surgeon
using the new equipment should have demonstrated
competency using the device, resulting in the
granting of privileges. Leaders of each surgically
oriented department will determine the specific
requirements for granting privileges to their members for the use of new techniques or equipment. It
is never appropriate for nonmedical, noncredentialed individuals, such as industry representatives,
to perform the actual surgery. Such individuals
should be excluded from the operating room if their
presence would present a distraction or discomfort
for any member of the essential operating room team.
Stress and Fatigue

A well-recognized source of human error is unusual
stress and fatigue. According to the Health and
Safety Laboratory, Britains leading industrial health
and safety facility and an agency of the British
Health and Safety Executive, Disrupted sleep patterns and inadequate sleep can result in fatigue and
reduced levels of cognitive performance thus
increasing the risk of an accident. [H]uman error
arising from fatigue may have catastrophic results in
safety critical environments (3). Sleep deprivation
can cause errors in performing even the most familiar tasks; for example, the National Traffic Safety
Administration reports that sleepy drivers cause at
least 100,000 automobile accidents annually in the
United States, resulting in approximately 40,000
injuries and 1,500 deaths (4). For this reason, many
industries have already imposed strict limitations on
working hours for individuals in vulnerable occupations, such as truck drivers, airline pilots and crew
members, air traffic controllers, and power plant
personnel. The Accreditation Council on Graduate
Medical Education (ACGME) has enacted restrictions on resident work hours to prevent sleep deprivation, stress, and fatigue that might increase the
risk of error (5, 6). Although no legal restrictions
have yet been imposed on the work hours of practicing physicians, common sense dictates that the surgeon and the surgical team should be alert and well
rested when initiating major surgical procedures.
Emergency situations may be particularly hazardous
as an environment for error, especially if the surgical team is stressed and fatigued already. Adequate
backup personnel should be available to relieve individuals who detect diminished performance in
themselves or others due to fatigue, so that the risk
of errors is not increased.
Medication Errors
The surgical environment deserves heightened vigilance to prevent medication errors because medication orders often are given verbally rather than in
writing, making such orders particularly vulnerable
to misinterpretation or misapplication. Increased
stress or confusion during urgent situations in the
operating room may increase the possibility of error
in prescribing, administering, or monitoring medications. For these reasons, medication error in the
surgical arena may not be addressed by the safety
measures (eg, electronic order entry) proved effective in other environments. It may be wise for the
surgical team to agree on protocols for administering commonly used medications or treatments and
to practice their implementation. Timely and effective communication between the surgical and anes-
COMMITTEE OPINIONS
thesia teams during the entire procedure may help

avoid errors that could result from misunderstanding.
Teaching
Trainees, such as obstetricgynecologic residents,
surgical residents, anesthesiology residents, medical
students, nursing students, and operating room technician students, may be part of the surgical environment in the operating room or labor and delivery
suite. The education process in these environments
presents special challenges in protecting patient
safety. It is a fundamental principle that all trainees
must be meticulously supervised and assisted when
participating in surgery. Both the trainee and the
supervisor should be alert, well rested, and well prepared in advance for the surgical procedure being
performed. Because patient safety depends on effective communication among all members of the
health care team, trainees should be conversant in
the pertinent terminology before starting the procedure. The presence of noninvolved individuals as
observers in the operating room or delivery suite
may be a distraction to the surgical team and, therefore, should receive careful consideration before
they are admitted. The current development of virtual surgery training techniques may become useful
for students to learn and practice surgical skills
before attempting procedures in the operating room.
Obstetric Surgery
Operating on pregnant patients creates unique
responsibilities in ensuring patient safety because
two or more patients are involved simultaneously
the woman and the fetus(es)each with different
needs. Adequate personnel who will ensure proper
attention to the condition of each patient must be
present. Particular attention is needed to address
administration of the different medications appropriate for the pregnant patient and her fetus and the
newborn patient or patients, such as dosage and
timing of antibiotics or analgesics for mother or
newborn or both. The obstetric surgeon also is challenged to communicate with a pediatrics team in a
timely and effective manner to reduce the possibility of error in care of the neonate. The occasional use
of blood transfusion opens another potential avenue
for introduction of error because calling for the
administration of blood products may take place
under especially stressful and hectic conditions.
607
Much obstetric surgery is by nature unplanned as the

course of the delivery unfolds, and obstetric emergencies can progress rapidly, increasing the possibility of error if protocols and standardized procedures
are skipped or abbreviated.
Freestanding Surgical Units

In recent years, many surgical procedures traditionally performed only in hospitals or similar
institutions have increasingly been performed in
physicians offices, freestanding surgical facilities,
or surgi-centers. This trend has produced cost savings and convenience for patients as well as
providers and will likely continue. However, because
these facilities may not be subject to the same level
of scrutiny or administrative oversight as hospitals,
surgeons who use these facilities must be particularly
vigilant against inadequate training of personnel,
inappropriate or poorly maintained equipment and
instruments, and ineffective protocols or practices,
all of which may increase the likelihood of medical
error and jeopardy to patient safety.
Distractions
Beepers, radios, telephone calls, and other potential
distractions in the surgical environment should be
kept to a minimum, if allowed at all, especially during critical stages of the operation. Nonessential
conversation should be postponed until surgery is
finished. Similarly, it may be preferable to ask
nonessential personnel to remain outside the operating room while surgery is being performed.
Conclusion
Although medical errors can occur in any aspect of
medicine, the surgical environment presents additional, special challenges to safeguarding patient
safety. Because these injuries can be serious, particular care is appropriate in creating systems and routines that reduce the likelihood of wrong-patient,
wrong-side, and wrong-part surgical errors. The
wide variety of techniques, instruments, and technology used for surgical procedures makes granting
privileges of surgeons critically important.
Freestanding surgical units may need to be particularly vigilant in ensuring that personnel and equipment are in good condition for surgery. Protocols
and procedures to identify and manage stress and
608
fatigue in surgical personnel may help to avoid surgical errors and patient injuries. The operating room
is an appropriate educational environment, but the
presence of observers at any level must not be
allowed to compromise patient safety. Patient safety
in surgery demands the full attention of skilled individuals using well-functioning equipment under
adequate supervision.
References
1. A follow-up review of wrong site surgery. Joint Commission on Accreditation of Healthcare Organizations.
Sentinel Event Alert 2001;24. Available at: http://www.
jcaho.org/about+us/news+letters/sentinel+event+alert/
sea_24.htm. Retrieved September 15, 2005.
Organizations. Universal protocol for preventing wrong
site, wrong procedure, and wrong person surgery. Avail-
3.
4.
5.
6.
able at http://www.jcaho.org/accredited+organizations/
patient+safety/universal+protocol/wss_universal+
protocol.htm. Retrieved September 15, 2005.
Health and Safety Laboratory (UK). Case studies
fatigue and shiftwork in safety critical industries. Available at: http://www.hsl.gov.uk/case-studies/fatigue.htm.
National Highway Traffic Safety Administration. The
dangers of drowsy drivingsome startling statistics. Available at: http://www.nhtsa.dot.gov/people/injury/drowsy_
driving1/human/drows_driving. Retrieved September 15,
2005.
Accreditation Council for Graduate Medical Education.
Statement of justification/impact for the final approval of
common standards related to resident duty hours.
Available at: http://www.acgme.org/acwebsite/dutyhours/
dh_impactstatement.pdf. Retrieved September 15, 2005.
Buysse D, Barzansky B, Dinges D, Hogan E, Hunt CE,
Owens J, et al. Sleep, fatigue, and medical training: setting an agenda for optimal learning and patient care. Sleep
2003;26:21825.
COMMITTEE OPINIONS
ACOG
Committee on
Quality Improvement
and Patient Safety
Reaffirmed 2007
609
Committee
Opinion
Number 329, March 2006

Copyright March 2006
from the publisher.
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Tracking and reminder systems.

2006;107:745-7.
Tracking and Reminder Systems

ABSTRACT: An accurate and effective tracking or reminder system is useful
for the modern practice of obstetrics and gynecology. It is not adequate to
rely solely on the patient to complete all ordered studies and to follow up on
physician recommendations. Obstetriciangynecologists have an obligation
to their patients to encourage them to complete studies believed essential for
patient care within an acceptable time frame. Each office should establish a
simple, reliable tracking and reminder system to improve patient safety and
quality of care and to minimize missed diagnoses.
The accurate and timely flow of information between patients and clinicians
is important for safe and effective care. Patient visits often require some form
of follow-up involving further testing, referrals, communication of test
results, or consultations. Physicians offices should have procedures in place
to track these events effectively and to enhance quality of care and patient
safety. An effective and reliable reminder system need not be complex or
expensive but is a necessity for obstetric and gynecologic care in all practice
settings. Failure to follow up may cause delayed or missed diagnoses, which
may result in an adverse patient outcome and potential liability for the physician. Although it is recognized that patients have responsibility for following
through on their physicians recommendations, courts have held that the
health care professional is responsible for contacting patients about laboratory, imaging, or consultation results. An adequate tracking system can help
in reducing risks and providing safe, high-quality patient care. Clinicians
should recognize the potential to improve patient safety by adopting tracking and reminder systems.
The process for good patient follow-up begins with the practitioner
explaining to the patient at the initial visit any needed test, referral, or follow-up and documenting this discussion in the chart. Clear information and
instructions will help the patient participate in her care and understand why
a test or appointment is important. The next step is logging these open items
into a tracking or reminder system promptly and reviewing them frequently
and regularly according to the offices established procedures.
An appropriate tracking system can be manual or electronic. A successful system may be in the form of a log book, card files, file folders, computer system, or any system accessible for ongoing updating and monitoring.
610
Computerized systems can be helpful, but they also

may be expensive and time-consuming to establish
and are not necessary. In most clinical situations, a
simple paper-based tickler system can be developed. No matter what system is used, correct and
prompt data entry is a necessity.
Once information is entered into the system, it
should be retrieved and reviewed regularly with
accompanying documentation of any actions taken
or discussions with the patient. Information on each
patient should be reviewed throughout the entire
process from data input through resolution.
Allowing all personnel who participate in tracking to
provide input into the system design and implementation should encourage its use. To decrease risk of
system failure, the number of steps should be minimized and the number of responsible people limited.
However, if possible, the responsibility should not
rest with only one person.
Trackable Events
Each office should prioritize items according to their
importance for tracking. As the system is tested and
improved, additional elements can be added. The
following list reflects common tracking needs for
many obstetric and gynecologic practices.
Pap test results and follow-up, need for colposcopy
Mammography results and necessary follow-up
All laboratory tests and radiologic studies
Pathology reports
Routine as well as special obstetric testing, such
as multiple marker studies
After-hours and on-call emergencies, including
follow-up on laboratory and radiologic studies
from the hospital and emergency department
Follow-up appointments should be scheduled.
Patients should be reminded about the importance of
keeping their postoperative visits and other followup appointments. Whenever a patient does not
appear for a scheduled appointment, that fact should
be recorded in her medical record. Although patients
cannot be forced to keep their appointments, an
attempt should be made to contact them when an
appointment is missed and to assist them in rescheduling. Each office should develop a procedure for
dealing with patients who do not appear for an
appointment after several appointments have been

made. Because different state laws apply, the procedure should be appropriate to the state.
Referrals to consultants should be tracked, noting whether the patient has visited with the consultant and whether the consultants report has been
filed in the chart. Referrals of patients from other
clinicians also should be tracked, with notification to
the referring physician once the patient has been
seen.
Suggested Characteristics of the

Reminder System
The following characteristics are important for any
reminder system, whether electronic or paper-based.
Policies and procedures. An office policy and
procedure on tracking should be developed with
input from the staff. All office members should
agree to follow the same protocols. The office
policy should address how to contact the patient
and how to document the follow-up in the
patients chart. Usual time frames for when to
expect various types of results should be
defined, and a protocol should be established for
dealing with delayed or missing reports.
HIPAA compliance. When contacting patients,
physicians and their staff must follow Health
Insurance Portability and Accountability Act
(HIPAA) regulations. For example, postcard
reminders are not compliant. In addition, e-mail
is not HIPAA compliant unless both the office
and the patients systems are secure. Most personal e-mail services are not secure.
Specificity. The reminder system should contain
specific data and dates, including the dates for
receipt of information and timelines for notifying the patient.
Central location. The reminder system should be
centrally located in the office and should not be
kept in individual patient charts. Reminders
should be accessible to the entire staff.
Reliability. The tracking system should not be
the responsibility of a single individual. It
should be updated and monitored regularly.
Office staff should be cross-trained so that the
system is reliable and efficient.
COMMITTEE OPINIONS
Sample Tracking Form

A tracking form can pinpoint key follow-up areas.
Listed as follows are the important elements to be
tracked:
Date ordered
Patient name
Identifying number
Test, procedure, consult, or referral
Date of results
Follow-up required
Evaluation completed and patient notified
All printed results, including Pap tests, mammograms, consults, and pathology reports, should be
reviewed, initialed, and dated by a clinician who has
been designated to perform this function. Results
should then be filed permanently in the patient chart,
including a notation of what follow-up testing or
procedures are recommended.
The no news is good news approach is not
recommended as a standard practice for follow-up.
Patients should be made aware of the office practice
for notification of results and should be encouraged
to call back for results if they are not received in a
timely fashion. However, the office should not rely
solely on the patient to call back for results but
should have a more effective system. Computerized
tracking and reminder systems are available with
custom alerts, telephone reminders, and telephone
numbers to call for automated test results using individual identifying numbers. Such systems are not
required for appropriate follow-up and patient notification and can be difficult, time-consuming, and
expensive to implement. Any tracking and reminder
system may seem initially to require extra time
and cost; however, use of tracking systems rapidly
becomes routine for the practice and will enhance
the quality of care, patient outcomes, and patient satisfaction while helping to enhance patient safety.
Designing and implementing a tracking and
reminder system also provide an opportunity to
develop further a culture of safety in the office. A
system that is standardized, simple, and accessible
to all potential users will reduce the likelihood of
error. When problems or mistakes occur, staff should
be encouraged to report them. Errors are a valuable
way to learn why and how systems fail, and exploring the causes of errors provides an opportunity to
improve those systems. Ultimately, an informed and
611
involved patient, a well-designed tracking system,

and clinicians and staff who feel safe to discuss system failures will render safer patient care and
improve outcomes.
Resources
National Patient Safety Foundation
1120 MASS MoCA Way
North Adams, MA 01247
(413) 663-8900
http://www.npsf.org
Joint Commission on Accreditation of Healthcare
Organizations
One Renaissance Boulevard
Oakbrook Terrace, IL 60181
(630) 792-5000
http://www.jcaho.org/accredited+organization/patient+safety
Institute for Healthcare Improvement
20 University Road, 7th Floor
Cambridge, MA 02138
(617) 301-4800
http://www.ihi.org/ihi
Copic Companies
7351 Lowry Boulevard
Denver, CO 80230
(800) 421-1834
http://www.callcopic.com
Norcal Mutual Insurance Company
560 Davis Street
(800) 652-1051
www.norcalmutual.com
612
ACOG
Committee on
Quality Improvement
and Patient Safety
Reaffirmed 2007
Committee
Opinion
Number 331, April 2006

subject to change. The information
Copyright April 2006
directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Safe use of medication. ACOG

2006;107:96972.
Safe Use of Medication

ABSTRACT: Medication use errors are the largest single source of preventable adverse events. To minimize the risk of medication use errors, obstetriciangynecologists should focus on several elements of medication order
writing, such as the appropriate use of decimals and zeros, standard abbreviations, and assuring legibility. Additionally, it is important to assist the
patient in understanding the medical condition for which a medication is
prescribed. Focusing on elements that may prevent prescription errors and
helping patients understand how to use prescribed medication properly may
help lower the occurrence of medication use errors.
Safe use of medication is a systems issue, encompassing more than written

prescriptions. Physicians have an obligation to seek improvement in medication use safety, which entails the entire process of integrating medications
into the patients clinical setting. The following definition of a medication
error demonstrates the broad areas that the clinician should consider:
A medication error is any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the
health care professional, patient, or consumer. Such events may be related to professional practice, health care products, procedures, and systems, including prescribing; order communication; product labeling, packaging, and nomenclature;
compounding; dispensing; distribution; administration; education; monitoring;
and use. (1)
Some events listed in this definition are outside the purview of the physician, such as product labeling, color of medication, and nomenclature
assigned when a drug is introduced to the public. However, errors in the prescription, formulation, and administration of pharmaceutical agents are common and, in many cases, preventable causes of patient harm.
Medication Use
As part of their daily practice of medicine, clinicians should become familiar with the medications that are available to treat their patients, and there are
several steps they can take to accomplish this:
Maintaining up-to-date references of current medications
Understanding the indications of the medication considered, including
all alternative therapies
COMMITTEE OPINIONS
Considering conditions that may affect the efficacy of the medication, such as dosing schedules, route of administration, patient weight, and
renal and hepatic functioning
Understanding the interactions of considered
agents with other medications used by the
patient as well as therapies being considered
(including surgical treatments)
Ensuring that a patients current medication is
continued, if appropriate, when admitting that
patient to the hospital and that additional medication used during the hospital stay is compatible
with the patients current therapeutic regimen.
Medication ordering errors are the leading cause
of medical errors (2). Much of the published literature regarding medical errors has focused on the
types and causes of these errors, centering on clinical problems such as allergy-related contraindications that go undetected, inappropriate dosage
forms, and excessive dosing (34). Medication ordering errors also arise from more technical causes,
such as poorly written or misinterpreted handwritten
medication orders.
The complexity of prescribing drugs is attributed, in part, to the number of agents, which has
increased at a staggering rate. Prescription problems
such as illegible words, missing components, and
the inappropriate use of abbreviations have been
anecdotally reported for many years. The problem
has been compounded in recent years because of the
influx of new drugs with look-alike and soundalike names, making prescription interpretation
more difficult (5).
Medication Order Writing

Medication order writing is one aspect of medical
care that is within the control of every prescriber.
The essentials of safely writing medication orders
include focusing on certain elements of the order as
follows:
Medication order legibility

Missing medication order components
Decimals and zeros
Abbreviations
As needed (pro re nata) medication orders
Similarity of trade names
Sound-alike drugs
Verbal medication orders
613
Order Legibility
Computerized physician order entry systems virtually
eliminate prescription legibility concerns. However,
they are expensive and lack widespread implementation. Until computerized physician order entry systems become more widely available, prescribers
should be particularly diligent about the legibility of
their prescription orders (6).
Missing Medication Order Components
To prepare a complete, legible medication order, the
following components must be clearly written on the
medication order form:
Name of the drug

Dose to be given
Route of administration
Frequency of administration (or rate)
Reason or conditions under which the drug
should be administered (if prescribing pro re
nata)
Patients weight and age (if relevant to dosing)
If any of these components are missing, the medication order is incomplete. Filling an incomplete medication order substantially increases the risk of a
medication error. The prescribers signature and
identification number also should be written or
printed on the prescription.
Decimals and Use of Leading and Trailing Zeroes
One area that contributes to medication errors is the
misuse of leading and trailing zeroes with decimal
points. The decimal point often is not seen when
the medication order is read (especially when a
copy of the order is used to fill the prescription
rather than the original medication order), potentially causing a 10-fold overdose. A leading zero
should always be used when prescribing doses of
less than 1 (Fig. 1). Similarly, a whole number
should never be followed by a decimal point and a
zero (Fig. 2). A mnemonic for these constructions is,
always lead, never follow.
Inappropriate Abbreviations
In medication orders, the use of nonstandardized
abbreviations creates confusion and can contribute
to medication errors if the abbreviations are not
interpreted as they are intended by the prescriber.
Most health care institutions have standardized lists
of acceptable abbreviations. National organizations
614
.1 mg
0.1 mg
Incorrect
Correct
1.0 mg
1 mg
Incorrect
Correct
Fig. 1
Fig. 2
also have made recommendations about acceptable

abbreviations. Some organizations provide alerts
about dangerous abbreviations and other medication
safety related recommendations on their web sites
(see Resources). The following general guidelines
should be followed when using abbreviations:
Drug names should not be abbreviated.
Q.D. should not be used to abbreviate once
daily. Sometimes the dot that follows the Q
looks like an I and the abbreviation appears to
be QID. There is no safe abbreviation for once
daily; it should always be written out.
O.D. should not be used to abbreviate once
daily. O.D. is properly interpreted as right eye.
Use of this abbreviation to represent once daily
has resulted in prescription administration errors
with liquid medications such as saturated solution
of potassium. There is no safe abbreviation for
once daily; it should always be spelled out.
The metric system should be used.
The word unit should not be abbreviated. The
handwritten U or u may often look like a
0 (zero) and may cause a 10-fold overdose.
Pro Re Nata Medication Orders
When prescribing a medication, it is helpful to provide the reasons for giving the medication or para-
meters for giving a pro re nata dose. This is particularly helpful in preventing errors with sound-alike
and look-alike medications or for medications that
are to be given on an as-needed basis.
Verbal Medication Orders
Verbal medication orders should be limited to urgent
situations in which written (or electronic) medication orders are not feasible. To assure accuracy,
verbal medication orders (whether in person or by
telephone) should be followed by a request that the
person receiving the order repeats the order to the
prescriber. Because many drugs have sound-alike
names, it may be helpful to include the indication
for the drug in verbal medication orders.
Patient Education
Clinicians should assist the patient in understanding
the medical condition for which a medication has
been prescribed. Engaging the patient in her own
care improves compliance, outcome, and patient satisfaction and reduces error. This requires the concerted effort of all members of the medical team,
both in and out of the hospital. Such education may
take the form of oral communication or handouts
that explain the use, dosage, expected benefits, and
possible side effects of the medication that is pre-
COMMITTEE OPINIONS
scribed. Patients should be given ample opportunity

to ask questions and reiterate, to the clinicians satisfaction, their understanding of proper use of their
medications. Allergies should be well documented
and reviewed with the patient. A list of other medications currently in use by the patient should be documented, and the patient should retain a copy of this
list for personal benefit and to show to other
providers in the future. Including family members
who will assist the patient in medication use in such
education will help assure accurate use of the prescribed medication.
References
1. National Coordinating Council for Medication Error
Reporting and Prevention. About medication errors.
Available at: http://www.nccmerp.org/aboutMedErrors.
html. Retrieved January 28, 2005.
2. Thomas EJ, Studdert DM, Newhouse JP, Zbar BI, Howard
KM, Williams EJ, et al. Cost of medical injuries in Utah
and Colorado. Injury 1999;36:25564.
3. Lesar TS, Briceland L, Stein DS. Factors related to errors
in medication prescribing. JAMA 1997;277:3127.
4. Davis NM, Cohen MR, Teplitsky B. Look-alike and
sound-alike drug names: the problem and the solution.
Hosp Pharm 1992;27:95110.
5. Cabral JDY. Poor physician penmanship. JAMA 1997;278:
11167.
Conclusion
All physicians feel a strong sense of urgency to
reduce the medical errors that occur as a result of
their care. Because obstetricians often deal with both
the pregnant woman and her fetus, they have a measurably increased need to vigilantly protect their
patients. Following these suggestions will not only
reduce errors but, more importantly, will create the
awareness necessary to provide care more safely.
The Committee on Quality Improvement and Patient
Safety encourages physicians to begin examining all
aspects of patient safety, both in the hospital setting
as well as within their offices.
615
Resources
Institute for Safe Medication Practices
1800 Byberry Road, Suite 810
Huntingdon Valley, PA 19006
Tel: (215) 947-7707
E-mail: ismpinfo@ismp.org
Web: www.ismp.org
National Coordinating Council for Medication Error
Reporting and Prevention
Web: www.nccmerp.org
616
ACOG
Committee on Quality
Improvement and
Patient Safety
Committee
Opinion
Medical Emergency Preparedness

directed to:
222 Rosewood Drive
Danvers, MA 01923
(978) 750-8400
ISSN 1074-861X
409 12th Street, SW
PO Box 96920
Medical emergency preparedness.
2006;108:15979.
ABSTRACT: Patient care emergencies may occur at any time in a hospital or

an outpatient setting. To respond to these emergencies, it is important that
obstetriciangynecologists prepare themselves by assessing potential emergencies that might occur, creating plans that include establishing early
warning systems, designating specialized first responders, conducting emergency drills, and debriefing staff after actual events to identify what went
well and what are opportunities for improvement. Having such systems in
place may reduce or prevent the severity of medical emergencies.
A practicing obstetriciangynecologist may be faced with a sudden patient

emergency at any time. Whether it is severe shoulder dystocia, catastrophic
surgical hemorrhage, or an anaphylactic reaction to an injection in the office,
it will require prompt corrective action. Preparing for potential emergency
events requires planning for potential events, advance provisioning of
resources, establishing an early warning system, designating specialized first
responders, and holding drills to ensure that everyone knows what to do in
an emergency. Beyond these basics, certain principles of communication and
teamwork will enhance the effectiveness of the emergency response.
Planning
Planning for potential emergency events may be simple or complex. At a
minimum, it should involve an assessment of the potential or actual risks
related to the practice setting or the patient population. For instance, in the
outpatient setting, are medications given or procedures performed that may
result in anaphylaxis, airway embarrassment, or hemorrhage? In the inpatient setting, unit data or risk management data may reflect common and
uncommon emergency situations that have occurred.
Advance Provision of Resources

A common practice for health-care-related emergencies is the availability of
the crash cart. All physicians should be familiar with the crash cart. By
placing all necessary items in one place, one ensures that time is not lost
gathering supplies in an emergency. Appropriate changes should be made to
COMMITTEE OPINIONS
the cart as evidence-based changes are made to the

Advanced Cardiac Life Support protocol. Advance
provision of resources also may be extended to the
management of eclampsia and malignant hyperthermia. Physicians in outpatient settings may wish to
create a small kit for handling allergic reactions if
they are not able to maintain a full crash cart. As with
a crash cart, the kit must be maintained regularly to
ensure supplies are not expired. All providers need to
know how to access the kit.
Early Warning Systems

Some emergencies are truly sudden and catastrophic, such as a ruptured aneurysm, massive pulmonary embolus, or complete abruptio placentae in
the setting of trauma. However, many physiologic
emergencies are preceded by a period of instability
during which timely intervention may head off
ensuing disaster. The medical emergency team (discussed later) is set up to handle such emergencies.
Even without the use of a medical emergency team,
however, nurses and other bedside caregivers need
to realize that certain changes in a patients condition can indicate an emergency that requires immediate intervention and correction. These changes
include some events not usually understood as
emergencies, such as agitation or new onset difficulty with movement. Ideally, each service will
examine its own historical call data to determine
which events require activation of the early warning
system. It is imperative that bedside personnel be
able to request immediate help, without recrimination, when such changes occur. For example, the
nurse who calls the medical emergency team
regarding the anxious postoperative patient with
newly onset shortness of breath must not be dismissed as failing to recognize a panic attack but
instead thanked for following protocol. The protocol should provide for a full evaluation of the
problem. Some organizations have formalized the
emergency communication process with the
development of a communication tool, such as
SBAR (Situation, Background, Assessment, and
Recommendation); all providers are encouraged
to follow it to clearly communicate the patient
care issue. Standardized responses will increase
the efficiency of care and allow a continuous quality improvement process to assess the effectiveness of the interventions.
617
Specialized First Responders

Medical emergency teams are designated emergency response teams. Activation of the team to the
bedside occurs when predefined criteria are met,
although the team also may be activated for other
reasons. Activation should be a no-fault process.
The team is available at all times with authority to
summon further help as needed. By designating criteria that define an emergency, it becomes clear
when to call for help. For example, if a maternal or
postoperative heart rate of more than 140 beats per
minute is the criterion, the nurse who notes such
heart rate must immediately call the medical emergency team. This contrasts with the common practice of calling an attending physician and awaiting a
call back for orders before intervention. Activation
of the emergency response system before a full
arrest may lead to improved survival of hospitalized
patients and decreased admissions to an intensive
care unit. It is important to emphasize that if there is
a teaching service, calling the house officer does not
substitute triggering the medical emergency team.
Similarly, calling the in-house physician in a nonteaching setting does not substitute activating the
medical emergency team. Medical emergency teams
usually have advanced practice nurses and respiratory therapists as first responders and are expected to
respond to the problem in a standardized fashion.
The goal of standardized response and rapid effective recognition and correction of problems is better
met with a small stable group. Creation of medical
emergency teams is one of the patient safety initiatives currently being promoted by the Institute for
Healthcare Improvement and the American Medical
Association. Blueprints for setting up such a team,
as well as other resources, may be found at the web
sites of these organizations (see Resources for contact information).
Emergency Drills
The principle that standardized care can result in
safer care applies to emergencies as well as to routine care. Thus, each service should consider a protocol for management of common emergencies,
such as emergency cesarean deliveries. The fields of
aviation and anesthesia both have invested heavily in
the concept of simulation training or the emergency
drill. This training may use a sophisticated simulated environment but it also may use the everyday
work space in a mock event. Protocols also can be
618
reinforced by prominently displayed posters, pocket

cards, or other aids.
Using drills to train physicians to respond to
emergencies has several theoretical advantages.
Adult learning theory supports the importance of
experiential learning. Emergencies do not occur on
paper; they occur in a specific physical setting and
may involve a group of nurses, physicians, and other
health care providers attempting to respond. By conducting a drill in a realistic simulator or in the actual patient care setting, issues related to the physical
environment become obvious. Are the necessary
drugs readily available? Can the personnel in the
patient room easily obtain blood products or does
someone need to be designated to coordinate obtaining products with the nursing station? How much
time does it actually take to get from the farthest corner of the labor suite to the delivery room?
Emergency drills also allow physicians and others to practice principles of effective communication
in a crisis. Many aspects of the medical environment
work against effective communication, including the
often hierarchical nature of the training and work
setting and the different educational backgrounds
and levels of understanding of the care giving team.
Many physicians are accustomed to talking to
nurses. Effective teamwork requires talking with
each other. It requires that there be a team leader
coordinating the response, but it should also empower all members of the team to share information. By
practicing together, barriers hindering communication and teamwork can be overcome. Effective drills
may lead to improved standardization of response,
provider satisfaction, and patient outcomes.
Conclusion
The obstetriciangynecologist practices in an environment where true emergencies will eventually
occur. Preparation for these situations requires that

supplies and an educated team be in place before the
event. The exact nature of the preparation will
depend on the work environment and the resources
available.
Bibliography
Hamman WR. The complexity of team training: what we have
learned from aviation and its application to medicine. Qual Saf
Health Care 2004; 13(suppl):i729.
Resources
Institute for Healthcare Improvement
Establish a Rapid Response Team
20 University Road, 7th Floor
Cambridge, MA 02138
Tel: 866-787-0831
Web: http://www.ihi.org/IHI/Topics/CriticalCare/
IntensiveCare/Changes/EstablishaRapidResponse
Team.htm
American Medical Association
Advancing Quality Improvement in Patient Care
515 N. State Street
Chicago, IL 60610
Tel: 800-621-8335
Web: http://www.ama-assn.org/go/quality
MOREOB
Managing Obstetrical Risk Efficiently
The Society of Obstetricians and Gynecologists
of Canada
780 Echo Drive
Ottawa, ON K1S 5R7
Tel: 800-561-2416
Web: www.moreob.com
COMMITTEE OPINIONS
619

Number 366 May 2007
Disruptive Behavior
Committee on
Patient Safety and
Quality Improvement
ABSTRACT: Disruptive behavior may have a negative effect on patient care.

Consequently, it is important that a systematic process be in place to discourage, identify, and remedy episodes of disruptive behavior.
Reaffirmed 2009
patient safety and is subject to change. The information should not be construed as dictating an
followed.
A growing number of organizations recognize

that disruptive behavior may compromise
patient care. Numerous reports of disruptive
physician behavior in the media and literature demonstrate its effect on patient care
and other staff. The AMA Report of the
Council on Ethical and Judicial Affairs
defines disruptive behavior as a style of
interaction...that interferes with patient
care...[and] that tends to cause distress
among other staff and affect overall morale
within the work environment, undermining
productivity and possibly leading to high
staff turnover or even resulting in ineffective
or substandard care. (1) Several types of
behavior can create distress or negatively
affect morale in the work environment.
Example behaviors include:
Profane or disrespectful language
Yelling at or insulting others
Throwing instruments, charts, or other
objects
Bullying or demeaning behavior
Criticizing other caregivers in front of
patients or other staff
Sexual comments or innuendo (2)

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Yelling, insulting others, or a refusal to carry

out duties are among the most common
types of behaviors reported. The targets of
such behavior are often co-workers with less
power than the offending individual as exemplified by the relationships between staff
physicians and nurses, residents, or medical
students (3). A consequence of this type of

behavior is corruption of teamwork.
Best estimates suggest that a small number of physicians (35%) are responsible for
most of the reported disruptive behavior (3).
Although relatively few physicians exhibit
these behaviors, 95% of physician executives
reported knowing of disturbing, disruptive
and potentially dangerous behaviors on a
regular basis (4). A recent study concluded
that many disruptive physicians began to
show evidence of such behavior as medical
students (5), highlighting the potential
importance of recognizing behavioral patterns early in career development.
Ultimately, disruptive behavior may
have a negative effect on patient safety and
quality of care by causing others to avoid the
disruptive physician. Staff may refrain from
asking for help or clarification and hesitate
to make suggestions about care to the disruptive physician. Additionally, patients who
witness the behavior may lose confidence
in the health care provider as well as the
institution.
Several factors contribute to a reluctance to systematically confront disruptive
behavior, including financial concerns such
as physician referrals and fear of retribution
(eg, lawsuit for antitrust or defamation of
character) (6). Therefore, institutions should
develop a multifaceted approach for dealing
with disruptive behavior. It is essential that
administration fully support and show commitment to addressing disruptive behavior.
620
An effective approach would include the following

components (2).
Establishing a Code of Conduct

Institutions should consider establishing a code of
conduct that stipulates behavioral standards and the
consequences for failure to comply. Specific examples
of unacceptable behavior should be included to provide
guidance for leadership, employees, and staff in determining what constitutes disruptive behavior. If a formal
mechanism is adopted, at appointment and reappointment, each medical staff member should acknowledge
acceptance of both the behavioral standards and the consequences of failure to comply, as detailed in the code of
conduct, consistent with provisions contained in the
medical staff bylaws. A training program about the code
and attendant behavioral expectations may be included as
part of this approach.
Instituting a Monitoring and Reporting

System
A monitoring system may be considered. Systematic
review could include regular surveys of staff, focus
groups, peer and team member evaluations, and direct
observation to detect incidents of disruptive behavior (2).
Implementing a confidential system for reporting also
could include routine confidential evaluations and formal
analysis of complaints by patients, co-workers, or others.
These evaluations should be provided in a confidential
manner to the appropriate administrative individual,
such as the chair of the department of obstetrics and
gynecology or the chief of staff for resolution. The individual in question should be notified and given an opportunity to respond to the complaint.
Resolution
Any complaints should be handled in a confidential manner with interventions designed to assist in behavioral
change whenever possible. Complaint resolution should
be consistent with medical staff, departmental, or other
institutional policies and procedures. Appropriate steps
should be taken to resolve the problem. Disciplinary
actions should be appropriate to the type of infraction and
frequency of behavior, including any mitigating factors.
Each institution should establish thresholds for taking
action that depend on the severity of the behavior. Some
actions may merit zero tolerance. All attempts to address
disruptive behavior should be clearly and thoroughly documented. The department chair should be informed of
individuals with persistent problem behaviors and responsible for establishing an appropriate response. The
response may include some or all of the following steps:
Face-to-face meeting with the physician exhibiting
disruptive behavior
A follow-up meeting (if the problem is still unresolved), resulting in a behavioral contract setting
forth any disciplinary actions that may be taken if

disruptive behavior persists
Formal counseling
Administrative hearing
Summary suspension for egregious behavior
Assessment and treatment programs that are tailored to
the individual should be made available as necessary.
Special attention should be given to the possibility of substance abuse or psychiatric diagnosis, which can contribute to disruptive behavior. At least initially, these
programs should attempt to enable the individual to continue or resume practice.
Conclusion
Disruptive physician behavior creates a difficult working
environment for all staff and threatens the quality of
patient care and, ultimately, patient safety. Colleagues often
find confronting these individuals difficult. Therefore, it is
important that clear standards of behavior are established
and all staff are informed of such standards, as well as
the consequences of persistent disruptive behavior. Confidential reporting systems, as well as assistance programs
for the offending physician, should be established.
References
1. American Medical Association. Physicians with disruptive
behavior. In: Code of medical ethics: current opinions and
annotations. Chicago (IL): AMA: 2006. p. 27980.
2. Porto G, Lauve R. Disruptive clinician: a persistent threat
to patient safety. Patient Saf Qual Healthc 2006;144:
10715.
3. Leape LL, Fromson JA. Problem doctors: is there a systemlevel solution? Ann Intern Med 2006;144:107115.
4. Weber DO. For safetys sake disruptive behavior must be
tamed. Physician Exec 2004;30:167.
5. Papadakis MA, Teherani A, Banach MA, Knettler TR,
Rattner SL, Stern DT, et al. Disciplinary action by medical
boards and prior behavior in medical school. N Engl J Med
2005;353:267382.
6. ECRI. Disruptive practitioner behavior. HRC Risk Analysis
Supplement A. Plymouth Meeting (PA): ECRI; 2006.

Disruptive behavior. ACOG Committee Opinion No. 366. American
109:12612.
ISSN 1074-861X
COMMITTEE OPINIONS
621

Communication Strategies for Patient

Handoffs
Committee on
Patient Safety and
Quality Improvement
Reaffirmed 2009
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: Handoff communication, which includes up-to-date information regarding patient care, treatment and service, condition, and any recent or anticipated changes,
should be interactive to allow for discussion between the giver and receiver of patient
information. It requires a process for verification of the received information, including
read-back or other methods as appropriate.
Accurate communication of information

about a patient from one physician to another is a critical element of patient care and
safety; it is also one of the least studied and
taught elements of patient care that physicians use on a daily basis. In its 1999 publication, To Err is Human: Building a Safer
Health System, the Institute of Medicine
estimated that between 44,000 and 98,000
patients die each year in U.S. hospitals
because of injuries that result from errors (1).
One of the leading causes of these errors is a
breakdown in communication. Ineffective
communication was cited as the root cause of
66% of all reported sentinel events from 1995
to 2004 and accounted for 85% of sentinel
events related to maternal death and injury in
2005 (2). This breakdown in communication
may occur between health care providers at
every level of the health care system.
Physician-to-physician handoff of patient
information is one of the most important
factors to focus on to prevent discontinuity of
care, eliminate preventable errors, and provide a safer patient environment.
Communication is the process by which
information is exchanged between individuals, groups, and organizations. In order to be
effective, communication should be complete, clear, concise, and timely. Barriers to
effective communication include factors such
as lack of time, hierarchies, defensiveness,
varying communication styles, distraction,
fatigue, conflict, and workload.
A handoff may be described as the transfer of patient information and knowledge
along with authority and responsibility from
one physician or team of physicians to

another physician or provider. The Joint
Commission requires implementation of a
standardized approach to handoff communications (National Patient Safety Goal [NPSG]
2E) (3). Properly executed handoffs are interactive and include the opportunity for questions and answers. A handoff may occur
during the transfer of care in any of several
circumstances, including from one on-call
physician to another, from the office physician to the hospital laborist or vice versa, or
from the generalist obstetrician gynecologist
to the intensivist. It also may occur between
the attending physician and a resident or
between the attending physician and nursing
staff. Every important aspect of the patients
condition and circumstance must be accurately communicated and acknowledged
from one party to the other for a safe and
effective handoff to occur. Communication at
the time of the handoff should result in a
clear understanding by each provider about
who is responsible for which aspects of the
patients care. Unacknowledged messages,
such as voice mail, do not constitute an
acceptable form of handoff.
Patient handoffs can be improved.
Addressing aspects such as physical environment, confidentiality, language, organizational culture, communication method, and
documentation are key to improving the
process.
Physical Environment
The physical environment in which the
transfer takes place may hinder effective
622
communication. For example, a noisy nursing station is a

less desirable setting for communicating handoff information than a quiet conference room located away from
other distractions. Having discussions in an environment
without distractions will enhance communication during
handoffs. Clinical acuity of the patients condition must
be considered in deciding the circumstances, the setting,
and the content of the handoff.
Confidentiality
Care must be taken to maintain patient confidentiality by
allowing only those involved with her care to hear or view
protected health care information. Physicians must be
aware of and comply with Health Insurance Portability
and Accountability Act (HIPAA) regulations.
Language
Language differences may interfere with the accurate
transfer of information. Using standardized medical terminology avoids errors in communication that may
occur when colloquialisms are used. Awareness of cultural and gender differences in communication style is an
important factor in how handoffs may be presented and
received.
Organizational Culture
The hierarchy of personnel, particularly in teaching settings, also may inhibit the transfer of important information about the patient. When information about the
patients care is being conveyed, a first-year resident
should be made to feel as comfortable talking with the
senior attending physician as with another resident. Every
member of the health care team that is present should be
encouraged to participate in and contribute to the transfer of information without reluctance.
Communication Method
The method of communication may be a significant
barrier to the effective transfer of vital information.
Structured forms of communication, such as the Situation-Background-Assessment-Recommendation (SBAR)
technique, should be considered. Communication may be
verbal, written, or both (4). The Joint Commission NPSG
2A requires that the person receiving a verbal or phone
order or test result read back the complete order or test
result for verification (3). Verbal communication includes
a face-to-face conversation or a telephone call. Face-toface exchange of information is generally the preferred
form of verbal communication because it allows direct
interaction among those present. Not only may questions
be asked and answered, but further nonverbal information may be expressed by body language and facial
expression. Written communication may assist the person
handing off the patient in organizing his or her thoughts
and presenting important details. It also allows the receiving party to have a paper- or computer-generated hard
copy of information for reference. Written communica-
tion, however, lacks the subjective interpersonal aspect of

verbal communication. The most effective handoff of
patient information includes both verbal and written
components.
Documentation
The written component of the handoff may be produced
by hand or by computer using an electronic medical
record (EMR). One of the main advantages of an EMR is
that it eliminates illegibility. Illegible handwriting has
been shown to be a major contributor to errors in patient
care. This issue is being addressed by many different
groups, including the Joint Commission. Although there
is no universally accepted protocol for all of the information that a written handoff should contain, there are several key elements that should be present in any transfer of
patient care. These include pertinent demographic information, a brief history and the results of a physical examination, an active problem list, medications and allergies,
pending test results, ongoing or anticipated therapy, and
any other critical information. Such information as code
status, psychosocial status, family issues, and long-term
care issues also may be included as circumstances warrant.
Conclusion
Providing a safer health care environment for patients
must become the hallmark of future health care. By
improving the process for transferring information that
occurs during physician handoffs, the care that patients
receive will be optimized and ideally should be seamless.
Studies are currently underway to determine the most
effective methods to perform and teach the transfer of
patient information. Physicians must strive to improve
their communication skills, not only with each other, but
also when interacting with other members of the health
care team. Awareness of the importance and challenges of
effective communication and implementation of effective
communication processes, especially as it relates to handoffs, will decrease errors that result in adverse events and
provide a safer patient environment.
References
1. Institute of Medicine (US). To err is human: building a safer
health system. Washington, DC: The Institute; 1999.
2. Joint Commission on Accreditation of Healthcare Organizations. Sentinal event statistics. Oakbrook Terrace (IL):
JCAHO; 2006. Available at: http://www.jointcommission.
org/sentinel events/statistics. Retrieved February 15, 2007.
3. Joint Commission on Accreditation of Healthcare Organizations. Comprehensive accreditation manual for hospitals: CAMH. Oakbrook Terrace (IL): JCAHO; 2006.
4. Institute for Healthcare Improvement. SBAR technique for
communication: a situational briefing model. Cambridge
(MA): IHI; 2006. Available at: http://www.ihi.org/IHI/
Topics/PatientSafety/SafetyGeneral/Tools/SBARTechniquef
orCommunicationASituationalBriefingModel.htm.
Retrieved February 15, 2007.
COMMITTEE OPINIONS
JCAHOs 2006 National Patient Safety Goals: handoffs are
biggest challenge. Hosp Peer Rev 2005;30:8993.
Solet DJ, Norvell JM, Rutan GH, Frankel RM. Lost in translation:
challenges and opportunities in physician-to-physician communication during patient handoffs. Acad Med 2005;80:1094
Focus on five: strategies to improve hand-off communication:
implementing a process to resolve questions. Jt Comm Perspect
Pat Saf 2005;5(7):11.
623

Communication strategies for patient handoffs. ACOG Committee
ISSN 1074-861X
624

Fatigue and Patient Safety

Committee on
Patient Safety and
Quality Improvement
followed.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
ABSTRACT: It has long been recognized that fatigue can affect human cognitive and
physical function. Although there are limited published data on the effects of fatigue on
health care providers, including full-time practicing physicians, there is increasing awareness within the patient safety movement that fatigue, even partial sleep deprivation,
impairs performance. Most of the current literature reviews resident function after recent
work reform changes. However, the information available from many studies in health
care and other occupations can be applied to the work habits of practicing
obstetriciangynecologists.
A safe and effective health care system must

be structured to minimize error and confusion. Individuals who are tired are more likely to make mistakes. Reducing fatigue may
improve patient care and safety as well as
reduce the risk of adverse outcomes, improve
health care providers satisfaction, and
increase communication. One of the most
significant limitations in evaluating fatigue is
the absence of an available metric for measuring accurately fatigue and its subsequent
effect on patient care.
Physicians are expected to offer safe and
effective care to their patients. Maturity as a
clinician requires recognition that medicine
is a human endeavor. As individuals develop
their clinical skills, they become aware of
their own unique strengths and weaknesses.
Professionals regularly seek consultations
when a problem exceeds their experience or
expertise. Seeking assistance when one is
fatigued is beginning to be seen in a similar
light. Fatigue may greatly affect health care
providers skills and abilities, communication, and possibly outcomes. Because of a
lack of research on the subject, there are no
current guidelines placing any limits on the
volume of deliveries and procedures performed by a single individual or the length of
time one may be on call and still perform
procedures. Each physician must recognize
his or her limitations caused by fatigue that
can occur from an excessively busy practice
and impose limits. External factors not related to the practice of medicine also must be
considered. Physicians at all stages in their
careers need to be cognizant of the demands
placed on them professionally and personally and should strive to achieve a balance that
will not lead to excessive fatigue or overcommitment.
The National Sleep Foundation (www.
sleepfoundation.org) recommends 8 hours
of sleep per night for an adult (1). The average American adult sleeps only approximately 7 hours per night. Sleep deprivation can be
caused by insufficient sleep, fragmented
sleep, or both. Although there is wide variation in sleep needs, individuals do not get
accustomed to less sleep than their biologic
requirement. One cannot store up sleep.
Recovery from a period of insufficient sleep
requires at least two or three full nights of
adequate uninterrupted sleep (1).
A number of uncontrolled studies have
looked at the effect of sleep restriction on
cognitive function (24). One small study
compared reaction times and performance
on a driving simulator between residents
who had ingested alcohol but were rested and
residents who were on a call rotation every
fourth night and found a correlation.
Emergency department physicians who were
rested have been compared with others on
sequential night call. The disruption of sleep
produced by shift work had a significant
impact on both visual memory and cognitive
performance (5, 6).
Several reviews of the literature show
that even a single night of missed sleep
measurably affects cognitive performance.
When adults do not sleep at least 5 hours
per night, language and numeric skills,
retention of information, short-term mem-
COMMITTEE OPINIONS
ory, and concentration all decline on standardized testing. Speed of performance may be affected more than
accuracy. For example, surgeons operated more slowly
in simulated procedures when sleep deprived; emergency department physicians took longer to intubate a
mannequin (710).
In other industries, fatigue often is invoked as a cause
of error and accident. The National Transportation Safety
Board rates excessive sleepiness as the second leading
cause of driving accidents in the United States (11). A
recent study by the Federal Railroad Administration
showed that human factor errors are responsible for
almost 40% of all train accidents over the past 5 years and
that fatigue played a role in approximately 25% of the
accidents (12). However, there is no clear evidence in
health care that restricting work hours improves patient
outcome. Several potential explanations for this exist. In
the residency setting, work-hour restriction often has
been achieved through a night-float system, which has
not been shown to decrease fatigue. Repeated episodes of
night work may result in accumulating sleep debt as
physicians find themselves unable to rest during the day.
Even a single night of complete sleep loss can require up
to 3 days for recovery. Thus, any resident schedule of
every fourth night or more frequent call schedules,
regardless of total hours worked, may result in reduced
acuity and function. Reduced hours may not be enough
to show reduced fatigue or improved outcomes. Further,
supervision of residents by other caregivers may intercept
incipient errors (6, 13).
The inability to document improved outcome after
residency work-hour reform does not mean that fatigue
can safely be ignored by practicing physicians. Memory
consolidation and insight formation require sleep. Sleepdeprived adults tend to exhibit impaired complex problem solving and to continue with solutions that do not
work (14). The need for sleep, like the need for food, can
affect decision making. Fatigue may drive people to avoid
work responsibilities to address sleep deprivation. Safe
and effective care requires mindful communication
between the patient and the physician and between the
physician and other caregivers. Mood may be even more
affected by sleep deprivation than cognitive or motor performance and may have a significant impact on a physicians ability to communicate effectively (9).
Although the implication of the studies mentioned is
that quality of care may be enhanced by increased physician rest, there is no current evidence that proves this
premise. We should continue to study and consider the
potential benefit of limiting physician call schedules balanced against loss of continuity of care.
It would be prudent to consider adapting, when feasible, the following guidelines from the National Highway
Traffic Safety Administration to medical work (11):
Structure work to take advantage of circadian influences.
625
Recognize that the drive to sleep is very strong

between 2 AM and 9 AM, and especially between 3 AM
and 5 AM. Avoid unnecessary work at that time.
Sleep when sleepy.
Provide for backup during times impairment is likely.
After working a night shift, go immediately to sleep
to maximize sleep length.
Apply good sleep habits. The sleep environment
should be quiet and dark. It should have adequate
ventilation and a comfortable temperature to allow
daytime sleep.
Recognize behavioral changes such as irritability that
may indicate dangerous levels of fatigue.
Use naps strategically. A 2-hour nap before a night
shift will help prevent sleepiness. If a 2-hour nap cannot be scheduled, then sleep no more than 45 minutes to avoid deep sleep and subsequent difficulty
with arousal.
Each practicing physician and every group should
review their work habits with these principles in mind.
Even though there may be some economic impact of
changing schedules to accommodate avoidance of fatigue,
patient care and safety must take priority over economic
concerns. A balance needs to be found between reducing
work hours and providing appropriate continuity of care
for individual patients.
Each provider should consider the following questions:
Should I work a half day or a full clinic day after a
night on call (or work at all)?
Should I perform surgery if I have been awake most
of the previous night or should the procedure be
rescheduled?
What back-up system is available if I recognize a
worrisome level of fatigue?
What adjustments should be made to my call schedule to avoid a worrisome level of fatigue?
Because physicians may not easily be able to assess
the degree of their own fatigue, it also may be prudent for
groups or departments to develop processes that provide
backup care when physician fatigue may diminish the
quality of care. Physicians should consider postponing
tasks that can be performed more safely at a later time.
Departments and groups also should recognize that
fatigue may arise from obligations outside the workplace.
Some departments have systems that encourage collaboration between practices when a provider has not had a
sufficient period of uninterrupted sleep.
There is no question that the human factor of fatigue
can affect performance. Because of the issues of patient
safety, fatigue should be addressed by all practitioners,
and efforts should be made to adjust workloads, work
hours, and time commitments to avoid fatigue when caring for patients. Physicians should not fear economic or
other penalties for requesting assistance.
626
Additional research on the effects of fatigue on experienced practicing obstetriciangynecologists is necessary

before specific national guidelines that are evidence based
can be promulgated to improve overall patient safety and
care. In the meantime, practicing physicians should evaluate the effects that fatigue has on their professional and
personal lives.
9.
10.
References
1. Malik SW, Kaplan J. Sleep deprivation. Prim Care 2005;
32:47590.
2. Arnedt JT, Owens J, Crouch M, Stahl J, Carskadon MA.
Neurobehavioral performance of residents after heavy night
call vs after alcohol ingestion. JAMA 2005;294:102533.
3. Dawson D, Reid K. Fatigue, alcohol and performance
impairment. Nature 1997;388:235.
4. Australian Transport Safety Bureau. Development of measures of fatigue: using an alcohol comparison to validate the
effects of fatigue on performance. Road Safety Research
Report CR 189. Canberra: ATSB; 2000. Available at: http://
www.atsb.gov.au/publications/2000/pdf/Fatig_Alc.pdf.
5. Rollinson DC, Rathlev NK, Moss M, Killiany R, Sassower
KC, Auerbach S, et al. The effects of consecutive night shifts
on neuropsychological performance of interns in the emergency department: a pilot study. Ann Emerg Med 2003;
41:4006.
6. Dula DJ, Dula NL, Hamrick C, Wood GC. The effect of
working serial night shifts on the cognitive functioning of
emergency physicians. Ann Emerg Med 2001;38:1525.
7. Pilcher JJ, Huffcutt AI. Effects of sleep deprivation on performance: a meta-analysis. Sleep 1996;19:31826.
8. Jha AK, Duncan BW, Bates DW. Fatigue, sleepiness, and
medical errors. In: Agency for Healthcare Research and
Quality. Making health care safer: a critical analysis of
11.
12.
13.
14.
patient safety practices. Evidence Report/Technology

Assessment No. 43. Rockville (MD): AHRQ; 2001. p.
52337. Available at: http://www.ahrq.gov/clinic/ptsafety/
chap46a.htm. Retrieved August 27, 2007.
Friedman WA. Resident duty hours in American neurosurgery. Neurosurgery 2004;54:92531; discussion 9313.
Smith-Coggins R, Rosekind MR, Hurd S, Buccino KR.
Relationship of day versus night sleep to physician performance and mood. Ann Emerg Med 1994;24:92834.
National Transportation Safety Board. Factors that affect
fatigue in heavy truck accidents. NTSB Report No.
NTSB/SS-95/01. Washington, DC: NTSB; 1995.
Federal Railroad Administration. The railroad fatigue risk
management program at the federal railroad administration: past, present and future. Washington, DC: FRA; 2006.
Available at: http://www.fra.dot.gov/downloads/safety/
fatiguewhitepaper112706.pdf. Retrieved September 4, 2007.
Kuhn G. Circadian rhythm, shift work, and emergency
medicine. Ann Emerg Med 2001;37:8898.
Ellenbogen JM. Cognitive benefits of sleep and their loss
due to sleep deprivation. Neurology 2005;64:E257.

Fatigue and patient safety. ACOG Committee Opinion No. 398.
2008;111:4713.
ISSN 1074-861X
COMMITTEE OPINIONS
627

Technologic Advances to Reduce

Medication-Related Errors
Committee on
Patient Safety and
Quality Improvement
followed.
ABSTRACT: The Institute of Medicine estimates that up to 7,000 individuals die

each year as a result of medication errors. Despite the significant national attention medical errors are receiving, they continue to pervade the U.S. health care system.
Medication-related errors consistently rank at the top of all medical errors, accounting for
thousands of deaths annually in the United States. Many new technologies are available
that, when integrated into the various medication-related processes, can significantly
reduce the incidence of preventable medication errors. Practicing obstetriciangynecologists should be familiar with these technologies and the evidence supporting their use.
A report by the Institute of Medicine (IOM)

on medication-related errors suggests that
despite the attention and progress in patient
safety since the book To Err is Human:
Building a Safer Health System was published
in 2000 (1), medication-related errors consistently rank at the top of all medical errors
(2). Errors are common at every step of the
medication administration process. In hospitals, errors occur most frequently when medication is prescribed and administered. There
is at least one medication error per hospital
patient per day (2), but not all errors result in
injury. Studies indicate, however, that
400,000 preventable drug-related injuries
occur each year in hospitals (2). It is estimated that preventable drug-related injuries in
hospitals resulted in at least $3.5 billion in
additional medical costs in 2007 (2).
Human factors inherently limit the safety of health care processes. These factors
include fatigue, inattention, memory lapse,
ignorance, failure to communicate, use of
poorly designed equipment, noisy working
conditions, and numerous other personal
and environmental factors. Leading patient
safety organizations universally have focused
on improving practices involving medication
administration and have endorsed automated systems technology to reduce harmful
medication-related errors. The Committee
on Patient Safety and Quality Improvement
considers three of these automated systems
to have potential relevance to practicing
obstetriciangynecologists: 1) computerized
physician order entry, 2) bar coding, and 3)
intravenous infusion technology; ie, smart
pumps (Table 1).
Table 1. Summary of Automated System Technologies for Medication Error Reduction

Computerized Order
Entry
Medication Process
Affected
Estimated time to
implementation

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Strength of supporting
evidence*
Bar Coding
Smart Pumps
OrderingTranscription
Dispensing
Administration
Administration
1836 months
6+ months
3+ months
Good
Fair
Fair
*Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, et al. Current methods of the US Preventive Services Task Force:
a review of the process. Methods Work Group, Third US Preventive Services Task Force. Am J Prev Med 2001;20(suppl):2135.
628
Computerized Physician Order Entry

Computerized physician order entry refers to a computer-based system of ordering medications, laboratory tests,
diagnostic tests, and consultations. Practitioners directly
enter orders into a computer system that ensures standardized, legible, and complete orders. To maximize its
benefits, computerized physician order entry should be
linked to some form of a clinical decision support system.
A clinical decision support system is an active knowledge
system that uses two or more items of patient data to generate case-specific advice (3). The system typically is
designed to integrate a medical knowledge base, patient
data, and an inference engine to generate case-specific
advice. Computerized physician order entry has been
evaluated and endorsed by the IOM, Agency for
Healthcare Research and Quality, The Leapfrog Group,
National Quality Forum, Institute for Safe Medication
Practices, and the American Hospital Association (2, 4, 5).
Benefits
Computerized physician order entry is a useful tool for
preventing medication-related errors as follows:
Eliminates adverse drug events related to illegible
handwriting and decimal point errors
Improves processes when linked to a clinical decision
support system by including defaults for drug dosages,
routes, and frequencies; alerting health care professionals to drugdrug and drugallergy interactions;
screening for drug dosage according to patient age,
weight, or renal function; and reducing problems
with look-alike or sound-alike drugs, duplicate therapies, and dosage calculations
Eliminates transcription errors, if implemented with
an electronic medication administration record
Standardizes care by incorporating approved order
sets that improve compliance with evidence-based
best practices
Improves efficiency of care delivery by reducing calls,
turnaround time, and data re-entry
Reduces costs by alerting physicians to charges associated with diagnostic tests and medications
It also should be noted that although e-prescribing is
a function usually found within computerized physician
order entry systems and embedded in many, if not all,
electronic medical records, there also are freestanding eprescribing solutions that are very inexpensive to implement. These programs are Web accessible and can be used
with existing office computers or wireless personal digital
assistants. These systems can contribute to patient safety
by reducing the chances that illegible prescriptions or
improper unsafe dosages are accidentally written. In
addition, the direct transmission of a prescription to the
pharmacy, and the formulary checks many systems can
perform, have the potential to reduce phone calls from
pharmacists requesting clarification.
Brigham and Womens Hospital recently reported

significant return on investment with its internally developed and implemented computerized physician order
entry system. Brigham and Womens Hospital spent $11.8
million to develop, implement, and operate the system
between 1993 and 2002. Over 10 years, Brigham and
Womens Hospital saved $28.5 million, including cumulative net savings of $16.7 million and net operating budget savings of $9.5 million, given the institutional 80%
prospective reimbursement rate (6). Other organizations
have documented similar improvements:
In 1995, Latter Day Saints Hospital in Salt Lake City
experienced a 70% reduction in antibiotic-related
adverse drug events and drug costs with further
reductions in length of stay and overall hospital costs
after implementation of a computerized physician
order entry system with a clinical decision support
system (7).
In 2000, Ohio State University Medical Center
reported reductions in medication turnaround time
(64%), radiologic procedure completion time (43%),
and laboratory result reporting time (25%) (8).
Limitations
The computerized physician order entry system primarily is beneficial during the ordering and transcription
processes. Errors still can occur if physicians override system alerts and they can occur during the administration
steps.
Bar Coding for Medication

Administration
Bar coding refers to methods of encoding data for fast
and accurate electronic readability. Barcodes are a series
of alternating bars and spaces representing encoded
information that can be read by electronic readers. The
U.S. Food and Drug Administration (FDA) requires bar
coding on most prescription drugs, certain over-thecounter drugs, and blood and blood components intended for transfusion.
Benefits
In order to achieve reductions in dispensing errors, all
administered medications should have bar codes. The use
of bar coding also can help prevent medication-related
medical errors in the following ways:
Adds automation to help ensure the traditional five
rights (right patient, right medication, right dosage,
right route, and right time) of medication administration
Streamlines nurse workflow if bar coding is implemented with an electronic medication administration
record. The medication record immediately is updated in the hospital information system, ensuring accuracy and saving nurses time in the charting process.
COMMITTEE OPINIONS
Positive outcomes have been reported from the use

of bar coding. In 1994, the medication-related error rate
was reduced by 71% at the North Colorado Medical
Center (9). In 2001, at Veterans Administrations
Colmery-ONeill Medical Center, the overall medicationrelated error rate was reduced from 22 incidents per
100,000 units dispensed to 3 incidents per 100,000 units
dispensed, an 86% reduction (10).
Limitations
When the bar-code rule was fully implemented in 2006,
FDA estimated that it would help prevent nearly 500,000
adverse drug events and transfusion errors in 20 years.
The economic benefit of reducing health care costs,
patient pain and suffering, and lost work time is estimated at $93 billion over the same period (1114). However,
no national standard has been established for the medication bar-code format. It is estimated that less than 50% of
all available medications are currently bar coded at the
unit-dose level.
Intravenous Infusion Technology:

Smart Pumps
Approximately 38% of adverse drug events occur during
the administration steps with only 2% intercepted before
the event occurs (15). Advances with smart pumps now
offer programmable limits and other safety mechanisms
beyond the standard free-flow protection, which can
reduce risks of dosage errors. A smart pump is a parenteral infusion pump equipped with intravenous medication
error-prevention software that alerts operators or interrupts the infusion process when a pump setting is programmed outside of preconfigured limits. Smart pumps
are designed to recognize prescription errors, dosage misinterpretations, and keypad programming errors (16, 17).
Benefits
Smart pumps have the following features that work to
reduce the rates of medication-related errors:
Smart pumps incorporate dose error reduction systems, a safety feature that warns users when a programmed dose falls outside predefined limits.
Dose limits can be set for minimal and maximal limits and may be categorized as soft or hard alerts.
An event tracking log captures programming details,
and data can be exported to a spreadsheet for analysis and performance improvement.
Positive outcomes have been reported with the use of
smart pumps. Pooled analysis of aggregated tracking data
from seven hospitals (average size, 350 beds) demonstrated that one potentially life-threatening intravenous medication-related error was averted every 2.6 days using
smart pumps (18). At the Nebraska Medical Center, over
8 months, 157 infusions were reprogrammed; 17 infusions (11%) involved potentially fatal errors (19).
629
Limitations
As with computerized physician order entry and bar coding, smart pumps alone will not prevent all medicationrelated errors. For example, dose error reduction systems
will not detect that a wrong patient, medication, or time
has been selected unless bar-coding technology also is
incorporated.
Global Challenges
Major challenges are involved in implementing automated system technology. Listed as follows are challenges that
can significantly affect their adoption, or effectiveness, or
both:
Lack of definitive standards and clear state-of-the-art
products with responsive, intuitive user interfaces
Cost to implement
Involvement of clinicians early in system design and
integration into health care processes
Clinician resistance to change and fears regarding
loss of control over clinical care and how data will be
used
Clinician workarounds that intentionally bypass
safety features
Studies have shown that physician acceptance of a
clinical decision support system is significantly improved
if they trust the system to help them take better care of
their patients, remind them of something they may have
forgotten, or provide them with information that was
previously unavailable (20).
Conclusion
In 2001, the IOM Committee on Quality Health Care in
America indicated that Healthcare has safety and quality
problems because it relies on outmoded systems of work.
Poor designs set the workforce up to fail, regardless of
how hard they try. If we want safer, higher-quality care, we
will need to have redesigned systems of care, including the
use of information technology to support clinical and
administrative processes (21).
It is clear from review of available evidence that automated health care technologies hold perhaps the greatest
potential for dramatically reducing the incidence of harm
related to medical errors and, in particular, medicationrelated errors. The evidence supporting the efficacy of
these technologies ranges from good (computerized
physician order entry systems) to fair (bar coding and
smart pumps). Equally clear is the fact that the impact of
these technologies depends on the speed with which
national standards emerge and the success with which
they are integrated into well-designed care processes.
References
health system. Washington, DC: National Academies Press;
2000.
630
2. Institute of Medicine (US). Preventing medication errors.

Washington, DC: National Academies Press; 2007.
3. Wyatt J, Spiegelhalter D. Field trials of medical decisionaids: potential problems and solutions. Proc Annu Symp
Comput Appl Med Care 1991;1991:37.
4. Kaushal R, Bates DW. Computerized physician order entry
(CPOE) with clinical decision support systems (CDSSs). In:
Agency for Healthcare Research and Quality. Making health
care safer: a critical analysis of patient safety practices.
Evidence Report/Technology Assessment No. 43. Rockville
(MD): AHRQ; 2001. p. 5969.
5. National Quality Forum. Safe practices for better healthcare
2006 update: a consensus report. Washington, DC: NQF;
2006.
6. Kaushal R, Jha AK, Franz C, Glaser J, Shetty KD, Jaggi T, et
al. Return on investment for a computerized physician
order entry system. Brigham and Womens Hospital CPOE
Working Group. J Am Med Inform Assoc 2006;13:2616.
7. Evans RS, Pestotnik SL, Classen DC, Clemmer TP, Weaver
LK, Orme JF Jr, et al. A computer-assisted management
program for antibiotics and other antiinfective agents. N
Engl J Med 1998;338:2328.
8. Mekhjian HS, Kumar RR, Kuehn L, Bentley TD, Teater P,
Thomas A, et al. Immediate benefits realized following
implementation of physician order entry at an academic
medical center. J Am Med Inform Assoc 2002;9:52939.
9. Puckett F. Medication-management component of a pointof-care information system. Am J Health Syst Pharm
1995;52:13059.
10. Johnson CL, Carlson RA, Tucker CL, Willette C. Using
BCMA software to improve patient safety in Veterans
Administration Medical Centers. J Healthc Inf Manag
2002;16:4651.
11. Bar code label requirement for human drug products and
biological products. Final rule. Food and Drug
Administration, HHS. Fed Regist 2004;69:911971.
12. Bar code label requirements. 21 CFR 201.25 (2007).
13. Bar code label requirements. 21 CFR 610.67 (2007).
14. Container label. 21 CFR 606.121 (2007).

15. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi
D, et al. Incidence of adverse drug events and potential
adverse drug events. Implications for prevention. ADE
Prevention Study Group. JAMA 1995;274:2934.
16. FAQs for the Joint Commissions 2007 national patient safety goals. (Updated 1/07). Oakbrook Terrace (IL): JC; 2007.
Available at http://www.jointcommission.org/NR/rdonlyres/B423198E-8EB1-468C-B01E-DBB0324B5C60/
0/07_NPSG_FAQs_3.pdf. Retrieved November 27, 2007.
17. The Joint Commission. Sentinel event statistics - June 30,
2007. Oakbrook Terrace (IL): JC; 2007. Available at:
http://www.jointcommission.org/SentinelEvents/Statistics.
Retrieved October 24, 2007.
18. Fields M, Peterman J. Intravenous medication safety system
averts high-risk medication errors and provides actionable
data. Nurs Adm Q 2005;29:7887.
19. Malashock CM, Shull SS, Gould DA. Effect of smart infusion pumps on medication errors related to infusion device
programming. Hosp Pharm 2004;39:4609.
20. Sittig DF, Krall MA, Dykstra RH, Russell A, Chin HL. A survey of factors affecting clinician acceptance of clinical decision support. BMC Med Inform Decis Mak 2006;6:6.
21. Institute of Medicine (US). Crossing the quality chasm: a
new health system for the 21st century. Washington, DC:
National Academies Press; 2001.
Technologic advances to reduce medication-related errors. ACOG
ISSN 1074-861X
COMMITTEE OPINIONS
631

Patient Safety in Obstetrics and

Gynecology
Committee on Patient
Safety and Quality
Improvement
followed.
ABSTRACT: Since publication of the Institute of Medicines landmark report To Err is

Human: Building a Safer Health System, emphasis on patient safety has steadily increased.
Obstetriciangynecologists should continuously incorporate elements of patient safety into
their practices and also encourage others to use these practices.

Gynecologists (ACOG) is committed to
improving quality and safety in womens
health care. The Institute of Medicine report,
To Err Is Human: Building a Safer Health
System, notes that errors in health care are a
significant cause of death and injury (1).
Despite disagreements over the actual numbers cited, all health care professionals agree
that patient safety is extremely important
and should be addressed by the overall health
care system. The American College of
Obstetricians and Gynecologists continues to
emphasize its long-standing commitment
to quality and patient safety by codifying a set
of objectives that should be adopted by
obstetriciangynecologists in their practices.
Obstetriciangynecologists are encouraged
to promulgate these principles in the hospitals and other settings where they practice.
Patient Safety Objectives

I.

of Obstetricians
and Gynecologists
Womens Health Care
Physicians
Develop a commitment to encourage a

culture of patient safety
Safety should be viewed as an essential
component of a broader commitment to
the provision of optimal health care for
women. Promoting safety requires that all
those in the health care environment recognize that the potential for errors exists
systemically. Womens health care should
be delivered in a learning environment
that encourages disclosure and exchange
of information in the event of errors, near
misses, and adverse outcomes.
A culture of safety should be the
framework for any effort to reduce
medical errors. According to the Agency

for Healthcare Research and Quality
(AHRQ), a safety culture refers to a
commitment to safety that permeates all
levels of an organization, from frontline
personnel to executive management
(2). Associated with a safety culture is the
concept of a just culture, which recognizes that competent professionals make
mistakes and acknowledges that even
competent professionals may develop
unhealthy norms, such as shortcuts or
routine rule violations, but has zero
tolerance for reckless behavior (2).
Frontline personnel feel comfortable
disclosing errorsincluding their own
while maintaining professional accountability (2). A just culture recognizes that
some rate of human error is inevitable,
especially in complex endeavors such as
the delivery of health care. Therefore, the
first step in the delivery of safe health
care should be to identify and study the
patterns and causes of error occurrence
within delivery systems. Obstetrician
gynecologists should adopt and develop
those safe practices that reduce the likelihood of system failures that can cause
adverse outcomes. Just culture also recognizes the responsibility of all health
care providers to follow these safe practices once established, and to avoid
behaviors that would be characterized as
at-risk behavior or reckless behavior.
At-risk behavior is the type of rule bending that tends to naturally occur over
time in systems where the rate of
632
adverse outcomes is very low. Reckless behavior is

the type of behavior that clearly puts patients at significant risk of harm and shows a conscious disregard of unreasonable risk. In a just culture, instances
of adverse outcomes or failure to follow safety protocols are investigated fairly and openly. The general
principle when dealing with these situations is summarized as console the human error; coach the atrisk behavior; and punish the reckless behavior (3).
Institution of these principles establishes an
atmosphere where all caregivers feel safe in reporting errors, near misses, and at-risk behaviors by
themselves and others. This will promote and
increase error reporting and identify potentially hidden problems, as well as motivate health care
providers to find system problems and collaborate
to resolve system failures.
The role of leadership, whether in the inpatient
or outpatient setting, is essential in facilitating an
effective patient safety program. Strong leadership
within obstetrics and gynecology is necessary to
advocate for the provision of both financial and
human resources to achieve patient safety goals.
Efforts devoted to optimizing communication and
collaboration among the various members of the
health care team are equally important in promoting these principles of patient safety.
II.
Implement recommended safe medication practices

Most medical errors are caused by problems associated with the use of medications; therefore, efforts
to reduce the occurrence of these errors should be
ongoing. Although computerized physician order
entry systems can be effective in reducing prescribing errors, they are costly and may not collect data
that support quality improvement activities (4, 5).
In the absence of computerized physician order
entry systems, the following steps should be adopted
to reduce errors in prescribing and administering
medications (6):
Improve legibility of handwriting

Avoid use of nonstandard abbreviations
Check for drug allergies and sensitivities
Always use a leading 0 for doses of less than 1
unit (eg, 0.1 mg, not .1 mg), and never use a trailing 0 after a decimal (eg, 1 mg, not 1.0 mg):
always lead, never follow
All verbal orders should be written down by the
individual receiving the order and read back to
the prescriber verbatim to ensure accuracy
III. Reduce the likelihood of surgical errors
Surgical errors may involve the performance of the
incorrect operation or a procedure on the wrong site
or wrong patient. Although these errors occur much
less frequently than medication errors, the consequences of these errors are always significant. The
attending obstetriciangynecologist who is ultimately responsible for the patients care should work
with other operating room personnel, such as nurses
and anesthesiologists, to be certain that systems are
in place to ensure proper patient and procedure
identification. The obstetriciangynecologist also
should use a preoperative verification process to
confirm, with the patient, the intended procedure to
be performed.
There are several resources available to promote
this verification process. The Joint Commission
developed the Universal Protocol and associated
Speak Up program to address this. It is designed to
ensure correct person, correct site, and correct
procedure through the elements of a preprocedure
verification process, marking the procedure site, and
performing a time-out before starting the procedure. The World Health Organizations Safe Surgery
Saves Lives program, endorsed by the International
Federation of Gynecology and Obstetrics (FIGO), has
recently been shown to significantly reduce surgical
morbidity and mortality in multiple settings (7). It is
a 19-item safe surgery checklist that includes a sign-in
procedure before induction of anesthesia, a time-out
procedure before skin incision, and a sign-out procedure before the patient leaves the operating room.
Universal application of these techniques should be
strongly advocated for and practiced by all obstetriciangynecologists as proven methods to improve
the safety of our patients in the operating room.
IV. Improve communication with health care providers
Communication between all members of the health
care team is a crucial element in patient safety. In its
analysis of sentinel events, the Joint Commission
found that almost two thirds of the events involved
communication failure as a root cause (8). Training
in teamwork and communication techniques is
increasingly being recognized as a cornerstone of a
robust patient safety program; AHRQ developed the
TeamSTEPPS program to address this issue (9).
One key communication tool that it advocates is
SBARSituation, Background, Assessment, and
Recommendation or Request. It is a structured system to communicate critical information clearly
and efficiently. It allows caregivers to provide information on what is happening to the patient, what
the clinical background is, what they think the problem is, and what they would recommend or what
action is being requested. This information can then
be appropriately understood and acted upon.
A time of great potential for miscommunication
is during patient handoffs. This occurs during shift
changes for nurses, laborists, or practice partners.
The Joint Commission states: The primary objec-
COMMITTEE OPINIONS
tive of a handoff is to provide accurate information

about a patients care, treatment and services, current condition, and any recent or anticipated
changes. The information communicated during a
handoff must be accurate to meet patient safety
goals (10). TeamSTEPPS includes a structured
technique for handoffs, which may facilitate the
transmission of clinical and patient safety information in a way that prevents the omission of critical
aspects of the treatment plan.
An increased awareness of the importance of
clear communication between all members of the
health care team will measurably enhance the safety
of the care delivered by obstetriciangynecologists.
Training around these issues for all health care
providers is highly recommended.
V.
Improve communication with patients

Communication is a core element of the physicianpatient relationship and is essential for the
delivery of high quality, safe patient care. According
to the Code of Professional Ethics of the American
College of Obstetricians and Gynecologists, the
patientphysician relationship has an ethical basis
and is built on confidentiality, trust, and honesty
(11). It also states the obstetriciangynecologist
should deal honestly with patients and colleagues.
Communication should be complete, clear, concise,
and timely (12). To be prepared for occurrences of
adverse events, ACOG encourages the development
and use of written policies that address the timing,
content, communication, and documentation of
disclosure. The American College of Obstetricians
and Gynecologists believes that it is the moral obligation of every physician to communicate honestly
with patients, particularly those who experience an
adverse outcome. Open communication and transparency in health care will increase trust, improve
patient satisfaction, and may decrease liability exposure (13).
VI. Establish a partnership with patients to improve

safety
Patients who are involved in making their health
care decisions have better outcomes than those who
are not (14). According to the ACOG Committee
Opinion, Informed Consent, the involvement of
patients in [decisions about their own medical care]
is good for their healthnot only because it is a
protection against treatment that patients might
consider harmful, but because it contributes positively to their well-being (15). Patients should be
encouraged to ask questions about medical procedures, the medications they are taking, and any
other aspect of their care. Patient education materials developed by ACOG and other organizations are
available.
633
VII. Make safety a priority in every aspect of practice

The discipline of obstetrics and gynecology has a
long tradition of leadership in quality assessment
activities, which have been associated with an increase in patient safety. The quest for patient safety
is an ongoing, continuously refined process incorporating information sharing and collaboration into
daily practice. Emphasizing compassion, communication, and patient-focused care will aid in creating
a culture of excellence. Opportunities to improve
patient safety should be used whenever identified.
References
health system. Washington, DC: National Academy Press;
2000.
2. Agency for Healthcare Research and Quality. Patient safety
network: glossary. Available at: http://www.psnet.ahrq.gov/
glossary.aspx. Retrieved July 31, 2009.
3. Marx D. Patient safety and the just culture: a primer for
health care executives. New York (NY): Trustees of
Columbia University in the City of New York. 2001.
Available at http://www.mers-tm.org/support/Marx_Primer.
4. Kelly WN, Rucker TD. Compelling features of a safe
medication-use system. Am J Health Syst Pharm. 2006;
63:14618.
5. Agency for Healthcare Research and Quality. Womens
health care in the United States: selected findings from the
2004 National Healthcare Quality and Disparities Reports.
AHRQ Pub No. 05-P021. Rockville (MD): AHRQ; 2005.
Available at http://www.ahrq.gov/qual/nhqrwomen/nhqrwomen.htm. Retrieved July 30, 2009.
6. Safe use of medication. ACOG Committee Opinion No. 331.
Gynecol 2006;107:96972.
7. Haynes AB, Weiser TG, Berry WR, Lipsitz SR, Breizat AH,
Dellinger EP, et al. A surgical safety checklist to reduce
morbidity and mortality in a global population. Safe Surgery
Saves Lives Study Group. N Engl J Med 2009;360:4919.
8. Joint Commission. Preventing infant death and injury during delivery. Sentinel Event Alert Issue No. 30. Oakbrook
Terrace (IL): Joint Commission; 2004. Available at:
http://www.jointcommission.org/SentinelEvents/Sentinel
EventAlert/sea_30.htm. Retrieved June 12, 2009.
9. Agency for Healthcare Research and Quality. TeamSTEPPS:
national implementation. Available at: http://teamstepps.
ahrq.gov/index.htm. Retrieved July 30, 2009.
Organizations. Patient safety: essentials for healthcare. 4th ed.
Oakbrook Terrace (IL): Joint Commission Resources; 2006.
of professional ethics of the American College of Obstetricians and Gynecologists. Washington, DC: ACOG; 2008.
Available at: http://www.acog.org/from_home/acogcode.pdf.
12. Communication strategies for patient handoffs. ACOG
634

15035.
13. Kraman SS, Hamm G. Risk management: extreme honesty
may be the best policy. Ann Intern Med 1999;131:9637.
14. Kaplan SH, Gandek B, Greenfield S, Rogers W, Ware JE.
Patient and visit characteristics related to physicians participatory decision-making style. Results from the Medical
Outcomes Study. Med Care 1995;33:117687.
15. Informed consent. ACOG Committee Opinion No. 439.
Gynecol 2009;114:4018.
The Just Culture Community, 2200 W. Spring Creek

Parkway, Suite A, Plano, TX 75023, (214) 778-2010, http://
www.justculture.org.
U.S. Department of Veterans Affairs. National Center for
Patient Safety. Available at http://www.patientsafety.gov.
World Health Organization: Safe surgery saves lives: the
second global patient safety challenge. Geneva: WHO;
2009. Available at http://www.who.int/patientsafety/
safesurgery/en. Retrieved July 30, 2009.
Agency for Healthcare Research and Quality. Medical
errors and patient safety. Available at http://www.ahrq.
gov/qual/errorsix.htm. Retrieved July 30, 2009.
Joint Commission. Universal protocol for preventing
wrong site, wrong person surgery. Oakbrook Terrace (IL):
Joint Commission; 2009. Available at http://www. jointcommission.org/PatientSafety/UniversalProtocol.
National Patient Safety Foundation. 268 Summer Street,
6th Floor, Boston, MA 02210, (617) 391-9900, http://
www. npsf.org.

ISSN 1074-861X
Patient safety in obstetrics and gynecology. ACOG Committee
PRACTICE BULLETINS
READING
THE
635
MEDICAL LITERATURE
READING
THE
MEDICAL LITERATURE
Reading the
Medical
Literature
Applying Evidence to Practice
Developed under the direction
of the ACOG Committee on
Practice Patterns:
James R. Scott, MD, Chair
Daniel W. Cramer, MD, ScD
Herbert B. Peterson, MD
Benjamin P. Sachs, MD
Mary L. Segars Dolan, MD, MPH
Stanley Zinberg, MD
Director of Practice Activities
Nancy E. OReilly, MHS
Manager, Practice Activities
Peter J. Sebeny
Research Associate
Reading the Medical Literature is designed as a resource for Fellows of the

American College of Obstetricians and Gynecologists (ACOG) and others to
offer a better understanding of evidence-based medicine, particularly as it
relates to the development of ACOGs clinical practice guidelines. As evidencebased medicine continues to develop and to be integrated into clinical practice,
an understanding of its basic elements is critical in translating the medical literature into appropriate clinical practice. The emphasis on evidence-based
medicine has taken on new and greater importance as the environment of clinical practice grows more diverse, with increased access to more information by
both physicians and patients and the changing allocation of resources.
Practice guidelines are a formal synthesis of evidence, developed according to
a rigorous research and review process. This document provides an overview
of ACOGs guideline development process, including elements of study design
that are linked to the strength of the evidence. Reading the Medical Literature
is not intended to serve as a comprehensive overview of the scientific methods
of epidemiology and study design. Rather, it is provided to serve as a readily
available introduction to and overview of the topic.
In 1995, ACOG began developing scientifically based practice guidelines,
formerly known as Practice Patterns and subsequently as Practice Bulletins.
The guidelines are derived from the best available evidence of clinical efficacy and consideration of costs, with recommendations explicitly linked to
the evidence. These evidence-based practice guidelines are intended to be a
means of improving the quality of health care, decreasing its cost, and diminishing professional liability. They are proscriptive in nature and, therefore,
directive in their approach.
This document describes how ACOG Practice Committees identify, evaluate, and synthesize evidence from the medical literature to produce practice
guidelines. In particular, this document briefly describes various study
637
638
designs evaluated in the production of evidence-based

guidelines and the decision-making steps used to construct
evidence-based recommendations on clinical issues. Also
highlighted are potential major flaws in study design that
affect the validity and applicability of study results, as well
as the strength of the evidence. This document includes a
glossary of commonly encountered epidemiologic and biostatistic terms found in reports of scientific evidence, as
well as suggestions for further reading.
Selection of Topics
Topics developed into evidence-based practice guidelines
are selected based on clinical issues in obstetrics and
gynecology with unexplained variations in practice or
because there are differences between what is known scientifically and what is practiced. Once a topic has been
identified, objectives of the guideline are developed and
research questions are formulated to guide the literature
search. The research questions highlight the most important aspects of a particular clinical issue, focusing on areas
relevant to practice and useful in patient management.
Searching the Literature
Literature Analysis
After results of the literature search are compiled, the study
abstracts are reviewed to assess the relevance of each study
or report. Those articles appropriate for further critical
appraisal are obtained and subdivided according to the
research question they address. The bibliographies of these
articles are also reviewed to identify additional studies that
may not have been identified in the initial literature search.
Types of Study Designs

Intervention Studies
Level I Evidence
Commonly referred to as clinical trials, intervention studies are characterized by the investigators roles in assigning subjects to exposed and nonexposed groups and
following the subjects to assess outcome. Intervention
studies may involve the use of a comparison group, which
may include subjects under another treatment, drug, test,
or placebo.
Randomized controlled trials are characterized by the
prospective assignment of subjects, through a random
method, into an experimental group and a control (placebo) group. The experimental group receives the drug
or treatment to be evaluated, while the control group
receives a placebo, no treatment, or the standard of care.
Both groups are followed for the outcome(s) of interest.
Randomization is the most reliable method to ensure that
the participants in both groups are as similar as possible
with respect to all known or unknown factors that might
affect the outcome.
In the ACOG Resource Center, medical librarians with

extensive subject expertise perform a literature search
based on the clinical questions and objectives. The search
includes a review of the MEDLINE database, the
Cochrane Library, ACOGs internal resources and documents, and other databases as appropriate. In addition,
ACOG librarians review more than 200 journals. This
process locates relevant articles from journals not indexed
in MEDLINE and those not yet indexed.
The search is limited to documents published in
English, and a specific strategy may be used to refine the
search further. This filter strategy restricts the search by
study design or publication type and is similar to the
process used by the Cochrane Library. No further screening or elimination of records is done by the librarians.
Updated searches are conducted as the topic is developed
or further revised.
The data in the literature are evaluated to provide

answers to the clinical questions. The articles obtained for
review are organized by study design to ascertain the possible strengths and weaknesses inherent in each study, as
well as the quality of evidence they may provide. Certain
aspects of a clinical issue may not be addressed in research studies, and expert opinion may be used and identified as such.
The levels of evidence used are based on the method
used by the U.S. Preventive Services Task Force. The U.S.
Preventive Services Task Force was a 20-member panel of
scientific and medical experts charged with developing
recommendations on appropriate use of clinical interventions. Their recommendations were based on a systematic
review of the evidence of clinical effectiveness.
Example
Postmenopausal women are identified from a
population and randomly assigned either to a
study group that will be prescribed hormone
replacement therapy or to a control group that
will be prescribed a placebo. Both groups of
women are observed prospectively to determine
who in each group subsequently develops
endometrial cancer. The rate at which women
prescribed hormone replacement therapy develop endometrial cancer is compared to that of
women in the control group.
PRACTICE BULLETINS
Major Study Flaws

Randomization was not valid and resulted in
a differential assignment of treatment that
affected the outcomes.
The sample size was too small to detect a
clinically important difference.
Poor compliance or loss to follow-up was
significant enough to affect the outcomes.
Level II-1 Evidence
of initiation of the study: retrospective (nonconcurrent) or

prospective (concurrent) studies. In a prospective cohort
study, the groups of exposed and unexposed subjects have
been identified and the investigator must conduct followup for an adequate period to ascertain the outcome of
interest. In a retrospective cohort study, both the exposure
and outcomes of interest already have occurred by the initiation of the study. The rate of disease in the exposed
group is divided by the rate of disease in the unexposed
group, yielding a rate ratio or relative risk.
Controlled trials without randomization are intervention

studies in which allocation to either the experimental or
control group is not based on randomization, making
assignment subject to biases that may influence study
results. Conclusions drawn from these types of studies are
considered to be less reliable than those from randomized
controlled trials.
Example
population and assigned in a nonrandomized
manner either to a study group that will be prescribed hormone replacement therapy or to a
control group that will be prescribed a placebo.
Both groups of women are observed prospectively to determine who subsequently develops
endometrial cancer. The rate at which women
prescribed hormone replacement therapy develop endometrial cancer is compared to that of
women in the control group.
Major Study Flaws

Nonrandom group assignment resulted in
unequal distribution of known and unknown
factors that may influence the outcome.
Other potential flaws are the same as those
for randomized controlled trial (Level I).
Observational Studies
Level II-2 Evidence
Example
A group of postmenopausal women who have
been prescribed hormone replacement therapy
is identified (study group), as is an otherwise
similar group of postmenopausal women who
have not been prescribed hormone replacement
therapy (control group). The study and control
groups are observed to determine who subsequently develops endometrial cancer. The rate at
which women using hormone replacement therapy develop endometrial cancer is compared
with that of women not using hormone replacement therapy who also develop endometrial
cancer.
Major Study Flaws
Criteria for determining exposure status were
inadequately defined.
The assessments of the outcome for the
exposed and nonexposed groups differed in a
biased manner.
The nonexposed comparison group was inappropriate.
A case-control study is a retrospective study in which a

group of subjects with a specified outcome (cases) and a
group without that same outcome (controls) are identified.
Thus, the starting point for a case-control study is disease
status. Investigators then compare the extent to which each
subject was previously exposed to the variable of interest
such as a risk factor, a treatment, or an intervention. A disadvantage of this study type is that assessment of exposure
may have been influenced by disease status, including the
possibility that cases recalled their exposure differently
than controls. The odds of exposure in the case group compared with the odds of exposure in the control group provide the measure of association between the disease and
exposure (odds ratio).
There are two types of observational studies in this category: cohort and case-control. In these studies, the investigator has no role in assignment of study exposures but,
rather, observes the natural course of events of exposure
and outcome.
The starting point for a cohort study is exposure status.
Subjects are classified on the basis of the presence or
absence of exposure to a risk factor, a treatment, or an
intervention and then followed for a specified period to
determine the presence or absence of disease. Cohort studies can be of two different types determined by the timing
639
Example
Researchers conduct a case-control study to
assess the relationship between hormone
replacement therapy and endometrial cancer. A
640
Major Study Flaws

The case or control group preferentially
included or excluded subjects with a particular exposure history.
Cases or controls were selectively more likely to recall or admit to a particular exposure.
The possibility of known or unknown factors
that may have been related to both exposure
status and outcome were not adequately considered and assessed.
same time to identify signs of osteoporosis. In

this cross-sectional study, a measure of calcium
intake in women with and without signs of
osteoporosis is compared.
group of women who have recently developed

endometrial cancer (cases) and a group of
women with similar characteristics who did not
develop endometrial cancer (controls) are identified. The use of hormone replacement therapy
for each woman in the case group and the control group is determined to assess exposure history. The odds that women who developed
endometrial cancer had used hormone replacement therapy are compared with the odds that
women who did not develop endometrial cancer
had used hormone replacement therapy. These
odds are calculated to determine any association
of hormone replacement therapy to endometrial
cancer.
Major Study Flaws

It is usually not possible to determine the
temporal relationship between disease and
exposure.
Other factors that may contribute to the disease, particularly past exposure to factors
other than the factor under study, are not
taken into consideration.
Level III Evidence

These studies provide limited information about the relationship between exposure and the outcome of interest.
This category includes descriptive studies, such as case
reports and case series, and expert opinion, which is often
based on clinical experience.
A case study describes clinical characteristics or other
interesting features of a single patient or a series of patients. The latter is referred to as a case series.
Expert opinion often is used to make recommendations. This type of evidence includes findings from expert
panels and committees and the opinions of respected
experts in a particular field.
Level II-3 Evidence

Cross-sectional studies are observational studies that
assess the status of individuals with respect to the presence
or absence of both exposure and outcome at a particular
time. In this type of study, one is unlikely to be able to discern the temporal relationship between an exposure and
outcome. Results from cross-sectional studies can yield
correlations and disease prevalence. Prevalence is defined
as the proportion of individuals with a disease at a specific time; in contrast, incidence is the number of new cases
occurring over a specified period.
Uncontrolled investigational studies report the results
of treatment or interventions in a particular group, but lack
a control group for comparison. They may demonstrate
impressive results, but in the absence of a control group
the results may be attributable to factors other than the
intervention or treatment.
Of all observational studies, cross-sectional and uncontrolled investigational studies provide the least evidence of
causation.
Example
population and surveyed at a particular time
about their current intake of calcium. Bone densitometry is evaluated in these women at the
Other Study Designs

A meta-analysis is a systematic structured process, not
merely a literature review. It combines results from more
than one investigation to obtain a weighted average of the
effect of a variable or intervention on a defined outcome.
This approach can increase precision of the exposure to
the outcome measured, although it is important to add that
the validity of the conclusions of the meta-analysis
depends largely on the quality of its component studies.
Results are usually presented in a graph that illustrates the
measure of association by each study type and the overall
summary association (Fig. 1).
A decision analysis is a type of study that uses mathematical models of the sequences of multiple strategies to
determine which are optimal. The basic framework is the
decision tree in which branches of the tree represent key
probabilities or decisions. Decision analysis is driven by key
assumptions. Ideally the assumptions are based on data that
may include findings from meta-analyses. Often a decision
analysis is undertaken when there are inadequate data to perform a meta-analysis (Fig. 2).
Cost-benefit analysis and cost-effectiveness analysis are
related analytic methods that compare health care practices
or techniques in terms of their relative economic efficiencies
PRACTICE BULLETINS
641
MacDonald
Depalo
Meta-analysis
M1
Breslow-Day P=0.69
Malkasean
Vergote
Meta-analysis
M2
0
0.1
P=0.58
10
No Adjuvant Therapy Deaths
100
Progestagen Deaths
Fig. 1. Effects on endometrial cancer deaths: progestagen versus no adjuvant treatment.
Long-Term Disability
Cured
Cured
Subtotal
Operative
Complication
Uneventful
Recovers
Long-Term Disability
Death from Cervical Cancer
Surgical Death
Healthy
Dysfunction
Healthy
Uneventful
Hysterectomy
Recovers
Death
Dysfunction
Total
Death from Vaginal Cancer
Operative
Complication
Surgical Death
(Reprinted from the European Journal of Obstetrics, Gynecology, and Reproductive Biology, Vol. 65. Martin-Hirsch PL, Lilford RJ, Jarvis GJ. Adjuvant progestagen therapy for the treatment of endometrial cancer: review and meta-analyses of published randomized controlled trials, p. 205, 1996, with permission from Elsevier Science Ireland Ltd, Bay 15K, Shannon Industrial Estate, Co. Clare, Ireland.)
Death
Fig. 2. Decision model. Square at far left, choice between two treatment options: total or subtotal hysterectomy. Round nodes,
chance outcomes; end branches, final outcome states.
(Scott JR, Sharp HT, Dodson MK, Norton PA, Warner HR. Subtotal hysterectomy in modern gynecology: a decision analysis. Am J Obstet Gynecol
1997;176:1187. Reprinted with permission.)
642
in providing health benefits. In a cost-effectiveness analysis,

the net monetary costs of a health care intervention are compared with some measure of clinical outcome or effectiveness. In a cost-benefit analysis, the net monetary costs of a
health care intervention typically are compared with the net
monetary costs of the clinical outcome or effectiveness.
Therefore, a cost-benefit analysis compares costs associated
with an intervention with monetary benefits from the use of
that intervention. The advantage of a cost-benefit analysis is
the ability to use dollars for comparison across interventions.
The disadvantage is the difficulty in assigning a monetary
value to health status or quality of life.
Having stated the clinical question and assembled and graded the literature using the levels just outlined, recommendations are formulated according to the quality and quantity of
evidence. Based on the highest available level of evidence,
recommendations are provided and graded according to the
following categories:
A There is good evidence to support the recommendation.
B There is fair evidence to support the recommendation.
C There is insufficient evidence to support the recommendation; however, the recommendation may be made on
other grounds.
D There is fair evidence against the recommendation.
E There is good evidence against the recommendation.
This method explicitly links recommendations to the evidence. Determination of the quality of the evidence and the
strength of recommendations are based on good, fair, or
insufficient evidence. These descriptors address the levels of
evidence and also provide a qualitative review of the evidence in terms of its methodologic strengths and weaknesses. A prerequisite for inclusion of each study in the analysis
is that it provides overall evidence of good quality.
It is important to note that an exact correlation does not
exist between the strength of the recommendation and the
level of evidence (ie, an A grade does not necessarily
require Level I evidence, nor does Level I evidence necessarily lead to an A grade). For example, for some clinical
issues a randomized trial is not possible for medical or ethical reasons, and recommendations must be based on evidence from other types of studies (Level II-2, II-3). In other
cases, high-quality studies have produced conflicting results,
or evidence of significant benefit is offset by evidence of
important harm from the intervention. Although these studies may be randomized controlled trials (Level I), insufficient or conflicting evidence would result in a C recommendation.
Medicine will continue to face the rapid introduction of

new technologies, rationing of health resources, and
increasing attention to the quality and outcomes of medical care. Physicians will have to acquire the skills necessary to review the medical literature critically to identify
the best evidence in managing patients. This process for
developing practice guidelines identifies available evidence and constructs recommendations based on the best
evidence so that obstetriciangynecologists can continue
to provide the highest quality of care.
Developing Evidence-Based
Recommendations
Implications for Practice
Glossary *
Accuracy: The degree to which a measurement or an estimate based on measurements represents the true value of
the attribute that is being measured.
Bias: Deviation of results or inferences from the truth, or
processes leading to such deviation; it is any trend in the
collection, analysis, interpretation, publication, or review
of data that can lead to conclusions that are systematically
different from the truth. Three frequently occurring types
of bias include selection bias, information bias, and confounding. Selection bias is error due to systematic differences in characteristics between those who are selected for
study and those who are not. Information bias, also called
observational bias, is a flaw in measuring exposure or outcome data that results in different quality (accuracy) of
information between comparative groups. Recall bias is an
example of information bias. The third example of bias,
confounding, describes a situation in which the effects of
two processes are not separated; it is the distortion of the
apparent effect of an exposure on risk brought about by the
association with other factors that can influence the outcome.
Confidence interval: An indication of the variability of a
point estimate, such as an odds ratio or relative risk. In
general, the wider the confidence interval, the less precise
the point estimate. The 95% confidence interval is often
used. As an example, if the 95% confidence interval does
not overlap 1.0, then one would reject the null hypothesis.
Confounding variable (syn: confounder): A variable that
can cause or prevent the outcome of interest, is not an
intermediate variable, and is associated with the factor
under investigation. Unless it is possible to adjust for confounding variables, their effects cannot be distinguished
from those factor(s) being studied. Bias can occur when
adjustment is made for any factor that is caused in part by
the exposure and is also correlated with the outcome.
*Adapted from A Dictionary of Epidemiology, third edition. Last JM, ed. Used
by permission of Oxford University Press.
PRACTICE BULLETINS
Incidence: The number of instances of illness commencing, or persons falling ill, during a given period in a specified population. More generally, the number of new
events (eg, new cases of a disease in a defined population)
within a specified period.
Null hypothesis (test hypothesis): The statistical hypothesis that one variable has no association with another variable or set of variables, or that two or more population
distributions do not differ from one another. In simplest
terms, the null hypothesis states that the results observed
in a study, experiment, or test are no different from what
might have occurred as a result of the operation of chance
alone.
Odds ratio (syn: cross product ratio, relative odds): The
ratio of two odds. The exposure odds ratio for a set
of case control data is the ratio of the odds in favor
of exposure among the cases (a/b) to the odds in favor of
exposure among noncases (c/d). A 2 2 table (Table 1) can
be used to illustrate this calculation of odds ratios.
Table 1. Odds Ratio Calculations*
Disease
No disease
Exposed
a
c
Unexposed
b
d
643
ignated time; sometimes used to mean prevalence rate.

When used without qualification, the term usually refers to
the situation at a specified time (point prevalence).
Relative risk: The ratio of risk of disease or death among
the exposed to that of the risk among the unexposed; this
usage is synonymous with risk ratio. If the relative risk is
above 1.0, then there is a positive association between the
exposure and the disease; if it is less than 1.0, then there is
a negative association.
Sensitivity and specificity: Sensitivity is the proportion of
truly diseased persons in the screened population who are
identified as diseased by the screening test. Specificity is
the proportion of truly nondiseased persons who are so
identified by the screening test. Table 2 illustrates these
quantities.
In screening and diagnostic tests, the probability that a
person with a positive test is a true positive (ie, does have
the condition) is referred to as the predictive value of a positive test. The predictive value of a negative test is the probability that a person with a negative test does not have the
condition. The predictive value of a screening test is determined by the sensitivity and specificity of the test and by
the prevalence of the condition for which the test is being
used.
Positive predictive value = a/a+b
*The odds ratio is ad/bc.
Negative predictive value = d/c+d

P-value: The probability that a test statistic would be as
extreme or more extreme than observed if the null hypothesis were true. The letter P, followed by the abbreviation
n.s. (not significant) or by the symbol < (less than) and a
decimal notation such as 0.01 or 0.05, is a statement of the
probability that the difference observed could have
occurred by chance if the groups were really alike (ie,
under the null hypothesis). Investigators may arbitrarily
set their own significance levels, but in most biomedical
and epidemiologic work, a study result whose probability
value is less than 5% (P <0.05) or 1% (P <0.01) is considered sufficiently unlikely to have occurred by chance
and would justify the designation statistically significant. By convention, most investigators choose P <0.05
as statistically significant.
Power (statistical power): The ability of a study to demonstrate an association if one exists. The power of the study
is determined by several factors, including the frequency
of the condition under study, the magnitude of the effect,
the study design, and sample size.
Prevalence: The number of events (eg, instances of a given
disease or other condition) in a given population at a des-
Table 2. Sensitivity and Specificity Calculations

True Status
Screening Test
Results
Positive
Negative
Total
Diseased
Not Diseased
Total
a
c
a+c
b
d
b+d
a+b
c+d
a+b+c+d
a = Diseased individuals detected by the test (true positives)

b = Nondiseased individuals positive by the test (false positives)
c = Diseased individuals not detected by the test (false negatives)
d = Nondiseased individuals negative by the test (true negatives)
Sensitivity = a/a+c; specificity = d/b+d.
Type I error: The error of rejecting a true null hypothesis

(ie, declaring that a difference exists when it does not).
Type II error: The error of failing to reject a false null
hypothesis (ie, declaring that a difference does not exist
when in fact it does).
644
Suggested Reading
Asilomar Working Group on Recommendations for Reporting

of Clinical Trials in the Biomedical Literature. Checklist of
information for inclusion in reports of clinical trials. Ann Intern
Med 1996;124:741743
Chalmers TC, Smith H Jr, Blackburn B, Silverman B, Schroeder
B, Reitman D, et al. A method for assessing the quality of a randomized control trial. Control Clin Trials 1981; 2:3149
DuRant RH. Checklist for the evaluation of research articles.
J Adolesc Health 1994;15:48
Grisso JA. Making comparisons. Lancet 1993;342:157160
Guyatt GH, Sackett DL, Cook DJ. Users guides to the medical
literature. II. How to use an article about therapy or prevention.
A. Are the results of the study valid? Evidence-Based Medicine
Working Group. JAMA 1993;270:25982601
Guyatt GH, Sackett DL, Cook DJ. Users guides to the medical
literature. II. How to use an article about therapy or prevention.
B. What were the results and will they help me in caring for my
patients? Evidence-Based Medicine Working Group. JAMA
1994;271:5963
Guyatt GH, Sackett DL, Sinclair JC, Hayward R, Cook DJ,
Cook RJ. Users guides to the medical literature. IX. A method
for grading health care recommendations. Evidence-Based
Medicine Working Group. JAMA 1995;274:18001804
Hadorn DC, Baker D, Hodges JS, Hicks N. Rating the quality
of evidence for clinical practice guidelines. J Clin Epidemiol
1996;49:749754
Hayward RS, Wilson MC, Tunis SR, Bass EB, Guyatt G. Users
guides to the medical literature. VIII. How to use clinical practice guidelines. A. Are the recommendations valid? The
Evidence-Based Medicine Working Group. JAMA 1995;
274:570574
Jaeschke R, Guyatt GH, Sackett DL. Users guides to the medical literature. III. How to use an article about a diagnostic test.
B. What are the results and will they help me in caring for my
Copyright 1998
409 12th Street, SW
PO Box 96920
patients? The Evidence-Based Medicine Working Group.

JAMA 1994;271:703707
Laupacis A, Wells G, Richardson WS, Tugwell P. Users guides
to the medical literature. V. How to use an article about prognosis. Evidence-Based Medicine Working Group. JAMA
1994;272:234237
Naylor CD, Guyatt GH. Users guides to the medical literature.
X. How to use an article reporting variations in the outcomes of
health services. The Evidence-Based Medicine Working Group.
JAMA 1996;275:554558
Naylor CD, Guyatt GH. Users guides to the medical literature.
XI. How to use an article about a clinical utilization review.
Evidence-Based Medicine Working Group. JAMA 1996;275:
14351439
Oxman AD. Checklists for review articles. BMJ 1994;309:
648651
Oxman AD, Cook DJ, Guyatt GH. Users guides to the medical
literature. VI. How to use an overview. Evidence-Based
Oxman AD, Sackett DL, Guyatt GH. Users guides to the medical literature. I. How to get started. The Evidence-Based
Peipert JF, Gifford DS, Boardman LA. Research design and
methods of quantitative synthesis of medical evidence. Obstet
Gynecol 1997;90:473478
Richardson WS, Detsky AS. Users guides to the medical literature. VII. How to use a clinical decision analysis. A. Are the
results of the study valid? Evidence-Based Medicine Working
Group. JAMA 1995;273:12921295
Wilson MC, Hayward RS, Tunis SR, Bass EB, Guyatt G. Users
guides to the medical literature. VIII. How to use clinical practice guidelines. B. What are the recommendations and will they
help you in caring for your patients? The Evidence-Based
PRACTICE BULLETINS
COMMITTEE
ON
PRACTICE BULLETINSOBSTETRICS
PRACTICE BULLETINS
COMMITTEE
ON
PRACTICE BULLETINSOBSTETRICS
ACOG
PRACTICE
BULLETIN
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 4, MAY 1999
(Replaces Educational Bulletin Number 147, October 1990)
This Practice Bulletin was

developed by the ACOG Committee on Practice Bulletins
Obstetrics with the assistance
of Michael L. Socol, MD, and
T. Flint Porter, MD, MPH. The
information is designed to aid
practitioners in making decisions about appropriate obstetric and gynecologic care.
These guidelines should not be
construed as dictating an exclusive course of treatment or
procedure. Variations in practice may be warranted based on
the needs of the individual patient, resources, and limitations
unique to the institution or type
of practice.
Prevention of Rh D
Alloimmunization
Before the introduction of anti-D immune globulin (formerly referred to as
Rho[D] immune globulin), hemolytic disease of the fetus and newborn affected
910% of pregnancies and was a major cause of perinatal morbidity and mortality (1, 2). Among Rh D-alloimmunized pregnancies, mild-to-moderate
hemolytic anemia and hyperbilirubinemia occur in 2530% of fetuses/neonates,
and hydrops fetalis occurs in another 25% of such cases (3). The administration
of anti-D immune globulin is successful in reducing the rate of developing antibodies to the D antigen. Protocols for the antenatal and postpartum administration of anti-D immune globulin have been responsible for the dramatic decrease
in alloimmunization and subsequent hemolytic disease in the past two decades.
However, Rh D alloimmunization remains a clinical concern, with many cases
due to failure to follow established protocols. Finally, there is concern that
overuse of anti-D immune globulin may lead to a worldwide shortage. The purpose of this document is to provide direction for the appropriate and efficient
management of patients at risk in order to further decrease the frequency of Rh
D alloimmunization.
Reaffirmed 2009
Background
Nomenclature
Nomenclature of blood group systems, including the Rh system, may appear
confusing to the clinician. According to the American Medical Association
Manual of Style, erythrocyte antigen and phenotype terminology should use single letters or dual letters depending on the antigen in question (eg, O, AB, Le,
Rh) (4). A second designation should be used for specific subtypes (eg, Rh D, Rh
C). This publication uses the designation Rh D to signify the erythrocyte antigen.
647
648
Women who carry the Rh D antigen are identified as Rh D

positive, and those who do not carry the Rh D antigen are
identified as Rh D negative. The use of immune globulin to
counter the Rh D antigen is referred to as anti-D immune
globulin.
Causes of Rh D Alloimmunization
One study indicates that 17% of Rh D-negative women
who do not receive anti-D immune globulin prophylaxis
during pregnancy will become alloimmunized (5). Nearly
90% of these cases result from fetomaternal hemorrhage at
delivery. Approximately 10% of cases result from spontaneous antenatal fetomaternal hemorrhage, and most of
these cases occur in the third trimester. The amount of Rh
D-positive blood required to cause alloimmunization is
small. Most women who become alloimmunized do so as
a result of fetomaternal hemorrhage of less than 0.1 mL
(6).
Several first- and second-trimester clinical events may
cause Rh D alloimmunization. Therapeutic and spontaneous abortions are associated respectively with a 45%
and a 1.52% risk of alloimmunization in susceptible
(nonalloimmunized) women (68). Ectopic pregnancy also
is associated with alloimmunization in susceptible women.
Threatened abortion infrequently causes alloimmunization, although approximately 10% of women with threatened abortion have evidence of fetomaternal hemorrhage
(9).
Clinical procedures, which may breach the integrity of
the choriodecidual space, also may cause Rh D alloimmunization. Chorionic villus sampling is associated with a
14% risk of fetomaternal hemorrhage (10) of more than
0.6 mL (11), and amniocentesis is associated with a
715% risk of fetomaternal hemorrhage, even if the placenta is not traversed (5, 12). Likewise, cordocentesis and
other percutaneous fetal procedures pose a risk for fetomaternal hemorrhage, although the actual risk of alloimmunization has not been quantified (13, 14). External
cephalic version, whether or not it is successful, results in
fetomaternal hemorrhage in 26% of cases (15, 16).
Anti-D Immune Globulin to Prevent

Alloimmunization
The correct administration of anti-D immune globulin dramatically reduces the rate of alloimmunization. Initial
studies proved that the postpartum administration of a single dose of anti-D immune globulin to susceptible Rh Dnegative women within 72 hours of delivery reduced the
alloimmunization rate by 90% (17). It was subsequently
recognized that third-trimester antenatal alloimmunization
posed a lingering and significant problem; later it was
shown that the routine antenatal administration of anti-D
immune globulin to Rh D-negative women at 2829 weeks
of gestation reduced the rate of third-trimester alloimmunization from nearly 2% to 0.1% (6). With the effectiveness of anti-D immune globulin clearly demonstrated,
authorities recommended its administration to Rh D-negative women who were undergoing clinical events or
procedures associated with potential fetomaternal hemorrhage.
In the United States, recommendations for the
administration of anti-D immune globulin were introduced in the 1970s. The current antenatal immunoprophylaxis regimen of a single dose of 300 g at 28 weeks
of gestation was based on recommendations from the
1977 McMaster Conference, and is associated with a low
failure rate (18). The efficacy of the single antenatal dose
of 300 g at 28 weeks of gestation is comparable to the
same dose given at both 28 weeks and 34 weeks of gestation (6). In one study of antenatal prophylaxis, three
women who delivered more than 12 weeks after their
antenatal dose was administered became alloimmunized.
Based on these limited data, some authorities recommend
that if delivery has not occurred within 12 weeks of the
injection, at 28 weeks of gestation, a second 300 g dose
of anti-D immune globulin should be given (5).
In the United Kingdom, recommendations (19, 20)
differ somewhat from those in the United States in that
antenatal prophylaxis is given at both 28 weeks and 34
weeks of gestation, and the dose for each antenatal administration, as well as the dose given after delivery, is
100 g. These recommendations are based on two studies (21, 22) that demonstrated the superiority of a regimen of 100 g of anti-D immune globulin at 28 weeks
and 34 weeks of gestation and postpartum compared with
a regimen of only postpartum administration. The British
regimen uses less anti-D immune globulin (300 g versus 600 g) to achieve similarly low rates of alloimmunization (7, 20), but requires a third injection at 34 weeks
of gestation.
Anti-D immune globulin is extracted by cold alcohol
fractionation from plasma donated by individuals with
high-titer D immune globulin G antibodies. It has been
shown experimentally that one prophylactic dose of 300
g of anti-D immune globulin can prevent Rh D alloimmunization after an exposure to up to 30 mL of Rh Dpositive blood or 15 mL of fetal cells (23). For exposure
to larger volumes of Rh D-positive blood, more anti-D
immune globulin is required. Accordingly, the American
Association of Blood Banks and the National Blood
Transfusion Service of the United Kingdom recommend
that Rh D-negative mothers delivering Rh D-positive
infants undergo a test to screen for fetomaternal hemorrhage in excess of the amount covered by the standard
dose of anti-D immune globulin. This test will determine
if additional anti-D immune globulin is necessary (24,
25). In the past, the American College of Obstetricians
PRACTICE BULLETINS
and Gynecologists recommended that only women with

certain high-risk conditions, such as those experiencing
abruptio placenta or manual removal of the placenta, be
screened for excess fetomaternal hemorrhage. However,
this policy has been shown to miss 50% of cases requiring
more than the standard postpartum dose of anti-D immune
globulin (26).
The risk of transmission of viral infections (human
immunodeficiency virus [HIV] and hepatitis B and hepatitis C viruses) through anti-D immune globulin is minimal
to absent (27). All plasma lots used for the production of
anti-D immune globulin have been tested for viral infection since 1985. Moreover, the fractionation process used
to prepare anti-D immune globulin effectively removes
any viral particles that may be present.
Failure to Prevent Rh D
Alloimmunization
In spite of recommendations for immunoprophylaxis,
0.10.2% of susceptible Rh D-negative women still
become alloimmunized (21). There are two primary reasons for the continuing problem.
One reason women become alloimmunized is failure
to implement recommended immunoprophylaxis protocols, resulting in preventable Rh D alloimmunizations.
Two recent studies from the United Kingdom emphasize
the scope of the problem. One study of more than 900 Rh
D-negative women reported that only 59% received recommended treatment with anti-D immune globulin after
potentially alloimmunizing clinical events (8). Another
study showed that 16% of 63 cases of Rh D alloimmunization occurred because of failure to follow recommendations for administration of anti-D immune globulin (28).
Preventable Rh D alloimmunization occurs in susceptible
Rh D-negative women for the following three reasons:
1.
2.
3.
Failure to administer an antenatal dose of anti-D

immune globulin at 2829 weeks of gestation
Failure to recognize clinical events that place patients
at risk for alloimmunization and failure to administer
anti-D immune globulin appropriately
Failure to administer or failure to administer timely
anti-D immune globulin postnatally to women who
have given birth to an Rh D-positive or untyped fetus
The second reason for the continuing problem of Rh

D alloimmunization is the small rate (0.10.2%) of spontaneous immunization despite the recommended prophylaxis protocol. These cases most often occur in pregnancies
during which there have been no prior overt sensitizing
events. This problem may become the largest single cause
of new Rh D alloimmunization, because alloimmunization
from other causes has decreased proportionally (28).
649
Potential Shortage of Anti-D Immune

Globulin
Anti-D immune globulin is collected by apheresis from
volunteer donors who have high titers of circulating antiRh D antibodies. The donated plasma is pooled and fractionated by commercial manufacturers, and anti-D
immune globulin is prepared in varying doses. The number of potential donors may be dwindling worldwide,
raising concern about future supplies of anti-D immune
globulin (29, 30). Experts in the United Kingdom estimate
that supplies of anti-D immune globulin are inadequate
for immunoprophylaxis of all susceptible Rh D-negative
women, both primigravidas and multiparas, if standard
recommendations are followed (19). In Australia, a shortage prompted importation of anti-D immune globulin.
Subsequently, some physicians proposed strictly limiting
the dose given for first-trimester indications and discontinuing administration of anti-D immune globulin after
external cephalic version (unless fetomaternal hemorrhage
is documented), ectopic pregnancy, or threatened miscarriage (31). Others disagreed, considering it unethical to
withhold anti-D immune globulin in any situation.
Estimates regarding future needs compared with potential supply in the United States have not been published;
however, limiting doses for first-trimester indications and
using lower doses of Rh D immune globulin for antenatal prophylaxis may be necessary.
Cost-Effectiveness of Rh D Prophylaxis
Programs
The cost-effectiveness of preventing perinatal mortality
and morbidity secondary to Rh D hemolytic disease of
the newborn is an important consideration. Economic
analysis of anti-D immune globulin prophylaxis is based
on the cost of anti-D immune globulin and the number of
alloimmunizations that would be prevented. In 1977, the
McMaster Conference concluded that routine postnatal
prophylaxis was cost-effective but that routine antenatal
treatment should be undertaken only if supplies of anti-D
immune globulin were adequate and if cases of hemolytic
disease of the newborns occurred that might have been
prevented by antenatal treatment (7). Some experts concluded that antenatal prophylaxis is effective only in
primigravidas (32), and the debate regarding the costeffectiveness of antenatal prophylaxis of all pregnant
women remains unsettled (20, 3237). The Scottish
National Blood Transfusion Service has concluded that
the administration of 100 g of anti-D immune globulin
at 28 weeks and 34 weeks of gestation is cost-effective
only in primigravidas (38). Others estimate that the most
cost-effective antenatal regimen is a single dose of 250 g
of anti-D immune globulin at 28 weeks of gestation (39).
650
Should anti-D immune globulin ever be withheld from a woman undergoing sterilization?
How should one deal with the issue of paternity?
If the father is known to be Rh D negative, antenatal prophylaxis is unnecessary. If there is doubt about the fathers
identity or his blood type, anti-D immune globulin prophylaxis should be given.
Is it necessary to repeat antibody screening in

patients at 28 weeks of gestation prior to the
administration of anti-D immune globulin?
The American Association of Blood Banks recommends

that the physician should consider a repeat antibody screen
prior to the administration of antenatal anti-D immune
globulin if the patient was screened for antibodies prior to
28 weeks of gestation (24). The primary rationale for
repeating the antibody screen is to identify women who
have become alloimmunized before 28 weeks of gestation
How should a Du blood type be interpreted,

and what management should be undertaken?
In the past, a woman whose blood was typed as Du was

thought to have blood cells positive for a variant of the
Rh D antigen. Nomenclature and practice have changed
in recent years, and currently the Du designation has been
changed to weak D positive (24). Patients with this
designation are considered Rh D positive and should not
receive anti-D immune globulin. In some centers, the Du
antigen is not assessed, and women may unnecessarily
receive anti-D immune globulin. In the rare circumstance
of delivery by a woman whose antenatal Rh status is negative or unknown and whose postpartum screen reveals a
Du-positive or weak D-positive result, anti-D immune
globulin should be given, and the possibility of fetomaternal hemorrhage should be investigated (24).
The use of anti-D immune globulin following postpartum

and postabortal sterilization should be guided by the
patients desire for protection against any chance of
alloimmunization. Proponents of its use maintain that antiD immune globulin administration will preserve the future
option of transfusing Rh D-positive blood in times of emergency (40). Opponents of this view cite the low probability
of sensitization with the previous pregnancy and the
improbability of receiving Rh D-incompatible blood (41).
Is anti-D immune globulin indicated in a sensitized pregnancy?
If Rh D antibodies are present, anti-D immune globulin

is not beneficial, and management should proceed in
accordance with protocols for Rh D-alloimmunized pregnancies.
Clinical Considerations and

Recommendations
in order to manage their pregnancies properly. However,

the incidence of Rh D alloimmunization occurring prior
to 28 weeks of gestation is reported to be as low as 0.18%
(18), and the cost-effectiveness of routinely repeating the
antibody test has not been studied. The consequences of
antenatal Rh D alloimmunization can be severe, but the
decision to obtain a repeat antibody screen should be dictated by individual circumstances and left to the judgment of the physician.
The use of anti-D prophylaxis in the case of certain

clinical events is even more controversial. For example, the
risk of Rh D alloimmunization from threatened abortion in
the first trimester is uncertain, though probably very small.
The cost-effectiveness of anti-D immune globulin for
threatened abortion, which has never been studied, is questionable (19).
In summary, the cost-effectiveness of antenatal Rh D
immune globulin to all Rh D-negative pregnant women
and in all circumstances wherein fetomaternal hemorrhage
might occur has not been proved. Available data support
that third-trimester antenatal prophylaxis is cost-effective
in primigravidas. As long as the supply of anti-D immune
globulin is adequate and data do not exist to support other
recommendations, most experts believe that it is unethical
to withhold anti-D immune globulin from any patient at
risk of Rh D alloimmunization (19). Recommendations for
the use of anti-D immune globulin in this document will be
made accordingly.
Is threatened abortion an indication for anti-D

immune globulin prophylaxis?
Whether to administer anti-D immune globulin to a

patient with threatened abortion and a live embryo or fetus
at or before 12 weeks of gestation is controversial, and no
evidence-based recommendation can be made. The Rh D
antigen has been reported on fetal erythrocytes as early as
38 days of gestation (42), and fetomaternal hemorrhage
has been documented in women with threatened abortion
from 7 to 13 weeks of gestation (9). However, Rh D alloimmunization apparently attributable to threatened
abortion is exceedingly rare. Experts have compared the
overall benefit with the cost of the widespread use of antiD immune globulin for a condition as common as threatened abortion (19, 43), and, thus, many physicians do not
routinely administer anti-D immune globulin to women
with threatened abortion and a live embryo or fetus up to
12 weeks of gestation.
PRACTICE BULLETINS
How much anti-D immune globulin should be

given for first-trimester events and procedures?
Because the red cell mass of the first-trimester fetus is

small, the dose of anti-D immune globulin necessary for
first-trimester events is 50 g to protect against sensitization by 2.5 mL of red blood cells (5, 44). If therapeutic or
spontaneous abortion occurs after the first trimester, the
standard 300 g dose is recommended (5).
Should anti-D immune globulin be given in

cases of molar pregnancy?
Is second- or third-trimester antenatal hemorrhage an indication for anti-D immune globulin

prophylaxis?
In patients with second- or third-trimester antenatal hemorrhage, the risk of Rh D alloimmunization is uncertain.
Although the efficacy of anti-D immune globulin in this
clinical situation has not been tested in properly designed
trials, authorities agree that anti-D immune globulin should
be administered to Rh D-negative women with second- or
What should be done if an Rh D-negative

patient is discharged without receiving anti-D
immune globulin after a potentially sensitizing
event?
Volunteers have been shown to receive partial protection

if anti-D immune globulin was given as late as 13 days
after exposure (58). The longer prophylaxis is delayed
the less likely it is that the patient will be protected, but
it has been recommended that a patient may still receive
some benefit from anti-D immune globulin as late as 28
days postpartum (5).
Fetal death is due to fetomaternal hemorrhage in 1113%

of cases in which no obvious other cause (eg, maternal
hypertensive disease, fetal anomalies) is found (50, 51). Rh
D alloimmunization has been reported in cases of fetal
death from massive fetomaternal hemorrhage (52), although
the influence of this cause on the overall problem of Rh D
alloimmunization is unknown. The efficacy of anti-D
immune globulin in this clinical situation has not been tested in properly designed trials. However, authorities agree
that anti-D immune globulin should be administered to Rh
D-negative women who experience fetal death in the second or third trimester. All such cases should be screened for
excessive fetomaternal hemorrhage to determine if additional anti-D immune globulin is required (25, 53).
Is anti-D immune globulin prophylaxis indicated after abdominal trauma in susceptible

pregnant women?
Although the exact risk of Rh D alloimmunization is

unknown, abdominal trauma may be associated with
fetomaternal hemorrhage, which may lead to alloimmunization (5457). The efficacy of anti-D immune globulin
in this clinical situation has not been tested in properly
designed trials. However, authorities agree that anti-D
immune globulin should be administered to Rh D-negative women who have experienced abdominal trauma
(25, 53). Also, all of these patients should be screened for
excessive fetomaternal hemorrhage.
Should anti-D immune globulin be given in

cases of intrauterine fetal death occurring in the
second or third trimester?
third-trimester hemorrhage (25, 53). Management of the

patient with persistent or intermittent antenatal bleeding
is complex. Though unproven, one commonly used strategy is to monitor the Rh D-negative patient with continuing antenatal hemorrhage with serial indirect Coombs
testing approximately every 3 weeks. If the result is positive, indicating the persistence of anti-D immune globulin, no additional treatment is necessary. If the Coombs
test is negative, excessive fetomaternal hemorrhage may
have occurred, and a Kleihauer-Betke test should be performed in order to determine the amount of additional
anti-D immune globulin necessary.
Although reported (45), the risk of Rh D alloimmunization

in cases of hydatidiform mole is unknown. In theory, Rh D
alloimmunization would not occur in cases of classic complete molar pregnancy because organogenesis does not
occur, and Rh D antigens are probably not present on trophoblast cells, although this theory has been disputed
(4648). In partial and transitional molar pregnancies,
however, the embryo may not die until after erythrocyte
production has begun, making maternal exposure to the Rh
D antigen possible (49). Given that the diagnosis of partial
versus complete molar pregnancy depends on pathologic
and cytogenetic evaluations, it seems reasonable to administer anti-D immune globulin to Rh D-negative women who
are suspected of molar pregnancy and who undergo uterine
evacuation.
651
How long does the effect of anti-D immune

globulin last?
The half-life of anti-D immune globulin is 24 days,

although titers decrease over time. If delivery occurs within 3 weeks of the standard antenatal anti-D immune globulin administration, the postnatal dose may be withheld
in the absence of excessive fetomaternal hemorrhage
(53). The same is true when anti-D immune globulin is
given for antenatal procedures, such as external cephalic
version or amniocentesis, or for third-trimester bleeding.
An excessive amount of fetal erythrocytes not covered by
anti-D immune globulin administration can be assumed
to have entered maternal blood if either the results of the
Kleihauer-Betke test are positive or the results of the
indirect Coombs test are negative.
652
The risk of excessive fetomaternal hemorrhage exceeding

30 mL (the amount covered by the standard 300 g dose
of anti-D immune globulin) at the time of delivery is approximately 1 in 1,250 (5). Previous American College of
Obstetricians and Gynecologists documents have recommended that only pregnancies designated as high risk be
screened for excessive fetomaternal hemorrhage, including cases of abdominal trauma, abruptio placentae,
placenta previa, intrauterine manipulation, multiple gestation, or manual removal of the placenta. However, such
a screening program has been reported to detect only 50%
of patients who required additional anti-D immune globulin (26). Based on this finding, the American Association
of Blood Banks has recommended that all Rh D-negative
women who deliver Rh D-positive infants be screened
using the Kleihauer-Betke or rosette test (24).
Summary
The reduction in the incidence of Rh D alloimmunization
is a prototype for the effectiveness of preventive medicine.
Some controversies remain, however, such as the use of
anti-D immune globulin in patients with either threatened
abortion or antenatal hemorrhage. Similarly, it may not be
cost-effective either to screen all Rh D-negative patients
with an indirect Coombs test at 2428 weeks of gestation
or to screen all postpartum patients for excessive fetomaternal hemorrhage.
After a first-trimester pregnancy loss

After invasive procedures, such as chorionic villus
sampling, amniocentesis, or fetal blood sampling
The following recommendations are based primarily on consensus and expert opinion (Level C):
Anti-D immune globulin prophylaxis should be considered if the patient has experienced:
Should all Rh D-negative women be screened

for excessive fetomaternal hemorrhage after
delivery of an Rh D-positive infant?
Within 72 hours after the delivery of an Rh D-positive infant
One study found that three patients became alloimmunized to the Rh D antigen when delivery occurred more
than 12 weeks after the standard prophylaxis at 28 weeks
of gestation (5). Based on these limited data, some
experts have recommended that if delivery has not
occurred within 12 weeks after injection at 28 weeks of
gestation, a second antenatal dose should be given (5).
Because this recommendation is based on so few cases,
the final decision whether to administer a second dose
should be left to the physicians judgment.
Should administration of anti-D immune globulin be repeated in patients with a postdate

pregnancy?
Threatened abortion
Second- or third-trimester antenatal bleeding
External cephalic version
Abdominal trauma
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The MEDLINE database, the Cochrane Library, and

ACOGs own internal resources and documents were used
to conduct a literature search to locate relevant articles published between January 1980 and December 1998. The
search was restricted to articles published in the English
language. Priority was given to articles reporting results of
original research, although review articles and commentaries also were consulted. Abstracts of research presented at
symposia and scientific conferences were not considered
adequate for inclusion in this document. Guidelines published by organizations or institutions such as the National
Institutes of Health and the American College of Obstetricians and Gynecologists were reviewed, and additional
studies were located by reviewing bibliographies of identified articles. When reliable research was not available, expert opinions from obstetriciangynecologists were used.
Studies were reviewed and evaluated for quality according
to the method outlined by the U.S. Preventive Services Task
Force:
I
Evidence obtained from at least one properly designed randomized controlled trial.
II-1 Evidence obtained from well-designed controlled

trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncontrolled experiments could also be regarded as this
type of evidence.
III
Opinions of respected authorities, based on clinical

experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,

Level ARecommendations are based on good and consistent scientific evidence.
Level BRecommendations are based on limited or inconsistent scientific evidence.
Level CRecommendations are based primarily on consensus and expert opinion.
Copyright May 1999 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written
ISSN 1099-3630
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PRACTICE BULLETINS
655
ACOG
PRACTICE
BULLETIN
NUMBER 6, SEPTEMBER 1999

of Robert M. Silver, MD,
Richard L. Berkowitz, MD,
and James Bussel, MD. The
practitioners in making decisions about appropriate obstetric and gynecologic care.
construed as dictating an
exclusive course of treatment
or procedure. Variations in
practice may be warranted
Reaffirmed 2009
Thrombocytopenia
in Pregnancy
Thrombocytopenia in pregnant women is diagnosed frequently by obstetricians
because platelet counts are now included with automated complete blood cell
counts (CBCs) obtained during routine prenatal screening (1). The condition is
common, occurring in 78% of pregnancies (2). Thrombocytopenia can result
from a variety of physiologic or pathologic conditions, several of which are
unique to pregnancy. Some causes of thrombocytopenia are serious medical
disorders that have the potential for profound maternal and fetal morbidity. In
contrast, other conditions, such as gestational thrombocytopenia, are benign
and pose no maternal or fetal risks. Because of the increased recognition of
maternal and fetal thrombocytopenia, there are numerous controversies regarding obstetric management. Clinicians must weigh the risks of maternal and
fetal bleeding complications against the costs and morbidity of diagnostic tests
and invasive interventions.
Background
Platelet Function
Unlike other bleeding disorders in which bruising often is the initial clinical
manifestation, platelet disorders, such as thrombocytopenia, usually result in
bleeding into mucous membranes. Although bruising can occur, the most common manifestations of thrombocytopenia are petechiae, ecchymoses, epistaxis,
gingival bleeding, and menometrorrhagia. In contrast to hemophilia, bleeding
into joints usually does not occur; life-threatening bleeding is less common but
can occur, resulting in hematuria, gastrointestinal bleeding, and, although rare,
intracranial hemorrhage.
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Definition of Thrombocytopenia
The normal range of the platelet count in nonpregnant
individuals is 150,000400,000/L. In this population,
thrombocytopenia is defined as any platelet value less
than 150,000/L, with counts of 100,000150,000/L
indicative of mild thrombocytopenia, 50,000100,000/L
indicative of moderate thrombocytopenia, and less than
50,000/L indicative of severe thrombocytopenia. The
definition of thrombocytopenia is somewhat arbitrary and
not necessarily clinically relevant. Clinically significant
bleeding usually is limited to patients with platelet counts
less than 10,000/L. Serious bleeding complications are
rare, even in those with severe thrombocytopenia (3).
Excessive bleeding associated with trauma or surgery is
uncommon unless the patients platelet count is less than
50,000/L. The mean platelet count in pregnant women is
lower than in nonpregnant individuals (4, 5).
Differential Diagnosis of
Thrombocytopenia
Thrombocytopenia is due to either increased platelet
destruction or decreased platelet production. In pregnancy, the former is responsible for most cases (2). Increased
platelet destruction can be caused by an immunologic
destruction, abnormal platelet activation, or platelet consumption resulting from excessive bleeding or exposure
to abnormal vessels. Decreased platelet production is less
common, and usually is associated with either leukemia,
aplastic anemia, or folate deficiency (6, 7).
The most common cause of thrombocytopenia during pregnancy is gestational thrombocytopenia, which
accounts for about two thirds of cases (2) (see the box).
Gestational Thrombocytopenia
Gestational thrombocytopenia, also termed essential
thrombocytopenia or benign or incidental thrombocytopenia of pregnancy, is by far the most common cause of
mild thrombocytopenia during pregnancy, affecting up to
8% of gestations (2). There are several characteristics of
this condition (2). First, the thrombocytopenia is relatively mild with platelet counts usually remaining greater
than 70,000/L. However, a lower threshold for gestational thrombocytopenia has never been established.
Second, women are asymptomatic with no history of
bleeding. The thrombocytopenia usually is detected as
part of routine prenatal screening. Third, women have no
history of thrombocytopenia prior to pregnancy (except in
previous pregnancies). Although gestational thrombocytopenia may recur in subsequent pregnancies (8), the
recurrence risk is unknown. Fourth, platelet counts usually return to normal within 212 weeks following delivery.
Causes of Thrombocytopenia in Pregnancy

Gestational thrombocytopenia
Pregnancy-induced hypertension
HELLP syndrome
Pseudothrombocytopenia (laboratory artifact)
Human immunodeficiency virus (HIV) infection
Immune thrombocytopenic purpura
Systemic lupus erythematosus
Antiphospholipid syndrome
Hypersplenism
Disseminated intravascular coagulation
Thrombotic thrombocytopenic purpura
Hemolytic uremic syndrome
Congenital thrombocytopenias
Medications (heparin, quinine, quinidine,
zidovudine, sulfonamides)
Finally, there is an extremely low risk of fetal or neonatal

thrombocytopenia. In a large, prospectively evaluated
cohort study of 756 women with gestational thrombocytopenia, only one womans infant had a platelet count of
less than 50,000/L (9). However, this infant had thrombocytopenia due to congenital bone marrow dysfunction.
Another study confirmed the extremely low risk of fetal
thrombocytopenia in women with gestational thrombocytopenia (10). Thus, women with gestational thrombocytopenia are not at risk for maternal or fetal hemorrhage or
bleeding complications.
Although its cause is uncertain, gestational thrombocytopenia may be due to accelerated platelet consumption
(4). Antiplatelet antibodies often are detectable in women
with gestational thrombocytopenia, but neither their presence nor their absence can be used to diagnose the disorder
or differentiate it from immune thrombocytopenic purpura
(ITP) (11). Indeed, there are no specific diagnostic tests to
definitively distinguish gestational thrombocytopenia from
mild ITP (1). The primary means of differentiation is to
monitor platelet counts closely, to look for levels that
decrease below the 50,00070,000/L range, and to document a normal neonatal platelet count and a restoration of
normal maternal platelet values after delivery.
Thrombocytopenia with an
Immunologic Basis
Thrombocytopenia with an immunologic basis during
pregnancy can be broadly classified as two disorders:
neonatal alloimmune thrombocytopenia and ITP, an
PRACTICE BULLETINS
autoimmune condition. Neonatal alloimmune thrombocytopenia has no effect on the mother but probably is responsible for more intracranial hemorrhage due to thrombocytopenia than all the other primary thrombocytopenic conditions
combined. In contrast, ITP may affect both mothers and
fetuses, but with appropriate management the outcome for
both is excellent.
Neonatal Alloimmune Thrombocytopenia

Neonatal alloimmune thrombocytopenia is the platelet
equivalent of hemolytic (Rh) disease of the newborn,
developing as a result of maternal alloimmunization to
fetal platelet antigens. It affects one in 1,0002,000 live
births and can be a serious and potentially life-threatening
condition (12, 13). Unlike Rh disease, neonatal alloimmune thrombocytopenia can occur during a first pregnancy. Almost half of the clinically evident cases of neonatal
alloimmune thrombocytopenia are discovered in the first
live-born infant (14).
In typical cases of unanticipated neonatal alloimmune
thrombocytopenia, the mother is healthy and has a normal
platelet count, and her pregnancy, labor, and delivery are
indistinguishable from those of other low-risk obstetric
patients. The neonates, however, are either born with evidence of profound thrombocytopenia or develop symptomatic thrombocytopenia within hours after birth. Affected
infants often manifest generalized petechiae or ecchymoses over the presenting fetal part. Hemorrhage into viscera and bleeding following circumcision or venipuncture
also may ensue. The most serious complication of neonatal alloimmune thrombocytopenia is intracranial hemorrhage, which occurs in 1020% of infants (14, 15). Fetal
intracranial hemorrhage due to neonatal alloimmune
thrombocytopenia can occur in utero, and 2550% of fetal
intracranial hemorrhage in untreated mothers may be
detected by ultrasonography before the onset of labor (16).
Ultrasonographic findings may include intracranial hemorrhage, porencephalic cysts, and obstructive hydrocephalus. These observations are in contrast to neonatal
intracranial hemorrhage due to ITP, which is exceedingly
rare and usually occurs during the neonatal period.
Several polymorphic, diallelic antigen systems residing on platelet membrane glycoproteins are responsible
for neonatal alloimmune thrombocytopenia. Many of
these antigen systems have several names because they
were identified in different parts of the world concurrently. Recently, a uniform nomenclature has been adopted
that describes these antigens as human platelet antigens
(HPA-1 and HPA-2), with alleles designated as a or b
(17). Although there are at least 10 officially recognized
platelet-specific antigens at this time, more than 50% of
the reported cases in Caucasians and most of the severe
657
cases have occurred as a result of sensitization against

HPA-1a, also known as PlA1 and Zwa.
Fetal thrombocytopenia due to HPA-1a sensitization
tends to be severe and can occur early in gestation. In a
cohort study of 107 fetuses with neonatal alloimmune
thrombocytopenia (97 with HPA-1a incompatibility)
studied in utero before receiving any therapy, 50% had
initial platelet counts of less than 20,000/L (13). This
percentage included 21 of 46 fetuses tested before 24
weeks of gestation. Furthermore, this series documented
that the fetal platelet count decreases at a rate of more
than 15,000/L per week in the absence of therapy.
The recurrence risk of neonatal alloimmune thrombocytopenia is extremely high and approaches 100% in
cases involving HPA-1a if the subsequent sibling carries
the pertinent antigen (13). Thus, the recurrence risk is
related to the zygosity of the father. As with red cell
alloimmunization, the disease tends to be equally severe
or progressively worse in subsequent pregnancies.
Immune Thrombocytopenic Purpura

Acute ITP is a self-limited disorder that usually occurs in
childhood. It may follow a viral infection and rarely persists. Chronic ITP typically occurs in the second or third
decade of life and has a female to male ratio of 3:1 (18).
Estimates of the frequency of ITP during pregnancy vary
widely, affecting one in 1,00010,000 pregnancies (19).
Immune thrombocytopenic purpura is characterized
by immunologically mediated platelet destruction. The
patient produces IgG antiplatelet antibodies that recognize platelet membrane glycoproteins. This process leads
to increased platelet destruction by cells of the reticuloendothelial system (18). The rate of destruction
exceeds the compensatory ability of the bone marrow to
produce new platelets, which leads to thrombocytopenia.
Most of the platelet destruction occurs in the spleen,
although other sites also are involved.
There are no pathognomonic signs, symptoms, or
diagnostic tests for ITP; it is a diagnosis of exclusion.
However, four findings have been traditionally associated with the condition: 1) persistent thrombocytopenia
(platelet count <100,000/L with or without accompanying megathrombocytes on the peripheral smear), 2) normal or increased numbers of megakaryocytes determined
from bone marrow, 3) exclusion of other systemic disorders or drugs that are known to be associated with thrombocytopenia, and 4) absence of splenomegaly.
Most women with ITP have a history of bruising easily and petechiae, or of possible epistaxis and gingival
bleeding, which precedes their pregnancy, but some
women are completely asymptomatic. Important hemorrhagic symptoms rarely occur unless the platelet count is
658
Pregnancy-Induced Hypertension
Pregnancy-induced hypertension (PIH) is reported to be
the cause of 21% of cases of maternal thrombocytopenia
(9). The thrombocytopenia usually is moderate, and
platelet counts rarely decrease below 20,000/L. Clinical
hemorrhage is uncommon unless the patient develops
disseminated intravascular coagulopathy, but a decreasing maternal platelet count generally is considered a sign
of worsening disease and is an indication for delivery.
In some cases, microangiopathic hemolytic anemia
and elevated liver function tests are associated with
thrombocytopenia in individuals with PIH. Such individuals are considered to have HELLP syndrome.
The cause of thrombocytopenia in women with
severe PIH is unknown. The disease is associated with a
state of accelerated platelet destruction, platelet activation, increased platelet volume, and increased megakaryocyte activity (21). Increased levels of platelet-associated
IgG have been detected in patients with PIH (24).
However, this finding is nonspecific and does not necessarily imply an immunologic basis for the thrombocy-
topenia. Platelet function also may be impaired in women

with PIH, even if their platelet count is normal. It is noteworthy that the platelet count may decrease before the
other clinical manifestations of PIH are apparent (25).
The neonates of mothers with PIH are at increased
risk of neonatal thrombocytopenia (2). However, this is
true only for infants born prematurely, and especially
those with growth restriction. Term infants of mothers
with PIH are no more likely to have thrombocytopenia
than are controls. In a study of 1,414 mothers with hypertension, neonatal thrombocytopenia associated with PIH
rarely decreased below 20,000/L and caused no fetal
bleeding complications (9).

Recommendations
less than 20,000/L. It is believed that the course of ITP

usually is not affected by pregnancy, although there have
been anecdotal reports of patients conditions worsening
during pregnancy and improving postpartum (20, 21).
Pregnancy may be adversely affected by severe thrombocytopenia, and the primary risk to the mother is hemorrhage during the peripartum period.
Maternal IgG antiplatelet antibodies can cross the
placenta, placing the fetus and neonate at risk for the
development of thrombocytopenia. Retrospective case
series of ITP in pregnancy indicate that 1215% of
infants born to mothers with ITP will develop platelet
counts less than 50,000/L (22, 23). Sometimes, this
results in minor clinical bleeding such as purpura,
ecchymoses, or melena. On rare occasions, fetal thrombocytopenia associated with ITP leads to intracranial
hemorrhage unrelated to the mode of delivery. When it
occurs, intracranial hemorrhage can result in severe neurologic impairment and even death. Serious bleeding
complications are estimated to occur in 3% of infants
born to women with ITP, and the rate of intracranial hemorrhage is less than 1% (22, 23). These data may overestimate the risk, as a result of publication bias. In a
prospective, population-based study of almost 16,000
pregnancies delivered at a single center, no infant born to
a mother with ITP suffered intracranial hemorrhage (9).
The only three infants with intracranial hemorrhage had
neonatal alloimmune thrombocytopenia, not ITP. The
platelet count of the affected newborn usually will
decrease after delivery, and the nadir may not be reached
for several days (20).
What is the appropriate workup for maternal

thrombocytopenia?
When thrombocytopenia is diagnosed in a pregnant

woman, it is important that the diagnosis be as precise as
possible. The differential diagnosis of thrombocytopenia
in pregnancy includes gestational thrombocytopenia,
pseudothrombocytopenia, HIV infection, drug-induced
thrombocytopenia, PIH, HELLP syndrome, thrombotic
thrombocytopenic purpura, hemolytic uremic syndrome,
disseminated intravascular coagulation, systemic lupus
erythematosus, antiphospholipid syndrome, and congenital thrombocytopenias. These disorders usually can be
determined on the basis of a detailed medical and family
history and a physical examination, with attention to
blood pressure, splenomegaly, HIV serology, and adjunctive laboratory studies as appropriate.
A CBC and examination of the peripheral blood
smear generally are indicated in the evaluation of maternal
thrombocytopenia. A CBC is helpful to exclude pancytopenia. Evaluation of the peripheral smear serves to rule
out platelet clumping that may be associated with
pseudothrombocytopenia. Bone marrow biopsy rarely is
needed to distinguish between inadequate platelet production and increased platelet turnover. Numerous assays have
been developed for both platelet-associated (direct) antibodies and circulating (indirect) antiplatelet antibodies.
Although many individuals with ITP will have elevated
levels of platelet-associated antibodies and sometimes circulating antiplatelet antibodies, these assays are not recommended for the routine evaluation of maternal thrombocytopenia (26). Tests for antiplatelet antibodies are nonspecific, poorly standardized, and subject to a large degree
of interlaboratory variation (1). Also, gestational thrombocytopenia and ITP cannot be differentiated on the basis of
antiplatelet antibody testing (11).
PRACTICE BULLETINS
If drugs and other medical disorders are excluded, the

primary differential diagnosis in the first and second
trimesters will be either gestational thrombocytopenia or
ITP. It should be noted that although gestational thrombocytopenia can occur in the first trimester, it typically
becomes manifest later in pregnancy. In general, in a
woman with no history of thrombocytopenia or the milder
the thrombocytopenia, the more likely she is to have gestational thrombocytopenia. If the platelet count is less than
70,000/L, ITP is more likely to be present, and if the
platelet count is less than 50,000/L, ITP is almost certainly present. During the third trimester or postpartum
period, the sudden onset of significant maternal thrombocytopenia should lead to consideration of PIH, thrombotic
thrombocytopenic purpura, hemolytic uremic syndrome,
acute fatty liver, or disseminated intravascular coagulation,
although ITP can present this way as well.
When should women with ITP receive medical

therapy?
What therapy should be used to treat ITP during pregnancy?
What additional specialized care should

women with ITP receive?
Other than serial assessment of the maternal platelet

count (every trimester in asymptomatic women in remission and more frequently in thrombocytopenic individuals), little specialized care is required. Pregnant women
with ITP should be instructed to avoid nonsteroidal antiinflammatory agents, salicylates, and trauma. Individuals
with splenectomies should be immunized against pneumococcus, Hemophilus influenzae, and meningococcus.
If the diagnosis of ITP is made, consultation and ongoing
evaluation with a physician experienced in such matters
is appropriate.
The first line of treatment for ITP is prednisone, usually

initiated in a dosage of 12 mg/kg/d. A response to antenatal corticosteroids usually occurs within 37 days and
reaches a maximum within 23 weeks. Once platelet
counts reach acceptable levels, the dosage can be tapered
by 1020% per week until the lowest dosage required to
maintain a platelet count greater than 50,000/L is
reached. An increase in the platelet count occurs in about
70% of patients, and up to 25% will achieve complete
remission (27).
Intravenous immune globulin (IVIG) is appropriate
therapy for cases refractory to steroids as well as in cir-
cumstances such as platelet counts less than 10,000/L in

the third trimester, or platelet counts less than 30,000/L
associated with bleeding or with preoperative or predelivery status. A response to therapy can be expected in as
few as 6 hours or in as many as 72 hours. In 70% of
cases, the platelet count will return to pretreatment levels
within 30 days after treatment (26, 28). Intravenous
immune globulin is costly and of limited availability.
When considering use of IVIG, it is prudent to seek consultation from a physician experienced in such cases.
Splenectomy is associated with complete remission
in approximately 66% of patients with ITP (18); however, it often is not successful in patients who do not
respond to intravenous immunoglobulin (29). The procedure usually is avoided during pregnancy because of fetal
risks and technical difficulties late in gestation. However,
splenectomy can be accomplished safely during pregnancy, ideally in the second trimester. It is appropriate for
severe cases (platelet counts of less than 10,000/L) that
have failed treatment with antenatal corticosteroids and
IVIG (26).
Platelet transfusions should be used only as a temporary measure to control life-threatening hemorrhage or
to prepare a patient for surgery. The usual increase in
platelets of approximately 10,000/L per unit of platelets
transfused is not achieved in patients with ITP because of
the decreased survival of donor platelets. Thus, 610 U of
platelet concentrate should be transfused. Other drugs
used to treat ITP such as colchicine, azathioprine, vinca
alkaloids, cyclophosphamide, and danazol have potential
adverse fetal effects.
The goal of medical therapy during pregnancy in women

with ITP is to minimize the risk of bleeding complications associated with severe thrombocytopenia. Because
the platelet function of these patients usually is normal, it
is not necessary to maintain their counts in the normal
range. There is general agreement that asymptomatic
pregnant women with platelet counts greater than
50,000/L do not require treatment. Also, most authorities recommend treatment in the presence of a platelet
count significantly less than 50,000/L or in the presence
of bleeding. However, the degree of thrombocytopenia in
asymptomatic pregnant women that requires treatment is
somewhat controversial, and consultation from a physician experienced in these matters should be considered.
Higher counts (eg, >50,000/L) are desirable for invasive
procedures and delivery, which may be associated with
hemorrhage, the need for surgery, or the desire to use
regional anesthesia. Bleeding times are not useful in
assessing platelet function in patients with ITP.
659
Can fetal or neonatal intracranial hemorrhage

be prevented in pregnancies complicated by
ITP?
It is logical to assume that therapies known to increase

the maternal platelet count in patients with ITP also
would improve the fetal platelet count. However, medical
therapies such as IVIG (30) and steroids (22, 3032) do
not reliably prevent fetal thrombocytopenia or improve
660
What is the appropriate neonatal care for

infants born of pregnancies complicated by
ITP?
Regardless of the mode, delivery should be accomplished in a setting where an available clinician familiar
with the disorder can treat any neonatal complications
and have access to the medications needed for treatment.
No maternal test or characteristic can reliably predict the

severity of thrombocytopenia in all cases of infants born
to mothers with ITP. Maternal characteristics and serology, including prior splenectomy, platelet count, and the
presence of platelet-associated antibodies, all correlate
poorly with neonatal thrombocytopenia (39, 40). Fetal
thrombocytopenia is rare in the absence of circulating
antiplatelet antibodies (10), but exceptional cases have
been reported (41). Also, these assays are difficult to perform and have a low positive predictive value (10).
Is there any role for fetal platelet count determination in ITP?
At this time, most obstetricians do not obtain fetal

platelet counts (42). Scalp sampling is fraught with inaccuracies and technical difficulties, and cordocentesis carries a 12% risk of necessitating an emergent cesarean
delivery for fetal indications (43). The low incidence of
intracranial hemorrhage and the lack of demonstrated
difference in neonatal outcome between vaginal and
cesarean deliveries also supports the opinion that the
determination of fetal platelet count is unwarranted for
ITP (22, 23, 31, 37, 44). A substantial minority of perinatologists (42) feel that the 5% risk of fetal thrombocytopenia of less than 20,000/L and the attendant theoretically increased risk of an intracranial hemorrhage warrant
informing patients of the availability of cordocentesis or
scalp sampling during labor when choosing mode of
delivery (4547).
What tests or characteristics can be used to

predict fetal thrombocytopenia in pregnancies
complicated by ITP?
fetal outcome. Because some of these therapies (eg,

IVIG) have not been adequately tested in appropriate trials, there are insufficient data to recommend maternal
medical therapy for fetal indications.
Some investigators have recommended cesarean
delivery to decrease the risk of intracranial hemorrhage
by avoiding the potential trauma associated with vaginal
birth (33). This strategy was based on anecdotal reports
of intracranial hemorrhage associated with vaginal delivery (34) as well as the biologic plausibility of the hypothesis. Others have proposed that cesarean delivery be
reserved for fetuses with platelet counts less than
50,000/L (35, 36). This tactic was prompted by the
observation that the risk of fetal bleeding is inversely proportional to the platelet count, and bleeding problems are
extremely rare in fetuses with platelet counts more than
50,000/L (31, 37).
Cesarean delivery has never been proven to prevent
intracranial hemorrhage reliably. Several reports indicate
that hemorrhagic complications in infants with thrombocytopenia are unrelated to the mode of delivery (22, 31,
37, 38). In a review of 474 neonates born to mothers with
ITP, 29% of infants born vaginally with thrombocytopenia had a bleeding complication, compared with 30%
delivered by cesarean birth (31). In this study, the rate of
intracranial hemorrhage also was similar for both modes
of delivery: 4% after vaginal delivery and 3% after
cesarean delivery. In addition, it is unclear that intracranial hemorrhage is an intrapartum phenomenon. The
neonatal platelet count often dramatically decreases after
delivery. Thus, intracranial hemorrhage during the
neonatal period could be mistakenly attributed to intrapartum events. No case of intracranial hemorrhage has
been proven definitively to have occurred during labor
(22, 23). Because cesarean delivery does not clearly prevent intraventricular hemorrhage, many obstetricians
choose the mode of delivery in ITP based on obstetric
considerations alone.
Can a patient with thrombocytopenia be given

regional anesthesia?
The literature offers only limited and retrospective data

to address this issue. However, two studies (48, 49)
reported on a total of 184 patients with platelet counts
less than 150,000/L. Of these, 113 patients received
epidural anesthesia without neurologic complication or
sequelae. In all of these patients, the diagnosis was gestational thrombocytopenia. Another study of patients
with platelet counts less than 100,000/L due to
preeclampsia, ITP, or infection also received epidural
anesthesia without complication (50). Although the complication of greatest concern is that of epidural
hematoma, there are only two cases in the literature of
parturients who developed an epidural hematoma after
regional anesthesia. One patient had preeclampsia and a
lupus anticoagulant (51) and the other had an ependymoma (52). Cases reported in nonparturients have almost
always been associated with anticoagulant therapy.
Although limited, data support the safety of epidural anesthesia in patients with platelet counts greater than
100,000/L. In women with gestational thrombocytopenia with platelet counts less than 99,000/L but greater
than 50,000/L, epidural anesthesia also may be safe, but
its use in such patients will require a consensus among
PRACTICE BULLETINS
the obstetrician, anesthesiologist, and patient. When

platelet counts are less than 50,000/L, epidural anesthesia should not be given.
When should an evaluation for possible

neonatal alloimmune thrombocytopenia be
initiated, and what tests are useful in making
the diagnosis?
How can one determine the fetal platelet count

in pregnancies complicated by neonatal alloimmune thrombocytopenia?
Unfortunately, as with ITP, there are no good indirect

methods to determine the fetal platelet count. Maternal
antiplatelet antibody titers correlate poorly with the

severity of the disease. Also, characteristics such as the
outcome of previously affected siblings (eg, birth platelet
count or intracranial hemorrhage recognized after delivery) do not reliably predict the severity of fetal thrombocytopenia (13). Currently, the only accurate means of
estimating the fetal platelet count is to sample the fetal
blood directly, although this may increase the risk of fetal
exsanguination.
The most appropriate screening program incorporates

evaluation of patients with a history of infants with otherwise unexplained bleeding or thrombocytopenia.
Neonatal alloimmune thrombocytopenia should be
suspected in cases of otherwise unexplained fetal or
neonatal thrombocytopenia, porencephaly, or intracranial
hemorrhage (either in utero or after birth). The laboratory diagnosis includes determination of platelet type and
zygosity of both parents and the confirmation of maternal
antiplatelet antibodies with specificity for paternal (or
fetalneonatal) platelets and the incompatible antigen.
Platelet typing may be determined serologically or by
genotyping because the genes and polymorphisms
responsible for most cases of neonatal alloimmune
thrombocytopenia have been identified. This is helpful
when the father is heterozygous for the pertinent antigen
because fetal platelet antigen typing can be performed
using amniocytes (53). Chorionic villus sampling should
not be performed because of its potential increased sensitization to antiplatelet antibodies. The laboratory evaluation of neonatal alloimmune thrombocytopenia can be
complex, results may be ambiguous, and an antigen
incompatibility cannot always be identified. Accordingly,
testing for this disorder should be performed in an experienced regional laboratory that has special interest and
expertise in neonatal alloimmune thrombocytopenia.
There is a theoretical benefit from population-based
screening for platelet antigen incompatibility. However,
such a program has not been shown to be clinically useful or cost-effective and is not currently recommended.
Another area of controversy is the patient whose sister
has had a pregnancy complicated by neonatal alloimmune thrombocytopenia. It may be worthwhile to evaluate these patients for platelet antigen incompatibility or
human leukocyte antigen phenotype. However, the theoretical advantages of testing these women must be
weighed against the potential for anxiety, cost, and morbidity without proven benefit.
661
What is the appropriate obstetric management

of neonatal alloimmune thrombocytopenia?
The primary goal of the obstetric management of pregnancies complicated by neonatal alloimmune thrombocytopenia is to prevent intracranial hemorrhage and its
associated complications. In contrast to ITP, however, the
higher frequency of intracranial hemorrhage associated
with neonatal alloimmune thrombocytopenia justifies
more aggressive interventions. Also, strategies intended
to avoid intracranial hemorrhage must be initiated antenatally because of the risk of in utero intracranial hemorrhage.
The optimal management of fetuses at risk for
neonatal alloimmune thrombocytopenia (those testing
positive for the incompatible antigen or those whose
fathers are homozygous for the antigen) remains controversial. The management decisions for these cases should
be individualized and are best made after consultation
with obstetric and pediatric specialists familiar with the
disorder as soon as the diagnosis is made. Several therapies have been used in an attempt to increase the fetal
platelet count and to avoid intracranial hemorrhage,
including maternal treatment with IVIG, with or without
steroids (15, 5460), and fetal platelet transfusions (59,
61, 62). Intravenous immune globulin administered to the
mother appears to be the most consistently effective
antepartum therapy for neonatal alloimmune thrombocytopenia (15). However, none of these therapies is effective in all cases. Direct fetal administration of IVIG does
not reliably improve the fetal platelet count, although
only a few cases have been reported. Platelet transfusions
with maternal platelets are consistently effective in raising the fetal platelet count. However, the short half-life of
transfused platelets requires weekly procedures and may
worsen the alloimmunization.
It is unknown whether it is necessary to determine
the fetal platelet count before initiating therapy. The risks
of cordocentesis in the setting of neonatal alloimmune
thrombocytopenia must be weighed against the ability to
determine the need for and the effectiveness of therapy.
Although unproven, the benefit of transfusing maternal
platelets at the time of cordocentesis may reduce the risk
662
of bleeding complications from the procedure (63). The

optimal time during gestation to first assess the fetal
platelet count also is controversial. When fetal blood
sampling is indicated, performance at 2224 weeks of
gestation may optimize medical therapy.
Most investigators recommend determination of the
fetal platelet count once fetal pulmonary maturity is
achieved, but before the onset of labor (eg, 37 weeks of
gestation). A trial of labor is permitted for fetuses with
platelet counts greater than 50,000/L, while those with
severe thrombocytopenia are delivered by cesarean birth.
Although this strategy is of unproven efficacy, the high
rate of intracranial hemorrhage in neonatal alloimmune
thrombocytopenia is considered to warrant these interventions. Delivery should be accomplished in a setting
equipped to handle a neonate with severe thrombocytopenia.
What is appropriate obstetric management for

gestational thrombocytopenia?

treated with IVIG as the initial approach when fetal
thrombocytopenia is documented.
The following recommendations are based on limited or inconsistent scientific evidence (Level B):
The mode of delivery in pregnancies complicated by
ITP should be chosen based on obstetric considerations alone. Prophylactic cesarean delivery does not
appear to reduce the risk of fetal or neonatal hemorrhage.
Epidural anesthesia is safe in patients with platelet

counts greater than 100,000/L.
Mild maternal thrombocytopenia ( 70,000/L) in

asymptomatic pregnant women with no history of
bleeding problems is usually benign gestational
thrombocytopenia. These women should receive
routine prenatal care with periodic repeat platelet
counts (monthly to bimonthly).
Platelet counts of at least 50,000/L rarely require

treatment.
The primary treatment of maternal thrombocytopenia in

the setting of PIH or HELLP syndrome is delivery.
Although antepartum reversal of thrombocytopenia has
been reported with medical therapy (64), this course of
treatment is not usual (65, 66). More importantly, the
underlying pathophysiology of PIH will only resolve following birth. Thus, other than to allow for medical stabilization, the effect of betamethasone on fetal pulmonary
maturity, or in special cases at preterm gestations, severe
thrombocytopenia due to PIH is an indication for delivery (66).
Major hemorrhage is infrequent in patients with PIH
but minor bleeding such as operative site oozing during
cesarean delivery is common. Platelet transfusions occasionally are needed to improve hemostasis in patients
with severe thrombocytopenia or DIC. However, transfusions are less effective in these women because of accelerated platelet destruction. Therefore, platelet transfusions
are best reserved for patients with severe thrombocytopenia and active bleeding. An exception is the patient
undergoing cesarean delivery. Although of uncertain benefit, many authorities recommend platelet transfusions to
The following recommendation is based on good

Is it necessary to treat thrombocytopenia associated with PIH?
Summary
Pregnancies with gestational thrombocytopenia are not at

risk for maternal bleeding complications or fetal thrombocytopenia (4, 9). Thus, such interventions as the determination of the fetal platelet count or cesarean delivery
are not indicated in patients with this condition. Women
with gestational thrombocytopenia do not require any
additional testing or specialized care, except follow-up
platelet counts.
increase the platelet count to more than 50,000/L before

cesarean delivery (66).
Platelet counts often decrease for 2448 hours after
birth, followed by a rapid recovery (6769). Most
patients will achieve normal platelet counts within a few
days to a week postpartum (67, 69). However, although
rare, thrombocytopenia may continue for a prolonged
period, which often is associated with persistent multisystem dysfunction (68). Plasma exchange has been
reported to improve the platelet count in women with
HELLP syndrome (70), but the efficacy remains
unproven. Although thrombocytopenia associated with
PIH or HELLP syndrome may improve after treatment
with steroids or uterine curettage (71, 72), the clinical
benefit of these therapies also is uncertain.

suspected in cases of otherwise unexplained fetal or
neonatal thrombocytopenia, hemorrhage, or porencephaly.
PRACTICE BULLETINS
Prior to initiating any plan of treatment for a woman

based on thrombocytopenia in her fetus, consultation
should be sought from a physician with experience
dealing with that problem.
Laboratory testing for neonatal alloimmune thrombocytopenia should be performed in a regional laboratory with special interest and expertise in dealing
with the problem.
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35. Ayromlooi J. A new approach to the management of
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47. Scioscia AL, Grannum PA, Copel JA, Hobbins JC. The use
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48. Beilin Y, Zahn J, Comerford M. Safe epidural analgesia in
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49. Rolbin SH, Abbott D, Musclow E, Papsin F, Lie LM,
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50. Rasmus KT, Rottman RL, Kotelko DM, Wright WC, Stone
JJ, Rosenblatt RM. Unrecognized thrombocytopenia and
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51. Lao TT, Halpern SH, MacDonald D, Huh C. Spinal subdural haematoma in a parturient after attempted epidural
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1984;9:672675 (Level III)
53. McFarland JG, Aster RH, Bussel JB, Gianopoulos JG,
Derbes RS, Newman PJ. Prenatal diagnosis of neonatal
alloimmune thrombocytopenia using allele-specific oligonucleotide probes. Blood 1991;78:22762282 (Level III)
54. Bussel JB, Berkowitz RL, McFarland JG, Lynch L,
Chitkara U. Antenatal treatment of neonatal alloimmune
thrombocytopenia. N Engl J Med 1988:319:13741378
(Level II-2)
55. Lynch L, Bussel JB, McFarland JG, Chitkara U, Berkowitz
RL. Antenatal treatment of alloimmune thrombocytopenia.
56. Marzusch K, Schnaidt M, Dietl J, Weist E, Hofstaetter C,
Golz R. High-dose immunoglobulin in the antenatal treatment of neonatal alloimmune thrombocytopenia: case
report and review. Br J Obstet Gynaecol 1992;99:260262
(Level III)
57. Mir N, Samson D, House MJ, Kovar IZ. Failure of antenatal high-dose immunoglobulin to improve fetal platelet
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58. Bowman J, Harman C, Mentigolou S, Pollack J.
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59. Nicolini U, Tannirandorn Y, Gonzalez P, Fisk NM,
Beacham J, Letsky EA, et al. Continuing controversy in
alloimmune thrombocytopenia: fetal hyperimmunoglobu-
PRACTICE BULLETINS
linemia fails to prevent thrombocytopenia. Am J Obstet

60. Zimmermann R, Huch A. In-utero fetal therapy with
immunoglobulin for alloimmune thrombocytopenia.
Lancet 1992;340:606 (Level III)
61. Kaplan C, Daffos F, Forestier F, Cox WL, Lyon-Caen D,
Dupuy-Montbrun MC, et al. Management of alloimmune
thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets. Blood 1988;72:340343
(Level III)
62. Murphy MF, Pullon HW, Metcalfe P, Chapman JF, Jenkins
E, Waters AH, et al. Management of fetal alloimmune
thrombocytopenia by weekly in utero platelet transfusions.
Vox Sang 1990;58:4549 (Level III)
63. Paidas MJ, Berkowitz RL, Lynch L, Lockwood CJ,
Lapinski R, McFarland JG, et al. Alloimmune thrombocytopenia: fetal and neonatal losses related to cordocentesis.
Am J Obstet Gynecol 1995;172:475479 (Level II-2)
64. Clark SL, Phelan JR, Allen SH, Golde SR. Antepartum
reversal of hematologic abnormalities associated with the
HELLP syndrome. A report of three cases. J Reprod Med
1986;31:7072 (Level III)
65. Weinstein L. Syndrome of hemolysis, elevated liver
enzymes, and low platelet count: a severe consequence of
hypertension in pregnancy. Am J Obstet Gynecol
1982;142:159167 (Level III)
66. Sibai BM. The HELLP syndrome (hemolysis, elevated
liver enzymes, and low platelets): much ado about nothing? Am J Obstet Gynecol 1990;162:311316 (Level III)
67. Katz VL, Thorp JM Jr, Rozas L, Bowes WA Jr. The natural history of thrombocytopenia associated with preeclampsia. Am J Obstet Gynecol 1990;163:11421143
(Level II-3)
68. Martin JN Jr, Blake PG, Lowry SL, Perry KG Jr, Files JC,
Morrison JC. Pregnancy complicated by preeclampsiaeclampsia with the syndrome of hemolysis, elevated liver
enzymes, and low platelet count: how rapid is postpartum
recovery? Obstet Gynecol 1990;76:737741 (Level II-3)
69. Neiger R, Contag SA, Coustan DR. The resolution of
preeclampsia-related thrombocytopenia. Obstet Gynecol
1991;77:692695 (Level II-3)
70. Martin JN Jr, Files JC, Blake PG, Norman PH, Martin RW,
Hess LW, et al. Plasma exchange for preeclampsia. I.
Postpartum use for persistently severe preeclampsiaeclampsia with HELLP syndrome. Am J Obstet Gynecol
1990;162:126137 (Level III)
71. Magann EF, Martin JN Jr, Isaacs JD, Perry KG Jr, Martin
RW, Meydrech EF. Immediate postpartum curettage:
accelerated recovery from severe preeclampsia. Obstet
Gynecol 1993;81:502506 (Level I)
72. Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin
RW, Martin JN Jr. Antepartum corticosteroids: disease stabilization in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Am J
Obstet Gynecol 1994;171:11481153 (Level I)
665

ACOGs own internal resources were used to conduct a literature search to locate relevant articles published between
January 1985 and January 1999. The search was restricted
to articles published in the English language. Priority was
given to articles reporting results of original research,
although review articles and commentaries also were consulted. Abstracts of research presented at symposiums and
scientific conferences were not considered adequate for
inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of
Health and ACOG were reviewed, and additional studies
were located by reviewing bibliographies of identified articles. When reliable research was not available, expert opinions from obstetriciangynecologists were used.
Force:
I
Evidence obtained from at least one properly

designed randomized controlled trial.

without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this
type of evidence.
III
Opinions of respected authorities, based on clinical

committees.

Copyright September 1999 by the American College of
Obstetricians and Gynecologists. All rights reserved. No part of
this publication may be reproduced, stored in a retrieval system,
or transmitted, in any form or by any means, electronic,
Requests for authorization to make photocopies should be directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
666
ACOG
PRACTICE
BULLETIN
NUMBER 9, OCTOBER 1999
(Replaces Technical Bulletin Number 188, January 1994)

of Dwight J. Rouse, MD. The
practitioners in making decisions about appropriate obstetric and gynecologic care. These
guidelines should not be construed as dictating an exclusive
course of treatment or procedure. Variations in practice
may be warranted based on
the needs of the individual
patient, resources, and limitations unique to the institution
or type of practice.
Reaffirmed 2009
Antepartum Fetal
Surveillance
The goal of antepartum fetal surveillance is to prevent fetal death. Antepartum
fetal surveillance techniques based on assessment of fetal heart rate patterns
have been in clinical use for almost three decades. More recently, real-time
ultrasonography and Doppler velocimetry have been used to evaluate fetal
well-being. Antepartum fetal surveillance techniques are now routinely used to
assess the risk of fetal death in pregnancies complicated by preexisting maternal conditions (eg, type 1 diabetes mellitus) as well as those in which complications have developed (eg, intrauterine growth restriction). This document will
review the current indications for and techniques of antepartum fetal surveillance and outline management guidelines for antepartum fetal surveillance,
consistent with the best contemporary scientific evidence.
Background
Physiology of Fetal Heart Response and Fetal
Behavioral State Alteration
In both animals and humans, fetal heart rate pattern, level of activity, and degree
of muscular tone are sensitive to hypoxemia and acidemia (14). Redistribution
of fetal blood flow in response to hypoxemia may result in diminished renal perfusion and oligohydramnios (5). Surveillance techniques such as cardiotocography, real-time ultrasonography, and maternal perception of fetal movement can
identify the fetus that is either suboptimally oxygenated or, with increasing
degrees of placental dysfunction, acidemic. Identification of suspected fetal
compromise provides the opportunity to intervene before progressive metabolic
acidosis can lead to fetal death. However, acute, catastrophic changes in fetal status, such as those that can occur with abruptio placentae or an umbilical cord
accident, are generally not predicted by tests of fetal well-being. Therefore, fetal
deaths from such events are not as amenable to prevention.
PRACTICE BULLETINS
In humans, the range of normal umbilical blood gas

parameters has been established by cordocentesis performed in pregnancies in which the fetus ultimately
proved to be healthy, and ranges vary by gestational age
(6). Although the degree of hypoxemia and acidemia at
which various indices of fetal well-being become abnormal is not known with precision, it can be estimated,
based on data from published studies. In one investigation, the fetal biophysical profile (BPP) was performed
immediately before cordocentesis. Fetuses with a nonreactive nonstress test (NST) were found to have a mean
( standard deviation) umbilical vein pH of 7.28 0.11.
Cessation of fetal movement appears to occur at lower
pH levels; fetuses with abnormal movement were found
to have an umbilical vein pH of 7.16 0.08 (7). Thus, a
reasonable correlation between certain measurable
aspects of fetal heart rate and behavior and evidence of
fetal metabolic compromise can be inferred.
However, when abnormal antepartum fetal surveillance results are compared with evidence of hypoxia or
acidemia, the degree of acidbase disturbance may
range from mild to severe. Furthermore, factors other
than acidbase and oxygenation status (eg, prematurity,
fetal sleepwake cycle, maternal medication exposure,
and fetal central nervous system abnormalities) can
adversely affect biophysical parameters. Finally, neither
the degree nor the duration of intrauterine hypoxemia
and acidemia necessary to adversely affect short- and
long-term neonatal outcome has been established with
any precision.
Antepartum Fetal Surveillance

Techniques
Several antepartum fetal surveillance techniques (tests)
are in use. These include fetal movement assessment,
NST, contraction stress test (CST), BPP, modified BPP,
and umbilical artery Doppler velocimetry.
Fetal Movement Assessment

A diminution in the maternal perception of fetal movement often but not invariably precedes fetal death, in
some cases by several days (8). This observation provides the rationale for fetal movement assessment by the
mother (kick counts) as a means of antepartum fetal
surveillance.
Although several counting protocols have been
employed, neither the optimal number of movements nor
the ideal duration for counting movements has been
defined. Thus, numerous protocols have been reported
and appear to be acceptable. In one approach, the
woman lies on her side and counts distinct fetal movements (9). Perception of 10 distinct movements in a peri-
667
od of up to 2 hours is considered reassuring. Once 10

movements have been perceived, the count may be discontinued. In another approach, women are instructed to
count fetal movements for 1 hour three times per week
(10). The count is considered reassuring if it equals or
exceeds the womans previously established baseline
count. In the absence of a reassuring count, further fetal
assessment is recommended.
Contraction Stress Test

The CST is based on the response of the fetal heart rate
to uterine contractions. It relies on the premise that fetal
oxygenation will be transiently worsened by uterine
contractions. In the suboptimally oxygenated fetus, the
resultant intermittent worsening in oxygenation will, in
turn, lead to the fetal heart rate pattern of late decelerations. Uterine contractions also may provoke or accentuate a pattern of variable decelerations caused by fetal
umbilical cord compression, which in some cases is
associated with oligohydramnios.
With the patient in the lateral recumbent position,
the fetal heart rate and uterine contractions are simultaneously recorded with an external fetal monitor. If at
least three spontaneous contractions of 40 seconds duration each or longer are present in a 10-minute period, no
uterine stimulation is necessary. If fewer than three
contractions of at least 40 seconds duration occur in 10
minutes, contractions are induced with either nipple stimulation or intravenous administration of dilute oxytocin.
Nipple stimulation usually is successful in inducing
an adequate contraction pattern and allows completion
of testing in approximately half the time required when
intravenous oxytocin is given (11). In one nipple stimulation technique, the woman is instructed to rub one
nipple through her clothing for 2 minutes or until a contraction begins (11). If by that time the contraction frequency has not become adequate (as defined previously), stimulation is stopped and restarted again after 5
minutes. If nipple stimulation is unsuccessful, or if the
use of oxytocin is preferred, an intravenous infusion of
dilute oxytocin may be initiated at a rate of 0.5 mU/min
and doubled every 20 minutes until an adequate contraction pattern is achieved (12).
The CST is interpreted according to the presence or
absence of late fetal heart rate decelerations (13), which
are defined as decelerations that reach their nadir after
the peak of the contraction and that usually persist
beyond the end of the contraction. The results of the
CST are categorized as follows:
Negative: no late or significant variable decelerations
668
Positive: late decelerations following 50% or more

of contractions (even if the contraction frequency is
fewer than three in 10 minutes)
Equivocalsuspicious: intermittent late decelerations
or significant variable decelerations
Equivocalhyperstimulatory: fetal heart rate decelerations that occur in the presence of contractions more
frequent than every 2 minutes or lasting longer than
90 seconds
Unsatisfactory: fewer than three contractions in 10
minutes or an uninterpretable tracing
Relative contraindications to the CST generally
include conditions associated with an increased risk of
preterm labor and delivery, uterine rupture, or uterine
bleeding. These include the following (12):
Preterm labor or certain patients at high risk of preterm labor
Preterm membrane rupture
History of extensive uterine surgery or classical
cesarean delivery
Known placenta previa
Nonstress Test
The NST is based on the premise that the heart rate of the
fetus that is not acidotic or neurologically depressed will
temporarily accelerate with fetal movement. Heart rate
reactivity is thought to be a good indicator of normal fetal
autonomic function. Loss of reactivity is associated most
commonly with a fetal sleep cycle but may result from
any cause of central nervous system depression, including
fetal acidosis.
With the patient in the lateral tilt position, the fetal
heart rate is monitored with an external transducer.
Ideally, the patient should not have smoked recently,
because this may adversely affect test results (14). The
tracing is observed for fetal heart rate accelerations that
peak (but do not necessarily remain) at least 15 beats per
minute above the baseline and last 15 seconds from baseline to baseline. It may be necessary to continue the tracing
for 40 minutes or longer to take into account the variations
of the fetal sleepwake cycle. Acoustic stimulation of the
nonacidotic fetus may elicit fetal heart rate accelerations
that appear to be valid in the prediction of fetal wellbeing. Such stimulation offers the advantage of safely
reducing overall testing time without compromising
detection of the acidotic fetus (1517). To perform
acoustic stimulation, an artificial larynx (ideally one of
the commercially available models especially designed
for this purpose) is positioned on the maternal abdomen
and a stimulus of 12 seconds is applied. This may be
repeated up to three times for progressively longer durations of up to 3 seconds to elicit fetal heart rate accelerations.
Nonstress test results are categorized as reactive or
nonreactive. Various definitions of reactivity have been
used. Using the most common definition, the NST is considered reactive (normal) if there are two or more fetal
heart rate accelerations (as defined previously) within a
20-minute period, with or without fetal movement discernible by the woman (18). A nonreactive NST is one
that lacks sufficient fetal heart rate accelerations over a
40-minute period. The NST of the noncompromised
preterm fetus is frequently nonreactive: from 24 to 28
weeks of gestation, up to 50% of NSTs may not be reactive (19), and from 28 to 32 weeks of gestation, 15% of
NSTs are not reactive (20, 21).
Variable decelerations may be observed in up to 50%
of NSTs (22). If nonrepetitive and brief (<30 seconds),
they indicate neither fetal compromise nor the need for
obstetric intervention (22). Repetitive variable decelerations (at least 3 in 20 minutes), even if mild, have been
associated with an increased risk of cesarean delivery for
a nonreassuring intrapartum fetal heart rate pattern (23,
24). Fetal heart rate decelerations during an NST that persist for 1 minute or longer are associated with a markedly
increased risk of both cesarean delivery for a nonreassuring fetal heart rate pattern and fetal demise (2527).
Biophysical Profile
The BPP consists of an NST combined with four observations made by real-time ultrasonography (28). Thus, the
BPP comprises five components:
1. Nonstress test (which, if all four ultrasound components are normal, may be omitted without compromising the validity of the test results) (28)
2. Fetal breathing movements (one or more episodes of
rhythmic fetal breathing movements of 30 seconds or
more within 30 minutes)
3. Fetal movement (three or more discrete body or limb
movements within 30 minutes)
4. Fetal tone (one or more episodes of extension of a
fetal extremity with return to flexion, or opening or
closing of a hand)
5. Determination of the amniotic fluid volume (a single
vertical pocket of amniotic fluid exceeding 2 cm is
considered evidence of adequate amniotic fluid) (29,
30)
Each of the five components is assigned a score of
either 2 (normal or present as defined previously) or 0
(abnormal, absent, or insufficient). A composite score of 8
PRACTICE BULLETINS
or 10 is normal, a score of 6 is considered equivocal, and

a score of 4 or less is abnormal. Regardless of the composite score, in the presence of oligohydramnios (largest
vertical pocket of amniotic fluid volume 2 cm), further
evaluation is warranted (30).
Modified Biophysical Profile
Umbilical Artery Doppler Velocimetry

Doppler ultrasonography is a noninvasive technique
used to assess the hemodynamic components of vascular
impedance. Umbilical artery Doppler flow velocimetry
has been adapted for use as a technique of fetal surveillance, based on the observation that flow velocity
waveforms in the umbilical artery of normally growing
fetuses differ from those of growth-restricted fetuses.
Specifically, the umbilical flow velocity waveform of
normally growing fetuses is characterized by highvelocity diastolic flow, whereas with intrauterine growth
restriction, there is diminution of umbilical artery diastolic flow (3234). In some cases of extreme intrauterine
growth restriction, flow is absent or even reversed. The
perinatal mortality rate in such pregnancies is quite high
(35). Abnormal flow velocity waveforms have been correlated histopathologically with small-artery obliteration
in placental tertiary villi (36) and functionally with fetal
hypoxia and acidosis (37), as well as with perinatal morbidity and mortality (35). Commonly measured flow
indices, based on the characteristics of peak systolic frequency shift (S), end-diastolic frequency shift (D), and
mean peak frequency shift over the cardiac cycle (A), include the following:
Systolic to diastolic ratio (S/D)
Resistance index (S-D/S)

Pulsatility index (S-D/A)
Randomized studies (3844) of the utility of umbilical artery Doppler velocimetry generally have defined
abnormal flow as either absent end diastolic flow, or a
flow index greater than two standard deviations above the
mean for gestational age. To maximize interpretability,
multiple waveforms should be assessed, and wall-filter
settings should be set low enough (typically <150 Hz) to
avoid masking diastolic flow.

Recommendations
In the late second- or third-trimester fetus, amniotic fluid

reflects fetal urine production. Placental dysfunction may
result in diminished fetal renal perfusion, leading to oligohydramnios (5). Amniotic fluid volume assessment can
therefore be used to evaluate long-term uteroplacental
function. This observation fostered the development of
what has come to be termed the modified BPP as a primary mode of antepartum fetal surveillance. The modified
BPP combines the NST (with the option of acoustic stimulation), as a short-term indicator of fetal acidbase status, with the amniotic fluid index (AFI), which is the sum
of measurements of the deepest cord-free amniotic fluid
pocket in each of the abdominal quadrants, as an indicator of long-term placental function (15). An AFI greater
than 5 cm generally is considered to represent an adequate
volume of amniotic fluid (31). Thus, the modified BPP is
considered normal if the NST is reactive and the AFI is
more than 5, and abnormal if either the NST is nonreactive or the AFI is 5 or less.
669
Is there compelling evidence that any form of

antepartum fetal surveillance decreases the
risk of fetal demise or otherwise improves perinatal outcome?
There is a dearth of evidence from randomized controlled

trials that antepartum fetal surveillance decreases the
risk of fetal death (45). Moreover, in one comprehensive
review, antepartum fetal surveillance was categorized as
a form of care likely to be ineffective or harmful (46).
In spite of its unproven value, antepartum fetal surveillance is widely integrated into clinical practice in the
developed world. Therefore, a definitive evaluation of
antepartum fetal surveillance (which would require the
random allocation of gravidas to prenatal care that
included some form of antepartum fetal surveillance
versus prenatal care that did not include any form of
antepartum fetal surveillance) is unlikely to be conducted in a setting that can be generalized to current U.S.
obstetric practice. In the absence of a definitive, relevant randomized clinical trial, evidence for the value of
antepartum fetal surveillance will remain circumstantial
and rest principally on the observation that antepartum
fetal surveillance has been consistently associated with
rates of fetal death that are substantially lower than the
rates of fetal death in both untested (and presumably
lower-risk) contemporaneous pregnancies from the same
institutions (15, 16, 47) and pregnancies with similar
complicating factors that were managed before the advent
of currently employed techniques of antepartum fetal
surveillance (historic controls). However, these perceived benefits of antepartum fetal surveillance may be
influenced by the low incidence of adverse fetal outcome in the general population. The lower the incidence
of adverse outcomes, the more likely favorable outcomes will be achieved regardless of test performance.
670
What are the indications for antepartum fetal

surveillance?
When during gestation should antepartum

fetal surveillance be initiated?
Choosing the appropriate point in gestation to begin

antepartum testing depends on balancing several considerations, including the prognosis for neonatal survival,
the severity of maternal disease, the risk of fetal death,
and the potential for iatrogenic prematurity complications resulting from false-positive test results. The importance of the last consideration is illustrated by the
experience of one large center, in which 60% of infants
delivered because of an abnormal antepartum test result
had no evidence of short-term or long-term fetal compromise (16). Both theoretic models (48) and large clinical
studies (49, 50) confirm that initiating testing at 3234
weeks of gestation is appropriate for most at-risk
patients. However, in pregnancies with multiple or particularly worrisome high-risk conditions (eg, chronic
hypertension with suspected intrauterine growth restric-
What is the proper frequency of testing?
How frequently to perform fetal testing depends on several factors, including clinical judgment. If the indication
for testing is not persistent (eg, a single episode of
decreased fetal movement followed by reassuring testing
in an otherwise uncomplicated pregnancy), it need not be
repeated. When the clinical condition that prompted testing persists, the test should be repeated periodically until
delivery to monitor for continued fetal well-being. If the
maternal medical condition is stable and CST results are
negative, the CST is typically repeated in 1 week (12).
Other tests of fetal well-being (NST, BPP, or modified
BPP) are typically repeated at weekly intervals (16), but
in the presence of certain high-risk conditions, such as
postterm pregnancy, type 1 diabetes, intrauterine growth
restriction, or pregnancy-induced hypertension, some
investigators have performed twice-weekly NST, BPP, or
modified BPP testing. Any significant deterioration in
the maternal medical status requires fetal reevaluation,
as does any acute diminution in fetal activity, regardless
of the amount of time that has elapsed since the last test.
Maternal conditions
Hyperthyroidism (poorly controlled)
Hemoglobinopathies (hemoglobin SS, SC,
or S-thalassemia)
Cyanotic heart disease
Chronic renal disease
Type 1 diabetes mellitus
Hypertensive disorders
Pregnancy-related conditions
Decreased fetal movement
Oligohydramnios
Polyhydramnios
Intrauterine growth restriction
Postterm pregnancy
Isoimmunization (moderate to severe)
Previous fetal demise (unexplained or recurrent
risk)
Multiple gestation (with significant growth discrepancy)
Because antepartum fetal surveillance results have not

been definitively demonstrated to improve perinatal outcome, all indications for antepartum testing must be considered somewhat relative. In general, antepartum fetal
surveillance has been employed in pregnancies in which
the risk of antepartum fetal demise is increased. Accordingly, some of the conditions under which testing may be
appropriate include the following:
tion), testing might begin as early as 2628 weeks of

gestation.
How reassuring is a normal test result?
In most cases, a normal test result is highly reassuring, as

reflected in the false-negative rate of antepartum fetal surveillance, defined as the incidence of stillbirth occurring
within 1 week of a normal test result. The stillbirth rate,
corrected for lethal congenital anomalies and unpredictable causes of demise, was 1.9 per 1,000 in the largest
series of NSTs (5,861) versus 0.3 per 1,000 in 12,656
CSTs (13), 0.8 per 1,000 in 44,828 BPPs (51), and 0.8
per 1,000 in 54,617 modified BPPs (16). Based on these
data, the negative predictive value of the NST is 99.8%,
and greater than 99.9% for the CST, BPP, and modified
BPP. Although similar data from a large series are not
available for umbilical artery Doppler velocimetry, in one
randomized clinical trial among women with pregnancies
complicated by intrauterine growth restriction (38), no
stillbirths occurred in 214 pregnancies in which umbilical
artery Doppler velocimetry was the primary means of
antepartum fetal surveillance (negative predictive value
of 100%). The low false-negative rate of these tests
depends on an appropriate response to any significant
deterioration in the maternal clinical status, including
retesting of the fetal condition. As mentioned previously,
these tests generally do not predict stillbirths related to
acute changes in maternalfetal status, such as those that
occur with abruptio placentae or an umbilical cord accident. Moreover, recent, normal antepartum fetal test
PRACTICE BULLETINS
results should not preclude the use of intrapartum fetal

monitoring.
How should one respond to an abnormal test

result?
Therefore, the response to an abnormal test result

should be tailored to the clinical situation. Maternal
reports of decreased fetal movement should be evaluated
by an NST, CST, BPP, or modified BPP; these results, if
normal, usually are sufficient to exclude imminent fetal
jeopardy. A nonreactive NST or an abnormal modified
BPP generally should be followed by additional testing
(either a CST or a full BPP). A positive CST result suggests that NST nonreactivity is a consequence of hypoxia-induced acidosis, whereas a negative result implies that
the NST nonreactivity exists for another reason, such as a
premature fetus, maternal exposure to certain drugs or
medications, a fetal sleep cycle, or preexisting neurologic
damage. In many circumstances, a positive CST result
generally indicates that delivery is warranted. However,
the combination of a nonreactive NST and a positive CST
result is associated frequently with serious fetal malformation and justifies ultrasonographic investigation for
anomalies whenever possible (53). Indeed, evaluation for
grossly abnormal fetal anatomy should precede any intervention for suspected fetal compromise whenever possible.
A BPP score of 6 is considered equivocal; in the term
fetus, this score generally should prompt delivery, whereas in the preterm fetus, it should result in a repeat BPP in
24 hours (30). In the interim, maternal corticosteroid
administration should be considered for pregnancies of
less than 34 weeks of gestation. Repeat equivocal scores
should result either in delivery or continued intensive surveillance. A BPP score of 4 usually indicates that delivery
is warranted, although in extremely premature pregnancies, management should be individualized. Biophysical
profiles less than 4 should result in expeditious delivery.
Regardless of the overall score, oligohydramnios always
requires further evaluation.
In the absence of obstetric contraindications, delivery
of the fetus with an abnormal test result often may be
attempted by induction of labor, with continuous monitoring of both the fetal heart rate and contractions.
An abnormal fetal test result should always be considered

in the context of the overall clinical picture, taking into
account the substantial possibility that the test result is
falsely positive. Certain acute maternal conditions (eg,
diabetic ketoacidosis, pneumonia with hypoxemia) can
result in abnormal test results, which generally will
become normal as the maternal condition improves. In
these circumstances, stabilizing the maternal condition
and retesting the fetus may be appropriate.
In cases where an abnormal test result is not associated with any clinical evidence of worsening in the maternal status, a sequenced approach to the investigation of
the fetal condition should be undertaken. Such an
approach takes advantage of the high negative predictive
value generally exhibited by all commonly used antepartum tests (see above), and minimizes the potential for
unnecessary delivery based on a false-positive (ie, abnormal) test result. False-positive rates, in contrast to falsenegative rates, have typically not been calculated using
the outcome of stillbirth. This is because most antepartum
tests were introduced into clinical practice before an unbiased evaluation of their sensitivity and specificity. In clinical practice, abnormal test results usually are followed by
another test or delivery is effected, which obscures the
relationship between a positive test result and the subsequent risk of stillbirth. Therefore, in the absence of
unbiased evaluations, the positive predictive value of
antepartum tests has been estimated using surrogate
markers, such as the rate of positive follow-up test results
when the primary test result is positive. For example, it
has been observed that up to 90% of nonreactive NSTs are
followed by a negative CST result (18). Based on this
observation, the positive predictive value of an NST is
only 10%. Another way that the false-positive rate of fetal
testing has been estimated is to calculate the incidence of
abnormal test results that prompt delivery but are not
associated with evidence of fetal compromise, as manifested by a nonreassuring intrapartum fetal heart rate,
meconium-stained amniotic fluid, 5-minute Apgar scores
of less than 7, or birth weight greater than the 10th percentile for gestational age. By this latter definition, in one
large series, a testing scheme in which abnormal modified
BPPs were followed by full BPPs had a false-positive rate
of 60% (positive predictive value = 40%) (18). In another
study in which the physicians were blinded to test results,
a CST was found to have a positive predictive value of
less than 35% (52).
671
Are there clinical circumstances in which one

test is distinguished by its utility or lack thereof?
A large-scale, definitive randomized trial comparing the

relative efficacy of one technique of antepartum fetal testing to another has not yet been performed. Accordingly, in
most clinical situations, no single antepartum fetal test
can be considered superior to any other.
As mentioned previously, in certain clinical situations, the CST is considered relatively contraindicated
(increased risk of preterm labor and delivery, uterine rupture, and uterine bleeding), although even in these situa-
672
tions the value of the information provided by the test

may outweigh its potential risks.
When should oligohydramnios prompt delivery?
Amniotic fluid volume is estimated using ultrasonography. One widely used definition of oligohydramnios is no
measurable vertical pocket of amniotic fluid greater than
2 cm (29), and another is an AFI of 5 cm or less (31).
Nevertheless, from a clinical standpoint, an ideal cutoff
level for intervention using the AFI has yet to be established. Determining when to intervene for oligohydramnios depends on several factors, including gestational
age, the maternal and fetal clinical condition as determined by other indices of fetal well-being, and the
actual measured AFI value. Because rupture of the fetal
membranes can cause diminished amniotic fluid volume,
an evaluation for membrane rupture may be appropriate.
In postterm pregnancy, oligohydramnios is common
and is associated with an increased risk of meconium
staining of the amniotic fluid and cesarean delivery for
nonreassuring fetal heart rate (54, 55). Thus, oligohydramnios has been considered an indication for delivery
of the postterm pregnancy (15), although the effectiveness of this approach in improving perinatal outcome has
not been established by randomized investigation.
In a term pregnancy complicated by oligohydramnios, delivery often is the most appropriate course of
action. However, management should be individualized,
and in certain situations, delivery may be safely postponed (eg, an uncomplicated pregnancy with an AFI of
5 cm but otherwise reassuring fetal testing and an unfavorable cervix at 37 weeks of gestation).
In the preterm fetus, depending on the maternal and
fetal condition, expectant management may be the most
appropriate course of action (eg, with preterm premature
rupture of membranes or in the presence of fetal anomalies). Once oligohydramnios is diagnosed, if delivery is
not undertaken, follow-up amniotic fluid volume and
fetal growth assessments are indicated. If the oligohydramnios is persistent, close monitoring of the maternal
condition and ongoing antepartum fetal surveillance
should be performed to guide further management. If the
oligohydramnios results from fetal membrane rupture,
follow-up amniotic fluid volume assessment often may
be safely omitted.
What is the role of Doppler velocimetry?
At least three randomized trials (38, 56, 57) have evaluated the utility of umbilical artery Doppler velocimetry as a
technique of antepartum fetal surveillance in pregnancies
complicated by suspected intrauterine growth restriction.
In the first and largest of these trials (38), 214 pregnancies

were allocated to Doppler umbilical artery velocimetry as
the primary technique of fetal surveillance, and 212 were
allocated to cardiotocography (NST). Overall, women in
the Doppler group were significantly less likely to undergo obstetric intervention, including antepartum hospital
admission, labor induction, and emergency cesarean
delivery for nonreassuring fetal status. On average, women in the Doppler group underwent antenatal testing less
frequently (4 times) than women in the cardiotocography
group (8 times). Other perinatal outcomes, such as gestational age at birth, birthweight, Apgar scores, and cesarean birth rates, did not differ between the groups.
Subsequent trials (56, 57) have supported the findings of less frequent antenatal monitoring (56) and shorter durations of maternal hospitalization (56, 57) in the
Doppler group. However, rates of obstetric interventions,
such as antepartum admission and labor induction, were
not lower in the Doppler groups, and perinatal outcome
was not improved. On balance, the available evidence
suggests that primary antepartum surveillance of suspected intrauterine growth restriction with umbilical artery
Doppler velocimetry can achieve at least equivalent (and
possibly better) fetal and neonatal outcomes as primary
antepartum surveillance based on results of the NST.
Furthermore, frequency of antepartum testing and certain
aspects of obstetric intervention are reduced with use of
Doppler (58). If umbilical artery Doppler velocimetry is
used, decisions regarding timing of delivery should be
made using a combination of information from the
Doppler ultrasonography and other tests of fetal wellbeing, such as amniotic fluid volume assessment, NST,
CST, and BPP, along with careful monitoring of maternal
status.
No benefit has been demonstrated for umbilical
artery velocimetry for conditions other than suspected
intrauterine growth restriction, such as postterm gestation,
diabetes mellitus, systemic lupus erythematosus, or
antiphospholipid syndrome. Doppler ultrasonography has
not been shown to be of value as a screening test for
detecting fetal compromise in the general obstetric population, and its use for this purpose cannot be recommended (59). In addition to the umbilical artery, it is possible to
evaluate blood flow in major fetal vessels. Multiple investigators have observed a correlation between increased
flow resistance (elevated S/D ratio) in the umbilical artery
and decreased resistance to flow (reduced S/D ratio) in
the middle cerebral artery. This phenomenon has been
attributed to a brain sparing adaptive response to fetal
hypoxemia, and it has been suggested that the ratio of
middle cerebral artery S/D ratio to umbilical artery S/D
ratio might serve as a useful predictor of fetal compromise (60). However, the only randomized clinical trial of
PRACTICE BULLETINS
middle cerebral artery Doppler velocimetry failed to

demonstrate any clinical benefit to assessing this parameter (61). Moreover, women in this trial who were allocated to standard fetal evaluation plus assessment of the
ratio of middle cerebral artery or umbilical artery
Doppler flow, or both, were delivered on average 5.7
days earlier after the institution of fetal testing than
women who were allocated to standard fetal evaluation
without assessment of middle cerebral artery blood flow.
This suggests that incorporation of middle cerebral artery
Doppler flow assessment into clinical practice might
increase unnecessary intervention. Therefore, at present,
middle cerebral artery Doppler flow measurement should
be considered investigational.
Should all women perform daily fetal movement assessment?
(7% versus 5%) underwent fetal heart rate testing, and

more (5% versus 4%) were admitted antenatally to the
hospital. However, the rates of labor induction and elective cesarean delivery did not differ significantly between
the two groups. It should be noted that in the counting
group, only 46% of women with decreased fetal movement alerted their care providers. Compliance for both
recording fetal movements and reporting when they were
diminished was even lower for women who experienced
a stillbirth.
Consistent evidence that a formal program of fetal
movement assessment will result in a reduction in fetal
deaths is lacking. Moreover, whether fetal movement
assessment adds benefit to an established program of regular fetal surveillance has not been evaluated. One of the
two randomized studies of fetal movement assessment
suggests that its use may reduce stillbirths; the other does
not. Formal movement assessment may increase, by a
small degree, the number of antepartum visits and fetal
evaluations. In the randomized trials, however, this
increased surveillance did not result in a higher rate of
intervention (10, 62).
Summary
Women with high-risk factors for stillbirth should

undergo antepartum fetal surveillance using the NST,
CST, BPP, or modified BPP.
Initiating testing at 3234 weeks of gestation is

appropriate for most pregnancies at increased risk of
stillbirth, although in pregnancies with multiple or
particularly worrisome high-risk conditions, testing
may be initiated as early as 2628 weeks of gestation.
When the clinical condition that has prompted testing

persists, a reassuring test should be repeated periodically (either weekly or, depending on the test used
and the presence of certain high-risk conditions,
twice weekly) until delivery. Any significant deterioration in the maternal medical status or any acute
diminution in fetal activity requires fetal reevaluation,
regardless of the amount of time that has elapsed
since the last test.
Whether programs of fetal movement assessment actually can reduce the risk of stillbirth is not clear. Only two
randomized trials have addressed this issue. The first was
conducted in a mixed high-risk (39%) and low-risk
(61%) population of 3,111 Danish women who, after 32
weeks of gestation, were randomly assigned to an experimental (counting) group or a control group (10). Women
in the experimental group were asked to count fetal
movements for 1 hour three times a week and to contact
their hospital immediately if they detected fewer movements than their previously established baseline. The
control group of women were given no special fetal
movement assessment instructions but were asked about
fetal movement at their prenatal visits. Of the 1,583
women in the counting group, three experienced stillbirths of normally formed infants weighing more than
1,500 g, versus 12 stillbirths among the 1,569 women in
the control group (P<0.05). Of women allocated to the
counting group, 80% complied well with the protocol for
counting, and 4% were evaluated for decreased fetal
movement. The rates of operative vaginal birth and
cesarean delivery did not differ significantly between the
groups.
The second randomized study to evaluate fetal
movement allocated 68,000 women at 2832 weeks of
gestation to a counting policy (in which normal fetal
movement was defined as the perception of 10 movements within 10 hours) or to routine care in which no
special counting policies were employed (62). Women in
the counting group with fewer than 10 movements in 10
hours for two successive days were instructed to alert
their care provider, at whose discretion further evaluation
was undertaken. Overall fetal death rates were low in this
trial and did not differ significantly between the two
groups (2.9/1,000 in the counting group versus 2.7/1,000
in the control group). More women in the counting group
673
An abnormal NST or modified BPP usually should be

further evaluated by either a CST or a full BPP.
Subsequent management should then be predicated
on the results of the CST or BPP, the gestational age,
the degree of oligohydramnios (if assessed), and the
maternal condition.
674
Oligohydramnios, defined as either no ultrasonographically measurable vertical pocket of amniotic

fluid greater than 2 cm or an AFI of 5 cm or less,
requires (depending on the degree of oligohydramnios, the gestational age, and the maternal clinical
condition) either delivery or close maternal or fetal
surveillance.
In the absence of obstetric contraindications, delivery

of the fetus with an abnormal test result often may be
attempted by induction of labor with continuous
monitoring of the fetal heart rate and contractions. If
repetitive late decelerations are observed, cesarean
delivery generally is indicated.
Recent, normal antepartum fetal test results should

not preclude the use of intrapartum fetal monitoring.
Umbilical artery Doppler velocimetry has been found

to be of benefit only in pregnancies complicated by
intrauterine growth restriction. If used in this setting,
decisions regarding timing of delivery should be made
using a combination of information from the Doppler
ultrasonography and other tests of fetal well-being,
along with careful monitoring of maternal status.
Middle cerebral artery Doppler velocimetry should

be considered an investigational approach to antepartum fetal surveillance.
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1988;27:187196 (Level III)
34. Reuwer PJ, Bruinse HW, Stoutenbeek P, Haspels AA.
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35. Karsdorp VH, van Vugt JM, van Geijn HP, Kostense PJ,
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36. Giles WB, Trudinger BJ, Baird PJ. Fetal umbilical artery
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37. Nicolaides KH, Bilardo CM, Soothill PW, Campbell S.
Absence of end diastolic frequencies in umbilical artery: a
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38. Almstrom H, Axelsson O, Cnattingius S, Ekman G,
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42. Pattinson RC, Norman K, Odendaal HJ. The role of

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43. Trudinger BJ, Cook CM, Giles WB, Connelly A,
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in high-risk pregnancy. Randomised controlled trial.
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44. Tyrrell SN, Lilford RJ, Macdonald HN, Nelson EJ, Porter
J, Gupta JK. Randomized comparison of routine vs highly
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45. Thacker SB, Berkelman RL. Assessing the diagnostic
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1993;168:18201826 (Level III)
50. Pircon RA, Lagrew DC, Towers CV, Dorchester WL,
Gocke SE, Freeman RK. Antepartum testing in the hypertensive patient: when to begin. Am J Obstet Gynecol
1991;164:15631570 (Level III)
51. Manning FA, Morrison I, Harman CR, Lange IR,
Menticoglou S. Fetal assessment based on fetal biophysical profile scoring: experience in 19,221 referred high-risk
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53. Garite TJ, Linzey EM, Freeman RK, Dorchester W. Fetal
heart rate patterns and fetal distress in fetuses with congenital anomalies. Obstet Gynecol 1979;53:716720
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Santos-Ramos R, Toofanian A, et al. Prolonged pregnancy.
I. Observations concerning the causes of fetal distress. Am
55. Phelan JP, Platt LD, Yeh SY, Broussard P, Paul RH. The
role of ultrasound assessment of amniotic fluid volume in
the management of the postdate pregnancy. Am J Obstet
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56. Haley J, Tuffnell DJ, Johnson N. Randomised controlled
trial of cardiotocography versus umbilical artery Doppler
in the management of small for gestational age fetuses. Br
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57. Nienhuis SJ, Vles JS, Gerver WJ, Hoogland HJ. Doppler
ultrasonography in suspected intrauterine growth retardation: a randomized clinical trial. Ultrasound Obstet
58. Neilson JP, Alfirevic Z. Doppler ultrasound for fetal
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Randomised comparison of routine versus highly selective
use of Doppler ultrasound in low risk pregnancies. Br J
Obstet Gynaecol 1993;100:130133 (Level I)
60. Mari G, Deter RL. Middle cerebral artery flow velocity
waveforms in normal and small-for-gestational-age fetuses. Am J Obstet Gynecol 1992;166:12621270 (Level II2)
61. Ott WJ, Mora G, Arias F, Sunderji S, Sheldon G.
Comparison of the modified biophysical profile to a new
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artery to umbilical artery velocity flow systolic/diastolic
ratio. Am J Obstet Gynecol 1998;178:13461353 (Level I)
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to conduct a literature search to locate relevant articles published between January 1985 and February 1999. The
studies were located by reviewing bibliographies of identified articles. When reliable research was not available,
expert opinions from obstetriciangynecologists were used.
Force:
I
type of evidence.
III Opinions of respected authorities, based on clinical
committees.
and Gynecologists. All rights reserved. No part of this publication may
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or by any means, electronic, mechanical, photocopying, recording, or
otherwise, without prior written permission from the publisher.
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Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA
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ISSN 1099-3630
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PRACTICE BULLETINS
677
ACOG
PRACTICE
BULLETIN
NUMBER 12, JANUARY 2000

of Susan M. Cox, MD. The information is designed to aid
course of treatment or procedure. Variations in practice may
be warranted based on the
resources, and limitations
of practice.
Reaffirmed 2008
Intrauterine Growth
Restriction
Intrauterine growth restriction (IUGR) is one of the most common and complex
problems in modern obstetrics. Diagnosis and management are complicated by
the use of ambiguous terminology and a lack of uniform diagnostic criteria. In
addition, some authors do not make a clear distinction between suspected prenatal growth restriction and confirmed IUGR in the perinatal period.
Furthermore, size alone is not an indication of a complication. As a result of
this confusion, underintervention and overintervention can occur. This bulletin
will focus on the etiology, diagnosis, and management of intrauterine growth
restriction.
Background
Definitions
Several factors have contributed to the confusion in terminology associated
with IUGR:
By definition, 10% of infants in any population will have birth weights at
or below the 10th percentile. Intrauterine growth restriction could be manifest at a weight above the population determined at the 10th percentile (eg,
an undernourished infant born at the 15th percentile whose genetic makeup would have placed it at the 90th percentile). Distinctions between
normal and pathologic growth often cannot reliably be made in clinical
practice, especially prior to birth.
Although defining a pathologic condition using a 10th percentile cutoff
makes statistical sense, it may not be clinically relevant. One study suggests that adverse perinatal outcome generally is confined to those infants
with birth weights below the 5th percentile, and in most cases below the
3rd percentile (1).
678
Although specific ethnic- and geographic-based

growth curves are increasingly used to evaluate birth
weight, it remains unclear whether this is appropriate. These distinctions become even more difficult in
ethnically heterogeneous and geographically mobile
populations, such as those in the United States. Birth
weight also is related to maternal height, parity,
paternal height, and the fetus sex.
The use of the terms small for gestational age
(SGA) and intrauterine growth restriction has been confusing, and the terms often are used interchangeably. For
the purpose of this document, SGA will be used only in
reference to the infant and IUGR to the fetus.
Small for Gestational Age

Infants with a birth weight at the lower extreme of the
normal birth weight distribution are termed SGA. In the
United States, the most commonly used definition of
SGA is a birth weight below the 10th percentile for gestational age (2, 3).
Risk Factors for Intrauterine Growth Restriction

Maternal medical conditions
Hypertension
Renal disease
Restrictive lung disease
Diabetes (with microvascular disease)
Cyanotic heart disease
Collagen-vascular disease
Hemoglobinopathies
Smoking and substance use and abuse
Severe malnutrition
Primary placental disease
Multiple gestation
Infections (viral, protozoal)
Genetic disorders
Exposure to teratogens
Intrauterine Growth Restriction

Intrauterine growth restriction is a term used to describe a
fetus whose estimated weight appears to be less than
expected, usually less than the 10th percentile, which is
the convention this document will adopt. The term IUGR
includes normal fetuses at the lower end of the growth
spectrum, as well as those with specific clinical conditions in which the fetus fails to achieve its inherent growth
potential as a consequence of either pathologic extrinsic
influences (such as maternal smoking) or intrinsic genetic defects (such as aneuploidy).
Etiology
Several conditions have been found to be associated with
IUGR (see the box). These antecedents can be divided
into several broad categories: maternal, fetal, or placental.
Maternal behavioral conditions include substance use
(including smoking and alcohol use) (46), extremes of
reproductive age (younger than 16 years and older than 35
years), little maternal weight gain (7), malnutrition, and
low prepregnancy weight (7). In addition, low socioeconomic status is associated with IUGR (7).
Maternal Medical Conditions

Medical complications that affect the microcirculation
causing fetal hypoxemia or vasoconstriction or a reduction in fetal perfusion also are significantly associated
with IUGR (8). These include hypertension, both chronic
and acute (as in preeclampsia) (9), and severe chronic diseases, such as renal insufficiency (10), systemic lupus
erythematosus, antiphospholipid antibody syndrome,

chronic anemia, and pregestational diabetes (especially
Whites classifications C, D, F, and R). Growth restriction
may be preceded by defective maternal volume adaptation in early pregnancy (11, 12).
Placental association with IUGR is unique in that it
can be the primary cause (eg, mosaicism) or merely
involved in an adaptive process of a pregnancy complication. The placenta and impaired placental perfusion are
the most common cause of SGA in nonanomalous infants
(13), as seen in early-onset preeclampsia, which produces
the most severe IUGR (14). Intrauterine growth restriction also is related to other placental abnormalities,
including partial abruptions, previa, infarcts, and
hematomas (15). In unexplained IUGR, placental
mosaicism may be identified in up to 25% of patients
(16). Factors not associated with IUGR include caffeine
use in nonsmokers (6, 17) and passive smoking (18).
Substance Use and Abuse

Maternal alcohol abuse is associated with impaired fetal
growth; virtually all neonates with fetal alcohol syndrome
will exhibit significant growth restriction (6, 19). It is
unknown whether a threshold effect exists for alcohol, but
effects on the fetus are related to the amount consumed.
Women who smoke have a 3.5-fold increase of SGA
infants, compared with nonsmokers (9). Newborns of
smokers are smaller at every gestational age. Women who
PRACTICE BULLETINS
stop smoking before 16 weeks of gestation have infants

with birth weights similar to those of babies of women
who never smoked (20), and women who quit as late as
the seventh month have mean birth weights higher than
those who smoked during the entire pregnancy (21).
The incidence of IUGR is markedly increased in
pregnant women who use illicit drugs, but it is difficult to
differentiate the drug effect from the effects of other
behaviors associated with drug use. The incidence of
SGA infants in mothers with heroin addiction is as high
as 50% (22) and is reported to be as high as 35% in
patients managed with methadone (23). Cocaine abuse in
pregnancy is associated with delivery of an SGA neonate
in 30% or more of cases (24).
Malnutrition
There is a common belief that severe maternal malnutrition will result in fetal growth restriction. The data from
studies of the Siege of Leningrad during World War II
(25) and the Dutch famine of the same period (26) suggest
that maternal intake must be reduced to below 1,500 kilocalories per day before a measurable effect on birth
weight becomes evident. In these studies, it is not entirely clear, however, how much of the effect on birth weight
was the result of IUGR and how much the result of
preterm delivery.
Although low prepregnancy weight and low maternal weight gain have been positively associated with an
increase in IUGR (7, 27, 28), and increased weight gain
has been associated with decreased IUGR in some populations (29), there is as yet no demonstration that altering
dietary recommendations or habits can affect birth
weight in a positive manner. Rather, although there are
associations between maternal prepregnancy weight,
maternal weight gain, and birth weight, there has been no
trial showing that any intervention to alter pregnancy
weight gain has a beneficial effect on fetal weight gain.
Placental Disease
Primary placental disease (such as chorioangioma) is a
rare but recognized cause of growth restriction (30).
Placenta previa has been associated with an increase in
growth restriction, presumably secondary to abnormal
placental implantation. Confined placental mosaicism has
been identified three times more frequently from placentas of SGA infants than in infants of normal growth (16).
Multiple Gestation
Intrauterine growth restriction is a common complication
of multiple gestation. It is more pronounced in higher
order multiple gestations when compared with twin gestations (31). Investigators have reported a greater likeli-
679
hood of IUGR among surviving fetuses after multifetal

reduction (32, 33). The growth restriction is a result of
placental reserve inadequate to sustain the normal growth
of more than one fetus. Growth restriction can occur in
dizygotic twin gestations but is more common and severe
in monozygotic twins. It is evident that equal sharing of
functional placental mass is not the norm; rather, one
twin is more likely to have a larger share of functional
placental mass than the other (31).
Infections
Viral infections have been estimated to be etiologic in less
than 5% of all growth-restricted fetuses (34). However,
when evaluated in documented cases of in utero viral
infection, the frequency of IUGR can be strikingly high.
Fetal rubella infection is associated with growth restriction in up to 60% of cases (35). Cytomegalovirus also is a
recognized cause of growth restriction (36). In one study,
approximately 40% of fetuses with varicella syndrome
exhibited growth restriction (37). Bacterial infections
have not been shown to cause growth restriction. Some
protozoal infections, such as Toxoplasma gondii,
Trypanosoma cruzi (Chagas disease), and syphilis, are
associated with growth restriction (38, 39).
Genetic Disorders
Chromosome anomalies are a major cause of IUGR (40,
41). Many fetal structural anomalies also are associated
with an increased risk of growth restriction, with a relative risk ranging from as high as 24.7 with anencephaly
to as low as 1.2 with pyloric stenosis (42).
Exposure to Teratogens
Maternal ingestion of certain medications is a recognized
cause of growth restriction; the incidence and severity
vary by substance, gestational age at exposure, duration
of exposure, and dosage. Therapeutic agents known to be
associated with growth restriction include anticonvulsants (eg, trimethadione, phenytoin) (4345), folic acid
antagonists (eg, methotrexate) (46), and warfarin (47,
48).
Morbidity and Mortality

Fetal Morbidity and Mortality
Perinatal morbidity and mortality is significantly
increased in the presence of low birth weight for gestational age, especially with weights below the 3rd percentile for gestational age (1). One study found that 26%
of all stillbirths were SGA (49). The risk of death in the
presence of IUGR also is affected by gestational age and
the primary etiology and may be further modified by the
680
severity and progression of associated maternal etiologic

factors (eg, hypertension) (50) (see Table 1).
Both intrapartum and neonatal complications are
increased in the presence of IUGR. During labor, up to
50% of growth-restricted fetuses exhibit abnormal heart
rate patterns, most often variable decelerations, and such
fetuses have an increased cesarean delivery rate (51, 52).
Oligohydramnios is a common finding in growth-restricted fetuses and may render the umbilical cord vulnerable
to compression (5355). Sustained antepartum cord compression in growth-restricted fetuses is a presumed cause
of sudden fetal death (51, 55). Incidences of low Apgar
scores and cord blood acidemia increase significantly in
SGA neonates (56).
Neonatal Morbidity
Neonatal complications in the SGA infant include polycythemia, hyperbilirubinemia, hypoglycemia, hypothermia, and apneic episodes (57, 58), as well as low Apgar
scores, umbilical artery pH less than 7.0, need for intubation in the delivery room, seizures, sepsis, and neonatal death (1). It is uncertain whether IUGR accelerates
fetal pulmonary maturity. One study found a decreased
incidence of both respiratory distress syndrome and
intraventricular hemorrhage in infants with SGA compared with a control group of infants of appropriate size
for their gestational age (59). In contrast, other studies
failed to document a difference in lung profile in a
matched series (60) and found no difference in the need
for ventilatory support in newborns with SGA when
compared with controls. The use of glucocorticoids in
fetuses with IUGR has not been studied, but current recommendations are to give glucocorticoids to women with
Table 1. Corrected Perinatal Mortality Rates (Excluding Lethal

Anomaly) Among Low-risk and High-risk (Screened/Unscreened)
Pregnancies and Among SGA Fetuses (Screened/Unscreened),
Manitoba Experience
Category
Number of Cases
All cases
144,786
All low risk
101,350
All high risk
43,436
Screened high risk
31,740
All SGA (7% total population) 10,135
Unscreened SGA
7,460
Screened SGA*
2,675
Corrected Perinatal
Mortality Rates
(per 1,000 live births)
5.6
3.8
9.8
2.2
17.8
21.3
8.4
* Serial fetal assessment management by fetal biophysical profile score.

Manning FA. Intrauterine growth retardation, etiology, pathophysiology, diagnosis, and treatment. In: Fetal medicine: principles and practice. Norwalk,
Connecticut: Appleton & Lange, 1995:372
complicated pregnancies who are likely to deliver before

34 weeks of gestation (61).
Long-term development of infants born with SGA
depends in part on the cause of the growth failure. In
infants with karyotype abnormalities or viral infection,
the etiology rather than the weight percentile ultimately
will determine the outcome. There are conflicting data on
whether infants catch up in growth. Most otherwise normal infants with SGA secondary to placental insufficiency will exhibit normal catch-up growth by the age of 2
years, although this pattern may not be seen universally in
severely affected infants (58, 6264) or in preterm
growth-restricted infants (65). A comparison of 714
neonates of appropriate size for age with 347 SGA
neonates, derived from several studies, indicated a
twofold increase of major neurologic sequelae among
SGA infants (54). There is no evidence to suggest that any
specific management scheme or delivery route prevents
neurologic injury in such fetuses. Long-term follow-up of
infants with SGA shows that they are more prone to develop adult-onset hypertension and cardiovascular complications (66). It is important to note that IUGR and SGA both
have a multitude of etiologies, and there is a danger in
grouping them. There may be no consequences of low
birth weight under some circumstances; under others, it
may be devastating.
Antenatal Diagnosis of Intrauterine

Growth Restriction
There are two essential steps involved in the antenatal
recognition of growth restriction. The first step involves
the elucidation of maternal risk factors associated with
growth restriction and the clinical assessment of uterine
size in relation to gestational age. The second step
involves the ultrasonographic assessment of fetal size and
growth, supplemented by invasive fetal testing for aneuploidy or viral infection in select cases.
Clinical Evaluation
The key physical finding in IUGR is a uterine size that is
smaller than expected for gestational age. Several methods are available for clinical determination of uterine size,
the most common of which is an objective measurement
of fundal height. Such techniques, however, are prone to
considerable inaccuracy and should be used for screening
only, not as a sole guide to obstetric management in the
presence of risk factors for or suspicions of IUGR. These
inaccuracies are revealed in clinical studies suggesting
that growth restriction is undetected in about one third of
cases and is incorrectly diagnosed about 50% of the time
(3, 67).
PRACTICE BULLETINS

Recommendations
Which pregnancies should be screened for

intrauterine growth restriction, and how is
screening accomplished?
Unfortunately, approximately one half of growth-restricted fetuses are not diagnosed until delivery. In essence, all
pregnancies are screened for IUGR using serial fundal
height measurements. A single measurement at 3234
weeks of gestation is approximately 7085% sensitive
and 96% specific for detecting the growth-restricted fetus
(82). A third-trimester ultrasound examination, with a single measurement of abdominal circumference, detects
about 80% of IUGR fetuses (70). Even so, this does not
justify ultrasonography as a screening tool, because fundal height measurement performs comparably (70). All
pregnancies should be screened with serial fundal height
assessments, reserving ultrasonography for those with
risk factors, lagging growth, or no growth (69, 83, 84).
Women who have previously given birth to an SGA
infant are at an increased risk for this condition in subsequent pregnancies (9). Physicians should consider an
early ultrasound examination to confirm gestational
age, as well as subsequent ultrasonography to evaluate
sequential fetal growth, in women with significant risk
factors.
Prior to birth, the diagnosis of IUGR is not precise.

Currently, the use of ultrasonographically estimated fetal
weight, head- or femur-to-abdomen ratios, or serial observation of biometric growth patterns (growth velocity) are
all acceptable and widely used methods to diagnose
IUGR (6872). This document does not address the concept of asymmetrical versus symmetrical IUGR, because
it is unclear whether the distinction is important with
respect to etiology or neonatal outcome.
Four standard fetal measurements generally are
obtained as part of any complete obstetric ultrasound
examination after the first trimester: 1) fetal abdominal
circumference, 2) head circumference, 3) biparietal diameter, and 4) femur length (73). Fetal morphologic parameters can be converted to fetal weight estimates using
published formulas and tables (74). An abdominal circumference within the normal range reliably excludes
growth restriction with a false-negative rate of less than
10% (71). A small abdominal circumference or fetal
weight estimate below the 10th percentile suggests the
possibility of growth restriction, with the likelihood
increasing as the percentile rank decreases (71). When
IUGR is suspected, serial measurements of fetal biometric parameters provide an estimated growth rate. Such
serial measurements are of considerable clinical value in
confirming or excluding the diagnosis and assessing the
progression and severity of growth restriction. Given the
high incidence of genetic and structural defects associated with IUGR, a detailed ultrasound survey for the presence of fetal structural and functional defects may be
indicated.
Amniotic fluid volume is an important diagnostic and
prognostic parameter in fetuses with IUGR (75, 76).
Oligohydramnios is highly suggestive of growth failure
and indicates an increased risk of fetal death. Oligohydramnios is diagnosed ultrasonographically in approximately 7783% of pregnancies with growth-restricted
fetuses (7577). In contrast, amniotic fluid volume often
is normal even in a fetus with significant growth restriction; thus, the absence of oligohydramnios should not
detract from the diagnosis of IUGR.
Although Doppler velocimetry of the umbilical arteries is not useful as a screening technique for IUGR (78,
79), it has been demonstrated to be useful once IUGR has
been diagnosed. Not only are Doppler velocimetry findings normal in growth-restricted fetuses with chromosomal or other structural etiologies (80) but Doppler
velocimetry has been shown to both reduce interventions
and improve fetal outcome in pregnancies at risk for
IUGR (81). Thus, once IUGR is suspected or diagnosed,
Doppler velocimetry may be useful as a part of fetal evaluation. Fetuses with normal flow patterns seem less likely to benefit from consideration of early delivery than do
their counterparts with abnormal studies.
681
What are the best ways to evaluate and monitor a pregnancy complicated by suspected
intrauterine growth restriction?
Once IUGR is suspected (ie, lagging fundal height), it

should be confirmed using multiple ultrasonographic
parameters, such as estimated weight percentile, amniotic fluid volume, elevated head circumference and abdominal circumference ratio, and possibly Doppler criteria (ie,
elevated systolicdiastolic ratio or reversed or absent enddiastolic flow) (85). Identification of IUGR is improved
by recording growth velocity or through two sets of
examinations generally 24 weeks apart.
The diagnosis of IUGR as the fetus approaches term
may be an indication for delivery (86). If pregnancy is remote
from term or if delivery is not elected, the optimal mode of
monitoring has not been established. Periodic fetal assessment (approximately weekly) using Doppler velocimetry,
contraction stress test, traditional biophysical profile (BPP),
modified BPP, or nonstress test (NST) are all accepted monitoring techniques. Randomized controlled trials have demonstrated that monitoring with Doppler velocimetry reduces the
risk of perinatal morbidity (81). Comparable studies for the
other methods have not been done.
682
Serial ultrasonograms to determine the rate of growth

should be obtained approximately every 24 weeks.
Measurements at shorter intervals (<2 weeks) may overlap with measurement errors. If any test result is abnormal
(decreased amniotic fluid volume or low BPP scores),
more frequent testing, possibly daily, may be indicated.
An abnormal result from fetal heart rate testing
(decreased variability) coupled with abnormal results
from Doppler velocimetry suggests poor fetal well-being
and a potential need for delivery, despite prematurity (72).
What interventions improve pregnancy

outcome in cases of intrauterine growth
restriction or suspected intrauterine growth
restriction?
Is there any evidence that prenatal diagnosis

or suspicion of intrauterine growth restriction
with antenatal surveillance alters outcome?
The nonanomalous fetus with IUGR should be monitored

serially for risk of perinatal mortality and morbidity. Risk
to the fetus can be determined by several methods: traditional or modified BPP, contraction stress test, NST,
amniotic fluid volume, or Doppler velocimetry of fetal
vessels. Unfortunately, these tests are performed to determine the optimal time for delivery and are not predictive
of individual fetuses at greatest risk for a complicated
neonatal course (100).
There are no randomized trials of interventions in a
fetus with abnormal heart rate tracings. Thus, in the case
of a very premature infant, delivery or expectant manage-
Evidence from randomized controlled trials finds few

interventions beneficial in preventing or treating IUGR.
Avoidance of smoking during pregnancy has been shown
to have a positive effect on birth weight (20). Treatment
of infections such as malaria in endemic areas has been
shown to be of some benefit (87, 88).
A number of interventions have been suggested for
which there is insufficient evidence from randomized
clinical trials to conclude either benefit or harm. Among
them are bed rest, which demonstrated no benefit in one
small study (89), and early delivery in the presence of pulsatile flow in waveforms from the umbilical vein, which
remains to be assessed in a randomized control trial.
Other interventions of questionable efficacy and safety
include nutrient treatment or supplementation (90), zinc
supplementation (91), calcium supplementation (92),
plasma volume expansion (93), maternal oxygen therapy
(94), heparin (47), and low-dose aspirin (9599). Thus,
such interventions should be used only in experimental
protocols.
ment are the usual courses of action at present. Overall

experience with the NST confirms that with a reactive
NST the fetus is not likely to die in utero immediately. In
several studies, nonreactive or abnormal NSTs were
found in fetuses with acidosis, hypoxemia, or both (101,
102). In four randomized clinical trials comparing BPP
with conventional fetal monitoring in high-risk pregnancies (including those with IUGR), there was no obvious
benefit for pregnancy outcome using BPP for surveillance (103), although different results might have been
obtained in an IUGR-only population.
Doppler ultrasound has been shown to be useful in
the assessment of the growth-restricted fetus (104).
Absent or reversed end-diastolic flow velocities in the
umbilical arteries have a poor positive predictive value
but are associated with poor perinatal outcome and high
perinatal mortality (105107). In contrast, a normal
systolicdiastolic ratio in a growth-restricted fetus has
excellent negative predictive value and may be used as a
rationale to delay delivery with some reassurance.
Currently, there are not enough data to warrant cordocentesis in the management of IUGR.
With the exception of Mannings data, which
includes IUGR among other high-risk conditions, there is
no evidence that antenatal surveillance in fetuses with
suspected IUGR alters perinatal outcome. Instead, it is
used to predict which fetuses are at risk for in utero
demise and thus may potentially benefit from preterm
delivery. Currently, there are no intrauterine therapies
available for affected fetuses; therefore, delivery is the
optimal treatment in the mature fetus, but must be
weighed against gestational age for the immature fetus.
How does knowledge of the etiology of

intrauterine growth restriction alter management?
If maternal medical conditions are thought to be the cause

of IUGR, there is no evidence that changes in maternal
medical management other than delivery alter outcome.
For example, antihypertensive therapy has not been
shown to have a benefit with respect to IUGR (108).
However, it is still important to optimize maternal treatment.
Although the etiology and manifestations of IUGR
are numerous, a concerted effort should be made to determine the underlying cause. If a lethal anomaly is identified, one would not usually undertake antepartum
surveillance.
A detailed ultrasound survey should be performed to
detect fetal structural defects. Fetal karyotype determinations are not routinely indicated in the assessment of
growth-restricted fetuses, but should be considered when
PRACTICE BULLETINS
The general approach to management of the fetus with

ultrasonographically suspected IUGR involves risk factor
modification when possible and the initiation of antepartum fetal surveillance, ultrasonography, and delivery
when the risks of continued in utero development outweigh the benefits.
The risks to the growth-impaired fetus are well documented. Currently, although the incidence of IUGR has
not changed appreciably, the prognosis for SGA infants
has improved dramatically. It must be emphasized, however, that perinatal morbidity and mortality will continue
to occur despite optimal management of the fetus with
suspected IUGR. In those fetuses managed expectantly,
antepartum injury or death may occur because current
methods of fetal surveillance are less than perfect in the
prediction of fetal outcome.
Summary
The use of Doppler ultrasonography to measure

umbilical artery waveforms in the management of
IUGR is associated with a reduction in perinatal
death, and may be considered a part of fetal evaluation once IUGR is suspected or diagnosed.
Nutrient treatment or supplementation, zinc or calcium supplementation, plasma volume expansion,
maternal oxygen therapy, antihypertensive therapy,
heparin, and aspirin therapy have not been shown to
be effective for prevention or treatment of IUGR.
The following recommendations are based primarily on

consensus and expert opinion (Level C):
The fetus should be delivered if the risk of fetal death

exceeds that of neonatal death, although in many cases
these risks are difficult to assess. The timing of delivery in
the growth-restricted fetus should be individualized. Early
delivery may yield an infant with all the serious sequelae of
prematurity, whereas delaying delivery may yield a hypoxic, acidotic infant with long-term neurologic sequelae.
Gestational age and the findings of antenatal surveillance
should be taken into account. The decision to deliver is
based often on nonreassuring fetal assessment or a complete cessation of fetal growth assessed ultrasonographically over a 24-week interval. When extrauterine survival
is likely despite significantly abnormal antenatal testing,
delivery should be seriously considered.
When should a growth-restricted fetus be

delivered?
The following recommendations are based on good and

consistent scientific evidence (Level A):
early or severe IUGR is detected or when the fetus has a

recognized structural anomaly. It is estimated that about
10% of structurally abnormal fetuses with fetal growth
restriction will have a karyotype anomaly.
Prenatal diagnosis of in utero infections also can be
accomplished via amniotic fluid or fetal blood analyses.
Viral infections associated with IUGR, such as rubella,
cytomegalovirus, or varicella, can be diagnosed by polymerase chain reaction or by measuring viral-specific
immunoglobulin M antibodies. There are, however, no in
utero treatments for these infections. However, if toxoplasmosis is identified, medication taken by the mother
may prevent the spread of maternal infection to the fetus
(38).
683
Antepartum surveillance should be instituted once

the possibility of extrauterine survival for the
growth-restricted fetus has been determined. This
may include Doppler velocimetry, contraction stress
testing, NST with amniotic fluid volume assessment,
and BPP.
Routine screening for IUGR in low-risk patients
should comprise classical clinical monitoring techniques. Ultrasound evaluation of the fetus is appropriate in patients determined to be at high risk.
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688

January 1985 and March 1999. The search was restricted to
articles published in the English language. Priority was
although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of Health
and the American College of Obstetricians and Gynecologists were reviewed, and additional studies were located by
reviewing bibliographies of identified articles. When reliable research was not available, expert opinions from obstetriciangynecologists were used.
Force:
I
type of evidence.
committees.
Copyright January 2000 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
PRACTICE BULLETINS
689
ACOG
PRACTICE
BULLETIN
NUMBER 13, FEBRUARY 2000
(Replaces Practice Pattern Number 4, July 1997)

Obstetrics. The information is
designed to aid practitioners
in making decisions about
appropriate obstetric and gynecologic care. These guidelines
should not be construed as
treatment or procedure. Variations in practice may be warranted based on the needs of the
individual patient, resources,
and limitations unique to the
institution or type of practice.
Reaffirmed 2009
In the United States, there is a widespread belief that the overall cesarean delivery rate is higher than necessary. Efforts are being directed toward decreasing
the number of these procedures, in part by encouraging physicians to make
changes in their management practices. Because breech presentations are associated with a high rate of cesarean delivery, there is renewed interest in techniques such as external cephalic version (ECV) and vaginal breech delivery.
The purpose of this document is to provide information about ECV by summarizing the relevant evidence presented in published studies and to make recommendations regarding its use in obstetric practice.
Background
Breech presentation occurs in 34% of term pregnancies. In 1997, 84.5% of all
malpresentations, including breech presentation, resulted in cesarean deliveries
(1). External cephalic version involves applying pressure to the mothers abdomen
to turn the fetus in either a forward or backward somersault to achieve a vertex presentation. The goal of ECV is to increase the proportion of vertex presentations
among fetuses that were formerly in the breech position near term. Once a vertex
presentation is achieved, the chances for a vaginal delivery increase.

Recommendations
Which patients are candidates for external cephalic version?
Patients who have completed 36 weeks of gestation are preferred candidates for
ECV for several reasons. First, if spontaneous version is going to occur, it is likely to have taken place by 36 completed weeks of gestation (2, 3). Second, risk of
a spontaneous reversion is decreased after external cephalic version at term com-
690
pared with earlier gestations. Preterm version attempts are

associated with high initial success rates but also with higher reversion rates, necessitating additional procedures (4, 5).
Third, if complications arise during an attempted version,
emergency delivery of a term infant can be accomplished
(6). Finally, most of the evidence pertaining to ECV comes
from recent studies that selected patients near term.
There is scant information concerning ECV attempts
among women who have a preexisting uterine scar or who
undergo the procedure during the early stages of labor.
For women with a previous cesarean delivery, compared
with those who had not experienced cesarean delivery,
results from one small randomized controlled trial indicate that they experience comparable success rates (7).
Although no serious adverse events occurred in a small
series (8), larger studies would be needed to establish the
risk of uterine rupture. There are scattered reports of successful ECV performed during early labor; to date, however, no large study has been published (4, 5, 9, 10).
Contraindications to ECV are based on a commonsense approach designed to minimize the risks of an
adverse outcome and to maximize the chances for success. Clearly any indication for a cesarean delivery in a
patient, such as placenta previa, would be a contraindication to ECV (4, 9, 1120), but there is insufficient evidence to construct a comprehensive list.
associated with ECV do not occur often, but there have

been a few reported cases of placental abruption and
preterm labor. A report from Copenhagen described two
cases of intrauterine death 2 and 5 weeks after version
among 316 women and one instance of premature partial
separation of the placenta 2 days following an unsuccessful version attempt, but the two deaths could not be
causally linked to ECV with certainty (16). In the study
including mothers at 36 weeks of gestation or less, two
placental abruptions and one premature labor occurred
shortly after version, resulting in one neonatal and two
fetal deaths (25). Subsequently, there has been a follow-up
study at the same institution, but changes in management
practices and selection criteria had been made (18). Only
term gestations were selected, and tocolytic agents as well
as fetal monitoring were used during version attempts.
There were no fetal deaths causally linked to ECV. The
authors concluded that ECV can substantially decrease
breech presentations and the cesarean delivery rate for
these patients (18). A more recent study reported a placental abruption during an ECV attempt requiring emergency
cesarean delivery of a viable but depressed infant (28). It
was the only major complication attributed to ECV among
113 women. Although the incidence of serious complications associated with ECV is low, the potential is present,
making it prudent to perform ECV in a facility that has
ready access to cesarean delivery services.
What are the benefits and risks of external

cephalic version?
The immediate benefit of successful version is an

increased probability that the fetus will be in a vertex presentation for delivery. The ultimate goal is an uncomplicated vaginal delivery. Reports from published studies
indicate there are fewer cesarean deliveries among women
who have undergone successful version compared with
women who have not undergone attempted version (4, 6,
18, 2124). One randomized trial found no significant difference between the cesarean delivery rates of patients
with an ECV attempt and controls who did not undergo
ECV (25). In this study, however, the majority of patients
undergoing ECV were between 33 and 36 weeks of gestation rather than closer to term as in the other reports. An
additional randomized trial reported similar rates of
cesarean delivery for women who underwent ECV and for
those who did not, but the rate of breech vaginal deliveries
was very high; approximately 80% of breech presentations
in each group was delivered vaginally, resulting in an
unusually low cesarean delivery rate (4).
Fetal heart rate changes during attempted versions are
not uncommon but usually stabilize when the procedure is
discontinued (4, 21, 23, 26, 27). Serious adverse effects
What are the success rates for external

cephalic version, and what factors are
predictive of either success or failure?
A review of 20 studies indicates that success rates for

ECV range from 35% to 86%, with an average success
rate of 58% (4, 6, 9, 1214, 1618, 2125, 27, 2931).
Most authors report a positive association between parity
and successful version (4, 6, 13, 2125, 30, 31). A transverse or oblique lie is associated with higher immediate
success rates (13, 29, 30). Opinion is divided about the
predictiveness of other factors, including amniotic fluid
volume, location of placenta, and maternal weight. Some
reports indicate an association between normal or
increased amounts of amniotic fluid and successful ECV
(12, 13, 24, 32), whereas other reports do not (20). Two
authors reported an association between successful ECV
and placenta location (20, 24), whereas others failed to
find an association (12, 13, 29). Two authors found obesity to be associated with a higher failure rate (23, 30),
whereas others found maternal weight not to be a significant predictor of success (12, 13, 19, 20).
Although scoring systems have been developed to
predict which candidates will have a successful version
PRACTICE BULLETINS
attempt, these have not been validated by multiple studies. One system considered parity, dilatation, estimated
fetal weight, placenta location, and station. Nulliparity,
advanced dilatation, fetal weight of less than 2,500 g,
anterior placenta, and low station were less likely to be
associated with success (20). Such variables may provide
useful clinical information for obtaining informed consent from individuals for ECV; no single system, however, has been shown to have complete accuracy.
How does the use of tocolysis affect the success rate of external cephalic version?
Does successful version translate into lower

cesarean delivery rates?
How does the use of anesthesia affect the success rate of external cephalic version?
A randomized study found a significantly greater success

rate associated with the use of epidural anesthesia,
although the success rate was unusually low for the
women who did not receive epidural anesthesia (32%)
(38). Two studies reported results for women in whom
ECV was performed while using epidural anesthesia (10,
15). In one study, use of epidural anesthesia was associated with a significantly greater success rate compared
with no use of epidural anesthesia (15). However, the
procedure was administered selectively to patients
according to physician preference, raising the potential
for selection bias. The other study merely noted that ECV
was performed without difficulty on three women undergoing epidural anesthesia (10). It also has been suggested that epidural anesthesia be considered for women who
failed a previous version attempt (39). Another randomized trial addressed the use of spinal anesthesia before the
version attempt and found no significant difference
between treatment groups (40). Currently, there is not
enough consistent evidence to make a recommendation
favoring spinal or epidural anesthesia during ECV
attempts.
Whether ECV results in a lower cesarean delivery rate for

women with breech presentation who elect this procedure
compared with those women who do not depends upon
several factors. Obviously, the first factor is whether the
version is successful. Clearly, women who have successful version have lower cesarean delivery rates than those
who do not (6, 9, 1214, 2124, 26, 29, 30). Two randomized studies also have shown a significant decrease in
cesarean delivery rates among patients assigned to version compared with those not assigned to version (18,
23). Factors that tend to lessen overall differences
between version and nonversion groups include spontaneous conversion of presentation from breech to vertex or
vice versa and the willingness of providers to perform
vaginal breech deliveries. Clearly, cesarean delivery rates
for version and nonversion groups will be less when there

is a greater willingness to attempt a vaginal breech delivery. The need to perform a cesarean delivery for other
indications in women who have had a successful version
also may lessen the overall impact of version on the
cesarean delivery rate. One author has reported that
women who have had successful ECV have higher
cesarean delivery rates due to fetal distress and dystocia
compared with matched controls who never required the
procedure (31).
Although ECV may not lead to a substantial reduction in the national cesarean delivery rate, it is nonetheless a valuable management technique. In a properly
selected population, this procedure poses little risk to
either mother or fetus. If successful, ECV provides a
clear benefit to the individual woman by allowing her an
opportunity for a successful vertex vaginal delivery.
Two of six randomized controlled trials failed to find a

significant advantage in using tocolytics during ECV
attempts (19, 27). One third reported significantly greater
success associated with hexoprenaline but not with ritodrine (33). An additional randomized study reported an
initial advantage associated with the use of ritodrine,
specifically among nulliparous women. However, as the
physicians became proficient at the ECV technique, the
advantage diminished (34). The largest randomized study
using a ritodrine infusion found significant improvement
only among nulliparous patients (35). Finally, a randomized study of terbutaline found the success rate of version
associated with use of this tocolytic to be almost double
the rate without its use (36). In the vast majority of published studies, a tocolytic agent was used routinely (6,
1118, 2023, 2729, 37). Several studies used tocolytics
selectively (5, 7, 9, 34), and some used no tocolytic
agents (4, 25). Existing evidence may support the use of
a tocolytic agent during ECV attempts, particularly in
nulliparous patients.
691
What is an example of a standard protocol

for performing an external cephalic version
attempt?
Prior to attempting ECV, patients must provide informed

consent and should undergo an ultrasound examination.
The ultrasound examination is necessary to confirm the
breech position of the fetus and rule out the presence of
any anomalies that would complicate a vaginal delivery.
692
Fetal well-being should be assessed by a prior nonstress

test or concurrent biophysical profile (see Fig. 1).
Because there is a chance that an expedient delivery
may become necessary, patients should have ready access
to a facility that is equipped to perform emergency cesarean deliveries. One version technique involves lifting the
breech upward from the pelvis with one hand and providing pressure on the head with the other hand to produce a
forward roll. If the forward roll fails, a backward somer-
sault may be attempted. Version may be performed by one

person or two. A version attempt will be abandoned if
there is significant fetal bradycardia, if there is discomfort
to the patient, or if the attempt cannot be completed easily
or is unsuccessful after a brief period. Following the
attempt, fetal evaluation is repeated and the patient is monitored until stable. Rh-negative patients may receive anti-D
immune globulin. There is no support for routine practice
of immediate induction of labor to minimize reversion.
Confirmed breech presentation at

36 completed weeks of gestation
Figure 1. Algorithm for patient
management for external cephalic version.
Review contraindications
Obtain informed consent
Consider tocolytics
for nulliparas
Assess nonstress test

or biophysical profile
Cephalic version attempt
Successful
Unsuccessful
Revert to breech
Consider retrial
of version
Remains breech
No further
attempts
at version
Consider
retrial of
version
Spontaneously
converts to vertex
Continues vertex
PRACTICE BULLETINS
What are the cost implications of external

cephalic version?

Because the risk of an adverse event occurring as a

result of ECV is small and the cesarean delivery rate
is significantly lower among women who have
undergone successful version, all women near term
with breech presentations should be offered a version attempt.
Patients should have completed 36 weeks of gestation before attempting ECV.
Previous cesarean delivery is not associated with a

lower rate of success; however, the magnitude of the
risk of uterine rupture is not known.
There is insufficient evidence to recommend routine

tocolysis for ECV attempts for all patients, but it
may particularly benefit nulliparous patients.
Evidence is inconsistent regarding the benefits of

anesthesia use during ECV attempts.
Cost-effectiveness depends upon utilization of vaginal breech deliveries and costs of the version protocol
at a particular institution, but at least one decision
analysis suggests the policy is cost effective.
Fetal assessment before and after the procedure is

recommended.
Summary
A recent decision analysis measuring cost implications

associated with four potential methods of managing term
pregnancies with breech presentations predicted that use
of ECV would result in fewer cesarean deliveries and
lower costs than either scheduled cesarean delivery or
trial of labor without an ECV attempt (41). Even if failed
ECV attempts were followed by routine cesarean delivery, the overall cesarean delivery rate would be lower
than that of a trial of labor without an ECV attempt.
Sensitivity analysis revealed that as long as less than 52%
of all breech presentations are eligible for a trial of labor,
a policy of attempting ECV followed by either a trial of
labor or routine cesarean delivery (for failed attempts)
would be less expensive than a policy of routine cesarean delivery or trial of labor without ECV (41). It should
be noted that the decision analysis included X-ray
pelvimetry to assess eligibility for a trial of labor, a practice that may not be widely accepted.
693
External cephalic version should be attempted only

in settings in which cesarean delivery services are
readily available.
References
1. Ventura SJ, Martin JA, Curtin SC, Mathews TJ. Births:
final data for 1997. Natl Vital Stat Rep 1999;47(18):196
(Level II-3)
2. Hickok DE, Gordon DC, Milberg JA, Williams MA,
Daling JR. The frequency of breech presentation by gestational age at birth: a large population-based study. Am J
3. Westgren M, Edvall H, Nordstrom L, Svalenius E,
Ranstam J. Spontaneous cephalic version of breech presentation in the last trimester. Br J Obstet Gynaecol 1985;
92:1922 (Level II-3)
4. Van Veelen AJ, Van Cappellen AW, Flu PK, Straub MJ,
Wallenburg HC. Effect of external cephalic version in
late pregnancy on presentation at delivery: a randomized
controlled trial. Br J Obstet Gynaecol 1989;96:916921
(Level I)
5. Kornman MT, Kimball KT, Reeves KO. Preterm external
cephalic version in an outpatient environment. Am J
Obstet Gynecol 1995;172:17341738; discussion
17381741 (Level II-2)
6. Goh JT, Johnson CM, Gregora MG. External cephalic version at term. Aust N Z J Obstet Gynaecol
1993;33:364366 (Level II-2)
7. Flamm BL, Fried MW, Lonky NM, Giles WS. External
cephalic version after previous cesarean section. Am J
Obstet Gynecol 1991;165;370372 (Level I)
8. de Meeus JB, Ellia F, Magnin G. External cephalic version
after previous cesarean section: a series of 38 cases. Eur J
Obstet Gynecol Reprod Biol 1998;81:6568 (Level III)
9. Cook HA. Experience with external cephalic version and
selective vaginal breech delivery in private practice.
Am J Obstet Gynecol 1993;168:18861889; discussion
18891890 (Level II-3)
10. Ferguson JE 2d, Dyson DC. Intrapartum external cephalic
version. Am J Obstet Gynecol 1985;152:297298 (Level
II-3)
11. Lau TK, Stock A, Rogers M. Fetomaternal haemorrhage
after external cephalic version at term. Aust N Z J Obstet
12. Shalev E, Battino S, Giladi Y, Edelstein S. External cephalic version at termusing tocolysis. Acta Obstet Gynecol
Scand 1993;72:455457 (Level II-3)
13. Hellstrom AC, Nilsson B, Stange L, Nylund L. When does
external cephalic version succeed? Acta Obstet Gynecol
Scand 1990;69:281285 (Level II-3)
694
14. Morrison JC, Myatt RE, Martin JN Jr, Meeks GR, Martin
RW, Bucovaz ET, et al. External cephalic version of the
breech presentation under tocolysis. Am J Obstet Gynecol
1986;154:900903 (Level II-3)
15. Carlan SJ, Dent JM, Huckaby T, Whittington EC, Shaefer
D. The effect of epidural anesthesia on safety and success of external cephalic version at term. Anesth Analg
1994;79:525528 (Level II-3)
16. Thunedborg P, Fischer-Rasmussen W, Tollund L. The benefit of external cephalic version with tocolysis as a routine
procedure in late pregnancy. Eur J Obstet Gynecol Reprod
Biol 1991;42:2327 (Level II-3)
17. Bewley S, Robson SC, Smith M, Glover A, Spencer JA.
The introduction of external cephalic version at term into
routine clinical practice. Eur J Obstet Gynecol Reprod
Biol 1993;52:8993 (Level II-3)
18. Mahomed K, Seeras R, Coulson R. External cephalic version at term. A randomized controlled trial using tocolysis.
Br J Obstet Gynaecol 1991;98:813 (Level I)
19. Tan GW, Jen SW, Tan SL, Salmon YM. A prospective randomised controlled trial of external cephalic version comparing two methods of uterine tocolysis with a non-tocolysis
group. Singapore Med J 1989;30:155158 (Level I)
20. Newman RB, Peacock BS, VanDorsten JP, Hunt HH.
Predicting success of external cephalic version. Am J
Obstet Gynecol 1993;169:245249; discussion 249250
(Level II-3)
21. Dyson DC, Ferguson JE 2d, Hensleigh P. Antepartum
external cephalic version under tocolysis. Obstet Gynecol
1986;67:6368 (Level II-2)
22. Marchick R. Antepartum external cephalic version with
tocolysis: a study of term singleton breech presentations.
23. Brocks V, Philipsen T, Secher NJ. A randomized trial of
external cephalic version with tocolysis in late pregnancy.
Br J Obstet Gynaecol 1984;91:653656 (Level II-1)
24. Hofmeyr GJ, Sadan O, Myer IG, Galal KC, Simko G.
External cephalic version and spontaneous version rates:
ethnic and other determinants. Br J Obstet Gynaecol
1986;93:1316 (Level II-2)
25. Kasule J, Chimbira TH, Brown IM. Controlled trial of
external cephalic version. Br J Obstet Gynaecol 1985;
92:1418 (Level I)
26. Stine LE, Phelan JP, Wallace R, Eglinton GS, Van Dorsten
JP, Schifrin BS. Update on external cephalic version performed at term. Obstet Gynecol 1985;65:642646 (Level
II-3)
27. Robertson AW, Kopelman JN, Read JA, Duff P, Magelssen
DJ, Dashow EE. External cephalic version at term: is a
tocolytic necessary? Obstet Gynecol 1987;70:896899
(Level I)
28. Calhoun BC, Edgeworth D, Brehm W. External cephalic

version at a military teaching hospital: predictors of success.
Aust N Z J Obstet Gynaecol 1995;35:277279 (Level II-3)
29. Donald WL, Barton JJ. Ultrasonography and external
cephalic version at term. Am J Obstet Gynecol 1990;162:
15421545; discussion 15451547 (Level II-3)
30. Mauldin JG, Mauldin PD, Feng TI, Adams EK, Durkalski
VL. Determining the clinical efficacy and cost savings of
successful external cephalic version. Am J Obstet Gynecol
1996;175:16391644 (Level II-3)
31. Lau TK, Lo KW, Wan D, Rogers MS. Predictors of successful external cephalic version at term: a prospective
study. Br J Obstet Gynaecol 1997;104:798802 (Level II-3)
32. Healey M, Porter R, Galimberti A. Introducing external
cephalic version at 36 weeks or more in a district general
hospital: a review and an audit. Br J Obstet Gynaecol
1997;104:10731079 (Level II-3)
33. Stock A, Chung T, Rogers M, Ming WW. Randomized,
double blind, placebo controlled comparison of ritodrine
and hexoprenaline for tocolysis prior to external cephalic
version at term. Aust N Z J Obstet Gynaecol 1993;
33:265268 (Level I)
34. Chung T, Neale E, Lau TK, Rogers M. A randomized, double blind, controlled trial of tocolysis to assist external
cephalic version in late pregnancy. Acta Obstet Gynecol
Scand 1996;75:720724 (Level I)
35. Marquette GP, Boucher M, Theriault D, Rinfret D. Does
the use of a tocolytic agent affect the success rate of external cephalic version? Am J Obstet Gynecol 1996;175:
859861 (Level I)
36. Fernandez CO, Bloom SL, Smulian JC, Ananth CV,
Wendel GD Jr. A randomized placebo-controlled evaluation of terbutaline for external cephalic version. Obstet
37. Hanss JW Jr. The efficacy of external cephalic version and
its impact on the breech experience. Am J Obstet Gynecol
1990;162:14591463; discussion 14631464 (Level II-3)
38. Schorr SJ, Speights SE, Ross EL, Bofill JA, Rust OA,
Norman PF, et al. A randomized trial of epidural anesthesia to improve external cephalic version success. Am J
39. Neiger R, Hennessey MD, Patel M. Reattempting failed
external cephalic version under epidural anesthesia. Am J
40. Dugoff L, Stamm CA, Jones OW 3rd, Mohling SI,
Hawkins JL. The effect of spinal anesthesia on the success
rate of external cephalic version: a randomized trial.
41. Gifford DS, Keeler E, Kahn KL. Reductions in cost and
cesarean rate by routine use of external cephalic version: a
decision analysis. Obstet Gynecol 1995;85:930936
(Level III)
PRACTICE BULLETINS

to conduct a literature search to locate relevant articles published between January 1981 and May 1999. The search
was restricted to articles published in the English language.
Priority was given to articles reporting results of original
research, although review articles and commentaries also
were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate
for inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of
Health and the American College of Obstetricians and Gynecologists were reviewed, and additional studies were
located by reviewing bibliographies of identified articles.
When reliable research was not available, expert opinions
from obstetriciangynecologists were used.
Force:
I
without the intervention. Dramatic results in uncontrolled experiments could also be regarded as
this type of evidence.
committees.
695
Copyright February 2000 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
696
ACOG
PRACTICE
BULLETIN
NUMBER 17, JUNE 2000
(Replaces Technical Bulletin Number 196, August 1994)

of Michael Belfort, MD. The
of practice.
Reaffirmed 2009
Operative Vaginal
Delivery
The incidence of operative vaginal delivery in the United States is estimated to
be 1015% (1), and although these procedures are safe in appropriate circumstances, controversy about them persists. Recent reports have highlighted the
potential for maternal and neonatal complications associated with operative
vaginal delivery, although the risks associated with alternative procedures also
must be considered. This document will address specific controversial issues
about the use of forceps and vacuum extractors for operative vaginal delivery
and present the available information on which to base decisions concerning
their use. The technical aspects of the use of forceps and vacuum extractors are
beyond the scope of this publication.
Background
Clinical studies performed before the 1970s suggested that the risk of fetal morbidity and mortality was higher when the second stage of labor exceeded 2
hours. Currently, more intensive intrapartum surveillance provides the ability to
identify the fetus that may not be tolerating labor well. Thus, the length of the
second stage of labor is not in itself an absolute or even strong indication for
operative termination of labor. When other obstetric factors prevail, however,
there is a place for forceps or vacuum-assisted operations.
Operative vaginal deliveries are accomplished by applying direct traction
on the fetal skull with forceps, or by applying traction to the fetal scalp by
means of a vacuum extractor. The indications for operative vaginal delivery
performed with either the vacuum extractor or forceps are the same (see the
box, Indications for Operative Vaginal Delivery).
The rate of cesarean deliveries in the United States has declined from
22.8% in 1987 to 20.8% in 1997 (2). During the same period, the percentage of
births delivered by forceps or vacuum extraction increased slightly, from 9.0%
to 9.4% (2). Of this number, the percentage of forceps deliveries has decreased
PRACTICE BULLETINS
Indications for Operative Vaginal Delivery

No indication for operative vaginal delivery is absolute.
The following indications apply when the fetal head is
engaged and the cervix is fully dilated.
Prolonged second stage:
Nulliparous women: lack of continuing progress
for 3 hours with regional anesthesia, or 2 hours
without regional anesthesia
Multiparous women: lack of continuing progress
for 2 hours with regional anesthesia, or 1 hour
without regional anesthesia
Suspicion of immediate or potential fetal compromise.
Shortening of the second stage for maternal benefit.
and the percentage of vacuum extraction deliveries has

increased. Although some authors have suggested that
operative vaginal deliveries have been replaced by cesarean deliveries, the relationship remains unclear. Geographic
differences in operative delivery rates have been reported,
with the lowest rate in the northeast United States and the
highest rate in the South.
In 1988, ACOG redefined the classification of station
and types of forceps deliveries. The revised classification
uses the level of the leading bony point of the fetal head
in centimeters at or below the level of the maternal ischial
spines to define station (05 cm), instead of the previously used method of describing the birth canal in terms of
thirds (03+).
The definitions of types of forceps deliveries also
were refined to avoid the inclusion of either trivial or
extremely difficult deliveries under the category of midforceps (see the box, Criteria for Types of Forceps
Deliveries). Before this reclassification, a rotational
delivery from occiput posterior at 0 station was classified
the same as a delivery from left occiput anterior on the
perineum. In a validation of ACOGs reclassification,
investigators demonstrated that the lower the fetal head
and the less rotation required, the less the risk of injury to
the mother and the child (3). Assessment of clinical
pelvimetry and fetal position is important in predelivery
evaluation (see the box, Predelivery Considerations).
Clinical Issues
Complications of Operative Vaginal
Delivery
General statements about the applicability of operative
vaginal delivery and the procedures for implementation in
697
a particular situation are difficult. Selection of the appropriate instrument and decisions about the potential maternal and fetal consequences should be based on clinical
findings at the time of delivery. Research into the complications of operative vaginal delivery is hampered by a
number of potential biases, including the level of experience of the operators, the small numbers of patients studied under similar circumstances, changes in practice and
definition, and the inability to achieve statistical power to
answer relevant questions. The following discussion is
based on currently available evidence and attempts to
address maternal and fetal complications associated with
operative vaginal delivery.
In a randomized trial comparing elective low-forceps
delivery with spontaneous vaginal delivery in 50 term
patients, there were no significant immediate differences
in maternal or neonatal outcome variables. The
researchers did show that in the forceps group, the mean
time to delivery was shorter (10.2 minutes versus 18 minutes) and the cord arterial pH was higher (7.27 versus
7.23) (4). However, a larger randomized study comparing
outlet forceps delivery with spontaneous vaginal delivery
in 333 women at term showed that, although the use of
forceps had no immediate adverse effects on the neonate,
there was no significant shortening of the second stage of
labor. However, the incidence of maternal perineal trauma increased in primiparous women (5).
Criteria for Types of Forceps Deliveries

Outlet forceps
1. Scalp is visible at the introitus without separating
labia.
2. Fetal skull has reached pelvic floor.
3. Sagittal suture is in anteroposterior diameter or
right or left occiput anterior or posterior position.
4. Fetal head is at or on perineum.
5. Rotation does not exceed 45.
Low forceps
Leading point of fetal skull is at station +2 cm and
not on the pelvic floor.
Rotation is 45 or less (left or right occiput anterior to
occiput anterior, or left or right occiput posterior to
occiput posterior).
Rotation is greater than 45.
Midforceps
Station is above +2 cm but head is engaged.
High forceps
Not included in classification.
698
Predelivery Considerations
Position: the relationship of the fetal presenting part

to the maternal pelvis. In a cephalic presentation
the designated point is the occiput, while in a
breech presentation it is the sacrum. The position
always is described in relation to the maternal left
and right sides of the pelvis.
Presentation: the relationship between the leading
fetal part and the maternal pelvic inlet. The fetus
may have a cephalic, breech, or shoulder presentation.
Lie: the relationship between the fetal and maternal
longitudinal axes, which may be longitudinal,
oblique, or transverse.
Engagement: the relationship that is present when
the widest diameter of the fetal presenting part
(biparietal diameter in a cephalic presentation,
and bitrochanteric diameter in a breech presentation) has passed beyond the plane of the maternal
pelvic brim. In a cephalic presentation the head
usually is engaged when the leading point of the
skull is at or below the maternal ischial spines.
Asynclitism: the relationship between the anterior
and posterior parietal bones and the sagittal
suture with the maternal pelvis. When neither of
the parietal bones precedes the sagittal suture, the
head is synclitic; if the anterior parietal bone precedes the sagittal suture, there is anterior asynclitism; and when the posterior parietal bone precedes the sagittal suture, there is posterior asynclitism.
Clinical Pelvimetry: assessment of the maternal
pelvis before performing midpelvic delivery.
A meta-analysis comparing vacuum extraction to forceps delivery showed that vacuum extraction was associated with significantly less maternal trauma and less need
for general and regional anesthesia. Overall, fewer cesarean deliveries were carried out in the vacuum extractor
group (6). Other studies comparing vacuum extraction to
forceps delivery indicate that more maternal morbidity
(soft tissue injury, discomfort) occurs with forceps delivery (7, 8).
Both forceps delivery and vacuum extraction have
been associated with the development of maternal
hematomas, (9) and possibly linked to pelvic floor injury.
However, other factors associated with pelvic floor injury
include normal spontaneous vaginal delivery, episiotomy,
prolonged second stage of labor, and increased fetal size
(10).
To evaluate the risk of operative vaginal delivery with
suspected fetal macrosomia, one study compared 2,924
macrosomic infants (birth weight >4,000 g) to those with
a birth weight between 3,000 g and 3,999 g. Macrosomic
infants delivered by forceps had a sixfold higher rate of

significant injury (relative risk = 6.7; confidence interval,
6.56.9). Forceps delivery in this situation also was associated with a fourfold risk of clinically persistent neurologic abnormalities when compared with spontaneous
vaginal delivery or cesarean delivery. The overall incidence of persistent injury was low (0.3%), and the
authors calculated that as many as 258 elective cesarean
deliveries would have to be performed for macrosomia to
prevent a single case of persistent injury (11). In addition,
a randomized study of forceps and vacuum-assisted vaginal delivery identified three factors associated with the
development of shoulder dystocia: use of vacuum device
(P = 0.04), time required for delivery (P = 0.03), and
birth weight (P = 0.0001) (12). Therefore, a trial of labor
and judicious use of operative vaginal delivery techniques for macrosomic infants are not contraindicated,
although caution should be used given the possibility of
shoulder dystocia.
Potential Newborn Complications of

Vacuum-Assisted Deliveries
With forceps, almost unlimited compression and traction
can be applied to the fetal head and cervical spine.
Vacuum extractors are designed to limit the amount of
traction on the fetal skull because detachment can occur.
Nevertheless, traction achieved with vacuum extraction is
substantial (up to 50 lb) (13) and can result in significant
fetal injury if misused. The vacuum cup can cause scalp
lacerations if torsion is excessive. In addition, separation
of the scalp from the underlying structures can lead to
cephalohematoma, which is more common in infants
delivered by vacuum extractor (1416%) than in those
delivered with forceps (2%) (6, 7). The incidence of subgaleal hematomas (collections of blood occurring in the
potential space between the cranial periosteum and the
epicranial aponeurosis) following vacuum deliveries is
estimated to range from 26 to 45 per 1,000 vacuum deliveries (14, 15).
Other potential neonatal complications associated
with vacuum deliveries include intracranial hemorrhage,
hyperbilirubinemia, and retinal hemorrhage. The higher
rates of neonatal jaundice associated with vacuum delivery may be related to the higher rate of cephalohematoma
(16). There is a higher rate of retinal hemorrhages (38%)
with vacuum delivery than with forceps delivery (17%)
(6, 7, 17, 18). However, corneal abrasions and external
ocular trauma are more common with forceps delivery
than with normal spontaneous delivery and are rare with
vacuum extraction unless the cup is inadvertently placed
over the eye. Long-term sequelae are extremely rare, and
ophthalmologic screening should be reserved for specific cases (18). Overall, the incidence of serious complica-
PRACTICE BULLETINS
tions with vacuum extraction is approximately 5% (19).

Given the maternal and neonatal risks associated with
operative vaginal delivery, it is important that the patient
be made aware of the potential complications of the proposed procedure.
In 1998, the U.S. Food and Drug Administration
(FDA) released a Public Health Advisory to alert individuals that vacuum extractors may cause serious or fatal
complications, including subgaleal (subaponeurotic)
hematoma and intracranial hemorrhage (20). The FDA
indicated that between 1994 and 1998, 12 deaths and nine
serious injuries were reported among neonates on whom
vacuum-assisted devices had been used. This rate was
greater than five times the rate for the preceding 11 years.
According to the advisory, data collected from 1989 to
1995 showed that use of the vacuum cup had increased
from 3.5% to 5.9% of all deliveries. Among the FDA recommendations for use of the vacuum device, two are particularly useful:
1. Rocking movements or torque should not be applied
to the device; only steady traction in the line of the
birth canal should be used.
2. Clinicians caring for the neonate should be alerted
that a vacuum device has been used so that they can
adequately monitor the neonate for the signs and
symptoms of device-related injuries.
A recent study evaluating the incidence of severe
birth trauma following operative deliveries assessed the
outcome of 83,340 singleton infants born to nulliparous
women between 1992 and 1994 in California (21). A
database was created linking birth and death certificates
with hospital discharge records of maternal and neonatal
outcomes. The lowest risk of fetal injury was found in
infants delivered spontaneously. An intermediate risk was
observed for those infants delivered by forceps or vacuum
alone or by cesarean delivery during labor. The highest
risk of fetal injury was reported for those infants who were
delivered with combined forceps and vacuum extraction
or who were delivered by cesarean following failed operative vaginal delivery. There was no difference in outcome between vacuum and forceps delivery versus
cesarean delivery during labor (Table 1). The morbidity
that previously had been thought to be due to operative
vaginal delivery actually may have resulted from the
process of abnormal labor that led to the need for intervention. The study population was large, but data were collected retrospectively from medical records and hospital
discharge reports. Therefore, detailed information on the
operative vaginal delivery, frequency of congenital anom-
699
Table 1. Effect of Delivery on Neonatal Injury

Delivery Method
Death
Intracranial
Hemorrhage
Other*
Spontaneous vaginal
delivery
1/5,000
1/1,900
1/216
Cesarean delivery during

labor
1/1,250
1/952
1/71
Cesarean delivery after

vacuum/forceps
N/R
1/333
1/38
Cesarean delivery with

no labor
1/1,250
1/2,040
1/105
Vacuum alone
1/3,333
1/860
1/122
Forceps alone
1/2,000
1/664
1/76
Vacuum and forceps
1/1,666
1/280
1/58
Abbreviation: N/R indicates not reported.

*Facial nerve/brachial plexus injury, convulsions, central nervous system depression, mechanical ventilation
Data from Towner D, Castro MA, Eby-Wilkens E, Gilbert WM. Effect of mode of
delivery in nulliparous women on neonatal intracranial injury. N Engl J Med
1999;341:17091714
alies, or number of infants readmitted following the initial discharge was not available. Despite its limitations,
this study confirms that injury can occur before operative
delivery as a result of abnormal labor forces and that not
all neonatal injuries are the result of poor operative technique.
Long-Term Infant Consequences

One randomized comparison of vacuum versus forceps
delivery that evaluated children at 9 months of age found
no statistically significant differences between the two
groups regarding head circumference, weight, head-circumference-to-weight ratio, hearing, or vision (22). The
study did note that infants delivered with the vacuum
device were more likely to have been readmitted with
jaundice than were those delivered with forceps.
In another study, the effects of forceps delivery on
cognitive development were examined in a cohort of
3,413 children. No significant differences were seen in
the 1,192 children delivered with forceps (114 were midforceps), compared with the 1,499 delivered spontaneously (23). A 10-year matched follow-up evaluation of
295 children delivered by vacuum extractor and 302 control patients who had been delivered spontaneously at the
same hospital revealed no differences between the two
groups in terms of scholastic performance, speech, ability of self-care, or neurologic abnormality (24).
700

Recommendations
What are contraindications to operative vaginal delivery?
Is there a role for a trial of operative vaginal

delivery?
Few studies address the issue of maternal and neonatal

outcome after an unsuccessful attempt at operative delivery. Earlier published reports were small retrospective
studies that suggested outcome was no worse after failed
operative delivery (26, 27). In a recent report of 102 cases
of failed instrument delivery, almost half (43%) of cases
where a trial of operative vaginal delivery was attempted
resulted in the need for cesarean delivery. Of those where
success was expected, only 3% went on to cesarean delivery (28). In addition, the California study previously discussed demonstrated significantly higher incidences of
intracranial hemorrhage and other birth trauma following
a failed operative vaginal delivery (21). Unless the preoperative assessment is highly suggestive of a successful outcome, trial of operative vaginal delivery is best avoided.
Is there a role for the use of alternative

instruments after a failed attempt?
Persistent efforts to obtain a vaginal delivery using different instruments may increase the potential for maternal
Under certain circumstances, operative vaginal delivery

should be avoided or, at the least, carefully considered in
terms of relative maternal and fetal risk. Most authorities
consider vacuum extraction inappropriate in pregnancies
before 34 weeks of gestation because of the risk of fetal
intraventricular hemorrhage. Operative delivery also is
contraindicated if a live fetus is known to have a bone demineralization condition (eg, osteogenesis imperfecta), a
bleeding disorder (eg, alloimmune thrombocytopenia, hemophilia, or von Willebrands disease) is present, the fetal head
is unengaged, or the position of the fetal head is unknown.
Operative vaginal delivery should be performed only
by individuals with privileges for such procedures and in
settings in which personnel are readily available to perform a cesarean delivery in the event the operative vaginal delivery is unsuccessful. One study showed that in
cases in which the vacuum extractor was used to deliver
fetuses with nonreassuring fetal heart rate patterns, blood
gas parameters did not differ from those in cases with normal spontaneous deliveries. The authors concluded that
the use of vacuum extraction is not contraindicated in
cases of nonreassuring fetal heart rate patterns (25).
and fetal injury and often indicates cephalopelvic disproportion. Although studies are limited, the weight of available evidence appears to be against attempting multiple
efforts at operative vaginal delivery with different instruments, unless there is a compelling and justifiable reason
(28). The California study reported that the incidence of
intracranial hemorrhage was highest in infants delivered
by combined vacuum and forceps compared with other
reported methods of delivery (21). The incidences of other
injuries also were increased with combined methods of
operative vaginal delivery.
What special equipment and techniques

should be considered with the use of a
vacuum extractor?
Vacuum extractors differ substantially from the original

metal cup and currently vary by material, cup size and
shape, and the method of vacuum application to the fetal
scalp (manual or automatic). The proliferation and increased
use of these instruments have resulted in the development
of a number of different techniques. Randomized trials
comparing soft vacuum cups to the original metal cup
indicate that the pliable cup is associated with decreased
fetal scalp trauma but increased rates of detachment from
the fetal head (2932). However, there are no differences
between Apgar scores, cord pH, neurologic outcome, retinal hemorrhage, maternal trauma, and blood loss (32).
These findings support those of another study, which
found a 22% incidence of significant fetal scalp trauma
with the soft cup, as opposed to a 37% incidence with the
metal cup. This study also concluded the soft cup was
more likely to fail than the metal cup when excessive
caput was present (29).
Data show that the use of rapid vacuum application
leads to a reduction in time to delivery (33, 34). No differences in detachment from the fetal scalp or in maternal
or neonatal morbidity between the two techniques have
been noted (33, 34). Specifically, one randomized study of
94 women comparing a one-step rapid application of vacuum with conventional stepwise application of vacuum
found a significant reduction in the time from application
to delivery (6 minutes) in the rapid application group
without any differences in maternal or neonatal morbidity
(33).
Cephalohematoma has been shown to be more likely
to develop as the duration of vacuum application increases. One study demonstrated that 28% of neonates in
whom the application-to-delivery time exceeded 5 minutes developed cephalohematoma (35). A further technical issue that has raised questions is whether the vacuum
should be reduced between contractions to prevent fetal
scalp injury. A randomized controlled trial involving 322
PRACTICE BULLETINS
patients at 34 weeks or more of gestation highlighted factors involved in the development of fetal cephalohematoma from vacuum extraction using the M-cup (a
semirigid plastic cup, modeled after the Malmstrom cup).
To prevent fetal loss of station, 164 patients had continuous vacuum application (600 mm Hg) during and
between contractions as well as during active efforts at
delivery. In the comparison group, 158 patients had intermittent suction (reduction of vacuum application to 100
mm Hg between contractions) and no effort to prevent
loss of station between contractions. Time to delivery,
method failure, maternal lacerations, episiotomy extension, incidence of cephalohematoma, and neonatal outcome were similar between the two groups. Overall, the
efficacy of the vacuum cup was 93.5%, and the cephalohematoma rate was 11.5%. The authors concluded that
there are no differences in maternal or fetal outcome with
intermittent reduction in vacuum or attempts to prevent
loss of station. They also concluded that the results
obtained with the M-cup are comparable to those reported with the stainless-steel Malmstrom cup (36).
Is there a role for midforceps rotational deliveries in current practice?
There are no randomized controlled studies of longterm follow-up from which to draw conclusions.
However, retrospective casecontrol analyses seem to
indicate no differences in outcome between midforceps
delivery and cesarean delivery or vacuum extraction (41,
42). A matched-pairs analysis of patients 2 years after a
midforceps delivery compared with a group delivered via
cesarean delivery (matched for the immediate indication
for operative delivery, birth weight, gestational age, sex,
and race) found no difference in abnormal outcomes
between the groups (41). An 18-year follow-up study of
males delivered by midcavity Kiellands forceps rotation
did not show any late adverse effects when subjects were
compared with males delivered by vacuum extractor (42).
Thus, there appears to be a role for midforceps rotational
deliveries in current practice. However, given the potential complications, this procedure is only for practitioners
skilled in midforceps delivery and for cases where maternal and fetal assessment prior to the operation suggest a
high chance of success.
Summary
The following recommendations are based on good
Both forceps and vacuum extractors are acceptable

and safe instruments for operative vaginal delivery.
Operator experience should determine which instrument should be used in a particular situation.
The vacuum extractor is associated with an increased

incidence of neonatal cephalohematomata, retinal
hemorrhages, and jaundice when compared with forceps delivery.
Operators should attempt to minimize the duration of

vacuum application, because cephalohematoma is
more likely to occur as the interval increases.
Midforceps operations should be considered an appropriate procedure to teach and to use under the correct
circumstances by an adequately trained individual.
The decrease in experienced teachers and the increase in

medicallegal concerns have reduced the number of current practitioners skilled in the art of midcavity rotational delivery. Studies comparing midforceps and cesarean
deliveries indicate that midforceps delivery is not associated with worse neonatal outcome (Apgar score, cord
blood gas, neonatal intensive care admissions, birth trauma) than is cesarean delivery (37, 38). In addition, outcome appeared no worse for those infants in whom
Kiellands forceps rotation was attempted but was unsuccessful (38). One retrospective analysis compared 358
midforceps deliveries with 486 cesarean deliveries and
found maternal morbidity (intraoperative and postoperative complications, blood loss, and length of stay) to be
higher in the cesarean delivery group (37). Another study
reported similar findings in a 5-year retrospective study
involving 253 patients (38).
A retrospective study compared 552 deliveries with
Kiellands forceps rotation, 95 cases using Scanzoni
maneuver with a different type of forceps, and 160 cases
using manual rotation and forceps. Investigators found no
significant differences in maternal or neonatal outcomes
between the groups regardless of whether the indication
was relative dystocia or nonreassuring fetal status (39).
An earlier study found that Kiellands forceps rotation
was associated with a higher incidence of neonatal trauma, although the analysis did not specify the indications
for operative delivery (40).
701
The incidence of intracranial hemorrhage is highest

among infants delivered by cesarean following a
failed vacuum or forceps delivery. The combination
of vacuum and forceps has a similar incidence of
intracranial hemorrhage. Therefore, an operative
vaginal delivery should not be attempted when the
probability of success is very low.
702
Operative vaginal delivery is not contraindicated in

cases of suspected macrosomia or prolonged labor;
however, caution should be used because the risk of
shoulder dystocia increases with these conditions.
Neonatal care providers should be made aware of the

mode of delivery in order to observe for potential complications associated with operative vaginal delivery.
References
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3. Hagadorn-Freathy AS, Yeomans ER, Hankins GD.
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6. Johanson RB, Menon BKV. Vacuum extraction versus forceps for assisted vaginal delivery (Cochrane Review). In:
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8. Johanson R, Pusey J, Livera N, Jones P. North Staffordshire/Wigan assisted delivery trial. Br J Obstet Gynaecol
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9. Gei AF, Belfort MA. Forceps-assisted vaginal delivery.
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10. Handa VL, Harris TA, Ostergard DR. Protecting the pelvic
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11. Kolderup LB, Laros RK Jr, Musci TJ. Incidence of persistent
birth injury in macrosomic infants: association with mode of
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12. Bofill JA, Rust OA, Devidas M, Roberts WE, Morrison JC,
Martin JN Jr. Shoulder dystocia and operative vaginal delivery. J Matern Fetal Med 1997;6:220224 (Level I)
13. Moolgaoker AS, Ahamed SOS, Payne PR. A comparison of

different methods of instrumental delivery based on electronic measurements of compression and traction. Obstet
14. Boo NY. Subaponeurotic haemorrhage in Malaysian
neonates. Singapore Med J 1990;31:207210 (Level II-3)
15. Govaert P, Defoort P, Wigglesworth JS. Cranial haemorrhage
in the term newborn infant. Clin Dev Med 1993;129:
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16. Vacca A, Grant A, Wyatt G, Chalmers I. Portsmouth operative delivery trial: a comparison of vacuum extraction
and forceps delivery. Br J Obstet Gynaecol 1983;90:
11071112 (Level I)
17. Williams MC, Knuppel RA, OBrien WF, Weiss A, Kanarek
KS. A randomized comparison of assisted vaginal delivery
by obstetric forceps and polyethylene vacuum cup. Obstet
18. Holden R, Morsman DG, Davidek GM, OConnor GM,
Coles EC, Dawson AJ. External ocular trauma in instrumental and normal deliveries. Br J Obstet Gynaecol 1992;
99:132134 (Level II-2)
19. Robertson PA, Laros RK Jr, Zhao RL. Neonatal and maternal outcome in low-pelvic and midpelvic operative deliveries. Am J Obstet Gynecol 1990;162:14361442; discussion
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20. Center for Devices and Radiological Health. FDA Public
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http://www.fda.gov/cdrh/fetal598.html. Retrieved December
31, 1999 (Level III)
21. Towner D, Castro MA, Eby-Wilkens E, Gilbert WM. Effect
of mode of delivery in nulliparous women on neonatal
intracranial injury. N Engl J Med 1999; 341:17091714
(Level II-2)
22. Carmody F, Grant A, Mutch L, Vacca A, Chalmers I. Follow
up of babies delivered in a randomized controlled comparison of vacuum extraction and forceps delivery. Acta Obstet
Gynecol Scand 1986;65:763766 (Level I)
23. Wesley BD, van den Berg BJ, Reece EA. The effect of forceps delivery on cognitive development. Am J Obstet
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24. Ngan HY, Miu P, Ko L, Ma HK. Long-term neurological
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Guzman ER, Knuppel RA. Effect of vacuum extraction on
umbilical cord blood acid-base measurements. J Matern
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26. Revah A, Ezra Y, Farine D, Ritchie K. Failed trial of vacuum
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28. Edozien LC, Williams JL, Chattopadhyay I, Hirsch PJ.
Failed instrumental delivery: how safe is the use of a second instrument? J Obstet Gynaecol 1999;19:460462
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PRACTICE BULLETINS
29. Chenoy R, Johanson R. A randomized prospective study

comparing delivery with metal and silicone rubber vacuum
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(Level I)
30. Cohn M, Barclay C, Fraser R, Zaklama M, Johanson R,
Anderson D, et al. A mulitcentre randomized trial comparing delivery with a silicone rubber cup and rigid metal vacuum extractor cups. Br J Obstet Gynaecol 1989;96:
545551 (Level I)
31. Hofmeyr GJ, Gobetz L, Sonnendecker EW, Turner MJ.
New design rigid and soft vacuum extractor cups: a preliminary comparison of traction forces. Br J Obstet
32. Kuit JA, Eppinga HG, Wallenburg HC, Huikeshoven FJ. A
randomized comparison of vacuum extraction delivery
with a rigid and a pliable cup. Obstet Gynecol 1993;
82:280284 (Level I)
33. Lim FT, Holm JP, Schuitemaker NW, Jansen FH, Hermans
J. Stepwise compared with rapid application of vacuum in
ventouse extraction procedures. Br J Obstet Gynaecol
1997;104:3336 (Level I)
34. Svenningsen L. Birth progression and traction forces
developed under vacuum extraction after slow or rapid
application of suction. Eur J Obstet Gynecol Reprod Biol
1987;26:105112 (Level II-2)
35. Bofill JA, Rust OA, Devidas M, Roberts WE, Morrison JC,
Martin JN Jr. Neonatal cephalohematoma from vacuum
extraction. J Reprod Med 1997;42:565569 (Level I)
36. Bofill JA, Rust OA, Schorr SJ, Brown RC, Roberts WE,
Morrison JC. A randomized trial of two vacuum extraction
techniques. Obstet Gynecol 1997;89:758762 (Level I)
37. Bashore RA, Phillips WH Jr, Brinkman CR 3rd. A comparison of the morbidity of midforceps and cesarean delivery.
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38. Traub AI, Morrow RJ, Ritchie JW, Dornan KJ. A continuing use for Kiellands forceps? Br J Obstet Gynaecol
1984;91:894898 (Level II-2)
39. Healy DL, Quinn MA, Pepperell RJ. Rotational delivery of
the fetus: Kiellands forceps and two other methods compared. Br J Obstet Gynaecol 1982;89:501506 (Level II-2)
40. Chiswick ML, James DK. Kiellands forceps: association
with neonatal morbidity and mortality. Br Med J 1979;
1:79 (Level II-3).
41. Dierker LJ Jr, Rosen MG, Thompson K, Lynn P.
Midforceps deliveries: long-term outcome of infants. Am J
42. Nilsen ST. Boys born by forceps and vacuum extraction
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1984;63:549554 (Level II-2)
703

to conduct a literature search to locate relevant articles published between January 1985 and November 1999. The
search was restricted to articles published in the English language. Priority was given to articles reporting results of
Institutes of Health and the American College of Obstetricians and Gynecologists were reviewed, and additional studies were located by reviewing bibliographies of identified
articles. When reliable research was not available, expert
opinions from obstetriciangynecologists were used.
Force:
I
type of evidence.
committees.
Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories:
Copyright June 2000 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
704
ACOG
PRACTICE
BULLETIN
(Replaces Educational Bulletin Number 234, March 1997)

of Linda A. Barbour, MD,
MSPH. The information is designed to aid practitioners in
making decisions about appropriate obstetric and gynecologic
care. These guidelines should
exclusive course of treatment
or procedure. Variations in
practice may be warranted
Thromboembolism in
Pregnancy
During pregnancy, women have a fivefold increased risk of venous thromboembolism (VTE), compared with nonpregnant women. The absolute risk of symptomatic venous thrombosis during pregnancy is between 0.5 and 3.0 per 1,000
women based on studies using radiographic documentation (13). Pulmonary
embolism (PE) is a leading cause of maternal death in the United States (4).
The prevalence and severity of this condition warrant consideration of anticoagulant therapy in pregnancy for women at risk for VTE. Such therapy includes
the treatment of acute thrombotic events, prophylaxis for patients with a history of thrombotic events or identified acquired or congenital thrombophilias,
and prevention and treatment of systemic embolization in women with valvular
heart disease. The purpose of this document is to review the current literature
on the prevention and management of thromboembolism in obstetric patients,
discuss the data behind sometimes conflicting guidelines from expert panels,
and offer evidence-based recommendations to address the most clinically relevant issues in the management of these patients.
Reaffirmed 2008
Background
Numerous changes in the coagulation system account for the hypercoagulable
state associated with pregnancy (see the box). Recently, it has been recognized
that up to half of women who have thrombotic events during pregnancy possess
an underlying congenital or acquired thrombophilia (5). The most common
thrombophilias in the Caucasian population are the factor V Leiden mutation,
which has a prevalence of 5% in this population, and the prothrombin gene
mutation G20210A, which has a prevalence of 2% in this population (5, 6). In
approximately 50% of patients with a hereditary thrombophilia, the initial thrombotic event occurs in the presence of an additional risk factor such as pregnancy,
oral contraceptive use, orthopedic trauma, immobilization, or surgery (7, 8).
PRACTICE BULLETINS
705
Heparin
Pregnancy-Associated Changes in Coagulation
Increases in clotting factors (I, VII, VIII, IX, X)
Decreases in protein S
Decreases in fibrinolytic activity
Increased venous stasis
Vascular injury associated with delivery
Increased activation of platelets
Resistance to activated protein C
Risk of Thromboembolism During

Pregnancy
Traditionally, it was believed that the risk of venous
thrombosis was greatest in the third trimester and immediately postpartum. More recent studies using objective
criteria for diagnosis have found that antepartum deep
vein thrombosis (DVT) is at least as common as postpartum thrombosis and occurs with equal frequency in all
three trimesters (1). However, PE is more common postpartum.
Women with a history of thromboembolism have an
increased risk of recurrence when they become pregnant;
however, the estimates of recurrence are based primarily
on two retrospective studies and range from 7.5% to 12%
(9, 10). No studies differentiated the risk of recurrence
based on underlying factors such as acquired or congenital thrombophilias, use of oral contraceptives, pregnancy, orthopedic trauma, recent surgery, or the occurrence
of the event in the antepartum versus postpartum period.
Most of the estimates of recurrence are based on women
who had their initial event during oral contraceptive use
or pregnancy. Risk factors for thromboembolic disorders
are noted in the box.
Anticoagulation Medications in
Pregnancy
Although many terms have been used to classify anticoagulant regimens, the following terminology will be used
in this document:
Low-dose prophylaxisa fixed dose of anticoagulant
given 12 times per day without use of routine monitoring to verify a therapeutic prolongation of the
activated partial thromboplastin time (APTT).
Adjusted-dose prophylaxisanticoagulant administered for prophylaxis to achieve traditional therapeutic effects, given 23 times per day with frequent
laboratory testing to verify adequate APTT prolongation of at least 1.5 to 2.5.
There is considerable clinical experience with heparin

use in pregnancy (11). Heparin requirements appear to
increase during pregnancy because of increases in
heparin-binding proteins, plasma volume, renal clearance, and heparin degradation by the placenta, which
reduces the bioavailability of heparin (12). There are no
prospective trials that have determined adequate prophylactic doses in pregnancy. The major concerns with
heparin use during pregnancy are not fetal but maternal
and include heparin-induced osteoporosis and heparininduced thrombocytopenia (HIT).
Two prospective trials of pregnant women exposed
to heparin confirmed a mean bone loss of 5% (13, 14),
with approximately one third sustaining a 10% or greater
decrease in bone density (13). The complete reversibility
of this process has not been clearly established, nor does
there appear to be a clear dose-response relationship (15).
In selected patients, such as those who have a strong family history of osteoporosis or are smokers, postpartum
evaluation of bone density may have prognostic and therapeutic implications (13, 14).
There are two types of heparin-induced thrombocytopenia. The more common type is the benign, reversible
nonimmune form, which occurs in patients within the first
few days of therapy and typically resolves by 5 days. This
Risk Factors for Deep Vein Thrombosis and

Thromboembolic Disorders
Hereditary Thrombophilia (prevalence in general
population)
Factor V Leiden mutation (59%)*
AT-III deficiency (0.020.2%)
Protein C deficiency (0.20.5%)
Protein S deficiency (0.08%)
Hyperhomocystinemia (111%)
Prothrombin gene mutation (24%)
Prior history of deep vein thrombosis
Mechanical heart valve
Atrial fibrillation
Trauma/prolonged immobilization/major surgery
Other familial hypercoagulable states
*For African Americans, about 1%; for Caucasians, 611%.
Data from Lockwood CJ. Heritable coagulopathies in pregnancy. Obstet
Gynecol Surv 1999;54:754765
706
Low-Molecular-Weight Heparin
Low-molecular-weight heparin may reduce three of the
complications caused by standard heparin: bleeding, osteoporosis, and thrombocytopenia (16, 18, 19). However, virtually all data on LMWH come from nonpregnant patients.
It has been conclusively demonstrated that LMWH does
not cross the placenta into the fetal circulation (20, 21).
Although the bioavailability of LMWH should be
improved over standard heparin because of the reduction of
heparin binding, the increases in renal clearance and volume of distribution of the drug may necessitate dosage
increases in pregnancy (22, 23). Another advantage of
LMWH is that dosing can be limited to once or twice daily
(22, 24). If laboratory monitoring is used, monitoring peak
antifactor Xa levels every 46 weeks should be utilized
particularly when twice daily dosing is given. The APTT
does not correlate well with the anticoagulant effect of
LMWH.
Warfarin
Warfarin derivatives cross the placenta and in most cases
are relatively contraindicated in pregnancy; therefore,
they primarily are used postpartum or in patients with
certain types of mechanical heart valves (2529). Warfarin use should be restricted to the second or early third
trimester in selected patients in whom prolonged highdose heparin therapy is relatively contraindicated. A
skeletal embryopathy resulting in stippled epiphyses and
nasal and limb hypoplasia can occur when warfarin is
given between 6 and 12 weeks of gestation (30).
Midtrimester exposure may result in optic atrophy,
microcephaly, and developmental delay. Bleeding can
occur in the fetus at any time, resulting in a high fetal loss
rate (30).

Recommendations
condition does not require cessation of heparin therapy.

The less common but more severe type is the immune form
of HIT, which occurs within 514 days of full-dose
heparin therapy in as many as 3% of patients (16) and may
result in widespread thrombosis (17, 18). The occurrence
of autoimmune thrombocytopenia from prophylactic doses
of heparin has been reported, but is rare. Deep vein thrombosis and PE are the most frequent clinical presentations of
the immune form of HIT. It has been recommended, therefore, that platelet counts be checked on day 5 and then
periodically for the first 2 weeks of heparin therapy. If the
HIT is severe, heparin therapy must be stopped and alternative anticoagulation therapy initiated; low-molecularweight heparin (LMWH) may not be a safe alternative
because it has a low cross reactivity with heparin. In such
situations, consultation with someone with expertise in the
field may be needed (17, 18).
Who are candidates for thromboprophylaxis

in pregnancy?
Thromboprophylaxis is defined as administration of anticoagulants because of an increased risk of VTE during

pregnancy rather than treatment for an acute event. Often
this can be accomplished using relatively low doses,
which have a minimal effect on laboratory measures of
coagulation. Such low-dose prophylaxis carries fewer
risks than full therapeutic anticoagulation. There are certain high-risk conditions that require dosage adjustments
to achieve higher therapeutic levels of anticoagulation
(adjusted-dose heparin prophylaxis). Each patients regimen should be individualized once the risks of heparin
therapy are weighed against the benefits (31).
Patients with the following conditions are at highest
risk and should have adjusted-dose heparin prophylaxis
(12):
Artificial heart valves (some investigators recommend warfarin therapy after the first trimester in
certain circumstances) (2629)
Antithrombin-III (AT-III) deficiency (with or without a history of thrombosis; also referred to as antithrombin deficiency) (32, 33)
Antiphospholipid syndrome (some investigators recommend low-dose prophylaxis for this condition if
there is no history of DVT) (34, 35)
History of rheumatic heart disease with current atrial fibrillation (36)
Homozygous factor V Leiden mutation, homozygous prothrombin G20210A mutation
Patients receiving chronic anticoagulation for recurrent thromboembolism
Patients who are identified carriers of other inherited
thrombophilias who do not have a history of thrombosis
but have a strong family history of thrombosis (36) and
noncarriers with a history of thromboembolic events
before the current pregnancy (34) appear to be at lower
risk and may be candidates for low-dose prophylaxis.
However, no data exist to support or refute this approach.
It is not clear whether patients with a history of
thrombosis identified with a protein C or protein S deficiency should receive low-dose or adjusted-dose heparin
prophylaxis during pregnancy. It is also not known
whether asymptomatic women who have been identified
as carriers of inherited thrombophilia (except AT-III or
homozygosity to the factor V Leiden or prothrombin
G20210A mutation) and who are without a personal or
PRACTICE BULLETINS
family history of thromboembolism should receive

heparin prophylaxis because there is marked variation in
the penetrance of the thrombotic trait.
Patients with a history of idiopathic thrombosis,
extensive or life-threatening thrombosis, recurrent thrombosis, thrombosis related to a high estrogen state, or who
have an underlying thrombophilia or postthrombotic syndrome are likely to be at a higher risk of recurrence in
pregnancy than patients with a definite transient provocation (orthopedic trauma or surgery) without any of these
risk factors. The former group should consider antepartum
thromboprophylaxis beginning in the first trimester and
continuing until 6 weeks postpartum. It is unclear whether
patients who have sustained VTE from a transient and
highly thrombogenic provocation (eg, orthopedic trauma)
and who have no other risk factors may benefit from
antepartum prophylaxis. Their risk of recurrence is likely
higher than the baseline population, and an increasing
number of thrombophilic states are being identified in
patients who sustain thromboses in the setting of recognized transient provocations (37). Although data are limited, some experts recommend that, at minimum, such
patients be given postpartum prophylaxis with warfarin.
How should a prophylactic heparin regimen

be administered during pregnancy?
Because of the absence of adequate prospective trials, a

number of different prophylactic regimens have been
offered by varying consensus panels, often based on nonpregnant patient studies (34, 38, 39) (see the box).
One study determined that during pregnancy, a doubling of the dose of heparin was required to achieve the
same anticoagulant response of a nonpregnant patient taking 5,000 U of heparin twice daily for low-dose prophylaxis (12). Some patients who are AT-III deficient will not
respond to heparin and may require AT-III factor therapy
(40).
Pregnant patients who require adjusted-dose heparin
for anticoagulation for long-term prophylaxis may theoretically benefit from the higher bioavailability and more consistent therapeutic anticoagulation with LMWH (41, 42).
Who should be tested for inherited or acquired

thrombophilias?
Women who have a history of thrombosis should be

offered testing, especially if such testing would affect
management. It is controversial whether to test women
who do not have a history of thrombosis but have a fami-
707
Prophylactic Heparin Regimens in Pregnancy

Unfractionated Heparin
Lowdose prophylaxis:
1. 5,0007,500 U every 12 hours during the
first trimester
7,50010,000 U every 12 hours during the
second trimester
10,000 U every 12 hours during the third
trimester unless the APTT* is elevated. The
APTT may be checked near term and the
heparin dose reduced if prolonged
OR
2. 5,00010,000 U every 12 hours throughout
pregnancy
Adjusted-dose prophylaxis:
10,000 U twice a day to three times a day to
achieve APTT of 1.52.5
Low-Molecular-Weight Heparin
Low-dose prophylaxis:
Dalteparin, 5,000 U once or twice daily, or enoxaparin, 40 mg once or twice daily
Adjusted-dose prophylaxis:
Dalteparin, 5,00010,000 U every 12 hours, or
enoxaparin, 3080 mg every 12 hours
*APTT indicates activated partial thromboplastin time.
Data from Colvin BT, Barrowcliffe TW. The British Society for
Haematology guidelines on the use and monitoring of heparin 1992:
second revision. J Clin Pathol 1993;46:97103. Ginsberg JS, Hirsh J.
Use of antithrombotic agents during pregnancy. Chest 1998;114:
524S530S. Maternal and Neonatal Haemostasis Working Party of the
Haemostasis and Thrombosis Task. Guidelines on the presentation,
investigation and management of thrombosis associated with pregnancy. J Clin Pathol 1993;46:489496
ly history of thrombosis. Women who have a first-degree

relative with an AT-III deficiency or homozygous factor
V Leiden or prothrombin G20210A mutation may benefit from testing. Individuals with a strong family history of
thrombophilias may be more likely to have multiple
inherited risk factors with an increased risk of thrombosis
(4 40%) during pregnancy (32, 43, 44). The coexistence
of multiple inherited risk factors has been demonstrated.
In one study, 15% of patients with protein C deficiency
and 39% with protein S deficiency also were positive for
factor V Leiden mutations, which markedly increased the
risk of thrombosis for the patient (45).
708
Which tests should be ordered?
The following tests may be ordered to evaluate the risk for

thromboembolic events in women with a history of
thrombosis, a family history of thrombosis, or a firstdegree relative with a specific mutation:
Lupus anticoagulant (for women with a personal history of VTE)
Anticardiolipin antibodies (for women with a personal history of VTE)
Factor V Leiden mutation
Prothrombin G20210A mutation
AT-III antigen activity levels
Fasting homocysteine levels or the MTHFR mutation
prothrombin G20210A mutation, and the MTHFR mutation are reliable in pregnancy.
Patients with a history of thrombosis, recurrent fetal

loss, early or severe preeclampsia, or severe unexplained
intrauterine growth restriction may be tested for antiphospholipid antibodies. Prophylactic anticoagulation for
patients with antiphospholipid syndrome has been shown
to improve pregnancy outcome (35, 46).
Deficiencies in protein C, protein S, and AT-III and
mutations, including factor V Leiden, prothrombin
G20210A, and C677T in the methylenetetrahydrofolate
reductase (MTHFR) gene associated with hyperhomocystinemia, also have been associated with severe early
preeclampsia, unexplained fetal loss or stillbirth, and
placental abruption (4749). However, there are no randomized clinical trials supporting the efficacy of anticoagulation therapy in preventing these conditions. It is important
to discuss with the patient the implications of a positive test
result for one of these thrombophilias and to determine
whether patient management would be altered during the
pregnancy or in the future if the test results are positive.
How is deep vein thrombosis detected in pregnancy?
A high index of suspicion is required for the diagnosis of

DVT in pregnancy because some of the symptoms of
DVT are similar to the common symptoms of pregnancy.
Noninvasive testing for DVT includes compression ultrasound (CUS), which uses firm compression with the
ultrasound transducer probe to detect an intraluminal filling defect and impedance plethysmography (IPG), which
measures impedance flow with pneumatic cuff inflation
around the thigh. In the symptomatic nonpregnant patient,
IPG has a sensitivity of 83% and specificity of 92% of
detecting proximal DVT. Compression ultrasound has a
sensitivity of 95% for proximal DVT (73% for distal
DVT) and specificity of 96% for detecting all DVT (54),
with a negative predictive value of 98% and a positive
predictive value of 97% in the nonpregnant symptomatic
patient. It has been shown that if serial (3 or more followup tests over 714 days) IPGs have normal results in a
symptomatic pregnant patient with a suspected DVT, it
appears safe to withhold anticoagulation (55).
If the clinical suspicion is high and noninvasive test
results are negative, limited venography with abdominal
shielding that results in fetal exposure less than 0.05 rads
should be considered (56). If iliac or pelvic thrombosis is
suspected, full venography can be performed (bilateral
venography without shielding results in fetal exposure
<1.0 rads) (56). Diagnosis of pelvic vein thrombosis and
internal iliac thrombosis is difficult. Although the use of
venography is widespread, MRI may become the imaging
modality of choice in these circumstances, but its role still
is not well defined in the pregnant patient (57).
Protein C antigen activity levels

Given the low prevalence of AT-III and the variable
pathogenicity of protein C and protein S, consideration
should be given to testing only when all other studies have
yielded negative results. It is important to note that physiologic changes in normal pregnancy result in marked
alterations in protein S and activated protein C resistance,
which is associated with the factor V Leiden mutation;
therefore, deferral of testing until after pregnancy may be
warranted. For example, protein S levels decline by 40%
in pregnancy (50, 51). Also, testing for AT-III, protein C,
and protein S in the setting of extensive clotting, warfarin
use, or heparin administration may result in falsely low
values (33, 52, 53). DNA testing for the factor V Leiden,
Protein S antigen activity levels (free and total)
How is the diagnosis of pulmonary embolism

made if suspected clinically?
The diagnosis of PE has traditionally been evaluated initially with ventilationperfusion scanning (V/Q). A V/Q
scan results in minimal radiation exposure to the fetus
(<0.1 rads). However, any outcome other than high probability or normal requires further testing because of insufficient accuracy to rule out PE in patients for which there is
a high clinical suspicion (58). Unfortunately, about
4060% of V/Q scans are nondiagnostic in the nonpregnant
population (neither high probability nor normal), and further evaluation becomes necessary. If noninvasive testing
(IPG, CUS) reveals a proximal DVT, then anticoagulation
therapy can be initiated. If the results of these tests are neg-
PRACTICE BULLETINS
How should heparin be administered to

women with acute thrombosis or embolism
during pregnancy?
How is anticoagulation managed in the intrapartum and postpartum period?
Intrapartum care is complicated, and treatment approaches vary. In such situations, it may be helpful to consult
with personnel who have expertise in the intrapartum
management of such patients. Patients requiring therapeutic adjusted-dose heparin during pregnancy, including
those with recent thromboembolism, and patients with
mechanical heart valves may be switched to intravenous
heparin at the time of labor and delivery to take advantage of its short half-life (112 hours). Patients can then be
switched to warfarin postpartum. Heparin and warfarin
therapy should be overlapped for the first 57 days postpartum until an international normalized ratio (INR) of
approximately 2.03.0 has been achieved (67).
Patients receiving prophylactic anticoagulation with
heparin should be instructed to withhold their injections
at the onset of labor. Patients requiring adjusted-dose,
prophylactic anticoagulation for high-risk conditions can
resume their heparin injections 48 hours after an
uncomplicated delivery, and warfarin can be administered the following morning. Postpartum dosing for
women on low-dose prophylactic heparin varies widely,
although all concur that the postpartum period is one of
high risk. There are no definitive studies to guide ones
approach in such situations.
Acute thromboembolism associated with pregnancy

requires an intravenous heparin bolus of 5,000 U (80
IU/kg) followed by continuous infusion of at least 30,000
IU for 24 hours titrated to achieve full anticoagulation (3,
65). Intravenous anticoagulation should be maintained for
at least 57 days. The patient can then be changed to subcutaneous adjusted-dose heparin therapy. Subcutaneous
injections should be given to pregnant patients every 8
hours to prolong the APTT at least 1.52.5 times control
throughout the dosing interval, similar to patients who are
not pregnant (58, 66). The APTT cannot gauge the adequacy of anticoagulation with therapeutic heparin in
patients with antiphospholipid syndrome for which small
amounts of heparin may markedly increase the APTT.
Levels of antifactor Xa may be used instead.
Therapeutic heparinization with subcutaneous dosing
every 812 hours should be continued for at least 3
months after the acute event. After 3 months of therapeutic heparinization, experts differ as to what should be
done for the remainder of the pregnancy. Some recommend using a lower dose of subcutaneous heparin. Others
recommend continuing therapeutic anticoagulation for
the remainder of the pregnancy (34).
Low-molecular-weight heparin may be an alternative
treatment for acute thromboembolism. Although the actual dosing is unclear in pregnancy, dosage should be adjusted based on maternal weight. Although laboratory testing
appears not to be essential in the nonpregnant patient, the
role of monitoring antifactor Xa levels is not clear in the
pregnant patient. The effectiveness of LMWH is less
affected by changes in maternal physiology than is
heparin, but there are still changes as pregnancy progresses. Therefore, it may be warranted to periodically reevalu-
ate antifactor Xa levels during pregnancy in a woman on

adjusted-dose or full anticoagulation. Ideally, dosing
should be enough to achieve a peak antifactor Xa level of
0.51.2 U/mL (22, 34). Some experts also check trough
levels to ensure that they remain in the lower limits of the
anticoagulation range. Pending further informative data,
the clinician may either use peak or trough levels, or both,
to assess anticoagulation.
ative, but clinical suspicion is high, then pulmonary

angiography should be considered (54).
Spiral computed tomography (CT) may be useful for
diagnosing PE; however, there is still difficulty reliably
identifying emboli below the segmental level (59). Both
sensitivity and specificity of spiral CT in nonpregnant
patients for central pulmonary artery embolus are approximately 94%. It also may detect abnormalities other than
PE responsible for symptoms (pleural effusions, consolidation, emphysema, pulmonary masses) and may be more
specific in patients with underlying cardiopulmonary disease (6062). Magnetic resonance angiography also may
be promising, but current technology limits adequate
visualization of subsegmental defects (63, 64). Both techniques are unstudied in pregnancy.
709
Can regional anesthesia be administered to

patients receiving anticoagulants?
The use of major conduction anesthesia (spinal or epidural) in patients receiving thromboembolic prophylaxis is
controversial (68, 69). Intraoperative or postoperative anticoagulation after regional anesthesia is thought to be safe;
however, the safety of LMWH, unfractionated heparin, or
oral anticoagulants administered before the procedure is
unclear. Because there are no studies addressing anticoagulation in pregnancy relative to the use of conduction
anesthesia, data from nonpregnant patients must be used.
Unfractionated low-dose heparin (5,000 IU twice
daily) appeared not to pose a significant risk for spinal
hematoma in over 5,000 nonpregnant patients who received
it in combination with spinal or epidural anesthesia (70).
710
Pregnant patients with a history of idiopathic

thrombosis, thrombosis related to pregnancy or oral
contraceptive use, or a history of thrombosis accompanied by an underlying thrombophilia other than
homozygous for the factor V Leiden mutation, heterozygous for both the factor V Leiden and the prothrombin G20210A mutation, or AT-III deficiency
should be offered antepartum and postpartum lowdose heparin prophylaxis.
Patients without a history of thrombosis but who

have an underlying thrombophilia and have a strong
family history of thrombosis also are candidates for
antepartum and postpartum prophylaxis. At the minimum, postpartum prophylaxis should be offered.
Pregnant patients with a history of life-threatening

thrombosis, with recent thrombosis, with recurrent
thrombosis, receiving chronic anticoagulation, or
patients with thrombosis found to be AT-III deficient, homozygous for the factor V Leiden mutation
or prothrombin G20210A mutation, heterozygous
for both the factor V Leiden and the prothrombin
G20210A mutation should be given adjusted-dose
heparin every 8 hours to maintain the APTT at least
1.5 times control throughout the dosing interval.
Low-molecular-weight heparin administered twice
daily also is an alternative.
Patients at risk for thrombosis should receive warfarin postpartum for 6 weeks to achieve an INR of
approximately 2.03.0. Heparin should be given
immediately postpartum with warfarin for at least 5
days until the INR is therapeutic.
Patients with antiphospholipid syndrome and a history of thrombosis require adjusted-dose prophylactic anticoagulation.
Patients who are candidates for either prophylactic

or therapeutic heparin may be given enoxaparin or
dalteparin during pregnancy. However, because of
the lack of data regarding adequate dosing during
pregnancy, antifactor Xa levels may be monitored.
Summary
has been excluded may be offered heparin prophylaxis or no prophylaxis during the antepartum period. However, they should be counseled that their risk
of thromboembolism is likely to be higher than the
normal population. Prophylactic warfarin should be
offered for 6 weeks postpartum.
Although extensive clinical testing in Europe during

the past decade suggested that there was no increased risk
in patients receiving perioperative LMWH thromboprophylaxis, the U.S. Food and Drug Administration reported cases of epidural or spinal hematomas in nonpregnant
patients with concurrent use of enoxaparin (a low-molecular-weight heparin) and spinal or epidural anesthesia or
spinal puncture (71). Many of the epidural or spinal
hematomas caused neurologic injury, including longterm or permanent paralysis. The discrepancy in the incidence of epidural or spinal hematomas in the European
versus the United States literature may be related to higher dosing and preference in the United States of continuous epidurals rather than single shot spinals (70, 72). In
one British study of pregnant women, there were no
spinal hematomas in the 43 women receiving LMWH
thromboprophylaxis who also received epidural analgesia (22). However, the doses given were lower than are
currently employed and usually administered once a day.
The American Society of Regional Anesthesia has
recommended that patients receiving higher doses of
LMWH (specifically enoxaparin, 1 mg/kg twice daily)
should not receive neuraxial blocks for 24 hours from the
last dose (73). Also, obtaining an antifactor Xa level
before placing the block was not recommended because
it was believed not to be adequately predictive of the risk
of bleeding. Needle placement in patients receiving lowdose, once daily LMWH should occur at least 1012
hours after the LMWH dose. No specific recommendations were made for patients using an intermediate dose
of 3040 mg of enoxaparin twice daily. However, given
that twice daily dosing may maintain antifactor Xa levels
between 0.1 and 0.2 IU/mL 12 hours after injection, it
would seem prudent to delay epidural anesthesia for 24
hours after the last injection. Alternatively, patients could
be switched to standard heparin at term because a normal
APTT usually is sufficient to ensure the safety of epidural anesthesia in a heparin anticoagulated patient as long
as the platelet count also is normal.
The safety of epidural anesthesia with twice-daily

dosing of LMWH is of concern and should be withheld until 24 hours after the last injection.
Pregnant patients with a history of isolated venous

thrombosis directly related to a transient, highly
thrombogenic event (orthopedic trauma, complicated surgery) in whom an underlying thrombophilia
PRACTICE BULLETINS
Epidural anesthesia appears to be safe in women taking unfractionated low-dose heparin if the APTT is
normal.
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to miscarriage or placental infarction. Am J Obstet
Gynecol 1997;177:402405 (Level II-2)
49. Kupferminc MJ, Eldor A, Steinman N, Many A, Bar-Am
A, Jaffa A, et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N
Engl J Med 1999;340:913 (Level II-2)
50. Faught W, Garner P, Jones C, Ivey B. Changes in protein
C and protein S levels in normal pregnancy. Am J Obstet
Gynecol 1995;172:147150 (Level II-3)
51. Lefkowitz JB, Clarke SH, Barbour LA. Comparison of
protein S functional and antigenic assays in normal pregnancy. Am J Obstet Gynecol 1996;175:657650 (Level II-3)
52. Rao AK, Kaplan R, Sheth S. Inherited thrombophilic states.
Semin Thromb Hemost 1998;24(suppl 1):312 (Level III)
53. Reiter W, Ehrensberger H, Steinbrckner B, Keller F.
Parameters of haemostasis during acute venous thrombosis. Thromb Haemost 1995;74:596601 (Level III)
54. Douketis JD, Ginsberg JS. Diagnostic problems with
venous thromboembolic disease in pregnancy.
Haemostasis 1995;25:5871 (Level III)
55. Hull RD, Raskob GE, Carter CJ. Serial impedance
plethysmography in pregnant patients with clinically suspected deep-vein thrombosis. Clinical validity of negative
findings. Ann Intern Med 1990;112:663667 (Level II-3)
56. Ginsberg JS, Hirsh J, Rainbow AJ, Coates G. Risks to the
fetus of radiologic procedures used in the diagnosis of
maternal venous thromboembolic disease. Thromb
Haemost 1989;61:189196 (Level III)
40. Lechner K, Kyrle PA. Antithrombin III concentratesare

they clinically useful? Thromb Haemost 1995;73:340348
(Level III)
57. Spritzer CE, Evans AC, Kay HH. Magnetic resonance

imaging of deep venous thrombosis in pregnant women
with lower extremity edema. Obstet Gynecol 1995;85:
603607 (Level III)
41. Barbour LA. Current concepts of anticoagulant therapy in

pregnancy. Obstet Gynecol Clin North Am 1997;24:
499521 (Level III)
58. Ginsberg JS. Management of venous thromboembolism. N

Engl J Med 1996;335(24):18161828 (Level III)
42. Weitz JI. Drug therapy: low molecular weight heparin. N

Engl J Med 1997;337:688698 (Level III)
59. Hansell DM. Spiral computed tomography and pulmonary

embolism: current state. Clin Radiol 1997;52:575581 (Level
III)
43. Miletich JP. Thrombophilia as a multigenic disorder. Semin

Thromb Hemost 1998;24(suppl 1):1320 (Level III)
60. Cross JJ, Kemp PM, Walsh CG, Flower CD, Dixon AK. A
randomized trial of spiral CT and ventilation perfusion
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scintigraphy for the diagnosis of pulmonary embolism.

Clin Radiol 1998;53:177182 (Level I)
61. Lipchik RJ, Goodman LR. Spiral computed tomography in
the evaluation of pulmonary embolism. Clin Chest Med
1999;20:731738 (Level III)
62. Kim KI, Muller NL, Mayo JR. Clinically suspected pulmonary embolism: utility of spiral CT. Radiology
1999;210:693697 (Level III)
63. Meaney JF, Weg JG, Chenevert TL, Stafford-Johnson D,
Hamilton BH, Prince MR. Diagnosis of pulmonary
embolism with magnetic resonance angiography. N Engl J
Med 1997;336:14221427 (Level II-2)
64. Woodard PK, Yusen RD. Diagnosis of pulmonary
embolism with spiral computed tomography and magnetic
resonance angiography. Curr Opin Cardiol 1999;14:
442447 (Level III)
65. Bates SM, Ginsberg JS. Thrombosis in pregnancy. Curr
Opin Hematol 1997;4:335343 (Level III)
66. Ramin SM, Ramin KD, Gilstrap LC. Anticoagulants and
thrombolytics during pregnancy. Semin Perinatol 1997;21:
149153 (Level III)
67. Hyers TM, Agnelli G, Hull RD, Weg JG, Morris TA,
Samama M, et al. Antithrombotic therapy for venous
thromboembolic disease. Chest 1998;114:561S578S
(Level III)
68. Haljame H. Thromboprophylaxis, coagulation disorders,
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1996;40:10241040 (Level III)
69. Hynson JM, Katz JA, Bueff HU. Epidural hematoma associated with enoxaparin. Anesth Analg 1996;82:10721075
(Level III)
70. Horlocker TT, Wedel DJ. Neuraxial block and low-molecular-weight heparin: balancing perioperative analgesia and
thromboprophylaxis. Reg Anesth Pain Med 1998;23(6
Suppl 2);164177 (Level III)
71. U.S. Department of Health and Human Services. FDA
Public Health Advisory, Subject: reports of epidural or
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72. Tryba M. European practice guidelines: thromboembolism
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73. American Society of Regional Anesthesia (ASRA).
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713

to conduct a literature search to locate relevant articles published between January 1985 and March 1998. The search
Force:
I
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
714
ACOG
PRACTICE
BULLETIN
(Replaces Educational Bulletin Number 177, February 1993)

of Kim Boggess, MD. The information is designed to aid
of practice.
Reaffirmed 2009
Perinatal Viral and

Parasitic Infections
Many viral and parasitic infections are associated with significant maternal
and fetal consequences if acquired during pregnancy. In the United States,
some of the most commonly encountered infections with subsequent perinatal
effects include cytomegalovirus (CMV), parvovirus B19, varicella zoster virus
(VZV), and toxoplasmosis. The purpose of this document is to describe these
infections, their modes of transmission, and their maternal and fetal effects,
and to offer guidelines for counseling about and management of these infections
during pregnancy.
Background
In general, perinatal infections have more severe fetal consequences when they
occur early in gestation, because first-trimester infections may disrupt organogenesis. Second- and third-trimester infections can cause neurologic impairment or growth disturbances. In utero infection may be associated with certain
ultrasound findings, including intrauterine growth restriction, echogenic bowel,
intracranial or intrahepatic calcifications, hydrocephalus, microcephaly, isolated ascites, pericardial or pleural effusions, or nonimmune hydrops, although
congenital infections also can be asymptomatic.
Cytomegalovirus
Cytomegalovirus is a double-stranded DNA herpesvirus that is transmitted by
contact with infected blood, saliva, or urine, or by sexual contact. The incubation period of CMV is 2860 days, with a mean of 40 days. Infection induces an
immunoglobulin M (IgM) antibody response that disappears within 3060 days.
Viremia can be detected 23 weeks following primary infection. Primary CMV
infection in adults generally is asymptomatic. Occasionally, patients experience
a mononucleosislike syndrome, with leukocytosis, lymphocytosis, abnormal
PRACTICE BULLETINS
liver function tests, fever, malaise, myalgias, and chills

(1). After the initial infection, CMV remains latent in host
cells; recurrent infection can occur following reactivation
of latent virus. In rare cases, recurrent CMV infection can
occur by infection with a new strain of virus.
Prevalence of both primary and recurrent infection in
pregnant women varies regionally from 0.7% to 4% for
primary infection and up to 13.5% for recurrent infection
(2). Vertical transmission of CMV may occur as a result
of transplacental infection after primary or recurrent
CMV infection, exposure to contaminated genital tract
secretions at parturition, or breastfeeding. Most infants
with congenital CMV are asymptomatic at birth. Clinical
findings of symptomatic congenital CMV infection
include jaundice, petechiae, thrombocytopenia, hepatospleno-megaly, growth restriction, and nonimmune
hydrops (3, 4). The annual cost of treating the complications of CMV infections in the United States is estimated
to be approximately $2 billion (2), which reflects the
5080% seropositivity rate of pregnant women.
Cytomegalovirus is the most common congenital infection, occurring in 0.22.2% of all neonates (5), and is
the leading cause of congenital hearing loss. Vertical transmission may occur at any stage of pregnancy, with the
overall risk of infection greatest when the infection occurs
during the third trimester. However, more serious fetal
sequelae occur after maternal CMV infection during the
first trimester. With primary maternal CMV infection, the
risk of transmission to the fetus is 3040% (6). Of those
infected in utero following a primary infection, 10% will
have signs and symptoms of CMV infection at birth and
develop sequelae (7). Approximately 30% of severely
infected infants die, and 80% of survivors have severe neurologic morbidity (5, 8). The incidence of severe fetal
infection is much lower after recurrent maternal infection
than after primary infection. Vertical transmission after a
recurrent infection is 0.152% (8, 9). Infants infected
after maternal CMV reactivation generally are asymptomatic at birth. Congenital hearing loss is typically the most
severe sequela of secondary infection, and congenital
infection following recurrent infection is unlikely to produce multiple sequelae (9). Cytomegalovirus infection
acquired as a result of exposure to infected cervical
secretions or breast milk is typically asymptomatic and is
not associated with severe neonatal sequelae.
Parvovirus B19
Parvovirus B19 is a single-stranded DNA virus that causes the childhood exanthem erythema infectiosum, also
known as fifth disease. In immunocompetent adults, the
most common symptoms of parvovirus B19 infection are
a reticular rash on the trunk and peripheral arthropathy,
715
although approximately 33% of infections are asymptomatic (10). Another manifestation of parvovirus B19
infection is transient aplastic crisis, which is more common in those with an underlying hemoglobinopathy.
Most infections are mild; most individuals recover completely from parvovirus B19 infection and require only
supportive care.
Transmission of parvovirus B19 most commonly
occurs through respiratory secretions and hand-to-mouth
contact. The infected person generally is infectious 510
days after exposure prior to the onset of the rash or other
symptoms and is no longer infectious with the onset of
the rash (11). Both IgM and IgG are produced in
response to infection. The IgM response, which persists
for 1 to several months, is indicative of a recent infection.
IgG antibodies persist indefinitely and, in the absence of
IgM, indicate prior infection and immunity. Prevalence
of seropositivity to parvovirus B19 increases with age
and is greater than 60% in adolescents and adults (11).
The risk of maternal infection of parvovirus B19 varies
with level of exposure to the infected individual.
Exposure to a household member infected with parvovirus B19 is associated with an approximate 50% risk
of seroconversion (1215). The risk of transmission in a
child care setting or classroom is lower, ranging from
approximately 20% to 50% (1517).
Recent maternal infection with parvovirus B19 constitutes a low risk for fetal morbidity (18), although some
cases have been associated with adverse fetal effects.
Transplacental transmission has been reported to be as
high as 33% (19), and fetal infection with parvovirus B19
has been associated with spontaneous abortion, hydrops
fetalis, and stillbirth. The rate of fetal loss among women
with serologically proven parvovirus B19 infection ranges
from 2% to 9% (2022). In utero, parvovirus B19 infection is responsible for up to 18% of cases of nonimmune
hydrops fetalis in some series (23, 24). Hydrops fetalis
results from aplastic anemia, myocarditis, or chronic
fetal hepatitis. Severe effects are seen most frequently
among fetuses when maternal parvovirus B19 infection
occurs at less than 20 weeks of gestation (20). Stillbirth
resulting from maternal infection has occurred from 1 to
11 weeks after maternal infection. However, hydrops is
unlikely to develop if it has not occurred by 8 weeks after
maternal infection (23). Long-term development appears
to be normal in fetuses with congenital parvovirus B19
infection that do not succumb to the disease (25, 26).
Varicella Zoster Virus

Varicella zoster virus is a DNA herpesvirus that is highly
contagious and is transmitted by respiratory droplets or
close contact. The attack rate among susceptible contacts
716
is 6090% after exposure. The incubation period after

infection is 1020 days, with a mean of 14 days (27). The
period of infectivity begins 48 hours before the rash
appears and lasts until the vesicles crust over. The primary infection causes chickenpox, which is characterized by
fever, malaise, and a maculopapular pruritic rash that
becomes vesicular. After the primary infection, VZV
remains dormant in sensory ganglia and can be reactivated
to cause a vesicular erythematous skin rash known as herpes
zoster. The antibody to VZV develops within a few days
after the onset of infection, and prior infection with VZV
confers lifelong immunity.
Varicella infection is uncommon in pregnancy
(occurring in 0.40.7 per 1,000 patients), because of the
high prevalence of natural immunity (28). Pregnancy
complicated by maternal varicella infection is associated
with untoward maternal, fetal, and neonatal effects. The
disease usually is a benign and self-limited illness in children; however, varicella national mortality data indicate
that although less than 5% of varicella cases occur among
adults 20 years of age or older, that group contributes to
55% of varicella-related deaths (29). Severe complications, such as encephalitis and pneumonia, are more
common in adults than in children; VZV pneumonia in
pregnancy is a risk factor for maternal mortality (30, 31).
In pregnancy, varicella may be transmitted across the
placenta, resulting in congenital or neonatal chickenpox.
The risk of congenital varicella syndrome is limited to
exposure during the first 20 weeks of gestation, occurs
uncommonly (up to 2%), and is characterized by skin
scarring, limb hypoplasia, chorioretinitis, and microcephaly (3234). Neonatal VZV infection is associated
with a high neonatal death rate when maternal disease
develops from 5 days before delivery up to 48 hours postpartum as a result of the relative immaturity of the neonatal immune system and the lack of protective maternal
antibody (35, 36).
phadenopathy, with symptoms occurring in only 1020%

of adult cases. Other symptoms include fever, malaise,
night sweats, myalgias, and hepatosplenomegaly. Parasitemia can occur after infection, which, in pregnant
women, can seed the placenta and cause subsequent fetal
infection. Congenital transmission of T gondii from an
infected woman was the first form of transmission to be
recognized, and transmission depends on the time of
acquisition of maternal infection. The later in gestation
that the infection occurs, the more likely transmission is
to occur. The rate of vertical transmission increases from
10% to 15% in the first trimester, to 25% in the second
trimester, and to more than 60% in the third trimester (37,
38). The severity of infection depends on gestational age
at the time of transmission. The earlier the fetus is infected, the more severe the disease. Most infected infants do
not have clinical signs of infection at birth, but 5585%
will develop sequelae, including chorioretinitis (leading
to severe impairment of vision), hearing loss, or mental
retardation (3941). Other clinical manifestations of congenital toxoplasmosis include rash, hepatosplenomegaly,
ascites, fever, periventricular calcifications, ventriculomegaly, and seizures (4244).
After an acute infection, IgM antibodies appear early
and reach maximum levels in 1 month. IgG antibodies
appear after IgM antibodies, are detectable within a few
weeks after infection, and confer immunity. High titers of
both IgG and IgM may persist for years. In the immunocompetent adult, the clinical course is benign and selflimited.

Recommendations
Cytomegalovirus
Toxoplasmosis
Toxoplasmosis is caused by the intracellular parasite
Toxoplasma gondii. T gondii exists in several forms: a
trophozoite, which is the invasive form, and a cyst or an
oocyst, which are latent forms. Human infection is
acquired by consuming cysts in undercooked meat of
infected animals, by insect contamination of food, by
contact with oocysts from the feces of infected cats (the
only definitive hosts), or by contact with infected materials or insects in soil. Infection with T gondii usually is
asymptomatic, although after an incubation of 518 days,
some nonspecific symptoms may occur. Most often, toxoplasmosis presents as asymptomatic cervical lym-
How is maternal CMV infection diagnosed?
The majority of adult CMV infections are asymptomatic,

which makes diagnosis of primary infection difficult.
Cytomegalovirus may be detected by culture or polymerase chain reaction (PCR) of infected blood, urine,
saliva, cervical secretions, or breast milk, although diagnosis of CMV infection in adults usually is confirmed by
serologic testing. Serum samples collected 34 weeks
apart, tested in parallel for anti-CMV IgG, are essential
for the diagnosis of primary infection. Seroconversion
from negative to positive or a significant increase (greater
than fourfold, eg, from 1:4 to 1:16) in anti-CMV IgG
titers is evidence of infection. The presence of CMV-specific IgM is a useful but not completely reliable indica-
PRACTICE BULLETINS
How is fetal CMV infection diagnosed?
How are maternal, fetal, and congenital

neonatal infections with cytomegalovirus
treated?
Currently, no therapies are available for the treatment of

maternal or fetal CMV infection. Antiviral treatment with
ganciclovir or foscarnet is approved only for treatment of
CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). However, ganciclovir has been
shown in vitro to cross the placenta by simple diffusion
(66), and there are reports of its postnatal use for the treatment of congenital CMV (6769). Ganciclovir and CMV
hyperimmune gamma globulin have shown promise for
the treatment of neonates with congenital CMV infection
(7072). The effectiveness of treatment in the prevention
of long-term neurologic sequelae has not been proven.
A live attenuated vaccine using the Towne 125 strain
has been developed, and appears to be safe, somewhat
protective (7376), and economically beneficial (77).
There is reluctance to embrace vaccination because of
concerns about the ability of the vaccine strain to reactivate and potentially infect the host, the potential for viral
shedding from the cervix or breast milk, and the possible
oncogenic potential of vaccine virus (78). However, the
science in this area is advancing rapidly, and new treatment options may become available.
How should women at high risk be counseled

about prevention of CMV?
Factors associated with an increased risk of CMV infection include history of abnormal cervical cytology, lower
socioeconomic status, birth outside North America, first
pregnancy at younger than 15 years, and infection with
other sexually transmitted diseases. The greatest impact
obstetriciangynecologists can have on reducing CMV
disease is by educating patients about preventive measures.
Counseling should cover careful handling of potentially
infected articles, such as diapers, and thorough hand-washing when around young children or immunocompromised
individuals, explaining that careful attention to hygiene is
effective in helping to prevent transmission (3, 12, 79). In
addition, women should be counseled, when appropriate,
about the avoidance of high-risk behaviors, such as intravenous drug use and sharing of needles. Condom use
should be encouraged as a method of contraception.
Congenital CMV may be suspected prenatally after a documented maternal primary infection or, more typically,
after detection of ultrasound findings suggestive of infection (46). These include abdominal and liver calcifications,
calcification of the lateral border of the lateral ventricles,
hydrops, echogenic bowel, ascites, hepatosplenomegaly,
and ventriculomegaly (4653). Fetuses that demonstrate
abnormalities, particularly if they involve the central nervous system, generally have a much poorer prognosis (46,
54).
Cytomegalovirus has been diagnosed prenatally by
detection of anti-CMV IgM in fetal blood (5557),
although this test has a high false-positive rate (58). In
addition, IgM is not detectable in the first half of pregnancy, presumably because of the immaturity of the fetal
immune system, limiting the usefulness of fetal serologic testing. Testing for fetal thrombocytopenia or abnormal liver function has been suggested as a method to
diagnose congenital CMV. However, these tests are not
specific for CMV, and normal results do not preclude
severe infection.
Cytomegalovirus can be detected in the amniotic
fluid of infected fetuses by either culture or PCR. The
sensitivity of CMV culture ranges from 50% to 69%,
compared with a sensitivity of 77100% for PCR. Negative and positive predictive values are comparable
between amniotic fluid culture and PCR (5557, 5964).
The sensitivity of amniotic fluid testing for prenatal diagnosis of congenital CMV infection is markedly lower if
performed before 21 weeks of gestation (65), and the
time interval between maternal infection and testing may
influence the reliability (62). Although these tests are
promising, neither amniotic fluid culture nor PCR can
detect all cases of congenital CMV infection. In addition,
the detection of CMV in amniotic fluid does not predict
the severity of congenital CMV infection. A combination
of amniotic fluid culture and PCR has been suggested to
have a sensitivity of 80100% in identifying infected
fetuses (56). Fetal blood sampling is less sensitive than
amniotic fluid testing (64). Specific ultrasonographic
findings may further assist in the accurate diagnosis of a
congenitally infected infant with a poor prognosis.
tion of a primary infection. IgM titers may not be positive

during an acute infection, or they may persist for months
after the primary infection (45). A small proportion of
women with recurrent infection will demonstrate antiCMV IgM (7). The reported sensitivity of CMV IgM
serologic assays ranges from 50% to 90% (45).
717
Should women at high risk be screened before

or during pregnancy?
Currently, routine serologic testing for CMV during pregnancy is not recommended (4, 7, 80, 81). Maternal IgM
718
Parvovirus B19
Which methods are available to diagnose

maternal parvovirus B19 infection?
What methods are available for diagnosing

fetal parvovirus B19 infection?
Diagnosis of fetal parvovirus B19 infection can be

accomplished by isolation of viral particles in abortuses
or placental specimens (89, 90). Polymerase chain reaction also has been used to detect parvovirus B19 in fetal
specimens, including autopsy tissue, serum, amniotic
fluid, and placenta (9195).
How are maternal, fetal, and congenital

neonatal infections with parvovirus B19
managed?
After documented exposure to parvovirus B19, the

woman should have serologic testing to determine if she
is immune with evidence of antiparvovirus IgG. If nonimmune, the test should be repeated in 34 weeks and
paired samples tested to document whether the woman is
seropositive for parvovirus. If seroconversion does not
occur, the fetus is not at risk for in utero infection. If seroconversion does occur, the fetus should be monitored for
10 weeks by serial ultrasound examination to evaluate for
presence of hydrops fetalis, placentomegaly, and growth
disturbances (9).
In a series of 618 pregnant women exposed to parvovirus, only 311 (50.3%) were susceptible to infection.
Of those susceptible, only 52 contracted parvovirus.
None of the 52 infants exposed to maternal parvovirus
developed hydrops fetalis (14). However, if hydrops
fetalis develops, percutaneous umbilical blood sampling
should be performed to determine the fetal hematocrit,
leukocyte and platelet count, and viral DNA in preparation for supportive care using transfusion (97, 98).
Intrauterine transfusion should be considered if anemia is
present (21, 99).
Maternal serology is the most commonly used test to

diagnose acute infection with parvovirus B19. Enzymelinked immunosorbent assay (ELISA), radioimmunoassay, and Western blot tests can measure the antibody to
parvovirus B19 (20). The sensitivity of IgM and IgG
assays is generally 79% (10, 87). Identification of parvovirus-specific IgM in maternal serum is diagnostic of a
primary infection, although a laboratory with experience
should measure titers, because false-positive results can
occur. Previous exposure and infection with parvovirus
B19 is indicated by the presence of antiparvovirus B19
IgG in the absence of IgM and has not been associated
with adverse perinatal outcome.
Parvovirus B19 can be identified by direct visualization of viral particles in infected tissues or serum by electron microscopy or by identification of characteristic
intranuclear inclusions within erythroblasts (88).
Sensitivity of PCR for detection of parvovirus may

be as high as 100%, although data are limited by small
sample sizes (94, 96). Reliable serologic tests for specific IgM antibodies in the fetus are not available. As with
other intrauterine infections, IgM antibodies appear in
the fetal circulation after 22 weeks of gestation, limiting
the usefulness of such tests.
Ultrasonography has been the mainstay for diagnosing fetal parvovirus infection. Severely infected fetuses
typically have evidence of hydrops fetalis. Serial ultrasound examinations for up to 10 weeks after maternal
infection are indicated. If the fetus shows no signs of
hydrops fetalis, additional tests are unnecessary.
antibody screening is limited for differentiating primary

from recurrent infection, which makes it difficult to use
such results in counseling patients about fetal risk. In
addition, maternal immunity does not eliminate the possibility of fetal infection.
Although the virus is not highly contagious, some
groups of women are at higher risk for the acquisition of
CMV infection. Eleven percent of seronegative child care
workers demonstrate seroconversion within 10 months of
hire (82), and 53% of families of young children have
one or more family members seroconvert within a year
(83, 84). In two cross-sectional studies, increasing parity
had an independent effect on increasing CMV seroprevalence, demonstrating the possibility of child-to-mother
transmission (85). Therefore, women with young children or those who work with young children should be
advised that the risk of infection can be reduced significantly by safe-handling techniques, such as the use of
latex gloves and rigorous hand-washing after handling
diapers or after exposure to respiratory secretions (3, 12,
86).
Should seronegative women with work-related exposure be taken out of work?
When outbreaks of parvovirus B19 infection occur in situations in which prolonged, close-contact exposure
occurs, as in schools, homes, or child care centers,
options for prevention of transmission are limited (20).
Exposure cannot be eliminated by identifying and
excluding persons with acute parvovirus B19 infection;
up to 20% are asymptomatic, and those with infection are
infectious before they develop symptoms. Exclusion of
pregnant women from the workplace during endemic
PRACTICE BULLETINS
periods is controversial, and a policy to routinely exclude

members of high-risk groups from work during an outbreak of parvovirus B19 is not recommended (14, 20).
Varicella Zoster Virus
How is maternal VZV infection diagnosed?
Usually, this diagnosis is based on clinical findings, and

laboratory testing is not needed, especially if a rash
occurs after known exposure. If laboratory diagnosis is
required, the VZV antigen can be demonstrated within
skin lesions or vesicular fluid by immunofluorescence.
Varicella infection also can be documented by the detection of the fluorescence antibody to the membrane antigen or of the VZV antibody by ELISA (28).
Although two small studies estimate the rate of congenital varicella syndrome after maternal infection with
VZV to be 12% (32, 34), these studies were subject to
bias, and these rates may be overestimated. The risk of
congenital varicella syndrome is small; however, the outcome for the affected infant is serious enough that a reliable method of prenatal diagnosis would be valuable.
Fetal varicella can be suspected by the presence
of ultrasonographic abnormalities. Ultrasound findings
suggestive of congenital varicella include hydrops, hyperechogenic foci in the liver and bowel, cardiac malformations, limb deformities, microcephaly, and intrauterine
growth restriction. In one series, five fetuses with congenital VZV demonstrated some ultrasound findings that
suggested infection, and all the infants died by 4 months
of age (100). However, not all fetuses with congenital
VZV that have ultrasound abnormalities do poorly (101).
Although the sensitivity of ultrasonography is unknown, it
is the preferred method of diagnosis of congenital VZV.
Invasive prenatal diagnosis in women who acquire
VZV in the first half of pregnancy may serve to provide
reassurance if test results are negative (102). However, if
the virus is present, identifying it by culture or viral DNA
by PCR in chorionic villi, amniotic fluid or fetal blood, or
the viral-specific antibody does not accurately predict the
severity of fetal infection (101, 103).
What therapies are available and effective for

maternal, fetal, and congenital neonatal
infections with varicella?
Oral acyclovir, if instituted within 24 hours of the rash, has

been shown to reduce the duration of new lesion formation
and the total number of new lesions and to improve constitutional symptoms in children, adolescents, and adults
(104106). Oral acyclovir appears to be safe and can be

prescribed for pregnant women if lesions develop (107).
Maternal varicella complicated by pneumonia should be
treated with intravenous acyclovir, because intravenous
acyclovir may reduce maternal morbidity and mortality
associated with varicella pneumonia (31, 108).
Maternal treatment with acyclovir has not been
shown to ameliorate or prevent the fetal effects of congenital varicella syndrome (109). Varicella-zoster
immune globulin (VZIG) should be given to infants born
to women who develop varicella between 5 days before
and 2 days after delivery, although this does not universally prevent neonatal varicella (110). Infants who develop varicella within the first 2 weeks of life should be
treated with intravenous acyclovir (107, 111).
How is fetal VZV infection diagnosed?
719
What preventive strategies are effective for

varicella?
Nonpregnant women of childbearing age should be questioned about previous infection with varicella preconceptionally and offered vaccination if no report of chickenpox
is elicited. Varicella vaccine has been available since
March 1995 and is approved for use in healthy susceptible persons 12 months or older (112). Conception should
be delayed until 1 month after the second vaccination
dose is given.
Among women who do not recall a history of varicella, 7090% have detectable antibodies (112).
Antenatal VZV screening of all pregnant women with
negative or indeterminate varicella histories is not
believed to be cost-effective by some (113). However,
others argue that from a cost-effectiveness/cost-benefit
standpoint, management based on immune testing is
preferable to universal VZIG administration when caring
for pregnant women exposed to VZV with a negative or
indeterminate infection history (114). Patients known to
be nonimmune to VZV should be counseled to avoid contact with individuals who have chickenpox. If exposure
does occur, prophylactic intervention with VZIG early in
the incubation period can prevent or attenuate the disease
manifestations of VZV in susceptible contacts at high
risk from this infection (106). Expeditious determination
of the VZV membrane antigen or equivalent anti-VZV
antibody status in pregnant women exposed to VZV
appears to be a rapid, satisfactory method for determining who should promptly receive VZIG passive immunization (115). Although VZIG is effective in reducing
the severity of maternal varicella when administered up
to 72 hours after exposure, it should be given as soon as
possible (116, 117). Maternal administration of VZIG
does not ameliorate or prevent fetal infection.
720
Toxoplasmosis
How is maternal toxoplasmosis infection

diagnosed?
Which methods are available for diagnosing

and monitoring fetal infection?
Ultrasonography can demonstrate severe congenital toxoplasmosis; suggestive findings include ventriculomegaly,
intracranial calcifications, microcephaly, ascites, hepatosplenomegaly, and intrauterine growth restriction.
Testing fetal blood samples after 20 weeks of gestation
for the presence of specific IgM is the most sensitive test
in diagnosing congenital toxoplasmosis (119). Using
fetal blood for antibody testing or mouse inoculation,
amniotic fluid for PCR, or fetal ultrasonography to detect
ventriculomegaly, 7793% of infected infants were identified prenatally, although no single test was very sensitive (43, 120). Successful identification of T gondii
intrauterine infection with PCR testing of amniotic fluid
allows for earlier testing than fetal blood sampling, with
high sensitivity (37, 121124), although false-positive
and false-negative findings do occur (125).
How are maternal, fetal, and congenital neonatal infections with toxoplasmosis treated?
Treatment of the pregnant woman with acute toxoplasmosis reduces but does not eliminate the risk of congen-
Isolation of T gondii from blood or body fluids establishes

that the infection is acute; however, serologic testing for
the detection of the specific antibody to T gondii is the
primary method of diagnosis. Numerous antibody assays
are available. The Sabin-Feldman dye test is the IgG test
with which all others are compared, but it is performed at
only a few reference laboratories. Indirect fluorescent
antibody, indirect hemagglutination and agglutination
tests, and ELISA also are available to detect the antitoxoplasma antibody. However, serologic assays for toxoplasmosis are not well standardized and have a high
false-positive rate. IgM titers may persist at high levels
(eg, 1:512) for years in healthy individuals (118). Both
IgG and IgM testing should be used for the initial evaluation of patients suspected to have toxoplasmosis.
Testing of serial specimens 3 weeks apart in parallel
gives the most accurate assessment if the initial test
results are equivocal. In cases in which clinical suspicion
is high, specimens should be saved for repeat testing
because of the wide variation between laboratories. Repeat
testing in a well-recognized reference laboratory should
be performed if there is evidence of a primary infection.
ital infection (42, 43). Identification of acute maternal

infection necessitates immediate institution of treatment
until results of fetal testing are known. Spiramycin,
which concentrates in the placenta, may reduce the risk
of fetal transmission by 60% (126), but as a single agent,
it does not treat established fetal infection. Spiramycin is
available only through the U.S. Food and Drug Administration after serologic confirmation at a reference laboratory; it is recommended for pregnant women at risk
unless fetal infection is documented. If fetal infection is
established, pyrimethamine, sulfonamides, and folinic
acid are added to the regimen because they more effectively eradicate parasites in the placenta and in the fetus
than spiramycin alone (127). With treatment, even early
fetal infection with toxoplasmosis can result in successful pregnancy outcomes (128).
Treatment of infants with symptomatic congenital
toxoplasmosis consists of pyrimethamine and sulfadiazine, alternating monthly with spiramycin, for 1 year
(127). Treatment will diminish or resolve intracranial calcifications if present, suggesting improved neurologic
function (129).
Should women be screened for toxoplasmosis

during pregnancy?
A multicenter study in the United States found that

approximately 38% of pregnant women have evidence
of prior toxoplasmosis infection (130). Evidence of
previous infection signifies that the future mother is not
at risk of giving birth to a child with congenital toxoplasmosis. Serologic screening as a way to prevent
congenital toxoplasmosis would have the most impact
in countries with a high frequency of seropositivity,
and routine prenatal screening is performed in France
and Austria (39). However, in the United States, routine
screening during pregnancy currently is not recommended, except in women infected with human immunodeficiency virus (HIV). Serologic screening during
pregnancy may yield equivocal results, because IgM
antibodies can persist for long periods (131). Exceptional circumstances may justify toxoplasmosis titer
screening for pregnant women who are cat owners. One
study in Belgium demonstrated a 63% reduction in the
rate of maternal toxoplasmosis infection after institution
of an educational program that recommended avoiding
eating undercooked or raw meat, wearing gloves when
working with soil, and avoiding caring for cats unless
they are strictly indoor cats whose food is rigidly controlled (131).
PRACTICE BULLETINS
Summary
The following recommendations are based on limited and inconsistent scientific data (Level B):
Pregnant women who are seronegative for VZV and

exposed to chickenpox should receive VZIG.
Pregnant women who develop chickenpox should be

treated with oral acyclovir to minimize maternal
symptoms; if pneumonia develops, they should be
treated with intravenous acyclovir.
Pregnant women who have acute parvovirus B19

infection during pregnancy should be monitored with
serial ultrasound examinations for at least 10 weeks
following infection for the presence of hydrops fetalis.
Fetuses with evidence of hydrops should undergo

fetal blood sampling and transfusion as needed.
Pregnant women who acquire toxoplasmosis should

be treated with spiramycin. When diagnosed, fetal
toxoplasmosis should be treated with a combination
of pyrimethamine, sulfadiazine, and folinic acid,
alternating with spiramycin.
Routine serologic screening of all pregnant women

for CMV and toxoplasmosis is not recommended.
Nonpregnant women of reproductive age who have

no history of varicella infection should be offered
varicella vaccine.
The diagnosis of toxoplasmosis should be confirmed

by a reliable reference laboratory.
Pregnant women exposed to parvovirus B19 should

have serologic screening performed to determine if
they are at risk for seroconversion.
Pregnant women should be counseled about methods

to prevent acquisition of CMV or toxoplasmosis during pregnancy.
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108. Cox SM, Cunningham FG, Luby J. Management of varicella pneumonia complicating pregnancy. Am J Perinatol
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109. American Academy of Pediatrics Committee on
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91:674676 (Level III) [erratum Pediatrics 1993;91:858]
110. Miller E, Cradock-Watson JE, Ridehalgh MK. Outcome
in newborn babies given anti-varicella-zoster immunoglobulin after perinatal maternal infection with varicellazoster virus. Lancet 1989;8659:371373 (Level II-3)
111. Williams H, Latif A, Morgan J, Ansari BM. Acyclovir in
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112. Centers for Disease Control and Prevention. Prevention
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Mortal Wkly Rep 1996;45(RR-11):136 (Level III)
113. Glantz JC, Mushlin AI. Cost-effectiveness of routine
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114. Rouse DJ, Gardner M, Allen SJ, Goldenberg RL.
Management of the presumed susceptible varicella
(chickenpox)-exposed gravida: a cost-effectiveness/costbenefit analysis. Obstet Gynecol 1996;87:932936
(Level III)
115. McGregor JA, Mark S, Crawford GP, Levin MJ.
Varicella zoster antibody testing in the care of pregnant
women exposed to varicella. Am J Obstet Gynecol 1987;
157:281284 (Level II-3)
116. Brunell PA, Ross A, Miller LH, Kuo B. Prevention of
varicella by zoster immune globulin. N Engl J Med
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117. Varicella-zoster immune globulin for the prevention of
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118. Montoya JG, Remington JS. Toxoplasma gondii. In:

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119. Fricker-Hidalgo H, Pelloux H, Racinet C, Grefenstette I,
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121. Grover CM, Thulliez P, Remington JS, Boothroyd JC.
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122. van de Ven E, Melchers W, Galama J, Camps W,
Meuwissen J. Identification of Toxoplasma gondii infections by BI gene amplification. J Clin Microbiol
1991;29:21202124 (Level III)
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726

to conduct a literature search to locate relevant articles published between January 1985 and January 2000. The search
Priority was given to articles reporting results of original research, although review articles and commentaries also were
consulted. Abstracts of research presented at symposia and
scientific conferences were not considered adequate for inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of Health
Force:
I
type of evidence.
committees.
Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories:
Copyright September 2000 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of
or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior
written permission from the publisher.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
PRACTICE BULLETINS
727
ACOG
PRACTICE
BULLETIN
NUMBER 22, NOVEMBER 2000
(Replaces Technical Bulletin Number 159, September 1991)
Fetal Macrosomia
of William H. Barth, Jr, MD.
The information is designed to
aid practitioners in making
decisions about appropriate
obstetric and gynecologic care.
construed as dictating an exclusive course of treatment or procedure. Variations in practice
of practice.
Reaffirmed 2009
Suspected fetal macrosomia is a common obstetric condition. As birth weight

increases, the likelihood of labor abnormalities, shoulder dystocia, birth trauma, and permanent injury to the neonate increases. The purpose of this document is to quantify those risks, address the accuracy and limitations of methods
for estimating fetal weight, and suggest clinical management for the pregnancy
with suspected fetal macrosomia.
Background
Definition
Two terms identify excessive fetal growth: large for gestational age and macrosomia. The term large for gestational age generally implies a birth weight equal
to or greater than the 90th percentile for a given gestational age. For years, clinicians have relied on popular fetal growth curves to identify weight cutoffs for
the 90th percentile for a given gestational age (13). A national reference for
fetal growth is now available. A study using the 1991 U.S. Live Birth File of the
National Center for Health Statistics reported data for fetal growth based on
more than 3.8 million births (4). The 50th, 90th, and 95th percentiles for birth
weight from 37 to 42 completed weeks of gestation are shown in Table 1.
The term fetal macrosomia implies growth beyond a specific weight, usually 4,000 g or 4,500 g, regardless of the gestational age. Although the risks of
morbidity for infants and mothers when birth weight is between 4,000 g and
4,500 g are greater than those of the general obstetric population, these risks
increase sharply beyond 4,500 g (510). Recent large cohort studies (1114)
further support the continued use of 4,500 g as an appropriate estimated weight
beyond which the fetus should be considered macrosomic.
Rather than assigning a different minimum estimated fetal weight for
macrosomia among infants of women with diabetes, understanding that maternal diabetes is an independent predictor of fetal morbidity will help avoid confusion. Regardless of their birth weight, infants of women with diabetes have
Table 1. Percentiles for Birth Weight for Gestational Age:

U.S. 1991 Single Live Births to Resident Mothers 3742
Completed Weeks
Birth Weight (g)
Gestational Age
50th
Percentile
90th
Percentile
95th
Percentile
37
3,117
3,755
3,956
38
3,263
3,867
4,027
39
3,400
3,980
4,107
40
3,495
4,060
4,185
41
3,527
4,094
4,217
42
3,522
4,098
4,213
Modified from Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United
States national reference for fetal growth. Obstet Gynecol 1996;87:163168
an increased risk of shoulder dystocia, clavicular fracture,

and brachial plexus injury (14, 1517).
Frequency of Occurrence
Information from the National Center for Health Statistics
shows that 10% of all liveborn infants in the United States
weigh more than 4,000 g (18). In contrast, only 1.5%
weigh more than 4,500 g. The most serious complication
of fetal macrosomia is shoulder dystocia. Fortunately,
shoulder dystocia is rare, complicating only 1.4% of all
vaginal deliveries (19). When birth weight exceeds 4,500
g, however, the risk of shoulder dystocia is increased,
with rates reported from 9.2% to 24% (8, 1114). In the
presence of maternal diabetes, birth weights greater than
4,500 g have been associated with rates of shoulder dystocia from 19.9% to 50% (8, 12, 14). Figure 1 shows the
relationship between birth weight, maternal diabetes status, spontaneous or assisted vaginal delivery, and the
mean frequency of shoulder dystocia based on a study of
more than 175,000 deliveries in California in 1992 (14).
Several issues complicate attempts to define precisely
the incidence of shoulder dystocia among macrosomic
infants. First, clinicians tend to underreport the occurrence
of shoulder dystocia (20, 21). Second, the incidence of
shoulder dystocia and the likelihood of subsequent fetal
injury vary depending on the criteria used to render a diagnosis of dystocia (22). Studies requiring the use of auxiliary maneuvers other than gentle downward traction and
episiotomy to effect delivery (16) report a lower overall
incidence of shoulder dystociabut greater proportional
fetal morbiditythan those studies with less precise definitions (11). Finally, although macrosomia clearly increases
risk, it is important to note that most instances of shoulder
dystocia occur unpredictably among infants of normal
birth weight (19, 23).
Risk Factors for

Macrosomia
A number of factors predispose to newborn macrosomia.
A large casecontrol study examined the relative contributions of proposed risk factors for macrosomia, excluding preexisting diabetes (24). In decreasing order of
importance, these risk factors included a prior history of
macrosomia, maternal prepregnancy weight, weight gain
during pregnancy, multiparity, male fetus, gestational age
greater than 40 weeks, ethnicity, maternal birth weight,
maternal height, maternal age younger than 17 years, and
a positive 50-g glucose screen with a negative result on
the 3-hour glucose tolerance test. Although maternal
smoking decreases the likelihood of newborn macrosomia (25), it should not be recommended as a protective
measure for obvious reasons.
Both pregestational diabetes and gestational diabetes
are associated with fetal macrosomia. Even in patients
without diabetes, observational cohort studies and case
control studies demonstrate that graded increases in the
level of maternal glycemia are associated with increases in
newborn birth weight (26, 27). A study reported that 6% of
mothers with untreated borderline gestational diabetes
delivered infants exceeding 4,500 g, compared with only
2% of women with normal glucose tolerance (28). If gestational diabetes is unrecognized and untreated, the risk of
macrosomia may be as high as 20% (29).
Shoulder dystocia incidence per 1,000
728
400
Assisted, with diabetes
350
Unassisted, with diabetes
300
Assisted, no diabetes
Unassisted, no diabetes
250
150
100
200
50
3,5003,750
4,0004,250
4,5004,750
3,7504,000
4,2504,500
4,7505,000
Birth weight (g)

Figure 1. Frequency of shoulder dystocia for increasing birth
weight by maternal diabetes status and method of vaginal
deliveryspontaneous or assisted. (Nesbitt TS, Gilbert WM,
Herrchen B. Shoulder dystocia and associated risk factors with
macrosomic infants born in California. Am J Obstet Gynecol
1998;179:476480)
PRACTICE BULLETINS
Anthropometric studies suggest that the macrosomia

produced by maternal glucose intolerance is different
from that associated with other predisposing factors (30,
31). These macrosomic infants tend to have greater total
body fat, greater shoulder and upper-extremity circumferences, greater upper-extremity skin-fold measurements,
and smaller head-to-abdominal-circumference ratios than
macrosomic infants of mothers without diabetes. Some
have suggested that it is this altered fetal body shape that
is responsible for the higher incidence of shoulder dystocia seen among infants of women with diabetes (31).
The relative contributions of maternal diabetes and
obesity to fetal macrosomia remain controversial. One
study reported that the risk for fetal macrosomia associated with unrecognized gestational diabetes persisted after
controlling for both maternal body mass index and maternal weight gain (29). In a study among women with dietcontrolled gestational diabetes, adjusting for maternal
weight decreased the relative risk for large infants
(greater than the 90th percentile) from 2.5 to 1.5 (32).
Although both diabetes and maternal obesity increase the
risk of fetal macrosomia, most agree that maternal obesity
plays a greater role (7, 24, 33).
The interaction of maternal weight, weight gain during pregnancy, and newborn macrosomia is complex.
There is little doubt that birth weight, in general, increases with maternal body mass index (3436). Almost all
authors report that obese women are more likely than
women of normal weight to have large infants (35, 37).
However, several issues confound this observation. First,
obese women are more likely to have diabetes mellitus.
One study demonstrated that morbidly obese women
(>300 lb) are eight times more likely to deliver an infant
exceeding 4,500 g (38). Second, high weight gain during
pregnancy is itself a risk factor for excessive fetal growth
(39). The risk of newborn macrosomia associated with
excessive maternal weight gain is greater for obese
women than for nonobese women (35, 37).
Understandably, gestational age influences birth
weight and the risk of macrosomia. Among all races in the
United States, the risk of macrosomia increases from
1.6% at term to 2.5% if gestational age exceeds 42 weeks
(18). However, as Table 1 shows, there is little additional
weight gain after 41 weeks of gestation.
A number of maternal historic factors and habits also
influence infant birth weight. Women who have previously delivered an infant weighing more than 4,000 g are five
to 10 times more likely to deliver an infant exceeding
4,500 g than women without such a history (5, 24, 40). To
a degree, maternal birth weight may predict newborn
weight. Women whose own birth weight exceeded 8 lb
(approximately 3,600 g) are twice as likely to deliver
infants greater than 4,000 g than are women whose birth
729
weight was between 6 lb and 7.9 lb (approximately

2,7003,500 g) (41). Finally, three cohort studies show that
multiparity and grand-multiparity ( 5 deliveries) increase
the risk of macrosomia (4244).
Genetic, racial, and ethnic factors also influence birth
weight and the risk of macrosomia. Male infants typically weigh more than female infants at any gestational age
and, therefore, constitute a greater proportion of infants
with birth weights exceeding 4,500 g (12, 45). The risk of
macrosomia varies with race and ethnicity as well. Two
reports, both of which controlled for diabetes, have
demonstrated that Hispanic women have a higher risk of
fetal macrosomia than do white, black, or Asian women
(46, 47). Genetic factors such as parental height and race
play a role in determining newborn birth weight, but these
factors interact in a complex manner with environmental
factors during pregnancy (48, 49). No combination of
these risk factors predicts macrosomia well enough to
be used clinically. Much of the variation in birth
weights remains unexplained, and most infants greater
than 4,500 g do not have identifiable risk factors (6).
Diagnosis
An accurate diagnosis of macrosomia can be made only
by weighing the newborn after delivery. Unfortunately,
the prenatal diagnosis of fetal macrosomia remains
imprecise. Methods used to predict birth weight include
assessment of maternal risk factors, clinical examination,
and ultrasound measurement of the fetus. Although ultrasonography enables the direct measurement of various
fetal body parts, its accuracy in predicting macrosomia
has been unreliable (5052). Furthermore, the superiority
of ultrasound-derived estimates of fetal weight over clinical estimates has not been established (5355). Indeed,
parous women are able to predict the weight of their newborns as well as clinicians who use ultrasound measurements or Leopolds maneuvers (56).
Risks Associated with

Macrosomia
Maternal Morbidity
The primary maternal risk associated with macrosomia is
an increased risk of cesarean delivery. With birth weights
greater than 4,500 g, cohort studies show that the risk of
cesarean delivery for women attempting a vaginal delivery is at least double that of controls (5, 7, 13, 40). Almost
all the increased risk is attributed to labor abnormalities
730
Fetal Morbidity and Mortality

The fetal injuries most commonly associated with macrosomia and shoulder dystocia are fracture of the clavicle
and damage to the nerves of the brachial plexus, specifically C5 and C6, producing Erb-Duchenne paralysis.
Fracture of the clavicle complicates 0.30.7% of all deliveries and usually resolves without permanent sequelae
(6163). For macrosomic infants, the risk of clavicular
fracture is increased approximately 10-fold (63).
Brachial plexus injury is rare, with an incidence
reported between 0.5 and 1.89 injuries per 1,000 vaginal
deliveries (9, 15, 17, 6365). Casecontrol studies
demonstrate that the risk of brachial plexus injury
among infants delivered vaginally is increased 18- to 21fold when birth weight exceeds 4,500 g (9, 17, 63).
Recent reports place the occurrence of brachial plexus
injury for macrosomic infants delivered vaginally
between 4% and 8% (12, 13, 65). Even though shoulder
dystocia is underreported (20), the occurrence of
brachial plexus injury in the absence of documented
shoulder dystocia is well described (14, 21). Brachial
plexus injury has been associated with cesarean delivery
(66). As with clavicular fracture, most brachial plexus
injuries resolve without permanent handicap. Among 59
confirmed brachial plexus injuries described in the
Collaborative Perinatal Project, only 6 (12%) were still
evident by age 4 months (64). By age 2 years, all but 4
(7%) had resolved. Other large case series confirm that
8090% of brachial plexus injuries will resolve by age 1
year (23, 67). However, persistent injury may be more
common with birth weights greater than 4,500 g (68).
Nonetheless, as with shoulder dystocia, most brachial
plexus injuries occur in nonmacrosomic infants (65).
Macrosomia is associated with a number of other

risks to the newborn. These infants face an increased risk
of depressed 5-minute Apgar scores and increased rates of
admission to a neonatal intensive care unit (65). However,
most of this risk likely is the result of complications of the
birth process, because macrosomic infants do not have
higher rates of fetal heart rate abnormalities in labor (5).
Finally, overweight newborns are more likely to be overweight later in life than are normal-weight newborns (69).

Recommendations
(5, 11). Not surprisingly, a study has demonstrated that

the inaccurate ultrasonographic prediction of macrosomia
predisposes to the diagnosis of labor abnormalities and
cesarean delivery independent of actual birth weight (57).
The risks of postpartum hemorrhage and significant
vaginal lacerations also are elevated with macrosomia. A
casecontrol study of risk factors for major obstetric hemorrhage (estimated blood loss >1 L) reported that a birth
weight greater than 4,000 g doubled the odds of significant maternal blood loss (odds ratio [OR]: 1.9, 95% confidence interval [CI]: 1.382.6) (58). Although the risk of
third- and fourth-degree lacerations is slightly increased
with macrosomia (12), this is especially true if delivery is
complicated by shoulder dystocia (59). Maternal infectious
morbidity generally is limited to urinary tract infection in
women undergoing elective cesarean delivery (60) and
puerperal fever in women undergoing cesarean delivery
after a trial of labor (12).
How accurate are clinical estimates of fetal

weight?
The two primary methods for clinical estimation of fetal

weight are Leopolds maneuvers (abdominal palpation)
and measurement of the height of the uterine fundus
above the maternal symphysis pubis. In a prospective
study of 602 term patients, clinical palpation alone predicted macrosomia as accurately as any reported ultrasonographic method (53). A study of more than 1,700
women concluded that although ultrasound-derived estimates are more accurate for newborns weighing between
2,500 g and 4,000 g, above this level, ultrasound measurement and clinical palpation have similar accuracy
(70).
Measurement of the symphysisfundal height alone
is a poor predictor of fetal macrosomia. Although the
average fundal height measurement is greater for fetuses
exceeding 4,500 g (71), the utility of this measurement
alone is questionable (72). To be useful, measurement
of the uterine fundal height must be combined with clinical palpation or Leopolds maneuvers. Prospective studies designed to evaluate Leopolds maneuvers with
fundal height measurement for the detection of
macrosomia report sensitivities of 1043%, specificities of 99.099.8%, and positive predictive values
between 28% and 53% (55, 73). Ultrasound measurements of those women with suspected fetal macrosomia
on the basis of clinical examination alone decreased sensitivity and positive predictive value without measurably
affecting specificity (73). Prospective studies among
women with diabetes also have shown that clinical estimates of macrosomia are as predictive as those derived
with ultrasonography (54).
Finally, simply asking a parous woman her estimate
of the fetal weight may provide an estimate as accurate
as any other. In one study, a parous womans ability to
PRACTICE BULLETINS
predict birth weight greater than 4,000 g was as accurate

as that of clinicians using Leopolds maneuvers alone (56).
How accurate is ultrasound measurement in

determining fetal weight?
Are interventions for treating suspected

macrosomia available?
For mothers without diabetes, no clinical interventions

designed to treat or curb fetal growth when macrosomia is
suspected have been reported. For pregnancies that are

complicated by diabetes mellitus, one clinical trial suggests that the addition of insulin to diet therapy may treat
early macrosomia diagnosed between 29 and 33 weeks of
gestation (81). This study randomized 98 women with a
fetal abdominal circumference exceeding the 75th percentile for gestational age to either diet therapy alone or
diet therapy with twice-daily insulin. The addition of
insulin therapy decreased the likelihood of birth weight
greater than the 90th percentile from 45% among those
treated with diet only to 13% among those receiving
insulin (P <0.01) (81).
Three large cohort studies confirm that excessive
weight gain during pregnancy is associated with fetal
macrosomia, suggesting a possible role for caloric restriction (35, 37, 39). One of these studies demonstrated that
for most women, excessive weight gain doubled the risk
of delivering an infant weighing more than 4,500 g.
Although this relationship held true for average, obese,
and very obese women, the actual incidence of macrosomia was still low (between 2.7% and 5.6%). Although
dietary regulation has long been a mainstay of therapy for
gestational diabetes, a recent meta-analysis of four randomized clinical trials examining primary diet therapy for
women with impaired glucose tolerance showed no significant reduction in the number of newborns weighing
more than 4,000 g (OR: 0.73, 95% CI: 0.451.35) (82).
Although maternal obesity and weight gain during pregnancy are two of the strongest birth weight predictors, no
randomized clinical trials have investigated dietary intervention to prevent macrosomia among obese women
without diabetes.
Ultrasound-derived estimates of fetal weight are

obtained by entering the measurements of various fetal
body parts, usually including the abdominal circumference, into one of several popular regression equations
(74, 75). Most commercially available ultrasound units
have one or more of these equations already programmed into the software of the system, allowing
immediate calculation of estimated fetal weights.
Unfortunately, most of the regression formulas currently in use are associated with significant errors when the
fetus is macrosomic. For example, Hadlocks formula to
predict fetal weight has a mean absolute percent error of
13% for infants greater than 4,500 g, compared with 8%
for nonmacrosomic infants (76).
Ultrasound-derived diagnosis of an estimated fetal
weight exceeding 4,500 g is not as accurate as many
believe it to be. Among women without diabetes, ultrasound biometry used to detect macrosomia has a sensitivity of 2244%, a specificity of 99%, a positive predictive
value of 3044%, and a negative predictive value of
9799% (77, 78). Reports demonstrating greater accuracy
generally rely on less stringent criteria for macrosomia,
such as birth weight greater than 4,000 g or that exceeding the 90th percentile for a given gestational age.
However, when birth weight exceeds 4,500 g, only 50%
of fetuses weigh within 10% of the ultrasound-derived
estimate (79). Using existing formulas, an estimated fetal
weight would have to exceed 4,800 g for the fetus to have
more than a 50% chance of being macrosomic (77, 80).
These observations suggest that the usefulness of ultrasonography for obtaining estimated weights is limited,
and these limitations are neither operator-dependent nor
equipment-dependent (79).
As with clinical estimates of fetal weight, the true
value of ultrasonography in the management of expected
fetal macrosomia may be its ability to rule out the diagnosis, which may help avoid maternal morbidity. One study
revealed that clinicians who suspected fetal macrosomia
on the basis of an ultrasonogram were more likely to diagnose labor abnormalities and were more likely to perform
cesarean deliveries despite normal birth weights (57).
731
When is cesarean delivery appropriate for

suspected macrosomia at a particular
estimated fetal weight?
Controversy surrounds the question of cesarean delivery

for suspected fetal macrosomia. First, the risk of birth
trauma associated with vaginal delivery increases with
birth weight (9, 17, 63). Second, cesarean delivery
reducesbut does not eliminatethe risk of birth trauma
and brachial plexus injury associated with fetal macrosomia (7, 9, 17, 83). The protective effect of cesarean delivery is large. Using a multivariate analysis to investigate
risk factors for brachial plexus injury, investigators
reported an odds ratio for cesarean delivery of 0.010.20
(17). It thus seems logical that for each woman, there
must be a fetal weight beyond which the risks of vaginal
delivery to the fetus are high enough to warrant cesarean
delivery.
Despite such reasoning, the clinical effectiveness of
offering prophylactic cesarean delivery to women with
732
4,500 g, no permanent sequelae were identified by age

2 months (12). The risks of short-term morbidity associated with vaginal delivery in this group are low, and those
of permanent injury are even lower.
In conjunction with published cost-effectiveness
data, the sum of these reports does not support a policy of
prophylactic cesarean delivery for suspected fetal macrosomia with estimated weights less than 5,000 g (86).
Along with a description of the limitations of estimating
fetal weight, the obstetrician should present accurate statistics for the short- and long-term risks of maternal and
fetal morbidity for both vaginal and cesarean delivery as
discussed previously.
Despite the poor predictive value of an estimated
fetal weight beyond 5,000 g and a lack of evidence supporting cesarean delivery at any estimated fetal weight,
most, but not all, authors agree that consideration should
be given to cesarean delivery in this situation (7, 13, 65).
Among infants with birth weights exceeding 5,000 g,
there are reports of cesarean delivery rates of 3560%,
brachial paralysis rates of 711%, and a perinatal death
rate as high as 2.4% (7). In contrast, despite reporting an
OR of 45 (95% CI: 16129) for brachial plexus injury
among vaginally delivered infants exceeding 5,000 g,
some investigators suggest that ultrasound-derived fetal
weight estimates alone should not be used to determine
the route of delivery (17, 52).
any specific estimated fetal weight has not been established in randomized clinical trials. Currently, only one
observational study has evaluated a policy of using ultrasound-derived fetal weight estimates to determine the
route of delivery (84). The use of historic controls, the
nonrandomized design of the study, the use of multiple
interventions, and the small sample size severely limit the
usefulness of conclusions from the study. In this study,
1,337 women with diabetes were offered elective cesarean delivery based on ultrasound-derived fetal weight estimates beyond 4,250 g and induction of labor if ultrasound
measurements resulted in a prediction of a large-for-gestational-age infant with an estimated fetal weight less
than 4,250 g (84). The study cohort was compared with a
historic control group of 1,227 women with diabetes who
were managed without intervention for accelerated fetal
growth during the 3 years preceding implementation of
the study protocol. Implementation of the study protocol
was associated with a nonsignificant reduction in the risk
of shoulder dystocia from 2.4% in controls to 1.1% in the
intervention group. In addition, a significant increase in
the institutional cesarean delivery rate from 21.7% in controls to 25.1% in the intervention group was reported.
Although the sample size was insufficient for comparison, the risk of birth trauma was not eliminated (2 versus
1 brachial plexus injury, 12 versus 6 fractures).
Currently, no prospective studies have assessed the
true risk of either shoulder dystocia or brachial plexus
injury in conjunction with estimated fetal weight alone.
Until well-designed randomized clinical trials of sufficient sample size are available, clinicians must rely on retrospective data to make clinical management decisions.
In addition, recent large cohort and casecontrol
studies demonstrate the safety of allowing a trial of labor
for estimated birth weights of more than 4,000 g (12, 13).
Among the 2,924 infants previously identified with birth
weights greater than 4,000 g in utero, only 48 injuries
(1.6%) related to shoulder dystocia were noted. Among
the 22 brachial plexus injuries with documented followup, only 5 (17%) were clinically evident at 6 months (68).
A second study reported 27 episodes (11.4%) of shoulder
dystocia and 3 instances (1.3%) of brachial plexus paralysis in a group of 236 neonates weighing at least 4,200 g
(85). In an additional series of 87 infants with birth
weights greater than 4,500 g who were delivered vaginally, investigators reported only 5 cases (5.7%) of ErbDuchenne paralysis. By 3 months of age, all affected
infants were without evidence of brachial plexus paralysis (13). A fourth study reported that of the 157 infants
delivered vaginally with birth weights greater than
Is there a role for induction of labor in the

management of term patients with suspected
fetal macrosomia?
Current evidence from cohort studies does not support a

policy of early induction of labor in term patients with
suspected fetal macrosomia. Three recent reports show
that induction of labor at least doubles the risk of cesarean delivery without reducing shoulder dystocia or newborn morbidity (8789). Although the increased risk of
cesarean delivery with induction of labor is clear, on the
basis of these reports, one cannot rule out the possibility
of a small beneficial effect on fetal outcome. These studies, however, are affected by small sample size and possible bias introduced by their retrospective nature.
One randomized clinical trial of women without
diabetes has addressed the role of induction of labor for
suspected fetal macrosomia at term. A total of 273
women with ultrasound-derived estimated fetal weights
between 4,000 g and 4,500 g were randomized to either
planned induction of labor or expectant management
(90). Inductions were performed with oxytocin or
prostaglandins followed by oxytocin, depending on the
PRACTICE BULLETINS
How many elective cesarean deliveries for

suspected fetal macrosomia would have to be
performed to prevent one case of brachial
plexus injury?
How should a diagnosis of suspected fetal

macrosomia affect the management of labor
and vaginal delivery?
Perhaps the most important consideration for labor and

delivery with suspected fetal macrosomia is the decision
to conduct a midpelvic operative vaginal delivery. As
depicted in Figure 1, the risk of shoulder dystocia is associated with assisted vaginal delivery. Casecontrol and
cohort studies consistently demonstrate an increased risk
of shoulder dystocia when the macrosomic fetus is delivered by forceps, especially midforceps for a prolonged
second stage (8, 10, 14, 19, 92). Rates of shoulder dystocia with midforceps deliveries of infants greater than
4,500 g have been reported to be above 50%. Barring
extreme emergencies, cesarean delivery should be performed for midpelvic arrest of the fetus with suspected
macrosomia. If a decision is made to proceed with cesarean delivery in the presence of suspected macrosomia, the
incision should be large enough to avoid a difficult
abdominal delivery.
Suspected fetal macrosomia is not a contraindication to
attempt vaginal birth after prior cesarean delivery. A cohort
study compared maternal and fetal outcomes associated
with a trial of labor for infants suspected to be macrosomic
and with documented birth weights less than 4,000 g versus
those greater than 4,000 g (93). The success rate for vaginal
delivery was 58% for birth weights between 4,000 g and
4,499 g and 43% for birth weights of 4,500 g and higher.
Maternal and newborn morbidities were equal. A
casecontrol study examining risk factors for uterine rupture during a trial of labor found no association between
rupture and birth weight greater than 4,000 g (94).
Summary
The diagnosis of fetal macrosomia is imprecise. For

suspected fetal macrosomia, the accuracy of estimated fetal weight using ultrasound biometry is no
better than that obtained with clinical palpation
(Leopolds maneuvers).
The cost-effectiveness of elective cesarean delivery for

fetal macrosomia usually is expressed as the number of
cesarean deliveries required to prevent one brachial
plexus injury or the cost, in dollars, of each brachial
plexus injury avoided. A casecontrol study of brachial
plexus paralysis demonstrated that 51 cesarean deliveries
would be needed to prevent one case of brachial plexus
paralysis if the cutoff for cesarean delivery were 4,500 g
among patients without diabetes (17). For a cutoff of
5,000 g, this number decreased to 19. Assuming persistent rates for brachial plexus impairment are between 5%
and 22%, the authors suggested that to prevent a single
permanent injury, the number of cesarean deliveries
increases to between 233 and 1,026 for a birth weight cutoff of 4,500 g, and from 85 to 373 for a cutoff of
5,000 g. Another study using similar methods concluded
that 155588 cesarean deliveries are needed to prevent a
single permanent injury using a cutoff of 4,500 g for
infants of women without diabetes (65). However,
because the authors did not consider the imperfect predictive values of ultrasonography for macrosomia, they
underestimated the number of cesarean deliveries that
would be needed to implement such a policy.
In two reports analyzing a policy of prophylactic
cesarean delivery for macrosomia, which took into
account the reported sensitivity and specificity of ultrasonography for the detection of macrosomia (4,500 g), it
was calculated that 3,695 cesarean deliveries would be
required to prevent one permanent injury at a cost of $8.7
million for each injury avoided (86, 91). For pregnancies
complicated by diabetes, these figures were still high at
443 cesarean deliveries to prevent a single permanent
injury. In summary, because of the lack of well-designed
and well-executed randomized clinical trials, a policy of
prophylactic cesarean delivery for suspected fetal macrosomia less than 5,000 g may not be effective for pregnancies without diabetes. Furthermore, even for pregnancies
complicated by diabetes, the cost-effectiveness of such a
policy is doubtful.
condition of the cervix. The cesarean delivery rates were

similar: 19.4% for the induction group and 21.6% for the
expectant group. There were 11 cases of shoulder dystocia, 5 in the induction group and 6 in the expectant group.
All were managed without brachial plexus injury or other
trauma.
733
Suspected fetal macrosomia is not an indication for

induction of labor, because induction does not
improve maternal or fetal outcomes.
734
Labor and vaginal delivery are not contraindicated

for women with estimated fetal weights up to
5,000 g in the absence of maternal diabetes.
With an estimated fetal weight greater than 4,500 g,

a prolonged second stage of labor or arrest of descent
in the second stage is an indication for cesarean
delivery.
Although the diagnosis of fetal macrosomia is imprecise, prophylactic cesarean delivery may be considered for suspected fetal macrosomia with estimated
fetal weights greater than 5,000 g in women without
diabetes and greater than 4,500 g in women with diabetes.
Suspected fetal macrosomia is not a contraindication

to attempted vaginal birth after a previous cesarean
delivery.
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type of evidence.
committees.
Copyright November 2000 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of
or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
738
ACOG
PRACTICE
BULLETIN

of Sandra A. Carson, MD, and
D. Ware Branch, MD. The information is designed to aid
of practice.
Reaffirmed 2008
Management of
Recurrent Early
Pregnancy Loss
Recurrent pregnancy loss is a common clinical problem in reproduction, occurring in approximately 1% of reproductive-aged women (1). A definite cause is
established in no more than 50% of couples, and several alleged causes of
recurrent pregnancy loss are controversial. Moreover, in the field of recurrent
pregnancy loss, inappropriate emphasis often is given to unproven hypotheses
and poorly designed clinical studies. Seeking a solution, some patients and
physicians explore less-well-accepted etiologies and empirical or alternative
treatments. This bulletin will provide the practitioner with a rational, modern
approach to the management of recurrent pregnancy loss. New and controversial etiologies will be presented so that the practitioner can discuss them with
couples who have a history of recurrent pregnancy loss.
Background
Broadly defined, pregnancy loss includes any type of loss of the conceptus from
fertilized ovum to neonate. This bulletin covers the repetitive loss of recognized
pregnancies in the first or early second trimester (<15 weeks of gestation). It
usually is referred to as recurrent spontaneous abortion, miscarriage, or recurrent early pregnancy loss.
Recurrent abortion must be distinguished from sporadic spontaneous abortions that are nonconsecutive pregnancy losses occurring randomly during a
womans reproductive years. Sporadic pregnancy loss occurs in 1015% of all
clinically recognized pregnancies as first- or early second-trimester spontaneous
abortions. Most of these pregnancy losses are clinically evident by the 12th week
of gestation and are preembryonic or embryonic losses in which the demise of
the conceptus precedes clinical features of pregnancy loss by one or more weeks.
PRACTICE BULLETINS
Recurrent pregnancy loss typically is defined as two

or three or more consecutive pregnancy losses. Most
women with recurrent pregnancy loss have recurrent preembryonic or embryonic losses. Recurrent fetal loss is
less common, and recurrent fetal loss at or beyond 14
weeks of gestation is infrequent.
739
mal in 48% or more of cases (5, 6), raising the possibility of recurrent aneuploidy despite normal parental karyotypes. Supportive evidence comes from studies of
preimplantation genetic studies of women with recurrent
pregnancy loss in which more than 50% of embryos were
found to have aneuploidy (7, 8).
Hormonal and Metabolic Disorders
Causes of Recurrent
Pregnancy Loss
Genetic Abnormalities
Parental Structural Chromosome
Abnormalities
In approximately 24% of couples with recurrent pregnancy loss, one partner will have a genetically balanced
structural chromosome rearrangement. Balanced translocations account for the largest percentage of these karyotypic abnormalities. They can cause pregnancy loss
because segregation during meiosis results in gametes
with duplication or deficiency of chromosome segments.
Other genetically balanced structural chromosome
abnormalities, such as chromosome inversions, account
for a small percentage of abnormal parental karyotypes
among couples with recurrent pregnancy loss.
Molecular Genetic Abnormalities

In the past decade, the development of techniques for
DNA analysis has resulted in identification of molecular
genetic abnormalities as causes of various human
diseases. One report indicated that highly skewed
X-chromosome inactivation is associated with otherwise
unexplained recurrent pregnancy loss (2). As yet, however, commercially available tests for this and other related
molecular genetic abnormalities are not widely available.
Recurrent Preembryonic or Embryonic

Aneuploidy
Analyses of karyotypes in consecutive abortions suggest
that recurrent aneuploidy in the conceptus may be a cause
of recurrent pregnancy loss. In one analysis of data, the
karyotype of a second successive spontaneous abortion
was abnormal in nearly 70% of cases when aneuploidy
was found in the first abortus, but in only 20% of cases
where the first abortus was chromosomally normal (3).
However, these aneuploid losses may have been a result
of the older age of the mothers, rather than a nonrandom
event in predisposed couples (4). More recently, two
groups of investigators using different techniques of
analysis have shown that the next abortion in women
with recurrent pregnancy loss was chromosomally abnor-
Luteal Phase Defect

The luteal phase defect (LPD) has long been thought to
be a cause of spontaneous abortion, but the evidence linking LPD to recurrent abortion is subject to criticism.
Investigators initially hypothesized that with LPD, the
corpus luteum failed to make enough progesterone to
establish a mature endometrial lining suitable for placentation. This theory has evolved to implicate poor follicular-phase oocyte development, which results in disordered estrogen secretion and subsequent dysfunction of
either the corpus luteum or progesterone effect. In turn,
these effects could result from excess luteinizing hormone or hyperandrogenic states. Some investigators
believe that LPD is a common cause of recurrent pregnancy loss, accounting for approximately 2540% of
cases. However, studies of this disorder have not included concurrently tested controls, a serious oversight given
that normal women have endometrial histology suggestive of LPD in up to 50% of single menstrual cycles and
25% of sequential cycles (9). Thus, the association
between LPD and recurrent pregnancy loss remains speculative.

Investigators have found that 3656% of women with
recurrent pregnancy loss have polycystic ovary syndrome
(PCOS) diagnosed by ultrasound examination of the
ovaries (1012). One group (11) demonstrated that more
than half of women with ultrasonographic evidence of
PCOS also had hypersecretion of luteinizing hormone. But
ultrasonographic evidence of PCOS in women with recurrent pregnancy loss does not predict worse pregnancy outcome than in women with recurrent pregnancy loss without PCOS (10, 12, 13). However, it has been reported that
women with PCOS who miscarry have higher levels of circulating androgens (10). There is no known therapy for
reducing the risk of pregnancy loss in women with PCOS.
Other Metabolic Abnormalities

Maternal endocrinologic and metabolic disorders have
been implicated as a cause of recurrent pregnancy loss.
Women with poorly controlled type 1 (insulin-dependent) diabetes mellitus have an increased rate of abortion
(14). However, there is no evidence that asymptomatic
740
endocrinologic or metabolic disorders, such as mild thyroid disease or glucose intolerance, cause recurrent pregnancy loss.
Uterine Anatomic Abnormalities

Congenital uterine abnormalities have been associated
most often with second-trimester pregnancy loss.
However, 1015% of women with recurrent early pregnancy loss have congenital uterine abnormalities. The
most common malformations associated with pregnancy
loss are variations of the double uterus (bicornuate, septate, or didelphic), with septate uterus predominating.
The contribution of arcuate uterus to recurrent pregnancy
loss is debated. A recent study using three-dimensional
ultrasonography and hysteroscopy found that 15% of 61
women with recurrent pregnancy loss had an arcuate
uterus, compared with only 3% of more than 1,000
women attending a gynecology clinic (15, 16). Other
investigators doubt an association between an arcuate
uterus and recurrent pregnancy loss (17, 18). Severe uterine synechiae (Ashermans syndrome) and uterine
abnormalities associated with in utero exposure to
diethylstilbestrol also may be associated with pregnancy
loss. An association between submucosal leiomyoma and
recurrent pregnancy loss is controversial.
Some investigators believe that poor vascularization
of the uterine septum is a cause of spontaneous abortion,
but studies provide mixed results. In one study of 12
pregnancies, all four successful pregnancies became
implanted away from the uterine septum (19). However,
the vascular density in uterine septa removed at the time
of metroplasty is similar to that of the normal uterine
wall (20).
Infectious Causes
Certain infectious agents, such as Listeria monocytogenes, are known to cause sporadic pregnancy loss, but
no infectious agent has been proven to cause recurrent
pregnancy loss. In addition, Toxoplasma gondii and some
viruses (eg, rubella, herpes simplex, and measles viruses;
cytomegalovirus; and coxsackieviruses) have been linked
to sporadic abortion. However, none has been convincingly associated with recurrent pregnancy loss.
Environmental Factors, Occupational

Factors, and Personal Habits
Although a common concern of patients, environmental
factors rarely have been linked to sporadic pregnancy
loss, and no associations between environmental factors
and recurrent pregnancy loss have been established.
Likewise, occupational exposures to certain products,
such as certain organic solvents, rarely have been linked

to sporadic pregnancy loss (21). However, no associations between occupational exposure or working itself
and recurrent pregnancy loss have been established.
Study results are conflicting on the association of
smoking, use of alcohol, and use of caffeine with sporadic pregnancy loss. They may act in a dose-dependent
fashion or synergistically to increase the rate of sporadic
pregnancy loss. However, none of these habits has been
associated with recurrent pregnancy loss. Exercise does
not appear to increase the rate of sporadic pregnancy loss,
particularly in women in good physical condition, and
there are no studies of exercise effects in women with
recurrent pregnancy loss.
Thrombophilia
The most common inherited thrombophilic disorders are
factor V Leiden and prothrombin G20210A mutation,
found in approximately 8% and 3%, respectively, of
Caucasian women in the United States. These mutations
are associated with approximately 25% of isolated
thrombotic events and approximately 50% of familial
thrombosis. Other less common thrombophilias include
deficiencies of the anticoagulants protein C, protein S,
and antithrombin III. Some investigators have (2225),
and some have not (13, 2629), found that one or more of
these thrombophilic mutations are associated with recurrent pregnancy loss. In two studies (22, 30), however,
these heritable thrombophilias were associated with second- or third-trimester fetal loss, not with first-trimester
loss. Also, one group has found that next pregnancy outcomes among women with recurrent pregnancy losses
are no different with or without factor V Leiden (13).
Despite the recent interest in this field, no treatment
trials have been performed. Thus, which therapy, if any,
is effective in promoting successful pregnancy among
women with recurrent pregnancy loss and thrombophilia
is uncertain.
Autoimmune Disorders
Antiphospholipid Antibodies
Antiphospholipid syndrome (APS) is an autoimmune
disorder characterized by the presence of significant levels of antiphospholipid antibodies and one or more clinical features, among which are recurrent pregnancy loss,
fetal death, and thrombosis (31). Antiphospholipid syndrome may occur as a primary condition in women with
no other recognizable autoimmune disease, or as a secondary condition in patients with underlying autoimmune disease (eg, systemic lupus erythematosus). The
PRACTICE BULLETINS
diagnosis of APS is made by demonstrating lupus anticoagulant, anticardiolipin antibodies, or both.

Some investigators have found that a small percentage of women with recurrent pregnancy loss who test
negative for anticardiolipin antibodies have antibodies to
other phospholipids, such as phosphatidylserine or phosphatidylethanolamine (32). Others have found that no
such relationship exists (33) or that testing for antibodies
other than lupus anticoagulant and anticardiolipin antibodies does not increase the rate of diagnosis of APS
(34). In addition, assays for phospholipid-binding antibodies other than anticardiolipin are not standardized.
Finally, there is no proven treatment for women with
recurrent pregnancy loss and phospholipid-binding antibodies other than lupus anticoagulant and anticardiolipin
antibodies.
Thyroid Antibodies
Autoantibodies to thyroid antigens (thyroglobulin and
thyroid peroxidase) are associated with an increased rate
of pregnancy loss if identified in early pregnancy or
immediately before pregnancy (35, 36). However, current
evidence does not allow a definite conclusion regarding
the association of antithyroid antibodies and recurrent
pregnancy loss, and no treatment options have been
proven beneficial.
Antinuclear Antibodies
A significant percentage (approximately 15%) of women
with recurrent pregnancy loss have detectable antinuclear
antibodies (ANA) (37, 38). Without treatment, subsequent pregnancy outcomes among women with a positive
ANA test result are similar to those among women with
a negative ANA test result. More important, a randomized treatment trial of women with recurrent pregnancy
loss and a positive autoantibody result, including ANA,
found no difference in pregnancy outcomes between
women treated with prednisone and low-dose aspirin and
women treated with placebo (39). Thus, currently available data do not support testing women with recurrent
pregnancy loss for ANA.
Alloimmune Disorders
Alloimmune traitsimmunologic differences between
individualshave been proposed as factors between
reproductive partners that cause otherwise unexplained
recurrent pregnancy loss. The tendency for 1) partners
with recurrent loss to share human leukocyte antigens,
2) the female partner to fail to produce serum blocking
factor, and 3) the female partner to produce antileukocytotoxic antibodies against paternal leukocytes have been
741
described. Others have refuted the significance of each of

these factors. In addition, no test for these traits provides
results that predict the next pregnancy outcome in
patients treated or untreated for recurrent pregnancy loss
(40, 41). More recently, some researchers have claimed
that flow cytometric assays for maternal antibodies to
paternal leukocytes are useful in evaluating couples with
recurrent pregnancy loss. However, studies of these
assays have lacked appropriate controls and are of
unproven value in terms of indicating an efficacious
treatment.
More recent investigations of the maternalfetal
immunologic relationship suggest that pregnancy losses
may result from dysregulation of normal immune mechanisms, probably operating at the maternalfetal interface. It has been proposed that a predominance of Th-2
lymphocytic cytokines is crucial for successful pregnancy and that Th-1 lymphocytic cytokines, such as interferon- and tumor necrosis factor-, adversely affect
embryo and trophoblast viability (4244). The presence
of natural killer (NK)-like cells secreting a transforming
growth factor at the maternalfetal interface may be necessary for successful pregnancy (45). Clinical studies
have found decreased (45, 46) or increased (47) numbers
of these cells in the luteal phase endometria of women
with recurrent pregnancy loss. Pregnancy outcomes may
be worse in women with recurrent pregnancy loss found
to have increased numbers of NK-like cells in the luteal
phase endometria (48), but further studies are necessary
before valid conclusions can be drawn. One group has
found that an embryotoxic factor, similar to interferon-,
generated by patient leukocytes in vitro predicted pregnancy failure in the next pregnancy attempt (44), but others have not been able to reproduce these findings (49).
Others have found that an increased percentage of circulating NK cells in women with recurrent pregnancy loss
predicts a relatively poor next pregnancy outcome (50,
51). There is, however, no proven treatment for women
with recurrent pregnancy loss found to have increased
percentages of circulating NK cells.
Unexplained Recurrent Pregnancy Loss

In 50% or more of couples with recurrent pregnancy loss,
an evaluation, including parental karyotypes, hysterosalpingography or hysteroscopy, and antiphospholipid
antibody testing will be negative. Therefore, a majority
(approximately 5075%) of couples with recurrent pregnancy loss will have no certain diagnosis. Informative
and sympathetic counseling appears to serve an important role in this situation. Live birth rates between 35%
and 85% are commonly reported in couples with unexplained recurrent pregnancy loss who undertake an
742
untreated or placebo-treated subsequent pregnancy (12,

5255). Meta-analysis of randomized, prospective studies suggests that 6070% of women with unexplained
recurrent pregnancy loss will have a successful next pregnancy (56), figures that many couples will view as optimistic.

Recommendations
When is a diagnosis of recurrent pregnancy

loss appropriate?
Should all couples with recurrent pregnancy

loss have chromosomal analysis performed?
Parents with recurrent pregnancy loss should be analyzed

for balanced chromosome abnormalities because: 1) couples would like to know why they are experiencing repetitive pregnancy loss; 2) a couple in which one partner
carries a balanced chromosome abnormality is at increased risk for having a fetus with an unbalanced chromosome abnormality and may benefit from prenatal
genetic testing; and 3) the apparently normal offspring of
a couple in which one partner carries a balanced chromosome abnormality is at risk for carrying the same balanced chromosome abnormality and, thus, is at risk for
reproductive complications.
Balanced chromosome abnormalities occurring in
one partner are relatively infrequent among couples with
Traditionally, recurrent pregnancy loss has been defined

as three consecutive spontaneous abortions. However, the
risk of abortion after two successive abortions (30%) is
clinically similar to the risk of recurrence among women
with three or more consecutive abortions (33%) (37,
5766). Thus, patients with two or more consecutive
spontaneous abortions are candidates for an evaluation to
determine the etiology, if any, for their pregnancy losses.
The number of previous pregnancy losses influences
the likelihood of successful pregnancy. One study reported recurrent pregnancy loss rates of 29%, 27%, 44%,
and 53% after 3, 4, 5, and 6 or more recurrent pregnancy
losses, respectively (67). In addition, maternal age influences the recurrent pregnancy loss rate (67, 68), with a
recurrent pregnancy loss rate of approximately 25% in
women aged 30 years or younger and a recurrent pregnancy loss rate of 5060% in those 40 years or older.
Some investigators have found the prognosis for a successful pregnancy is increased by 1020% in women with
at least one previous live birth (58, 69), but others did not
(67).
only recurrent pregnancy loss but no other adverse perinatal outcomes (eg, stillborns, anomalous infants). One
study reported that of couples with recurrent loss, only
2.4% of female partners and 1.6% of male partners with
a history of stillbirths or anomalous infants had a balanced chromosome abnormality, compared with 4.6% of
female partners and 1.7% of male partners with a history
of adverse perinatal outcomes (70). However, no historic
factor unequivocally allows the clinician to determine
which couples may benefit from karyotype analyses. In
addition, phenotypically normal offspring do not exclude
the possibility of a balanced chromosome abnormality in
a couple with recurrent pregnancy loss.
Parental cytogenetic analysis should be offered to all
couples with recurrent pregnancy loss. In addition, all
couples in which one partner has been found to have a
balanced translocation or inversion should be offered prenatal genetic diagnosis because of the increased risk of a
karyotypic abnormality in the conceptus.
In addition, many experts obtain a karyotype of the
abortus tissue when a couple with recurrent pregnancy
loss experiences a subsequent spontaneous abortion. The
rationale is that if the abortus is aneuploid, the physician
and patient may conclude that a maternal cause of pregnancy loss is excluded. Also, an abnormal abortus karyotype is a legitimate explanation for the loss that may
provide a source of comfort to the couple. However, no
published evidence supports these hypotheses, and definite recommendations for routinely obtaining abortus
karyotypes cannot be made.
How should the uterine cavity be evaluated in

a woman with recurrent pregnancy loss, and
how should abnormal findings be treated?
Uterine anatomic abnormalities are diagnosed by hysterosalpingography, hysteroscopy, or sonohysteroscopy.

Three-dimensional ultrasonography, although not routinely available in the United States, also has been shown
to be useful in the diagnosis of uterine abnormalities.
Suspicious or confusing cases can be evaluated further by
magnetic resonance imaging. However, the relationship
between uterine abnormalities and recurrent pregnancy
loss is uncertain, and some authorities do not recommend
routinely evaluating the uterine cavity by hysterosalpingography, hysteroscopy, or sonohysteroscopy (71).
No prospective, controlled trials have proved that the
correction of uterine anatomic abnormalities benefits the
next pregnancy outcome. Retrospectively analyzed case
series suggest that 7085% of women with recurrent
pregnancy loss with bicornuate and septate uteri who
undergo surgical correction will deliver viable live born
infants in their next pregnancies (72), but these seeming-
PRACTICE BULLETINS
ly excellent results are subject to criticism because of the

methods of patient selection and the lack of controls.
Hysteroscopic resection has been used successfully
for treatment of the uterine septum, and subsequent pregnancy results are comparable to those for metroplasty
(72). It is preferable to abdominal surgery because it is an
outpatient procedure with low morbidity and allows for
labor with expected vaginal delivery. Uterine synechiae
also may be treated hysteroscopically.
Should thyroid tests and tests for glucose

intolerance be performed in women with
recurrent pregnancy loss?
An association between recurrent pregnancy loss and

asymptomatic endocrinologic or metabolic disorders such
as mild thyroid disease or glucose intolerance has not been
established. Thus, tests for thyroid dysfunction or glucose
intolerance are not required in the evaluation of otherwise
normal women with recurrent pregnancy loss.
An association between antithyroid antibodies and
recurrent pregnancy loss has been reported by some
investigators (31, 8083). Very few patients identified in
these studies are clinically hypothyroid, and less than
20% have abnormal thyroid-stimulating hormone test
results (80). In addition, no treatments have proved to
benefit next pregnancy outcome in women found to have
antithyroid antibodies. Thus, tests for antithyroid antibodies are not required in the evaluation of women with
recurrent pregnancy loss.
Although assessment of luteal phase progesterone production or effect is firmly entrenched in the traditional
evaluation of women with recurrent pregnancy loss, the
evidence supporting this practice is scant. The endometrium is considered out of phase when the histologic dating
lags behind the menstrual dating by 2 days or more.
However, interobserver variation in the interpretation
of the biopsies is considerable (73), and modest intraobserver variation occurs (74). Because of 1) such variation, 2) the frequent finding of out-of-phase endometrial
histology in normal women, and 3) the inconsistent
expression of luteal phase defect in affected women,
luteal phase defect is diagnosed only when two consecutive biopsies are out of phase. The measurement of luteal
phase progesterone concentrations is not an adequate
method for diagnosing or excluding luteal phase defect.
No properly designed studies have evaluated the role
of progesterone treatment in women with recurrent pregnancy loss with luteal phase defect. Two meta-analyses
of studies from the 1950s and 1960s reached conflicting
conclusions regarding the efficacy of progesterone treatment in variously selected women with recurrent abortion (75, 76). The studies included in these meta-analyses
are difficult to interpret because they 1) did not assess
patients for luteal phase defect using currently accepted
criteria, 2) employed 17-OH progesterone caproate or
medroxyprogesterone as treatment, 3) used various inclusion criteria, and 4) entered patients after pregnancy had
progressed to at least 8 weeks of gestation. Also, these
studies totaled only 130 patients, and one of them (77)
was not randomized. In addition, in a more recent randomized trial, a subgroup of women with PCOS and
three or more miscarriages were randomized to treatment
with either progesterone or placebo pessaries (78). There
was no difference in the pregnancy outcomes.
Human chorionic gonadotropin has been used in an
attempt to stimulate the corpus luteum support of pregnancy in women with recurrent abortion. One international multicentered trial randomized 75 women to
receive either placebo or 10,000 IU of human chorionic
gonadotropin at the first diagnosis of pregnancy and

5,000 IU weekly thereafter (79). No significant difference in the successful pregnancy rates (83% versus 79%)
between the groups was found.
In summary, the relationship between the luteal
phase defect and recurrent pregnancy loss remains a subject of controversy. It has not been shown conclusively
that progesterone treatment or corpus luteum support
influences pregnancy outcome in women with recurrent
pregnancy loss.
Should women with recurrent pregnancy loss

be evaluated for luteal phase defect?
743

be evaluated for possible infectious causes,
and should they be treated?
Endocervical Chlamydia and Mycoplasma have been

implicated as causes of recurrent pregnancy loss, but
study results are conflicting. Bacterial vaginosis may be
associated with midtrimester pregnancy loss (84, 85), and
one study found an increased rate of pregnancy loss in
women with bacterial vaginosis undergoing in vitro fertilization (86). However, there is no direct evidence (confirmed by cultures) of Chlamydia, Mycoplasma, and
organisms causing bacterial vaginosis in systematically
analyzed recurrent abortus specimens. These infectious
agents are very common. Mycoplasma may be recovered
from the endocervix of one third of sexually active
adults. One group of investigators found that women with
recurrent pregnancy loss have a significantly higher rate of
endometrial colonization with Ureaplasma urealyticum
compared with controls, raising the speculation that
endometrial (but not endocervical) colonization with
744

be evaluated for antiphospholipid syndrome?

be evaluated for thrombophilias?
The role of thrombophilia in recurrent pregnancy loss is

a controversial subject of current research interest. Tests
for factor V Leiden, the prothrombin G20210A mutation,
or deficiencies of protein C, protein S, or antithrombin III
should be considered in cases of otherwise unexplained
fetal death in the second or third trimesters. However, the
role of these heritable thrombophilias in recurrent early
pregnancy loss is uncertain at present, and tests for these
thrombophilias are not required as part of the evaluation.
Whether antithrombotic treatment improves subsequent
pregnancy outcomes in women with evidence of thrombophilia is uncertain.

be evaluated for possible alloimmune causes?
Results of tests for human leukocyte antigen types,

maternal serum blocking factors, or maternal antileukocytic antibodies directed against the male partners
leukocytes have not been shown to predict subsequent
pregnancy outcome. Therefore, testing is not recommended, and treatment is not warranted. Luteal phase
biopsy to determine the status of NK-like cells is not recommended because of mixed results in the literature, the
uncertainty of prognostic implications, and the lack of an
effective treatment. Finally, in the absence of a proven
effective treatment, tests for embryotoxic factor or determination of the percentage of circulating NK cells in
women with recurrent pregnancy loss is not beneficial.
Antiphospholipid syndrome is associated with pregnancy

loss in 315% of women with recurrent pregnancy loss
(33, 8790). Some investigators have emphasized the
relationship between APS and second- or early thirdtrimester fetal death (91), whereas others have found that
a small percentage of women with recurrent firsttrimester pregnancy loss have antiphospholipid antibodies (90). Women with a previous fetal death (33, 92) and
high levels of anticardiolipin immunoglobulin G (IgG)
antibodies (92) are at the greatest risk of fetal loss in subsequent pregnancies. Therefore, women with recurrent
pregnancy loss should be tested for antiphospholipid syndrome using standard assays for anticardiolipin antibodies and lupus anticoagulant.
Antiphospholipid syndrome is identified in a woman
with recurrent pregnancy loss by the detection of lupus
anticoagulant, 2-glycoprotein Idependent anticardiolipin antibodies, or both on two occasions at least
6 weeks apart (31). The IgG isotype of anticardiolipin is
most relevant clinically, but tests repeatedly positive for
IgM anticardiolipin may be used to make the diagnosis.
In individuals demonstrating only anticardiolipin antibodies, definite APS is diagnosed when the antibody levels are repeatedly 20 units or greater. Repeatedly positive
test results for anticardiolipin antibodies with levels of
less than 20 units are of uncertain significance.
Women with APS benefit from treatment with
heparin and low-dose aspirin during pregnancy. Two
studies have shown that women with recurrent early
pregnancy loss and positive test results for antiphospholipid antibodies benefit from treatment with low-dose
aspirin and heparin. Successful pregnancy rates for these
women are 7075%, compared with less than 50% for
the untreated patients (93, 94). These studies used
heparin dosages in the range of 10,00025,000 U/d, and
neither study included women with a history of thrombosis or systemic lupus erythematosus.
Mycoplasma may play a role in recurrent pregnancy loss.

Existing nonrandomized studies of the effects of antibiotic treatment on subsequent pregnancy outcome in
women with endocervical Mycoplasma colonization have
yielded conflicting results.
Currently, routine serologic or endocervical cultures
for Chlamydia or Mycoplasma and vaginal evaluation for
bacterial vaginosis are not useful in evaluating otherwise
healthy women presenting with recurrent abortion. In
addition, empiric treatment with antibiotics in the
absence of documented infection is not warranted.
Is paternal lymphocyte immunization or

intravenous immune globulin (IVIG) an
effective treatment for recurrent pregnancy
loss?
The most widely used immunotherapeutic treatment regimen for women with unexplained recurrent loss involves
immunizing the female partner with the male partners
leukocytes. Of several randomized, prospective studies
(53, 54, 95), only one found a benefit to leukocyte immunization (96). The largest trial, and the only multicenter
effort, found that women undergoing leukocyte immunization actually had a higher rate of pregnancy loss than
placebo controls (55), suggesting that the treatment may
be harmful. In addition, there is no consensus regarding
patient selection or the dose, route, or timing of leukocyte
immunization, and immunization using viable leukocytes
carries risks similar to those of blood transfusion, including the transmission of viral diseases.
PRACTICE BULLETINS
Cultures for bacteria or viruses and tests for glucose

intolerance, thyroid abnormalities, antibodies to
infectious agents, antinuclear antibodies, antithyroid
antibodies, paternal human leukocyte antigen status,
or maternal antipaternal antibodies are not beneficial
and, therefore, are not recommended in the evaluation of otherwise normal women with recurrent
pregnancy loss.
The second immunomodulatory therapy used as a

treatment for recurrent pregnancy loss is IVIG (97).
Initial interest in this therapy derives from the observation that IVIG contains antibodies that block antibody-mediated immune damage (98). Other known
immunomodulating effects of IVIG include T cell receptor blockade, inhibition of NK-cell activity, inhibition of
Th-1 cytokine secretion, Fc receptor blockade, complement inactivation, down-regulation of B cell responsiveness, and enhanced T cell suppressor cell function (99).
However, only one of five randomized trials using IVIG
treatment in women with recurrent pregnancy loss
demonstrated a benefit (52); results of the others were
negative (100103). In addition, the results of two metaanalyses also were negative (104, 105).
745
Couples with otherwise unexplained recurrent pregnancy loss should be counseled regarding the potential for successful pregnancy without treatment.
References
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Summary
The following recommendations are based on
good and consistent scientific evidence (Level A):
Women with recurrent pregnancy loss should be

tested for lupus anticoagulant and anticardiolipin
antibodies using standard assays. If test results are
positive for the same antibody on two consecutive
occasions 68 weeks apart, the patient should be
treated with heparin and low-dose aspirin during her
next pregnancy attempt.
Mononuclear cell (leukocyte) immunization and

IVIG are not effective in preventing recurrent pregnancy loss.
An association between the luteal phase defect and

recurrent pregnancy loss is controversial. If a diagnosis of luteal phase defect is sought in a woman
with recurrent pregnancy loss, it should be confirmed
by endometrial biopsy.
Luteal phase support with progesterone is of unproven efficacy.
Couples with recurrent pregnancy loss should be tested for parental balanced chromosome abnormalities.
Women with recurrent pregnancy loss and a uterine

septum should undergo hysteroscopic evaluation and
resection.
2. Lanasa MC, Hogge WA, Kubic C, Blancato J, Hoffman

EP. Highly skewed X-chromosome inactivation is associated with idiopathic recurrent spontaneous abortion. Am J
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T. Does the karyotype of a spontaneous abortion predict
the karyotype of a subsequent abortion? Evidence from
273 women with two karyotyped spontaneous abortions.
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11. Clifford K, Rai R, Watson H, Regan L. An informative

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102. Stephenson MD, Dreher K, Houlihan E, Wu V. Prevention
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1997;12:23882392 (Level I)
104. Daya S, Gunby J, Clark DA. Intravenous immunoglobulin
therapy for recurrent spontaneous abortion: a meta-analysis. Am J Reprod Immunol 1998;39:6976 (Meta-analysis)
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(Meta-analysis)
749

to conduct a literature search to locate relevant articles published between January 1985 and October 2000. The search
Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were
Force:
I
type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
750
ACOG
PRACTICE
BULLETIN
NUMBER 29, JULY 2001
(Replaces Technical Bulletin Number 219, January 1996)

of Larry C. Gilstrap III, MD
and Susan M. Ramin, MD.
of practice.
Reaffirmed 2008
Chronic Hypertension
in Pregnancy
Chronic hypertension occurs in up to 5% of pregnant women; rates vary
according to the population studied and the criteria used for confirming the
diagnosis (1, 2). This complication may result in significant maternal, fetal, and
neonatal morbidity and mortality. There has been confusion over the terminology and criteria used to diagnose this complication, as well as the benefit and
potential harm of treatment during pregnancy. The purpose of this document is
to review the effects of chronic hypertension on pregnancy, to clarify the terminology and criteria used to define and diagnose it during pregnancy, and to
review the available evidence for treatment options.
Background
Definition
According to the National High Blood Pressure Education Program Working
Group on High Blood Pressure in Pregnancy, chronic hypertension is defined as
hypertension present before the 20th week of pregnancy or hypertension present
before pregnancy (3). The blood pressure (BP) criteria used to define hypertension are a systolic pressure of 140 mmHg, a diastolic pressure of 90 mmHg,
or both (see the box). Chronic hypertension during pregnancy is most commonly classified as mild (BP >140/90 mmHg) or as severe (BP 180/110 mmHg)
(4). The diagnosis is relatively easy to make in women taking antihypertensive
medications before conception. However, the diagnosis can be difficult to establish or distinguish from preeclampsia when the woman presents with hypertension late in gestation. In this latter scenario, hypertension that persists longer
than the postpartum period (12 weeks post delivery) is classified as chronic.
Hypertension should be documented on more than one occasion.
According to the National High Blood Pressure Education Program Working
PRACTICE BULLETINS
Criteria for Diagnosis of Chronic Hypertension

in Pregnancy
Mild:
Systolic blood pressure 140 mmHg

Diastolic blood pressure 90 mmHg
Severe: Systolic blood pressure 180 mmHg
Diastolic blood pressure 110 mmHg
Use of antihypertensive medications before pregnancy
Onset of hypertension before 20th week of gestation
Persistence of hypertension beyond the usual postpartum period
Group on High Blood Pressure in Pregnancy, the diastolic blood pressure is that pressure at which the sound
disappears (Korotkoff phase V) (3). In order to reduce
inaccurate readings, an appropriate size cuff should be
used (length 1.5 times upper arm circumference or a cuff
with a bladder that encircles 80% or more of the arm).
Pressure should be taken with the patient in an upright
position, after a 10-minute or longer rest period. For
patients in the hospital, the blood pressure can be taken
with either the patient sitting up or in the left lateral
recumbent position with the patients arm at the level of
the heart (5). The patient should not use tobacco or caffeine for 30 minutes preceding the measurement (6, 7).
Although validated electronic devices can be used, a mercury sphygmomanometer is preferred (6, 7).
Chronic hypertension usually can be distinguished
from preeclampsia because preeclampsia typically
appears after 20 weeks of gestation in a woman who was
normotensive before pregnancy. Moreover, preeclampsia
resolves during the postpartum period. Additionally,
preeclampsia is frequently associated with proteinuria
and characteristic symptoms such as headache, scotomata, or epigastric pain. Women with preeclampsia also may
have hemolysis, elevated liver enzymes, and low platelet
count (HELLP syndrome). However, the development of
superimposed preeclampsia in pregnant women with
chronic hypertension is relatively common and is often
difficult to diagnose. The acute onset of proteinuria and
worsening hypertension in women with chronic hypertension is suggestive of superimposed preeclampsia.
An additional diagnostic complication may arise in
women with chronic hypertension who begin prenatal
care after 20 weeks of gestation. A physiologic decrease
in blood pressure normally occurs early in the second
trimester, and may be exaggerated in women with chronic hypertension. This decrease may lead to an erroneous
assumption that the blood pressure is normal at this stage
of gestation (3). By the third trimester, the blood pressure
usually returns to its prepregnancy level (5).
751
Effects of Chronic Hypertension

on Pregnancy
Chronic hypertension complicates pregnancy and is associated with several adverse outcomes, including premature birth, intrauterine growth restriction (IUGR), fetal
demise, placental abruption, and cesarean delivery (4).
The incidence of these potential adverse effects is related
to the degree and duration of hypertension and to the
association of other organ system involvement or damage. As many as one third of women with severe chronic
hypertension may have a small-for-gestational-age
(SGA) infant, and two thirds may have a preterm delivery (8). In a study of 211 pregnant women with mild
chronic hypertension, the uncorrected perinatal mortality
rate was 28 per 1,000 and was highest in the 21 pregnancies complicated by superimposed preeclampsia. The
perinatal mortality rate was 5 per 1,000 in the 190 pregnancies not complicated by preeclampsia (9).
In another study, pregnancy outcomes were reviewed
in 44 pregnant women with severe chronic hypertension
in the first trimester (10). Slightly more than half developed superimposed preeclampsia; in this subgroup of
patients, perinatal death and neonatal morbidity were significantly increased. Comparing women who developed
superimposed preeclampsia with women who did not, the
incidence of prematurity was 100% versus 38%, the incidence of SGA infants was 78% versus 15%, and the perinatal mortality rate was 48% versus 0%.
Other studies also have reported an increase in perinatal mortality of 24 times more than the general population (1113). For example, a study of 337 pregnancies
complicated by chronic hypertension reported a perinatal
mortality rate of 45 per 1,000 compared with a rate of 12
per 1,000 in the general population (11).
A study of outcomes in 763 pregnant women with
chronic hypertension indicated that women with baseline
proteinuria (300 mg or greater of urinary protein in 24
hours at initial evaluation at 1326 weeks of gestation)
were at significant risk of preterm delivery (odds ratio
[OR], 3.1; 95% confidence interval [CI], 1.85.3) and
SGA infants (OR, 2.8; 95% CI, 1.65.0) independent of
superimposed preeclampsia (14). The development of
preeclampsia (defined as new-onset proteinuria) was significantly associated with perinatal death (OR, 2.3; 95%
CI, 1.14.8). Preeclampsia also was associated with an
increase in placental abruption (3% versus 1%). In a metaanalysis of seven casecontrol and six cohort studies, the
risk of placental abruption was related to both cigarette
smoking and chronic hypertension, as well as preeclampsia (15). A systematic review of the management of chronic hypertension during pregnancy revealed that chronic
hypertension doubled the risk for placental abruption (OR,
2.1; 95% CI, 1.1, 3.9) and tripled the risk for perinatal
mortality (OR, 3.4; 95% CI, 3.0, 3.7) (4, 16). Several of the
752
studies included in this review also showed an association

between chronic hypertension and preeclampsia (variously defined) and preterm, SGA, or low-birth-weight infants
when compared with normotensive women or the general
obstetric population. The risk of these complications was
increased even in the absence of superimposed preeclampsia, although the absolute increased risk from mild
hypertension could not be calculated from the available
data (4).
Effects of Pregnancy on Hypertension

Recommendations
In the initial evaluation of a pregnant woman

with hypertension, which clinical tests are
useful?
Are other adjunctive tests useful in evaluating

a pregnant woman with hypertension?
Many women with chronic hypertension are under the

care of a primary care physician and already have been
evaluated for causes of secondary hypertension, such as
pheochromocytoma or Cushings disease. However,
young women in whom hypertension has been diagnosed
for the first time in early pregnancy, especially those with
severe hypertension (systolic pressure 180 mmHg or
diastolic pressure 110 mmHg), are more likely to have
secondary hypertension and to benefit from further evaluation for potentially reversible causes (3). Women with
paroxysmal hypertension, frequent hypertensive crisis,
seizure disorders, or anxiety attacks should be evaluated
for pheochromocytoma with measurements of 24-hour
urine vanillylmandelic acid, metanephrines, or unconjugated catecholamines (21). Magnetic resonance imaging
after the first trimester or computed tomography also
may be useful for adrenal tumor localization (19).
Cushings syndrome is rare in pregnancy and is difficult to diagnose because of pregnancy-related changes
in steroids (22). Fortunately, this condition is diagnosed
in most women before pregnancy. Primary aldosteronism
also is rare in pregnancy. Women with this disorder may
present with severe hypertension and hypokalemia.
Imaging studies may be helpful in demonstrating an
adrenal adenoma.
A young woman (younger than 30 years) with severe
hypertension (especially with no family history) who has
not been previously evaluated may benefit from Doppler
flow studies or magnetic resonance angiography to detect
renal artery stenosis (7). Renal artery stenosis appears to
be more prevalent in patients with type-2 diabetes and
coexistent hypertension (23, 24). Negative results from
renal ultrasonography do not rule out renal artery stenosis.
The age of onset, results of previous evaluation, severity

and duration of hypertension, and physical examination
are important determinants of which clinical tests may be
useful. Ideally, a woman with chronic hypertension should
be evaluated before conception to ascertain potentially
reversible causes and possible end-organ involvement (eg,
heart or kidney). Women who have had hypertension for
several years are more likely to have cardiomegaly,
ischemic heart disease, renal involvement, and retinopathy
(3). Thus, these women are more likely to benefit from
various specialized clinical tests at the initial evaluation
during pregnancy or preconceptionally. Tests may
include electrocardiography, echocardiography, ophthalmologic examination, and renal ultrasonography (7). The
information obtained from these tests may prove useful in
assessing risks of hypertension during pregnancy, as well
as providing information for prenatal counseling. Women
with significant left ventricular hypertrophy secondary to
Several physiologic changes occur in pregnant women

that can affect chronic hypertension. One of the most significant changes is the increase in blood volume, which
may further burden an already stressed heart and, along
with the decrease in colloid oncotic pressure, may lead to
cardiac decompensation. Another important change is the
physiologic decrease in blood pressure, which begins by
the end of the first trimester and reaches its lowest level at
1618 weeks of gestation (16). This change can mask
either the course or the detection of chronic hypertension
in early pregnancy (3). Besides superimposed preeclampsia or eclampsia, pregnancy complicated by chronic
hypertension (especially if severe) may be associated with
worsening or malignant hypertension, central nervous
system hemorrhage, cardiac decompensation, and renal
deterioration or failure.
hypertension may experience cardiac decompensation and

heart failure as pregnancy progresses.
Women with significant renal disease (serum creatinine >1.4 mg/dL) may experience deterioration of renal
function, although it may be difficult to separate the effects
of pregnancy from the disease process (3, 17, 18). Many
women with the diagnosis of peripartum cardiomyopathy
are found to have underlying causes, chronic hypertension
being one of the most common (19, 20). However, most
pregnant women with mild chronic hypertension have
uneventful pregnancies with no end-organ involvement.
Are laboratory tests useful in evaluating a

pregnant woman with essential hypertension?
In pregnant women with known essential hypertension

(primary hypertension or hypertension not secondary to
underlying renal or adrenal disease), baseline laboratory
PRACTICE BULLETINS
evaluations that may prove clinically useful include tests

of renal function such as serum creatinine, blood urea
nitrogen, and 24-hour urine evaluation for total protein
and creatinine clearance (1, 7, 25). This initial laboratory
assessment is important in identifying women with
underlying renal disease because this complication may
adversely affect pregnancy outcome (26). The subsequent development of proteinuria in a woman with essential hypertension also may be helpful in identifying the
development of superimposed preeclampsia.
As pregnancy progresses, other laboratory testsin
addition to repeating those mentioned previouslymay
be clinically useful in evaluating worsening renal disease
and in diagnosing superimposed preeclampsia. These
include liver function tests, hemoglobin/hematocrit evaluation, and platelet count (27). Periodic measurement of
urine protein may be useful in detecting worsening renal
disease or the development of superimposed preeclampsia (28). It has been reported that the random proteincreatinine ratio may be useful for the quantitation of
proteinuria during pregnancy. The correlation coefficient
between this ratio and the 24-hour urine total protein was
0.94 (29). Investigators also reported high sensitivity and
specificity between the protein/creatinine ratio from a
single urine sample and proteinuria of 300 mg or greater
in a 24-hour specimen (30).
Although an elevated serum uric acid level represents a useful confirmatory test for the diagnosis of
preeclampsia, it has very poor predictive value among
patients without preexisting hypertension. However,
when the patient has chronic hypertension, the serum uric
acid level may be of some value. One investigator has
reported that a serum uric acid level of 5.5 mg/dL could
identify women with an increased likelihood of having
superimposed preeclampsia (31).
Who are candidates for treatment of chronic

hypertension in pregnancy?
Women with mild hypertension (140179 mmHg systolic or 90109 mmHg diastolic pressure) generally do
well during pregnancy and do not, as a rule, require antihypertensive medication (3). There is, to date, no scientific evidence that antihypertensive therapy will improve
perinatal outcome (25, 3234). In a review of 263 women
with mild hypertension randomized to methyldopa,
labetalol, or no treatment at 613 weeks of gestation,
treatment with antihypertensive medications did not
decrease the incidence of complications such as IUGR,
superimposed preeclampsia, placental abruption, or perinatal mortality (25).
There also is a paucity of scientific data regarding the
most appropriate management of women with well-con-
753
trolled or mild hypertension already taking antihypertensive medications at the time of pregnancy. Although such
therapy may offer long-term benefits to the mother, such
therapy is of unproven short-term benefit and could interfere with uteroplacental blood flow and fetal growth (3,
35). In one review of 298 pregnant women in whom antihypertensive medications were stopped or whose dosage
was reduced, there was no difference in the incidence of
preeclampsia, placental abruption, or perinatal death
compared with untreated groups (11). In a meta-analysis
of 623 women with mild chronic hypertension from 7 trials comparing antihypertensive treatment to no treatment, treatment was associated with a decrease in the
incidence of severe hypertension but did not improve
perinatal outcomes (36). In a follow-up meta-analysis
that included these 7 trials of pregnant women with
chronic hypertension and 38 trials of women with lateonset hypertension receiving therapy versus no therapy,
there was an increase in the frequency of SGA infants
associated with treatment-induced reduction in mean
arterial pressure (35).
Thus, the data are inconclusive with regard to both the
benefits and potential adverse fetal effects of treatment of
mild chronic hypertension during pregnancy. It would
seem reasonable not to start antihypertensive therapy in
women with mild hypertension who become pregnant
unless they have other complicating factors (eg, cardiovascular or renal disease) and to either stop or reduce medication in women who are already taking antihypertensive
therapy. As suggested by the National High Blood
Pressure Education Program Working Group on High
Blood Pressure in Pregnancy, therapy could be increased
or reinstituted for women with blood pressures exceeding
150 160 mmHg systolic or 100110 mmHg diastolic
(3). In women with severe chronic hypertension (systolic
pressure 180 mmHg or diastolic pressure 110 mmHg),
antihypertensive therapy should be initiated or continued
(10).
In addition, a systematic review of management of
chronic hypertension during pregnancy concluded that
the evidence base regarding pharmacologic management of chronic hypertension during pregnancy is too
small to either prove or disprove moderate to large benefits (>20 percent improvements) of antihypertensive therapy (16). The report further concluded that the efficacy
of antihypertensive therapy for chronic hypertension in
pregnant women was still uncertain. In this latter systematic review, the authors also were unable to identify trials
that compared nonpharmacologic interventions with antihypertensive agents or with no interventions for chronic
hypertension.
754
What medications are most often prescribed

for the treatment of chronic hypertension in
pregnancy?
Angiotensinconverting enzyme (ACE) inhibitors are

contraindicated during the second and third trimesters of
pregnancy. Although the data regarding their use during
pregnancy are limited to captopril, enalapril, and lisino-
Is there a role for fetal surveillance in pregnancies complicated by hypertension?
There is no consensus as to the most appropriate fetal

surveillance test(s) or the interval and timing of testing in
women with chronic hypertension. Thus, such testing
should be individualized and based on clinical judgment
and on severity of disease. A recent systematic review
concluded that there are no conclusive data to address
either the benefits or the harms of various monitoring
strategies for pregnant women with chronic hypertension
(16). However, other studies have indicated that most of
the increased morbidity associated with this condition is
secondary to superimposed preeclampsia or IUGR (3).
Thus, these investigators recommend that baseline ultrasonography be obtained at 1820 weeks of gestation and
that ultrasonography should be repeated at 2832 weeks
of gestation and monthly thereafter until delivery to monitor fetal growth. If growth restriction is detected or suspected, fetal status should be monitored frequently with
nonstress testing or biophysical profile testing (3). If
growth restriction is not present and superimposed
preeclampsia is excluded, these tests are not indicated
(3).
Are certain medications used to treat chronic

hypertension contraindicated during pregnancy?
Although there are numerous antihypertensive agents

that have been used for the treatment of chronic hypertension during pregnancy, methyldopa has been commonly used. It is preferred by most practitioners, and it
appears to be relatively safe (3, 16, 37, 38). Methyldopa
appears to have limited effects on uteroplacental blood
flow (3, 32, 33, 38).
Labetalol, a combined alpha- and beta-blocker, also
can be used during pregnancy as an alternative to methyldopa. In one study on the treatment of chronic hypertension with labetalol versus methyldopa, the authors reported
no differences in outcomes between the two medications
(25).
In a meta-analysis of beta-receptor blockers prescribed for pregnancies complicated by hypertension,
there was an increase in SGA infants born to those
women who took oral beta-blockers for mild hypertension
(OR, 2.46; 95% CI, 1.02, 5.92) (39). Calcium-channel
blockers or antagonists also have been used with limited
experience (1, 3). In one randomized study that compared
nifedipine (n=145) versus expectant management
(n=138) for mild hypertension in pregnancy, there was no
benefit to pregnancy outcome but also no increase in
adverse effects (34).
Diuretics also have been used to treat chronic hypertension, but there has been concern regarding the potential effect of these medications on normal blood volume
expansion associated with pregnancy. In one study of 20
women with mild hypertension, diuretics prevented normal expansion of the blood volume but did not adversely
affect perinatal outcome (40). Moreover, a meta-analysis
of 9 trials involving diuretics during pregnancy reported
no increase in adverse perinatal effects (41). The
National High Blood Pressure Education Program
Working Group on High Blood Pressure in Pregnancy
concluded, If diuretics are indicated, they are safe and
efficacious agents that can markedly potentiate the
response to other antihypertensive agents and are not
contraindicated in pregnancy except in settings in which
uteroplacental perfusion is already reduced (preeclampsia and IUGR) (3).
pril, the teratogenic risk appears to be similar for the

entire drug class. These ACE inhibitors have been associated with severely underdeveloped calvarial bone, renal
failure, oligohydramnios, anuria, renal dysgenesis, pulmonary hypoplasia, IUGR, fetal death, neonatal renal
failure, and neonatal death (4246). Fetal risks with ACE
inhibitors depend on timing and dose. For example, the
use of ACE inhibitors during the first trimester (before
renal tubular function begins) has not been associated
with an increase in birth defects (47, 48).
Should patients with chronic hypertension be

delivered before term?
Pregnant women with uncomplicated chronic hypertension of a mild degree generally can be delivered vaginally at term (25); most have good maternal and neonatal
outcomes (3). Cesarean delivery should be reserved for
other obstetric indications. Women with mild hypertension during pregnancy and a prior adverse pregnancy
outcome (eg, stillbirth) may be candidates for earlier
delivery after documentation of fetal lung maturity (as
long as fetal status is reassuring). Women with severe
chronic hypertension during pregnancy most often either
deliver prematurely or have to be delivered prematurely
for fetal or maternal indications (10).
There are no randomized clinical trials that specifically address the timing of delivery in women with
PRACTICE BULLETINS
chronic hypertension and superimposed preeclampsia.

However, the combination of chronic hypertension and
superimposed preeclampsia represents a complicated situation, and the clinician should consider consultation
with someone who has expertise in such clinical matters.
Delivery should be considered in all women with superimposed severe preeclampsia at or beyond 28 weeks of
gestation and in women with mild superimposed
preeclampsia at or beyond 37 weeks of gestation (49).
Women with superimposed severe preeclampsia in whom
it is elected to continue the pregnancy should be monitored in a center with maternal and neonatal intensive
care capability (49). In women with superimposed severe
preeclampsia and the HELLP syndrome (a form of severe
preeclampsia) delivery should be considered, even
remote from term.
Are there intrapartum concerns unique to

pregnant women with chronic hypertension?
concluded that the data regarding safety of epidural anesthesia in women with severe hypertension are limited by
both the heterogeneity of diagnoses and the uncontrolled
nature of the study. It would seem reasonable to conclude
that if regional anesthetic techniques are used in women
with severe hypertension, clinicians with specialized training in obstetric anesthesia should be available.
General anesthesia may pose a risk in pregnant
women with severe hypertension or superimposed
preeclampsia. Intubation and extubation may be associated with acute and significant elevations in blood pressure
and an agent such as labetalol usually is given acutely to
minimize this effect (3). Ketamine, because of its association with hypertension, is not considered first line therapy for the induction of general anesthesia (52).
Magnesium sulfate should be used for women with
superimposed severe preeclampsia to prevent seizures.
However, its benefit in women with mild preeclampsia is
unclear (3).
How is chronic hypertension distinguished

from preeclampsia when the woman presents
late in pregnancy?
It is often difficult, if not impossible, to distinguish worsening chronic hypertension from superimposed severe
preeclampsia, especially when the patient presents late in
pregnancy. In the woman with chronic hypertension and
renal disease, it may not be possible to distinguish
between the two entities. If the same woman has only
hypertension without proteinuria and no symptoms of
preeclampsia, such as headache, epigastric pain, or scotomata, the diagnosis may be more difficult. However,
the vast majority of young, nulliparous women presenting with hypertension for the first time during late pregnancy will have preeclampsia. In addition to testing for
proteinuria, other tests that may be helpful include
hemoglobin and hematocrit evaluation, platelet count,
and liver function tests. These latter tests are useful in the
diagnosis of the HELLP syndrome. Oliguria and an elevated hemoglobin/hematocrit level usually indicate
hemoconcentrationmore indicative of preeclampsia.
Serum creatinine levels also may be elevated in women
with preeclampsia.
Summary of
Recommendations
The majority of pregnant women with chronic hypertension have uncomplicated mild hypertension and can be
managed the same as normal, nonhypertensive women
during the intrapartum period. In contrast, women with
severe hypertension or hypertension that is complicated
by cardiovascular or renal disease may present special
problems during the intrapartum period. Women with
severe hypertension may require antihypertensive medications for acute elevation of blood pressure. Although no
well-designed studies specifically address the treatment of
severe chronic hypertension during the intrapartum period, it is generally recommended that antihypertensive
medications be given to women with preeclampsia for
systolic blood pressure of >160 mmHg or diastolic blood
pressure of 105110 mmHg or greater (3).
Women with chronic hypertension complicated by
significant cardiovascular or renal disease require special
attention to fluid load and urine output because they may
be susceptible to fluid overload with resultant pulmonary
edema. There are insufficient data to address the benefits
and potential harm of central invasive hemodynamic
monitoring in women with pregnancy related hypertensive disorders (3, 50).
There are limited data to address the issue of analgesia
or anesthesia in pregnant women with chronic hypertension. In one study of 327 women with severe hypertension
in labor (158 of whom had chronic hypertension), there
was no increase in maternal pulmonary edema, renal failure, or cesarean delivery in women with an epidural
(n=209) or without an epidural (n=118). However, there
was a higher cesarean delivery rate in the subgroup of
women with chronic hypertension who received an epidural (51). There also were no significant differences in
neonatal outcomes between the two groups. Mild hypertension was not addressed in this cohort. The authors
755
Angiotensin-converting enzyme inhibitors are contraindicated during pregnancy and are associated
with fetal and neonatal renal failure and death.
756
8. McCowan LM, Buist RG, North RA, Gamble G. Perinatal

morbidity in chronic hypertension. Br J Obstet Gynaecol
1996;103:123129 (Level II-2)
Antihypertensive therapy should be used for pregnant women with severe hypertension for maternal
benefit.
9. Sibai BM, Abdella TN, Anderson GD. Pregnancy outcome

in 211 patients with mild chronic hypertension. Obstet
Methyldopa and labetalol are appropriate first-line

antihypertensive therapies.
10. Sibai BM, Anderson GD. Pregnancy outcome of intensive

therapy in severe hypertension in first trimester. Obstet
Treatment of women with uncomplicated mild

chronic hypertension is not beneficial because it
does not improve perinatal outcome.
11. Rey E, Couturier A. The prognosis of pregnancy in women

with chronic hypertension. Am J Obstet Gynecol 1994;
171:410416 (Level II-3)
The beta-blocker atenolol may be associated with

growth restriction and is not recommended for use in
pregnancy.
12. Ananth CV, Savitz DA, Bowes WA Jr. Hypertensive disorders of pregnancy and stillbirth in North Carolina, 1988 to
1991. Acta Obstet Gynecol Scand 1995;74:788793
(Level II-3)
13. Jain L. Effect of pregnancy-induced and chronic hypertension on pregnancy outcome. J Perinatol 1997; 17:425427
(Level II-3)
Women with chronic hypertension should be evaluated for potentially reversible etiologies, preferably
prior to pregnancy.
Women with long-standing hypertension should be

evaluated for end-organ disease, including cardiomegaly, renal insufficiency, and retinopathy,
preferably prior to pregnancy.
When chronic hypertension is complicated by IUGR

or preeclampsia, fetal surveillance is warranted.
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4. Ferrer RL, Sibai BM, Mulrow CD, Chiquette E, Stevens
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P, Klebanoff M, et al. Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among
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18. Jones DC. Pregnancy complicated by chronic renal disease. Clin Perinatol 1997;24:483496 (Level III)
19. Cunningham FG, Pritchard JA, Hankins GD, Anderson
PL, Lucas MK, Armstrong KF. Peripartum heart failure:
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20. Mabie WC, Hackman BB, Sibai BM. Pulmonary edema
associated with pregnancy: echocardiographic insights and
implications for treatment. Obstet Gynecol 1993;81:
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21. Botchan A, Hauser R, Kupfermine M, Grisaru D, Peyser
MR, Lessing JB. Pheochromocytoma in pregnancy: case
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22. Buescher MA, McClamrock HD, Adashi EY. Cushing syndrome in pregnancy. Obstet Gynecol 1992;79: 130137
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23. Valabhji J, Robinson S, Poulter C, Robinson AC, Kong C,
Henzen C, et al. Prevalence of renal artery stenosis in sub-
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Diabetes Care 2000;23:539543 (Level II-3)
fetal hemodynamics in pregnancy-induced hypertension.

24. Courreges JP, Bacha J, Aboud E, Pradier P. Prevalence of

renal artery stenosis in type 2 diabetes. Diabetes Metab
2000;26 Suppl 4:9096 (Level II-3)
39. Magee LA, Elran E, Bull SB, Logan A, Koren G. Risks

and benefits of beta-receptor blockers for pregnancy
hypertension: overview of the randomized trials. Eur J
Obstet Gynecol Reprod Biol 2000;88:1526 (Meta-analysis)
25. Sibai BM, Mabie WC, Shamsa F, Villar MA, Anderson

GD. A comparison of no medication versus methyldopa or
labetalol in chronic hypertension during pregnancy. Am J
Obstet Gynecol 1990;162:960966; discussion 966967
(Level I)
40. Sibai BM, Grossman RA, Grossman HG. Effects of diuretics on plasma volume in pregnancies with long-term
hypertension. Am J Obstet Gynecol 1984;150:831835
(Level II-1)
26. Katz AL, Davison JM, Hayslett JP, Singson E, Lindheimer

MD. Pregnancy in women with kidney disease. Kidney
Intl 1980;18:192206 (Level II-3)
41. Collins R, Yusuf S, Peto R. Overview of randomized trials

of diuretics in pregnancy. Br Med J (Clin Res Ed) 1985;
27. Weinstein L. Syndrome of hemolysis, elevated liver

enzymes, and low platelet count: a severe consequence of
hypertension in pregnancy. Am J Obstet Gynecol 1982:
142:159167 (Level II-3)
42. Barr M Jr, Cohen MM Jr. ACE inhibitor fetopathy and

hypocalvaria: the kidney-skull connection. Teratology
1991;44:485495 (Level III)
28. Evans W, Lensmeyer JP, Kirby RS, Malnory ME,

Broekhuizen FF. Two-hour urine collection for evaluating
renal function correlates with 24-hour urine collection in
pregnant patients. J Matern Fetal Med 2000;9:233237
(Level II-3)
29. Robert M, Sepandj F, Liston RM, Dooley KC. Random
protein-creatinine ratio for the quantitation of proteinuria
in pregnancy. Obstet Gynecol 1997;90:893895 (Level II-2)
30. Ramos JG, Martins-Costa SH, Mathias MM, Guerin YL,
Barros EG. Urinary protein/creatinine ratio in hypertensive pregnant women. Hypertens Pregnancy 1999;18:
209 218 (Level II-3)
31. Lim KH, Friedman SA, Ecker JL, Kao L, Kilpatrick SJ.
The clinical utility of serum uric acid measurements in
hypertensive diseases of pregnancy. Am J Obstet Gynecol
1998;178:10671071 (Level II-2)
32. Cunningham FG, MacDonald PC, Gant NF, Leveno KJ,
Gilstrap LC III, Hankins GD, et al. Endocrine disorders.
In: Williams obstetrics. 20th ed. Stamford, Connecticut:
Appleton & Lange, 1997:12231238 (Level III)
33. Sibai BM. Treatment of hypertension in pregnant women.
N Engl J Med 1996;335:257265 (Level III)
34. Nifedipine versus expectant management in mild to moderate hypertension in pregnancy. Gruppo di Studio
Ipertensione in Gravidanza. Br J Obstet Gynaecol 1998;
105:718722 (Level I)
35. von Dadelszen P, Ornstein MP, Bull SB, Logan AG, Koren
G, Magee LA. Fall in mean arterial pressure and fetal
growth restriction in pregnancy hypertension: a metaanalysis. Lancet 2000;355:8792 (Meta-analysis)
36. Magee LA, Ornstein MP, von Dadelszen P. Fortnightly
review: management of hypertension in pregnancy. BMJ
1999;318:13321336 (Meta-analysis)
37. Ounsted M, Cockburn J, Moar VA, Redman CW. Maternal
hypertension with superimposed pre-eclampsia: effects on
child development at 7 1/2 years. Br J Obstet Gynaecol
1983;90:644649 (Level II-2)
38. Montan S, Anandakumar C, Arulkumaran S, Ingemarsson
I, Ratnam SS. Effects of methyldopa on uteroplacental and
43. Hanssens M, Keirse MJ, Vankelecom F, Van Assche FA.

Fetal and neonatal effects of treatment with angiotensinconverting enzyme inhibitors in pregnancy. Obstet
44. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy
and lactation: a reference guide to fetal and neonatal risk.
5th ed. Baltimore: Williams & Wilkins, 1998 (Level III)
45. Buttar HS. An overview of the influence of ACE inhibitors
on fetal-placental circulation and perinatal development.
Mol Cell Biochem 1997;176:6171 (Level III)
46. Pryde PG, Sedman AB, Nugent CE, Barr M Jr.
Angiotensin-converting enzyme inhibitor fetopathy. J Am
Soc Nephrol 1993;3:15751582 (Level III)
47. Postmarketing surveillance for angiotensin-converting
enzyme inhibitor use during the first trimester of pregnancyUnited States, Canada, and Israel, 19871995.
MMWR Morb Mortal Wkly Rep 1997;46:240242
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48. Bar J, Hod M, Merlob P. Angiotensin converting enzyme
inhibitors use in the first trimester of pregnancy. Int J Risk
Saf Med 1997;10:2326 (Level III)
49. Sibai BM. Management of pre-eclampsia remote from
term. Eur J Obstet Gynecol Reprod Biol 1991;42:S96
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50. Practice guidelines for obstetrical anesthesia: a report by
the American Society of Anesthesiologists Task Force on
Obstetrical Anesthesia. Anesthesiology 1999;90:600611
(Level III)
51. Hogg B, Hauth JC, Caritis SN, Sibai BM, Lindheimer M,
Van Dorsten JP, et al. Safety of labor epidural anesthesia
for women with severe hypertensive disease. National
Maternal-Fetal Medicine Units Network. Am J Obstet
Gynecol 1999;181:10961101 (Level II-3)
52. Cheek TG, Samuels P. Pregnancy-induced hypertension.
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386411 (Level III)
758

to conduct a literature search to locate relevant articles published between January 1985 and August 2000. The search
Force:
I
type of evidence.
committees.

Gynecologists. All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system, or transmitted, in any form or
by any means, electronic, mechanical, photocopying, recording, or
01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW,
PO Box 96920
Chronic Hypertension in Pregnancy. ACOG Practice Bulletin No. 29.
2001;98:177185
PRACTICE BULLETINS
759
ACOG
PRACTICE
BULLETIN
(Replaces Technical Bulletin Number 200, December 1994)
of Donald R. Coustan, MD. The
of practice.
Reaffirmed 2008
Gestational diabetes mellitus (GDM) is one of the most common clinical issues
facing obstetricians and their patients. A lack of data from well-designed studies has contributed to the controversy surrounding the diagnosis and management of this condition. The purpose of this document is to provide a brief
overview of our understanding of GDM and provide management guidelines
that have been validated by appropriately conducted clinical research. When
outcomes-based research is not available, expert opinion is provided to aid the
practitioner.
Background
Definition and Prevalence
Diabetes is classified as type 1 or type 2 according to whether the patient
requires insulin injections to avoid ketoacidosis. Gestational diabetes mellitus
has been characterized as carbohydrate intolerance that begins or is first recognized during pregnancy. The prevalence of GDM varies in direct proportion to
the prevalence of type-2 diabetes in a given population or ethnic group.
Reported prevalence in the United States ranges from 1% to 14%, with 25%
being the most common figure (1).
Maternal and Fetal Complications

Women with GDM are more likely to develop hypertensive disorders than
women without GDM (2). Some of this additional risk may be related to the
underlying risk factors for GDM (eg, increased maternal age and obesity). The
diagnosis of GDM may prompt health care providers to intervene more readily
for perceived problems (3). In women without GDM, there is a significant association between increasing carbohydrate intolerance and both preeclampsia and
cesarean delivery (4). Women with GDM in Korea have a higher incidence of
preeclampsia and primary cesarean delivery, yet only 10% of the women are
obese (5). Whether the relationship with GDM is causal or not, clinicians
760
should be aware of these risks. In addition, women with

GDM have an increased risk of developing diabetes later
in life.
The offspring of women with GDM are prone to such
adverse events as macrosomia with its potential complications and hyperbilirubinemia. Infants of women with
GDM are at increased risk for operative delivery, shoulder
dystocia, and birth trauma. Because the risk factors for
GDM (particularly obesity) are independent risk factors
for fetal macrosomia, the role of maternal hyperglycemia
has been widely debated. Although controlling for maternal obesity eliminated the apparent relationship between
hyperglycemia and macrosomia in some studies (6, 7),
these results may have been confounded because the
women with GDM were treated. The relationship between
GDM, fetal macrosomia, and other adverse outcomes
has been confirmed in cohort studies in which maternal
obesity and other potential confounders were controlled
(8, 9), in a study of Korean women among whom only
10% were obese (5), and in another study of women
whose abnormal glucose tolerance tests (GTTs) went
clinically unrecognized (10). In women without GDM,
there is an independent relationship between GTT levels
and macrosomia (4, 11). When data were corrected for
maternal weight, age, parity, and race, the 12% risk of
macrosomia was independently attributable to GDM (9).
A number of studies also have linked maternal hyperglycemia with long-term obesity and diabetes in the offspring (1214). Nevertheless, considerable contro-versy
remains regarding the exact relationship of these complications to maternal hyperglycemia.
Controversy of Current Screening

Practices and Treatment Benefits
At one time, screening for GDM consisted of taking the
patients history. In 1973, OSullivan and Mahan proposed the 50-g, 1-hour laboratory screening test. This
test has become widely used94% of obstetric groups
surveyed reported universal testing (15)despite the
absence of data to demonstrate a benefit to the population
as a whole. However, as noted previously, maternal
hyperglycemia is related to at least some of the adverse
perinatal outcomes seen with GDM. Available evidence
does not support the concept that women with GDM who
do not have risk factors are of less concern than are those
who do (16).
The use of traditional historic risk factors (family or
personal history of diabetes, previous adverse pregnancy
outcome, glycosuria, obesity) to identify GDM will miss
approximately half of women with GDM (17, 18). If the
risks of adverse outcomes are related to the presence or
absence of confounding risk factors, rather than the
GDM, then limited screening based on risk may be rea-
sonable. The U.S. Preventive Services Task Force has

concluded that although there is insufficient evidence to
recommend universal screening, screening high-risk
women may be beneficial (19).
Despite the lack of population-derived data supporting the benefit of making the diagnosis of GDM, clinical
recommendations often must be made without unassailable epidemiologic evidence. Older, admittedly flawed,
studies suggested an increased perinatal mortality rate
among undiagnosed or untreated women with GDM (20,
21). More recent studies that did not demonstrate an
increase in perinatal mortality risk all included interventions of diet or insulin, antepartum testing, or merely
making the diagnosis, which has been shown to be a
powerful intervention in and of itself (3). If the perinatal
mortality rate in undiagnosed and untreated GDM were
double the background rate, as suggested in earlier studies, and GDM occurs in 25% of the population, any
increase in overall perinatal loss attributable to discontinuing screening programs would likely go unnoticed.
Another important issue to consider is the possibility that some patients diagnosed with GDM may have
preexisting type-2 diabetes, which can only be confirmed
postpartum. One study found such patients to have a perinatal mortality rate 6 times higher than those with milder
forms of GDM (22). Another study found mothers with
GDM who had infants with birth defects were more likely to have high fasting glucose values, suggesting the
presence of undiagnosed preexisting diabetes (23).
For the population to benefit from the diagnosis of
GDM, there should be an effective treatment for the condition. Although a number of comparative studies of various treatments are available, there is little information
regarding the effectiveness of treatment versus no treatment. In a pilot randomized trial comparing strict metabolic control with routine obstetric care in 300 women
with GDM, there was no difference in the rate of macrosomia or other pregnancy outcomes (24). However, even
the control subjects monitored their own glucose levels 1
day each week, and 10% were removed from the study
and treated for hyperglycemia.
The first consideration in selecting a therapy for
GDM is a determination of the treatment goals. Although
the degree, if any, of excess perinatal mortal-ity associated with milder GDM has not been established, management plans typically include some type of fetal surveillance. A second goal of treatment may be the prevention
of adverse pregnancy outcomes, such as macrosomia and
its attendant consequences of operative delivery, shoulder
dystocia, and birth trauma. Potential treatments toward
this goal include diet, exercise, and insulin; oral agents
also have been suggested. Safety, efficacy, and patient
acceptance should be considered in choosing a treatment.
PRACTICE BULLETINS
The goal of treatment is to lower the likelihood of

macrosomia and its consequences; neonatal hypoglycemia also may be reduced (25). Although the quality of the
information varies, evidence is available to confirm these
benefits. However, there has been no demonstrated treatment benefit on long-term outcomes for the offspring
such as obesity and the development of diabetes. It
should be emphasized that although the evidence is
inconclusive that treating GDM can prevent maternal and
fetal complications, universal screening and treatment
are widely practiced.

Recommendations
How should screening for GDM be

accomplished?
to base the definition of high and low risk for GDM on

the prevalence of type-2 diabetes in each ethnic group.
The relationship between obesity and GDM is most likely a continuum, so that the definition of the upper limit of
normal weight suggested by the Institute of Medicine (ie,
a body mass index 25) (29) should reasonably serve to
identify individuals who are not obese. A low-risk individual meets all of the following criteria (30):
1. Age younger than 25 years
2. Not a member of an ethnic group with an increased
risk for the development of type-2 diabetes (examples of high-risk ethnic groups include women of
Hispanic, African, Native American, South or East
Asian, or Pacific Islands ancestry)
3. Body mass index of 25 or less
4. No previous history of abnormal glucose tolerance
5. No previous history of adverse obstetric outcomes
usually associated with GDM
6. No known diabetes in first degree relative
When the 1997 criteria, similar to those listed previously
for low risk, were applied to data from more than 18,000
pregnancies in a predominantly Caucasian population,
researchers determined that only 3% of women with
GDM would not have been diagnosed (31). However,
only 10% of the population would have been exempted
from screening. For this reason, many physicians elect to
screen all pregnant patients as a practical matter.
All pregnant patients should be screened for GDM,

whether by patients history, clinical risk factors, or a laboratory screening test to determine blood glucose levels.
The optimal method of screening is controversial, and
there are insufficient data from which to draw firm conclusions.
A number of clinical risk factors have been demonstrated to be associated with an increased likelihood of
GDM, including age, ethnicity, obesity, family history of
diabetes, and past obstetric history (26). In one study,
more than 3,000 pregnant women underwent both the 50g, 1-hour screening test and the diagnostic oral GTT (27).
Using a complex scoring system of weighted risk factors,
the study found test thresholds for the 1-hour screening
test varied depending on individual risk status.
Sensitivity rates were similar to those of universal screening, and one third of the subjects avoided the glucose
screening test. Thus, it appears it is possible to use historic risk factors to identify individuals who may have
such a low risk for GDM that glucose challenge testing
may not be worthwhile. Conversely, there may be groups
of individuals at such high risk for GDM that it may be
more convenient and cost-effective to proceed directly to
the diagnostic GTT without obtaining the laboratory
screening test.
Specific risk factors and the degree of their influence
on GDM prevalence are difficult to quantify across populations. For example, in one Canadian study, African
race was not associated with an increased risk of GDM
(27), whereas in another large, observational study
African race was found to be an independent predictor of
the likelihood of GDM, even when investigators controlled for obesity (28). Because no single study can be
generalized to the entire population, it seems reasonable
761
At what gestational age should laboratory

screening be performed?
A number of studies have demonstrated that the prevalence of GDM increases with advancing gestation
(3236). It has been customary to recommend the 50-g,
1-hour oral glucose challenge test be administered at
2428 weeks of gestation. This arbitrary recommendation results from an attempt to balance two competing
interests. Insulin resistance increases as pregnancy progresses, therefore, testing later in pregnancy will result in
a higher yield of abnormal tests. However, the later the
abnormality is diagnosed, the less time will be available
for intervention. Although many practitioners choose to
screen high-risk patients early in pregnancy, the benefit
of early treatment of women with GDM identified early
in pregnancy has not been demonstrated but rather has
been accepted on a theoretical basis.
Patients who had GDM in a previous pregnancy have
a 3350% likelihood of recurrence in a subsequent pregnancy (3739). If such patients were not tested between
pregnancies, some of these recurrences may represent
preexisting diabetes undetected between pregnancies. In
such individuals there should still be a benefit to making
762
the diagnosis of diabetes during the first half of pregnancy. Unlike typical patients with GDM, patients with
abnormal glucose tolerance in the first half of pregnancy
may manifest severe degrees of hyperglycemia.
How is laboratory screening accomplished?
Should venous or capillary blood be used?
Is there an appropriate threshold value for

the laboratory screening test?
The screening test threshold at which a diagnostic GTT

is recommended will be arbitrary. The higher the threshold, the lower the sensitivity but the better the specific-ity
and the lower the likelihood of a false-positive test result.
The lower the threshold, the higher the sensitivity but the
higher the likelihood of a false-positive test result and
thus the performance of an unnecessary diagnostic GTT.
OSullivan and Mahan (17) used venous whole blood
samples and the Somogyi-Nelson method of glucose
analysis. At the recommended threshold of 130 mg/dL,
the screening test had a sensitivity of 79% and a specificity of 87%. When venous plasma and specific enzymatic methods of glucose analysis were used, 10% of
women with GDM manifested screening test values
between 130139 mg/dL (18). Absolute sensitivity levels
could not be determined because women with screening
test values below 130 mg/dL did not undergo oral GTTs.
When the threshold was lowered from 140 mg/dL to 130
mg/dL, the number of women requiring glucose tolerance testing increased from 14% to 23%, or approximately one quarter of patients.
Although a threshold of 140 mg/dL was recommended in the past, the most recent position statement of
the American Diabetes Association ascribes a sensitivity
of approximately 80% to this cutoff and 90% sensitivity
with a threshold of 130 mg/dL and leaves the choice open
(49). Because the precise cost-benefit ratio of diagnosing
GDM remains unresolved, either threshold is acceptable.
The original description of the screening test used venous

whole blood (17), but laboratories have switched from
whole blood to plasma or serum samples. Studies of the
screening test have generally used venous plasma.
Convenient and relatively inexpensive meters for measuring glucose in capillary blood samples raise the possibility of performing the screening test in an office setting
without expensive and complicated laboratory equipment. During fasting, capillary and venous blood have
similar glucose concentrations, but after a meal or glucose challenge, capillary glucose is higher than venous
glucose. Laboratory instruments are generally checked
for quality against standard samples at regular intervals
to ensure accuracy. Precision is an important factor. Two
studies of various meters used in pregnancy demonstrated
inadequate precision for all but one or two meter systems
tested (47, 48). Therefore, if capillary blood samples are
to be used for GDM screening, the precision of the meter
should be known, and its correlation with simultaneous-
Although the use of random glucose measurements or

fasting glucose measurements have been advocated to
screen for GDM, inadequate data are available to evaluate the relative effectiveness of these approaches.
Random glucose screening does not appear to be adequately sensitive (40). The screening test most commonly used in the United States is the 50-g, 1-hour glucose
challenge, using a pure glucose load of 50 g in 150 mL of
fluid. Glucose polymer solutions, which provide a lower
osmotic load for a given glucose load, appear to be associated with fewer gastrointestinal symptoms and have
been demonstrated to yield fair correlation with
monomeric glucose solutions (4143). The use of jelly
beans instead of a pure glucose challenge has been shown
to be better tolerated, but this method has poor sensitivity (40%) when compared with glucose polymer solutions
(8090%) (44).
Among subjects with GDM, for whom the function
of the screening test is most critical, either higher (45) or
similar (46) values were reported when the test was
administered in the fasting state. Therefore, given the
lack of evidence that fasting improves the accuracy of the
screening test and the fact that fasting may pose significant logistic problems, the 50-g, 1-hour screening test
may be administered without regard to the time elapsed
since the last meal.
ly obtained venous samples should be ascertained.

Appropriate thresholds can then be derived. Office-based
glucose testing is not recommended because of the difficulty in complying with required federal standards for
testing. However, if used, it may be most practical to continue to use venous plasma samples and published thresholds for further testing.
How is GDM diagnosed?
The diagnostic test specific for pregnancy and about

which the greatest body of data exists is the 100-g, 3-hour
oral GTT. Diagnostic criteria were originally derived by
OSullivan and Mahan (50). Cutoff levels two standard
deviations above the mean were found to be the best predictors for developing diabetes later in life. There are no
well-designed studies that demonstrate whether these
diagnostic criteria are optimal to identify pregnancies at
risk for maternal or perinatal morbidity. The relationship
between maternal glucose intolerance and adverse pregnancy outcomes appears to be more or less continuous
with no absolute threshold (4). Two sets of criteria were
adapted from the original OSullivan and Mahan values
PRACTICE BULLETINS
when laboratories switched to venous plasma or serum.

These samples yield results approximately 14% higher
than does whole blood. The National Diabetes Data
Group published conversions derived by adding 15% to
each of the four thresholds (51). Lower thresholds were
subsequently derived by also correcting for the change to
enzymatic methods of glucose analysis (52). Expert panels have supported both criteria, but there are no data
from clinical trials to determine which is superior (Table
1) (53).
A positive diagnosis requires that two or more
thresholds be met or exceeded. The test is administered in
the morning after an overnight fast. Patients should not
smoke before the test and should remain seated during
the test. Patients should be instructed to follow an unrestricted diet, consuming at least 150 g of carbohydrate
per day for at least 3 days prior to the test. This should
avoid carbohydrate depletion, which could cause spuriously high values on the GTT.
Patients with only one abnormal value have been
demonstrated to manifest increased risk for macrosomic
infants and other morbidities (54, 55). However, because
the relationship between carbohydrate metabolism,
macrosomia, and other morbidity is a continuum (4, 56),
and because not all of this morbidity arises from carbohydrate intolerance, it should be anticipated that no
threshold will identify all patients at risk.
How should blood glucose be monitored in a

woman with GDM?
The optimal frequency of blood glucose testing in

patients with GDM has not been established. Whether
daily testing is essential for women with GDM has not
been proven. One large, prospective trial compared
seven-times-daily self-glucose monitoring using memory-based reflectance meters with weekly fasting and 2hour laboratory glucose determinations supplemented by
763
four-times-daily self-monitoring with only test strips and

no meters (57). The more intensively monitored group
had fewer primary cesarean deliveries and fewer macrosomic neonates, and their infants were less likely to experience shoulder dystocia and neonatal hypoglycemia than
the more conventionally monitored group. Other centers
have reported similar results with four-times-daily glucose monitoring (25, 58). Although daily self-glucose
monitoring has not been demonstrated to reduce perinatal mortality in women with GDM, it appears to be useful in reducing potentially adverse outcomes such as
macrosomia. However, evidence from well-designed,
randomized trials that compare daily self-glucose monitoring with less frequent assessment in women with
GDM is still needed.
Further uncertainty surrounds the timing of glucose
determinations and the selection of appropriate thresholds for intervention. In nonpregnant individuals, diabetes is most often managed using preprandial glucose
determinations. However, the fetus may be more sensitive to glucose excesses than to the nadirs of glucose values at various times of the day. In studies of preexisting
diabetes, 1-hour postprandial glucose values were found
to be more predictive of fetal macrosomia than were fasting values (59), and a 1-hour value of 130 mg/dL or more
was found to be an appropriate threshold (60). A randomized trial compared preprandial with 1-hour postprandial glucose measurements in 66 women whose
GDM was severe enough to require insulin treatment by
30 weeks of gestation (25). Macrosomia, neonatal hypoglycemia, and cesarean deliveries for shoulder dystocia
were significantly lower among those who had postprandial monitoring, and their glycohemoglobin levels also
decreased more markedly than did the levels of the subjects who used preprandial monitoring. No studies are
available to compare the efficacy of 1-hour postprandial
versus the more traditional 2-hour postprandial glucose
determinations.
Table 1. Two Diagnostic Criteria for Gestational Diabetes Mellitus

Plasma or Serum Glucose Level
Carpenter/Coustan Conversion
Plasma Level
National Diabetes Data Group Conversion
mg/dL
mmol/L
mg/dL
mmol/L
95
5.3
105
5.8
One hour
180
10.0
190
10.6
Two hours
155
8.6
165
9.2
Three hours
140
7.8
145
8.0
Status
Fasting
Adapted from Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes
Mellitus. Diab Care 2000;23(suppl 1):S4S19
764
Because these studies only included individuals with

preexisting diabetes or those with GDM severe enough to
require insulin treatment by 30 weeks of gestation, it
remains to be established whether fasting or preprandial
glucose measurements will suffice for individuals with
milder forms of GDM. One study demonstrated a moderate correlation between fasting and 2-hour postprandial
glucose values in GDM; if the fasting value was below
105 mg/dL, then only 17% of the 2-hour values exceeded
120 mg/dL (61). Given the available data, postprandial
glucose values appear to be most effective at determining
the likelihood of macrosomia and other adverse pregnancy outcomes in patients with GDM.
Is there a role for diet therapy in the treatment of GDM?
Although there are no available data comparing medical

nutrition therapy (diet) with no treatment in women with
GDM, there is one such randomized trial of women who
had abnormal glucose challenge test results but normal
oral GTT results (62). Those on the prescribed diet delivered fewer macrosomic infants. Nutritional intervention
in women with GDM should be designed to achieve normal glucose levels and avoid ketosis, while maintaining
appropriate nutrition and weight gain. The American
Diabetes Association recommends nutritional counseling, if possible by a registered dietitian, with individualization of the nutrition plan based on height and weight
(49). The American Diabetes Association also recommends an average of 30 kcal/kg/d based on prepregnant
body weight for nonobese individuals (49). The most
appropriate diet for women with GDM has yet to be
established.
The American Diabetes Association suggests that
obese women (body mass index >30) may do well with
moderate caloric restriction (30 33%) (49). Caloric
restriction of 30% in obese women with GDM was associated with pregnancy outcomes (birth weight and
macrosomia) similar to those of a group of matched controls who had normal values on the glucose challenge
screening tests (63). One concern about caloric restriction is that, although glucose levels may decrease, there
is the possibility that it may cause starvation ketosis (64).
Levels of glucose, free fatty acids, and ketone bodies
have been assessed during each trimester in long-term
follow-up studies of infants of women with and without
diabetes. These studies have reported an inverse association between maternal circulating levels of ketone acids
in the second and third trimesters and psychomotor
development and intelligence in the offspring at 35
years of age and through 9 years of age (65, 66). Even
when investigators reevaluated their findings by taking
into account socioeconomic status, race or ethnicity, and
the presence of gestational or preexisting diabetes, this

association persisted. Although the correlation between
IQ and ketone levels was weak (r = 0.2), it was statistically significant (P = 0.02); therefore, it would be prudent to avoid excessive ketonemia or ketonuria during
pregnancy. When obese women with GDM were placed
on moderate caloric restriction (25 kcal/kg of ideal nonpregnant weight per day), no ketonuria was detected during weekly clinic visits (67). Serum ketones were not
reported. Available evidence does not support a recommendation for or against moderate caloric restriction in
obese women with GDM. However, if caloric restriction
is used, the diet should be restricted by no more than
33%, and ketonuria should be avoided.
Supplemental dietary fiber may improve glycemic
control in women with type-2 diabetes. In a cohort study,
increasing dietary fiber enrichment did not improve
glucose control in patients with GDM (68). Available evidence does not support the prescription of fiber supplements for GDM.
Is there a role for insulin in the treatment of

GDM?
Some (6971) but not all (72) prospective trials have

demonstrated that insulin treatment of all women with
GDM can reduce the likelihood of delivering a macrosomic baby. However, using such a paradigm would
require that 100% of individuals be treated although less
than half (between 9% and 40%) would benefit. It would
be preferable to select the most appropriate patients for
treatment.
One traditional approach has been to add insulin if
medical nutrition therapy does not maintain fasting plasma glucose below 105 mg/dL or 2-hour values below 120
mg/dL or both. These thresholds have been extrapolated
from recommendations for managing pregnancy in
women with preexisting diabetes. A randomized trial
demonstrated that using a 1-hour postmeal goal of 140
mg/dL was effective in preventing adverse outcomes in
women with GDM severe enough to require insulin (25).
It would be logical, although unproven, that similar
thresholds should be used for initiating insulin treatment.
A study of individuals with preexisting diabetes found
the most appropriate target 1-hour postprandial glucose
level for preventing macrosomia was 130 mg/dL (60). It
may be reasonable to apply these data to women with
GDM. Women with higher fasting glucose levels are
more likely to require insulin therapy to achieve optimal
glucose control than women with lower fasting glucose
levels. Thirty-eight percent of women with GDM with an
initial fasting plasma glucose level of 95 mg/dL or less
required insulin to achieve optimized control (mean of
seven daily values <100 mg/dL), whereas 70% required
PRACTICE BULLETINS
Exercise often is recommended for individuals with diabetes, both as a way to achieve weight reduction and as a
treatment to improve glucose metabolism. At least three
Is there a role for oral antidiabetic agents in

the treatment of GDM?
Oral antidiabetic agents have been contraindicated in

pregnancy. The early-generation sulfonylureas crossed
the placenta and had the potential to stimulate the fetal
pancreas, leading to fetal hyperinsulinemia. There also
was concern about the potential for teratogenicity,
although diabetes itself is teratogenic, and it is difficult to
distinguish the effects of the treatment from those of the
disease. Glyburide, a second-generation sulfonylurea,
was compared with insulin in a randomized trial among
patients with GDM who failed to achieve adequate
glycemic control with diet alone (80). Glucose control
was similar, and the glyburide group had pregnancy outcomes similar to those of the insulin group, including
rates of cesarean delivery, preeclampsia, macrosomia (>4
kg), and neonatal hypoglycemia. Cord serum analyses
showed no detectable glyburide in the infants. At this
time, no other oral agent has been shown to be safe and
effective in GDM, and this study has not been confirmed.
Further study is recommended before the use of newer
oral hypoglycemic agents can be supported for use in
pregnancy.
Is there a role for exercise in the treatment of

GDM?
randomized trials have explored exercise as an adjunct to,

or substitute for, insulin in GDM. When women with
GDM who needed intervention were randomly assigned
to insulin or an exercise program, there was no difference
in the likelihood of macrosomic infants, although glucose
levels were not reported (77). A randomized trial of diet
and exercise versus diet alone found improvement in both
fasting plasma glucose and the response to a 50-g challenge in those who exercised (78) while a third study
found improvement in cardiorespiratory fitness but no
differences in glucose control with exercise (79). A regular exercise program has clear benefits for all women and
may offer additional advantages for women with GDM.
Women with GDM who lead an active lifestyle should be
encouraged to continue a program of exercise approved
for pregnancy.
insulin when the initial fasting value was 95104 mg/dL

(73). Although each fasting glucose group delivered a
similar, low proportion of babies with birth weights
above the 90th percentile, large-for-gestational-age
(LGA) babies were born to 29% of those treated with diet
and 10% of those treated with insulin. All subjects with
fasting values above 105 mg/dL were treated with
insulin, and 14% had LGA offspring. These data suggest
that insulin therapy should be considered for patients
treated with medical nutrition therapy when 1-hour postprandial values exceed 130140 mg/dL or 2-hour postprandial values exceed 120 mg/dL or fasting glucose
exceeds 95 mg/dL.
Early third-trimester ultrasonography may help in
identifying women with GDM who would benefit from
insulin therapy despite relatively good metabolic control
on diet. In a randomized trial of women with mild gestational diabetes, ultrasound abdominal circumference
greater than the 75th percentile at 2933 weeks of gestation was effective in selecting patients among whom the
LGA rate was reduced to 13% with insulin therapy compared with 45% in those randomized to diet alone (74).
A frequent question is how long to attempt dietary
management before adding insulin. One study suggested
diet be tried for 2 weeks before adding insulin if the initial fasting plasma glucose was 95 mg/dL or less (75). In
women with GDM with initial fasting values above 95
mg/dL, the results of diet therapy alone were less salutary. The available evidence does not support a clear recommendation as to the number of times glucose values
should exceed targets before insulin is added or the
dosage increased.
No particular insulin regimen or insulin dose has
been demonstrated to be superior for GDM. Generally, it
is easiest for the patient to start with the simplest regimen
and work up to a more complex regimen as needed.
Regardless of the starting dosage, subsequent dosage
adjustments should be based on the blood glucose levels
at particular times of day. Because free insulin apparently does not cross the placenta, all types of insulin have
been used in patients with GDM. Insulin lispro
(Humalog), an analog of human insulin with a single
amino acid substitution, has a more rapid onset of action
than regular insulin and may be useful in improving postprandial glucose concentrations. It has been used in
GDM and has been demonstrated not to cross the placenta (76).
765
Is fetal assessment indicated in pregnancies

complicated by GDM?
Antepartum fetal testing is recommended for patients

with preexisting diabetes (81). If the increased risk of
fetal demise in patients with preexisting diabetes is related to suboptimal metabolic control, it would be expected
that patients with GDM who have poor metabolic control
also would be at risk and thus merit antepartum fetal surveillance. Patients with well-controlled GDM are presumably at lower risk for fetal death than are those whose
condition is not well controlled or who require insulin
766
therapy, but there is no consensus regarding antepartum

testing in women with well-controlled GDM. There are
no data available from randomized trials of antepartum
testing in patients with GDM. Most case series report
good outcomes with a given testing protocol and conclude the protocol used is appropriate. Twice-weekly
nonstress tests and amniotic fluid volume determinations
were associated with no stillbirths and a 4.9% rate of
cesarean delivery for nonreassuring fetal status in a
cohort of women with GDM who had fasting glucose
levels below 105 mg/dL (82).
Another cohort study of women with GDM who
required only diet therapy and were monitored by daily
fetal movement determinations beginning at 28 weeks of
gestation and who underwent nonstress testing beginning
at 40 weeks of gestation found no stillbirths or neonatal
deaths (83). Patients requiring insulin or who had previous stillbirths, chronic hypertension, or pregnancyinduced hypertension underwent earlier fetal testing as
did patients with preexisting diabetes. Because this latter
study lacked sufficient power to evaluate perinatal mortality, it is not possible to make an unequivocal recommendation. Despite the lack of conclusive data, it would seem
reasonable that women whose GDM is not well controlled, who require insulin, or have other risk factors such
as hypertension or adverse obstetric history should be
managed the same as individuals with preexisting diabetes. The particular antepartum test selected, whether
nonstress test, contraction stress test, or biophysical profile, may be chosen according to local practice.
Ultrasonography has been used to estimate fetal
weight, especially to predict macrosomia prior to delivery. However, the reliability of these measures has not
been established (8486). Regression formulas using
combined fetal measures for weight estimates are associated with systematic errors. Using existing formulas, an
estimated fetal weight would have to exceed 4,800 g for
the fetus to have more than a 50% chance of being
macrosomic (87, 88). In addition, the use of ultrasoundderived measures of fetal weight have not been shown to
be superior to clinical measures.
When and how should delivery occur in pregnancies complicated by GDM?
The timing of delivery in patients with GDM remains relatively open. When glucose control is good and no other
complications supervene, there is no good evidence to
support routine delivery before 40 weeks of gestation. In
a study in which women with insulin-treated GDM and
fetuses believed to be of appropriate weight for gestational age were randomized at 38 weeks of gestation to
induction of labor within 1 week or expectant management, there was no difference in cesarean delivery rates
(89). However, the induction group delivered a smaller

proportion of LGA babies. In a cohort multiple time
series study, a policy of induction of labor at 3839
weeks of gestation for women with insulin-treated GDM
was compared with the results in expectantly managed
historic controls (90). There was no significant difference
in macrosomia or cesarean delivery rates, but shoulder
dystocia was experienced by 10% of the expectant management group beyond 40 weeks of gestation versus
1.4% in the group induced at 3839 weeks of gestation.
Although significant, these data have not been confirmed
by additional studies.
Available data do not address women with GDM not
treated with insulin or those believed to have macrosomic fetuses. Individuals whose metabolic control does
not meet the goals described earlier, or is undocumented,
or those with risk factors such as hypertensive disorders
or previous stillbirth should be managed the same as
those with preexisting diabetes.
When GDM is well controlled and dates are well
documented, respiratory distress syndrome at or beyond
39 weeks of gestation is rare enough that routine amniocentesis for pulmonary maturity is not necessary (91). At
earlier gestational ages, or when control is poor or undocumented, pulmonary maturity should be assessed before
induction. However, when early delivery is planned
because of maternal or fetal compromise, the urgency of
the indication should be considered in the decision to perform amniocentesis.
Cesarean delivery rates are higher in women with
GDM compared with controls, and the difference is not
entirely attributable to fetal macrosomia (3, 9). It may be
that caregivers are more prone to perform cesarean deliveries in patients with GDM because of concern about the
likelihood of shoulder dystocia. There are no data to support a policy of cesarean delivery purely on the basis of
GDM. However, macrosomia is distinctly more common
in women with GDM, and shoulder dystocia is more likely at a given birth weight in pregnancies complicated by
diabetes than in nondiabetic pregnancies (92, 93). It may
be reasonable, therefore, to recommend cesarean delivery
without a trial of labor at some particular threshold of
fetal weight.
One of the problems in trying to apply such a threshold is the poor accuracy of ultrasound prediction of birth
weight. In particular, a study reported that when birth
weight exceeds 4,500 g, only 50% of the fetuses weigh
within 10% of the ultrasound-derived estimate (94). A
decision analytic model was developed to estimate the
potential effectiveness and costs of a policy of elective
cesarean delivery for fetal macrosomia diagnosed by
ultrasonography (95). Investigators factored in such considerations as the poor predictive accuracy of ultrasonography, the background cesarean delivery rates at various
PRACTICE BULLETINS
fetal weights, and the effect of maternal diabetes. The

analysis predicted that in women with diabetes it would
be necessary to perform 489 cesarean deliveries to prevent one permanent brachial plexus injury at a threshold
of 4,000 g estimated fetal weight, or 443 cesarean deliveries at a threshold of 4,500 g estimated fetal weight.
These figures are one fifth to one eighth of the figures
developed for pregnancies of women without diabetes.
The authors concluded such a policy may be tenable,
although the merits are debatable. On the basis of available data, it is not possible to determine whether the
potential benefits of cesarean delivery without labor at a
given estimated fetal weight are similar for patients with
GDM and those with preexisting diabetes. It would
appear reasonable to recommend that patients with GDM
be counseled regarding possible cesarean delivery without labor when the estimated fetal weight is 4,500 g or
greater. When the estimated weight is 4,0004,500 g,
additional factors such as the patients past delivery history, clinical pelvimetry, and the progress of labor may be
helpful to consider in determining mode of delivery.
With an estimated fetal weight greater than 4,500 g,
prolonged second stage of labor or arrest of descent in the
second stage is an indication for cesarean delivery.
Because of the higher likelihood of shoulder dystocia at
a given birth weight in the pregnancies of women with
diabetes, it may be best to apply the above recommendation to an estimated fetal weight greater than 4,000 g for
GDM. Operative deliveries from the midpelvis should be
avoided, if possible, in patients with GDM who have an
estimated fetal weight of 4,000 g or more and a prolonged second stage of labor (92, 96).
Should women with a history of GDM be

screened postpartum?
Women with a history of GDM are at increased risk for

developing diabetes (generally type-2 diabetes) later in
767
life (97, 98). Diabetes will be diagnosed in some women

soon after pregnancy, suggesting they had preexisting
diabetes that was not diagnosed prior to pregnancy.
Populations with a high prevalence of type-2 diabetes
who do not have access to screening when not pregnant
are at particularly high risk for this phenomenon (99).
Current recommendations for the diagnosis and classification of diabetes in the nonpregnant state are based on
the recommendations of an expert committee of the
American Diabetes Association and are depicted in Table
2 (100). Diagnostic testing for diabetes may be performed after the immediate effects of pregnancy on glucose metabolism have dissipated and is most convenient
at around the time of the postpartum checkup. However,
there are no long-term follow-up studies that verify the
benefit of postpartum diagnostic testing.
Although the American Diabetes Association advocates the use of a fasting plasma glucose determination as
being less cumbersome than the oral GTT, the oral GTT
will more accurately identify those women who had
GDM and now have impaired glucose tolerance (101).
Because the presence of such a condition may be important in counseling for future pregnancies, there may be
advantages to performing the oral GTT as the initial diagnostic test after pregnancy complicated by GDM. If the
results of both the fasting plasma glucose and the oral
GTT are normal, subsequent follow-up tests may use the
fasting plasma glucose.
The estimate of long-term risk for developing diabetes among women who had GDM depends on the diagnostic test used, the duration of follow-up, age, and other
characteristics of the population studied; reported rates
vary widely (102). In follow-up studies up to 28 years on
the cohort of patients used to derive the OSullivan and
Mahan criteria for GDM, diabetes was found in 50% of
women who had GDM compared with 7% of controls
(103). Factors identifiable during or shortly after pregnancy that increase the risk for subsequent diabetes
Table 2. Criteria for the Diagnosis of Diabetes Mellitus in the Nonpregnant State*
Normal Values
Impaired Fasting Glucose or

Impaired Glucose Tolerance
Diabetes Mellitus
FPG <110 mg/dL
FPG 110125 mg/dL
FPG 126 mg/dL
75-g, 2-h OGTT
75-g, 2-h OGTT
75-g, 2-h OGTT
2-h PG <140 mg/dL
2-h PG 140199 mg/dL
2-h PG 200 mg/dL

Symptoms of diabetes and
PG (without regard to time
since last meal) 200 mg/dL
*Abbreviations: FPG, fasting plasma glucose; OGTT, oral glucose tolerance test; PG, plasma glucose. The diagnosis of diabetes mellitus should be confirmed on a separate day by any of these three tests.
Data from Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes
Mellitus. Diab Care 2000;23(suppl 1):S4S19
768
include the degree of abnormality of the diagnostic GTT,

the presence or absence of obesity, the gestational age at
diagnosis of GDM, and the degree of abnormality of the
postpartum oral GTT (104, 105). Individuals at increased
risk should be counseled regarding diet, exercise, and
weight reduction or maintenance to forestall or prevent
the onset of type-2 diabetes.
3.
4.
5.
6.
high prevalence of diabetes (eg, Hispanic,

African, Native American, South or East
Asian, or Pacific Islands ancestry)
Body mass index of 25 or less
No history of abnormal glucose tolerance
No previous history of adverse pregnancy outcomes usually associated with GDM
No known diabetes in first degree relative
Either the plasma or serum glucose level established

by Carpenter and Coustan or the plasma level designated by the National Diabetes Data Group conversions are appropriate to use in the diagnosis of GDM.
The laboratory screening test should consist of a 50g, 1-hour oral glucose challenge at 2428 weeks of
gestation, which may be administered without regard
to the time of the last meal.
There is insufficient evidence to determine the optimal antepartum testing regimen for women with
GDM with relatively normal glucose levels on diet
therapy and no other risk factors.
Summary of
Recommendations
A screening test threshold of 140 mg/dL has 10%

less sensitivity than a threshold of 130 mg/dL but
fewer false-positive results; either threshold is
acceptable.
The screening test generally should be performed on

venous plasma or serum samples using well-calibrated
and well-maintained laboratory instruments.
Available evidence does not support a recommendation for or against moderate caloric restriction in
obese women with GDM. However, if caloric
restriction is used, the diet should be restricted by no
more than 33% of calories.
For women with GDM and an estimated fetal weight

of 4,500 g or more, cesarean delivery may be considered because it may reduce the likelihood of permanent brachial plexus injury in the infant.
When medical nutritional therapy has not resulted in

fasting glucose levels less than 95 mg/dL or 1-hour
postprandial values less than 130140 mg/dL or 2hour postprandial values less than 120 mg/dL,
insulin should be considered.
Although universal glucose challenge screening for

GDM is the most sensitive approach, there may be
pregnant women at low risk who are less likely to
benefit from testing. Such low-risk women should
have all of the following characteristics:
1. Age younger than 25 years
2. Not a member of a racial or ethnic group with
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to conduct a literature search to locate relevant articles published between January 1985 and June 2000. The search
Force:
I
type of evidence.
committees.
Copyright September 2001 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in
recording, or otherwise, without prior written permission from the
publisher.
01923, (978) 750-8400.
ISSN 1099-3630
Gestational Diabetes. ACOG Practice Bulletin No. 30. American
2001;98:525538
PRACTICE BULLETINS
773
ACOG
PRACTICE
BULLETIN
(Replaces Technical Bulletin Number 206, June 1995; Committee
Opinion Number 172, May 1996; Committee Opinion Number 187,
September 1997; Committee Opinion Number 198, February 1998;
and Committee Opinion Number 251, January 2001)

of Jodi F. Abbott, MD. The
of practice.
Reaffirmed 2008
Assessment of Risk
Factors for Preterm Birth
Preterm birth is the second leading cause of neonatal mortality in the United
States (1) (second only to birth defects), and preterm labor is the cause of most
preterm births (2). Neonatal intensive care has improved the survival rate for
babies at the cusp of viability, but it also has increased the proportion of survivors with disabilities (3). The incidence of multiple births also has increased
along with the associated risk of preterm delivery (4). Interventions to delay
preterm delivery in these settings have not shown conclusive effectiveness.
Because the morbidity of babies born after 3435 weeks of gestation has diminished, most efforts to identify preterm deliveries have focused on deliveries
before this age. This document describes the various methods proposed for predicting preterm birth and the evidence for their roles in clinical practice.
Background
Preterm labor is defined as regular contractions associated with cervical change
before the completion of 37 weeks of gestation. Spontaneous preterm birth
includes preterm labor, preterm spontaneous rupture of membranes, and cervical incompetence; it does not include indicated preterm delivery for maternal or
fetal conditions (5). Preterm delivery accounted for 11.8% of births in the
United States in 1999; this figure has increased steadily from 9.4% in 1981 (6).
The pathophysiologic events that trigger preterm parturition are largely
unknown but may include decidual hemorrhage (abruption), mechanical factors
(uterine overdistention or cervical incompetence), and hormonal changes (perhaps mediated by fetal or maternal stress) (79). In addition, several bacterial
infections have been associated with preterm labor. Commonly identified
organisms are Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella
774
vaginalis, Peptostreptococcus, and Bacteroides species

(10). Because these bacteria usually are of low virulence,
it is unclear whether they are truly etiologic or are associated with an acute inflammatory response of another
etiology.
Value of Predicting Risk

The ability to predict whether a woman is at risk of
preterm delivery has value only if an intervention is available that is likely to improve the outcome. The opportunity to administer maternal corticosteroid ther-apy is an
important intervention recommended by the National
Institutes of Health because it is strongly associated with
decreased morbidity and mortality (1113). In addition,
maternal tocolytic therapy may prolong pregnancy for up
to 48 hours in some women, during which time corticosteroids can be administered (14). Because tocolytic and
steroid therapy may result in untoward maternal and fetal
consequences, use of these therapies should be limited to
women with true preterm labor at high risk for spontaneous preterm birth. Finally, in women being managed at
hospitals without appropriate neonatal resources, identifying women at risk allows for appropriate maternal
transport to a tertiary care center. Conversely, identifying
those women at low risk for preterm delivery would avert
the use of unnecessary interventions.
Risk Factors
Risk factors for preterm birth include demographic characteristics, behavioral factors, and aspects of obstetric
history. Demographic characteristics that carry a high
risk for preterm birth include nonwhite race (African
American relative risk [RR]=3.3), age younger than 17
years or older than 35 years (RR=1.471.95), low socioeconomic status (RR=1.832.65), and low prepregnancy
weight (odds ratio=2.72) (15, 16). Maternal his-tory of
preterm birth, particularly in the second trimester, has a
strong statistical association with the risk of preterm
delivery (17); this risk appears to be associated with prior
spontaneous preterm birth with or without rupture of
membranes and increases the relative risk sixfold to
eightfold. Risk also increases with vaginal bleeding in
more than one trimester (18). Controversy exists as to
whether an excessively physically stressful job can lead
to early delivery; one study has shown an increase in
spontaneous preterm birth associated with long periods
of standing (>40 hours per week) (19). Smoking increases the risk of preterm birth (20) and low birth weight, and
some evidence suggests it increases the risk for spontaneous abortion (21). Despite the identification of a number of risk factors, attempts to determine the risk of
preterm delivery based on historic and epidemiologic risk
scoring systems (2224) have been unable to reliably
identify women who will give birth preterm.
Biologic Markers for Predicting Preterm

Birth
Home Uterine Activity Monitoring
Tocodynamometry has long been used for hospital-based
evaluation of uterine contractions. Home uterine activity
monitoring (HUAM) has been proposed as a method for
predicting preterm birth in high-risk women. It consists
of a combination of telemetric recordings of uterine contractions with the use of a tocodynamometer and daily
telephone calls from a health care practitioner to offer
patient support and advice. Uterine activity beyond an
arbitrary cutoff triggers notification of the patients
health care practitioner. This approach was based on the
observation that some women who subsequently give
birth before term have an increase in uterine activity earlier in pregnancy than women who give birth at term (25)
and that these prodromal uterine contractions otherwise
may not be recognized by the patient.
Salivary Estriol
Activation of the fetal hypothalamic pituitaryadrenal
axis precedes some spontaneous preterm births. Adrenal
production of dehydroepiandrosterone results in
increased placental estrogen synthesis. Observational
studies have shown that maternal levels of serum estradiol and salivary estriol increase before the onset of spontaneous term and preterm labor (26). These findings
prompted the design of a test to predict preterm delivery
by measuring salivary estriol; however, maternal estriol
levels show diurnal variation, peaking at night (27). Also,
estriol levels may be suppressed by betamethasone
administration (28).
Bacterial Vaginosis
Bacterial vaginosis (BV) is a common alteration of the
normal vaginal flora and has been found in 1025% of
patients in general gynecologic and obstetric clinics and
in up to 64% of patients in clinics for sexually transmitted diseases (29). Fifty percent of women with BV are
asymptomatic (30). Bacterial vaginosis also has been
found more frequently in African-American women
(22%) than in white women (8%) (10, 31). The presence
of BV has been associated with preterm delivery independent of other known risk factors (32, 33).
Fetal Fibronectin Screening

Fetal fibronectin (fFN) is a basement membrane protein
produced by the fetal membranes that functions as an
adhesion binder of the placenta and membranes to the
decidua (34, 35). It is normally present in cervical secretions until 1620 weeks of gestation. Numerous trials
have shown both an association with the presence of fFN
PRACTICE BULLETINS
Cervical Ultrasonography
Transvaginal cervical ultrasonography has been shown to
be a reliable and reproducible way to assess the length of
the cervix (38). A prospective blinded trial showed an
association between cervical length and preterm delivery
(39). This study established the normal distribution of
cervical length in pregnancy after 22 weeks of gestation.
It also looked at various cervical measurements as criteria for the prediction of preterm delivery.
Does the use of HUAM predict preterm birth?
The usefulness of HUAM as a screening test depends on

both its ability to detect women at higher risk for preterm
birth as well as the effectiveness of any intervention to
then prevent preterm birth. At least 13 randomized
controlled trials examining the efficacy of HUAM have
published results (4052). The studies vary in design,
criteria for inclusion of patients, and measurements of
endpoints and outcomes. These differences make comparisons difficult. Furthermore, many of these studies
had limitations with their research design, including sample size (power) or numbers of patients, that preclude
reaching conclusions about the usefulness of HUAM.
Results vary, with some trials reporting no difference and
some reporting a difference in outcome in monitored and
unmonitored women. The largest study involved 2,422
women at risk and showed no improvement in outcome
(41).
Earlier studies that showed a reduction in the incidence of preterm birth with HUAM have been criticized
for their flawed design (53, 54); some studies have been
identified as having biases and errors sufficient to warrant dismissing the results (55). The U.S. Preventive
Services Task Force performed an independent review
and concluded the device was not effective (56).
Although the U.S. Food and Drug Administration has
approved a HUAM device for women with a prior
preterm birth, there is no demonstrated role for HUAM in
Does salivary estriol determination predict

preterm birth?
There have been two prospective trials evaluating

whether salivary estriol levels can predict preterm delivery (59, 60); they showed that salivary estriol was more
predictive than traditional risk assessment. However, the
results of the second trial showed a relatively poor sensitivity of 71%, specificity of 77%, and a false-positive rate
of 23% (using delivery before 37 weeks of gestation as
the outcome measure) (60). Because the test carries a
high percentage of false-positive results, its use could add
significantly to the cost of prenatal care, particularly if
used in a low-risk population. Although the hormonal
pathway etiology for some cases of preterm birth is
intriguing, trials with salivary estriol testing to predict
preterm birth have failed to establish its usefulness for
anything more than investigational purposes at present.

Recommendations
the prevention of preterm birth. Data are insufficient to

support a benefit from HUAM in preventing preterm
birth (13, 57, 58); therefore, this system of care is not recommended.
and preterm birth (5, 34, 36) and a decrease in the risk of
preterm birth when the test result for the presence of this
protein is negative. The basis for the association of fFN
and preterm birth is unclear. It has been hypothesized that
fFN is a marker for the disruption of the chorioamnion
and underlying decidua due to inflammation with or
without infection (34). A positive midtrimester fFN test
result has been associated with subsequently diagnosed
maternal and fetal infection (37).
775
Do screening and treatment for BV affect the

likelihood of preterm birth?
Trials of screening and treatment for BV in pregnant

women to reduce the incidence of preterm delivery have
been conducted in mixed populations with varying
results. Some small studies found screening and treatment of women at risk for preterm birth reduced the risk
of preterm birth (61, 62), but other studies have not confirmed these findings (63, 64).
A recent meta-analysis reviewed five trials involving
1,504 women (65). The analysis included trials of women
without risk factors for preterm birth as well as studies
that screened general obstetric populations. Treatments
used in these trials included amoxicillin, clindamycin,
and metronidazole. Although investigators found antibiotic therapy effective at eradicating BV, the difference in
the rate of preterm birth between the two groups was not
statistically significant. However, looking at the subgroup of women with a previous preterm birth, the difference was significant, with an odds ratio of 0.37 (95%
confidence interval, 0.230.60). This meta-analysis did
not include results from the most recent and largest double-blind, randomized controlled trial. This trial of 1,953
women found no difference in the rates of preterm birth
between the treatment and placebo groups, and no subgroup demonstrated a statistically significant difference
in preterm birth rates (64).
Although some trials have shown an association with
the presence of BV and preterm birth, most large trials
designed to determine whether treatment of BV can pre-
776
vent preterm birth have failed. Currently, there are insufficient data to suggest screening and treating women at
either low or high risk will reduce the overall rate of
preterm birth (66). There is speculation that BV could be
either a marker or a cause of choriodecidual inflammation without intraamniotic infection (24). However,
research testing this hypothesis by serial fFN screening in
women with BV was unable to confirm an association
(67).
Does screening for fFN predict preterm birth?
Does cervical ultrasonography predict

preterm birth?
Numerous studies have confirmed the association of cervical shortening with preterm delivery, but they have varied widely in their predictive value (13, 7577). A review
of 35 studies using cervical length (determined by ultrasonography) to predict preterm delivery found sensitivi-
A meta-analysis of 27 studies showed consistent moderate success using fFN screening to predict preterm birth
(68). Using delivery at less than 34 weeks of gestation as
the outcome, sensitivity was 61% and specificity was
83% (68). A study that analyzed the relationship between
fFN, short cervix, BV, and designated traditional risk factors for spontaneous preterm birth showed the highest
association of preterm birth with positive fFN test result,
followed by a cervical length less than 25 mm and a history of preterm birth (69). The negative predictive value
of the fFN test to identify symptomatic women who are
actually at low risk for imminent preterm delivery ranges
from 69% to 92% before 37 weeks of gestation, with a
greater than 95% likelihood of not delivering within 14
days of a negative test result (13, 70, 71).
Although a negative test result appears to be useful
in ruling out preterm delivery that is imminent (ie, within 2 weeks) (13, 72, 73), the clinical implications of a
positive test result have not been evaluated fully because
no obstetric intervention has been shown to decrease the
risk of preterm delivery. The test should not be routinely
used to screen low-risk, asymptomatic women, because
the incidence of preterm birth in this population is low
and the test, therefore, has limited usefulness (68).
If the test is to be used in specific high-risk groups,
the following criteria should be met: intact amniotic
membranes, minimal cervical dilatation (<3 cm), and
sampling performed no earlier than 24 weeks and 0 days
of gestation and no later than 34 weeks and 6 days of gestation (74). If the test is to be clinically useful, the results
must be available from a laboratory within a time frame
that allows for clinical decision making (ideally within
24 hours).
ties ranging from 68% to 100%, with specificities from

44% to 79% (78).
A prospective trial of more than 2,900 women evaluated by serial transvaginal ultrasonography at 24 weeks
of gestation and again at 28 weeks of gestation showed
the RR of preterm delivery increased as the cervical
length decreased. Specifically, at 28 weeks of gestation,
when cervical lengths were 40 mm or less, RR was 2.80;
at 35 mm or less, RR was 3.52; at 30 mm or less, RR was
5.39; at 26 mm or less, RR was 9.57; at 22 mm or less,
RR was 13.88; and at 13 mm or less, RR was 24.94 (39).
Despite the usefulness of cervical length determination by ultrasonography as a predictor of preterm labor,
routine use is not recommended because of the lack of
proven treatments affecting outcome (79). Until effective
treatment options are identified, cervical length measurement has limited clinical application.
Should fFN and cervical ultrasonography be

used together to better identify those at highest risk?
In a multicenter trial, investigators found a short cervix

(defined as <25 mm), particularly if associated with a
positive fFN test result, to be a strong predictor of
preterm birth (80). A more recent trial by the National
looked at the sequential use of both methods to try to
stratify risk groups as well as discern etiologies of
preterm birth (69) (see Table 1). The presence of either a
cervix less than 25 mm in length at less than 35 weeks of
gestation or a positive fFN test result was strongly associated with preterm birth, especially in women with a history of preterm birth. These data were particularly useful
in decreasing the assessed risk of preterm birth in women
with classic risk factors and negative results of one or
both tests. The success of interventions once a short
cervix is identified or positive fFN test result is determined remains uncertain (13).
Table 1. Recurrence Risk of Spontaneous Preterm Birth at
<35 Weeks of Gestation According to Cervical Length and
Fetal Fibronectin in Women with a Prior Preterm Birth
Fetal
Cervical Length (mm) Fibronectin + (%)
Fetal
Fibronectin (%)
25
65
25
2635
45
14
>35
25
Fetal fibronectin and cervical length assessed at 24 weeks of gestation. Cervical length assessed by transvaginal ultrasonography.
Data from: Iams JD, Goldenberg RL, Mercer BM, Moawad A, Thom E, Meis PJ, et
al. The Preterm Prediction Study: recurrence risk of spontaneous preterm birth.
National Institute of Child Health and Human Development Maternal-Fetal
Medicine Units Network. Am J Obstet Gynecol 1998;178:10351040
PRACTICE BULLETINS
Summary of
Recommendations
There are no current data to support the use of salivary estriol, HUAM, or BV screening as strategies to
identify or prevent preterm birth.
Screening for risk of preterm labor by means other

than historic risk factors is not beneficial in the general obstetric population.
Ultrasonography to determine cervical length, fFN

testing, or a combination of both may be useful in
determining women at high risk for preterm labor.
However, their clinical usefulness may rest primarily with their negative predictive value given the lack
of proven treatment options to prevent preterm birth.
Fetal fibronectin testing may be useful in women

with symptoms of preterm labor to identify those
with negative values and a reduced risk of preterm
birth, thereby avoiding unnecessary intervention.
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78. Leitich H, Brunbauer M, Kaider A, Egarter C, Husslein P.

Cervical length and dilatation of the internal cervical os
detected by vaginal ultrasonography as markers for
preterm delivery: a systematic review. Am J Obstet
66. Berg AO. Screening for bacterial vaginosis in pregnancy.

Recommendations and rationale. Am J Prev Med
2001;20(3 Suppl):5961 (Level III)
79. Ultrasound cervical assessment in predicting preterm

birth. SOGC Clinical Practice Guidelines 102. J SOGC
2001;23:418421 (Level III)
67. Goldenberg RL, Andrews WW, Guerrant RL, Newman M,

Mercer B, Iams J, et al. The preterm prediction study: cer-
80. Iams JD, Goldenberg RL, Mercer BM, Moawad A, Thom

E, Meis PJ, et al. The Preterm Prediction Study: recurrence
780
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Medicine Units Network. Am J Obstet Gynecol
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Force:
I
type of evidence.
committees.

01923, (978) 750-8400.
ISSN 1099-3630
Assessment of risk factors for preterm birth. ACOG Practice Bulletin
Gynecol 2001;98:709716
PRACTICE BULLETINS
781
ACOG
PRACTICE
BULLETIN

of Larry C. Gilstrap III, MD,
and Susan M. Ramin, MD.
of practice.
Reaffirmed 2008
Diagnosis and
Management of
Preeclampsia and
Eclampsia
Hypertensive disease occurs in approximately 1222% of pregnancies, and it is
directly responsible for 17.6% of maternal deaths in the United States (1, 2).
However, there is confusion about the terminology and classification of these
disorders. This bulletin will provide guidelines for the diagnosis and management of hypertensive disorders unique to pregnancy (ie, preeclampsia and
eclampsia), as well as the various associated complications. Chronic hypertension has been discussed elsewhere (3).
Background
Definition
The National High Blood Pressure Education Program Working Group (hereafter
referred to as the Working Group) has recommended that the term gestational hypertension replace the term pregnancy-induced hypertension to describe
cases in which elevated blood pressure without proteinuria develops in a woman
after 20 weeks of gestation and blood pressure levels return to normal postpartum (4). According to the criteria established by the Working Group, in pregnant women, hypertension is defined as a systolic blood pressure level of 140
mm Hg or higher or a diastolic blood pressure level of 90 mm Hg or higher that
occurs after 20 weeks of gestation in a woman with previously normal blood
pressure (4). As many as one quarter of women with gestational hypertension
will develop proteinuria, ie, preeclampsia (5).
Preeclampsia is a syndrome defined by hypertension and proteinuria that
also may be associated with myriad other signs and symptoms, such as edema,
782
visual disturbances, headache, and epigastric pain.

Laboratory abnormalities may include hemolysis, elevated liver enzymes, and low platelet counts (HELLP syndrome). Proteinuria may or may not be present in patients
with HELLP syndrome. Proteinuria is defined as the presence of 0.3 g or more of protein in a 24-hour urine specimen. This finding usually correlates with a finding of 1+
or greater but should be confirmed using a random urine
dipstick evaluation and a 24-hour or timed collection
(4). See the box for the criteria for diagnosing preeclampsia. Many practitioners have traditionally used these criteria to diagnose preeclampsia, although they have not been
substantiated by research, and other definitions exist.
These also are the criteria frequently used in research protocols. Severe preeclampsia is defined in the box.
In the past, hypertension indicative of preeclampsia
has been defined as an elevation of more than 30 mm Hg
systolic or more than 15 mm Hg diastolic above the
patients baseline blood pressure; however, this definition
has not proved to be a good prognostic indicator of outcome (6, 7). The so-called 3015 rule is not part of the
criteria for preeclampsia established by the Working
Group (4). According to the Working Group, however,
women who demonstrate an elevation of more than 30
mm Hg systolic or more than 15 mm Hg diastolic above
baseline warrant close observation.
Eclampsia is defined as the presence of new-onset
grand mal seizures in a woman with preeclampsia. Other
causes of seizures in addition to eclampsia include a
bleeding arteriovenous malformation, ruptured aneurysm,
or idiopathic seizure disorder. These diagnoses may be
more likely in cases in which new-onset seizures occur
after 4872 hours postpartum.
The diagnostic criteria for superimposed preeclampsia include new-onset proteinuria in a woman with
hypertension before 20 weeks of gestation, a sudden
increase in proteinuria if already present in early gestation, a sudden increase in hypertension, or the develop-
Criteria for Diagnosis of Preeclampsia*

Blood pressure of 140 mm Hg systolic or higher or
90 mm Hg diastolic or higher that occurs after 20
weeks of gestation in a woman with previously normal blood pressure
Proteinuria, defined as urinary excretion of 0.3 g
protein or higher in a 24-hour urine specimen
*Preeclampsia is a pregnancy-specific syndrome that usually occurs
after 20 weeks of gestation.
Data from Report of the National High Blood Pressure Education
Program Working Group Report on High Blood Pressure in Pregnancy.
Am J Obstet Gynecol 2000;183:S1S22
Diagnosis of Severe Preeclampsia

Preeclampsia is considered severe if one or more of the
following criteria is present:
Blood pressure of 160 mm Hg systolic or higher or
110 mm Hg diastolic or higher on two occasions at
least 6 hours apart while the patient is on bed rest
Proteinuria of 5 g or higher in a 24-hour urine specimen or 3+ or greater on two random urine samples
collected at least 4 hours apart
Oliguria of less than 500 mL in 24 hours
Cerebral or visual disturbances
Pulmonary edema or cyanosis
Epigastric or right upper-quadrant pain
Impaired liver function
Thrombocytopenia
Fetal growth restriction
ment of HELLP syndrome (4). Women with chronic

hypertension who develop headache, scotomata, or epigastric pain also may have superimposed preeclampsia.
Epidemiology and Risk Factors

The exact incidence of preeclampsia is unknown but it
has been reported to be approximately 58% (8, 9). Preeclampsia is primarily a disorder of first pregnancies.
Other risk factors include multifetal gestations, preeclampsia in a previous pregnancy, chronic hypertension,
pregestational diabetes, vascular and connective tissue disease, nephropathy, antiphospholipid antibody syndrome,
obesity, age 35 years or older, and African-American race
(1, 8, 1012).
The precise role of genetic and environmental factors on the risk and incidence of preeclampsia is unclear,
although emerging data suggest the tendency to develop
preeclampsia may have a genetic basis (1315). Women
with thrombophilias also may have a genetic predisposition to preeclampsia.
Pathophysiology
The etiology of preeclampsia is unknown, although much
of the literature has focused on the degree of trophoblastic invasion by the placenta (4). In cases of preeclampsia,
invasion by the trophoblast appears to be incomplete
(1618). Moreover, the severity of hypertension may be
related to the degree of trophoblastic invasion (19).
Preeclampsia also may be associated with significant
alterations in the immune response (4).
PRACTICE BULLETINS
783
Vascular Changes
HELLP Syndrome
Hemoconcentration, in addition to hypertension, is a

significant vascular change, because women with the
preeclampsiaeclampsia syndrome may not develop the
normal hypervolemia of pregnancy (20). Changes in vascular reactivity may be mediated by prostaglandins (21,
22). The interaction of various vasoactive agents, such as
prostacyclin (vasodilator), thromboxane A2 (potent vasoconstrictor), nitric oxide (potent vasodilator), and
endothelins (potent vasoconstrictors) cause another
pathophysiologic change seen in preeclampsia: intense
vasospasm. The vasospasm and subsequent hemoconcentration are associated with contraction of the intravascular space. Because of capillary leak and decreased
colloid oncotic pressure often associated with this syndrome, attempts to expand the intravascular space in
these women with vigorous fluid therapy may result in
elevation of the pulmonary capillary wedge pressure and
even pulmonary edema. A study using invasive hemodynamic monitoring in women with preeclampsia found
that before aggressive intravenous fluid therapy, the
women had hyperdynamic ventricular function with
low pulmonary capillary wedge pressure (23). However,
after aggressive fluid therapy, the pulmonary capillary
wedge pressure increased significantly above normal
levels (23).
Women with severe preeclampsia and hepatic involvement may develop HELLP syndrome. In one study,
HELLP syndrome occurred in approximately 20% of
women with severe preeclampsia (26). As with severe
preeclampsia, HELLP syndrome is associated with an
increased risk of adverse outcomes, including placental
abruption, renal failure, subcapsular hepatic hematoma,
recurrent preeclampsia, preterm delivery, and even fetal
or maternal death (2630).
Hematologic Changes
Various hematologic changes also may occur in women
with preeclampsia, especially when the preeclampsia is
severe. Both thrombocytopenia and hemolysis may occur
as part of the HELLP syndrome, although the etiology is
unknown. Interpretation of hematocrit levels in the face
of severe preeclampsia should take into consideration
that hemolysis or hemoconcentration or both may occur.
Thus, the hematocrit level may be very low because of
hemolysis or very high secondary to hemoconcentration
in the absence of hemolysis. Lactate dehydrogenase is
present in erythrocytes in high concentration. A disproportionate elevation of levels of lactate dehydrogenase in
serum may be a sign of hemolysis.
Hepatic Changes
Eclampsia remains a cause of maternal mortality (31,

32), usually in association with intracranial hemorrhage
(33). Although uncommon, temporary blindness (lasting
a few hours to up to a week) also may accompany severe
preeclampsia and eclampsia (34). Other nervous system
manifestations include headache, blurred vision, scotomata (4), and hyperreflexia.
Renal Changes
As a result of vasospasm, the normal expected increase in
glomerular filtration rate and renal blood flow and the
expected decrease in serum creatinine may not occur in
women with preeclampsia, especially if the disease is
severe. Oliguria, commonly (albeit arbitrarily) defined as
less than 500 mL in 24 hours, also may occur secondary
to the hemoconcentration and decreased renal blood
flow. Rarely, persistent oliguria may reflect acute tubular
necrosis, which may lead to acute renal failure (8).
Fetal Changes
As a result of impaired uteroplacental blood flow or placental infarction, manifestations of preeclampsia also
may be seen in the fetal placental unit. These include
intrauterine growth restriction, oligohydramnios, placental abruption, and nonreassuring fetal status demonstrated on antepartum surveillance.

Recommendations
Hepatic function may be significantly altered in women

with severe preeclampsia. Alanine aminotransferase and
aspartate aminotransferase may be elevated. Hyperbilirubinemia may occur, especially in the presence of
hemolysis. Hepatic hemorrhage, which usually manifests
as a subcapsular hematoma, also may occur, especially in
women with preeclampsia and upper abdominal pain
(24). Rarely, hepatic rupture, which is associated with a
high mortality rate, occurs (25).
Neurologic and Cerebral Manifestations
Are there effective methods for identifying

women at risk for preeclampsia?
No single screening test for preeclampsia has been found

to be reliable and cost-effective (3537). Uric acid is one
of the most commonly used tests but it has a positive predictive value of only 33% and has not proved useful in
predicting preeclampsia (38). Doppler velocimetry of the
uterine arteries was reported not to be a useful test for
784
screening pregnant women at low risk for preeclampsia

(35, 39).
How should the blood pressure be taken?
According to the Working Group, the diastolic blood

pressure is that pressure at which the sound disappears
(Korotkoff phase V) (4). To reduce inaccurate readings,
an appropriate size cuff should be used (length 1.5 times
upper arm circumference or a cuff with a bladder that
encircles 80% or more of the arm). The blood pressure
level should be taken with the patient in an upright position, after a 10-minute or longer rest period. For patients
in the hospital, the blood pressure can be taken with
either the patient sitting up or in the left lateral recumbent
position with the patients arm at the level of the heart
(40). The patient should not use tobacco or caffeine for
30 minutes preceding the measurement (37, 41).
Although validated electronic devices can be used, a mercury sphygmomanometer is preferred because it is the
most accurate device (37, 41).
No large randomized clinical trials have compared

conservative versus aggressive management of women
with HELLP syndrome. Considering the serious nature
of this complication, it seems reasonable to conclude that
women with HELLP syndrome should be delivered
regardless of their gestational age. Expectant management of this syndrome in women before 32 weeks of gestation should be undertaken only in tertiary care centers
or as part of randomized clinical trials with appropriate
safeguards and consent (4).
According to the Working Group (4):
Hospitalization is often initially recommended for

women with new-onset preeclampsia. After maternal and fetal conditions are serially assessed, subsequent management may be continued in the hospital,
at a day-care unit, or at home on the basis of the initial assessment. Prolonged hospitalization for the
duration of pregnancy allows rapid intervention in
case of fulminant progression to hypertensive crisis,
eclampsia, or abruptio placentae. These complications are rare in compliant women who have mild
[disease]. Ambulatory management at home or at
a day-care unit has been evaluated as an option for
monitoring women with mild gestational hypertension or preeclampsia remote from term. A number of
observational and randomized studies suggest a
place for ambulatory management of selected
women. If day care or home management is selected, it should include frequent maternal and fetal
evaluation and access to health care providers. If
worsening of preeclampsia is diagnosed, as determined by laboratory findings, symptoms, and clinical signs, hospitalization is indicated.
What is the optimal treatment for preeclampsia?
Women who have difficulty with compliance, including

logistic barriers, who manifest signs of disease progression
or who have severe preeclampsia should be hospitalized.
The decision to deliver a patient with preeclampsia must

balance both the maternal and fetal risks. Continued
observation is appropriate for the woman with a preterm
fetus only if she has mild preeclampsia (4). Such therapy
consists of fetal and maternal evaluation. No randomized
trials have determined the best tests for fetal evaluation.
The Working Group recommends weekly nonstress tests,
biophysical profiles, or both, which should be repeated as
indicated according to maternal condition. Testing is recommended twice weekly for suspected fetal growth
restriction or oligohydramnios. Daily fetal movement
assessment also may prove useful. The Working Group
also recommends ultrasound examination for fetal
growth and amniotic fluid assessment every 3 weeks (4).
Maternal evaluation consists primarily of frequent
evaluation for worsening preeclampsia. Initial laboratory
tests consist of evaluation of platelet count, liver enzymes,
and renal function and a 12-hour to 24-hour urine collection for protein (4). With mild disease and no progression,
these tests can be repeated weekly. The tests should be
repeated sooner if disease progression is questionable.
The management of a woman with severe preeclampsia remote from term is best accomplished in a
tertiary care setting or in consultation with an obstetrician
gynecologist with training, experience, and demonstrated
competence in the management of high-risk pregnancies,
such as a maternalfetal medicine subspecialist (4, 4244).
Laboratory evaluation and fetal surveillance may be indicated on a daily basis depending on the severity and progression of the disorder (4).
Is there a role for outpatient management in

women with preeclampsia?
Is medical management beneficial during

labor and delivery in women with preeclampsia?
The two main goals of management of women with

preeclampsia during labor and delivery are prevention of
seizures or eclampsia and control of hypertension.
Although there is no unanimity of opinion regarding the
prophylactic use of magnesium sulfate for the prevention
of seizures in women with mild preeclampsia or gestational hypertension, a significant body of evidence attests
to the efficacy of magnesium sulfate in women with
severe preeclampsia and eclampsia. A randomized, con-
PRACTICE BULLETINS
For mild preeclampsia, vaginal delivery at term is preferred. No randomized clinical trials have evaluated the
optimal method of delivery for women with severe
preeclampsia or eclampsia. Two retrospective studies
comparing induction of labor with cesarean delivery in
women with severe preeclampsia remote from term concluded that induction of labor was reasonable and was
not harmful to low-birth-weight infants (49, 50). The
decision to perform cesarean delivery should be individualized.
Hydralazine: 510-mg doses intravenously every 1520

minutes until desired response is achieved*
Labetalol: 20-mg intravenous bolus dose followed by
40 mg if not effective within 10 minutes; then, 80 mg
every 10 minutes to maximum total dose of 220 mg
*Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC III, Hauth JC,
Wenstrom KD. Hypertensive disorders in pregnancy. In: Williams
obstetrics. 21st ed. New York: McGraw-Hill, 2001:567618
Report of the National High Blood Pressure Education Program

Working Group on High Blood Pressure in Pregnancy. Am J Obstet
Gynecol 2000;183:S1S22
How should women with eclampsia be

managed?
Women with eclampsia require prompt intervention.

When an eclamptic seizure occurs, the woman should be
medically stabilized. First, it is important to control convulsions and prevent their recurrence with intravenous or
intramuscular magnesium sulfate (8). One protocol is a
4-g to 6-g loading dose diluted in 100 mL fluid and
administered intravenously for 1520 minutes, followed
by 2 g per hour as a continuous intravenous infusion (8).
Antihypertensive medications should be used for women
with diastolic blood pressure levels of 105110 mm Hg
or higher.
The patient with eclampsia should be delivered in a
timely fashion. Fetal bradycardia frequently occurs during an eclamptic seizure; usually, this can be managed by
maternal treatment, and cesarean delivery is not necessary. Once the patient is stabilized, the method of delivery should depend, in part, on factors such as gestational
age, fetal presentation, and the findings of the cervical
examination.
Antihypertensive Treatment for Preeclampsia
Is anesthesia contraindicated during labor

and delivery in women with preeclampsia?
With improved techniques over the past two decades,

regional anesthesia has become the preferred technique
for women with severe preeclampsia and eclampsia
both for labor and delivery (4). A secondary analysis of
women with severe preeclampsia in the National Institute
of Child Health and Human Developments Maternal
Fetal Medicine Units Network trial of low-dose aspirin
reported that epidural anesthesia was not associated with
an increased rate of cesarean delivery, pulmonary edema,
or renal failure (51). Moreover, general anesthesia carries
more risk to pregnant women than does regional anesthesia (52). However, regional anesthesia is generally contraindicated in the presence of a coagulopathy because of
the potential for hemorrhagic complications.
What is the optimal mode of delivery for

women with preeclampsia?
trolled trial of 822 women with severe preeclampsia (699

evaluated) receiving either intravenous magnesium sulfate or placebo reported one case (0.3%) of eclampsia
among the 345 women in the magnesium group versus 11
(3.2%) of 340 in the placebo group (relative risk, 0.09;
95% confidence interval, 0.010.69; P = 0.003) (45). A
review of the literature on magnesium sulfate therapy in
women with either preeclampsia or eclampsia identified
19 randomized controlled trials, five retrospective studies, and eight observational studies (46). In the randomized controlled trials of women with eclampsia, recurrent
seizures occurred in 23% of 935 women who received
either phenytoin or diazepam compared with 9.4% of 932
women who received magnesium sulfate. In the randomized trials of women with severe preeclampsia, seizures
occurred in 2.8% of 793 women treated with antihypertensives compared with only 0.9% in women treated with
magnesium sulfate. Thus, the data support the use of
magnesium sulfate to prevent seizures in women with
severe preeclampsia or eclampsia (31, 4547).
Although no large randomized clinical trials have
compared treatment with placebo, antihypertensive therapy is generally recommended for diastolic blood pressure levels of 105110 mm Hg or higher (4, 8, 48).
Hydralazine and labetalol are the two agents most commonly used for this purpose (see box).
785
Is there a role for invasive hemodynamic

monitoring?
Most women with severe preeclampsia or eclampsia can

be managed without invasive hemodynamic monitoring.
A review of 17 women with eclampsia reported that use
of a pulmonary artery catheter aided in clinical management decisions (53). However, no randomized trials support their routine use in women with severe preeclampsia.
Invasive hemodynamic monitoring may prove beneficial
in preeclamptic women with severe cardiac disease,
severe renal disease, refractory hypertension, oliguria, or
pulmonary edema (8, 5456).
786
Magnesium sulfate should be used for the prevention

and treatment of seizures in women with severe
preeclampsia or eclampsia.
If analgesia/anesthesia is required, regional or neuraxial analgesia/anesthesia should be used because it

is efficacious and safe for intrapartum management
of women with severe preeclampsia in the absence
of coagulopathy.
Low-dose aspirin has not been shown to prevent

preeclampsia in women at low risk and, therefore, is
not recommended.
Daily calcium supplementation has not been shown

to prevent preeclampsia and, therefore, is not recommended.
The management of a woman with severe preeclampsia remote from term is best accomplished in
a tertiary care setting or in consultation with an
obstetriciangynecologist with training, experience,
and demonstrated competence in the management of
high-risk pregnancies, such as a maternalfetal medicine subspecialist.
Practitioners should be aware that although various
laboratory tests may be useful in the management of
women with preeclampsia, to date there is no reliable predictive test for preeclampsia.
Women should be considered as having severe

preeclampsia if they have blood pressure levels of
160 mm Hg systolic or higher or 110 mm Hg diastolic or higher on two occasions at least 6 hours apart
while the patient is on bed rest, proteinuria of 5 g or
higher in a 24-hour urine specimen or 3+ or greater
on two random urine samples collected at least 4
hours apart, oliguria of less than 500 mL in 24 hours,
cerebral or visual disturbances, pulmonary edema or
cyanosis, epigastric or right upper-quadrant pain,
elevated liver enzymes, thrombocytopenia, or fetal
growth restriction.
Expectant management should be considered for
women remote from term who have mild preeclampsia.

Summary of
Recommendations
Invasive hemodynamic monitoring should be considered in preeclamptic women with severe cardiac
disease, renal disease, refractory hypertension, pulmonary edema, or unexplained oliguria.
Much of the obstetric research in the past several decades

has been directed at finding ways to prevent preeclampsia and eclampsia. Recent studies have focused on lowdose aspirin, calcium supplementation, and antioxidant
therapy. Most evidence suggests that low-dose aspirin
therapy is of little, if any, benefit in preventing preeclampsia in low-risk women (4, 5760).
Although there is some controversy regarding the
use of calcium supplementation to prevent preeclampsia,
large, randomized, controlled trials have shown no benefit (58, 61, 62). Recently, antioxidant therapy with 1,000
mg per day of vitamin C and 400 mg per day of vitamin
E has shown promise in preventing preeclampsia (63).
These results need to be confirmed in larger randomized
trials.
Can preeclampsia be prevented?
Antihypertensive therapy (with either hydralazine or

labetalol) should be used for treatment of diastolic
blood pressure levels of 105110 mm Hg or higher.
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39. Irion O, Masse J, Forest JC, Moutquin JM. Prediction of

pre-eclampsia, low birthweight for gestation and prematurity by uterine artery blood flow velocity waveform analysis in low risk nulliparous women. Br J Obstet Gynaecol
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54. Clark SL, Cotton DB, Hankins GD, Phelan JP. Critical
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M, Papiernik E, et al. Screening with a uterine Doppler in
low risk pregnant women followed by low dose aspirin in
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46. Witlin AG, Sibai BM. Magnesium sulfate therapy in

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Z J Obstet Gynaecol 1999;39:1218 (Level I)
49. Nassar AH, Adra AM, Chakhtoura N, Gomez-Marin O,

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PRACTICE BULLETINS

Force:
I
type of evidence.
committees.
789
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
Diagnosis and management of preeclampsia and eclampsia. ACOG

Practice Bulletin No. 33. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2002;99:159167
790
ACOG
PRACTICE
BULLETIN
Obstetric Analgesia and

Anesthesia
of Laura M. Goetzl, MD, MPH.
of practice.
Reaffirmed 2008
Labor results in severe pain for many women. There is no other circumstance
in which it is considered acceptable for a person to experience untreated severe
pain, amenable to safe intervention, while under a physicians care. In the
absence of a medical contraindication, maternal request is a sufficient medical
indication for pain relief during labor. Pain management should be provided
whenever it is medically indicated. The purpose of this document is to help
obstetriciangynecologists understand the available methods of pain relief to
facilitate communication with their colleagues in the field of anesthesia, thereby, optimizing patient comfort while minimizing the potential for maternal and
neonatal morbidity and mortality.
Background
Labor Pain
Uterine contractions and cervical dilation result in visceral pain (T-10 through
L-1). As labor progresses, the descent of the fetal head and subsequent pressure
on the pelvic floor, vagina, and perineum generate somatic pain transmitted by
the pudendal nerve (S24). Ideally, methods of obstetric pain relief will ameliorate both sources of pain in the patient in labor.
Available Methods of Anesthesia and Analgesia

Parenteral
Various opioid agonists and opioid agonistantagonists are available for systemic analgesia (Table 1). These agents can be given in intermittent doses on
patient request or via patient-controlled administration. Recent reports suggest
that the analgesic effect of parenteral agents used in labor is limited, and the primary mechanism of action is heavy sedation (1). In randomized trials compar-
PRACTICE BULLETINS
791
Table 1. Parenteral Agents for Labor Pain

Agent
Meperidine
Usual Dose
Frequency
Onset
Neonatal Half-Life
2550 mg (IV)
Q 12 h
5 min (IV)
1322.4 h
50100 mg (IM)
Q 24 h
3045 min (IM)
63 h for active metabolites
Fentanyl
50100 g (IV)
Q1h
1 min
5.3 h
Nalbuphine
10 mg (IV or IM)
Q3h
23 min (IV)
4.1 h
Butorphanol
12 mg (IV or IM)
Q4h
Morphine
25 mg (IV)
Q4h
15 min (IM)
10 mg (IM)
12 min (IV)
Not known
1030 min (IM)
Similar to nalbuphine in adults
5 min (IV)
7.1 h
3040 min (IM)
Abbreviations: IM, intramuscularly; IV, intravenously; Q, every.

Data from Lieberman BA, Rosenblatt DB, Belsey E, Packer M, Redshaw M, Mills M, et al. The effects of maternally administered pethidine or epidural bupivacaine on
the fetus and newborn. B J Obstet Gynaecol 1979;86:598606; Koehntop DE, Rodman JH, Brundage DM, Hegland MG, Buckley JJ. Pharmacokinetics of fentanyl in
neonates. Anesth Analg 1986;65:227232; Kuhnert BR, Kuhnert PM, Philipson EH, Syracuse CD. Disposition of meperidine and normeperidine following multiple doses
in labor. II. Fetus and neonate. Am J Obstet Gynecol 1985;151:410415; Nicolle E, Devillier P, Delanoy B, Durand C, Bessard G. Therapeutic monitoring of nalbuphine:
transplacental transfer and estimated pharmacokinetics in the neonate. Eur J Clin Pharmacol 1996;49:485489; Chay PC, Duffy BJ, Walker JS. Pharmacokinetic-pharmacodynamic relationships of morphine in neonates. Clin Pharmacol Ther 1992;51:334342; Lynn AM, Slattery JT. Morphine pharmacokinetics in early infancy.
Anesthesiology 1987;66:136139
ing intermittent intravenous meperidine (2, 3), intermittent

nalbuphine (4, 5), intermittent butorphanol (6), or patientcontrolled administration of meperidine (7) with regional
analgesia, parenteral agents resulted in significantly higher visual analog pain scores. Except when large doses of
meperidine are used via patient-controlled administration
(mean dose: 139 mg; 24% >200 mg) (7), administration of
parenteral agents results in absent-to-minimal reductions
in pain scores (26). However, when women receive high
doses of meperidine, the number of infants requiring
naloxone therapy increases fourfold when compared with
women receiving epidural analgesia (7).
Although regional analgesia provides superior pain
relief, some women are satisfied with the level of analgesia provided by narcotics when large enough doses are
used (7). However, patients exposed to doses of this magnitude are at increased risk of aspiration and respiratory
arrest. The use of shorter-acting agents, such as patientcontrolled administration of fentanyl, may decrease some
of the neonatal risks posed by meperidine. The decision
to use parenteral agents to manage labor pain should be
made in collaboration with the patient after a careful discussion of the risks and benefits.
The American Society of Anesthesiologists (ASA)
and the American College of Obstetricians and Gynecologists (ACOG) have received reports that some third-party
payers have denied reimbursement for regional analgesia
and anesthesia during labor unless a physician has documented the presence of a medical indication for regional
analgesia and anesthesia (8). Of the various pharmaco-
logic methods of pain relief during labor and delivery,

regional analgesia techniquesspinal, epidural, and combined spinal epiduralare the most flexible, effective, and
least depressing to the central nervous system, allowing
for an alert, participating woman and an alert neonate. It is
the opinion of the ASA and ACOG that third-party payers
who provide reimbursement for obstetric services should
not deny reimbursement for regional analgesia and anesthesia because of an absence of other medical indications.
Regional Analgesia
In obstetric patients, regional analgesia refers to a partial
to complete loss of pain sensation below the T8 to T10
level. In addition, a varying degree of motor blockade
may be present, depending on the agents used.
Epidural. Epidural analgesia offers the most effective
form of pain relief (27) and is used by most women in the
United States (9). In most obstetric patients, the primary
indication for epidural analgesia is the patients desire for
pain relief. Medical indications for epidural analgesia during labor may include anticipated difficulty in intubation,
a history of malignant hyperthermia, selected forms of cardiovascular and respiratory disease, and prevention or
treatment of autonomic hyperreflexia in parturients with a
high spinal cord lesion. A catheter is placed in the epidural space, allowing for continuous epidural infusion of local
anesthetic agents or narcotics. The advantage of this
method is that medication can be titrated over the course of
labor as needed. In addition, epidural catheters placed for
792
labor analgesia can be used for cesarean delivery or postpartum tubal ligation. Modern epidural preparations that
combine a low-dose local anesthetic, such as bupivacaine,
levobupivacaine, or ropivacaine, with an opioid agonist
are preferred because they decrease motor blockade and
result in an increased rate of spontaneous vaginal delivery
(10). Some women who receive epidural analgesia may be
candidates for ambulation.
Spinal. Single-shot spinal analgesia provides excellent
pain relief for procedures of limited duration, such as
cesarean delivery, the second stage of labor, rapidly progressing labor, and postpartum tubal ligation. A longacting local anesthetic often is used, with or without an
opioid agonist. The duration of anesthesia is approximately 30250 minutes depending on the drugs used
(11). However, because of its inability to extend the
duration of action, single-shot spinal analgesia is of limited use for the management of labor.
Combined Spinal Epidural. Combined spinal epidural
offers the rapid onset of spinal analgesia combined with
the ability to use the epidural catheter to prolong the duration of analgesia with a continuous epidural infusion for
labor, to convert to anesthesia for cesarean delivery, or to
provide postcesarean delivery pain control. This method
of obstetric analgesia is increasing in popularity, especially with the advent of needle-through-needle techniques
that eliminate the need for more than one skin puncture.
In addition, the use of newer atraumatic spinal needles
is associated with a dramatically decreased risk of spinal
headache (12). The spinal component of combined spinal
epidural may be an intrathecal narcotic plus a small
amount of a local anesthetic. In one randomized, prospective study, intrathecal use of the short-acting, lipid-soluble
narcotic sufentanil was associated with a small but
increased incidence of profound fetal bradycardia within
60 minutes of the administration of the combined spinal
epidural and an increased risk of cesarean delivery for
nonreassuring fetal status (13). Emergency cesarean
delivery for fetal bradycardia also occurred in 1.5% of
cases in which combined spinal epidural was used, compared with none in cases using only epidural analgesia;
the outcomes were the same in both groups. Increased
fetal bradycardia after the use of intrathecal fentanyl also
was seen in a retrospective study (14) but it was not significant because of the small sample size of the study.
Failure of the spinal component occurs at a rate of 4%
with combined spinal epidural (12, 15), but the block can
be supplemented with the epidural catheter.
Side Effects of Regional Analgesia. Common side
effects of regional analgesia are described in Table 2. The
most common side effect is hypotension, which cannot be
wholly prevented with prehydration with crystalloid or
the use of prophylactic ephedrine (16, 17). It is common practice, however, to prehydrate women with
5001,000 mL of nonglucose-containing isotonic crystalloid. Uterine perfusion also should be maximized at
the time of cesarean delivery by maintaining left uterine
displacement before delivery. Although prophylactic
ephedrine is not commonly administered before epidural
analgesia for labor pain, obstetriciangynecologists
should be prepared for the frequent occurrence of hypotension that should be treated with intravenous ephedrine
to prevent decreased uterine perfusion. There is a reported 8% incidence of transient fetal heart rate deceleration,
which often is related to epidural analgesia and is responsive to conservative management techniques, such as
hydration, discontinuation of the epidural infusion, repositioning the woman so she is lying on her side, administration of oxygen, or administration of ephedrine (14).
Postdural puncture headache is possible with spinal
analgesia but also can occur with combined spinal
epidural and epidural analgesia (12, 15). Early conservative therapy for headache includes analgesics, supine
positioning, and hydration. However, in 36% of cases,
postdural puncture headache after spinal or combined
spinal epidural is severe enough to require an autologous
epidural blood patch (12). This rate is higher after unanticipated dural puncture during epidural analgesia (wet
tap) because of the larger needle size. The initial blood
patch procedure is approximately 6175% effective in
the treatment of postdural puncture headache (18, 19).
Transient neurologic symptomspainful sensations
in the buttocks or lower extremitiescan occur with
spinal anesthesia, although the incidence is low, occurring in approximately 37% of cases (20). Pruritus is
extremely common after intrathecal or epidural opioids
but it can be treated, as needed, with either naloxone or
nalbuphine (10, 21). Approximately 10% of patients will
have inadequate anesthesia with an epidural block but
this often can be managed with further epidural boluses
(22). Because a portion of an epidural narcotic enters the
systemic circulation, close attention to the patients total
narcotic dosage over the course of parturition is important. Total spinal blockade, epidural or spinal hematoma,
abscess, and neurotoxicity are all rare complications of
regional analgesia. Fever (temperature >100.4F) is one
of the most common side effects of epidural analgesia; it
occured in 24% of nulliparous women randomized to
epidural analgesia compared with 5% of nulliparous
women receiving parenteral narcotics (23). Although the
overall risk of fever in multiparous women is not significantly higher than in controls (4% versus 3%), the risk
of fever increases with the duration of labor; therefore,
multiparous women who experience prolonged labor are
at increased risk (23, 24).
PRACTICE BULLETINS
793
Table 2. Complications of Regional Analgesia

Complication
Incidence (%)
Hypotension (in prehydrated women undergoing cesarean delivery)

Spinal
25671,2
Epidural (in prehydrated women in labor)
283135
Epidural
8.596,7
Fever >100.4 (excess rate over women treated with narcotics)

Nulliparous women
198
Multiparous women
18
Postdural puncture headache

Spinal
1.539,10
Epidural
211
Combined spinal epidural
12.771113
Transient fetal heart decelerations
814
Pruritus (with added opioid only)

Epidural
1.32611,15
Spinal and combined spinal epidural
418516,17,11,18
Inadequate pain relief: epidural
91519,6
1
Vercauteren MP, Coppejans HC, Hoffmann VH, Mertens E, Adriaensen HA. Prevention of hypotension by a single 5-mg dose of ephedrine during small-dose spinal
anesthesia in prehydrated cesarean delivery patients. Anesth Analg 2000;90:324327
2
Park GE, Hauch MA, Curlin F, Datta S, Bader AM. The effects of varying volumes of crystalloid administration before cesarean delivery on maternal hemodynamics and
colloid osmotic pressure. Anesth Analg 1996;83:299303
3
Fong J, Gurewitsch ED, Press RA, Gomillion MC, Volpe L. Prevention of maternal hypotension by epidural administration of ephedrine sulfate during lumbar epidural
anesthesia for cesarean section. Am J Obstet Gynecol 1996;175:985990
4
Sharma SK, Sidawi JE, Ramin SM, Lucas MJ, Leveno KJ, Cunningham FG. Cesarean delivery: a randomized trial of epidural versus patient-controlled meperidine analgesia during labor. Anesthesiology 1997;87:487494
5
Brizgys RV, Dailey PA, Shnider SM, Kotelko DM, Levinson G. The incidence and neonatal effects of maternal hypotension during epidural anesthesia for cesarean section.
Anesthesiology 1987;67:782786
6
Eberle RL, Norris MC, Eberle AM, Naulty JS, Arkoosh VA. The effect of maternal position on fetal heart rate during epidural or intrathecal labor analgesia. Am J Obstet
Gynecol 1998;179:150155
7
Collis RE, Davies DW, Aveling W. Randomized comparison of combined spinal-epidural and standard epidural analgesia in labour. Lancet 1995;345:14131416
8
Philip J, Alexander JM, Sharma SK, Leveno KJ, McIntire DD, Wiley J. Epidural analgesia during labor and maternal fever. Anesthesiology 1999;90:12711275
9
Sears DH, Leeman MI, Jassy LJ, ODonnell LA, Allen SG, Reisner LS. The frequency of postdural puncture headache in obstetric patients: a prospective study comparing the 24-gauge versus the 22-gauge Sprotte needle. J Clin Anesth 1994;6:4246
10
Vallejo MC, Mandell GL, Sabo DP, Ramanathan S. Postdural puncture headache: a randomized comparison of five spinal needles in obstetric patients. Anesth Analg
2000;91:916920
11
Norris MC, Grieco WM, Borkowski M, Leighton BL, Arkoosh VA, Huffnagle HJ, et al. Complications of labor analgesia: epidural versus combined spinal epidural techniques. Anesth Analg 1994;79:529537
12
Collis RE, Plaat FS, Morgan BM. Comparison of midwife top-ups, continuous infusion and patient-controlled epidural analgesia for maintaining mobility after a lowdose combined spinal-epidural. Br J Anaesth 1999;82:233236
13
Herbstman CH, Jaffee JB, Tuman KJ, Newman LM. An in vivo evaluation of four spinal needles used for the combined spinal-epidural technique. Anesth Analg 1998;86:520522
14
Palmer CM, Maciulla JE, Cork RC, Nogami WM, Gossler K, Alves D. The incidence of fetal heart rate changes after intrathecal fentanyl labor analgesia. Anesth Analg
1999;88:577581
15
Vertommen JD, Vandermeulen E, Van Aken H, Vaes L, Soetens M, Van Steenberge A, et al. The effects of the addition of sufentanil to 0.125% bupivacaine on the quality of analgesia during labor and on the incidence of instrumental deliveries. Anesthesiology 1991;74:809814
16
Gambling DR, Sharma SK, Ramin SM, Lucas MJ, Leveno KJ, Wiley J, et al. A randomized study of combined spinal-epidural analgesia versus intravenous meperidine
during labor: impact on cesarean delivery rate. Anesthesiology 1998;89:13361344
17
Dahl JB, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients
undergoing cesarean section with spinal anesthesia: a qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology 1999;91:
19191927
18
Shah MK, Sia AT, Chong JL. The effect of the addition of ropivacaine or bupivacaine upon pruritus induced by intrathecal fentanyl in labour. Anaesthesia 2000;55:10081013
19
Beilin Y, Zahn J, Bernstein HH, Zucker-Pinchoff B, Zenzen WJ, Andres LA. Treatment of incomplete analgesia after placement of an epidural catheter and administration of local anesthetic for women in labor. Anesthesiology 1998;88:15021506
794
General Anesthesia
Because general anesthesia results in a loss of maternal
consciousness, it must be accompanied by airway management by trained anesthesia personnel. Nitrous oxide
may be supplemented with halogenated hydrocarbons,
such as isoflurane, desflurane, and sevoflurane, at low
concentrations. The use of intravenous agents, such as
sodium pentothal, followed by rapid sequence induction
is used to minimize the risk of aspiration. All inhaled
anesthetic agents readily cross the placenta and have
been associated with neonatal depression. Ideally, induction-to-delivery time should be minimized when general
anesthesia is used. One study reported that fetal exposure
of more than 8 minutes was associated with increased
neonatal depression (25).
Halogenated agents are potent uterine relaxants
when administered in high inhalation concentrations.
This property can be useful to obstetricians in circumstances in which uterine relaxation is desirable, such as
management of uterine inversion, internal podalic version, or fetal entrapment (either during vaginal or cesarean delivery), although intravenous nitroglycerin and
terbutaline may achieve the same goal with fewer side
effects. Increased uterine relaxation, however, is a concern because of its potential for increasing blood loss
during cesarean delivery. Although some investigators
have reported increased blood loss (26), especially with
higher dosages (27), others have found no increased risk
when women at high risk were excluded (28).
Local
Various local anesthetic agents are available for local
infiltration of the perineum and vagina to provide analgesia before episiotomy and during repair of lacerations.
Common rapidly acting agents include lidocaine (12%)
and 2-chloroprocaine (13%), which provide local anesthesia for a duration of 2040 minutes. Toxic effects of
local anesthetic agents are rare and include seizures,
hypotension, and cardiac arrhythmias. Toxicity is highest
with intravascular injection; therefore, it is critical to
aspirate for blood before injecting a local anesthetic into
the vascular tissues of the vagina and perineum. The total
dosage of plain lidocaine should not exceed the recommended dosage because of the increased incidence of
lidocaine toxicity.
Local anesthetic agents also can be used by an obstetriciangynecologist to perform a pudendal block (a type
of regional block), an adequate form of temporary pain
relief that can aid outlet operative vaginal deliveries in
women not using regional analgesia. Complications from
pudendal block include intravascular injection of anesthetic agents, hematoma, and infection. Paracervical blocks
have been strongly associated with fetal bradycardia (29).
Infiltration of local anesthesia, although time consuming, has been used for cesarean delivery in rare circumstances when adequate general or regional anesthesia
is unavailable (30). In slightly more common but still rare
situations, practitioners have initiated a cesarean delivery
under local anesthesia until the regional anesthesia has
taken effect.
Maternal Mortality
Complications of anesthesia remain an important and
often preventable cause of pregnancy-related mortality
(31), accounting for more than 5% of maternal deaths (32).
Anesthesia-related maternal mortality has decreased with
time and is currently estimated at 1.7 per 1,000,000 live
births (33). The removal from the market of 0.75% bupivacaine by the U.S. Food and Drug Administration in 1984
coupled with the increase in popularity of fractionated dosing of local anesthetics led to a sharp decrease in deaths
from local anesthetic toxicity. The increased safety of
regional analgesia has increased the relative risk of general anesthesia; the case fatality rate of general anesthesia for
cesarean delivery is estimated to be approximately 32 per
1,000,000 live births compared with 1.9 per 1,000,000 live
births for regional anesthesia (33). Failed intubation occurs
in 1 out of 250 cases of general anesthesia administered to
pregnant patients (34). This rate is approximately 10-fold
higher than it is in the nonpregnant population. The significant added morbidity of general anesthesia over regional
anesthesia for cesarean delivery suggests that regional
anesthesia is the preferred method of pain control and
should be used unless a contraindication to regional anesthesia is present (see box). Although general anesthesia
may be indicated in some cases of fetal heart rate abnormality, the severity of the abnormality should be considered before incurring the excess risk of maternal mortality
associated with general anesthesia. In patients with an
increased risk of urgent cesarean delivery (eg, severe
intrauterine growth restriction), it is reasonable to encourage early regional analgesia during labor. This approach
has the potential benefit of reducing the need for emergent
general anesthesia and its attendant risks.
Absolute Contraindications to Regional Anesthesia
Refractory maternal hypotension
Maternal coagulopathy
Maternal use of once-daily dose of low-molecularweight heparin within 12 hours
Untreated maternal bacteremia
Skin infection over site of needle placement
Increased intracranial pressure caused by a mass lesion
PRACTICE BULLETINS

Recommendations
What factors should be considered in the

choice of parenteral agent for labor pain?
choice in the treatment of maternal respiratory and neurobehavioral depression secondary to opioid agonist
drugs. Studies have suggested that naloxone may be associated with neonatal withdrawal seizures, especially in
women who are opioid dependent (51). Because it is a
pure antagonist, it does not cause additional respiratory
depression. Naloxone should be given intravenously
when possible; intramuscular or subcutaneous administration may delay absorption in the neonate who is
stressed and vasoconstricted. Because naloxone has a relatively short duration of action, it may be necessary to
repeat the dose.
What is the role of patient-controlled epidural

analgesia during labor?
The goal of epidural analgesia is to provide satisfactory

pain control for labor with the lowest dose of analgesic
drugs needed to minimize motor blockade and simultaneously reduce the potential side effects of epidural analgesia during the course of labor. Patient-controlled
epidural analgesia provides pain control similar to that of
standard epidural analgesia (5254). Intermittent bolus
patient-controlled epidural analgesia results in lower total
dosages of anesthetic agents than continuous infusion
epidural (52, 53, 55) and results in less motor blockade
(53). When compared with practitioner-administered
intermittent bolus techniques, some studies have found
an increased use of anesthetic agents with patient-controlled epidural analgesia (53), while others have found
no difference (55, 56). Motor blockade appears to be similar between patient-controlled epidural analgesia and
intermittent bolus epidural analgesia (53, 54). Patientcontrolled epidural analgesia is an acceptable alternative
method of labor analgesia but does not appear to have
additional benefits over standard epidural techniques.
Patient satisfaction with all epidural techniques is high
and is not significantly improved with patient-controlled
epidural analgesia in most studies (5355).
Historically, meperidine has been the most widely used

systemic opioid. However, the use of drugs in the opioid
agonistantagonist class has become more popular
because they are associated with less nausea and vomiting (35, 36) and respiratory depression is less likely, even
when higher doses of nalbuphine are used (37).
Conversely, nalbuphine has been associated with
increased maternal sedation (35, 36). Fentanyl also has
been used during labor as an alternative drug because of
its relatively short half-life; it is associated with significantly less nausea, vomiting, and sedation than meperidine (38). Butorphanol may increase blood pressure
levels and should be avoided in patients with chronic
hypertension or preeclampsia (39).
There is significant transplacental passage of all parenteral drugs. A recent meta-analysis of several randomized trials revealed that parenteral analgesia is associated
with a twofold to threefold increased risk of Apgar scores
lower than 7 at 5 minutes and a fourfold increased need
for neonatal naloxone (40), although the overall incidence of both was low. Although most neonatal depression is short-lived and can be treated as needed with
naloxone, the long neonatal half-life of normeperidine
(63 hours), an active metabolite of meperidine, has raised
concerns regarding the prolonged duration of neonatal
sedation following the administration of parenteral
meperidine during labor (41, 42). Infants exposed to
meperidine during labor demonstrate dose-dependent
neurobehavioral depression that can be demonstrated on
day 2 (43) and day 3 (44, 45) of life. Unlike other parenteral drugs, the neonatal effects of meperidine increase
with a prolonged drug-to-delivery interval because of the
accumulation of normeperidine (44, 45). Neonates
exposed to transplacental nalbuphine are demonstrated to
have a decreased response to sound and decreased tone
and alertness for more than 24 hours after birth (35).
Fentanyl also crosses the placenta but has not been associated with neonatal neurobehavioral depression (38).
All parenteral drugs can have a significant effect on
intrapartum fetal heart rate tracing. Meperidine (46, 47),
fentanyl (38), and nalbuphine (48) have all been associated with decreased heart rate variability. Nalbuphine and
fentanyl also have been associated with transient sinusoidal fetal heart rate tracings (49, 50). Caution should be
used in administering these drugs in the setting of diminished short- or long-term fetal heart rate variability.
Naloxone is a pure opioid antagonist that is the drug of
795
Is chronic back pain associated with epidural

use?
Retrospective studies have found an association between

epidural analgesia and chronic back pain (5759). One
proposed explanation is that motor block of the lower
back and legs leads to prolonged periods of poor posture
and decreased perception of muscle strain. However, retrospective studies are plagued by recall bias and patients
perceptions of an association between epidural analgesia
and chronic back pain. Prospective cohort studies and
one small, randomized controlled trial have found no significant association between epidural analgesia and
chronic back pain (6062).
796
What is the effect of epidural analgesia on

maternal fever?
Does epidural analgesia increase the rate of

operative delivery?
Although neuraxial techniques (epidural, spinal, and

combined spinal epidural) provide the most effective and
least depressant analgesia for labor, the question of
whether their use is associated with an increased risk of
cesarean delivery remains controversial. Several randomized prospective studies have shown an increased
risk of cesarean delivery with epidural analgesia (2, 3),
while others have shown no increased risk with epidural
analgesia (7) or combined spinal epidural analgesia (13).
Limitations to analysis of these studies include high
crossover rates between study populations, substantial
bias, and small numbers of patients.
Less controversial is the causal role epidural analgesia plays in prolonging labor by 4090 minutes (2, 7, 13,
40) and in the approximate twofold increased need for
oxytocin augmentation (3, 7). These findings are supported by most prospective studies as well as metaanalysis (40, 59). An increased risk of a second stage of
labor longer than 2 hours (2, 13) in women with epidural analgesia likely contributes to the higher rates of operative vaginal delivery seen in most prospective studies.
The four best prospective studies, in which elective forceps use was not permitted (2, 3, 7, 13), yielded a combined relative risk of 1.9 (95% confidence interval,
No well-designed, randomized trial has specifically

addressed the issue of epidural-associated fever.
However, studies in which women were randomized to
receive epidural analgesia or parenteral drugs for other
objectives have consistently shown an increased rate of
fever in the epidural group (2, 7, 23). In three randomized studies with mixed populations of nulliparous and
multiparous women, the relative risk for fever in the
epidural group was between 4.0 and 4.6 (2, 7, 23). In the
one randomized study in which logistic regression was
performed to control for potential confounders, the risk
of fever in the population receiving epidural was fourfold higher (95% confidence interval, 2.07.7) (23).
The mechanism for fever is not known. Theories
include thermoregulation and chorioamnionitis. In one
study, placental inflammation was more common with
epidural analgesia (63). Epidural-related fever is not
benign. Although there is no increased risk of neonatal
sepsis, there is a statistically significant increase in
neonatal sepsis evaluations (23, 24). Epidural-related
fever results in a statistically significant risk of maternal
antibiotic treatment (64, 65) and a statistically significant
increase in neonatal antibiotic treatment (23).
1.42.5) of forceps delivery in women who received

epidural analgesia. Some investigators have found a
decreased risk of operative delivery with combined
spinal epidural when compared with low-dose epidural
(66). This finding is difficult to interpret, because elective forceps were not excluded in this study, and the rate
of forceps use was high (2840%). Excessive operative
vaginal deliveries have been implicated in the increased
rate of third- and fourth-degree lacerations seen in
women with epidural analgesia (67).
What is the effect of the timing of epidural

analgesia on the course of labor and the risk
of cesarean delivery?
Reports regarding the effect of the timing of epidural

analgesia on the course of labor offer conflicting results.
Several retrospective studies have shown an increased risk
of cesarean delivery in nulliparous women in whom
epidural analgesia was administered before cervical
dilatation of 4 cm (68) or 5 cm (69). Another retrospective
study found an increased risk of cesarean delivery with
higher station at epidural placementbut not related to
cervical dilatationafter using logistic regression to control for potential confounders (70). A prospective trial
comparing laboring women who were randomized to
either an epidural group or an intravenous meperidine
group, reported a 25% cesarean delivery rate in the
epidural group and a 2.2% cesarean delivery rate in the
narcotic group (P<0.05) (3). Limitations of this study
included the small number of patients randomized in each
group, as well as the small number of patients who
required cesarean delivery. Another prospective randomized trial of 334 nulliparous women found no difference
in the cesarean delivery rate for early (10%) compared
with late (8%) epidural placement (4). This study was
limited by only a small difference in timing and cervical
dilatation between both groups, a median of 4 cm cervical dilatation for early administration and 5 cm for late
administration. Other studies have shown conflicting
results, and further studies are needed to identify whether
early placement of epidural analgesia significantly
increases the risk of cesarean delivery and to prospectively determine the risk at each level of cervical dilatation.
At this time, it appears to be possible that very early
placement of epidural analgesia may increase the risk of
cesarean delivery and that the risk decreases with
delayed epidural placement. After weighing this conflicting data, the ACOG Task Force on Cesarean
Delivery Rates recommended that, when feasible,
obstetric practitioners should delay the administration of
epidural analgesia in nulliparous women until cervical
dilatation reaches 45 cm and that other forms of anal-
PRACTICE BULLETINS
How can the risks of epidural or spinal

hematoma be minimized?
How does preeclampsia influence the choice

of analgesia or anesthesia?
Regional anesthesia is preferred for women with

preeclampsia and eclampsiaboth for labor and delivery (80). A secondary analysis of women with severe
preeclampsia in the National Institute of Child Health
and Human Developments MaternalFetal Medicine
Units Network trial of low-dose aspirin reported epidural anesthesia was not associated with an increased rate of
cesarean delivery, pulmonary edema, or renal failure
(81). Moreover, general anesthesia carries more risk to
pregnant women than does regional anesthesia (33).
Regional analgesia in women with preeclampsia is
associated with an overall 1525% reduction in systemic
mean arterial pressure (8284). Although the peripheral
vasodilation seen with regional analgesia may be helpful
in decreasing severe hypertension, hypotension that
requires cautious treatment with ephedrine may occur
(83, 84). In addition, prehydration with crystalloid combined with intraoperative fluid boluses for hypotension
results in an average additional fluid challenge of
600800 mL in women with preeclampsia receiving
regional analgesia (82, 84).
How can the risk of maternal aspiration be

minimized?
There is insufficient evidence to address the safest level

of maternal oral intake during labor. The ASA Task
Force on Obstetric Anesthesia recommends allowing a
modest intake of clear liquids in patients experiencing normal labor (72). However, a fasting period of
68 hours for solids is preferable before elective cesarean delivery.
For both elective and indicated cesarean delivery,
agents to decrease gastric acidity should be used.
Sodium citrate with citric acid has been shown to
neutralize the gastric contents of 88.5% of women
undergoing cesarean delivery (85) and should be
administered when the decision is made to perform
cesarean delivery.
Epidural or spinal hematoma is a rare but morbid complication of regional analgesia. Patients at higher risk
include those with underlying bleeding dyscrasias or
thrombocytopenia and those taking medications that may
affect coagulation. Although it is not necessary to obtain
a platelet count before using regional analgesia in healthy
women experiencing normal labor (72), certain groups of
patients may benefit from such evaluations, including
those with severe preeclampsia, idiopathic thrombocytopenic purpura, known placental abruption, or other risk
factors for disseminated intravascular coagulation.
Most anesthesiologists will administer regional
analgesia to a patient with a platelet count higher than
100,000/L. However, the management of patients with
platelet counts lower than 100,000/L is controversial.
Several studies reported no complications in women who
received epidural analgesia with platelet counts between
50,00099,000/L (7375).
Patients who are taking anticoagulants also are at
risk for epidural or spinal hematoma. Patients on unfractionated heparin therapy should be able to receive
regional analgesia if they have a normal activated partial
thromboplastin time (aPTT). Patients taking prophylactic doses of unfractionated heparin or low-dose aspirin
are not at increased risk (76, 77) and can be offered
regional analgesia. Low-molecular-weight heparin has
been associated with multiple case reports of epidural
and spinal hematoma, and the U.S. Food and Drug
Administration has issued a public health advisory on
this issue (78). Low-molecular-weight heparin has a
longer half-life than standard heparin, and its anticoagulant activity is not reflected in the aPTT. In patients
receiving once-daily, low-dose low-molecular-weight
heparin, regional anesthesia should not be offered until
12 hours after the last injection of low-molecular-weight
heparin (79). In addition, low-molecular-weight heparin
should be withheld for at least 2 hours after the removal
of an epidural catheter. The safety of regional analgesia
in patients receiving twice-daily low-molecular-weight
heparin has not been studied sufficiently, and it is not
known whether delaying regional analgesia for 24 hours

after the last injection is adequate. Because the onset of
labor often is difficult to predict, it may be reasonable to
convert patients to unfractionated heparin as they
approach term.
gesia be used until that time (71). However, 4 cm of

dilatation is an arbitrary cutoff because decreased risk
with increased cervical dilatation is a continuum.
Therefore, the decision of when to place epidural analgesia should be made individually with each patient,
with other factors, such as parity, taken into consideration. Women in labor should not be required to reach
45 cm of cervical dilatation before receiving epidural
analgesia.
797
What are the potential negative effects of

analgesia and anesthesia on breastfeeding?
Although it is clear that both maternally administered

opioids and local anesthetics used either parenterally
798
(45, 86) or in epidural analgesia (8789) enter the fetal

bloodstream, the effects on breastfeeding have not been
well studied. Intrapartum opioid use may decrease
neonatal rooting reflexes and delay initiation of breastfeeding (86, 90); however, there is limited evidence that
these delays affect the ultimate success of breastfeeding.
Few studies have examined the more clinically relevant
outcomes of short- or long-term breastfeeding success.
More recently, a study that controlled for potential
confounders found no relationship between either parenteral opioids or epidural analgesia and breastfeeding
success of neonates at age 6 weeks (91).
Postdelivery analgesia also has the potential to
affect breastfeeding success because of the ongoing
delivery of narcotics to breast milk (41). Postcesarean
patient-controlled analgesia with morphine results in
less neurobehavioral depression than meperidine (42),
possibly because of the accumulation of the slowly
metabolized active metabolite of meperidine (normeperidine) in the neonatal bloodstream. Postoperative
analgesia via the epidural route decreases maternal opioid requirements (42). Additionally, continuous bupivacaine epidural analgesia results in significantly increased
milk production and greater infant weight gain when
compared with diclofenac suppositories alone for
postcesarean pain management (92). Further studies are
needed to address the effect of postoperative pain control
on breastfeeding success, milk production, and infant
weight gain.
What are the optimal agents for postoperative

analgesia?
Opioid therapy is the mainstay of postoperative pain

management. Various routes of administration are available, including intravenous, intrathecal, and epidural
(with or without local anesthetics). For patients undergoing cesarean delivery with spinal or epidural anesthesia,
the most cost-effective regimen of pain management for
the first 24 hours is preservative-free morphine hydrochloride placed in the intrathecal space at the time of the
initial spinal anesthesia (93, 94) or after delivery when
using epidural anesthesia. This method provides effective pain control in the first 1224 hours following
cesarean delivery (95, 96) without the added cost associated with an infusion pump. Initial concerns regarding
the possibility of delayed respiratory depression with
intrathecal morphine have led to a lowering of the standard dosage to 100250 g (9598).
In patients undergoing cesarean delivery under
epidural anesthesia, patient-controlled epidural analgesia
for the first 24 hours is a reasonable choice. This strate-
gy minimizes the dosage of maternally administered opioids (99, 100) and maternal sedation (99) compared with
intravenously administered opioids (patient-controlled
administration) and uses the preexisting catheter.
Although patient-controlled epidural analgesia using a
combination of opioid and local anesthesia reduces the
cumulative opioid dosage, it results in increased motor
weakness (101, 102), which may inhibit patient mobilization. Even low concentrations of local anesthesia
result in significant motor weakness and can make
ambulation difficult in up to 43% of patients (103).
Consideration should be given to removing the epidural
catheter after 24 hours to reduce side effects, such as urinary retention (100) pruritus and infection risk, as well
as to minimize costs. All intrathecal and epidural opioid
administration is accompanied by a dose-dependent,
3556% incidence of maternal pruritus severe enough
to require treatment (104107). Effective treatment
includes intravenous nalbuphine (105, 108, 109), prophylactic oral naltrexone (110), and intravenous
ondansetron (111, 112).
In institutions where patient-controlled epidural
analgesia is not available or in patients who received
general anesthesia intraoperatively, intravenous patientcontrolled administration is a reasonable choice because
it is associated with increased patient satisfaction (113)
and decreased sedation levels compared with intramuscular narcotics (113, 114). Morphine, hydromorphone
hydrochloride, and fentanyl are all acceptable drugs
for intravenous patient-controlled administration.
Meperidine should be avoided because of the accumulation of its slowly metabolized active metabolite
normeperidine in the neonate and its subsequent neurobehavioral effects (42).
An important goal of postoperative pain management should be minimizing the cumulative maternal opioid dosage to reduce maternal sedation and neonatal
side effects. Maternal nonsteroidal antiinflammatory
drugs are useful in achieving this goal and are effective
at reducing maternal opioid consumption by 3039%
(115, 116).
When is it appropriate to obtain an anesthesia consultation?
Failed intubation and pulmonary aspiration remain the

leading causes of anesthesia-related maternal morbidity
and mortality (34). Identifying women with risk factors
for failed intubation or other complications of anesthesia
and referring them for antepartum anesthesia consultation may reduce this risk, although this has not been
studied (see box).
PRACTICE BULLETINS
Risk Factors that May Prompt

Anesthetic Consultation
Patients with platelet counts of 50,000100,000/L

may be considered potential candidates for regional
analgesia.
Regional analgesia is preferred in women with

preeclampsia unless a contraindication to regional
analgesia is present.
Identifying women with risk factors for failed intubation or other complications of anesthesia and
referring them for antepartum anesthesia consultation may reduce this risk.
To avoid respiratory depression, close monitoring of the cumulative narcotic dosage given to a
patient antepartum, intrapartum, and postpartum is
essential.
Parenteral pain medications for labor pain decrease

fetal heart rate variability and may limit the obstetriciangynecologists ability to interpret the fetal
heart rate tracing. Consideration should be given to
other drugs in the setting of diminished short- or
long-term fetal heart rate variability.
Sodium citrate should be administered promptly to

neutralize gastric contents following the decision to
perform a cesarean delivery.
Regional analgesia provides a superior level of pain

relief during labor when compared with systemic
drugs and, therefore, should be available to all
women.
Clear liquid intake may be allowed in patients in

labor without complications.

It is not necessary to routinely obtain a platelet

count before administration of regional analgesia
or anesthesia in a pregnant patient without complications.
Summary of
Recommendations
American Academy of Pediatrics, American College of Obstetricians and

Gynecologists. Guidelines for perinatal care. 4th ed. Elk Grove Village,
Illinois: AAP; Washington DC: ACOG, 1997
Breastfeeding does not appear to be affected by the

choice of anesthesia; therefore, the choice should be
based on other considerations.
Anesthetic consultation may be considered when any of

the following risk factors are present:
Marked obesity
Severe edema or anatomical abnormalities of the face
or neck or spine, including trauma or surgery
Abnormal dentition, small mandible, or difficulty opening the mouth
Extremely short stature, short neck, or arthritis of the
neck
Goiter
Serious maternal medical problems, such as cardiac,
pulmonary, or neurologic disease
Bleeding disorders
Severe preeclampsia
Previous history of anesthetic complications
Obstetric complications likely to lead to operative delivery, eg, placenta previa or high-order multiple gestation
799
The decision of when to place epidural analgesia

should be made individually with each patient, with
other factors, such as parity, taken into consideration. Women in labor should not be required to reach
45 cm of cervical dilatation before receiving
epidural analgesia.
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SE, Leighton BL. Effect of labor analgesia on breastfeeding success. Birth 1999;26:8388 (Level II-2)
92. Hirose M, Hara Y, Hosokawa T, Tanaka Y. The effect of
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93. Gerancher JC, Floyd H, Eisenach J. Determination of
an effective dose of intrathecal morphine for pain relief
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94. Cohen SE, Subak LL, Brose WG, Halpern J. Analgesia
after cesarean delivery: patient evaluations and cost of
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95. Abboud TK, Dror A, Mosaad P, Zhu J, Mantilla M, Swart
F, et al. Mini-dose intrathecal morphine for the relief of
post-cesarean pain: safety, efficacy, and ventilatory
responses to carbon dioxide. Anesth Analg 1988;67:
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803
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Lertmaharit S, Ngamprasertwong P, Nimcharoendee K.
Nalbuphine versus propofol for treatment of intrathecal
morphine-induced pruritus after cesarean delivery. Anesth
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105. Alhashemi JA, Crosby ET, Grodecki W, Duffy PJ, Hull
KA, Gallant C. Treatment of intrathecal morphineinduced Pruritus following cesarean section. Can J
Anaesth 1997;44:10601065 (Level I)
106. Rapp-Zingraff N, Bayoumeu F, Baka N, Hamon I, Virion
JM, Laxenaire MC. Analgesia after caesarean section:
patient-controlled intravenous morphine vs epidural morphine. Int J Obstet Anesth 1997;6:8792 (Level II-1)
107. Harrison DM, Sinatra R, Morgese L, Chung JH. Epidural
narcotic and patient-controlled analgesia for post-cesarean section pain relief. Anesthesiology 1988;68:454457
(Level I)
108. Cohen SE, Ratner EF, Kreitzman TR, Archer JH,
Mignano LR. Nalbuphine is better than naloxone for treatment of side effects after epidural morphine. Anesth
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96. Abouleish E, Rawal N, Fallon K, Hernandez D.

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R. Optimal dose of nalbuphine for treatment of intrathecal-morphine induced pruritus after caesarean section. J
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97. Yang T, Breen TW, Archer D, Fick G. Comparison of

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110. Abboud TK, Lee K, Zhu J, Reyes A, Afrasiabi A, Mantilla

M, et al. Prophylactic oral naltrexone with intrathecal
morphine for cesarean section: effects on adverse reactions and analgesia. Anesth Analg 1990;71:367370
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98. Milner AR, Bogod DG, Harwood RJ. Intrathecal administration of morphine for elective Caesarean section. A
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99. Paech MJ, Moore JS, Evans SF. Meperidine for patientcontrolled analgesia after cesarean section. Intravenous
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100. Parker RK, White PF. Epidural patient-controlled analgesia: an alternative to intravenous patient-controlled analgesia for pain relief after cesarean delivery. Anesth Analg
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AM, Tomich P, et al. Pain control after cesarean birth.
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101. Cooper DW, Ryall DM, McHardy FE, Lindsay SL,

Eldabe SS. Patient-controlled extradural analgesia with
bupivacaine, fentanyl, or a mixture of both, after cesarean
section. Br J Anaesth 1996;76:611615 (Level II-1)
114. Rayburn WF, Geranis BJ, Ramadei CA, Woods RE, Patil
KD. Patient-controlled analgesia for post-cesarean section
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102. Parker RK, Sawaki Y, White PF. Epidural patientcontrolled analgesia: influence of bupivacaine and hydromorphone basal infusion on pain control after cesarean
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115. Olofsson CI, Legeby MH, Nygards EB, Ostman KM.

Diclofenac in the treatment of pain after caesarean delivery. An opioid-saving strategy. Eur J Obstet Gynecol
Reprod Biol 2000;88:143146 (Level I)
103. Cohen S, Amar D, Pantuck CB, Pantuck EJ, Weissman

AB. Adverse effects of epidural 0.03% bupivacaine during
analgesia after cesarean section. Anesth Analg 1992;
75:753756 (Level II-1)
116. Lim NL, Lo WK, Chong JL, Pan AX. Single dose
diclofenac suppository reduces post-Cesarean PCEA
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804

to conduct a literature search to locate relevant articles published between January 1985 and April 2001. The search
Force:
I
type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
Obstetric analgesia and anesthesia. ACOG Practice Bulletin No. 36.

2002;100:177191
PRACTICE BULLETINS
805
ACOG
PRACTICE
BULLETIN
(Replaces Practice Bulletin Number 32, November 2001)

of Sarah Kilpatrick, MD, PhD.
of practice.
Reaffirmed 2008
Thyroid Disease in
Pregnancy
Because thyroid disease is the second most common endocrine disease affecting women of reproductive age, obstetricians often care for patients who have
been previously diagnosed with alterations in thyroid gland function. In addition, both hyperthyroidism and hypothyroidism may initially manifest during
pregnancy. Obstetric conditions, such as gestational trophoblastic disease or
hyperemesis gravidarum, may themselves affect thyroid gland function. This
document will review the thyroid-related pathophysiologic changes created by
pregnancy and the maternalfetal impact of thyroid disease.
Background
Definitions
Thyrotoxicosis is the clinical and biochemical state that results from an excess
production of and exposure to thyroid hormone from any etiology. In contrast,
hyperthyroidism is thyrotoxicosis caused by hyperfunctioning of the thyroid
gland (1). Graves disease is an autoimmune disease characterized by production
of thyroid-stimulating immunoglobulin (TSI) and thyroid-stimulating hormonebinding inhibitory immunoglobulin (TBII) that act on the thyroid-stimulating
hormone (TSH) receptor to mediate thyroid stimulation or inhibition, respectively. Thyroid storm is characterized by a severe, acute exacerbation of the signs
and symptoms of hyperthyroidism.
Hypothyroidism is caused by inadequate thyroid hormone production.
Postpartum thyroiditis is an autoimmune inflammation of the thyroid gland that
presents as new-onset, painless hypothyroidism, transient thyrotoxicosis, or
thyrotoxicosis followed by hypothyroidism within 1 year postpartum.
806
Physiologic Changes in Thyroid

Function During Pregnancy
Table 1 depicts how thyroid function test (TFT) results
change in normal pregnancy and in hyperthyroid and
hypothyroid states. The concentration of thyroid binding
globulin (TBG) increases in pregnancy because of
reduced hepatic clearance and estrogenic stimulation of
TBG synthesis (2). The test results that change significantly in pregnancy are those that are influenced by
serum TBG concentration. These tests include total thyroxine (TT4), total triiodothyronine (TT3), and resin triiodothyronine uptake (RT3U). Although there may be a
transient increase in free thyroxine (FT4) and free thyroxine index (FTI) in the first trimester (possibly related
to human chorionic gonadotropin [hCG] stimulation),
this increase does not result in elevations beyond the normal nonpregnant range (3).
Plasma iodide levels decrease during pregnancy
because of fetal use of iodide and increased maternal
renal clearance of iodide (2). This alteration is associated with a noticeable increase in thyroid gland size in
approximately 15% of women (2, 4). In two longitudinal
studies of more than 600 women without thyroid disease,
thyroid volume, measured by ultrasonography, significantly increased in pregnancy (with a mean increase in
size of 18% that was noticeable in most women) and
returned to normal in the postpartum period (4, 5). None
of these women had abnormal TFT results despite their
enlarged thyroid glands.
hypothyroidism, enough maternal thyroid hormone

crosses the placenta to prevent the overt stigmata of
hypothyroidism at birth and maintain cord blood thyroid
hormone levels at 2550% of normal (7). However, thyrotropin-releasing hormone (TRH), iodine, and TSH
receptor immunoglobulins do cross the placenta, as do
the thioamides propylthiouracil (PTU) and methimazole.
Hyperthyroidism
Signs and Symptoms
Hyperthyroidism occurs in 0.2% of pregnancies; Graves
disease accounts for 95% of these cases (8). The signs
and symptoms of hyperthyroidism include nervousness,
tremors, tachycardia, frequent stools, excessive sweating, heat intolerance, weight loss, goiter, insomnia, palpitations, and hypertension. Distinctive symptoms of
Graves disease are ophthalmopathy (signs including lid
lag and lid retraction) and dermopathy (signs include
localized or pretibial myxedema). Although some symptoms of hyperthyroidism are similar to symptoms of
pregnancy or nonthyroid disease, serum TFTs differentiate thyroid disease from nonthyroid disease.
Inadequately treated maternal thyrotoxicosis is associated with a greater risk of preterm delivery, severe
preeclampsia, and heart failure than treated, controlled
maternal thyrotoxicosis (9, 10). Although untreated hyperthyroidism has been associated with miscarriage (8, 11), it
is difficult to find concrete data to support this claim.
Thyroid Function and the Fetus
Fetal and Neonatal Effects
The fetal thyroid begins concentrating iodine at 1012

weeks of gestation and is controlled by pituitary TSH by
approximately 20 weeks of gestation. Fetal serum levels
of TSH, TBG, FT4, and free triiodothyronine (FT3)
increase throughout gestation, reaching mean adult levels at approximately 36 weeks of gestation (6). Thyroidstimulating hormone does not cross the placenta, and
only small amounts of thyroxine (T4) and triiodothyronine (T3) cross the placenta. In neonates with congenital
Inadequately treated hyperthyroidism also is associated

with an increase in medically indicated preterm deliveries, low birth weight (LBW), and possibly fetal loss (9,
10). In one study, all of seven fetal losses occurred in
women with persistent hyperthyroidism (9).
Fetal and neonatal risks associated with Graves disease are related either to the disease itself or to thioamide
treatment of the disease. The possibility of fetal thyrotoxicosis should be considered in all women with a
Table 1. Changes in Thyroid Function Test Results in Normal Pregnancy and in Thyroid Disease
Maternal
Status
TSH
FT4
FTI
TT4
TT3
RT3U
Pregnancy
No change
No change
No change
Increase
Increase
Decrease
Hyperthyroidism
Decrease
Increase
Increase
Increase
Increase or
no change
Increase
Hypothyroidism
Increase
Decrease
Decrease
Decrease
Decrease or
no change
Decrease
Abbreviations: TSH, thyroid-stimulating hormone; FT4, free thyroxine; FTI, free thyroxine index; TT4, total thyroxine; TT3, total triiodothyronine; RT3U, resin T3 uptake.
PRACTICE BULLETINS
history of Graves disease (8). If fetal thyrotoxicosis is

diagnosed, consultation with a clinician with expertise in
such conditions is warranted.
Because a large proportion of thyroid dysfunction in
women is mediated by antibodies that cross the placenta
(Graves disease and chronic autoimmune thyroiditis),
there is a legitimate concern for risk of immune-mediated hypothyroidism and hyperthyroidism to develop in
the neonate. Women with Graves disease have TSI and
TBII that can stimulate or inhibit the fetal thyroid. The
latter (TBII) may cause transient hypothyroidism in
neonates of women with Graves disease (12, 13). One to
five percent of these neonates have hyperthyroidism or
neonatal Graves disease caused by the transplacental
passage of maternal TSI (11). The incidence is low
because of the balance of stimulatory and inhibitory antibodies with thioamide treatment (14). Maternal antibodies are cleared less rapidly than thioamides in the
neonate, resulting in a sometimes delayed presentation
of neonatal Graves disease (14). The incidence of
neonatal Graves disease is unrelated to maternal thyroid
function. The neonates of women who have been treated
surgically or with radioactive iodine 131 (I-131) prior to
pregnancy and require no thioamide treatment are at
higher risk for neonatal Graves disease because they
lack suppressive thioamide (14).
Etiology and Differential Diagnosis

The most common cause of hyperthyroidism is Graves
disease. The other clinical characteristics of Graves disease also are immune-mediated but they are less understood. The diagnosis of Graves disease is generally made
by documenting elevated levels of FT4 or an elevated FTI,
with suppressed TSH in the absence of a nodular goiter or
thyroid mass. Although most patients with Graves disease have TSH receptor, antimicrosomal, or antithyroid
peroxidase antibodies, measurement of these is neither
required nor recommended to establish the diagnosis
(11). Other etiologies of thyrotoxicosis are excess production of TSH, gestational trophoblastic neoplasia,
hyperfunctioning thyroid adenoma, toxic multinodular
goiter, subacute thyroiditis, and extrathyroid source of
thyroid hormone.
807
Signs and Symptoms

The classic signs and symptoms of hypothyroidism are
fatigue, constipation, intolerance to cold, muscle cramps,
hair loss, dry skin, prolonged relaxation phase of deep tendon reflexes, and carpal tunnel syndrome. These are initially indolent and nonspecific but may progress to weight
gain, intellectual slowness, voice changes, and insomnia.
If left untreated, hypothyroidism will progress to myxedema and myxedema coma. It is unusual for advanced
hypothyroidism to present in pregnancy. Subclinical
hypothyroidism is defined as elevated TSH with normal
FTI in an asymptomatic patient. Untreated hypothyroidism is associated with an increased risk of preeclampsia,
but it is not clear from the available data whether subclinical hypothyroidism carries a similar risk (16, 17).
Fetal and Neonatal Effects

In retrospective studies, a high incidence of LBW in
neonates was associated with inadequately treated
hypothyroidism (16, 17). The etiology of LBW in these
studies was preterm delivery (medically indicated),
preeclampsia, or placental abruption. One study reported
two stillbirths, both of which were associated with placental abruption and preeclampsia (17). It is not clear
whether hypothyroidism is associated with intrauterine
growth restriction independent of other complications.
Women with iodine-deficient hypothyroidism are at significant risk of having babies with congenital cretinism
(growth failure, mental retardation, and other neuropsychologic deficits). In an iodine-deficient population,
treatment with iodine in the first and second trimesters of
pregnancy significantly reduces the incidence of the neurologic abnormalities of cretinism (18).
Untreated congenital hypothyroidism also results in
cretinism. The incidence of congenital hypothyroidism is
1 per 4,000 newborns, and only 5% of neonates are identified by clinical symptoms at birth, likely because of the
ameliorative effects of maternal thyroid hormone (2). All
50 states and the District of Columbia offer screening of
newborns for congenital hypothyroidism. If identified
and treated within the first few weeks of life, near-normal
growth and intelligence can be expected (19).
Hypothyroidism
It is well accepted that having one autoimmune disease
increases the likelihood of developing another; autoimmune thyroid dysfunction is no exception. For example,
there is a 58% incidence of hypothyroid disease in
patients with type 1 (insulin-dependent) diabetes (15).
Women with type 1 diabetes also have a 25% risk of
developing postpartum thyroid dysfunction (15).
Etiology and Differential Diagnosis

Most cases of hypothyroidism are the result of a primary thyroid abnormality; a small number of cases are
caused by hypothalamic dysfunction. The most common
etiologies of hypothyroidism in pregnant or postpartum
women are Hashimotos disease (chronic thyroiditis or
chronic autoimmune thyroiditis) (1), subacute thyroidi-
808

Recommendations
What laboratory tests are used to diagnose

and manage thyroid disease during
pregnancy?
The mainstay of thyroid function evaluation is TSH testing; such testing is now performed using monoclonal
antibodies, making it more sensitive than the original
radioimmunoassay. The American Association of Clinical Endocrinologists (21) and the American Thyroid
Association (22) recommend TSH testing as the initial
test for the screening and evaluation of symptomatic disease for all men and women. The free component is the
biologically active portion and is not subject to change in
conditions that alter TBG, such as pregnancy. In a pregnant patient suspected of being hyperthyroid or hypothyroid, TSH and FT4 or FTI should be measured. Free
thyroxine assessment by either direct immunoradiometric or chemiluminescent methods generally is available
and preferred over the equilibrium dialysis method.
However, FTI can be calculated as the product of TT4
and RT3U if FT4 is not available. Measurement of FT3
usually is only pursued in patients with thyrotoxicosis
with suppressed TSH but normal FT4 measurements.
Elevated FT3 indicates T3 toxicosis, which may occur
before excessive FT4 production develops (11, 23).
Another test of thyroid function is the TRH stimulation test, which evaluates the secretory ability of the
pituitary. The various antibody tests include TSH receptor antibodies, which can be either stimulatory (TSI) or
inhibitory (TBII), and antimicrosomal antibodies. The
usefulness of these various antibodies in pregnancy is
complex and will be discussed as follows.
Although the incidence of neonatal Graves disease

is associated with extremely high levels of maternal TSI,
the clinical usefulness of evaluating these levels is not
clear. In general, perinatal experts suggest there is no
practical use for measuring TSI routinely (8), while
endocrinologists suggest that measuring TSI in the third
trimester is useful (11, 14, 24, 25). Routine evaluation of
maternal TSI levels is not recommended, but such evaluation may be helpful in some circumstances.
tis, thyroidectomy, radioactive iodine treatment, and

iodine deficiency. In developed countries, Hashimotos
disease is the most common etiology (20) and is characterized by the production of antithyroid antibodies,
including thyroid antimicrosomal and antithyroglobulin
antibodies. Both Hashimotos disease and iodine deficiency are associated with goiter (a sign of compensatory TSH production), while subacute thyroiditis is not
associated with goiter.
Worldwide, the most common cause of hypothyroidism is iodine deficiency (8). Although iodine deficiency is rare in the United States, some populations may
benefit from consideration of this etiology of hypothyroidism, including certain immigrant populations and
those with poor nutrition.
What medications can be used to treat hyperthyroidism and hypothyroidism in pregnancy,

and how should they be administered and
adjusted during pregnancy?
Hyperthyroidism in pregnancy is treated with thioamides,

specifically PTU and methimazole, which decrease
thyroid hormone synthesis by blocking the organification
of iodide. Propylthiouracil also reduces the peripheral
conversion of T4 to T3 and, thus, may have a quicker suppressant effect than methimazole. Traditionally, PTU has
been preferred in pregnant patients because it was believed
that PTU crossed the placenta less well than methimazole
and because methimazole was associated with fetal aplasia
cutis, a congenital skin defect of the scalp (26). However,
recent data have refuted both of these arguments. One
study comparing FT4 and TSH in newborn umbilical cord
blood samples of women treated with PTU with those of
women treated with methimazole found no significant difference in mean FT4 or TSH levels. Furthermore, there was
no relationship between maternal dosage of thioamide and
umbilical cord blood levels of TSH or FT4 (27). A retrospective study that compared 99 women treated with PTU
with 36 women treated with methimazole reported no
cases of aplasia cutis and similar rates of fetal anomalies
(3%) (28). Finally, there was no significant difference in
the incidence of aplasia cutis between control women
without thyroid disease and women with hyperthyroidism
who were treated with methimazole (26).
Thioamide treatment of Graves disease can suppress fetal and neonatal thyroid function. However, it
usually is transient and rarely requires therapy. Fetal goiter also has been associated with thioamide treatment for
Graves disease, presumably caused by drug-induced
fetal hypothyroidism (29). Fetal thyrotoxicosis secondary to maternal antibodies is rare, but all fetuses of
women with Graves disease should be monitored for
appropriate growth and normal heart rate. However, in
the absence of these findings, routine screening for fetal
goiter by ultrasonography is unnecessary. All neonates
of women with thyroid disease are at risk for neonatal
thyroid dysfunction, and the neonates pediatrician
should be aware of the maternal diagnosis.
PRACTICE BULLETINS
istering levothyroxine at sufficient dosages to normalize

TSH levels. It takes approximately 4 weeks for the thyroxine therapy to alter the TSH level. Therefore, levothyroxine therapy should be adjusted at 4-week intervals
until TSH levels are stable. Data indicate pregnancy
increases maternal thyroid hormone requirements in
women with hypothyroidism diagnosed before pregnancy (2, 35). In these studies, TSH levels increased while
FTI decreased during pregnancy in these women, necessitating an increase in mean thyroxine dosage from
0.1 mg/day before pregnancy to 0.148 mg/day during
pregnancy (35). In stable patients, it is prudent to check
TSH levels every trimester in pregnant women with
hypothyroidism (21).
Women taking PTU may breastfeed because only

small amounts of the medication cross into breast milk.
Studies have demonstrated that TFT results were normal
in neonates after 18 months of breastfeeding from
women taking PTU (30, 31). Methimazole also is considered safe for breastfeeding; however, it is present in a
higher ratio in breast milk (30).
The goal of management of hyperthyroidism in pregnancy is to maintain the FT4 or FTI in the high normal
range using the lowest possible dosage of thioamides to
minimize fetal exposure to thioamides. Thus, once treatment has started, it may be helpful to measure FT4 or FTI
every 24 weeks and titrate the thioamide until FT4 or
FTI are consistently in the high normal range (8). In more
than 90% of patients, improvement will be seen within
24 weeks after thioamide treatment begins (11).
One side effect of thioamides is agranulocytosis.
The incidence of agranulocytosis is 0.10.4%; it usually presents with a fever and sore throat. If a patient on
thioamides develops these symptoms, a complete blood
cell count should be drawn and the medication should be
discontinued. Treatment with the other thioamide carries
a significant risk of cross reaction. Other major side
effects of thioamides, including thrombocytopenia,
hepatitis, and vasculitis, occur in less than 1% of
patients; minor side effects, including rash, nausea,
arthritis, anorexia, fever, and loss of taste or smell, occur
in 5% of patients (11).
Beta-blockers may be used during pregnancy to
ameliorate the symptoms of thyrotoxicosis until
thioamides decrease thyroid hormone levels. Propranolol
is the most common -blocker used for this indication.
Thyroidectomy should be reserved for women in whom
thioamide treatment is unsuccessful.
Iodine 131 is contraindicated in pregnant women
because of the risk of fetal thyroid ablation; therefore,
women should avoid pregnancy for 4 months after I-131
treatment (23). Unfortunately, our understanding of fetal
thyroid ablation and the consequent risk of fetal
hypothyroidism from exposure to maternal I-131 comes
from the inadvertent treatment of pregnant women (32,
33). Counseling of women exposed to I-131 in pregnancy should focus on the gestational age at exposure. If the
woman was at less than 10 weeks of gestation when
exposed to I-131, it is unlikely the fetal thyroid was
ablated. If exposure occurred at 10 weeks of gestation or
later, the woman must consider the risks of induced congenital hypothyroidism and consider whether to continue the pregnancy. Breastfeeding should be avoided for at
least 120 days after treatment with I-131 (34).
Treatment of hypothyroidism in pregnant women is
the same as for nonpregnant women and involves admin-
809
What changes in thyroid function occur with

hyperemesis gravidarum, and should TFTs
be performed routinely in women with hyperemesis?
Nausea and vomiting of pregnancy have been attributed

to the high hCG levels in the first trimester, and women
with hyperemesis gravidarum have been assumed to
have particularly high hCG levels and to be at risk for
hyperthyroidism. In a prospective study of 67 women
with singleton pregnancies and hyperemesis, 66% were
found to have biochemical hyperthyroidism with an
undetectable level of TSH or elevated FTI or both (36).
The biochemical hyperthyroidism resolved in all of the
women without treatment by 18 weeks of gestation (36).
Further, the women with the most severe hyperemesis
had significantly higher FTIs than those with mild or
moderate disease.
Complete resolution of biochemical and clinical
hyperthyroidism also has been reported in other studies
(37, 38). These studies have reported that some women
with hyperemesis gravidarum required a short course of
thioamides; however, most of these women had resolution of their signs and symptoms without treatment (38,
39). Women who required treatment throughout the
remainder of their pregnancies had other symptoms of
thyroid disease, including thyroid enlargement, persistent tachycardia despite fluid replacement, and abnormal
response to TRH stimulation (39). In a study comparing
pregnant women with hyperemesis and those without
hyperemesis, there was no difference in mean TSH or
FT3 levels (40). Levels of FT4 and hCG were significantly higher in the women with hyperemesis, but hCG levels correlated significantly and positively with FT4 levels
and negatively with TSH levels only in the hyperemesis
group. Other studies have replicated these results and
shown suppression of TSH when compared with controls (37). Hyperemesis gravidarum is associated with
810
biochemical hyperthyroidism but rarely with clinical

hyperthyroidism and is largely transitory, requiring no
treatment. Routine measurements of thyroid function are
not recommended in patients with hyperemesis gravidarum unless other overt signs of hyperthyroidism are
evident.
Treatment of Thyroid Storm in Pregnant Women
1. Propylthiouracil (PTU), 600800 mg orally, stat,

then 150200 mg orally every 46 hours. If oral
administration is not possible, use methimazole
rectal suppositories.
2. Starting 12 hours after PTU administration,
saturated solution of potassium iodide (SSKI),
25 drops orally every 8 hours, or
sodium iodide, 0.51.0 g intravenously every
8 hours, or
Lugols solution, 8 drops every 6 hours, or
lithium carbonate, 300 mg orally every 6 hours.
3. Dexamethasone, 2 mg intravenously or intramuscularly every 6 hours for four doses.
4. Propranolol, 2080 mg orally every 46 hours,
or propranolol, 12 mg intravenously every
5 minutes for a total of 6 mg, then 110 mg
intravenously every 4 hours.
If the patient has a history of severe bronchospasm:
Reserpine, 15 mg intramuscularly every
46 hours
Guanethidine, 1mg/kg orally every
12 hours
Diltiazem, 60 mg orally every 68 hours
5. Phenobarbital, 3060 mg orally every 68 hours
as needed for extreme restlessness.
How is thyroid storm diagnosed and treated

in pregnancy?
Data from Ecker JL, Musci TJ. Thyroid function and disease in
pregnancy. Curr Probl Obstet Gynecol Fertil 2000;23:109122;
and Molitch ME. Endocrine emergencies in pregnancy. Baillieres
Clin Endocrinol Metab 1992;6:167191
ultrasonography, biophysical profile, or nonstress test

depending on the gestational age of the fetus. In general,
it is prudent to avoid delivery in the presence of thyroid
storm unless fetal indications for delivery outweigh the
risks to the woman.
Thyroid storm is a medical emergency characterized by

an extreme hypermetabolic state. It is rareoccurring in
1% of pregnant patients with hyperthyroidismbut has
a high risk of maternal heart failure (9). Older literature
described a maternal mortality of up to 25% but this has
not been substantiated by more recent data (9, 41).
Thyroid storm is diagnosed by a combination of the following signs and symptoms: fever; tachycardia out of
proportion to the fever; changed mental status, including
restlessness, nervousness, confusion, and seizures; vomiting; diarrhea; and cardiac arrhythmia (42). Often there
is an identified inciting event such as infection, surgery,
labor, or delivery. However, the diagnosis can be difficult
to make and requires expedient treatment to avoid the
severe consequences of untreated thyroid storm, which
include shock, stupor, and coma. If thyroid storm is suspected, serum FT4, FT3, and TSH levels should be evaluated to help confirm the diagnosis, but therapy should
not be withheld pending the results.
Therapy for thyroid storm consists of a standard
series of drugs (see box) (8, 42). Each drug has a specific role in the suppression of thyroid function. Propylthiouracil or methimazole blocks additional synthesis of
thyroid hormone, and PTU also inhibits peripheral conversion of T4 to T3. Saturated solution of potassium
iodide and sodium iodide block the release of thyroid
hormone from the gland. Dexamethasone decreases thyroid hormone release and peripheral conversion of T4 to
T3, and propranolol inhibits the adrenergic effects of
excessive thyroid hormone. Finally, phenobarbital can be
used to reduce extreme agitation or restlessness and may
increase the catabolism of thyroid hormone (42). In
addition to pharmacologic management, general supportive measures should be undertaken, including
administration of oxygen, maintenance of intravascular
volume and electrolytes, use of antipyretics, use of a
cooling blanket, and appropriate maternal and fetal monitoring; invasive central monitoring and continuous
maternal cardiac monitoring in an intensive care setting
may be indicated. Coincident with treating the thyroid
storm, the perceived underlying cause of the storm
should be treated. As with other acute maternal illnesses,
fetal well-being should be appropriately evaluated with
How should a thyroid nodule or thyroid

cancer during pregnancy be assessed?
The incidence of thyroid cancer in pregnancy is 1 per

1,000 (43). Any thyroid nodule discovered during pregnancy should be diagnostically evaluated, because
malignancy will be found in up to 40% of these nodules
(34, 44). Pregnancy itself does not appear to alter the
course of thyroid cancer (43, 45). Whether pregnancy
increases the risk of recurrence of thyroid cancer or the
risk that a thyroid nodule becomes cancerous is less clear
PRACTICE BULLETINS
How is postpartum thyroiditis diagnosed and

treated?
Postpartum thyroiditis occurs in 5% of women who do

not have a history of thyroid disease (47). Studies have
found that approximately 44% of women with postpartum thyroiditis have hypothyroidism, while the remaining women are evenly split between thyrotoxicosis and
thyrotoxicosis followed by hypothyroidism (47, 48). In
one study, goiter was present in 51% of women with
postpartum thyroiditis (48). Postpartum thyroiditis also
may occur after pregnancy loss and has a 70% risk of
recurrence (49, 50).
The diagnosis of postpartum thyroiditis is made by
documenting new-onset abnormal levels of TSH or FT4
or both. If the diagnosis is in doubt, measuring anti-
microsomal or thyroperoxidase antithyroid peroxidase

antibodies may be useful to confirm the diagnosis.
The need for treatment in women with postpartum
thyroiditis is less clear. In a prospective study of 605
asymptomatic pregnant and postpartum women, only
five women, or 11% of the women diagnosed with postpartum thyroiditis, developed permanent hypothyroidism (48). Furthermore, none of the women with
thyrotoxicosis required treatment, and only 40% of those
with hypothyroidism required treatment (48). Those who
were treated received T4 for extremely high levels of
TSH with suppressed T4 or increasing goiter size.
Because of the low incidence of postpartum thyroiditis
and the low likelihood of requiring treatment, screening
with TFTs and antimicrosomal antibodies in asymptomatic women is not warranted (47, 51).
Women who develop a goiter in pregnancy or postpartum or who develop postpartum hypothyroid or hyperthyroid symptoms (including excessive fatigue, weight
gain, dry skin, dry hair, cold intolerance, persistent amenorrhea, difficulty concentrating, depression, nervousness,
or palpitations) should have their TSH and FT4 levels evaluated (47, 48, 51). As noted previously, thyroid antimicrosomal or antithyroid peroxidase antibodies also may be
useful. Because some of these symptoms are common in
the postpartum state, clinicians must use their judgment to
determine whether the symptoms warrant evaluation. If
the patient has hypothyroidism, the decision to treat
depends on the severity of abnormality and symptoms.
Women with the highest levels of TSH and antithyroid
peroxidase antibodies have the highest risk for developing
permanent hypothyroidism (48).
(34). In a cohort study comparing thyroid cancer in pregnant or postpartum women with nonpregnant women,
there were no differences in the presenting physical findings, tumor type, tumor size, presence of metastases,
time between diagnosis and treatment, recurrence rates,
or death rates (43). Women in this study were monitored
for a median of 20 years. These data strongly suggest
that pregnancy does not affect the outcome of thyroid
cancer. In addition, except for the time between diagnosis and surgery, there was no difference in outcome
between those women who had thyroidectomy during
pregnancy and those who had the procedure after pregnancy. Significantly more pregnant women had no
symptoms, emphasizing the importance of the physical
examination during pregnancy.
Another study compared pregnancy outcomes
among women with thyroid cancer who fell into 1 of 3
categories: 1) before treatment, 2) after thyroidectomy
but before I-131 treatment, and 3) after treatment with
both thyroidectomy and I-131 (46). The study found no
differences in stillbirths, LBW, or malformations among
the three groups. The incidence of spontaneous abortion
was significantly higher in women who had any treatment for thyroid cancer but was not different between
those women who had surgery only and those who had
surgery and I-131 treatment.
If a diagnosis of cancer is made, a multidisciplinary
treatment plan should be determined. The options are
pregnancy termination, treatment during pregnancy, and
preterm or term delivery with treatment after pregnancy.
This decision will be affected by the gestational age at
diagnosis and the tumor characteristics. Definitive treatment for thyroid cancer is thyroidectomy and radiation.
Thyroidectomy can be performed during pregnancy,
preferably in the second trimester, but radiation should be
deferred until after pregnancy. Breastfeeding should be
avoided for at least 120 days after I-131 treatment (34).
811
Which pregnant patients should be screened

for thyroid dysfunction?
It is appropriate to perform indicated testing of thyroid

function in women with a personal history of thyroid disease or symptoms of thyroid disease. The performance
of TFTs in asymptomatic pregnant women who have a
mildly enlarged thyroid is not warranted. Development
of a significant goiter or distinct nodules should be evaluated as in any patient.
An observational study has drawn considerable attention to the subject of maternal subclinical hypothyroidism
and resulted in calls from some professional organizations
for universal screening for maternal hypothyroidism (20).
Investigators screened maternal serum samplesobtained
in the second trimester for purposes of maternal serum
alphafetoprotein screening for neural tube defectsfor
elevated TSH levels (20). Out of 25,216 samples, only 75
women had TSH levels above the 99.7th percentile. The
investigators then compared the results of neuropsycho-
812
Indicated testing of thyroid function may be performed in women with a personal history of thyroid
disease or symptoms of thyroid disease.
The presence of maternal thyroid disease is important information for the pediatrician to have at the
time of delivery.
logic testing for 62 children of hypothyroid women with

those of 124 children of matched women with normal thyroid glands when the children were approximately 8 years
of age. They found no significant difference in mean IQ
scores between the children of hypothyroid women and
controls (P = 0.06). There was a significant difference in
mean IQ scores when the children of untreated hypothyroid women were compared with controls but not between
children of untreated and treated hypothyroid women.
Among the children of the untreated women, 19% had
full-scale IQ scores of 85 or lower, compared with only
5% of the children of women with normal thyroid glands.
It is important to acknowledge the limitations of the
current understanding of this issue. The data available are
observational. There have been no intervention trials to
demonstrate the efficacy of screening and treatment to
improve neuropsychologic performance in the offspring of
hypothyroid women. The available data are consistent
with the possibility that maternal hypothyroidism is associated with a decrement in some neuropsychologic testing.
However, the association needs further testing to document its validity and, if confirmed, evidence that treatment
ameliorates the effect. For all of these reasons, it would be
premature to recommend universal screening for hypothyroidism during pregnancy.
Thyroid nodules should be investigated to rule out

malignancy.
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I
type of evidence.
committees.
01923, (978) 750-8400.
ISSN 1099-3630
Thyroid disease in pregnancy. ACOG Practice Bulletin No. 37.
2002;100:387396
PRACTICE BULLETINS
815
ACOG
PRACTICE
BULLETIN
(Replaces Committee Opinion Number 163, November 1995)

of Richard Depp, MD, and
James Lemons, MD. The information is designed to aid practitioners in making decisions
about appropriate obstetric and
gynecologic care. These guidelines should not be construed as dictating an exclusive
of practice.
Reaffirmed 2008
Perinatal Care at the

Threshold of Viability
The survival rate for extremely preterm or extremely low-birth-weight (LBW)
newborns born at the threshold of viability (25 or fewer completed weeks of
gestation) improved in the early 1990s, largely as the result of a greater use of
assisted ventilation in the delivery room and surfactant therapy. Increased use
of antenatal and neonatal corticosteroids also may have influenced survival
rates (14). However, this improvement in survival has not been associated
with an equal improvement in morbidity. The incidence of chronic lung disease,
sepsis, and poor growth remains high and may even have increased. There is
concern that the treatment of extremely preterm and extremely LBW newborns
may result in unforeseen effects into adulthood (4, 5), and that the neurodevelopmental outcome and cognitive function of extremely preterm and extremely
LBW infants may be suboptimal (68). The purpose of this document is to
describe the potential consequences of extremely preterm birth and to provide
clinical management guidelines based on the best available data.
Background and Research Limitations

Early preterm birth or birth of an extremely LBW newborn (<1,000 g), especially those weighing less than 750 g, poses a variety of complex medical,
social, and ethical considerations. The impact of such births on the infants, their
families, the health care system, and society is profound. Although the prevalence of such births is less than 1%, they account for nearly one half of all cases
of perinatal mortality (9). Until recently, discussion of clinical management and
ethical and economic considerations of extremely preterm births were hampered by conflicting and insufficiently detailed outcome data (1, 3, 4).
Although early reports on birth outcomes before 26 weeks of gestation
often were helpful in counseling patients, most reports had one or more relative
816
portant for these newborns because even a few days

difference in age can be associated with a dramatic difference in expected outcome. Death and disability rates
are inversely related to gestational age in newborns at
2225 completed weeks of gestation (9, 15, 16).

Recommendations
weaknesses that limited their clinical value. For example,

denominators differed from study to study, being reported variously as all births (stillbirths and liveborns), only
liveborns, or only liveborns who survived long enough to
be admitted to a neonatal intensive care unit. Potential
survival may be overstated by as much as 100% at
23 weeks of gestation and by 56% at 24 weeks of gestation if the denominator included only infants admitted to
the neonatal intensive care unit instead of using all fetal
deaths and live births (10). The length of time that constituted survival also varied widely. Many studies failed
to obtain complete outcome data, and children from
lower socioeconomic backgrounds were more likely to
be lost to follow-up.
Until the 1990s, when ultrasonography became more
widely used, outcomes were largely reported only in
terms of birth weight because of the uncertainty of gestational age. Studies based on birth weight were confounded by the inclusion of infants with intrauterine growth
restriction (11); such newborns exhibited neurodevelopment consistent with their age and not their weight and,
therefore, had an advantage when compared with newborns of the same size who were gestationally less
mature (12, 13). Studies based on gestational age also
could be inaccurate; use of the Ballard estimate of gestational age at birth consistently yields an age 10 days older
than the age determined by the best obstetric estimate
(14). In addition, the influence of sex on survival rates
was rarely considered.
Data derived from many years of experience in caring for patients at a single institution often were limited
by small numbers of infants, with few representatives
among the lowest birth weight categories. In addition,
many series included infants cared for over a relatively
long time, during which many changes in management
practices were likely. For these reasons, it is controversial
whether individual institutions should use their own data
on morbidity and survival rates for extremely preterm
and extremely LBW births when counseling patients and
their families. All of these concerns are important
because at the threshold of viability, gestational age,
weight, sex, and management are each important determinants of survival.
Information from large multicenter studies, such as
those sponsored by the National Institute of Child Health
and Human Development (NICHD), provides sufficiently detailed data to assist the perinatal team in developing
an evidence-based approach to managing the extremely
preterm and extremely LBW fetus. Data from the
NICHD Neonatal Research Network are divided into
subgroups based on gestational age in weeks or birth
weight. Data by week of gestation are particularly im-
How should the patient and her family be

counseled about the likelihood of survival of
an extremely preterm or extremely LBW
infant?
An effort should be made to provide patients with information specific to the gestational age, estimated weight,
and sex of their fetus. A multidisciplinary team approach
to counseling may be helpful in ensuring that the information provided is consistent and represents a range of
concerns and areas of clinical care. Counseling from a
practitioner with additional experience and expertise in
extremely preterm and extremely LBW births may be
appropriate.
Data are now available from the most recent NICHD
Neonatal Research Network trial, a large prospective
study of 4,633 infants weighing between 400 g and
1,500 g at birth, conducted at 14 tertiary centers across
the United States between 1995 and 1996 (14). In this
study, gestational age was determined by the best obstetric estimate, using last menstrual period, standard obstetric parameters, and ultrasound examination. All liveborn
infants were included, including those not admitted to the
neonatal intensive care unit. Because mortality was
defined as death occurring before patient discharge, the
reported rates do not include deaths during labor or
deaths after 120 days of life; conversely, survival rates
refer to those infants who lived to at least 120 days.
This study showed that a significant increase in survival
of newborns occurs for each completed week from
21 weeks of gestation (0% survival) to 25 weeks of gestation (75% survival) (Table 1). In terms of birth weight
(Table 2), survival was 11% at a birth weight of 400 g,
26% at birth weights of 500601 g, and increased progressively to 75% at birth weights of 701800 g (14).
Infants delivered before 24 weeks of gestation (ie, up to
23 6/7 weeks) were not likely to survive, and those that
did survive were not likely to be neurologically intact.
When gestational age, birth weight, and sex are
combined (Fig. 1), it becomes evident that at each gestational age, a lower birth weight carries a higher mortal-
PRACTICE BULLETINS
Table 1. Newborn Deaths by Gestational Age
Table 2. Newborn Deaths by Birth Weight
Completed Weeks
of Gestation
Birth Weight (g)

Number of Deaths
Percentage of Deaths
21
12
100
22
56
79
23
216
70
24
301
50
25
379
25
26
436
20
27
519
10
28
569
29
535
30
472
31
362
32
225
33
185
3442
156
Data from Lemons JA, Bauer CR, Oh W, Korones SB, Papile LA, Stoll BJ, et al. Very
low birth weight outcomes of the National Institute of Child Health and Human
Development Neonatal Research Network, January 1995 through December
1996. NICHD Neonatal Research Network. Pediatrics 2001;107:E1.
ity risk. This effect is most pronounced in the lower

ranges of gestational age and birth weight. In addition,
when infants of similar gestational age and weight are
compared, mortality rates are higher for males than for
females. For example, a male born at 24 weeks of gestation weighing 700 g has a predicted mortality rate of 51%,
whereas a female of the same age and weight has a predicted mortality rate of 35% (14).
These data apply to liveborn infants. Many of the
smallest infants do not survive labor, do not respond to
resuscitation, or are so small that resuscitation in the
delivery room is not attempted. Among those who survive resuscitation in the delivery room, most deaths
occur within the first 3 days of life (15, 16). It is significant that the small proportion of infants weighing less
than 500 g who do survive resuscitative efforts in the
delivery room usually are female, small-for-gestationalage newborns (4).
Two recent large, prospective studies addressing morbidityone using gestational age and one using birth
weightprovide useful data. A gestational-age-based
population study of 811 extremely preterm newborns
Percentage of Deaths
401500
195
89
501600
317
71
601700
449
38
701800
439
25
801900
419
12
9011,000
462
10
1,0011,100
398
1,1011,200
430
1,2011,300
465
1,3011,400
488
1,4011,500
571
Data from Lemons JA, Bauer CR, Oh W, Korones SB, Papile LA, Stoll BJ, et al. Very
low birth weight outcomes of the National Institute of Child Health and Human
Development Neonatal Research Network, January 1995 through December
1996. NICHD Neonatal Research Network. Pediatrics 2001;107:E1.
used data collected in 1995 and found that disabilities in

mental and psychomotor development, neuromotor function, or sensory and communication function were present in about one half of the large cohort of survivors at
30 months of corrected age (16). Approximately one
quarter met the criteria for severe disability (16). Male
newborns had lower psychomotor scores and were significantly more likely to have cerebral palsy than female
newborns. A similar disadvantage for male newborns has
been reported by others (2, 17).
The most recent NICHD Neonatal Research
Network study, which used data based on the birth
weights of infants delivered at 14 tertiary care centers,
reported similar results. Of all infants weighing 501750 g,
100% had growth failure, 50% had intraventricular hemorrhage, 25% had grades IIIIV intraventricular hemorrhage, and 78% had respiratory distress syndrome (RDS)
(14). The major morbidities influencing later development in these children included chronic lung disease,
severe brain injury (intraventricular hemorrhage and
periventricular leukomalacia), necrotizing enterocolitis,
nosocomial infections, and retinopathy of prematurity.
How should patients and their families be

counseled about the morbidity associated
with extremely preterm or extremely LBW
infants?
Number of Deaths
817
What are the risk factors for cerebral palsy at

the threshold of viability?
A study from the NICHD Neonatal Research Network

provided the first multicenter, prospective outcome data
regarding the neurodevelopmental, neurosensory, and
functional outcome of 1,151 extremely LBW newborns
evaluated from birth to 1822 months corrected age
(Table 3) (2). Importantly, the sample size was sufficient
818
Figure 1. Estimated mortality risk by birth weight and gestational age based on singleton infants
born in NICHD Neonatal Research Network Centers between January 1, 1995 and December 31,
1996. (Reproduced with permission from Pediatrics, Vol. 107, Page(s) e1, Figure 1, Copyright 2001.)
to overcome some of the limitations that hampered the

clinical applicability of earlier longitudinal outcome
studies. One quarter of the children had an abnormal neurologic examination, approximately one third had a
Bayley II Mental Development Index score less than 70
or a Psychomotor Developmental Index score less than
70 (normal for both these indices is >80), and 10% had
visual or hearing impairment. Significant risk factors
associated with cerebral palsy were grades IIIIV intraventricular hemorrhage, periventricular leukomalacia
(odds ratio [OR], 3.05), and necrotizing enterocolitis
(OR, 2.01). Risk factors for abnormal neurologic examination or Mental Development Index or Psychomotor
Developmental Index scores less than 70 included grades
IIIIV intraventricular hemorrhage, periventricular
leukomalacia, chronic lung disease, use of postnatal
steroids, necrotizing enterocolitis, a mother with less
than a high school education, and male sex of the fetus.
How does the assessment of gestational age

affect counseling?
Gestational age often is well established. However, if

gestational age is uncertain, it is important that the clinician consider a wide range of prognoses and care options and counsel the patient about a range of possible
outcomes. Even relatively small discrepancies of 1 or

2 weeks in gestational age or 100200 g in birth weight
may have major implications for survival and long-term
morbidity.
In some casesfor example, in patients with little or
no prenatal carethe gestational age is not established,
and the clinician must consider data from fetal ultrasound
measurements obtained near the time of anticipated
delivery. Such measurements generally are not used to
determine estimated gestational age unless they are the
only data available. Although no single method has been
determined to be superior, most ultrasound fetal weight
formulas that include measurements of the fetal head,
abdomen, and femur will yield a weight estimate within
15% of the actual weight (for weights <1,500 g) and a
gestational age estimate within 2 weeks of the actual gestational age (from 20 to 30 weeks) (18). If there is a discrepancy of 2 weeks or more between the age based on
menstrual dating and the age based on ultrasound measurements, or the woman is uncertain about the date of
her last menstrual period, the physician may decide to
make management decisions based on the ultrasound
measurements, especially if measurements indicate a
gestational age older than previously thought. If the measurements suggest a younger fetus, the possibility that the
fetus is growth restricted should always be considered.
PRACTICE BULLETINS
819
Table 3. Neurologic and Sensory Findings at 18 Months by Birth Weight*
Neurologic Finding
401500 g
(%)
n = 14
501600 g
(%)
n = 94
601700 g
(%)
n = 202
701800 g
(%)
n = 224
Normal examination
57
71
70
72
Cerebral palsy
29
17
21
17
Seizure disorder
21
10
12
13
Unilateral blindness
Bilateral blindness
14
Hearing impairment
11
14
Wears hearing aid
Any visual impairment
*Eighteen percent of the cohort were small for gestational age. Because these data are based on birth weight, it is
likely the figures include intrauterine-growth-restricted infants who were gestationally more mature.
Reproduced and modified with permission from Pediatrics, Vol. 105, Page(s) 12161226, Table 3, Copyright 2000.
Does the mode of delivery affect neonatal

outcome?
Is there a benefit to the use of antenatal corticosteroids for extremely preterm births?
Although antenatal corticosteroids decrease the incidence of RDS in newborns at 2934 weeks of gestation,
randomized controlled trials have not shown a benefit in
newborns treated between 24 and 28 weeks of gestation
(27). In the largest randomized trial conducted on patients
with intact membranes at 2428 weeks of gestation,
there was no benefit in the overall incidence or severity
of RDS, but there was a significant reduction in the incidence of grades III and IV intraventricular hemorrhage
(P = 0.01) (28). Although the precise impact of corticosteroids on RDS in pregnancies between 22 and 25 weeks
of gestation has not been fully determined, the National
Institutes of Health consensus conference statements on
antenatal corticosteroid use recommended that all pregnant women at risk of preterm delivery between 24 and
34 weeks of gestation be considered candidates for a single course of corticosteroids (27, 29).
Few studies have evaluated the influence of obstetric

management on the outcome of infants at the threshold of
viability. Retrospective, nonrandomized studies have
consistently failed to document a benefit of cesarean
delivery for the extremely preterm fetus (1923). It has
even been difficult to document improved outcome with
cesarean delivery for the extremely preterm fetus in
breech position (20, 21, 24).
No prospective randomized studies of antenatal
transfer of the extremely LBW infant to a tertiary care
center have been reported. Retrospective data are difficult
to analyze because the rapidity of labor, the severity of
antepartum complications and the stability of the mother,
the distance to the nearest high-risk nursery, and other
factors all influence transfer decisions. However, data
from retrospective studies have demonstrated a decreased
mortality risk for very LBW infants delivered at hospitals
with a level III neonatal intensive care unit compared
with delivery at hospitals with level I or level II neonatal
intensive care units (25, 26). Therefore, based on limited
data, maternal transport to a tertiary care center should be
considered when possible.
Ultrasonography also may provide useful information regarding the presence or absence of fetal malformations that may alter the prognosis of the fetus.
However, fetal measurement and anatomic evaluation
can be difficult in cases of multiple gestation or reduced
amniotic fluid volume. Evaluation of multiple gestation
also can be problematic because the prognosis for one
infant may differ from that of the other(s).
What are the current recommendations and

ethical considerations regarding resuscitation
and continued support of the extremely
preterm fetus?
Ethical decisions regarding the extent of resuscitative

efforts and the subsequent support of the neonate are
complex (3032). The decision to withhold or withdraw
support should not be made entirely on the basis of gestational age or birth weight, but should be individualized
based on the newborns condition at birth, survival and
morbidity data, and the parents preferences.
820
Based on data from retrospective studies, maternal
transport to a tertiary care center before delivery
should be considered when possible.
The effects of aggressive resuscitation at birth on the

outcome of the extremely preterm fetus also are
unclear. Therefore, management decisions regarding
the extremely preterm fetus must be individualized.
The effect of antenatal steroid use in the extremely

preterm fetus is unclear; however, it is recommended that all women at risk of preterm delivery
between 24 and 34 weeks of gestation be considered
candidates for a single course of corticosteroids.
Prospectively collected outcome data for extremely

preterm fetuses are available. Whenever possible,
data specific to the age, weight, and sex of the individual extremely preterm fetus should be used to aid
management decisions made by obstetricians and
parents of fetuses at risk for preterm delivery before
26 completed weeks of gestation. This information
may be developed by each institution and should
indicate the population used in determining estimates of survivability.
When extremely preterm birth is anticipated, the

estimated gestational age and weight should be carefully assessed, the prognosis for the fetus should be
determined, and each member of the health care
team should make every effort to maintain a consistent theme in their discussion with family members
regarding the assessment, prognosis, and recommendations for care.
Summary of
Recommendations
before 24 weeks of gestation are less likely to survive, and those who do are not likely to survive
intact. Disabilities in mental and psychomotor development, neuromotor function, or sensory and communication function are present in approximately
one half of extremely preterm fetuses.
Each member of the health care team should make

every effort to maintain a consistent theme in their discussions with family members regarding the assessment,
prognosis, and recommendations for care. However, parents should understand that decisions about neonatal
management made before delivery may be altered
depending on the condition of the neonate at birth, the
postnatal gestational age assessment, and the newborns
response to resuscitative and stabilization measures. It
also is important that parents understand that the outcome depends on many factors (such as infection), some
of which may not be obvious before delivery or even at
the time of resuscitation. Recommendations regarding
the extent of continuing support depend on frequent
reevaluations of the neonates condition, trends, and
prognosis. The course of an individual newborn may
change with time.
There are circumstances in which the withdrawal of
life support may be appropriate, recognizing that the
views of the parents are of prime importance. Compassionate care should be provided to the infant, including careful handling, maintenance of a neutral thermal
environment, and gentle monitoring of vital signs.
Because it is difficult to predict how an individual
extremely preterm newborn will develop, proactive programs to assess and support the infant through early
school years are desirable (4). When the extremely
preterm newborn does not survive, support should be
provided to the family by physicians, nurses, and other
staff after the infants death. Perinatal loss support
groups, intermittent contact by telephone, and a later
conference with the family to review the medical events
surrounding the infants death and to evaluate the grieving response of the parents often are helpful.
Because it is difficult to predict how an individual

extremely preterm newborn will develop, proactive
programs to assess and support the infant through
early school years are desirable. When the extremely preterm newborn does not survive, support should
be provided to the family by physicians, nurses, and
other staff after the infants death.

In general, parents of anticipated extremely preterm

fetuses can be counseled that the neonatal survival
rate for newborns increases from 0% at 21 weeks of
gestation to 75% at 25 weeks of gestation, and from
11% at 401500 g birth weight to 75% at 701800 g
birth weight. In addition, females generally have a
better prognosis than males.
In general, parents of anticipated extremely preterm

fetuses can be counseled that infants delivered
PRACTICE BULLETINS
References
1. Cole FS. Extremely preterm birthdefining the limits of
hope. N Engl J Med 2000;343:42930. (Level III)
2. Vohr BR, Wright LL, Dusick AM, Mele L, Verter J,
Steichen JJ, et al. Neurodevelopmental and functional
outcomes of extremely low birth weight infants in the
National Institute of Child Health and Human Development Neonatal Research Network, 19931994. Pediatrics
2000;105:121626. (Level II-2)
3. McCormick MC. Conceptualizing child health status:
observations from studies of very premature infants.
Perspect Biol Med 1999;42:37286. (Level III)
4. Hack M, Fanaroff AA. Outcomes of children of extremely low birthweight and gestational age in the 1990s. Early
Hum Dev 1999;53:193218. (Level III)
5. Hack M, Flannery DJ, Schluchter M, Carter L, Borawski
E, Klein N. Outcomes in young adulthood for very-lowbirth-weight infants. N Engl J Med 2002;346;14957.
(Level II-2)
6. Hack M, Taylor HG, Klein N, Eiben R, Schatschneider C,
Mercuri-Minich N. School-age outcomes in children with
birth weights under 750 g. N Engl J Med 1994;331:7539.
(Level II-2)
7. Hack M, Friedman H, Fanaroff AA. Outcomes of
extremely low birth weight infants. Pediatrics 1996;98:
9317. (Level II-3)
8. Peterson BS, Vohr B, Staib LH, Cannistraci CJ, Dolberg
A, Schneider KC, et al. Regional brain volume abnormalities and long-term cognitive outcome in preterm infants.
JAMA 2000;284:193947. (Level II-2)
9. Bottoms SF, Paul RH, Iams JD, Mercer BM, Thom EA,
Roberts JM. Obstetric determinants of neonatal survival:
influence of willingness to perform cesarean delivery on
survival of extremely low-birth-weight infants. National
Network of Maternal-Fetal Medicine Units. Am J Obstet
Gynecol 1997;176:9606. (Level II-2)
10. Evans DJ, Levene MI. Evidence of selection bias in
preterm survival studies: a systematic review. Arch Dis
Child Fetal Neonatal Ed 2001;84:F7984. (Level III)
11. Arnold CC, Kramer MS, Hobbs CA, McLean FH, Usher
RH. Very low birth weight: a problematic cohort for epidemiologic studies of very small or immature neonates.
Am J Epidemiol 1991;134:60413. (Level II-3)
12. Pena IC, Teberg AJ, Finello KM. The premature smallfor-gestational-age infant during the first year of life:
comparison by birth weight and gestational age. J Pediatr
1988;113:106673. (Level II-2)
13. McCarton CM, Wallace IF, Divon M, Vaughan HG Jr.
Cognitive and neurologic development of the premature,
small for gestational age infant through age 6: comparison
by birth weight and gestational age. Pediatrics 1996;98:
116778. (Level II-2)
14. Lemons JA, Bauer CR, Oh W, Korones SB, Papile L, Stoll
BJ, et al. Very low birth weight outcomes of the National
821

Neonatal Research Network, January 1995 through
December 1996. NICHD Neonatal Research Network.
Pediatrics 2001;107:E1. (Level III)
through December 1994. Am J Obstet Gynecol 1998;179:
16329. (Level II-3)
16. Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson
AR. Neurologic and developmental disability after
extremely preterm birth. EPICure Study Group. N Engl J
Med 2000;343:37884. (Level II-2)
17. Tin W, Wariyar U, Hey E. Changing prognosis for babies
of less than 28 weeks gestation in the north of England
between 1983 and 1994. Northern Neonatal Network.
BMJ 1997;314:10711. (Level III)
18. Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK.
Estimation of fetal weight with the use of head, body, and
femur measurementsa prospective study. Am J Obstet
19. Hack M, Fanaroff AA. Outcomes of extremely low birth
weight infants between 1982 and 1988. N Engl J Med
1989;321:16427. (Level II-3)
20. Malloy MH, Rhoads GG, Schramm W, Land G.
Increasing cesarean section rates in very low-birth weight
infants. Effect on outcome. JAMA 1989;262:14758.
(Level II-2)
21. Malloy MH, Onstad L, Wright E. The effect of cesarean
delivery on birth outcome in very low birth weight infants.
National Institute of Child Health and Human Development Neonatal Research Network. Obstet Gynecol
1991;77:498503. (Level II-2)
22. Worthington D, Davis LE, Grausz JP, Sobocinski K.
Factors influencing survival and morbidity with very low
birth weight delivery. Obstet Gynecol 1983;62:5505.
(Level II-2)
23. Kitchen W, Ford GW, Doyle LW, Rickards AL, Lissenden
JV, Pepperell RJ, et al. Cesarean section or vaginal delivery at 24 to 28 weeks gestation: comparison of survival
and neonatal and two-year morbidity. Obstet Gynecol
1985;66:14957. (Level II-2)
24. Gravenhorst JB, Schreuder A, Veen S, Brand R, VerlooveVanhorick SP, Verweij RA, et al. Breech delivery in very
preterm and very low birthweight infants in The
Netherlands. Br J Obstet Gynaecol 1993;100:4115.
(Level II-3)
25. Phibbs CS, Bronstein JM, Buxton E, Phibbs RH. The
effects of patient volume and level of care at the hospital
of birth on neonatal mortality. JAMA 1996;276:10549.
(Level II-3)
26. Yeast JD, Poskin M, Stockbauer JW, Shaffer S. Changing
patterns in regionalization of perinatal care and the impact
on neonatal mortality. Am J Obstet Gynecol 1998;178:
1315. (Level II-3)
822

outcomes. NIH Consensus Statement 1994;12:124.
(Level III)
28. Garite TJ, Rumney PJ, Briggs GG, Harding JA, Nageotte
MP, Towers CV, et al. A randomized, placebo-controlled
trial of betamethasone for the prevention of respiratory
distress syndrome at 24 to 28 weeks gestation. Am J
Obstet Gynecol 1992;166:64651. (Level I)
Consensus Statement 2000;17:118. (Level III)
30. Rhoden NK. Treating Baby Doe: the ethics of uncertainty. Hastings Cent Rep 1986;16:3442. (Level III)
31. Lantos JD, Meadow W, Miles SH, Ekwo E, Paton J,
Hageman JR, et al. Providing and forgoing resuscitative
therapy for babies of very low birth weight. J Clin Ethics
1992;3:2837. (Level II-2)
32. Allen MC, Donohue PK, Dusman AE. The limit of viabilityneonatal outcome of infants born at 22 to 25 weeks
gestation. N Engl J Med 1993;329:15971601. (Level II-3)

to conduct a literature search to locate relevant articles published between between January 1985 and January 2001.
The search was restricted to articles published in the English
Force:
I
type of evidence.
committees.
Copyright September 2002 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in
recording, or otherwise, without prior written permission from the publisher.
01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
Perinatal care at the threshold of viability. ACOG Practice Bulletin No.

Gynecol 2002;100:61724.
PRACTICE BULLETINS
823
ACOG
PRACTICE
BULLETIN
(Replaces Practice Pattern Number 7, October 1997)
Shoulder Dystocia
This Practice Bulletin was developed by the ACOG Committee on
Practice BulletinsObstetrics with
the assistance of Robert J. Sokol,
MD, and Sean C. Blackwell, MD.
The information is designed to aid
practitioners in making decisions
gynecologic care. These guidelines
should not be construed as dictating an exclusive course of treatment or procedure. Variations in
practice may be warranted based on
the needs of the individual patient,
resources, and limitations unique to
the institution or type of practice.
Reaffirmed 2008
Shoulder dystocia is most often an unpredictable and unpreventable obstetric

emergency. Failure of the shoulders to deliver spontaneously places both the
pregnant woman and fetus at risk for injury. Several maneuvers to release
impacted shoulders have been developed, but the urgency of this event makes
prospective studies impractical for comparing their effectiveness. The purpose
of this document is to provide clinicians with information based on published
studies regarding management of deliveries at risk for or complicated by shoulder dystocia.
Background
Shoulder dystocia is most often defined as a delivery that requires additional
obstetric maneuvers following failure of gentle downward traction on the fetal
head to effect delivery of the shoulders (1). Retraction of the delivered fetal
head against the maternal perineum (turtle sign) may be present and may assist
in the diagnosis. Shoulder dystocia is caused by the impaction of the anterior
fetal shoulder behind the maternal pubis symphysis. It also can occur from
impaction of the posterior fetal shoulder on the sacral promontory. Because the
delivering attendant must determine whether ancillary maneuvers are actually
necessary, the diagnosis of shoulder dystocia has a subjective component.
Although severe cases are readily apparent, milder forms may be overdiagnosed or underdiagnosed. The reported incidence ranges from 0.6% to 1.4%
among vaginal deliveries of fetuses in the vertex presentation (27). Differences in reported rates are partly because of clinical variation in describing
shoulder dystocia and the patient population being studied.
Maternal Complications
A study of 236 shoulder dystocia cases reported an 11% rate of postpartum
hemorrhage and a 3.8% rate of fourth-degree lacerations (8). These complications were not more common with rotational maneuvers or other fetal manipu-
824
Neonatal Complications

Recommendations
Can shoulder dystocia be predicted accurately?
Does labor induction for suspected fetal

macrosomia affect the risk of shoulder dystocia or brachial plexus injury?
A small, randomized trial of 273 patients with an ultrasound-estimated fetal weight of 4,0004,500 g comparing labor induction with expectant management reported
no significant difference in the rate of shoulder dystocia
(3.7% versus 4.3%) or brachial plexus palsy (0% versus 1.4%) (33). Another retrospective study found labor
induction with an antenatal diagnosis of macrosomia significantly increased the cesarean delivery rate (36% versus 17%) (34). Labor induction in a woman who does not
have diabetes for the sole indication of suspected macrosomia has not been shown to be effective in decreasing
the occurrence of shoulder dystocia or decreasing the rate
of cesarean delivery (35).
Shoulder dystocia is most often unpredictable and unpreventable. Although fetal macrosomia and maternal diabetes increase the risk of shoulder dystocia (3, 5, 6, 22,
2428), a substantial proportion of cases occur among
women who do not have diabetes and among infants with
birth weights less than 4,000 g. In one study, the presence
of both diabetes and macrosomia accurately predicted only
55% of cases of shoulder dystocia (5). Additional studies
failed to find any combination of risk factors that could
accurately predict which pregnancies would be complicated by shoulder dystocia (3, 4, 6, 25, 26). Maternal obesity
is associated with macrosomia, and, thus, obese women
are at risk for shoulder dystocia. Other antepartum conditions associated with shoulder dystocia include multiparity, postterm gestation, previous history of a macrosomic
birth, and a previous history of shoulder dystocia (5, 29).
Associated intrapartum factors include labor induction,
epidural anesthesia, and operative vaginal delivery (forceps and vacuum-assisted delivery) (3, 4). In each case,
risk factors can be identified, but their predictive value is
not high enough to be useful in a clinical setting.
Do labor abnormalities predict shoulder

dystocia?
Three studies have specifically evaluated labor patterns

in patients who develop shoulder dystocia (3032). The
largest study, comparing 276 consecutive cases of shoulder dystocia with 600 matched controls, did not identify
labor patterns as predictive among any of the cohort, even
those with diabetes or macrosomia (30). Another found a
significant association between active-phase abnormality
and shoulder dystocia, but it included only 36 patients
(31). A retrospective analysis of 52 cases of shoulder dystocia reported no difference in protracted dilatation and
mean duration of second stage of labor (32). Therefore,
data are inadequate to suggest that the labor curve is a
useful predictor of shoulder dystocia.
Brachial plexus injuries and fractures of the clavicle and

humerus are associated with shoulder dystocia. The
reported incidence of brachial plexus injuries following a
delivery complicated by shoulder dystocia varies widely
from 4% to 40% (2, 3, 5, 6, 1118). Fortunately, most
cases resolve without permanent disability; that is, fewer
than 10% of all cases of shoulder dystocia result in a persistent brachial plexus injury (3, 1416). Data suggest
that a significant proportion (3447%) of brachial plexus
injuries are not associated with shoulder dystocia; in fact,
4% occur after cesarean delivery (11, 1921).
Some severe cases of shoulder dystocia may result in
hypoxic-ischemic encephalopathy and even death (22,
23). A study of outcomes from 6,238 cases of shoulder
dystocia found that asphyxia was more common among
births complicated by shoulder dystocia regardless of
maternal diabetic status (22).
lation when compared with the McRoberts maneuver

alone (8). It should be noted that the performance of certain heroic maneuvers in cases of catastrophic shoulder
dystocia, such as the Zavanelli maneuver and symphysiotomy, may be associated with significant maternal morbidity (9, 10).
Is there any benefit to planned cesarean

delivery for the prevention of shoulder dystocia in cases of suspected fetal macrosomia?
A policy of planned cesarean delivery for suspected

macrosomic fetuses (>4,000 g) in women who do not
have diabetes is not recommended. Ultrasonography is
not an accurate predictor of macrosomia (3638). Furthermore, most macrosomic infants do not experience
this complication. Consequently, if all fetuses suspected
of being macrosomic underwent cesarean delivery, the
cesarean delivery rate would increase disproportionately
when compared with the reduction in the rate of shoulder
dystocia (6, 24). For example, one study projected a 27%
increase in the total cesarean delivery rate (increasing
from 15.1% to 19.1%) if cesarean deliveries were performed for all patients with fetuses that weighed 4,000 g
or more; unfortunately, the number of shoulder dystocia
cases would be reduced by only 42% (6). Another study
PRACTICE BULLETINS
reported similar results among fetuses with estimated

birth weights of 4,000 g or more; in that study, an additional 76 cesarean deliveries would have prevented only
five cases of shoulder dystocia, none of which resulted in
permanent injury (39). A study using a decision analysis
model estimated an additional 2,345 cesarean deliveries
would be requiredat a cost of $4.9 million annually
to prevent one permanent injury resulting from shoulder
dystocia if all fetuses suspected of weighing 4,000 g or
more underwent cesarean delivery (11). Although the
diagnosis of fetal macrosomia is imprecise, prophylactic
cesarean delivery may be considered for suspected fetal
macrosomia with estimated fetal weights greater than
5,000 g in women without diabetes and greater than
4,500 g in women with diabetes (40).
What should the obstetrician do in cases of

shoulder dystocia?
Shoulder dystocia cannot be predicted or prevented because accurate methods for identifying which
fetuses will experience this complication do not
exist.
Elective induction of labor or elective cesarean
delivery for all women suspected of carrying a fetus
with macrosomia is not appropriate.
In patients with a history of shoulder dystocia, estimated fetal weight, gestational age, maternal glucose intolerance, and the severity of the prior
neonatal injury should be evaluated and the risks
and benefits of cesarean delivery discussed with the
patient.
Planned cesarean delivery to prevent shoulder dystocia may be considered for suspected fetal macrosomia with estimated fetal weights exceeding
5,000 g in women without diabetes and 4,500 g in
women with diabetes.
A history of shoulder dystocia is associated with a recurrence rate ranging from 1% to 16.7% (3, 26, 4951).
Summary of
Recommendations
How should a woman with a history of delivery complicated by shoulder dystocia be

counseled regarding subsequent deliveries?
However, the true incidence may remain unknown

because physicians and patients often choose not to
attempt a trial of labor when there is a history of a complicated delivery or an injured infant.
Because most subsequent deliveries will not be
complicated by shoulder dystocia, the benefit of universal elective cesarean delivery is questionable in patients
who have such a history of shoulder dystocia. Other factors that may aid in the decision-making process for
mode of delivery include the present estimate of fetal
weight compared with the prior pregnancy birth weight,
gestational age, the presence of maternal glucose intolerance, and the severity of the prior neonatal injury. A
discussion and review of the prior delivery events should
be undertaken with the patient, preferably before the
intrapartum period. After discussion with the patient,
either method of delivery is appropriate.
The performance of the McRoberts maneuver is a reasonable initial maneuver (41). One study described this
maneuver as involving hyperflexion and abduction of the
hips causing cephalad rotation of the symphysis pubis
and flattening of the lumbar lordosis that frees the
impacted shoulder (42). Suprapubic pressure may be
used at the same time to assist in dislodging the impacted shoulder (1). In contrast, fundal pressure may further
worsen impaction of the shoulder and also may result in
uterine rupture (12, 17). Controversy exists as to whether
episiotomy is necessary, because shoulder dystocia typically is not caused by obstructing soft tissue. Direct fetal
manipulation with either rotational maneuvers or delivery
of the posterior arm also may be used (43). In these circumstances, performance of a proctoepisiotomy may be
helpful to create more room within the posterior vagina.
In cases of severe shoulder dystocia that are not
responsive to commonly used maneuvers, more aggressive approaches may be warranted. Cephalic replacement
(Zavanelli maneuver) has been described for relieving catastrophic cases (9, 10, 4446); however, it is associated
with a significantly increased risk of fetal morbidity and
mortality and maternal morbidity. Intentional fracture of
the fetal clavicle may help decrease the bisacromial diameter; however it may be difficult to perform in emergent
situations. It is clear that brachial plexus injury can occur
regardless of the procedure or procedures used to disimpact the shoulders (3, 4, 47, 48).
825
There is no evidence that any one maneuver is superior to another in releasing an impacted shoulder or
reducing the chance of injury. However, performance of the McRoberts maneuver is a reasonable
initial approach.
826
References
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7. Gherman RB, Ouzounian JG, Miller DA, Kwok L,
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Ouzounian JG, Paul RH. The McRoberts maneuver for
the alleviation of shoulder dystocia: how successful is it?
Am J Obstet Gynecol 1997;176:656 61. (Level II-3)
9. OLeary JA. Cephalic replacement for shoulder dystocia:
present status and future role of the Zavanelli maneuver.
18. Gonik B, Hollyer VL, Allen R. Shoulder dystocia recognition: differences in neonatal risks for injury. Am J
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19. Gilbert WM, Nesbitt TS, Danielsen B. Associated factors
in 1611 cases of brachial plexus injury. Obstet Gynecol
1999;93:53640. (Level II-3)
20. Gherman RB, Ouzounian JG, Goodwin TM. Brachial
plexus palsy: an in utero injury? Am J Obstet Gynecol
1999;180:13037. (Level III)
21. Graham EM, Forouzan I, Morgan MA. A retrospective
analysis of Erbs palsy cases and their relation to birth
weight and trauma at delivery. J Matern Fetal Med 1997;
6:15. (Level II-3)
22. Nesbitt TS, Gilbert WM, Herrchen B. Shoulder dystocia
and associated risk factors with macrosomic infants born
in California. Am J Obstet Gynecol 1998;179:47680.
(Level II-3)
23. Hope P, Breslin S, Lamont L, Lucas A, Martin D, Moore
I, et al. Fatal shoulder dystocia: a review of 56 cases
reported to the Confidential Enquiry into Stillbirths and
Deaths in Infancy. Br J Obstet Gynaecol 1998;105:
125661. (Level III)
24. Langer O, Berkus MD, Huff RW, Samueloff A. Shoulder
dystocia: should the fetus weighing greater than or equal
to 4000 grams be delivered by cesarean section? Am J
Obstet Gynecol 1991;165:8317. (Level II-2)
25. Sandmire HF, OHalloin TJ. Shoulder dystocia: its incidence and associated risk factors. Int J Gynaecol Obstet
1988;26:6573. (Level II-2)
10. Goodwin TM, Banks E, Millar LK, Phelan JP. Catastrophic shoulder dystocia and emergency symphysiotomy. Am Obstet Gynecol 1997;177:463 4. (Level III)
26. Bahar AM. Risk factors and fetal outcome in cases of

shoulder dystocia compared with normal deliveries of a
similar birthweight. Br J Obstet Gynaecol 1996;103:
86872. (Level II-2)
14806. (Level III)
27. Gonen R, Spiegel D, Abend M. Is macrosomia predictable,

and are shoulder dystocia and birth trauma preventable?
12. el Madany AA, Jallad KB, Radi FA, el Hamdan H, Odeh

HM. Shoulder dystocia: anticipation and outcome. Int J
Gynaecol Obstet 1990;34:712. (Level II-2)
13. Hassan AA. Shoulder dystocia: risk factors and prevention.
Aust N Z J Obstet Gynaecol 1988;28:1079. (Level III)
14. Morrison JC, Sanders JR, Magann EF, Wiser WL. The
diagnosis and management of dystocia of the shoulder.
Surg Gynecol Obstet 1992;175:51522. (Level III)
15. al-Najashi S, al-Suleiman SA, el-Yahia A, Rahman MS,
Rahman J. Shoulder dystociaa clinical study of 56
cases. Aust & N Z J of Obstet Gynaecol 1989;29:12932.
(Level II-3)
16. Keller JD, Lopez-Zeno JA, Dooley SL, Socol ML.
Shoulder dystocia and birth trauma in gestational diabetes:
a five-year experience. Am J Obstet Gynecol 1991;165:
92830. (Level II-2)
17. Gross TL, Sokol RJ, Williams T, Thompson K. Shoulder
dystocia: a fetal-physician risk. Am J Obstet Gynecol 1987;
156:140818. (Level II-2)
labor with midpelvic delivery. Obstet Gynecol 1978;
52:5269. (Level II-3)
29. Acker DB, Sachs BP, Friedman EA. Risk factors for shoulder dystocia in the average-weight infant. Obstet Gynecol
1986;67:6148. (Level II-2)
30. McFarland M, Hod M, Piper JM, Xenakis EM, Langer O.
Are labor abnormalities more common in shoulder dystocia? Am J Obstet Gynecol 1995;173:12114. (Level II-2)
31. Gemer O, Bergman M, Segal S. Labor abnormalities as a
risk factor for shoulder dystocia. Acta Obstet Gynecol
Scand 1999;78:7356. (Level II-2)
32. Lurie S, Levy R, Ben-Arie A, Hagay Z. Shoulder dystocia:
could it be deduced from the labor partogram? Am J
33. Gonen O, Rosen DJ, Dolfin Z, Tepper R, Markov S, Fejgin
MD. Induction of labor versus expectant management in
macrosomia: a randomized study. Obstet Gynecol 1997;
89:9137. (Level I)
PRACTICE BULLETINS
827
34. Leaphart WL, Meyer MC, Capeless EL. Labor induction

with a prenatal diagnosis of fetal macrosomia. J Matern
Fetal Med 1997;6:99102. (Level II-2)
43. OLeary JA, Leonetti HB. Shoulder dystocia: prevention

and treatment. Am J Obstet Gynecol 1990;162:59.
(Level III)

trial of active induction of labor and expectant management. Am J Obstet Gynecol 1993;169:6115. (Level I)
44. Gherman R. Catastrophic shoulder dystociawhat is the

etiology? Am J Obstet Gynecol 1998;178:417. (Level III)
36. Smith GC, Smith MF, McNay MB, Fleming JE. The relation between fetal abdominal circumference and birthweight: findings in 3512 pregnancies. Br J Obstet
Gynaecol 1997;104:18690. (Level II-3)
37. OReilly-Green CP, Divon MY. Receiver operating characteristic curves of sonographic estimated fetal weight for
prediction of macrosomia in prolonged pregnancies.
Ultrasound Obstet Gynecol 1997;9:4038. (Level II-3)
38. Benacerraf BR, Gelman R, Frigoletto FD Jr. Sonographically estimated fetal weights: accuracy and limitation. Am
J Obstet Gynecol 1988;159:111821. (Level II-2)
39. Delpapa EH, Mueller-Heubach E. Pregnancy outcome following ultrasound diagnosis of macrosomia. Obstet
Gynecol 1991;78:340 3. (Level II-3)
14806. (Level III)
41. Gherman RB, Tramont J, Muffley P, Goodwin TM.
Analysis of McRoberts maneuver by X-ray analysis.
42. Gonik B, Stringer CA, Held B. An alternate maneuver for
management of shoulder dystocia. Am J Obstet Gynecol
1983;145:8824. (Level II)
45. Sandberg EC. The Zavanelli maneuver: a potentially revolutionary method for the resolution of shoulder dystocia.
Am J Obstet Gynecol 1985;152:47984. (Level III)
46. Sandberg EC. The Zavanelli maneuver: 12 years of
recorded experience. Obstet Gynecol 1999;93:3127.
(Level III)
47. Gherman RB, Ouzounian JG, Goodwin TM. Obstetric
maneuvers for shoulder dystocia and associated fetal
morbidity. Am J Obstet Gynecol 1998;178:112630.
(Level II-2)
48. McFarland MB, Langer O, Piper JM, Berkus MD.
Perinatal outcome and the type and number of maneuvers
in shoulder dystocia. Int J Gynaecol Obstet 1996;55:
21924. (Level II-3)
49. Smith RB, Lane C, Pearson JF. Shoulder dystocia: what
happens at the next delivery? Br J Obstet Gynaecol 1994;
101:7135. (Level II-3)
50. Ginsberg NA, Moisidis C. How to predict recurrent shoulder dystocia. Am J Obstet Gynecol 2001;184:14279; discussion 142930. (Level II-2)
51. Lewis DF, Raymond RC, Perkins MB, Brooks GG,
Heymann AR. Recurrence rate of shoulder dystocia. Am J
828

ACOGs own internal resources and documents were used to
conduct a literature search to locate relevant articles published between January 1985 and November 2000. The
search was restricted to articles published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries
also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Guidelines published
by organizations or institutions such as the National Institutes of Health and the American College of Obstetricians
and Gynecologists were reviewed, and additional studies
Force:
I
type of evidence.
committees.

01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
Shoulder dystocia. ACOG Practice Bulletin No. 40. American

2002;100:104550.
PRACTICE BULLETINS
829
ACOG
PRACTICE
BULLETIN
Number 43, May 2003

of John M. Thorp Jr, MD.
of practice.
Reaffirmed 2008
Management of
Preterm Labor
Preterm birth is the leading cause of neonatal mortality in the United States,
and preterm labor precedes 4050% of preterm births (13). Preterm birth
accounts for 35% of all U.S. health care spending for infants and 10% of all
such spending for children (4). Approximately 467,000 live births annually
(11.5% of all live births) occur before term in the United States, and preterm
births are responsible for three quarters of neonatal mortality and one half of
long-term neurologic impairments in children (1, 57). The purpose of this document is to present the various methods proposed to manage preterm labor and
the evidence for their roles in clinical practice. Despite the numerous management methods proposed, the incidence of preterm birth has changed little over
the past 40 years (Fig. 1) (1, 8, 9). Uncertainty persists about the best strategies for managing preterm labor.
Background
Preterm labor generally can be defined as regular contractions that occur before
37 weeks of gestation and are associated with changes in the cervix. Although
the causes of preterm labor are not well understood, the incidence and burden
of preterm births are more clear. Preterm labor is the most common cause of
antenatal hospitalization (10). It is important to recognize that preterm labor is
not the only mechanism leading to preterm birth; numerous preterm births are
preceded by either rupture of membranes or other medical problems (Fig. 2)
(10, 11).
Historically, nonpharmacologic treatments to prevent preterm births in
women who have symptoms of preterm labor have included bed rest, abstention
from intercourse and orgasm, and hydration, either orally or parenterally. The
effectiveness of these interventions is uncertain.
Incidence of preterm birth: 19802000

14
Preterm birth (%)
12
10
8
6
4
2
0
1980 1982 1984
1986 1988 1990 1992 1994 1996 1998 2000

Year
Figure 1. Incidence of preterm birth: 19802000. (Data from Martin JA, Hamilton
BE, Ventura SJ, Menacker F, Park MM, Sutton PD. Births: final data for 2001. Natl
Vital Stat Rep 2002;51:1104; Ventura SJ, Martin JA, Curtin SC, Mathews TJ. Report
of final natality statistics, 1996. Monthly vital statistics report; vol. 46, no. 11, supl.
Hyattsville (MD): National Center for Health Statistics; 1998; and Ventura SJ,
Martin JA, Taffel SM, Matthews ST, Clarke SC. Advance report of final natality statistics, 1992. Monthly vital statistics report; vol. 43, no. 5, suppl. Hyattsville (MD):
National Center for Health Statistics; 1994.)
60
50
Preterm birth (%)
830
40
30
20
10
0
<30 weeks
n=354
3134 weeks
n=461
3536 weeks
n=630
Gestational age
Spontaneous n=671
Indicated n=374
Premature rupture of membranes n=400
Figure 2. Gestational age distributions of spontaneous, indicated, and premature

rupture of membranes preterm births. (Modified from Tucker JM, Goldenberg RL,
Davis RO, Copper RL, Winkler CL, Hauth JC. Etiologies of preterm birth in an indigent population: is prevention a logical expectation? Obstet Gynecol 1991;
77:3437.)
PRACTICE BULLETINS
831
Tocolytic Drugs for Treatment of

Preterm Labor
Antibiotics for Treatment of

Preterm Labor
Tocolytic drugs inhibit myometrial contractions. Many

agents have been used, including ethanol, magnesium
sulfate, calcium channel blockers, oxytocin antagonists,
nonsteroidal antiinflammatory drugs (NSAIDs), and betamimetic agonists. Tocolytics can be administered either
parenterally or orally. Table 1 describes various tocolytic
drugs, their mechanisms of action, and their side effects.
Women who present with symptoms of preterm labor

may have infections of the upper genital tract (12, 13).
It has been theorized that infections or inflammation
are associated with contractions, and this theory provided the rationale for studies using antibiotics to
decrease the risk of spontaneous preterm birth. Studies
have shown mixed results, but most of the evidence has
Table 1. Tocolytics for Preterm Labor

Tocolytic
Agent
Dosage and
Administration
Maternal Side
Effects
Contraindications
Fetal and Neonatal

Side Effects
Terbutaline, .25 mg subcutaneously every 20 min

to 3 hr (hold for pulse
>120 beats per minute)
Cardiac arrhythmias
Cardiac or
cardiopulmonary
arrhythmias, pulmonary
edema, myocardial
ischemia, hypotension,
tachycardia
Fetal tachycardia, hyperinsulinemia, hyperglycemia,

myocardial and septal
hypertrophy, myocardial
ischemia
Ritodrine initial dose of

50100 g/min, increase
50 g/min every 10 min
until contractions cease or
side effects develop
Poorly controlled thyroid

disease
Metabolic hyperglycemia,
hyperinsulinemia,
hypokalemia, antidiuresis,
altered thyroid function
Neonatal tachycardia,
hypoglycemia, hypocalcemia, hyperbilirubinemia,
hypotension, intraventricular hemorrhage
Maximum dose =
350 g/min
Poorly controlled diabetes

mellitus
Physiologic tremor, palpitations, nervousness, nausea or vomiting, fever,

hallucinations
Magnesium
sulfate
46 g bolus for 20 min,

then 23 g/hr
Myasthenia gravis
Flushing, lethargy,
headache, muscle weakness, diplopia, dry mouth,
pulmonary edema, cardiac
arrest
Lethargy, hypotonia,
respiratory depression,
demineralization with
prolonged use
Calcium channel
blockers
30 mg loading dose, then

1020 mg every 46 hr
Cardiac disease, use caution with renal disease,

maternal hypotension
(<90/50 mm Hg), avoid
concomitant use with
magnesium sulfate
Flushing, headache,
dizziness, nausea, transient
hypotension
None noted as yet
Prostaglandin
synthetase
inhibitors
Indomethacin loading dose

of 50 mg rectally or
50100 mg orally, then
2550 mg orally every
6 hr 48 hr
Significant renal or hepatic

impairment
Nausea, heartburn
Constriction of ductus
arteriosus, pulmonary
hypertension, reversible
decrease in renal function
with oligohydramnios,
intraventricular hemorrhage, hyperbilirubinemia,
necrotizing enterocolitis
Ketorolac loading dose of

60 mg intramuscularly,
then 30 mg intramuscularly
every 6 hr 48 hr
Active peptic ulcer disease
Sulindac, 200 mg orally

every 12 hr 48 hr
Coagulation disorders or
thrombocytopenia,
NSAID-sensitive asthma,
other sensitivity to NSAIDs
Beta-mimetic
Abbreviation: NSAIDs, nonsteroidal antiinflammatory drugs

Hearne AE, Nagey DA. Therapeutic agents in preterm labor: tocolytic agents. Clin Obstet Gynecol 2000;43:787801.
832
failed to show a benefit from treatment with antibiotics

(1426).
Antenatal Corticosteroid Use

Recommendations
In 80% of women with presumptive preterm labor,
preterm delivery will not occur (29). Many factors influence the decision to intervene when women have symptoms of preterm labor, including the probability of
progressive labor, gestational age, and the risks of treatment (30). Historically, the clinical criteria commonly
suggested for determining when intervention is needed
included regular uterine activity that does not diminish
with bed rest or hydration, cervical change during an
observation period, or a cervix that is dilated on presentation. However, all of these clinical conditions are inaccurate predictors of preterm delivery (31).
Gestational age is inversely proportional to the risk
of neonatal morbidity and mortality. The upper limit of
gestational age for the use of tocolytic drugs may be a
function of the neonatal treatment capabilities in the
hospital where a clinician practices. Examples of general
contraindications for tocolysis may include severe
preeclampsia, placental abruption, intrauterine infection, lethal congenital or chromosomal abnormalities,
advanced cervical dilatation, and evidence of fetal compromise or placental insufficiency.
Are there tests that can help identify patients

at risk for progressing to preterm birth?
Many tests to identify women at risk of preterm birth

have been proposed and evaluated; however, only ultra-
Does tocolytic therapy improve neonatal

outcome?
Tocolytic drugs may prolong gestation for 27 days,

which can provide time for administration of steroids and
maternal transport to a facility with a neonatal intensive
care unit (26). The benefits of prolonging pregnancy for
27 days are otherwise unclear (3944).
Who are appropriate candidates for

intervention?
The most beneficial intervention for patients in true

preterm labor is the administration of corticosteroids. A
recent meta-analysis confirmed that antenatal corticosteroids significantly reduced the incidence and severity
of neonatal respiratory distress syndrome (27). The incidence of intraventricular hemorrhage and necrotizing
enterocolitis also are reduced by the use of antenatal corticosteroids. The administration of betamethasone has
been shown to decrease neonatal mortality (28). All
women who are at risk for preterm delivery between
24 weeks and 34 weeks of gestation are potential candidates for corticosteroid therapy. Treatment should consist
of either two doses of betamethasone or four doses of
dexamethasone, both administered intramuscularly.
sonography and fetal fibronectin testing have been shown

to have benefit (3237). Ultrasonography to determine
cervical length, fetal fibronectin testing, or a combination
of both may be useful in determining which women are
at high risk for preterm delivery. However, their clinical
usefulness may rest primarily with their ability to identify women who are least likely to deliver (ie, their negative predictive value) given the lack of proven treatment
options to prevent preterm birth. Fetal fibronectin testing
may be useful in women with symptoms of preterm labor
to identify those with negative values and a reduced risk
of preterm birth, thereby avoiding unnecessary intervention (38).
Is there a clear first-line tocolytic drug?
Comparison studies of the effectiveness of different

tocolytic drugs show conflicting results between betamimetics, magnesium sulfate, calcium channel blockers,
and NSAIDs (4558). However, all have demonstrated
only limited benefit. Hence, there is no clear first-line
tocolytic drug. If tocolytic drugs are used, the choice of
drug should be individualized and based on maternal
condition, potential drug side effects, and gestational age
(see Table 1). Prolonged use of any tocolytic drug may
potentially increase the maternalfetal risk without offering a clear benefit.
Serious adverse events are rare but potentially lifethreatening. Beta-mimetics, magnesium sulfate, and calcium channel blockers are all associated with an
increased risk of pulmonary edema. Beta-mimetics are
potent cardiovascular stimulants and can cause serious
complications, such as maternal myocardial ischemia,
metabolic derangements (eg, hyperglycemia and hypokalemia), and fetal cardiac effects. Magnesium sulfate
may cause maternal lethargy, drowsiness, double vision,
nausea, and vomiting. The NSAIDs appear to have the
fewest maternal risks, but fetal effects include oligohydramnios and premature closure of the ductus arteriosus.
Calcium channel blockers used as a single agent appear
to have a good maternal and fetal safety profile. However,
concomitant use of calcium channel blockers and magnesium sulfate is potentially harmful and has resulted in
cardiovascular collapse (59). Combining tocolytic drugs
PRACTICE BULLETINS
potentially increases maternal morbidity and should be

used with caution (60).
Is there a role for adjunctive antibiotics?
Should women with preterm contractions

without cervical change be treated?
Is tocolysis warranted for recurrent preterm

labor?
The role of repeated acute tocolytic therapy in women

with recurring symptoms of preterm labor is unknown.
Given the limited benefits of an initial course of treatment with a tocolytic drug and current recommendations
that corticosteroids be administered only as a single
course (71), the effectiveness of subsequent acute tocolysis is uncertain. Maternal transport is a potential rationale
for a subsequent treatment course (72).
Regular preterm contractions are common. However,

their presence does not reliably predict who will have
subsequent progressive cervical change (65). In a study
of 763 women who had unscheduled visits for symptoms
of preterm labor, only 18% delivered before 37 weeks of
gestation, and only 3% delivered within 2 weeks of presenting with symptoms (29). Although bed rest, pelvic
rest, and hydration are commonly recommended to
women with symptoms of preterm labor to prevent
preterm delivery, the effectiveness of these measures is
not known, and their potential harms (eg, thrombosis
from stasis in the lower extremities) or negative impacts
(eg, loss of employment) should not be underestimated
Is there a role for maintenance treatment

after completing acute treatment?
Studies of maintenance tocolytic therapy in women who

present with symptoms of preterm labor and receive
tocolysis acutely show no differences in effectiveness
between treatment and control groups (30). Meta-analysis likewise fails to demonstrate any benefit of maintenance tocolysis in terms of gestational age at birth,
pregnancy prolongation, or birth weight (30). Prolonged
oral, subcutaneous, or intravenous tocolytic treatment is
not effective. Two prospective randomized trials showed
the terbutaline pump was no more effective than saline
(69, 70).
Because of the large variations in symptoms of preterm

labor and the inability of routine clinical tools to precisely determine a womans risk, the assessment of preterm
delivery risk is fraught with inaccuracy (29, 63, 64).
Previously, when symptoms of preterm delivery were
present, most clinicians handled this uncertainty by recommending reduced maternal activity and administering
fluids with the aim of stopping the uterine activity. Most
advocated awaiting clinical detection of cervical change
before administering tocolytic drugs. Prophylactic therapy, including tocolytic drugs, bed rest, hydration, and
sedation, in asymptomatic women at increased risk for
preterm delivery has not been demonstrated to be effective (30, 61).
Should women with multiple gestations be

treated differently?
Women with multiple gestations who have preterm contractions but no cervical change do not require tocolytic
therapy. Although women with multiple gestations who
are experiencing preterm labor may benefit from shortterm tocolysis to allow for steroid administration, they
have a greater risk of pulmonary edema when exposed to
beta-mimetics or magnesium sulfate (68).
Is preventive treatment efficacious?
(66). No evidence exists to support the use of tocolytic

therapy (67), home uterine activity monitoring, elective
cerclage, or narcotics to prevent preterm delivery in
women with contractions but no cervical change.
An array of antibiotics and bacteriostatic drugs have been

evaluated in randomized, controlled trials to determine if
they can prevent preterm birth in women with preterm
labor, but these studies have reported mixed results. A
recent meta-analysis assessed eight randomized controlled trials comparing antibiotic treatment with placebo
for patients with documented preterm labor (26). No difference was noted between the antibiotic treatment and
placebo for prolonging pregnancy or preventing preterm
delivery respiratory distress syndrome or neonatal sepsis.
Treating women in preterm labor with antibiotics for the
sole purpose of preventing preterm delivery is not recommended (61). At present, it seems prudent to follow
protocols for antibiotic prophylaxis against early-onset
group B streptococcal sepsis, but there is little evidence
that this approach also will prolong gestation (62).
833
Is there a role for amniocentesis?
Amniocentesis to determine fetal lung maturity may have

some benefit in guiding clinical decision making in
women with symptoms of preterm labor. There is no evidence to suggest that routine amniocentesis to check for
infection in these women can provide information that
could be used to improve perinatal outcomes (30). In a
multicenter study in women with preterm labor and intact
membranes, the overall prevalence of microbial invasion
of the amniotic cavity as documented by amniocentesis
was 5.8% (17). Both amniotic fluid Gram stain and glu-
834
cose levels have been used as rapid diagnostic tests of

intraamniotic infection (73, 74). The results of amniotic
fluid cultures, the best method for diagnosing intraamniotic infection, are unlikely to be available quickly enough
to affect decision making.
3. Kramer MS. Preventing preterm birth: are we making any

progress? Yale J Biol Med 1997;70:22732. (Level III)
4. Lewit EM, Baker LS, Corman H, Shiono PH. The direct
cost of low birth weight. Future Child 1995;5:3556.
(Level III)
5. Goldenberg RL, Rouse DJ. Prevention of premature birth.
N Engl J Med 1998;339:31320. (Level III)
Summary of
Recommendations
6. Paneth NS. The problem of low birth weight. Future Child

1995;5:1934. (Level II)
7. McCormick MC. The contribution of low birth weight to
infant mortality and childhood morbidity. N Engl J Med
1985;312:8290. (Level III)
There are no clear first-line tocolytic drugs to

manage preterm labor. Clinical circumstances and
physician preferences should dictate treatment.
Antibiotics do not appear to prolong gestation and

should be reserved for group B streptococcal prophylaxis in patients in whom delivery is imminent.
9. Ventura SJ, Martin JA, Taffel SM, Mathews TJ, Clarke SC.
Advance report of final natality statistics, 1992. Monthly
vital statistics report; vol. 43, no. 5, suppl. Hyattsville
(MD): National Center for Health Statistics; 1994.
(Level III)
Neither maintenance treatment with tocolytic drugs

nor repeated acute tocolysis improve perinatal outcome; neither should be undertaken as a general
practice.
10. Savitz DA, Blackmore CA, Thorp JM. Epidemiologic

characteristics of preterm delivery: etiologic heterogeneity. Am J Obstet Gynecol 1991;164:46771. (Level III)
8. Ventura SJ, Martin JA, Curtin SC, Mathews TJ. Report of

final natality statistics, 1996. Monthly vital statistics
report; vol. 46, no. 11, suppl. Hyattsville (MD): National
Center for Health Statistics; 1998. (Level III)
Tocolytic drugs may prolong pregnancy for 27 days,

which may allow for administration of steroids to
improve fetal lung maturity and the consideration of
maternal transport to a tertiary care facility.
Cervical ultrasound examination and fetal fibronectin testing have good negative predictive value;
thus, either approach or both combined may be
helpful in determining which patients do not need
tocolysis.
Amniocentesis may be used in women in preterm

labor to assess fetal lung maturity and intraamniotic
infection.
Bed rest, hydration, and pelvic rest do not appear to

improve the rate of preterm birth and should not be
routinely recommended.
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51. Caritis SN, Carson D, Greebon D, McCormick M,

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Papiernik E, et al. The association between occupational
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53. Kupferminc M, Lessing JB, Yaron Y, Peyser MR.

Nifedipine versus ritodrine for suppression of preterm
labour. Br J Obstet Gynaecol 1993;100:10904. (Level I)
54. Neldam S, Osler M. Premature rupture of the membranes
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for preventing preterm birth in threatened preterm labour
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Berkowitz RL. Efficacy and side effects of magnesium
sulfate and ritodrine as tocolytic agents. Am J Obstet
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RA. Efficacy and safety of indomethacin versus ritodrine
in the management of preterm labor: a randomized study.
69. Guinn DA, Goepfert AR, Owen J, Wenstrom KD, Hauth

JC. Terbutaline pump maintenance therapy for prevention
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The use of ritodrine and magnesium sulfate in the arrest of
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subcutaneous terbutaline pump for long-term tocolysis.
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60. Hatjis CG, Swain M, Nelson LH, Meis PJ, Ernest JM.
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Consensus Statement 2000;17(2):110. (Level III)
72. Treatment of preterm labor with the beta-adrenergic agonist ritodrine. The Canadian Preterm Labor Investigators
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73. Greig PC, Ernest JM, Teot L. Low amniotic fluid glucose
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74. Hussey MJ, Levy ES, Pombar X, Meyer P, Strassner HT.
Evaluating rapid diagnositic tests of intra-amniotic infection: Gram stain, amniotic fluid glucose level, and amniotic fluid to serum glucose level ratio. Am J Obstet
PRACTICE BULLETINS

Force:
I
type of evidence.
committees.
837
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
Management of preterm labor. ACOG Practice Bulletin No. 43.

2003;101:103947.
838
ACOG
PRACTICE
BULLETIN
(Replaces Committee Opinion Number 252, March 2001)
Neural Tube Defects

of Nancy Cheschier, MD. The
of practice.
Reaffirmed 2008
Neural tube defects (NTDs) are congenital structural abnormalities of the brain
and vertebral column that occur either as an isolated malformation, along with
other malformations, or as part of a genetic syndrome. Isolated (ie, nonsyndromic) NTDs occur in 1.42 per 1,000 pregnancies and are the second most
common major congenital anomaly worldwide (cardiac malformations are
first) (1). In the United States, approximately 4,000 fetuses are affected each
year, of which one third are either aborted or spontaneously lost (2).
Anencephaly accounts for one half of all cases of NTDs and is incompatible
with life; with treatment, 8090% of infants with spina bifida survive with varying degrees of disability (2, 3). Most importantly, NTDs are among the few birth
defects for which primary prevention is possible; prenatal screening and diagnosis are widely available, and prenatal therapy is being investigated.
Background
Embryology
The neural plate appears during the third week of gestation and gives rise to the
neural folds that fuse in the midline to form the neural tube. Recent animal and
human data suggest that neural tube closure occurs in multiple regions, which
then fuse (4, 5). Defects result either from failure of closure of one site or failure of two sites to meet. Neural tube closure is normally complete by the end
of the fourth week after conception (6 weeks after the last period), a time when
many women do not yet realize they are pregnant.
Pathophysiology
Neural tube defects can be categorized as either cranial or spinal defects (see
Table 1). Cranial defects include abnormalities in skull, scalp, and brain tissue
formation. These conditions, with the exception of small encephaloceles, are
lethal. Abnormalities of the caudal portion of the neural tube generally are
known as spina bifida. The various types of spina bifida include malformations
PRACTICE BULLETINS
Table 1. Neural Tube Defect Pathophysiology

Neural Tube Defect
Malformation
Cranial
Anencephaly
Failure of fusion of cephalic portion of

neural folds; absence of all or part of
brain, neurocranium, and skin
Exencephaly
Failure of scalp and skull formation;

exteriorization of abnormally formed
brain
Encephalocele
Failure of skull formation; extrusion of

brain tissue into membranous sac
Iniencephaly
Defect of cervical and upper thoracic

vertebrae; abnormally formed brain
tissue and extreme retroflexion of upper
spine
Spinal
Spina bifida
Failure of fusion of caudal portion of

neural tube, usually of 35 contiguous
vertebrae; spinal cord or meninges or
both exposed to amniotic fluid
Meningocele

neural tube; meninges exposed
Meningomyelocele

neural tube; meninges and neural tissue
exposed
Myeloschisis

neural tube; flattened mass of neural
tissue exposed
Holorachischisis
Failure of fusion of vertebral arches;

entire spinal cord exposed
Craniorachischisis
Co-existing anencephaly and rachischisis
of the spinal cord, meninges, and vertebrae, and most of

these conditions are compatible with life. The majority of
NTDs affecting the spine are associated with ventriculomegaly, or enlargement of the cerebral ventricles, usually the result of an Arnold-Chiari type II malformation
(3, 6, 7).
Clinical Consequences of Neural Tube

Defects
The increased intracranial pressure caused by ventriculomegaly usually is relieved by placement of a ventricular-peritoneal shunt. Most infants with spina bifida and
ventriculomegaly require shunting in their first year, and
at least two thirds require several nonelective shunt revisions over the course of their lifetime (8, 9). Worsening
of the Arnold-Chiari malformation, due in part to the
small size of the posterior fossa, can cause severe or even
lethal neurologic dysfunction, leading to respiratory and
swallowing abnormalities. Surgical decompression of the
posterior fossa involves significant risk.
839
With aggressive therapy at birth, including surgical

closure of the defect within the first 48 hours of life, the
degree of motor and sensory handicap associated with
spina bifida is predicted most accurately by the level of
the lesion: the higher the lesion, the worse the prognosis.
Most individuals with thoracic lesions are wheelchairbound, while 90% of those with sacral lesions can ambulate (10, 11). In one study reporting long-term follow-up
of 101 children with meningomyelocele, 85% of those
with quadriceps function (L2, L3, and L4 intact) ambulated independently, and another 8% walked at home and
used a wheelchair only in public (11). In contrast, only
9% of those without quadriceps function were ambulatory even occasionally.
Most individuals with spina bifida, even those with
low lesions, have some impairment of bowel and bladder
function; urinary tract infections and stones are a common cause of chronic morbidity and even mortality
caused by sepsis or renal failure (12). Sexual function
may be affected by lack of genital sensation and difficulty achieving erection and ejaculation (13). Endocrine
abnormalities, tethered cord, kyphosis, syringomyelia,
and syringobulbia may develop as a result of the neurologic defect or its repair (14). At least one third of individuals with an NTD have a severe allergy to latex and
can have life-threatening reactions after exposure (3).
Although most children with spina bifida have a normal intelligence quotient, intelligence may be affected
(6). Several investigators have reported that in the
absence of increased intracranial pressure, no correlation
exists between ventricular size and intellectual performance in children with spina bifida (8,15). However, a
reduction in mental functioning may occur as a result of
central nervous system infection or increased intracranial
pressure caused by shunt malfunction. One study of 167
children with myelodysplasia found an average intelligence quotient of 102 in children without hydrocephalus,
95 in those with hydrocephalus requiring a shunt, and 73
in those with a shunt and a history of shunt infection (15).
Intellectual decline also may be associated with intraoperative complications during repair of an Arnold-Chiari
malformation or another neurosurgical procedure.
Etiology
Isolated (nonsyndromic) NTDs are believed to be the
result of a combination of genetic predisposition and
environmental influences (16). Genetic predisposition is
illustrated by the fact that NTDs tend to occur more frequently in certain families, and parents who have had one
child with an NTD are at significantly increased risk of
having another child with the same or similar defect
(Table 2) (17). However, only 5% of NTDs occur in families with a positive family history (18). More than 90%
840
Table 2. Recurrence Risk of Neural Tube Malformations

Affected Relatives
Risk of Anencephaly
and Spina Bifida (%)
No siblings
Neither parent
0.3
One parent
4.5
Both parents
30
One sibling
Neither parent
One parent
12
Both parents
38
Two siblings
Neither parent
10
One parent
20
Both parents
43
One sibling and one second-degree

relative
Neither parent
One parent
18
Both parents
42
One sibling and one third-degree

relative
Neither parent
5.5
One parent
16
Both parents
42
Nussbaum RL, McInnes RR, Willard HF. Genetics of disorders with complex
inheritance. In: Thompson & Thompson genetics in medicine. 6th ed.
Philadelphia (PA): WB Saunders; 2001. p. 289310 (reprinted with permission
from Elsevier Science).
occur in families with no prior history, possibly because

genetically susceptible individuals had not been exposed
to the environmental influences necessary to produce a
defect in their offspring. Thus, most individuals at
increased risk do not realize it until they have an affected
child.
Any environmental influence must be present during
the first 28 days of gestation, when the neural tube is
forming, to produce a defect. Factors known to be associated with NTDs include geographic region, ethnicity,
diet, teratogen exposure, maternal diabetes, and high
maternal core temperature (1923). Regions with the
highest NTD incidence include the British Isles, China,
Egypt, and India. Certain ethnic and racial groups also
appear to be at high risk. For example, a study using
5 years of population-based data from California found
that Hispanic women (1.12 per 1,000, 95% confidence
interval [CI], 1.041.21), and Caucasian women (0.96
per 1,000, 95% CI, 0.891.04) were at highest risk.
African-American women (0.75 per 1,000, 95% CI,
0.590.91) and Asian women (0.75 per 1,000, 95% CI,

0.600.90) were at lower risk (24). Some of the ethnic
differences observed may reflect geography and diet in
addition to genetic predisposition. For example, Sikhs
living in India have more than twice the incidence of
NTDs as Sikhs living in Canada (17).
Most isolated NTDs occur in association with abnormal folate metabolism, discussed as follows. Genetic syndromes that can include an NTD and are likely to have a
genetic etiology other than abnormal folate metabolism
include Meckel-Gruber, Roberts, Jarcho-Levin, and
HARD syndromes, as well as trisomy 13, trisomy 18, and
triploidy. Cloacal exstrophy and sacrococcygeal teratoma
may be associated with spina bifida, and amniotic bands
may cause spina bifida or anencephaly (25).
Role of Folic Acid

The most important environmental influence on NTD
formation appears to be diet or, more specifically, the
intake of folic acid. It has long been known that women
with pregnancies complicated by fetal NTDs have lower
plasma levels of vitamin B12 and folate than women
whose pregnancies are unaffected. Many of the medications known to cause fetal NTDs, such as diphenylhydantoin, aminopterin, or carbamazepine, interfere with
folic acid metabolism. Several clinical studies showed
that folic acid supplementation before conception
reduces the recurrence of fetal NTDs (2629). However,
the benefits of folic acid were not widely accepted until
1991, when the Medical Research Council Vitamin Study
Research Group published the results of a large, prospective, randomized, double-blind study of folic acid supplementation conducted at 33 centers in seven countries
(30). A total of 1,817 women at high risk by virtue of a
previously affected pregnancy were enrolled in the study
and randomly assigned to receive folic acid, other vitamins, both, or neither. Women assigned to take 4 mg of
folic acid per day before pregnancy and through the 12th
week of gestation experienced a 72% reduction in their
recurrence risk (odds ratio, 0.28; 95% CI, 0.150.53).
The Medical Research Council study included only
women who already had an affected pregnancy, which
accounts for only 5% of cases of NTDs. However, a
double-blind, placebo-controlled, randomized trial subsequently showed that periconceptional folic acid supplementation decreased the risk of a first occurrence of an
NTD as well (31). The efficacy of periconceptional folic
acid supplementation for preventing both recurrence and
occurrence of NTDs has since been confirmed by many
other studies (32, 33).
The genetic basis for the relationship between folate
metabolism and NTDs is now being investigated. The
most important metabolic reaction that requires folate is
PRACTICE BULLETINS
the conversion of homocysteine to methionine; evidence

indicates that this pathway is critically involved in the
genesis of NTDs. Several studies have shown that parents
who have had a pregnancy complicated by an NTD and
their affected offspring are more likely to carry a mutation in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR) than the unaffected
population. For example, in the Netherlands, 1416% of
mothers, 1015% of fathers, and 1318% of children
with spina bifida are homozygous for the MTHFR mutation compared with 5% of the general population
(3436). Other mutations in this enzyme with similar
effects also have been reported (36). Therefore, it seems
possible that folic acid supplementation helps to overcome the effects of this enzyme mutation, resulting in
more normal levels of homocysteine and adequate production of methionine (21). Methionine is important
because it provides the methyl group necessary for gene
regulation and for a wide variety of metabolic reactions
essential for tissue growth and development.

Recommendations
Is folic acid supplementation useful in preventing NTDs?
Although folic acid is now widely acknowledged as beneficial in preventing isolated nonsyndromic NTDs, it
must be ingested before conception and at least through
the first 4 weeks of fetal development to be effective.
Because the neural tube is nearly formed by the time of
the first missed period, initiating folic acid supplementation at that time is not sufficient. Although women of
reproductive age should be advised to ingest a diet that
includes folate-rich foods, several studies have shown
that diet alone is not effective in increasing serum folate
levels. Folic acid supplementation should, therefore, be
encouraged. Specific recommendations regarding the
dose are evolving.
In 1991, the Centers for Disease Control and
Prevention recommended that all women with a previous
pregnancy complicated by a fetal NTD ingest 4 mg of
folic acid daily before conception and through the first
trimester (37). The following year, the U.S. Public Health
Service recommended that all women capable of becoming pregnant take 400 g of folic acid daily, and many
groups, including the American College of Obstetricians
and Gynecologists, subsequently endorsed these recommendations.
Few women actually take a folic acid supplement
routinely. Even though women might take folic acid dur-
841
ing a pregnancy, more than one half of all pregnancies are

unplanned (38), and in these cases, the neural tube has
already formed before pregnancy is recognized and before
folic acid supplementation has been initiated. Therefore,
most pregnancies in this country have not benefited from
this preventive measure. Since January 1, 1998, the U.S.
Food and Drug Administration has required folic acid fortification of cereal grains (39). Because of this requirement, the average woman eating a standard diet now
ingests an extra 200 g of folic acid each day (40).
Although grain fortification has improved the folate
intake of all Americans, many authorities feel the current
level of fortification is inadequate to prevent NTDs. An
analysis of 13 published studies clarified the doseresponse relationship of folic acid for NTD prevention
(41). Women in western countries typically have a baseline serum folate level of approximately 5 ng/mL (normal
range 620 ng/mL). This analysis determined that ingestion of an additional 200 g of folic acid each day would
reduce the incidence of NTDs by only approximately
20% (41). These calculations are supported by data from
the U.S. Public Health Service that confirm since grain
fortification began, the incidence of NTDs in the United
States has decreased by only 19% (42).
It currently is recommended that women of reproductive age take a 400 g folic acid supplement daily.
Calculations based on existing data predict that the
400 g dose recommended for women at low risk would
reduce the incidence of NTDs by 36%. In this same
analysis, the 4 mg dose, currently recommended only for
women at high risk, was predicted to reduce the incidence by 82%, and a 5 mg dose was predicted to reduce
the incidence by 85% (41).
The risks of higher levels of folic acid supplementation are believed to be minimal. Folic acid is considered
nontoxic even at very high doses and is rapidly excreted
in the urine. There have been concerns that supplemental
folic acid could mask the symptoms of pernicious anemia
and thus delay treatment. However, folic acid cannot
mask the neuropathy typical of this diagnosis. Currently,
12% of patients with pernicious anemia present with neuropathy alone (43). With folic acid supplementation, this
proportion may be increased, but there is no evidence that
initiating treatment after the development of a neuropathy results in irreversible damage (44). A small number
of women taking seizure medication (diphenylhydantoin,
aminopterin, carbamazepine) may have lower serum drug
levels and experience an associated increase in seizure
frequency while taking folic acid supplements (45).
Monitoring drug levels and increasing the dosage as
needed may help to avert this complication.
Some over-the-counter multivitamin supplements
and most prenatal vitamins contain 400 g of folic acid.
842
Which NTDs may not be affected by folic

acid?
There is limited evidence to indicate that folic acid supplementation may not decrease the risk of NTDs in
women with high first-trimester blood glucose levels, or
high first-trimester maternal temperature, or in women
who take valproic acid. In women with high glucose levels, the exact mechanism is unknown but may involve
inhibition of fetal glycolysis, a functional deficiency of
arachidonic acid or myoinositol in the developing
embryo, or alterations in the yolk sac (23). First-trimester
maternal fever and sauna use both increase the relative
risk of NTDs (to 2.66.2), although the duration and
intensity necessary to produce an effect and the embryologic mechanism are unknown (47). First-trimester valproic acid use results in a 12% risk of having a fetus
with spina bifida, but the mechanism may be different
from that of other antiepileptic agents (19). Fetuses with
aneuploidy or genetic syndromes may have NTDs as a
result of their specific genetic abnormality. These NTDs
are not prevented by folic acid.
Is maternal serum alpha-fetoprotein testing

useful in screening for NTDs?
Amniotic fluid and maternal serum alpha-fetoprotein

(MSAFP) levels are elevated in 89100% of pregnancies
complicated by fetal NTDs (47). Many large prospective
trials of MSAFP screening have shown that most affected
pregnancies can be identified by an elevated MSAFP
level, usually defined as more than 2.5 times the normal
median for singleton pregnancies (4851).
Because more than 90% of all children with NTDs
are born to women with no family history of NTD and no
obvious risk factors, MSAFP screeningwhich usually
is performed as part of broader screening for aneuploidymakes it possible to identify affected fetuses in
such women. Most screening programs strive to identify
most cases of NTDs without unduly increasing the falsepositive rate, which requires a trade-off between sensitivity and specificity. When the screen-positive cutoff is set
at 2.5 multiples of the median (MoM), the screen-positive
rate is typically 5% or less, and approximately 85% of all
NTDs in singleton pregnancies and 80% in twin pregnancies will be identified (4851). The false-positive rate can
be decreased by performing an ultrasound examination

before MSAFP screening to verify gestational age and
identify multiple gestations and cases of intrauterine fetal
demise.
Higher levels of supplementation should be achieved by

taking an additional folic acid supplement and not by taking excess multivitamins. In particular, vitamin A is
potentially teratogenic at high doses, and pregnant
women should not take more than the 5,000 IU per day,
which is typically found in one multivitamin/mineral supplement (46).
How should the diagnosis of NTDs be

established?
Maternal serum alpha-fetoprotein evaluation is an effective screening test for NTDs and should be offered to all
pregnant women unless they plan to have amniotic fluid
alpha-fetoprotein (AFP) measurement as part of prenatal
diagnosis for chromosomal abnormalities or other genetic diseases. The MSAFP test is a screening test and,
therefore, has a high false-positive rate. Only 2% of all
women with a positive test result are carrying a fetus with
an NTD, and these affected pregnancies can only be identified by performing a diagnostic test. Women with
MSAFP levels higher than a predetermined cutoff (usually 22.5 MoM) should, therefore, be referred for genetic
counseling and consideration of a diagnostic test. Women
already known to be at high risk of having a fetus with an
NTD because of a previously affected pregnancy, a positive family history, medication exposure, diabetes, or
another risk factor, can be offered a diagnostic test directly. Although MSAFP does not function as a screening test
in these women because they will be offered a diagnostic
test regardless of the results, it still may be helpful in
evaluating the fetus.
The traditional diagnostic test offered to women with
a positive MSAFP test result is genetic amniocentesis. If
the amniotic fluid AFP level is elevated, an assay is performed to determine the presence or absence of acetylcholinesterase. Elevated amniotic fluid AFP together with
the presence of acetylcholinesterase is considered diagnostic for a fetal NTD. In a study of almost 10,000 singleton pregnancies at 1423 weeks of gestation with
known outcomes, the amniotic fluid acetylcholinesterase
level identified 100% of cases of anencephaly, 100% of
cases of open spina bifida, and 20% of ventral wall
defects, with a false-positive rate of 2.2 per 1,000 amniocenteses (52).
One advantage of amniocentesis is that amniotic
fluid also can be obtained for determination of the fetal
karyotype. Several studies suggest that elevated MSAFP
levels independently increase the risk of fetal aneuploidy
(53). In pregnancies complicated by an elevated MSAFP
level, the incidence of fetal aneuploidy is 0.61% in ultrasonographically determined normal fetuses and 16% in
abnormal fetuses (54, 55). Performing a genetic amniocentesis in all women at increased risk of an NTD would
result in a 98% detection rate for NTDs and a 100%
detection rate for aneuploidy. However, based on the high
PRACTICE BULLETINS
Table 3. Relative Risk of Poor Pregnancy Outcomes with

Elevated Maternal Serum Alpha-fetoprotein Level
Condition
Open neural tube defect
Relative Risk
225
Other anomalies
4.7
Fetal death
8.1
Neonatal death
4.7
Low birth weight
4.0
Newborn complications
3.6
Oligohydramnios
3.4
Abruption
3.0
Preeclampsia
2.3
Milunsky A, Jick SS, Bruell CL, MacLaughlin DS, Tsung YK, Jick H, et al. Predictive
values, relative risks, and overall benefits of high and low maternal serum alphafetoprotein screening in singleton pregnancies: new epidemiologic data. Am J
Obstet Gynecol 1989;161:2917 (reprinted with permission from Elsevier
Science).
false-positive rate of the MSAFP screening test, a policy

of universal amniocentesis for all high-risk women
would mean many would undergo amniocentesis unnecessarily. Although second-trimester amniocentesis is a
relatively safe procedure, it is associated with a postprocedure pregnancy loss rate of approximately 1 in 200
(56).
Ultrasound technology has improved remarkably
since MSAFP screening was adopted. Centers with special
expertise in obstetric ultrasonography report excellent
sensitivity and specificity in detecting fetal NTDs, especially in high-risk patients, and many now offer specialized ultrasound examination as a diagnostic test for
women at high risk of NTDs (57). In the hands of experienced operators, ultrasonography alone has up to 97%
sensitivity and 100% specificity in the diagnosis of NTDs
(57). In less experienced hands, however, ultrasonography
is only a screening test that can have a high false-negative
rate. In a large multicenter trial of ultrasound screening in
low-risk women, only 35% of major anomalies were
detected in tertiary hospital settings and only 13% in nontertiary settings; 7 of 8 NTDs were identified (58).
To take advantage of both types of testing and to
minimize risk, many centers now offer specialized ultrasound examinations initially to all high-risk women, and
perform amniocenteses only in a subset of patients. If a
high-quality ultrasound examination is performed and no
fetal defects are identified, the risks and benefits of both
amniocentesis and specialized ultrasound examination
can be discussed with the patient. A decision about invasive testing can then be made that takes into account the
degree of risk associated with the MSAFP level or the
patients history, the quality and findings of the specialized ultrasound examination, the patients age, and the
patients wishes. Many high-risk patients decide against
amniocentesis after a reassuring specialized ultrasound
examination. Alternatively, amniocentesis is offered for
confirmation to those patients in whom a fetal defect is
identified or for reassurance to those in whom visualization of the fetus is suboptimal and the ultrasound examination is not helpful in making a diagnosis (59). Women
with a very high MSAFP level also may be offered
amniocentesis because there is a direct relationship
between the degree of MSAFP elevation and the incidence of anomalies. With an MSAFP of 2.5 MoM, there
is a 3.4% risk of anomalies; at 7 MoM, the risk increases
to 40.3% (Table 3) (60). Some women at high risk for a
fetal NTD may choose amniocentesis because they also
are at increased risk for fetal aneuploidy. Some authorities dispute the use of ultrasonography as a diagnostic
test and recommend that amniocentesis be offered to all
women with elevated MSAFP levels (6163).
843
Are there special considerations in the obstetric management and route of delivery of a
fetus with an NTD?
Most pregnancies complicated by fetal spina bifida will

result in delivery at term unless there is obstetric intervention. Fetal spina bifida does not increase the risk of
uteroplacental insufficiency or oligohydramnios; anencephaly can be associated with hydramnios as a result of
decreased fetal swallowing. There is no evidence that
antenatal testing for the sole indication of a fetal NTD
improves outcome. Furthermore, the structurally abnormal fetus frequently has an abnormal fetal heart rate
pattern, which can be difficult to interpret (64). Serial
ultrasound examinations to monitor fetal growth and ventricular size may be helpful in planning delivery.
The fetus with spina bifida should be delivered at a
hospital with neonatal intensive care facilities and personnel capable of managing the spine defect and any immediate complications; evidence suggests that outcomes are
better in such settings (65). Because individuals with an
NTD are at risk of developing a severe, potentially lifethreatening allergy to latex (3), clinicians handling the
infant should wear wear latex-free gloves. Generally,
delivery at term is preferred. However, once fetal lung
maturity has been documented, rapidly increasing ventriculomegaly may prompt delivery before term so that a
ventriculo-peritoneal shunt can be placed. Each case
should be managed individually in consultation with personnel with experience and knowledge of such complications and personnel from the neurosurgical and neonatal
services.
844
Breech presentation, resulting from fetal neurologic

dysfunction or hydrocephalus with an enlarged head, is
common in pregnancies complicated by fetal spina bifida. For the breech fetus with an NTD, cesarean delivery
is standard (66). The best delivery route for the vertex
fetus remains controversial. No prospective randomized
trial of vaginal delivery versus cesarean delivery for vertex fetuses with spina bifida has been performed. All
studies in the current literature are retrospective with various biases. At least five studies representing a total of
400 patients suggest that vaginal delivery does not
adversely affect neonatal outcome, while one large study
of 200 patients suggests the opposite (6671).
Most studies on this subject also are limited by lack
of long-term follow-up, which is essential in evaluating
medical care for these infants because loss of function
and other neurologic reversals are common even when
surgery is performed early to correct an NTD. Because it
is still not clear whether or how the method of delivery
significantly affects neurologic outcome in these infants,
decisions about the timing and route of delivery should
be made individually in consultation with personnel with
experience and knowledge of such complications, which
may include maternalfetal medicine specialists, neonatologists, and pediatric neurosurgeons.
Is there a role for fetal surgery for NTDs?
The two-hit hypothesis describes the likely cause of

neurologic damage that occurs with NTDs: the first hit
is the developmental abnormality that caused the open
spina bifida, and the second hit is the inflammation and
damage to the neural tissues possibly caused by chronic
exposure to amniotic fluid, fetal movement, contact with
the uterine wall, or pressure from labor and delivery.
Although no prenatal intervention can eliminate the
effects of the first hit once it has occurred, researchers
investigating in utero surgical closure of fetal spina bifida theorize that fetal surgery might prevent the kind of
trauma characterized as the second hit (72).
Approximately 220 in utero closures of fetal spina
bifida were performed in four centers in the United States
between 1997 and 2002. These procedures were not performed as part of a randomized study and generally were
offered to women whose fetuses had lesions at or below
the lower thoracic spine. Data gathered from this cohort
suggest no improvement in bowel or bladder function or
ambulatory ability beyond the degree of impairment predicted by the level of the lesion (73, 74). However, these
children appear to require shunt placement less frequently or at least later in life. They also seem to experience an
improvement in the degree of hindbrain herniation after
in utero surgery, which, if confirmed, might help to prevent serious morbidity or mortality from worsening
Arnold-Chiari type II malformation (75, 76). Because of
selection bias in the cohort and the nonstandard neurosurgical follow-up, it is difficult to know whether the
medical need for shunting truly decreases or whether
decreased herniation corresponds to improved function.
Maternalfetal surgery is a risky procedure. The
woman incurs the risks attendant with any surgical procedure (anesthetic complications, hemorrhage, bladder
injury, chorioamnionitis) twice during the index pregnancy. First, a hysterotomy is placed in the muscular portion
of the uterus during the late second trimester to provide
access to the fetus. Because the hysterotomy confers an
increased risk of uterine rupture, the woman then must
undergo cesarean delivery for the index and all future
pregnancies (77).
One of the most significant potential risks to the
fetus is preterm delivery and its secondary complications
(76). A fetus that has undergone in utero neurosurgical
repair is delivered at approximately 33 weeks of gestation, with up to 40% being delivered before 32 weeks of
gestation (75, 76, 78). One study of 29 infants who
underwent in utero neurosurgery reported preterm labor
in 50%, preterm premature rupture of the membranes in
28%, and oligohydramnios in 48% of the women who
had fetal surgery, while only 4% of the controls had these
complications (78). A study of 33 infants with known
neurologic outcome after undergoing a variety of fetal
surgery procedures found that additional central nervous
system injuries occurred in 21% (79). Contributing factors included intraoperative fetal bradycardia, significant
maternal blood loss, maternal respiratory failure or
hypotension, neonatal hypotension, uterine contractions,
and exposure to terbutaline and nitroglycerin.
Information on long-term complications for women
and fetuses who undergo maternalfetal surgery is only
starting to accrue. Data from one large fetal surgery center documented no long-term effects on fertility in 70
women who underwent maternalfetal surgery (80).
However, an increased incidence of early tethered cord
has been reported in fetuses undergoing in utero
meningomyelocele repair (81). The parent(s) must understand these risks and recognize the potential for additional complications before undergoing such a procedure.
The ethical issues relevant to maternalfetal surgery
for fetal spina bifida are complex, and maternalfetal
surgery for repair of fetal spina bifida currently is considered investigational. A National Institutes of Healthsupported prospective randomized trial of prenatal
surgical closure of fetal spina bifida began in January
2003 and is expected to resolve many of these issues.
PRACTICE BULLETINS
845
Summary of
Recommendations
3. Bowman RM, McLone DG, Grant JA, Tomita T, Ito JA.

Spina bifida outcome: a 25-year prospective. Pediatr
Neurosurg 2001;34:11420. (Level III)

4. Van Allen MI, Kalousek DK, Chernoff GF, Juriloff D,

Harris M, McGillivray BC, et al. Evidence for multi-site
closure of the neural tube in humans. Am J Med Genet
1993;47:72343. (Level III)
Periconceptional folic acid supplementation is recommended because it has been shown to reduce the
occurrence and recurrence of NTDs.
5. Seller MJ. Sex, neural tube defects, and multisite closure

of the human neural tube. Am J Med Genet 1995;58:
3326. (Level II-2)
For low-risk women, folic acid supplementation of

400 g per day currently is recommended because
nutritional sources alone are insufficient. Higher levels of supplementation should not be achieved by
taking excess multivitamins because of the risk of
vitamin A toxicity.
For women at high risk of NTDs or who have had a

previous pregnancy with an NTD, folic acid supplementation of 4 mg per day is recommended.
Maternal serum alpha-fetoprotein evaluation is an

effective screening test for NTDs and should be
offered to all pregnant women.
Women with elevated serum AFP levels should have

a specialized ultrasound examination to further
assess the risk of NTDs.
The fetus with an NTD should be delivered at a facility that has personnel capable of handling all aspects
of neonatal complications.
The ideal dose for folic acid supplementation has not

been appropriately evaluated in prospective clinical
studies. A 400 g supplement currently is recommended for women capable of becoming pregnant.
The route of delivery for the fetus with an NTD

should be individualized because data are lacking
that any one route provides a superior outcome.
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Force:
I
type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Neural tube defects. ACOG Practice Bulletin No. 44. American
102:20313.
PRACTICE BULLETINS
849
ACOG
PRACTICE
BULLETIN
Cervical Insufficiency
of James H. Harger, MD. The
of practice.
Reaffirmed 2008
The inability of the uterine cervix to retain a pregnancy to term is referred to as

cervical insufficiency. Controversy exists in the medical literature pertaining to
issues of pathophysiology, screening, and management of cervical insufficiency. The purpose of this document is to provide a review of current evidence on
cervical insufficiency, including screening of asymptomatic at-risk women, and
offer management guidelines.
Background
Definition
The terms cervical insufficiency and cervical incompetence have been used
to describe the inability of the uterine cervix to retain a pregnancy in the
absence of contractions or labor. Historically, the function of the cervix has
been the primary consideration: the cervix was either considered to be fully
functional (competent) or nonfunctional (incompetent). The distinction
between the 2 states was based on a history of painless cervical dilation after
the first trimester with subsequent expulsion of the pregnancy out of the uterus
without contractions or labor. More recently, with the advent of ultrasonographic assessment, cervical function has been viewed more as a continuous
variable with a range of degrees of competency that may be expressed differently in subsequent pregnancies.
Incidence and Prevalence

The lack of objective findings and clear diagnostic criteria make the incidence
of cervical insufficiency difficult to ascertain. According to the National
Center for Health Statistics, in 2000, 23,000 discharge records from short-stay
hospitals included the diagnosis of cervical incompetence (1). Older studies
provided crude estimates by reporting the number of deliveries in a medical
facility during the period when a given number of cerclages were performed.
850
Midrange estimates have suggested that the ratio of cerclage procedures to deliveries ranged from 1 per 222 (2)
to 1 per 182 deliveries (3). A Danish study from 1980 to
1990 applied the diagnosis of cervical insufficiency to
2,756 women, resulting in an incidence of 4.6 cerclages
per 1,000 births, or 1 per 217 deliveries (4). At the
extremes of the frequency range, an American study of
110 cerclages in the 1950s suggested 1 cerclage for
every 1,842 deliveries (5), while an Israeli study of 410
cerclages in a 5-year period reported 1 cerclage for
every 54 deliveries (6). This wide disparity reflects confusion about the diagnostic criteria foras well as
uncertainty about the proper treatment ofcervical
insufficiency.
The success rate of cerclage is equally difficult to
estimate. Some studies suggest cerclage is not necessarily an effective treatment. Others report a more than 70%
chance of a normal birth without cerclage in the next
pregnancy after recurrent pregnancy loss (7, 8). Although
these studies lacked any controls, later studies used
patients as their own controls. These studies reported
infant viability to be only 25% before cerclage was used
and 7590% in the next pregnancy when cerclage was
used (9). The lack of properly designed studies allows for
speculation regarding the frequency and necessity of cerclage (10).
Causes
Several investigators have postulated that most cases of
cervical insufficiency occur as a result of surgical trauma
to the cervix from conization, loop electrosurgical excision procedures, overdilation of the cervix during pregnancy termination, or obstetric lacerations, although data
confirming this association are limited (1113). Other
proposed etiologies include congenital mllerian anomalies, deficiencies in cervical collagen and elastin, and in
utero exposure to diethylstilbestrol (DES).
Emerging Theories
Several investigators have proposed an alternative, multifactorial model for cervical insufficiency. It reflects data
generated by serial transvaginal ultrasound measurements of cervical length, dilation, and funneling of the
membranes into the cervical canal and comparison of the
measurements with pregnancy outcome (1113). This
model takes into account individual observations that the
cervix during pregnancy is a dynamic structure responding to different factors, and that cervical compliance and
length vary from woman to woman. In this model, cervical length is a marker for cervical competence operating
as a continuum, where cervical insufficiency may represent the lowermost end of the continuum (11).
Diagnostic Criteria
The diagnosis of cervical insufficiency remains elusive.
Historically, cervical dilation associated with painful
uterine contractions or bleeding was believed to represent
preterm labor or abruption or both. The diagnosis of cervical insufficiency has been made, historically, based on
the presence of painless cervical dilation. A history of
prior cervical trauma, pregnancy loss in the second or
early third trimester, pelvic pressure, increased mucoid
discharge, or cervical dilation without appreciable discomfort or perceived contractions and hourglassing
membranes was considered sufficient to make the diagnosis of cervical insufficiency.
Various diagnostic tests have been suggested to confirm the presence of cervical insufficiency. These include
hysterosalpingography and radiographic imaging of balloon traction on the cervix (14), assessing the patulous
cervix with Hegar or Pratt dilators, the use of a balloon
elastance test (15), and calculation of a cervical resistance index using graduated cervical dilators (16). None
of these tests have been validated in rigorous scientific
studies.
Ultrasonographic assessment of normal cervices
during pregnancy demonstrates that cervical length normally has a wide range before 20 weeks of gestation, perhaps because endovaginal ultrasonography cannot easily
distinguish between the upper portion of the true cervix
and the myometrium of the lower uterine segment during
that period of gestation. Studies using transvaginal ultrasonography have demonstrated that in women who gave
birth at term, the cervical length is stable in the first
30 weeks of pregnancy, whereas in the last trimester, the
cervix shortens progressively. One study demonstrated a
mean cervical length of approximately 4 cm (4.16 +/
1.02 cm) between 14 and 28 weeks of gestation in normal
pregnancies, which gradually decreased between 28 and
40 weeks of gestation (3.23 +/ 1.16 cm) (17). These
findings were confirmed by other studies (18, 19), one of
which demonstrated that cervical length was almost constant during the first 16 weeks of pregnancy and then
gradually decreased from 4.3 cm to 2.5 cm at term (19).
Gravidity and parity do not seem to influence cervical
length.
Ultrasound evidence of cervical effacementie,
funnelingcan be found when the internal cervical os is
marked by visible separation of the 2 sidewalls of the
upper end of the cervical canal, producing a wedgeshaped space. Noninvasive stress techniques, including
transfundal pressure, coughing, and standing, have been
used to elicit ultrasonographic cervical changes (20).
Lastly, serial ultrasound assessment of cervical length in
women between 24 and 28 weeks of gestation has been
PRACTICE BULLETINS
correlated with preterm delivery, the relative risk of

preterm delivery increasing with decreasing cervical
length (12).
discriminatory power to recommend its routine use for

screening.
Treatment Options

Recommendations
Is there a role for routine ultrasound screening of the cervix?
Serial ultrasound assessments of the cervix in low-risk

women have demonstrated both low sensitivity and
low positive-predictive values (28), which means
numerous false-positive test results would be needed
to detect even 1 true positive case of preterm cervical
shortening. As a result, ultrasonography lacks enough
What is the role of ultrasonography in evaluating the cervix of a woman who has had a
prior pregnancy loss?
Ultrasonography may play a role in the woman with a

history of 1 or more pregnancy losses in the second or
early third trimesters. One prospective observational
study of 106 women at high risk for preterm delivery
found 12.3% of the women demonstrated an open internal os at rest or cervical shortening and funneling in
response to fundal pressure at or before 24 weeks of gestation (29). This study found a specificity for preterm
delivery of 0.94 (29). In addition, a prospective, nonrandomized study monitored 168 asymptomatic high-risk
women from 14 to 24 weeks of gestation with serial
transvaginal ultrasound evaluation of the cervix (30).
Among 63 (37.5%) patients identified as having a cervical length less than 25 mm or funneling of more than
25% or both, 23 (37%) had preterm deliveries; whereas
among 105 patients with no cervical changes, 8 (8%) had
preterm deliveries (relative risk, 4.8; 95% confidence
interval 2.3, 10.1). These studies suggest that serial
transvaginal ultrasound examination may be considered
in women with a history of second- or early thirdtrimester deliveries. Because the upper portion of the
cervix is not easily distinguished from the lower uterine
segment in early pregnancy, such assessments should
begin no earlier than 1620 weeks of gestation. There is
no role for ultrasonography as a screening tool for cervical insufficiency in women with a history of firsttrimester pregnancy losses.
Historically, several surgical and nonsurgical modalities

have been proposed to treat cervical insufficiency.
Nonsurgical approaches, including modified activity,
bed rest, pelvic rest, and pessaries, have been used but
have not yet been proved to be effective (21). The standard cerclage methods currently used are modifications
of the Shirodkar and McDonald techniques. The
Shirodkar procedure attempts to place the suture as close
to the internal os as possible. The bladder and rectum are
dissected from the cervix in a cephalad manner, the
suture is placed and tied, and the mucosa is replaced over
the knot (5, 22). Currently, polyester fiber or polypropylene sutures are commonly used.
The most commonly used cerclage technique is the
McDonald procedure, in which a simple purse-string
suture of monofilament suture (such as silk or
polypropylene) or polyester fiber tape is inserted at the
cervicovaginal junction (23). Retrospective analyses
have not demonstrated the superiority of one technique
over another (3).
Transabdominal cervicoisthmic cerclage is rarely
indicated and generally is reserved for patients with congenital cervical hypoplasia, a cervix badly lacerated or
scarred because of prior surgery or obstetric injury, or in
the case of failed transvaginal cerclage procedures. If
indicated, patients generally are referred to a physician
with prior experience in managing such cases. After dissection of the bladder from the lower uterine segment, a
polyester fiber suture band is tunneled around the upper
cervix. The knot can be left in place between pregnancies with subsequent cesarean delivery or can be tied
posteriorly and cut through a posterior colpotomy incision if indicated (2427).
851
In whom is a cerclage indicated?
Historically, patient selection for elective cerclage has

been based on congenital or acquired visible defects in
the ectocervix or classic historical features of cervical
incompetence (see box). Four randomized clinical trials
have reported on the efficacy of elective cerclage in
women chosen because of various historical features
alone. Three of the trials found no significant improvement in outcomes among women treated with cerclage
(3133).
The largest study, the Medical Research Council/
Royal College of Obstetricians and Gynaecologists
international, randomized, intent-to-treat trial of 1,292
women with singleton pregnancies at risk for preterm
delivery, divided the study subjects into 6 mutually
exclusive cohorts: 1) history of 1 second-trimester abortion or preterm delivery and no history of cone biopsy or
852
Historical Features of Cervical Insufficiency

History of 2 or more second-trimester pregnancy
losses (excluding those resulting from preterm labor
or abruption)
History of losing each pregnancy at an earlier gestational age
History of painless cervical dilation of up to 46 cm
Absence of clinical findings consistent with placental
abruption
History of cervical trauma caused by
Cone biopsy
Intrapartum cervical lacerations
Excessive, forced cervical dilation during pregnancy
termination
Data from Harger JH. Cerclage and cervical insufficiency: an evidencebased analysis. Obstet Gynecol 2002;100:131327.
cervical amputation, 2) history of 2 second-trimester

abortions or preterm deliveries and no history of cone
biopsy or cervical amputation, 3) history of 3 or more
second-trimester abortions or preterm deliveries and no
history of cone biopsy or cervical amputation, 4) history
of cone biopsy or cervical amputation, 5) previous
first-trimester spontaneous abortion, cervical or uterine
anomaly on examination, or previous termination of pregnancy, and 6) twin gestation (34). Only in the subgroup of
107 women with at least 3 previous second-trimester
pregnancy losses or preterm deliveries was there a significant benefit in reducing the frequency of delivery before
33 weeks of gestation (15% in the cerclage group versus
32% in the control group, P .05). In the other 5 subgroups, there was no statistically significant improvement
in neonatal outcome or preterm delivery rate.
On the basis of this limited clinical information,
elective cerclage for purely historical factors generally
should be confined to patients with 3 or more otherwise
unexplained second-trimester pregnancy losses or
preterm deliveries. In keeping with the protocols used in
these randomized trials, the cerclage should be performed at 1316 weeks gestation after ultrasound evaluation has demonstrated the presence of a live fetus with
no apparent anomalies.
Urgent, or therapeutic, cerclage often is recommended for women who have ultrasonographic changes consistent with a short cervix or the presence of funneling.
These women usually are undergoing ultrasonography
because they have risk factors for early delivery or may
have reported nonspecific symptoms, such as backache,
uterine contractions, vaginal spotting, pelvic pressure, or
mucoid vaginal discharge. Numerous retrospective studies

have addressed this group of urgent cerclages, with variable results (3539). One randomized trial of 61 women
with ultrasonographic evidence of dilation of the internal
cervical os between 16 and 24 weeks of gestation compared women assigned to receive a McDonald cerclage (n
= 31) with women who did not receive a cerclage (n = 30)
(40). All patients were evaluated with amniocentesis and
urogenital cultures and treated with indomethacin and
antibiotics before randomization. There was no significant
difference in gestational age at delivery or perinatal outcome between the 2 groups. The final results of the
Cervical Incompetence Prevention Randomized Cerclage
Trial (CIPRACT) yielded different conclusions (41). In
this study of 35 women, preterm delivery before 34 weeks
of gestation occurred in 7 of the 16 women (44%) treated
with bed rest alone, compared with none (0/19) in those
treated with McDonald cerclage plus bed rest (P = .002).
In addition, neonatal morbidity was significantly higher in
the bed rest alone group (8/16) than the cerclage-plus-bed
rest group (1/19, P = .005). However, small patient numbers limit both of these studies. In addition, given the limited number of well-designed randomized studies on
urgent cerclage, the management of women who have
ultrasound findings of a short cervix or funneling remains
speculative, and the decision to proceed with cerclage
should be made with caution.
Women who present with advanced cervical dilation
in the absence of labor and abruption have historically
been candidates for emergency cerclage. No randomized
trials have studied this situation. Although retrospective
studies are numerous (39, 4245), their findings are limited by selection bias, inadequate patient numbers, and
inconsistent selection criteria.
How should the finding of a short cervix in

the second trimester be treated?
Assessment of cervical length may occur as part of a

complete obstetric ultrasonographic survey or in response
to patient symptoms or previous obstetric history. If
transvaginal ultrasonography before 1620 weeks of gestation identifies a short cervix, the examination should be
repeated because of the inability to adequately distinguish the cervix from the lower uterine segment in early
pregnancy (1113). Identification of a short cervix at or
after 20 weeks of gestation should prompt assessment of
1) the fetus for anomalies, 2) uterine activity to rule out
preterm labor, and 3) maternal factors to rule out
chorioamnionitis. Reduction of other factors affecting
preterm labor may be considered, such as modification of
activity, cessation of coitus, and cessation of tobacco use.
In addition, serial evaluations may be performed (particularly in patients with pelvic pressure, backache, or
PRACTICE BULLETINS
How should the finding of a short cervix in

the third trimester be treated?
The appropriate evaluation of a woman whose cervical

length is below the tenth percentile (25 mm) for gestational age at or after fetal viability includes ultrasound
assessment of fetal anatomy to exclude anomalies, tocodynamometry to detect the presence of uterine contractions, and assessment of maternal factors to exclude
chorioamnionitis. If the woman is in labor, tocolytic therapy may delay delivery long enough to promote fetal lung
maturation with maternal glucocorticoid therapy. The
presence of chorioamnionitis warrants immediate delivery and the use of broad-spectrum antibiotics. In the
absence of labor or chorioamnionitis, modification of
activity, pelvic rest, and tobacco cessation, in addition to
expectant management, may be considered. The role of
cerclage in the treatment of patients with cervical insufficiency after fetal viability has not been adequately
assessed.
Is there a role for scheduled early or firsttrimester cerclage in patients with a suspicious
clinical history (eg, a few contractions or short
or dilated cervix at 20 weeks of gestation)?
There are no well-designed studies that compare firsttrimester cerclage with the success rate of the standard
timing of cerclage at 1416 weeks of gestation. In spite
of the current accuracy and resolution of first-trimester
ultrasound fetal assessment, cerclage in the first trimester

might have an adverse impact on the pregnancy and
could result in suturing the cervix with an abnormal fetus
in the uterus. The evidence-based risk-benefit ratio does
not support first-trimester cerclage, even with transabdominal procedures.
increased mucoid discharge) every few days to avoid

missing rapid changes in cervical dilation or until the
trend in cervical length can be characterized.
A patient with a history of 3 or more midtrimester
pregnancy losses or preterm deliveries may be candidates
for elective cerclage (34). In patients with a history of
fewer second-trimester pregnancy losses, urgent cerclage
is not supported by evidence-based studies, and further
transvaginal ultrasound surveillance may be the more
prudent approach.
If cervical shortening or funneling is detected, the
appropriate management remains unclear, and the decision to proceed with urgent cerclage should be made with
caution. Cervical change documented before fetal viability is a better indication for cerclage than cervical change
identified after fetal viability has been achieved.
Lastly, a woman with advanced cervical effacement
or dilatation or both should be counseled about the paucity of data to support the efficacy of emergency cerclage,
as well as the potential associated maternal and neonatal
morbidity. However, emergency cerclage may be considered in such women in the absence of clinical chorioamnionitis or labor.
853
Is cerclage placement associated with an

increase in morbidity?
Rupture of membranes, chorioamnionitis, and suture displacement are the most common complications associated with cerclage placement, and their incidence varies
widely in relation to the timing and indications for the
cerclage. Elective cerclage placement is associated with
rupture of membranes in 1.118% of published reports
and chorioamnionitis within 4 weeks of surgery in
0.77.7% of cases (Table 1) (3, 38). Postoperative displacement of the cerclage is reported in 313% of elective cerclages and is believed to occur as a result of
contractile activity from the foreign-body effect of the
cerclage suture (3).
Urgent and emergency cerclages are associated with
a higher incidence of morbidity as a result of cervical
shortening and exposure of the fetal membranes to the
vaginal ecosystem. Retrospective studies of emergency
cerclage revealed a risk of ruptured membranes within
Table 1. Cerclage Placement: Incidence of Complication
Type of Cerclage
Complication
Percentage (%)
Elective
Rupture of membranes
0.818
Chorioamnionitis
16.2
Urgent
365.2
Chorioamnionitis
Approximately 3035
051
Chorioamnionitis
Approximately 937
Emergency
Data from Harger JH. Comparison of success and morbidity in cervical cerclage
procedures. Obstet Gynecol 1980;56:5438; Hassan SS, Romero R, Maymon E,
Berry SM, Blackwell SC, Treadwell MC, et al. Does cervical cerclage prevent
preterm delivery in patients with a short cervix? Am J Obstet Gynecol
2001;184:13259; discussion 132931; Kuhn RJ, Pepperell RJ. Cervical ligation:
a review of 242 pregnancies. Aust N Z J Obstet Gynaecol 1977;17:7983; Kurup
M, Goldkrand JW. Cervical incompetence: elective, emergent, or urgent cerclage.
Am J Obstet Gynecol 1999;181:2406; Latta RA, McKenna B. Emergent cervical
cerclage: predictors of success or failure. J Matern Fetal Med 1996;5:227; Lipitz
S, Libshitz A, Oelsner G, Kokia E, Goldenberg M, Mashiach S, et al. Outcome of
second-trimester, emergency cervical cerclage in patients with no history of cervical incompetence. Am J Perinatol 1996;13:41922; Novy MJ, Gupta A, Wothe
DD, Gupta S, Kennedy KA, Gravett MG. Cervical cerclage in the second trimester
of pregnancy: a historical cohort study. Am J Obstet Gynecol 2001;184:144754;
discussion 14546; Olatunbosun OA, al-Nuaim L, Turnell RW. Emergency cerclage compared with bed rest for advanced cervical dilatation in pregnancy. Int
Surg 1995;80:1704; Peters WA 3rd, Thiagarajah S, Harbert GM Jr. Cervical cerclage: twenty years experience. South Med J 1979;72:9337; and Rana J, Davis
SE, Harrigan JT. Improving the outcome of cervical cerclage by sonographic follow-up. J Ultrasound Med 1990;9:2758.
854
Should perioperative antibiotics and tocolytics be used in association with cerclage

placement?
Does a patient who was exposed to diethylstilbestrol require cerclage?
Diethylstilbestrol appears to cause some congenital cervical malformations, and there is concern that in utero exposure also may cause functional deficiencies in the cervix,
leading to cervical insufficiency (49, 50). To date no
definitive epidemiologic studies have proved that cervical
insufficiency is more frequent in women exposed to DES
than in comparable controls. In addition, there are no randomized trials of cerclage in such patients. One retrospective analysis (51) and one casecontrol study (52)
noted similar pregnancy outcomes between DES-exposed
Does a patient who has had a cervical biopsy

need cerclage?
No studies are available on the incidence of cervical

insufficiency based on the extent of prior cervical
surgery. A simple punch biopsy or limited loop electrosurgical excision procedure is less likely to remove or
disrupt much of the functional structure of the cervix. An
extensive cervical conization, however, is more likely to
produce functional, as well as anatomical, damage to the
cervix. Generally, prophylactic cerclage is not warranted
unless there is evidence that the biopsy disrupted the
functional capacity of the cervix or if severe anatomical
damage is apparent. It may be prudent to await the outcome of at least 1 pregnancy before assuming that cervical insufficiency is present. Serial evaluation of the
cervix after 1620 weeks of gestation may help establish
the diagnosis of cervical insufficiency. If there is anatomic absence of the portio vaginalis, a transabdominal cerclage might be indicated (2427, 46, 47).
Many investigators have used various antibiotic and

tocolytic regimens in an attempt to reduce postoperative
uterine contractions and infection after cerclage placement (39). Studies using perioperative antibiotics have
been small, nonrandomized, and inconclusive. One
casecontrol study comparing cerclage patients with controls noted no difference in pregnancy outcome or the
rate of bacterial colonization in cerclage patients who
were treated with antibiotics compared with untreated
patients (48). The use of unnecessary antibiotics may
lead to the development of resistant strains of bacteria
and other morbidity for the woman and her fetus. Thus,
caution should be used if this unproven practice is
considered.
No randomized studies have shown that use of
tocolytic therapy after cerclage is efficacious. In most
retrospective or observational studies, multivariable
regression analysis has not been performed to separate
the confounding effects of antibiotics, bed rest, and
tocolytics. The lack of clear benefit for these adjunctive
treatments suggests that these drugs should be used with
caution.
women treated with cerclage and those managed conservatively without surgery. Therefore, a woman exposed to
DES may be evaluated for cervical insufficiency using the
same clinical criteria as a nonexposed woman.
2 weeks of the operation of up to 65% of the patients

(37). Chorioamnionitis occurred in 937% of the patients
studied (see Table 1) (38, 45).
Transabdominal cerclage can be complicated by rupture of membranes and chorioamnionitis. It carries the
added risk of intraoperative hemorrhage from the uterine
veins when the cerclage band is tunneled between the
bifurcation of the uterine artery, as well as the known
risks associated with laparotomy (2427, 46, 47). Lastly,
life-threatening complications of uterine rupture and
maternal septicemia are extremely rare but have been
reported with all types of cerclage.
When is removal of cerclage indicated in a

patient with preterm labor or preterm rupture
of membranes?
Small, retrospective, nonrandomized studies have

reported disparate results of delaying cerclage removal
after preterm rupture of membranes. One study reported
no difference in infection rates and neonatal outcome
between patients with premature rupture of membranes
who underwent immediate cerclage removal and controls without cerclage (53). A later study reported high
neonatal mortality (70%), mainly caused by neonatal
sepsis, in 10 preterm infants delivered after delayed cerclage removal, compared with a 20% perinatal mortality
rate with immediate cerclage removal (54). Two articles
reached differing conclusions on this issue. One comparison of 25 immediate cerclage removals with 37
delayed removals found a prolonged latent period
between rupture of membranes and delivery without
improvement of neonatal morbidity or mortality and no
increase in maternal infectious morbidity (55). Another
report comparing 30 immediate cerclage removals with
51 delayed removals found no significant prolongation
of latency, again with no improvement in neonatal outcome (56). Because the available studies are small and
nonrandomized, the optimal timing of cerclage removal
is unclear.
PRACTICE BULLETINS
Summary of
Recommendations
Serial assessments in low-risk women to screen for

cervical insufficiency are of low yield and should not
be done routinely.
Serial ultrasound examinations should be considered

in a patient with historical risk factors for cervical
insufficiency and should be initiated between 16 and
20 weeks of gestation or later.
An elective cerclage can be considered in a patient

with a history of 3 or more unexplained midtrimester
pregnancy losses or preterm deliveries.
Women exposed to DES in utero may be evaluated

for cervical insufficiency using the same clinical criteria as nonexposed individuals.
The evaluation of a patient with cervical shortening

or funneling should include a comprehensive ultrasonographic assessment of the fetus to rule out
anomalies, as well as physical and laboratory assessments to rule out labor and chorioamnionitis.
Given the advances in neonatal care and the potential

maternal and fetal morbidity associated with cerclage,
surgical correction of cervical insufficiency should
be limited to pregnancies before fetal viability has
been achieved.
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27. Anthony GS, Walker RG, Cameron AD, Price JL, Walker
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Am J Obstet Gynecol 1999;181:80915. (Level II-2)
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32. Lazar P, Gueguen S, Dreyfus J, Renaud R, Pontonnier G,
Papiernik E. Multicentered controlled trial of cervical cerclage in women at moderate risk of preterm delivery. Br J
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34. Final report of the Medical Research Council/Royal
College of Obstetricians and Gynaecologists multicentre
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Working Party on Cervical Cerclage. Br J Obstet

35. Dijkstra K, Funai EF, ONeill L, Rebarber A, Paidas MJ,
Young BK. Change in cervical length after cerclage as a
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36. Guzman ER, Forster JK, Vintzileos AM, Ananth CV,
Walters C, Gipson K. Pregnancy outcomes in women
treated with elective versus ultrasound-indicated cervical
cerclage. Ultrasound Obstet Gynecol 1998;12:3237.
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37. Hassan SS, Romero R, Maymon E, Berry SM, Blackwell
SC, Treadwell MC, et al. Does cervical cerclage prevent
preterm delivery in patients with a short cervix? Am J
(Level II-2)
38. Kurup M, Goldkrand JW. Cervical incompetence: elective,
emergent, or urgent cerclage. Am J Obstet Gynecol 1999;
181:2406. (Level II-3)
39. Novy MJ, Gupta A, Wothe DD, Gupta S, Kennedy KA,
Gravett MG. Cervical cerclage in the second trimester of
pregnancy: a historical cohort study. Am J Obstet Gynecol
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40. Rust OA, Atlas RO, Reed J, van Gaalen J, Balducci J.
Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage therapy may
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41. Althuisius SM, Dekker GA, Hummel P, Bekedam DJ, van
Geijn HP. Final results of the Cervical Incompetence
Prevention Randomized Cerclage Trial (CIPRACT): therapeutic cerclage with bed rest versus bed rest alone. Am J
42. Barth WH Jr, Yeomans ER, Hankins GD. Emergent cerclage. Surg Gynecol Obstet 1990;170:3236. (Level III)
43. Latta RA, McKenna B. Emergent cervical cerclage: predictors of success or failure. J Matern Fetal Med 1996;
5:227. (Level II-2)
44. Lipitz S, Libshitz A, Oelsner G, Kokia E, Goldenberg M,
Mashiach S, et al. Outcome of second-trimester, emergency cervical cerclage in patients with no history of
cervical incompetence. Am J Perinatol 1996;13:41922.
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45. Olatunbosun OA, al-Nuaim L, Turnell RW. Emergency
cerclage compared with bed rest for advanced cervical
dilatation in pregnancy. Int Surg 1995;80:1704.
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46. Mahran M. Transabdominal cervical cerclage during pregnancy. A modified technique. Obstet Gynecol 1978;52:
5026. (Level III)
47. Novy MJ. Transabdominal cervicoisthmic cerclage: a reappraisal 25 years after its introduction. Am J Obstet Gynecol
48. Kessler I, Shoham Z, Lancet M, Blickstein I, Yemini M,
Miskin A, et al. Complications associated with genital colonization in pregnancies with and without cerclage. Int J
PRACTICE BULLETINS
49. Ludmir J, Landon MB, Gabbe SG, Samuels P, Mennuti

MT. Management of the diethylstilbestrol-exposed pregnant patient: a prospective study. Am J Obstet Gynecol
1987;157:6659. (Level II-2)
50. Mangan CE, Borow L, Burtnett-Rubin MM, Egan V,
Giuntoli RL, Mikuta JJ. Pregnancy outcome in 98 women
exposed to diethylstilbestrol in utero, their mothers, and
unexposed siblings. Obstet Gynecol 1982;59:3159.
(Level II-2)
51. Levine RU, Berkowitz KM. Conservative management
and pregnancy outcome in diethylstilbestrol-exposed
women with and without gross genital tract abnormalities.
52. Michaels WH, Thompson HO, Schreiber FR, Berman JM,
Ager J, Olson K. Ultrasound surveillance of the cervix
during pregnancy in diethylstilbestrol-exposed offspring.
53. Blickstein I, Katz Z, Lancet M, Molgilner BM. The outcome of pregnancies complicated by preterm rupture of
the membranes with and without cerclage. Int J Gynaecol
Obstet 1989;28:23742. (Level II-2)
54. Ludmir J, Bader T, Chen L, Lindenbaum C, Wong G. Poor
perinatal outcome associated with cerclage in patients
with premature rupture of membranes. Obstet Gynecol
1994;84:8236. (Level II-2)
55. Jenkins TM, Berghella V, Shlossman PA, McIntyre CJ,
Maas BD, Pollock MA, et al. Timing of cerclage removal
after preterm premature rupture of membranes: maternal
and neonatal outcomes. Am J Obstet Gynecol 2000;183:
84752. (Level II-3)
56. McElrath TF, Norwitz ER, Lieberman ES, Heffner LJ.
Management of cervical cerclage and preterm premature
rupture of the membranes: should the stitch be removed?
857

to conduct a literature search to locate relevant articles published between January 1985 and July 2003. The search
Force:
I
Evidence obtained from at least 1 properly designed
randomized controlled trial.
than 1 center or research group.
type of evidence.
committees.

01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
Cervical insufficiency. ACOG Practice Bulletin No. 48. The American
10919.
858
ACOG
PRACTICE
BULLETIN
NUMBER 49, DECEMBER 2003
(Replaces Technical Bulletin Number 218, December 1995)

of Andrew Satin, MD. The information is designed to aid
of practice.
Reaffirmed 2009
Dystocia and
Augmentation of Labor
Dystocia, characterized by the slow, abnormal progression of labor, is the leading indication for primary cesarean delivery in the United States. Currently, 1
in every 10 women who give birth in the United States has had a previous
cesarean delivery (1). Because many repeat cesarean deliveries are performed
after primary operations for dystocia, an estimated 60% of all cesarean deliveries in the United States are attributable to the diagnosis of dystocia (2). Thus,
with decreasing rates of vaginal birth after cesarean delivery, dystocia is the
leading cause of both operative vaginal delivery and cesarean delivery and
their accompanying complications.
Despite the high prevalence of labor disorders, considerable variability exists
in the diagnosis, management, and criteria for dystocia that requires intervention. The purpose of this document is to provide a review of the definition of dystocia, risk factors associated with dystocia, the criteria that require delivery, and
approaches to clinical management of labor complicated by dystocia.
Background
Definitions
The definition of labor is the presence of uterine contractions of sufficient
intensity, frequency, and duration to bring about demonstrable effacement and
dilation of the cervix. At present, there is much uncertainty about the definition
of the latent phase of labor, but there is agreement that women in labor enter the
active phase when cervical dilatation is between 3 cm and 4 cm (3). The active
phase is characterized by the most rapid changes in cervical dilatation as plotted against time. The active phase of labor includes both an increased rate of
cervical dilation and, ultimately, descent of the presenting fetal part. This document focuses on labor subsequent to entering the active phase, diagnosis of
active-phase abnormalities, clinical considerations, and management recommendations for the active phase and the second stage of labor.
PRACTICE BULLETINS
Dystocia is defined as abnormal labor that results

from what have been categorized classically as abnormalities of the power (uterine contractions or maternal
expulsive forces), the passenger (position, size, or presentation of the fetus), or the passage (pelvis or soft tissues). The term cephalopelvic disproportion has been
used to describe a disparity between the size of the
maternal pelvis and the fetal head that precludes vaginal
delivery. Because dystocia can rarely be diagnosed with
certainty, the relatively imprecise term failure to
progress has been used, which includes lack of progressive cervical dilation or lack of descent of the fetal
head or both. The diagnosis of dystocia should not be
made before an adequate trial of labor has been
achieved. A more practical classification is to categorize
labor abnormalities as slower-than-normal (protraction
disorders) or complete cessation of progress (arrest
disorders).
Augmentation refers to stimulation of uterine contractions when spontaneous contractions have failed to
result in progressive cervical dilation or descent of the
fetus. Augmentation should be considered if the frequency of contractions is less than 3 contractions per 10 minutes or the intensity of contractions is less than 25 mm Hg
above baseline or both. Before augmentation, an assessment of the maternal pelvis and cervix and fetal position,
station, and well-being should be performed. Contraindications to augmentation are similar to those for labor
induction and may include placenta or vasa previa,
umbilical cord presentation, prior classical uterine incision, active genital herpes infection, pelvic structural
deformities, or invasive cervical cancer.
Second-Stage Arrest
In a retrospective review of nearly 7,000 women with
minimal intervention, the mean length of the second
stage of labor was 19 minutes for multiparous women
and 54 minutes for nulliparous women, without regard
for anesthesia (4). The use of conduction anesthesia
increased the mean duration of the second stage by
2030 minutes (4, 5). In a nulliparous woman, the diagnosis of a prolonged second stage should be considered
when the second stage exceeds 3 hours if regional anesthesia has been administered or 2 hours if no regional
anesthesia is used. In multiparous women, the diagnosis
can be made when the second stage exceeds 2 hours with
regional anesthesia or 1 hour without. A prolonged second stage of labor warrants clinical reassessment of the
woman, fetus, and expulsive forces. These statistical
parameters are useful for defining when labor becomes
prolonged and intervention should be considered.
859
Criteria for Arrest that Require Delivery

Oxytocin administration should be considered when a
patient has a protraction or arrest disorder. The goal of
oxytocin administration is to effect uterine activity sufficient to produce cervical change and fetal descent
while avoiding uterine hyperstimulation and fetal compromise. Minimally effective uterine activity has been
defined as 3 contractions per 10 minutes averaging
greater than 25 mm Hg above baseline. However, adequate labor encompasses a wide range of uterine activity,
as previously noted. The amplitude of each contraction
may vary from 25 mm Hg to 75 mm Hg, and contractions may occur for a total of 24.5 minutes in every
10-minute window, achieving 95395 Montevideo units
(the peak of contractions in millimeters of mercury multiplied by the frequency per 10 minutes). Typically, a
goal of a maximum of 5 contractions in a 10-minute
period with resultant cervical dilation is considered adequate. As a general guideline, hyperstimulation may be
defined as a persistent pattern of more than 5 contractions in 10 minutes, contractions lasting 2 minutes or
more, or contractions of normal duration occurring
within 1 minute of each other, and may or may not
include nonreassuring fetal heart rate measurements.
The term tachysystole has been used to define hyperstimulation without corresponding fetal heart rate
abnormalities to distinguish this complication from
hyperstimulation with fetal heart rate changes.
In a retrospective report of induction of labor
with oxytocin, 91% of women achieved at least
200224 Montevideo units, and 40% achieved at least
300 Montevideo units (6). Accordingly, it has been suggested that before an arrest disorder can be diagnosed in
the first stage of labor, the following 2 criteria should be
met: 1) the latent phase is completed, and 2) a uterine
contraction pattern exceeds 200 Montevideo units for
2 hours without cervical change. However, there is no
convincing evidence to demonstrate a reduction in the
rate of cesarean deliveries or improvement in perinatal
outcome attributable to the use of the sophisticated measurements of uterine activity as compared with external
tocodynamometry.
The 2-hour rule for the diagnosis of arrest in active
labor has recently been challenged. In a clinical trial, 542
women were managed by a protocol in which, after
active-phase arrest was diagnosed, oxytocin was initiated
with the intent to achieve a sustained uterine contraction
pattern of greater that 200 Montevideo units (7).
Cesarean delivery was not performed for labor arrest
until there were at least 4 hours of a sustained uterine
contraction pattern of greater than 200 Montevideo units,
860
or a minimum of 6 hours of oxytocin augmentation if the

contraction pattern could not be achieved. The protocol
resulted in a high rate of vaginal delivery (92%) with
no severe adverse maternal or fetal outcomes. Thus,
extending the minimum period of oxytocin augmentation
for active-phase arrest from 2 hours to 4 hours appears
effective.
Reassessment of the fetus may identify those that are
not tolerating labor. Intervention is not necessary for all
factors solely based on time (8). Contemporary practice
patterns may be associated with more variation in duration of the second stage of labor (5). If progress is being
made, the duration of the second stage alone does not
mandate intervention by operative delivery. Once a second-stage arrest disorder is diagnosed, the obstetrician
has 3 options: 1) continued observation, 2) operative
vaginal delivery, or 3) cesarean delivery. The decision to
perform an operative delivery in the second stage versus
continued observation should be made on the basis of
clinical assessment of the woman and the fetus and the
skill and training of the obstetrician.
Risk Factors for Dystocia
Dystocia may be associated with serious complications

for both the woman and the fetus. Infection, namely
chorioamnionitis, is a consequence of prolonged labor,
especially in the setting of ruptured membranes (14). In
one report analyzing more than 500 women, labor was
4.7 hours longer on average when chorioamnionitis was
diagnosed late in labor (12). Fetal infection and bacteremia, including pneumonia caused by aspiration of
infected amniotic fluid, is linked to prolonged labor.
There is debate whether a prolonged second stage may be
associated with injuries of the pelvic floor (15, 16). In
cases of neglected, obstructed labors (more likely to be
seen in developing countries), pressure necrosis after
very prolonged second stages may result in vesicovaginal, vesicocervical, or rectovaginal fistulas (17, 18).
In the past, labor, particularly the second stage, was
thought to be a time of asphyxial risk for the fetus. In one
large study of more than 6,000 women with normal fetal
heart rate monitoring tracings in labor, duration in and of
itself was not associated with low 5-minute Apgar scores,
neonatal seizures, or admission to the neonatal intensive
care unit (8).
Role of Allied Personnel

Continuous support during labor from caregivers, including nurses, midwives, or lay individuals, has a number of
benefits for women and their newborns, with no apparent
harmful effects (19). The continuous presence of a support person may reduce the likelihood of the use of medication for pain relief, operative delivery, and patient
dissatisfaction (1921).

Recommendations
Cesarean delivery for dystocia or arrest of labor that

requires delivery may occur in either the first or second
stage of labor. Cesarean delivery rates for dystocia are
similar but are associated with different factors when
performed in the first or second stage (9, 10). In a retrospective review of nearly 150,000 deliveries, patients
with nonprogressive labor in the first stage were significantly older and more likely to have complications,
such as previous perinatal death, diabetes, hypertension, infertility treatment, premature rupture of
membranes, and amniotic fluid abnormalities, when
compared with patients experiencing second-stage
arrest (9). Labors that failed to progress during the first
stage were significantly associated with nonreassuring
fetal heart rate patterns when compared with pregnancies with dystocia in the second stage. The significant
increase in cesarean deliveries during the first stage of
labor among women at high risk can reflect exaggerated concern of caregivers. A variety of labor interventions and complications have been associated with slow
progress in labor, including epidural analgesia,
chorioamnionitis, pelvic contractions, and macrosomia
(11, 12). Several factors have been shown to be associated with longer duration of the second stage, including
epidural analgesia, occiput posterior position, longer
first stage of labor, nulliparity, short maternal stature,
birth weight, and high station at complete cervical dilation (13).
Relationship of Dystocia to Other

Adverse Outcomes
Can dystocia be predicted?
The ability to accurately predict which women or fetuses

will ultimately benefit from operative delivery has been
disappointing (13). Generally, orderly, spontaneous progression to full dilation indicates that vaginal delivery
most likely will be successful. Abnormal labor or dystocia in the first or second stage of labor can be associated
with 1 or more abnormalities of the cervix, uterus, maternal pelvis, or fetus. In addition, advanced maternal age,
nulliparity, maternal anxiety, multiple gestation, and
intrauterine infections have been reported to be associated with longer active labors (12, 22). Epidural analgesia,
PRACTICE BULLETINS
How does epidural analgesia affect the

progress of labor?
Is there a role for intrauterine pressure

catheters in diagnosing dystocia?
Uterine activity can be monitored by palpation, external

tocodynamometry, or internal pressure catheters. Current
Does ambulation affect the course of labor?
Women experiencing normal labor should be encouraged

to assume a position in which they are most comfortable.
Walking during labor has not been shown to enhance or
impair progress in labor. Investigators who randomized
more than 1,000 women in active labor at term to either
walking or no walking found no differences in the duration of labor, need for oxytocin, use of analgesia, operative vaginal delivery, or cesarean delivery between study
groups (32). Neonatal outcomes also were similar, and
walking was not harmful to the women or their newborns. Ambulatory epidural analgesia with walking or
sitting does not appear to shorten labor duration. In a randomized trial, 160 nulliparous women were assigned to
receive epidural either with or without ambulation (33).
There was no difference in time from epidural placement
to complete dilation between the groups. Thus, ambulation in labor is not harmful, and mobility may result in
greater comfort and ability to tolerate labor (34).
In a systematic review of 11 randomized trials involving

3,157 women, epidural analgesia was associated with
increases in the duration of the first and second stages of
labor, incidence of fetal malpositions, use of oxytocin,
and operative vaginal delivery (11). Nevertheless, epidural analgesia was not shown to increase the cesarean delivery rate for dystocia.
Less controversial is the causal role epidural analgesia plays in prolonging labor by 4090 minutes (2427)
and in the approximate 2-fold increased need for oxytocin augmentation (27, 28). These findings are supported by most prospective studies as well as meta-analyses
(11, 25). An increased risk of a second stage of labor
longer than 2 hours (24, 26) in women with epidural
analgesia likely contributes to the higher rates of operative vaginal delivery seen in most prospective studies.
The 4 best prospective studies, in which elective forceps
use was not permitted (24, 2628), yielded a combined
relative risk (RR) of 1.9 (95% confidence interval [CI]
1.4, 2.5) of forceps delivery in women who received
epidural analgesia. Some investigators have found a
decreased risk of operative vaginal delivery with combined spinal epidural when compared with low-dose
epidural (29). This finding is difficult to interpret because
elective forceps were not excluded in this study, and the
rate of forceps use was high (2840%). High rates of
operative vaginal deliveries have been implicated in the
increased rate of third- and fourth-degree lacerations seen
in women who had epidural analgesia (30).
evidence does not support routine use of intrauterine

pressure catheters for labor management. In a randomized trial of 250 patients undergoing labor augmentation
with contractions monitored by either external tocotransducers or intrauterine catheters, there were no significant
differences between the groups regarding length of labor,
dose of oxytocin, hyperstimulation, cesarean delivery, or
neonatal outcomes (31). Nevertheless, intrauterine pressure catheters may be beneficial for women when the
evaluation of contractions is difficult because of such factors as obesity or lack of one-on-one nursing care or
when response to oxytocin is limited.
prolonged first stage of labor, nulliparity, large fetuses,

and high station at complete cervical dilation are associated with a longer second stage (13).
In an attempt to identify risk factors for difficult
delivery among nulliparous women in the second stage of
labor, investigators used a multivariate analysis of 1,862
women and found that the risk of difficult delivery was
increased for women of short stature (less than 150 cm),
age greater than 35 years, gestational age greater than
41 weeks, interval between epidural induction and full
cervical dilation of greater than 6 hours, fetal station above
+2 cm at full cervical dilation, or occiput posterior fetal
position (23). Importantly, a multivariable predictive
model of difficult delivery found a sensitivity of only 57%,
specificity of 75%, and positive predicative value of 35%.
861
Is there a role for pelvimetry in the management of dystocia?
A systematic review that included more than 1,000

women in 4 trials found that women undergoing X-ray
pelvimetry were more likely to undergo cesarean delivery
(odds ratio [OR], 2.17; 95% CI 1.63, 2.88) without any
significant impact on perinatal outcome (35). Although
the reasons for the increase in cesarean delivery rates are
not clearly defined, the author concluded there is not
enough evidence to support the use of X-ray pelvimetry
in women whose fetuses have cephalic presentations.
Other investigators expanded the use of X-ray pelvimetry
by developing the fetal-pelvic index as a predictor of the
likelihood of vaginal delivery in women at high risk for
cesarean delivery (36). The test incorporates the determination of fetal weight by ultrasonography compared with
the size of the pelvis as determined by X-ray pelvimetry.
Initial studies in patients at risk for cesarean delivery
demonstrated significant diagnostic ability of the test
862
Are there data supporting the benefits of

caregivers providing continuous support during labor?
Continuous support during labor from caregivers (nurses,

midwives, or lay individuals) may have a number of
benefits for women and their newborns. A randomized
trial of 413 nulliparous women compared one-on-one
nursing care with usual care (1 nurse monitoring 2 or 3
laboring women) and found a reduction in the need for
oxytocin stimulation (RR, 0.83%; 95% CI 0.67, 1.04)
(21). There were no differences in labor duration, cesarean deliveries, epidural analgesia, or neonatal intensive
care admissions. A comparison of continuous support of
a doula with an inconspicuous observer found that continuous labor support was associated with a reduction in
cesarean deliveries (8% versus 13%) and forceps deliveries (8% versus 21%) (20). A systematic review that
included more than 12,000 women in 15 trials found that
the continuous presence of a support person reduced the
likelihood of medication for pain relief, operative vaginal
delivery, cesarean delivery, and 5-minute Apgar scores
less than 7 (19, 39). Few data compare differences in
benefits on the basis of level of training of support personnelthat is, whether the caregivers were nurses,
midwives, or doulas. Continuous support during labor
has several benefits without any evidence of harmful
effects.
Does the degree of hydration affect the

course of labor?
In many obstetric centers, establishing an intravenous

infusion of fluids in early labor has become routine.
Although not necessary in all normally laboring women,
intravenous fluids are beneficial before epidural analgesia, and the practice provides intravenous access and the
ability to administer oxytocin prophylaxis for postpartum
hemorrhage. On the basis of knowledge that increased

fluids improve skeletal muscle performance during prolonged exercise, scientists speculated that increased
intravenous fluids may affect labor progress (40). Nearly
200 nulliparous women with uncomplicated pregnancies
in spontaneous active labor were randomized to receive
either 125 mL or 250 mL of intravenous fluid per hour.
The frequency of labor lasting longer than 12 hours was
higher in the 125-mL group (26% versus 13%). Furthermore, there was a lower frequency of oxytocin administration for dystocia in the higher fluid rate group (49%
versus 65%). The potential of natural hydration status to
affect the course of labor warrants further investigation.
(37). However, further prospective studies are necessary

to establish the usefulness of this diagnostic modality to
predict dystocia.
Clinical pelvimetry can be useful to qualitatively
identify the general architectural features of the pelvis
and identify patients at risk for dystocia. Researchers correlated pelvimetry data from postpartum magnetic resonance imaging (MRI) with fetal and neonatal dimensions
to evaluate criteria for diagnosis of cephalopelvic disproportion (38). Fetal head volume estimates exceeded
MRI-measured capacity in nearly 90% of nulliparous
women who underwent cesarean delivery because of
cephalopelvic disproportion. A prospective investigation
of MRI has not been performed, and the use of MRI to
measure pelvic capacity remains investigational.
Is there a role for active management of

labor?
A system of labor management for nulliparous women,

termed active management of labor, was developed
in Ireland (41). Although many obstetricians have
focused on the use of high-dose oxytocin as the principal
component of the active management of labor, it is
important to emphasize that high-dose oxytocin is just
one part of this approach. In fact, most women undergoing active management of labor do not receive
oxytocin.
Active management of labor is confined to nulliparous women with singleton, cephalic presentations at
term that show no evidence of fetal compromise. Active
management of labor, as developed and practiced in
Ireland, involves several distinct entities: patient education, strict criteria for the diagnosis of labor, strict criteria for the determination of abnormal progress of labor,
high-dose oxytocin infusion, one-to-one nursing support
in labor, strict criteria for interpretation of fetal compromise, and peer review of operative deliveries.
The safety of active management of labor has been
demonstrated by several randomized trials involving
more than 3,000 patients (10, 4244). Active management of labor has not been associated with an increase in
maternal or neonatal morbidity and mortality (44, 45).
Unfortunately, success in decreasing cesarean delivery
rates with active management of labor has not been uniform. One large randomized trial reported a statistically
significant reduction in cesarean deliveries only after
controlling for numerous confounding variables (43). A
meta-analysis of 4 randomized trials failed to show a
reduction in cesarean deliveries related to active management of labor (RR, 0.93; 95% CI 0.8, 1.08) (44).
Active management of labor is not associated with
untoward maternal or neonatal outcomes. It may lead to
shortened labor in nulliparous women but has not consistently led to a reduction in cesarean deliveries.
PRACTICE BULLETINS
Is low-dose oxytocin superior to high-dose

regimens for augmentation?
Should women with twin gestations undergo

augmentation of labor?
Twin gestation is not a contraindication to augmentation

of labor, but it does warrant special attention. In a retrospective report, 62 women with twin gestations were
Table 1. Labor Augmentation with Oxytocin: Examples of

Low-Dose and High-Dose Regimens
Regimen
Starting
Dose
(mU/min)
Low-Dose
0.51*
3040
20
12
15
40
15
40
6, 3, 1
2040
42
High-Dose
Incremental
Increase
(mU/min)
Dosage
Interval
(min)
Maximum
Dose
(mU/min)
*Seitchik J, Amico JA, Castillo M. Oxytocin augmentation of dysfunctional labor.

V. An alternative oxytocin regimen. Am J Obstet Gynecol 1985;151:75761.
Hauth JC, Hankins GD, Gilstrap LC 3rd, Strickland DM, Vance P. Uterine contraction pressures with oxytocin induction/augmentation. Obstet Gynecol
1986;68:3059.
ODriscoll K, Foley M, MacDonald D. Active management of labor as an alternative to cesarean section for dystocia. Obstet Gynecol 1984;63:48590.
Satin AJ, Maberry MC, Leveno KJ, Sherman ML, Kline DM. Chorioamnionitis: a
harbinger of dystocia. Obstet Gynecol 1992;79:9135.
matched by parity, cervical dilatation at initiation of oxytocin, gestational age, oxytocin dosage regimen, and
indications for oxytocin with controls with singleton
pregnancies (51). Twenty-seven women received oxytocin for augmentation and 35 for induction. Women with
twin pregnancies responded similarly to those with singleton pregnancies regarding the maximum oxytocin
dosage, time to delivery, and successful vaginal delivery.
The authors concluded that twin gestation has no adverse
impact on the effectiveness or efficacy of oxytocin used
for labor stimulation. In a small study of women with
twin gestations undergoing labor induction and oxytocin
augmentation, no adverse neonatal outcomes were
observed (52). In a retrospective review of 134 women
with twin gestations who underwent a trial of labor, 49
women required augmentation (53). Augmentation was
not found to be a significant risk factor for cesarean
delivery or adverse outcomes. Thus, twin gestation does
not preclude the use of oxytocin for labor augmentation.
Hypocontractile uterine activity is treated with oxytocin,

the only medication approved by the U.S. Food and Drug
Administration for labor stimulation. Numerous protocols
for initial dose, incremental increases, and time intervals
between doses have been studied. Regardless of whether a
low-dose or high-dose oxytocin regimen is used, oxytocin
is infused to titrate dose to effect because prediction of a
womans response to a particular dose is not possible (46).
In a blinded, randomized study comparing a high-dose
(4.5 mU/min every 30 minutes) with a low-dose
(1.5 mU/min every 30 minutes) oxytocin protocol for augmentation, high-dose oxytocin was associated with a significant shortening of labor without a significant difference
in cesarean delivery rates (47). No differences in neonatal
outcomes were noted between groups. In another randomized trial of more than 300 women, use of high-dose oxytocin for augmentation benefited both nulliparous women
and parous women by decreasing the mean time to correct
the labor abnormality by nearly 2 hours and decreasing the
need for cesarean delivery (10.4% versus 25.7%) (48).
In a prospective trial involving 1,676 women, comparing high-dose (6 mU/min every 20 minutes) with lowdose (12 mU/min every 20 minutes) oxytocin regimens
for augmentation, the high-dose regimen was associated
with fewer cesarean deliveries for dystocia (9% versus
12%), a 3-hour reduction in mean time to delivery, fewer
incidences of chorioamnionitis (8% versus 12%), and
fewer cases of neonatal sepsis (0.3% versus 2%) (49).
The high-dose regimen was associated with an increase
in hyperstimulation, but no adverse fetal effects were
observed. In another small randomized trial, a high-dose
regimen was associated with a shorter second stage of
labor without measurable differences in neonatal outcomes (50). Thus, the current data available do not
support the notion that low-dose oxytocin regimens are
superior to high-dose regimens for augmentation of
labor. Low-dose regimens are associated with less uterine
hyperstimulation and lower maximum doses. High-dose
regimens may be used for multiparous women, but there
are no data available to support the use of high-dose oxytocin regimens for augmentation in a woman with a previously scarred uterus. Importantly, a wide variety of
oxytocin regimens may be used for labor augmentation
provided proper precautions are met (Table 1).
863
How does amniotomy affect labor?
Amniotomy is commonly performed to induce or augment labor. Surprisingly few studies exist focusing on the
impact of amniotomy on augmentation. A recent systematic review primarily addressed the effect of amniotomy
on the rate of cesarean delivery (54). This review included controlled trials of amniotomy during the first stage of
labor. Amniotomy was associated with a reduction in
labor duration of 12 hours and a decrease in the use of
oxytocin (OR, 0.79; 95% CI 0.67, 0.92). In a trial of 459
women randomized to undergo either elective amniotomy
(amniotomy group) or no amniotomy unless there were
specific indications (intact group), analysis of fetal heart
rate patterns revealed more mild or moderate variable
864
X-ray pelvimetry alone as a predictor of dystocia

has not been shown to have benefit, and, therefore,
is not recommended.
Intrauterine pressure catheters may be helpful in the
management of dystocia in selected patients, such as
those who are obese.
Patients should be counseled that walking during

labor does not enhance or improve progress in labor
nor is it harmful.
Amniotomy may be used to enhance progress in

active labor, but may increase the risk of maternal
fever.

Active management of labor may shorten labor in

nulliparous women, although it has not consistently
been shown to reduce the rate of cesarean delivery.
Summary of
Recommendations
No overwhelming evidence has identified the most effective method of fetal heart rate surveillance when oxytocin
is used for augmentation. A systematic review of continuous electronic heart rate monitoring for fetal assessment
during labor identified 13 randomized trials addressing
efficacy and safety of electronic fetal monitoring (56).
Routine electronic fetal monitoring was associated with a
statistically significant decrease in neonatal seizures.
(RR, 0.51; 95% CI 0.32, 0.82). No differences were seen
in low Apgar scores, neonatal intensive care unit admissions, perinatal deaths, or cerebral palsy. Electronic fetal
monitoring was associated with an increase in cesarean
deliveries (RR, 1.41; 95% CI 1.23, 1.61) and operative
vaginal deliveries (RR, 1.2; 95% CI 1.11, 1.3). Well-controlled studies of intermittent auscultation of the fetal
heart rate have shown it to be equivalent to continuous
electronic fetal monitoring when performed at specific
intervals with a one-to-one nurse-to-patient ratio (5761).
There are no comparative data indicating the optimal frequency at which intermittent auscultation should be performed in the absence of risk factors.
Continuous support during labor from caregivers

should be encouraged because it is beneficial for
women and their newborns.
Should electronic fetal monitoring be used

during oxytocin augmentation?
decelerations in the active phase of labor in the amniotomy group (55). Importantly, there was no difference in
nonreassuring heart rates or operative deliveries. Amniotomy was associated with a decreased need for oxytocin
augmentation (36% versus 76%) and a shorter active phase
of labor (4 hours, 35 minutes, versus 5 hours, 56 minutes).
Another randomized trial addressed the impact of
amniotomy after an arrest disorder was diagnosed in the
active phase (14). Women with an active phase arrest were
randomized to receive either oxytocin with intact membranes or oxytocin with amniotomy and internal monitoring. A trend toward longer labor (44 minutes longer) was
seen in the intact group with no differences in cesarean
deliveries. The amniotomy group had a higher incidence
of fever. Thus, amniotomy may enhance progress in the
active phase and negate the need for oxytocin augmentation but may increase the risk of chorioamnionitis.
Women with twin gestations may undergo augmentation of labor.
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WR. A randomized controlled trial of the effect of
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PRACTICE BULLETINS

Force:
I

type of evidence.
committees.
867
Copyright December 2003 by the American College of

of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic,
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
Dystocia and augmentation of labor. ACOG Practice Bulletin No. 49.
2003;102:144554.
868
ACOG
PRACTICE
BULLETIN
NUMBER 52, APRIL 2004

of T. Murphy Goodwin, MD.
of practice.
Reaffirmed 2009
Nausea and Vomiting of

Pregnancy
Nausea and vomiting of pregnancy is a common condition that affects the
health of both the pregnant woman and her fetus. It can diminish the womans
quality of life and also contributes significantly to health care costs and time
lost from work (1). Because morning sickness is common in early pregnancy, the presence of nausea and vomiting of pregnancy may be minimized by
health care providers and by pregnant women (1) and, thus, undertreated. One
investigator found that fewer than 50% of women who called a nausea and
vomiting of pregnancy hotline and who subsequently terminated their pregnancies because of severe nausea and vomiting of pregnancy had been offered any
sort of antiemetic therapy (2, 3). Of those offered treatment, 90% were offered
regimens that were not likely to be effective. Furthermore, some women do not
seek treatment because of concerns about safety (4). Yet, once symptoms of nausea and vomiting of pregnancy progress, treatment can become more difficult;
treatment in the early stages may prevent more serious complications, including hospitalization (5). Mild cases of nausea and vomiting of pregnancy may be
resolved with lifestyle and dietary changes, and safe and effective treatments
are available for more severe cases. The womans perception of the severity of
her symptoms plays a critical role in the decision of whether, when, and how to
treat nausea and vomiting of pregnancy. In addition, nausea and vomiting of
pregnancy should be distinguished from nausea and vomiting related to other
causes. The purpose of this document is to review the best available evidence
about the diagnosis and management of nausea and vomiting of pregnancy.
Definition and Incidence

Nausea and vomiting of pregnancy is a common condition that affects 7085%
of pregnant women (6). Fifty percent of pregnant women have both nausea and
vomiting, 25% have nausea only, and 25% are unaffected (7, 8). One study has
PRACTICE BULLETINS
attempted to categorize nausea and vomiting of pregnancy into degrees of severity by assessing the duration
of nausea and vomiting each day (from less than 1 hour
in mild cases to more than 6 hours in severe cases) and
the amount of vomiting and retching per day (up to twice
for mild and moderate nausea and vomiting of pregnancy; more than 5 times in severe cases) (1). However,
although these categories recognize nausea and vomiting
of pregnancy as a continuum, they may not be clinically
useful. The womans perception of the severity of her
symptoms and her desire for treatment are more likely to
influence clinical decision making.
From an epidemiologic perspective, hyperemesis
gravidarum appears to represent the extreme end of the
spectrum of nausea and vomiting of pregnancy (9). The
incidence of hyperemesis gravidarum is approximately
0.52% of pregnancies. The reported incidence varies
because of different diagnostic criteria and ethnic variation in study populations. There is no single accepted
definition of hyperemesis gravidarum; it is a clinical
diagnosis of exclusion based on a typical presentation in
the absence of other diseases that could explain the findings (10). The most commonly cited criteria include persistent vomiting not related to other causes, a measure of
acute starvation (usually large ketonuria), and some discrete measure of weight loss, most often at least 5% of
prepregnancy weight (11). Electrolyte, thyroid, and liver
abnormalities also may be present. Hyperemesis gravidarum is the most common indication for admission to
the hospital during the first part of pregnancy and is second only to preterm labor as the most common reason for
hospitalization during pregnancy (12, 13).
Differential Diagnosis
The timing of the onset of nausea and vomiting is important: symptoms of nausea and vomiting of pregnancy
manifest before 9 weeks of gestation in virtually all
affected women. When a patient experiences nausea and
vomiting for the first time after 9 weeks of gestation,
other conditions should be carefully considered in the
differential diagnosis (see box). A history of a chronic
condition associated with nausea and vomiting that predates pregnancy should be sought (eg, cholelithiasis or
diabetic autonomic dysfunction). Rare cases of hyperemesis gravidarum related to a mendelian disorder of
hormone-receptor interaction (14) and mitochondrial disorders (15) suggest that at least some portion of hyperemesis is caused by discrete disease states unmasked or
exacerbated in pregnancy.
A number of physical findings point to conditions
other than nausea and vomiting of pregnancy as the cause
869
Differential Diagnosis of Nausea and

Vomiting of Pregnancy
Gastrointestinal Conditions
Gastroenteritis
Gastroparesis
Achalasia
Biliary tract disease
Hepatitis
Intestinal obstruction
Peptic ulcer disease
Pancreatitis
Appendicitis
Genitourinary Tract Conditions
Pyelonephritis
Uremia
Ovarian torsion
Kidney stones
Degenerating uterine leiomyoma
Metabolic Disease
Diabetic ketoacidosis
Porphyria
Addisons disease
Hyperthyroidism
Neurologic Disorders
Pseudotumor cerebri
Vestibular lesions
Migraines
Tumors of the central nervous system
Miscellaneous
Drug toxicity or intolerance
Psychologic
Pregnancy-Related Conditions
Acute fatty liver of pregnancy
Preeclampsia
Modified from Goodwin TM. Hyperemesis gravidarum. Clin Obstet
Gynecol 1998;41:597605.
of the nausea and vomiting. Abdominal pain is not a

prominent characteristic of nausea and vomiting of pregnancy; abdominal pain or tenderness other than mild epigastric discomfort after retching is not seen with nausea
870
and vomiting of pregnancy. Fever is not present in nausea and vomiting of pregnancy but is characteristic of
many other diseases associated with nausea and vomiting. Headache is not characteristic of nausea and vomiting of pregnancy. An abnormal neurologic examination
suggests a primary neurologic disorder as the cause of
the nausea and vomiting, although it may rarely be
encountered as a consequence of severe nausea and
vomiting of pregnancy (eg, thiamine-deficient encephalopathy or central pontine myelinolysis). Although
biochemical hyperthyroidism may be seen with hyperemesis gravidarum, goiter is not found with nausea and
vomiting of pregnancy. If a goiter is present, primary
thyroid disease should be suspected.
Etiology and Risk Factors

The etiology of nausea and vomiting of pregnancy is
unknown. Various theories have been proposed, including a psychologic predisposition (16), evolutionary
adaptation (17), and hormonal stimulus. The question of
whether certain personality types or specific psychologic disorders predispose to hyperemesis gravidarum has
been raised in the literature for many years. Two general
hypotheses have been proposed to explain nausea and
vomiting of pregnancy as a manifestation of psychopathology: 1) psychoanalytic theories describing hyperemesis gravidarum as a conversion or somatization
disorder and 2) inability of the woman to respond to
excessive life stress. There have been no controlled studies to support these hypotheses.
A recent review of psychologic theories proposed to
explain the etiology of nausea and vomiting of pregnancy concluded that the evidence that nausea and vomiting of pregnancy is caused by a conversion disorder or
an abnormal response to stress is questionable at best
(18). It is likely that the concept that nausea and vomiting of pregnancy reflects a psychologic disorder has
impeded progress toward a greater understanding of the
true etiology of the condition (19).
It also has been posited that nausea and vomiting of
pregnancy is an evolutionary adaptation that developed
to protect the woman and her fetus from foods that might
be potentially dangerous (20). This theory may explain
the temporary aversions to tastes and smells that pregnant women experience. Proponents of the adaptation
theory suggest nausea and vomiting of pregnancy is a
healthy, protective response to pregnancy. Clinical application of this theory, however, may lead to undertreatment of women whose quality of life is diminished by
nausea and vomiting of pregnancy.
Hormones
Human Chorionic Gonadotropin
Because of the close temporal relationship between peak
human chorionic gonadotropin (hCG) concentrations and
peak symptoms of nausea and vomiting of pregnancy,
hCG has been considered a likely candidate for the emetogenic stimulus arising from the placenta. A role for
hCG also is suggested by the fact that almost all studies
of thyroid hormones in pregnancy show an association
between transient hyperthyroidism and nausea and vomiting of pregnancy. It has been shown conclusively that
hCG is the thyroid stimulator of pregnancy (21); because
hyperthyroidism itself rarely causes vomiting, this finding has focused attention back on hCG and its relationship to nausea and vomiting of pregnancy. Among the
many studies comparing nonthyroidal hormone concentrations in women with and without vomiting, only hCG
and estradiol have been found to have an association.
The failure of some studies to show an association of
nausea and vomiting of pregnancy with hCG may be
related to the varying biologic activity of different hCG
isoforms as well as variation in the susceptibility of the
individual woman to any emetogenic stimulus. The
extent of the hCG stimulus may be modified by placental conditions that increase its concentration (eg, multiple gestation, molar gestation) and by hormone-receptor
interactions modifying the effect of the hormone.
Estrogen
Another hormone known to influence nausea and vomiting of pregnancy is estrogen. Nausea and vomiting of
pregnancy is more common when estradiol levels are
increased and less common when estradiol levels are
decreased (22, 23). Cigarette smoking is associated with
lower levels of both hCG and estradiol (24), and numerous studies have shown that smokers are less likely to
have hyperemesis gravidarum. Estrogens in the combined oral contraceptive pill were shown to induce nausea and vomiting in a dose-related fashion (25). Women
with nausea and vomiting after estrogen exposure were
more likely to have nausea and vomiting of pregnancy
than women who did not demonstrate such sensitivity to
estrogens (26).
Risk Factors
Women with increased placental mass (eg, advanced
molar gestation, multiple gestation) are at risk for hyperemesis gravidarum. Other risk factors include family history (genetics) or a history of hyperemesis gravidarum in
a previous pregnancy. One study found that approximately two thirds of women who described their vomit-
PRACTICE BULLETINS
ing as severe in one pregnancy had similar symptoms in

the next pregnancy; one half of women who described
their symptoms as mild in one pregnancy found that the
symptoms worsened in the next (7). Daughters and sisters of women who had hyperemesis gravidarum are
more likely to have the same problem, as are women carrying a female fetus (27). Other risk factors include a
history of motion sickness or migraines (26).
Maternal Effects of Nausea

and Vomiting of Pregnancy
Fetal Effects of Nausea and

Vomiting of Pregnancy
The effect of maternal vomiting on the embryo and fetus
depends on the severity of the condition. With mild or
moderate vomiting, there is little apparent effect on pregnancy outcome. The outcome most frequently examined
is the incidence of low birth weight (LBW). Seven studies have identified no increase in LBW with nausea and
vomiting of pregnancy (9, 10, 3943). Three of these
studies found a higher incidence of LBW among women
who did not have nausea and vomiting of pregnancy
(4143). Among women with hyperemesis gravidarum,
however, a higher incidence of LBW has been reported
(4449).
Numerous studies have documented a lower rate of

miscarriage among women with nausea and vomiting of
pregnancy and hyperemesis gravidarum when compared
with controls. This result is thought to be related to robust
placental synthesis in a healthy pregnancy rather than a
protective effect of vomiting. It is unlikely that hyperemesis gravidarum is associated with a significantly
increased risk of malformations in offspring (50). Little
is known about the long-term health of children or
women after pregnancies complicated by hyperemesis
gravidarum. Although some cases of fetal death are still
reported, they are very rare and usually are limited to
cases of extreme hyperemesis gravidarum. It is appropriate to reassure patients that the presence of nausea and
vomiting of pregnancy and even hyperemesis gravidarum
most often portends well for pregnancy outcome.

Recommendations
Many studies mix patients with hyperemesis gravidarum
and those with other degrees of nausea and vomiting of
pregnancy. Because it is likely that hyperemesis gravidarum is part of the continuum of nausea and vomiting of
pregnancy and because evidence indicates that failure to
treat early manifestations of nausea and vomiting of
pregnancy increases the likelihood of hospital admission
for hyperemesis gravidarum (37, 38), the following discussion focuses on treatment for all stages of nausea and
vomiting of pregnancy.
Until 60 years ago, nausea and vomiting of pregnancy

was an important cause of maternal mortality. In the
1930s in the United States, 7 deaths were reported among
85 women with severe vomiting (28). Although death from
nausea and vomiting of pregnancy is reported rarely today,
significant morbidity, such as Wernickes encephalopathy,
splenic avulsion, esophageal rupture, pneumothorax, and
acute tubular necrosis, have been reported in recent
years (2936). Thirty-three cases of Wernickes encephalopathy (caused by a vitamin B1 deficiency) related to
hyperemesis gravidarum have been reported in the past
20 years. It often is associated with maternal death or permanent neurological disability (2931). In addition to
increased hospital admissions (37, 38), some women
experience significant psychosocial morbidity caused by
nausea and vomiting of pregnancy, resulting in pregnancy termination.
A number of reversible responses to subacute disease states have been described in nausea and vomiting of
pregnancy, including depression, somatization, and
hypochondriasis (16). Poor support by their partners was
reported by 85% of women who called a hotline for nausea and vomiting of pregnancy (3).
871
Are nonpharmacologic therapies effective

for the treatment of nausea and vomiting of
pregnancy?
Treatment of nausea and vomiting of pregnancy begins

with prevention. Two studies found that women who
were taking a multivitamin at the time of conception
were less likely to need medical attention for vomiting
(51, 52). Therefore, it is reasonable to advise women with
a history of nausea and vomiting or hyperemesis gravidarum in a previous pregnancy to take a multivitamin at
the time of the next conception.
The womans perception of the severity of her symptoms and her desire for treatment are influential in clinical decision making. Common recommendations to
alleviate initial signs of nausea and vomiting of pregnancy include rest and avoidance of sensory stimuli that
may provoke symptoms. Frequent, small meals often are
recommended. Obstetriciangynecologists often suggest
avoiding spicy or fatty foods; eliminating pills with iron;
and eating bland or dry foods, high-protein snacks, and
872
crackers in the morning before arising (53). However,

there is little published evidence regarding the efficacy of
dietary changes for prevention or treatment of nausea and
vomiting of pregnancy. A small study showed that protein meals were more likely to alleviate nausea and vomiting of pregnancy than carbohydrate or fatty meals (54).
A study comparing powdered ginger capsules,
250 mg, with placebo in 27 women with hyperemesis
gravidarum found the ginger reduced episodes of vomiting (55). Another study using a similar ginger regimen in
70 women with nausea and vomiting of pregnancy of
varying severity found significant improvement in nausea
and vomiting (56).
Pressure or electrical stimulation at the P6 (or
Neguian) point on the inside of the wrist has been studied for nausea and vomiting of pregnancy with conflicting results. The preponderance of the literature does
show a benefit, but many of the studies had significant
methodologic flaws, and the 2 largest, best-designed
studies showed no benefit over sham stimulation (57).
Interestingly, the findings in both of these studies were
consistent with a large placebo effect. A randomized,
controlled trial of acustimulation with a commercial transcutaneous electrical stimulation device for varying
degrees of nausea and vomiting of pregnancy found that
acustimulation improved nausea and vomiting symptoms
in the first trimester (58).
Are pharmacologic therapies effective

for treatment of nausea and vomiting of
pregnancy?
Effective pharmacologic therapy is available, but agreement on the appropriate timing of antiemetic therapy has
changed in recent years. Two randomized controlled trials have evaluated pyridoxine (vitamin B6) for treatment
of varying degrees of severity of nausea and vomiting of
pregnancy. One compared pyridoxine, 25 mg every
8 hours, with placebo and found a significant reduction in
severe vomiting but minimal effect on mild vomiting
(59). A larger study (n = 342) used pyridoxine, 10 mg
every 8 hours, and found a reduction in both nausea and
vomiting compared with placebo (60). When the combination of vitamin B6, 10 mg, plus doxylamine, 10 mg,
was available in the United States from 1958 to 1983, it
is estimated that 2530% of all pregnant women received
this agent. Analysis of hospital admissions during this
period suggests that the ready availability of vitamin B6
and doxylamine for the treatment of the spectrum of nausea and vomiting of pregnancy was associated with fewer
hospital admissions for hyperemesis gravidarum (38).
After the combination was removed from the U.S. market in 1983, use of antiemetics to treat nausea and vomit-
ing of pregnancy diminished considerably, and hospitalization rates for nausea and vomiting of pregnancy
increased (38).
Figure 1 depicts a hierarchy of therapeutic interventions that balances safety and efficacy. Despite the fact
that the combination of doxylamine and vitamin B6 is no
longer commercially available in the United States, it
remains among the first-line therapies. Individual compounding pharmacies in many communities will make up
the combination of 10 mg of pyridoxine and 10 mg of
doxylamine on request. The only randomized, placebocontrolled trials have shown a 70% reduction in nausea
and vomiting (6163). Several casecontrol and cohort
studies involving more than 170,000 exposures have
found the combination to be safe with regard to fetal
effects (64).
Many other conventional antiemetics have been
described in the literature for treatment of nausea and
vomiting of pregnancy (Table 1). Data that suggest safety and efficacy are available on several classes of these
medications. The safety of antihistamine H1 receptor
blockers (eg, doxylamine) is supported by a review of
more than 200,000 first-trimester exposures (65).
Phenothiazines were identified as a possible cause of
malformations in one study (66), but the aggregate of
studies attest to their safety (67). Three studies attest to
the safety of trimethobenzamide (6870).
Medications for which there are some safety data but
no conclusive evidence of efficacy include anticholinergics and metoclopramide. Additionally, evidence is limited on the safety or efficacy of the 5-hydroxytryptamine 3
inhibitors (eg, ondansetron) for nausea and vomiting of
pregnancy; however, because of their effectiveness in
reducing chemotherapy-induced emesis, their use
appears to be increasing. Although the evidence is not
strong, doses of droperidol greater than 25 mg were associated with a prolonged Q-T interval that in some cases
has led to the potentially fatal arrhythmia torsades de
pointes. This drug should be used with caution.
Several case series in the past 10 years have suggested a benefit of corticosteroids in the treatment of
hyperemesis gravidarum. A randomized trial comparing
methylprednisolone (16 mg, 3 times per day for 3 days,
followed by a 2-week taper) with oral promethazine
showed equal rates of improvement among hospitalized
patients; however, readmission to the hospital within
2 weeks of discharge occurred significantly less frequently in those taking steroids (71). In contrast, a later
randomized controlled trial of intravenous methylprednisolone followed by a tapered dose of an oral prednisone
among women hospitalized for hyperemesis gravidarum
found the use of corticosteroids did not reduce the need
for rehospitalization (72).
PRACTICE BULLETINS
Pharmacologic treatment of nausea and vomiting of pregnancy* (if no improvement, proceed to the next step)
Monotherapy: Vitamin B6 , 1025 mg, 3 or 4 times per day
Add: Doxylamine, 12.5 mg, 3 or 4 times per day

Adjust schedule and dose according to severity of patients symptoms
Add: Promethazine, 12.525 mg every 4 hours, orally or rectally

Or
Dimenhydrinate, 50100 mg every 46 hours, orally or rectally (not to exceed 400 mg per day; not to exceed 200 mg per
day if patient also is taking doxylamine)
No dehydration
Dehydration
Add any of the following

(presented here in alphabetical order):
Metoclopramide, 510 mg every
8 hours, intramuscularly or orally
Or
Promethazine, 12.525 mg every 4 hours,
intramuscularly, orally, or rectally
Or
Trimethobenzamide, 200 mg every
68 hours, rectally
Intravenous fluid replacement
Add any of the following (presented here in alphabetical order):

Dimenhydrinate, 50 mg (in 50 mL saline, over 20 min) every
46 hours, intravenously
Or
Metoclopramide, 510 mg every 8 hours, intravenously
Or
Promethazine, 12.525 mg every 4 hours, intravenously
Add: Methylprednisolone, 16 mg every 8 hours, orally or intravenously,

for 3 days. Taper over 2 weeks to lowest effective dose.
If beneficial, limit total duration of use to 6 weeks.
Or
Ondansetron, 8 mg, over 15 minutes, every 12 hours, intravenously
*This algorithm assumes other causes of nausea and vomiting have been ruled out. At any step, consider parenteral nutrition if
dehydration or persistent weight loss is noted. Alternative therapies may be added at any time during the sequence depending on patient acceptance and clinician familiarity; consider P6 acupressure with wrist bands or acustimulation or ginger capsules, 250 mg 4 times daily.
In the United States, doxylamine is available as the active ingredient in some over-the-counter sleep aids; one half of a scored
25-mg tablet can be used to provide a 12.5-mg dose of doxylamine.
Thiamine, intravenously, 100 mg daily for 23 days (followed by intravenous multivitamins), is recommended for every woman
who requires intravenous hydration and has vomited for more than 3 weeks. No study has compared different fluid replacements for nausea and vomiting of pregnancy.
Corticosteroids appear to increase risk for oral clefts in the first 10 weeks of gestation.
Safety, particularly in the first trimester of pregnancy, not yet determined; less effect on nausea.
Figure 1. Pharmacologic treatment of nausea and vomiting of pregnancy. (Adapted from Levichek
Z, Atanackovic G, Oepkes D, Maltepe C, Einarson A, Magee L, et al. Nausea and vomiting of pregnancy. Evidence-based treatment algorithm. Can Fam Physician 2002;48:2678, 277.)
873
874
Table 1. Summary of Drugs Used to Treat Nausea and Vomiting of Pregnancy

Agent
Randomized Controlled Trial*
H1 blockers
Doxylamine
Dimenhydrinate
Cetirizine
Meclizine
Buclizine
Hydroxyzine
Diphenhydramine
Comments on Efficacy
Comments on Safety
Effective in reducing nausea and

vomiting of pregnancy
No increased risk of malformations
No effectiveness trials for nausea and

No increased risk of malformations

No trials regarding efficacy
No known malformations
Anticholinergics
Scopolamine
Dopamine Antagonists
Benzamides
Trimethobenzamide
Metoclopramide
Butyrophenones
Droperidol
No known malformations
One study of limited power identified no
known malformations
Maternal risk of prolonged Q-T interval
Haloperidol
Phenothiazines
Promethazine

Bulk of evidence indicates no teratogenicity (isolated case report discounted

in meta-analysis)
One trial found equal effectiveness to

promethazine
No malformations noted
Prochlorperazine
Chlorpromazine
Perphenazine
Benzodiazepines
Diazepam
5-Hydroxytryptamine 3
receptor agonists
Ondansetron
Steroids
Adrenocorticotropic hormone
Corticosteroids
Pooled results do not suggest benefit in

decreasing nausea and vomiting of
pregnancy
Small increased risks of clefts
*The drug has been evaluated in at least 1 randomized, controlled trial.
Rumeau-Rouquette C, Goujard J, Huel G. Possible teratogenic effect of phenothiazines in human beings. Teratology 1977;15:5764.
Data from Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy (Cochrane Review). In: The Cochrane Library, Issue 4, 2003. Chichester, UK:
John Wiley & Sons, Ltd.; and Magee LA, Mazzotta P, Koren G. Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of
pregnancy (NVP). Am J Obstet Gynecol 2002;186:S25661.
Three recent studies have confirmed an association

between oral clefts and methylprednisolone use in the
first trimester (7375). The teratogenic effect is weak,
probably accounting for no more than 1 or 2 cases per
1,000 treated women (76). Nevertheless, in view of this
probable association, corticosteroid use for hyperemesis
gravidarum should be used with caution and avoided
before 10 weeks of gestation.
Corticosteroids may be considered as a last resort in

patients who will require enteral or parenteral nutrition
because of weight loss. The most commonly described
regimen is methylprednisolone, 48 mg daily for 3 days,
given orally or intravenously. Patients who do not
respond within 3 days are not likely to respond, and
treatment should be stopped. For those who do respond,
the dose may be tapered over a period of 2 weeks. For
PRACTICE BULLETINS
Is there a role for laboratory or radiologic

assessment in the diagnosis of hyperemesis
gravidarum?
When is enteral or parenteral nutrition

recommended?
The principal criterion for introducing additional nutritional strategies is persistent weight loss. Serious complications of hyperemesis gravidarum for the woman and
fetus arise in the group of women who cannot maintain
their weight despite antiemetic therapy. Intravenous
hydration should be used for the patient who cannot tolerate oral liquids for a prolonged period or if clinical signs
of dehydration are present. Correction of ketosis and vitamin deficiency should be strongly considered. Dextrose
and vitamins, especially thiamine, should be included in
the therapy when prolonged vomiting is present.
No randomized trials compare enteral with parenteral nutrition in women with nausea and vomiting of
pregnancy who continue to lose weight despite antiemetic therapy. Several case reports and a small series (83)
suggest that enteral tube feeding is well tolerated in
pregnancy. Because life-threatening complications of
parenteral nutrition have been described (35, 36, 84), it
is reasonable to attempt enteral tube feeding initially.
Peripheral parenteral nutrition using a high-lipid formula can be used for patients whose calorie requirements
are not great and those whose length of treatment is
anticipated to be no more than several days. For women
who need longer-term support and who cannot tolerate
enteral tube feedings, the use of total parenteral nutrition
has been described for hyperemesis gravidarum in case
reports and 2 small series (35, 85). A peripherally inserted central catheter can be used to avoid some of the complications of central access (86), but it is still associated
with significant morbidity (87).
Most patients with nausea and vomiting of pregnancy do

not require laboratory evaluation, but in those with nausea and vomiting of pregnancy that is severe, prolonged,
or extended, laboratory assessment may help in the differential diagnosis of hyperemesis gravidarum and to
assess the severity of the condition. Common laboratory
abnormalities in hyperemesis gravidarum include
increased liver enzymes (usually <300 U/L), serum
bilirubin (<4 mg/dL), and serum amylase or lipase concentrations (up to 5 times greater than normal levels).
Primary hepatitis as a cause of nausea and vomiting of
pregnancy results in increased liver enzyme levels, often
in the thousands; bilirubin concentrations usually are
greatly increased as well. Acute pancreatitis may cause
vomiting and elevated amylase concentrations, but
serum amylase concentrations usually are 510 times
greater than the elevations associated with nausea and
vomiting of pregnancy. A hypochloremic metabolic
alkalosis can be seen with severe vomiting of any cause.
Serum concentrations of hCG are not helpful in determining whether vomiting is caused by hyperemesis
gravidarum. Urinalysis may show elevated specific gravity or ketonuria or both. Patients with persistent hyperemesis gravidarum that is unresponsive to standard
therapy may have an ulcer; treatment with antibiotics
and H2 receptor antagonists is safe (78, 79) and has been
reported to be beneficial in case reports (80).
Up to 70% of patients with hyperemesis gravidarum
will have suppressed thyroid-stimulating hormone levels
or elevated free thyroxine concentrations (81). For the
patient who has no history of hyperthyroidism before
pregnancy and no goiter, the hyperthyroidism of hyperemesis gravidarum can be expected to resolve by
20 weeks of gestation without specific antithyroid therapy. Hyperthyroidism itself rarely may present with
significant vomiting (82), but in the patient who has no
goiter, thyroid tests are not needed routinely to clarify
the differential diagnosis. To confirm the diagnosis of
hyperthyroidism in the setting of nausea and vomiting of
pregnancy, measurement of free thyroxine and free triiodothyronine concentrations should be obtained.
An ultrasound evaluation may be useful in cases of
severe presumed nausea and vomiting of pregnancy. It
may identify a predisposing factor, such as multiple gestation or molar gestation.
recurrent vomiting, the tapered dose may be stopped and

the patient continued on the effective dose for up to 6
weeks. To limit serious maternal side effects, corticosteroids should not be continued beyond this period for
the treatment of hyperemesis gravidarum (77).
875
When is hospitalization indicated?
No controlled trials compare hospitalization with outpatient management of hyperemesis gravidarum. When a
woman cannot tolerate liquids without vomiting and has
not responded to outpatient management, hospitalization
for evaluation and treatment is recommended. After the
patient has been hospitalized on one occasion and a
workup for other causes of severe vomiting has been
undertaken, intravenous hydration, nutritional support,
and modification of antiemetic therapy often can be
accomplished at home. Nevertheless, the option of hospitalization for observation and further assessment
should be preserved for patients who experience a
change in vital signs or a change in affect or who continue to lose weight.
876

Intravenous hydration should be used for the patient
who cannot tolerate oral liquids for a prolonged
period or if clinical signs of dehydration are present.
Correction of ketosis and vitamin deficiency should
be strongly considered. Dextrose and vitamins,
especially thiamine, should be included in the therapy when prolonged vomiting is present.
Summary of
Recommendations
Treatment of severe nausea and vomiting of pregnancy or hyperemesis gravidarum with methylprednisolone may be efficacious in refractory cases;
however, the risk profile of methylprednisolone suggests it should be a treatment of last resort.
There is little evidence for a therapeutic effect of traditional psychotherapy in hyperemesis gravidarum. No
controlled trials have evaluated behavioral therapy in
nausea and vomiting of pregnancy, but there are data to
indicate that delayed and anticipatory nausea and vomiting after chemotherapy is diminished by systematic
desensitization (88) and relaxation therapy (89).
It has been suggested that hypnotized women with
severe nausea and vomiting of pregnancy are more easily influenced by suggestion than controls, and at least
one controlled study supports this hypothesis (90). In a
limited number of studies, all lacking controls, hypnosis
has been shown to decrease vomiting in patients undergoing chemotherapy (91, 92) and those with hyperemesis gravidarum (93, 94).
Is there a role for psychotherapy in

treatment?
Enteral or parenteral nutrition should be initiated for

any patient who cannot maintain her weight because
of vomiting.
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decrease the severity of nausea and vomiting of
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with vitamin B6 or vitamin B6 plus doxylamine is
safe and effective and should be considered first-line
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Atanackovic G, et al. The burden of illness of severe nausea and vomiting of pregnancy in the United States. Am J
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have suppressed thyroid-stimulating hormone levels,
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to conduct a literature search to locate relevant articles published between January 1985 and December 2003. The
Force:
I

type of evidence.
committees.
reproduced, stored in a retrieval system, or transmitted, in any form or
by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher.
01923, (978) 750-8400.
ISSN 1099-3630
Nausea and vomiting of pregnancy. ACOG Practice Bulletin No. 52.
2004;103:80315
PRACTICE BULLETINS
881
ACOG
PRACTICE
BULLETIN
(Replaces Practice Bulletin Number 5, July 1999)

of T. Flint Porter, MD and
Carolyn M. Zelop, MD. The
of practice.
Reaffirmed 2009
Vaginal Birth After

Previous Cesarean
Delivery
A trial of labor after previous cesarean delivery has been accepted as a way to
reduce the overall cesarean delivery rate (1). Although vaginal birth after
cesarean delivery (VBAC) is appropriate for most women with a history of a lowtransverse cesarean delivery, several factors increase the likelihood of a failed
trial of labor, which in turn leads to increased maternal and perinatal morbidity. The purpose of this document is to review the current risks and benefits of
VBAC in various situations and provide practical management guidelines.
Background
Between 1970 and 1988, the cesarean delivery rate in the United States
increased dramatically from 5% to nearly 25% (13). The rapid growth was
likely a result of increased pressure that discouraged physicians from performing vaginal breech deliveries and midpelvic forceps deliveries. At the same
time, increasing reliance on continuous electronic monitoring of fetal heart rate
and uterine contraction patterns led to an increase in the number of cesarean
deliveries performed for presumed fetal compromise and dystocia, respectively. With few exceptions, major improvements in newborn outcomes as a result
of the increased cesarean delivery rate are yet to be proved (4).
Changing Concepts
The dictum once a cesarean, always a cesarean, which dominated obstetric
practice in the United States for nearly 70 years (5), began changing gradually
approximately 30 years ago as improvements in obstetric care made a trial of
labor after a previous cesarean delivery safer for both the woman and the fetus.
Based on the findings of several large series that documented the relative safety
of a trial of labor after a previous cesarean delivery (69), organizations such as
the National Institutes of Health and the American College of Obstetricians and
882
Gynecologists enthusiastically embraced VBAC as a way

to decrease the cesarean delivery rate in the United States.
The national enthusiasm for VBAC led to a decrease
in the cesarean delivery rate, which reached 20.7% in
1996 (10). During the same period (19891996), the
VBAC rate increased from less than 18.9% to 28.3%.
Some third-party payers and managed care organizations
even mandated that all women who had previous cesarean deliveries undergo trials of labor (11, 12). Many
physicians were pressured into offering VBAC to unsuitable candidates or to women who wanted to have a repeat
cesarean delivery. As the VBAC rate increased, so did the
number of well-publicized reports of uterine rupture and
other complications during trials of labor after previous
cesarean deliveries (11, 13, 14). As a result, many physicians and hospitals have discontinued the practice altogether. This abrupt change in practice has contributed to
the cesarean delivery rate in the United States increasing
again, reaching an all-time high of 26.1% in 2002, while
the VBAC rate has decreased by 55% to 12.6% (15).
Supportive Evidence
Despite thousands of citations in the worlds literature,
there are currently no randomized trials comparing
maternal or neonatal outcomes for both repeat cesarean
delivery and VBAC. Instead, VBAC recommendations
have been based on data from large clinical series suggesting that the benefits of VBAC outweigh the risks in
most women with a previous low-transverse cesarean
delivery (69, 1618). Most have been conducted in university or tertiary-level centers with full-time in-house
obstetric and anesthesia coverage (19). Only a few studies have documented the relative safety of VBAC in
smaller community hospitals or facilities where resources
may be more limited (17, 2022). Furthermore, the early
series of women attempting a trial of labor after a previous cesarean delivery focused on successful VBAC and
maternal mortality. It has become apparent that women
who fail a trial of labor are at risk for several maternal
complications, including uterine rupture, hysterectomy,
the need for transfusion, and endometritis (16, 19, 23), as
well as perinatal morbidity and mortality (24, 25).

Recommendations
Who are candidates for a trial of labor?
The preponderance of evidence suggests that most

patients who have had a low-transverse uterine incision
from a previous cesarean delivery and who have no con-
traindications for vaginal birth are candidates for a trial

of labor. Following are selection criteria useful in identifying candidates for VBAC:
One previous low-transverse cesarean delivery

Clinically adequate pelvis
No other uterine scars or previous rupture
Physician immediately available throughout active
labor capable of monitoring labor and performing an
emergency cesarean delivery
Availability of anesthesia and personnel for emergency cesarean delivery
Based on the findings from several retrospective studies,
it may be reasonable to offer a trial of labor to women in
the following other specific obstetric circumstances.
More Than One Previous

Cesarean Delivery
Women who have had 2 previous low-transverse cesarean deliveries have traditionally been considered candidates for a trial of labor. However, the few studies that
address this issue report a risk of uterine rupture ranging
between 1% and 3.7% (9, 26, 27). In the only study that
controlled for other potential confounding variables, the
risk of uterine rupture during labor was nearly 5 times
greater for women with 2 previous cesarean deliveries
when compared with women who had 1 previous cesarean delivery (27). Women with a previous vaginal delivery
followed by a cesarean delivery were only approximately one fourth as likely to sustain uterine rupture during a
trial of labor (27). Therefore, for women with 2 prior
cesarean deliveries, only those with a prior vaginal delivery should be considered candidates for a spontaneous
trial of labor.
Macrosomia
Although macrosomia (usually birth weight greater than
4,000 g or 4,500 g, regardless of gestational age) is associated with a lower likelihood of successful VBAC (2831),
6090% of women attempting a trial of labor who give
birth to infants with macrosomia are successful (30, 31).
The rate of uterine rupture appears to be increased only in
those women without a previous vaginal delivery (31).
Gestation Beyond 40 Weeks

Awaiting spontaneous labor beyond 40 weeks of gestation
decreases the likelihood of successful VBAC, but the risk
of uterine rupture does not increase (32, 33). In one study
of more than 1,200 women attempting a trial of labor
after 40 weeks of gestation, only labor induction was
associated with an increased risk of uterine rupture (33).
PRACTICE BULLETINS
Previous Low-Vertical Incision

In 1 case series and 4 retrospective studies, women with
a previous low-vertical uterine incision were just as
likely to have successful VBAC as women with a previous low-transverse uterine incision (3437). In addition,
there was no increase in maternal or perinatal morbidity.
Unknown Uterine Scar Type
Twin Gestation
The safety of VBAC in women with twin gestations has
been examined in small case series and 2 small, retrospective studies (4144). In the 2 trials, which included
a total of only 45 women with twin gestations, the rates
of successful VBAC and uterine rupture did not differ
significantly between study subjects and women with
singleton gestations who also were attempting VBAC.
What is the success rate for trials of labor?
Most published series of women attempting a trial of

labor after a previous cesarean delivery indicate that
6080% have successful vaginal births (17, 23, 4548).
The earliest studies usually included only those subjects
who met strict inclusion criteria, excluding those who
were not felt to be appropriate VBAC candidates.
However, in a population-based study of nearly 40,000
women from hospitals throughout California, 61.4% of
women who attempted VBAC were successful (17).
There is no completely reliable way to predict
whether a trial of labor will be successful in an individual patient (4952). Generally, success rates for
women whose first cesarean delivery was performed
for a nonrecurring indication are similar to those of
patients who have not undergone a previous cesarean
delivery (46, 53, 54). Most women who have undergone a cesarean delivery because of dystocia also can
have a successful VBAC, but the percentage may be
lower (5080%) than for those with nonrecurring indications (7586%) (46, 5558). If the prior cesarean
delivery for dystocia was performed before complete
cervical dilation (59 cm), 6773% of VBAC attempts
are successful compared with only 13% if the prior
cesarean delivery was performed after complete cervical dilation (56). Other aspects of obstetric history also
influence the likelihood of a successful VBAC. Women
who have given birth vaginally at least once are 928
times more likely to have a successful trial of labor than
women who have not undergone vaginal delivery (14,
59). If the most recent delivery was a successful VBAC,
the likelihood of failure is reduced by 3090% (52, 60).
Factors that negatively influence the likelihood of successful VBAC include labor augmentation and induction (52, 61, 62), maternal obesity (63, 64), gestational
age beyond 40 weeks (33), birth weight greater than
4,000 g (30), and interdelivery interval of less than
19 months (65).
The type of uterine incision performed at the time of a

prior cesarean delivery cannot be confirmed in some
patients. Many authorities question the safety of offering
VBAC under these circumstances; others suggest that
the uterine scar type usually can be inferred based on the
indication for the prior cesarean delivery. Two case
series, both carried out at large tertiary care facilities,
reported rates of VBAC success and uterine rupture similar to those from other contemporaneous studies of
women with documented previous low-transverse uterine incisions (38, 39). In one small, randomized controlled trial (n = 197) comparing labor augmentation
with no intervention in women with a previous cesarean
delivery and unknown scar, 5 uterine scar disruptions
occurred in the group that received labor augmentation
while no scar disruptions occurred in the group without
augmentation (40).
883
What are the risks and benefits associated

with VBAC?
Neither elective repeat cesarean delivery nor VBAC is

without risk. Generally, successful VBAC is associated
with shorter maternal hospitalizations, less blood loss and
fewer transfusions, fewer infections, and fewer thromboembolic events than cesarean delivery (8, 16, 23, 25).
However, a failed trial of labor may be associated with
major maternal complications, such as uterine rupture,
hysterectomy, and operative injury (16, 18, 23, 25, 48), as
well as increased maternal infection and the need for
transfusion (23). Neonatal morbidity also is increased
with a failed trial of labor, as evidenced by the increased
incidence of arterial umbilical cord blood gas pH levels
below 7, 5-minute Apgar scores below 7, and infection
(25, 47, 66). However, multiple cesarean deliveries also
carry maternal risks, including an increased risk of placenta previa and accreta (67, 68). Based on these risks,
one decision model analysis found it is reasonable to consider a trial of labor if the chance of success is 50% or
greater, and the desire for future pregnancy after cesarean
delivery is at least 1020% (67).
The incidence of maternal death with VBAC is
extremely low. In a recent meta-analysis, only 3 maternal deaths were reported among the more than 27,000
women who attempted a trial of labor after a prior
cesarean delivery (25). Although the incidence of perinatal death is low (generally less than 1%), it is more
likely to occur during a trial of labor than an elective
884
A true analysis of the cost-effectiveness of VBAC should

include hospital and physician costs, the method of reimbursement, potential professional liability expenses, and
the probability that a woman will continue with child-
Should women with a previous cesarean

delivery undergo induction or augmentation
of labor?
Spontaneous labor is more likely to result in a successful

VBAC rather than labor induction or augmentation (52,
61, 62). A meta-analysis of studies published before 1989
found no relationship between the use of oxytocin and
rupture of the uterine scar (83). In contrast, several more
recent large studies have shown an increased risk (37, 61,
62, 84). In one large retrospective study of more than
20,000 women, uterine rupture was nearly 5 times more
common among women undergoing labor induction with
oxytocin compared with those who had an elective repeat
cesarean delivery (37). However, uterine rupture occurred
in less than 1% of women in both groups. Furthermore,
among the women attempting VBAC, the rate of uterine
rupture was not different between those who received
oxytocin and those who labored spontaneously.
There is considerable evidence that cervical ripening with prostaglandin preparations increases the likelihood of uterine rupture (37, 61, 8587). In a review of
Washington State birth records, the rate of uterine rupture
during labor induced with prostaglandin was 24.5 in
1,000, which was 15-fold higher than that of women
electing to have a repeat cesarean delivery (37).
Likewise, misoprostol has been associated with an unacceptably high rate of uterine rupture in women with a
previous cesarean delivery (8891). Therefore, the use of
prostaglandins for induction of labor in most women with
a previous cesarean delivery should be discouraged.
What factors should be taken into consideration when evaluating the cost-effectiveness of
a trial of labor after a previous cesarean delivery and an elective repeat cesarean delivery?
bearing after her first attempt at VBAC (79). Higher costs

may be incurred by a hospital if a woman has a prolonged
labor or has significant complications or if the newborn
is admitted to a neonatal intensive care unit. Additionally,
evidence suggests that cost savings are not achieved
unless at least 70% of women who attempt a trial of labor
are successful (8082).
repeat cesarean delivery (18, 25, 47, 69). Uterine rupture

has been associated with fetal death, as well as severe
neonatal neurologic injury (24, 7072).
Uterine rupture during a trial of labor after a previous cesarean delivery is a life-threatening complication
that has been directly attributed to attempted VBAC. In
most cases, the cause of uterine rupture is unknown, but
poor obstetric outcomes can result even in women who
are appropriate candidates for VBAC. The exact incidence of uterine rupture is difficult to determine because
reports in the literature have sometimes grouped true, catastrophic uterine ruptures together with asymptomatic
scar dehiscences. Additionally, early case series included
ruptures in the absence of labor as well as ruptures during labor in women with previous classical incisions (24).
The rate of uterine rupture is largely dependent on the
type and location of the previous incision. Uterine rupture rates in women with previous classical incisions and
T-shaped incisions range between 4% and 9% (73).
Although uterine rupture occurs more often in women
undergoing a trial of labor than women who elect repeat
cesarean delivery, rupture rates during attempted VBAC
generally are less than 1% (17, 18, 25).
The risk of uterine rupture also is influenced by
obstetric history. A previous vaginal birth significantly
reduces the risk of uterine rupture (74). The risk of uterine rupture appears to be inversely related to the length of
time between deliveries, ie, the longer the interval
between deliveries, the lower the risk of rupture (7577).
Women who attempt VBAC who have interdelivery intervals of less than 24 months have a 23-fold increased risk
of uterine rupture when compared with women who
attempt VBAC more than 24 months after their last delivery (76). Finally, the findings of one nonrandomized trial
suggest that compared with a double layer closure, a single layer closure of the hysterotomy incision in the primary cesarean delivery may increase the risk of uterine
rupture 4-fold during a subsequent trial of labor (78).
Common signs of uterine rupture are a nonreassuring fetal heart rate pattern with decelerations or bradycardia (18). Other findings are more variable and include
uterine or abdominal pain, loss of station of the presenting part, vaginal bleeding, and hypovolemia.
How should midtrimester delivery be accomplished in women with a previous cesarean

delivery?
Some women with a history of a cesarean delivery will

require delivery during the midtrimester in a subsequent
pregnancy, usually because of fetal demise or the presence of anomalies. The published data on midtrimester
VBAC are limited to single cases and small case series
that report both successful and failed VBAC, as well as
uterine rupture during a trial of labor (9294). The induction agents in these reports are typically prostaglandin
preparations, including misoprostol. A second-trimester
PRACTICE BULLETINS
hysterotomy is associated with its own risks, and the

decision to attempt a trial of labor in the midtrimester
should probably be based on individual circumstances,
including but not limited to the number of previous
cesarean deliveries, gestational age, placentation, and the
womans desire to preserve reproductive function.
What are contraindications for VBAC?
A trial of labor is not recommended in patients at high

risk for uterine rupture. Circumstances under which a
trial of labor should not be attempted are as follows:
Previous classical or T-shaped incision or extensive
transfundal uterine surgery
Previous uterine rupture
Medical or obstetric complication that precludes
vaginal delivery
Inability to perform emergency cesarean delivery
because of unavailable surgeon, anesthesia, sufficient staff, or facility
Two prior uterine scars and no vaginal deliveries
In addition, a combination of factors that would not ordinarily constitute a compelling case to proceed with a
primary cesarean delivery might be considered sufficient
to choose repeat cesarean delivery instead of VBAC in
some situations.
How should patients be counseled?
The enthusiasm for VBAC varies greatly among patients

and physicians. It is reasonable for women to undergo a
trial of labor in a safe setting, but the potential complications should be discussed thoroughly and documented. If
the type of previous incision is in doubt, attempts should
be made to obtain the patients medical records. After
thorough counseling that weighs the individual benefits
and risks of VBAC, the ultimate decision to attempt this
procedure or undergo a repeat cesarean delivery should be
made by the patient and her physician. Global mandates
for a trial of labor after a previous cesarean delivery are
inappropriate because individual risk factors are not considered. It should be recognized that there are repeat elective cesarean deliveries that are clinically indicated (95).
The informed consent process and the plan of management should be documented in the medical record.
How does management of labor differ for

patients undergoing VBAC?
Despite extensive data on VBAC, there is relatively little

information on how labor should be conducted. Management of labor varies in different situations.
885

There are limited data about external cephalic version for
breech presentation and VBAC. The data suggest that it
may be as successful in VBAC candidates as in women
who have not undergone a previous cesarean delivery
(96).
Analgesia
Vaginal birth after cesarean delivery is not a contraindication to epidural anesthesia, and adequate pain relief
may encourage more women to choose a trial of labor
(97, 98). Success rates for VBAC are similar in women
who do and do not receive epidural analgesia, as well as
in those women who receive other types of pain relief
(99, 100). Epidural analgesia rarely masks the signs and
symptoms of uterine rupture.
Intrapartum Management
Once labor has begun, a patient attempting VBAC should
be evaluated promptly. Most authorities recommend continuous electronic monitoring. However, no data suggest
monitoring with intrauterine pressure catheters is superior to external monitoring. Personnel who are familiar
with the potential complications of VBAC should be present to watch for nonreassuring fetal heart rate patterns
and inadequate progress in labor.
Augmentation
The safety of oxytocin for augmentation of contractions
during a trial of labor after a previous low-transverse
cesarean delivery has been examined in several studies.
Reported uterine rupture rates vary widely in the early
studies (0.48%), which may reflect the inadvertent
inclusion of asymptomatic scar dehiscence among cases
of catastrophic uterine rupture (83, 101, 102). Nevertheless, in a recent study of 1,072 patients receiving
oxytocin augmentation, the rate of symptomatic uterine
rupture was 1% compared with 0.4% in those who
labored spontaneously (84). In a nested casecontrol
study, there was no association between uterine rupture
and oxytocin dosing intervals, total oxytocin received,
and mean duration of oxytocin administration (103).
Delivery
There is nothing unique about the delivery of the fetus
during a trial of labor. The need to explore the uterus after
a successful vaginal delivery is controversial. Most
asymptomatic scar dehiscences heal well, and there are
no data to suggest that future pregnancy outcome is better if the dehiscence is surgically repaired. Excessive
vaginal bleeding or signs of hypovolemia at delivery
886
require prompt and complete assessment of the previous

scar and the entire genital tract.
How should future pregnancies be managed

after uterine rupture?
If the site of the ruptured scar is confined to the lower

segment of the uterus, the rate of repeat rupture or
dehiscence in labor is 6% (104). If the scar includes the
upper segment of the uterus, the repeat rupture rate is
32% (104, 105). Therefore, women who have had a previous uterine rupture should give birth by repeat cesarean delivery before the onset of labor.
Summary of
Recommendations
Most women with one previous cesarean delivery

with a low-transverse incision are candidates for
VBAC and should be counseled about VBAC and
offered a trial of labor.
Epidural anesthesia may be used for VBAC.
Women with a vertical incision within the lower

uterine segment that does not extend into the fundus
are candidates for VBAC.
The use of prostaglandins for cervical ripening or

induction of labor in most women with a previous
cesarean delivery should be discouraged.
Because uterine rupture may be catastrophic, VBAC

should be attempted in institutions equipped to
respond to emergencies with physicians immediately available to provide emergency care.
After thorough counseling that weighs the individual

benefits and risks of VBAC, the ultimate decision to
attempt this procedure or undergo a repeat cesarean
delivery should be made by the patient and her
physician. This discussion should be documented in
the medical record.
Vaginal birth after a previous cesarean delivery is

contraindicated in women with a previous classical
uterine incision or extensive transfundal uterine
surgery.
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890

Force:
I

type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
Vaginal birth after previous cesarean delivery. ACOG Practice Bulletin
Gynecol 2004;104:20312.
PRACTICE BULLETINS
891
ACOG
PRACTICE
BULLETIN
(Replaces Practice Pattern Number 6, October 1997)
This Practice Bulletin was developed by the ACOG Committee

on Practice BulletinsObstetrics
with the assistance of Errol R.
Norwitz, MD, PhD and Julian
N. Robinson, MD. The information is designed to aid practitioners in making decisions
gynecologic care. These guidelines should not be construed as
Reaffirmed 2009
Management of
Postterm Pregnancy
Postterm pregnancy, by definition, refers to a pregnancy that has extended to or
beyond 42 weeks of gestation (294 days, or estimated date of delivery [EDD]
+14 days). Accurate pregnancy dating is critical to the diagnosis. The term
postdates is poorly defined and should be avoided. Although some cases of
postterm pregnancy likely result from an inability to accurately define the EDD,
many cases result from a true prolongation of gestation. The reported frequency of postterm pregnancy is approximately 7% (1).
Accurate assessment of gestational age and diagnosis of postterm gestation,
as well as recognition and management of risk factors, may reduce the risk of
adverse sequelae. Antenatal surveillance and induction of labor are 2 widely
used strategies that theoretically may decrease the risk of an adverse fetal outcome; maternal risk factors for postterm pregnancy also should be considered.
The purpose of this document is to examine the evidence and provide recommendations about these 2 management strategies.
Background
Etiologic Factors
The most frequent cause of an apparently prolonged gestation is an error in dating (2, 3). When postterm pregnancy truly exists, the cause usually is unknown.
Primiparity and prior postterm pregnancy are the most common identifiable
risk factors for prolongation of pregnancy (4, 5). Rarely, postterm pregnancy
may be associated with placental sulfatase deficiency or fetal anencephaly.
Male sex also has been associated with prolongation of pregnancy (6). Genetic
predisposition may play a role in prolonging pregnancy (5, 7).
892
Assessment of Gestational Age

Accurate pregnancy dating is important for minimizing
the false diagnosis of postterm pregnancy. The EDD is
most reliably and accurately determined early in pregnancy. It may be determined on the basis of the known
last menstrual period in women with regular, normal
menstrual cycles.
Inconsistencies or concern about the accuracy of the
estimated gestational age requires further assessment
with ultrasonography. Useful measurements include the
crownrump length of the fetus during the first trimester
and the biparietal diameter or head circumference and
femur length during the second trimester. Because of the
normal variations in size of infants in the third trimester,
dating the pregnancy at that time is less reliable
(21 days). Although recent data have highlighted the
accuracy of first trimester ultrasonography, the variation
by ultrasonography generally is 7 days up to 20 weeks
of gestation, 14 days between 20 and 30 weeks of gestation, and 21 days beyond 30 weeks of gestation. If the
estimated gestational age by a patients last menstrual
period differs from the ultrasound estimate by more than
these accepted variations, the ultrasound estimate of gestational age should be used instead of the patients menstrual cycle estimate.
Risks to the Fetus
Risks to the Pregnant Woman

Postterm pregnancy also is associated with significant
risks to the pregnant woman, including an increase in
labor dystocia (912% versus 27% at term), an increase
in severe perineal injury related to macrosomia (3.3%
versus 2.6% at term), and a doubling in the rate of cesarean delivery (2123). Cesarean delivery is associated with
higher risks of complications, such as endometritis, hemorrhage, and thromboembolic disease. Finally, postterm
pregnancy can be a source of substantial anxiety for the
pregnant woman.

Recommendations
Are there interventions that decrease the rate

of postterm pregnancy?
Accurate dating on the basis of ultrasonography performed early in pregnancy can reduce the incidence of
pregnancies diagnosed as postterm (odds ratio [OR],
0.68; 95% confidence interval [CI], 0.570.82) (2) and
thereby minimize unnecessary intervention (3, 24). However, routine early ultrasonography has not been recommended as a standard of prenatal care in the United States.
Breast and nipple stimulation at term have not been shown
to affect the incidence of postterm pregnancy (2). The
data regarding sweeping of the membranes at term to
reduce postterm pregnancy are conflicting: some studies
show a benefit (25, 26), whereas others have found no
difference in the incidence of postterm pregnancy (27).
Postterm pregnancy is associated with significant risks to

the fetus. The perinatal mortality rate (stillbirths plus
early neonatal deaths) at greater than 42 weeks of gestation is twice that at term (47 deaths versus 23 deaths
per 1,000 deliveries) and increases 6-fold and higher at
43 weeks of gestation and beyond (810). Uteroplacental
insufficiency, meconium aspiration, and intrauterine infection contribute to the increased rate of perinatal deaths
(11). Postterm pregnancy also is an independent risk factor for low umbilical artery pH levels at delivery and low
5-minute Apgar scores (12). For these reasons, the trend
has been toward delivery by 41 completed weeks of gestation (42 weeks, 294 days, EDD +14 days).
Although postterm infants are larger than term
infants and have a higher incidence of fetal macrosomia
(2.510% versus 0.81%) (13, 14), no evidence supports
inducing labor as a preventive measure in such cases.
Complications associated with fetal macrosomia include
prolonged labor, cephalopelvic disproportion, and shoulder dystocia with resultant risks of orthopedic or neurologic injury.
Approximately 20% of postterm fetuses have dysmaturity syndrome, which refers to infants with characteristics resembling chronic intrauterine growth restriction
from uteroplacental insufficiency (15, 16). These pregnancies are at increased risk of umbilical cord compres-
sion from oligohydramnios, meconium aspiration, and

short-term neonatal complications (such as hypoglycemia, seizures, and respiratory insufficiency) and
have an increased incidence of nonreassuring fetal testing, both antepartum and intrapartum (17). Whether such
infants also are at risk of long-term neurologic sequelae
is not clear. In a large, prospective, follow-up study of
children at ages 1 and 2 years, the general intelligence
quotient, physical milestones, and frequency of intercurrent illnesses were not significantly different between
normal infants born at term and those born postterm (18).
Fetuses born postterm also are at increased risk of
death within the first year of life (10, 19, 20). Although
some of these infant deaths clearly result from peripartum complications (such as meconium aspiration syndrome), most have no known cause.
When should antepartum fetal testing begin?
Because of ethical and medicolegal considerations, no

studies have included postterm patients who were not
PRACTICE BULLETINS
6
Stillbirth
Neonatal death
Postneonatal death
4
0
28 29
30
31
32
33
34
35
36
37
38
39
40
41
42 43+
Gestational age (weeks)

Figure 1. Perinatal mortality per 1,000 ongoing pregnancies.
(Reproduced from BJOG Volume 105, Hilder L, Costeloe K,
Thilaganathan B, Prolonged pregnancy: evaluating gestationspecific risks of fetal and infant mortality, 16973, 1998, with the
permission of the Royal College of Obstetricians and
Gynaecologists.)
What form of antenatal surveillance should

be performed, and how frequently should a
postterm patient be reevaluated?
The literature is inconsistent regarding both the type and

frequency of antenatal surveillance among postterm
patients (2, 3142). Options for evaluating fetal wellbeing include nonstress testing, biophysical profile
(BPP) or modified BPP (nonstress test plus amniotic
fluid volume estimation), contraction stress testing, and
a combination of these modalities, but practices vary
widely. No single method has been shown to be superior
(2). Assessment of amniotic fluid volume appears to be
important. Delivery should be effected if there is evidence of fetal compromise or oligohydramnios (43, 44).
Adverse pregnancy outcome (nonreassuring fetal heart
rate tracing, neonatal intensive care unit admission, low
Apgar score) is more common when oligohydramnios is
present (4547). However, a consistent definition of low
amniotic fluid volume in the postterm pregnancy has not
been established. Options include 1) no vertical fluid
pocket that is measurable and more than 23 cm in depth
or 2) amniotic fluid index less than 5 (43, 48). Of note,
Doppler velocimetry has no proven benefit in monitoring
the postterm fetus and is not recommended for this indication (49, 50). Although no firm recommendation can
be made on the basis of published research regarding the
frequency of antenatal surveillance among postterm
patients, many practitioners use twice-weekly testing.
Mortality per 1,000 ongoing pregnancies
(3136). Finally, there is insufficient evidence to indicate

whether routine antenatal surveillance of low-risk
patients between 40 and 42 weeks of gestation improves
perinatal outcome (2, 28).
monitored; it is unlikely that any future studies will

include an unmonitored control group. The published
studies are of insufficient power to demonstrate a benefit of monitoring. However, there is no evidence that
antenatal fetal monitoring adversely affects patients
experiencing postterm pregnancy. Data suggest a gradual
increase in perinatal morbidity and mortality during this
period (Fig. 1) (10). Therefore, despite evidence that it
does not decrease perinatal mortality, antenatal fetal surveillance for postterm pregnancies has become a common practice on the basis of universal acceptance.
Patients who have passed their EDD but who have
not yet reached 42 weeks of gestation constitute another
group for whom antenatal fetal surveillance has been
proposed. Some studies report a greater complication
rate among women giving birth during the latter half of
this 2-week period (2123, 28, 29). However, no randomized controlled trial has demonstrated an improvement in perinatal outcome attributable to fetal surveillance
between 40 and 42 weeks of gestation (30). Despite the
lack of evidence demonstrating a beneficial effect, antenatal fetal surveillance often is performed during this
period. To further complicate matters, in most studies of
postterm pregnancies, women are recruited and fetal
monitoring initiated before 42 weeks of gestation
893
For a postterm patient with a favorable

cervix, does the evidence support labor
induction or expectant management?
Management of low-risk postterm pregnancy is controversial. Because delivery cannot always be brought
about readily, maternal risks and considerations may
complicate this decision. Factors to consider include
gestational age; results of antepartum fetal testing; the
condition of the cervix; and maternal preference after
discussion of the risks, benefits, and alternatives to
expectant management with antepartum monitoring versus labor induction.
Many studies of postterm pregnancies comparing
outcomes of labor induction with those of expectant
management excluded women with favorable cervices
(3336, 3941). Moreover, when women allocated to
expectant management experienced a change in cervical
status, expectant management ceased and labor induction was initiated (32, 33, 36, 37, 40). In studies on post-
894
term pregnancy in which women with favorable cervices

were managed expectantly, there was no indication that
expectant management had a deleterious effect on the
outcome, but results were not stratified according to the
condition of the cervix (31, 32, 38, 42, 51, 52).
For women who are experiencing postterm pregnancies and have favorable cervices, data are insufficient to
determine whether labor induction or expectant management yields a better outcome. However, labor generally is
induced in postterm pregnancies in which the cervix is
favorable because the risk of failed induction and subsequent cesarean delivery is low.
For a postterm patient with an unfavorable

cervix, does the evidence support labor induction or expectant management?
What is the role of prostaglandin preparations in managing a postterm pregnancy?
Prostaglandin (PG) is a valuable tool for improving cervical ripeness and inducing labor. Several placebo-controlled clinical trials have reported significant changes in
Bishop scores, shorter durations of labor, lower maximum
doses of oxytocin, and a reduced incidence of cesarean
delivery among postterm patients who received PGE2 gel
(5759). In contrast, a National Institute of Child Health
and Human Development study reported no reduction in
the cesarean delivery rate or the induction-to-delivery
interval among postterm patients who were randomized to
receive PGE2 gel as compared with those receiving placebo, although the gel was more effective in initiating persistent contractions in nulliparous women (36). Both
PGE2 (dinoprostone) (31, 33, 35, 36, 42, 5962) and PGE1
(misoprostol) preparations (6365) have been used for
labor induction in postterm pregnancies.
Although multiple studies have used PG to induce
labor in postterm pregnancies, no standardized dose or
dosing interval has been established. Overall, the medications were well tolerated with few reported side
effects. Higher doses of PG (especially PGE1) have been
associated with an increased risk of uterine tachysystole
and hyperstimulation leading to nonreassuring fetal testing results (55, 66). As such, lower doses are preferable.
When PG is used, fetal heart rate monitoring should be
done routinely to assess fetal well-being because of the
risk of uterine hyperstimulation.
Both expectant management and labor induction are associated with low complication rates and good perinatal
outcomes in low-risk postterm women with unfavorable
cervices (2436, 39, 40). However, there appears to be a
small advantage to labor induction using cervical ripening
agents, when indicated, regardless of parity or method of
induction. The introduction of preinduction cervical maturation has resulted in fewer failed and serial inductions,
reduced fetal and maternal morbidity, reduced medical
cost, and possibly a reduced rate of cesarean delivery in
the general obstetric population (2, 35, 36, 5355).
Although postterm pregnancy is defined as a pregnancy of 42 weeks or more of gestation, several large
multicenter randomized studies of management of pregnancy beyond 40 weeks of gestation reported favorable
outcomes with routine induction as early as the beginning
of 41 weeks of gestation (2, 35, 36). The largest study to
date randomly assigned 3,407 low-risk women with
uncomplicated singleton pregnancies at 41 weeks of gestation to labor induction (with or without cervical ripening agents) within 4 days of randomization or expectant
management until 44 weeks of gestation (35). Elective
induction resulted in a lower cesarean delivery rate
(21.2% versus 24.5%), primarily related to fewer surgeries performed for nonreassuring fetal heart rate tracings. However, the authors could not identify a particular
cause related to postterm pregnancy status. Patient satisfaction was significantly higher in women randomly
assigned to labor induction.
A meta-analysis of 19 trials of routine versus selective labor induction in postterm patients found that routine induction after 41 weeks of gestation was associated
with a lower rate of perinatal mortality (OR, 0.2; 95% CI,
0.060.7) and no increase in the cesarean delivery rate
(OR, 1.02; 95% CI, 0.751.38) (2). Routine labor induction also had no effect on the instrumental delivery rate,
use of analgesia, or incidence of fetal heart rate abnor-
mality. The risk of meconium-stained amniotic fluid was

reduced, but the risks of meconium aspiration syndrome
and neonatal seizures were unaffected (2). The actual risk
of stillbirth during the 41st week of gestation is estimated at 1.041.27 per 1,000 undelivered women, compared
with 1.553.1 per 1,000 women at or beyond 42 weeks of
gestation (56). Taken together, these data suggest that
routine induction at 41 weeks of gestation has fetal benefit without incurring the additional maternal risks of a
higher rate of cesarean delivery (2, 20).
This conclusion has not been universally accepted.
Smaller studies report mixed results regarding cesarean
delivery rates; some show an increase (33, 38), and others show no difference in the cesarean delivery rate (31,
34, 36, 37, 39, 40). Two studies reported an increase in
cesarean delivery rates only among certain subgroups of
patients (eg, high-risk groups) (32, 42).
Is there a role for vaginal birth after cesarean

delivery in the management of postterm
pregnancy?
Vaginal birth after cesarean delivery (VBAC) has been

promoted as a reasonable alternative to elective repeat
PRACTICE BULLETINS
cesarean delivery for some women. The risk of uterine

rupture does not appear to increase substantially after
40 weeks of gestation (67, 68), but the risk appears to be
increased with labor induction with PG or pitocin regardless of gestational age (68, 69). In a population-based,
retrospective cohort analysis, the risk of uterine rupture
with VBAC was 1.6 per 1,000 women with repeat cesarean delivery without labor, 5.2 per 1,000 women with
spontaneous onset of labor, 7.7 per 1,000 women whose
labor was induced without PG, and 24.5 per 1,000
women who underwent a PG induction of labor (69).
There is limited evidence on the efficacy or safety of
VBAC after 42 weeks of gestation. As such, no firm recommendation can be made.
Summary of
Recommendations
Women with postterm gestations who have unfavorable cervices can either undergo labor induction or
be managed expectantly.
Prostaglandin can be used in postterm pregnancies to

promote cervical ripening and induce labor.
Delivery should be effected if there is evidence of

fetal compromise or oligohydramnios.
Despite a lack of evidence that monitoring improves

perinatal outcome, it is reasonable to initiate antenatal surveillance of postterm pregnancies between
41 weeks (287 days; EDD +7 days) and 42 weeks
(294 days; EDD +14 days) of gestation because of
evidence that perinatal morbidity and mortality
increase as gestational age advances.
895
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898

Force:
I

type of evidence.
committees.
Copyright September 2004 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of
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Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
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PO Box 96920
Management of postterm pregnancy. ACOG Practice Bulletin No. 55.
Gynecol 2004;104:63946.
PRACTICE BULLETINS
899
ACOG
PRACTICE
BULLETIN
(Replaces Educational Bulletin Number 253, November 1998)
Obstetrics, the Society for
Maternal-Fetal Medicine and
ACOG Joint Editorial Committee with the assistance of
Katharine Wenstrom, MD, and
contributors John Elliot, MD;
Roger Newman, MD; Alan
Peaceman, MD; and Suneet
Chahaun, MD. The information
is designed to aid practitioners
in making decisions about
appropriate obstetric and gynecologic care. These guidelines
Reaffirmed 2009
The Society for

Maternal-Fetal Medicine
Multiple Gestation:
Complicated Twin,
Triplet, and High-Order
Multifetal Pregnancy
In 2002, more than 130,000 infants were born of multifetal gestations in the
United States (1). Since 1980, there has been a 65% increase in the frequency
of twins and a 500% increase in triplet and high-order births (1). Most of this
increase results from increased use of ovulation induction agents and assisted
reproductive technology (ART); the risk of multiple gestation associated with
these therapies may be as high as 25% (2). Similar increases in multifetal gestation have occurred worldwide (36).
Although multifetal births account for only 3% of all live births, they are
responsible for a disproportionate share of perinatal morbidity and mortality
(Table 1). They account for 17% of all preterm births (before 37 weeks of gestation), 23% of early preterm births (before 32 weeks of gestation), 24% of lowbirth-weight infants (<2,500 g), and 26% of very-low-birth-weight infants
(<1,500 g) (1, 79). Although twins do have an increased risk of morbidity and
mortality, a far greater proportion of triplet and high-order multiple gestations
have poor outcomes. All survivors of preterm multifetal births have an increased
risk of mental and physical handicap.
The purpose of this document is to address the risks associated with these
pregnancies and present an evidence-based approach to management when
possible. Because the literature on high-order multiple gestation is still largely
composed of case reports or small series, experience is important in the decision-making process for complicated twin or high-order multiple gestations.
900
Background
Infant and Maternal Morbidity
One fifth of triplet pregnancies and one half of quadruplet pregnancies result in at least 1 child with a major
long-term handicap, such as cerebral palsy (10). Cerebral
palsy occurs 17 times more often in triplet pregnancies
and more than 4 times more often in twin pregnancies
than in singleton pregnancies (10, 11). This risk is not
solely related to preterm birth. When matched for gestational age at delivery, infants from multifetal pregnancies
have a nearly 3-fold greater risk of cerebral palsy (12,
13). One confounding factor may be growth restriction,
which complicates approximately 5060% of triplet and
quadruplet pregnancies (14). Growth-restricted preterm
infants, regardless of plurality, have a significantly higher risk of morbidity (including an excess of neurodevel-
opmental abnormalities) and mortality than appropriately grown infants of the same gestational age (1519).
Multifetal gestations also are associated with significantly higher maternal morbidity and associated health
care costs. Women with multiple gestations are nearly
6 times more likely to be hospitalized with complications, including preeclampsia, preterm labor, preterm
premature rupture of membranes, placental abruption,
pyelonephritis, and postpartum hemorrhage (2026).
Hospital costs for women with multiple gestations are on
average 40% higher than for women with gestationalage-matched singleton pregnancies because of their
longer length of stay and obstetric complications.
Neonatal intensive care unit (NICU) admission is
required for one fourth of twins, three fourths of triplets,
and virtually all quadruplets, with average NICU stays of
18 days, 30 days, and 58 days, respectively (20, 2325,
2729).
Table 1. Morbidity and Mortality in Multiple Gestation

Characteristic
Average birth weight1
Twins
Triplets
Quadruplets
2,347 g
1,687 g
1,309 g
35.3 wk
32.2 wk
29.9 wk
Average gestational age at delivery

Percentage with growth restriction
1425
5060
5060
Percentage requiring admission to

neonatal intensive care unit3
25
75
100
Average length of stay in neonatal

intensive care unit39
18 days
30 days
58 days
Percentage with major handicap9, 10

Risk of cerebral palsy9, 10
1113
Risk of death by age 1 year
20
50
4 times more than singletons
17 times more than singletons
7 times higher than singletons
20 times higher than singletons
Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F, Munson ML. Births: final data for 2002. Natl Vital Stat Rep 2003;52(10):1102.
Mauldin JG, Newman RB. Neurologic morbidity associated with multiple gestation. Female Pat 1998;23(4):278, 30, 356, passim.
Ettner SL, Christiansen CL, Callahan TL, Hall JE. How low birthweight and gestational age contribute to increased inpatient costs for multiple births. Inquiry
199798;34:32539.
4
McCormick MD, Brooks-Gunn J, Workman-Daniels K, Turner J, Peckham GJ. The health and developmental status of very low-birth-weight children at school age. JAMA
1992;267:22048.
5
Luke B, Bigger HR, Leurgans S, Sietsema D. The cost of prematurity: a case-control study of twins vs singletons. Am J Public Health 1996;86:80914.
Albrecht JL, Tomich PG. The maternal and neonatal outcome of triplet gestations. Am J Obstet Gynecol 1996;174:15516.
Newman RB, Hamer C, Miller MC. Outpatient triplet management: a contemporary review. Am J Obstet Gynecol 1989;161:54753; discussion 5535.
Seoud MA, Toner JP, Kruithoff C, Muasher SJ. Outcome of twin, triplet, and quadruplet in vitro fertilization pregnancies: the Norfolk experience. Fertil Steril
1992;57:82534.
9
Elliott JP, Radin TG. Quadruplet pregnancy: contemporary management and outcome. Obstet Gynecol 1992;80:4214.
10
Grether JK, Nelson KB, Cummins SK. Twinning and cerebral palsy: experience in four northern California counties, births 1983 through 1985. Pediatrics
1993;92:8548.
11
Luke B, Minogue J. The contribution of gestational age and birth weight to perinatal viability in singletons versus twins. J Mat-Fetal Med 1994;3:26374.
12
Kiely JL, Kleinman JC, Kiely M. Triplets and higher order multiple births: time trends and infant mortality. Am J Dis Child 1992;146:8628.
13
Luke B, Keith LG. The contribution of singletons, twins, and triplets to low birth weight, infant mortality, and handicap in the United States. J Reprod Med
1992;37:6616.
PRACTICE BULLETINS
Role of Assisted Reproductive

Technology
In 1980, there were 37 pregnancies delivered of triplets
or more for every 100,000 live births; by 2002, this number had increased to 184 pregnancies per 100,000 live
births (1). This marked increase in the number of highorder multiple gestations was a result of the increased
use of ART and ovulation-induction agents during this
period. A similar proportion of triplet and high-order
gestations result from ART procedures and ovulation
induction (43% and 38%, respectively), whereas spontaneous conception accounts for the remainder (19%) (30).
Major morbidity in these pregnancies results from the
associated high rates of preterm birth and low birth
weight (see Table 1), although the characteristics of
women seeking these therapies also may be a factor.
One unexpected complication of ART is the high
incidence of monochorionic twins. One group evaluated
218 ART pregnancies and found the incidence of monochorionicity was 3.2%, compared with the background
rate of 0.4% (31). Other studies have reported an incidence of monochorionicity ranging from 1% to 5% in
association with both ART and ovulation induction (32).
Both animal and human data indicate that manipulation
of the zona pellucida or slowed movement through the
fallopian tube can provoke monozygotic twinning
(3335), and both of these may occur during fertility
treatments. Monozygotic twinning not only increases the
incidence of high-order multiple gestations (ie, 3
embryos are implanted but 4 fetuses result), but also
complicates fetal growth and development and can lead
to rare complications, such as twintwin transfusion syndrome or acardiac twinning. It also increases the morbidity of a pregnancy reduction procedure.
Maternal Age
The a priori risk of a poor perinatal outcome in a highorder multiple gestation is further increased by the
womans age. The growing proportion of older women
successfully undergoing fertility treatment has resulted
in an increase in pregnancies complicated by adult-onset
diseases, such as hypertension and diabetes, labor abnormalities, and cesarean delivery.
Multifetal gestations in older women also complicates prenatal genetic screening and diagnosis. Increased
maternal age alone increases the risk of fetal trisomies,
such as Down syndrome. The presence of multiple fetuses increases the mathematical probability that 1 or more
fetuses will be affected and, thus, results in a higher risk
for the pregnancy than that attributed to maternal age
alone. For example, because either 1 or both fetuses in a
twin pair could have Down syndrome, the ultimate risk
901
of Down syndrome in a twin pregnancy carried by a

33-year-old woman is the same as the risk in a singleton
pregnancy carried by a 35-year-old woman (36).
Accordingly, a Down syndrome risk equivalent to that of
a 35-year-old woman will occur at successively younger
maternal ages as the number of fetuses increases.
Prenatal Diagnosis
Amniocentesis or chorionic villous sampling may be
technically difficult to accomplish in patients with multiple gestations (3742). Technical problems unique to
high-order multiple gestation include the need to traverse
another fetus sac to reach a different fetus for sampling,
incorrect fetal karyotype caused by cross contamination
with other sacs, difficulty in accurately mapping the
fetuses and determining which fetus is being sampled,
difficulty in accurately determining whether any of the
fetuses are monochorionic twins, and difficulty in locating and reducing only the affected fetus in the event an
aneuploidy is diagnosed and termination chosen.
Complications of
Pregnancy
The incidence of gestational diabetes in twin pregnancies is higher than in singleton pregnancies (43), and the
incidence in triplet pregnancies is higher than in twin
pregnancies; up to 2239% of triplet pregnancies are
complicated by gestational diabetes, compared with
36% of twin pregnancies (44, 45). One study of 95 twin
and 26 triplet pregnancies, which controlled for other
factors that influence the incidence of gestational diabetes, such as maternal age, weight, and parity, estimated
that each additional fetus increases the risk of gestational diabetes by a factor of 1.8 (45). Another study has
shown that pregnancy reduction significantly reduces the
incidence of gestational diabetes from 22% in triplet
pregnancies to 6% in reduced twin pregnancies (44).
Many aspects of the diagnosis and management of
gestational diabetes in multiple gestation remain unexamined. The best time for testing, the ideal number of daily
calories, the optimal weight gain, whether women treated
with oral hypoglycemic agents for polycystic ovary syndrome should continue taking them, the best form of
insulin to use, the best method of fetal surveillance, and
the ideal time for delivery are all currently unknown.
Consultation with an obstetriciangynecologist who has
expertise in the management of pregnant women with
diabetes, such as a maternalfetal medicine specialist,
and with a dietitian would be helpful.
902
Hypertension and Preeclampsia

Multiple gestations are at higher risk than singleton
gestations of developing gestational hypertension. The
incidence of preeclampsia is 2.6 times higher in twin gestations than in singleton gestations (46) and is higher in
triplet gestations than in twin gestations (47). In addition,
when multiple gestation is complicated by preeclampsia,
it is significantly more likely to occur earlier and to be
severe (46, 48, 49). Gestational hypertension before
35 weeks of gestation, preeclampsia before 35 weeks of
gestation, and hypertension with a diastolic blood pressure level greater than 110 mm Hg occur 12.4 times, 6.7
times, and 2.2 times more often, respectively, in twin gestations compared with singleton gestations (48).
Placental abruption also is 8.2 times more likely (48).
Multiple gestations as a result of ART seem to be at
greater risk of developing hypertensive complications
than spontaneous multiple gestations, for reasons that are
not entirely known. One study of 198 ART multiple gestations compared with 330 spontaneous multiple gestations found that the ART pregnancies were at increased
risk (relative risk, 2.1) of developing mild or severe
preeclampsia even after controlling for maternal age and
parity (50). High-order multiple gestations also are more
likely to develop atypical preeclampsia (51). One study
of women with triplet or quadruplet pregnancies and
preeclampsia found that only 50% had hypertension,
only 38% had edema, and only 19% had proteinuria
before delivery, whereas 60% had epigastric pain and
56% had hemolysis, elevated liver enzymes, and low
platelets (HELLP) syndrome (52). Multifetal reduction
may decrease the risk of preeclampsia. One study reported that 14% of 59 twin pregnancies remaining after multifetal reduction developed preeclampsia compared with
30% of 54 triplet pregnancies (53).
The management of hypertensive complications in
high-order multiple gestations has not been studied
prospectively. Although many women with high-order
multiple gestations are placed on bed rest, this therapy
has been associated with increased fetal weight but not
with prolongation of pregnancy or avoidance of hypertensive complications (54). If severe preeclampsia,
HELLP syndrome, or another serious hypertensive complication develops before term, transfer to a tertiary care
center may improve outcome for both the woman and her
fetuses. It is unclear whether the risks associated with
postponing delivery to administer steroids are outweighed by the benefits of antenatal steroid exposure in
multifetal pregnancies.
Other Pregnancy Complications

Multiple gestations also are disproportionately affected
by more serious pregnancy complications, such as acute
fatty liver (55). Acute fatty liver, which is marked by

severe coagulopathy, hypoglycemia, and hyperammonemia, can lead to fetal or maternal death (55). Although
delivery usually halts the disease process, the postpartum
period can be complicated by pancreatitis or diabetes
insipidus or both. The coagulopathy makes delivery itself
difficult in high-order multiple gestations because cesarean delivery usually is required. Diagnosis is frequently
delayed because the symptoms, which typically include
anorexia, nausea and vomiting, and malaise beginning
late in pregnancy and developing over several days or
weeks, are vague and nonspecific, and there is concurrent
evidence of preeclampsia in at least one third of affected
women (56).
Acute fatty liver is rare, occurring in 1 in 10,000 singleton gestations. However, 14% of reported cases have
occurred in twin gestations even though they represent
fewer than 2% of all pregnancies, and recent reports
indicate that the rate may be as high as 7% in triplet pregnancies (55, 57). Many cases are associated with an autosomal recessive disorder, long-chain 3-hydroxyacyl-CoA
dehydrogenase deficiency (58, 59). Disease occurs only
when both the woman and the fetus are carrying at least 1
affected gene; multiple gestations are disproportionately
affected with this and other genetic conditions because
the more fetuses there are, the greater the chance that at
least 1 of them has inherited the womans gene mutation.
Pulmonary embolism is a leading cause of maternal
death in the United States and around the world (60, 61),
and thromboembolism is 6 times more likely during
pregnancy or the puerperium than in the nonpregnant
state. The factors most commonly associated with thromboembolism are multiple pregnancy, cesarean delivery,
delivery before 36 weeks of gestation, a body mass index
of 25 or higher, and maternal age of 35 years or older; all
are more common in multiple gestation (62). In addition,
women with multiple gestation frequently are placed on
bed rest, and the enlarged uterus mechanically obstructs
venous return and contributes to lower extremity stasis.
One study of more than 395,000 births found that multiple gestation was associated with significantly increased
risk of thromboembolism even after controlling for all
other associated risks (62).
Prompt and sustained anticoagulation is needed for
confirmed thrombosis or thromboembolism. Because the
volume of distribution is increased to a much greater
degree in multiple gestations than in singleton gestations,
it may be difficult to achieve a therapeutic level of anticoagulation. In addition, because high-order multiple
gestations are at significantly increased risk of preterm
labor, cesarean delivery, and bleeding complications,
such as abruption, the form of anticoagulation chosen
should be readily reversible. Consultation with an indi-
PRACTICE BULLETINS
vidual with expertise in maternalfetal medicine or

hematology may be helpful.
Other less common pregnancy complications occur
more frequently in multiple gestations than in singleton
gestations. A recent study of 142 multiple gestations
found that 3% of twin gestations and 14% of triplet gestations were complicated by pruritic urticarial papules
and pustules of pregnancy, compared with only 0.5% of
singleton gestations (63). Pruritic urticarial papules and
pustules of pregnancy is a dermatosis that most commonly affects primigravid women in the third trimester
(63). It usually starts in abdominal striae, and striae are
common in multiple gestations because of excessive
weight gain and rapid abdominal distention. Recently,
fetal DNA has been detected in the dermis of affected
women, which suggests that fetalmaternal cell trafficking and immune phenomena play a role (64).
Multifetal Reduction and Selective

Fetal Termination
remaining twins only when the starting number of fetuses was 5 or more (70).
Monochorionicity can complicate the reduction procedure; if one fetus of a monochorionic twin pair is inadvertently reduced, sudden hypotension and thrombotic
phenomena could result in death or damage of the
remaining twin fetus. This is illustrated by one series of
high-order multiple gestations (quadruplets and quintuplets) in which every pregnancy included a monochorionic twin pair (71). In each case, although the authors
selectively reduced only 1 of the monochorionic twins by
injection of potassium chloride, subsequent demise of all
the co-twins was confirmed.
Selective fetal termination is the application of the
fetal reduction technique to the selective termination of an
anomalous or aneuploid fetus that is part of a multiple gestation. The risks of this procedure are higher than those
associated with multifetal reduction (72). The pregnancy
usually is more advanced by the time the anomaly is diagnosed (ie, 1822 weeks of gestation compared with 1012
weeks of gestation), and the location of the anomalous
fetus may be associated with increased risk. The risk of
losing the whole pregnancy, having a preterm birth, or having an infant with a birth weight less than 2,500 g is highest when the reduced fetus overlies the cervix and when
the pregnancy is at or beyond 20 weeks of gestation (73).

Recommendations
High-order multiple gestation creates a medical and ethical dilemma. If a pregnancy with 4 or more fetuses is
continued, the probability is high that not all fetuses will
survive intact and that the woman will experience serious
morbidity. However, fetal reduction to triplet or twin gestations is associated with a significant risk of losing
either another fetus or the whole pregnancy. Most studies
have concluded that the risks associated with a quadruplet or higher pregnancy clearly outweigh the risks associated with fetal reduction.
The largest report of perinatal outcome after fetal
reduction, which included 1,789 reduction procedures
over a period of 9 years, noted an overall postprocedure
pregnancy loss rate of 11.7% and a very early preterm (ie,
between 25 and 28 weeks of gestation) delivery rate of
4.5% (65). The chance of losing either an additional fetus
or the whole pregnancy, and the chance of early preterm
delivery, increased according to the starting number of
fetuses; 23% of pregnancies that started with 6 or more
fetuses were lost before 24 weeks of gestation, and only
20% were delivered at 37 weeks of gestation or later.
Whether to reduce high-order multiple gestations to twin
or triplet gestations and whether to reduce triplet gestations at all are both areas of controversy.
Fetal reduction of a high-order multiple pregnancy
has been associated with an increased risk of intrauterine
fetal growth restriction (IUGR) in the remaining twins in
some studies but not in others (6669). One study found
the incidence of IUGR was 36% in twins reduced from
triplets, 42% in twins reduced from quadruplets, and
50% in twins reduced from quintuplets or greater, compared with 19% in twins who had not been reduced (67).
Another study found a significant risk of IUGR in the
903
Can preterm labor be predicted in multiple

gestation?
Cervical Length Measurement by

Ultrasonography
A shortened cervix identified by endovaginal ultrasonography is strongly predictive of preterm delivery in twin
pregnancies (7476). A large multicenter study of cervical length in twin pregnancies found that a cervix shorter
than 25 mm at 24 weeks of gestation was the best predictor of delivery before 32, 35, and 37 weeks of gestation (74) and was significantly more common in twin
gestations than in singleton gestations at both 24 and
28 weeks of gestation. One study of 32 triplet pregnancies reported similar data, with cervical measurements
comparable to those reported for twin pregnancies (77).
Cervical Length Measurement by

Digital Examination
Serial digital examinations by an experienced examiner,
assessing both cervical length and dilation, have been
reported to have positive predictive values of 6070% in
904
twin and triplet gestations (7779). However, digital

examination may be less objective than ultrasonographic
measurement and does not allow assessment of the internal os.
Fetal Fibronectin
Fetal fibronectin is a high-molecular-weight extracellular
matrix glycoprotein that is normally found in fetal membranes, placental tissues, and amniotic fluid. Its presence
in cervicalvaginal fluids at concentrations higher than
50 ng/mL is abnormal and has been shown to predict
preterm delivery in singleton gestations. Four studies
examining the utility of measuring fetal fibronectin in
twin or triplet gestations showed that a single fetal
fibronectin test had a high negative predictive value, and
serial tests had a fairly high positive predictive value
(range: 3853%) (74, 8082). However, at least 1 study
found that fetal fibronectin levels were not predictive of
preterm delivery in twin gestations after controlling for
cervical length (74).
Home Uterine Activity Monitoring
Are there interventions that can prolong

pregnancy in multiple gestation?
Current data from U.S. birth records indicate that

5557% of all multiple gestations are delivered preterm,
and 4963% of these infants weigh less than 2,500 g
(84). Twelve percent of twin pregnancies, 36% of triplet
pregnancies, and 60% of quadruplet pregnancies are born
before 32 weeks of gestation, when perinatal morbidity
and mortality are greatest. The same factors that contribute to preterm birth in singleton pregnancies affect
multiple gestations and may be more common: lower and
upper genital tract infection; uterine overdistension; cervical incompetence; maternal medical complications;
maternal stress; and fetal, placental, or uterine abnormalities. However, the identification of these risk factors has
not lead to the development of effective protocols or therapies to prevent preterm delivery, although many different therapies have been investigated.
The value of prophylactic cerclage in prolonging highorder multiple gestation has not been assessed, but its use
in twin pregnancy has been studied in at least 2 prospective trials, including 50 and 74 sets of twins, respectively;
cerclage did not prolong gestation or improve perinatal
outcome in either study (85, 86). The studies of cerclage
in triplet pregnancies are all retrospective, making bias in
assignment of this therapy highly likely.
Routine Hospitalization
No trials of routine hospitalization of high-order multiple
gestations have been published. Four prospective randomized trials and one retrospective study have shown
that bed rest in the hospital does not prolong twin gestation (54, 8790). Retrospective series assessing the value
of elective hospitalization for triplet pregnancies also
have failed to identify any significant differences in perinatal outcome after hospitalization (91, 92).
Restriction of Activities and

Rest at Home
Although this is the most commonly prescribed therapy
for multiple gestation, it has not been evaluated in a
prospective randomized manner. Most of the retrospective analyses of bed rest for multiple gestation are strongly biased by the indications for bed rest, and some
studies were performed so long ago that bed rest was not
instituted until the third trimester because the multiple
pregnancy was not diagnosed until then (9395).
Although initially presented as a potentially effective tool

for identifying preterm labor early enough to allow for
treatment, several studies have now cast considerable
doubt on the utility of home uterine activity monitoring
for this purpose. In one large randomized prospective
trial, 2,422 pregnant women, including 844 twin pregnancies, were randomly assigned to weekly contact with
a perinatal nurse, daily contact with a perinatal nurse, or
daily contact with a perinatal nurse and home uterine
activity monitoring (83). There was no difference in outcome among the twin gestations in the 3 groups.
Prophylactic Cerclage
How is preterm labor managed in multiple

gestation?
Tocolytics
If effective tocolytic therapy were available, identifying
women at risk of preterm delivery could reduce the incidence of preterm birth. The use of prophylactic tocolysis
in twin gestations has been examined in at least 7
prospective studies (96102). These trials showed no
consistent effect on preterm birth, birth weight, or neonatal mortality. Importantly, the risks associated with each
tocolytic are amplified in multiple gestations. Betamimetics are associated with increased maternal and fetal
cardiac stress and gestational diabetes; these complications occur more frequently in multiple gestations even
without -mimetic therapy (103, 104). In addition,
women with multiple gestations are at increased risk of
developing pulmonary edema resulting in severe respiratory distress when tocolytic agents, steroids, and intravenous fluids are administered together (105, 106).
PRACTICE BULLETINS
Therefore, because of the associated risks of tocolytics

in high-order pregnancies, they should be used
judiciously.
Corticosteroids
The effect of antenatal steroid administration and the
possible effects of steroid dose on efficacy in multiple
gestations have not been examined. Nevertheless, the
National Institutes of Health recommends that all
women in preterm labor who have no contraindications
to steroid use be given one course of steroids, regardless
of the number of fetuses (107).
How should growth restriction or discordant

growth be diagnosed and managed in multiple gestation?
ferent sexes. They would not be expected to be more

similar in weight than any other siblings. If 2 fetuses are
discordant but both have normal estimated weights and
grow appropriately on their own growth curves, the discordance may not indicate a pathologic process (111).
Conversely, concordance would not be desirable if both
fetuses are growth restricted. One study of 279 twin pairs
showed that when birth weight and gestational age at
delivery were evaluated separately, discordance itself
was not a strong predictor of neonatal outcome (112).
However, attribution of fetal weight differences to
zygosity should only be considered once other more serious etiologies have been ruled out.
Discordance can be caused by structural or genetic
fetal anomalies; discordant infection; an unfavorable
placental implantation or umbilical cord insertion site;
placental damage (ie, partial abruption); or complications related to monochorionic placentation, such as
twintwin transfusion syndrome. All of these complications occur more frequently in high-order multiple gestations. The workup should include a review of all
prenatal exposures, a specialized ultrasound examination, and, depending on the gestational age, a test of fetal
well-being.
Because of the inherent difficulty in fully evaluating
each fetus, the ultrasound examination should be performed by someone with skill and experience in scanning multiple gestations. If an anomaly is identified, the
patient should receive counseling, and testing should be
offered, if applicable. In rare cases (for example,
twintwin transfusion syndrome), therapy may be available. Before performing a preterm delivery to benefit the
growth-restricted fetus, the well-being of the other fetuses needs to be considered. A consultation with an obstetriciangynecologist with expertise in the management
of high-risk pregnancies, such as a maternalfetal medicine specialist, may be helpful.
Fetuses of a multiple gestation generally do not grow at

the same rate as singleton fetuses. One obvious etiology
is placental pathology; multiple gestations are at
increased risk to include at least 1 fetus with a suboptimal placental implantation site or abnormal umbilical
cord morphology. For example, one study of 39 sets of
triplets found that 28% included at least 1 fetus with a
velamentous cord insertion site that was likely to be
growth restricted as a result (108). Depending on the
number of fetuses, a diminution in fetal growth may be
discernible as early as 22 weeks of gestation (68). The
long held theory that low-birth-weight infants from a
multiple gestation do better than low-birth-weight singleton infants is not correct. Because infants of multiple
gestations are likely to be both preterm and low birth
weight, their outcome may actually be worse (109).
Abnormally slow fetal growth in a multiple gestation may be easier to recognize when not all of the fetuses are affected equally. Discordant fetal growth is
common in multiple gestation and usually is defined by
a 1525% reduction in the estimated fetal weight of the
smaller fetus when compared with the largest (110).
Most published studies examine discordance in twins;
twin weight discordance is associated with structural
malformations, stillbirth, IUGR, preterm delivery,
cesarean delivery for nonreassuring fetal heart tracing,
umbilical arterial pH less than 7.1, admission to the
NICU, respiratory distress syndrome, and neonatal death
within 7 days of delivery (6, 8, 9). The threshold at
which discordant growth is most strongly associated
with adverse outcomes is still a matter of debate, even in
twin gestations (1, 6, 7).
Some discordance is expected in multiple gestations, especially those resulting from ovulation induction
or the implantation of 3 or more embryos, when the
fetuses are not genetically identical and may be of dif-
905
How is the death of one fetus managed?
Multiple gestations, especially high-order multiple gestations, are at increased risk of losing 1 or more fetuses
remote from delivery. One report described the outcome
of every twin, triplet, and higher order multiple gestation
delivered at one perinatal center during a 5-year period
(113). Of 310 twin and 45 triplet or higher pregnancies,
19 were complicated by the spontaneous demise of one
fetus, a loss rate of 6%. Six losses occurred in the first
trimester and 13 in the second or third trimester; an additional 9 pregnancies underwent fetal reduction, and one
of these pregnancies was miscarried afterward. The
causes of the first-trimester losses could not be determined, but the later losses were caused by twintwin
906
Multiple gestations are at increased risk of stillbirth. The

risk in multifetal pregnancies is higher than the risk in
singleton pregnancies at each week of gestation, and the
loss is likely to occur at a much earlier gestational age
than in singleton or twin pregnancies (117). The most
effective fetal surveillance system for such pregnancies
is not known. Because of the increased risk, clinicians
frequently initiate fetal heart rate testing. Both the nonstress test and the fetal biophysical profile have been
shown to be effective in identifying the compromised
twin or triplet gestation (118122). However, none of
these data are based on prospective study and none per-
How is delayed delivery of the second twin

managed?
Rarely, preterm labor results in expulsion of a single

fetus followed by cessation of uterine contractions and
uterine quiescence. Often, the placenta remains in situ,
with the umbilical cord visibly protruding through the
cervical os. Whether such an event should prompt delivery of the remaining fetuses is controversial. In view of
the paucity of objective, prospective, randomized data
and the risk involved, consultation with individuals with
training, experience, and expertise in maternalfetal
medicine and neonatology is indicated.
Is there a role for routine antepartum fetal

surveillance?
tain to high-order multiple gestations. Additionally, several issues have not been resolved. For example, it is not
known at what gestational age testing should be initiated, whether testing should be performed once or twice
per week, or whether there is a need to test normally
growing dichorionic twins. At present, antepartum fetal
surveillance in multiple gestations is recommended in all
situations in which surveillance would ordinarily be performed in a singleton pregnancy (eg, IUGR, maternal
disease, decreased fetal movement). Further studies are
needed to determine whether routine antepartum fetal
surveillance provides objective benefit in the absence of
other high-risk conditions.
transfusion syndrome (n = 4), severe IUGR (n = 3), placental insufficiency (n = 4), and placental abruption
(n = 1); the cause of 1 loss was unknown. Because highorder multiple gestations are significantly more likely to
sustain the complications causing fetal demise in this
study and others, the loss rates for high-order multiple
gestations may be considerably higher than 6%.
No fetal monitoring protocol has been shown to predict most of these losses. In addition, authorities disagree
about the preferred antepartum surveillance method and
management once a demise has occurred. Some investigators have advocated immediate delivery of the remaining fetuses (114). However, if the death is the result of an
abnormality of the fetus itself rather than maternal or
uteroplacental pathology, and the pregnancy is remote
from term, expectant management may be appropriate.
The most difficult cases are those in which the fetal
demise occurs in 1 fetus of a monochorionic twin pair.
Because virtually 100% of monochorionic placentas
contain vascular anastomoses that link the circulations of
the 2 fetuses, the surviving fetus is at significant risk of
sustaining damage caused by the sudden, severe, and
prolonged hypotension that occurs at the time of the
demise or by embolic phenomena that occurs later (115,
116). By the time the demise is discovered, the greatest
harm has most likely already been done, and there may
not be any benefit in immediate delivery, especially if the
surviving fetuses are very preterm and otherwise healthy.
In such cases, allowing the pregnancy to continue may
provide the most benefit.
Although maternal disseminated intravascular coagulopathy (DIC) remains a theoretical risk, it rarely
occurs. One series of 28 multiple gestations complicated
by the demise of one fetus remote from term included no
cases of DIC (113). Fibrinogen and fibrin degradation
product levels can be monitored serially until delivery,
and delivery can be expedited if DIC develops.
How are problems caused by monochorionic

placentation managed?
TwinTwin Transfusion Syndrome

Twintwin transfusion syndrome is believed to occur as
the result of uncompensated arteriovenous anastomoses
in a monochorionic placenta, which lead to greater net
blood flow going to one twin at the expense of the other
(123). The donor twin usually is anemic and growth
restricted and appears stuck to one spot in the uterus
because the lack of amniotic fluid in its sac precludes
movement; the recipient twin usually is plethoric and
much larger, and hydramnios is evident. The syndrome
usually becomes apparent in the second trimester and
can rapidly lead to premature rupture of membranes,
preterm labor, or early mortality because of heart failure
in either of the fetuses (124126). A variety of therapies
have been attempted, but serial therapeutic amniocenteses of the recipient twins amniotic sac is most frequently used. This therapy is believed to work by favorably
changing intraamniotic pressure and, thus, placental
intravascular pressure, allowing redistribution of placental blood flow and normalization of amniotic fluid volumes in each sac (123127). More aggressive therapies,
which usually are considered only for very early, severe
PRACTICE BULLETINS
cases, include abolishing the placental anastomoses by

endoscopic laser coagulation or selective feticide by
umbilical cord occlusion (128131). Because both twins
are at significantly increased risk of sudden death resulting from either hypovolemic or hypervolemic heart failure, these pregnancies should be monitored closely.
Death of one fetus has been reported to result in the sudden transfusion of blood from the viable fetus to the low
pressure system of the dead fetus, resulting in exsanguination of the viable twin (132, 133). If the gestational age is such that survival is likely, immediate delivery
should be considered, recognizing that damage to the
remaining viable fetus may already have occurred.
Rare Complications
Are there special considerations for timing of

delivery in multiple gestations?
Are there special considerations for route of

delivery for multiple gestations?
The route of delivery for twins should be determined by

the position of the fetuses, the ease of fetal heart rate
monitoring, and maternal and fetal status. Data are insufficient to determine the best route of delivery for highorder multiple gestations. There are retrospective case
series that validate vaginal delivery as a potential mode of
delivery, especially for triplet gestations. However, most
such pregnancies are delivered by cesarean delivery.
Summary of
Recommendations
The nadir of perinatal mortality for twin pregnancies

occurs at approximately 38 completed weeks of gestation and at 35 completed weeks of gestation for triplets;
the nadir for quadruplet and other high-order multiple
gestations is not known (137). Fetal and neonatal morbidity and mortality begin to increase in twin and triplet
pregnancies extended beyond 37 and 35 weeks of gestation, respectively (137, 138). However, no prospective
randomized trials have tested the hypothesis that elective
delivery at these gestational ages improves outcomes in
these pregnancies. If the fetuses are appropriate in size
for gestational age with evidence of sustained growth

and there is normal amniotic fluid volume and reassuring
antepartum fetal testing in the absence of maternal complications, such as preeclampsia or gestational diabetes,
the pregnancy can be continued. Alternatively, if the
woman is experiencing morbidities that would improve
with delivery but do not necessarily mandate delivery
(eg, worsening dyspnea, inability to sleep, severe dependent edema, painful superficial varicosities), delivery
may be considered at these gestational ages.
Determination of fetal pulmonary maturity before
delivery may be necessary for twin and other multiple
gestations if prenatal care was late, if the woman desires
a scheduled delivery, or if the pregnancy is complicated
by preterm labor or preterm premature rupture of
membranes. Several reports have noted that beyond
3132 weeks of gestation, the biochemical markers of
pulmonary maturity (lecithin/sphingomyelin ratio or fluorescence polarization immunoassay) are higher in twin
pregnancies than in singleton pregnancies at comparable
gestational ages (139, 140). Recent publications note
that asynchronous pulmonary maturity occurs in more
than 5% of twins, regardless of fetal sex and size. Before
32 weeks of gestation, 25% of twin pairs have a significant disparity, usually resulting from one twin having a
lecithin/sphingomyelin ratio that is more mature than
expected for gestational age (141). Accordingly, some
authorities recommend that the gestational sac of each
twin be sampled if technically feasible. There are insufficient data to make a similar recommendation for pregnancies with 3 or more fetuses.
An acardiac or acephalus twin is a monozygotic fetus

without a normally developed heart or brain, respectively, as the result of abnormal division of the zygote at the
time of twinning. These fetuses are nonviable and survive antenatally only because they receive blood flow
from their monochorionic co-twin. Because the pump
twin is supplying blood flow to both its own body and
that of its abnormal twin, death from heart failure is a
common complication (134). Such pregnancies require
close monitoring, with consideration of early delivery or
selective feticide of the abnormal co-twin by umbilical
cord occlusion if heart failure develops (135).
When division of the embryonic disc is not complete, twins can be joined at the head, thorax, abdomen,
or spine and often share organs. Management of conjoined twins is directed by their chance of long-term
survival. If postnatal separation or survival without separation is possible, the twins should be monitored closely for heart failure or other signs of stress and be
delivered atraumatically, usually by cesarean delivery
(136). Pregnancies in which survival of either fetus is
unlikely can be managed expectantly but also may
require cesarean delivery for dystocia.
907
Tocolytic agents should be used judiciously in multiple gestations.
908
Women with high-order multiple gestations should

be queried about nausea, epigastric pain, and other
unusual third-trimester symptoms because they are
at increased risk to develop HELLP syndrome, in
many cases before symptoms of preeclampsia have
appeared.
The higher incidence of gestational diabetes

and hypertension in high-order multiple gestations
warrants screening and monitoring for these
complications.
The National Institutes of Health recommends that

women in preterm labor with no contraindication to
steroid use be given one course of steroids, regardless of the number of fetuses.
Cerclage, hospitalization, bed rest, or home uterine

activity monitoring have not been studied in highorder multiple gestations, and, therefore, should not
be ordered prophylactically. There currently is no
evidence that their prophylactic use improves outcome in these pregnancies.
6. Roberts CL, Raynes-Greenow CH, Algert CS, Peat B.

Higher order multiple pregnancies in New South Wales
19901999. Aust N Z J Obstet Gynaecol 2002;42:514.
(Level III)
through December 1994. Am J Obstet Gynecol 1998;
179:16329. (Level II-3)
8. Powers WF, Kiely JL. The risk confronting twins: a
national perspective. Am J Obstet Gynecol 1994;170:
45661. (Level II-2)
9. Donovan EF, Ehrenkranz RA, Shankaran S, Stevenson
DK, Wright LL, Younes N, et al. Outcomes of very low
birth weight twins cared for in the National Institute of
Child Health and Human Development Neonatal
Research Networks intensive care units. Am J Obstet
10. Yokoyama Y, Shimizu T, Hayakawa K. Incidence of handicaps in multiple births and associated factors. Acta Genet
Med Gemellol (Roma) 1995;44:8191. (Level II-2)
11. Petterson B, Nelson KB, Watson L, Stanley F. Twins,
triplets, and cerebral palsy in births in Western Australia
in the 1980s. BMJ 1993;307:123943 (Level II-3)
12. Grether JK, Nelson KB, Cummins SK. Twinning and
cerebral palsy: experience in four northern California
counties, births 1983 through 1985. Pediatrics 1993;92:
8548. (Level II-3)
Women should be counseled about the risks of highorder multiple gestation before beginning ART.
13. Mauldin JG, Newman RB. Neurologic morbidity associated with multiple gestation. Female Pat 1998;23(4):
278, 30, 356, passim. (Level III)
Because the risks of invasive prenatal diagnosis procedures, such as amniocentesis and chorionic villus
sampling, are inversely proportional to the experience of the operator, only experienced clinicians
should perform these procedures in high-order multiple gestations.
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Management of discordant growth restriction or

death of one fetus in a high-order multiple gestation
should be individualized, taking into consideration
the welfare of the other fetus(es).
14. Skrablin S, Kuvacic I, Pavicic D, Kalafatic D, Goluza T.

Maternal neonatal outcome in quadruplet and quintuplet
versus triplet gestations. Eur J Obstet Gynecol Reprod
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(Level I)
101. Cetrulo CL, Freeman RK. Ritodrine HCL for the prevention of premature labor in twin pregnancies. Acta Genet
Med Gemellol (Roma) 1976;25:3214. (Level I)
102. Ashworth MF, Spooner SF, Verkuyl DA, Waterman R,
Ashurst HM. Failure to prevent preterm labour in twin
pregnancy using prophylactic oral salbutamol. Br J
103. Fletcher SE, Fyfe DA, Case CL, Wiles HB, Upshur JK,
Newman RB. Myocardial necrosis in a newborn after
long-term subcutaneous terbutaline infusion for suppression of preterm labor. Am J Obstet Gynecol 1991;
165:14014. (Level III)
104. Gabriel R, Harika G, Saniez D, Durot S, Quereux C,
Wahl P. Prolonged intravenous ritodrine therapy: a comparison between multiple and singleton pregnancies.
(Level II-1)
912
105. Perry KG Jr, Morrison JC, Rust OA, Sullivan CA, Martin
RW, Naef RW 3rd. Incidence of adverse cardiopulmonary effects with low-dose continuous terbutaline
infusion. Am J Obstet Gynecol 1995;173:12737.
(Level II-3)
106. Katz M, Robertson PA, Creasy RK. Cardiovascular complications associated with terbutaline treatment for
(Level II-3)
107. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement 1994;12:124.
(Level III)
108. Feldman DM, Borgida AF, Trymbulak WP, Barsoom MJ,
Sanders MM, Rodis JF. Clinical implications of velamentous cord insertion in triplet gestations. Am J Obstet
109. Kaufman GE, Malone FD, Harvey-Wilkes KB, Chelmau
D, Penzias AS, DAlton MD. Neonatal morbidity and
mortality associated with triplet pregnancy. Obstet
110. Talbot GT, Goldstein RF, Nesbitt T, Johnson JL, Kay HH.
Is size discordancy an indication for delivery of preterm twins? Am J Obstet Gynecol 1997;177:10504.
(Level II-2)
111. Warner BB, Kiely JL, Donovan EF. Multiple births and
outcome. Clin Perinatal 2000;27:34761, ix. (Level III)
112. Hsieh TT, Chang TC, Chiu TH, Hsu JJ, Chao A. Growth
discordancy, birth weight and neonatal adverse events in
third trimester twin gestations. Gynecol Obstet Invest
1994;38:36 4 0. (Level III)
113. Petersen IR, Nyholm HC. Multiple pregnancies with single intrauterine demise. Description of twenty-eight
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114. DAlton ME, Newton ER, Cetrulo CL. Intrauterine fetal
demise in multiple gestation. Acta Genet Med Gemellol
(Roma) 1984;33:439. (Level III)
115. Robertson EG, Neer KJ. Placental injection studies in
twin gestation. Am J Obstet Gynecol 1983;147:1704.
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116. Langer B, Boudier E, Gasser B, Christmann D, Messer J,
Schlaeder G. Antenatal diagnosis of brain damage in the
survivor after the second trimester death of a monochorionic monoamniotic co-twin: case report and literature
review. Fetal Diagn Ther 1997;12:28691. (Level III)
117. Sairam S, Costeloe K, Thilaganathan B. Prospective risk
of stillbirth in multiple-gestation pregnancies: a population-based analysis. Obstet Gynecol 2002;100:63841.
(Level III)
120. Devoe LD, Azor H. Simultaneous nonstress fetal heart

rate testing in twin pregnancy. Obstet Gynecol 1981;58:
4505. (Level II-3)
121. Knuppel RA, Rattan PK, Scerbo JC, OBrien WF.
Intrauterine fetal death in twins after 32 weeks of gestation. Obstet Gynecol 1985;65:1725. (Level III)
122. Lodeiro JG, Vintzileos AM, Feinstein SJ, Campbell WA,
Nochimson DJ. Fetal biophysical profile in twin gestation. Obstet Gynecol 1986;67:8247. (Level II-3)
123. Talbert DG, Bajoria R, Sepulveda W, Bower S, Fisk NM.
Hydrostatic and osmotic pressure gradients produce
manifestations of fetofetal transfusion syndrome in a
computerized model of monochorial twin pregnancy. Am
J Obstet Gynecol 1996;174:598608. (Level III)
124. De Lia J, Fisk N, Hecher K, Machin G, Nicolaides K,
Hyett J, et al. Twin-to-twin transfusion syndrome
debates on the etiology, natural history and management.
Ultrasound Obstet Gynecol 2000;16:2103. (Level III)
125. Mahony BS, Petty CN, Nyberg DA, Luthy DA, Hickok
DE, Hirsch JH. The stuck twin phenomenon: ultrasonographic findings, pregnancy outcome, and management with serial amniocenteses. Am J Obstet Gynecol
1990;163:151322. (Level III)
126. Urig MA, Clewell WH, Elliott JP. Twin-twin transfusion
syndrome. Am J Obstet Gynecol 1990;163:15226.
(Level III)
127. Dickinson JE. Severe twin-twin transfusion syndrome:
current management concepts. Aust N Z J Obstet
Gynaecol 1995;35:1621. (Level III)
128. De Lia JE, Kuhlmann RS, Harstad TW, Cruikshank DP.
Fetoscopic laser ablation of placental vessels in severe
previable twin-twin transfusion syndrome. Am J Obstet
Gynecol 1995;172:12028; discussion 120811.
(Level II-3)
129. Quintero RA, Comas C, Bornick PW, Allen MH, Kruger
M. Selective versus non-selective laser photocoagulation
of placental vessels in twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 2000;16:2306.
(Level II-1)
130. Quintero RA, Bornick PW, Allen MH, Johnson PK.
Selective laser photocoagulation of communicating vessels in severe twin-twin transfusion syndrome in women
with an anterior placenta. Obstet Gynecol 2001;97:
47781. (Level II-1)
131. Tanawattanacharoen S, Tantivatana J, Charoenvidhya D,
Wisawasukmongchol W, Uerpairojkit B, Wacharaprechanont T, et al. Occlusion of umbilical artery using a
Guglielmi detachable coil for the treatment of TRAP
sequence. Ultrasound Obstet Gynecol 2002; 19:3135.
(Level III)
118. Bailey D, Flynn AM, Kelly J, OConor M. Antepartum

fetal heart rate monitoring in multiple pregnancy. Br J
132. Fusi L, Gordon H. Twin pregnancy complicated by single intrauterine death. Problems and outcome with conservative management. Br J Obstet Gynaecol 1990;
119. Blake GD, Knuppel RA, Ingardia CJ, Lake M, Aumann

G, Hanson M. Evaluation of nonstress fetal heart rate
testing in multiple gestations. Obstet Gynecol 1984;63:
52832. (Level II-3)
133. Ohkuchi A, Minakami H, Shiraishi H, Suzuki I, Ohki T,

Sato I. Intrauterine death of one twin, with rescue of the
other, in twin-twin transfusion syndrome. Ultrasound
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134. Moore TR, Gale S, Bernirschke K. Perinatal outcome of

forty-nine pregnancies complicated by acardiac twinning. Am J Obstet Gynecol 1990;163:90712. (Level III)
135. Quintero RA, Reich H, Puder KS, Bardicef M, Evans MI,
Cotton DB, et al. Brief report: umbilical-cord ligation of
an acardiac twin by fetoscopy at 19 weeks of gestation.
136. van den Brand SF, Nijhuis JG, van Dongen PW. Prenatal
ultrasound diagnosis of conjoined twins. Obstet Gynecol
Surv 1994;49:65662. (Level III)
137. Luke B. Reducing fetal deaths in multiple births: optimal
birthweights and gestational ages for infants of twin and
triplet births. Acta Genet Med Gemellol (Roma) 1996;
45:33348. (Level II-3)
138. Minakami H, Sato I. Reestimating date of delivery in
multifetal pregnancies [published erratum appears in
JAMA 1996;276:452]. JAMA 1996;275:14324.
(Level II-3)
139. Leveno KJ, Quirk JG, Whalley PJ, Herbert WN, Trubey
R. Fetal lung maturation in twin gestation. Am J Obstet
Gynecol 1984;148:40511. (Level II-2)
140. McElrath TF, Norwitz ER, Robinson JN, Tanasijevic MJ,
Lieberman ES. Differences in TDx fetal lung maturity
assay values between twin and singleton gestations. Am
141. Whitworth NS, Magann EF, Morrison JC. Evaluation of
fetal lung maturity in diamniotic twins. Am J Obstet
Gynecol 1999;180:1438 41. (Level II-2)
913

for inclusion in this document. Guidelines published by
organizations or institutions such as the National Institutes
of Health and the American College of Obstetricians and
Force:
I
type of evidence.
committees.
01923, (978) 750-8400.
ISSN 1099-3630
Multiple gestation: complicated twin, triplet, and high-order multifetal
pregnancy. ACOG Practice Bulletin No. 56. American College of
914
ACOG
PRACTICE
BULLETIN
NUMBER 60, MARCH 2005

of Steven G. Gabbe, MD. The
of practice.
Reaffirmed 2007
Pregestational
Diabetes Mellitus
Pregestational diabetes mellitus represents one of the most challenging medical
complications of pregnancy. This document provides an overview of the current
understanding of pregestational diabetes mellitus and suggests management
guidelines during pregnancy. Because few well-designed studies have been performed, many of the guidelines are based on expert and consensus opinion.
Background
Definition and Prevalence
More than 8 million women in the United States have pregestational diabetes
mellitus, and it is observed in 1% of all pregnancies (1, 2). Type 2 pregestational diabetes mellitus is most common and is characterized by onset later in
life; peripheral insulin resistance; relative insulin deficiency; obesity; and the
development of vascular, renal, and neuropathic complications. The rapidly
increasing incidence of type 2 pregestational diabetes mellitus is caused, in
part, by increasing obesity in the United States (3). Although 90% of diabetes
cases encountered during pregnancy are gestational diabetes mellitus (GDM),
more than one half of these women eventually develop type 2 pregestational
diabetes mellitus later in life. Type 1 diabetes mellitus tends to occur early in
life. In contrast to type 2 pregestational diabetes mellitus, type 1 pregestational
diabetes mellitus is characterized by an autoimmune process that destroys the
pancreatic cells, leading to the need for insulin therapy.
Management of Diabetes During Pregnancy

Pregnancy is characterized by increased insulin resistance and reduced sensitivity to insulin action. Late in the first trimester, relatively higher levels of
estrogen enhance insulin sensitivity and, when associated with nausea and vomiting, increase the risk for maternal hypoglycemia. The increase in insulin resistance is largely the result of a mixture of placental hormones, including human
PRACTICE BULLETINS
placental lactogen, progesterone, prolactin, placental

growth hormone, and cortisol. More recently, tumor
necrosis factor and leptin have been implicated as contributors to the insulin resistant state of pregnancy (4). Insulin resistance is greatest in the third
trimester.
The management of diabetes in pregnancy must
focus on excellent glucose control achieved using a careful combination of diet, exercise, and insulin therapy
(58). Patients may need to be seen every 12 weeks during the first two trimesters and weekly after 2830 weeks
of gestation. During pregnancy, caloric requirements are
increased approximately 300 kcal higher than basal
needs in patients with a singleton fetus (9, 10).
Carbohydrate counting increases dietary flexibility and is
extremely useful as long as the total daily caloric intake
is considered to avoid excessive weight gain. A registered
dietitian may be of value in providing an individualized
nutrition program. Women with normal body weights
usually require 3035 kcal/kg/d. Women who are less
than 90% of desirable body weight may need to increase
their caloric requirements to 3040 kcal/kg, whereas
those who are more than 120% of desirable body weight
should decrease their caloric intake to 24 kcal/kg/d.
Caloric composition includes 4050% from complex,
high-fiber carbohydrates; 20% from protein; and 3040%
from primarily unsaturated fats. The calories may be distributed as follows: 1020% at breakfast; 2030% at
lunch; 3040% at dinner; and up to 30% for snacks, especially a bedtime snack to reduce nocturnal hypoglycemia
(9). Artificial sweeteners, including saccharin, aspartame, and acesulfame-k, may be safely used in moderate
amounts. Patients should be encouraged to keep a log of
food intake several days each week so that this information can be correlated with insulin dosages, exercise, and
glucose values.
Most insulin used in the treatment of pregestational
diabetes mellitus is biosynthetic human insulin. Insulin
requirements will increase throughout pregnancy, most
markedly in the period between 2832 weeks of gestation
(11). On average, insulin needs increase from a range of
0.70.8 U/kg/d in the first trimester, to 0.81 U/kg/d in
the second trimester, to 0.91.2 U/kg/d in the third
trimester (7, 12). The goal of therapy is to maintain capillary glucose levels as close to normal as possible,
including a fasting glucose level of 95 mg/dL or less, premeal values of 100 mg/dL or less, 1-hour postprandial
levels of 140 mg/dL or less, and 2-hour postprandial values of 120 mg/dL or less. During the night, glucose levels should not decrease to less than 60 mg/dL. Mean
capillary glucose levels should be maintained at an average of 100 mg/dL with a glycosylated hemoglobin A1C
(Hb A1C) concentration no higher than 6% (13, 14).
915
Short- or rapid-acting insulins (short-acting regular

insulin, insulin lispro, and insulin aspart) are administered before meals to reduce glucose elevations associated with eating (15, 16) (Table 1). Although insulin lispro
may be used in place of regular insulin, the two are not
interchangeable. Regular insulin should be given approximately 30 minutes before eating. Insulin lispro should be
given immediately before eating (17). Although its rapid
onset of action improves compliance and patient satisfaction, insulin lispro can cause significant hypoglycemia in
the unprepared patient.
Longer acting insulins are used to restrain hepatic
glucose production between meals and in the fasting state
(see Table 1). Intermediate-acting insulin (15, 16) usually is given before breakfast with a rapid- or short-acting
insulin and before the evening meal or at bedtime.
Bedtime dosing is preferred because an injection given
with the evening meal may increase the risks of nocturnal hypoglycemia. Extended insulin zinc suspension has
a prolonged duration of action that may make it difficult
to determine the timing of its effect, especially if it is
given twice daily. Glargine is a recently developed
human insulin analog produced with recombinant DNA
(18). The absorption of this insulin analog is delayed,
creating a steady basal insulin state with no peak and a
24-hour duration. Glargine cannot be mixed in the same
syringe with other insulins. Experience with glargine in
pregnancy has been limited. In patients who are highly
insulin resistant, regular U500 (concentrated) insulin
may be valuable (14).
Frequent self-monitoring of blood glucose is essential to achieve euglycemia without significant hypoglycemia during pregnancy (19). Capillary glucose levels
should be checked using a glucose meter and recorded in
the fasting state, before and 1 or 2 hours after each meal,
Table 1. Action Profile of Commonly Used Insulins
Type
Onset of
Action
Peak of
Action (hours)
Duration of
Action (hours)
Insulin lispro
115 minutes
12
45
Insulin aspart
115 minutes
12
45
Regular insulin
3060 minutes
24
68
Isophane insulin
suspension
13 hours
57
1318
Insulin zinc
suspension
13 hours
48
1320
Extended insulin
zinc suspension
24 hours
814
1830
Insulin glargine
1 hour
No peak
24
Modified from Gabbe SG, Graves CR. Management of diabetes mellitus complicating pregnancy. Obstet Gynecol 2003;102:85768.
916
and before bed. Results may differ depending on

whether the meter tests whole blood, serum, or plasma.
Fasting glucose levels reflect the action of overnight
basal insulin, whereas glucose concentrations before
meals indicate daytime basal insulin activity (15). Levels
after meals reveal the effect of the meal and recent
insulin doses. In selected patients, especially those on
insulin pumps, glucose determinations at 23 AM may
help detect nocturnal hypoglycemia caused by excessive
basal insulin or an inadequate bedtime snack or nocturnal hyperglycemia caused by insufficient basal insulin or
pump failure. Generally, insulin doses are changed by
20% in response to hyperglycemia or hypoglycemia. A
Hb A1C measurement provides an indication of glycemic
control over the past 23 months and should be performed during each trimester. An Hb A1C value of 8%
reflects a mean glucose level of 180 mg/dL, with each
1% higher or lower than 8% equal to a change of
30 mg/dL (13). Patients should check urine ketones
when their glucose levels exceed 200 mg/dL and immediately report positive results to their health care teams.
Even with meticulous monitoring, hypoglycemia is
more frequent in pregnancy than at other times, particularly in patients with type 1 pregestational diabetes mellitus. Patients should be questioned to determine if they
can recognize when their glucose levels decrease to less
than 60 mg/dL. Patients and their families should be
taught how to respond quickly and appropriately to
hypoglycemia. A glass of milk is preferable to fruit
juices containing high levels of glucose. In addition,
patients should have glucagon on hand for severe hypoglycemia and loss of consciousness.
Maternal Morbidity
Pregnancy has been associated with exacerbation of
many diabetes-related complications. Poorly controlled
pregestational diabetes mellitus leads to serious endorgan damage that may eventually become life threatening. In turn, preexisting diabetes-related end-organ
disease may have deleterious effects on obstetric
outcomes.
Diabetic retinopathy, the leading cause of blindness
between ages 24 and 64 years, is classified as 1) background retinopathy, characterized by retinal microaneurysms and dot-blot hemorrhages; and 2) proliferative
retinopathy, marked by neovascularization (20). The
rapid institution of strict glycemic control in women
with diabetes during pregnancy has been associated with
acute progression of retinopathy, particularly in women
with hypertensive disorders, including preeclampsia
(21). Proliferative retinopathy is best treated with laser
therapy, ideally before conception (22). Women with
diabetes who become pregnant should have a compre-
hensive eye examination in the first trimester and be

monitored closely throughout pregnancy (23).
Diabetic nephropathy is estimated to occur in
510% of pregnancies (24, 25). Most studies have failed
to demonstrate permanent deterioration in renal function
associated with pregnancy in women with mild-to-moderate diabetic nephropathy. However, progression to endstage renal disease has been reported in women with
serum creatinine levels exceeding 1.5 mg/dL or severe
proteinuria (>3 g per 24 hours) (26). Women with preexisting diabetic nephropathy are at significantly higher
risk for several adverse obstetric complications, including hypertensive disorders, uteroplacental insufficiency,
and iatrogenic preterm birth, because of worsening
renal function (27, 28). Before conception, a baseline
evaluation of renal function by serum creatinine and
assessment of urinary protein excretion (urine albuminto-creatinine ratio or 24-hour albumin excretion) is recommended with follow-up measurements at regular
intervals throughout pregnancy (29).
Chronic hypertension is observed in approximately
510% of pregnant patients with pregestational diabetes
mellitus (30). Hypertension, especially in the presence
of nephropathy, increases the risk of preeclampsia,
uteroplacental insufficiency, and stillbirth (31). Ideally,
hypertension should be controlled before conception. In
nonpregnant patients, treatment is likely to include an
angiotensin-converting enzyme inhibitor or an angiotension II receptor blocker. Because of their adverse fetal
effects, these medications should be discontinued before
conception and should not be used during pregnancy.
Symptomatic coronary artery disease in women
with pregestational diabetes mellitus is most commonly
seen in those with long-standing disease, nephropathy,
and hypertension (32). Preexisting symptomatic coronary artery disease may be a potential contraindication to
pregnancy because of the pregnancy-associated hemodynamic changes that may result in myocardial infarction
and death (9). Diabetic neuropathy is not well-studied in
pregnancy but may manifest as recalcitrant nausea and
vomiting secondary to gastroparesis (33).
Diabetic Ketoacidosis
Diabetic ketoacidosis is a life-threatening emergency
observed in 510% of all pregnancies complicated by
pregestational diabetes mellitus (34, 35). Because diabetic ketoacidosis is caused by an absolute or relative
insulin deficiency, it is most commonly observed in
women with type 1 pregestational diabetes mellitus.
Enhanced insulin resistance probably plays a role in the
higher incidence of diabetic ketoacidosis observed during pregnancy, as well as the propensity for diabetic
ketoacidosis to develop more rapidly and at less severe
PRACTICE BULLETINS
levels of hyperglycemia and even normal glucose levels.

Common risk factors for diabetic ketoacidosis during
pregnancy include new onset diabetes; infections, such
as influenza and urinary tract infection; poor patient
compliance; insulin pump failure; and treatment with
-mimetic tocolytic medications and antenatal corticosteroids (36).
Typical clinical presentation of diabetic ketoacidosis
in pregnancy includes abdominal pain, nausea and vomiting, and altered sensorium. Abnormal laboratory findings commonly include a low arterial pH (<7.3), a low
serum bicarbonate level (<15 mEq/L), an elevated anion
gap, and positive serum ketones (36). Continuous fetal
heart rate monitoring commonly demonstrates recurrent
late decelerations. However, this pattern usually resolves
as the maternal condition improves, and delivery is rarely
indicated.
Treatment regimens are based on aggressive hydration and intravenous insulin (see box). Because hypoglycemia and hypokalemia are frequent complications of
diabetic ketoacidosis therapy, glucose and potassium
concentrations should be monitored closely. Although
maternal mortality is rare, fetal mortality has ranged from
35% of cases to, more recently, 10% of cases (35, 37).
1.
2.
3.
4.
5.
Perinatal Morbidity and Mortality

The perinatal mortality rate in pregnancies complicated
by pregestational diabetes mellitus has decreased
markedly in recent years. Overall perinatal outcome is
best when glucose control is achieved before conception
and in the absence of maternal vascular disease (7, 38).
The relationship between maternal end-organ disease and
adverse pregnancy outcome was first illustrated by
Priscilla White, whose classification system attempted to
predict perinatal risk according to the age at onset of diabetes; duration of diabetes; and the presence of renal
(class F), proliferative retinal (class R), and cardiac (class
H) complications (39).
Major congenital anomalies are the leading cause of
perinatal mortality in pregnancies complicated by pregestational diabetes mellitus, occurring in 612% of infants
of women with diabetes (40). Studies have linked the
increased rate of congenital malformations, as well as
spontaneous abortion, to poor preconceptional glucose
control (41, 42). Hyperglycemia during organogenesis
(58 weeks after the last menstrual period) is thought to
play a critical role in abnormal development (43); however, hypoglycemia has not been associated with adverse
fetal outcome (44). Glycosylated hemoglobin levels correlate directly with the frequency of anomalies. A level
less than 1% higher than the upper limit of normal, or
approximately 56%, is associated with a fetal malformation rate close to that observed in normal pregnancies
6.
917
Management of Diabetic Ketoacidosis

During Pregnancy
Laboratory assessment
Obtain arterial blood gases to document degree of
acidosis present; measure glucose, ketones, and
electrolyte levels at 1- to 2-hour intervals
Insulin
Low-dose, intravenous
Loading dose: 0.20.4 U/kg
Maintenance: 210 U/h
Fluids
Isotonic sodium chloride
Total replacement in first 12 hours equals 46 L
1 L in first hour
5001,000 mL/h for 24 hours
250 mL/h until 80% replaced
Glucose
Begin 5% dextrose in normal saline when plasma
level reaches 250 mg/dL (14 mmol/L)
Potassium
If initially normal or reduced, an infusion rate up to
1520 mEq/h may be required; if elevated, wait
until levels decrease into the normal range, then
add to intravenous solution in a concentration of
2030 mEq/L
Bicarbonate
Add one ampule (44 mEq) to 1 L of 0.45 normal
saline if pH is <7.1
Reprinted with permission from Elsevier. Landon MB, Catalano PM,

Gabbe SG. Diabetes mellitus. In: Gabbe SG, Niebyl JR, Simpson JL,
editors. Obstetrics: normal and problem pregnancies. 4th edition.
New York (NY): Churchill Livingstone; 2002. p. 1102.
(23%), whereas an Hb A1C concentration near 10% is

associated with a fetal anomaly rate of 2025% (40, 45).
Complex cardiac defects; central nervous system anomalies, such as anencephaly and spina bifida; and skeletal
malformations, including sacral agenesis are most common (14, 46, 47).
Adverse perinatal outcomes later in pregnancy also
are increased in women with pregestational diabetes mellitus (14). Facilitated diffusion of glucose across the placenta leads to transient fetal hyperglycemia. Subsequent
stimulation of the fetal pancreatic cells results in fetal
hyperinsulinemia with several fetal and neonatal consequences. Because insulin is a potent growth hormone,
918
Obstetric Complications
Spontaneous preterm labor appears to be more common
in women with pregestational diabetes mellitus (55). The
increased incidence of hydramnios may be a cause of
preterm labor in some patients with pregestational diabetes mellitus, particularly those with poor glycemic control (56).
Preeclampsia is observed in 1520% of pregnancies complicated by type 1 diabetes mellitus without
nephropathy and approximately 50% in the presence of
nephropathy (55, 57). Preeclampsia also is more likely in
women with hypertension and poor glucose control (24,
25, 27). In the setting of hypertension and nephropathy,
the risk of fetal intrauterine growth restriction is more
than doubled. The rate of primary cesarean delivery is
increased in women with pregestational diabetes mellitus
(56, 58).
Is there a role for preconceptional

counseling?
Preconceptional counseling for women with pregestational diabetes mellitus has been reported to be beneficial
and cost-effective and should be encouraged (59).
Because fewer than one third of women with diabetes
mellitus seek preconceptional counseling (60), any visit
to a health care provider should be used as an opportunity to review the aspects of diabetes management during
pregnancy. Preconceptional counseling should focus on
the importance of euglycemic control before pregnancy,
as well as the adverse obstetric and maternal outcomes
that can result from poorly controlled diabetes. A search
Is there a role for continuous subcutaneous

insulin infusion during pregnancy?
With continuous subcutaneous insulin infusion therapy

(the insulin pump), insulin can be delivered in a pattern
that closely resembles physiologic insulin secretion
(6264). A rapid-acting insulin, such as insulin lispro, is
most appropriate for infusion pumps (65). Usually
5060% of the total daily dose is administered at a continuous basal rate, with boluses before meals and snacks
comprising 4050% of the total daily dose (64). Patients
who use continuous subcutaneous insulin infusion must
be highly motivated and compliant. The advantages of
the pump include improved patient satisfaction, a
decrease in severe hypoglycemia, and better control of
hyperglycemia. Major disadvantages include the
increased cost of the pump and pump supplies. In addition, if the delivery of insulin is interrupted or impaired
by battery failure or infection at the infusion site, diabetic ketoacidosis may develop rapidly (66).

Recommendations
for underlying vasculopathy is advisable and, in selected

patients, may include a retinal examination by an ophthalmologist, a 24-hour urine collection for protein
excretion and creatinine clearance, and electrocardiography. Because up to 40% of young women with type 1 diabetes mellitus also may have thyroid dysfunction, thyroid
function studies also should be obtained (61). Multivitamins containing at least 400 g of folic acid should
be prescribed to all women contemplating pregnancy.
This is particularly important in women with diabetes
given their increased risk of neural tube defects. Higher
doses of folic acid may be beneficial in some cases, especially in the presence of other risk factors for neural tube
defects.
excessive fetal growth occurs, particularly in adipose tissue (48). The fetus of a woman with poorly controlled
diabetes is at increased risk of intrauterine fetal death and
is more likely to weigh more than 4,000 g with a disproportionate concentration of fat around the shoulders and
chest, which more than doubles the risk of shoulder
dystocia at vaginal delivery (14). Elevated postprandial
values may be most closely related to the risk for macrosomia (49, 50).
The neonatal consequences of poorly controlled pregestational diabetes mellitus during pregnancy include
profound hypoglycemia, a higher rate of respiratory distress syndrome, polycythemia, organomegaly, electrolyte
disturbances, and hyperbilirubinemia. Long-term outcomes for type 1 diabetes mellitus include obesity and
carbohydrate intolerance (5154).
Is there a role for oral hypoglycemic agents

in pregnancy?
Oral hypoglycemic agents, used widely in the treatment

of nonpregnant patients, have not been well studied in
pregnancy (67). However, glyburide, a second-generation
sulfonylurea, does not cross the placenta and has been
used to treat GDM. Its onset of action is approximately
4 hours and its duration of action is approximately
10 hours. In a study of 404 pregnant women with treatment initiated between 11 and 33 weeks of gestation,
glyburide was found to be comparable to insulin in improving glucose control without evidence of adverse
maternal and neonatal complications. Metformin has
been used as a treatment for infertility in polycystic ovary
syndrome (68). Metformin is a category B drug, and
although there are more reports of its use during pregnancy (69), the long-term effects of in utero exposure
PRACTICE BULLETINS
have not been well studied. The use of all oral agents for
control of type 2 diabetes mellitus during pregnancy
should be limited and individualized until data regarding
the safety and efficacy of these drugs become available.
What fetal assessment is appropriate in

women with pregestational diabetes mellitus?
When and how should delivery occur?
Optimal timing of delivery relies on balancing the risk of

intrauterine fetal death with the risks of preterm birth. In
poorly controlled patients, an amniocentesis for fetal
lung maturity is advised for delivery before 39 weeks of
gestation. If corticosteroids are administered to accelerate lung maturation, an increased insulin requirement
over the next 5 days should be anticipated, and the
patients glucose levels should be closely monitored (77).
Early delivery may be indicated in some patients with
vasculopathy, nephropathy, poor glucose control, or a
prior stillbirth. In contrast, patients with well-controlled
diabetes may be allowed to progress to their expected

date of delivery as long as antenatal testing remains reassuring (78). Expectant management beyond the estimated due date generally is not recommended. Although an
ultrasound estimate of fetal weight may help to rule out
macrosomia, ultrasonography has not proved to be more
accurate than clinical assessment in determining the size
of the large fetus (7981). To prevent traumatic birth
injury, cesarean delivery may be considered if the estimated fetal weight is greater than 4,500 g in women with
diabetes (74). Induction of labor in pregnancies with a
fetus with suspected macrosomia has not been found to
reduce birth trauma and may increase the cesarean delivery rate (82).
An ultrasound examination early in gestation can be used

not only to demonstrate fetal viability but to accurately
date the pregnancy as well. Most major anomalies can be
detected at 1820 weeks of gestation by a specialized (or
targeted) ultrasound examination that includes a carefully performed assessment of fetal cardiac structure,
including the great vessels (70, 71). Echocardiography
also may be indicated in cases of suspected cardiac
defects or when the fetal heart and great vessels cannot
be visualized by ultrasonography. Thereafter, periodic
ultrasound examinations may be used to confirm appropriate fetal growth.
Antepartum fetal monitoring, including fetal movement counting, the nonstress test, the biophysical profile,
and the contraction stress test when performed at appropriate intervals, is a valuable approach and can be used to
monitor the pregnancies of women with pregestational
diabetes mellitus (7274). Initiation of testing is appropriate for most patients at 3234 weeks of gestation.
However, testing at earlier gestational ages may be warranted in some pregnancies complicated by additional
high-risk conditions. In response to a report of an
increased stillbirth rate in patients with a reactive nonstress test within 1 week of delivery, twice weekly testing
has been widely adopted (75). Daily fetal movement
counting is a simple technique for antepartum assessment
that also should be considered. However, if maternal glucose control deteriorates, fetal condition may change,
and repeat testing for fetal well-being may be indicated.
Doppler velocimetry of the umbilical artery may be useful in monitoring pregnancies with vascular complications and poor fetal growth (76).
919
How should glucose control be managed during labor?
During induction of labor, maternal glycemia can be controlled with an intravenous infusion of regular insulin
titrated to maintain hourly readings of blood glucose levels less than 110 mg/dL (6, 13, 83) (see box). Avoiding
intrapartum maternal hyperglycemia may prevent fetal
hyperglycemia and reduce the likelihood of subsequent
neonatal hypoglycemia (54). During active labor, insulin
may not be needed. Patients who are using an insulin
pump may continue their basal infusion during labor.
Insulin Management During Labor and Delivery

Usual dose of intermediate-acting insulin is given at
bedtime.
Morning dose of insulin is withheld.
Intravenous infusion of normal saline is begun.
Once active labor begins or glucose levels decrease
to less than 70 mg/dL, the infusion is changed from
saline to 5% dextrose and delivered at a rate of
100150 cc/h (2.5 mg/kg/min) to achieve a glucose
level of approximately 100 mg/dL.
Glucose levels are checked hourly using a bedside
meter allowing for adjustment in the insulin or glucose infusion rate.
Regular (short-acting) insulin is administered by
intravenous infusion at a rate of 1.25 U/h if glucose
levels exceed 100 mg/dL.
Data from Coustan DR. Delivery: timing, mode, and management.
In: Reece EA, Coustan DR, Gabbe SG, editors. Diabetes in women:
adolescence, pregnancy, and menopause. 3rd ed. Philadelphia (PA):
Lippincott Williams & Wilkins; 2004; and Jovanovic L, Peterson CM.
Management of the pregnant, insulin-dependent diabetic woman.
Diabetes Care 1980;3:638.
920
Breastfeeding should be encouraged in women with pregestational diabetes mellitus. An additional 500 kcal/d
more than the prepregnancy caloric intake is required.
Small snacks before breastfeeding may reduce the risks
of hypoglycemia (9).
Family planning options include low-dose combination oral contraceptives for women without vasculopathy
who do not smoke, whereas progestin-only pills can be
prescribed for women with vascular disease (84). Barrier
methods, although less effective, will not affect glucose
control or vasculopathy. Limited data suggest no
increased complications for intrauterine device use in
women with diabetes (85, 86). Sterilization should be
considered for women with serious vasculopathy or for
those who have completed their families.
Summary of
Recommendations and
Conclusions
Suspected fetal macrosomia is not an indication for

induction of labor because induction does not
improve maternal or fetal outcomes.
Antepartum fetal monitoring, including fetal movement counting, the nonstress test, the biophysical
profile, and the contraction stress test when performed at appropriate intervals, is a valuable
approach and can be used to monitor the pregnancies of women with pregestational diabetes mellitus.
Adequate maternal glucose control should be maintained near physiologic levels before conception and
throughout pregnancy to decrease the likelihood of
spontaneous abortion, fetal malformation, fetal macrosomia, intrauterine fetal death, and neonatal morbidity.
Patients and their families should be taught how to

respond quickly and appropriately to hypoglycemia.
Preconceptional counseling for women with pregestational diabetes mellitus has been reported to
The use of oral agents for control of type 2 diabetes

mellitus during pregnancy should be limited and
individualized until data regarding the safety and
efficacy of these drugs become available.
Are special postpartum considerations

necessary?
be beneficial and cost-effective and should be

encouraged.
Insulin requirements decrease rapidly after delivery.

One half of the predelivery dose may be reinstituted after
starting regular food intake (13). For patients with
cesarean delivery, rapid-acting insulin may be used to
treat glucose values greater than 140150 mg/dL after a
regular meal pattern has been established.
To prevent traumatic birth injury, cesarean delivery

may be considered if the estimated fetal weight is
greater than 4,500 g in women with diabetes.
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924

Force:
I
type of evidence.
committees.
Copyright March 2005 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
Pregestational diabetes mellitus. ACOG Practice Bulletin No. 60.
2005;105:67585.
PRACTICE BULLETINS
925
ACOG
PRACTICE
BULLETIN
(Replaces Educational Bulletin 244, February 1998)

of M. Sean Esplin, MD. The
of practice.
Reaffirmed 2007
Antiphospholipid
Syndrome
Antiphospholipid syndrome is an autoimmune disorder defined by the presence
of characteristic clinical features and specified levels of circulating antiphospholipid antibodies (Table 1). Because approximately 70% of individuals with
antiphospholipid syndrome are female (1), it is reasonably common among
women of reproductive age. Antiphospholipid antibodies are a diverse group of
antibodies with specificity for protein binding negatively charged phospholipids
on cell surfaces. Despite the prevalence and clinical significance of antiphospholipid syndrome, there is controversy about the indications for antiphospholipid syndrome testing and the tests that should be ordered to diagnose the
condition. Much of the debate results from a lack of well-designed and controlled
studies on the diagnosis and management of antiphospholipid syndrome. The
purpose of this document is to evaluate the data for diagnosis and treatment of
antiphospholipid syndrome.
Background
The lupus anticoagulant and anticardiolipin antibodies, the most widely accepted antibodies of clinical use, have been associated with a variety of medical
problems, including arterial and venous thromboses, autoimmune thrombocytopenia, and fetal loss (27). In addition to fetal loss, several obstetric complications have been associated with antiphospholipid antibodies, including
preeclampsia, intrauterine growth restriction, placental insufficiency, and
preterm delivery (8, 9). Primary antiphospholipid syndrome refers to patients
with antiphospholipid syndrome but no other recognized autoimmune disorders
(3, 4, 10). However, other autoimmune conditions such as systemic lupus erythematosus often coexist with the condition. When it occurs in the setting
of other autoimmune disease, it is referred to as secondary antiphospholipid
syndrome (2, 4).
926
Antiphospholipid
Antibodies
The two antiphospholipid antibodies that are best characterized are lupus anticoagulant and anticardiolipin antibodies. Although many women with lupus anticoagulant
also have anticardiolipin antibodies, the correlation is
imperfect (1, 11). Approximately 80% of patients with
lupus anticoagulant have anticardiolipin antibodies, and
20% of patients positive for anticardiolipin antibodies
have lupus anticoagulant. Although some investigators
suggest that lupus anticoagulant and anticardiolipin antibodies are the same antibody detected by different
methods (12), the fact that lupus anticoagulant and anticardiolipin antibodies may be separated in the laboratory
(13) would indicate that they may be related but
different immunoglobulins. Regardless, lupus anticoagulant and anticardiolipin antibodies are both independently
associated with the clinical features of antiphospholipid
syndrome, and the presence of only one of these
antibodies is adequate for the laboratory diagnosis of
antiphospholipid syndrome.
Lupus Anticoagulant
Lupus anticoagulant is present in many individuals without systemic lupus erythematosus and is associated with
thrombosis, not anticoagulation. The presence of lupus
anticoagulant is assessed indirectly, and a series of tests
are needed for the laboratory diagnosis (Table 1). The initial laboratory test for lupus anticoagulant can be one of
several phospholipid-dependent clotting assays, such as
the activated partial thromboplastin time (APTT), kaolin
plasma clotting time, and dilute Russells viper venom
time. Lupus anticoagulants are antibodies directed
against plasma proteins (such as 2-glycoprotein I, prothrombin, or annexin V) that bind to anionic or hexagonal phase phospholipids (14, 15). Lupus anticoagulants
paradoxically block phospholipid-dependent clotting
assays by interfering with the assembly of the prothrombin complex. The sensitivity and specificity of each test
for lupus anticoagulant are greatly affected by the
reagents used and vary among laboratories.
Because prolonged clotting times in these assays can
result from factors other than lupus anticoagulant, such
as improperly processed specimens, anticoagulant medications, clotting factor deficiencies, and factor-specific
inhibitors, plasma suspected of containing lupus anticoagulant based on a prolonged clotting time is subjected to
additional testing. If the prolonged clotting time is caused
by a factor deficiency, the addition of normal plasma
(containing the missing factor) results in a normal clotting time on repeat testing. In contrast, if an inhibitor
such as lupus anticoagulant is present, the clotting time

remains prolonged despite the addition of normal plasma.
A second confirmatory test involving the addition or
removal of phospholipid from the assay has been recommended. For example, preincubation of plasma with
phospholipid binds and removes lupus anticoagulant
from the sample being tested and normalizes clotting
time. Regardless of the assays used, lupus anticoagulant
cannot be quantified and is reported only as present or
absent.
Anticardiolipin Antibodies
Like lupus anticoagulants, anticardiolipin antibodies
react to the complex of negatively charged phospholipids, such as cardiolipin or phosphatidylserine bound to
proteins such as 2-glycoprotein I, prothrombin, or
annexin V. However, these antibodies are detected by
conventional immunoassays using purified cardiolipin as
the phospholipid matrix. Historically, interlaboratory
variation in this assay resulted in inappropriate diagnosis
and various treatments and outcomes (16, 17). The development of standard sera, available from the Antiphospholipid Standardization Laboratory in Atlanta, Georgia
(18), has greatly improved the reliability of this test
among different laboratories. Assays using these standard positive serum calibrators are quite reliable and
allow for the semiquantitation of antibody levels.
Standard sera have been assigned numeric values termed
GPL (immunoglobulin G [IgG] binding), MPL (IgM
binding), and APL (IgA binding) units. Test results are
reported as negative, low-positive, medium-positive, or
high-positive.
Low-positive anticardiolipin antibodies (<20 GPL
or MPL units) of any quantity are of questionable clinical significance and should not be considered diagnostic
of antiphospholipid syndrome (19). The relevance of
positive test results for IgA anticardiolipin antibodies of
any level also is uncertain. Low levels of IgG anticardiolipin antibodies and IgM anticardiolipin antibodies are
sometimes found in healthy individuals (18) and can
result from infection (20) and nonspecific binding. In the
general obstetric population, the prevalence of anticardiolipin antibodies has been reported to be between 2.7%
and 7.0% (2123). In contrast, several studies have
shown a correlation between increasing titers of anticardiolipin antibodies and disorders related to antiphospholipid antibodies (5, 19, 24). Thus, only medium to high
levels of IgG (>20 GPL units) or IgM (>20 MPL units)
anticardiolipin antibodies or positive lupus anticoagulant are considered sufficient laboratory criteria for the
diagnosis of antiphospholipid syndrome (2, 4). Positive
test results for antiphospholipid antibodies can be tran-
PRACTICE BULLETINS
sient and should be confirmed on two occasions at least

several weeks apart (4, 25). The diagnosis of antiphospholipid syndrome is not based on laboratory testing
alone. Rather, a diagnosis of antiphospholipid syndrome
must be based on an appropriate clinical history and laboratory criteria.
Other Antibodies Associated With

Antiphospholipid Syndrome
The antibody responsible for the biologic false-positive
serologic test for syphilis (BFP STS) also is an antiphospholipid antibody and often is present in patients with
lupus anticoagulant or anticardiolipin antibodies.
Compared with lupus anticoagulant and anticardiolipin
antibodies, the BFP STS correlates poorly with the
development of medical problems associated with
antiphospholipid antibodies. Thus, the BFP STS is not
recommended in the routine evaluation of antiphospholipid syndrome. Laboratories often report antibodies
to other phospholipids (ie, antiphosphatidylserine, antiphosphatidylinositol, antiphosphatidylethanolamine,
antiphosphatidylcholine, and antiphosphatidylglycerol).
However, these assays have not been subjected to quality control or standardization and are of uncertain clinical
value. In contrast, tests for antiphospholipid antibodies
other than lupus anticoagulant and anticardiolipin antibodies that appear to correlate with thrombotic risk
include antiprothrombin, antiannexin V, and anti-2-glycoprotein I antibodies. However, although they may
prove useful in the future, they cannot be recommended
for clinical use at this time.
Medical Complications of
Antiphospholipid
Syndrome
The most common and serious complications associated
with antiphospholipid syndrome are venous and arterial
thromboses (4, 5, 26). Most thrombotic events (65
70%) are venous (27, 28). Approximately 2% of all
patients with venous thrombosis will test positive for
antiphospholipid antibodies (29). Although the most
frequent site of venous thrombosis is a lower extremity,
thrombosis can occur in almost any blood vessel in the
body, and occlusions in unusual locations should
prompt clinicians to consider the diagnosis of antiphospholipid syndrome. It is estimated that between 0.5%
and 2% of the asymptomatic people incidentally found
to have antiphospholipid antibodies eventually will
develop thromboses each year (30). Up to one half of
927
patients with an antiphospholipid syndromeassociated

thrombosis will have at least one pulmonary embolus.
One retrospective cohort study of 147 subjects found a
thrombosis recurrence rate of 25% per year in untreated
patients with antiphospholipid syndrome and prior
thrombosis, but that recurrence can be minimized with
anticoagulation (27).
The risk of thrombosis is significantly increased
during pregnancy in patients with antiphospholipid syndrome. In a large cohort study, up to 25% of thrombotic events in patients with antiphospholipid syndrome
occurred during pregnancy or the postpartum period
(31). These findings were confirmed in prospective
studies indicating a 512% risk of thrombosis during
pregnancy or the puerperium in women with antiphospholipid syndrome (8, 9).
Arterial thrombosis also is associated with antiphospholipid antibodies and can occur in atypical sites, such
as retinal, subclavian, digital, or brachial arteries. Stroke
is the most common arterial event, and the most frequently involved vessel is the middle cerebral artery.
Transient ischemic attacks (TIAs) and amaurosis fugax
also are associated with antiphospholipid antibodies (19,
31). Antiphospholipid antibodies are present in 46% of
otherwise healthy individuals with stroke who are
younger than 50 years (32, 33). Coronary occlusions
also are reported (3). Individuals with unexplained arterial thrombosis, stroke, amaurosis fugax, or transient
ischemic attacks should undergo testing for antiphospholipid antibodies.
Autoimmune thrombocytopenia occurs in 4050%
of individuals with primary antiphospholipid syndrome
(2, 3, 34). Thrombocytopenia associated with antiphospholipid antibodies is extremely difficult to distinguish
from idiopathic thrombocytopenic purpura, although
the pertinent platelet antigens appear to differ in
antiphospholipid syndrome and idiopathic thrombocytopenic purpura. Thrombocytopenia caused by idiopathic thrombocytopenic purpura is treated the same as
thrombocytopenia caused by antiphospholipid syndrome.
A variety of other medical conditions have been
associated with antiphospholipid antibodies, including
autoimmune hemolytic anemia, livedo reticularis, cutaneous ulcers, chorea gravidarum, multiinfarct dementia,
and transverse myelitis (2, 3). A recently described condition termed catastrophic antiphospholipid syndrome
occurs in some individuals who develop progressive
thromboses and multiorgan failure (35). Others have a
severe illness postpartum primarily consisting of cardiopulmonary failure and fever, as well as renal insufficiency and multiple thromboses (3638).
928
Obstetric Complications

Recommendations
A large proportion of pregnancy losses related to

antiphospholipid antibodies are second-trimester or
third-trimester fetal deaths. Although fetal deaths
normally account for only a small proportion of all pregnancy losses in the general population (39), 50% of
pregnancy losses in a cohort of 76 women (333 pregnancies) with antiphospholipid syndrome were fetal deaths
(40). Of the 76 women in this study, 80% had at least
one fetal death.
Antiphospholipid antibodies also are associated with
recurrent early pregnancy loss. Observational studies
have consistently documented positive test results for
antiphospholipid antibodies in a higher proportion of
women with recurrent spontaneous abortion than in controls (25, 4149). Most studies report positive test results
for antiphospholipid antibodies in 520% of women with
recurrent pregnancy loss. However, many positive results
are low titer or IgM isotype only. Although low levels of
antiphospholipid antibodies may prove relevant to obstetric outcome, as stated earlier, they identify a distinct
population at lower risk for disorders related to antiphospholipid antibodies than patients with antiphospholipid
syndrome (19). In contrast to recurrent pregnancy loss,
antiphospholipid antibodies are not associated with sporadic preembryonic or embryonic pregnancy loss (50).
Preeclampsia is associated with antiphospholipid syndrome (8, 9). In one observational study of 54 women,
50% of those with antiphospholipid syndrome had
preeclampsia and 25% had severe preeclampsia (8).
Between 11% and 17% of women with preeclampsia will
test positive for antiphospholipid antibodies (5154). The
association is strongest in women with severe, early onset
(<34 weeks of gestation) preeclampsia. However, term
preeclampsia is not associated with increased levels of
antiphospholipid antibodies (55).
Intrauterine growth restriction (IUGR) complicates
pregnancies in women with antiphospholipid syndrome,
occurring in 1530% in most series (8, 9, 43, 56). There
is conflicting evidence of the link between antiphospholipid antibodies and IUGR (57). Although some studies
have not found a correlation between antiphospholipid
antibodies and IUGR (22, 58), this discrepancy may
result from the inclusion of some women with low-positive test results for antiphospholipid antibodies (9, 24,
43).
Uteroplacental insufficiency, preeclampsia, and
IUGR all increase the risk of indicated preterm delivery
in women with antiphospholipid syndrome. The risk is
greatest in women with high titers of antiphospholipid
antibodies who meet strict criteria for antiphospholipid
syndrome. In one report, approximately one third of
pregnancies in women with antiphospholipid syndrome

resulted in live births that occurred before 34 weeks of
gestation (8).
Who should be tested for antiphospholipid

antibodies?
The principal manifestations of antiphospholipid syndrome are venous or arterial thromboses, pregnancy
loss, and morbidity. Generally accepted indications for
antiphospholipid antibody testing are listed in Table 1.
Although most are straightforward, the obstetric indications are a matter of some controversy. In part, this results
from poorly characterized obstetric details in available
studies and the need for additional information. The preliminary criteria for antiphospholipid syndrome (10)
developed in 1999 by an international group of experts
recognized obstetric complications occurring in both the
preembryonicembryonic period and the fetalneonatal
periods and divided them into three categories, one
encompassing early pregnancy loss and the other two
relating primarily to complications in second or third
trimesters. Thus, the accepted obstetric clinical criteria
are 1) one or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of
gestation, 2) one or more premature births of a morphologically normal neonate at or before the 34th week of
gestation resulting from preeclampsia, eclampsia, or placental insufficiency, or 3) three or more unexplained consecutive spontaneous abortions before the 10th week of
gestation. Unexplained venous or arterial thrombosis, or
a small-vessel thrombosis (in the absence of inflammation of the vessel wall), are the nonobstetric clinical criteria for antiphospholipid syndrome.
Other conditions associated with antiphospholipid
syndrome include hemolytic anemia, autoimmune
thrombocytopenia, amaurosis fugax, livedo reticularis,
systemic lupus erythematosus, and a false-positive RPR.
These conditions are not considered clinical criteria for
antiphospholipid syndrome; therefore, testing individuals
with these conditions alone is not warranted.
Antiphospholipid antibodies, especially low-level or
IgM anticardiolipin antibodies, are present in a few
healthy people (18, 21) and are probably meaningless.
Clinicians who test for antiphospholipid antibodies in
women without clinical features of antiphospholipid syndrome may be left with an uninterpretable positive test
result and a management dilemma. It is best to avoid such
PRACTICE BULLETINS
Table 1. Preliminary Classification Criteria for

Antiphospholipid Syndrome*
Criteria
Definition
Clinical
Obstetric
1) Three or more consecutive spontaneous abortions

before the 10th week of gestation
2) One or more unexplained fetal deaths at or beyond
the 10th week of gestation
3) Severe preeclampsia or placental insufficiency
necessitating birth before the 34th week of
gestation
Vascular
thrombosis
1) Unexplained venous thrombosis

2) Unexplained arterial thrombosis
3) Small-vessel thrombosis in any tissue or organ,
without significant evidence of inflammation
of the vessel wall
929
positive screening test result for lupus anticoagulant must

be further investigated according to established criteria
(Table 1). A prolongation of the phospholipid-based clotting assay must be confirmed by mixing with normal plasma. The subsequent normalization of the clotting time is
an indication of other causes and not the presence of
antiphospholipid antibodies. Although lupus anticoagulant is interpreted as either present or absent, anticardiolipin must be abnormal in moderate to high (>20 GPL or
>20 MPL) titers to be considered clinically significant.
Positive results require a repeat test after several weeks to
exclude a transient, clinically unimportant antibody. Other
antibodies, such as antiphosphatidylserine, antiphosphatidylinositol, antiphosphatidylethanolamine, antiphosphatidylcholine, and antiphosphatidylglycerol, are not
used as laboratory criteria for the diagnosis of antiphospholipid syndrome.
Laboratory
Lupus
Lupus anticoagulant present in plasma, on two or
anticoagulant more occasions at least 6 weeks apart, detected
according to guidelines of the International Society on
Thrombosis and Hemostasis, in the following steps:
1) Demonstration of a prolonged phospholipiddependent coagulation screening test (eg, activated
partial thromboplastin time, kaolin clotting time,
dilute Russells viper venom time, dilute prothrombin time)
2) Failure to correct the prolonged screening test by
mixing with normal platelet-poor plasma
3) Shortening or correction of the prolonged screening
test by the addition of excess phospholipids
4) Exclusion of other coagulopathies (eg, factor VIII
inhibitor, heparin) as clinically indicated
*Definite antiphospholipid syndrome is considered to be present if at least one
of the clinical criteria and one of the laboratory criteria are met.
Adapted from Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette
JC, et al. International consensus statement on preliminary classification criteria
for definite antiphospholipid syndrome: report of an international workshop.
Arthritis Rheum 1999;42:130911. Copyright Wiley-Liss Inc. Reprinted with
permission of Wiley-Liss Inc., a subsidiary of John Wiley & Sons, Inc.
problems by testing only patients with disorders clearly

related to antiphospholipid antibodies.
What laboratory criteria are used for the

diagnosis of antiphospholipid syndrome?
The initial diagnosis of antiphospholipid syndrome

requires testing for anticardiolipin antibodies by enzymelinked immunosorbent assay and lupus anticoagulant with
two sensitive phospholipid-dependent clotting assays. A
Anticardiolipin Anticardiolipin antibody of IgG or IgM isotype in

medium to high titers, on two or more occasions at
least 6 weeks apart, measured by standardized
enzyme-linked immunosorbent assay
How should antiphospholipid syndrome be

managed during pregnancy and the postpartum period?
The goals of treatment for antiphospholipid syndrome

during pregnancy are to improve maternal and fetal
neonatal outcome by reducing the risk of pregnancy loss,
preeclampsia, placental insufficiency, and preterm birth
and to reduce or eliminate the maternal thrombotic risk of
antiphospholipid syndrome during pregnancy. Two
recent reviews (59, 60) have emphasized that case series
and treatment trials tend to include individuals whose
antiphospholipid syndrome diagnosis falls into one of
two groups: those with a history of thrombotic events and
those without a history.
Treatment of women with antiphospholipid syndrome without a thrombotic event is controversial. A
recent meta-analysis suggested that, for women with
recurrent miscarriage as the clinical criteria, prophylactic
heparin and low-dose aspirin may reduce pregnancy loss
by 50% (61). This combined therapy appears superior to
low-dose aspirin alone or prednisone. Few data from
controlled trials are available on the efficacy of various
treatment regimens for women with antiphospholipid
syndrome with other obstetric clinical events (severe
preeclampsia, uteroplacental insufficiency). Many
experts recommend prophylactic heparin and aspirin in
these women. For women with antiphospholipid syndrome without a history of a thrombotic event, some
physicians recommend initiation of heparin before conception, although no clinical trial supports this recommendation. Most experts recommend 68 weeks of
postpartum thromboprophylaxis in women with obstetric
antiphospholipid syndrome (59).
For women with antiphospholipid syndrome who
have had a thrombotic event, most experts recommend
930
Summary of
Recommendations and
Conclusions
The following recommendation is based on limited
or inconsistent scientific evidence (Level B):
Testing for antiphospholipid antibodies should be
limited to those women with appropriate medical or
obstetric histories.
Women with antiphospholipid syndrome and no

thrombotic history should receive prophylactic doses
of heparin and low-dose aspirin during pregnancy
and the postpartum period (68 weeks).
Pregnant women with antiphospholipid syndrome should

be examined frequently and instructed about the signs
and symptoms of preeclampsia and thrombosis. The primary goal of prenatal visits after 20 weeks of gestation is
the detection of preeclampsia or growth restriction.
Because of the risk for growth restriction, consideration
should be given to serial ultrasonographic assessment.
Antepartum testing should be considered after 32 weeks
of gestation, or earlier if there are signs of growth
restriction.
What is appropriate long-term management

of antiphospholipid syndrome?
Long-term risks for women with antiphospholipid syndrome include thrombosis and stroke. In studies of
women with antiphospholipid syndrome, including studies of women without prior thrombosis, one half developed thromboses during 310 years of follow-up and
10% developed systemic lupus erythematosus (30, 31,
68). The studied populations were highly selected referral populations; thus selection may have been biased
toward severe disease. However, no method currently
predicts which patients with antiphospholipid syndrome
using anticoagulants will develop recurrent thrombosis
once treatment is discontinued. In addition, no evidence
exists to support long-term treatment when thrombotic
events occur in the presence of other risk factors (30).
Therefore, for long-term management, patients with
antiphospholipid syndrome should be referred to a physician with expertise in treatment of the syndrome, such as
an internist or hematologist.
Pregnancy and the use of estrogen-containing oral
contraceptives appear to increase the risk for thrombosis
in women with antiphospholipid syndrome. In retrospective analyses of women with antiphospholipid syndrome,
most thromboses occurred in association with pregnancy
or oral contraceptive use (8, 31). Thus, estrogen-containing oral contraceptives in women with well-characterized
antiphospholipid syndrome should be avoided.
Should women with antiphospholipid

syndrome have antepartum surveillance?
full heparin anticoagulation (62). Patients enrolled in

most published series also received low-dose aspirin, but
the benefit of adding aspirin is unknown. Several
approaches to the peripartum management of anticoagulation therapy in these patients are available, thus treatment should be individualized.
Anticoagulation should be continued for a minimum
of 6 weeks postpartum to minimize the risk of maternal
thromboembolism (59). After delivery, this can be safely
accomplished with coumarin. Patients with antiphospholipid syndrome should be referred to an internist or
hematologist after delivery to prescribe anticoagulation
therapy outside of pregnancy.
Other therapies that have been suggested for treatment
of pregnant women with antiphospholipid syndrome
include corticosteroids and intravenous immunoglobulin
(IVIG). Several case series have reported a 6070% rate of
successful pregnancies in women with antiphospholipid
syndrome treated with prednisone and low-dose aspirin
(63). However, a meta-analysis of therapeutic trials
showed no reduction in pregnancy loss in women treated
with prednisone and low-dose aspirin (61). Direct comparison of studies is difficult because subjects had different clinical and laboratory features and dosing regimens,
and many trials were nonrandomized and poorly controlled. Thus, the efficacy of prednisone in pregnancies
complicated by antiphospholipid syndrome remains
uncertain.
Treatment with IVIG has been promising in a small
number of cases refractory to heparin or prednisone
(6466). Obstetric complications have been rare in
patients treated with IVIG (66). However, most of these
women also were treated with heparin or prednisone and
low-dose aspirin. A recent small randomized controlled
study demonstrated no greater benefit from IVIG (plus
heparin and aspirin) than with heparin and aspirin alone
(67). Because the efficacy of IVIG has not been proved in
appropriately designed studies and the drug is extremely
expensive, it is not recommended as primary therapy.
Women with antiphospholipid syndrome and previous history of thrombosis should receive full anticoagulation throughout pregnancy and the postpartum
period (68 weeks).
PRACTICE BULLETINS
Women with antiphospholipid syndrome should be

referred to an internist or hematologist for long-term
follow-up.
Women with antiphospholipid syndrome should

avoid estrogen-containing oral contraceptives.
Because of the risk for growth restriction, consideration should be given to serial ultrasonographic
assessment. Antepartum testing should be considered after 32 weeks of gestation, or earlier if there
are signs of growth restriction.
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case-control study. N Engl J Med 1991;325:10636.
(Level II-2)
51. Branch DW, Andres R, Digre KB, Rote NS, Scott JR. The
association of antiphospholipid antibodies with severe
preeclampsia. Obstet Gynecol 1989;73:5415. (Level
II-2)
52. Milliez J, Lelong F, Bayani N, Jannet D, el Medjadji M,
Latrous H, et al. The prevalence of autoantibodies during
third-trimester pregnancy complicated by hypertension or
idiopathic fetal growth retardation. Am J Obstet Gynecol
1991;165:516. (Level II-2)
53. Moodley J, Bhoola V, Duursma J, Pudifin D, Byrne S,
Kenoyer DG. The association of antiphospholipid antibodies with severe early-onset pre-eclampsia. S Afr Med J
1995;85:1057. (Level III)
54. Sletnes KE, Wisloff F, Moe N, Dale PO. Antiphospholipid
antibodies in pre-eclamptic women: relation to growth
retardation and neonatal outcome. Acta Obstet Gynecol
Scand 1992;71:1127. (Level II-2)
55. Scott RA. Anti-cardiolipin antibodies and pre-eclampsia.
Br J Obstet Gynaecol 1987;94:6045. (Level III)
56. Caruso A, De Carolis S, Ferrazzani S, Valesini G, Caforio
L, Mancuso S. Pregnancy outcome in relation to uterine
artery flow velocity waveforms and clinical characteristics
in women with antiphospholipid syndrome. Obstet
57. Polzin WJ, Kopelman JN, Robinson RD, Read JA, Brady
K. The association of antiphospholipid antibodies with
PRACTICE BULLETINS
pregnancies complicated by fetal growth restriction.

58. Pattison NS, Chamley LW, McKay EJ, Liggins GC,
Butler WS. Antiphospholipid antibodies in pregnancy:
prevalence and clinical associations. Br J Obstet Gynaecol
1993;100:90913. (Level II-3)
59. Branch DW, Khamashta MA. Antiphospholipid syndrome: obstetric diagnosis, management, and controversies. Obstet Gynecol 2003;101:133344. (Level III)
60. Derksen RH, Khamashta MA, Branch DW. Management
of the obstetric antiphospholipid syndrome. Arthritis
Rheum 2004;50:102839. (Level III)
61. Empson M, Lassere M, Craig JC, Scott JR. Recurrent
pregnancy loss with antiphospholipid antibody: a systematic review of therapeutic trials. Obstet Gynecol 2002;99:
13544. (Level III)
62. Bates SM, Greer IA, Hirsh J, Ginsberg JS. Use of
antithrombotic agents during pregnancy: the Seventh
ACCP Conference on Antithrombotic and Thrombolytic
Therapy. Chest 2004;126(suppl 3):627S 44S. (Level III)
63. Lubbe WF, Walkom P, Alexander CJ. Hepatic and splenic
haemorrhage as a complication of toxaemia of pregnancy
in a patient with circulating lupus anticoagulant. N Z Med
J 1982;95:8424. (Level III)
64. Carreras LD, Perez GN, Vega HR, Casavilla F. Lupus
anticoagulant and recurrent fetal loss: successful treatment with gammaglobulin. Lancet 1988;2:3934. (Level
III)
65. Scott JR, Branch DW, Kochenour NK, Ward K.
Intravenous immunoglobulin treatment of pregnant
patients with recurrent pregnancy loss caused by
antiphospholipid antibodies and Rh immunization. Am J
66. Spinnato JA, Clark AL, Pierangeli SS, Harris EN.
Intravenous immunoglobulin therapy for the antiphospholipid syndrome in pregnancy. Am J Obstet Gynecol
1995;172:6904. (Level III)
67. Branch DW, Peaceman AM, Druzin M, Silver RK, ElSayed Y, Silver RM, et al. A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy.
The Pregnancy Loss Study Group. Am J Obstet Gynecol
2000;182:1227. (Level I)
68. Shah NM, Khamashta MA, Atsumi T, Hughes GR.
Outcome of patients with anticardiolipin antibodies: a 10
year follow-up of 52 patients. Lupus 1998;7:36. (Level
II-2)
933
The MEDLINE database, the Cochrane Library, and the

American College of Obstetricians and Gynecologists own
internal resources and documents were used to conduct a
literature search to locate relevant articles published between January 1985 and June 2005. The search was restricted to articles published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries also
Force:
I
type of evidence.
committees.

01923, (978) 750-8400.
ISSN 1099-3630
Antiphospholipid syndrome. ACOG Practice Bulletin No. 68. American College of Obstetricians and Gynecologists. Obstet Gynecol
2005;106:111321.
934
ACOG
PRACTICE
BULLETIN
Episiotomy
of John T. Repke, MD. The information is designed to aid
of practice.
Reaffirmed 2008
Episiotomy is one of the most commonly performed procedures in obstetrics. In

2000, approximately 33% of women giving birth vaginally had an episiotomy
(1). Historically, the purpose of this procedure was to facilitate completion of
the second stage of labor to improve both maternal and neonatal outcomes.
Maternal benefits were thought to include a reduced risk of perineal trauma,
subsequent pelvic floor dysfunction and prolapse, urinary incontinence, fecal
incontinence, and sexual dysfunction. Potential benefits to the fetus were
thought to include a shortened second stage of labor resulting from more rapid
spontaneous delivery or from instrumented vaginal delivery. Despite limited
data, this procedure became virtually routine resulting in an underestimation of
the potential adverse consequences of episiotomy, including extension to a
third- or fourth-degree tear, anal sphincter dysfunction, and dyspareunia. The
purpose of this document is to examine the risks and benefits of episiotomy and
to make recommendations regarding the use of this procedure in current obstetric practice.
Background
History
Episiotomy has been described in the medical literature for more than 300
years, but it was not until the 1920s, with the publication of papers by DeLee
(2) and Pomeroy (3), that more routine use of episiotomy became accepted.
However, there was certainly not unanimity about the utility of this approach at
that time (4). The shift to in-hospital deliveries in the 20th century was associated with decreased morbidity and an increase in the use of episiotomy and proliferation of many other obstetric practices (eg, use of forceps, use of cesarean
delivery, use of anesthesia). More recently, in 1992 more than 1.6 million episiotomies were performed in the United States, with a background cesarean
delivery rate of 22.3%. In 2003, 716,000 episiotomies were performed with a
PRACTICE BULLETINS
background cesarean delivery rate of 27.5%, suggesting

that use of this procedure in obstetrics is decreasing (5, 6).
Techniques of Episiotomy
In general, two types of episiotomy have been described:
the median (or midline or medial) episiotomy and the
mediolateral episiotomy. In the United States, the more
commonly used technique is the median episiotomy. It
gained popularity because it is easy to perform and to
repair. Postpartum pain is reported to be reduced with
this technique, as is postpartum dyspareunia (4). Median
episiotomy, however, is associated with a greater risk of
extension to include the anal sphincter (third-degree
extension) or rectum (fourth-degree extension) (710).
Mediolateral episiotomy, an incision at least 45
degrees from the midline, is more commonly performed
outside the United States and is favored by some because
it maximizes perineal space for delivery while reducing
the likelihood of third- or fourth-degree extension (8, 11).
Reported disadvantages of the mediolateral procedure
include difficulty of repair, greater blood loss, and, possibly, more early postpartum discomfort (4).
Technique of Repair
Complications

Recommendations
What are the indications for episiotomy?
The indications for episiotomy are varied and based largely on clinical opinion. It has been suggested that episiotomy is indicated in cases where expediting delivery in the
second stage of labor is warranted or where the likelihood
of spontaneous laceration seems high. Such clinical circumstances would include a nonreassuring fetal heart rate
pattern, operative vaginal delivery, shoulder dystocia, and
cases where the perineal body is thought to be unusually
short. The data supporting these claims are largely
descriptive or anecdotal. Several trials suggest the lack of
evidence supporting use of episiotomy in these circumstances. Two recent trials also failed to show that episiotomy improved neonatal outcome, provided better
protection of the perineum, or facilitated operative vaginal
delivery (22, 23). Current data and clinical opinion suggest that there are insufficient objective evidence-based
criteria to recommend episiotomy, and especially routine
use of episiotomy, and that clinical judgment remains the
best guide for use of this procedure (24).
Bleeding from the episiotomy site is one of the most frequent complications. Such bleeding often is easily controlled with conservative measures and compression, but
substantial hematoma formation may occur. Infection
also may complicate episiotomy healing. In most cases,
such infections are localized and may resolve with perineal wound care. In rare cases, an abscess may form,
which will result in either the need for disruption of the
repair to allow for evacuation of the abscess or spontaneous breakdown of the repair. In extreme cases, infections such as necrotizing fasciitis can cause maternal
death if not effectively evaluated and treated. In cases of
less severe infection with wound breakdown, several
approaches can be used. For superficial breakdowns not
involving the rectum or anal sphincter, expectant management with perineal care may allow for spontaneous
healing to occur over a period of several weeks. For more
extensive breakdowns, or when the logistics of many follow-up visits may be prohibitive, primary closure of the
defect may be attempted. Data suggest that early closure
of episiotomy dehiscence in properly selected cases may
be appropriate (20). In rare cases, inadequately repaired
episiotomies may lead to rectovaginal fistula formation
(21). Repair of such defects can be challenging, depending on size and location, and should be repaired by someone familiar with fistula repair techniques.
The median episiotomy tends to be a simpler incision to

repair, even if it requires repair of the rectal mucosa and
anal sphincter. For either technique, a two-layered closure has been shown to decrease postpartum pain and
healing complications compared with a three-layer closure (1214). Compared with interrupted, transcutaneous
suturing, one study reported less postpartum pain at
3 months with continuous subcutaneous suturing (15).
Although a second study reported no difference (16),
both studies found a lower need for suture removal with
the continuous method (15, 16).
Various suture materials have been used for episiotomy repair, with limited data to suggest the superiority of
one type of material over another. A minimally reactive,
absorbable polyglycolic acid suture may be preferable to
chromic catgut because there may be less perineal pain and
dyspareunia (13, 16, 17). The drawback of using less reactive materials is a slower resorption profile that rarely may
result in the need for suture removal (18, 19). For this reason, many clinicians now use monofilament absorbable
sutures or more rapidly absorbable polyglactin derivatives.
935
How does episiotomy affect the rate and

severity of perineal lacerations?
A systematic review of seven trials comparing routine

episiotomy with restrictive use of the procedure found
936
that an intact perineum was more common in the restricted group, but anterior labial lacerations also were more
common. There were no differences in rectal injuries
(24). Another systematic review suggests that routine
mediolateral episiotomy compared with restricted use
does not protect against anal sphincter trauma, and median episiotomy caused more anal sphincter tears (25).
Nonetheless, anterior lacerations are not associated with
an increased need for suturing, suggesting that these
tears are less severe than posterior tears. Thus, restrictive
use of episiotomy appears to reduce the likelihood of
perineal lacerations.
Can episiotomy prevent pelvic muscle relaxation leading to incontinence?
How does episiotomy affect postpartum pain

and sexual functioning?
What are the fetal benefits of episiotomy?
Proposed fetal benefits of episiotomy include cranial

protection, especially for premature infants, reduced
perinatal asphyxia, less fetal distress, better Apgar
scores, less fetal acidosis, and reduced complications
from shoulder dystocia. Despite these claims, few data
are available to support any of them. Even the presumption that episiotomy shortens the second stage of labor
has not been conclusively shown.
Although increasing perineal space would seem
intuitively beneficial with respect to the prevention and
management of shoulder dystocia, few data other than
anecdotes support this notion. A systematic review of the
literature (13) found only one study that addressed this
issue and concluded that the use of episiotomy had no
influence on the risk of shoulder dystocia (39). However,
if shoulder dystocia occurs, episiotomy may be useful to
facilitate its management. No data support or refute the
benefits of episiotomy with operative vaginal delivery.
Postpartum recovery is an area of obstetrics that lacks

systematic study and analysis. Recovery depends on
many factors, and a number of investigators have
attempted to determine what factors, if any, lead to more
expeditious recovery and return of normal function.
There is consensus that the risk of incontinence increases with increasing degrees of pelvic trauma. One study
of extended episiotomies demonstrated that the occurrence of a fourth-degree extension was more highly associated with anal incontinence (26). The single greatest
risk factor for third- or fourth-degree lacerations seems
to be the performance of a median episiotomy, suggesting that avoiding episiotomy itself may be the best way
to minimize the risk of subsequent extensive damage to
the perineum (27). In four cohort studies, investigators
asked women about anal incontinence episodes; one
study also included physical examinations (25, 2830).
Episiotomy was not found to be associated with reduced
risk of incontinence of stool or flatus (24). Similarly, in
another study of perineal muscle function, women who
had an episiotomy had less recovery of postpartum perineal muscle function than did women who did not
undergo episiotomy, leading the investigators to conclude that use of episiotomy for preservation of perineal
muscle function is not warranted (31). A prospective
study of 519 primiparous women compared those who
had a mediolateral episiotomy with those who had an
intact perineum or first- or second-degree lacerations
(28). No differences in urinary or anal incontinence or
genital prolapse were reported. A systematic review of
routine versus restrictive episiotomy found no evidence
to support episiotomy in preventing pelvic floor damage
(24).
Whether episiotomy contributes to immediate postpartum pain is debated. One study suggests that duration of
the second stage of labor correlated most closely with
acute postpartum pain (32), whereas other studies suggest that immediate postpartum pain is well correlated
with degree of perineal trauma and, therefore, with episiotomy use (27, 33, 34). The most studied measure of
postpartum sexual function is the time from delivery
until resumption of sexual intercourse. Most data suggest that 90% of women in the postpartum period have
resumed intercourse within 34 months of delivery (34).
In at least two studies, episiotomy was not identified as
an independent risk factor for dyspareunia or delayed
return to sexual activity when compared with equally
severe perineal trauma in women who did not have an
episiotomy (34, 35). Prospective cohort studies did not
find differences in dyspareunia or resumption of intercourse at 3 months (24).
Another aspect of postpartum discomfort relates to
method of episiotomy closure or repair of a spontaneous
laceration. A number of trials have reported on different
techniques of perineal closure aimed at reducing postpartum pain and facilitating expeditious healing (12, 13,
36). Newer approaches using more rapidly absorbing
synthetic sutures, either braided or monofilament, have
been reported. Larger trials are needed before a conclusion can be reached about their efficacy (13, 15, 37, 38).
Which type of episiotomy (median or mediolateral) is favored?
Median episiotomies are associated with a greater risk of

extension into the rectum and compromise of the exter-
PRACTICE BULLETINS
Restricted use of episiotomy is preferable to routine

use of episiotomy.
Median episiotomy is associated with higher rates of
injury to the anal sphincter and rectum than is mediolateral episiotomy.
The following recommendation and conclusion

are based on limited or inconsistent scientific evidence (Level B):
Mediolateral episiotomy may be preferable to median episiotomy in selected cases.
The best available data do not support liberal or routine

use of episiotomy. Nonetheless, there is a place for episiotomy for maternal or fetal indications, such as avoiding
severe maternal lacerations or facilitating or expediting
difficult deliveries. According to a recent systematic evidence review (24), although episiotomy is performed in
approximately 3035% of vaginal births in the United
States, prophylactic use of episiotomy does not appear to
result in maternal or fetal benefit. Another systematic
review comparing routine episiotomy with restrictive use
reported that the group routinely using episiotomy had an
overall incidence of 72.7%, versus 27.6% in the restricted-use group (46). The restricted-use group had significantly lower risks of posterior perineal trauma, suturing,
and healing complications, but a significant increase in
anterior perineal trauma. No statistically significant differences were reported for severe vaginal or perineal
trauma, dyspareunia, or urinary incontinence, leading the
reviewers to conclude that restrictive-use protocols are
preferable to routine use of this procedure.
The following recommendation and conclusion

are based on good and consistent scientific evidence (Level A):
Should episiotomy be routine or restricted in

clinical practice?
Summary of
Recommendations and
Conclusions
nal anal sphincter muscle (7). Mediolateral episiotomies

have been linked to greater postpartum pain, more blood
loss, more difficulty in effecting proper repair, and more
dyspareunia (4), especially when compared with spontaneous tears (28, 40). Also, because of the potential for
greater expansion of the pelvic floor with mediolateral
episiotomy, it has been suggested that use of this procedure may provide more protection against the development of incontinence (41). Multiple studies using an
endpoint of avoiding anal sphincter or rectal injury have
demonstrated that mediolateral episiotomy is superior to
median episiotomy (9, 42, 43). However, there may be
other drawbacks to the use of mediolateral episiotomy,
including increased perineal trauma not involving the
sphincter (44). There does not appear to be evidence to
support a protective effect of mediolateral episiotomy
with respect to subsequent development of genital prolapse (28). In addition, although the data are insufficient
to determine the superiority of either approach, data do
suggest that both median and mediolateral episiotomies
have similar outcomes, including pain from the incision
and time to resumption of intercourse (7).
The timing of episiotomy has long been the subject
of debate (2, 3). There are no data to show that early episiotomy results in decreased pelvic floor trauma. It has
been demonstrated that episiotomy, whether median or
mediolateral, is associated with increased maternal blood
loss at the time of delivery (45).
937
Routine episiotomy does not prevent pelvic floor

damage leading to incontinence.
Proposed Performance
Measure
For patients with episiotomy, the percentage for whom the
indication for episiotomy is included in the delivery notes
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Raynes-Greenow C. A randomised trial, conducted by
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MA, Meuwissen SG. Third degree obstetric perineal tears:
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43. De Leeuw JW, Vierhout ME, Struijk PC, Hop WC,
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Verkerk PH. Episiotomies and the occurrence of severe
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939

literature search to locate relevant articles published between January 1985 and May 2005. The search was restricted to articles published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries also
Force:
I
type of evidence.
committees.

from the publisher.
01923, (978) 750-8400.
ISSN 1099-3630
Episiotomy. ACOG Practice Bulletin No. 71. American College of
940
ACOG
PRACTICE
BULLETIN
(Replaces Educational Bulletin Number 227, August 1996)

of Calla Holmgren, MD, and
T. Flint Porter, MD. The information is designed to aid practitioners in making decisions
Reaffirmed 2008
Management of
Alloimmunization
During Pregnancy
When any fetal blood group factor inherited from the father is not possessed by
the mother, antepartum or intrapartum fetalmaternal bleeding may stimulate
an immune reaction in the mother. Maternal immune reactions also can occur
from blood product transfusion. The formation of maternal antibodies, or
alloimmunization, may lead to various degrees of transplacental passage of
these antibodies into the fetal circulation. Depending on the degree of antigenicity and the amount and type of antibodies involved, this transplacental
passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed
and untreated, alloimmunization can lead to significant perinatal morbidity
and mortality. Advances in Doppler ultrasonography have led to the development of noninvasive methods of management of alloimmunization in pregnant
women. Together with more established protocols, Doppler ultrasound evaluation may allow for a more thorough and less invasive workup with fewer risks
to the mother and fetus. Prevention of alloimmunization is addressed in another
Practice Bulletin (1).
Background
Nomenclature
The nomenclature for the Rh (CDE) blood group system is complex and often
confusing. Five major antigens can be identified with known typing sera, and
there are many variant antigens. Of the numerous nomenclature systems that
have been developed, the FisherRace nomenclature is best known and most
compatible with our understanding of the inheritance of the Rho (or D) antigen
and the clinical management of Rh alloimmunization (2). The FisherRace
PRACTICE BULLETINS
nomenclature presumes the presence of three genetic

loci, each with two major alleles. The antigens produced
by these alleles originally were identified by specific
antisera and have been lettered C, c, D, E, and e. No antiserum specific for a d antigen has been found, and use
of the letter d indicates the absence of an evident
allelic product. Anti-C, anti-c, anti-D, anti-E, and anti-e
designate specific antibodies directed against their
respective antigens.
An Rh gene complex is described by the three appropriate letters. Eight gene complexes are possible (listed in
decreasing order of frequency among whites): CDe, cde,
cDE, cDe, Cde, cdE, CDE, and CdE. Genotypes are indicated as pairs of these gene complexes, such as CDe/cde.
Certain genotypes, and thus certain phenotypes, are more
prevalent than others. The genotypes CDe/cde and
CDe/CDe are the most common, with approximately
55% of all whites having the CcDe or CDe phenotype
(3). The genotype CdE has never been demonstrated in
vivo (2).
Most of the cases of Rh alloimmunization causing
transfusion reactions or serious hemolytic disease in the
fetus and newborn are the result of incompatibility with
respect to the D antigen. For this reason, the designation
Rh positive usually indicates the presence of the D antigen and Rh negative indicates the absence of D antigen
on erythrocytes.
In addition to the five major antigens of the Rh system, more than 30 antigenic variants have been identified. Among these are the Cw antigen and the Du antigen,
which is now referred to as weak D. The latter is a
heterogeneous group of clinically important D antigen
variants. Some weak D-positive patients are capable of
producing the anti-D antibody, although alloimmunization
rarely occurs.
Other Antibodies
The most frequently encountered antibodies other than D
are Lewis (Lea and Leb) and I antibodies. Like most cold
agglutinins, Lewis and I antigens do not cause erythroblastosis fetalis because they are predominantly of the
immunoglobulin M type and they are poorly expressed
on fetal and newborn erythrocytes. In contrast, Kell antibodies (anti-K) can produce erythroblastosis fetalis. A
more complete list of antibodies and their effects can be
found in Table 1. Often, Kell alloimmunization is caused
by prior transfusion because Kell compatibility was not
considered when the blood was cross-matched. Care of
patients with sensitization to antigens other than D that
are known to cause hemolytic disease should be the same
as that for patients with D alloimmunization. A possible
exception is Kell sensitization, in which amniotic fluid
941
analysis has been reported to correlate poorly with the

severity of fetal anemia (4). These patients may benefit
from more aggressive fetal assessment, such as measurement of the peak systolic velocity in the fetal middle
cerebral artery; however, optimal care of Kell-sensitized
patients is controversial (4).
Incidence of Rh-Incompatible
Pregnancy
The incidence of Rh incompatibility varies by race and
ethnicity. Approximately 15% of whites are Rh negative,
compared with only 58% of African Americans and
12% of Asians and Native Americans. Among whites,
an Rh-negative woman has an approximate 85% chance
of mating with an Rh-positive man, 60% of whom are
heterozygous and 40% of whom are homozygous at the
D locus.
Causes of Rh Alloimmunization
Rh alloimmunization can occur only if a sufficient number of erythrocytes from an Rh-positive fetus gain access
to the circulation of its Rh-negative mother. The volume
necessary to cause alloimmunization varies from patient
to patient and is probably related to the immunogenic
capacity of the Rh-positive erythrocytes and the immune
responsiveness of the mother. Fetomaternal hemorrhage
sufficient to cause alloimmunization occurs most commonly at delivery, in 1550% of births (58). Specific
clinical factors such as cesarean delivery, multifetal gestation, bleeding placenta previa or abruption, manual
removal of the placenta, and intrauterine manipulation
may increase the volume of fetomaternal hemorrhage. In
most cases, though, excessive fetomaternal hemorrhage
occurs with uncomplicated vaginal delivery (9, 10). The
volume of fetal blood entering the maternal circulation is
0.1 mL or less in most cases resulting in alloimmunization (8, 11). Approximately 12% of Rh alloimmunization is caused by antepartum fetomaternal hemorrhage
(12). In one large series, fetomaternal hemorrhage was
detected in 7% of patients during the first trimester, in
16% of patients during the second trimester, and in 29%
of patients during the third trimester (5). Detectable fetomaternal hemorrhage resulting in alloimmunization may
occur in first-trimester spontaneous and induced abortion
(13). Alloimmunization also has been reported after
threatened abortion and ectopic pregnancy (14, 15).
Several obstetric procedures may lead to fetomaternal
hemorrhage and, in turn, maternal alloimmunization.
These include chorionic villus sampling, pregnancy termination, amniocentesis, and external cephalic version
(1618).
942
Table 1. Atypical Antibodies and Their Relationship to Fetal Hemolytic Disease

Blood Group
System
Antigens Related to
Hemolytic Disease
Hemolytic Disease Severity
Proposed Management
Lewis
Kell
K
k
Ko
Kpa
Kpb
Jsa
Jsb
Mild to severe
Mild
Mild
Mild
Mild
Mild
Mild
Fetal assessment
Routine obstetric care
Rh (non-D)
E
C
C
Mild to severe
Mild to severe
Mild to severe
Fetal assessment
Fetal assessment
Fetal assessment
Duffy
Fya
Fyb
By3
Mild to severe
Mild
Fetal assessment
Kidd
Jka
Jkb
Jk3
Mild to severe
Mild
Mild
Fetal assessment
MNSs
M
N
S
s
U
Mia
Mild to severe
Mild
Mild to severe
Mild to severe
Mild to severe
Moderate
Fetal assessment
Fetal assessment
Fetal assessment
Fetal assessment
Fetal assessment
MSSs
Mta
Vw
Mur
Hil
Hut
Moderate
Mild
Mild
Mild
Mild
Fetal assessment
Lutheran
Lua
Lub
Mild
Mild

Diego
D1a
Dib
Mild to severe
Mild to severe
Fetal assessment
Fetal assessment
Xg
Xga
Mild
PP1pk (Tja )
Mild to severe
Fetal assessment
Public antigens
Yt
Ytb
Lan
Ena
Ge
Jra
Coa
Co1-b-
Moderate to severe
Mild
Mild
Moderate
Mild
Mild
Severe
Mild
Fetal assessment
Fetal assessment
Fetal assessment
Private antigens
Batty
Becker
Berrens
Mild
Mild
Mild

(continued)
PRACTICE BULLETINS
943
Table 1. Atypical Antibodies and Their Relationship to Fetal Hemolytic Disease (continued)
Blood Group
System
Private antigens
Antigens Related to
Hemolytic Disease
Hemolytic Disease Severity
Biles
Evans
Gonzales
Good
Heibel
Hunt
Jobbins
Radin
Rm
Ven
Wrighta
Wrightb
Zd
Moderate
Mild
Mild
Severe
Moderate
Mild
Mild
Moderate
Mild
Mild
Severe
Mild
Moderate
Proposed Management
Fetal assessment
Fetal assessment
Fetal assessment
Fetal assessment
Fetal assessment
Fetal assessment
*Not a proven cause of hemolytic disease of the newborn
With hydrops fetalis
Not a cause of hemolytic disease of the newborn

Adapted from Weinstein L. Irregular antibodies causing hemolytic disease of the newborn: a continuing problem. Clin Obstet Gynecol 1982;25:321.
Anti-D Immune Globulin to Prevent

Alloimmunization
Anti-D immune globulin is not indicated for patients previously sensitized to D. However, it is indicated for
patients who might be sensitized to other blood group
antigens.

Recommendations
What are the best screening methods for

detecting alloimmunization in women?
At what antibody titer should an additional

evaluation be initiated?
The usefulness of maternal serum antibody titers is determined by the patients reproductive history. For a woman
All pregnant women should be tested at the time of the

first prenatal visit for ABO blood group and Rh-D type
and screened for the presence of erythrocyte antibodies.
These laboratory assessments should be repeated in each
subsequent pregnancy. The American Association of
Blood Banks also recommends repeated antibody screening before administration of anti-D immune globulin at
28 weeks of gestation, postpartum, and at the time of any
event in pregnancy. Patients who are weak D (Du) positive are not at risk for alloimmunization and should not
receive anti-D immunoprophylaxis.
with a history of a previously affected fetus or neonate,

serial titer assessment is inadequate for surveillance of
fetal anemia. Titer values are reported as the integer of
the greatest tube dilution with a positive agglutination
reaction. Variation in titer results from different laboratories is not uncommon, so titers should be obtained in the
same laboratory when monitoring a patient, and a change
of more than one dilution is significant. A critical titer is
that titer associated with a significant risk for severe
erythroblastosis fetalis and hydrops, and in most centers
this is between 1:8 and 1:32. If the initial antibody titer is
1:8 or less, the patient may be monitored with titer
assessment every 4 weeks. For patients with alloimmunization involving antigens other than D, similar titer levels should be used to guide care except in Kell-sensitized
patients because Kell antibodies do not correlate with
fetal status (19).
What ancillary tests should follow identification of maternal antibodies to diagnose

hemolytic disease in the fetus?
Determination of Paternal Genotype

The initial management of a pregnancy involving an
alloimmunized patient is determination of the paternal
erythrocyte antigen status. If the father is negative for the
erythrocyte antigen in question (and it is certain that he is
the father of the fetus), further assessment and intervention are unnecessary. In cases of Rh-D alloimmunization
in which the father is Rh positive, the probability that he
944
Determination of Fetal Genotype
Spectral Analysis of Amniotic Fluid

Historically, measurement of amniotic fluid bilirubin levels using spectral analysis at 450 nm (OD450) has been
the accepted method of assessing the severity of erythroblastosis in utero. Fetal status was determined by plotting the OD450 measurement on either a Liley graph in
the late second and third trimesters (25) or on the
Queenan curve for earlier gestational ages (1925
weeks). The current trend is management with middle
cerebral artery Doppler ultrasonography.
What is the role of middle cerebral artery

Doppler testing to predict fetal anemia?
Recent advances in Doppler technology have lead to the

development of noninvasive methods to assess the degree
of fetal anemia. Doppler was used to measure the peak
systolic velocity in the fetal middle cerebral artery in 111
fetuses at risk for fetal anemia secondary to red cell
alloimmunization (Fig. 1) (26). Moderate or severe anemia was predicted by values of peak systolic velocity in
the fetal middle cerebral artery above 1.5 times the median for gestational age with a sensitivity of 100% and a
false-positive rate of 12%. Correct technique is a critical
factor when determining peak systolic velocity in the
fetal middle cerebral artery with Doppler ultrasonography. This procedure should be used only by those with
adequate training and clinical experience.
Studies have reported a good correlation between the
peak systolic velocity in the fetal middle cerebral artery
and hemoglobin in fetuses that have undergone two previous transfusions, expanding the clinical use of this
Doppler test (27, 28).
There are some limitations of this technology.
Multiple studies have suggested that there is a higher
false-positive rate after 3435 weeks of gestation (21). In
addition, as with any new technology, the measurements
must be done by a practitioner specifically trained to perform Doppler for measurement of peak systolic velocity
in the fetal middle cerebral artery. In a center with trained
personnel and when the fetus is at an appropriate gestational age, middle cerebral artery Doppler measurements
seem to be an appropriate noninvasive means to monitor
pregnancies complicated by red cell alloimmunization.
The fetal antigen type should be assessed when the paternal genotype is thought to be heterozygous or is
unknown. Amniocentesis is the primary modality used to
determine fetal blood type using polymerase chain reaction (PCR) on uncultured amniocytes in 2 mL of amniotic fluid. The sensitivity and specificity of PCR typing are
reported as 98.7% and 100%, respectively, with positive
and negative predictive values of 100% and 96.9% (20).
Chorionic villus biopsy also has been employed for this
purpose, but its use should be discouraged because disruption of the villi may result in unnecessary fetomaternal hemorrhage and worsening alloimmunization (21). If
the fetus is found to be negative for the erythrocyte antigen in question, further testing may not be warranted
(20). Although the false-negative rate is low (13%),
periodic noninvasive assessment may be warranted (20).
Detection of fetal D by molecular analysis of maternal plasma or serum can be assessed in the second
trimester with greater than 99% accuracy (22, 23). This
is possible because of high concentrations of fetal DNA
found in maternal plasma (24). It should be noted, however, that this is not a widely used clinical tool.
is heterozygous for the D antigen can be reliably estimated by using Rh-D antisera to determine his most likely genotype. This involves mixing antisera, containing
antibodies to the D antigen, with the fathers cells to determine if the D antigen is present. A positive result is determined by agglutination caused by the cross-linking of the
antibody with the corresponding antigen. If the father is
homozygous for the D antigen, all his children will be Rh
positive; if he is heterozygous, there is a 50% likelihood
that each pregnancy will have an Rh-negative fetus that is
not at risk of anemia. Given that the genes coding for the
D antigen are known, a DNA-based diagnosis is commercially available. This form of diagnosis also can be used to
identify a number of minor antigens (C, c, E, and e).
Evaluation of alloimmunization to other erythrocyte antigens known to be associated with erythroblastosis fetalis
(Table 1) should be performed in the same manner.
What are strategies for care of a patient

positive for non-D antigens at the first
prenatal visit?
The use of anti-D immune globulin to prevent red cell

alloimmunization has led to a relative increase in the
number of non-Rh-D alloimmunizations causing fetal
anemia and hemolytic disease of the newborn. Hundreds
of other distinct antigens, known as minor antigens,
exist on the red blood cell surface. Most cases of alloimmunization due to these minor antigens are caused by
incompatible blood transfusion. Overall, antibodies to
minor antigens occur in 1.52.5% of obstetric patients.
Although many antibodies directed against minor
antigens do not cause erythroblastosis fetalis, some do
(Table 1). In general, care of the pregnant patient with
antibodies to one of the clinically significant minor antigens is similar to care of Rh-D alloimmunized pregnant
women. An important exception involves alloimmuniza-
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0
945
1.16
Median
0.84
Mild anemia
Moderate anemia
Severe anemia
16
18
20
22
24
26
28
30
32
34
0.65
0.55
Multiples of the median
Hemoglobin (g/dL)
PRACTICE BULLETINS
36
Gestational age (weeks)

Figure 1. Hemoglobin concentrations in 265 healthy fetuses and 111 fetuses that underwent cordocentesis. The reference range in the healthy fetuses was between 0.84 and 1.16 times the median
(corresponding to the 5th and 95th percentiles). Values for the 111 fetuses that underwent cordocentesis are plotted individually. Solid circles indicate fetuses with hydrops. (Mari G, Deter RL,
Carpenter RL, Rahman F, Zimmerman R, Moise KJ Jr, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for
Doppler Assessment of the Blood Velocity of Anemic Fetuses. N Engl J Med 2000:342:914. Copyright
2000 Massachusetts Medical Society. All rights reserved.)
tion to the K or K1 antigens of the Kell blood group system. Kell alloimmunization appears to be less predictable
and often results in more severe fetal anemia than alloimmunization due to other erythrocyte antigens. Some
authorities believe the mechanism of anemia due to Kell
alloimmunization to be different than with Rh-D alloimmunization, and experience suggests that maternal Kell
antibody titers and amniotic fluid OD450 values are not
as predictive of the degree of fetal anemia as with Rh-D
sensitization (4).
Amniotic fluid bilirubin measurements may be misleading in cases of Kell alloimmunization. Doppler measurements, however, appear to be accurate in predicting
severe fetal anemia (29).
When is the best time to deliver the infant of

an alloimmunized patient?
Delivery of the infant of an alloimmunized patient is a

controversial subject, and literature on the subject is limited. Standard treatment is to prolong the pregnancy until
the fetus reaches a gestational age necessary for survival.
If the history and antenatal studies indicate only mild

fetal hemolysis, it is reasonable to proceed with delivery
by induction of labor at 3738 weeks of gestation.
Induction may be considered earlier if fetal pulmonary
maturity is documented by amniocentesis.
With severely sensitized pregnancies requiring
multiple invasive procedures, the risks of continued
cord blood sampling and transfusions must be considered and compared with those neonatal risks associated
with early delivery. Given that the overall neonatal survival rate after 32 weeks of gestation in most neonatal
intensive care nurseries is greater than 95%, it is prudent to time procedures so that the last transfusion is
performed at 3032 weeks of gestation, with delivery at
3234 weeks of gestation after maternal steroid administration to enhance fetal pulmonary maturity (30).
Several authors recommend intrauterine transfusion up
to 36 weeks of gestation when intravascular transfusion
is feasible in order to limit neonatal morbidity (31).
Delivery can then be accomplished between 37 and 38
weeks of gestation.
946
Recommendations and
Conclusions
In a center with trained personnel and when the

fetus is at an appropriate gestational age, Doppler
measurement of peak systolic velocity in the fetal
middle cerebral artery is an appropriate noninvasive
means to monitor pregnancies complicated by red
cell alloimmunization.
The initial management of a pregnancy involving an

alloimmunized patient is determination of the paternal erythrocyte antigen status.
Serial titers are not useful for monitoring fetal status

when the mother has had a previously affected fetus
or neonate.
Antibody titers are not appropriate for monitoring

Kell-sensitized patients because Kell antibodies do
not correlate with fetal status.
Anti-D immune globulin is indicated only in Rh-negative women who are not previously sensitized to D.
Measure
Further evaluation of patients found to have significant
antibodies associated with fetal anemia
References
Prevention of Rh D alloimmunization. ACOG Practice
Bulletin No. 4. Washington, DC: ACOG; 1999.
2. Race RR, Sanger R. Blood groups in man. 6th ed. Oxford
(UK): Blackwell Scientific Publications; 1975. (Level III)
3. Rote NS. Pathophysiology of Rh isoimmunization. Clin
4. McKenna DS, Nagaraja HN, OShaughnessy R.
Management of pregnancies complicated by anti-Kell
isoimmunization. Obstet Gynecol 1999;93:66773.
(Level II-3)
5. Cohen F, Zuelzer WW, Gustafson DC, Evans MM.
Mechanisms of isoimmunization. I. The transplacental
passage of fetal erythrocytes in homospecific pregnancies.
Blood 1964;23:62146. (Level III)
6. Lloyd LK, Miya F, Hebertson RM, Kochenour NK, Scott
JR. Intrapartum fetomaternal bleeding in Rh-negative
women. Obstet Gynecol 1980;5:2858. (Level III)
7. Woodrow JC. Rh immunisation and its prevention. Ser

Haematol 1970;3:1151. (Level III)
8. Zipursky A, Israels LG. The pathogenesis and prevention
of Rh immunization. Can Med Assoc J 1967;97:124557.
(Level III)
9. Stedman CM, Baudin JC, White CA, Cooper ES. Use of
the erythrocyte rosette test to screen for excessive fetomaternal hemorrhage in Rh-negative women. Am J Obstet
10. Ness PM, Baldwin ML, Niebyl JR. Clinical high-risk designation does not predict excess fetal-maternal hemorrhage. Am J Obstet Gynecol 1987;156:1548. (Level II-3)
11. Bowman JM. The management of Rh-isoimmunization.
12. Davey M. The prevention of rhesus-isoimmunization.
Clin Obstet Gynaecol 1979;6:50930. (Level III)
13. Litwalk O, Taswell HF, Banner EA, Keith L. Fetal erythrocytes in maternal circulation after spontaneous abortion. JAMA 1970;214:5314. (Level II-3)
14. Von Stein GA, Munsick RA, Stiver K, Ryder K.
Fetomaternal hemorrhage in threatened abortion. Obstet
15. Dayton VD, Anderson DS, Crosson JT, Cruikshank SH. A
case of Rh isoimmunization: should threatened firsttrimester abortion be an indication for Rh immune globulin prophylaxis? Am J Obstet Gynecol 1990;163:634.
(Level III)
16. Leong M, Duby S, Kinch RA. Fetal-maternal transfusion
following early abortion. Obstet Gynecol 1979;54:4246.
(Level II)
17. Katz J, Marcus RG. The risk of Rh isoimmunization in
ruptured tubal pregnancy. Br Med J 1972;3(828):6679.
(Level III)
18. Mennuti MT, Brummond W, Crombleholme WR,
Schwarz RH, Arvan DA. Fetal-maternal bleeding associated with genetic amniocentesis. Obstet Gynecol 1980;
55:4854. (Level II-3)
19. Hackney DN, Knudtson EJ, Rossi KQ, Krugh D,
OShaughnessy RW. Management of pregnancies complicated by anti-c isoimmunization. Obstet Gynecol 2004;
103:2430. (Level III)
20. Van den Veyver IB, Moise KJ Jr. Fetal RhD typing by
polymerase chain reaction in pregnancies complicated by
rhesus alloimmunization. Obstet Gynecol 1996;88:
10617. (Level III)
21. Moise KJ Jr. Management of rhesus alloimmunization in
pregnancy [published erratum appears in Obstet Gynecol
2002;100:833]. Obstet Gynecol 2002;100:60011. (Level
III)
22. Lo YM, Hjelm NM, Fidler C, Sargent IL, Murphy MF,
Chamberlain PF, et al. Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. N Engl J
Med 1998;339:17348. (Level II-3)
23. Gautier E, Benachi A, Giovangrandi Y, Ernault P, Olivi M,
Gaillon T, et al. Fetal RhD genotyping by maternal serum
analysis: a two-year experience. Am J Obstet Gynecol
2005;192:6669. (Level III)
PRACTICE BULLETINS
24. Pertl B, Bianchi D. Fetal DNA in maternal plasma:

emerging clinical applications. Obstet Gynecol 2001;98:
48390. (Meta-analysis)
25. Liley AW. Intrauterine transfusion of foetus in haemolytic
disease. Br Med J 1963;5365:11079. (Level III)
26. Mari G, Deter RL, Carpenter RL, Rahman F, Zimmerman
R, Moise KJ Jr, et al. Noninvasive diagnosis by Doppler
ultrasonography of fetal anemia due to maternal red-cell
alloimmunization. Collaborative Group for Doppler
Assessment of the Blood Velocity of Anemic Fetuses. N
27. Mari G, Zimmermann R, Moise KJ Jr, Deter RL.
Correlation between middle cerebral artery peak systolic
velocity and fetal hemoglobin after 2 previous intrauterine
transfusions. Am J Obstet Gynecol 2005;193:111720.
(Level II-3)
28. Pereira L, Jenkins TM, Berghella V. Conventional management of maternal red cell alloimmunization compared
with management by Doppler assessment of middle cerebral artery peak systolic velocity. Am J Obstet Gynecol
2003;189:10026. (Level II-3)
29. Van Dongen H, Klumper FJ, Sikkel E, Vandenbussche FP,
Oepkes D. Non-invasive tests predict fetal anemia in Kellalloimmunized pregnancies. Ultrasound Obstet Gynecol
2005;25:3415. (Level III)
30. Bowman JM. Maternal alloimmunization and fetal
hemolytic disease. In: Reece EA, Hobbins JC, editors.
Medicine of the fetus and mother. 2nd ed. Philadelphia
(PA): Lippincott-Raven Publishers; 1999. p. 124169.
(Level III)
31. Boggs TR Jr. Survival rates in Rh sensitizations: 140
interrupted versus 141 uninterrupted pregnancies.
947

literature search to locate relevant articles published between November 1965 and June 2005. The search was restricted to articles published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries also
Force:
I
type of evidence.
committees.
be reproduced, stored in a retrieval system, posted on the Internet, or
from the publisher.
01923, (978) 750-8400.
ISSN 1099-3630
Management of alloimmunization during pregnancy. ACOG Practice
Bulletin No. 75. American College of Obstetricians and Gynecologists.
948
ACOG
PRACTICE
BULLETIN
(Replaces Committee Opinion Number 266, January 2002)
Postpartum Hemorrhage
of William N. P. Herbert, MD,
and Carolyn M. Zelop, MD.
of practice.
Reaffirmed 2008
Severe bleeding is the single most significant cause of maternal death worldwide. More than half of all maternal deaths occur within 24 hours of delivery,
most commonly from excessive bleeding. It is estimated that, worldwide,
140,000 women die of postpartum hemorrhage each yearone every 4 minutes
(1). In addition to death, serious morbidity may follow postpartum hemorrhage.
Sequelae include adult respiratory distress syndrome, coagulopathy, shock, loss
of fertility, and pituitary necrosis (Sheehan syndrome).
Although many risk factors have been associated with postpartum hemorrhage, it often occurs without warning. All obstetric units and practitioners
must have the facilities, personnel, and equipment in place to manage this
emergency properly. Clinical drills to enhance the management of maternal
hemorrhage have been recommended by the Joint Commission on Accreditation
of Healthcare Organizations (2). The purpose of this bulletin is to review the
etiology, evaluation, and management of postpartum hemorrhage.
Background
The physiologic changes over the course of pregnancy, including a plasma volume increase of approximately 40% and a red cell mass increase of approximately 25%, occur in anticipation of the blood loss that will occur at delivery
(3). There is no single, satisfactory definition of postpartum hemorrhage. An
estimated blood loss in excess of 500 mL following a vaginal birth or a loss of
greater than 1,000 mL following cesarean birth often has been used for the
diagnosis, but the average volume of blood lost at delivery can approach these
amounts (4, 5). Estimates of blood loss at delivery are notoriously inaccurate,
with significant underreporting being the rule. Limited instruction on estimating blood loss has been shown to improve the accuracy of such estimates (6).
Also, a decline in hematocrit levels of 10% has been used to define postpartum
hemorrhage, but determinations of hemoglobin or hematocrit concentrations
may not reflect the current hematologic status (7). Hypotension, dizziness, pal-
PRACTICE BULLETINS
Etiology of Postpartum Hemorrhage

Primary
Uterine atony
Retained placentaespecially placenta accreta
Defects in coagulation
Uterine inversion
Secondary
Subinvolution of placental site
Retained products of conception
Infection
Inherited coagulation defects
Adapted from Cunningham FG, Leveno KJ, Bloom SL, Hauth JC,
Gilstrap L 3rd, Wenstrom KD. Obstetric hemorrhage. In: Williams
obstetrics. 22nd ed. New York (NY): McGraw-Hill; 2005. p. 80954
and Alexander J, Thomas P, Sanghera J. Treatments for secondary
postpartum haemorrhage. The Cochrane Database of Systematic
14651858.CD002867.
future fertility. At times, immediate surgery is required

because time spent using other treatment methods would
be dangerous for the patient. There are few randomized
controlled studies relevant to the management of postpartum hemorrhage, so management decisions usually
are made based on clinical judgment.
Evaluation and Management

Considerations
In an effort to prevent uterine atony and associated bleeding, it is routine to administer oxytocin soon after delivery.
This may be given at the time of delivery of the anterior
shoulder of the fetus, or more commonly in the United
States, following delivery of the placenta.
It may be helpful to post protocols for hemorrhage
management in delivery rooms or operating suites. A sample poster from the New York City Department of Health
and Mental Hygiene is available at http://home2.nyc.gov/
html/doh/downloads/pdf/ms/ms-hemorr-poster.pdf.

Recommendations
lor, and oliguria do not occur until blood loss is substantial10% or more of total blood volume (8).
Postpartum hemorrhage generally is classified as
primary or secondary, with primary hemorrhage occurring within the first 24 hours of delivery and secondary
hemorrhage occurring between 24 hours and 612 weeks
postpartum. Primary postpartum hemorrhage, which
occurs in 46% of pregnancies, is caused by uterine
atony in 80% or more of cases (7). Other etiologies are
shown in the box Etiology of Postpartum Hemorrhage,
with risk factors for excessive bleeding listed in the box
Risk Factors for Postpartum Hemorrhage.
If excessive blood loss is ongoing, concurrent evaluation and management are necessary. A number of general medical supportive measures may be instituted,
including provision of ample intravenous access; crystalloid infusion; blood bank notification that blood products
may be necessary; prompt communication with anesthesiology, nursing, and obstetriciangynecologists; and
blood collection for baseline laboratory determinations.
When treating postpartum hemorrhage, it is necessary to balance the use of conservative management techniques with the need to control the bleeding and achieve
hemostasis. A multidisciplinary approach often is
required. In the decision-making process, less-invasive
methods should be tried initially if possible, but if unsuccessful, preservation of life may require hysterectomy.
Management of postpartum hemorrhage may vary greatly among patients, depending on etiology of the bleeding,
available treatment options, and a patients desire for
949
What should be considered in the initial evaluation of a patient with excessive bleeding in
the immediate puerperium?
Because the single most common cause of hemorrhage is

uterine atony, the bladder should be emptied and a
bimanual pelvic examination should be performed. The
finding of the characteristic soft, poorly contracted
(boggy) uterus suggests atony as a causative factor.
Compression or massage of the uterine corpus can diminish bleeding, expel blood and clots, and allow time for
other measures to be implemented.
If bleeding persists, other etiologies besides atony
must be considered. Even if atony is present, there may
be other contributing factors. Lacerations should be ruled
out by careful visual assessment of the lower genital
tract. Proper patient positioning, adequate operative
assistance, good lighting, appropriate instrumentation
(eg, Simpson or Heaney retractors), and adequate anesthesia are necessary for the identification and proper
repair of lacerations. Satisfactory repair may require
transfer to a well-equipped operating room.
Genital tract hematomas also can lead to significant
blood loss. Progressive enlargement of the mass indicates
a need for incision and drainage. Often a single bleeding
source is not identified when a hematoma is incised.
Draining the blood within the hematoma (sometimes
950
Risk Factors for Postpartum Hemorrhage

Prolonged labor
Augmented labor
Rapid labor
History of postpartum hemorrhage
Episiotomy, especially mediolateral
Preeclampsia
Overdistended uterus (macrosomia, twins,
hydramnios)
Operative delivery
Asian or Hispanic ethnicity
Chorioamnionitis
Data from Stones RW, Paterson CM, Saunders NJ. Risk factors for
major obstetric haemorrhage. Eur J Obstet Gynecol Reprod Biol
1993;48:158 and Combs CA, Murphy EL, Laros RK. Factors associated with hemorrhage in cesarean deliveries. Obstet Gynecol
1991;77:7782.
placing a drain in situ), suturing the incision, and if

appropriate, packing the vagina are measures usually
successful in achieving hemostasis. Interventional radiology is another option for management of a hematoma.
Genital tract hematomas may not be recognized until
hours after the delivery, and they sometimes occur in the
absence of vaginal or perineal lacerations. The main
symptoms are pelvic or rectal pressure and pain.
The possibility that additional products of conception remain within the uterine cavity should be considered. Ultrasonography can help diagnose a retained
placenta. Retained placental tissue is unlikely when
ultrasonography reveals a normal endometrial stripe.
Although ultrasonographic images of retained placental
tissue are inconsistent, detection of an echogenic mass in
the uterus is more conclusive. Ultrasound evaluation for
retained tissue should be performed before uterine
instrumentation is undertaken (9). Spontaneous expulsion of the placenta, apparent structural integrity on
inspection, and the lack of a history of previous uterine
surgery (suggesting an increased risk of abnormal placentation) make a diagnosis of retained products of the
placenta less likely, but a curettage may identify a succenturiate lobe of the placenta or additional placental tissue. When a retained placenta is identified, a large, blunt
instrument, such as a banjo curette or ring forceps, guided by ultrasonography, makes removal of the retained
tissue easier and reduces the risk of perforation.
Less commonly, postpartum hemorrhage may be
caused by coagulopathy. Clotting abnormalities should
be suspected on the basis of patient or family history
or clinical circumstances. Hemolysis, elevated liver

enzymes, and low platelet count (HELLP) syndrome,
abruptio placentae, prolonged intrauterine fetal demise,
sepsis, and amniotic fluid embolism are associated with
clotting abnormalities. Significant hemorrhage from any
cause can lead to consumption of clotting factors.
Observation of the clotting status of blood recently lost
can provide important information. When a coagulopathy is suspected, appropriate testing should be ordered,
with blood products infused as indicated. In some situations, the coagulopathy may be caused or perpetuated by
the hemorrhage. In such cases, simultaneous surgery and
blood product replacement may be necessary.
Baseline studies should be ordered when excessive
blood loss is suspected and should be repeated periodically as clinical circumstances warrant. Clinicians
should remember that the results of some studies may be
misleading because equilibration may not have occurred.
In addition, response to hemorrhage may be required
before laboratory results are known. Baseline studies
include a complete blood count with platelets, a prothrombin time, an activated partial thromboplastin time,
fibrinogen, and a type and cross order. The blood bank
should be notified that transfusion may be necessary.
The clot observation test provides a simple measure
of fibrinogen (10). A volume of 5 mL of the patients
blood is placed into a clean, red-topped tube and
observed frequently. Normally, blood will clot within
810 minutes and will remain intact. If the fibrinogen
concentration is low, generally less than 150 mg/dL, the
blood in the tube will not clot, or if it does, it will undergo partial or complete dissolution in 3060 minutes.
What is the appropriate medical management

approach for excessive postpartum bleeding?
Ongoing blood loss in the setting of decreased uterine

tone requires the administration of additional uterotonics
as the first-line treatment for hemorrhage (Table 1).
Some practitioners prefer direct injection of methylergonovine maleate and 15-methyl prostaglandin (PG) F2
into the uterine corpus. Human recombinant factor VIIa
is a new treatment modality shown to be effective in
controlling severe, life-threatening hemorrhage by acting
on the extrinsic clotting pathway. Intravenous dosages
vary by case and generally range from 50 to 100 mcg/kg
every 2 hours until hemostasis is achieved. Cessation of
bleeding ranges from 10 minutes to 40 minutes after
administration (1114). Concern has been raised because of apparent risk of subsequent thromboembolic
events following factor VIIa use (15). Compared with
other agents, factor VIIa is extremely expensive.
Additional clinical experience in all specialties will help
PRACTICE BULLETINS
951
Table 1. Medical Management of Postpartum Hemorrhage

Drug*
Dose/Route
Frequency
Comment
Oxytocin (Pitocin)
IV: 1040 units in 1 liter

normal saline or lactated
Ringers solution
IM: 10 units
Continuous
Avoid undiluted rapid IV infusion,

which causes hypotension.
Methylergonovine
(Methergine)
IM: 0.2 mg
Every 24 h
Avoid if patient is hypertensive.
15-methyl PGF2
(Carboprost)
(Hemabate)
IM: 0.25 mg
Every 1590 min,

8 doses maximum
Avoid in asthmatic patients;

relative contraindication if
hepatic, renal, and cardiac
disease. Diarrhea, fever,
tachycardia can occur.
Dinoprostone
(Prostin E2)
Suppository: vaginal
or rectal
20 mg
Every 2 h
Avoid if patient is hypotensive.

Fever is common. Stored frozen,
it must be thawed to room
temperature.
Misoprostol
(Cytotec, PGE1)
8001,000 mcg rectally
Abbreviations: IV, intravenously; IM, intramuscularly; PG, prostaglandin.

*All agents can cause nausea and vomiting.
Modified from Dildy GA, Clark SL. Postpartum hemorrhage. Contemp Ob/Gyn 1993;38(8):219.
determine factor VIIas role in the treatment of patients

with postpartum hemorrhage.
When is packing or tamponade of the uterine

cavity advisable?
When uterotonics fail to cause sustained uterine contractions and satisfactory control of hemorrhage after vaginal
delivery, tamponade of the uterus can be effective in
decreasing hemorrhage secondary to uterine atony (Table
2). Such approaches can be particularly useful as a temporizing measure, but if a prompt response is not seen,
preparations should be made for exploratory laparotomy.
Packing with gauze requires careful layering of the
material back and forth from one cornu to the other using
a sponge stick, packing back and forth, and ending with
extension of the gauze through the cervical os. The same
effect often can be derived more easily using a Foley
catheter, Sengstaken-Blakemore tube, or, more recently,
the SOS Bakri tamponade balloon (16), specifically tailored for tamponade within the uterine cavity in cases of
postpartum hemorrhage secondary to uterine atony.
When are surgical techniques used to control

uterine bleeding?
When uterotonic agents with or without tamponade measures fail to control bleeding in a patient who has given
birth vaginally, exploratory laparotomy is indicated. A
midline vertical abdominal incision usually is preferred
to optimize exposure. Several techniques are available to
control bleeding (Table 3). Hypogastric artery ligation is

performed much less frequently than in years past. Its
purpose is to diminish the pulse pressure of blood flowing to the uterus via the internal iliac (hypogastric) vessels. Practitioners are less familiar with this technique,
and the procedure has been found to be considerably less
successful than previously thought (17). Bilateral uterine
artery ligation (OLeary sutures) accomplishes the same
goal, and this procedure is quicker and easier to perform
(18, 19). To further diminish blood flow to the uterus,
similar sutures can be placed across the vessels within the
uteroovarian ligaments.
The B-Lynch technique is a newer procedure for
stopping excessive bleeding caused by uterine atony (20).
The suture provides even pressure to compress the uterine
corpus and decrease bleeding. One study reported more
Table 2. Tamponade Techniques for Postpartum Hemorrhage
Technique
Comment
Uterine tamponade
Packing
4-inch gauze; can soak with

5,000 units of thrombin in 5 mL
of sterile saline
Foley catheter
Insert one or more bulbs; instill

6080 mL of saline
SengstakenBlakemore tube
SOS Bakri tamponade balloon
Insert balloon; instill 300500 mL

of saline
952
Table 3. Surgical Management of Postpartum Hemorrhage

Technique
Comment
Uterine curettage
Uterine artery ligation
Bilateral; also can ligate uteroovarian

vessels
B-Lynch suture
Hypogastric artery ligation
Less successful than earlier thought;

difficult technique; generally
reserved for practitioners
experienced in the procedure
Repair of rupture
Hysterectomy
than 1,000 B-Lynch procedures with only seven failures

(21). However, because the technique is new, many clinicians have limited experience with this procedure (22).
Hemostatic multiple square suturing is another new
surgical technique for postpartum hemorrhage caused by
uterine atony, placenta previa, or placenta accreta. The
procedure eliminates space in the uterine cavity by suturing both anterior and posterior uterine walls. One study
reported on this technique in 23 women after conservative treatment failed. All patients were examined after 2
months, and ultrasound findings confirmed normal
endometrial linings and uterine cavities (23).
What are the clinical considerations for

suspected placenta accreta?
The patient should be counseled about the likelihood

of hysterectomy and blood transfusion.
Blood products and clotting factors should be available.
Cell saver technology should be considered if available.
The appropriate location and timing for delivery
should be considered to allow access to adequate
surgical personnel and equipment.
A preoperative anesthesia assessment should be
obtained.
The extent (area, depth) of the abnormal attachment
will determine the responsecurettage, wedge resection,
medical management, or hysterectomy. Uterine conserving options may work in small focal accretas, but abdominal hysterectomy usually is the most definitive treatment.
Under what circumstances is arterial

embolization indicated?
A patient with stable vital signs and persistent bleeding,

especially if the rate of loss is not excessive, may be a candidate for arterial embolization. Radiographic identification of bleeding vessels allows embolization with Gelfoam,
coils, or glue. Balloon occlusion is also a technique used in
such circumstances. Embolization can be used for bleeding
that continues after hysterectomy or can be used as an
alternative to hysterectomy to preserve fertility.
Abnormal attachment of the placenta to the inner uterine

wall (placenta accreta) can cause massive hemorrhage. In
fact, accreta and uterine atony are the two most common
reasons for postpartum hysterectomy (24, 25). Risk factors
for placenta accreta include placenta previa with or without previous uterine surgery, prior myomectomy, prior
cesarean delivery, Ashermans syndrome, submucous
leiomyomata, and maternal age older than 35 years (26).
Prior cesarean delivery and the presence of placenta
previa in a current pregnancy are particularly important risk
factors for placenta accreta. In a multicenter study of more
than 30,000 patients who had cesarean delivery without
labor, the risk of placenta accreta was approximately 0.2%,
0.3%, 0.6%, 2.1%, 2.3%, and 7.7% for women experiencing their first through sixth cesarean deliveries, respectively. In patients with placenta previa in the current pregnancy, the risk of accreta was 3%, 11%, 40%, 61%, and 67%
for those undergoing their first through their fifth or greater
cesarean deliveries, respectively (27).
Women with placenta previa or placenta accreta
have a higher incidence of postpartum hemorrhage and
are more likely to undergo emergency hysterectomy
(28). In the multicenter study cited previously, hysterectomy was required in 0.7% for the first cesarean delivery
and increased with each cesarean delivery up to 9% for
patients with their sixth or greater cesarean delivery.
In the presence of previa or a history of cesarean
delivery, the obstetric care provider must have a high
clinical suspicion for placenta accreta and take appropriate precautions. Ultrasonography may be helpful in
establishing the diagnosis in the antepartum period.
Color Doppler technology may be an additional adjunctive tool for suspected accreta (29). Despite advances in
imaging techniques, no diagnostic technique affords the
clinician complete assurance of the presence or absence
of placenta accreta.
If the diagnosis or a strong suspicion is formed
before delivery, a number of measures should be taken:
When is blood transfusion recommended?

Is there a role for autologous transfusions
or directed donor programs?
Transfusion of blood products is necessary when the

extent of blood loss is significant and ongoing, particularly if vital signs are unstable. Postpartum transfusion
PRACTICE BULLETINS
What is the management approach for

hemorrhage due to a ruptured uterus?
Rupture can occur at the site of a previous cesarean delivery or other surgical procedure involving the uterine wall
from intrauterine manipulation or trauma or from congenital malformation (small uterine horn), or it can occur
spontaneously. Abnormal labor, operative delivery, and
placenta accreta can lead to rupture. Surgical repair is
required, with the specific approach tailored to reconstruct the uterus, if possible. Care depends on the extent
and site of rupture, the patients current clinical condition, and her desire for future childbearing. Rupture of a
previous cesarean delivery scar often can be managed by
revision of the edges of the prior incision followed by
primary closure. In addition to the myometrial disruption, consideration must be given to neighboring structures, such as the broad ligament, parametrial vessels,
ureters, and bladder. Regardless of the patients wishes
for the avoidance of hysterectomy, this procedure may
be necessary in a life-threatening situation.
rates vary between 0.4% and 1.6% (30). Clinical judgment is an important determinant, given that estimates of
blood loss often are inaccurate, determination of hematocrit or hemoglobin concentrations may not accurately
reflect the current hematologic status, and symptoms and
signs of hemorrhage may not occur until blood loss
exceeds 15% (8). The purpose of transfusion of blood
products is to replace coagulation factors and red cells for
oxygen-carrying capacity, not for volume replacement.
To avoid dilutional coagulopathy, concurrent replacement with coagulation factors and platelets may be necessary. Table 4 lists blood components, indications for
transfusion, and hematologic effects.
Autologous transfusion (donation, storage, retransfusion) has been shown to be safe in pregnancy (31, 32).
However, it requires anticipation of the need for transfusion, as well as a minimal hematocrit concentration often
above that of a pregnant woman. Autologous transfusion
generally is reserved for situations with a high chance of
transfusion in a patient with rare antibodies, where the
likelihood of identifying compatible volunteer-provided
blood is very low. Blood donated by directed donors has
not been shown to be safer than blood from unknown,
volunteer donors. Cell saver technology has been used
successfully in patients undergoing cesarean delivery. In
a multicenter study of 139 patients using such devices, no
untoward outcomes were noted when compared with
control patients (33).
What is the management approach for an

inverted uterus?
Uterine inversion, in which the uterine corpus descends

to, and sometimes through, the uterine cervix, is associated with marked hemorrhage. On bimanual examination, the finding of a firm mass below or near the cervix,
coupled with the absence of identification of the uterine
corpus on abdominal examination, suggests inversion.
If the inversion occurs before placental separation,
detachment or removal of the placenta should not be
undertaken; this will lead to additional hemorrhage.
Replacement of the uterine corpus involves placing the
palm of the hand against the fundus (now inverted and
lowermost at or through the cervix), as if holding a tennis ball, with the fingertips exerting upward pressure
circumferentially (34). To restore normal anatomy, relaxation of the uterus may be necessary. Terbutaline,
magnesium sulfate, halogenated general anesthetics, and
nitroglycerin have been used for uterine relaxation.
Manual replacement with or without uterine relaxants usually is successful. In the unusual circumstance in
which it is not, laparotomy is required. Two procedures
have been reported to return the uterine corpus to the
abdominal cavity. The Huntington procedure involves
Table 4. Blood Component Therapy

Product
Packed red cells
Platelets
Fresh frozen plasma
Cryoprecipitate
Volume (mL)
953
Contents
Effect (per unit)
240
Red blood cells,

white blood cells, plasma
Increase hematocrit 3 percentage

points, hemoglobin by 1 g/dL
50
Platelets, red blood cells,

white blood cells, plasma
Increase platelet count 5,000

10,000/mm3 per unit
250
Fibrinogen, antithrombin III,

factors V and VIII
Increase fibrinogen by 10 mg/dL
40
Fibrinogen, factors VIII and

XIII, von Willebrand factor
Increase fibrinogen by 10 mg/dL
Modified from Martin SR, Strong TH Jr. Transfusion of blood components and derivatives in the obstetric intensive care
patient. In: Foley MR, Strong TH Jr, Garite TJ, editors. Obstetric intensive care manual. 2nd ed. New York (NY): McGraw-Hill;
2004. Produced with permission of The McGraw-Hill Companies.
954
progressive upward traction on the inverted corpus using

Babcock or Allis forceps (35). The Haultain procedure
involves incising the cervical ring posteriorly, allowing
for digital repositioning of the inverted corpus, with subsequent repair of the incision (36).
What is the management approach for

secondary postpartum hemorrhage?
Management may vary greatly among patients,

depending on etiology and available treatment
options, and often a multidisciplinary approach is
required.
When uterotonics fail following vaginal delivery,

exploratory laparotomy is the next step.
Regardless of the cause of postpartum hemorrhage, subsequent replacement of the red cell mass is important.
Along with a prenatal vitamin and mineral capsule daily
(which contains about 60 mg of elemental iron and
1 mg folate), two additional iron tablets (ferrous sulfate,
300 mg, each yielding about 60 mg of elemental iron) will
maximize red cell production and restoration. Erythropoietin can hasten red cell production in postpartum anemic patients to some extent, but it is not approved by the
U.S. Food and Drug Administration for postoperative anemia, and it can be costly (40). Postpartum hemorrhage in
a subsequent pregnancy occurs in approximately 10% of
patients (8).
Uterotonic agents should be the first-line treatment

for postpartum hemorrhage due to uterine atony.
What is the best approach to managing

excessive blood loss in the postpartum period
once the patients condition is stable?
The following recommendations and conclusions

are based primarily on consensus and expert opinion (Level C):
Secondary hemorrhage occurs in approximately 1% of

pregnancies; often the specific etiology is unknown.
Postpartum hemorrhage may be the first indication for
von Willebrands disease for many patients and should
be considered. The prevalence of von Willebrands disease is reported to be 1020% among adult women with
menorrhagia (37). Hence, testing for bleeding disorders
should be considered among pregnant patients with a
history of menorrhagia because the risk of delayed or
secondary postpartum hemorrhage is high among
women with bleeding disorders (38, 39).
Uterine atony (perhaps secondary to retained products of conception) with or without infection contributes to secondary hemorrhage. The extent of bleeding
usually is less than that seen with primary postpartum
hemorrhage. Ultrasound evaluation can help identify
intrauterine tissue or subinvolution of the placental site.
Treatment may include uterotonic agents, antibiotics,
and curettage. Often the volume of tissue removed by
curettage is minimal, yet bleeding subsides promptly.
Care must be taken in performing the procedure to avoid
perforation of the uterus. Concurrent ultrasound assessment at the time of curettage can be helpful in preventing this complication. Patients should be counseled
about the possibility of hysterectomy before initiating
any operative procedures.
Summary of
Recommendations and
Conclusions
In the presence of conditions known to be associated with placenta accreta, the obstetric care provider
must have a high clinical suspicion and take appropriate precautions.
Measure
If hysterectomy is performed for uterine atony, there
should be documentation of other therapy attempts.
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literature search to locate relevant articles published between January 1901 and June 2006. The search was restricted to articles published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries also
Force:
I
type of evidence.
committees.

from the publisher.
01923, (978) 750-8400.
ISSN 1099-3630
Postpartum hemorrhage. ACOG Practice Bulletin No. 76. American
103947.
PRACTICE BULLETINS
957
ACOG
PRACTICE
BULLETIN
Replaces Practice Bulletin Number 27, May 2001, and Committee Opinion Number 296, July 2004

on Practice BulletinsObstetrics, the ACOG Committee on
Genetics, and the Society for
MaternalFetal Medicine Publications Committee with the assistance of Ray Bahado-Singh, MD,
and Deborah Driscoll, MD. The
practitioners in making decisions
individual patient, resources, and
Reaffirmed 2008
The Society for

Maternal-Fetal Medicine
Screening for Fetal

Chromosomal
Abnormalities
In the past decade, numerous markers and strategies for Down syndrome
screening have been developed. Algorithms that combine ultrasound and serum
markers in the first and second trimesters have been evaluated. Furthermore,
the practice of using age cutoffs to determine whether women should be offered
screening or invasive diagnostic testing has been challenged. The purpose of
this document is to 1) present and evaluate the best available evidence for the
use of ultrasonographic and serum markers for selected aneuploidy screening
in pregnancy and 2) offer practical recommendations for implementing Down
syndrome screening in practice.
Background
Historically, maternal age 35 years or older at the time of delivery has been
used to identify women at highest risk of having a child with Down syndrome,
and these women have been offered genetic counseling and amniocentesis or
chorionic villus sampling (CVS). Biochemical serum screening for Down syndrome in women younger than 35 years was introduced in 1984, when an association between low maternal serum alpha-fetoprotein (AFP) levels and Down
syndrome was reported (1). In the 1990s, human chorionic gonadotropin (hCG)
and unconjugated estriol were used in combination with maternal serum AFP
to improve the detection rates for Down syndrome and trisomy 18. The average
maternal serum AFP level in Down syndrome pregnancies is reduced to 0.74
multiples of the median (MoM) observed in euploid pregnancies (2). Intact
hCG is increased in affected pregnancies, with an average level of 2.06 MoM,
whereas unconjugated estriol is reduced to an average level of 0.75 MoM (2).
When the levels of all three markers (triple test) are used to modify the mater-
958
nal age-related Down syndrome risk, the detection rate

for Down syndrome is approximately 70%; approximately 5% of all pregnancies will have a positive screen
result. Typically, the levels of all three markers are
reduced when the fetus has trisomy 18. Adding inhibin A
to the triple test (quadruple screen) improves the detection rate for Down syndrome to approximately 80%. The
median value of the maternal inhibin A level is increased
at 1.77 MoM in Down syndrome pregnancies (3), but
inhibin A is not used in the calculation of risk for trisomy
18. Screening with biochemical markers, ultrasonography, or both is being offered increasingly to the entire
pregnant population to provide a more accurate estimate
of individual Down syndrome risk. Higher sensitivity or
detection rates (defined as the percentage of Down syndrome pregnancies identified with a positive test result)
at low false-positive rates have led to increased use of
screening and a decline in the number of amniocenteses
performed.
Studies done in the early and mid-1990s revealed a
strong association between the size of a fluid collection
at the back of the fetal neck in the first trimester, referred
to as nuchal translucency, and the risk of trisomy 21
(4). An increase in nuchal translucency is now widely
recognized to be an early presenting feature of a broad
range of fetal chromosomal, genetic, and structural
abnormalities. However, considerable variability in the
detection rates for Down syndrome among the early studies of nuchal translucency measurement limited the
practical utility of the test (5). Now guidelines for the
systematic measurement of nuchal translucency have
been standardized (6). Specific training for a standardized method of measurement and ongoing audits of
examination quality are recommended for screening programs that include nuchal translucency measurement (7).
Other first-trimester ultrasonographic markers such as
nonvisualization of the nasal bone and tricuspid regurgitation are being evaluated for their potential as screening
tests for Down syndrome, but their clinical usefulness
remains uncertain.
A significant breakthrough in first-trimester screening for Down syndrome was achieved when large studies
in the United States and the United Kingdom demonstrated that, when expressing the nuchal translucency
measurement as an MoM, it could be combined with two
first-trimester serum analytes, free -hCG and pregnancy-associated plasma protein A (PAPP-A). The average
level of free -hCG in first-trimester Down syndrome
pregnancies is elevated to 1.98 MoM (8), and the average
level of PAPP-A, a glycoprotein that, like hCG, is produced by the trophoblast, is reduced to approximately
0.43 MoM (9). Maternal serum analytes, PAPP-A, and
hCG or free -hCG are effective for screening in the first
trimester, whereas AFP, unconjugated estriol, and inhibin

A are useful only in the second trimester.
Several approaches to Down syndrome screening in
the first and second trimesters have been evaluated and
are described in this document (Table 1). Not all strategies include nuchal translucency measurement because
this screening approach is not available in all regions due
to the need for specialized training to obtain it, and this
measurement might not be obtained successfully in an
individual patient.
Table 1. Down Syndrome Screening Tests and Detection
Rates (5% Positive Screen Rate)
Screening Test
Detection Rate (%)
First Trimester
NT measurement
6470*
NT measurement, PAPP-A,
free or total -hCG
8287*
Second trimester
Triple screen (MSAFP, hCG,
unconjugated estriol)
69*
Quadruple screen (MSAFP, hCG,

unconjugated estriol, inhibin A)
81*
First Plus Second Trimester

Integrated (NT, PAPP-A, quad screen)
9496*
Serum integrated (PAPP-A, quad screen)
8588*
Stepwise sequential
95*
First-trimester test result:

Positive: diagnostic test offered
Negative: second-trimester test
offered
Final: risk assessment incorporates first
and second results
Contingent sequential
8894%
First-trimester test result:

Positive: diagnostic test offered
Negative: no further testing
Intermediate: second-trimester test offered
Final: risk assessment incorporates first and
second results
Abbreviations: hCG, human chorionic gonadotropin; MSAFP, maternal serum
alpha-fetoprotein; NT, nuchal translucency; PAPP-A, pregnancy-associated plasma protein A; quad, quadruple.
*From the FASTER trial (Malone F, Canick JA, Ball RH, Nyberg DA, Comstock CH,
Buckowski R, et al. First-trimester or second-trimester screening, or both, for
Downs syndrome. First- and Second-Trimester Evaluation of Risk (FASTER)
Research Consortium. N Engl J Med 2005;353:200111.)
Also referred to as combined first-trimester screen
Modeled predicted detection rates (Cuckle H, Benn P, Wright D. Down syndrome screening in the first and/or second trimester: model predicted performance using meta-analysis parameters. Semin Perinatol 2005;29:2527.)
PRACTICE BULLETINS

Recommendations
Should all patients be counseled about
screening for aneuploidy?
Ideally, all women should be offered aneuploidy screening before 20 weeks of gestation, regardless of maternal
age. It is not practical to have patients choose from
among the large array of screening strategies that might
be used. Before deciding which strategy or strategies to
offer patients, review the evidence presented in this document, identify which tests are available in your area,
and determine which strategy or strategies will best meet
the needs of your patients. The options for women who
are first seen during the second trimester are limited to
quadruple (or quad) screening and ultrasound examination. A strategy that incorporates both first- and second-trimester screening should be offered to women
who seek prenatal care in the first trimester.
Regardless of which screening tests you decide to
offer your patients, information about the detection and
false-positive rates, advantages, disadvantages, and limitations, as well as the risks and benefits of diagnostic
procedures, should be available to patients so that they
can make informed decisions. Patients may decline Down
syndrome screening because they would not use the
information in deciding whether to have a diagnostic test
or because they wish to avoid the chance of a false-positive screening test result. The choice of screening test
depends on many factors, including gestational age at
first prenatal visit, number of fetuses, previous obstetric
history, family history, availability of nuchal translucency
measurement, test sensitivity and limitations, risk of invasive diagnostic procedures, desire for early test results,
and options for earlier termination. Some patients may
benefit from a more extensive discussion with a genetics
professional or a maternalfetal medicine specialist, especially if there is a family history of a chromosome abnormality, genetic disorder, or congenital malformation.
What are the advantages and disadvantages

of screening for aneuploidy compared with
diagnostic testing?
Screening for aneuploidy identifies a population of
women whose fetuses are at increased risk for Down
syndrome, trisomy 18, or trisomy 13. If women who
have had a positive screening test result choose to undergo a diagnostic procedure, such as CVS or amniocentesis, there is a higher chance of identifying an affected
fetus than there would be if the diagnostic test was performed in an unscreened population. Fewer invasive pro-
959
cedures will be required to identify an aneuploid fetus

in patients who have screening, thus resulting in a
decreased number of procedure-related losses of normal
fetuses.
The main disadvantage of screening approaches for
the detection of aneuploidies is that not all affected fetuses will be detected. Although the currently available
approaches have relatively high detection rates (sensitivity) at low screen positive rates, women should understand
that screening provides an individual risk assessment but
is not diagnostic and thus will not detect all chromosomal
abnormalities. Counseling should be provided regarding
the specific detection rates and false-positive rates of the
screening strategy or strategies they are considering.
In comparison with the sensitivity of screening, the
main advantage of invasive diagnostic testing is that all
autosomal trisomies will be detected. Diagnostic testing
also will reliably detect sex chromosome aneuploidies,
large deletions or duplications of chromosomes, and chromosomal mosaicism. However, in an unscreened population, more invasive procedures will be performed for each
affected fetus identified, resulting in a greater loss of normal fetuses when compared with a screened population.
Patients informed of the risks, particularly those at
increased risk of having an aneuploid fetus, may opt to
have diagnostic testing without first having screening.
How are aneuploidy screening test results

interpreted?
Laboratories that report screening test results generally
provide the clinician with numerical information
regarding the patients age-related risk and a revised
risk assessment based on age, the serum analyte levels,
and nuchal translucency measurement if available.
Communicating a numerical risk assessment after
screening enables women and their partners to balance
the risk and the consequences of having a child with the
particular problem against the risk and consequences of
an invasive diagnostic test. Because this decision involves
personal values, it is preferable to provide patients with
their numerical risk determined by the screening test,
rather than a positive versus negative screening result
using an arbitrary cutoff. It is often useful to contrast this
risk with the general population risk and their age-related
risk before screening.
Screening test results may be reported as screen
positive or screen negative based on fixed cutoff values.
The use of fixed cutoffs in clinical studies is of value
because they provide a basis for comparison of sensitivity (detection rates), false-positive rates, and acceptability to patients within various study groups or between
different studies. Often these fixed cutoffs have been
960
arbitrarily selected at levels that are comparable with the

risk for women at certain ages and seem to provide an
appropriate balance against the risk of pregnancy loss as
the result of an invasive diagnostic test. Fixed screening
cutoffs also are useful in public policy considerations
when the benefits, risks, and costs in a population are
being considered.
maintain the detection rate. This has resulted in Down

syndrome detection rates of 72% at a screen-positive rate
of 5% in an unselected population (10). In addition,
74.8% of trisomy 18 cases, 72% of trisomy 13 cases,
87% of Turners syndrome cases, 59% of triploidy cases,
and 55% of other significant chromosomal defects were
detected. A recent review of prospective first-trimester
screening studies performed in the past 10 years, which
included 871 Down syndrome cases, reported a Down
syndrome detection rate with nuchal translucency measurement alone of 76.8%, with a screen- positive rate of
4.2% (11). Among first-trimester fetuses with increased
nuchal translucency measurement, approximately one
third will have chromosome defects. Down syndrome
accounts for approximately 50% of these chromosomal
disorders (10).
Is nuchal translucency measurement alone a

sensitive screening test for aneuploidy in the
first trimester?
Despite the relatively high detection rate using nuchal
translucency measurement alone, recent trials in the United
States and the United Kingdom demonstrate improved detection of Down syndrome at lower false-positive rates when
nuchal translucency measurement is combined with biochemical markers. Nuchal translucency measurements may
be useful in the evaluation of multifetal gestations, for which
serum screening is not as accurate (twins) or is unavailable
(triplets or higher), compared with a singleton gestation.
Use of standardized techniques for measuring nuchal
translucency has resulted in higher detection rates for
Down syndrome, trisomy 18, trisomy 13, and Turners
syndrome. The optimal time to schedule nuchal translucency measurement appears to be 1213 weeks of gestation, although the measurement is valid from 1047 to 1367
weeks. Training is required to learn standardized techniques for measuring nuchal translucency, and specific
guidelines for measuring it must be adhered to in order to
What is the sensitivity of first-trimester

screening?
Several large, multicenter trials have shown that, in the
first trimester, a combination of nuchal translucency measurement, serum markers (PAPP-A and free or total hCG), and maternal age is a very effective screening test
for Down syndrome (Table 2). This approach has been
called combined screening. The detection rates for firsttrimester Down syndrome screening are comparable to
the second-trimester quadruple screen for women
younger than 35 years at the time of delivery. For older
women (35 years or older), the detection rate is approxi-
Table 2. Combined First-Trimester Screening Prospective Study Outcomes*

Study
BUN
Patients
Down Syndrome Cases
Detection Rate (%)
8,216
61
79
FASTER
33,557
84
83
SURUSS
47,053
101
83
OSCAR#
15,030
82
90
103,856
328
84
Total
*First-trimester detection rate (DR) at 5% of false-positive rate (FPR)
95% CI: 79.787.0%
Wapner RJ, Thom EA, Simpson JL, Pergament E, Silver R, Filkins K, et al. First-trimester screening for trisomies
21 and 18. First Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study
Group. N Engl J Med 2003;349:140513.
Malone FD, Wald NJ, Canick JA, Ball RH, Nyberg DA, Comstock CH, et al. First- and second-trimester evaluation of risk (FASTER) trial: principal results of the NICHD multicenter Down syndrome screening study
[abstract]. Am J Obstet Gynecol 2003;189:(suppl 1):s56.
Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM. First and second trimester antenatal
screening for Downs syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS)
[published erratum appears in J Med Screen 2006;13:512]. J Med Screen 2003;10:56104.
#Spencer K, Spencer CE, Power M, Dawson C, Nicolaides KH. Screening for chromosomal abnormalities in the
first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years
prospective experience. BJOG 2003;110:2816.
Reprinted from: Wapner RJ. First trimester screening: the BUN study. Semin Perinatol 2005;29:2369. With permission from Elsevier.
PRACTICE BULLETINS
mately 90%, but at a higher screen-positive rate (approximately 1622%) (12, 13). For women of all ages, 90% of
trisomy 18 cases are detected at a 2% screen-positive rate
(13).
What is the advantage of first-trimester

screening?
The advantage of first-trimester screening is that women
who present for prenatal care before 14 weeks of gestation can have information sooner. If the woman is found
to be at an increased risk of fetal aneuploidy, she can be
offered genetic counseling and CVS, if the procedure is
available. Alternatively, she may choose to have a second-trimester amniocentesis.
Should first- and second-trimester screening

tests be performed independently?
When first-trimester and second-trimester screening tests
are performed during the pregnancy and interpreted independently, there is a high Down syndrome detection rate
(9498%); however, the false-positive rates are additive,
leading to many more unnecessary invasive procedures
(1117%) (12, 14). For this reason, women who have had
first-trimester screening for aneuploidy should not
undergo independent second-trimester serum screening
in the same pregnancy. Instead, women who want a higher detection rate can have an integrated or a sequential
screening test, which combines both first- and secondtrimester screening results.
What is integrated screening?

The integrated approach to screening uses both the firsttrimester and second-trimester markers to adjust a
womans age-related risk of having a child with Down syndrome (15). The results are reported only after both firstand second-trimester screening tests are completed. In the
FASTER (First- and Second-Trimester Evaluation of Risk)
trial, the detection rate was 9496% at a 5% screen-positive
rate (12). Similar results were achieved in the SURUSS
(Serum, Urine, and Ultrasound Screening Study) trial (16).
Further refinements in interpretation may result in additional sensitivity and reduction of screen-positive rates.
Integrated screening also can be performed using
only first- and second-trimester serum markers, without
incorporating a nuchal translucency measurement. In the
FASTER trial, the serum integrated screen resulted in an
8588% detection rate (12). This approach is ideal for
patients without access to nuchal translucency measurement or for whom reliable measurement cannot be
obtained. A recent prospective trial of serum-only integrated screening in a population with limited access to
961
CVS reported acceptance of this screening algorithm by

most patients surveyed (17).
What are the advantages and disadvantages

of having an integrated first- and secondtrimester Down syndrome screening test
(first- and second-trimester markers analyzed
together [integrated], with only one result
given in the second trimester)?
Integrated screening best meets the goal of screening by
providing the highest sensitivity with the lowest falsepositive rate. The lower false-positive rate results in
fewer invasive tests and thus fewer procedure-related
losses of normal pregnancies (12, 18). Although some
patients value early screening, others are willing to wait
several weeks if doing so results in an improved detection
rate and less chance that they will need an invasive diagnostic test (19). Concerns about integrated screening
include possible patient anxiety generated by having to
wait 34 weeks between initiation and completion of the
screening and the loss of the opportunity to consider CVS
if the first-trimester screening indicates a high risk of
aneuploidy (20). The possibility that patients might fail
to complete the second-trimester portion of the screening
test after performing the first-trimester component is
another potential disadvantage because the patient would
be left with no screening results.
Is there an advantage to using a sequential

screening test for Down syndrome?
Sequential screening approaches that obviate some of the
disadvantages of integrated screening have been developed. With this strategy, the patient is informed of the
first-trimester screening result. Those at highest risk
might opt for an early diagnostic procedure and those at
lower risk can still take advantage of the higher detection
rate achieved with additional second-trimester screening.
Two strategies have been proposed: stepwise sequential screening and contingent sequential screening. In
the stepwise model, women determined to be at high risk
(Down syndrome risk above a predetermined cutoff) after
the first-trimester screen are offered genetic counseling
and the option of invasive diagnostic testing, and women
below the cutoff are offered second-trimester screening.
Contingent sequential screening has been proposed as a
model, but large clinical trials using this approach have not
yet been published. The contingent model classifies pregnancy risk as high, intermediate, or low on the basis of the
first-trimester screen results; women at high risk would be
offered CVS, and those at low risk would have no further
screening or testing. Only women at intermediate risk
962
would be offered second-trimester screening. Hence,

fewer women would go on to second-trimester screening.
In both the stepwise and contingent models, the patients at
highest risk identified by first-trimester screening are
offered an early diagnostic procedure. Both first- and second-trimester results are used to calculate a final risk for
aneuploidy in patients at lower risk. The sequential
approach takes advantage of the higher detection rate
achieved by incorporating the first- and second-trimester
results with only a marginal increase in the false-positive
rate. Theoretically, the contingent approach should maintain high detection rates with low false-positive rates while
reducing the number of second-trimester tests performed.
What subsequent evaluation should be

offered after first-trimester screening?
Women found to have an increased risk of aneuploidy with
first-trimester screening should be offered genetic counseling and diagnostic testing by CVS or a second-trimester
genetic amniocentesis. Neural tube defect screening
should be offered in the second trimester to patients who
elected to have only first-trimester screening for aneuploidy or who have had a normal result from CVS. Neural
tube defect screening may include second-trimester serum
AFP screening or ultrasonography. Patients who have a
fetal nuchal translucency measurement of 3.5 mm or
greater in the first trimester, despite a negative result on an
aneuploidy screen, normal fetal chromosomes, or both,
should be offered a targeted ultrasound examination, fetal
echocardiogram, or both, because such fetuses are at a significant risk for nonchromosomal anomalies, including
congenital heart defects, abdominal wall defects, diaphragmatic hernias, and genetic syndromes (2125).
Patients with abnormal first-trimester serum markers
or an increased nuchal translucency measurement also
may be at increased risk for an adverse pregnancy outcome such as spontaneous fetal loss before 24 weeks of
gestation, fetal demise, low birth weight, or preterm birth
(26, 27). At the present time, there are no data indicating
whether or not fetal surveillance in the third trimester
will be helpful in the care of these patients.
The significance of ultrasonographic markers identified by a second-trimester ultrasound examination in a
patient who has had a negative first-trimester screening test
result is unknown. A variety of ultrasound findings have
been associated with Down syndrome. A major anomaly,
such as a cardiac defect, deserves further evaluation. More
subtle findings (soft markers), such as pyelectasis, shortened femur or humerus, or echogenic bowel individually,
do not significantly increase the risk of Down syndrome.
However, these findings should be considered in the context of the screening results, patients age, and history.
Are there other first-trimester ultrasonographic markers that are useful for Down
syndrome screening?
Several other first-trimester ultrasonographic markers,
including nonvisualized nasal bone, tricuspid regurgitation, crownrump length, femur and humeral length,
head and trunk volumes, and umbilical cord diameters,
have been evaluated as potential markers for aneuploidy
in the first trimester. Studies in high-risk first-trimester
populations indicate a high rate of nonvisualization of
the nasal bone in fetuses with Down syndrome. Three
European studies reported a 66.780% Down syndrome
detection rate at a 0.21.4% false-positive rate (2830).
The value of nasal bone assessment as a Down syndrome
screening test in the general population is controversial.
A first-trimester study performed in the United States
did not find the test to be useful (12). In addition, there
are considerable ethnic differences in the prevalence of
absent nasal bone; absence of the nasal bone in a euploid
fetus is found in only 2.8% of Caucasians, compared
with 6.8% of Asians and 10.4% of Afro-Caribbeans (31).
It has been suggested that standardization of nasal bone
assessment (32), along with extensive teaching and quality control programs, should be developed before this
technique is used in the general population (33).
Strategies restricting assessment of nasal bone to a subset of pregnant women at the highest risk after firsttrimester combined screening, rather than the entire
population, appear to be more practical and are being
investigated.
What are the benefits and limitations of

second-trimester ultrasound examination
as a screening test for Down syndrome?
Individual second-trimester ultrasonographic markers,
such as echogenic bowel, intracardiac echogenic focus,
and dilated renal pelvis, have a low sensitivity and specificity for Down syndrome particularly when used to
screen a low-risk population (34). Studies indicate that
the highest detection rate is achieved with systematic
combination of ultrasonographic markers and gross
anomalies, such as thick nuchal fold or cardiac defects
(35, 36). Studies done in high-risk populations have
reported detection rates of approximately 5075% in the
second trimester. However, the false-positive rates are
high (eg, a 21.9% false-positive rate for a 100% Down
syndrome detection rate) (37). One group has reported
that if no abnormal ultrasonographic markers are identified after a carefully performed scan at a specialized center with skilled ultrasonographers, the a priori risk of
Down syndrome in a high-risk patient (advanced mater-
PRACTICE BULLETINS
nal age, abnormal serum screen) may be reduced by

8288% (38). Because the RADIUS (Routine Antenatal
Diagnostic Imaging With Ultrasound) trial (39) and
others showed that even major fetal anomalies are frequently missed by ultrasound examination, the disadvantages of relying solely on ultrasonography for Down
syndrome screening should be considered carefully.
Combining second-trimester ultrasonographic and biochemical markers is a relatively new development that
has been shown to be a feasible method to improve
Down syndrome screening performance over either
ultrasonography or second-trimester serum markers by
themselves (40), provided that the ultrasound examination
is performed as part of a specific screening protocol (37).
A major limitation of the use of second-trimester
ultrasonographic markers has been the lack of standardization in measurements and definitions of what constitutes
abnormal findings. This has contributed to variability in
the diagnostic performance reported by different groups.
Recent prospective studies that used specific criteria to
define abnormal markers in large groups of unselected
patients in the United States confirm a statistically significant increase in the frequency of individual ultrasonographic markers in Down syndrome compared with
normal second-trimester cases (41, 42). At this time, risk
adjustment based on second-trimester ultrasonographic
markers should be limited to centers with ultrasonographic expertise and centers engaged in clinical research to
develop a standardized approach to evaluating these markers. However, an abnormal second-trimester ultrasound
finding identifying a major congenital anomaly significantly increases the risk of aneuploidy and warrants further counseling and the offer of a diagnostic procedure.
How does screening for aneuploidy differ in

multifetal gestations?
Serum screening tests are not as sensitive in twin or
triplet gestations, in part because data from multiple gestations that include an aneuploid fetus is so scarce that
expected analyte levels must be estimated by mathematical modeling. In addition, analytes from both the normal
and the affected fetuses enter the maternal serum and are
in effect averaged together, thus masking the abnormal
levels of the affected fetus. In monochorionic twin
pregnancies, the median nuchal translucency values are
larger in 38% of twin pairs destined to develop severe
twintwin transfusion syndrome (43). Furthermore,
counseling is more complex because women must consider a different set of options in the event that only one
of the fetuses is affected. Nuchal translucency screening
in the first trimester with the option of a CVS and earlier
selective reduction may be desirable for some women.
963
Experience is limited with triplet gestations, but studies

suggest that nuchal translucency measurement is feasible.
Until further studies are done, however, risk assessment
in multiple gestations should be performed judiciously,
and patients who are at increased risk of aneuploidy
should be counseled regarding diagnostic testing.
Should invasive diagnostic testing for aneuploidy be available to all women?

All women, regardless of age, should have the option of
invasive testing. A womans decision to have an amniocentesis or CVS is based on many factors, including the
risk that the fetus will have a chromosomal abnormality,
the risk of pregnancy loss from an invasive procedure,
and the consequences of having an affected child if diagnostic testing is not done. Studies that have evaluated
womens preferences have shown that women weigh
these potential outcomes differently. The decision to
offer invasive testing should take into account these preferences and should not be solely age based. The differences between screening and diagnostic testing should
be discussed with all women. Thus, maternal age of 35
years alone should no longer be used as a cutoff to determine who is offered screening versus who is offered
invasive testing.
With so many Down syndrome screening tests

available, how do I decide which tests to offer?
The goal is to offer screening tests with high detection
rates and low false-positive rates that also provide
patients with the diagnostic options they might want to
consider. Ideally, patients seen early in pregnancy should
be offered aneuploidy screening that combines first- and
second-trimester testing (integrated or sequential). The
screening strategy chosen will depend on availability of
CVS and of personnel trained in nuchal translucency
measurement in the area. When CVS is not available, it
makes sense to offer integrated screening to patients who
present in the first trimester in order to take advantage of
the improved detection rate and low false-positive rate
and to offer second-trimester screening to patients who
present after 1367 weeks. If nuchal translucency measurement is not available or cannot be obtained in an
individual patient, a reasonable approach is to offer
serum integrated screening to patients who present early
and second-trimester screening to those who present
later. In areas where every screening strategy is possible,
it is reasonable to choose two screening strategies for the
practice, such as sequential screening for patients who
present for prenatal care before 14 weeks of gestation
(because it provides them with a first-trimester risk
assessment and the option of waiting until the second
964
trimester for an adjusted risk assessment that includes

their second-trimester serum results), and secondtrimester serum screening for patients who present after
1367 weeks of gestation. In some instances, patients who
would consider first-trimester termination of pregnancy
but not second-trimester termination of pregnancy may
want only first-trimester screening.
Summary of
Recommendations and
Conclusions
First-trimester screening using both nuchal translucency measurement and biochemical markers is an
effective screening test for Down syndrome in the
general population. At the same false-positive rates,
this screening strategy results in a higher Down syndrome detection rate than does the second-trimester
maternal serum triple screen and is comparable to
the quadruple screen.
Measurement of nuchal translucency alone is less
effective for first-trimester screening than is the
combined test (nuchal translucency measurement
and biochemical markers).
Women found to have increased risk of aneuploidy
with first-trimester screening should be offered
genetic counseling and the option of CVS or second-trimester amniocentesis.
Specific training, standardization, use of appropriate
ultrasound equipment, and ongoing quality assessment are important to achieve optimal nuchal
translucency measurement for Down syndrome risk
assessment, and this procedure should be limited to
centers and individuals meeting these criteria.
Neural tube defect screening should be offered in
the second trimester to women who elect only firsttrimester screening for aneuploidy.
Screening and invasive diagnostic testing for aneuploidy should be available to all women who present
for prenatal care before 20 weeks of gestation
regardless of maternal age. Women should be counseled regarding the differences between screening
and invasive diagnostic testing.
Integrated first- and second-trimester screening is

more sensitive with lower false-positive rates than
first-trimester screening alone.
Serum integrated screening is a useful option in
pregnancies where nuchal translucency measurement is not available or cannot be obtained.
An abnormal finding on second-trimester ultrasound examination identifying a major congenital
anomaly significantly increases the risk of aneuploidy and warrants further counseling and the offer
of a diagnostic procedure.
Patients who have a fetal nuchal translucency measurement of 3.5 mm or higher in the first trimester,
despite a negative aneuploidy screen, or normal fetal
chromosomes, should be offered a targeted ultrasound examination, fetal echocardiogram, or both.
Down syndrome risk assessment in multiple gestation using first- or second-trimester serum analytes
is less accurate than in singleton pregnancies.
First-trimester nuchal translucency screening for
Down syndrome is feasible in twin or triplet gestation but has lower sensitivity than first-trimester
screening in singleton pregnancies.
After first-trimester screening, subsequent secondtrimester Down syndrome screening is not indicated
unless it is being performed as a component of the
integrated test, stepwise sequential, or contingent
sequential test.
Subtle second-trimester ultrasonographic markers
should be interpreted in the context of a patients
age, history, and serum screening results.
Measure
Percentage of patients with documentation of discussion
regarding Down syndrome screening
Glossary
Aneuploidy: In this condition there is an extra or
missing chromosome.
Screen-positive rate: percentage of the population
with a positive screening test result. This includes true
positives and false positives.
Nuchal translucency measurement: Accumulated
fluid behind the fetal neck is measured in a standardized way.
PRACTICE BULLETINS
References
1. Merkatz IR, Nitowsky HM, Macri JN, Johnson WE. An
association between low maternal serum alpha-fetoprotein and fetal chromosomal abnormalities. Am J Obstet
Gynecol 1984;148:88694. (Level II-2)
2. Wald NJ, Kennard A, Hackshaw A, McGuire A. Antenatal
screening for Downs syndrome. Health Technol Assess
1998;2:iiv,1112. (Level III)
3. Spencer K, Wallace EM, Ritoe S. Second-trimester dimeric inhibin-A in Downs syndrome screening. Prenat Diagn
1996;16:110110. (Level II-3)
4. Nicolaides KH, Snijders RJ, Gosden CM, Berry C,
Campbell S. Ultrasonographically detectable markers of
fetal chromosomal abnormalities. Lancet 1992;340:
7047. (Level III)
5. Malone FD, Berkowitz RL, Canick JA, DAlton ME.
First-trimester screening for aneuploidy: research or standard of care? Am J Obstet Gynecol 2000;182:4906.
(Level III)
6. Nicolaides KH, Heath V, Liao AW. The 11-14 week scan.
Baillieres Best Pract Res Clin Obstet Gynaecol
2000;14:58194. (Level III)
7. Snijders RJ, Thom EA, Zachary JM, Platt LD, Greene N,
Jacson LG, et al. First-trimester trisomy screening: nuchal
translucency measurement training and quality assurance
to correct and unify technique. Ultrasound Obstet
8. Cuckle H. Biochemical screening for Down syndrome. Eur
J Obstet Gynecol Reprod Biol 2000;92:97101. (Level III)
9. Spencer K, Souter V, Tul N, Snijders R, Nicolaides KH. A
screening program for trisomy 21 at 10-14 weeks using
fetal nuchal translucency, maternal serum free betahuman chorionic gonadotropin and pregnancy-associated
plasma protein-A. Ultrasound Obstet Gynecol 1999;13:
2317. (Level II-3)
10. Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH.
UK multicentre project on assessment of risk of trisomy
21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine
Foundation First Trimester Screening Group. Lancet
1998;352:3436. (Level III)
11. Nicolaides KH. Nuchal translucency and other firsttrimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol 2004;191:4567. (Level III)
12. Malone F, Canick JA, Ball RH, Nyberg DA, Comstock
CH, Buckowski R, et al. First-trimester or secondtrimester screening, or both, for Downs syndrome. Firstand Second-Trimester Evaluation of Risk (FASTER)
Research Consortium. N Engl J Med 2005;353:200111.
(Level II-2)
13. Wapner R, Thom E, Simpson JL, Pergament E, Silver R,
Filkins K, et al. First-trimester screening for trisomies 21
and 18. First Trimester Maternal Serum Biochemistry and
Fetal Nuchal Translucency Screening (BUN) Study
Group. N Engl J Med 2003;349:140513. (Level II-3)
14. Platt LD, Greene N, Johnson A, Zachary J, Thom E,
Krantz D, et al. Sequential pathways of testing after first
965
trimester screening for trisomy 21. First Trimester

Maternal Serum Biochemistry and Fetal Nuchal
Translucency Screening (BUN) Study Group. Obstet
15. Wald NJ, Watt HC, Hackshaw AK. Integrated screening
for Downs syndrome on the basis of tests performed during the first and second trimesters. N Engl J Med 1999;
341:4617. (Level III)
16. Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L,
Mackinson AM. First and second trimester antenatal
screening for Downs syndrome: the results of the Serum,
Urine and Ultrasound Screening Study (SURUSS) [published erratum appears in J Med Screen 2006;13:512]. J
Med Screen 2003;10:56104 (Level II-2)
17. Palomaki GE, Knight GJ, Neveux LM, Pandian R,
Haddow JE. Maternal serum invasive trophoblast antigen
and first-trimester Down syndrome screening. Clin Chem
2005;51:1499504. (Level II-3)
18. Wald NJ, Rodeck C, Hackshaw AK, Rudnicka A.
SURUSS in perspective. BJOG 2004;111:52131. (Level
II-2)
19. Bishop AJ, Marteau TM, Armstrong D, Chitty LS,
Longworth L, Buxton MJ, et al. Women and health care
professionals preferences for Downs syndrome screening tests: a conjoint analysis study. BJOG 2004;111:
7759. (Level III)
20. Copel JA, Bahado-Singh RO. Prenatal screening for
Downs syndromea search for the familys values. N
Engl J Med 1999;341:5212. (Level III)
21. Makrydimas G, Sotiriadis A, Huggon IC, Simpson J,
Sharland G, Carvalho JS, et al. Nuchal translucency and
fetal cardiac defects: a pooled analysis of major fetal
echocardiography centers. Am J Obstet Gynecol
2005;192:8995. (Level II-3)
22. Bahado-Singh RO, Wapner R, Thom E, Zachary J, Platt L,
Mahoney MJ, et al. Elevated first-trimester nuchal
translucency increases the risk of congenital heart defects.
First Trimester Maternal Serum Biochemistry and Fetal
Nuchal Translucency Screening Study Group. Am J
23. Hyett J, Perdu M, Sharland G, Snijders R, Nicolaides KH.
Using fetal nuchal translucency to screen for major congenital cardiac defects at 10-14 weeks of gestation: population based cohort study. BMJ 1999;318:815. (Level II-3)
24. Souka AP, Von Kaisenberg CS, Hyett JA, Sonek JD,
Nicolaides KH. Increased nuchal translucency with normal karyotype [published erratum appears in Am J Obstet
Gynecol 2005;192:2096]. Am J Obstet Gynecol 2005;
192:100521. (Level III)
25. Comstock CH, Malone FD, Ball RH, Nyberg DA, Saade
GR, Berkowitz RL, et al. Is there a nuchal translucency
millimeter measurement above which there is no added
benefit from first trimester serum screening? FASTER
Research Consortium. Am J Obstet Gynecol 2006;195:
8437. (Level III)
26. Dugoff L, Hobbins JC, Malone FD, Porter TF, Luthy D,
Comstock CH, et al. First-trimester maternal serum
PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associ-
966
ated with obstetric complications: a population-based

screening study (the FASTER Trial). Am J Obstet
Gynecol 2004;191:144651. (Level II-3)
27. Smith GC, Shah I, Crossley JA, Aitken DA, Pell JP,
Nelson SM, et al. Pregnancy-associated plasma protein A
and alpha-fetoprotein and prediction of adverse perinatal
outcome. Obstet Gynecol 2006;107:1616. (Level II-2)
28. Zoppi MA, Ibba RM, Axiana C, Floris M, Manca F,
Monni G. Absence of fetal nasal bone and aneuploides at
first-trimester nuchal translucency screening in unselected
pregnancies. Prenat Diagn 2003;23:496500. (Level III)
29. Orlandi F, Bilardo CM, Campogrande M, Krantz D,
Hallahan T, Rossi C, et al. Measurement of nasal bone
length at 11-14 weeks of pregnancy and its potential role
in Down syndrome risk assessment. Ultrasound Obstet
30. Viora E, Masturzo B, Errante G, Sciarrone A, Bastonero
S, Campogrande M. Ultrasound evaluation of fetal nasal
bone at 11 to 14 weeks in a consecutive series of 1906
fetuses. Prenat Diagn 2003;23:7847. (Level II-3)
31. Cicero S, Longo D, Rembouskos G, Sacchini C,
Nicolaides KH. Absent nasal bone at 11-14 weeks of gestation and chromosomal defects. Ultrasound Obstet
Gynecol 2003:22:315. (Level III)
32. Sonek JD. Nasal bone evaluation with ultrasonography: a
marker for fetal aneuploidy. Ultrasound Obstet Gynecol
2003;22:115. (Level III)
33. Senat MV, Bernard JP, Boulvain M, Ville Y. Intra- and
interoperator variability in fetal nasal bone assessment at
11-14 weeks of gestation. Ultrasound Obstet Gynecol
2003;22:13841. (Level III)
34. Smith-Bindman R, Hosmer W, Feldstein V, Deeks J,
Goldberg J. Second-trimester ultrasound to detect fetuses
with Down syndrome. JAMA 2001;285:104455. (Metaanalysis)
35. Vintzileos AM, Campbell WA, Rodis JF, Guzman ER,

Smulian JC, Knuppel RA. The use of second-trimester
genetic sonogram in guiding clinical management of
patients at increased risk for fetal trisomy 21. Obstet
36. Bromley B, Benacerraf BR. The genetic sonogram scoring index. Semin Perinatol 2003;27:1249. (Level III)
37. Bahado-Singh RO, Oz U, Mendilicioglu I, Mahoney M.
The mid-trimester genetic sonogram. Semin Perinatol
2005;29:20914. (Level III)
38. Yeo L, Vintzileos AM. The use of genetic sonography
to reduce the need for amniocentesis in women at high
risk of Down syndrome. Semin Perinatol 2003;27;1529.
(Level III)
RP, McNellis D. Effect of prenatal ultrasound screening
on perinatal outcome. RADIUS Study Group. N Engl J
Med 1993;329:8217. (Level I)
40. Benn PA, Kaminsky LM, Ying J, Borgida AF, Egan JF.
Combined second-trimester biochemical and ultrasound
screening for Down syndrome. Obstet Gynecol 2002;
100:116876. (Level II-3)
41. Schluter PJ, Pritchard B. Mid trimester sonographic findings for the prediction of Down syndrome in a sonographically screened population. Am J Obstet Gynecol
2005;192:106. (Level II-2)
42. Benacerraf BR. The role of the second trimester genetic
sonogram in screening for fetal Down syndrome. Semin
Perinatol 2005;29:38694. (Level III)
43. Sebire NJ, DErcole C, Hughes K, Carvalho M,
Nicolaides KH. Increased nuchal translucency thickness
at 1014 weeks of gestation as a predictor of severe twinto-twin transfusion syndrome. Ultrasound Obstet Gynecol
1997;10:869. (Level II-3)
PRACTICE BULLETINS

literature search to locate relevant articles published between January 1985 and September 2006. The search was
restricted to articles published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries also
Force:
I
type of evidence.
committees.
967

from the publisher.
01923, (978) 750-8400.
ISSN 1099-3630
Screening for fetal chromosomal abnormalities. ACOG Practice
968
ACOG
PRACTICE
BULLETIN
(Replaces Practice Bulletin Number 64, July 2005)

of John Williams III, MD. The
of practice.
Reaffirmed 2008
Hemoglobinopathies in
Pregnancy
The hemoglobinopathies are a heterogeneous group of single-gene disorders
that includes the structural hemoglobin variants and the thalassemias. More
than 270 million people worldwide are heterozygous carriers of hereditary disorders of hemoglobin, and at least 300,000 affected homozygotes or compound
heterozygotes are born each year (1). The purpose of this document is to review
the most common hemoglobinopathies and to provide recommendations for
screening and clinical management of hemoglobinopathies during pregnancy.
Background
Hemoglobin Structure
Hemoglobin consists of four interlocking polypeptide chains, each of which has
an attached heme molecule. The polypeptide chains are called alpha (), beta
(), gamma (), delta (), epsilon (), and zeta (). Adult hemoglobins consist
of two -chains and either two -chains (hemoglobin A), two -chains (hemoglobin F), or two -chains (hemoglobin A2). Hemoglobin F (fetal hemoglobin,
Hb F) is the primary hemoglobin of the fetus from 12 to 24 weeks of gestation.
In the third trimester, production of Hb F decreases as production of -chains
and Hb A begins. The genes that code for -globin chains are located on the
short arm of chromosome 16, and the -globin gene is located on the short arm
of chromosome 11.
Sickle Cell Disease

Sickle cell disease refers to a group of autosomal recessive disorders involving
abnormal hemoglobin (hemoglobin S). Hemoglobin S differs from the normal
Hb A because of a single nucleotide substitution of thymine for adenine in the
-globin gene; this alteration causes a substitution of valine for glutamic acid in
the number six position of the -globin polypeptide. Asymptomatic individuals
PRACTICE BULLETINS
with heterozygous Hb S genotypes (carriers) are said to

have sickle cell trait. The most severe form of the disease,
Hb SS (homozygous Hb S), is called sickle cell anemia.
Sickle cell disorders are found not only in patients
who have the hemoglobin genotype SS, but also in those
who have Hb S and one other abnormality of -globin
structure or -globin production. The most common of
these are Hb SC disease and Hb S/-thalassemia. In Hb C,
the same nucleotide involved in the Hb S mutation is
altered with the substitution of adenine for guanine,
which results in the amino acid substitution of lysine for
glutamic acid. This and other abnormal hemoglobins,
when inherited with Hb S, may cause clinically significant vasoocclusive phenomena and hemolytic anemia
similar to Hb SS.
Sickle cell disease occurs most commonly in people
of African origin. Approximately 1 in 12 African Americans has sickle cell trait (2). One in every 300 AfricanAmerican newborns has some form of sickle cell disease,
and approximately 1 in 600 has sickle cell anemia. Hemoglobin S also is found in high frequency in other populations such as Greeks, Italians (particularly Sicilians),
Turks, Arabs, Southern Iranians, and Asian Indians (3).
The classical clinical feature of patients with sickle
cell disease is seen under conditions of decreased oxygen
tension, in which the red blood cells become distorted
into various shapes, some of which resemble sickles. The
distorted red cells lead to increased viscosity, hemolysis,
and anemia and a further decrease in oxygenation. When
sickling occurs within small blood vessels, it can cause
logjams that can interrupt blood supply to vital organs
(vasoocclusive crisis). Repeated vasoocclusive crises
result in widespread microvascular obstruction with
interruption of normal perfusion and function of several
organs, including the spleen, lungs, kidneys, heart, and
brain. Adults with Hb SS are functionally asplenic, having undergone autosplenectomy by adolescence. Absence
of the spleen contributes to the increased incidence and
severity of infection in patients with sickle cell disease.
The most significant threat to patients with sickle
cell disease is acute chest syndrome. Chest syndrome is
characterized by a pulmonary infiltrate with fever that
leads to hypoxemia and acidosis. The infiltrates are not
infectious in origin but rather are due to vasoocclusion
from sickling or embolization of marrow from long
bones affected by sickling (4).
The diagnosis of hemoglobinopathies, including
sickle cell disorders, is made by hemoglobin electrophoresis. In the homozygous form, nearly all the hemoglobin is Hb S with small amounts of Hb A2 and Hb F.
Heterozygous sickle cell trait (Hb AS) is identified by a
larger percentage of Hb A and an asymptomatic course.
Solubility tests (Sickledex) alone are inadequate for diag-
969
nosis of sickle cell disorders because they cannot distinguish between the heterozygous AS and homozygous SS
genotypes. In addition, they fail to detect other pathologic variants such as Hb C trait, -thalassemia trait,
Hb E trait, Hb B trait, and Hb D trait.
The Thalassemias
The thalassemias represent a wide spectrum of hematologic disorders that are characterized by a reduced synthesis of globin chains, resulting in microcytic anemia.
Thalassemias are classified according to the globin chain
affected, with the most common types being -thalassemia and -thalassemia. Many different molecular
mechanisms lead to thalassemia in populations from different areas of the world (5).
Alpha-Thalassemia
Alpha-thalassemia usually results from a gene deletion of
two or more copies of the four -globin genes. Deletion
of one -globin gene (-/) is clinically unrecognizable, and laboratory testing yields normal results.
Deletion of two -globin genes causes -thalassemia
trait, a mild asymptomatic microcytic anemia. The deletions can be on the same chromosome or in cis (/--),
or on each chromosome or in trans (-/-). Individuals
with these chromosomal abnormalities are referred to as
carriers and are at an increased risk for having a child
with a more severe form of thalassemia caused by deletions of three or four copies of the -globin gene (-thalassemia major). The possible genetic combinations are
summarized in Table 1.
Alpha-thalassemia trait (-thalassemia minor) is
common among individuals of Southeast Asian, African,
and West Indian descent. It also is common in individuals
with Mediterranean ancestry. Individuals with Southeast
Asian ancestry are more likely to carry two gene deletions in cis or on the same chromosome (--/) and are
at an increased risk for offspring with Hb Barts or Hb H
disease. Hemoglobin H disease, which is caused by the
deletion of three -globin genes, usually is associated
with mild to moderate hemolytic anemia. Alpha-thalassemia major (Hb Barts) results in the absence of globin (--/--); this is associated with hydrops fetalis,
intrauterine death, and preeclampsia (3).
In individuals of African descent, -thalassemia usually is due to a deletion of a single -globin gene on each
chromosome 16 (-/-). This is in contrast to the common Asian genotype, which is a deletion of both -globin genes on one chromosome 16 (cis) (/--).
Hemoglobin Barts disease does not typically develop in
fetuses of -thalassemia carriers of African origin.
Because Hb S results from an abnormality of the
-chain, both heterozygous (AS) and homozygous (SS)
970
Table 1. Classification of Alpha-Thalassemias

Number of
Globin Genes
Genotype
Description
Clinical
Features
Normal
Normal
-/
Heterozygous
+-thalassemia
Asymptomatic
-/-
Homozygous
+-thalassemia
Mild
anemia
/--
Heterozygous
o-thalassemia
-/--
+-Thalassemia/
o-thalassemia
Hb H disease
hemolytic anemia
--/--
Homozygous
o-thalassemia
Hb Barts disease
hydrops fetalis
forms can be inherited with heterozygous or homozygous +-thalassemia. In individuals with sickle cell trait
(Hb AS), -thalassemia lowers the proportion of
Hb S, and in those with Hb SS, it lessens the severity of
sickle cell disease.
Alpha-thalassemia also may occur as a result of a
gene mutation. In this case, the genes are present but not
functioning normally. This may result from mutation in
the stop codon leading to synthesis of a longer and unstable -chain (Hb Constant Spring), from substitutions
impairing dimer formation (Hb Qong Sze), and from
point substitutions in the poly A region at the 3' end of
the gene (TSaudi).
Beta-Thalassemia
Beta-thalassemia is caused by a mutation in the -globin
gene that causes deficient or absent -chain production,
which results in absence of Hb A. Classification of
-thalassemias is based on a description of the molecular mutation or by clinical manifestations. Individuals
who are heterozygous for this mutation have -thalassemia minor. Those who are homozygous have -thalassemia major (Cooleys anemia) or a milder form
called thalassemia intermedia. Beta-thalassemia major
is characterized by severe anemia with resultant
extramedullary erythropoesis, delayed sexual development, and poor growth. Elevated levels of Hb F in individuals with -thalassemia major partially compensate
for the absence of Hb A; however, death usually occurs
by age 10 years unless treatment is begun early with
periodic blood transfusions. With transfusion, the severe
anemia is reversed and extramedullary erythropoesis is
suppressed. In homozygotes with the less severe +-thalassemia mutations, often referred to as -thalassemia
intermedia, variable but decreased amounts of -chains
are produced and, as a result, variable amounts of Hb A

are produced. The genes for Hb S and -thalassemia usually behave as alleles, with only one gene inherited from
each parent. The expression of the resulting Hb S/-thalassemia is determined by the type of -thalassemia
mutation (6).
Beta-thalassemia minor, common in individuals of
Mediterranean, Asian, Middle Eastern, Hispanic, and West
Indian descent, varies in severity of disease. Depending
on the amount of -chain production, it usually is associated with asymptomatic mild anemia. Beta-thalassemia minor often occurs in association with Hb S. In
the most severe form, no normal -globin chains are
produced. This results in a clinically severe syndrome
called sickle cell0-thalassemia, in which no Hb A is
produced.

Recommendations
Who should be screened for hemoglobinopathies and how should this be accomplished?
Genetic screening can identify couples at risk for offspring with hemoglobinopathies and allow them to make
informed decisions regarding reproduction and prenatal
diagnosis (3). Individuals of African, Southeast Asian,
and Mediterranean ancestry are at a higher risk for being
carriers of hemoglobinopathies and should be offered
carrier screening. Ethnic groups considered to be at low
risk for hemoglobinopathies include northern Europeans, Japanese, Native Americans, Inuit (Eskimo), and
Koreans. If both parents are determined to be carriers,
genetic counseling is recommended. It should be noted
PRACTICE BULLETINS
that ethnicity is not always a good predictor of risk

because individuals from at-risk groups may marry outside their ethnic group (3).
A combination of laboratory tests may be required to
provide the information necessary to counsel couples
who are carriers of one of the thalassemias or sickle cell
disease (Fig. 1). To ensure accurate hemoglobin identification, which is essential for genetic counseling, a
complete blood count (CBC) is the appropriate initial
laboratory test for individuals of non-African descent. In
individuals of African descent, a hemoglobin electrophoresis should be performed in addition to a CBC.
Several tests, including solubility testing such as a test for
the presence of Hb S (Sickledex), isoelectric focusing,
and high-performance liquid chromatography (HPLC),
have been used for primary screening. However, solubility tests alone are inadequate for screening and fail to
identify important transmissible hemoglobin gene abnormalities affecting fetal outcome (eg, Hb C trait, -thalassemia trait, Hb E trait, Hb B trait, Hb D trait). Many
individuals with these genotypes are asymptomatic, but if
their partners have the sickle cell trait or other hemoglobinopathies, they may produce offspring with more seri-
ous hemoglobinopathies, such as Hb S/-thalassemia and

Hb SC disease. Solubility testing may be valuable, however, for rapid screening for sickling when this information is critical for immediate patient care.
Determination of mean corpuscular volume (MCV)
is recommended for patients who are at risk for - or
-thalassemia. Patients who have a low MCV (less than
80 fL) may have one of the thalassemia traits and are
candidates for hemoglobin electrophoresis. These individuals also may have iron deficiency anemia, and
measurement of serum ferretin levels is recommended.
Beta-thalassemia is associated with elevated Hb F and
elevated Hb A2 levels (more than 3.5%). Neither hemoglobin electrophoresis nor solubility testing can identify
individuals with -thalassemia trait; only molecular
genetic testing can identify this condition. If the MCV is
below normal, iron deficiency anemia has been excluded,
and the hemoglobin electrophoresis is not consistent with
-thalassemia trait (ie, there is no elevation of Hb A2 or
Hb F), then DNA-based testing should be used to detect
-globin gene deletions characteristic of -thalassemia.
The hematologic features of some of the common
hemoglobinopathies are shown in Table 2. If both part-
CBC and RBC indices
Patients of Southeast Asian or Mediterranean descent
Patients of African descent
Anemia (with reduced MCV

and normal iron status)
No abnormality
Hemoglobin electrophoresis
Hb AS, AC, SS, SC, elevated A2, and

other abnormal hemoglobin
Normal
If Southeast Asian, evaluate for -thalassemia
Not a carrier of
-thalassemia
971
Carrier of
-thalassemia
Offer testing of partner to assess reproductive risk
Figure 1. Specialized antepartum evaluation for hematologic assessment of patients of African,

Southeast Asian, or Mediterranean descent. Patients of Southeast Asian or Mediterranean descent
should undergo electrophoresis if their blood test results reveal anemia. Abbreviations: CBC, complete
blood count; Hb, hemoglobin; MCV, mean corpuscular volume; RBC, red blood cell.
972
Table 2. Hematologic Features of Main Hemoglobinopathies

Disorder
Heterozygous State
Homozygous State
DNA Analysis
Thalassemia (-)
02% Hb Barts at birth
510% Hb Barts in the neonatal

period, low MCV
S. blot: -gene probe,

abnormal band with Bam H1
o Thalassemia (--)
510% Hb Barts in the neonatal

period, low MCV, normal Hb A2
Hb Barts hydrops fetalis
S. blot or PCR: absence of:

-gene band in homozygote
o Thalassemia
Low MCH & MCV, Hb A2 3.57.0%
Thalassemia major: Hb F 98%

Hb A2 2%
PCR, ASO dot blot, S. blot

-gene probe
+ Thalassemia (severe)
Thalassemia major: Hb F 7095%

-gene probe
+ Thalassemia (mild)
Thalassemia intermedia:
Hb F 2040%

-gene probe
Hb S
Hb A, Hb S, Hb A2
Hb S, Hb F (115%), Hb A2
PCR: Dde 1 digestion

PCR, ASO dot blot
Hb S/-Thalassemia
If o thalassemia, severe sickle

cell anemia; if + thalassemia,
less severe
PCR: Dde 1 digestion

PCR, ASO dot blot
Hb E/-Thalassemia
Thalassemia major or intermedia:

Hb E 6070%, Hb F 3040%
PCR: Hb E by Mnl 1 digestion
Abbreviations: ASO, allele specific oligonucleotide; Hb, hemoglobin; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; PCR, polymerase chain
reaction; S. blot, Southern blot.
Modified from Milunsky, Aubrey, MB.B.Ch., D.Sc., F.R.C.P., F.A.C.M.G., D.C.H., ed. Genetic Disorders and the Fetus, fifth edition: Diagnosis, Prevention, and Treatment.
pp. 665, Table 19.1. 2004 Aubrey Milunsky. Reprinted with permission of The Johns Hopkins University Press.
ners are identified as carriers of a gene for abnormal

hemoglobins, genetic counseling is recommended.
For couples with an increased risk for having

an affected offspring, what methods are
available for genetic diagnosis of the fetus or
embryo?
Couples at risk for having a child with a hemoglobinopathy may benefit from genetic counseling to review the
natural history of these disorders, prospects for treatment
and cure, their risk, availability of prenatal genetic testing,
and reproductive options. Prenatal diagnostic testing for
the single mutation responsible for sickle cell disease is
widely available. Testing for - and -thalassemia is possible if the mutations and deletions have been previously
identified in both parents. These DNA-based tests can be
performed using chorionic villi obtained by chorionic
villus sampling (CVS) at 1012 weeks of gestation or
using cultured amniotic fluid cells obtained by amniocentesis after 15 weeks of gestation. For some couples,
preimplantation genetic diagnosis in combination with in
vitro fertilization may be a desirable alternative to avoid
termination of an affected pregnancy. Preimplantation
genetic diagnosis has been successfully performed for
sickle cell disease and most cases of -thalassemia.
Although the advances in prenatal diagnosis of
hemoglobinopathies have been impressive, use of the
technology has been somewhat limited because of ethical, social, and cultural concerns. Prenatal diagnosis is
most commonly requested by families who have had a
child with sickle cell disease and who wish to be certain
that their next child is not affected. In many respects,
these families are self-counseled. The difficulty in
counseling families who have not had an affected child
lies in the variable severity of the disease and the inability to predict its course (6). One investigator found that
nearly 70% of families in whom prenatal diagnosis confirmed that the fetus was affected with Hb SS elected to
continue the pregnancy (7).
How is sickle cell disease in pregnancy

managed?
Pregnancy in women with sickle cell disease is associated with an increased risk of morbidity and mortality
because of the combination of underlying hemolytic
anemia and multiorgan dysfunction associated with this
disorder. Morbidity and mortality have decreased
markedly over the past 3 decades because of improvements in general medical care for patients with sickle cell
disease, improvements in transfusion medicine, and
advancements in neonatal care (8, 9). In spite of the
decline in maternal and perinatal mortality rates, however, pregnancy is still a significant clinical risk for many
patients with sickle cell disease. The magnitude of the
PRACTICE BULLETINS
risk varies with genotype and severity of anemia. When

compared with Hb AA patients, women with Hb SS have
increased risk for maternal complications, such as preterm labor, premature rupture of membranes, antepartum
hospitalization, and postpartum infection. In addition,
patients with Hb SS are at higher risk for fetal complications, such as intrauterine growth restriction (IUGR), low
birth weight, and preterm delivery (9, 10). Patients with
Hb SC disease also are at risk for the aforementioned
complications but to a lesser extent than patients with
Hb SS disease (10).
Pregnant patients with sickle cell disease need
increased prenatal folic acid supplementation. The standard 1 mg of folate in prenatal vitamins is not adequate
for patients with hemoglobinopathies; 4 mg per day of
folic acid should be prescribed because of the continual
turnover of red blood cells.
Routine cesarean delivery for women with sickle cell
disease is not indicated and should be performed only for
obstetric indications. Epidural analgesia usually is well
tolerated as long as care is taken to avoid hypotension
and hypoxemia. Pregnant patients should, if possible, be
cared for at institutions that are able to manage both the
complications of sickle cell disease and high-risk pregnancies. They also should have regular prenatal care by
or in consultation with obstetricians who are experienced
in the management of sickle cell disease.
The most common cause of recurrent morbidity in
Hb SS disease is painful crisis. If possible, precipitating
factors, such as cold environment, heavy physical exertion, dehydration, and stress, should be avoided. Hydroxyurea has been shown to reduce the frequency of painful
crises in nonpregnant patients with severe sickle cell disease (11). However, the use of hydroxyurea is not recommended during pregnancy because it is teratogenic.
Painful crises in pregnancy as well as in the nonpregnant patient are managed with rapid assessment of
the level of pain and prompt administration of analgesia.
Pain, respiratory rate, and level of sedation should be
assessed until pain is controlled. Opiates can be given
orally or parenterally by the intravenous, intramuscular,
or subcutaneous route. Oxygen should be given if the O2
saturation is less than 95% by pulse oximetry. The initial
clinical assessment also should focus on detection of
serious medical complications requiring specific therapy,
such as acute chest syndrome (fever tachypnea, chest
pain, and hypoxia), infection, dehydration, severe anemia, cholecystitis, and hypersplenism. A multidisciplinary approach should be used involving obstetricians,
hematologists, and anesthesiologists (12). Painful crises
in the third trimester may have a prolonged course and
may not resolve until after delivery.
973
What is the role of transfusion or prophylactic exchange transfusion for pregnancies

complicated by sickle cell anemia?
Controversy exists regarding the role of prophylactic
blood transfusion in the management of sickle cell disease in pregnancy (1315). By limiting transfusion to
situations in which it is clinically indicated, patients are
not subjected to the increased risk for alloimmunization
(16), viral infections, and iron overload. Major complications (eg, worsening anemia; intrapartum complications such as hemorrhage, septicemia, and cesarean
delivery; painful crisis; and chest syndrome) may
require intervention with an exchange transfusion. There
is no consensus regarding the exact hematocrit value
below which transfusion should be considered.
However, when a transfusion is clinically indicated in
the patient with sickle cell disease, the objective is to
lower the percentage of Hb S to approximately 40%
while simultaneously raising the total hemoglobin concentration to about 10 g/dL. Hemoglobin levels and the
percentage of Hb S should be monitored serially during
the remainder of the pregnancy to determine the need for
subsequent transfusions.
Prophylactic exchange transfusion was first proposed by Ricks in 1965, who recommended exchange
transfusion 46 weeks before the delivery date (17).
Preliminary results appeared to show a benefit in that all
women and infants survived (18). Subsequently, several
studies have shown improvement in maternal and fetal
outcome with prophylactic transfusion (15, 19). However, the evidence is not conclusive that transfusion is
responsible for the improvement; similar improvement
has been observed in programs that do not use prophylactic transfusion. In the only randomized controlled trial
published to date, prophylactic transfusion was associated with a decreased risk for painful crisis and severe
anemia, but no difference was observed for pregnancy
outcome (14). It appears from the available evidence that
the reduction in morbidity and mortality of sickle cell
disease in pregnancy is attributable to improvements in
general management of pregnancy rather than prophylactic transfusion per se.
Is fetal surveillance useful in pregnancies

complicated by sickle cell anemia?
Pregnancies in women with sickle cell disease are at
increased risk for spontaneous abortion, preterm labor,
IUGR, and stillbirth (20). For this reason, a plan for serial ultrasound examinations and antepartum fetal testing
is reasonable. Published data on antenatal fetal surveillance in women with sickle cell disease are limited. In a
974
retrospective review of 58 pregnancies in women with

sickle cell disease undergoing prophylactic transfusion,
no patients had a nonreactive nonstress test result or positive contraction stress test result (21). All pregnancy
outcomes were normal. The investigators concluded that
placental reserve and fetal reactivity were uncompromised and that these tests were as sensitive for assessment of fetal well-being in women with sickle cell
disease as for women with other indications for antenatal
testing.
Because patients with sickle cell crisis usually
require narcotics for pain control, the results of abnormal
antepartum testing should be interpreted with caution.
One small study has shown that nonstress test results and
biophysical profiles may be abnormal during an episode
of crisis but revert back to normal with resolution of the
episode (22). The clinical significance of this is unclear.
How is thalassemia in pregnancy managed?

The course of pregnancy in women with the -thalassemia trait is not significantly different from that of
women with normal hemoglobin. Pregnancy in women
with Hb H disease has been reported, and with the
exception of mild to moderate chronic anemia, outcomes
have been favorable. However, the number of reports is
too few to draw definite conclusions regarding pregnancy outcome in all women with Hb H disease (23).
Until recently, pregnancy in women with -thalassemia major was extremely rare. Initially, this was
because delay of growth and sexual development and
early death in untreated patients prevented reproduction.
After the introduction of transfusion therapy in the 1960s,
pregnancy was still uncommon because of infertility
(secondary to hypothalamic dysfunction and anovulation
caused by hemosiderin deposition). Since the introduction of hypertransfusion and iron chelation therapy with
deferoxamine in the late 1970s, several reports and case
series have documented favorable pregnancy outcomes in
women with -thalassemia major (24, 25). Pregnancy in
women with -thalassemia major is recommended only
for those with normal cardiac function who have had prolonged hypertransfusion therapy to maintain hemoglobin
levels at 10 g/dL and iron chelation therapy with deferoxamine (25). During pregnancy, hemoglobin levels
should be maintained at or near 10 g/dL with transfusions. Deferoxamine usually is discontinued because the
safety of iron chelation therapy during pregnancy has not
been established. Fetal growth should be monitored with
serial ultrasonography. In cases in which fetal growth is
suboptimal, patients should have fetal surveillance. The
mode of delivery should be individualized, with cesarean
delivery reserved for obstetric indications.
Beta-thalassemia minor usually causes mild asymptomatic anemia. In the absence of documented iron deficiency, replacement beyond prophylactic doses of iron is
not indicated. Studies involving fairly small numbers of
patients suggest that pregnancy outcome is favorable in
women with -thalassemia minor. A study of 261 pregnant
women with -thalassemia minor found a significantly
higher rate of IUGR and oligohydramnios than is found in
nonthalassemic patients (26). No differences were noted in
perinatal outcomes such as low Apgar scores, congenital
malformations, or perinatal mortality (26).
Summary of
Recommendations and
Conclusions
Individuals of African, Southeast Asian, and
Mediterranean descent are at increased risk for
being carriers of hemoglobinopathies and should be
offered carrier screening and, if both parents are
determined to be carriers, genetic counseling.
A complete blood count and hemoglobin electrophoresis are appropriate laboratory tests for screening for hemoglobinopathies. Solubility tests alone
are inadequate for screening because they fail to
identify important transmissible hemoglobin gene
abnormalities affecting fetal outcome.
Couples at risk for having a child with sickle cell
disease or thalassemia should be offered genetic
counseling to review prenatal testing and reproduction options. Prenatal diagnosis of hemoglobinopathies is best accomplished by DNA analysis of
cultured amniocytes or chorionic villi.
References
1. Angastiniotis M, Modell B. Global epidemiology of hemoglobin disorders. Ann N Y Acad Sci 1998;850:25169.
(Level II-3)
2. Motulsky AG. Frequency of sickling disorders in U.S.
blacks. N Engl J Med 1973;288:313. (Level III)
3. Davies SC, Cronin E, Gill M, Greengross P, Hickman M,
Normand C. Screening for sickle cell disease and thalassemia: a systematic review with supplementary research.
Health Technol Assess 2000;4:iv, 199. (Level III)
4. Duffy TP. Hematologic aspects of pregnancy. In: Burrow
GN, Duffy TP, Copel JA, editors. Medical complications
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975
during pregnancy. 6th ed. Philadelphia (PA): Elsevier

Saunders; 2004. p. 6986. (Level III)
patients with sickle cell hemoglobinopathies: benefit versus risk. Obstet Gynecol 1980;56:27480. (Level III)
5. Kazazian HH Jr. The thalassemia syndromes: molecular

basis and prenatal diagnosis in 1990. Semin Hematol
1990;27:20928. (Level III)
16. Brumfield CG, Huddleston JF, DuBois LB, Harris BA Jr.

A delayed hemolytic transfusion reaction after partial
exchange transfusion for sickle cell disease in pregnancy:
a case report and review of literature. Obstet Gynecol
1984;63(suppl):13s15s. (Level III)
6. Serjeant GR, Serjeant BE. Sickle cell disease. 3rd ed. New
York (NY): Oxford University Press; 2001. (Level III)
7. Alter BP. Prenatal diagnosis of hematologic diseases,
1986 update. Acta Haematol 1987;78:13741. (Level II-3)
8. Smith JA, Espeland M, Bellevue R, Bonds D, Brown AK,
Koshy M. Pregnancy in sickle cell disease: experience of
the Cooperative Study of Sickle Cell Disease. Obstet
Gynecol 1996;87:199204. (Level II-2)
9. Sun PM, Wilburn W, Raynor BD, Jamieson D. Sickle cell
disease in pregnancy: twenty years of experience at Grady
Memorial Hospital, Atlanta, Georgia. Am J Obstet
Gynecol 2001;184:112730. (Level II-2)
10. Powars DR, Sandhu M, Niland-Weiss J, Johnson C, Bruce
S, Manning PR. Pregnancy in sickle cell disease. Obstet
11. Charache S. Mechanism of action on hydroxyurea in the
management of sickle cell anemia in adults. Semin
Hematol 1997;34(suppl 3):1521. (Level I)
12. Rees DC, Olujohungbe AD, Parker NE, Stephens AD,
Telfer P, Wright J. Guidelines for the management of the
acute painful crisis in sickle cell disease. British
Committee for Standards in Haematology General
Haematology Task Force by the Sickle Cell Working
Party. Br J Haematol 2003;120:74452. (Level III)
13. Tuck SM, James CE, Brewster EM, Pearson TC, Studd
JW. Prophylactic blood transfusion in maternal sickle cell
syndromes. Br J Obstet Gynaecol 1987;94:1215. (Level
III)
14. Koshy M, Burd L, Wallace D, Moawad A, Baron J.
Prophylactic red-cell transfusions in pregnant patients
with sickle cell disease. A randomized cooperative study.
N Engl J Med 1988;319:144752. (Level I)
15. Morrison JC, Schneider JM, Whybrew WD, Bucovaz ET,
Menzel DM. Prophylactic transfusions in pregnant
17. Ricks P Jr. Exchange transfusion in sickle cell anemia in

pregnancy. Obstet Gynecol 1965;25:1179. (Level III)
18. Ricks P Jr. Further experience with exchange transfusion
in sickle cell anemia in pregnancy. Am J Obstet Gynecol
1968;100:108790. (Level III)
19. Morrison JC, Wiser WL. The use of prophylactic partial
exchange transfusion in pregnancies associated with sickle
cell hemoglobinopathies. Obstet Gynecol 1976;48:51620.
(Level III)
20. Serjeant GR, Loy LL, Crowther M, Hambleton IR, Thame
M. Outcome of pregnancy in homozygous sickle cell disease. Obstet Gynecol 2004;103:127885. (Level II2)
21. Morrison JC, Blake PG, McCoy C, Martin JN Jr, Wiser
WL. Fetal health assessment in pregnancies complicated
by sickle hemoglobinopathies. Obstet Gynecol 1983;61:
224. (Level III)
22. Anyaegbunam A, Morel MI, Merkatz IR. Antepartum
fetal surveillance tests during sickle cell crisis. Am J
23. Ong HC, White JC, Sinnathuray TA. Haemoglobin H disease and pregnancy in a Malaysian woman. Acta
Haematol 1977;58:22933. (Level III)
24. Jensen CE, Tuck SM, Wonke B. Fertility in beta thalassemia major: a report of 16 pregnancies, preconceptual
evaluation and a review of the literature. Br J Obstet
25. Aessopos A, Karabatsos F, Farmakis D, Katsantoni A,
Hatziliami A, Youssef J, et al. Pregnancy in patients with
well-treated beta-thalassemia: outcome for mothers and
newborn infants. Am J Obstet Gynecol 1999;180:3605.
(Level III)
26. Sheiner E, Levy A, Yerushalmi R, Katz M. Beta-thalassemia minor during pregnancy. Obstet Gynecol 2004;103:
12737. (Level II-2)
976

Force:
I
type of evidence.
committees.
publication may be reproduced, stored in a retrieval system,
means, electronic, mechanical, photocopying, recording, or
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
Hemoglobinopathies in pregnancy. ACOG Practice Bulletin No. 78.
2007;109:22937.
PRACTICE BULLETINS
977
ACOG
PRACTICE
BULLETIN
(Replaces Practice Bulletin Number 1, June 1998)

of Brian Mercer, MD. The information is designed to aid
of practice.
Premature Rupture of
Membranes
Preterm delivery occurs in approximately 12% of all births in the United States
and is a major factor contributing to perinatal morbidity and mortality (1, 2).
Despite extensive research in this area, the rate of preterm birth has increased
by 38% since 1981 (3). Premature rupture of membranes (PROM) is a complication in approximately one third of preterm births. It typically is associated
with brief latency between membrane rupture and delivery, increased potential
for perinatal infection, and in utero umbilical cord compression. Because of
this, both PROM at and before term can lead to significant perinatal morbidity
and mortality. There is some controversy over the optimal approaches to clinical assessment and treatment of women with term and preterm PROM.
Management hinges on knowledge of gestational age and evaluation of the relative risks of preterm birth versus intrauterine infection, abruptio placentae,
and cord accident that could occur with expectant management. The purpose of
this document is to review the current understanding of this condition and to
provide management guidelines that have been validated by appropriately conducted outcome-based research. Additional guidelines on the basis of consensus and expert opinion also are presented.
Background
The definition of PROM is rupture of membranes before the onset of labor.
Membrane rupture that occurs before 37 weeks of gestation is referred to as
preterm PROM. Although term PROM results from the normal physiologic
process of progressive membrane weakening, preterm PROM can result from a
wide array of pathologic mechanisms acting individually or in concert (4). The
gestational age and fetal status at membrane rupture have significant implications in the etiology and consequences of PROM. Management may be dictat-
978
ed by the presence of overt intrauterine infection,

advanced labor, or fetal compromise. When such factors
are not present, especially with preterm PROM, obstetric
management may have a significant impact on maternal
and infant outcomes. An accurate assessment of gestational age and knowledge of the maternal, fetal, and
neonatal risks are essential to appropriate evaluation,
counseling, and care of patients with PROM.
Etiology
Membrane rupture may occur for a variety of reasons. At
term, weakening of the membranes may result from
physiologic changes combined with shearing forces created by uterine contractions (58). Intraamniotic infection has been shown to be commonly associated with
preterm PROM, especially if preterm PROM occurs at
earlier gestational ages (9). In addition, factors such as
low socioeconomic status, second- and third-trimester
bleeding, low body mass index (calculated as weight in
kilograms divided by the square of height in meters) less
than 19.8, nutritional deficiencies of copper and ascorbic
acid, connective tissue disorders (eg, EhlersDanlos syndrome), maternal cigarette smoking, cervical conization
or cerclage, pulmonary disease in pregnancy, uterine
overdistention, and amniocentesis have been linked to the
occurrence of preterm PROM (1019). The risk of recurrence for preterm PROM is between 16% and 32% (20,
21). In addition, women with a previous preterm birth
(especially if it is due to PROM), those with a short cervical length (less than 25 mm) in the second trimester,
and women with preterm labor or symptomatic contractions in the current pregnancy are at increased risk for
PROM (12, 22). Although each of these risk factors can
act individually or in concert to cause PROM, in many
cases PROM will occur in the absence of recognized risk
factors. As a result, it has been difficult to identify effective treatment strategies for the prevention of PROM.
Recent studies have suggested progesterone therapy to
reduce the risk of recurrent spontaneous preterm birth
resulting from preterm labor or PROM (23, 24).
However, because most cases of PROM occur in women
without identifiable risk factors, the mainstay of care has
been treatment after membrane rupture occurs.
Term Premature Rupture

of Membranes
At term, PROM complicates approximately 8% of pregnancies and generally is followed by the prompt onset of
spontaneous labor and delivery. In a large randomized trial,
half of women with PROM who were managed expectantly gave birth within 5 hours, and 95% gave birth within 28
hours of membrane rupture (25). The most significant
maternal risk of term PROM is intrauterine infection, a risk
that increases with the duration of membrane rupture
(2529). Fetal risks associated with term PROM include
umbilical cord compression and ascending infection.
Leakage of Fluid After

Amniocentesis
When leakage of amniotic fluid occurs after amniocentesis, the outcome is better than after spontaneous preterm
PROM. In studies involving women who had secondtrimester amniocentesis for prenatal diagnosis of genetic
disorders, the risk of PROM was 11.2%, and the attributable risk of pregnancy loss was 0.06% (30). In most
patients, the membranes reseal with restoration of normal
amniotic fluid volume (31, 32).
Preterm Premature
Rupture of Membranes
Regardless of obstetric management or clinical presentation, birth within 1 week is the most likely outcome for
any patient with preterm PROM in the absence of adjunctive treatments. The earlier in gestation that PROM
occurs, the greater is the latency period. With expectant
management, 2.813% of women can anticipate cessation of fluid leakage and possible restoration of normal
amniotic fluid volume (28, 32).
Of women with preterm PROM, clinically evident
intraamniotic infection occurs in 1360%, and postpartum infection occurs in 213% (3337). The incidence of
infection increases with decreasing gestational age at
membrane rupture (38, 39) and increases with digital
vaginal examination (40). Fetal malpresentation is
increased with preterm PROM. Abruptio placentae affects
412% of pregnancies with preterm PROM (41, 42). However, serious maternal sequelae are uncommon (35, 43).
The most significant risks to the fetus after preterm
PROM are complications of prematurity. At all gestational ages before term, respiratory distress has been reported to be the most common complication of preterm birth
(4, 44). Other serious forms of morbidity, including
neonatal infections, intraventricular hemorrhage, and
necrotizing enterocolitis, also are associated with prematurity, but these are less common nearer to term. Preterm
PROM and exposure to intrauterine inflammation have
been associated with an increased risk of neurodevelopmental impairment (9, 45). Early gestational age at mem-
PRACTICE BULLETINS
brane rupture also has been associated with an increased

risk of neonatal white matter damage (P <.001), after
controlling for corticosteroid administration, latency
interval, gestational age at delivery, and birth weight
(46). However, no data exist that suggest immediate
delivery after presentation with PROM will avert these
risks. The presence of maternal infection poses the additional risk of neonatal infection. Infection, cord accident,
and other factors contribute to the 12% risk of antenatal fetal demise after preterm PROM (43).
Previable Premature
Rupture of Membranes
The fetal survival rate subsequent to PROM at 2426
weeks of gestation has been reported to be approximately 57% (47). A recent systematic review of 201 cases
from 11 studies revealed a 21% perinatal survival rate
after expectant management of PROM before viability
(48). Survival data may vary by institution. Most studies
of second-trimester and previable PROM have been retrospective and have included only those patients appropriate for and accepting of expectant management,
potentially exaggerating latency and improving apparent
outcomes.
A small number of patients with previable PROM
will have an extended latency period. In a review of 12
studies evaluating patients with second-trimester PROM,
the mean latency period ranged from 10.6 to 21.5 days
(47), with 57% of patients giving birth within 1 week
and 22% remaining pregnant for 1 month or more. The
incidence of stillbirth subsequent to PROM at 1628
weeks of gestation ranges from 3.8% to 22% (11, 33, 49)
compared with 02% at 3036 weeks of gestation (50,
51). This increased rate of death may be explained by
increased susceptibility of the umbilical cord to compression or of the fetus to hypoxia and intrauterine infection. Alternatively, this finding may reflect the lack of
intervention for fetal compromise before viability.
Significant maternal complications occurring after
second trimester and previable PROM have been reported to include intraamniotic infection, endometritis,
abruptio placentae, retained placenta, and postpartum
hemorrhage. Maternal sepsis is a rare but serious complication reported in approximately 1% of cases, and
isolated maternal deaths due to infection have been
reported in this setting (52). Outcomes of survivors of
preterm PROM depend on the gestational age, presence
of infection, length of latency, and other maternal and
fetal complications.
A variety of conditions associated with fetal lung
compression or oligohydramnios or both can result in
979
pulmonary hypoplasia. Reported risks of pulmonary

hypoplasia after PROM at 1626 weeks of gestation vary
from less than 1% to 27% (37, 52). Lethal pulmonary
hypoplasia rarely occurs with membrane rupture subsequent to 24 weeks of gestation, presumably because
alveolar growth adequate to support postnatal development already has occurred (53, 54). Early secondtrimester membrane rupture, severe oligohydramnios,
and duration of membrane rupture longer than 14 days
are primary determinants of the risk of pulmonary
hypoplasia (55, 56). Prolonged oligohydramnios also is
associated with in utero deformation, including abnormal facies (ie, low-set ears and epicanthal folds) and
limb contractures and other positioning abnormalities.

Recommendations
How is premature rupture of membranes
diagnosed?
Most cases of PROM can be diagnosed on the basis of
the patients history and physical examination.
Examination should be performed in a manner that minimizes the risk of introducing infection, particularly
before term. Because digital cervical examinations
increase the risk of infection and add little information to
that available with speculum examination, digital examinations should be avoided unless the patient is in active
labor or imminent delivery is planned (40, 5759).
Sterile speculum examination provides an opportunity to
inspect for cervicitis and umbilical cord or fetal prolapse, assess cervical dilatation and effacement, and
obtain cultures as appropriate.
The diagnosis of membrane rupture is confirmed by
the visualization of fluid passing from the cervical canal.
If the diagnosis remains in question, the pH of the vaginal sidewalls or from fluid in the posterior vaginal fornix
can be assessed. The pH of the vaginal secretions is generally 4.56.0, whereas amniotic fluid usually has a pH
of 7.17.3. False-positive results may occur in the presence of blood or semen contamination, alkaline antiseptics, or bacterial vaginosis. Alternatively, false-negative
results may occur with prolonged leakage and minimal
residual fluid. Additional information can be obtained by
swabbing the posterior fornix (avoiding cervical mucus)
and allowing the vaginal fluid to dry on a microscope
slide. The presence of arborization (ferning) under microscopic visualization further suggests membrane rupture.
Ultrasound examination of amniotic fluid volume
may be a useful adjunct in documenting oligohydramnios, but is not diagnostic. When the clinical history or
980
physical examination is unclear, membrane rupture can

be diagnosed unequivocally with ultrasonographically
guided transabdominal instillation of indigo carmine dye
(1 mL in 9 mL of sterile normal saline), followed by
observation for passage of blue fluid from the vagina.
What does the initial management involve

once PROM has been confirmed?
In all patients with PROM, gestational age, fetal presentation, and well-being should be determined. At any gestational age, a patient with evident intrauterine infection,
abruptio placentae, or evidence of fetal compromise is
best cared for by expeditious delivery. In the absence of
an indication for immediate delivery, swabs for diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae may be obtained from the cervix, if appropriate.
The need for group B streptococcal intrapartum prophylaxis should be determined if preterm PROM occurs
(60).
In patients with preterm PROM, electronic fetal
heart rate monitoring and uterine activity monitoring
offer the opportunity to identify occult umbilical cord
compression and to evaluate for asymptomatic contractions. In one study, variable decelerations occurred in
32% of women with preterm PROM (61). Biophysical
profile test scores of 6 or less within 24 hours of delivery
also have been demonstrated to correlate with positive
amniotic fluid cultures and perinatal infection. At least
eight studies have confirmed this association (62). Most
of these studies have included daily fetal assessment
after preterm PROM. An abnormal test result should lead
to reassessment of the clinical circumstances and may
lead to a decision to proceed to delivery. It is important
to remember that heart rate testing at less than 32 weeks
of gestation may not yield a reactive result in an immature but otherwise healthy fetus. However, once a reactive result has been achieved, a subsequently nonreactive
test should be considered suspicious. Consensus has not
been reached among experts on the optimal frequency of
and modality of fetal testing in the face of PROM.
What is the optimal method of initial management for a patient with PROM at term?
Fetal heart rate monitoring should be used to assess fetal
status. Dating criteria should be reviewed to assign gestational age because virtually all aspects of subsequent
care will hinge on that information. Because optimal
results are seen with 4 hours between group B streptococcal prophylaxis and birth, when the decision to deliver is made, group B streptococcal prophylaxis should be
given based on prior culture results or risk factors if cultures have not been previously performed (60).
The largest randomized study to date found that oxytocin induction reduced the time interval between PROM
and delivery as well as the frequencies of chorioamnionitis, postpartum febrile morbidity, and neonatal antibiotic
treatments, without increasing cesarean deliveries or
neonatal infections (25). These data suggest that for
women with PROM at term, labor should be induced at
the time of presentation, generally with oxytocin infusion, to reduce the risk of chorioamnionitis. An adequate
time for the latent phase of labor to progress should be
allowed.
When is delivery recommended for the

preterm fetus in the presence of premature
rupture of membranes?
The decision to deliver is based on gestational age and
fetal status (Table 1), and the time considered optimal
may vary among institutions. At 3233 completed weeks
of gestation, the risk of severe complications of prematurity is low if fetal pulmonary maturity is evident by
amniotic fluid samples collected vaginally or by amniocentesis (51). Therefore, labor induction may be considered if pulmonary maturity has been documented. If
pulmonary maturity cannot be established, expectant
management may be beneficial. The efficacy of corticosteroid use at 3233 completed weeks of gestation has
not been specifically addressed for women with PROM
but has been recommended by some experts.
Because of the increased risk of chorioamnionitis
(63, 64), and because antenatal corticosteroids are not
recommended after 34 weeks of gestation to accelerate
fetal pulmonary maturity, delivery is recommended when
PROM occurs at or beyond 34 weeks of gestation. The
patient who experiences PROM between 24 weeks and
31 completed weeks of gestation should be cared for
expectantly if no maternal or fetal contraindications exist
until 33 completed weeks of gestation. Prophylaxis using
antibiotics to prolong latency and a single course of antenatal corticosteroids can help reduce the risks of infection and gestational age-dependent neonatal morbidity.
What general approaches are used in cases of

preterm PROM managed expectantly?
Expectant management of preterm PROM generally consists of modified bed rest to enhance reaccumulation of
amniotic fluid and complete pelvic rest. Patients should
be assessed periodically for evidence of infection, abruptio placentae, umbilical cord compression, fetal wellbeing, and labor. There is no consensus on the frequency
of assessment that is optimal, but an acceptable strategy
would include periodic ultrasound monitoring of amniotic fluid volume and fetal heart rate monitoring. In a
PRACTICE BULLETINS
981
Table 1. Management of Premature Rupture of Membranes Chronologically

Gestational Age
Management
Term (37 weeks or more)
Proceed to delivery, usually by induction of labor

Group B streptococcal prophylaxis recommended
Near term (34 weeks to 36 completed

weeks)
Same as for term
Preterm (32 weeks to 33 completed

weeks)
Expectant management, unless fetal pulmonary

maturity is documented
Corticosteroidno consensus, but some experts
recommend
Antibiotics recommended to prolong latency if there
are no contraindications
Preterm (24 weeks to 31 completed

weeks)
Expectant management
Single-course corticosteroid use recommended
Tocolyticsno consensus
Antibiotics recommended to prolong latency if there
are no contraindications
Less than 24 weeks*
Patient counseling
Expectant management or induction of labor
Group B streptococcal prophylaxis is not recommended
Corticosteroids are not recommended
Antibioticsthere are incomplete data on use in prolonging latency
*The combination of birthweight, gestational age, and sex provide the best estimate of chances of survival and should
be considered in individual cases.
patient with preterm PROM, a temperature exceeding

38.0C (100.4F) may indicate infection, although some
investigators have suggested that fever, with additional
factors such as uterine tenderness and maternal or fetal
tachycardia, is a more accurate indicator of maternal
infection (34, 65). Leukocyte counts are nonspecific
when there is no clinical evidence of infection, especially if antenatal corticosteroids have been administered.
Low initial amniotic fluid volume (amniotic fluid
index less than 5 cm or maximum vertical fluid pocket
less than 2 cm) has been associated with shorter latency
to delivery and an increased risk of neonatal morbidity,
including respiratory distress syndrome (RDS), but not
with increased maternal or neonatal infection after
PROM (66). However, the predictive value of a low
amniotic fluid volume for adverse outcomes is poor.
Several investigators have evaluated the utility of
endovaginal ultrasound assessment of cervical length for
prediction of latency during expectant management of
PROM remote from term. Some experts have suggested
a short cervical length after PROM to be associated with
shorter latency (6769). In the most recent study, the
likelihood of delivery within 7 days was 83% if the initial cervical length was 110 mm (versus 18% for cervical length more than 30 mm); however, the number of
women in these categories was small (N = 24 and 17,

respectively) (67). Although the combination of clinical
and ultrasound markers may yield improved predictive
models in the future, initial amniotic fluid volume determination and cervical length generally should not be
used in isolation to direct management of PROM.
Should tocolytics be considered for patients

with preterm PROM?
Use of prophylactic tocolysis after preterm PROM has
been shown to prolong latency in the short term (7072),
whereas the use of therapeutic tocolysis (ie, instituting
tocolysis only after contractions have ensued) has not
been shown to prolong latency (73). A retrospective
study compared the use of aggressive tocolysis (84% of
antepartum days) with limited tocolysis as needed for
contractions only during the first 48 hours (7% of
antepartum days). Aggressive therapy was found not to
be associated with significantly longer latency to delivery (3.8 versus 4.5 days, P = .16) (74). However, a recent
retrospective study compared the prolonged use of tocolysis for longer than 48 hours plus antibiotics and steroids
with gestational age-matched infants not treated for
PROM. The investigators concluded that chorioamnioni-
982
tis and a latency of greater than 1 week achieved by prolonged use of tocolysis lessens the advantages of extended gestational age and decreased predischarge neonatal
morbidity (75).
The effect of tocolysis to permit antibiotic and antenatal corticosteroid administration in the patient with
preterm PROM who is having contractions has yet to be
conclusively evaluated; therefore, specific recommendations for or against tocolysis administration cannot be
made. As detailed as follows, use of both antibiotics and
antenatal corticosteroids improves outcome in patients
with preterm PROM who are being treated expectantly.
Should antenatal corticosteroids be administered to patients with preterm PROM?

The impact of antenatal corticosteroid administration
after preterm PROM on neonatal outcomes has been
evaluated in a number of clinical trials. Multivariate
analysis of prospective observational trials also has suggested a benefit of antenatal corticosteroid use regardless
of membrane rupture (76), and the National Institutes of
Health Consensus Development Panel has recommended
a single course of antenatal corticosteroids for women
with PROM before 32 weeks of gestation in the absence
of intraamniotic infection (77, 78). Several meta-analyses
have addressed this issue (7982). Early reviews resulted
in conflicting conclusions regarding the impact of antenatal steroids on the occurrence of RDS. Two more
recent meta-analyses suggest that steroid therapy significantly reduces the risks of RDS, intraventricular hemorrhage, and necrotizing enterocolitis without increasing
the risks of maternal or neonatal infection regardless of
gestational age (82, 83). The risk of infection from corticosteroid use at 3233 completed weeks of gestation is
unclear, but based on available evidence, their use has
been recommended by some experts, particularly if pulmonary immaturity is documented. Studies of the combined use of corticosteroids and prophylactic antibiotics
after preterm PROM suggest significant reductions in
RDS, perinatal mortality, and other morbidities with no
evident increase in perinatal infections after steroid
administration (84, 85).
Should antibiotics be administered to patients

with preterm PROM?
The issue of adjunctive antibiotic therapy to treat or prevent ascending decidual infection in order to prolong
pregnancy and reduce neonatal infections and gestational
age-dependent morbidity has been widely studied (43,
86, 87). In the most recent meta-analysis, investigators
suggested prophylactic antibiotic administration to delay
delivery and reduce major markers of neonatal morbidity, but suggested that amoxicillinclavulanic acid be
avoided because of the increased risk of neonatal necrotizing enterocolitis (87).
Two large, multicenter clinical trials have adequate
power to evaluate the utility of adjunctive antibiotics in
this setting (65, 88). The National Institutes of Child
Health and Human Development Maternal Fetal
Medicine Research Units (NICHD-MFMU) Research
Network found that the combination of initial intravenous
therapy (48 hours) with ampicillin and erythromycin, followed by oral therapy of limited duration (5 days) with
amoxicillin and enteric-coated erythromycin-base at
2432 weeks of gestation, decreased the likelihood of
chorioamnionitis and delivery for up to 3 weeks, as well
as the number of infants with one or more major morbidities (defined as death, RDS, early sepsis, severe intraventricular hemorrhage, or severe necrotizing enterocolitis)
(65). In addition, therapy reduced the likelihood of individual gestational agedependent morbidities, including
RDS, stage 34 necrotizing enterocolitis, patent ductus
arteriosus, and chronic lung disease. Neonatal sepsis and
pneumonia were less frequent in the antibiotic group for
those who were not carriers of group B streptococci.
(Group B streptococci carriers in both study arms received
ampicillin for 1 week and then again during labor.)
A second large multicenter trial that examined the
use of oral antibiotic therapy with erythromycin, amoxicillinclavulanic acid, or both for up to 10 days after
preterm PROM before 37 weeks of gestation found that
oral erythromycin therapy 1) prolonged pregnancy only
briefly (not significant at 7 days), 2) reduced the need for
supplemental oxygen, and 3) reduced the frequency of
positive blood cultures with no improvement in the primary outcome (one or more outcomes of death, chronic
lung disease, or major cerebral abnormality on ultrasonography) (88). Oral amoxicillinclavulanic acid
reduced delivery within 7 days and reduced the need for
supplemental oxygen but was associated with an
increased risk of necrotizing enterocolitis (1.9% versus
0.5%, P = .001) without preventing other neonatal morbidities. The finding of increased necrotizing enterocolitis with oral amoxicillinclavulanic acid differs from the
NICHD-MFMU trial finding of reduced stage 2 or 3
necrotizing enterocolitis with amoxicillinerythromycin
therapy in a higher risk population, and review of the
current literature does not reveal a consistent pattern
regarding an increased risk with broad-spectrum antibiotic therapy. Several recent studies have attempted to
determine whether a shorter duration of antibiotic therapy is adequate after preterm PROM, but these studies
are of inadequate size and power to demonstrate equivalent effectiveness against infant morbidity (89, 90).
PRACTICE BULLETINS
Based on available information, a 7-day course of

parenteral and oral therapy with ampicillin or amoxicillin and erythromycin is recommended during expectant management of preterm PROM remote from term to
prolong pregnancy and to reduce infectious and gestational age-dependent neonatal morbidity. Use of the
combination of oral erythromycin and extended-spectrum ampicillinclavulanic acid in women near term
does not appear to be beneficial, may be harmful, and is
not recommended. Antibiotic administration to prolong
latency must be distinguished from well-established protocols directed at prevention of group B streptococcal
infection in term and preterm patients (60). The prophylactic antibiotic regimen would appropriately treat group
B streptococcal infections during expectant management
of preterm PROM remote from term. However, women
with PROM and a viable fetus, who are known carriers
of group B streptococci and those who give birth before
carrier status can be delineated, should receive intrapartum prophylaxis to prevent vertical transmission
regardless of earlier treatments.
Can preterm PROM be managed with home

care?
Generally, hospitalization for bed rest and pelvic rest is
indicated after preterm PROM once viability is reached.
Recognizing that latency is frequently brief, that
intrauterine and fetal infection may occur suddenly, and
that the fetus is at risk for umbilical cord compression,
ongoing surveillance of both the woman and her fetus is
recommended once the limit of potential viability has
been reached.
For a woman with preterm PROM and a viable
fetus, the safety of expectant management at home has
not been established. One clinical trial of discharge after
preterm PROM suggested that relatively few patients
will be eligible for discharge to home care (91). Only 67
of 349 women (18%) were eligible for antepartum home
care after 72 hours (negative cervical cultures and no evident labor, intrauterine infection, or fetal compromise).
There were no identifiable differences in latency or in
the incidences of intraamniotic infection, variable decelerations, or cesarean delivery. Infant outcomes were similar, but the power of this study to identify differences in
these outcomes was low. Although the potential for a
reduction in health care costs with antepartum discharge
is enticing, it is important to ensure that such management will not be associated with increased risks and
costs related to perinatal morbidity and mortality. Any
cost savings from antenatal discharge may be rapidly lost
with a small increase in the stay in the neonatal intensive
care unit.
983
How should a patient with preterm PROM

and a cervical cerclage be treated?
There are no prospective studies available with which to
guide the care of women with preterm PROM and a cervical cerclage in situ. Retrospective studies have found
that removal of cerclage after PROM is associated with
similar pregnancy outcomes to those with PROM but no
cerclage (92, 93). Cerclage retention after preterm
PROM has been associated with trends toward increased
maternal infectious morbidity (9496), reaching statistical significance in one evaluation (97), and with only
brief pregnancy prolongation. One study found increased
infant mortality and sepsis-related death when the cerclage was left in place after PROM (94). One study
found significant pregnancy prolongation with cerclage
retention by comparing differing practices at two institutions; however, this could reflect population or practice
differences at these institutions (95). Because the available studies are small and nonrandomized, the optimal
timing of cerclage removal is unclear. However, no controlled study has found cerclage retention after PROM to
improve neonatal outcomes. The risks and benefits of
short-term cerclage retention pending completion of
antenatal corticosteroid therapy to enhance fetal maturation have not been evaluated.
What is the optimal treatment for a patient

with preterm PROM and herpes simplex
virus infection?
Neonatal herpes simplex virus infection usually results
from maternalfetal transmission during the delivery
process. Neonatal infection occurs in 3480% of infants
delivered in the setting of primary maternal infection, and
in 15% with secondary infections (98, 99). Based on a
small case series of women with active genital herpes
infection in 1971, totaling just 36 patients, it has been
believed that latency of more than 46 hours after membrane rupture is associated with an increased risk of
neonatal infection (100, 101). However, a more recent
case series of 29 women treated expectantly with active
recurrent herpes simplex virus lesions and PROM before
32 weeks of gestation found none of the infants developed
neonatal herpes infection (102). Latency from membrane
rupture to delivery ranged from 1 to 35 days, and cesarean delivery was performed if active lesions were present
at the time of delivery. These data suggest that the risk of
prematurity should be weighed against the potential risk
of neonatal herpes simplex virus in considering expectant
management of PROM complicated by recurrent maternal herpes simplex virus infection. Prophylactic treatment
with antiviral agents (eg, acyclovir) may be considered.
984
How does care differ for patients with PROM

that occurs before the threshold of potential
neonatal viability?
Women presenting with PROM before potential viability
should be counseled regarding the impact of immediate
delivery and the potential risks and benefits of expectant
management. Counseling should include a realistic
appraisal of neonatal outcomes, including the availability
of obstetric monitoring and neonatal intensive care facilities. Because of advances in perinatal care, morbidity
and mortality rates continue to improve rapidly (43, 44,
103). An attempt should be made to provide parents with
the most up-to-date information possible.
Although no evidence or consensus of opinion
exists regarding the benefit of an initial period of inpatient observation in these patients, this approach may
include strict bed and pelvic rest to enhance the opportunity for resealing, as well as early identification of
infection and abruptio placentae if expectant management is pursued. In addition to clinical follow-up, it
may be useful to instruct patients to abstain from intercourse, limit their activities, and monitor their temperatures.
Typically, women with previable PROM who have
been cared for as outpatients are readmitted to the hospital for bed rest and observation for infection, abruptio
placentae, labor, and nonreassuring fetal heart rate patterns once the pregnancy has reached the limit of viability. Administration of antenatal corticosteroids for fetal
maturation is appropriate at this time given that early
delivery remains likely.
Summary of
Recommendations and
Conclusions
For women with PROM at term, labor should be
induced at the time of presentation, generally with
oxytocin infusion, to reduce the risk chorioamnionitis.
Patients with PROM before 32 weeks of gestation
should be cared for expectantly until 33 completed
weeks of gestation if no maternal or fetal contraindications exist.
A 48-hour course of intravenous ampicillin and erythromycin followed by 5 days of amoxicillin and
erythromycin is recommended during expectant
management of preterm PROM remote from term to
prolong pregnancy and to reduce infectious and gestational agedependent neonatal morbidity.
All women with PROM and a viable fetus, including those known to be carriers of group B streptococci and those who give birth before carrier status
can be delineated, should receive intrapartum chemoprophylaxis to prevent vertical transmission of group
B streptococci regardless of earlier treatments.
A single course of antenatal corticosteroids should
be administered to women with PROM before 32
weeks of gestation to reduce the risks of RDS, perinatal mortality, and other morbidities.

are based on limited and inconsistent scientific
evidence (Level B):
Delivery is recommended when PROM occurs at or
beyond 34 weeks of gestation.
With PROM at 3233 completed weeks of gestation, labor induction may be considered if fetal pulmonary maturity has been documented.
Digital cervical examinations should be avoided in
patients with PROM unless they are in active labor
or imminent delivery is anticipated.

A specific recommendation for or against tocolysis
administration cannot be made.
The efficacy of corticosteroid use at 3233 completed weeks is unclear based on available evidence, but
treatment may be beneficial particularly if pulmonary immaturity is documented.
For a woman with preterm PROM and a viable
fetus, the safety of expectant management at home
has not been established.
Measure
The percentage of patients with PROM and a viable fetus
who are known group B streptococci carriers or whose
status as a carrier is unknown who receive intrapartum
group B streptococcal prophylaxis
PRACTICE BULLETINS
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78. Antenatal corticosteroid therapy for fetal maturation.
79. Ohlsson A. Treatments of preterm premature rupture of
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80. Crowley PA. Antenatal corticosteroid therapy: a metaanalysis of the randomized trials, 1972 to 1994. Am J
Obstet Gynecol 1995;173:32235. (Meta-analysis)
81. Lovett SM, Weiss JD, Diogo MJ, Williams PT, Garite TJ.
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69. Carlan SJ, Richmond LB, OBrien WF. Randomized trial

of endovaginal ultrasound in preterm premature rupture of
membranes. Obstet Gynecol 1997;89:45861. (Level I)
82. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm
birth. Cochrane Database of Systematic Reviews 2006,
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70. Christensen KK, Ingemarsson I, Leideman T, Solum H,

Svenningsen N. Effect of ritodrine on labor after premature rupture of the membranes. Obstet Gynecol 1980;55:
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Burlison S, London SN. Preterm premature ruptured
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85. Pattinson RC, Makin JD, Funk M, Delport SD,
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86. Egarter C, Leitich H, Karas H, Wieser F, Husslein P,
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94. Ludmir J, Bader T, Chen L, Lindenbaum C, Wong G. Poor
perinatal outcome associated with retained cerclage in
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95. Jenkins TM, Berghella V, Shlossman PA, McIntyre CJ,
Maas BD, Pollock MA, et al. Timing of cerclage removal
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Perinatal outcome after preterm premature rupture of
membranes with in situ cervical cerclage. Am J Obstet
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pregnancies. Aust N Z J Obstet Gynecol 1977;17:7983.
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98. Chuang T. Neonatal herpes: incidence, prevention, and
consequences. Am J Prev Med 1988;4:4753. (Level III)
99. Amstey MS. Management of pregnancy complicated by
genital herpes virus infection. Obstet Gynecol 1971;37:
51520. (Level II-3)
100. Nahmias AJ, Josey WE, Naib ZM, Freeman MG,
Fernandez RJ, Wheeler JH. Perinatal risk associated with
maternal genital herpes simplex virus infection. Am J
101. Gibbs RS, Amstey MS, Lezotte DC. Role of cesarean
delivery in preventing neonatal herpes virus infection.
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premature rupture of membranes: a randomized study of
home versus hospital management. Obstet Gynecol
1993;81:614. (Level I)
102. Major CA, Towers CV, Lewis DF, Garite TJ. Expectant
management of preterm premature rupture of membranes
complicated by active recurrent genital herpes. Am J
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92. Blickstein I, Katz Z, Lancet M, Molgilner BM. The outcome of pregnancies complicated by preterm rupture of
the membranes with and without cerclage. Int J Gynaecol
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PRACTICE BULLETINS

Force:
I
type of evidence.
committees.
989
Copyright April 2007 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Premature rupture of membranes. ACOG Practice Bulletin No. 80.
2007;109:100719.
990
ACOG
PRACTICE
BULLETIN
(Replaces Practice Bulletin Number 8, October 1999)

of Lisa Hollier, MD. The information is designed to aid practitioners in making decisions
Reaffirmed 2009
Management of Herpes
in Pregnancy
Genital herpes simplex virus (HSV) infection during pregnancy poses a risk to
the developing fetus and newborn. Genital herpes infection occurs in one in five
women in the United States. Because many women of childbearing age are
infected or are becoming infected with HSV, the risk of maternal transmission
of this virus to the fetus or newborn is a major health concern. The purpose of
this document is to outline the spectrum of maternal and neonatal infection,
including risks of transmission, and provide management guidelines supported
by appropriately conducted outcome-based research. Additional guidelines
based on consensus and expert opinion also are presented to permit a review of
most clinical aspects of HSV.
Background
Etiology
Herpes simplex virus is a double-stranded DNA virus that can be differentiated
into HSV type 1 (HSV-1) and HSV type 2 (HSV-2) based on the glycoproteins
in the lipid bilayer envelope. Glycoprotein G2 is associated with HSV-2, and
glycoprotein G1 is associated with HSV-1. Herpes simplex virus type 1 is the
primary etiologic agent of herpes labialis, gingivostomatitis, and keratoconjunctivitis. Most genital infections with HSV are caused by HSV-2, but genital
HSV-1 infections are becoming increasingly common, particularly among adolescent and young women (1).
Herpes simplex virus is transmitted from person to person through direct
contact. Infection is initiated when the virus contacts mucosa or abraded skin.
The incubation period after acquisition of HSV-1 or HSV-2 ranges from 2 days
to 12 days. Herpes simplex virus then replicates in the epidermis and dermis, with
resulting cellular destruction and inflammation. During the initial infection, the
virus gains access to the sensory neurons, and then the infection becomes latent
PRACTICE BULLETINS
in the sensory ganglia. Reactivation of viral replication

occurs and may manifest clinically as recurrent ulcerative
lesions or subclinically as asymptomatic viral shedding.
Both the cellular and humoral immune systems play an
important role in controlling this viral infection (2).
Herpes virus has a characteristic protein coat, and
each of the viral types has identifiable proteins. Typespecific antibodies to the viral proteins develop within
the first several weeks of infection and persist. Antibodies to HSV can be detected by most assays within 23
weeks after infection with the virus (3).
Genital infection with HSV is a primary infection
when HSV-1 or HSV-2 is detected in individuals with no
evidence of antibodies to either viral type in the serum. An
outbreak is considered a nonprimary first episode when one
viral type is detected in an individual with serologic evidence of past infection with the other viral type. Recurrent
episodes are characterized by isolation of HSV-1 or HSV-2
in the presence of antibodies of the same serotype.
Incidence
Herpes simplex virus infection of the genital tract is one
of the most common sexually transmitted infections. The
true incidence of genital HSV infection is not known
because it is not a reportable disease. It is estimated
that approximately 45 million adolescent and adult
Americans have been infected with HSV-2 (4). In a large,
national serologic study, it was found that approximately
26% of women had serologic evidence of HSV-2 infection (4). It should be emphasized that serologic studies of
HSV-2 underestimate the prevalence of genital herpes
because HSV-1 also causes genital disease.
Most individuals who are infected with HSV are
unaware that they have contracted the virus. Only
approximately 515% of infected individuals report
recognition of their infection (4, 5). The increasing burden of infection has important implications for health
care providers. The number of initial visits to physicians
offices as a result of genital HSV infection increased
from approximately 75,000 per year in 1978 to nearly
270,000 per year in 2004 (6). Risk factors for HSV infection include female gender, duration of sexual activity,
minority ethnicity, previous genital infection, family
income, and number of sex partners (4, 7).
Whereas HSV-2 is virtually always a genital
pathogen, HSV-1 is increasingly recognized as the etiologic agent of genital herpes infection. Up to 80% of new
genital infections among all women may be caused by
HSV-1 (8, 9). This increase in initial infections with
HSV-1 is particularly pronounced in the adolescent and
young adult populations. In these populations, genital
infection with HSV-1 may have surpassed new genital
infection with HSV-2 (1).
991
Among women with serologic test results that indicate susceptibility to HSV infection, the incidence of new
HSV-1 or HSV-2 infection during pregnancy is approximately 2% (10). Approximately 10% of women who are
HSV-2 seronegative have partners who are seropositive
and are at risk for transmission of HSV-2 during the pregnancy (11). Consistent with nonpregnant patients, most
new infections in pregnant patients are asymptomatic
(10). The timing of infection is relatively evenly distributed, with approximately one third of women becoming
infected in each trimester (10). Among women with
recurrent genital HSV, approximately 75% can expect
at least one recurrence during pregnancy, and approximately 14% of patients will have prodromal symptoms or
clinical recurrence at delivery (12, 13).
Neonatal herpes usually is acquired during the intrapartum period through exposure to the virus in the genital tract, although in utero and postnatal infections are
rare but can occur. Approximately 80% of infected
infants are born to mothers with no reported history of
HSV infection (14). Although the actual incidence is
unknown because neonatal herpes infection is not a
reportable disease, estimates suggest that approximately
1,2001,500 cases occur each year in the United States
(15). Approximately one third to one half of cases of
neonatal herpes are caused by HSV-1 (15, 16). Neonatal
HSV infections can be classified as disseminated disease
(25%); central nervous system disease (30%); and disease limited to the skin, eyes, or mouth (45%) (14).
Mortality has decreased substantially over the past two
decades, decreasing to 30% for disseminated disease and
4% for central nervous system disease. Approximately
20% of survivors of neonatal herpes have long-term neurologic sequelae (17).

Recommendations
How can the diagnosis of herpes simplex
virus be established?
All suspected herpes virus infections should be confirmed through viral or serological testing. A diagnosis of
genital herpes based on the clinical presentation alone
has a sensitivity of 40% and specificity of 99% and a
false-positive rate of 20% (18). The tests used to confirm
the presence of HSV infection can be divided into two
basic groups: 1) viral detection techniques and 2) antibody detection techniques. Primary viral DNA testing
techniques are viral culture and HSV antigen detection
by polymerase chain reaction (PCR). The antibody detection techniques include the use of both laboratory-based
992
and point-of-care serologic tests to detect the presence of

antibodies to either HSV-1 or HSV-2. With viral detection techniques, negative results do not rule out the
presence of infection. The diagnosis of HSV should be
confirmed either serologically or with viral culture.
Isolation of HSV in cell culture is the preferred virologic test for patients who seek medical treatment for
genital ulcers or other mucocutaneous lesions and allows
differentiation of the type of virus (HSV-1 versus HSV2) (18). The sensitivity of this test is limited because of
several issues related to sampling and transportation of
the specimen (19). Primary lesions are more likely than
recurrent lesions to yield positive cultures (80% versus
40% of patients, respectively) (20, 21). Additionally, as
the lesions heal, they are less likely to be culture positive
(21). Thus, a positive genital culture provides conclusive
evidence of genital HSV infection; however, a negative
result does not exclude the presence of infection. When
a genital specimen is collected for HSV culture, the vesicles should be unroofed, if present, and vesicular fluid
should be collected.
Polymerase chain reaction techniques involve the
amplification of particular sequences of DNA or RNA
before detection and can thus detect evidence of viral
DNA at low concentrations. Because of the increased
sensitivity of PCR, unroofing vesicles is unnecessary. In
one very large study, PCR results were three to five times
more likely to be positive than were cultures (19).
Cultures were more likely to be positive at increasing
concentrations of virus, as demonstrated by a linear relationship between the proportion of positive cultures and
copy numbers of HSV DNA in samples. Polymerase
chain reaction techniques are commercially available
and can differentiate between HSV-1 and HSV-2.
Polymerase chain reaction provides increased sensitivity over culture (19, 20, 22) and may ultimately replace
culture as the standard of care for diagnosis. Presently,
however, there are no interlaboratory standards that
ensure that identical specimens processed in different
laboratories will yield identical results. Additionally,
the PCR tests are not U.S. Food and Drug Administration (FDA) approved for clinical testing of genital specimens (18).
For patients who do not present with active lesions
or whose lesions have negative culture or PCR test
results, accurate type-specific serologic assays that accurately distinguish between HSV-1 and HSV-2 antibodies
are now commercially available. Currently, there are several FDA-approved type-specific tests, and others are
under development (see box). The sensitivity of these
assays varies from 93100% and specificity from
9398% (23). The predictive value of a positive test
result is influenced by the prevalence of the disease in
U.S. Food and Drug AdministrationApproved Type-Specific Tests

Laboratory-based assays
HerpeSelect-1 and 2 ELISA IgG
HerpeSelect 1 and 2 Immunoblot IgG
Captia HSV-1 and 2 ELISA
Rapid tests (formerly known as the POCkit test)
BiokitHSV-2 Rapid Test
Sure-Vue HSV-2
the population tested. In a high-risk population, the positive predictive value for the ELISA test results was
8094% (24, 25). Repeat testing, using a different typespecific assay, has been shown to increase the positive
predictive value of a single test result, and this may be
especially important in populations with low HSV prevalence (24).
Because HSV-2 is an uncommon cause of oral
infection, detection of HSV-2 antibodies is virtually
diagnostic of genital HSV infection (26). Conversely,
detection of HSV-1 antibodies alone may represent orolabial infection or may be indicative of genital infection.
Correlation with direct viral identification techniques
and the patients symptoms is important.
How can primary herpes simplex virus infection be distinguished from a nonprimary first
episode during pregnancy?
It is not possible to distinguish primary from nonprimary
herpes simplex virus infection on the basis of clinical
findings alone (27). Diagnosis is based on the combination of positive viral detection and negative serologic test
results or evidence of seroconversion.
A primary outbreak in the first trimester of pregnancy has been associated with neonatal chorioretinitis,
microcephaly, and skin lesions in rare cases (28).
Although HSV has been associated with an increased
risk for spontaneous abortion, recent studies do not support such a risk (29).
How should a primary outbreak be managed

in pregnancy?
At the time of the initial outbreak, antiviral treatment
may be administered orally to pregnant women to reduce
the duration and the severity of the symptoms as well as
reduce the duration of viral shedding (Table 1) (30). In
patients who have severe disease, oral treatment can be
PRACTICE BULLETINS
993
Table 1. Recommended Doses of Antiviral Medications for Herpes in Pregnancy

Indication
Acyclovir
Valacyclovir
Primary or first-episode infection
400 mg orally, three times daily,

for 710* days
1 g orally, twice daily, for 710* days
Symptomatic recurrent episode

for 5 days or 800 mg orally,
twice daily, for 5 days
500 mg orally, twice daily, for 3 days

or 1 g orally, daily, for 5 days
Daily suppression

from 36 weeks estimated
gestational age until delivery
500 mg orally, twice daily, from 36

weeks estimated gestational age until
delivery
Severe or disseminated disease
510 mg/kg, intravenously, every

8 hours for 27 days, then oral
therapy for primary infection to
complete 10 days
*Treatment may be extended if healing is incomplete after 10 days.

Adapted from Sexually transmitted diseases treatment guidelines, 2006 [published erratum appears in MMWR Recomm Rep
2006;55:997]. Centers for Disease Control and Prevention. MMWR Recomm Rep 2006;55(RR11):194.
extended for more than 10 days if lesions are incompletely healed at that time (18).
Acyclovir may be administered intravenously to
pregnant women with severe genital HSV infection or
with disseminated herpetic infections. Case reports have
associated significant improvement in expected survival
with acyclovir treatment in cases of pregnant women
with disseminated HSV, herpes pneumonitis, herpes
hepatitis, and herpes encephalitis (3133).
Primary genital herpes infection during pregnancy
constitutes a higher risk for perinatal transmission than
does recurrent infection. The risk of vertical transmission
to the neonate when a primary outbreak occurs at the
time of delivery is approximately 3060% (10, 15).
Several factors likely contribute to the increased risk.
First, when women have acquired infection near the time
of delivery, there is likely reduced transplacental passage
of protective HSV-2 specific antibodies. Higher titers of
neutralizing antibodies in the neonate have been associated with a reduced risk of neonatal infection (34).
Second, neonatal exposure to the virus in the genital tract
may be increased. The genital viral shedding in women
with primary infection is of higher concentration and
longer duration than shedding that occurs with recurrent
episodes. Women with primary herpes that is untreated
have a mean duration of viral shedding of 15 days (30).
In addition, cervical shedding was detected by viral culture in 90% of women with primary infection (30).
Data regarding interventions to reduce vertical
transmission in the specific setting of primary herpes are
limited. One randomized trial of acyclovir versus placebo given from 36 weeks of gestation until delivery to
women with their first episode of genital herpes infection
during pregnancy found a significant reduction in clinical recurrences at delivery (35). The number of cesarean
deliveries for clinical herpes recurrences was reduced;

however, the total number of cesarean deliveries in the
treatment and placebo groups was similar. The number of
deliveries was insufficient to evaluate efficacy of antiviral treatment to prevent neonatal herpes. Evidence of the
effectiveness of cesarean delivery before labor for the
prevention of vertical transmission is lacking.
How should recurrent herpes simplex virus

infection in pregnant women be managed?
All women should be asked early in pregnancy about
symptoms of genital herpes, including prodromal symptoms. Women with a history of herpes should be examined for external herpetic lesions when they present for
evaluation in labor and delivery (6).
Among women with recurrent lesions at the time of
delivery, the rate of transmission with a vaginal delivery
is only 3% (36). For women with a history of recurrent
disease and no visible lesions at delivery, the transmission risk has been estimated to be 2/10,000 (15, 36). The
low risk is in part attributed to the presence and transplacental passage of antiherpes antibodies (15, 34, 36).
Cesarean delivery is not indicated in women with a history of HSV in the absence of active genital lesions or
prodromes.
The efficacy of suppressive therapy during pregnancy to prevent recurrences near term has been evaluated in numerous studies (13, 35, 3741). Because many
of the individual trials were small, a recent systematic
review of randomized controlled trials was performed to
assess the effectiveness of acyclovir suppression therapy
given to prevent a clinical recurrence at delivery, cesarean delivery for recurrent genital herpes, and the detection of HSV at delivery (42). The risk of recurrence at
994
delivery was reduced by 75%, and the rate of cesarean

delivery for recurrent genital herpes was reduced by 40%
for women who received suppression therapy after 36
weeks of gestation. Viral detection at delivery using culture or PCR was reduced by 90% among treated women,
but shedding was not completely eliminated (in one trial,
virus was detected in one woman receiving acyclovir)
(13). There were no cases of neonatal herpes in any of the
studies. Several trials demonstrating similar efficacy of
valacyclovir have been published since the meta-analysis
(12, 43). Women with active recurrent genital herpes
should be offered suppressive viral therapy at or beyond
36 weeks of gestation. The doses of antiviral medication
used in the randomized trials in pregnancy are higher
than the corresponding doses in nonpregnant women.
(Table 1.) Although neutropenia is a recognized, transient complication of acyclovir treatment of neonatal
HSV infection, it has not been reported following maternal suppressive therapy (17). The acyclovir concentrations at which neutropenia occurred were approximately
530 times higher than were observed in umbilical vein
plasma in a pharmacokinetic study of valacyclovir in
pregnancy (44).
What medications are available for treatment

of herpes simplex virus infection during
pregnancy?
There are three antiviral agents that are commonly used
to treat HSV infections. Acyclovir, famciclovir, and valacyclovir are all FDA pregnancy category B medications.
These drugs are all approved for the treatment of primary genital herpes, the treatment of episodes of recurrent
disease, and the daily treatment for suppression of outbreaks of recurrent genital herpes.
Acyclovir is a nucleoside analogue that enters virally
infected cells and acts specifically to inhibit the viral
thymidine kinase and, thus, DNA replication. The
bioavailability of oral acyclovir is approximately 20%,
which necessitates more frequent dosage intervals (45).
Valacyclovir is a prodrug of acyclovir and is rapidly converted to acyclovir after metabolism in the liver. The
bioavailability of acyclovir after doses with valacyclovir
is approximately 54% (46). This is three to five times
higher than achieved with oral acyclovir and, at a dose of
1 gm, approximates levels achieved with intravenous
doses of acyclovir. The pharmacokinetics of both drugs
have been evaluated in pregnancy. After doses of acyclovir and valacyclovir, there was evidence of acyclovir
concentration in the amniotic fluid but no evidence of
preferential fetal drug accumulation (44, 47).
Famciclovir also is a prodrug that is rapidly transformed
into penciclovir in the body. The bioavailability of the
active drug from an oral dose is approximately 77%, so

the dosage interval is less frequent than with acyclovir
(48). There are no published data on the use of famciclovir in pregnancy.
Development of viral resistance to acyclovir has not
been a problem in immunocompetent patients. In two
large, laboratory-based studies, a very low prevalence of
acyclovir resistance in viruses isolated from immunocompetent patients has been estimated (0.30.6%),
whereas acyclovir-resistant HSV infections occur more
commonly among patients who are immunocompromised (67%) (49, 50).
There are no documented increases in adverse fetal
effects because of medication exposure (39, 50, 51). The
manufacturer of acyclovir and valacyclovir, in cooperation with the Centers for Disease Control and Prevention,
maintained a registry for exposure to these drugs during
pregnancy through 1999. More than 700 infants reported
were exposed to acyclovir during the first trimester, and
there was no increase in adverse fetal or neonatal effects,
although the safety has not been definitely established
(18). There are insufficient data on valacyclovir and famciclovir exposure in the pregnancy registry for analyses
(52). Topical therapy offers limited benefit and should be
discouraged.
Is there a role for routine screening for

genital herpes during pregnancy or at
delivery?
In the past, screening referred to the use of a viral detection method, most commonly culture, to assess whether
viral shedding was present. Asymptomatic shedding during the antepartum period does not predict asymptomatic
shedding at delivery (53, 54). Thus, routine antepartum
genital HSV cultures in asymptomatic patients with
recurrent disease are not recommended.
With the advent of serologic tests that can reliably
detect disease in asymptomatic patients, screening now
refers to the detection of HSV infection. Maternal HSV
screening has been proposed to reduce neonatal herpes
by identifying women infected (seropositive) with genital herpes and offering suppressive antiviral therapy near
term. It also may identify susceptible women (seronegative) whose partners could be offered screening, allowing
for counseling of at-risk couples about strategies to
reduce the possibility of new maternal infection during
pregnancy. Several analyses have evaluated the costeffectiveness of various screening protocols for pregnant
patients to reduce the incidence of neonatal HSV infection (5559). The results from these analyses are highly
variableestimates of the cost to prevent one case of
neonatal herpes range from $200,000 to $4,000,000.
PRACTICE BULLETINS
A number of factors influence these cost estimates, including the costs of testing and counseling, effectiveness of
antiviral therapy, the probability of lesions or shedding at
delivery in asymptomatic women in whom HSV has been
diagnosed only by the screening test, and the likelihood of
neonatal herpes with vaginal delivery (54, 55). Currently,
there is no evidence of cost-effectiveness of screening
strategies from clinical trials or well-designed cohort studies in pregnancy. Whereas screening may be beneficial in
particular populations or couples, routine HSV screening
of pregnant women is not recommended.
When should cesarean delivery be performed

to prevent perinatal herpes simplex virus
transmissions?
Cesarean delivery is indicated in women with active genital lesions or prodromal symptoms, such as vulvar pain
or burning at delivery, because these symptoms may indicate an impending outbreak. The incidence of neonatal
disease is low when there is recurrent maternal disease,
but cesarean delivery is recommended because of the
potentially serious nature of the disease. In a large cohort
study, women who had given birth by cesarean delivery
were much less likely to transmit HSV infection to their
infants (15). Among women with HSV detected at delivery, neonatal herpes occurred in 1.2% of infants delivered
by cesarean delivery compared with 7.7% of infants
delivered vaginally (15).
Cesarean delivery does not completely prevent vertical transmission to the neonate. Transmission has been
documented in the setting of cesarean delivery performed
before membrane rupture (14, 60). Cesarean delivery is
not recommended for women with a history of HSV
infection but no active genital disease during labor (61).
Is cesarean delivery recommended for women

with recurrent herpes simplex virus lesions
on the back, thigh, or buttock?
Cesarean delivery is not recommended for women with
nongenital lesions. These lesions may be covered with an
occlusive dressing, and the patient then can give birth
vaginally. However, women with lesions elsewhere also
may have cervical lesions and should be examined.
The risk of transmission among women with recurrent HSV at the time of labor is low, estimated to be less
than 1% (18, 62). As with other women with recurrent
herpes, the low risk is probably related to preexisting
maternal type-specific antibodies. Thus, the risk of
neonatal HSV associated with vaginal delivery in a
woman with recurrent HSV and nongenital lesions would
appear to be very low.
995
In a patient with active herpes simplex virus

genital infection and ruptured membranes,
should cesarean delivery be performed to
prevent perinatal transmission?
In patients with active HSV infection and ruptured membranes at or near term, a cesarean delivery should be
performed as soon as the necessary personnel and equipment can be readied. There is no evidence that there is a
duration of rupture of membranes beyond which the
fetus does not benefit from cesarean delivery (63). At
any time after rupture of membranes, cesarean delivery
is recommended.
How should a woman with active herpes simplex virus and preterm premature rupture of
membranes be managed?
In a patient with preterm premature rupture of membranes
and active HSV, the risks of prematurity should be
weighed against the risk of neonatal HSV disease in considering expectant management. In pregnancies remote
from term, especially in women with recurrent disease,
there is increasing support for continuing the pregnancy to
gain benefit from time and use of corticosteroids (64, 65).
There is no consensus on the gestational age at which the
risks of prematurity outweigh the risks of HSV. When
expectant management is elected, treatment with an antiviral agent may be considered. The decision to use corticosteroids should be based on the balance between the risk
of pulmonary immaturity and the risk of neonatal herpes.
Are invasive procedures contraindicated in

pregnant women with herpes simplex virus?
In women with a history of recurrent HSV, transabdominal
invasive procedures, such as chorionic villus sampling,
amniocentesis, and percutaneous umbilical cord blood
sampling, may be performed even when genital lesions are
present. Because cervical shedding is associated with genital recurrences, it seems reasonable to delay transcervical
procedures until lesions appear to have resolved.
Invasive monitoring, such as fetal scalp electrodes, is
a risk factor for transmission of HSV, increasing the risk
of neonatal infection approximately six times compared
with externally monitored patients (15). However, if there
are indications for fetal scalp monitoring, it is reasonable
in a woman who has a history of recurrent HSV and no
active lesions.
Should women with active herpes simplex

virus breastfeed or handle their infants?
Unless there is a lesion on the breast, breastfeeding is not
contraindicated. To prevent postnatal transmission,
996
mothers with herpetic lesions on any part of the body

should be advised to take special consideration of handwashing. Postnatally acquired disease can be as lethal as
that acquired during delivery. Oropharyngeal or cutaneous lesions can be an effective source of virus for
transmission to the newborn. Because the herpes virus is
transmitted through direct contact (eg, hand-to-mouth),
neonatal infection may be acquired from family members other than the mother and from sites other than the
genital tract (66, 67). Most strains of HSV responsible
for nosocomial neonatal disease are HSV-1 rather than
HSV-2. Mothers with active lesions should use caution
when handling their babies.
Valacyclovir appears to be safe for breastfeeding
mothers. Although acyclovir was found in the breast milk
in concentrations that were higher than the maternal
serum, the amount of acyclovir in the breast milk was only
2% of that used for therapeutic doses in neonates (68).
Summary of
Recommendations and
Conclusions
Women with active recurrent genital herpes should
be offered suppressive viral therapy at or beyond 36
weeks of gestation.
Cesarean delivery is indicated in women with active
genital lesions or prodromal symptoms, such as
vulvar pain or burning at delivery, because these
symptoms may indicate an impending outbreak.

are based primarily on consensus and expert
opinion (Level C):
In women with premature rupture of membranes,
there is no consensus on the gestational age at which
the risks of prematurity outweigh the risks of HSV.
Cesarean delivery is not recommended for women
with a history of HSV infection but no active genital disease during labor.
Routine antepartum genital HSV cultures in asymptomatic patients with recurrent disease are not recommended.
Routine HSV screening of pregnant women is not
recommended
Measure
The percentage of pregnant women who have been asked
about their history of herpes
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999

Force:
I

type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Management of herpes in pregnancy. ACOG Practice Bulletin No. 82.
2007;109:148998.
1000
ACOG
PRACTICE
BULLETIN
(Replaces Educational Bulletin Number 248, July 1998)

of Neil S. Silverman, MD. The
of practice.
Reaffirmed 2009
Viral Hepatitis in
Pregnancy
Viral hepatitis is one of the most common and potentially serious infections that
can occur in pregnant women. Six forms of viral hepatitis have now been identified, two of which, hepatitis A and hepatitis B, can be prevented effectively
through vaccination. The purpose of this document is to describe the specific
subtypes of hepatitis, their implications during pregnancy, the risk of perinatal
transmission, and issues related to both treatment and prevention of infection.
Background
Hepatitis A
The hepatitis A virus is a small (27 nm) RNA virus that produces either symptomatic or asymptomatic infection in humans after an average incubation period of 28 days (range, 1550 days). Hepatitis A virus (HAV) replicates within
the liver and is excreted in bile, with highest viral concentrations late in the incubation period in the feces; this represents the window of greatest infectivity.
In the prevacccine era, approximately one third of cases of acute hepatitis
in the United States were attributable to HAV infection. Person-to-person transmission through fecaloral contamination is the primary means of HAV infection in the United States, most often in household and extended family settings
(1). Because children usually have asymptomatic or unrecognized infection,
they can play a key role in infecting others. Studies have demonstrated that up
to 40% of adults without an identifiable source of infection had close contact
with a child younger than 6 years (2), which underscores the importance of primary HAV prevention within families of women of reproductive age.
Poor hygiene and poor sanitation can result in common-source outbreaks
of HAV infection. Food also can be contaminated after cooking, as commonly
occurs in outbreaks associated with HAV-infected food handlers whose hygiene
practices are substandard (3). Depending on conditions, HAV can be stable in
PRACTICE BULLETINS
the environment for months. Heating foods to above

185F for 1 minute or disinfecting surfaces with a dilute
solution of household bleach can inactivate the virus.
Serious complications of HAV infection are uncommon; the overall casefatality ratio among reported cases
is less than 1%, but reaches 2% among adults older than
50 years. Hepatitis A does not lead to chronic infection,
although 1015% of symptomatic individuals can have
prolonged or relapsing disease lasting up to 6 months (4).
Hepatitis B
Hepatitis B is caused by a small DNA virus. The intact
virus is termed the Dane particle. Hepatitis B virus
(HBV) contains three principal antigens. Hepatitis B surface antigen (HBsAg) is present on the surface of the
virus and circulates freely in the serum in spherical and
filamentous forms. The middle portion of the Dane particle contains hepatitis B core antigen (HBcAg). The core
antigen is present only in hepatocytes and does not circulate in the serum. Hepatitis B e antigen (HBeAg) is encoded by the same portion of the viral genome that codes for
the core antigen. The presence of HBeAg indicates an
extremely high viral inoculum and active virus replication.
Hepatitis B virus is transmitted by parenteral and
sexual contact. Although HBsAg has been detected in a
variety of body fluids, only serum, semen, and saliva
have been proved to be infectious (5, 6). The virus is relatively stable in the environment, can be viable for up to
7 days on surfaces at room temperature, and may cause
transmission via surfaces at concentrations of only
102103 virions per milliliter, even if there is no visible
blood (7). Individuals at greatest risk of becoming infected are those who have multiple sexual partners, inject
drugs percutaneously, or have sexual partners who
engage in these risk-taking behaviors. Sexual contact is
an efficient mechanism for spreading the virus.
Approximately 25% of the frequent sexual contacts of
infected individuals will themselves become infected (8).
All blood donors are screened routinely for HBsAg.
Transmission of HBV by transfusion of blood or blood
products is rare as a result of both donor screening and
blood banking viral inactivation procedures. Recently, it
has been estimated that the risk of transfusion-attributable HBV infection is 1 per 137,000 transfused units of
screened blood (9, 10). In contrast, however, HBV transmission has been reported via patient-to-patient use of
institution-based fingerstick devices for blood sampling,
such as blood glucose meters (11). Appropriate attention
to hygiene and universal precautions is critical within
households and institutions using such devices (12).
The mortality associated with acute hepatitis B is
approximately 1%. Of adult patients who become infected, 8590% experience complete resolution of their
1001
physical findings and develop protective levels of the

antibody. The other 1015% of patients become chronically infected. They continue to have detectable serum
levels of HBsAg but are asymptomatic, and most have no
biochemical evidence of hepatic dysfunction. In a small
subgroup (1530%) of those chronically infected, viral
replication continues and is manifested by persistence of
the e antigen and active viral DNA synthesis. These individuals risk subsequent development of chronic or persistent hepatitis and cirrhosis, and approximately
4,0005,000 die annually of complications of chronic
liver disease, including hepatocellular carcinoma (12, 13).
Hepatitis C
At least six distinct hepatitis C virus (HCV) genotypes
have been identified, with broad geographic variation and
widely ranging prognoses for both disease progression
and response to therapy (14). Among presumably lowrisk volunteer blood donors in developed countries, rates
of HCV seropositivity of 0.51.4% have been reported.
Groups at higher risk for HCV infection include patients
in sexually transmitted disease (STD) clinics (seroprevalence, 1.56.2%), hemophiliacs (6486%), and intravenous drug users (5686%) (1517).
The principal risk factors for HCV transmission have
been transfusion of blood products and use of intravenous drugs. At least 90% of cases of posttransfusion
hepatitis have been traceable to HCV, usually within
510 weeks of the transfusion. Mass screening of the
blood supply for HCV has markedly decreased the risk
of HCV infection to less than 1 per 1,000,000 screened
units of blood. Because the risk of HCV infection from
blood transfusions has decreased, the number of HCV
infections attributable to drug use has significantly
increased, from 20% to at least 60% (18).
Acute HCV infection occurs after an incubation
period of 3060 days. Asymptomatic infection occurs in
75% of patients, and at least 50% of infected individuals
progress to chronic infection, regardless of the mode of
acquisition or severity of initial infection. Chronic HCV
infection also has been associated with an increased risk
of developing both B-cell lymphomas and cryoglobulinemia. Although at least 20% of chronic HCV infections
lead to chronic active hepatitis or cirrhosis, whether a
link to hepatocellular carcinoma exists is controversial
and may vary by geographic region (19). Hepatitis C
and HIV share common transmission routes, and concomitant infection has been reported to accelerate the
progression and severity of hepatic injury (18).
Hepatitis D
Hepatitis D virus (HDV) is an incomplete viral particle
that causes disease only in the presence of HBV, from
1002
which it acquires a viral envelope consisting entirely of

excess HBsAg produced by HBV. Infection with HDV
occurs either simultaneously with HBV infection (coinfection) or may be acquired after HBV (superinfection).
Transmission is primarily through blood; approximately
2025% of chronic HBV carriers also have evidence of
HDV infection (20, 21).
Chronic hepatitis D produces severe disease more
often than other forms of chronic hepatitis. Of patients
with chronic hepatitis D, 7080% ultimately develop cirrhosis and portal hypertension, 15% of whom develop an
unusually rapid progression to cirrhosis within 2 years of
the initial onset of acute illness. Mortality as a result of
hepatic failure approaches 25%. In contrast, only
1530% of patients with chronic hepatitis B virus infection develop cirrhosis and portal hypertension, and the
disease progression typically is much slower (21).
Hepatitis E
The epidemiologic features of hepatitis E virus (HEV) are
similar to those of hepatitis A. The disease has been
reported only rarely in the United States, and the highest
rates of infection occur in regions of the developing world
where inadequate sanitation promotes transmission of the
virus. Hepatitis E is primarily a waterborne disease; epidemics have been reported in areas where fecal contamination of drinking water is common. The ingestion of raw
or undercooked shellfish also has been a source of sporadic cases of HEV infection in endemic areas (22).
In general, HEV produces a self-limited viral infection followed by recovery; the incubation period is 38
weeks, with a mean of 40 days. Among pregnant women,
however, a higher risk of fulminant hepatitis E has been
reported in a number of small series, with maternal mortality rates as high as 20% after infection in the third trimester (22, 23). In one report, HEV infection in women
coinfected with HIV resulted in a 100% mortality rate
(24).
Vaccinations
Hepatitis A
The hepatitis A vaccination is indicated for adults in
groups at increased risk for hepatitis A or its adverse
consequences (25). Medical indications include persons
with chronic liver disease and persons who receive clotting factor concentrates. Behavioral risk populations are
men who have sex with men and persons who use illegal
drugs. Occupational risks include persons working with
HAV-infected primates or with HAV in a research laboratory setting. Other indications are persons traveling to
or working in countries that have high or intermediate
endemicity of hepatitis A (a list of countries is available
at http://www.cdc.gov/travel/diseases.htm) and any person who would like to obtain immunity.

The hepatitis A vaccine is available as both a singleantigen vaccine and as a combination vaccine (containing both HAV and HBV antigens). Both vaccines use
inactivated HAV, and the HBV component is a recombinant protein nonviral antigen. There are two HAV vaccines available that are given in two doses, either 612
months apart or 618 months apart. The combination
vaccine is given in three doses at 0, 1, and 6 months. The
HAV vaccine is 94100% immunogenic after the first
dose (26) and is highly effective in both reducing disease
incidence and interrupting ongoing epidemics (27, 28).
Immune globulin remains available for postexposure
prophylaxis, although primary vaccine-based prevention
is preferred. Hepatitis A vaccination should still be
administered in addition to immune globulin even in the
context of postexposure prevention. Studies of HAV vaccine alone have shown protection against infection in a
limited series (29), although no trials comparing the vaccine with immune globulin have been conducted to date.
This strategy of administering HAV vaccine alone for
postexposure prophylaxis in individuals younger than 40
years has recently been proposed by some experts.
Hepatitis B
All individuals with risk factors, particularly health care
workers, should be vaccinated against HBV infection.
Other groups at increased risk include hemodialysis
patients, injection drug users, persons with more than
one sexual partner during the past 3 months or in whom
an STD has been diagnosed recently, clients and staff in
centers for the developmentally delayed, and international travelers who will be in high or intermediate
prevalence areas for HBV infection (list of countries at
http://www.cdc.gov/travel/yellowBookCh4-HepB.
aspx#333) (30).
In general, prevaccination testing is not recommended. It may be cost-effective to screen for the antibody to HBV in women who belong to groups with a
high risk of infection in order to avoid vaccinating adults
who have had or currently have hepatitis B infection. In
most other low-risk groups, antibody screening before
vaccination probably is not indicated.
Two single antigen vaccines for hepatitis B virus have
been developed (Table 1). Currently available vaccines are
prepared from yeast cultures by using recombinant DNA
technology. They are highly immunogenic and result in
seroconversion in more than 95% of recipients. There is
one combination vaccine available for adults at risk of both
hepatitis A and B virus infection (Twinrix); it contains
recombinant HBsAg and inactivated hepatitis A virus. The
dosage of the hepatitis A component in the combination
PRACTICE BULLETINS
1003
Table 1. Recommended Dosages and Schedules of Single-Antigen Hepatitis B Vaccines

Vaccine
Engerix-B
(GlaxoSmithKline)
Recombivax HB
(Merck & Co.)
Age Group
Dose
Volume
No. of Doses
Schedule*
019 y
10 mcg
0.5 mL
Infants: birth, age 14, 618 mo

Alternative for older children: 0, 12, 4 mo
20 y and older
20 mcg
1.0 mL
0, 1, 6 mo
019 y
5 mcg
0.5 mL
Infants: birth, age 14, 618 mo

Alternative for older children: 0, 12, 4 mo
1115 y
10 mcg
1.0 mL
0, 46 mo
20 y and older
10 mcg
1.0 mL
0, 1, 6 mo
*The schedule for hepatitis B vaccination is flexible and varies. Consult the Advisory Committee on Immunization Practices (ACIP) statements on hepatitis B (12/2005
and 12/2006) or the package insert for details.
For adult dialysis patients, the Engerix-B dose required is 40 mcg/2.0 mL (use the adult 20 mcg/mL formulation) on a schedule of 0, 1, 2, and 6 months.
For Recombivax HB, a special formulation for dialysis patients is available. The dose is 40 mcg/1.0 mL and it is given on a schedule of 0, 1, and 6 months.
Immunization Action Coalition. Hepatitis A & B vaccines: be sure your patient gets the correct dose! St. Paul (MN): IAC; 2005. Available at:
http://www.immunize.org/catg.d/2081ab.pdf. Retrieved July 20, 2007.
vaccine is lower than that in the single-antigen hepatitis A

vaccine, allowing it to be administered in a three-dose
schedule (0, 1, and 6 months) instead of the two-dose
schedule used for the single-antigen vaccine. An accelerated schedule (0, 7, 2130 days, followed by a booster dose
at 12 months) is an option when a rapid immune response
is needed for an occupational or behavioral imminent risk
for hepatitis A and B or for international travel (31).
The vaccine should be administered into the deltoid
muscle. Intragluteal and intradermal injections result in
lower rates of seroconversion. Pregnancy is not a contraindication to vaccination. In fact, susceptible pregnant
women who are at risk for HBV infection should be
specifically targeted for vaccination (32).
Unvaccinated individuals or persons known not to
have responded to a complete hepatitis B vaccine series
and who have been exposed to HBV through a discrete,
identifiable exposure to blood or to body fluids that contain blood should receive passive immunization with
hepatitis B immune globulin (HBIG) and start the immunization series. Immunoprophylaxis should be administered as soon as possible after exposure (preferably within
24 hours). For sexual exposures, HBIG should not be
administered more than 14 days after exposure (8).

Recommendations
What are the clinical manifestations of
hepatitis?
The usual subjective symptoms in patients with acute
viral hepatitis are malaise, fatigue, anorexia, nausea, and
right upper quadrant or epigastric pain. Typical physical

findings include jaundice, upper abdominal tenderness,
and hepatomegaly, although many cases of hepatitis are
anicteric. The patients urine usually is darkened, and the
stool may be gray or acholic. In cases of fulminant
hepatitis, signs of coagulopathy and encephalopathy may
be present.
In patients with hepatitis A or E, clinical manifestations usually are related temporally to recent travel to an
endemic area or exposure to an infected person.
Similarly, infections with hepatitis B, C, or D typically
ensue after parenteral exposure to contaminated blood or
sexual contact with an infected partner. The evolution of
acute clinical illness in patients with hepatitis D often follows a biphasic course. In the initial phase of infection,
patients with hepatitis D are indistinguishable from individuals with acute hepatitis B. Two to four weeks after
apparent resolution of symptoms, patients typically have
a relapse, which usually is of a milder nature and is associated with a second episode of elevation in serum
transaminases. At this time serologic assay results for
hepatitis D virus usually are positive.
As noted previously, in some patients with acute
hepatitis B, C, or D, symptomatic infection resolves, and
some become chronic carriers of viral infection.
Although most viral hepatitis carriers initially are asymptomatic, up to one third subsequently develop chronic
active or persistent hepatitis or cirrhosis. Once cirrhosis
ensues, patients have the typical signs of end-stage liver
disease, such as jaundice, muscle wasting, ascites, spider
angioma, palmar erythema, and, ultimately, hepatic
encephalopathy. Hepatitis C is the leading cause of
chronic liver disease in the United States, whereas hepatitis B virus is the leading cause worldwide (13, 18).
1004
may be present (18). Although liver biopsy is rarely indicated in pregnancy, viral hepatitis may be distinguished
histologically from other causes of hepatic injury by its
characteristic pattern of extensive hepatocellular injury
and inflammatory infiltrate. Initial evaluation of the
patient with suspected viral hepatitis should include specific tests.
How is acute hepatitis managed in pregnant

women?
Patients with acute hepatitis should be hospitalized if
they have encephalopathy, coagulopathy, or severe debilitation. Nutritional needs should be addressed within the
context of the severity of the disease. Fluid and electrolyte abnormalities should be corrected. If a coagulopathy is present, administration of erythrocytes, platelets,
and clotting factors such as fresh frozen plasma or cryoprecipitate may be necessary. Activity should be limited,
and the patient should be protected from upper abdominal trauma (32).
Women who are less severely ill may be treated as
outpatients. They should reduce their level of activity,
avoid upper abdominal trauma, and maintain good nutrition. Infected women also should avoid intimate contact
with household members and sexual partners until these
individuals receive appropriate prophylaxis (32).
Specific Tests
If hepatitis is suspected based on the initial evaluation
and general tests, the type of virus is determined through
laboratory analysis.
Hepatitis A
The diagnosis of acute hepatitis A is confirmed by detecting specific immunoglobulin M (IgM) antibodies to the
virus. A chronic carrier state for this infection does not
exist, but immunoglobulin G (IgG) antibodies to hepatitis A virus will persist in patients with either previous
infection or prior vaccination (32, 33).
General Tests
Coincident with the onset of symptoms, patients with
acute hepatitis usually have a marked increase in the
serum concentration of alanine aminotransferase (ALT,
previously known as serum glutamate pyruvate transaminase) and aspartate aminotransferase (AST, previously
known as serum glutamic oxaloacetic transaminase). In
addition, the serum bilirubin concentration often is
increased. In patients who are moderately to severely ill,
coagulation abnormalities and hyperammonemia also
Hepatitis B
The appearance of HBsAg predates clinical symptoms by
4 weeks on average and remains detectable for 16
weeks (Fig. 1). The chronic carrier state for HBV is
defined by persistence of HBsAg and the absence of
hepatitis B surface IgG antibody (anti-HBs), which is the
protective antibody that defines immunity (Fig. 2). Titers
of anti-HBs (in noncarriers) increase slowly during clin-
Symptoms
HBeAg
Anti-HBe
Titer
Total anti-HBc
IgM anti-HBc
Anti-HBs
HBsAg
12
16
20
24
28
32
36
52
100
Weeks after exposure

Figure 1. Typical serologic course of acute hepatitis B virus infection with recovery. (Centers for Disease Control and Prevention slide
set adapted from Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization
Practices [ACIP] part II: immunization of adults. MMWR Recomm Rep 2006;55(RR-16):133; quiz CE14.)
PRACTICE BULLETINS
ical recovery and continue to increase for up to 1012

months after HBsAg has been cleared. In most patients
with self-limited acute HBV infection, anti-HBs and
HBsAg do not coexist detectably in serum, and anti-HBs
is seen only after HBsAg has been cleared. The chronic
carrier state usually can be predicted by HBsAg seropositivity for more than 20 weeks (8, 13, 32, 33).
A serologic window has been described for HBV
infection when, despite clinical symptoms, HBsAg is
clearing and undetectable but anti-HBs is not yet
detectable either. In this period, HBV infection can still
be diagnosed by detection of hepatitis B core IgG antibody (anti-HBc), which appears 35 weeks after
HBsAg. Hepatitis B core IgG antibody is present only
in the context of natural HBV infection and is not a protective antibody. It does not distinguish acute resolving
infections from the chronic infection state, which is
done only by persistence or clearance of HBsAg. An
IgM antibody to the hepatitis B core antigen (IgM antiHBc) appears during acute or after recent HBV infection and is present for approximately 6 months. In
contrast, only anti-HBs becomes detectable in serum of
vaccinated individuals. Therefore, the detection of antiHBs in the absence of HBsAg and anti-HBc distinguishes
vaccine-mediated immunity from natural infection-based
immunity (where anti-HBc and anti-HBs are both present without HBsAg). Hepatitis B core antigen is not
detectable outside of research laboratory assays, and
tests for it should not be ordered as part
of a hepatitis B panel (8, 13, 32, 33). With the variety
1005
of HBV-specific antigens and antibodies identified,

interpretation of hepatitis B serologies is complex
(Table 2).
Hepatitis C
The diagnosis of hepatitis C is confirmed by the identification of the antibody to hepatitis C virus, via a second- or third-generation enzyme immunoassay (ELISA)
(34). The antibody may not be present until 610 weeks
after the onset of clinical illness. Hepatitis C viral RNA
can be detected by polymerase chain reaction assay of
serum soon after infection, as well as in chronic disease.
These other more specific tests for HCV, including
HCV-specific RNA testing and genotyping, are available
to define the specificity of infection, given that there are
small but real false-positive rates associated with antibody testing or screening that vary with prevalence or
risk of the disease in the screened populations. Such
DNA-based specific testing usually is best interpreted by
specialists trained in the treatment of hepatitis, to whom
patients with positive serologic antibody test results
should be referred (34). A reference table for the interpretation of these tests is available from the Centers for
Disease Control and Prevention (Table 3).
Hepatitis D
Laboratory tests that may be used to confirm the diagnosis of acute hepatitis D are the detection of D antigen
in hepatic tissue or serum and the identification of the
IgM antibody to hepatitis D virus. Hepatitis D antigene-
Acute
(6 months)
Chronic
(Years)
HBeAg
Anti-HBe
HBsAg
Titer
Total anti-HBc
IgM anti-HBc
4 8 12 16 20 24 28 32 36
52
Weeks after exposure

Figure 2. Progression to chronic hepatitis B virus infection: typical serologic course. (Centers for Disease Control and Prevention slide
set adapted from Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization
Practices (ACIP) part II: immunization of adults. MMWR Recomm Rep 2006;55(RR-16):133; quiz CE1-4.
1006
Table 2. Interpretation of Hepatitis B Virus (HBV) Testing

Test
Results
Interpretation
HBsAg
Anti-HBc
Anti-HBs
Negative
Negative
Negative
Susceptible
HBsAg
Anti-HBc
Anti-HBs
Negative
Positive
Positive
Immune due to natural infection
HBsAg
Anti-HBc
Anti-HBs
Negative
Negative
Positive
Immune due to hepatitis B vaccination*
HBsAg
Anti-HBc
IgM anti-HBc
Anti-HBs
Positive
Positive
Positive
Negative
Acutely infected
HBsAg
Anti-HBc
IgM anti-HBc
Anti-HBs
Positive
Positive
Negative
Negative
Chronically infected
HBsAg
Anti-HBc
Anti-HBs
Negative
Positive
Negative
Four interpretations possible
*Antibody response (anti-HBs) can be measured quantitatively or qualitatively. A protective antibody response is reported quantitatively as
10 or more milli-international units (10 mIU/mL or less) or qualitatively as positive. Postvaccination testing should be completed 12
months after the third vaccine dose for results to be meaningful.
Four interpretations:
Might be recovering from acute HBV infection
Might be distantly immune and test not sensitive enough to detect very low level of anti-HBs in serum
Might be susceptible with a false-positive anti-HBc
Might be undetectable level of HBsAg present in the serum and the person is actually chronically infected
Definitions
Hepatitis B surface antigen (HBsAg): A serologic marker on the surface of HBV. It can be detected in high levels in serum during acute or
chronic hepatitis. The presence of HBsAg indicates that the person is infectious. The body normally produces antibodies to HBsAg as part
of the normal immune response to infection.
Hepatitis B surface antibody (anti-HBs): The presence of anti-HBs generally is interpreted as indicating recovery and immunity from HBV
infection. Anti-HBs also develops in a person who has been successfully vaccinated against hepatitis B.
Total hepatitis B core antibody (anti-HBc): Appears at the onset of symptoms in acute hepatitis B and persists for life. The presence of antiHBc indicates previous or ongoing infection with hepatitis B virus (HBV) in an undefined time frame.
IgM antibody to hepatitis B core antigen (IgM anti-HBc): This antibody appears during acute or recent HBV infection and is present for
approximately 6 months.
Centers for Disease Control and Prevention. Interpretation of the hepatitis B panel. Atlanta (GA): CDC; 2006. Available at: http://www.
cdc.gov/ncidod/diseases/hepatitis/b/Bserology.htm. Retrieved July 11, 2007.
mia usually persists in patients with chronic hepatitis D

despite the appearance of the IgG antibody to the virus.
Thus, as in hepatitis C and HIV infection, viremia and
end-organ damage can continue despite the presence of
the antibody to the virus (35).
Hepatitis E
The diagnosis of infection with hepatitis E is documented
by the presence of virus-specific antibodies in individuals
with risk factors. The primary risk factor is travel exposure (33).
How are pregnant patients who are presumed

chronic hepatitis carriers treated?
Persons with diagnosed chronic HBV and HCV infection should be referred for evaluation to a physician
experienced in the management of chronic liver disease.
Diagnosis in the context of pregnancy-specific screening
opens the opportunity for individuals who might otherwise have not ever been tested to receive appropriate
subspecialty care for counseling and targeted treatment,
usually after delivery. Women who are chronic carriers
of HBV or HCV should inform sexual, household, and
PRACTICE BULLETINS
1007
Table 3. Interpretation of Hepatitis C Virus (HCV) Test Results

If HCV Test Result Is:
Anti-HCV Screening
Test Result*
Interpretation
Anti-HCV Supplemental Test Result

RIBA
HCV RNA
Anti-HCV Result
HCV Infection
Action
Additional Testing
or Evaluation
Negative
Not needed
Not needed
Negative
None
No
Positive
Not done
Not done
Not known
Not known
Supplemental anti-HCV
(RIBA) or HCV RNA
Positive
Not done
Negative
Not known
Not known
Supplemental anti-HCV
(RIBA)
Positive
(high s/co ratios)
Not done
Not done
Positive
Past/current
Evaluate for chronic

infection and liver
disease
Positive
Negative
Not needed
Negative
None
No
Positive
Positive
Not done
Positive
Past/current

infection and liver
disease
Positive
Positive
Negative
Positive
Past/current
Repeat HCV RNA
Positive
Positive/not done
Positive
Positive
Current

infection and liver
disease
Positive
Indeterminate
Not done
Indeterminate
Not known
Test for HCV RNA or

repeat anti-HCV testing
Positive
Indeterminate
Positive
Indeterminate
Current

infection and liver
disease
Positive
Indeterminate
Negative
Negative
None
No
*EIA, enzyme immunoassay or CIA, enhanced chemiluminescence immunoassay
Recombinant immunoblot assay, a more specific anti-HCV assay viremia.
Samples with high signal-to-cutoff (s/co) ratios usually more than 95%) confirm positive, but supplemental serologic testing was not performed. Less than 5 of every
100 test results might represent false-positives; more specific testing should be requested, if indicated.
Single negative HCV RNA result cannot determine infection status; patients might have intermittent viremia.
Centers for Disease Control and Prevention. Reference for interpretation of HCV test results. Atlanta (GA): CDC; 2006. Available at: http://www.cdc.gov/ncidod/
diseases/hepatitis/resource/PDFs/hcv_graph.pdf. Retrieved July 11, 2007.
needle-sharing contacts of their status and learn about

and use methods to prevent or reduce the risk of transmission of infections to others. All HBsAg-positive laboratory results should be reported to the state or local
health department in accordance with state requirements
for reporting of chronic HBV infection (8, 13).
How can the risk of vertical transmission of

HBV be reduced?
Because hepatitis B virus is highly pathogenic and infectious, perinatal transmission of infection represents the
single largest cause of chronically infected individuals
worldwide. Because risk-factor-based prenatal screening
protocols have been shown to detect at most 60% of
women who are HBV carriers, routine prenatal screening of all pregnant women with HBsAg is recommended
(13). Approximately 1020% of women who are seropositive for HBsAg alone transmit the virus to their
neonates in the absence of neonatal immunoprophylaxis.
In women who are seropositive for both HBsAg and
HBeAg, the frequency of vertical transmission increases
to approximately 90% without neonatal prophylaxis. For
adult-acquired HBV infection, the risk of chronic infection and its sequelae is only 510%. In contrast, HBV
infection acquired perinatally carries an 8595% risk of
persistence and chronic infection, with a 2530% lifetime risk of serious or fatal liver disease.
In patients with acute hepatitis B, the frequency of
vertical transmission also depends on the time during
gestation that maternal infection occurs. When it occurs
in the first trimester, up to 10% of neonates will be seropositive for HBsAg. In women acutely infected in the
third trimester, 8090% of offspring will be infected (13).
1008
The Centers for Disease Control and Prevention recommends universal active immunization of all infants
born in the United States. The immunization schedule
for infants of women who have been screened and have
negative results should be started preferably before discharge, but by no later than 2 months of age. Preterm
infants weighing less than 2,000 g and born to women
who are HBsAg negative should have their first vaccine
dose delayed until 1 month after birth or hospital discharge (13).
Current guidelines stipulate that infants of women
who are HBsAg positive or whose status is unknown at
the time of delivery also should receive both HBIG and
hepatitis B vaccine within 12 hours of birth given simultaneously at different sites intramuscularly. It should
then be followed by two more injections of hepatitis B
vaccine in the first 6 months of life. The physician
responsible for the care of a newborn delivered of a
woman with chronic hepatitis B should be informed of
her carrier status so that the appropriate doses of hepatitis B vaccine and HBIG can be given as soon as possible
after delivery (13).
Neonatal immunoprophylaxis will not prevent HBV
infection in newborns who are already infected in utero;
therefore, current research is focusing on the potential
efficacy of antepartum treatment of HBV-infected
women to lower the risk of such infection, particularly in
women who have risk factors for transmission (3639).
In addition, women who did not receive prenatal care
will have unknown HBV status at the time of delivery,
and these women have been shown to have significantly
higher rates of being chronic HBV carriers than women
enrolled in prenatal care (40). The combination of passive and active immunization has been particularly effective (8595% efficacy) in reducing the frequency of perinatal transmission of hepatitis B virus.
How can transmission of other forms of

hepatitis be prevented?
Hepatitis C virus seroprevalence rates of 0.66.6% have
been reported in study cohorts of pregnant women
worldwide (4144). Vertical HCV transmission rates of
28% have been demonstrated, with maternal viremia
(detectable presence of HCV RNA in blood) an almost
uniform prerequisite for transmission (35, 4547). In
pregnancies among HCV-infected mothers who were
HCV RNA negative, vertical transmission was rare.
Maternal coinfection with HIV significantly increases
the risk of vertical HCV transmission to as much as
44% (45, 47). In a recent cohort study, risk factors
associated with an increased rate of vertical HCV transmission to include higher maternal HCV viral titer, pro-
longed membrane rupture during labor (6 hours or

longer), and use of internal fetal monitoring during
labor were reported (48). If duration of membrane rupture and internal fetal monitoring are confirmed to be
associated with transmission in further investigations,
interventions may be possible to decrease the risk of
transmission.
Currently, no preventive measures are available to
lower the risk of vertical HCV infection of neonates as
there are for HBV. Routine prenatal HCV screening is
not recommended; however, women with significant risk
factors for infection (see the box) should be offered antibody screening. Testing for HCV RNA should not be
used for screening purposes.
Vertical transmission of hepatitis D virus has been
documented. Transmission is uncommon, however,
Risk Factors Warranting Hepatitis C

Screening: CDC Guidelines
Individuals who should be screened routinely:
1. Persons who ever injected illegal drugs (even once)
2. Persons notified that they received blood products
before 1987 or from a donor who later tested positive for hepatitis C virus (HCV)
3. Recipients of transfusions or organ transplants, particularly if received before July 1992
4. Persons ever on long-term hemodialysis
5. Persons with persistently elevated alanine aminotransferase (ALT) or other evidence of liver disease
6. Persons seeking evaluation or care for a sexually
transmitted infection, including human immunodeficiency virus
Individuals for whom routine testing is of uncertain
need:
1. Recipients of tissue transplants (eg, cornea, skin,
sperm, ova)
2. Users of intranasal cocaine or other illegal noninjected drugs
3. Persons with a history of tattooing or body piercing
4. Persons with a history of sexually transmitted diseases or multiple sexual partners
5. Long-term steady sex partner of an HCV-infected
individual
Centers for Disease Control and Prevention. Recommendations for
prevention and control of hepatitis C virus (HCV) infection and HCVrelated chronic disease. MMWR 1998;47(RR-19):133 and Centers
for Disease Control and Prevention. Sexually transmitted diseases
treatment guidelines, 2006. MMWR 2006;55(RR-11):194.
PRACTICE BULLETINS
because the measures used to prevent perinatal infection

with hepatitis B virus are almost uniformly effective in
preventing infection by hepatitis D. Vertical transmission of HEV has been reported, but information is
limited.
Are there special considerations for intrapartum care in the context of maternal
hepatitis infection?
Between 85% and 95% of cases of perinatal transmission of HBV occur as a consequence of intrapartum
exposure of the infant to infected blood and genital tract
secretions. The remaining cases result from hematogenous transplacental dissemination and close postnatal
contact between the infant and the infected parent. Risk
factors for intrauterine HBV infection have been reported to include maternal HBeAg seropositivity, history of
threatened preterm labor, higher HBsAg and HBV DNA
titers, and the presence of HBV DNA in villous capillary
endothelial cells (49). Adequate data regarding the risk
of transmission with operative vaginal delivery or internal fetal monitoring are not available to make recommendations.
The route of delivery has not been shown to influence the risk of vertical HCV transmission (35, 50).
Cesarean delivery should be performed in HCV-infected
women only for obstetric indications.
What is the safety of invasive prenatal

diagnostic procedures for patients with
chronic hepatitis?
The risk of transmission through amniocentesis appears
to be low for women who are chronically infected with
hepatitis B or hepatitis C, although the number of
exposed cases in the literature is small. Of the 115
women reported to be positive for hepatitis B surfaceantigen who underwent second-trimester amniocentesis,
the rate of neonatal infection was no different than in
women who did not have an amniocentesis. All of the
infants received hepatitis B vaccination and immunoprophylaxis beginning at birth (5053). There is only
one series of 22 HCV-positive women reported in the
literature who underwent second-trimester amniocentesis. No infants in this series were found to be hepatitis
C RNA positive on postnatal testing. This group included one woman with hepatitis C RNA-positive amniotic
fluid (54). Data are insufficient in the literature to assess
the risk of chorionic villus sampling in these women or
to estimate the risk of fetal infection among women
with anterior placentas, those who are HBe antigen pos-
1009
itive, or those with high hepatitis B or hepatitis C viral

loads.
Because of the limited information regarding the risk
of invasive procedures in women chronically infected with
hepatitis B or hepatitis C, it would be prudent to discuss
noninvasive screening options with these women.
Is breastfeeding contraindicated for infants

of women with hepatitis?
In HAV-infected women, breastfeeding is permissible
with appropriate hygienic precautions. Although
immune globulin has been administered to newborns in
specific situations, the efficacy of this practice has not
been established. Breastfeeding is not contraindicated
for women who are HBsAg positive at the time of delivery. In addition, breastfeeding is not contraindicated in
women chronically infected with HBV if the infant
receives HBIG passive prophylaxis and vaccine active
prophylaxis (13). There are no data from which to make
a recommendation for HBeAg positive patients. In addition, breastfeeding has not been associated with an
increased risk of neonatal HCV infection (5659) and,
therefore, is not contraindicated in HCV-infected mothers
(58, 59).
Breastfeeding was not detrimental to newborns of
HEV-infected women in one recent series of 93 pregnancies. In this cohort, anti-HEV antibody and HEV
RNA were present in clostral samples, but at significantly lower levels than in maternal serum (60).
Immunotherapy
What is the role of specific immunotherapy
in the treatment of chronic hepatitis in
pregnancy?
Hepatitis A
Given the nonchronic and usually self-limited course of
symptomatic HAV infection, no specific antiviral agent
is used for its treatment. The hepatitis A vaccine is not
contraindicated during pregnancy. In populations that
have expected high rates of previous HAV infection, prevaccination testing may be considered to reduce costs by
not vaccinating persons who are already immune.
Prevaccination serologic testing may be cost-effective
for adults who were born in or lived for extended periods
in HAV-endemic areas; adults in certain population groups
(Native Americans, Alaska Natives, and Hispanics); and
adults in groups with a high prevalence of infection (eg,
injection drug users) (25).
Patients who have had close personal or sexual contact with an HAV-infected individual should receive
1010
postexposure prophylaxis if they have not been immunized. Immune globulin does not pose a risk to either a
pregnant woman or her fetus and should be administered
during pregnancy if indicated. Immune globulin provides
protection through passive antibody transfer. For postexposure prophylaxis, a single intramuscular dose of 0.02
mL/kg should be administered as soon as possible after
contact with the infected individual; this confers protection for up to 3 months at an 8090% efficacy level.
Administration of immune globulin more than 2 weeks
after exposure is not effective in preventing or ameliorating the severity of hepatitis A (25). The HAV vaccination
series also should be initiated in conjunction with postexposure administration of IgG. Although some studies
suggest that HAV vaccine alone also may prevent postexposure infection, no comparative trials have been conducted (29). This strategy of administering HAV
vaccine alone for postexposure prophylaxis in individuals
younger than 40 years has been proposed by some experts.
associated with an increased risk of transmission (44,

46). Recent advances in combination therapy for HCV
infection in nonpregnant adults have made sustained normalization of transaminase levels and clearance of HCV
RNA possible, even in individuals with HCV genotypes
that have a poorer prognosis (62). More recently, the
modification of interferon alfa-2a via a branched-chain
polyethylene glycol moiety has produced a compound,
peginterferon alfa-2a, with prolonged absorption, slower
clearance, and a longer half-life than standard interferon,
allowing once-weekly dosing (63). Randomized trials
have shown peginterferon to be superior to standard
interferon, either alone or in combination with ribavirin,
for the treatment of chronic HCV infection in adults
(64). Even though the use of ribavirin is contraindicated
in pregnancy, interferon has been used safely for the
treatment of T-cell leukemias during pregnancy (65, 66),
and its potential role as an anti-HCV therapy for both
maternal benefit and fetal and neonatal benefit warrants
further study.
Hepatitis B
No specific therapy is available for treatment of acute
HBV infection. Persons with chronic HBV infection
should be referred for evaluation to a physician experienced in the management of chronic liver disease.
Therapeutic agents have been approved by the FDA
for treatment of chronic HBV infection and can achieve
sustained suppression of HBV replication and remission
of liver disease in some persons (32). One of these
agents, the antiviral agent lamivudine, also has been
shown to be effective, in combination with other medications, for both the treatment of infections with the
human immunodeficiency virus (HIV) and for the interruption of vertical HIV transmission. Recent research
has demonstrated potential benefit from lamivudine
treatment in decreasing the risk of in utero HBV infection in women who were HBV carriers during the last
months of pregnancy (37, 39). Other investigators have
studied the use of hepatitis B immune globulin (HBIG)
administered to the mother toward the end of pregnancy
to achieve similar results (36, 38).
Hepatitis C
Optimal obstetric care of women infected with HCV is
limited by the lack of any available prenatal or postnatal
pharmacologic or immunologic measures to decrease the
risk of vertical transmission. Use of antiretroviral treatment to decrease both maternal viral titers and the risk of
neonatal HIV infections (61) raises the question of the
potential for comparable treatment of maternal HCV
infection, given that maternal HCV titer also has been
How can accidental or occupational

exposures to hepatitis virus be managed?
Accidental exposures are classified as occupational or
nonoccupational for management recommendations.
Guidelines for postexposure prophylaxis of occupational
exposures have been published by the Centers for
Disease Control and Prevention (13, 67, 68) and are
intended for use in settings in which postvaccination
testing is recommended for certain employees and in
which programs are available to implement testing and
follow-up algorithms. There are also specific guidelines
for care of persons with nonoccupational exposure to
HBV through exposure to blood or body fluids (13).
All health care workers who may be exposed to
blood or blood products should be vaccinated against
hepatitis B. The principal mechanism of transmission of
HBV from patient to health care workers is through
injury from a sharp object that is contaminated with
infected blood. Of all the bloodborne transmissible
viruses (including HCV and HIV), HBV exists in highest concentrations in blood. Hepatitis B requires much
smaller volumes for transmission and, therefore, can be
injected without hollow-bore needles or deep penetrating
injuries. The risk of infection per injury with HBVinfected blood is 2030%. Transmission of HBV also
has been reported by mucosal contamination from body
fluid splash exposures.
The risk of health care workers acquiring HCV
infection through workplace exposure to infected blood
is lower than the risk of acquiring HBV (30%) and high-
PRACTICE BULLETINS
er than the risk of acquiring HIV (0.3%) (68, 69).

Standard precautions such as not recapping used needles
has been shown to decrease the risk of workplace injury;
however, recent research has demonstrated that even
practitioners in high-risk subspecialties failed to routinely
practice standard universal precautions (69).
Measure
Summary of
Recommendations and
Conclusions
References

Routine prenatal screening of all pregnant women
by HBsAg testing is recommended.
Newborns born to hepatitis B carriers should receive
combined immunoprophylaxis consisting of HBIG
and hepatitis B vaccine within 12 hours of birth.
Hepatitis B infection is a preventable disease, and
all at-risk individuals, particularly health care workers, should be vaccinated. All infants should receive
the hepatitis B vaccine series as part of the recommended childhood immunization schedule.
Breastfeeding is not contraindicated in women with
HAV infection with appropriate hygienic precautions, in those chronically infected with hepatitis B
if the infant receives HBIG passive prophylaxis and
vaccine active prophylaxis, or in women with HCV
infection.
Routine prenatal HCV screening is not recommended; however, women with significant risk factors for
infection should be offered antibody screening.
Route of delivery has not been shown to influence
the risk of vertical HCV transmission, and cesarean
delivery should be reserved for obstetric indications
in women with HCV infection.
The risk of transmission of hepatitis B associated
with amniocentesis is low.
Susceptible pregnant women who are at risk for
hepatitis B infections should be specifically targeted
for vaccination.
1011
Percentage of women receiving prenatal care who are

screened for hepatitis B by hepatitis B surface antigen
testing
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RA, Schalm SW, Janssen HL. Lamivudine treatment during
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from a heterogeneous prenatal population. Am J Obstet
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Cunningham FG. Seroprevalence and risk factors for
hepatitis C virus antibody in pregnant women. Obstet
43. Choy Y, Gittens-Williams L, Apuzzio J, Skurnick J,
Zollicoffer C, McGovern PG. Risk factors for hepatitis C
infection among sexually transmitted disease-infected,
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2003;11:1918. (Level II-3)
44. Okamoto M, Nagata I, Murakami J, Kaji S, Iitsuka T,
Hoschika T, et al. Prospective reevaluation of risk factors
in mother-to-child transmission of hepatitis C virus: high
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45. Ferrero S, Lungaro P, Bruzzone BM, Gotta C, Bentivoglio
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46. Tajiri H, Miyoshi Y, Funada S, Etani Y, Abe J, Onodera T,
et al. Prospective study of mother-to-infant transmission
of hepatitis C virus. Pediatr Infect Dis J 2001;20:104.
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47. Granovsky MO, Minkoff HL, Tess BH, Waters D,
Hatzakis A, Devoid DE, et al. Hepatitis C virus infection
in the mothers and infants cohort study. Pediatrics
1998;102:3559. (Level II-2)
48. Mast EE, Hwang LY, Seto DS, Nolte FS, Nainan OV,
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hepatitis C virus (HCV) and the natural history of HCV
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49. Xu DZ, Yan YP, Choi BC, Xu JQ, Men K, Zhang JX, et al.
Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case-control study. J Med Virol
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50. Towers CV, Asrat T, Rumney P. The presence of hepatitis
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53. Ko TM, Tseng LH, Chang MH, Chen DS, Hsieh FJ,
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increased risk of hepatitis B virus infection. Arch Gynecol
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62. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS,
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65. Hiratsuka M, Minakami H, Koshizuka S, Sato I.
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to conduct a literature search to locate relevant articles published between January 1985 and February 2007. The search
Force:
I
type of evidence.
committees.
Copyright October 2007 by the American College of
means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Viral hepatitis in pregnancy. ACOG Practice Bulletin No. 86. American
2007;110:94155.
PRACTICE BULLETINS
1015
ACOG
PRACTICE
BULLETIN

Obstetrics and the Committee
on Genetics with the assistance
of James Goldberg, MD. The
of practice.
Reaffirmed 2009
Invasive Prenatal Testing

for Aneuploidy
Prenatal diagnosis of fetal chromosomal abnormalities is the most common
indication for invasive prenatal testing. The prevalence of chromosomal abnormalities in clinically recognized early pregnancy loss is greater than 50% (1).
Fetuses with aneuploidy account for 611% of all stillbirths and neonatal
deaths (2). Chromosomal abnormalities that are compatible with life but cause
considerable morbidity occur in 0.65% of newborns, and structural chromosomal rearrangements that will eventually affect reproduction occur in 0.2% of
newborns (3). Consequently, screening and diagnostic programs to detect the
most common autosomal trisomies in liveborn infants, including Down syndrome, are well established. The purpose of this document is to provide clinical
management guidelines for the prenatal diagnosis of these aneuploidies.
Background
There are many strategies available to screen for chromosomal abnormalities
(4). These incorporate maternal age and a variety of first- and second-trimester
ultrasound and biochemical markers that include nuchal translucency measurement and pregnancy-associated plasma protein A, human chorionic gonadotropin, alpha-fetoprotein, estriol, and inhibin levels. All of these approaches
provide an adjusted risk for Down syndrome and trisomy 18. Whereas these
risk figures provide a more accurate risk for Down syndrome and trisomy 18
than maternal age alone, they do not exclude the possibility of an affected fetus
because the test sensitivity is less than 100%, so not all fetuses can be identified. Studies have shown that many factors influence a womans decision to
undergo an invasive procedure (5). These include feelings about having a child
in whom a chromosomal abnormality has been diagnosed and feelings about
the loss of a normal child as a result of the diagnostic procedure.
1016
Down syndrome and other trisomies are primarily

the result of meiotic nondisjunction, which increases
with maternal age. Women contemplating screening versus diagnostic testing for aneuploidy may find it helpful
to compare their adjusted risk after screening with their
age-related risk (Table 1).
Fetuses with aneuploidy may have major anatomic
malformations that often are discovered during an ultrasound examination that is performed for another indication. Abnormalities involving a major organ or structure,
with a few notable exceptions, or the finding of two or
more minor structural abnormalities in the same fetus
indicate increased risk of fetal aneuploidy (6, 7) (Table 2).
There are genetic and nongenetic causes of structural
anomalies. If an aneuploidy is suspected, only a cytogenetic analysis of fetal cells can provide a definitive diagnosis. In some cases, a fetal karyotype will be sufficient
but, in other situations, adjunct testing such as fluorescence in situ hybridization or other genetic testing may
be required to detect chromosomal microdeletions or
duplications or to further characterize marker chromosomes or chromosomal rearrangements.
Amniocentesis
Traditional genetic amniocentesis usually is offered
between 15 weeks and 20 weeks of gestation. Many
large, multicenter studies have confirmed the safety of
genetic amniocentesis as well as its cytogenetic diagnostic accuracy (greater than 99%) (8). All of the large collaborative studies in which the risk of amniocentesis was
evaluated were performed before the use of high-resolution concurrent ultrasonography. In more recent studies,
it is suggested that the procedure-related loss rate is as
low as 1 in 300500 and may be even lower with experienced individuals or centers (9, 10). Complications,
which occur infrequently, include transient vaginal spotting or amniotic fluid leakage in approximately 12% of
all cases and chorioamnionitis in less than 1 in 1,000
cases. The perinatal survival rate in cases of amniotic
fluid leakage after midtrimester amniocentesis is greater
than 90% (11). Needle injuries to the fetus have been
reported but are very rare when amniocentesis is performed under continuous ultrasound guidance. Amniotic
fluid cell culture failure occurs in 0.1% of samples. In
several studies, it has been confirmed that the incidence
of pregnancy loss, blood-contaminated specimens, leaking of amniotic fluid, and the need for more than one
needle puncture are related to the experience of the operator, the use of small-gauge needles, and ultrasound
guidance (1214).
Early amniocentesis performed from 11 weeks to 13
weeks of gestation has been widely studied, and the tech-
Table 1. Risk Table for Chromosomal Abnormalities By

Maternal Age at Term
Age at Term
15*
16*
17*
18*
19*
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
Risk for
Trisomy 21
Risk for Any

Chromosome
Abnormality
1:1578
1:1572
1:1565
1:1556
1:1544
1:1480
1:1460
1:1440
1:1420
1:1380
1:1340
1:1290
1:1220
1:1140
1:1050
1:940
1:820
1:700
1:570
1:456
1:353
1:267
1:199
1:148
1:111
1:85
1:67
1:54
1:45
1:39
1:35
1:31
1:29
1:27
1:26
1:25
1:454
1:475
1:499
1:525
1:555
1:525
1:525
1:499
1:499
1:475
1:475
1:475
1:454
1:434
1:416
1:384
1:384
1:322
1:285
1:243
1:178
1:148
1:122
1:104
1:80
1:62
1:48
1:38
1:30
1:23
1:18
1:14
1:10
1:8
1:6
Data from Cuckle HS, Wald NJ, Thompson SG. Estimating a womans risk of
having a pregnancy associated with Downs syndrome using her age and
serum alpha-fetoprotein level. Br J Obstet Gynaecol 1987;94:387402.
Data from Morris JK, Wald NJ, Mutton DE, Alberman E. Comparison of models
of maternal age-specific risk for Down syndrome live births. Prenat Diagn
2003;23:2528.
Risk for any chromosomal abnormality includes the risk for trisomy 21 and trisomy 18 in addition to trisomy 13, 47,XXY, 47,XYY, Turner syndrome genotype,
and other clinically significant abnormalities, 47,XXX not included. Data from
Hook EB. Rates of chromosome abnormalities at different maternal ages. Obstet
Gynecol 1981;58:2825.
Data not available
PRACTICE BULLETINS
1017
Table 2. Aneuploid Risk of Major Anomalies

Structural Defect
Population Incidence
Aneuploidy
Risk
Most Common
Aneuploidy
Cystic hygroma
1/120 EU1/6,000 B
6075%
45X (80%);
21,18,13,XXY
Hydrops
1/1,5004,000 B
3080%*
13,21,18,45X
Hydrocephalus
38/10,000 LB
38%
13,18, triploidy
Hydranencephaly
2/1,000 IA
Minimal
Holoprosencephaly
1/16,000 LB
4060%
13,18,18p-
Cardiac defects
79/1,000 LB
530%
21,18,13,22,8,9
4070%
21
1/3,5004,000 LB
2025%
13,18,21,45X
13,18
Complete atrioventricular canal

Diaphragmatic hernia
Omphalocele
1/5,800 LB
3040%
Gastroschisis
1/10,00015,000 LB
Minimal
Duodenal atresia
1/10,000 LB
2030%
21
Bladder outlet obstruction
12/1,000 LB
2025%
13,18
Facial cleft
1/700 LB
1%
13,18, deletions
Limb reduction
46/10,000 LB
8%
18
Club foot
1.2/1,000 LB
6%
18,13,4p-,18q-
Single umbilical artery
1%
Minimal
Abbreviations: B, birth; EU, early ultrasonography; LB, livebirth; IA, infant autopsy
*30% if diagnosed at 24 weeks of gestation or later; 80% if diagnosed at 17 weeks of gestation or earlier
Data from Shipp TD, Benacerraf BR. The significance of prenatally identified isolated clubfoot: is amniocentesis indicated? Am
J Obstet Gynecol 1998;178:600602 and Nyberg DA, Crane JP. Chromosome abnormalities. In: Nyberg DA, Mahony BS,
Pretorius DH. Diagnostic ultrasound of fetal anomalies: text and atlas. Chicago (IL): Year Book Medical; 1990. p. 676724.
nique is similar to traditional amniocentesis (1517);

however, performing early amniocentesis results in
significantly higher rates of pregnancy loss and complication than performing traditional amniocentesis. In a
multicenter randomized trial, the spontaneous pregnancy
loss rate after early amniocentesis was 2.5%, compared
with 0.7% with traditional amniocentesis (18). The overall incidence of talipes was 1.4% after the early procedure, compared with 0.1% (the same as the background
rate) after traditional amniocentesis, and membrane rupture was more likely after the early procedure.
Significantly more amniotic fluid culture failures
occurred after the early procedure, necessitating an additional invasive procedure for diagnosis. For these reasons,
early amniocentesis (at less than 14 weeks of gestation)
should not be performed.
Chorionic Villus Sampling

Chorionic villus sampling (CVS) generally is performed
after 9 completed weeks of gestation. Placental villi may
be obtained through transcervical or transabdominal
access to the placenta. There is no difference in fetal loss
rates after transcervical or transabdominal CVS (8). The

primary advantage of CVS over amniocentesis is that
results are available earlier in pregnancy, which provides
reassurance for parents when results are normal and,
when results are abnormal, may allow for earlier and
safer methods of pregnancy termination.
The overall pregnancy loss rate after CVS is greater
than the rate after midtrimester amniocentesis because of
the increased background rate of spontaneous pregnancy
loss between 9 weeks and 16 weeks of gestation.
Although recent data are limited, the procedure-related
pregnancy loss rate for CVS appears to approach, and
may be the same as, the rate for midtrimester amniocentesis (1922).
In several studies, it has been shown that there is a
significant learning curve associated with the safe performance of CVS (23, 24). Consequently, the pregnancy loss
data described previously is only valid in experienced
centers.
Although there have been reports of associations
between CVS and limb reduction and oromandibular
defects, the risk for these anomalies is unclear (25). In an
1018
analysis by the World Health Organization, an incidence

of limb-reduction defects of 6 per 10,000 was reported,
which is not significantly different from the incidence in
the general population (26). However, a workshop on
CVS and limb reduction defects sponsored by the U.S.
National Center for Environmental Health and the Centers
for Disease Control and Prevention concluded that transverse limb deficiencies appeared to be more common after
CVS. The frequency of limb reduction defects is highest
when CVS is performed before 9 weeks of gestation (27,
28). In addition, a panel convened by the National Institute
of Child Health and Development and the American
College of Obstetricians and Gynecologists concluded
that oromandibularlimb hypogenesis appeared to be
more common among infants who were exposed to CVS
and appeared to correlate with, but may not be limited to,
CVS performed earlier than 7 weeks of gestation (25).
Women considering CVS who are concerned about the
possible association of CVS with limb defects can be reassured that when the procedure is performed after 9 weeks
of gestation, the risk is low and probably not greater than
the general population risk of limb defects.
Other complications after CVS include vaginal spotting or bleeding, which may occur in up to 32.2% of
patients after transcervical CVS is performed. The incidence after transabdominal CVS is performed is less (29).
The incidence of culture failure, amniotic fluid leakage,
or infection after CVS is performed is less than 0.5%
(29).
Cordocentesis
Cordocentesis, also known as percutaneous umbilical
blood sampling, involves puncturing the umbilical vein
under direct ultrasound guidance. Karyotype analysis of
fetal blood usually can be accomplished within 2448
hours. The procedure-related pregnancy loss rate has
been reported to be less than 2% (30). Cordocentesis is
rarely needed but may be useful to further evaluate chromosomal mosaicism discovered after CVS or amniocentesis is performed.

Recommendations
Who should have the option of prenatal diagnosis for fetal chromosomal abnormalities?
Invasive diagnostic testing for aneuploidy should be
available to all women, regardless of maternal age.
Pretest counseling should include a discussion of the
risks and benefits of invasive testing compared with
screening tests; how many women will have a positive

result (screen-positive rate) and, of those, how many will
have a true positive result (detection rate); the detection
rate of aneuploidies other than Down syndrome; and the
type and prognosis of the aneuploidies likely to be
missed by serum screening. Counseling should be provided by a practitioner familiar with these details. The
differences between screening and diagnostic testing
should be discussed with all women. A womans decision
of whether to have screening, an amniocentesis, or CVS
is based on many factors, including the risk that the fetus
will have a chromosomal abnormality, the risk of pregnancy loss from an invasive procedure, and the consequences of having an affected child. Studies that have
evaluated womens preferences have shown that women
weigh these potential outcomes differently. The decision
to perform invasive testing should take into account these
preferences and should not be based solely on age.
Maternal age of 35 years alone should no longer be used
as a threshold to determine who is offered screening versus who is offered invasive testing.
How is the risk of aneuploidy assessed?

The risk for fetal aneuploidy can be determined by referring to maternal age-specific aneuploidy risk tables or
using age-adjusted risks after screening. It may be helpful to compare the patients individual risks with risk cutoffs used to indicate a positive screening test result.
These cutoffs are based on the specific detection rate and
screen-positive rate of the screening approach that is
used.
Who is at increased risk for aneuploidy?

Patients with an increased risk of fetal aneuploidy
include the following categories:
Previous fetus or child with autosomal trisomy
Recently, a large collaborative study reported that
the risk of trisomy recurrence is 1.68.2 times the
maternal age risk depending on the type of trisomy,
whether the index pregnancy was a spontaneous
abortion, maternal age at initial occurrence, and the
maternal age at subsequent prenatal diagnosis (31).
Structural anomalies identified by ultrasonographyThe presence of one major or at least two
minor fetal structural abnormalities increases the
likelihood of aneuploidy (6, 7). However, there are
some isolated malformations that are not usually
associated with aneuploidy and that may not require
further testing (Table 2).
Previous fetus or child with sex chromosome abnormalityNot all sex chromosome abnormalities have
PRACTICE BULLETINS
maternal origin, and not all have a risk of recurrence.

As with autosomal trisomies, the recurrence risk is
1.62.5 times the maternal age risk. A woman whose
previous offspring had a 47,XYY karyotype is not at
increased risk of recurrence because the extra chromosome is paternal in origin. Turner syndrome
(45,X) has a nominal risk of recurrence. Parents of
children with 47,XYY or 45,X karyotypes may still
request prenatal diagnosis in future pregnancies for
reassurance.
Parental carrier of chromosome translocation
Women or men carrying balanced translocations,
although phenotypically normal themselves, are at
risk of producing unbalanced gametes, resulting in
abnormal offspring. For most translocations, the
observed risk of abnormal liveborn children is less
than the theoretic risk because some of these
gametes result in nonviable conceptions. In general,
carriers of chromosome translocations that are identified after the birth of an abnormal child have a
530% risk of having unbalanced offspring in the
future, whereas those identified for other reasons
(eg, during an infertility workup) have a 05% risk
(1). Genetic counseling may be helpful in such situations.
Parental carrier of chromosome inversionAn
inversion occurs when two breaks occur in the same
chromosome and the intervening genetic material is
inverted before the breaks are repaired. Although no
genetic material is lost or duplicated, the rearrangement may alter gene function. Each carriers risk of
having a liveborn abnormal child is related to the
method of ascertainment, the chromosome involved,
and the size of the inversion; thus, risks should be
determined individually. The observed risk is
approximately 510% if the inversion is identified
after the birth of an abnormal child and 13% if
ascertainment occurs at some other time (1). One
exception is a pericentric inversion of chromosome
9, which is a common variant in the general population and of no clinical consequence.
Parental aneuploidy or mosaicism for aneuploidy
Women with trisomy 21, although subfertile, have
approximately a 50% risk of having trisomic offspring. Women with 47,XXX and men with 47,XYY
usually are fertile and have no discernible increase
in risk of having trisomic offspring. In men with a
normal karyotype who have oligospermia or whose
partners conceive from intracytoplasmic sperm
injection, there is an increased incidence of abnormal karyotype in the sperm (32).
1019
What type of laboratory test should be performed to diagnose aneuploidy?

Metaphase analysis of cultured amniocytes or chorionic
villus cells is the preferred method for karyotype analysis. This approach is highly accurate, with results typically available 12 weeks after the procedure.
Fluorescence in situ hybridization (FISH) analysis provides a more rapid result for specific chromosomes, most
commonly chromosomes 13, 18, 21, X, and Y. Whereas
FISH analysis has been shown to be accurate, false-positive and false-negative results have been reported.
Therefore, clinical decision making should be based on
information from FISH and at least one of the following
results: confirmatory traditional metaphase chromosome
analysis or consistent clinical information, such as an
abnormal ultrasound finding or a positive screening test
result for Down syndrome or trisomy 18 (33).
Comparative genomic hybridization (CGH) is an
evolving method that identifies submicroscopic chromosomal deletions and duplications. This approach has
proved useful in identifying abnormalities in individuals
with developmental delay and physical abnormalities
when results of traditional chromosomal analysis have
been normal (34). The use of CGH in prenatal diagnosis,
at present, is limited because of the difficulty in interpreting which DNA alterations revealed through CGH may be
normal population variants. Until there are more data
available, use of CGH for routine prenatal diagnosis is not
recommended.
How often does chromosomal mosaicism

occur in amniocentesis or chorionic villus
sampling results?
Chromosomal mosaicism, the presence of more than one
cell line identified during cytogenetic analysis, occurs in
approximately 0.25% of amniocentesis specimens and
1% of chorionic villus specimens. After mosaicism is
found by CVS, amniocentesis typically is performed to
assess whether mosaicism is present in amniocytes. In
most cases, the amniocentesis result is normal, and the
mosaicism is assumed to be confined to the trophoblast.
Although this is unlikely to cause defects in the fetus, it
may result in third-trimester growth restriction. Clinical
manifestations depend on the specific mosaic cell line(s)
and may range from completely normal to findings consistent with the abnormal chromosome result.
Counseling following the finding of chromosomal
mosaicism is complex, and referral for genetic counseling may be useful in these cases. In some instances, cordocentesis may be recommended.
A special case of mosaicism is maternal cell contamination of the fetal specimen. This can be minimized by
1020
discarding the first 12 milliliters of the amniocentesis

specimen and by careful dissection of chorionic villi from
maternal decidua.
How should you counsel women who have

chronic infections, such as hepatitis B,
hepatitis C or human immunodeficiency
virus, about invasive prenatal testing?
The risk of neonatal infection through amniocentesis in
women who are chronically infected with hepatitis B or
hepatitis C appears to be low, although the number of
exposed cases in the literature is small (35). Of 115 women
reported to be positive for the hepatitis B surface antigen
who underwent second-trimester amniocentesis, the rate
of neonatal infection was no different than in women who
did not have an amniocentesis. All of the infants received
hepatitis B vaccination and immunoprophylaxis beginning
at birth (3639). There is only one series reported in the literature in which 22 women who were positive for hepatitis C underwent second-trimester amniocentesis. No
infants in this series were found to be hepatitis C RNA
positive on postnatal testing. This group included one
woman with amniotic fluid that was hepatitis C RNA positive (40). There are insufficient data in the literature to
assess the risk of CVS in these women or to estimate the
risk of fetal infection among women with anterior placentas, those who are hepatitis B e antigen positive or those
with high hepatitis B or hepatitis C viral loads.
Amniocentesis in women with human immunodeficiency virus (HIV) has been shown to increase the vertical
transmission rate in women who do not receive retroviral
therapy (41). In a recent report of a small number of cases,
it is suggested that amniocentesis or CVS does not increase
the neonatal infection rate in newborns of women infected
with HIV who are receiving retroviral therapy (42).
Because of the limited information regarding the risk
of invasive procedures in women chronically infected with
hepatitis B, hepatitis C, or HIV, it would be prudent to discuss noninvasive screening options with these women.
How does prenatal diagnosis differ for

women with multiple gestations?
Diagnostic options are more limited in high-order gestations (43). In women with twins, the risk of aneuploidy
should be calculated by considering the maternal agerelated risk of aneuploidy, population risk of dizygosity,
and the probability that either one or both fetuses could
be affected. Formulas and tables are available in the literature to help with these calculations (44). Counseling in
this situation should include a discussion of options for
pregnancy management if only one fetus is found to be
affected. These options include terminating the entire

pregnancy, selective second-trimester termination of the
affected fetus, and continuing the pregnancy.
Scant data exist concerning fetal loss in women with
twin gestation when amniocentesis or CVS is performed.
According to some small series, the fetal loss rate is
approximately 3.5% when amniocentesis is performed in
women with multiple gestations; this was not higher than
the background loss rate for twins in the second trimester
in one series with a control group (30, 45, 46). There are
no data concerning loss rates after amniocentesis is performed in women with high-order multiple gestations.
Similar information for twin gestations from small, nonrandomized series exists for CVS (4648).
A complex counseling issue arises in the presence of
a monochorionic twin gestation, in which case the likelihood of discordance in the karyotype is low, and patients
may opt for having a karyotype analysis performed on a
single fetus. In this situation, it is important to discuss the
accuracy of determining chorionicity by ultrasonography.
The determination of chorionicity is most accurate if
ultrasonography is performed at or before 14 weeks of
gestation. The positive predictive value of monochorionicity is 97.8% at this stage of pregnancy. This decreases
to 88% if the ultrasound examination is performed after
14 weeks of gestation (49).
What information should be provided after

the diagnosis of fetal aneuploidy?
After the diagnosis of a chromosomal abnormality, the
patient should receive detailed information, if known,
about the natural history of individuals with the specific
chromosomal finding. In many cases, it may be very
helpful to refer the patient to a genetic counselor or clinical geneticist and national groups such as The National
Down Syndrome Society (www.ndss.org) or National
Down Syndrome Congress (www.ndsccenter.org) to help
the patient make an informed decision. The option of
pregnancy termination also should be discussed. Patients
may benefit from additional ultrasonography or fetal
echocardiography and referral to appropriate obstetric
and pediatric specialists or neonatologists to discuss
pregnancy and neonatal management issues. Referral to
parent support groups, counselors, social workers, or
clergy may provide additional information and support.
Is there value in prenatal diagnosis for the

patient who would decline pregnancy
termination?
Prenatal diagnosis is not performed solely for assistance
in the decision of pregnancy termination. It can provide
PRACTICE BULLETINS
useful information for the physician and the patient.

Nondirective counseling before prenatal diagnostic testing does not require a patient to commit to pregnancy
termination if the result is abnormal. If it is determined
that the fetus has a chromosomal abnormality, the physicians and family can plan ahead and develop a management plan for the remainder of the pregnancy, labor, and
delivery (50).
1021
Measure
The percentage of pregnant women undergoing invasive testing who were counseled about the risks of the
procedure
References
Summary of
Recommendations and
Conclusions
Early amniocentesis (at less than 15 weeks of gestation) should not be performed because of the higher
risk of pregnancy loss and complications compared
with traditional amniocentesis (15 weeks of gestation or later)
The following conclusions are based on limited or

inconsistent scientific evidence (Level B):
Amniocentesis at 15 weeks of gestation or later is
a safe procedure. The procedure-related loss rate
after midtrimester amniocentesis is less than 1 in
300500.
In experienced individuals and centers, CVS procedure-related loss rates may be the same as those for
amniocentesis.
The following recommendation and conclusions

Invasive diagnostic testing for aneuploidy should be
available to all women, regardless of maternal age.
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and genetic counseling. 3rd ed. New York (NY): Oxford
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5. Kuppermann M, Nease RF, Learman LA, Gates E,
Blumberg B, Washington AE. Procedure-related miscarriages and Down syndrome-affected births: implications
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6. Williamson RA, Weiner CP, Patil S, Benda J, Varner MW,
Abu-Yousef MM. Abnormal pregnancy sonogram: selective indication for fetal karyotype. Obstet Gynecol
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7. Wladimiroff JW, Sachs ES, Reuss A, Stewart PA, Pijpers
L, Niermeijer MF. Prenatal diagnosis of chromosome
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8. Jackson LG, Zachary JM, Fowler SE, Desnick RJ, Golbus
MS, Ledbetter DH, et al. A randomized comparison of
transcervical and transabdominal chorionic-villus sampling. The U.S. National Institute of Child Health and
Human Development Chorionic-Villus Sampling and
Amniocentesis Study Group. N Engl J Med 1992;327:
5948. (Level I)
9. Mazza V, Pati M, Bertucci E, Re C, Ranzi A, Percesepe A,
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Patients with an increased risk of fetal aneuploidy

include women with a previous fetus or child with
an autosomal trisomy or sex chromosome abnormality, one major or at least two minor fetal structural defects identified by ultrasonography, either
parent with a chromosomal translocation or chromosomal inversion, or parental aneuploidy.
10. Eddleman KA, Malone FD, Sullivan L, Dukes K,

Berkowitz RL, Kharbutli Y, et al. Pregnancy loss rates
after midtrimester amniocentesis. Obstet Gynecol
2006;108:106772. (Level II-2)
Nondirective counseling before prenatal diagnostic

testing does not require a patient to commit to pregnancy termination if the result is abnormal.
11. Borgida AF, Mills AA, Feldman DM, Rodis JF, Egan JF.
Outcome of pregnancies complicated by ruptured membranes after genetic amniocentesis. Am J Obstet Gynecol
2000;183:9379. (Level II-2)
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12. Mennuti MT, DiGaetano A, McDonnell A, Cohen AW,

Liston RM. Fetal-maternal bleeding associated with
genetic amniocentesis: real-time versus static ultrasound.
13. Romero R, Jeanty P, Reece EA, Grannum P, Bracken M,
Berkowitz R, et al. Sonographically monitored amniocentesis to decrease intraoperative complications. Obstet
14. Leschot NJ, Verjaal M, Treffers PE. Risks of midtrimester
amniocentesis; assessment in 3,000 pregnancies. Br J
Obstet Gynaecol 1985 Aug;92(8):8047. (Level III)
15. Nicolaides K, Brizot Mde L, Patel F, Snijders R.
Comparison of chorionic villus sampling and amniocentesis for fetal karyotyping at 1013 weeks gestation [published erratum appears in: Lancet 1994;344:830]. Lancet
1994;344:4359. (Level II-2)
16. Johnson JM, Wilson RD, Winsor EJ, Singer J, Dansereau J,
Kalousek DK. The early amniocentesis study: a randomized clinical trial of early amniocentesis versus
midtrimester amniocentesis. Fetal Diagn Ther 1996; 11:
8593. (Level I)
17. Sundberg K, Bang J, Smidt-Jensen S, Brocks V,
Lundsteen C, Parner J, et al. Randomised study of risk of
fetal loss related to early amniocentesis versus chorionic
villus sampling. Lancet 1997;350:697703. (Level I)
18. Randomised trial to assess safety and fetal outcome of
early and midtrimester amniocentesis. The Canadian
Early and Mid-trimester Amniocentesis Trial (CEMAT)
Group. Lancet 1998;351:2427. (Level I)
19. Multicentre randomised clinical trial of chorion villus
sampling and amniocentesis. First report. Canadian
Collaborative CVS-Amniocentesis Clinical Trial Group.
Lancet 1989;1:16. (Level I)
20. Rhoads GG, Jackson LG, Schlesselman SE, de la Cruz FF,
Desnick RJ, Golbus MS, et al. The safety and efficacy of
chorionic villus sampling for early prenatal diagnosis of
cytogenetic abnormalities. N Engl J Med 1989;320:
60917. (Level II-3)
21. Caughey AB, Hopkins LM, Norton ME. Chorionic villus
sampling compared with amniocentesis and the difference
in the rate of pregnancy loss. Obstet Gynecol 2006;108:
6126. (Level II-2)
22. Mujezinovic F, Alfirevic Z. Procedure-related complications of amniocentesis and chorionic villous sampling: a
systematic review. Obstet Gynecol 2007;110:68794.
23. Silver RK, MacGregor SN, Sholl JS, Hobart ED, Waldee
JK. An evaluation of the chorionic villus sampling learning curve. Am J Obstet Gynecol 1990;163:91722. (Level
III)
24. Wijnberger LD, van der Schouw YT, Christiaens GC.
Learning in medicine: chorionic villus sampling. Prenat
Diagn 2000;20:2416. (Level II-3)
25. Holmes LB. Report of National Institute of Child Health
and Human Development Workshop on Chorionic Villus
Sampling and Limb and Other Defects, October 20, 1992.
Teratology 1993;48:713. (Level III)
26. Kuliev A, Jackson L, Froster U, Brambati B, Simpson JL,

Verlinsky Y, et al. Chorionic villus sampling safety. Report
of World Health Organization/EURO meeting in association with the Seventh International Conference on Early
Prenatal Diagnosis of Genetic Diseases, Tel-Aviv, Israel,
May 21, 1994. Am J Obstet Gynecol 1996;174: 80711.
(Level III)
27. Botto LD, Olney RS, Mastroiacovo P, Khoury MJ, Moore
CA, Alo CJ, et al. Chorionic villus sampling and transverse
digital deficiencies: evidence for anatomic and gestationalage specificity of the digital deficiencies in two studies. Am
J Med Genet 1996;62:1738. (Level II-2)
28. Chorionic villus sampling and amniocentesis: recommendations for prenatal counseling. Centers for Disease
Control and Prevention. MMWR Recomm Rep 1995;44
(RR-9):112. (Level III)
29. Brambati B, Tului L. Prenatal genetic diagnosis through
chorionic villus sampling. In: Milunsky A. Genetic disorders and the fetus: diagnosis, prevention, and treatment. 5th
ed. Baltimore (MD): Johns Hopkins University Press;
2004. p. 179213. (Level III)
30. Ghidini A, Sepulveda W, Lockwood CJ, Romero R.
Complications of fetal blood sampling. Am J Obstet
Gynecol 1993;168:133944. (Level II-3)
31. Warburton D, Dallaire L, Thangavelu M, Ross L, Levin B,
Kline J. Trisomy recurrence: a reconsideration based on
North American data. Am J Hum Genet 2004;75:37685.
(Level III)
32. Burrello N, Vicari E, Calogero AE. Chromosome abnormalities in spermatozoa of patients with azoospermia and
normal somatic karyotype. Cytogenet Genome Res
2005;111:3635. (Level III)
33. Technical and clinical assessment of fluorescence in situ
hybridization: an ACMG/ASHG position statement. I.
Technical considerations. American College of Medical
Genetics. Genet Med 2000;2:35661. (Level III)
34. Kirchhoff M, Rose H, Lundsteen C. High resolution comparative genomic hybridisation in clinical cytogenetics.
J Med Genet 2001;38:7404. (Level III)
35. Amniocentesis and women with hepatitis B, hepatitis C, or
human immunodeficiency virus. SOGC Clinical Practice
Guidelines. Society of Obstetricians and Gynaecologists of
Canada. J Obstet Gynaecol Can 2003;25:14548, 14952.
(Level III)
36. Towers CV, Asra T, Rumney P. The presence of hepatitis B
surface antigen and deoxyribonucleic acid in amniotic fluid
and cord blood. Am J Obstet Gynecol 1999;184:
15148. (Level II-2)
37. Alexander JM, Ramus R, Jackson G, Sercely B, Wendel
GD Jr. Risk of hepatitis B transmission after amniocentesis
in chronic hepatitis B carriers. Infect Dis Obstet Gynecol
1999;7:2836. (Level III)
38. Grosheide PM, Quartero HW, Schalm SW, Heijtink RA,
Christiaens GC. Early invasive prenatal diagnosis in
HBsAg-positive women. Prenat Diagn 1994;14:5538.
(Level III)
39. Ko TM, Tseng LH, Chang MH, Chen DS, Hsieh FJ,
Chuang SM, et al. Amniocentesis in mothers who are hep-
PRACTICE BULLETINS
atitis B virus carriers does not expose the infant to an

increased risk of hepatitis B virus infection. Arch Gynecol
Obstet 1994;255:2530. (Level II-2)
40. Delamare C, Carbonne B, Heim N, Berkane N, Petit JC,
Uzan S, et al. Detection of hepatitis C virus RNA (HCV
RNA) in amniotic fluid: a prospective study. J Hepatol
1999;31:41620. (Level II-2)
41. Shapiro DE, Sperling RS, Mandelbrot L, Britto P,
Cunningham BE. Risk factors for perinatal human
immunodeficiency virus transmission in patients receiving zidovudine prophylaxis. Pediatric AIDS Clinical
Trials Group protocol 076 Study Group. Obstet Gynecol
1999;94:897908. (Level I)
42. Somigliana E, Bucceri AM, Tibaldi C, Alberico S,
Ravizza M, Savasi V, et al. Early invasive diagnostic techniques in pregnant women who are infected with the HIV:
a multicenter case series. Italian Collaborative Study on
HIV Infection in Pregnancy. Am J Obstet Gynecol 2005;
193:43742. (Level III)
43. Jenkins TM, Wapner RJ. The challenge of prenatal diagnosis in twin pregnancies. Curr Opin Obstet Gynecol
2000;12:8792. (Level III)
44. Rodis JF, Egan JF, Craffey A, Ciarleglio L, Greenstein
RM, Scorza WE. Calculated risk of chromosomal abnormalities in twin gestations. Obstet Gynecol 1990;76:
103741. (Level III)
45. Librach CL, Doran TA, Benzie RJ, Jones JM. Genetic
amniocentesis in seventy twin pregnancies. Am J Obstet
46. Wapner RJ, Johnson A, Davis G, Urban A, Morgan P,
Jackson L. Prenatal diagnosis in twin gestations: a comparison between second-trimester amniocentesis and firsttrimester chorionic villus sampling. Obstet Gynecol
1993;82:4956. (Level II-2)
47. De Catte L, Liebaers I, Foulon W, Bonduelle M, Van
Assche E. First trimester chorionic villus sampling in twin
gestations. Am J Perinatol 1996;13:4137. (Level II-3)
48. van den Berg C, Braat AP, Van Opstal D, Halley DJ,
Kleijer WJ, den Hollander NS, et al. Amniocentesis or
chorionic villus sampling in multiple gestations?
Experience with 500 cases. Prenat Diagn 1999;19:
234244. (Level II-3)
49. Lee YM, Cleary-Goldman J, Thaker HM, Simpson LL.
Antenatal sonographic prediction of twin chorionicity.
50. Clark SL, DeVore GR. Prenatal diagnosis for couples who
would not consider abortion. Prenat Diagn 1989;73:
10357. (Level III)
1023

to the method outlined by the U.S. Preventive Services
Task Force:
I

type of evidence.
committees.
Copyright December 2007 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Invasive prenatal testing for aneuploidy. ACOG Practice Bulletin No.
Gynecol 2007;110:145967.
1024
ACOG
PRACTICE
BULLETIN
Asthma in Pregnancy
of Mitchell P. Dombrowski, MD
and Michael Schatz, MD, MS.
of practice.
Reaffirmed 2009
Asthma is a common, potentially serious medical condition that complicates

approximately 48% of pregnancies (1, 2). In general, the prevalence of and
morbidity from asthma are increasing, although asthma mortality rates have
decreased in recent years. The purpose of this document is to review the best
available evidence about the management of asthma during pregnancy.
Background
Asthma is characterized by chronic airway inflammation, with increased airway responsiveness to a variety of stimuli, and airway obstruction that is partially or completely reversible (3). The pathogenesis of asthma involves airway
inflammation in nearly all cases. Current medical management for asthma
emphasizes treatment of airway inflammation in order to decrease airway
responsiveness and prevent asthma symptoms.
The National Asthma Education and Prevention Program has found that it
is safer for pregnant women with asthma to be treated with asthma medications
than it is for them to have asthma symptoms and exacerbations (4). Mild and
well-controlled moderate asthma can be associated with excellent maternal and
perinatal pregnancy outcomes (57). Severe and poorly controlled asthma may
be associated with increased prematurity, need for cesarean delivery, preeclampsia, growth restriction, other perinatal complications, and maternal morbidity
and mortality (812). The ultimate goal of asthma therapy in pregnancy is maintaining adequate oxygenation of the fetus by preventing hypoxic episodes in the
mother. Optimal management of asthma during pregnancy includes objective
monitoring of lung function, avoiding or controlling asthma triggers, educating
patients, and individualizing pharmacologic therapy to maintain normal pulmonary function. The step-care therapeutic approach uses the lowest amount of
drug intervention necessary to control a patients severity of asthma.
PRACTICE BULLETINS
Medications
Asthma medications generally are divided into longterm control medications and rescue therapy. Long-term
control medications are used for maintenance therapy to
prevent asthma manifestations and include inhaled
corticosteroids, cromolyn, long-acting -agonists, and
theophylline. Rescue therapy, most commonly inhaled
short-acting -agonists, provides immediate relief of
symptoms. Oral corticosteroids can either be used as a
form of rescue therapy to treat an asthma exacerbation or
as long-term control therapy for patients with severe persistent asthma.
Certain medications, possibly used during labor and
delivery, have the potential to worsen asthma. Nonselective -blockers, carboprost (15-methyl prostaglandin F2)
and ergonovine may trigger bronchospasm. Magnesium
sulfate is a bronchodilator, but indomethacin can induce
bronchospasm in patients who are sensitive to aspirin.
Prostaglandin E2 or prostaglandin E1 can be used for cervical ripening, the management of spontaneous or
induced abortions, or the management of postpartum
hemorrhage (13).
Asthma Severity Classification

In 2004, the National Asthma Education and Prevention
Program Working Group on Asthma and Pregnancy
defined mild intermittent, mild persistent, moderate persistent, and severe persistent asthma according to daytime and nighttime symptoms (wheezing, coughing, or
dyspnea) and objective tests of pulmonary function (4).
The most commonly used pulmonary function parameters are the peak expiratory flow rate (PEFR) and
forced expiratory volume in the first second of expiration (FEV1). Current National Asthma Education and
Prevention Program guidelines suggest classifying the
1025
degree of asthma severity in patients who are not taking

controller medication and the degree of asthma control in
patients who are taking controller medication (Table 1).
Effects of Pregnancy on Asthma

In a large prospective study, pregnant patients with mild
asthma had exacerbation rates of 12.6% and hospitalization rates of 2.3%, those with moderate asthma had exacerbation rates of 25.7% and hospitalization rates of
6.8%, and those with severe asthma had exacerbation
rates of 51.9% and hospitalization rates of 26.9% (14).
The effects of pregnancy on the course of asthma are
variablethe symptoms of 23% of women studied
improved and the symptoms of 30% became worse during pregnancy (14). Because many pregnant women
have increased symptoms, pregnant patients who have
asthma, even those with mild or well-controlled disease,
need to be monitored with PEFR and FEV1 testing as
well as by observing their symptoms during pregnancy.
Effects of Asthma on Pregnant Women

and Fetuses
There has been considerable consistency among results
of prospective studies of the effects of asthma during
pregnancy. Eight prospective studies, reporting maternal
and infant outcomes with at least 100 participants in
locations at or near sea level, have been published (57,
1520). These studies show that the gravid patient with
mild or moderate asthma can have excellent maternal
and infant outcomes. However, suboptimal control of
asthma during pregnancy may be associated with
increased maternal or fetal risk (7). In fact, a significant
relationship has been reported between decreased FEV1
during pregnancy and increased risk of low birth weight
and prematurity (21). Results of the two largest studies
Table 1. Classification of Asthma Severity and Control in Pregnant Patients

Asthma Severity*
(Control)
Symptom Frequency
Nighttime Awakening
Interference With
Normal Activity
FEV1 or Peak Flow

(Predicted Percentage
of Personal Best)
Intermittent
(well controlled)
2 days per week or less
Twice per month or less
None
More than 80%
Mild persistent
(not well controlled)
More than 2 days per week,

but not daily
More than twice per month
Minor limitation
More than 80%
Moderate persistent
(not well controlled)
Daily symptoms
More than once per week
Some limitation
6080%
Severe persistent
(very poorly controlled)
Throughout the day
Four times per week or more
Extremely limited
Less than 60%
Abbreviation: FEV1, forced expiratory volume in the first second of expiration

*Assess severity for patients who are not taking long-term-control medications.
Assess control in patients taking long-term-control medications to determine whether step-up therapy, step-down therapy, or no change in therapy is indicated.
1026
indicate that classification of asthma severity and therapy tailored according to asthma severity can result in
excellent infant and maternal outcomes (6, 7).
There are important caveats when interpreting the
study results of asthma in pregnancy. Fewer considerable
adverse associations have been found in the results of
prospective studies, possibly because of better asthma
surveillance and treatment. The excellent maternal and
infant outcomes were achieved at centers that tended to
manage asthma in pregnancy actively. In addition, women
who enroll in research studies tend to be more motivated
and adhere to therapeutic regimens more than the general
public. The lack of more adverse outcomes among
women with severe asthma also may be a function of the
relatively small number of participants in this cohort and
the resulting lack of power to find adverse outcomes that
were statistically significant. Although the results of these
prospective studies are reassuring in their consensus of
good pregnancy outcomes, they do not indicate that asthma
should be considered a benign condition because active
asthma management was a part of these studies and may
have had a positive impact on the outcomes.

Recommendations
How is asthma diagnosed during pregnancy?
Diagnosis of asthma in a pregnant patient is the same as
that for a nonpregnant patient. Asthma typically includes
characteristic symptoms (wheezing, chest cough, shortness of breath, chest tightness), temporal relationships
(fluctuating intensity, worse at night), and triggers (eg,
allergens, exercise, infections). Wheezing on auscultation would support the diagnosis, but its absence does
not exclude the diagnosis. Ideally, the diagnosis of asthma
would be confirmed by demonstrating airway obstruction on spirometry that is at least partially reversible
(greater than a 12% increase in FEV1 after bronchodilator). However, reversible airway obstruction may not be
demonstrable in some patients with asthma. In patients
with a clinical picture consistent with asthma, in whom
reversible airway obstruction cannot be demonstrated, a
trial of asthma therapy is reasonable. In such patients, a
positive response to asthma therapy can be used to diagnose asthma during pregnancy.
In patients presenting with new respiratory symptoms during pregnancy, the most common differential
diagnosis would be dyspnea of pregnancy. Dyspnea of
pregnancy usually can be differentiated from asthma by
its lack of cough, wheezing, chest tightness, or airway
obstruction. Other differential diagnoses include gastroe-
sophageal reflux, chronic cough from postnasal drip, and

bronchitis.
How should patients with asthma be assessed

during pregnancy?
Clinical evaluation includes subjective assessments and
pulmonary function tests. Because pulmonary function
and asthma severity may change during the course of
pregnancy, routine evaluation of pulmonary function in
pregnant women with persistent asthma is recommended.
For pulmonary function assessment during outpatient visits, spirometry is preferable, but peak expiratory flow
measurement with a peak flow meter also is sufficient.
Patients with worsening symptoms should be evaluated
with peak flow measurement and lung auscultation.
Severity and control of asthma should be assessed in
terms of symptom exacerbation and pulmonary impairment. It is important to identify a history of prior hospitalization (especially hospital stays that required intensive
care unit admission or intubation), emergency department
or other unscheduled visits for asthma treatment, or oral
corticosteroid requirements. In patients who are not taking controllers, it is useful to assess pulmonary impairment based on severity classification (Table 1). Patients
with two or more episodes of symptom exacerbation
requiring the use of oral corticosteroids in the prior
12 months also should be considered to have persistent
asthma. In patients who are taking controllers, it is useful
to assess control (Table 1). Assessing the impairment
domain of control consists of determining the frequency
of daytime symptoms, nocturnal symptoms, activity limitation, frequency of rescue therapy, and FEV1. The
assessment in a pregnant patient with asthma also should
include the effect of any prior pregnancies on asthma
severity or control because this may predict the course of
the asthma during subsequent pregnancies.
Can allergy shots be started or continued

during pregnancy?
The use of allergen immunotherapy, or allergy shots,
has been shown to be effective in improving asthma in
patients with allergies (4). In two studies, no adverse
effects of immunotherapy during pregnancy have been
found (22, 23). However, anaphylaxis is a risk of allergen injections, especially early in the course of
immunotherapy when the dose is being escalated, and
anaphylaxis during pregnancy has been associated with
maternal death, fetal death, or both. In a patient who is
receiving a maintenance or near-maintenance dose, not
experiencing adverse reactions to the injections and
apparently deriving clinical benefit, continuation of
immunotherapy is recommended. In such patients, a
PRACTICE BULLETINS
dose reduction may be considered to further decrease the

chance of anaphylaxis. Riskbenefit considerations do
not usually favor beginning allergen immunotherapy
during pregnancy.
What is appropriate rescue therapy for asthma

during pregnancy?
Inhaled short-acting 2-agonists are the rescue therapy of
choice for asthma during pregnancy. Inhaled albuterol is
the first-choice, short-acting 2-agonist for pregnant
women, although other agents also may be appropriate.
In general, patients should use up to two treatments of
inhaled albuterol (two to six puffs) or nebulized albuterol
at 20-minute intervals for most mild to moderate symptoms; higher doses can be used for severe symptom exacerbation. To avoid maternal and fetal hypoxia, patients
should be counseled to start rescue therapy at home when
they have an exacerbation of symptoms, such as coughing, chest tightness, dyspnea, wheezing, or a 20% decrease
in the PEFR. With a good response (ie, symptoms reduce
or resolve, and the PEFR reaches 80% of personal best)
the patient can continue normal activity. If the patient
does not have a good response or if she notices a
decrease in fetal activity, she should seek medical attention quickly.
What is first-line controller therapy for asthma

during pregnancy?
For those with mild, intermittent asthma, no controller
therapy is indicated. Use of inhaled corticosteroids is firstline controller therapy for persistent asthma during pregnancy. For patients with mild, persistent asthma, the use of
low-dose inhaled corticosteroids is recommended (see the
box). For patients with moderate persistent asthma or
whose symptoms are not controlled with the use of lowdose inhaled corticosteroids, the use of medium-dose
inhaled corticosteroids or low-dose inhaled corticosteroids and long-acting -agonists are indicated. See
Table 2 for typical inhaled corticosteroid regimens.
Budesonide is the preferred inhaled corticosteroid for use
during pregnancy (4). However, there are no data indicating that the other inhaled corticosteroid preparations are
unsafe during pregnancy. Therefore, the use of any inhaled
corticosteroids may be continued in patients whose asthma
was well controlled by these agents before pregnancy (4).
What is appropriate add-on controller therapy

for asthma during pregnancy?
Use of long-acting 2-agonists is the preferred add-on
controller therapy for asthma during pregnancy. This
therapy should be added when patients symptoms are
1027
Step Therapy Medical Management

of Asthma During Pregnancy
Mild Intermittent Asthma
No daily medications, albuterol as needed
Mild Persistent Asthma
PreferredLow-dose inhaled corticosteroid
AlternativeCromolyn, leukotriene receptor antagonist, or theophylline (serum level 512 mcg/mL)
Moderate Persistent Asthma
PreferredLow-dose inhaled corticosteroid and
salmeterol or medium-dose inhaled corticosteroid
or (if needed) medium-dose inhaled corticosteroid
and salmeterol
AlternativeLow-dose or (if needed) mediumdose inhaled corticosteroid and either leukotriene
receptor antagonist or theophylline (serum level
512 mcg/mL)
Severe Persistent Asthma
PreferredHigh-dose inhaled corticosteroid and
salmeterol and (if needed) oral corticosteroid
AlternativeHigh-dose inhaled corticosteroid and
theophylline (serum level 512 mcg/mL) and oral
corticosteroid if needed
not controlled with the use of medium-dose inhaled corticosteroids. Alternative add-on therapies are theophylline
or leukotriene receptor antagonists (montelukast, zafirlukast). However, the use of long-acting inhaled 2-agonists is preferred because it has been shown to be a more
effective add-on therapy in nonpregnant patients than
leukotriene receptor antagonists or theophylline. Longacting inhaled 2-agonists have fewer side effects than
theophylline, which has a narrow therapeutic index and
requires serum monitoring, and there are few data on the
use of leukotriene receptor antagonists in humans during
pregnancy. See Table 2 for typical medication dosages.
Because long-acting and short-acting inhaled 2-agonists
have similar pharmacology and toxicology, long-acting
inhaled 2-agonists are expected to have a safety profile
similar to that of albuterol. Two long-acting inhaled
2-agonists are available: 1) salmeterol and 2) formoterol.
Limited observational data exist on their use during pregnancy. A step-wise approach to management is advised in
order to achieve control. See the box for specific therapy.
For patients whose symptoms are not well controlled
(Table 1) with the use of medium-dose inhaled corticosteroids and long-acting inhaled 2-agonists, treatment
should be advanced to high-dose inhaled corticosteroids
1028
Table 2. Comparative Daily Doses for Inhaled Corticosteroids*

Corticosteroid
Low Dose
Medium Dose
High Dose
40 mcg per puff
26 puffs
More than 612 puffs
More than 12 puffs
80 mcg per puff
13 puffs
More than 36 puffs
More than 6 puffs
Budesonide
200 mcg per inhalation
13 puffs
More than 36 puffs
More than 6 puffs
Flunisolide
250 mcg per puff
24 puffs
48 puffs
More than 8 puffs
Fluticasone HFA
44 mcg per puff
26 puffs
110 mcg per puff
2 puffs
24 puffs
More than 4 puffs
12 puffs
More than 2 puffs
Beclomethasone HFA
Amount
220 mcg per puff

Fluticasone DPI
26 puffs
13 puffs
35 puffs
More than 5 puffs
1 puff
2 puffs
More than 2 puffs
Mometasone
1 puff
2 puffs
More than 2 puffs
Triamcinolone
75 mcg per puff
410 puffs
1020 puffs
More than 20 puffs
*Total daily puffs is usually divided into a twice-per-day regimen.

Abbreviations: DPI, dry powder inhaler; HFA, hydrofluoroalkane
Adapted from National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert panel report 3: guidelines for the diagnosis and management of asthma. NIH Publication No. 07-4051. Bethesda (MD): NHLBI; 2007. Available at:
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Retrieved September 10, 2007.
(Table 2) and long-acting inhaled 2-agonists (salmeterol,

one puff twice daily). Some patients with severe asthma
may require regular oral corticosteroid use to achieve adequate asthma control. For patients whose symptoms are
very poorly controlled (Table 1), a course of oral corticosteroids may be necessary to attain control, along with a
step up in therapy, as described previously and in the box.
What nonpharmacologic approaches should

be used for asthma during pregnancy?
Identifying and controlling or avoiding factors, such as
allergens and irritants, that contribute to asthma severity,
particularly tobacco smoke, can lead to improved maternal well-being with less need for medication (4). If gastroesophageal reflux is exacerbating the patients asthma,
nonpharmacologic measures, such as elevating the head
of the bed, eating smaller meals, not eating within 23
hours of bedtime, and avoiding triggering foods, may
help. Asthma control is enhanced by ensuring access to
education about asthma, the interrelationships between
asthma and pregnancy, and the skills necessary to manage asthma. These skills include self-monitoring, correct
use of inhalers, following a plan for long-term management of asthma, and promptly handling signs of worsening asthma (4). Specific measures to reduce mold, dust
mite exposure, animal dander, cockroaches, and other
environmental triggers may be important. Animal dander
control entails removing the animal from the home or, at
a minimum, keeping the animal out of the patients bed-
room. Cockroaches can be controlled by poison or bait

traps and eliminating exposed food or garbage.
How should asthma therapy be adjusted

during pregnancy?
The step-care therapeutic approach increases the number
and dosage of medications with increasing asthma severity (see the box). At each step of therapy, medications are
considered to be preferred or alternative based on
efficacy and safety considerations. Patients whose symptoms are not optimally responding to treatment should
receive a step up in treatment to more intensive medical
therapy. Once control is achieved and sustained for several months, a step-down approach can be considered, but
a change in therapy should be undertaken cautiously and
administered gradually to avoid compromising the stability of the asthma control. For some patients, it may be prudent to postpone, until after birth, a reduction of therapy
that is effectively controlling the patients asthma (4).
How should acute asthma be assessed during

pregnancy?
Initial assessment of a pregnant patient presenting with
acute asthma includes obtaining a brief medical history,
performing a physical examination, and examining physiologic measures of airway function and fetal well-being.
Pulmonary physiologic assessment includes measuring
FEV1 or PEFR and oxygen saturation. Fetal assessment
PRACTICE BULLETINS
depends on the stage of pregnancy, but continuous electronic fetal monitoring or biophysical profile or both
should be considered if the pregnancy has reached the
stage of fetal viability.
After initial treatment, repeat assessments of the
patient and fetus will determine the need for continuing
care. Patients with FEV1 or PEFR measurements greater
than or equal to 70% sustained for 60 minutes after last
treatment, no distress, and reassuring fetal status may be
discharged. For an incomplete response (FEV1 or PEFR
measurements greater than or equal to 50% but less than
70%, mild or moderate symptoms), the disposition (continued treatment in the emergency department, discharge
home, or hospitalization) will need to be individualized.
For patients with a poor response (FEV1 or PEFR measurements less than 50%), hospitalization is indicated. For
patients with a poor response and severe symptoms, drowsiness, confusion, or PCO2 level greater than 42 mm Hg,
intensive care unit admission is indicated and intubation
should be strongly considered.
What should be the discharge regimen after

an acute asthma episode?
Patients discharged after an acute asthmatic episode
should continue treatment with short-acting 2-agonists,
two to four puffs every 34 hours as needed. Oral corticosteroids should be continued at a dose of 4060 mg in
a single dose or two divided doses for 310 days. Inhaled
corticosteroids should be initiated or continued until
review at medical follow-up. Outpatient follow-up
should be arranged within 5 days of the acute visit.
What are considerations for fetal surveillance

in pregnancies complicated by asthma?
Ultrasound examinations and antenatal fetal testing
should be considered for women who have moderate or
severe asthma during pregnancy. First-trimester ultrasound dating should be performed, if possible, to facilitate
subsequent evaluations of fetal growth restriction and the
risk of preterm birth. Serial ultrasound examinations to
monitor fetal activity and growth should be considered
(starting at 32 weeks of gestation) for women who have
poorly controlled asthma or moderate-to-severe asthma
and for women recovering from a severe asthma exacerbation. All patients should be instructed to be attentive to
fetal activity.
1029
and should receive adequate analgesia in order to

decrease the risk of bronchospasm. Women who are currently receiving or recently have taken systemic corticosteroids should receive intravenous administration
of corticosteroids (eg, hydrocortisone 100 mg every
8 hours) during labor and for 24 hours after delivery to
prevent adrenal crisis (4).
Cesarean delivery for acute exacerbation of asthma
is rarely needed. Maternal and fetal compromise usually
will respond to aggressive medical management.
However, delivery may benefit the respiratory status of a
patient with unstable asthma who has a mature fetus.
Lumbar anesthesia can reduce oxygen consumption and
minute ventilation during labor (24). Regional anesthesia was reported to incur a 2% incidence of bronchospasm (25). Obstetric, anesthetic, and pediatric staff
should communicate to coordinate intrapartum and postpartum care.
How should women with asthma be counseled

about breastfeeding?
In general, only small amounts of asthma medications
enter breast milk. The National Asthma Education and
Prevention Program found that the use of prednisone,
theophylline, antihistamines, inhaled corticosteroids,
2-agonists, and cromolyn is not contraindicated for
breastfeeding (4, 26).
Summary of
Recommendations and
Conclusions
It is safer for pregnant women with asthma to be
treated with asthma medications than it is for them
to have asthma symptoms and exacerbations.
Clinical evaluation of asthma includes subjective
assessments and pulmonary function tests.
The ultimate goal of asthma therapy in pregnancy is
maintaining adequate oxygenation of the fetus by
preventing hypoxic episodes in the mother.
What intrapartum concerns are unique to

pregnant women with asthma?
The step-care therapeutic approach increases the

number and dosage of medications with increasing
asthma severity.
Asthma medication use should not be discontinued during labor and delivery. The patient should be kept hydrated
Inhaled corticosteroids are first-line controller therapy for persistent asthma during pregnancy.
1030
Budesonide is the preferred inhaled corticosteroid

for use during pregnancy.
References
Inhaled albuterol is recommended rescue therapy

for pregnant women with asthma.
1. Alexander S, Dodds L, Armson BA. Perinatal outcomes in

women with asthma during pregnancy. Obstet Gynecol
1998;92:43540. (Level II-2)
Identifying and controlling or avoiding factors such

as allergens and irritants, particularly tobacco
smoke, can lead to improved maternal well-being
with less need for medication.
2. Kwon HL, Belanger K, Bracken MB. Asthma prevalence

among pregnant and childbearing-aged women in the
United States: estimates from national health surveys.
Ann Epidemiol 2003;13:31724. (Level III)
Continuation of immunotherapy is recommended in

patients who are at or near a maintenance dose, not
experiencing adverse reactions to the injections, and
apparently deriving clinical benefit.
3. Schatz M, Zeiger RS, Hoffman CP. Intrauterine growth is

related to gestational pulmonary function in pregnant
asthmatic women. Kaiser-Permanente Asthma and
Pregnancy Study Group. Chest 1990;98:38992. (Level
II-2)
Use of prednisone, theophylline, antihistamines,

inhaled corticosteroids, 2-agonists, and cromolyn is
not contraindicated for breastfeeding.

Asthma self-management skills, including selfmonitoring, correct use of inhalers, and following a
plan for long-term management of asthma and
promptly handling signs of worsening asthma,
enhance asthma control.
For pulmonary function assessment of patients during outpatient visits, spirometry is preferable, but
peak expiratory flow measurement with a peak flow
meter also is sufficient.
Ultrasound examinations and antenatal fetal testing
should be considered for women who have moderate or severe asthma during pregnancy.
Pregnant patients with asthma, even those with mild
or well-controlled disease, need to be monitored
with PEFR and FEV1 testing as well as by observing
their symptoms during pregnancy.
Routine evaluation of pulmonary function in pregnant women with persistent asthma is recommended.
Because pulmonary function and asthma severity
may change during the course of pregnancy, routine
evaluation of pulmonary function in pregnant
women with persistent asthma is recommended.
Measure
The percentage of pregnant patients with persistent asthma
who have undergone pulmonary function testing
4. National Heart, Lung, and Blood Institute, National

Asthma Education and Prevention Program. Working
group report on managing asthma during pregnancy: recommendations for pharmacologic treatmentupdate
2004. NIH Publication No. 05-5236. Bethesda (MD):
NHLBI; 2005. Available at: http://www.nhlbi.nih.gov/
health/prof/lung/asthma/astpreg/astpreg_full.pdf.
Retrieved September 10, 2007. (Level III)
5. Schatz M, Zeiger RS, Hoffman CP, Harden K, Forsythe A,
Chilingar L, et al. Perinatal outcomes in the pregnancies of
asthmatic women: a prospective controlled analysis. Am J
Respir Crit Care Med 1995;151:11704. (Level II-2)
6. Bracken MB, Triche EW, Belanger K, Saftlas A, Beckett
WS, Leaderer BP. Asthma symptoms, severity, and drug
therapy: a prospective study of effects on 2205 pregnancies. Obstet Gynecol 2003;102:73952. (Level II-2)
7. Dombrowski MP, Schatz M, Wise R, Momirova V,
Landon M, Mabie W, et al. Asthma during pregnancy.
National Institute of Child Health and Human
Development MaternalFetal Medicine Units Network
and the National Heart, Lung, and Blood Institute. Obstet
8. Demissie K, Breckenridge MB, Rhoads GG. Infant and
maternal outcomes in the pregnancies of asthmatic
women. Am J Respir Crit Care Med 1998;158:10915.
(Level II-2)
9. Perlow JH, Montgomery D, Morgan MA, Towers CV,
Porto M. Severity of asthma and perinatal outcome. Am J
10. Kallen B, Rydhstroem H, Aberg A. Asthma during pregnancya population based study. Eur J Epidemiol
2000;16:16771. (Level II-2)
11. Greenberger PA, Patterson R. The outcome of pregnancy
complicated by severe asthma. Allergy Proc 1988;9:
53943. (Level II-3)
12. Bakhireva LN, Schatz M, Chambers CD. Effect of maternal asthma and gestational asthma therapy on fetal growth.
J Asthma 2007;44:7176. (Level III)
13. Towers CV, Briggs GG, Rojas JA. The use of prostaglandin E2 in pregnant patients with asthma. Am J
(Level II-2)
PRACTICE BULLETINS
14. Schatz M, Dombrowski MP, Wise R, Thom EA, Landon

M, Mabie W, et al. Asthma morbidity during pregnancy
can be predicted by severity classification. J Allergy Clin
Immunol 2003;112:2838. (Level II-2)
15. Stenius-Aarniala B, Piirila P, Teramo K. Asthma and pregnancy: a prospective study of 198 pregnancies. Thorax
1988;43:128. (Level II-2)
16. Mihrshahi S, Belousova E, Marks GB, Peat JK.
Pregnancy and birth outcomes in families with asthma.
Childhood Asthma Prevention Team. J Asthma 2003;
40:1817. (Level II-2)
17. Minerbi-Codish I, Fraser D, Avnun L, Glezerman M,
Heimer D. Influence of asthma in pregnancy on labor and
the newborn. Respiration 1998;65:1305. (Level II-2)
18. Stenius-Aarniala BS, Hedman J, Teramo KA. Acute asthma
during pregnancy. Thorax 1996;51:4114. (Level II-2)
19. Jana N, Vasishta K, Saha SC, Khunnu B. Effect of
bronchial asthma on the course of pregnancy, labour and
perinatal outcome. J Obstet Gynaecol 1995;21:22732.
(Level II-2)
20. Triche EW, Saftlas AF, Belanger K, Leaderer BP, Bracken
MB. Association of asthma diagnosis, severity, symptoms,
and treatment with risk of preeclampsia. Obstet Gynecol
2004;104:58593. (Level II-2)
21. Schatz M, Dombrowski MP, Wise R, Momirova V,
Landon M, Mabie W, et al. Spirometry is related to perinatal outcomes in pregnant women with asthma. National
MaternalFetal Medicine Units Network; National Heart,
Lung, and Blood Institute. Am J Obstet Gynecol 2006;
194:1206. (Level II-2)
22. Metzger WJ, Turner E, Patterson R. The safety of
immunotherapy during pregnancy. J Allergy Clin
Immunol 1978;61:26872. (Level II-3)
23. Shaikh WA. A retrospective study on the safety of
immunotherapy in pregnancy. Clin Exp Allergy 1993;23:
85760. (Level II-2)
24. Hagerdal M, Morgan CW, Sumner AE, Gutsche BB.
Minute ventilation and oxygen consumption during labor
with epidural analgesia. Anesthesiology 1983;59:4257.
(Level II-2)
25. Fung DL. Emergency anesthesia for asthma patients. Clin
Rev Allergy 1985;3:12741. (Level III)
26. Transfer of drugs and other chemicals into human milk.
American Academy of Pediatrics. Pediatrics 2001;108:
77689. (Level III)
1031

Task Force:
I

type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Asthma in pregnancy. ACOG Practice Bulletin No. 90. American
111:45764.
1032
ACOG
PRACTICE
BULLETIN
(Replaces Practice Bulletin Number 87, November 2007)

of Zachary N. Stowe, MD and
Kimberly Ragan, MSW. The
of practice.
Use of Psychiatric
Medications During
Pregnancy and Lactation
It is estimated that more than 500,000 pregnancies in the United States each
year involve women who have psychiatric illnesses that either predate or
emerge during pregnancy, and an estimated one third of all pregnant women
are exposed to a psychotropic medication at some point during pregnancy (1).
The use of psychotropic medications is a cause of concern for physicians and
their patients because of the potential teratogenic risk, the risk of perinatal syndromes or neonatal toxicity, and the risk for abnormal postnatal behavioral
development. With the limited information available on the risks of the psychotropic medications, clinical management must incorporate an appraisal of
the clinical consequences of offspring exposure, the potential effect of untreated
maternal psychiatric illness, and the available alternative therapies. The purpose of this document is to present current evidence on the risks and benefits of
treatment for certain psychiatric illnesses during pregnancy.
Reaffirmed 2009
Background
Advising a pregnant or breastfeeding woman to discontinue medication
exchanges the fetal or neonatal risks of medication exposure for the risks of
untreated maternal illness. Maternal psychiatric illness, if inadequately treated
or untreated, may result in poor compliance with prenatal care, inadequate
nutrition, exposure to additional medication or herbal remedies, increased alcohol and tobacco use, deficits in motherinfant bonding, and disruptions within
the family environment (see Table 1). All psychotropic medications studied to
date cross the placenta (1), are present in amniotic fluid (2), and can enter
human breast milk (3). For known teratogens, knowledge of gestational age is
PRACTICE BULLETINS
helpful in the decision about drug therapy because the

major risk of teratogenesis is during embryogenesis (ie,
during the third through the eighth week of gestation).
The U.S. Food and Drug Administration (FDA) has provided a system for categorizing individual medications
(see Table 2), although this system has considerable limitations. Categories of risk for neonates from drugs used
1033
while breastfeeding also are shown in Table 2. Electronic

resources for information related to the fetal and neonatal effects of psychotropic drug therapy in pregnancy and
with breastfeeding include Reprotox (www.reprotox.org)
and TERIS (http://depts.washington.edu/terisweb). Providing women with patient resources for online information that are well referenced is a reasonable option.
Table 1. Impact of Psychiatric Illness on Pregnancy Outcome

Impact on Outcome
Illness
Teratogenic Effects
Obstetric
Neonatal
Treatment Options
Anxiety disorders
N/A
Increased incidence of forceps

deliveries, prolonged labor,
precipitate labor, fetal distress,
preterm delivery, and
spontaneous abortion
Decreased developmental
scores and inadaptability;
slowed mental development
at 2 years of age
Benzodiazepines
Antidepressants
Psychotherapy
Major depression
N/A
Increased incidence of low birth

weight, decreased fetal growth,
and postnatal complications
Increased newborn cortisol and

catecholamine levels, infant
crying, rates of admission to
neonatal intensive care units
Antidepressants
Psychotherapy
ECT
Bipolar disorder
N/A
See major depression
See major depression
Lithium
Anticonvulsants
Antipsychotics
ECT
Increased incidence of preterm

delivery, low birth weight,
small for gestational age,
placental abnormalities, and
antenatal hemorrhage
Increased rates of postnatal

death
Antipsychotics
Schizophrenia
Congenital malformations,
especially of cardiovascular
system
Abbreviations: ECT, electroconvulsive therapy; N/A, not available (eg, no studies identified)
Table 2. Psychiatric Medications in Pregnancy and Lactation*

Generic Name
Trade Name
Pregnancy Risk
Category
American Academy
of Pediatrics Rating
Lactation Risk
Category
Unknown, of concern
L3
Anxiolytic Medications
Benzodiazepines
Alprazolam
Xanax
Dm
Chlordiazepoxide
Librium
N/A
L3
Clonazepam
Klonopin
Dm
N/A
L3
Clorazepate
Tranxene
N/A
L3
Diazepam
Valium
Unknown, of concern
L3, L4 if used chronically
Lorazepam
Ativan
Dm
Unknown, of concern
L3
Oxazepam
Serax
N/A
L3
Estazolam
ProSom
Xm
N/A
L3
Flurazepam
Dalmane
Xm
N/A
L3
Quazepam
Doral
Xm
Unknown, of concern
L2
Benzodiazepines for Insomnia
(continued)
1034
Table 2. Psychiatric Medications in Pregnancy and Lactation* (continued)

Generic Name
Pregnancy Risk
Category
Trade Name
American Academy
Lactation Risk
Category
Anxiolytic Medications (continued)

Benzodiazepines for Insomnia (continued)
Temazepam
Restoril
Xm
Unknown, of concern
L3
Triazolam
Halcion
Xm
N/A
L3
Nonbenzodiazepine Anxiolytics and Hypnotics

Buspirone
BuSpar
Bm
N/A
L3
Chloral hydrate
Noctec
Cm
Compatible
L3
Eszoplicone
Lunesta
Cm
N/A
N/A
Zaleplon
Sonata
Cm
Unknown, of concern
L2
Zolpidem
Ambien
Bm
N/A
L3
Antiepileptic and Mood Stabilizing Medications

Lithium carbonate
Eskalith, Lithobid, Lithonate
Contraindicated
L4
Valproic acid
Depakote (divalproex sodium) Dm
Compatible
L2
Carbamazepine
Tegretol
Dm
Compatible
L2
Lamotrigine
Lamictal
Cm
Unknown
L3
Antidepressants
Tricyclic and Heterocyclic Antidepressants
Amitriptyline
Elavil, Endep
Cm
Unknown, of concern
L2
Amoxapine
Asendin
Cm
Unknown, of concern
L2
||
L2
L2
Clomipramine
Anafranil
Cm
Unknown, of concern
Desipramine
Norpramin
Unknown, of concern
Doxepin
Sinequan, Adapin
Unknown, of concern
L5
Imipramine
Tofranil
Unknown, of concern
L2
Maprotiline
Ludiomil
Bm
N/A
L3
Nortriptyline
Pamelor, Aventyl
Unknown, of concern||
L2
Protriptyline
Vivactil
N/A
N/A
N/A
L3
Selective Serotonin Reuptake Inhibitors

Citalopram
Celexa
Cm
Escitalopram
Lexapro
Cm
N/A
L3 in older infants
Fluoxetine
Prozac
Cm
Unknown, of concern
L2 in older infants, L3 if
used in neonatal period
Fluvoxamine
Luvox
Cm
Unknown, of concern
L2
Paroxetine
Paxil
Dm
Unknown, of concern
L2
Sertraline
Zoloft
Cm
Unknown, of concern
L2
Other Antidepressants
Bupropion
Wellbutrin
Bm
Unknown, of concern
L3
Duloxetine
Cymbalta
Cm
N/A
N/A
Mirtazapine
Remeron
Cm
N/A
L3
Nefazodone
Serzone
Cm
N/A
L4
(continued)
PRACTICE BULLETINS
1035
Table 2. Psychiatric Medications in Pregnancy and Lactation* (continued)

Generic Name
Trade Name
Pregnancy Risk
Category
American Academy
Lactation Risk
Category
Antidepressants (continued)
Other Antidepressants (continued)
Trazodone
Desyrel
Cm
Unknown, of concern
L2
Venlafaxine
Effexor
Cm
N/A
L3
Unknown, of concern
L3
Antipsychotic Medications
Typical Antipsychotics
Chlorpromazine
Thorazine
Fluphenazine
Prolixin
N/A
L3
Haloperidol
Haldol
Cm
Unknown, of concern
L2
Loxapine
Loxitane
N/A
L4
Perphenazine
Trilafon
Unknown, of concern
N/A
Pimozide
Orap
Cm
N/A
L4
Thioridazine
Mellaril
N/A
L4
Thiothixene
Navane
N/A
L4
Trifluoperazine
Stelazine
Unknown, of concern
N/A
Abilify
Cm
N/A
L3
L3
Atypical Antipsychotics
Aripiprazole
Clozapine
Clozaril
Bm
Unknown, of concern
Olanzapine
Zyprexa
Cm
N/A
L2
Quetiapine
Seroquel
Cm
Unknown, of concern
L4
Risperidone
Risperdal
Cm
N/A
L3
Ziprasidone
Geodon
Unknown, of concern
L4
Abbreviation: N/A, not available

*The average half-life of elimination is listed for major metabolites.
The U.S. Food and Drug Administration classifies drug safety using the following categories: A, controlled studies show no risk; B, no evidence of risk in humans; C,
risk cannot be ruled out; D, positive evidence of risk; X, contraindicated in pregnancy. Risk category adapted from Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2005. The m subscript is for data taken from the manufacturers package insert.
American Academy of Pediatrics 2001
Lactation risk categories are listed as follows: L1, safest; L2, safer; L3, moderately safe; L4, possibly hazardous; L5, contraindicated. For more information, see Hale TW.
Medications in Mothers Milk. Amaraillo (TX): Pharmasoft Publishing, 2004.
||
Original committee report 1994 listed as compatible, and a correction was later published.
Not listed in Briggs. Risk category taken from Physicians Desk Reference 1992, 1993, 1994, 1996, and 2004.
General Treatment Concepts

Optimally, shared decision making among obstetric and
mental health clinicians and the patient should occur
before pregnancy. Whenever possible, multidisciplinary
management involving the obstetrician, mental health
clinician, primary health care provider, and pediatrician
is recommended to facilitate care.
A single medication at a higher dose is favored over
multiple medications for treatment of psychiatric illness
during pregnancy. Changing medications increases the
exposure to the offspring. The selection of medication to
minimize the risk of illness should be based on history of

efficacy, prior exposure during pregnancy, and available
reproductive safety information (see Table 3). Medications
with fewer metabolites, higher protein binding (decreases
placental passage), and fewer interactions with other medications are preferred.
Major Depression
Prevalence rates for depression are estimated at 17% for
adults in the United States (4); women twice as often as
men experience depression (5). The highest rates for
1036
Table 3. Management Issues Associated With Medication Use During Pregnancy and Lactation
Management Issues
Medication Class
Birth Defects
Pregnancy
Possible increased
incidence of cleft
lip or palate
Ultrasonography for
facial morphology
Floppy infant
syndrome
Withdrawal
syndrome
Infant sedation
reported
Clonazepam
Lorazepam
Alprazolam
Selective serotonin
None confirmed
reuptake inhibitors,
selective norepinephrine reuptake
inhibitors, and
tricyclic antidepressants
Decreased serum
concentrations
across pregnancy
None
Neonatal,
withdrawal
syndrome
None
Fluoxetine
Sertraline
Paroxetine
Citalopram
Nortriptyline
Lithium
Increased
incidence of
heart defects
Ultrasonography or
fetal echocardiography
for heart development
or both
Decreased serum
concentrations
across pregnancy
Intravenous fluids Increased risk for

Increased risk for lithium toxicity
lithium toxicity in in infant
mother
Monitor infant
complete blood
count, thyroidstimulating
hormone levels,
and lithium
levels
Sustained release
lithium
Antiepileptic Drugs
Increased incidence Decreased serum

None
of birth defects
concentrations across
pregnancy
Folate supplementation,
Vitamin K for some
antiepileptic drugs
Neonatal
symptoms,
Vitamin K for
some antiepileptic drugs
Monitor infant
complete blood
count, liver
enzyme levels,
antiepileptic
drug levels
Lamotrigine
Carbemazepine
Antipsychotic
Medications
None Confirmed
Possible risk for

neuroleptic
malignant
syndrome and
intestinal
obstruction
None
Haloperidol
Benzodiazepines
Avoid anticholinergic
medications for
side effects
depression occur in women between the ages of 25 years

and 44 years (6). Symptoms include depressed or irritable mood, anhedonia, weight loss or gain, appetite and
sleep changes, loss of energy, feelings of excessive guilt
or worthlessness, psychomotor agitation or retardation
and, in more severe cases, suicidal ideation (7).
Approximately 1016% of pregnant women fulfill diagnostic criteria for depression, and up to 70% of pregnant
women report symptoms of depression (6, 810). Many
symptoms of depression overlap with the symptoms of
pregnancy and often are overlooked (6, 11). Of women
taking antidepressants at conception, more than 60%
experienced symptoms of depression during the pregnancy (12). In a study of pregnant women taking antidepressants before conception, a 68% relapse of depression
was documented in those who discontinued medications
during pregnancy (13) compared with only a 25% relapse
in those who continued antidepressant medications.
Postpartum depression is classified as a major
episode of depression that occurs within the first 4 weeks
postpartum (7) or within the first 6 weeks postpartum
Delivery
None
Neonatal
Lactation
Treatment Options
(14). Many women in whom postpartum depression was

diagnosed reported having symptoms of depression during pregnancy (9, 1517). These symptoms may be difficult to differentiate from normal postpartum adaptation.
Survey tools (eg, Edinburgh Postnatal Depression Scale,
Beck Depression Inventory, and the Postpartum
Depression Screening Scale), are widely used to identify
depression during the perinatal period (18). The detection
rate is in the range of 68100% (better for severe depression) with specificities in the range of 7896% (19).
Untreated maternal depression is associated with an
increase in adverse pregnancy outcomes, including premature birth, low birthweight infants, fetal growth restriction, and postnatal complications. This association is
stronger when depression occurs in the late second to
early third trimester (20). Newborns of women with
untreated depression during pregnancy cry more and are
more difficult to console (2022). Maternal depression
also is associated with increased life stress, decreased
social support, poor maternal weight gain, smoking, and
alcohol and drug use (23), all of which can adversely
PRACTICE BULLETINS
affect infant outcome (2426). Later in life, children of

untreated depressed mothers are more prone to suicidal
behavior, conduct problems, and emotional instability and
more often require psychiatric care (27, 28).
Bipolar Disorder
Bipolar disorder, historically called manicdepressive
disorder, affects between 3.9% and 6.4% of Americans
and affects men and women equally (4, 2931). It commonly is characterized by distinct periods of abnormally
and persistently elevated, expansive, or irritable mood
and separate distinct periods of depressed mood or anhedonia (7). Women are more likely than men to experience
depressive episodes of bipolar disorder (32), rapid
cycling (33), and mixed episodes (34, 35). Typical onset
of bipolar disorder for women is in the teens or early
twenties.
Rates of postpartum relapse range from 32% (36) to
67% (37). In one study, it was reported that pregnancy had
a protective effect for women with bipolar disorder (38),
but the participants may have had milder illness. Perinatal
episodes of bipolar disorder tend to be depressive (37, 39)
and, when experienced with one pregnancy, are more
likely to recur with subsequent pregnancies (37). There
also is an increased risk of postpartum psychosis as high
as 46% (40, 41).
Anxiety Disorders
Anxiety disorders include panic disorder, obsessive
compulsive disorder (OCD), generalized anxiety disorder
(GAD), posttraumatic stress disorder (PTSD), social anxiety disorder, and specific phobias. Collectively, anxiety
disorders are the most commonly occurring psychiatric
disorders, with a prevalence of 18.1% among adults 18
years and older in the United States (42). Panic disorder,
GAD, PTSD, agoraphobia, and specific phobias are two
times more likely to be diagnosed in women than men.
Anxiety and stress during pregnancy are documented as
factors associated with poor obstetric outcomes, including spontaneous abortions (43), preterm delivery (44,
45), and delivery complications (46), such as prolonged
labor, precipitate labor, clinical fetal distress, and forceps
deliveries (47). A direct causal relationship has not been
established.
Panic disorder is characterized by recurrent panic
attacks that arise spontaneously in situations that are not
expected to cause anxiety. Most investigators agree that
women are at greatest risk for exacerbation of panic disorder during the postpartum period (48, 49). In a recent
study PTSD was reported to be the third most common
psychiatric diagnosis among economically disadvantaged
pregnant women, with a prevalence of 7.7% (50). Women
1037
with PTSD were significantly more likely to have a

comorbid condition, principally major depression or
GAD. Many reports have documented traumatic obstetric
experiences (eg, emergency delivery, miscarriage, and
fetal demise) as precipitants to PTSD-related symptomatology. The incidence of OCD during pregnancy is
unknown. Despite limited formal investigation, most clinicians and researchers agree that pregnancy seems to be a
potential trigger of OCD symptom onset, with 39% of the
women in a specialized OCD clinic experiencing symptom onset during pregnancy (51). It generally is accepted
that OCD worsens during the postpartum period.
Schizophrenia-Spectrum Disorders
Schizophrenia is a severe and persistent mental illness
characterized by psychotic symptoms, negative symptoms,
such as flat affect and lack of volition, and significant
occupational and social dysfunction (7). Schizophrenia
occurs in approximately 12% of women, with the most
common age of onset during the childbearing years (52).
A variety of adverse pregnancy outcomes in women
with schizophrenia have been reported, including preterm
delivery, low birth weight infants, small for gestational
age fetuses (53, 54), placental abnormalities and antenatal hemorrhage, increased rates of congenital malformations, especially of the cardiovascular system (55), and a
higher incidence of postnatal death (53). However, in one
study it was found that schizophrenic women were not at
higher risk for specific obstetric complications but were
at greater risk of requiring interventions during delivery,
including labor induction and assisted or cesarean delivery (56). If left untreated during pregnancy, schizophrenia-spectrum disorders can have devastating effects on
both mother and child, with rare reports of maternal selfmutilation (57, 58), denial of pregnancy resulting in
refusal of prenatal care (59), and infanticide (60, 61).

Recommendations
What is the evidence regarding the safety
and efficacy of treatment for depression during pregnancy?
Most data related to antidepressants in pregnancy are
derived from the use of selective serotonin reuptake
inhibitors (SSRIs) (fluoxetine, sertraline, citalopram, and
paroxetine). Overall, there is limited evidence of teratogenic effects from the use of antidepressants in pregnancy
or adverse effects from exposure during breastfeeding
(6264). There are two reports from GlaxoSmithKline
1038
based on a Swedish national registry and a U.S. insurance claims database that have raised concerns about a
1.52-fold increased risk of congenital cardiac malformations (atrial and ventricular septal defects) associated
with first-trimester paroxetine exposure (www.gskus.com/
news/paroxetine/paxil_letter_e3.pdf). The manufacturer
subsequently changed paroxetines pregnancy FDA category from C to D (www.fda.gov/cder/drug/advisory/
paroxetine200512.htm).
More recently, the teratogenic effect of SSRI use
during the first trimester of pregnancy was examined in
two large casecontrol studies from multisite surveillance programs (65, 66). In the National Birth Defects
Prevention Study, no significant associations were
found between SSRI use overall and congenital heart
defects (66). However, an association was found
between SSRI use (particularly paroxetine) during early
pregnancy and anencephaly, craniosynostosis, and
omphalocele. Importantly, these risks were found only
after more than 40 statistical tests were performed. Even
if findings were not the result of chance, the absolute
risks associated with SSRI use identified in this study
were small. For example, a twofold to threefold increase
in birth defects would occur for omphalocele
(1 in 5,000 births), craniosynostosis (1 in 1,800 births)
and anencephaly (1 in 1,000 births). In contrast, in the
Slone Epidemiology Center Birth Defects Study no
increased risk of craniosynostosis, omphalocele, or
heart defects associated with SSRI use overall during
early pregnancy was found (65). An association was
seen between paroxetine and right ventricular outflow
defects. Additionally, sertraline use was associated with
omphalocele and atrial and ventricular septum defects.
A limitation of this study is that the authors conducted
42 comparisons in their analyses for their main hypotheses. Both of these casecontrol studies were limited by
the small number of exposed infants for each individual
malformation. The current data on SSRI exposure during early pregnancy provide conflicting data on the risk
for both overall and specific malformations. Some
investigators have found a small increased risk of cardiac defects, specifically with paroxetine exposure. The
absolute risk is small and generally not greater than two
per 1,000 births; hence, these agents are not considered
major teratogens.
Exposure to SSRIs late in pregnancy has been associated with transient neonatal complications, including
jitteriness, mild respiratory distress, transient tachypnea
of the newborn, weak cry, poor tone, and neonatal intensive care unit admission (6771). A more recent FDA
public health advisory highlighted concerns about the
risk of an unconfirmed association of newborn persistent pulmonary hypertension with SSRI use (72)
(www.fda.gov/cder/drug/advisory/SSRI_PPHN
200607. htm).
The potential risk of SSRI use in pregnancy must be

considered in the context of the risk of relapse of depression if treatment is discontinued. Factors associated with
relapse during pregnancy include a long history of
depressive illness (more than 5 years) and a history of
recurrent relapses (more than four episodes) (13).
Therefore, treatment with all SSRIs or selective norepinephrine reuptake inhibitors or both during pregnancy
should be individualized. At this time, paroxetine use in
pregnant women and women planning pregnancy should
be avoided, if possible. Fetal echocardiography should be
considered for women exposed to paroxetine in early
pregnancy. Because abrupt discontinuation of paroxetine
has been associated with withdrawal symptoms, discontinuation of this agent should occur according to the
products prescribing information.
Tricyclic antidepressants (TCAs) have been available
in the United States since 1963 and were widely used by
women during pregnancy and lactation before the introduction of SSRIs. Results from initial studies, which suggested that TCA exposure might be associated with limb
anomalies (7375), have not been confirmed with subsequent studies (76, 77). Neonatal neurobehavioral effects
from fetal exposure have not been reported (78).
Acute effects associated with TCA exposure include
case reports of fetal tachycardia (79), neonatal symptoms
such as tachypnea, tachycardia, cyanosis, irritability,
hypertonia, clonus, and spasm (7282), and transient
withdrawal symptoms (83). In more recent studies, a significant link between prenatal exposure to TCAs and
perinatal problems has not been documented (64, 8486).
Atypical antidepressants are non-SSRI and nonTCA antidepressants that work by distinct pharmacodynamic mechanisms. The atypical antidepressants include
bupropion, duloxetine, mirtazapine, nefazodone, and
venlafaxine. The limited data of fetal exposure to these
antidepressants (70, 8589), do not suggest an increased
risk of fetal anomalies or adverse pregnancy events. In
the one published study of bupropion exposure in 136
patients, a significantly increased risk of spontaneous
abortion, but not an increased risk of major malformations, was identified (90). In contrast, the bupropion registry maintained at GlaxoSmithKline has not identified
any increased risk of spontaneous abortion, although
these data have not undergone peer review.
Antidepressant medication is the mainstay of treatment for depression, although considerable data show
that structured psychotherapy, such as interpersonal psychotherapy or cognitive behavioral therapy, are effective
treatments for mild to moderate depression and are beneficial adjuncts to medication. In addition, electroconvulsive therapy is an effective treatment for major depression
and is safe to use during pregnancy (91, 92).
PRACTICE BULLETINS

and efficacy of lithium for the treatment of
bipolar disorders during pregnancy?
Use of lithium in pregnancy may be associated with a
small increase in congenital cardiac malformations. The
initial retrospective data suggested that fetal exposure to
lithium was associated with a 400-fold increase in congenital heart disease, particularly Ebsteins anomaly (93,
94). A subsequent meta-analysis of the available data
calculated the risk ratio for cardiac malformations to be
1.27.7 and the risk ratio for overall congenital malformations to be 1.53 (95). In more recent small studies,
limited in their statistical power, the magnitude of early
estimates of teratogenic potential of lithium could not be
confirmed (9698).
Fetal exposure to lithium later in gestation has been
associated with fetal and neonatal cardiac arrhythmias
(99), hypoglycemia, nephrogenic diabetes insipidus
(100), polyhydramnios, reversible changes in thyroid
function (101), premature delivery, and floppy infant syndrome similar to that seen with benzodiazepine exposure
(102). Symptoms of neonatal lithium toxicity include
flaccidity, lethargy, and poor suck reflexes, which may
persist for more than 7 days (103). Neurobehavioral
sequelae were not documented in a 5-year follow-up of 60
school-aged children exposed to lithium during gestation
(104).
The physiologic alterations of pregnancy may affect
the absorption, distribution, metabolism and elimination
of lithium, and close monitoring of lithium levels during
pregnancy and postpartum is recommended. The decision
to discontinue lithium therapy in pregnancy because of
fetal risks should be balanced against the maternal risks
of exacerbation of illness. In a recent study, it was reported that abrupt discontinuation of lithium was associated with a high rate of bipolar relapse among pregnant
women (39). The following treatment guidelines have
been suggested for women with bipolar illness who are
treated with lithium and plan to conceive: 1) in women
who experience mild and infrequent episodes of illness,
treatment with lithium should be gradually tapered before
conception; 2) in women who have more severe episodes
but are only at moderate risk for relapse in the short term,
treatment with lithium should be tapered before conception but reinstituted after organogenesis; 3) in women
who have especially severe and frequent episodes of illness, treatment with lithium should be continued
throughout gestation and the patient counseled regarding
reproductive risks (95). Fetal assessment with fetal
echocardiography should be considered in pregnant
women exposed to lithium in the first trimester. For
1039
women in whom an unplanned conception occurs while

receiving lithium therapy, the decision to continue or discontinue the use of lithium should be in part based on disease severity, course of the patients illness, and the point
of gestation at the time of exposure.

and efficacy of the antiepileptic drugs valproate and carbamazepine for the treatment
of bipolar disorders during pregnancy?
Several anticonvulsants, including valproate, carbamazepine, and lamotrigine, currently are used in the
treatment of bipolar disorder. Data regarding fetal effects
of these drugs are derived primarily from studies of
women with seizures. Whether the underlying pathology
of epilepsy contributes to the teratogenic effect on the
fetus is unclear. Epilepsy may not contribute to the teratogenic effects of antiepileptic drugs based on the
results of a recent study that demonstrated similar rates
of anomalies between infants of women without epilepsy and infants of women with epilepsy but who had
not taken antiepileptic drugs during pregnancy (105).
Prenatal exposure to valproate is associated with a
13.8% risk of neural tube defects, with a corresponding
doseresponse relationship (106113). Other congenital
malformations associated with valproate use include
craniofacial anomalies (114), limb abnormalities (115),
and cardiovascular anomalies (116118). A fetal valproate syndrome has been described with features of
fetal growth restriction, facial dysmorphology, and limb
and heart defects (119121). Varying degrees of cognitive
impairment, including mental development delay (122),
autism (123126), and Aspergers syndrome (124), have
been reported with fetal valproate syndrome (124, 127,
128). Acute neonatal risks include hepatotoxicity (129),
coagulopathies (130), neonatal hypoglycemia (131), and
withdrawal symptoms (132).
Carbamazepine exposure in pregnancy is associated
with a fetal carbamazepine syndrome manifest by facial
dysmorphism and fingernail hypoplasia (124, 133136).
It is unclear whether carbamazepine use increases the risk
of fetal neural tube defects or developmental delay (124,
127, 133139). Fetal exposure to lamotrigine has not
been documented to increase the risk of major fetal
anomalies (140145), although there may be an increased
risk of midline facial clefts (0.89% of 564 exposures) as
reported by one pregnancy registry (143), possibly related
to higher daily maternal doses (greater than 200 mg/day)
(145). The reproductive safety of lamotrigine appears to
compare favorably with alternative treatments, but lacking are studies of the effectiveness of this antiepileptic
drug as a mood stabilizer in pregnancy.
1040
In managing bipolar disorders, the use of valproate

and carbamazepine are superior to that of lithium for
patients who experience mixed episodes or rapid cycling
but exhibit limited efficacy in the treatment of bipolar
depression. In contrast, lamotrigine is efficacious in the
prevention of the depressed phase of illness (146, 147).
Lamotrigine is a potential maintenance therapy option for
pregnant women with bipolar disorder because of its protective effects against bipolar depression, general tolerability, and growing reproductive safety profile relative to
alternative mood stabilizers. Because both valproate and
carbamazepine are associated with adverse effects when
used during pregnancy, their use, if possible should be
avoided especially during the first trimester. The effectiveness of folate supplementation in the prevention of
drug-associated neural tube defects has not been documented; however, folate supplementation of 4 mg/day
should be offered preconceptionally and for the first
trimester of pregnancy. Prenatal surveillance for congenital anomalies by maternal serum alpha-fetoprotein level
testing, fetal echocardiography, or a detailed ultrasound
examination of the fetal anatomy or a combination of
these procedures should be considered. Whether the use
of antiepileptic drugs such as carbamazepine increase the
risk of neonatal hemorrhage and whether maternal vitamin K supplementation is effective remains unclear
(148).
What is the evidence regarding the safety and

efficacy of treatment for anxiety disorders
during pregnancy?
Use of benzodiazepines does not appear to carry a significant risk of somatic teratogenesis. In early studies of
in utero exposure to diazepam, a benzodiazepine, an
increased risk of oral clefts was reported (149151). In a
subsequent meta-analysis, it was demonstrated that prenatal benzodiazepine exposure increased the risk of oral
cleft, although the absolute risk increased by 0.01%,
from 6 in 10,000 to 7 in 10,000 (76). In a recent
casecontrol study of 22,865 infants with congenital
anomalies and 38,151 infants without congenital anomalies, an association of congenital anomalies, including
oral clefts with exposure to five different benzodiazepines, was not found (152). Similar findings were
documented in a casecontrol study of clonazepam
(153). If discontinuation of benzodiazepine use is considered during pregnancy, benzodiazepines should not be
abruptly withdrawn.
The data regarding neonatal toxicity and withdrawal
syndromes are well documented, and neonates should be
observed closely in the postpartum period. Floppy infant
syndrome, characterized by hypothermia, lethargy, poor
respiratory effort, and feeding difficulties, is associated

with maternal use of benzodiazepines shortly before
delivery (154162). Neonatal withdrawal syndromes,
characterized by restlessness, hypertonia, hyperreflexia,
tremulousness, apnea, diarrhea, and vomiting, have been
described in infants whose mothers were taking alprazolam (163), chlordiazepoxide (164166), or diazepam
(167, 168). These symptoms have been reported to persist for as long as 3 months postpartum (81).
The long-term neurobehavioral impact of prenatal
benzodiazepine exposure is unclear. The existence of a
benzodiazepine-exposure syndrome, including growth
restriction, dysmorphism, and both mental and psychomotor retardation, in infants exposed prenatally to
benzodiazepines is disputed (169171). In one study, no
differences in the incidence of behavioral abnormalities
at age 8 months or IQ scores at age 4 years were found
among children exposed to chlordiazepoxide during gestation (172).

and efficacy of treatment for schizophrenia
during pregnancy?
The atypical antipsychotics (eg, clozapine, olanzapine,
quetiapine, risperidone, ziprasidone, and aripiprazole)
have replaced the typical agents as first-line medications
for psychotic disorders (Table 2). The atypical antipsychotics generally are better tolerated and possibly are
more effective in managing the negative symptoms of
schizophrenia. They also are used increasingly for bipolar disorder, obsessivecompulsive disorder, and treatment-resistant depression. The reproductive safety data
regarding the use of atypical antipsychotics remains
extremely limited. In a prospective comparative study of
pregnancy outcomes between groups exposed and
unexposed to atypical antipsychotics, outcomes of 151
pregnancies with exposure to olanzapine, risperidone,
quetiapine, and clozapine demonstrated a higher rate of
low birth weight (10% in the exposed versus 2% in the
nonexposed group) and therapeutic abortions (173).
The typical antipsychotic drugs have a larger reproductive safety profile and include haloperidol, thioridazine, fluphenazine, perphenazine, chlorpromazine, and
trifluoperazine. No significant teratogenic effect has been
documented with chlorpromazine, haloperidol, and perphenazine (174176). In a study of 100 women treated
with haloperidol (mean dose of 1.2 mg/day) for hyperemesis gravidarum, no differences in gestational duration, fetal viability, or birth weight were noted (177). In a
large prospective study encompassing approximately
20,000 women treated primarily with phenothiazines for
emesis (178), investigators found no significant associa-
PRACTICE BULLETINS
tion with neonatal survival rates or severe anomalies.

Similar results have been obtained in several retrospective studies of women treated with trifluoperazine for
repeated abortions and emesis (179, 180). In contrast,
other investigators reported a significant association of
major anomalies with prenatal exposure to phenothiazines
with an aliphatic side chain but not with piperazine or
piperidine class agents (181). Reanalysis of previously
reported data obtained also identified a significant risk of
malformations associated with phenothiazine exposure in
weeks 410 of gestation (182). In clinical neurobehavioral outcome studies encompassing 203 children
exposed to typical antipsychotics during gestation, no
considerable differences have been detected in IQ scores
at 4 years of age (183, 184), although relatively low
antipsychotic doses were used by many women in these
studies.
Fetal and neonatal toxicity reported with exposure to
the typical antipsychotics includes neuroleptic malignant
syndrome (185), dyskinesia (186), extrapyramidal side
effects manifested by heightened muscle tone and
increased rooting and tendon reflexes persisting for several months (187), neonatal jaundice (188), and postnatal
intestinal obstruction (189).
Fetuses and infants also may be exposed to drugs
used to manage the extrapyramidal side effects (eg,
diphenhydramine, benztropine, and amantadine). In a
casecontrol study, oral clefts were associated with a significantly higher rate of prenatal exposure to diphenhydramine than controls (149). In contrast, in several other
studies diphenhydramine use has not been found to be a
significant risk factor for fetal malformations (190, 191).
Clinical studies of the teratogenic potential of benztropine and amantadine use are lacking.
In summary, typical antipsychotics have been widely
used for more than 40 years, and the available data suggest the risks of use of these agents are minimal with
respect to teratogenic or toxic effects on the fetus. In particular, use of piperazine phenothiazines (eg, trifluoperazine and perphenazine) may have especially limited
teratogenic potential (181). Doses of typical antipsychotics during the peripartum should be kept to a minimum to limit the necessity of utilizing medications to
manage extrapyramidal side effects. There is likewise
little evidence to suggest that the currently available
atypical antipsychotics are associated with elevated
risks for neonatal toxicity or somatic teratogenesis. No
long-term neurobehavioral studies of exposed children
have yet been conducted. Therefore, the routine use of
atypical antipsychotics during pregnancy and lactation
cannot be recommended. In a woman who is taking an
atypical antipsychotic and inadvertently conceives, a
comprehensive riskbenefit assessment may indicate
1041
that continuing therapy with the atypical antipsychotic

(to which the fetus has already been exposed) during
gestation is preferable to switching to therapy with a
typical antipsychotic (to which the fetus has not yet
been exposed).
What is the risk of using psychiatric drugs

while breastfeeding?
Breastfeeding has clear benefits for both mother and
infant and, in making the decision to recommend breastfeeding, these benefits should be weighed against the
risks to the neonate of medication exposure while breastfeeding (Table 2). Most medications are transferred
through breast milk, although most are found at very low
levels and likely are not clinically relevant for the
neonate. For women who breastfeed, measuring serum
levels in the neonate is not recommended. Most clinical
laboratory tests lack the sensitivity to detect and measure
the low levels present. However, breastfeeding should be
stopped immediately if a nursing infant develops abnormal symptoms most likely associated with exposure to
the medication. Evaluation of the literature on drug levels in breast milk can facilitate the decision to breastfeed
(192).
In the treatment of depression, published reports
regarding SSRI use and lactation now consist of 173
motherinfant nursing pairs with exposure to sertraline,
fluoxetine, paroxetine, fluvoxamine, and citalopram (193,
194215). In results from studies, it has been shown that,
quantitatively, medication exposure during lactation is
considerably lower than transplacental exposure to these
same SSRIs during gestation (193, 201, 208, 216).
Generally, very low levels of SSRIs are detected in breast
milk. Only a few isolated cases of adverse effects have
been reported, although infant follow-up data are limited. The package insert for citalopram does report a case
of an infant who experienced a transient apneic episode.
Long-term neurobehavioral studies of infants exposed to
SSRI antidepressants during lactation have not been
conducted.
The TCAs also have been widely used during lactation. The only adverse event reported to date is respiratory depression in a nursing infant exposed to doxepin,
which led to the conclusion that doxepin use should be
avoided but that most TCAs are safe for use during
breastfeeding (217). Data regarding the use of atypical
antidepressants during lactation are limited to the use of
venlafaxine (218) and bupropion (219, 220).
The existing data regarding lithium use and lactation
encompass 10 motherinfant nursing dyads (103,
221225). Adverse events, including lethargy, hypotonia,
hypothermia, cyanosis, and electrocardiogram changes,
1042
were reported in two of the children in these studies (103,

223). The American Academy of Pediatrics consequently
discourages the use of lithium during lactation (226).
Because dehydration can increase the vulnerability to
lithium toxicity, the hydration status of nursing infants of
mothers taking lithium should be carefully monitored
(102). There are no available reports regarding the longterm neurobehavioral sequelae of lithium exposure during lactation.
Only one adverse event, an infant with thrombocytopenia and anemia (227), has been reported in studies
regarding valproate use and lactation, which includes 41
motherinfant nursing dyads (227235). Studies of the
neurobehavioral impact of valproate exposure during lactation have not been conducted. The American Academy
of Pediatrics and the World Health Organization (WHO)
Working Group on Drugs and Human Lactation have
concluded that use of valproate is compatible with breastfeeding (226, 236). Reported adverse effects of carbamazepine in breast milk include transient cholestatic
hepatitis (237, 238) and hyperbilirubinemia (239). The
WHO Working Group on Drugs and Human Lactation
has concluded that use of carbamazepine with breastfeeding is probably safe (236).
In the management of anxiety disorders, benzodiazepine use exhibits lower milk/plasma ratios than other
classes of psychotropics (240, 241). Some investigators
concluded that benzodiazepine use at relatively low doses
does not present a contraindication to nursing (242).
However, infants with an impaired capacity to metabolize
benzodiazepines may exhibit sedation and poor feeding
even with low maternal doses (243).
Of typical antipsychotic medications, chlorpromazine
has been studied in seven breastfeeding infants, none of
whom exhibited developmental deficits at 16-month and
5-year follow-up evaluations (244). However, three
breastfeeding infants in another study, whose mothers
were prescribed both chlorpromazine and haloperidol,
exhibited evidence of developmental delay at 1218
months of age (245).
Resources
Web: www.aap.org
American Psychiatric Association
Web: www.psych.org
National Institutes of Health
Daily medication:
http://dailymed.nlm.nih.gov/dailymed/about.cfm
Lactation medication:
toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Summary of
Recommendations and
Conclusions
Lithium exposure in pregnancy may be associated
with a small increase in congenital cardiac malformations, with a risk ratio of 1.27.7.
Valproate exposure in pregnancy is associated with
an increased risk of fetal anomalies, including neural tube defects, fetal valproate syndrome, and longterm adverse neurocognitive effects. It should be
avoided in pregnancy, if possible, especially during
the first trimester.
Carbamazepine exposure in pregnancy is associated
with fetal carbamazepine syndrome. It should be
avoided in pregnancy, if possible, especially during
the first trimester.
Maternal benzodiazepine use shortly before delivery
is associated with floppy infant syndrome.

Paroxetine use in pregnant women and women planning pregnancy should be avoided, if possible. Fetal
echocardiography should be considered for women
who are exposed to paroxetine in early pregnancy.
Prenatal benzodiazepine exposure increased the risk
of oral cleft, although the absolute risk increased by
0.01%.
Lamotrigine is a potential maintenance therapy
option for pregnant women with bipolar disorder
because of its protective effects against bipolar
depression, general tolerability, and a growing
reproductive safety profile relative to alternative
mood stabilizers.
Maternal psychiatric illness, if inadequately treated
or untreated, may result in poor compliance with
prenatal care, inadequate nutrition, exposure to
additional medication or herbal remedies, increased
alcohol and tobacco use, deficits in motherinfant
bonding, and disruptions within the family environment.
PRACTICE BULLETINS
1043

8. OHara MW, Neunaber DJ, Zekoski EM. Prospective

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predictive factors. J Abnorm Psychol 1984;93:15871.
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Whenever possible, multidisciplinary management

involving the patients obstetrician, mental health
clinician, primary health care provider, and pediatrician is recommended to facilitate care.
9. Gotlib IH, Whiffen VE, Mount JH, Milne K, Cordy NI.

Prevalence rates and demographic characteristics associated with depression in pregnancy and the postpartum. J
Consult Clin Psychol 1989;57:26974. (Level III)
Use of a single medication at a higher dose is

favored over the use of multiple medications for the
treatment of psychiatric illness during pregnancy.
The physiologic alterations of pregnancy may affect
the absorption, distribution, metabolism, and elimination of lithium, and close monitoring of lithium
levels during pregnancy and postpartum is recommended.
For women who breastfeed, measuring serum levels
in the neonate is not recommended.
Treatment with all SSRIs or selective norepinephrine reuptake inhibitors or both during pregnancy
should be individualized.
Fetal assessment with fetal echocardiogram should
be considered in pregnant women exposed to lithium in the first trimester.
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Force:
I

type of evidence.
committees.
1051
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Use of psychiatric medications during pregnancy and lactation. ACOG
Practice Bulletin No. 92. American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;111:100120.
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ACOG
PRACTICE
BULLETIN
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIANGYNECOLOGISTS
Anemia in Pregnancy
the assistance of Maureen Malee,
PhD, MD. The information is
designed to aid practitioners in
making decisions about appropriate
These guidelines should not be construed as dictating an exclusive
course of treatment or procedure.
Variations in practice may be warranted based on the needs of the
limitations unique to the institution

OBSTETRICIANS AND
GYNECOLOGISTS
WOMENS HEALTH CARE PHYSICIANS
Anemia, the most common hematologic abnormality, is a reduction in the concentration of erythrocytes or hemoglobin in blood. The two most common causes
of anemia in pregnancy and the puerperium are iron deficiency and acute blood
loss. Iron requirements increase during pregnancy, and a failure to maintain
sufficient levels of iron may result in adverse maternalfetal consequences. The
purpose of this document is to provide a brief overview of the causes of anemia
in pregnancy, review iron requirements, and provide recommendations for
screening and clinical management of anemia during pregnancy.
Background
Classification
The definition of anemia recommended by the Centers for Disease Control and
Prevention is a hemoglobin (Hgb) or hematocrit (Hct) value less than the fifth
percentile of the distribution of Hgb or Hct in a healthy reference population
based on the stage of pregnancy. Classification derived from an iron-supplemented population lists the following levels as anemic: Hgb (g/dL) and Hct
(percentage) levels below 11 g/dL and 33%, respectively, in the first trimester;
10.5 g/dL and 32%, respectively, in the second trimester; and 11 g/dL and 33%,
respectively, in the third trimester (1).
Anemias may be categorized by the underlying causative mechanism, red
blood cell morphology, or by whether they are inherited or acquired (see the
boxes). A mechanistic approach categorizes anemias caused by decreased red
blood cell production, increased red blood cell destruction, and blood loss.
Decreased production may result from a lack of nutrients, such as iron, vitamin
B12, or folate. This lack may be a result of dietary deficiency, malabsorption, or
bleeding. Bone marrow disorders or suppression, hormone deficiencies, and
chronic disease or infection also may lead to decreased production. Hemolytic
anemias are associated with increased destruction.
PRACTICE BULLETINS
Anemia Classification
Acquired
Deficiency anemia (eg, iron, vitamin B12, folate)
Hemorrhagic anemia
Anemia of chronic disease
Acquired hemolytic anemia
Aplastic anemia
Inherited
Thalassemias
Sickle cell anemia
Hemoglobinopathies (other than sickle cell anemia)
Inherited hemolytic anemias
Anemias Characterized by Mechanism

Decreased red blood cell production
Iron deficiency anemia
Anemia associated with vitamin B12 deficiency
Folic acid deficiency anemia
Anemia associated with bone marrow disorders
Anemia associated with bone marrow suppression
Anemia associated with low levels of erythropoietin
Anemia associated with hypothyroidism
Increased red blood cell destruction
Inherited hemolytic anemias
Sickle cell anemia
Thalassemia major
Hereditary spherocytosis
Acquired hemolytic anemias
Autoimmune hemolytic anemia
Hemolytic anemia associated with thrombotic
thrombocytopenic purpura
Hemolytic anemia associated with hemolytic
uremic syndrome
Hemolytic anemia associated with malaria
Hemorrhagic anemia
Anemias also may be classified by cell size. In contemporary practice, this typically is done by an automated
cell counter. Macrocytic anemias are associated with a
mean corpuscular volume (MCV) greater than 100 fL.
Reticulocytosis also may cause an increased MCV. A
1053
Anemias Classified by Mean Corpuscular Volume

Microcytic (MCV less than 80 fL)
Iron deficiency anemia
Thalassemias
Sideroblastic anemia
Anemia associated with copper deficiency
Anemia associated with lead poisoning
Normocytic (MCV 80100 fL)
Hemorrhagic anemia
Early iron deficiency anemia
Anemia associated with bone marrow suppression
Anemia associated with chronic renal insufficiency
Anemia associated with endocrine dysfunction
Autoimmune hemolytic anemia
Anemia associated with hypothyroidism or
hypopituitarism
Hereditary spherocytosis
Hemolytic anemia associated with paroxysmal
nocturnal hemoglobinuria
Macrocytic (MCV greater than 100 fL)
Folic acid deficiency anemia
Anemia associated with vitamin B12 deficiency
Drug-induced hemolytic anemia (eg, zidovudine)
Anemia associated with reticulocytosis
Anemia associated with liver disease
Anemia associated with ethanol abuse
Anemia associated with acute myelodysplastic
syndrome
Abbreviation: MCV, mean corpuscular volume
common cause of macrocytic anemia is folate deficiency.

Microcytic anemias are associated with an MCV less than
80 fL. The most common cause of microcytic anemia is
iron deficiency. Another common cause of microcytic
anemia in certain ethnic groups is hemoglobinopathy (2).
Anemia in Pregnancy
Pregnancy is associated with physiologic changes that
may complicate the diagnosis of hematologic disorders.
There is an increased iron requirement during pregnancy
because blood volume expands by approximately 50%
1054
(1,000 mL), and total red blood cell mass expands by

approximately 25% (300 mL) during a singleton gestation (3). The greater expansion in plasma typically is
reflected by decreases in Hgb and Hct levels.
The total amount of iron in the body is determined
by intake, loss, and storage (4). There are approximately
2.3 g of total body iron in women. Additional iron stores
during pregnancy (approximately 1 g) support this increased
red blood cell mass, the fetus and placenta, and the anticipated blood loss accompanying a vaginal delivery. When
there is adequate iron to meet needs, more than 70% is
classified as functional iron, and the remainder as storage
iron. Of the functional iron, more than 80% is found in
the red blood cell mass as hemoglobin, with the remainder in myoglobin and in respiratory enzymes (5).
Iron Deficiency Anemia

Iron deficiency can be defined as abnormal values on
biochemical test results, increases in hemoglobin concentrations of more than 1 g/dL after iron treatment, or
absent bone marrow iron stores as determined by a bone
marrow iron smear (1). The spectrum of iron deficiency
ranges from iron depletion, when stored iron is low, to
iron deficient erythropoiesis, when both stored and transport iron are low, to iron deficiency anemia, when stored,
transport, and functional iron are low (6).
Measurements of serum Hgb concentration or Hct
are the primary screening tests for identifying anemia
but are nonspecific for identifying iron deficiency.
Normal iron indices are listed in Table 1. Laboratory test
results characteristic of iron deficiency anemia are a
microcytic, hypochromic anemia with evidence of
depleted iron stores, low plasma iron levels, high total
iron-binding capacity, low serum ferritin levels, and
increased levels of free erythrocyte protoporphyrin.
Measurement of ferritin levels has the highest sensitivity and specificity for diagnosing iron deficiency in
anemic patients (7). Levels of less than 1015 micrograms/L confirm iron-deficiency anemia. The Centers for
Disease Control and Prevention recommends screening
for iron deficiency anemia in pregnant women and universal iron supplementation to meet the iron requirements
of pregnancy except in the presence of certain genetic disorders, such as hemochromatosis (1, 8). The rationale is
that treatment maintains maternal iron stores and may be
beneficial for neonatal iron stores. The typical diet confers 15 mg of elemental iron per day. The recommended
daily dietary allowance of ferrous iron during pregnancy
is 27 mg, which is present in most prenatal vitamins (8).
Available iron supplements are listed in Table 2. Perinatal
iron supplementation is important because the typical
American diet and endogenous stores are insufficient
sources for the increased iron requirements during pregnancy. Sustained-release or enteric-coated preparations
dissolve poorly and may be less effective.
Prevalence, Etiologies, and Risk Factors

A national study of anemia in pregnancy in the United
States found a prevalence of 21.55 per 1,000 women
when anemia was defined as a hemoglobin concentration
less than 10 g/dL (9). The prevalence of anemia in pregnancy in non-Hispanic black women (35.38 per 1,000
women) was two times higher than that of non-Hispanic
white women (18.02 per 1,000 women) (9). Teenaged
mothers had the highest prevalence of anemia in pregnancy of all races (9). Prevalence data specific to iron
deficiency anemia in pregnancy are limited (10). A
recent report estimates that in a low income, mostly
minority population, rates of iron deficiency anemia are
1.8% in the first trimester, 8.2% in the second trimester,
and 27.4% in the third trimester (11).
In reproductive-aged women of all races, risk factors for iron deficiency anemia include a diet poor in
iron-rich foods, such as clams, oysters, liver, beef,
shrimp, turkey, enriched breakfast cereals, beans, and
lentils; a diet poor in iron absorption enhancers, such as
orange juice, grapefruit, strawberries, broccoli, and peppers; a diet rich in foods that diminish iron absorption,
such as dairy products, soy products, spinach, coffee,
and tea; pica (eating nonfood substances such as clay or
laundry starch); gastrointestinal disease affecting
Table 2. Iron Supplements
Preparation
Dose
Table 1. Normal Iron Indices in Pregnancy
Ferrous fumarate
106 mg elemental iron per 325 mg tablet
Test
Ferrous sulfate
Plasma iron level
Normal Value
40175 micrograms/dL
Plasma total iron-binding capacity
216400 micrograms/dL
Transferrin saturation
1660%
Serum ferritin level
More than 10 micrograms/dL
Free erythrocyte protoporphyrin level
Less than 3 micrograms/g
Ferrous gluconate
Iron dextran
50 mg elemental iron per milliliter,

intramuscularly or intravenously
Ferric gluconate
12.5 mg iron per milliliter,

intravenously only
Iron sucrose
20 mg iron per milliliter, intravenously only
PRACTICE BULLETINS
absorption; heavy menses; short interpregnancy interval;

and blood loss at delivery exceeding that of an uncomplicated vaginal delivery.
Iron deficiency anemia during pregnancy has been
associated with an increased risk of low birth weight,
preterm delivery, and perinatal mortality (11, 12). In
addition, there may be an association between maternal
iron deficiency anemia and postpartum depression, with
poor results in mental and psychomotor performance
testing in offspring (1315).
Macrocytic Anemia
Macrocytic anemia may be megaloblastic or nonmegaloblastic. Causes of megaloblastic anemia include folate
and vitamin B12 deficiency and pernicious anemia. Causes
of nonmegaloblastic anemia include alcoholism, liver disease, myelodysplasia, aplastic anemia, hypothyroidism,
and an increased reticulocyte count. Macrocytic anemia is
characterized by an MCV greater than 100 fL. Levels
greater than 115 fL are almost exclusively seen in patients
with folic acid or vitamin B12 deficiencies. The diagnosis
may be confirmed by measurement of serum folic acid or
vitamin B12 levels. Measurement of red cell folate also has
been proposed (16). In the United States, macrocytic anemia beginning during pregnancy is overwhelmingly
caused by folic acid deficiency. It is associated with diets
lacking fresh leafy vegetables, legumes, or animal proteins. During pregnancy, folic acid requirements increase
from 50 micrograms to 400 micrograms per day.
Treatment of pregnancy-induced folic acid deficiency
should include a nutritious diet and folic acid and iron supplementation. Treatment with 1 mg of folic acid, administered orally, each day typically produces an appropriate
response. Macrocytic anemia in pregnancy caused by vitamin B12 (cyanocobalamin) deficiency may be encountered in women who have had a partial or total gastric
resection or in women with Crohn disease. Women who
have had a total gastrectomy require 1,000 micrograms of
vitamin B12, intramuscularly, at monthly intervals.

Recommendations
Who should be screened for anemia during
pregnancy?
All pregnant women should be screened for anemia during pregnancy. Those with iron deficiency anemia should
be treated with supplemental iron, in addition to prenatal
vitamins. Patients with anemia other than iron deficiency
anemia should be further evaluated.
1055
When should evaluation of an asymptomatic

patient with mild anemia be considered?
Asymptomatic women who meet the criteria for anemia
(Hct levels less than 33% in the first and third trimesters
and less than 32% in the second trimester) should be
evaluated. Living at a high altitude and tobacco abuse
cause a generalized upward shift in Hgb and Hct levels,
and adjustments for these potential confounders may be
appropriate (1719). Hemoglobin and Hct levels are
lower in African-American women compared with white
women, even after correction for income (20, 21). Thus,
applying the same criteria to all women could inappropriately classify almost 30% of African-American
women as iron deficient. For African-American adults,
the Institute of Medicine recommends lowering the cutoff levels for Hgb and Hct by 0.8 g/dL and 2%, respectively (21, 22).
How should asymptomatic pregnant women

with mild to moderate anemia be evaluated?
The initial evaluation of pregnant women with mild to
moderate anemia may include a medical history, physical
examination, and measurements of the complete blood
count, red blood cell indices, serum iron levels, and ferritin levels. Examination of a peripheral smear is helpful
for the diagnosis of hemolytic or parasitic disease. In certain ethnic groups, an Hgb electrophoresis is indicated (2).
Using biochemical tests, iron deficiency anemia is defined
by results of abnormal values for levels of serum ferritin,
transferrin saturation, and levels of free erythrocyte protoporphyrin, along with low Hgb or Hct levels (see Table 1
and Table 3). In practice, the diagnosis of mild to moderate iron deficiency anemia is often presumptive. In
patients without evidence of causes of anemia other than
iron deficiency, it may be reasonable to empirically initiate iron therapy without first obtaining iron test results.
When pregnant women with moderate iron deficiency
anemia are given adequate iron therapy, reticulocytosis
may be observed 710 days after iron therapy, followed by
an increase in Hgb and Hct levels in subsequent weeks.
Failure to respond to iron therapy should prompt further
investigation and may suggest an incorrect diagnosis,
coexisting disease, malabsorption (sometimes caused by
the use of enteric-coated tablets or concomitant use of
antacids), noncompliance, or blood loss.
Are there benefits of iron supplementation

for patients who are not anemic?
Iron supplementation decreases the prevalence of maternal anemia at delivery (23). However, it is unclear
1056
Table 3. Biochemical Tests for Diagnosis of Anemia

Test
Results Indicating
Iron Deficiency Anemia
Results Indicating
Thalassemia
Results Indicating
Anemia of Chronic Disease
Iron level
Decreased level
Normal
Decreased level
Total iron-binding capacity
Increased capacity
Normal
Decreased capacity
Ferritin level
Decreased level
Normal
Increased level
Iron/total iron-binding capacity
Less than 18%
Normal
More than 18%
whether iron supplementation in well-nourished pregnant women who are not anemic affects perinatal outcomes. There is little evidence that iron supplementation
results in morbidity beyond gastrointestinal symptoms,
except in patients with hemochromatosis or certain other
genetic disorders.
When should transfusion be considered in

the antepartum or preoperative patient?
Transfusions of red cells seldom are indicated unless
hypovolemia from blood loss coexists or an operative
delivery must be performed on a patient with anemia.
The need for transfusion in women with antepartum
complications can be predicted in only 24% of those
who ultimately require blood products (24). The most
common diagnoses associated with transfusion include
trauma caused by instrumented delivery, uterine atony,
placenta previa, retained products of conception, placental abruption, and coagulopathy (eg, the syndrome of
hemolysis, elevated liver enzymes, and low platelet
count [HELLP]). The presence of these diagnoses in a
patient with anemia should prompt consideration of
transfusion, particularly in the presence of unstable vital
signs (24).
Severe anemia with maternal Hgb levels less than 6
g/dL has been associated with abnormal fetal oxygenation, resulting in nonreassuring fetal heart rate patterns,
reduced amniotic fluid volume, fetal cerebral vasodilatation, and fetal death (25, 26). Thus, maternal transfusion
should be considered for fetal indications in cases of
severe anemia.
When should parenteral iron be used in

pregnant patients? Is there a role for
erythropoietin?
Parenteral iron is used in the rare patient who cannot
tolerate or will not take modest doses of oral iron.
Patients with a malabsorption syndrome and severe iron
deficiency anemia may benefit from parenteral therapy.
Anaphylactic reactions have been reported in 1% of
patients receiving parenteral iron dextran. In comparison

with patients who take iron dextran, patients who take
ferrous sucrose have fewer allergic reactions (8.7 versus
3.3 allergic events per 1,000,000 doses) and a significantly lower fatality rate (31 versus 0, P <.001) (27).
In a recent randomized trial of the use of oral versus
intravenous iron sucrose for postpartum anemia,
women treated with intravenous iron had significantly
higher Hgb levels on days 5 and 14 than women
treated with an oral supplement. However, by day 40,
there was no significant difference between the Hgb
levels of the two groups (28). Thus, in most clinical
circumstances, oral preparations are appropriate and
sufficient.
Few studies have examined the role of erythropoietin in pregnant patients with anemia. In a randomized,
controlled trial that examined the time to reach the targeted Hgb value and changes in efficacy measurements,
including reticulocyte count and Hct levels, the use of
both parenteral iron and parenteral iron plus erythropoietin improved measured parameters. However, the use
of adjuvant erythropoietin alone was associated with
a significantly shorter time to the targeted hemoglobin
level and improved indices (reticulocyte count, Hct levels) in less than 2 weeks after treatment was initiated.
No differences in maternalfetal safety parameters were
reported (29). In contrast, a randomized trial of women
with postpartum anemia showed no additional benefit
of the use of erythropoietin and iron versus iron alone
(30).
Is there a role for autologous transfusion?

Case reports suggest a role for autologous transfusion in
patients with diagnoses placing them at high risk of
symptomatic blood loss, such as placenta previa.
Suggested criteria for consideration of autologous donation include an Hct level greater than 32% at 32 weeks
of gestation (31). However, autologous transfusions
rarely are performed, and the inability to predict the
eventual need for transfusion has led to the conclusion
that they are not cost-effective (32).
PRACTICE BULLETINS
Summary of
Recommendations and
Conclusions
The following conclusion is based on good and
Iron supplementation decreases the prevalence of
maternal anemia at delivery.
The following recommendation and conclusions

are based on limited or inconsistent scientific data
(Level B):
Iron deficiency anemia during pregnancy has been
associated with an increased risk of low birth
weight, preterm delivery, and perinatal mortality.
Severe anemia with maternal Hgb levels less than
6 g/dL has been associated with abnormal fetal oxygenation resulting in nonreassuring fetal heart rate
patterns, reduced amniotic fluid volume, fetal cerebral vasodilatation, and fetal death. Thus, maternal
transfusion should be considered for fetal indications.
The following recommendations are based primarily on consensus and expert opinion (Level
C):
All pregnant women should be screened for anemia,
and those with iron deficiency anemia should be
treated with supplemental iron, in addition to prenatal vitamins.
Patients with anemia other than iron deficiency anemia should be further evaluated.
Failure to respond to iron therapy should prompt further investigation and may suggest an incorrect diagnosis, coexisting disease, malabsorption (sometimes
caused by the use of enteric-coated tablets or concomitant use of antacids), noncompliance, or blood loss.
Measure
Percentage of pregnant patients with iron deficiency anemia treated with supplemental iron in addition to prenatal vitamins
References
1. Recommendations to prevent and control iron deficiency
in the United States. Centers for Disease Control and
1057
Prevention. MMWR Recomm Rep 1998;47(RR-3):129.

(Level III)
2. Angastiniotis M, Modell B. Global epidemiology of
hemoglobin disorders. Ann N Y Acad Sci 1998;850:
25169. (Level II-3)
3. Pitkin RM. Nutritional influences during pregnancy. Med
Clin North Am 1977;61:315. (Level III)
4. Bothwell TH. Overview and mechanisms of iron regulation. Nutr Rev 1995;53:23745. (Level III)
5. Bothwell TH, Charlton RW. Iron deficiency in women.
Washington, DC: The Nutrition Foundation; 1981. (Level
III)
6. Baynes RD. Iron deficiency. In: Brock JH, Halliday JW,
Pippard MJ, Powell LW, editors. Iron metabolism in
health and disease. Philadelphia (PA): W.B. Saunders;
1994. p.189225. (Level III)
7. Ontario Association of Medical Laboratories. Guidelines
for the use of serum tests for iron deficiency. Guidelines
for Clinical Laboratory Practice CLP 002. North York
(ON): OAML; 1995. Available at: http://www.oaml.com/
PDF/CLP002.pdf. Retrieved April 4, 2008. (Level III)
8. Institute of Medicine (US). Dietary reference intakes for
vitamin A, vitamin K, arsenic, boron, chromium, copper,
iodine, iron, manganese, molybdenum, nickel, silicon,
vanadium, and zinc. Washington, DC: National Academy
Press 2002. (Level III)
9. Adebisi OY, Strayhorn G. Anemia in pregnancy and race
in the United States: blacks at risk. Fam Med 2005;37:
65562. (Level III)
10. Agency for Healthcare Research and Quality. Screening
for iron deficiency anemia in childhood and pregnancy:
update of the 1996 U.S. Preventive Task Force review.
AHRQ Publication No. 06-0590-EF-1. Rockville (MD):
AHRQ; 2006. (Level III)
11. Scholl TO. Iron status during pregnancy: setting the stage
for mother and infant. Am J Clin Nutr 2005;81:
1218S22S. (Level III)
12. Rasmussen K. Is there a causal relationship between iron
deficiency or iron-deficiency anemia and weight at birth,
length of gestation and perinatal mortality? J Nutr
2001;131:590S,601S; discussion 601S603S. (Level III)
13. Tamura T, Goldenberg RL, Hou J, Johnston KE, Cliver
SP, Ramey SL et al. Cord serum ferritin concentrations
and mental and psychomotor development of children at
five years of age. J Pediatr 2002;140:16570. (Level II-2)
14. Corwin EJ, Murray-Kolb LE, Beard JL. Low hemoglobin
level is a risk factor for postpartum depression. J Nutr
2003;133:413942. (Level II-3)
15. Perez EM, Hendricks MK, Beard JL, Murray-Kolb LE,
Berg A, Tomlinson M, et al. Mother-infant interactions
and infant development are altered by maternal iron deficiency anemia. J Nutr 2005;135:8505. (Level I)
16. Snow CF. Laboratory diagnosis of vitamin B12 and folate
deficiency: a guide for the primary care physician. Arch
Intern Med 1999;159:128998. (Level III)
17. CDC criteria for anemia in children and childbearing-aged
women. Centers for Disease Control (CDC). MMWR
Morb Mortal Wkly Rep 1989;38:4004. (Level III)
1058
18. Dirren H, Logman MH, Barclay DV, Freire WB. Altitude

correction for hemoglobin. Eur J Clin Nutr 1994;48:
62532. (Level II-3)
19. Nordenberg D, Yip R, Binkin NJ. The effect of cigarette
smoking on hemoglobin levels and anemia screening.
JAMA 1990;264:15569. (Level II-2)
20. Johnson-Spear MA, Yip R. Hemoglobin difference
between black and white women with comparable iron
status: justification for race-specific anemia criteria. Am J
Clin Nutr 1994;60:11721. (Level III)
21. Perry GS, Byers T, Yip R, Margen S. Iron nutrition does
not account for the hemoglobin differences between
blacks and whites. J Nutr 1992;122:141724. (Level II-3)
22. Institute of Medicine (US). Iron deficiency anemia: recommended guidelines for the prevention, detection, and
management among U.S. children and women of childbearing age. Washington, DC: National Academy Press;
1993. (Level III)
23. Pena-Rosas JP, Viteri FE. Effects of routine oral iron supplementation with or without folic acid for women during
pregnancy. Cochrane Database of Systematic Reviews
14651858.CD004736.pub2. (Level III)
24. Sherman SJ, Greenspoon JS, Nelson JM, Paul RH.
Obstetric hemorrhage and blood utilization. J Reprod
Med 1993;38:92934. (Level II-2)
25. Carles G, Tobal N, Raynal P, Herault S, Beucher G, Marret
H, et al. Doppler assessment of the fetal cerebral hemodynamic response to moderate or severe maternal anemia.
26. Sifakis S, Pharmakides G. Anemia in pregnancy. Ann N Y
Acad Sci 2000;900:12536. (Level III)
27. Faich G, Strobos J. Sodium ferric gluconate complex in
sucrose: safer intravenous iron therapy than iron dextrans.
Am J Kidney Dis 1999;33:46470. (Level III)
28. Bhandal N, Russell R. Intravenous versus oral iron therapy for postpartum anaemia. BJOG 2006;113:124852.
(Level I)
29. Breymann C, Visca E, Huch R, Huch A. Efficacy and safety of intravenously administered iron sucrose with and
without adjuvant recombinant human erythropoietin for the
treatment of resistant iron-deficiency anemia during pregnancy. Am J Obstet Gynecol 2001;184:6627. (Level I)
30. Wagstrom E, Akesson A, Van Rooijen M, Larson B,
Bremme K. Erythropoietin and intravenous iron therapy
in postpartum anaemia. Acta Obstet Gynecol Scand
2007;86: 95762. (Level I)
31. Toedt ME. Feasibility of autologous blood donation in
patients with placenta previa. J Fam Pract 1999;48:
21921. (Level II-3)
32. Etchason J, Petz L, Keeler E, Calhoun L, Kleinman S,
Snider C, et al. The cost effectiveness of preoperative
autologous blood donations. N Engl J Med 1995;332:
71924. (Level III)

to conduct a literature search to locate relevant articles published between January 1985 and September 2007. The
Task Force:
I

type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Anemia in pregnancy. ACOG Practice Bulletin No. 95. American
2017.
PRACTICE BULLETINS
1059
ACOG
PRACTICE
BULLETIN
Replaces Educational Bulletin Number 230, November 1996
Fetal Lung Maturity

the assistance of William N.P.
Herbert, MD, and Thomas Peng,
MD. The information is designed to
aid practitioners in making decisions about appropriate obstetric
and gynecologic care. These guidelines should not be construed as
treatment or procedure. Variations
in practice may be warranted based
on the needs of the individual
patient, resources, and limitations
unique to the institution or type of
practice.
Respiratory difficulties are common in neonates born with immature lung

development. Assessment of fetal lung maturity is an important component in
determining the timing of delivery in certain patients who experience complications during pregnancy. Enhancement of fetal pulmonary function with the
use of antenatal steroids and the administration of surfactant lessens the prevalence and severity of neonatal respiratory distress syndrome (RDS) and its
sequelae. However, RDS remains a major clinical issue. Commonly used tests
to determine fetal lung maturity are reviewed in this Practice Bulletin.
Background
The status of fetal lung maturation can assist the clinician in determining when
delivery should occur. Testing for fetal lung maturity should not be performed,
and is contraindicated, when delivery is mandated for fetal or maternal indications. Conversely, a mature fetal lung maturity test result before 39 weeks of
gestation, in the absence of appropriate clinical circumstances, is not an indication for delivery. Respiratory distress syndrome, intraventricular hemorrhage,
necrotizing enterocolitis, and other complications have been reported in premature newborns delivered with mature lecithin (phosphatidylcholine)/sphingomyelin ratios or the presence of phosphatidylglycerol (1, 2).
Indications for Assessing Fetal Maturity

To prevent iatrogenic prematurity, fetal pulmonary maturity should be confirmed before scheduled delivery at less than 39 weeks of gestation unless fetal
maturity can be inferred from any of the following historic criteria:
OBSTETRICIANS AND
GYNECOLOGISTS
Ultrasound measurement at less than 20 weeks of gestation supports gestational age of 39 weeks or greater.
Fetal heart tones have been documented as present for 30 weeks by
Doppler ultrasonography.
1060
It has been 36 weeks since a positive serum or urine

human chorionic gonadotropin pregnancy test result.
If any of these criteria confirms a gestational age of
39 weeks or more, it is appropriate to schedule delivery at
that time. Ultrasonography may be considered to confirm
menstrual dates if there is a gestational age agreement
within 1 week by crownrump measurements obtained in
the first trimester or within 10 days by an average of multiple fetal biometric measurements (eg, crownrump
length, biparietal diameter, head and abdominal circumference, and femur length) obtained in the second
trimester (up to 20 weeks of gestation).
The risk of RDS is increased significantly in infants
born by electively scheduled cesarean delivery between
37 07 weeks and 38 67 weeks of gestation (3). In a retrospective study of 1,284 elective cesarean deliveries, RDS
was diagnosed at a rate of 25 per 1,000 live births when
cesarean delivery occurred between 37 07 weeks and 38 67
weeks of gestation, versus a significantly lower rate of
RDS, 7 per 1,000 with cesarean delivery after 39 07
weeks of gestation. Neonatal RDS with vaginal deliveries did not vary (34/1000) across these gestational ages.
Physiology and Pathophysiology

Fetal Lung Development
The development of the pulmonary system begins
approximately 3 weeks after conception and continues
well into childhood. From approximately 1624 weeks
of gestation, early bronchioles develop, and the epithelium vascularizes and differentiates. It is in the alveolar
phase of pulmonary development, which begins at
approximately 2223 weeks of gestation, that subsequent bronchiolar division occurs such that thin spherical saccules known as alveoli develop. The concomitant
proliferation of capillaries around these alveoli makes
effective gas exchange possible after delivery.
The alveoli are lined by type II pneumocytes, which
produce phospholipids that are packaged into lamellar
bodies. Surfactant is the name given to a group of surface-active phospholipid compounds that can be
released from these lamellar bodies and reduce the surface tension within the alveolar spaces. Maintaining a
low surface tension within the alveoli allows the sacs to
remain expanded, which permits continuous and maximal effective gas exchange. During the latter portion of
pregnancy, fetal respiratory activity permits the passage
of surfactant into the amniotic fluid where its quantity or
function can be evaluated. The most prominent of these
surfactant compounds is lecithin, which generally
appears earlier in gestation than another component of
surfactant, phosphatidylglycerol.
Respiratory Distress Syndrome

A deficiency in the quantity of surfactant in premature
infants leads to higher surface tension within the alveoli,
causing alveolar collapse and difficult gas exchange. The
result is neonatal hypoxia, with further worsening of pulmonary status manifested by acidosis and increased
shunting within the lungs. Signs of RDS include neonatal tachypnea, grunting, inspiratory thoracic retractions,
and cyanosis, often occurring within several hours of
birth.
Other complications associated with RDS include
necrotizing enterocolitis, patent ductus arteriosus, intraventricular hemorrhage, and infection. Some survivors
will experience bronchopulmonary dysplasia, or chronic
lung disease.
Fetal Lung Maturity Tests

Laboratory tests measure either the concentration of particular components of pulmonary surfactant (biochemical tests) or the surface-active effects of these phospholipids (biophysical tests). Common biochemical tests
include measuring the lecithin/sphingomyelin ratio and
determining the presence of phosphatidylglycerol.
Biophysical tests include fluorescence polarization.
Lamellar body counts also are generally available. Less
frequently used tests include foam stability index and
optical density of amniotic fluid at 650 nm.
Commonly used fetal lung maturity tests include
fluorescence polarization (TDx-FLM II), lecithin/sphingomyelin ratio, phosphatidylglycerol presence, and
lamellar body counts. No test has been conclusively
shown to be superior, and each requires its own standard
to define the risk of neonatal RDS. Comparisons
between the different tests have shown varying results. A
comparison of lecithin/sphingomyelin ratio to lamellar
body counts in 833 neonates born within 72 hours of
fetal lung maturity testing (prevalence of RDS was 12%)
noted that both tests had similar sensitivity (proportion
of immature test result in neonates with RDS) of 81.8%
and 88.9%, respectively, and negative predictive values
(probability of no RDS with a mature fetal lung maturity
test result) 96.8% and 97.7%, respectively (4).
Comparisons of lamellar body counts (cutoff greater
than 50,000) and TDx-FLM II assay results (greater than
55 mg/g) also demonstrated similar test characteristics in
sensitivity (92% and 83%, respectively) and negative
predictive values (99% and 98%, respectively) (5).
Studies comparing lecithin/sphingomyelin ratios with
TDx-FLM II assay results demonstrate that both tests
yield high sensitivity for RDS and high negative predictive values. Neonates of 109 pregnant women were
delivered within 72 hours of the fetal lung maturity test,
PRACTICE BULLETINS
and RDS was diagnosed in 9 (8%) (6). In this study, using

cutoff values of 45 mg/g for TDx-FLM II assay results and
2 for lecithin/sphingomyelin ratios, the sensitivity and
negative predictive values were 100% for both tests (6).
A multiinstitutional study compared test characteristics of lecithin/sphingomyelin ratio, phosphatidylglycerol presence, lamellar body counts, and TDx-FLM II
assays. The investigators found that characteristics were
similar in a population of 220 neonates delivered within
48 hours of testing (7). Cutoff values were lecithin/
sphingomyelin ratios of 2.5, phosphatidylglycerol presence greater than 0.5, TDx-FLM II assay results greater
than 40 mg/g, and lamellar body counts greater than
30,000. Of the 13 (6%) neonates diagnosed with RDS,
the lecithin/sphingomyelin ratios were falsely reassuring
(greater than 2.5) in five, as were the TDx-FLM II assay
results, phosphatidylglycerol presence measurements,
and lamellar body counts in one amniotic fluid sample.
As noted by the authors, a probability risk of RDS that
takes into account the fetal gestation may be more helpful than a cutoff value to define mature versus immature
neonatal lung function.
Ideally, laboratories should develop their own reference standards for fetal lung maturity testing, but few
have a sufficient number of amniotic fluid samples and
outcomes for such internal evaluations. The predictive
values of fetal lung maturity tests will vary with the
prevalence of RDS in the population sampled. In addition, it should be noted that there is a risk of RDS even
with a positive mature fetal lung maturity test result and
that this risk varies by gestational age (79).
Fluorescence Polarization
Fetal lung maturity testing using fluorescence polarization is based on competitive binding of a fluorescent
probe to albumin and surfactant. When the probe is
bound to albumin, net polarization values are high; when
bound to surfactant, polarization values are low. In amniotic fluid samples, the fluorescence polarization measured by an automated analyzer reflects the ratio of
surfactant to albumin, a value that correlates with lung
maturity. Recent modifications of this concept provide a
simple, automated, rapid test that is widely available,
varies minimally between laboratories, and requires only
a small volume of amniotic fluid (typically 1 mL). In the
recently modified commercial version of this assay
(TDx-FLM II), values above 55 mg surfactant per 1 g
albumin are considered mature (10); values below 40 mg
surfactant per 1 g albumin are considered immature; and
values between 40 mg surfactant per 1 g albumin and 54
mg surfactant per 1 g albumin are considered indeterminate. In a retrospective analysis of 185 samples (15 with
1061
RDS and 170 without RDS), a cutoff value of greater

than or equal to 45 mg/g yielded a sensitivity of 100%
(95% confidence interval [CI], 82100%), specificity
(proportion of mature result in a neonate without RDS) of
84% (95% CI, 7889%) (11). The assay compares favorably with other direct tests, but blood and meconium contamination interfere with its interpretation (Table 1).
Lecithin/Sphingomyelin Ratio
The lecithin/sphingomyelin ratio measures the ratio of
lecithin to sphingomyelin in amniotic fluid. As gestational age advances, the concentration of lecithin
increases, whereas the concentration of sphingomyelin
remains relatively constant. Reporting results in a ratio
takes into account the increasing amniotic fluid volume
as gestational age progresses.
Determination of the lecithin/sphingomyelin ratio
involves thin-layer chromatography after organic solvent
extraction. A value of 2 is the commonly accepted standard indicating pulmonary maturity in the fetus,
although laboratories may define a different ratio to indicate fetal lung maturity.
Compared with newer tests, popularity of the
lecithin/sphingomyelin ratio has diminished substantially
in recent years. The technique is more costly, has a longer
turnaround time (average of 56 hours), and requires
highly trained personnel. Blood and meconium contamination can interfere with test interpretation (Table 1).
Phosphatidylglycerol Presence
Phosphatidylglycerol is a minor constituent of surfactant. Because phosphatidylglycerol enhances the spread
of phospholipids on the alveolar surface, its presence
indicates a more advanced state of fetal pulmonary
maturity. Phosphatidylglycerol can be determined using
thin-layer chromatography as an extension of the
lecithin/sphingomyelin ratio. In addition, a slide-agglutination test has been developed using antisera specific for
phosphatidylglycerol. This test can be performed quickly
and generally is not affected by the presence of blood,
meconium, or other contaminants. Its relatively late
appearance in pregnancy means that its false-postive rate
(proportion of neonates without RDS with an immature
FLM test result) for RDS is high. Older studies noted that
when phosphatidylglycerol was present, the risk of RDS
was very low (less than 1%). When phosphatidylglycerol
was absent, the risk of RDS was in the range of 25%,
which is poorly predictive of occurrence of RDS (12).
Lamellar Body Counts

Surfactant is stored within type II pneumocytes in the
form of lamellar bodies. These bodies are actively
1062
Table 1. Commonly Used Direct Tests of Fetal Lung Maturity
Test*
Technique
Time and
Ease
of Testing
Threshold
Typical Predictive
Value (%)
Mature
Immature
Blood
Negative
Positive Contamination
Predictive Predictive
Affects
Value
Value
Results
Meconium
Contamination
Affects
Results
Vaginal
Pool
Sample
Fluorescence
polarization
Fluorescence
polarization
with TDx-FLM II
1+
55 mg/g or
greater of
albumin
96100
4761
Yes
Yes
Yes
Lecithin/
sphingomyelin
ratio
Thin-layer
chromatography
4+
23.5
95100
3350
Yes
Yes
No
Phosphatidylglycerol
Thin-layer
chromatography
4+
Present (usually
greater than 3%
of total
phospholipids)
95100
2353
No
No
Yes
Antisera with
AminoStat-FLM
1+
0.5 = low positive

2 = high positive
95100
2353
No
No
Yes
Lamellar body
counts
Counts using
commercial
hematology
counter
2+
30,00040,000
(still
investigational)
9798
2935
Yes
No
Not
available
Optical density
at 650 nm
Spectrophotometric
reading
1+
Optical density
of 0.15 or greater
98
13
Not
available
Not
available
Not
available
Foam stability
index
Ethanol added
to amniotic fluid,
solution shaken,
presence of stable
bubbles at
meniscus noted
2+
4748 or greater
95
51
Yes
Yes
No
*Commercial versions are available for all tests except optical density and lamellar body counts.
Range in complexity: 1+ indicates procedure is simple, procedure is available all the time, procedure time is short, and personnel effort is not intensive; 4+ indicates
procedure is complex or difficult, time consuming, and, therefore, frequently not available at all times.
Positive predictive value is the probability of neonatal respiratory distress syndrome when the fetal lung maturity test result is immature.
The manufacturer has reformulated the product and revised the testing procedure. Currently, the threshold for maturity is 55; with the original assay, it was 70.
secreted into the alveoli space and hence into the amniotic fluid. The similarity of lamellar body size to that of
platelets permits the use of a standard hematologic
counter to determine lamellar body concentrations. Such
counting is simple, rapid, inexpensive, and reliably predictive of pulmonary maturity. However, there are no
clearly established protocols, consistent instrumentation,
guidelines, or consensus on cutoff values for a lamellar
body count that predicts absence of RDS.
Neonatal RDS may be reduced by acceptance of a
higher threshold, a higher lamellar body count. In a
cohort study of 527 neonates, two cutoff values, a lamellar body count of greater than 30,000 and a count of
greater than 50,000, were defined as indicating pulmonary maturity (13). Neonatal intensive care unit
admissions, neonatal respiratory assistance, and overall
neonatal complications were less frequent with a cutoff

value of greater than 50,000. A similar study of 80 pregnancies documented a negative predictive value of 93%
when a cutoff value for maturity of lamellar body counts
of greater than 50,000 was used (14). Meconium contamination may marginally increase the lamellar body
count, and blood contamination can lead to falsely
increased lamellar body counts because of platelet contamination (Table 1) (4, 15). If testing is not performed
rapidly, coagulation will reduce the lamellar body count.
Interpretation of Tests and Testing

Strategies
As shown in Table 1, the negative predictive value for
mature neonatal lung function is high, and if one of these
test results for fetal lung maturity is positive, RDS is
PRACTICE BULLETINS
Table 2. Fetal Lung Maturity Testing in Twin Gestations

Gestational Age
30 0732 67 weeks of gestation
0
Amniocentesis to Test
Fetal Lung Maturity
Both twins
33 735 7 weeks of gestation

Concordant gender
Either twin
Discordant gender and discordant

weight less than 10% or greater than
20%
Either twin
Discordant gender and discordant

weight 1020%
One twin (prefer

nonpresenting or male)
Greater than 35 67 weeks of gestation
Either twin
Data from Mackenzie MW. Predicting concordance of biochemical lung maturity in the preterm twin gestation. J Matern Fetal Neonat Med 2002;12:508.
unlikely. The main value for fetal lung maturity testing is

predicting the absence of RDS. An immature test result
for fetal lung maturity is less reliable in predicting the
presence of RDS.
Fetal lung maturity testing traditionally has been
based on the result alone, not taking into account the gestational age of the fetus. More recently, it has been
recognized that the probability of neonatal RDS is
dependent on both the fetal lung maturity test result and
the gestational age at which the fetal lung maturity test
was performed (7, 8, 16, 17). The prevalence of RDS
within a population will alter the positive predictive
value of the fetal lung maturity test results. Nonetheless,
combining test results and gestational age improves the
clinicians ability to counsel patients about perinatal
management and the neonatal risks, including the risk of
RDS, with elective delivery. Another factor in choosing
which amniotic fluid test to perform is the effect of various contaminants on test results (Table 1).

Recommendations
What are the complications of third-trimester
amniocentesis?
Complications from third-trimester amniocentesis for
fetal lung maturity are uncommon when performed with
ultrasound guidance (18, 19). One study of 562 amniocenteses documented a 0.7% rate of complications, which
included one each of preterm labor, premature rupture of
membranes, placental abruption, and fetalmaternal hemorrhage (18). None of the complications required urgent
delivery. One study documented complications requiring
urgent delivery on the day of amniocentesis in 6 patients
(0.7%) from 913 amniocenteses for fetal lung maturity.
1063
Complications were isolated events but included three

fetal heart rate abnormalities and one each of placental
bleeding, placental abruption, and uterine rupture.
Is there a gestational age below which there

is no utility of fetal lung maturity testing?
Before 32 weeks of gestation, fetal lung maturity testing
generally is not indicated because most test results will
indicate immaturity. Thus, delivery is indicated at this gestational age only for specific maternal or fetal indications.
What is the impact of corticosteroid administration on fetal lung maturity test results?
Corticosteroid administration significantly reduces the
incidence of RDS but may not have an impact on the
results of fetal lung maturity testing (20, 21). In a cohort
study of pregnant patients with hypertension and similar
gestational ages at the time of amniocenteses for fetal
lung maturity, 34 patients were treated with betamethasone before amniocentesis and 34 were not treated.
Amniocentesis for fetal lung maturity occurred within 5
days of the corticosteroid administration. Compared with
no corticosteroid exposure, patients with hypertension
who were treated with corticosteroids had significantly
higher values for lecithin/sphingomyelin ratios and
lamellar body counts, but no difference in phosphatidylglycerol presence. (21). No such increases in lecithin/
sphingomyelin ratios were noted in a subset of patients
enrolled in a study of dexamethasone versus placebo for
fetal lung maturation. No difference in the lecithin/sphingomyelin ratio was found in the amniotic fluid obtained a
week after dexamethasone administration in 25 women
compared with the placebo group of 20 women (20).
In a patient with a twin pregnancy, should

fetal lung maturity testing be performed for
each fetus?
Information concerning pulmonary maturation and testing in twin pregnancies is mixed. Studies have reported
that values of fetal maturity test results in twin pregnancies are higher compared with those in singleton pregnancies at similar gestations (22, 23). In a study of 27
twin pregnancies and 143 singleton pregnancies, the
higher values of TDx FLM assay results were noted in
the twin pregnancies after 31 weeks of gestation (23).
Other studies have found no difference (24).
In twin pregnancies, data are not clear as to whether
assessing fetal lung maturity in one twin is sufficient or
whether assessing both twins is necessary to predict the
risk of neonatal RDS. Several studies suggest good correlation of fetal lung maturity assay values between both
1064
twins with correlation coefficients of 0.830.86 (25, 26).

The correlation was not affected by the presenting versus
nonpresenting twin, by gender discordance, or by birthweight discordance (26). Discordant values (one twin
with a fetal lung maturity value in the mature range and
the other twin with a fetal lung maturity value in the
immature range) appear to occur more frequently at earlier gestational ages (26, 27). Many of these reports used
the lecithin/sphingomyelin ratio for fetal lung maturity
testing, which, because of larger differences in interlaboratory and intralaboratory variation, may have contributed
to the varying results in concordance. These data suggest
that amniocentesis of both twins be performed when the
gestation is between 30 07 weeks and 32 67 weeks of gestation. Amniocentesis of one twin appears to be sufficient
when gestation is greater than 32 67 weeks (27) (Table 2).
Before elective delivery, fetal lung maturity testing
in twins with well defined gestational ages of 38 07 weeks
or greater may not be necessary. A descriptive study of
126 twins electively delivered without fetal lung testing
noted five pregnancies in which one or both twins were
diagnosed with RDS (28). For all five, delivery occurred
at less than 38 07 weeks of gestation. Of the 47 twin pregnancies delivered at 38 07 weeks or greater, one infant
was affected by transient tachypnea of the newborn.
How do abnormal amniotic fluid volumes

(hydramnios, oligohydramnios) affect fetal
lung maturity test results?
Very few studies have addressed this question. Based on
the results of one clinical study, the effect of amniotic
fluid volume on the results of fetal lung maturity testing
appears to be minimal. In a study of patients with oligohydramnios (an amniotic fluid index of 5 cm or less), the
lecithin/sphingomyelin ratios, phosphatidylglycerol
presence, and lamellar body counts were similar to controls of similar gestation but with a normal amniotic
fluid index. However, in patients with polyhydramnios
(an amniotic fluid index greater than 25), the
lecithin/sphingomyelin ratios, lamellar body counts, and
phosphatidylglycerol presence were lower compared
with the control group (29).
Are results of fetal lung maturity tests

performed on samples collected vaginally
reliable?
Studies comparing results of fetal lung maturity tests of
amniotic fluid collected vaginally with those collected
by transabdominal amniocentesis demonstrated that
when results from fluid collected vaginally are mature,
the results are reliable (30, 31). In a study of 16 patients
with preterm premature rupture of membranes, amniotic
fluid was collected both vaginally and by transabdominal amniocentesis within twelve hours of each other.
Twelve samples collected by transabdominal amniocentesis indicated mature lung development compared with
four samples collected vaginally. Results of a TDx-FLM
assay were lower in the fluid collected vaginally then
fluid collected by transabdominal amniocentesis, but
when the assay of the fluid collected vaginally was
mature, it was always confirmed by results of the fluid
collected by transabdominal amniocentesis (31).
Compared with transabdominal amniocentesis, fluid collected vaginally for fetal lung maturity testing yields
higher specificity (100%) and positive predictive value
(100%) but had lower sensitivity (42%) and negative
predictive value (36%) for neonatal RDS.
How does blood and meconium contamination affect fetal lung maturity test results?
Contamination of amniotic fluid with blood appears to
increase the number of falsely immature fetal lung maturity test results. With an in vitro system, increasing
aliquots of blood added to samples of amniotic fluid produced fetal lung maturity test results that were less
mature (32). Table 1 lists the effects of various substances on the reliability of interpretation of tests of fetal
lung maturity.
How are results interpreted in the presence

of diabetes mellitus? Are there additional
tests that may be helpful?
In general, the same threshold values for fetal lung maturity tests that predict low risk of neonatal RDS in pregnancies of women who are not diabetic apply to pregnancies
of women who are diabetic, whether the woman has gestational diabetes mellitus or pregestational diabetes mellitus. Most studies have evaluated the performance of
lecithin/sphingomyelin ratios, tests for the presence of
phosphatidylglycerol, and TDx-FLM and TDx-FLM II
assays. The manufacturer of TDx-FLM II assays recommends a value of 55 mg/g or higher as compatible with a
mature lung profile. In a series of 45 pregnant women
with diabetes mellitus who gave birth within 72 hours of
the performance of a fetal lung maturity test, 40 had
fetuses with a mature profile (TDx-FLM II value was
equal to 55 mg/g or greater), and no neonatal RDS
occurred (17). The remaining five had fetuses with an
indeterminate profile (TDx-FLM II value between 40
mg/g and 55 mg/g), and one had RDS. Therefore, testing
with fluorescence polarization (TDx-FLM II), using a
defined mature profile of a value of 55 mg/g or greater, is
appropriate for the determination of risk of neonatal RDS
in pregnant women with diabetes mellitus.
PRACTICE BULLETINS
Similar findings were noted with the older version of

the fluorescence polarization test, TDx-FLM, in which values greater than 70 mg/g in amniotic fluid obtained by
amniocentesis were associated with a very low risk of
neonatal RDS (33, 34). In one series of 182 pregnant
women with diabetes mellitus, five neonates born within 4
days of the amniocentesis experienced severe RDS. The
TDx-FLM values of these five neonates ranged from 1859
mg/g. Mild RDS, requiring hood oxygenation, occurred in
three neonates with fetal lung maturity values of 47, 74, and
81 mg/g (33). In another series of 121 pregnant women
with diabetes mellitus who gave birth within 72 hours of
fetal lung maturity testing, one neonate had RDS with a
TDx-FLM value of 7.2 mg/g. No RDS was noted when the
value was 70 mg/g or greater (108 patients) (34).
Evaluation of lecithin/sphingomyelin ratios and tests
for the presence of phosphatidylglycerol in an older study
of pregnant women with and without diabetes mellitus
confirmed that a mature lecithin/sphingomyelin ratio predicted very low risk of neonatal RDS in both populations
(1.6% and 1.8%, respectively), and when phosphatidylglycerol was present, no RDS was identified in either
group (35).
The effect of diabetes mellitus or glucose control on
the development of a mature phospholipid profile in amniotic fluid is unclear (36). Some reports indicate a delay in
production of phosphatidylglycerol in fetuses of pregnant
women with diabetes mellitus (37, 38) and a higher proportion of immature profiles in women with poorly controlled compared with well controlled diabetes mellitus
(39). Others report no difference in phospholipid profiles
between patients with diabetes mellitus and patients without diabetes mellitus (40, 41). There is more of a consensus
that the extent of glycemic control is related to the timing
of pulmonary maturation and fetal lung maturity testing.
In pregnant women with diabetes mellitus and good
glycemic control, amniocentesis for fetal lung maturity
testing is not indicated before scheduled delivery at or
beyond 39 weeks of gestation. It has been suggested that
with the rare risk of RDS in pregnant women with wellcontrolled diabetes mellitus, amniocentesis for fetal lung
maturity may be eliminated in women with a well-dated
pregnancy at or beyond 38 weeks of gestation (42). In
patients with diabetes mellitus and poor glucose control,
fetal lung maturity testing is recommended if delivery is
contemplated at less than 39 weeks of gestation.
1065
making. The risks of untoward fetal or maternal outcome

if the pregnancy continues and the results of the testing
(very immature or indeterminate) can be helpful in such
situations. With an indeterminate test result, the practitioner should consider incorporation of the gestational
age of the fetus into the interpretation of the fetal lung
maturity value and risk of neonatal RDS.
For borderline lecithin/sphingomyelin ratios
(1.81.9), the risk of neonatal morbidity and mortality if
delivered within 72 hours of the test appear significant.
In a group of 63 pregnancies at a gestation of 2736
weeks delivered within 72 hours of the fetal lung maturity test, there was a 13% neonatal morbidity rate and 3%
neonatal mortality rate when the lecithin/sphingomyelin
ratio was 1.8 compared with a 3% morbidity rate and no
mortality when the lecithin/sphingomyelin ratio was 1.9.
All the major neonatal morbidity occurred in gestations
less than 3234 weeks (43). Increased risk of RDS was
noted with TDx-FLM II results in the indeterminate zone
(4055 mg/g), with proportional increases in the risk of
RDS as fetal gestation decreased (16).
No consensus exists as to whether repeat testing is
required or when to perform a repeat test when the fetal
lung maturity test is either immature or indeterminate.
TDx-FLM II results derived from two sequential amniocenteses in a group of 85 pregnant women documented
that as fetal gestation progresses, the increase in the
value of TDx-FLM II results appear to be constant,
increasing approximately 14.4 plus or minus 9.9 mg/g
(95% CI, 12.316.5) per week over a broad range of gestations (3138 weeks of gestation) (44). This may provide guidance on whether repeat testing is necessary and
when to consider repeat testing.
Summary of
Recommendations and
Conclusions
are based on limited or inconsistent scientific evidence (Level B:)
Testing for fetal lung maturity should not be performed, and is contraindicated, when delivery is
mandated for fetal or maternal indications.
How is an immature or indeterminate test

result managed? What is the interval for
repeat testing?
Fetal pulmonary maturity should be confirmed

before scheduled delivery at less than 39 weeks of
gestation unless fetal maturity can be inferred from
historic criteria.
If the test results following the first amniocentesis are

immature, individual circumstances can guide decision
The probability of neonatal RDS is dependent on

both the fetal lung maturity test result and the gesta-
1066
tional age at which the fetal lung maturity test was

performed.
Fluorescence polarization assays (TDx FLM II)
using a defined mature profile of 55 mg/g or greater
is appropriate for the determination of risk of neonatal RDS in pregnancies of women with diabetes
mellitus.
Fetal lung maturity test results from amniotic fluid
collected vaginally compared with those from fluid
collected by transabdominal amniocentesis demonstrate that when results from fluid collected vaginally
are mature, the results are reliable.
Complications from third-trimester amniocentesis
for fetal lung maturity are uncommon when performed with ultrasound guidance.
The following conclusions are based primarily on

In general, the same threshold values for fetal lung
maturity tests that predict low risk of neonatal RDS
in pregnancies of women who do not have diabetes
mellitus apply to pregnancies of women who have
diabetes mellitus, whether it is gestational diabetes
mellitus or pregestational diabetes mellitus.
Data suggest that amniocentesis of both twins be
performed when the gestation is between 30 07
weeks and 32 67 weeks of gestation. Amniocentesis
of one twin appears to be sufficient when gestation
is greater than 32 67 weeks.
Prior to elective delivery, fetal lung maturity testing
in twins with well defined gestational ages at 38 07
weeks or greater may not be necessary.
3. Zanardo V, Simbi AK, Franzoi M, Solda G, Salvadori A,

Trevisanuto D. Neonatal respiratory morbidity risk and
mode of delivery at term: influence of timing of elective
caesarean delivery. Acta Paediatr 2004;93:6437. (Level
II-2)
4. Neerhof MG, Haney EI, Silver RK, Ashwood ER, Lee IS,
Piazze JJ. Lamellar body counts compared with traditional
phospholipid analysis as an assay for evaluating fetal lung
maturity. Obstet Gynecol 2001;97:3059. (Level II-3)
5. Haymond S, Luzzi VI, Parvin CA, Gronowski AM. A
direct comparison between lamellar body counts and fluorescent polarization methods for predicting respiratory
distress syndrome. Am J Clin Pathol 2006;126:8949.
(Level II-3)
6. Winn-McMillan T, Karon BS. Comparison of the TDxFLM II and lecithin to sphingomyelin ratio assays in predicting fetal lung maturity. Am J Obstet Gynecol 2005;
193:77882. (Level II-3)
7. Karcher R, Sykes E, Batton D, Uddin Z, Ross G,
Hockman E, et al. Gestational age-specific predicted risk
of neonatal respiratory distress syndrome using lamellar
body count and surfactant-to-albumin ratio in amniotic
fluid. Am J Obstet Gynecol 2005;193:16804. (Level II-3)
8. Parvin CA, Kaplan LA, Chapman JF, McManamon TG,
Gronowski AM. Predicting respiratory distress syndrome
using gestational age and fetal lung maturity by fluorescent polarization. Am J Obstet Gynecol 2005;192:
199207. (Level III)
9. Pinette MG, Blackstone J, Wax JR, Cartin A. Fetal lung
maturity indicesa plea for gestational age-specific interpretation: a case report and discussion. Am J Obstet
10. Kesselman EJ, Figueroa R, Garry D, Maulik D. The usefulness of the TDx/TDxFLx fetal lung maturity II assay in
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Measure
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PRACTICE BULLETINS
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20. Farrell PM, Engle MJ, Zachman RD, Curet LB, Morrison
JC, Rao AV, et al. Amniotic fluid phospholipids after
maternal administration of dexamethasone. Am J Obstet
Gynecol 1983;145:48490. (Level II-2)
1067
comparison of vaginal pool samples with amniocentesis. J

Matern Fetal Neonatal Med 2002;11:3747. (Level
II-3)
32. Carlan SJ, Gearity D, OBrien WF. The effect of maternal
blood contamination on the TDx-FLM II assay. Am J
33. Livingston EG, Herbert WN, Hage ML, Chapman JF,
Stubbs TM. Use of the TDx-FLM assay in evaluating fetal
lung maturity in an insulin-dependent diabetic population.
The Diabetes and Fetal Maturity Study Group. Obstet
34. Del Valle GO, Adair CD, Ramos EE, Gaudier FL,
Sanchez-Ramos L, Morales R. Interpretation of the TDxFLM fluorescence polarization assay in pregnancies complicated by diabetes mellitus. Am J Perinatol
1997;14:2414. (Level II-3)
21. Piazze JJ, Maranghi L, Nigro G, Rizzo G, Cosmi EV,

Anceschi MM. The effect of glucocorticoid therapy on
fetal lung maturity indices in hypertensive pregnancies.
35. Curet LB, Tsao FH, Zachman RD, Olson RW, Henderson
PA. Phosphatidylglycerol, lecithin/sphingomyelin ratio
and respiratory distress syndrome in diabetic and non-diabetic pregnancies. Int J Gynaecol Obstet 1989;30: 1058.
(Level II-2)
22. Leveno KJ, Quirk JG, Whalley PJ, Herbert WN, Trubey
R. Fetal lung maturation in twin gestation. Am J Obstet
36. Langer O. The controversy surrounding fetal lung maturity in diabetes in pregnancy: a re-evaluation. J Matern
Fetal Neonatal Med 2002;12:42832. (Level III)
23. McElrath TF, Norwitz ER, Robinson JN, Tanasijevic MJ,

Lieberman ES. Differences in TDx fetal lung maturity
assay values between twin and singleton gestations. Am J
37. Piper JM, Xenakis EM, Langer O. Delayed appearance of

pulmonary maturation markers is associated with poor
glucose control in diabetic pregnancies. J Matern Fetal
Med 1998;7:14853. (Level II-2)
24. Winn HN, Romero R, Roberts A, Liu H, Hobbins JC.

Comparison of fetal lung maturation in preterm singleton
and twin pregnancies. Am J Perinatol 1992;9:3268.
(Level II-3)
38. Moore TR. A comparison of amniotic fluid fetal pulmonary phospholipids in normal and diabetic pregnancy.
25. Spellacy WN, Cruz AC, Buhi WC, Birk SA. Amniotic
fluid L/S ratio in twin gestation. Obstet Gynecol
1977;50:6870. (Level II-3)
26. Whitworth NS, Magann EF, Morrison JC. Evaluation of
fetal lung maturity in diamniotic twins. Am J Obstet
Gynecol 1999;180:143841. (Level II-3)
27. Mackenzie MW. Predicting concordance of biochemical
lung maturity in the preterm twin gestation. J Matern Fetal
Neonatal Med 2002;12:508. (Level II-3)
28. Chasen ST, Madden A, Chervenak FA. Cesarean delivery
of twins and neonatal respiratory disorders. Am J Obstet
Gynecol 1999;181:10526. (Level II-3)
29. Piazze JJ, Maranghi L, Cosmi EV, Anceschi MM. The
effect of polyhydramnios and oligohydramnios on fetal
lung maturity indexes. Am J Perinatol 1998;15:24952.
(Level II-2)
30. Edwards RK, Duff P, Ross KC. Amniotic fluid indices of
fetal pulmonary maturity with preterm premature rupture of
membranes. Obstet Gynecol 2000;96:1025. (Level II-3)
31. Cleary-Goldman J, Connolly T, Chelmow D, Malone F.
Accuracy of the TDx-FLM assay of amniotic fluid: a
39. Piper JM, Langer O. Does maternal diabetes delay fetal

pulmonary maturity? Am J Obstet Gynecol 1993;168:
7836. (Level II-2)
40. Berkowitz K, Reyes C, Saadat P, Kjos SL. Fetal lung maturation. Comparison of biochemical indices in gestational
diabetic and nondiabetic pregnancies. J Reprod Med
1997;42:793800. (Level II-2)
41. Piazze JJ, Anceschi MM, Maranghi L, Brancato V,
Marchiani E, Cosmi EV. Fetal lung maturity in pregnancies complicated by insulin-dependent and gestational
diabetes: a matched cohort study. Eur J Obstet Gynecol
Reprod Biol 1999;83:14550. (Level II-2)
42. Piper JM. Lung maturation in diabetes in pregnancy: if and
when to test. Semin Perinatol 2002;26:2069. (Level III)
43. Burkhart AE, Towers CV, Rumney PJ, Lewis DF.
Neonatal outcome when delivery follows a borderline
immature lecithin to sphingomyelin ratio. J Perinatol
2000;20:15760. (Level III)
44. Bildirici I, Moga CN, Gronowski AM, Sadovsky Y. The
mean weekly increment of amniotic fluid TDx-FLM II
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1068

Priority was given to articles reporting results of original research, although review articles and commentaries also
were consulted. Abstracts of research presented at symposia
and scientific conferences were not considered adequate for
Task Force:
I

type of evidence.
committees.
Copyright September 2008 by the American College of

Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Fetal lung maturity. ACOG Practice Bulletin No. 97. American College
71726.
PRACTICE BULLETINS
1069
ACOG
PRACTICE
BULLETIN
Critical Care in Pregnancy

the assistance of Lauren A. Plante,
MD, MPH. The information is
designed to aid practitioners in
Critical care in pregnancy is a field that remains unevenly researched. Although

there is a body of evidence to guide many recommendations in critical care,
limited research specifically addresses obstetric critical care. The purpose of
this document is to review the available evidence, propose strategies for care,
and highlight the need for additional research. Much of the review will, of
necessity, focus on general principles of critical care, extrapolating where possible to obstetric critical care.
Background
Recent case series suggest that between 0.1% and 0.8% of obstetric patients are
admitted to a traditional intensive care unit (ICU) (19). Among this population, the risk of death ranges from 2% to 11%. Although survival is better than
that in an unselected population, mortality is substantially higher than the
maternal mortality ratio in the developed world. In addition, approximately
12% of pregnant women receive critical care outside of a traditional ICU, but
within a specialized obstetric care unit (10, 11). Therefore, overall estimates
suggest that 13% of pregnant women require critical care services in the
United States each year, approximately 40,000120,000 women (based on 4
million births per year) (12).
Techniques for Critical Care

OBSTETRICIANS AND
GYNECOLOGISTS
Competence in a number of core procedural skills is necessary for any physician practicing in critical care. Except in very large maternity centers, there is
little opportunity to develop or maintain these skills, although alternative means
may be available. Some techniques can be performed under supervision in other
settings (eg, airway techniques under anesthesiologists supervision in the operating room), others can be rehearsed through electronic resources or online
(electrocardiogram interpretation), and still others lend themselves to task training through medical simulation.
1070
Organization of Critical Care

In an open ICU, any physician can write orders or perform procedures; management or consultation by a qualified intensive care physician is not mandatory. In a
closed ICU, only the critical care attending physician or
house staff can write orders and manage patient care.
The hybrid or transitional model allows all physicians to
write orders but requires an on-site critical care physician to provide consultation, conduct rounds, or co-manage all patient care. Additional terminology classifies
ICU physician staffing as high-intensity (closed ICU or
mandatory intensivist consultation) or low-intensity
(optional intensivist) (13). High-intensity ICU physician
staffing is associated with lower ICU mortality, lower
hospital mortality, and decreased length of stay in both
the ICU and the hospital, compared with low intensity
ICU physician staffing (13). Although there are limited
data specifically addressing the critical care obstetric
patient, it seems reasonable that these findings would
apply to this population as well (14, 15).
Critical care requires a multidisciplinary approach
to achieve the best outcomes (16). The usual ICU team
includes physicians, nurses, pharmacists, and respiratory
therapists. In critical care obstetrics, the team also should
include obstetricians or maternalfetal medicine subspecialists, obstetric nurses, and neonatologists.
The obstetrician transferring a patient to an ICU
must be familiar with the types of units available at the
institution, such as a general medicalsurgical ICU or a
specialty unit for cardiothoracic or neurologic or neurosurgical care as well as the role of the obstetrician within each unit (17).
There are three levels of adult critical care described
by the American College of Critical Care Medicine, with
Level I delivering the highest level of care. Alternatives
to traditional ICU care include intermediate-care or
high-dependency units such as post-ICU step-down units,
telemetry units for cardiac patients, and units for patients
requiring long-term ventilator use (10, 11, 18).
Admission to Intensive Care

Because ICU beds are a scarce resource, ICU admission
should be reserved for those patients who are likely to
benefit. Most obstetric patients will be admitted under
the objective parameters triage model. In this model,
specific criteria trigger ICU admission, regardless of
diagnosis. These triggers were achieved by consensus, in
response to the review by the Joint Commission (formerly the Joint Commission on Accreditation of
Healthcare Organizations), and are acknowledged to be
largely arbitrary. They include specific abnormalities in
vital signs, laboratory values, and imaging and physical
findings. Admission criteria for nonpregnant patients are
listed in the box Objective Parameters Model for

Admission of Nonpregnant Patients to an Intensive Care
Unit. A description of changes to normal laboratory values during pregnancy is provided in the box Key
Laboratory Values That are Different in Pregnancy.
Considerations in Transfer
The care of any pregnant woman requiring ICU services
should be managed in a facility with obstetric adult ICU
and neonatal ICU capability. Standard guidelines for
perinatal transfer have been published by the American
College of Obstetricians and Gynecologists and the
American Academy of Pediatrics and follow federal
Emergency Medical Treatment and Labor Act guidelines
(19). These guidelines generally recommend antenatal
rather than neonatal transfer and describe the responsibilities of the referring and receiving hospitals. In the
event that maternal transport is unsafe or impossible,
alternative arrangements for neonatal transport may be
necessary. In patients where imminent delivery is
expected, transfer should be held until after delivery.
The mimimal monitoring required for a critically ill
patient during transport includes continuous pulse
oximetry and electrocardiography as well as regular
assessment of vital signs (19, 20). All critically ill patients
must have secure venous access before transport.
Patients who already have arterial or central lines or
other invasive monitoring devices in place should have
those monitored as well. Women who are mechanically
ventilated must have the endotracheal tube position confirmed and secured before transport and must be
assessed for adequacy of oxygenation and ventilation.
There are no data to guide obstetric monitoring during transport of the critically ill obstetric patient. Fetal
and tocodynamic monitoring during transport is likely
feasible but of unproven utility (21). In some circumstances, identifying fetal compromise in transit may
allow for advance preparation for intervention, including
delivery, by the receiving institution. Simple measures,
such as left uterine displacement and supplemental oxygen, should be applied routinely during transport.

Recommendations
What are the findings in a pregnant or
postpartum woman that might prompt ICU
admission?
Patients should be transferred to an ICU if they need circulatory or pulmonary support. An obstetric service
should adopt site-specific guidelines for transfer based
PRACTICE BULLETINS
Objective Parameters Model for Admission of

Nonpregnant Patients to an Intensive Care Unit
Vital Signs
Heart rate of less than 40 beats per minute or
greater than 150 beats per minute
Blood pressure of less than 80 mm Hg systolic (or
20 mm Hg below the patients usual blood pressure)
Mean arterial pressure of less than 60 mm Hg
Blood pressure of greater than 120 mm Hg diastolic
Respiratory rate of greater than 35 per minute
Laboratory Values
Serum sodium level of less than 110 mEq/L or
greater than 170 mEq/L
Serum potassium level of less than 2 or greater than
7 mEq/L
PaO2 of less than 50 mm Hg
pH level of less than 7.1 or greater than 7.7
Serum calcium level of greater than 15 mg/dL
Serum glucose level of greater than 800 mg/dL
Toxic drug level in a hemodynamically or neurologically compromised patient
Imaging
Cerebrovascular hemorrhage, contusion, or subarachnoid hemorrhage with altered mental status or
focal neurologic findings
Ruptured viscus or esophageal varices with hemodynamic instability
Dissecting aortic aneurysm
Electrocardiography
Myocardial infarction with complex arrhythmia,
hemodynamic instability, or congestive heart failure
Sustained ventricular tachycardia or ventricular fibrillation
Complete heart block with hemodynamic instability
Physical Findings
Airway obstruction
Anuria
Burns of greater than 10% of body surface area
Cardiac tamponade
Coma
Continuous seizures
Cyanosis
Unequal pupils (unconscious patient)
Guidelines for intensive care unit admission, discharge, and triage.
Task Force of the American College of Critical Care Medicine,
Society of Critical Care. Crit Care Med 1999;27:6338.
1071
Key Laboratory Values That are

Different in Pregnancy
Hemodynamic Variables
Increased cardiac output
Decreased systemic vascular resistance
Decreased blood pressure
Increased heart rate
Decreased pulmonary vascular resistance
Respiratory Variables
Decreased functional residual capacity
Increased minute ventilation
Laboratory Variables
Increased PAO2 and PaO2
Decreased PaCO2
Decreased serum bicarbonate (HCO3)
Decreased hemoglobin and hematocrit levels
Increased white blood cell count
Decreased protein S levels
Decreased coagulation factors XI and XIII levels
Increased coagulation factors I, VII, VIII, IX, and
X levels
Increased fibrinogen levels
Increased D-dimer levels
Increased erythrocyte sedimentation rate
Decreased serum creatinine levels
Decreased blood urea nitrogen level (BUN)
Decreased uric acid level
Increased alkaline phosphatase level
Increased aldosterone level
Increased serum cortisol, free cortisol, cortisol-binding globulin, and adrenocorticotropic hormone level
Increased insulin level
Decreased fasting blood glucose level
Increased triglyceride level
Increased cholesterol, low-density lipoprotein, and
high-density lipoprotein levels
Data from Gabbe SG, Niebyl JR, Simpson JL, Galan H, Goetzl L,
Jauniaux ER, et al, editors. Obstetrics: normal and problem pregnancies. 5th ed. Philadelphia (PA): Churchill Livingstone Elsevier;
2007.
1072
on the level of care required. These guidelines also

should define and distinguish between levels of care that
can be provided on the labor floor or, if applicable, the
obstetric intermediate care unit.
Hemorrhage and hypertension are the most common
causes of ICU admission in obstetric patients (17, 9,
2236). Most of these patients typically require relatively simple interventions, monitoring, and supportive care.
Approximately 2030% of obstetric ICU patients
have nonobstetric causes for an ICU admission, such as
sepsis (1, 5, 7, 11). Early goal-directed therapy for sepsis should not be delayed until the admission to the ICU
but should begin as soon as septic shock is diagnosed
(3739). The patient should be stabilized, intravenous
access maintained, urine output and fluid volume managed, and antibiotics started for treatment of sepsis.
Broad-spectrum antibiotic therapy should be started
within 1 hour of the diagnosis of severe sepsis or septic
shock (37). Cultures, including blood cultures, should be
obtained, but should not delay initiating antibiotics. Fetal
resuscitation in utero through maternal oxygen therapy
and circulatory support is preferable to cesarean delivery
for nonreassuring fetal heart rate patterns in most cases.
Approximately 75% of obstetric ICU patients admitted
to the ICU are postpartum (5, 6, 25). This may be due to
specific postpartum causes, such as postpartum hemorrhage, or to ascertainment bias; obstetricians may be less
willing to transfer or intensivists less willing to accept a
patient whose fetus must still be considered in care planning. The process of transport itself is risky for a critically
ill patient, who requires ongoing monitoring and maintenance while in transport. In a viable pregnancy, fetal monitoring during transport between obstetric units and the ICU
may be prudent, especially if the patient is in labor (20).
Admission to the ICU is dependent on levels of care
available on a local level. Patients needing the following
procedures should be treated in a critical care unit:
1. Respiratory support, including airway maintenance
and endotracheal intubation
2. Treatment of pneumothorax
3. Cardiovascular support, including treatment with
pressors
4. Pulmonary artery catheterization (insertion, maintenance, and interpretation)
5. Abnormal electrocardiographic findings requiring
intervention, including cardioversion or defibrillation
interpretation
What is the obstetriciangynecologists role

in the transfer of a patient to a critical care
unit?
When obstetric patients are transferred to the ICU, the

obstetricians role will depend on the ICU model (open
or closed) and the patients status (antepartum or postpartum). Regardless of the primary caregiver, patient
care decisions must be made collaboratively between the
intensivist, obstetrician, and neonatologist, and should
involve the patient, her family, or both.
Obstetric input in the care of the postpartum ICU
patient may include evaluation of vaginal or intraabdominal bleeding, evaluation of obstetric sources of infection, duration of specific therapies, such as magnesium
for eclampsia prophylaxis, and feasibility of breast-feeding, especially compatibility of various medications with
breast-feeding. There may be issues related to surgical
interventions, including reexploration of the abdomen,
or reclosure of abdominal or vaginal incisions. Under
some circumstances, the obsterician and the neonatologist also will need to advocate for bringing together the
critically ill mother and her baby.
Multidisciplinary care is essential for the critically
ill obstetric patient. When a pregnant patient is transferred to the ICU, members of the care team should
assess the anticipated course of her condition or disease,
including possible complications, and set parameters for
delivery, if appropriate. The plan should be clear to the
medical team and to the patients family, and to the
patient herself if she is able to understand. Because the
riskbenefit calculation for a given intervention may
change as pregnancy progresses, it is important to reevaluate the care plan on a regular basis.
The plan for delivery should be made long before
delivery is imminent, and it must include decisions about
preferred location for delivery, preferred mode of delivery (vaginal versus cesarean), need for analgesia or anesthesia, and access to pediatricians. It also must include
an alternative plan or set of plans in the event that the
original plan cannot be followed.
If postpartum ICU admission is necessary, the
patient and her family may have questions regarding the
obstetric events that precipitated transfer even when
obstetric care has been optimal. Anger, dissatisfaction, or
legal action often follow a perceived bad outcome; in the
case of a postpartum complication or condition requiring
critical care, the obstetrician may bear the brunt of these
questions. Although a full discussion about disclosure
and review of adverse events is beyond the scope of this
document, resources are available to assist the obstetrician through this stressful time (40).
How should care be organized when a

laboring patient needs critical care?
If a laboring patient requires critical care services, it is
important to determine the optimal setting for her care.
PRACTICE BULLETINS
If the fetus is pre-viable or the duration of ICU services

is anticipated to be lengthy, the labor floor is unlikely to
be the best option. However during active labor, the labor
unit may be the best choice if adequate maternal support
can be provided. Advantages of vaginal delivery in the
ICU include the availability of critical care interventions
and staff. Disadvantages include lack of space to conduct
a vaginal delivery and to accommodate pediatric personnel and equipment, and unfamiliarity of critical care personnel with obstetric interventions and management.
Factors that will affect this decision include the degree of
patient instability, interventions required, staffing and
expertise available, anticipated duration of ICU stay, and
probability of delivery.
Delivery in the ICU is associated with an increased
likelihood of operative vaginal delivery. In part, this is
because patients with translaryngeal intubation cannot
close the glottis to push; therefore, an assisted second
stage of labor may be required. In addition, ICU patients
often have underlying cardiac or neurologic processes
where an assisted second stage of labor is recommended.
Adequate analgesia is required, although assessment of
pain may be complicated by altered mental status or intubation. Regional analgesia is preferred but may not be
possible because of coagulopathy, hemodynamic instability, or difficulties with patient positioning. Parenteral narcotics can be used instead of regional analgesia but are
less effective in preventing pain; suboptimally treated pain
may result in hemodynamic derangements that must be
anticipated and treated.
Cesarean delivery in the ICU is complex and has
significant disadvantages compared with procedures performed in a traditional operating room. These disadvantages include inadequate space for anesthetic, surgical,
and neonatal resuscitation equipment and attendant personnel unfamiliar with the operation. In addition, ICUs
have the highest rates of health care associated infections
in a hospital, so the risk of nosocomial infection with
drug-resistant organisms is increased (41, 42). Cesarean
delivery in the ICU should be restricted to cases in which
transport to the operating room or delivery room cannot
be achieved safely or expeditiously, or to a perimortem
procedure.
Are there special fetal considerations in the

care of a pregnant woman in a critical care
setting (eg, assessment of gestational age,
fetal monitoring, or complications related to
medications)?
Establishment of gestational age is crucial to determine
whether the fetus is of gestational age sufficient to
ensure a good chance of survival after birth. When pos-
1073
sible, prenatal care records should be obtained to establish the most accurate dating criteria. In the event that
gestational age remains uncertain, prompt ultrasound
evaluation should establish the best possible estimate
with documentation of the potential range of uncertainty.
Use of obstetric medications may pose particular
challenges in the critically ill patient; known side effects
must be carefully monitored and riskbenefit ratios should
be assessed in each individual situation. Examples of
common drug-related side effects include tachycardia and
decreased blood pressure with beta-agonists, effects on
platelet function and renal perfusion with indomethacin,
and negative inotropic effects on cardiac function with
magnesium. If preterm delivery may be necessary, a
course of antenatal corticosteroids should be given to promote fetal lung maturity in fetuses between 24 weeks of
gestation and 34 weeks of gestation, and are not contraindicated in an ICU setting even in the setting of sepsis.
Pregnancy often modifies drug effects or serum levels. Drugs that cross the placenta may have fetal effects;
for example, sedative or parasympatholytic drugs can
affect the fetal heart rate tracing. However, necessary
medications should not be withheld from a pregnant
woman because of fetal concerns. Additionally, necessary imaging studies should not be withheld out of
potential concern for fetal status, although attempts
should be made to limit fetal radiation exposure during
diagnostic testing.
Fetal surveillance often is used when a pregnant
patient is admitted to the ICU. Because fetal heart rate
monitoring reflects uteroplacental perfusion and maternal acidbase status, changes in baseline variability or
the new onset of decelerations may serve as an early
warning system for derangements in maternal end-organ
status. Changes in fetal monitoring should prompt
reassessment of maternal mean arterial pressure, hypoxia, acidemia, or compression of the inferior vena cava by
the gravid uterus. Correction of these factors may result
in improvement of the tracing and every attempt should
be made at intrauterine fetal resuscitation.
Is intraoperative fetal monitoring needed for

a pregnant patient?
Although there are no data to allow for a specific recommendation regarding fetal monitoring for nonobstetric
surgery, it is important for physicians to obtain obstetric
consultation before performing nonobstetric surgery.
Obstetricians are uniquely qualified to discuss aspects of
maternal physiology and anatomy that may affect intraoperative maternalfetal well-being. The decision to use
fetal monitoring should be individualized and, if used,
may be based on gestational age, type of surgery, and
1074
facilities available. Ultimately, each case warrants a team

approach (anesthesia, obstetrics, and surgery) for optimal maternal and fetal safety.
When is perimortem caesarean delivery

appropriate?
Although there are no clear guidelines regarding perimortem cesarean delivery, fetal survival is unlikely if
more than 1520 minutes have passed since the loss of
maternal vital signs. There are insufficient data on which
to base conclusions regarding the appropriateness of
cesarean delivery when efforts at resuscitation have
failed. Based on isolated case reports, cesarean delivery
should be considered for both maternal and fetal benefit
approximately 4 minutes after a woman has experienced
cardiopulmonary arrest in the third trimester (43, 44).
Summary of
Recommendations and
Conclusions
ICU and a hospital, compared with models in which

intensivist consultation is optional.
Decisions about care for a pregnant patient in the ICU
should be made collaboratively with the intensivist,
obstetrician, specialty nurses, and neonatologist.
The care of any pregnant woman requiring ICU services should be managed in a facility with obstetric
adult ICU and neonatal ICU capability.
Necessary medications should not be withheld from
a pregnant woman because of fetal concerns.
Necessary imaging studies should not be withheld
out of potential concern for fetal status, although
attempts should be made to limit fetal radiation
exposure during diagnostic testing.
Measure
Percentage of pregnant or postpartum patients in the ICU
who have documented involvement of an obstetrician
gynecologist
The following conclusions are based on good and

Pregnancy changes normal laboratory values and
physiologic parameters.
Approximately 75% of obstetric ICU patients are
admitted to the unit postpartum.
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during hospital admission for delivery: a retrospective
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Task Force:
I

type of evidence.
committees.
Copyright February 2009 by the American College of

Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Critical care in pregnancy. ACOG Practice Bulletin No. 100. American
113:44350.
PRACTICE BULLETINS
1077
ACOG
PRACTICE
BULLETIN
Ultrasonography in
Pregnancy
on Practice BulletinsObstetrics
with the assistance of Alfred Z.
Abuhamad, MD. The information
is designed to aid practitioners in

OBSTETRICIANS AND
GYNECOLOGISTS
Most women have at least one ultrasound examination during pregnancy. The
purpose of this document is to present evidence regarding the methodology
of, indications for, benefits of, and risks associated with obstetric ultrasonography in specific clinical situations. Portions of this document were developed
collaboratively with the American College of Radiology and the American
Institute of Ultrasound in Medicine. The sections that address physician qualifications and responsibilities, documentation, quality control, infection control,
and patient safety contain recommendations from the American College of
Background
Instrumentation
Ultrasound examination should be conducted with real-time scanners, using a
transabdominal or a transvaginal approach or both. Real-time ultrasonography
is necessary to confirm the presence of fetal life through observation of cardiac
activity and active movement. The choice of transducer frequency is a trade-off
between beam penetration and resolution. With modern equipment, abdominal
transducers with frequencies ranging from 3 MHz to 5 MHz allow sufficient
penetration in most patients while providing adequate resolution. A lower-frequency transducer (22.25 MHz) may be needed to provide adequate penetration for abdominal imaging in an obese patient. During early pregnancy, an
abdominal transducer with a frequency of 5 MHz or a transvaginal transducer
with a frequency of 510 MHz or higher may provide superior resolution while
still allowing adequate penetration. A method for storing the images also is
required. The equipment should be serviced at regular intervals according to the
manufacturers recommendations.
1078
Types of Examinations
The American College of Obstetricians and Gynecologists uses the terms standard (also called basic), limited, and specialized (also called detailed) to describe
various types of ultrasound examinations performed during the second or third trimesters. First-trimester ultrasound examination is distinct and is discussed separately.
Standard Examination
Ultrasonography is an accurate method of determining gestational age, fetal number, viability, and placental location.
A standard obstetric ultrasound examination in the second
or third trimester includes an evaluation of fetal presentation, amniotic fluid volume, cardiac activity, placental position, fetal biometry, and fetal number, plus an anatomic
survey. The maternal cervix and adnexa should be examined as clinically appropriate when technically feasible.
Fetal anatomy, as described in this document, may
be assessed adequately by ultrasonography after approximately 18 weeks of gestation. It may be possible to document normal structures before this time, although some
structures can be difficult to visualize because of fetal
size, position, and movement; maternal abdominal scars;
and increased maternal abdominal wall thickness. A second- or third-trimester ultrasound examination may pose
technical limitations for an anatomic evaluation because
of suboptimal imaging. When this occurs, the report of
the ultrasound examination should document the nature
of this technical limitation. A follow-up examination
may be helpful. The essential elements of a standard
examination of fetal anatomy are listed in the box.
Limited Examination
A limited examination does not replace a standard examination and is performed when a specific question requires
investigation. For example, a limited examination in the
second or third trimester could be performed to confirm
fetal heart activity in a patient experiencing vaginal bleeding or to establish fetal presentation in a laboring patient.
A limited examination also may be performed in any
trimester to evaluate interval growth, estimate amniotic
fluid volume, evaluate the cervix, and assess the presence
of cardiac activity.
Specialized Examination
A detailed or targeted anatomic examination is performed when an anomaly is suspected on the basis of
history, laboratory abnormalities, or the results of either
the limited or standard examination. Other specialized
examinations might include fetal Doppler ultrasonography, biophysical profile, amniotic fluid assessment, fetal
echocardiography, or additional biometric measure-
Essential Elements of Standard

Examination of Fetal Anatomy
Head, Face and Neck*
Cerebellum
Choroid plexus
Cisterna magna
Lateral cerebral ventricles
Midline falx
Cavum septi pellucidi
Upper lip
ChestHeart (The basic cardiac examination includes
a four-chamber view of the fetal heart. As part of the
cardiac screening examination, an attempt should be
made, if technically feasible, to view the outflow
tracts.)
Abdomen
Stomach (presence, size, and situs)
Kidneys
Bladder
Umbilical cord insertion site into the fetal abdomen
Umbilical cord vessel number
SpineCervical, thoracic, lumbar, and sacral spine
ExtremitiesLegs and arms (presence or absence)
SexMedically indicated in low-risk pregnancies
only for the evaluation of multiple gestations
*A measurement of the nuchal fold may be helpful during a specific

age interval to suggest an increased risk of aneuploidy.
American College of Radiology. ACR practice guideline for the performance of obstetrical ultrasound. In: ACR practice guidelines and
technical standards, 2007. Reston (VA): ACR; 2007. p. 10251033.
ments. Specialized examinations are performed by an

operator with experience and expertise in such ultrasonography who determines the components of the
examination on a case-by-case basis.
First-Trimester Ultrasound Examination

Indications. A first-trimester ultrasound examination is
an ultrasound examination performed before 13 weeks
and 6 days of gestation. Indications for performing firsttrimester ultrasound examinations are listed in the box.
Imaging Parameters. Scanning in the first trimester
may be performed either transabdominally or transvaginally. If a transabdominal examination is not definitive,
a transvaginal scan or transperineal scan should be per-
PRACTICE BULLETINS
Indications for First-Trimester Ultrasonography

To confirm the presence of an intrauterine
pregnancy
To evaluate a suspected ectopic pregnancy
To evaluate vaginal bleeding
To evaluate pelvic pain
To estimate gestational age
To diagnosis or evaluate multiple gestations
To confirm cardiac activity
As adjunct to chorionic villus sampling,
embryo transfer, or localization and removal
of an intrauterine device
To assess for certain fetal anomalies, such as
anencephaly, in patients at high risk
To evaluate maternal pelvic or adnexal masses or
uterine abnormalities
To screen for fetal aneuploidy
To evaluate suspected hydatidiform mole
formed whenever possible. The following factors should

be considered during the examination.
The uterus, including the cervix, and adnexa should
be evaluated for the presence of a gestational sac. If a
gestational sac is seen, its location should be documented. The gestational sac should be evaluated for the
presence or absence of a yolk sac or embryo, and the
crownrump length should be recorded, when possible.
The crownrump length is a more accurate indicator of
gestational (menstrual) age than is mean gestational sac
diameter. However, the mean gestational sac diameter
may be recorded when an embryo is not identified.
Caution should be used in presumptively diagnosing a
gestational sac in the absence of a definite embryo or
yolk sac. Without these findings, intrauterine fluid collection could represent a pseudogestational sac associated
with an ectopic pregnancy.
Presence or absence of cardiac activity should be
reported. With transvaginal scans, cardiac motion should
be observed when the embryo is 5 mm or greater in
length. An embryo should be visible by transvaginal
ultrasonography with a mean gestational sac diameter of
20 mm or greater. If an embryo less than 5 mm in length
is seen without cardiac activity, a subsequent scan at a
1079
later time may be needed to assess the presence or

absence of cardiac activity. Fetal number should be
reported. Amnionicity and chorionicity should be documented for all multiple gestations when possible.
Embryonic or fetal anatomy should be assessed according to gestational age.
The uterus, including adnexal structures, should be
evaluated. The presence, location, and size of adnexal
masses should be recorded. The presence of leiomyomas
should be recorded, and measurements of the largest or
any potentially clinically significant leiomyomas may
be recorded. The cul-de-sac should be evaluated for the
presence or absence of fluid.
For patients who desire an assessment of their individual risk of fetal aneuploidy, a standardized measurement of the nuchal translucency during a specific age
interval is necessary. Nuchal translucency measurements
should be used (in conjunction with serum biochemistry)
to determine the risk of Down syndrome, trisomy 13, trisomy 18, or other anatomic abnormalities, such as heart
defects. In this setting, it is important that the practitioner
measure the nuchal translucency according to established guidelines for measurement. In addition, a quality
assessment program is recommended to ensure accurate
results. Organizations currently providing guidelines and
ongoing quality assessment include the Nuchal
Translucency Quality Review program of the Maternal
Fetal Medicine Foundation and the program sponsored
by the Fetal Medicine Foundation.
Second- and Third-Trimester

Ultrasound Examination
Indications. Ultrasonography can be of benefit in many
situations in the second and third trimesters. Indications
for second- and third-trimester ultrasonography are listed
in the box.
Imaging Parameters for a Standard Fetal Examination. Fetal cardiac activity, fetal number, and fetal presentation should be reported. Any abnormal heart rates
or rhythms should be reported. Multiple gestations
require the documentation of additional information:
chorionicity, amnionicity, comparison of fetal sizes, estimation of amniotic fluid volume (increased, decreased,
or normal) on each side of the membrane, and fetal genitalia (when visualized).
Ultrasonography can detect abnormalities in amniotic fluid volume. An estimate of amniotic fluid volume
should be reported. Although it is acceptable for experienced examiners to qualitatively estimate amniotic fluid
volume, semiquantitative methods also have been described for this purpose (eg, amniotic fluid index, single
deepest pocket, two-diameter pocket).
1080
The placental location, appearance, and relationship

to the internal cervical os should be recorded. It is recognized that apparent placental position early in pregnancy may not correlate well with its location at the time
Indications for Second- and Third-Trimester

Ultrasonography
Estimation of gestational age
Evaluation of fetal growth
Evaluation of vaginal bleeding
Evaluation of cervical insufficiency
Evaluation of abdominal and pelvic pain
Determination of fetal presentation
Evaluation of suspected multiple gestation
Adjunct to amniocentesis or other procedure
Significant discrepancy between uterine size and
clinical dates
Evaluation of pelvic mass
Examination of suspected hydatidiform mole
Adjunct to cervical cerclage placement
Evaluation of suspected ectopic pregnancy
Evaluation of suspected fetal death
Evaluation of suspected uterine abnormality
Evaluation for fetal well-being
Evaluation of suspected amniotic fluid abnormalities
Evaluation of suspected placental abruption
Adjunct to external cephalic version
Evaluation for premature rupture of membranes or
premature labor
Evaluation for abnormal biochemical markers
Follow-up evaluation of a fetal anomaly
Follow-up evaluation of placental location for
suspected placenta previa
Evaluation for those with a history of previous
congenital anomaly
Evaluation of fetal condition in late registrants for
prenatal care
To assess findings that may increase the risk of
aneuploidy
To screen for fetal anomalies
of delivery. Therefore, if a low-lying placenta or placenta

previa is suspected early in gestation, verification in the
third trimester by repeat ultrasonography is indicated.
Transabdominal, transperineal, or transvaginal views
may be helpful in assessing cervical length or visualizing the internal cervical os and its relationship to the placenta. Transvaginal or transperineal ultrasonography
may be considered if the cervix appears shortened.
Gestational age is most accurately determined in the
first half of pregnancy. First-trimester crownrump
measurement is the most accurate means for ultrasound
dating of pregnancy. Beyond this period, a variety of
ultrasound parameters, such as biparietal diameter,
abdominal circumference, and femoral diaphysis length,
can be used to estimate gestational age. However, the
variability of gestational age estimations increases with
advancing pregnancy. Significant discrepancies between
gestational age and fetal measurements may suggest the
possibility of a fetal growth abnormality, intrauterine
growth restriction, or macrosomia. The pregnancy should
not be redated after a date has been calculated from an
accurate earlier scan that is available for comparison.
Biparietal diameter is measured at the level of the
thalami and cavum septi pellucidi. The cerebellar hemispheres should not be visible in this scanning plane. The
measurement is taken from the outer edge of the proximal skull to the inner edge of the distal skull. The head
shape may be flattened (dolichocephaly) or rounded
(brachycephaly) as a normal variant. Under these circumstances, measurement of the head circumference
may be more reliable than measurement of the biparietal
diameter for estimating gestational age. Head circumference is measured at the same level as the biparietal diameter, around the outer perimeter of the calvaria. This
measurement is not affected by head shape.
Femoral diaphysis length can be reliably used after
14 weeks of gestation. The long axis of the femoral shaft
is most accurately measured with the beam of insonation
being perpendicular to the shaft, excluding the distal
femoral epiphysis.
Abdominal circumference or average abdominal
diameter should be determined at the skin line on a true
transverse view at the level of the junction of the umbilical vein, portal sinus, and fetal stomach when visible.
Abdominal circumference or average abdominal diameter measurement is used with other biometric parameters
to estimate fetal weight and may allow detection of
intrauterine growth restriction or macrosomia.
Fetal weight can be estimated by obtaining measurements such as the biparietal diameter, head circumference, abdominal circumference or average abdominal
diameter, and femoral diaphysis length. Results from
various prediction models can be compared with fetal
PRACTICE BULLETINS
weight percentiles from published nomograms. If previous studies have been performed, appropriateness of
growth also should be reported. Scans for growth evaluation are typically performed at least 24 weeks apart.
A shorter scan interval may result in confusion as to
whether anatomic changes are caused by growth or
by variations in the measurement technique itself.
Currently, even the best fetal weight prediction methods
can yield errors as high as plus or minus 15%. This variability can be influenced by factors such as the nature
of the patient population, the number and types of
ana-tomic parameters being measured, technical factors
that affect the resolution of ultrasound images, and the
weight range being studied.
Evaluation of the uterus, adnexal structures, and
cervix should be performed when appropriate. The presence, location, and size of adnexal masses and the presence of at least the largest and potentially clinically
significant leiomyomas may be recorded. It may not be
possible to image the normal maternal ovaries during the
second and third trimesters.
Three-Dimensional Ultrasonography
Three-dimensional ultrasonography provides an advance
in imaging technology. With three-dimensional ultrasonography, the volume of a target anatomic region can be
acquired. The acquired volume then can be displayed in
three orthogonal two-dimensional planes, representing
the sagittal, transverse, and coronal planes of a reference
two-dimensional image within the volume. The volume
also can be displayed in its rendered format, which depicts
the topographic anatomy of the acquired volume. The
technical advantages of three-dimensional ultrasonography include its ability to acquire and manipulate an infinite
number of planes and to display ultrasound planes traditionally inaccessible by two-dimensional ultrasonography.
Despite these technical advantages, proof of a clinical
advantage of three-dimensional ultrasonography in prenatal diagnosis in general is still lacking. Potential areas of
promise include fetal facial anomalies, neural tube
defects, and skeletal malformations where three-dimensional ultrasonography may be helpful in diagnosis as an
adjunct to, but not a replacement for, two-dimensional
ultrasonography (1). Until clinical evidence shows a clear
advantage to conventional two-dimensional ultrasonography, three-dimensional ultrasonography is not considered
a required modality at this time.
Ultrasound Facility Accreditation

The American Institute of Ultrasound in Medicine and
the American College of Radiology offer ultrasound
facility accreditation. This process involves review of
1081
submitted ultrasound case studies, equipment use and

maintenance, report generation, storage of images, and
ultrasonographer and physician qualifications. Practices,
not individuals, may be accredited in ultrasonography for
obstetrics, gynecology, or both. Practices that receive
ultrasound accreditation have been shown to improve
compliance with published standards and guidelines for
the performance of obstetric ultrasound examinations (2).
Physicians who perform, evaluate, and interpret
diagnostic obstetric ultrasound examinations should be
licensed medical practitioners with an understanding of
the indications for such imaging studies, the expected
content of a complete obstetric ultrasound examination,
and a familiarity with the limitations of ultrasound imaging. They should be familiar with the anatomy, physiology, and pathophysiology of the pelvis, the pregnant
uterus, and the fetus. These physicians should have
undergone specific training in obstetric ultrasonography
either during or since their residency training and should
be able to document this training. Completion of an
approved residency in obstetrics and gynecology with
documentation of obstetric ultrasound experience and
training with certification by the American Board of
Obstetrics and Gynecology is evidence of the necessary
and appropriate training.
Physicians are responsible for the quality and accuracy of ultrasound examinations performed in their names,
regardless of whether they personally produced the
images. Physicians also are responsible for the quality of
the documentation of examinations and the quality control and safety of the environments and the procedures.
Documentation and Quality Assurance

Adequate documentation is essential for high-quality
patient care. There should be a record of the ultrasound
examination and its interpretation. Ideally, quality control is accomplished through careful record keeping of
obstetric ultrasound examination results, reliable archiving of reports and images, and clinical correlation with
clinical outcomes. The ultimate quality standard of any
imaging study is to correlate the study findings with clinical outcomes. Any practice active in obstetric ultrasonography should maintain such records and make
every effort to correlate imaging results with ultimate
clinical outcome data.
Patient Safety
Ultrasonography is safe for the fetus when used appropriately and when medical information about a pregnancy
is needed; however, ultrasound energy delivered to the
fetus cannot be assumed to be completely innocuous,
and the possibility exists that such biological effects may
1082
be identified in the future (3). Ultrasonography should be

performed only when there is a valid medical indication,
and the lowest possible ultrasound exposure setting
should be used to gain the necessary diagnostic information under the as-low-as-reasonably achievable principle
(4). Diagnostic levels of ultrasonography can produce
physical effects, such as mechanical vibrations (referred
to as cavitation) or an increase in tissue temperature
under laboratory conditions.
Although there is no reliable evidence of physical
harm to human fetuses from diagnostic ultrasound imaging using current technology, public health experts, clinicians, and industry representatives agree that casual use
of ultrasonography, especially during pregnancy, should
be avoided. The use of either two-dimensional or threedimensional ultrasonography only to view the fetus,
obtain a picture of the fetus, or determine the fetal sex
without a medical indication is inappropriate and contrary to responsible medical practice. Viewed in this
light, exposing the fetus to ultrasonography with no
anticipation of medical benefit is not justified (57). The
U.S. Food and Drug Administration views the promotion, sale, or lease of ultrasound equipment for making
keepsake fetal videos as an unapproved use of a medical device. Use of ultrasonography without a physicians order may be a violation of state or local laws or
regulations regarding the use of a prescription medical
device (8). Thus, ultrasonography should be used in a
prudent manner to provide medical benefit to the patient.
Cleaning and Sterilization

Use of ultrasound transducers, like any instrument used
on a patient, presents the possibility of microbial transmission if not properly cleaned after each patients use.
Transabdominal ultrasonography is not completely free
of this risk, although the risk is substantially lower than
it is for transvaginal ultrasonography. Transabdominal
ultrasound transducers may be adequately cleansed
between patients simply by wiping with a disposable
antiseptic paper towelette. Transvaginal ultrasound
transducers should always be covered with a single-use
disposable latex or nonlatex cover. However, disposable
protective covers are not without risk of rupture or
defect, and it is recommended that transvaginal ultrasound transducers undergo high-level disinfection
between each use. Steps involved in cleaning transvaginal ultrasound transducers include using running water
or a damp soft cloth to remove any residual gel or debris
from the probe, followed by high-level disinfection with
chemical agents (9, 10). The U.S. Food and Drug
Administration has published a list of approved highlevel disinfectants for use in processing reusable medical
devices (11). For all chemical disinfectants, precautions

must be taken to protect workers and patients from the
toxicity of the disinfectant. Practitioners should consult
the labels of proprietary products for specific instructions as well as instrument manufacturers regarding the
compatibility of these agents with probes.

Recommendations
Should all patients be offered ultrasonography, and what is the sensitivity of ultrasound
for detecting fetal anomalies?
Ultrasonography can be used to diagnose many major
fetal anomalies. It has been suggested that all patients be
offered routine ultrasound screening, given that 90% of
infants with congenital anomalies are born to women
with no risk factors (12). Significant controversy exists
with regard to the sensitivity of routine ultrasonography
in detecting fetal anomalies (1315). In a review of 36
studies involving more than 900,000 fetuses, an overall
sensitivity of 40.4% for detecting fetal anomalies was
noted, with a range of 13.382.4% (16). Studies on this
subject vary with regard to the definition of major versus
minor fetal anomalies, the level of risk in the study population (high risk versus low risk), the expertise of the
operators (tertiary versus nontertiary centers) and the
ascertainment of anomalies. In general, studies performed at tertiary centers showed a higher detection rate
for fetal anomalies (15, 17). Sensitivity tends to be higher
for defects of the central nervous system and urinary
tract than for the heart and great vessels (18). When an
ultrasound examination is performed, patients should be
counseled about the limitations of ultrasonography. This
should include a discussion of the sensitivity of the
examination for the detection of abnormalities and
potential false-positive findings.
Prenatal ultrasonography may reduce the rate of
perinatal mortality, primarily through pregnancy termination for prenatally diagnosed congenital malformations, but does not appear to reduce the rate of perinatal
morbidity. Ultrasonography provides more accurate estimation of gestational age, which prevents unnecessary
labor inductions for postterm pregnancy (19). Screening
detects multiple gestations, congenital anomalies, and
intrauterine growth restriction, but direct health benefits
from having this knowledge currently are unproven (20).
Despite the limitations of the evidence, given the detection rate of more than 80% for fetal anomalies in some
experienced centers, the benefits and limitations of ultrasonography should be discussed with all patients.
PRACTICE BULLETINS
However, if a patient requests ultrasonography, it is reasonable to honor the request. The decision ultimately
rests with the physician and patient jointly.
What gestational age represents the optimal

time for an obstetric ultrasound examination?
Ideally, all women should be offered aneuploidy screening before 20 weeks of gestation, regardless of maternal
age (21). For women presenting before 14 weeks of gestation, the option for first-trimester screening is available,
which may include ultrasonography for nuchal translucency measurement. Ultrasonography in the context of a
nuchal translucency measurement provides accurate dating of pregnancy and a very effective screening test for
Down syndrome and trisomy 18 when combined with
maternal age and serum markers (pregnancy-associated
plasma protein A and free or total -hCG) (22). However,
a complete anatomic assessment is not possible before 14
weeks of gestation.
In the absence of specific indications, ultrasound
examination between 1820 weeks of gestation allows for
a reasonable survey of fetal anatomy and an accurate estimation of gestational age. At 1820 weeks of gestation,
anatomically complex organs, such as the fetal heart and
brain, can be imaged with sufficient clarity to allow detection of many major malformations at a time when termination of pregnancy may still be an option. Therefore, the
optimal timing for a single ultrasound examination in the
absence of specific indications for a first-trimester examination is at 1820 weeks of gestation.
Should routine measurement of cervical

length be included in ultrasonography?
The value of routine cervical length measurement in lowrisk pregnancies has not been established; therefore, this
practice currently is not recommended. Although there is
an association between short cervix and preterm delivery,
there are no data to support routine screening for all
women. An effective screening protocol for assessing risk
of preterm birth that combines cervical measurements
and other risk factors has not been developed (2325).
For certain pregnant women at high risk, serial evaluation
of the cervical length may identify those at increased risk
of primary or recurrent preterm birth.
How and when is ultrasonography used to

adjust gestational age?
In general, ultrasound-established dates should take preference over menstrual dates when the discrepancy is
greater than 7 days in the first trimester and greater than
10 days in the second trimester. Ultrasonography may be
1083
considered to confirm menstrual dates if there is a gestational age agreement within 1 week by crownrump measurements obtained in the first trimester or within 10 days
by an average of multiple fetal biometric measurements
obtained in the second trimester (up to 20 weeks of gestation). Reassigning gestational age in the third trimester
should be done with caution because the accur-acy of
ultrasonography is within 34 weeks. Before 6 weeks of
gestation, dating can be done by measurement of the gestational sac, which is visible as early as 4 weeks of gestation and certainly by the fifth week of gestation. The mean
sac diameter, which is the average of three measurements
of the gestational sac, can accurately estimate gestational
age (mean sac diameter [mm] + 30 = gestational age
[days]) (26). Maximum embryo length at 610 weeks of
gestation and crownrump length, which represents the
maximum length of the fetus from the top of the head to
the rump region, are the most accurate at determining gestational age (27). When the crownrump length exceeds
60 mm, dating of pregnancy can be accomplished by other
biometric parameters, such as measurement of the biparietal diameter, head circumference, femur length, and
abdominal circumference. The head circumference is the
most predictive parameter of gestational age between
1422 weeks of gestation because it predicts gestational
age by 3.4 days (28). Combining various parameters
improves the prediction of gestational age slightly over the
use of head circumference measurement alone (28).
Formulas derived from singleton data can be used to
determine gestational age in twins and triplets (28). In the
third trimester, the best single measurement of gestational
age based on fetal biometry is the femur length. However,
reported accuracy of femur length ranges from 1 week in
the second trimester to 34 weeks at term (29, 30).
Guidelines for assignment of gestational age when a discrepancy exists between menstrual and ultrasound-established dates vary in different ultrasound units.
How is amniotic fluid volume evaluated

using ultrasonography?
Several techniques have been proposed for the estimation
of amniotic fluid during the ultrasound examination,
including a subjective assessment, single deepest pocket,
and amniotic fluid index (AFI). The technique of subjective assessment includes comparing the echo-free areas in
the uterus with the areas occupied by the fetus and placenta. This technique showed good intraobserver and
interobserver agreements among experienced examiners
(31) but does not allow for dissemination of criteria for use
by less experienced operators. Furthermore, this technique
does not allow for a longitudinal assessment of trends
in amniotic fluid estimation. The single deepest pocket
1084
technique involves finding the single largest pocket of

amniotic fluid on ultrasonography, free of cord and fetal
parts, and then measuring either the greatest vertical
dimension or the greatest vertical and horizontal dimensions with the ultrasound transducer perpendicular to the
floor. The AFI technique is based on the division of the
uterus into four quadrants and measuring the deepest vertical pocket of fluid in each quadrant and then adding the
four measurements together. Most ultrasonographers measure pockets of fluid that are free of cord and fetal parts.
The term oligohydramnios refers to decreased
amniotic fluid volume relative to gestational age.
Oligohy-dramnios is associated with genitourinary
abnormalities in the fetus, premature rupture of membranes, uteroplacental insufficiency, and postterm pregnancy. Oligohy-dramnios has been linked to increased
rates of perinatal morbidity and mortality (32).
Oligohydramnios is described in various ways. Two
acceptable definitions are 1) an AFI less than 5 cm or 2)
a maximum deepest vertical pocket of less than 2 cm. In
a randomized clinical trial, the use of amniotic fluid index
compared with single deepest pocket technique during
antepartum surveillance was associated with significantly
higher rates of suspected oligohydramnios, which led to
increased interventions without a demonstrable benefit
(33). Recent studies suggest that AFI is a weaker predictor of perinatal outcome than has been classically suggested (34).
The term polyhydramnios or hydramnios refers to
increased amniotic fluid volume relative to gestational
age. Hydramnios often is idiopathic but can be associated
with gestational and pregestational diabetes, isoimmunization, fetal structural and chromosomal abnormalities, fetal infections, multiple gestations with twintwin
transfusion syndrome, or fetalmaternal hemorrhage.
Idiopathic hydramnios, which represents 5060% of
cases of hydramnios, has been linked to fetal macrosomia and an increase in adverse pregnancy outcome (35).
Hydramnios commonly is described by an AFI greater
than or equal to 24 cm or a maximum deepest vertical
pocket of equal to or greater than 8 cm.
How may ultrasonography be used to detect

fetal chromosome abnormalities in the second
trimester?
A second-trimester specialized ultrasound examination,
often called a genetic ultrasound examination, may be
targeted to detect fetal aneuploidy. Individual secondtrimester ultrasound markers, such as echogenic bowel,
intracardiac echogenic focus, short femur or humerus, and
dilated renal pelvis, have a low sensitivity and specificity
for Down syndrome, particularly when used to screen a
low-risk population (36). Studies indicate that the highest

detection rate is achieved with a systematic combination
of markers and gross anomalies, such as thickened
nuchal fold or cardiac defects (37, 38). Studies done in
high-risk populations have reported detection rates of
approximately 5075% in the second trimester, albeit
with a high false-positive rate (39). If no abnormal ultrasound markers are identified after carefully performed
ultrasonography, the a priori risk of Down syndrome in a
patient at high risk may be reduced (40). This approach
has not been adequately studied in women at low risk.
With the current limitations of ultrasonography,
ultrasound evaluation is not recommended as a primary
screening modality for Down syndrome and other chromosomal abnormalities. A major limitation of the use of
second-trimester ultrasound markers has been the lack of
standardization in measurements and definitions of what
constitutes abnormal findings. Identification of an
echogenic intracardiac focus or echogenic bowel in a
fetus is based on a subjective assessment of the operator.
Furthermore, studies that defined the lower limits of fetal
long bone measurements for ultrasonography in screening for Down syndrome have primarily relied on a highrisk referral population. At this time, risk adjustment
based on second-trimester ultrasound markers should be
limited to individuals with expertise in this area.
How is ultrasonography used to detect

disturbances in fetal growth?
Ultrasonography is helpful in detecting fetal growth disturbances. Four standard fetal measurements generally
are obtained as part of any complete obstetric ultrasound
examination after the first trimester: 1) fetal abdominal
circumference, 2) head circumference, 3) biparietal
diameter, and 4) femur length (41). Fetal morphologic
parameters can be converted to fetal weight estimates
using published formulas and tables (42). Contemporary
ultrasound equipment calculates and displays an estimate of fetal weight on the basis of these formulas.
Although all of the published formulas for estimating
fetal weight show a good correlation with birth weight,
the variability of the estimate generally is plus or minus
1620% (2 standard deviations) (41). If the estimated
fetal weight is below the 10th percentile, further evaluation should be considered for intrauterine growth restriction (43). Similarly, if the estimated fetal weight is more
than 4,000 g or 4,500 g, evaluation should be considered
for fetal macrosomia (44).
Serial ultrasound measurements are of considerable
clinical value in confirming or excluding the diagnosis
and assessing the progression and severity of growth disturbances. Serial ultrasonography to determine the rate
PRACTICE BULLETINS
of growth should be obtained approximately every 24

weeks. Measurements at shorter intervals (less than 2
weeks) may overlap and cause interpretation errors.
Summary of
Recommendations and
Conclusions
The following conclusions are based on good and
consistent evidence (Level A):
Ultrasound examination is an accurate method of
determining gestational age, fetal number, viability,
and placental location.
Gestational age is most accurately determined in the
first half of pregnancy.
Ultrasonography can be used in the diagnosis of
many major fetal anomalies.
Ultrasonography is safe for the fetus when used
appropriately.

inconsistent evidence (Level B):
Ultrasonography is helpful in detecting fetal growth
disturbances.
Ultrasonography can detect abnormalities in amniotic fluid volume.
1085
2. Abuhamad AZ, Benacerraf BR, Woletz P, Burke BL. The

accreditation of ultrasound practices: impact on compliance with minimum performance guidelines. J Ultrasound Med 2004;23:10239. (Level II-3)
3. Abramowicz JS, Fowlkes JB, Skelly AC, Stratmeyer ME,
Ziskin MC. Conclusions regarding epidemiology for
obstetric ultrasound. J Ultrasound Med 2008;27:63744.
(Level III)
4. American Institute of Ultrasound in Medicine. Medical
ultrasound safety. Laurel (MD): AIUM; 1994; reapproved
2002. (Level III)
5. Stark CR, Orleans M, Haverkamp AD, Murphy J. Shortand long-term risks after exposure to diagnostic ultrasound in utero. Obstet Gynecol 1984;63:194200. (Level
II-2)
6. Lyons EA, Dyke C, Toms M, Cheang M. In utero exposure to diagnostic ultrasound: a 6-year follow-up.
Radiology 1988;166:68790. (Level II-2)
7. American Institute of Ultrasound in Medicine. Prudent
Use. Laurel (MD): AIUM; 1999; reapproved 2005. (Level
III)
8. Rados C. FDA cautions against ultrasound keepsake
images. FDA Consum 2004;38:126. (Level III)
9. American Institute of Ultrasound in Medicine. Guidelines for cleaning and preparing endocavitary ultrasound
transducers between patients. Laurel (MD): AIUM; 2000.
(Level III)
10. Centers for Disease Control and Prevention. Sterilization
or disinfection of medical devices. Atlanta (GA): CDC;
2002. Available at: http://www.cdc.gov/ncidod/dhqp/
bp_sterilization_medDevices.html. Retrieved June 9,
2008. (Level III)
The following conclusion and recommendation

11. Food and Drug Administration (US). FDA-cleared sterilants and high level disinfectants with general claims for
processing reusable medical and dental devices September 28, 2006. Rockville (MD): FDA; 2006.
Available at: http://www.fda.gov/cdrh/ode/germlab.html.
Retrieved June 9, 2008. (Level III)
The optimal timing for a single ultrasound examination in the absence of specific indications for a firsttrimester examination is at 1820 weeks of gestation.
12. Long G, Sprigg A. A comparative study of routine versus

selective fetal anomaly ultrasound scanning. J Med Screen
1998;5:610. (Level III)
The benefits and limitations of ultrasonography

should be discussed with all patients.
RP, McNellis D. Effect of prenatal ultrasound screening
on perinatal outcome. RADIUS Study Group. N Engl J
Med 1993;329:8217. (Level I)
Measure
14. Saari-Kemppainen A, Karjalainen O, Ylostalo P,

Heinonen OP. Fetal anomalies in a controlled one-stage
ultrasound screening trial. A report from the Helsinki
Ultrasound Trial. J Perinat Med 1994;22:27989. (Level I)
Documentation of the discussion of the benefits and limitations of ultrasonography
15. Grandjean H, Larroque D, Levi S. The performance of

routine ultrasonographic screening of pregnancies in the
Eurofetus Study. Am J Obstet Gynecol 1999;181:44654.
(Level II-2)
References
16. Levi S. Ultrasound in prenatal diagnosis: polemics around

routine ultrasound screening for second trimester fetal
malformations. Prenat Diagn 2002;22:28595. (Level III)
1. Goncalves LF, Lee W, Espinoza J, Romero R. Three- and

4-dimensional ultrasound in obstetric practice: does it
help? J Ultrasound Med 2005;24:1599624. (Level III)
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17. Crane JP, LeFevre ML, Winborn RC, Evans JK, Ewigman
BG, Bain RP, et al. A randomized trial of prenatal ultrasonographic screening: impact on the detection, management, and outcome of anomalous fetuses. The RADIUS
Study Group. Am J Obstet Gynecol 1994;171:3929.
(Level I)
and maternal height on fetal femur length calculations.

31. Goldstein RB, Filly RA. Sonographic estimation of amniotic fluid volume. Subjective assessment versus pocket
measurements. J Ultrasound Med 1988;7:3639. (Level
III)
18. Grandjean H, Larroque D, Levi S. Sensitivity of routine

ultrasound screening of pregnancies in the Eurofetus database. The Eurofetus Team. Ann N Y Acad Sci 1998;
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32. Baron C, Morgan MA, Garite TJ. The impact of amniotic

fluid volume assessed intrapartum on perinatal outcome.
19. Eik-Nes SH, Salvesen KA, Okland O, Vatten LJ. Routine

ultrasound fetal examination in pregnancy: the Alesund
randomized controlled trial. Ultrasound Obstet Gynecol
2000;15:4738. (Level I)
33. Chauhan SP, Doherty DD, Magann EF, Cahanding F,

Moreno F, Klausen JH. Amniotic fluid index vs single
deepest pocket technique during modified biophysical
profile: a randomized clinical trial. Am J Obstet Gynecol
2004;191:6617; discussion 6678. (Level I)
20. Woolf SH. The accuracy and effectiveness of routine population screening with mammography, prostate-specific
antigen, and prenatal ultrasound: a review of published
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Invasive Prenatal Testing for Aneuploidy. ACOG Practice
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22. Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock
CH, Bukowski R, et al. First-trimester or second-trimester
screening, or both, for Downs syndrome. First- and
Second-Trimester Evaluation of Risk (FASTER)
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(Level II-1)
23. Spong CY. Prediction and prevention of recurrent spontaneous preterm birth. Obstet Gynecol 2007;110:40515.
(Level III)
34. Ott WJ. Reevaluation of the relationship between amniotic fluid volume and perinatal outcome. Am J Obstet
Gynecol 2005;192:18039; discussion 1809. (Level II-2)
35. Magann EF, Chauhan SP, Doherty DA, Lutgendorf MA,
Magann MI, Morrison JC. A review of idiopathic
hydramnios and pregnancy outcomes. Obstet Gynecol
Surv 2007;62:795802. (Level III)
36. Smith-Bindman R, Hosmer W, Feldstein VA, Deeks JJ,
Goldberg JD. Second-trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis. JAMA
2001;285:104455. (Level III)
37. Vintzileos AM, Campbell WA, Rodis JF, Guzman ER,
Smulian JC, Knuppel RA. The use of second-trimester
genetic sonogram in guiding clinical management of
patients at increased risk for fetal trisomy 21. Obstet
24. Iams JD, Goldenberg RL, Mercer BM, Moawad AH, Meis
PJ, Das AF, et al. The preterm prediction study: can lowrisk women destined for spontaneous preterm birth be
identified? National Institute of Child Health and Human
Development Maternal-Fetal Medicine Units Network.
38. Bromley B, Benacerraf BR. The genetic sonogram scoring index. Semin Perinatol 2003;27:1249. (Level III)
25. Conoscenti G, Meir YJ, DOttavio G, Rustico MA,

Pinzano R, Fischer-Tamaro L, et al. Does cervical length
at 13-15 weeks gestation predict preterm delivery in an
unselected population? Ultrasound Obstet Gynecol
2003;21:12834. (Level II-2)
40. Yeo L, Vintzileos AM. The use of genetic sonography to

reduce the need for amniocentesis in women at high-risk
for Down syndrome. Semin Perinatol 2003;27:1529.
(Level III)
39. Bahado-Singh RO, Oz UA, Mendilcioglu I, Mahoney MJ.

The mid-trimester genetic sonogram. Semin Perinatol
2005;29:20914. (Level III)
26. Nyberg DA, Mack LA, Laing FC, Patten RM. Distinguishing normal from abnormal gestational sac growth in early
pregnancy. J Ultrasound Med 1987;6:237. (Level II-3)
41. Hadlock FP, Deter RL, Harrist RB, Park SK. Estimating
fetal age: computer-assisted analysis of multiple fetal
growth parameters. Radiology 1984;152:497501. (Level
II-3)
27. Wisser J, Dirschedl P, Krone S. Estimation of gestational

age by transvaginal sonographic measurement of greatest
embryonic length in dated human embryos. Ultrasound

Hobbins JC. An evaluation of two equations for predicting fetal weight by ultrasound. Am J Obstet Gynecol
1982; 142:4754. (Level III)
28. Chervenak FA, Skupski DW, Romero R, Myers MK,

Smith-Levitin M, Rosenwaks Z, et al. How accurate is
fetal biometry in the assessment of fetal age? Am J Obstet
Gynecol 1998;178:67887. (Level II-3)

Intrauterine Growth Restriction. ACOG Practice Bulletin
12. Washington, DC: ACOG; 2000. (Level III)
29. Stebbins B, Jaffe R. Fetal biometry and gestational age

estimation. In: Jaffe R, Bui TH, editors. Textbook of fetal
ultrasound. New York (NY): Parthenon Publishing; 1999.
30. Pierce BT, Hancock EG, Kovac CM, Napolitano PG,
Hume RF Jr, Calhoun BC. Influence of gestational age

Fetal macrosomia. ACOG Practice Bulletin 22.
Washington, DC: ACOG; 2000. (Level III)
PRACTICE BULLETINS

Task Force:
I

type of evidence.
committees.
1087
Copyright February 2009 by the American College of

Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Ultrasonography in pregnancy. ACOG Practice Bulletin No. 101.
Gynecol 2009;113:451 61.
1088
ACOG
PRACTICE
BULLETIN
(Replaces Committee Opinion Number 383, October 2007)
Management of Stillbirth
the assistance of Ruth C. Fretts,
practice.

OBSTETRICIANS AND
GYNECOLOGISTS
Stillbirth is one of the most common adverse pregnancy outcomes, complicating 1 in 160 deliveries in the United States. Approximately 25,000 stillbirths
at 20 weeks or greater of gestation are reported annually (1). The purpose
of this bulletin is to review the current information on stillbirth, including
definitions and management, the evaluation of a stillbirth, and strategies for
prevention.
Background
Definition
The United States National Center for Health Statistics defines fetal death as
the delivery of a fetus showing no signs of life as indicated by the absence of
breathing, heart beats, pulsation of the umbilical cord, or definite movements of
voluntary muscles (2). There is not complete uniformity among states with
regard to birth weight and gestational age criteria for reporting fetal deaths.
However, the suggested requirement is to report fetal deaths at 20 weeks or
greater of gestation (if the gestational age is known), or a weight greater than
or equal to 350 grams if the gestational age is not known (3). The cutoff of 350
grams is the 50th percentile for weight at 20 weeks of gestation.
The term stillbirth is preferred among parent groups, and more recent
research efforts have begun using this term in place of fetal death. Therefore, in
this document, the term stillbirth is used. It must be emphasized that the criteria for stillbirth do not imply a point of viability and were chosen to facilitate
uniform data collection.
In the United States, fetal losses related to terminations of pregnancy for
lethal fetal anomalies and inductions of labor for previable premature rupture
of membranes are specifically excluded from the stillbirth statistics and are
classified as terminations of pregnancy.
PRACTICE BULLETINS
Frequency of Occurrence
In 2004, the stillbirth rate in the United States was 6.2
per 1,000 births, down from 6.4 per 1,000 births in 2002
(1). Since 1990, the rate of early stillbirth (2027 weeks)
has remained stable at approximately 3.2 per 1,000
births, while the rate of late stillbirth (28 weeks or
greater) has decreased from 4.3 to 3.1 per 1,000 births.
Risk Factors
In developed countries, the most prevalent risk factors
associated with stillbirth are non-Hispanic black race,
nulliparity, advanced maternal age, and obesity (see
Table 1 for additional risk factors). From a public health
perspective, obesity, smoking, and drug and alcohol use
are common potentially modifiable risk factors for
adverse pregnancy outcome.
1089
pregestational diabetes (7, 8). However, with preconception care and optimal glycemic control, the risk of
perinatal death may be reduced (9, 10). Patients with a
personal history or family history of thromboembolism
or multiple inherited or acquired thrombophilias appear
to have an increased risk of stillbirth, but there is no evidence that screening an unselected population is either
clinically effective or cost-effective (11). Other reported
medical risk factors for stillbirth in the United States are
described in Table 2.
Obesity
In the United States, Hispanic, Asian, and Native American

women, and non-Hispanic white women all have stillbirth
rates of less than 6 per 1,000. In contrast, stillbirth rates
have been consistently and significantly higher in nonHispanic black women at a rate of 11.25 per 1,000 (1). The
reason for this health care disparity is multifactorial and
the subject of ongoing research. Higher rates of stillbirth
persist among non-Hispanic black women with adequate
prenatal care; this has been attributed to higher rates of diabetes mellitus, hypertension, placental abruption, and premature rupture of membranes (4, 5).
Obesity is defined as a prepregnancy body mass index

(BMI) (defined as weight in kilograms divided by height
in meters squared) of 30 or greater and is the fastest
growing health problem in the United States (12).
Obesity in pregnancy is associated with an increased risk
of both early fetal loss and stillbirth (13). In a national
database, the risk of stillbirth was 5.5/1,000 for nonobese
mothers, 8/1,000 for those with a BMI of 3039.9 and
11/1,000 for women with a BMI greater than 40.0 (14).
There is some evidence that the obesity-related stillbirth
risk increases with gestational age. In one study, the hazard ratio for stillbirth increased from 2.1 at 2836 weeks
to 4.6 at 40 weeks of gestation (15). The reason for this
association is likely multifactorial, but obesity is associated with a fivefold increase in stillbirth associated with
placental dysfunction. Obesity remains an independent
risk factor for stillbirth even after controlling for smoking, gestational diabetes, and preeclampsia. (1618).
Comorbidities
Multiple Gestations
Hypertension and diabetes are two of the most common

medical comorbid pregnancy conditions (6). Populationbased studies demonstrated a twofold to fivefold
increase in the risk of stillbirth among women with
The stillbirth rate among multiple gestations is four times

higher than among singletons (19.6 per 1,000) (19). Higher
rates are due both to complications specific to multiple gestation (such as twintwin transfusion syndrome), as well as
Racial Factors
Table 1. Commonly Reported Maternal Risk Factors and Causes for Stillbirth
Developed Countries
Developing Countries
Congenital and karyotypic anomalies
Obstructed and prolonged labor and associated asphyxia, infection,

and birth injury
Growth restriction and placental abnormalities
Infection especially syphilis and gram-negative infections
Medical diseases such as diabetes, systemic lupus erythematosus,

renal disease, thyroid disorders, and cholestasis of pregnancy
Hypertensive disease and complications of preeclampsia and eclampsia
Hypertensive disease and preeclampsia
Poor nutritional status
Infection such as human parvovirus B19, syphilis, streptococcal infection,

and listeria
Malaria
Smoking
Congenital anomalies
Sickle cell disease
Multiple gestation
Reproduced with permission by the International Federation of Gynecology and Obstetrics (FIGO) from: McClure EM, Nalubamba-Phiri M, Goldenberg RL. Stillbirth in
developing countries. Intl J Gynecol Obstet 2006;94(2):8290.
1090
Table 2. Estimates of Maternal Risk Factors and Risk of Stillbirth

Condition
Prevalence
All pregnancies
Estimated rate of stillbirth
OR*
6.4/1000
1.0
80%
4.05.5/1000
0.86
6%10%
625/1000
1.52.7
Mild
5.8%7.7%
951/1000
1.24.0
Severe
1.3%3.3%
1229/1000
1.84.4
Treated with diet
2.5%5%
610/1000
1.22.2
Treated with insulin
2.4%
635/1000
1.77.0
SLE
<1%
40150/1000
620
Renal disease
<1%
15200/1000
2.230
Thyroid disorders
0.2%2%
1220/1000
2.23.0
Thrombophilia
1%5%
1840/1000
2.85.0
Low-risk pregnancies
Hypertensive disorders
Chronic hypertension
Diabetes
Cholestasis of pregnancy
<0.1%
1230/1000
1.84.4
Smoking >10 cigarettes
10%20%
1015/1000
1.73.0
BMI 2529.9 kg/m2
21%
1215/1000
1.92.7
BMI >30
Obesity (prepregnancy)
20%
1318/1000
2.12.8
Low educational attainment (<12 y vs. 12 y+)
30%
1013/1000
1.62.0
Previous growth-restricted infant (<10%)
6.7%
1230/1000
24.6
Previous stillbirth
0.5%1.0%
920/1000
1.43.2
Twins
2.7%
12/1000
1.02.8
Triplets
0.14%
34/1000
2.83.7
3539 y
15%18%
1114/1000
1.82.2
40 y+
2%
1121/1000
1.83.3
15%
1214/1000
2.02.2
Multiple gestation
Advanced maternal age (reference <35 y)
Black women compared with white women
*OR of the factor present compared to the risk factor absent.

Reprinted from Am J Obstet Gynecol, 193, Fretts R, Etiology and prevention of stillbirth, 192335, 2005, with permission from Elsevier.
to increased risks of common complications such as

advanced maternal age, fetal abnormalities, and growth
restriction.
Maternal Age Older Than 35 years

Older maternal age is associated with an increased risk of
stillbirth in both nulliparous and multiparous women (9,
20). A significant proportion of perinatal deaths seen in
older women are related to lethal congenital and chromosomal anomalies. The introduction of population-based
screening for chromosomal abnormalities has contributed
to lower rates of this type of perinatal demise (21). Largescale studies suggest that an increased risk of unexplained
stillbirth late in pregnancy persists in older women, even
after controlling for risk factors such as hypertension, diabetes, placenta previa, and multiple gestation (20, 22, 23).
In addition, there appears to be an interaction between first
birth and advanced maternal age that places primiparous
older women at an increased risk (20). Based on one study,
the estimated risk of stillbirth is 1 in 116 in a 40-year-old
nulliparous woman after 37 weeks of gestation, compared
with 1 in 304 in a multiparous woman of the same age (20).
PRACTICE BULLETINS
Past Obstetric History

Women with previous pregnancy complications, such as
preterm delivery, growth restriction, or preeclampsia, are
at increased risk of stillbirth in subsequent pregnancies
(24). The relationship is strongest for explained stillbirth
and there also is a persistent 1.7-fold to 2-fold increase in
unexplained stillbirth associated with these pregnancy
complications. In addition, the risk of subsequent still
birth is twice as high for women with a prior live born,
growth restricted infant delivered before 32 weeks of gestation than for women with a prior stillbirth (25). The relationship between prior cesarean delivery and subsequent
stillbirth remains controversial. This association has not
been confirmed in three large studies from the United
States (2628). In the largest of these studies, the unexplained fetal death rates at term for women with and without a previous cesarean delivery were 0.8 and 0.7 per 1,000
births, respectively (27). In contrast, in two large studies
from the United Kingdom, previous cesarean delivery was
associated with an increased rate of explained (29) and
unexplained stillbirth (24) with an increased odds ratio of
1.5 for all causes of subsequent stillbirth.
Potential Causes of Stillbirth

The study of specific causes of stillbirth has been hampered by the lack of uniform protocols for evaluating and
classifying stillbirths and by decreasing autopsy rates. In
most cases, fetal death certificates are filled out before a
full postnatal investigation, and amended death certificates are rarely filed when additional information from
the stillbirth evaluation emerges. In any specific case, it
may be difficult to assign a definite cause to a stillbirth.
A significant proportion of stillbirths remain unexplained even after a thorough evaluation (22, 23).
Fetal Growth Restriction

Fetal growth restriction is associated with a significant
increase in the risk of stillbirth with the most severely
affected fetuses (weight less than the 2.5th percentile)
being at the greatest risk (30). The cumulative risk of
fetal death is approximately 1.5% at fetal weights less
than the 10th percentile, increasing to a risk of 2.5% at
less than the 5th percentile for gestational age (31, 32).
Fetal growth restriction is associated with some fetal
aneuplodies, fetal infection, maternal smoking, hypertension, autoimmune disease, obesity, and diabetes.
Placental Abruption
Placental abruption is another common cause of stillbirth. If abruption occurs in the preterm fetus, it is more
likely to cause stillbirth. The rates of abruption appear to
be increasing (33). Maternal cocaine and other illicit
1091
drug use, smoking, hypertension, and preeclampsia are

all significant contributors to abruption and stillbirth
(3437). Fetomaternal hemorrhage in the absence of placental abruption is a rare cause of stillbirth and occurs
mainly in unusual scenarios, such as chorioangioma or
choriocarcinoma.
Chromosomal and Genetic

Abnormalities
An abnormal karyotype can be found in approximately
813% of stillbirths (3840). The rate of karyotypic abnormalities exceeds 20% in fetuses with anatomic abnormalities or in those with growth restriction, but the rate of
chromosomal anomalies found in normally formed fetuses
was found to be 4.6% in one large series (40). If an abnormal karyotype is found in association with stillbirth, the
most common abnormalities are monosomy X (23%), trisomy 21 (23%), trisomy 18 (21%), and trisomy 13 (8%).
Confined placental mosaicism also has been associated
with an increased risk of stillbirth, but currently is not part
of standard testing (41). Karyotypic analysis underestimates the contribution of genetic abnormalities to stillbirth
because in up to 50% of karyotype attempts cell culture is
unsuccesful (39). One strategy to increase the yield of cell
culture is to perform an amniocentesis before the delivery.
This is typically performed after the woman has had an
opportunity to process the death of her baby and after an
epidural is placed. In a large Dutch study, invasive testing
had a much greater tissue culture rate (85%) than fetal tissue sampling after birth (28%) (40). In addition, routine
assessments for single gene defects and microdeletions currently are not recommended because of uncertainty of the
role of these genetic anomalies. However, it is likely that no
single-gene defect is likely to be responsible for a significant proportion of stillbirth. Genetic evaluation for specific
abnormalities should be guided by the clinical history and
detected fetal abnormalities. Approximately 20% of stillborn fetuses have dysmorphic features or skeletal abnormalities and 1520% have a major malformation (38, 42).
Infection
In developed countries, most stillbirths related to infection occur in the premature fetus. It has been estimated
that infection is implicated in up to 19% of stillbirths at
less than 28 weeks of gestation, but only 2% of stillbirths
at term (43). There is considerable variation in the
reported proportion of stillbirths related to infection due
in part to differences in classification methods.
Pathogens that are causally associated with stillbirth,
include parvovirus, cytomegalovirus, Listeria monocytogenes, and syphilis. In the developing world, malaria is a
significant preventable cause of stillbirth.
1092
Cord Events
Although many stillbirths are attributed to a cord accident, this diagnosis should be made with caution. Cord
abnormalities, including a nuchal cord, are found in
approximately 30% of normal births and may be an incidental finding (44). In order to attribute a stillbirth to a
cord accident there should be evidence of obstruction or
circulatory compromise on umbilical cord examination.
In addition, other causes of stillbirth should be excluded.
Management
Sensitivity is needed when discussing evaluation of a stillborn fetus with the family. In discussing options, clinicians
should refer to the fetus by name, if one was given. Griefstricken parents may be reluctant to consent to evaluation or
autopsy examination, and some may have religious or cultural objections. Parents should be informed about the reasons for autopsy, procedures (eg, the face usually is not
disfigured) and potential costs. Even though the bereaved
parents may not want the information initially, health care
providers should emphasize that results of the evaluation
may be useful to the patient and her family in planning
future pregnancies. If the family objects to a standard autopsy, they should be informed of the potential value of less
invasive methods of evaluation, including the use of photographs, X-ray imaging, ultrasonography, magnetic resonance imaging, and tissue sampling (blood or skin). These
methods may help to identify a syndrome or chromosomal
abnormality even without full autopsy data. Syndrome
identification may delineate etiologic and pathogenetic factors that could have predictive significance for recurrence
risk and the risk of other associated anomalies (45).
After a stillbirth or neonatal death, proper management includes obtaining a complete perinatal and family
history, performing a physical examination of the fetus
(with documentation by description and photography, if
possible), and obtaining laboratory studies (see Fig. 1). To
ascertain the etiology and provide appropriate counseling
to the family, clinicalpathologic correlation is best accomplished by a team comprising obstetricians, pediatricians
or neonatologists, pathologists, and geneticists. Initial evaluation by a geneticist or pathologist may help the team
coordinate the evaluation and the needed follow-up.
Clinical Considerations
What are the essential components of an
evaluation of a fetal death?
The most important tests in the evaluation of a stillbirth
are fetal autopsy; examination of the placenta, cord, and
membranes; and karyotype evaluation. An algorithm for
Inspect fetus and placenta:

Weight, head circumference, and length of fetus
Weight of placenta
Photographs of fetus and placenta
Frontal and profile photographs of whole body, face, extremities, palms, and any abnormalities
Document finding and abnormalities
Obtain consent from parents for cytologic specimens:

Obtain cytologic specimens with sterile techniques and
instruments
Acceptable cytologic specimens (at least one)
Amniotic fluid obtained by amniocentesis at time of
prenatal diagnosis of demise: particularly valuable if
delivery is not expected imminently
Placental block (1 1) cm taken from below the cord
insertion site on the unfixed placenta
Umbilical cord segment (1.5 cm)
Internal fetal tissue specimen, such as costochondral
junction or patella; skin is not recommended
Place specimens in a sterile tissue culture medium of lactated
Ringers solution and keep at room temperature when transported to cytology laboratory
Obtain parental consent for fetal autopsy
Fetal autopsy and placental

pathology (may include
fetal whole-body X-ray)
If no consent is given for

autopsy, send placenta
alone for pathology
Figure. 1. Flow chart for fetal and placental evaluation
evaluation is given in Figure 1. Specific aspects of the

evaluation are outlined as follows and in Table 3.
Examination of the Stillborn Fetus

The general examination of the stillborn fetus should be
done promptly, noting any dysmorphic features and
obtaining measurements of weight, length, and head circumference (4648). Foot length may be especially useful
before 23 weeks of gestation to ascertain gestational age.
Photographs of the whole body (unclothed); frontal and
profile views of the face, extremities, and palms; and
close-up photographs of specific abnormalities are vital
for subsequent review and consultation with a specialist,
particularly if no geneticist is available at the institution.
Even if parents have declined an autopsy, a description of
any obvious abnormalities of the stillborn fetus should be
PRACTICE BULLETINS
1093
Table 3. Alternatives to a Complete Autopsy

Examination
Placental examination and external examination by a perinatal
pathologist (generally includes measurements of the baby, X-rays,
and photographs)
Strengths and Limitations

Will be more likely to identify syndromes, congenital abnormality, and
timing of death as well as growth abnormalities. Will be able to
detect placental and cord infections
Will miss fetal infections and internal congenital and CNS anomalies
Placental examination and external examination by a perinatal

pathologist, and selected biopsies (this generally includes measurements
of the baby, X-rays, and photographs)
Same as above but will be more likely to identify fetal infections
Gross and microscopic placental examination and external and internal

examination of the fetus by a perinatal pathologist, organs are left with
the body, and the brain is not examined (this generally includes
measurements of the baby, X-rays, and photographs)
Allows the baby to be returned to the family with all of the organs.
Will miss central nervous system pathology, but will detect internal
congenital abnormalities and be able to assess the role of infection
Head sparing autopsy
Benefits of full autopsy, may miss some CNS pathology
MRI (plus or minus directed needle biopsy)
May be very useful when the family requires burial intact in a timely
manner. MRI is good in the identification of CNS pathology, but other
abnormalities such as cardiac abnormalities are more likely to be
missed. Infections will not be diagnosed unless additional needle
biopsies are considered. This strategy has not been compared with
traditional autopsy
Ultrasound
Best done while in utero, but can be done after birth. The head, kidney,
or abdomen can be evaluated, but only static images of the heart can
be seen. Not as good as MRI for the brain, but may be able to provide
some useful information if a previous fetal radiologic survey was not
performed. Limited by the degree of maceration, and does not assess
role of infection in the fetal death
Abbreviations: CNS, central nervous system; MRI, magnetic resonance imaging
included in the medical record. Measurements may be

accomplished by the obstetrician, pathologist, or other
specialist, such as a neonatologist, depending on the institutional protocol.
Autopsy as well as examination of the placenta should
be offered. This is especially true when dysmorphic features, inconsistent growth measurements, anomalies,
hydrops, or growth restriction are present. Parents should
be given the opportunity to hold the baby and perform cultural or religious activities, such as baptism, before the
autopsy. Whole-body X-ray with anteriorposterior and
lateral views may reveal an unrecognized skeletal abnormality or further define a grossly apparent deformity.
When a full autopsy is performed, it should follow
published guidelines for perinatal autopsy (49, 50). The
pathologist should be aware of the clinical history and
suspected genetic diagnoses, as well as any necessary tissue collection that needs to be performed for additional
analyses.
Examination of the Placenta

Gross and microscopic examination of the placenta is an
essential component of the evaluation of any stillbirth
and should include an examination of the membranes
and umbilical cord that may corroborate autopsy find-
ings. Even if the family declines fetal autopsy, histologic study of the placenta usually is acceptable and can be
valuable in identifying underlying etiologies (51, 52).
Fetal Laboratory Studies

Karyotypic analyses are of sufficient yield that it should
be performed in all cases of stillbirth after appropriate
parental permission is obtained (40). If chromosomal
culture is not successful, in situ hybridization can be
used to detect common chromosomal abnormalities.
Chromosomal information is particularly valuable if the
fetus displays dysmorphic features, inconsistent growth
measurements, anomalies, hydrops, or growth restriction. Fetal karyotype also is important if a parent carries
a balanced chromosomal rearrangement (eg, translocation or inversion) or has a mosaic karyotype. Samples of
amniotic fluid, umbilical cord, fetal tissue, or placenta
may be obtained for chromosomal and any other relevant
tests. Amniocentesis for fetal karyotyping has the highest yield and is particularly valuable if delivery is not
expected imminently (40).
After delivery, the most viable tissue generally is the
placenta or segment of umbilical cord closest to the placenta, followed by fetal cartilage obtained from the costochondral junction or patella (see Fig. 1) (5355).
1094
Appropriate history and physical findings should be sent

to the laboratory for the laboratory personnel to choose
any appropriate cytogenetic tests.
The Wisconsin Stillbirth Service program estimated
that the real cost of a stillbirth assessment was approximately $1,450 in 2001 (56). The most significant information gained was a change in the estimated risk of
recurrent stillbirth (42% of cases). Other consequences
were a change in the recommendations for subsequent
pregnancies with respect to prenatal diagnosis (in 22%)
and preconception management (in 1%).
Maternal Evaluation
A thorough maternal history should be taken looking
for known conditions or symptoms suggestive of those
that have been associated with stillbirth (Table 4). In
addition to obstetric history, including exposures
(eg, medications and viral infections), a family history
with a three-generation pedigree, if possible, should be
reviewed. Any pertinent information in the maternal or
paternal pedigree should be documented and investigated further. Relevant original medical records and documentation should be obtained whenever possible. The
gestational age by last menstrual period, maternal examinations, laboratory data, and ultrasound examination
should be recorded for correlation with the physical
examination of the neonate. Possible nongenetic causes,
such as infection, placental abruption, and umbilical
cord abnormality also should be considered.
Investigation for fetalmaternal hemorrhage should be
conducted shortly after the diagnosis of the demise (57).
Maternal testing for lupus anticoagulant, anticardiolipin
antibodies, human parvovirus B19 immunoglobulin G and
immunoglobulin M antibodies and thyroid stimulating
hormone may provide information that could affect future
pregnancy management (5860). In cases with severe
placental pathology, significant growth restriction, or in
the setting of a family or personal history of thrombosis,
factor V Leiden mutation, prothrombin mutation,
antithrombin III level, MTHFR gene mutation, protein C
activity, and protein S activity may provide information
that could affect future pregnancy management (5860).
However, routine testing for thrombophilias is controvesial and may lead to unnecessary interventions.
What are the options for management of the

current pregnancy after confirmation of a
diagnosis of fetal death?
Methods of Delivery
The method and timing of delivery after a fetal death
depends on the gestational age at which the death occur-
red, on the maternal history of a previous uterine scar, and

maternal preference. Although most patients will desire
prompt delivery, the timing of delivery is not critical;
coagulopathies are associated with prolonged fetal retention and are uncommon. In the second trimester, dilation
and evacuation can be offered if an experienced provider
is available, although patients should be counseled that
dilation and evacuation may limit efficacy of autopsy for
the detection of macroscopic fetal abnormalities.
Labor induction is appropriate at later gestational
ages, if second trimester dilation and evacuation is
unavailable, or based on patient preference. Much of the
data for management of fetal demise has been extrapolated fromrandomized trials of management of second
trimester pregnancy termination. Before 28 weeks of
gestation, vaginal misoprostol appears to be the most
efficient method of induction, regardless of cervical
Bishop score (61, 62), although high-dose oxytocin infusion also is an acceptable choice (63, 64). Typical
dosages for misoprostol use are 200400 mcg vaginally
every 412 hours. After 28 weeks of gestation, induction
of labor should be managed according to usual obstetric
protocols. Cesarean delivery for fetal demise should be
reserved for unusual circumstances because it is associated with potential maternal morbid-ity without any fetal
benefit.
Several studies have evaluated the use of misoprostol at a dosage of 400 mcg every 6 hours in women with
a stillbirth between 24 and 28 weeks of gestation and a
prior uterine scar (65, 66). Available evidence from randomized trials supports the use of vaginal misoprostol as
a medical treatment to terminate nonviable pregnancies
before 24 weeks of gestation (67). Further research is
required to assess effectiveness and safety, optimal route
of administration, and dose.
In patients after 28 weeks of gestation, cervical
ripening with a transcervical Foley catheter has been
associated with uterine rupture rates comparable to spontaneous labor (68) and this may be a helpful adjunct in
patients with an unfavorable cervical examination.
Therefore, based on limited data in patients with a prior
low transverse cesarean delivery, trial of labor remains a
favorable option. There are limited data to guide clinical
practice in a patient with a prior classical cesarean delivery, and the delivery plan should be individualized.
What support services and clinical counseling

should be offered to the patient with a fetal
death?
Patient support should include emotional support and
clear communication of test results. Referral to a bereavement counselor, religious leader, peer support group, or
PRACTICE BULLETINS
1095
Table 4. Elements of the Stillbirth Evaluation

Key Components
Patient history
Details
Comments
Family history
Recurrent spontaneous abortions
Venous thromboembolism or pulmonary embolism
Congenital anomaly or abnormal karyotype
Hereditary condition or syndrome
Developmental delay
Consanguinity
Maternal history
Prior venous thromboembolism or pulmonary embolism
Diabetes mellitus
Chronic hypertension
Thrombophilia
Autoimmune disease
Epilepsy
Severe anemia
Heart disease
Tobacco, alcohol, drug or medication abuse
Obstetric history
Recurrent miscarriages
Previous child with anomaly, hereditary condition, or
growth restriction
Previous gestational hypertension or preeclampsia
Previous gestational diabetes mellitus
Previous placental abruption
Previous fetal demise
Current pregnancy
Maternal age
Gestational age at fetal death
Medical conditions complicating pregnancy
Hypertension
Gestational diabetes mellitus
Cholestasis
Pregnancy weight gain and body mass index
Complications of multifetal gestation, such as
twintwin transfusion syndrome, twin reversed
arterial perfusion syndrome, and discordant growth
Placental abruption
Abdominal trauma
Preterm labor or rupture of membranes
Gestational age at onset of prenatal care
Abnormalities seen on an ultrasound image
Infections or chorioamnionitis
(continued)
1096
Table 4. Elements of the Stillbirth Evaluation (continued)

Key Components
Details
Comments
Fetal autopsy
If patient declines, external evaluation by a trained

perinatal pathologist. Other options include photographs,
X-ray imaging, ultrasonography, magnetic resonance
imaging, and sampling of tissues, such as blood or skin.
Fetal karyotype
Amniocentesis before delivery provides the greatest

Abnormalities found approximately 8%
yield (84%). Umbilical cord proximal to placenta if
amniocentesis declined (30%). Fluorescence in situ
hybridization may be useful if fetal cells cannot be cultured.
Placental examination
Includes evaluation for signs of viral or bacterial infection.

Discuss available tests with pathologist.
Maternal evaluation at time

of demise
Complete blood count

Fetalmaternal hemorrhage screen: KleihauerBetke
test or comparable test for fetal cells in maternal
circulation
Human parvovirus B-19 immunoglobulin G and
immunoglobulin M antibody
Provides important information in approximately

30% of cases
Provides additional information in 30% of cases.

Infection is more common in preterm stillbirth
(19% versus 2% at term)
Routine testing for thrombophilias is controversial
and may lead to unnecessary interventions.
Consider in cases with severe placental pathology
and or growth restriction, or in the setting of a
personal or family history of thromboembolic
disease.
Syphilis
Lupus anticoagulant
Anticardiolipin antibodies
Thyroid-stimulating hormone
Thrombophilia (selected cases only)
Factor V Leiden
Prothrombin gene mutation
Antithrombin III
Fasting homocysteine
Postpartum
Protein S and protein C activity (selected cases)

Parental karyotype (if appropriate)
In selected cases
Unproven benefit
Developing technology
Indirect Coombs test
If not performed previously in pregnancy.
Glucose screening (oral glucose tolerance test,

hemoglobin A1C)
In the large for gestational age baby
Toxicology screen
In cases of placental abruption or when drug use is

suspected
Antinuclear antibody test
Many times is an incidental finding and may lead

to unnecessary interventions
Serology for toxoplasmosis, rubella, cytomegalovirus,

herpes simplex virus
Rarely helpful, infection causing death is made by

history and examining the baby, placenta,
and cord
Comparative genomic hybridization

Testing for single-gene mutations
Testing for confined placental mosaicism and nucleic
acid-based testing for infection
The value of these has not yet been established
mental health professional may be advisable for management of grief and depression. Feelings of guilt or anger in
parents who have experienced a perinatal death are common and may be magnified when there is an abnormal
child or a genetic defect. However, some parents may
welcome discussion and find relief in autopsy results. The
results of the tests are important even when no specific

diagnosis is identified (69). The results of the autopsy,
placental examination, laboratory tests, and cytogenetic
studies should be communicated to the involved clinicians and to the family of the deceased infant in a timely
manner. If there was no growth of the fetal chromosomes
PRACTICE BULLETINS
(or these were not obtained), further consultation with a

genetics or maternalfetal medicine subspecialist is
advised to discuss the need for parental chromosomal
testing. A copy of the results of the tests and a list of diagnoses excluded should be provided to the patients.
For the patient with a history of an unexplained fetal death in a previous pregnancy,
how should clinical management be altered
in subsequent pregnancies?
Recurrence Counseling
Counseling can be hampered by insufficient information
regarding the etiology of the prior stillbirth. In many
cases, the prior stillbirth may be unexplained despite a
thorough evaluation. In patients in whom complete evaluation for previous stillbirth was not done, evaluation
should be completed with parental permission. When
specific risks are identified, the risk of recurrence may be
quantifiable. In low-risk women with unexplained stillbirth, the risk of recurrence stillbirth after 20 weeks is
estimated at 7.810.5/1,000 with most of this risk occurring before 37 weeks of gestation. The risk of recurrent
stillbirth after 37 weeks is very low at 1.8/1,000. In comparison, women with a history of a live birth complicated
by preterm fetal growth restriction have a stillbirth rate
of 21.8/1,000 in a subsequent pregnancy (25). Rates of
recurrent fetal loss are higher in women with medical
complications such as diabetes or hypertension or in
those with obstetric problems with a significant recurrence risk, such as placental abruption. Despite reassurances, the patient is likely to be anxious and to require
ongoing support.
Antepartum Surveillance
There is little evidence-based data to guide the treating
clinician in the antepartum surveillance of a patient who
had a prior unexplained stillbirth. In patients with a history of stillbirth, antepartum testing may be initiated at
3234 weeks of gestation. However, this approach is associated with potential morbidity and cost: rates of delivery
for abnormal or equivocal testing were 16.3% at or before
39 weeks of gestation and 1% before 36 weeks of gestation. Similarly, the authors of one study estimate that antenatal testing before 37 weeks of gestation results in a 1.5%
rate of iatrogenic prematurity for intervention based on
false- positive test results (70). The excess risk of infant
mortality due to late preterm birth is 8.8/1,000 at 3233
weeks of gestation and 3/1,000 at 3436 weeks of gestation (71), and this must be considered in any strategy that
may lead to iatrogenic late preterm birth.
1097
Fetal Kick Counting

Multiple studies have demonstrated that women who
report decreased fetal movement are at increased risk for
adverse perinatal outcome (72). Although fetal kick
counting is an inexpensive test of fetal well being, the
effectiveness in preventing stillbirth is uncertain (73).
Timing of Delivery
The decision to proceed with early delivery to prevent
stillbirth must incorporate an understanding of the
increased risks of maternal and neonatal complications
compared with the potential benefits. Deliveries before
39 weeks of gestation are associated with an increased
risk of admission to neonatal special care units for respiratory complications and other neonatal morbidities.
Details of pregnancy for women with a prior stillbirth are
listed in the box.
Summary of
Recommendations and
Conclusions
are based on good and consistent scientific
evidence. (Level A)
In low-risk women with unexplained stillbirth the
risk of recurrence stillbirth after 20 weeks of gestation is estimated at 7.810.5/1,000 with most of this
risk occurring before 37 weeks of gestation.
The most prevalent risk factors associated with stillbirth are non-Hispanic black race, nulliparity,
advanced maternal age, and obesity (Table 1).
The risk of subsequent still birth is twice as high for
women with a prior live born, growth restricted
infant delivered before 32 weeks of gestation than
for women with a prior stillbirth.
Amniocentesis for fetal karyotyping has the highest
yield and is particularly valuable if delivery is not
expected imminently.

are based primarily on limited or inconsistent
scientific evidence (Level B):
In the second trimester, dilation and evacuation can
be offered. Labor induction also is appropriate at
later gestational ages, if second trimester dilation
and evacuation is unavailable, or based on patient
preference.
1098
Management of Subsequent Pregnancy

After Stillbirth
Preconception or initial prenatal visit
Detailed medical and obstetric history
Evaluation and workup of previous stillbirth
Determination of recurrence risk
Smoking cessation
Weight loss in obese women (preconception only)
Genetic counseling if family genetic condition exists
Diabetes screen
Thrombophilia workup: antiphospholipid antibodies
(only if specifically indicated)
Induction of labor with vaginal misoprostol is safe

and effective in patients with a prior cesarean delivery with a low transverse uterine scar before 28
weeks of gestation.

are based primarily on consensus and expert
opinion (Level C):
The most important tests in the evaluation of a stillbirth are fetal autopsy; examination of the placenta,
cord, and membranes; and karyotype evaluation.
Patient support should include emotional support
and clear communication of test results. Referral to
a bereavement counselor, religious leader, peer support group, or mental health professional may be
advisable for management of grief and depression.
Support and reassurance

First trimester
Dating ultrasonography
First-trimester screen: pregnancy-associated plasma
protein A, human chorionic gonadotropin, and nuchal
translucency*
Performance Measure
The percentage of stillbirths for which placental evaluation was performed and autopsy was offered
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40. Korteweg FJ, Bouman K, Erwich JJ, Timmer A, Veeger
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47. Stocker JT, Dehner LP, editors. Pediatric pathology. 2nd
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57. Biankin SA, Arbuckle SM, Graf NS. Autopsy findings in
a series of five cases of fetomaternal haemorrhages.
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58. Fretts RC. Etiology and prevention of stillbirth. Am J
59. Leduc L, Farine D, Armson BA, Brunner M, Crane J,
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61. Dickinson JE, Evans SF. The optimization of intravaginal
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Obstet Gynecol 2005;193:597]. Am J Obstet Gynecol
2002;186:470-4. (Level I)
62. Tang OS, Lau WN, Chan CC, Ho PC. A prospective randomised comparison of sublingual and vaginal misoprostol in second trimester termination of pregnancy. BJOG
2004;111:10015. (Level I)
63. Toaff R, Ayalon D, Gogol G. Clinical use of high concentration oxytocin drip. Obstet Gynecol 1971;37:11220.
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Washington, DC: Armed Forces Institute of Pathology;
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66. Daskalakis GJ, Mesogitis SA, Papantoniou NE,

Moulopoulos GG, Papapanagiotou AA, Antsaklis AJ.
Misoprostol for second trimester pregnancy termination
in women with prior caesarean section. BJOG 2005;
112:979. (Level II-2)
67. Neilson JP, Hickey M, Vazquez J. Medical treatment for
early fetal death (less than 24 weeks). Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.:
CD002253. DOI: 10.1002/14651858.CD002253.pub3.
(Level 1)
68. Bujold E, Blackwell SC, Gauthier RJ. Cervical ripening
with transcervical foley catheter and the risk of uterine
69. Rushton DI. Prognostic role of the perinatal postmortem.
Br J Hosp Med 1994;52:4504. (Level III)
70. Miller DA, Rabello YA, Paul RH. The modified biophysical profile: antepartum testing in the 1990s. Am J Obstet
71. Kramer MS, Demissie K, Yang H, Platt RW, Sauve R,
Liston R. The contribution of mild and moderate preterm
birth to infant mortality. Fetal and Infant Health Study
Group of the Canadian Perinatal Surveillance System.
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72. Froen JF. A kick from withinfetal movement counting
and the cancelled progress in antenatal care. J Perinat Med
2004;32:1324. (Level III)
73. Grant A, Elbourne D, Valentin L, Alexander S. Routine
formal fetal movement counting and risk of antepartum
late death in normally formed singletons. Lancet 1989;
2:3459. (Level I)
1101

Task Force:
I

type of evidence.
committees.
Copyright March 2009 by the American College of

Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Management of stillbirth. ACOG Practice Bulletin No. 102. American
113:74861.
1102
ACOG
PRACTICE
BULLETIN
Bariatric Surgery and

Pregnancy
the assistance of Michelle A.
Kominiarek, MD. The information

OBSTETRICIANS AND
GYNECOLOGISTS
As the rate of obesity increases, it is becoming more common for providers of

womens health care to encounter patients who are either contemplating or have
had operative procedures for weight loss, also known as bariatric surgery. The
counseling and management of patients who become pregnant after bariatric
surgery can be complex. Although pregnancy outcomes generally have been
favorable after bariatric surgery, nutritional and surgical complications can
occur and some of these complications can result in adverse perinatal outcomes.
The purpose of this Practice Bulletin is to provide a summary of the risks of
obesity in pregnancy, review the available literature regarding outcomes of pregnancy after bariatric surgery, and provide recommendations for the care of the
patient during her pregnancy and delivery after bariatric surgery.
Background
Incidence
Obesity is an epidemic in the United States66% of adults were either overweight or obese in 2004 (1). The prevalence of maternal obesity, defined as a
body mass index (BMI) of 30 or more in the United States has been reported
to range from 10% to 36% (26). BMI is calculated as weight in kilograms
divided by height in meters squared. The prevalence of adult obesity increased
dramatically (from 16% to 26%) in the past decade, with 30 states reporting
prevalences greater than 25% (7, 8). Furthermore, the prevalence of obesity in
reproductive-aged women (2039 years) was 29% in 2004, affecting a greater
proportion of Mexican American (36%) and non-Hispanic black (50%) women
(1). A prepregnancy BMI of more than 30 or a prepregnancy weight of more
than 200 lbs can be used to stratify risk during pregnancy (2, 9, 10). In a population-based study of obesity trends in the United States, there was a 70%
increase in prepregnancy obesity from 1994 to 2003 (11).
PRACTICE BULLETINS
Maternal Effects of Obesity on Pregnancy

Obesity is associated with reduced fertility primarily as a
result of oligo-ovulation and anovulation (12). Therefore,
obese women are less likely to respond to ovulation
induction, even with higher doses of gonadotropins (13,
14).
In pregnancy, additional risks occur in obese patients.
The increased risks for gestational diabetes, preeclampsia, cesarean delivery, and infectious morbidity associated
with obesity are well established (6, 1518). In addition,
operative morbidity increases as a result of difficulty in
establishment of and recovery from regional and general
anesthesia (19, 20), prolonged operating times, increased
blood loss (21), and thromboembolism (22). Obese
patients also are less likely to have a successful vaginal
birth after cesarean delivery (2326). Although obese
patients have a higher incidence of preterm birth for
maternal or fetal indications, they are less likely to have
spontaneous preterm labor (2729). Obese patients are
more likely to be admitted earlier in labor, need labor
induction, require more oxytocin, and have longer labor
(30).
Fetal and Neonatal Effects of Obesity

in Pregnancy
Maternal obesity can have effects on the fetus, including
increased risks of congenital anomalies, growth abnormalities, miscarriage, and stillbirth (3134). The most
common types of obesity-associated birth defects are
related to the neural tube, cardiac systems, and facial
clefting, even after controlling for diabetes (35, 36). In
addition, increased body mass impairs visualization of
ultrasound images and can compromise prenatal diagnosis of fetal anomalies, such as neural tube or cardiac
defects (37, 38). However, increased maternal BMI does
not appear to compromise fetal weight estimations (39).
Although some studies have reported an increase in
small for gestational age infants, most studies report an
increase in large for gestational age and macrosomic
infants among women who are obese during pregnancy
(40, 41). The risk for stillbirth is 2.14.3-fold greater in
obese compared with normal weight women (5, 42). The
pathophysiology behind the increased risk for birth
defects and stillbirth in this population is not known.
Maternal obesity also has been associated with an
increase in subsequent childhood obesity (43, 44).
1103
35 or more and other comorbidities. Bariatric surgery is

the most effective therapy available for morbid obesity
and results in improvement or complete resolution of
comorbidities and improved quality of life (45, 46).
Two primary approaches to bariatric surgery weight
loss are restrictive and a combination of restrictive and malabsorptive operations. The types of procedures commonly
performed today include the Roux-en-Y gastric bypass (a
combination of restrictive and malabsorptive effect) and
adjustable gastric banding (restrictive). The Roux-en-Y
gastric bypass creates a roux limb (or straight limb) connected to the gastric pouch and the Y portion is downstream as the enteroenterostomy. The proximal stomach
is separated from the remaining part of the stomach with
staples. In the banding procedure, a fluid-filled band is
placed around the stomach near the fundus, reducing functional stomach volume. Both techniques can be performed
by laparoscopy or laparotomy. Vertical banded gastroplasty (restrictive) and biliopancreatic diversion (malabsorptive) are now less commonly used, and jejunoileal
bypass (purely malabsorptive) is no longer performed.
The number of bariatric surgical procedures performed annually has dramatically increased from 12,480
in 1998 to 113,500 in 2005 (47). The majority of these
patients are female (more than 80%) and one half of the
bariatric procedures in 2004 were performed in reproductive-aged women with a mean age of 40 years (48,
49). Bariatric surgery also is being used increasingly to
treat adolescents with morbid obesity (50).
Effect of Surgery on Future Fertility

Rapid weight loss follows bariatric surgery, resulting in
improvement of conditions such as polycystic ovary syndrome, anovulation, and irregular menses, thus leading to
higher fertility rates (5154). However, bariatric surgery
should not be considered a treatment for infertility (55).
Several studies have discussed the potential for compromised absorption of oral contraceptives (OCPs) after
bariatric surgery (56, 57), given the number of unintended
pregnancies that occurred after the procedures. There
may be decreased absorption of OCPs as a result of the
anatomic and physiologic alterations from malabsorptive
surgery (58, 59). The effect of bariatric surgery on miscarriage rates is difficult to evaluate because of small
numbers in studies (51, 53, 54, 60).
Bariatric Surgery
Effect of Surgery on Maternal

Nonsurgical approaches to weight loss include behavioral

changes, diet, exercise, and pharmacotherapy. Bariatric
surgery, first performed in the 1960s, may be available to
patients with a BMI of 40 or more or those with a BMI of
Weight loss outside of pregnancy, whether achieved via

surgical or nonsurgical methods, has been shown to be
the most effective intervention to improve medical
comorbidities, especially diabetes and hypertension (45,
1104
46). However, in the studies of pregnancy after bariatric

surgery many patients are still obese, with a reported
prevalence as high as 80% in one series (6163). The possibility of continued obesity after surgery is important to
consider when interpreting studies about this population.
In a study comparing 298 women who had bariatric
surgery to the general obstetric population of 158,912
women, patients who had bariatric surgery were more
likely to have had a prior cesarean delivery (15.4% versus
10.5%, P=0.006), develop gestational diabetes (9.4% versus 5.0%, P<0.001), and give birth via cesarean delivery
(25.2% versus 12.2%, P<0.001) (64). In one study comparing pregnancies before and after a Roux-en-Y gastric
bypass, the rate of hypertension (including chronic and
gestational hypertension and preeclampsia) (45.6% versus 8.7%, P<0.001) was decreased after surgery (65).
Similarly, the occurrence of pregestational diabetes was
decreased (OR, 0.42; 95% CI, 0.260.67) after bariatric
surgery of several types (66). A systematic review of pregnancy after bariatric surgery also described decreased
rates of gestational diabetes and preeclampsia (67).
Average weight gain during pregnancy also was
decreased in several studies after bariatric surgery (62,
65, 6871). Although preterm premature rupture of membranes was increased in patients after bariatric surgery
compared with the general population (64), preterm
delivery in other studies with more similar control
groups was unchanged (62, 63, 66). One study reported
higher cesarean delivery rates after bariatric surgery compared with rates for nonobese women who had not
undergone bariatric surgery (61.5% versus 36.2%,
P< 0.05). In this study, cesarean delivery rates for women
after bariatric surgery compared with obese (46.5%) and
severely obese controls (43.5%) was not significantly
different (71). The increase in cesarean delivery after
bariatric surgery may be attributed to previous cesarean
deliveries in this obese population (66).
Several case reports and small studies have identified significant late complications of previous bariatric
surgery that have occurred during pregnancy, including
maternal intestinal obstruction and gastrointestinal hemorrhage (61, 63, 69, 71-74). Exploratory surgery during
pregnancy may be required to treat these complications
from bariatric surgery. Maternal deaths have been reported
(75, 76). There should be a high index of suspicion for
gastrointestinal surgical complications when pregnant
women who have had these procedures present with significant abdominal symptoms.
Effect of Surgery on Fetal and Infant

The number of congenital anomalies after bariatric
surgery is not increased compared with the general pop-
ulation (64, 77). Some reports suggest a trend towards

lower mean birth weights indicating more appropriately
grown infants, fewer large for gestational age infants,
and more small for gestational age infants (53, 60, 65,
66, 6971). After bariatric surgery, maternal weight gain
during pregnancy is likely a predictor of birth weight (68,
78). Macro-somia (birth weight greater than 4,000 g)
also was decreased after Roux-en-Y gastric bypass (70,
71, 79). Pre-vious bariatric surgery is not associated with
an increase in perinatal death (60, 64, 65). The data are
limited on other neonatal outcomes.

Recommendations
How should contraception and preconception
be approached in patients after bariatric
surgery?
Contraception and preconception counseling should be a
component of the overall counseling for any reproductiveaged woman undergoing bariatric surgery. Contraceptive
counseling is especially important for adolescents
because pregnancy rates after bariatric surgery are double
the rate in the general adolescent population (12.8% versus
6.4%) (80). In addition, because there is an increased risk
of oral contraception failure after bariatric surgery with a
significant malabsorption component, nonoral administration of hormonal contraception should be considered
in these patients (55).
Some authorities have recommended waiting 1224
months after bariatric surgery before conceiving so that
the fetus is not exposed to a rapid maternal weight loss
environment and so that the patient can achieve full
weight loss goals (81). Should pregnancy occur before
this recommended time frame, closer surveillance of
maternal weight and nutritional status may be beneficial.
Use of ultrasound for serial monitoring of fetal growth
also may be useful and should be considered.
What are effective strategies for addressing

nutritional status during pregnancy in
women who have had bariatric surgery?
The most common nutritional deficiencies after Rouxen-Y gastric bypass surgery are of protein, iron, vitamin
B12, folate, vitamin D, and calcium. Several groups have
recommended a broad evaluation for micronutrient deficiencies at the beginning of pregnancy for women who
have had bariatric surgery, and it should be considered
(79, 8284). If there is a proven deficit, then appropriate
treatment should be instituted and monitored. In the
PRACTICE BULLETINS
absence of a deficiency, monitoring the blood count,

iron, ferritin, calcium, and vitamin D levels every trimester may be considered.
Beginning supplementation with oral forms is
appropriate, but parenteral forms should be considered if
laboratory studies do not improve. It is not known if
women require higher doses of folic acid (greater than
0.4 mg/d) after weight loss surgery to decrease the risk
of birth defects. Only 1459% of postoperative bariatric
surgery patients continue to take the prescribed multivitamin supplement long-term; therefore, patients without
appropriate preconception care may not have adequate
supplement levels at the start of pregnancy (85, 86). The
daily recommendation for protein intake of 60 g is the
same regardless of bariatric surgery status (9). Limited
evidence shows that caloric and protein restriction during pregnancy may impair fetal growth and is of no benefit in reducing other pregnancy comorbidities (87).
Consequently, even if patients continue to be overweight
after bariatric surgery, there is no recommendation for
caloric restriction during pregnancy.
Several studies have suggested that women who
become pregnant after bariatric surgery should take a
prenatal vitamin in addition to a multivitamin (79, 88). It
should be noted that an excess of vitamin A consumption
during pregnancy is associated with birth defects, so supplemental dosages of vitamin A should be limited to
5,000 international units per day during pregnancy.
Consultation with a nutritionist after conception may
help the patient adhere to dietary regimens and to cope
with the physiologic changes of pregnancy. One study
reported that if the bariatric surgery team monitored the
patient throughout the pregnancy, the weight gain was
optimal and similar to the Institute of Medicine (IOM)
recommendations (9.2 plus or minus 8.4 kg), compared
with patients who were not seen at all, not seen until
after the first trimester (poor weight gain of 4.8 plus or
minus 9.0 kg), or seen only in the first trimester (excessive weight gain of 13.0 plus or minus 9.7 kg, P= 0.009)
(68). Close surveillance should continue postpartum
because there are several case reports of nutritional deficiencies in infants who were breast-fed by women who
had under-gone bariatric procedures (89, 90).
Nutrient deficiencies also can occur after restrictive
surgical procedures (eg, adjustable gastric banding procedure). Patients may experience decreased food intake,
intolerance to certain foods, or both because the gastric
opening is narrowed after such procedures. Several
authors have described active band management
whereby fluid from the gastric band is removed or lessened during a pregnancy allowing for less gastric constriction and an increase in oral intake (62, 63, 69, 91).
Removing fluid from the gastric band also has been
1105
described to relieve nausea and vomiting during the first

trimester (62, 63, 70, 91). There is no consensus on the
management of patients during pregnancy who have
undergone an adjustable gastric banding procedure, but
early consultation with a bariatric surgeon is recommended.
Are there special considerations in the

antenatal period for women who have had
bariatric surgery?
In pregnancy, there may be a delay in the diagnosis of
bariatric-related operative complications. These complications include anastomotic leaks, bowel obstructions,
internal hernias, ventral hernias, band erosion, and band
migration. All gastrointestinal problems such as nausea,
vomiting, and abdominal pain, which occur commonly
during pregnancy, should be thoroughly evaluated in
patients who have had bariatric surgery. Early involvement of the bariatric surgeon in evaluating abdominal
pain is critical because the underlying pathology may
relate to the weight loss surgery.
Dumping syndrome can occur after gastric bypass
procedures. It is related to the ingestion of refined sugars
or high glycemic carbohydrates that the stomach rapidly
empties into the small intestine. Fluid shifts from the
intravascular compartment into the bowel lumen result in
small-bowel distention. Symptoms include abdominal
cramps, bloating, nausea, vomiting, and diarrhea.
Hyperinsulinemia and consequent hypoglycemia can
occur later, resulting in tachycardia, palpitations, anxiety, and diaphoresis. Patients with dumping syndrome
may not tolerate the 50-g glucose solution commonly
administered at 2428 weeks of gestation to screen for
gestational diabetes. Alternative measures to screen for
gestational diabetes should be considered for patients
who have undergone malabsorptive-type surgery. One
proposed alternative is home glucose monitoring (fasting
and 2-hour postprandial blood sugar) for approximately
1 week during the 2428 weeks of gestation (73, 92).
Other concerns for patients who have had bariatric
surgery relate to medication dosages. After operations
such as the Roux-en-Y gastric bypass, the absorptive
surface of the intestine is decreased, leading to decreased
time for absorption. Extended-release preparations are
not recommended in these patients; instead oral solutions or rapid release formulations are preferred (93). In
addition, the gastric pouch is smaller and bariatric surgeons have cautioned against using nonsteroidal
anti-inflammatory drugs postpartum to avoid gastric
ulceration (94, 95). In using medications in which a therapeutic drug level is critical, testing drug levels may be
necessary to ensure a therapeutic effect.
1106
Are there special considerations during labor

and delivery for women who have had
bariatric surgery?
Bariatric surgery should not alter the course of labor and
delivery, and as such does not significantly affect its management. However, many patients remain obese after
bariatric procedures and, as with obese women without
bariatric surgery, may be admitted earlier in labor, need
labor induction, require more oxytocin, and have longer
labor (30). Cesarean delivery rates are higher after
bariatric surgery, as high as 62% in one study (65, 66, 71,
79, 88). Similarly, in one study, even after controlling for
confounders (previous cesarean delivery, obesity, and fetal
macrosomia), bariatric surgery was found to be an independent risk factor for cesarean delivery (64). There is no
known physiologic reason for performing more cesarean
deliveries in women who have had bariatric surgery.
Therefore, the bariatric surgery itself should not be considered an indication for a cesarean delivery. If a patient
has had extensive and complicated abdominal surgery
from weight loss procedures, prelabor consultation with a
bariatric surgeon should be considered.
Summary of
Recommendations and
Conclusions
The following conclusions and recommendations
are based on limited or inconsistent scientific evidence (Level B:)
Contraceptive counseling is important for adolescents because pregnancy rates after bariatric surgery
are double the rate in the general adolescent population.
Because there is an increased risk of oral contraception failure after bariatric surgery with a significant
malabsorption component, nonoral administration
of hormonal contraception should be considered in
these patients.
In using medications in which a therapeutic drug
level is critical, testing drug levels may be necessary
to ensure a therapeutic effect.
The following conclusions and recommendations

There should be a high index of suspicion for gastrointestinal surgical complications when pregnant
women who have had these procedures present with

significant abdominal symptoms.
Bariatric surgery should not be considered a treatment for infertility.
Bariatric surgery should not be considered an indication for cesarean delivery.
There is no consensus on the management of
patients during pregnancy who have had an
adjustable gastric banding procedure, but early consultation with a bariatric surgeon is recommended.
Alternative testing for gestational diabetes should be
considered for those patients with a malabsorptivetype surgery.
Consultation with a nutritionist after conception
may help the patient adhere to dietary regimens and
cope with the physiologic changes of pregnancy.
A broad evaluation for micronutrient deficiencies at
the beginning of pregnancy for women who have
had bariatric surgery should be considered.
Measure
Documentation of counseling about weight gain and
nutrition in pregnancy
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1110

Task Force:
I

type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Bariatric surgery and pregnancy. ACOG Practice Bulletin No. 105.
2009;113:140513.
PRACTICE BULLETINS
1111
ACOG
PRACTICE
BULLETIN
Replaces Practice Bulletin Number 70, December 2005
Intrapartum Fetal Heart Rate

Monitoring: Nomenclature,
Interpretation, and General
Management Principles
the assistance of George A. Macones,
practice.

OBSTETRICIANS AND
GYNECOLOGISTS
In the most recent year for which data are available, approximately 3.4 million
fetuses (85% of approximately 4 million live births) in the United States were
assessed with electronic fetal monitoring (EFM), making it the most common
obstetric procedure (1). Despite its widespread use, there is controversy about
the efficacy of EFM, interobserver and intraobserver variability, nomenclature,
systems for interpretation, and management algorithms. Moreover, there is evidence that the use of EFM increases the rate of cesarean deliveries and operative vaginal deliveries. The purpose of this document is to review nomenclature
for fetal heart rate assessment, review the data on the efficacy of EFM, delineate the strengths and shortcomings of EFM, and describe a system for EFM
classification.
Background
A complex interplay of antepartum complications, suboptimal uterine perfusion, placental dysfunction, and intrapartum events can result in adverse neonatal outcome. Known obstetric conditions, such as hypertensive disease, fetal
growth restriction, and preterm birth, predispose fetuses to poor outcomes, but
they account for a small proportion of asphyxial injury. In a study of term pregnancies with fetal asphyxia, 63% had no known risk factors (2).
The fetal brain modulates the fetal heart rate through an interplay of sympathetic and parasympathetic forces. Thus, fetal heart rate (FHR) monitoring
can be used to determine if a fetus is well oxygenated. It was used among 45%
of laboring women in 1980, 62% in 1988, 74% in 1992, and 85% in 2002 (1).
1112
Despite the frequency of its use, limitations of EFM

include poor interobserver and intraobserver reliability,
uncertain efficacy, and a high false-positive rate.
Fetal heart rate monitoring may be performed externally or internally. Most external monitors use a Doppler
device with computerized logic to interpret and count the
Doppler signals. Internal FHR monitoring is accomplished with a fetal electrode, which is a spiral wire
placed directly on the fetal scalp or other presenting part.
Guidelines for Nomenclature and

Interpretation of Electronic Fetal
Heart Rate Monitoring
In 2008, the Eunice Kennedy Shriver National Institute
of Child Health and Human Development partnered with
the American College of Obstetricians and Gynecologists and the Society for MaternalFetal Medicine to
sponsor a workshop focused on electronic FHR monitoring (3). This 2008 workshop gathered a diverse group of
investigators with expertise and interest in the field to
accomplish three goals: 1) to review and update the definitions for FHR pattern categorization from the prior
workshop; 2) to assess existing classification systems for
interpreting specific FHR patterns and make recommendations about a system for use in the United States; and
3) to make recommendations for research priorities for
EFM. A complete clinical understanding of EFM necessitates discussion of uterine contractions, baseline FHR
rate and variability, presence of accelerations, periodic
or episodic decelerations, and the changes in these characteristics over time. A number of assumptions and factors common to FHR interpretation in the United States
are central to the proposed system of nomenclature
and interpretation (3). Two such assumptions are of particular importance. First, the definitions are primarily
developed for visual interpretation of FHR patterns, but
should be adaptable to computerized systems of interpretation. Second, the definitions should be applied to
intrapartum patterns, but also are applicable to antepartum observations.
Uterine contractions are quantified as the number of
contractions present in a 10-minute window, averaged
over a 30-minute period. Contraction frequency alone is
a partial assessment of uterine activity. Other factors
such as duration, intensity, and relaxation time between
contractions are equally important in clinical practice.
Listed as follows is terminology used to describe
uterine activity:
Normal: five contractions or less in 10 minutes,
averaged over a 30-minute window
Tachysystole: more than five contractions in 10 minutes, averaged over a 30-minute window
Characteristics of uterine contractions

The terms hyperstimulation and hypercontractility
are not defined and should be abandoned.
Tachysystole should always be qualified as to the
presence or absence of associated FHR decelerations.
The term tachysystole applies to both spontaneous
and stimulated labor. The clinical response to tachysystole may differ depending on whether contractions are spontaneous or stimulated.
Table 1 provides EFM definitions and descriptions
based on the 2008 National Institute of Child Health and
Human Development Working Group findings. Decelerations are defined as recurrent if they occur with at least
one half of the contractions.
Classification of Fetal Heart

Rate Tracings
A variety of systems for EFM interpretation have been
used in the United States and worldwide (46). Based on
careful review of the available options, a three-tiered
system for the categorization of FHR patterns is recommended (see box). It is important to recognize that FHR
tracing patterns provide information only on the current
acidbase status of the fetus. Categorization of the FHR
tracing evaluates the fetus at that point in time; tracing
patterns can and will change. An FHR tracing may move
back and forth between the categories depending on the
clinical situation and management strategies used.
Category I FHR tracings are normal. Category I FHR
tracings are strongly predictive of normal fetal acidbase
status at the time of observation. Category I FHR tracings may be monitored in a routine manner, and no specific action is required.
Category II FHR tracings are indeterminate. Category
II FHR tracings are not predictive of abnormal fetal
acidbase status, yet presently there is not adequate evidence to classify these as Category I or Category III.
Category II FHR tracings require evaluation and continued surveillance and reevaluation, taking into account
the entire associated clinical circumstances. In some circumstances, either ancillary tests to ensure fetal wellbeing or intrauterine resuscitative measures may be used
with Category II tracings.
Category III FHR tracings are abnormal. Category III
tracings are associated with abnormal fetal acidbase
status at the time of observation. Category III FHR tracings require prompt evaluation. Depending on the clinical situation, efforts to expeditiously resolve the abnor-
PRACTICE BULLETINS
1113
Table 1. Electronic Fetal Monitoring Definitions

Pattern
Definition
Baseline
The mean FHR rounded to increments of 5 beats per minute during a 10-minute segment, excluding:
Periodic or episodic changes
Periods of marked FHR variability
Segments of baseline that differ by more than 25 beats per minute
The baseline must be for a minimum of 2 minutes in any 10-minute segment, or the baseline for that time period
is indeterminate. In this case, one may refer to the prior 10-minute window for determination of baseline.
Normal FHR baseline: 110160 beats per minute
Tachycardia: FHR baseline is greater than 160 beats per minute
Bradycardia: FHR baseline is less than 110 beats per minute
Fluctuations in the baseline FHR that are irregular in amplitude and frequency
Variability is visually quantitated as the amplitude of peak-to-trough in beats per minute.
Absentamplitude range undetectable
Minimalamplitude range detectable but 5 beats per minute or fewer
Moderate (normal)amplitude range 625 beats per minute
Markedamplitude range greater than 25 beats per minute
A visually apparent abrupt increase (onset to peak in less than 30 seconds) in the FHR
At 32 weeks of gestation and beyond, an acceleration has a peak of 15 beats per minute or more above baseline,
with a duration of 15 seconds or more but less than 2 minutes from onset to return.
Before 32 weeks of gestation, an acceleration has a peak of 10 beats per minute or more above baseline, with a
duration of 10 seconds or more but less than 2 minutes from onset to return.
Prolonged acceleration lasts 2 minutes or more but less than 10 minutes in duration.
If an acceleration lasts 10 minutes or longer, it is a baseline change.
Visually apparent usually symmetrical gradual decrease and return of the FHR associated with a uterine contraction
A gradual FHR decrease is defined as from the onset to the FHR nadir of 30 seconds or more.
The decrease in FHR is calculated from the onset to the nadir of the deceleration.
The nadir of the deceleration occurs at the same time as the peak of the contraction.
In most cases the onset, nadir, and recovery of the deceleration are coincident with the beginning, peak, and
ending of the contraction, respectively.
Visually apparent usually symmetrical gradual decrease and return of the FHR associated with a uterine contraction
A gradual FHR decrease is defined as from the onset to the FHR nadir of 30 seconds or more.
The deceleration is delayed in timing, with the nadir of the deceleration occurring after the peak of the contraction.
In most cases, the onset, nadir, and recovery of the deceleration occur after the beginning, peak, and ending of
the contraction, respectively.
Visually apparent abrupt decrease in FHR
An abrupt FHR decrease is defined as from the onset of the deceleration to the beginning of the FHR nadir of less
than 30 seconds.
The decrease in FHR is 15 beats per minute or greater, lasting 15 seconds or greater, and less than 2 minutes in
duration.
When variable decelerations are associated with uterine contractions, their onset, depth, and duration commonly
vary with successive uterine contractions.
Visually apparent decrease in the FHR below the baseline
Decrease in FHR from the baseline that is 15 beats per minute or more, lasting 2 minutes or more but less than 10
minutes in duration.
If a deceleration lasts 10 minutes or longer, it is a baseline change.
Visually apparent, smooth, sine wave-like undulating pattern in FHR baseline with a cycle frequency of 35 per
minute which persists for 20 minutes or more.
Baseline variability
Acceleration
Early deceleration
Late deceleration
Variable deceleration
Prolonged deceleration
Sinusoidal pattern
Abbreviation: FHR, fetal heart rate.

Macones GA, Hankins GD, Spong CY, Hauth J, Moore T. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol 2008;112:6616.
1114
Three-Tiered Fetal Heart Rate Interpretation System

Category I
Category I FHR tracings include all of the following:
Baseline rate: 110160 beats per minute
Baseline FHR variability: moderate
Late or variable decelerations: absent
Early decelerations: present or absent
Accelerations: present or absent
Category II
Category II FHR tracings includes all FHR tracings not
categorized as Category I or Category III. Category II
tracings may represent an appreciable fraction of those
encountered in clinical care. Examples of Category II
FHR tracings include any of the following:
Baseline rate
Bradycardia not accompanied by absent baseline
variability
Tachycardia
Baseline FHR variability
Minimal baseline variability
Absent baseline variability with no recurrent
decelerations
Marked baseline variability
Accelerations
Absence of induced accelerations after fetal stimulation
Periodic or episodic decelerations
Recurrent variable decelerations accompanied by
minimal or moderate baseline variability
Prolonged deceleration more than 2 minutes but
less than10 minutes
Recurrent late decelerations with moderate baseline
variability
Variable decelerations with other characteristics such
as slow return to baseline, overshoots, or shoulders
Category III
Category III FHR tracings include either
Absent baseline FHR variability and any of the
following:
Recurrent late decelerations
Recurrent variable decelerations
Bradycardia
Sinusoidal pattern
Abbreviation: FHR, fetal heart rate
Macones GA, Hankins GD, Spong CY, Hauth J, Moore T. The 2008
National Institute of Child Health and Human Development workshop
report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol 2008;112:6616.
mal FHR pattern may include but are not limited to provision of maternal oxygen, change in maternal position,
discontinuation of labor stimulation, treatment of maternal hypotension, and treatment of tachysystole with FHR
changes. If a Category III tracing does not resolve with
these measures, delivery should be undertaken.
Guidelines for Review of Electronic

Fetal Heart Rate Monitoring
When EFM is used during labor, the nurses or physicians
should review it frequently. In a patient without complications, the FHR tracing should be reviewed approximately every 30 minutes in the first stage of labor and
every 15 minutes during the second stage. The corresponding frequency for patients with complications (eg,
fetal growth restriction, preeclampsia) is approximately
every 15 minutes in the first stage of labor and every 5
minutes during the second stage. Health care providers
should periodically document that they have reviewed
the tracing. The FHR tracing, as part of the medical
record, should be labeled and available for review if the
need arises. Computer storage of the FHR tracing that
does not permit overwriting or revisions is reasonable, as
is microfilm recording.

Recommendations
How efficacious is intrapartum electronic
fetal heart rate monitoring?
The efficacy of EFM during labor is judged by its ability to decrease complications, such as neonatal seizures,
cerebral palsy, or intrapartum fetal death, while minimizing the need for unnecessary obstetric interventions,
such as operative vaginal delivery or cesarean delivery.
There are no randomized clinical trials to compare the
benefits of EFM with any form of monitoring during
labor (7). Thus, the benefits of EFM are gauged from
reports comparing it with intermittent auscultation.
A meta-analysis synthesizing the results of the randomized clinical trials comparing the modalities had the
following conclusions (8):
The use of EFM compared with intermittent auscultation increased the overall cesarean delivery rate
(relative risk [RR], 1.66; 95% confidence interval
[CI], 1.302.13) and the cesarean delivery rate for
abnormal FHR or acidosis or both (RR, 2.37; 95%
CI, 1.883.00).
PRACTICE BULLETINS
The use of EFM increased the risk of both vacuum

and forceps operative vaginal delivery (RR, 1.16;
95% CI, 1.011.32).
The use of EFM did not reduce perinatal mortality
(RR, 0.85; 95% CI, 0.591.23).
The use of EFM reduced the risk of neonatal seizures
(RR, 0.50; 95% CI, 0.310.80).
The use of EFM did not reduce the risk of cerebral
palsy (RR, 1.74; 95% CI, 0.973.11).
There is an unrealistic expectation that a nonreassuring FHR tracing is predictive of cerebral palsy. The
positive predictive value of a nonreassuring pattern to
predict cerebral palsy among singleton newborns with
birth weights of 2,500 g or more is 0.14%, meaning that
out of 1,000 fetuses with a nonreassuring FHR pattern,
only one or two will develop cerebral palsy (9). The falsepositive rate of EFM for predicting cerebral palsy is
extremely high, at greater than 99%.
Available data, although limited in quantity, suggest
that the use of EFM does not result in a reduction in cerebral palsy (8). This is consistent with data that suggest
that the occurrence of cerebral palsy has been stable over
time, despite the widespread introduction of EFM (10).
The principal explanation for why the prevalence of
cerebral palsy has not diminished despite the use of EFM
is that 70% of cases occur before the onset of labor; only
4% of cases of encephalopathy can be attributed solely
to intrapartum events (11, 12).
Given that the available data do not show a clear
benefit for the use of EFM over intermittent auscultation,
either option is acceptable in a patient without complications. Logistically, it may not be feasible to adhere to
guidelines for how frequently the heart rate should be
auscultated. One prospective study noted that the protocol for intermittent auscultation was successfully completed in only 3% of the cases (13). The most common
reasons for unsuccessful intermittent auscultation
included the frequency of recording and the requirements for recording.
Intermittent auscultation may not be appropriate for
all pregnancies. Most of the clinical trials that compare
EFM with intermittent auscultation have excluded participants at high risk of adverse outcomes, and the relative safety of intermittent auscultation in such cases is
uncertain. The labor of women with high-risk conditions
(eg, suspected fetal growth restriction, preeclampsia, and
type 1 diabetes) should be monitored with continuous
FHR monitoring.
There are no comparative data indicating the optimal frequency at which intermittent auscultation should
be performed in the absence of risk factors. One method
1115
is to evaluate and record the FHR at least every 15 minutes in the active phase of the first stage of labor and at
least every 5 minutes in the second stage (14).
What is the interobserver and intraobserver

variability of intrapartum electronic fetal
heart rate monitoring assessment?
There is high interobserver and intraobserver variability
in the interpretation of FHR tracings. For example, when
four obstetricians examined 50 cardiotocograms, they
agreed in only 22% of the cases (15). Two months later,
during the second review of the same 50 tracings, the
clinicians interpreted 21% of the tracings differently
than they did during the first evaluation. In another study,
five obstetricians independently interpreted 150 cardiotoco-grams (16). The obstetricians interpreted the
tracings similarly in 29% of the cases, suggesting poor
interobserver reliability.
The interpretation of cardiotocograms is more consistent when the tracing is normal (17). With retrospective reviews, the foreknowledge of neonatal outcome may
alter the reviewers impressions of the tracing. Given the
same intrapartum tracing, a reviewer is more likely to
find evidence of fetal hypoxia and criticize the obstetricians management if the outcome was poor versus good
(18). Therefore, reinterpretation of the FHR tracing,
especially if neonatal outcome is known, may not be
reliable.
When should the very preterm fetus be

monitored?
The decision to monitor the very preterm fetus requires
a discussion between the obstetrician, pediatrician, and
patient concerning the likelihood of survival or severe
morbidity of the preterm child (based on gestational age,
estimated fetal weight, and other factors) and issues
related to mode of delivery. If a patient undergoes a
cesarean delivery for indications related to a preterm
fetus, continuous monitoring should be used rather than
intermittent auscultation. The earliest gestational age
that this will occur may vary.
Nonreassuring FHR patterns may occur with up to
60% of women with preterm labor, with the most common abnormality being deceleration and bradycardia,
followed by tachycardia and minimal or absent baseline
variability (19). Variable decelerations are more common among preterm (5570%) deliveries than term
(2030%) deliveries (20). If FHR abnormalities are persistent, intrauterine resuscitation, ancillary tests to
ensure fetal well-being, and possibly delivery should be
undertaken (21).
1116
What medications can affect the fetal heart

rate?
Fetal heart rate patterns can be influenced by the medications administered in the intrapartum period. Most
often, these changes are transient, although they sometimes lead to obstetric interventions.
Epidural analgesia with local anesthetic agents (ie,
lidocaine, bupivacaine) can lead to sympathetic blockade, maternal hypotension, transient uteroplacental insufficiency, and alterations in the FHR. Parenteral narcotics
also may affect the FHR. A randomized trial comparing
epidural anesthesia with 0.25% of bupivacaine and intravenous meperidine reported that the variability was
decreased, and FHR accelerations were significantly less
common with parenteral analgesia compared with
regional analgesia (22). The rates of decelerations and
cesarean delivery for nonreassuring FHR tracings
were similar for the two groups. A systematic review of
five randomized trials and seven observational studies
also noted that the rate of cesarean delivery for nonreassuring FHR was similar between those who did and
those who did not receive epidural analgesia during labor
(23).
Concern has been raised about combined spinal
epidural anesthesia during labor. An intent-to-treat
analysis of 1,223 laboring women randomized to combined spinalepidural anesthesia (10 mcg of intrathecal
sufentanil, followed by epidural bupivacaine and fentanyl at the next request for analgesia) or intravenous
meperidine (50 mg on demand, maximum 200 mg in
4 hours) noted a significantly higher rate of bradycardia and emergent cesarean delivery for abnormal FHR
in the group randomized to combined spinalepidural
anesthesia (24). Neonatal outcome, however, was not
significantly different between the two groups. There
are some methodological concerns with this study.
Another randomized controlled trial compared the
occurrence of FHR tracing abnormalities in laboring
women who received combined spinalepidural anesthesia (n = 41) to epidural anesthesia (n=46). In this
study, FHR abnormalities were more common in
women receiving combined spinalepidural anesthesia
(25). Additional trials are necessary to determine the
potential safety and efficacy of the combined spinal
epidural technique.
Other medications that influence FHR tracing have
been studied (see Table 2). Of note, multiple regression
analysis indicated that decreased variability attributed to
the use of magnesium sulfate was related to early gestational age but not the serum magnesium level (26).
Studies report different findings with regard to the effect
of magnesium on FHR patterns. Some show no independent effect; others show small changes in baseline or
variability. In general, however, caution should be used
in ascribing unfavorable findings on EFM to the use of
magnesium alone.
Transient sinusoidal FHR patterns occurred in 75%
of patients who received butorphanol during labor, but
this was not associated with adverse outcomes (27).
Fetuses exposed to cocaine did not exhibit any characteristic changes in the heart rate pattern, although they
did have frequent contractions even when labor was
unstimulated (28). As determined by computer analysis
of cardiotocograms, a randomized trial reported that
compared with meperidine, nalbuphine used for intrapartum analgesia decreased the likelihood of two 15-second accelerations over 20 minutes (29). In antepartum
patients, administration of morphine decreased not only
the fetal breathing movement but also the number of
accelerations (30).
The effect of corticosteroids, which are used to
enhance pulmonary maturity of fetuses during preterm
labor, on FHR has been studied (Table 2). Among twins
(31) and singletons (32, 33), the use of betamethasone
transiently decreased the FHR variability, which returned
to pretreatment status by the fourth to seventh day. There
also may be a decrease in the rate of accelerations with
the use of betamethasone. These changes, however, were
not associated with increased obstetric interventions or
with adverse outcomes (31). The biologic mechanism of
this is unknown. Computerized analysis of the cardiotocograms indicates that use of dexamethasone is not associated with a decrease in the FHR variability (33).
What findings on EFM are consistent with

normal fetal acidbase status?
The presence of FHR accelerations generally ensures that
the fetus is not acidemic. The data relating FHR variability to clinical outcomes, however, are sparse. Results of
an observational study suggest that moderate FHR variability is strongly associated with an arterial umbilical
cord pH higher than 7.15 (34). One study reported that in
the presence of late or variable decelerations, the umbilical arterial pH was higher than 7.00 in 97% of the cases
if the FHR tracing had normal variability (35). In another retrospective study, most cases of adverse neonatal outcome demonstrated normal FHR variability (36). This
study is limited because it did not consider other characteristics of the FHR tracing, such as the presence of accelerations or decelerations. However, in most cases, normal
FHR variability provides reassurance about fetal status
and the absence of metabolic acidemia.
PRACTICE BULLETINS
1117
Table 2. Effects of Commonly Used Medications on Fetal Heart Rate Patterns

Medications
Comments
References
Narcotics
At equivalent doses, all narcotics (with or without added antiemetics) have similar
effects: a decrease in variability and a decrease in the frequency of accelerations
75 mg meperidine = 10 mg morphine = 0.1 mg fentanyl = 10 mg nalbuphine
17
Butorphanol
Transient sinusoidal FHR pattern, slight increased mean heart rate compared with meperidine
8, 9
Cocaine
Decreased long-term variability
10, 11
Corticosteroids
Decrease in FHR variability with beta-methasone but not dexamethasone, abolishment

of diurnal fetal rhythms, increased effect at greater than 29 weeks of gestation
1215
Magnesium sulfate
A significant decrease in short-term variability, clinically insignificant decrease in FHR,

inhibits the increase in accelerations with advancing gestational age
16, 17
Terbutaline
Increase in baseline FHR and incidence of fetal tachycardia
18, 19
Zidovudine
No difference in the FHR baseline, variability, number of accelerations, or decelerations
20
Abbreviation: FHR, fetal heart rate.

References
1. Hill JB, Alexander JM, Sharma SK, McIntire DD, Leveno KJ. A comparison of the effects of epidural and meperidine analgesia during labor on fetal heart rate. Obstet
Gynecol 2003;102:3337.
2. Panayotopoulos N, Salamalekis E, Kassanos D, Vitoratos N, Loghis C, Batalias L. Intrapartum vibratory acoustic stimulation after maternal meperidine administration. Clin Exp Obstet Gynecol 1998;25:13940.
3. Zimmer EZ, Divon MY, Vadasz A. Influence of meperidine on fetal movements and heart rate beat-to-beat variability in the active phase of labor. Am J Perinatol
1988;5:197200.
4. Kopecky EA, Ryan ML, Barrett JF, Seaward PG, Ryan G, Koren G, et al. Fetal response to maternally administered morphine. Am J Obstet Gynecol 2000;183:42430.
5. Rayburn W, Rathke A, Leuschen MP, Chleborad J, Weidner W. Fentanyl citrate analgesia during labor. Am J Obstet Gynecol 1989;161:2026.
6. Nicolle E, Devillier P, Delanoy B, Durand C, Bessard G. Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the
neonate. Eur J Clin Pharmacol 1996;49:4859.
7. Poehlmann S, Pinette M, Stubblefield P. Effect of labor analgesia with nalbuphine hydrochloride on fetal response to vibroacoustic stimulation. J Reprod Med
1995;40:70710.
8. Hatjis CG, Meis PJ. Sinusoidal fetal heart rate pattern associated with butorphanol administration. Obstet Gynecol 1986;67:37780.
9. Quilligan EJ, Keegan KA, Donahue MJ. Double-blind comparison of intravenously injected butorphanol and meperidine in parturients. Int J Gynaecol Obstet
1980;18:3637.
10. Chazotte C, Forman L, Gandhi J. Heart rate patterns in fetuses exposed to cocaine. Obstet Gynecol 1991;78:3235.
11. Tabor BL, Soffici AR, Smith-Wallace T, Yonekura ML. The effect of maternal cocaine use on the fetus: changes in antepartum fetal heart rate tracings. Am J Obstet
Gynecol 1991;165:127881.
12. Senat MV, Minoui S, Multon O, Fernandez H, Frydman R, Ville Y. Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labour: a
randomised study. Br J Obstet Gynaecol 1998;105:74955.
13. Rotmensch S, Liberati M, Vishne TH, Celentano C, Ben-Rafael Z, Bellati U. The effect of betamethasone and dexamethasone on fetal heart rate patterns and biophysical activities. A prospective randomized trial. Acta Obstet Gynecol Scand 1999;78:493500.
14. Koenen SV, Mulder EJ, Wijnberger LD, Visser GH. Transient loss of the diurnal rhythms of fetal movements, heart rate, and its variation after maternal betamethasone administration. Pediatr Res 2005;57:6626.
15. Mulder EJ, Koenen SV, Blom I, Visser GH. The effects of antenatal betamethasone administration on fetal heart rate and behaviour depend on gestational age. Early
Hum Dev 2004;76:6577.
16. Hallak M, Martinez-Poyer J, Kruger ML, Hassan S, Blackwell SC, Sorokin Y. The effect of magnesium sulfate on fetal heart rate parameters: a randomized, placebocontrolled trial. Am J Obstet Gynecol 1999;181:11227.
17. Wright JW, Ridgway LE, Wright BD, Covington DL, Bobitt JR. Effect of MgSO4 on heart rate monitoring in the preterm fetus. J Reprod Med 1996;41:6058.
18. Mawaldi L, Duminy P, Tamim H. Terbutaline versus nifedipine for prolongation of pregnancy in patients with preterm labor. Int J Gynaecol Obstet 2008;100:658.
19. Roth AC, Milsom I, Forssman L, Ekman LG, Hedner T. Effects of intravenous terbutaline on maternal circulation and fetal heart activity. Acta Obstet Gynecol Scand
1990;69:2238.
20. Blackwell SC, Sahai A, Hassan SS, Treadwell MC, Tomlinson MW, Jones TB, et al. Effects of intrapartum zidovudine therapy on fetal heart rate parameters in women
with human immunodeficiency virus infection. Fetal Diagn Ther 2001;16:4136.
1118
Are there ancillary tests that can aid in the

management of Category II or Category III
fetal heart rate tracings?
There are some ancillary tests available that help to
ensure fetal well-being in the face of a Category II or
Category III FHR tracing, thereby reducing the high
false-positive rate of EFM.
In the case of an EFM tracing with minimal or
absent variability and without spontaneous acceleration,
an effort should be made to elicit one. A meta-analysis of
11 studies of intrapartum fetal stimulation noted that
four techniques are available to stimulate the fetus: 1)
fetal scalp sampling, 2) Allis clamp scalp stimulation,
3) vibroacoustic stimulation, and 4) digital scalp stimulation (37). Because vibroacoustic stimulation and digital scalp stimulation are less invasive than the other two
methods, they are the preferred methods. When there is
an acceleration following stimulation, acidemia is
unlikely and labor can continue.
When a Category III FHR tracing is persistent, a
scalp blood sample for the determination of pH or lactate
may be considered. However, the use of scalp pH assessment has decreased (38), and this test may not even be
available at some tertiary hospitals (39). There are likely
many reasons for this decrease, including physician
experience, difficulty in obtaining and processing an
adequate sample in a short amount of time, and the need
for routine maintenance and calibration of laboratory
equipment that may be used infrequently. More importantly, scalp stimulation, which is less invasive, provides
similar information about the likelihood of fetal
acidemia as does scalp pH.
In one study, the sensitivity and positive predictive
value of a low scalp pH (defined in the study as less than
7.21 because it is the 75th percentile) to predict umbilical arterial pH less than 7.00 was 36% and 9%, respectively (40). More importantly, the sensitivity and positive
predictive value of a low scalp pH to identify a newborn
with hypoxicischemic encephalopathy was 50% and
3%, respectively. However, the greater utility of scalp pH
is in its high negative predictive value (9799%). There
are some data to suggest that fetal scalp lactate levels
have higher sensitivity and specificity than scalp pH
(40). However, a recent large randomized clinical trial
that compared the use of scalp pH assessment to scalp
lactate level assessment in cases of intrapartum fetal
distress did not demonstrate a difference in the rate of
acidemia at birth, Apgar scores, or neonatal intensive
care unit admissions (41). Although scalp stimulation
has largely replaced scalp pH and scalp lactate assessment in the United States, if available, these tests may
provide additional information in the setting of a

Category III tracing.
Pulse oximetry has not been demonstrated to be a
clinically useful test in evaluating fetal status (4244).
Are there methods of intrauterine resuscitation that can be used for Category II or
Category III tracings?
A Category II or Category III FHR tracing requires evaluation of the possible causes. Initial evaluation and treatment may include the following:
Discontinuation of any labor stimulating agent
Cervical examination to determine umbilical cord
prolapse, rapid cervical dilation, or descent of the
fetal head
Changing maternal position to left or right lateral
recumbent position, reducing compression of the
vena cava and improving uteroplacental blood flow
Monitoring maternal blood pressure level for evidence of hypotension, especially in those with
regional anesthesia (if present, treatment with volume expansion or with ephedrine or both, or
phenylephrine may be warranted)
Assessment of patient for uterine tachysystole by
evaluating uterine contraction frequency and duration
Supplemental maternal oxygen commonly is used in
cases of an indeterminate or abnormal pattern. There are
no data on the efficacy or safety of this therapy. Often,
the FHR patterns persist and do not respond to change in
position or oxygenation. In such cases, the use of
tocolytic agents has been suggested to stop uterine contractions and perhaps avoid umbilical cord compression.
A meta-analysis reported the pooled results of three randomized clinical trials that compared tocolytic therapy
(terbutaline, hexoprenaline, or magnesium sulfate) with
untreated controls in the management of a suspected
nonreassuring FHR tracing (45). Compared with no
treatment, tocolytic therapy more commonly improved
the FHR tracing. However, there were no differences in
rates of perinatal mortality, low 5-minute Apgar score, or
admission to the neonatal intensive care unit between the
groups (possibly because of the small sample size).
Thus, although tocolytic therapy appears to reduce the
number of FHR abnormalities, there is insufficient evidence to recommend it.
Tachysystole with associated FHR changes can be
successfully treated with 2-adrenergic drugs (hexoprenaline or terbutaline). A retrospective study suggested that
98% of such cases respond to treatment with a -agonist
(46).
PRACTICE BULLETINS
When the FHR tracing includes recurrent variable

decelerations, amnioinfusion to relieve umbilical cord
compression may be considered (47). A meta-analysis of
12 randomized trials that allocated patients to no treatment or transcervical amnioinfusion noted that placement of fluid in the uterine cavity significantly reduced
the rate of decelerations (RR, 0.54; 95% CI, 0.430.68)
and cesarean delivery for suspected fetal distress (RR,
0.35; 95% CI, 0.240.52) (48). Because of the lower rate
of cesarean delivery, amnioinfusion also decreased the
likelihood that either the patient or the newborn will stay
in the hospital more than 3 days (48). Amnioinfusion can
be done by bolus or continuous infusion technique. A
randomized trial compared the two techniques of amnioinfusion and concluded that both have a similar ability to
relieve recurrent variable decelerations (49).
Another common cause of a Category II or Category
III FHR pattern is maternal hypotension secondary to
regional anesthesia. If maternal hypotension is identified
and suspected to be secondary to regional anesthesia,
treatment with volume expansion or intravenous ephedrine or both is warranted.
Summary of
Recommendations and
Conclusions
The false-positive rate of EFM for predicting cerebral palsy is high, at greater than 99%.
The use of EFM is associated with an increased
rate of both vacuum and forceps operative vaginal
delivery, and cesarean delivery for abnormal FHR
patterns or acidosis or both.
When the FHR tracing includes recurrent variable
decelerations, amnioinfusion to relieve umbilical cord
compression should be considered.
Pulse oximetry has not been demonstrated to be a
clinically useful test in evaluating fetal status.

There is high interobserver and intraobserver variability in interpretation of FHR tracing.
Reinterpretation of the FHR tracing, especially if
the neonatal outcome is known, may not be reliable.
1119
The use of EFM does not result in a reduction of

cerebral palsy.

expert opinion (Level C):
A three-tiered system for the categorization of FHR
patterns is recommended.
The labor of women with high-risk conditions should
be monitored with continuous FHR monitoring.
The terms hyperstimulation and hypercontractility
should be abandoned.
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34. Parer JT, King T, Flanders S, Fox M, Kilpatrick SJ. Fetal
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PRACTICE BULLETINS
40. Kruger K, Hallberg B, Blennow M, Kublickas M,

Westgren M. Predictive value of fetal scalp blood lactate
concentration and pH as markers of neurologic disability.
41. Wiberg-Itzel E, Lipponer C, Norman M, Herbst A,
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42. Garite TJ, Dildy GA, McNamara H, Nageotte MP, Boehm
FH, Dellinger EH, et al. A multicenter controlled trial of
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43. Bloom SL, Spong CY, Thom E, Varner MW, Rouse DJ,
Weininger S, et al. Fetal pulse oximetry and cesarean
delivery. National Institute of Child Health and Human
Development Maternal-Fetal Medicine Units Network. N
Engl J Med 2006;355:2195202. (Level I)
44. East CE, Chan FY, Colditz PB, Begg L. Fetal pulse
oximetry for fetal assessment in labour. Cochrane
Database of Systematic Reviews 2007, Issue 2. Art.
No.: CD004075. DOI: 10.1002/14651858.CD004075.
pub3. (Meta-analysis)
45. Kulier R, Hofmeyr GJ. Tocolytics for suspected intrapartum fetal distress. Cochrane Database of Systematic
Reviews 1998, Issue 2. Art. No.: CD000035. DOI: 10.
1002/14651858.CD000035. (Meta-analysis)
46. Egarter CH, Husslein PW, Rayburn WF. Uterine hyperstimulation after low-dose prostaglandin E2 therapy:
tocolytic treatment in 181 cases. Am J Obstet Gynecol
1990;163:7946. (Level II-2)
47. Miyazaki FS, Taylor NA. Saline amnioinfusion for relief
of variable or prolonged decelerations. A preliminary
report. Am J Obstet Gynecol 1983;146:6708. (Level III)
48. Hofmeyr GJ. Amnioinfusion for potential or suspected
umbilical cord compression in labour. Cochrane Database
of Systematic Reviews 1998, Issue 1. Art. No.: CD000013.
DOI: 10.1002/14651858.CD000013. (Meta-analysis)
49. Rinehart BK, Terrone DA, Barrow JH, Isler CM,
Barrilleaux PS, Roberts WE. Randomized trial of intermittent or continuous amnioinfusion for variable decelerations. Obstet Gynecol 2000;96:5714. (Level I)
1121

Task Force:
I

type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Intrapartum fetal heart rate monitoring: nomenclature, interpretation,
and general management principles. ACOG Practice Bulletin No. 106.
2009;114:192202.
1122
ACOG
PRACTICE
BULLETIN
Replaces Practice Bulletin Number 10, November 1999; Committee Opinion Number 228, November
1999; Committee Opinion Number 248, December 2000; Committee Opinion Number 283, May 2003
Induction of Labor
the assistance of Mildred Ramirez,
MD, and Susan Ramin, MD. The
information is designed to aid practitioners in making decisions about
appropriate obstetric and gynecologic care. These guidelines should
procedure. Variations in practice
resources, and limitations unique to
the institution or type of practice.
More than 22% of all gravid women undergo induction of labor in the United
States, and the overall rate of induction of labor in the United States has more
than doubled since 1990 to 225 per 1,000 live births in 2006 (1). The goal of
induction of labor is to achieve vaginal delivery by stimulating uterine contractions before the spontaneous onset of labor. Generally, induction of labor
has merit as a therapeutic option when the benefits of expeditious delivery outweigh the risks of continuing the pregnancy. The benefits of labor induction
must be weighed against the potential maternal and fetal risks associated with
this procedure (2). The purpose of this document is to review current methods
for cervical ripening and induction of labor and to summarize the effectiveness
of these approaches based on appropriately conducted outcomes-based
research. These practice guidelines classify the indications for and contraindications to induction of labor, describe the various agents used for cervical
ripening, cite methods used to induce labor, and outline the requirements for the
safe clinical use of the various methods of inducing labor.
Background
In 1948, Theobald and associates described their use of the posterior pituitary
extract, oxytocin, by intravenous drip for labor induction (3). Five years later,
oxytocin was the first polypeptide hormone synthesized by du Vigneaud and
associates (4). This synthetic polypeptide hormone has since been used to stimulate uterine contractions. Other methods used for induction of labor include
membrane stripping, amniotomy, nipple stimulation, and administration of
prostaglandin E analogues.
OBSTETRICIANS AND
GYNECOLOGISTS
Cervical Ripening
The goal of cervical ripening is to facilitate the process of cervical softening,
thinning, and dilating with resultant reduction in the rate of failed induction and
PRACTICE BULLETINS
induction to delivery time. Cervical remodeling is a critical component of normal parturition. Observed changes
not only include collagen breakdown and rearrangement
but also changes in the glycosaminoglycans, increased
production of cytokines, and white blood cell infiltration
(5). If induction is indicated and the status of the cervix
is unfavorable, agents for cervical ripening may be used.
The status of the cervix can be determined by the Bishop
pelvic scoring system (Table 1) (6). An unfavorable cervix generally has been defined as a Bishop score of 6 or
less in most randomized trials. If the total score is more
than 8, the probability of vaginal delivery after labor
induction is similar to that after spontaneous labor.
Effective methods for cervical ripening include the
use of mechanical cervical dilators and administration of
synthetic prostaglandin E1 (PGE1) and prostaglandin E2
(PGE2) (710). Mechanical dilation methods are effective in ripening the cervix and include hygroscopic dilators, osmotic dilators (Laminaria japonicum), Foley
catheters (1426 F) with inflation volume of 3080 mL,
double balloon devices (Atad Ripener Device), and
extraamniotic saline infusion using infusion rates of
3040 mL/h (1119). Laminaria japonicum ripens the
cervix but may be associated with increased peripartum
infections (7, 20). In women undergoing induction with
an unfavorable cervix, mechanical methods, except
extraamniotic saline infusion, are associated with a
decreased cesarean delivery rate when compared with
oxytocin alone (18). Multiple studies have demonstrated
the efficacy of mechanical cervical dilators. There is
insufficient evidence to assess how effective (vaginal
delivery within 24 hours) mechanical methods are compared with prostaglandins (18). Advantages of the Foley
catheter include low cost when compared with
prostaglandins, stability at room temperature, and
reduced risk of uterine tachysystole with or without fetal
heart rate (FHR) changes (18, 21).
Misoprostol, a synthetic PGE1 analogue, can be
administered intravaginally, orally, or sublingually and is
used for both cervical ripening and induction of labor. It
currently is available in a 100-mcg (unscored) or a 200mcg tablet, and can be broken to provide 25-mcg or 50mcg doses. There is extensive clinical experience with
this agent and a large body of published reports supporting its safety and efficacy when used appropriately. No
studies indicate that intrapartum exposure to misoprostol
(or other prostaglandin cervical ripening agents) has any
long-term adverse health consequences to the fetus in the
absence of fetal distress, nor is there a plausible biologic
basis for such a concern. Although misoprostol currently
is approved by the U.S. Food and Drug Administration
(FDA) for the prevention of peptic ulcers, the FDA in
2002 approved a new label on the use of misoprostol
during pregnancy for cervical ripening and for the induction of labor. This labeling does not contain claims
regarding the efficacy or safety of misoprostol, nor does
it stipulate doses or dose intervals. The majority of adverse maternal and fetal outcomes associated with misoprostol therapy resulted from the use of doses greater than
25 mcg.
Two PGE2 preparations are commercially available:
a gel available in a 2.5-mL syringe containing 0.5 mg of
dinoprostone and a vaginal insert containing 10 mg of
dinoprostone. Both are approved by the FDA for cervical ripening in women at or near term. The vaginal insert
releases prostaglandins at a slower rate (0.3 mg/h) than
the gel. Compared with placebo or oxytocin alone, vaginal prostaglandins used for cervical ripening increase the
likelihood of delivery within 24 hours, do not reduce the
rate of cesarean delivery, and increase the risk of uterine
tachysystole with associated FHR changes (22).
Methods of Labor Induction

Oxytocin
Oxytocin is one of the most commonly used drugs in the
United States. The physiology of oxytocin-stimulated
labor is similar to that of spontaneous labor, although
individual patients vary in sensitivity and response to
oxytocin. Based on pharmacokinetic studies of synthetic
Table 1. Bishop Scoring System

Factor
Score
Position of Cervix
Effacement (%)
Station*
Cervical Consistency
Closed
Posterior
030
Firm
12
Midposition
4050
Medium
34
Anterior
6070
1, 0
Soft
56
80
+1, +2
Dilation (cm)
1123
*Station reflects a 3 to +3 scale.

Modified from Bishop EH. Pelvic scoring for elective induction. Obstet Gynecol 1964;24:267.
1124
oxytocin, uterine response ensues after 35 minutes of

infusion, and a steady level of oxytocin in plasma is
achieved by 40 minutes (23). The uterine response to
oxytocin depends on the duration of the pregnancy; there
is a gradual increase in response from 20 to 30 weeks of
gestation, followed by a plateau from 34 weeks of gestation until term, when sensitivity increases (24). Lower
body mass index and greater cervical dilation, parity, or
gestational age are predictors of successful response to
oxytocin for induction (25).
Membrane Stripping
Stripping or sweeping the amniotic membranes is commonly practiced to induce labor. Significant increases in
phospholipase A2 activity and prostaglandin F2 (PGF2)
levels occur from membrane stripping (26). Stripping
membranes increases the likelihood of spontaneous
labor within 48 hours and reduces the incidence of induction with other methods (27). Although membrane sweeping has been associated with increased risk of prelabor
rupture of membranes (28), other published systematic
reviews, including one with 1,525 women, have not
corroborated this finding (27). Women who undergo
membrane stripping may experience discomfort from the
procedure as well as vaginal bleeding and irregular uterine contractions within the ensuing 24 hours (27). There
are insufficient data to guide clinical practice for membrane stripping in women whose group B streptococcus
culture is positive.
Amniotomy
Artificial rupture of the membranes may be used as a
method of labor induction, especially if the condition of
the cervix is favorable. Used alone for inducing labor,
amniotomy can be associated with unpredictable and
sometimes long intervals before the onset of contractions. There is insufficient evidence on the efficacy and
safety of amniotomy alone for labor induction (29). In a
trial of amniotomy combined with early oxytocin infusion
compared with amniotomy alone, the induction-to-delivery interval was shorter with the amniotomy-plus-oxytocin method (30). There are insufficient data to guide the
timing of amniotomy in patients who are receiving intrapartum prophylaxis for group B streptococcal infection.
Nipple Stimulation
Nipple stimulation or unilateral breast stimulation has
been used as a natural and inexpensive nonmedical
method for inducing labor. In a systematic review of 6
trials including 719 women that compared breast stimulation with no intervention, a significant decrease in the
number of women not in labor at 72 hours was noted, but
only in women with favorable cervices (31). None of the

women had uterine tachysystole with or without FHR
changes, and there were no differences in meconiumstained amniotic fluid or cesarean delivery rates (31).
Breast stimulation was associated with a decrease in
postpartum hemorrhage (31). This method has only been
studied in low-risk pregnancies.
Labor Induction Terminology

At a 2008 workshop sponsored by the American College
of Obstetricians and Gynecologists, the Eunice Kennedy
Shriver National Institute of Child Health and Human
Development, and the Society for MaternalFetal Medicine on intrapartum electronic FHR monitoring, the definitions for FHR pattern categorization were reviewed and
updated. The existing classification systems for FHR patterns were assessed and new recommendations for use in
the United States were made (32). In particular, it was
determined that the terms hyperstimulation and hypercontractility should be abandoned. It was recommended that
the term tachysystole, with or without corresponding FHR
decelerations, be used instead.
Uterine Contractions
Uterine contractions are quantified as the number of contractions present in a 10-minute window, averaged over
30 minutes. Contraction frequency alone is a partial assessment of uterine activity. Other factors such as duration,
intensity, and relaxation time between contractions are
equally important in clinical practice. The following represents terminology to describe uterine activity:
Normal: Five contractions or less in 10 minutes,
averaged over a 30-minute window
Tachysystole: More than five contractions in 10 minutes, averaged over a 30-minute window
Listed are characteristics of uterine contractions:
Tachysystole should always be qualified as to the
presence or absence of associated FHR decelerations.
The term tachysystole applies to both spontaneous
and stimulated labor. The clinical response to tachysystole may differ depending on whether contractions are spontaneous or stimulated.
The majority of literature cited in this Practice
Bulletin was published prior to the 2008 NICHD definitions and interpretations of FHR tracings. Consequently,
it is difficult to generalize the results of the cited literature, which used nonstandardized and ambiguous definitions for FHR patterns.
PRACTICE BULLETINS

Recommendations
What are the indications and contraindications to induction of labor?
Indications for induction of labor are not absolute but
should take into account maternal and fetal conditions,
gestational age, cervical status, and other factors.
Following are examples of maternal or fetal conditions
that may be indications for induction of labor:
Abruptio placentae
Chorioamnionitis
Fetal demise
Gestational hypertension
Preeclampsia, eclampsia
Premature rupture of membranes
Postterm pregnancy
Maternal medical conditions (eg, diabetes mellitus,
renal disease, chronic pulmonary disease, chronic
hypertension, antiphospholipid syndrome)
Fetal compromise (eg, severe fetal growth restriction, isoimmunization, oligohydramnios)
Labor also may be induced for logistic reasons, for
example, risk of rapid labor, distance from hospital, or
psychosocial indications. In such circumstances, at least
one of the gestational age criteria in the box should be
met, or fetal lung maturity should be established. A
mature fetal lung test result before 39 weeks of gestation,
in the absence of appropriate clinical circumstances, is
not an indication for delivery.
The individual patient and clinical situation should
be considered in determining when induction of labor is
contraindicated. Generally, the contraindications to labor
induction are the same as those for spontaneous labor
and vaginal delivery. They include, but are not limited to,
the following situations:
Vasa previa or complete placenta previa

Transverse fetal lie
Umbilical cord prolapse
Previous classical cesarean delivery
Active genital herpes infection
Previous myomectomy entering the endometrial cavity
What criteria should be met before the cervix

is ripened or labor is induced?
Assessment of gestational age and consideration of any
potential risks to the mother or fetus are of paramount
1125
Confirmation of Term Gestation

Ultrasound measurement at less than 20 weeks of
gestation supports gestational age of 39 weeks or
greater.
Fetal heart tones have been documented as present
for 30 weeks by Doppler ultrasonography.
It has been 36 weeks since a positive serum or urine
human chorionic gonadotropin pregnancy test result.
importance for appropriate evaluation and counseling

before initiating cervical ripening or labor induction. The
patient should be counseled regarding the indications for
induction, the agents and methods of labor stimulation,
and the possible need for repeat induction or cesarean
delivery. Although prospective studies are limited in
evaluating the benefits of elective induction of labor, nulliparous women undergoing induction of labor with
unfavorable cervices should be counseled about a twofold increased risk of cesarean delivery (33, 34, 35). In
addition, labor progression differs significantly for
women with an elective induction of labor compared
with women who have spontaneous onset of labor (36).
Allowing at least 1218 hours of latent labor before
diagnosing a failed induction may reduce the risk of
cesarean delivery (37, 38).
Additional requirements for cervical ripening and
induction of labor include assessment of the cervix,
pelvis, fetal size, and presentation. Monitoring FHR and
uterine contractions is recommended as for any high-risk
patient in active labor. Although trained nursing personnel can monitor labor induction, a physician capable
of performing a cesarean delivery should be readily
available.
What is the relative effectiveness of available

methods for cervical ripening in reducing the
duration of labor?
A systematic review found that in patients with an unfavorable cervix, Foley catheter placement before oxytocin
induction significantly reduced the duration of labor
(21). This review also concluded that catheter placement
resulted in a reduced risk of cesarean delivery. When the
Foley catheter was compared with PGE2 gel, the majority
of the studies have found no difference in duration of
induction to delivery or cesarean delivery rate. The use
of prostaglandins is associated with an increased risk of
tachysystole with or without FHR changes when compared with the Foley catheter (21). The use of different
size Foley catheters, insufflation volumes, as well as dif-
1126
ferent misoprostol protocols, yields inconsistent results

to determine induction to delivery times, cesarean delivery rate, and risk of meconium passage (18, 21). The
addition of oxytocin along with the use of the Foley
catheter does not appear to shorten the time of delivery
in a randomized controlled trial (39).
Studies examining extraamniotic saline infused
through the Foley catheter compared with use of the
Foley catheter with concurrent oxytocin administration
report conflicting results on the time from induction to
delivery (19, 40, 41). Differences in methodology could
explain the opposing findings. The Foley catheter is a
reasonable and effective alternative for cervical ripening
and inducing labor.
Intracervical or intravaginal PGE2 (dinoprostone)
commonly is used and is superior to placebo or no therapy
in promoting cervical ripening (42). Several prospective
randomized clinical trials and two meta-analyses have
demonstrated that PGE1 (misoprostol) is an effective
method for cervical ripening (4348). Misoprostol administered intravaginally has been reported to be either superior to or as efficacious as dinoprostone gel (4851).
Vaginal misoprostol has been associated with less use of
epidural analgesia, more vaginal deliveries within 24
hours, and more uterine tachysystole with or without FHR
changes compared with dinoprostone and oxytocin (48).
In contrast, misoprostol compared with oxytocin for cervical ripening resulted in longer intervals to active labor
and delivery in a randomized controlled trial (52). It is difficult, however, to compare the results of studies on misoprostol because of differences in endpoints, including
Bishop score, duration of labor, total oxytocin use, successful induction, and cesarean delivery rate. Pharmacologic methods for cervical ripening do not decrease the
likelihood of cesarean delivery.
How should prostaglandins be administered?

One quarter of an unscored 100-mcg tablet (ie, approximately 25 mcg) of misoprostol should be considered as
the initial dose for cervical ripening and labor induction.
The frequency of administration should not be more than
every 36 hours. In addition, oxytocin should not be
administered less than 4 hours after the last misoprostol
dose. Misoprostol in higher doses (50 mcg every 6
hours) may be appropriate in some situations, although
higher doses are associated with an increased risk of
complications, including uterine tachysystole with FHR
decelerations.
If there is inadequate cervical change with minimal
uterine activity after one dose of intracervical dinoprostone, a second dose may be given 612 hours later. The
manufacturers recommend a maximum cumulative dose
of 1.5 mg of dinoprostone (three doses or 7.5 mL of gel)

within a 24-hour period. A minimum safe time interval
between prostaglandin administration and initiation of
oxytocin has not been determined. According to the
manufacturers guidelines, after use of 1.5 mg of dinoprostone in the cervix or 2.5 mg in the vagina, oxytocin
induction should be delayed for 612 hours because the
effect of prostaglandins may be heightened with oxytocin. After use of dinoprostone in sustained-release
form, delaying oxytocin induction for 3060 minutes
after removal is sufficient. Limited data are available on
the use of buccal or sublingual misoprostol for cervical
ripening or induction of labor, and these methods are not
recommended for clinical use until further studies support their safety (53).
What are the potential complications with

each method of cervical ripening, and how
are they managed?
Tachysystole with or without FHR changes is more
common with vaginal misoprostol compared with vaginal
prostaglandin E2, intracervical prostaglandin E2, and oxytocin (48). Tachysystole (defined in some studies as greater
than 5 uterine contractions in 10 minutes in consecutive
10-minute intervals) and tachysystole with associated
FHR decelerations are increased with a 50-mcg or greater
dose of misoprostol (43, 47, 48, 54). There seems to be
a trend toward lower rates of uterine tachysystole with
FHR changes with lower dosages of misoprostol (25
mcg every 6 hours versus every 3 hours) (48).
The use of misoprostol in women with prior cesarean delivery or major uterine surgery has been associated
with an increase in uterine rupture and, therefore, should
be avoided in the third trimester (55, 56). An increase in
meconium-stained amniotic fluid also has been reported
with misoprostol use (47, 48). Although misoprostol appears
to be safe and effective in inducing labor in women with
unfavorable cervices, further studies are needed to determine the optimal route, dosage, timing interval, and pharmacokinetics of misoprostol. Moreover, data are needed on
the management of complications related to misoprostol
use and when it should be discontinued. If uterine tachysystole and a Category III FHR tracing (defined as either
a sinusoidal pattern or an absent baseline FHR variability
and any of the following: recurrent late decelerations, recurrent variable decelerations, or bradycardia) occurs with
misoprostol use and there is no response to routine corrective measures (maternal repositioning and supplemental oxygen administration), cesarean delivery should be
considered (32). Subcutaneous terbutaline also can be used
in an attempt to correct the Category III FHR tracing or
uterine tachysystole.
PRACTICE BULLETINS
The intracervical PGE2 gel (0.5 mg) has a 1% rate of

uterine tachysystole with associated FHR changes while
the intravaginal PGE2 gel (25 mg) or vaginal insert is
associated with a 5% rate (42, 57, 58). Uterine tachysystole typically begins within 1 hour after the gel or insert
is placed but may occur up to 9 1/2 hours after the vaginal insert has been placed (5759).
Removing the PGE2 vaginal insert usually will help
reverse the effect of uterine tachysystole. Irrigation of the
cervix and vagina is not beneficial. Maternal side effects
from the use of low-dose PGE2 (fever, vomiting, and diarrhea) are quite uncommon (60). Prophylactic antiemetics,
antipyretics, and antidiarrheal agents usually are not
needed. The manufacturers recommend that caution be
exercised when using PGE2 in patients with glaucoma,
severe hepatic or renal dysfunction, or asthma. However,
PGE2 is a bronchodilator, and there are no reports of bronchoconstriction or significant blood pressure changes after
the administration of the low-dose gel.
Increased maternal and neonatal infections have been
reported in connection with the use of Laminaria japonicum and hygroscopic dilators when compared with the
PGE2 analogues (7, 13, 20). The Foley catheter can cause
significant vaginal bleeding in women with a low-lying
placenta (21). Other reported complications include rupture of membranes, febrile morbidity, and displacement of
the presenting part (61).
What are the recommended guidelines for

fetal surveillance after prostaglandin use?
The prostaglandin preparations should be administered
where uterine activity and the FHR can be monitored
continuously for an initial observation period. Further
monitoring can be governed by individual indications for
induction and fetal status.
The patient should remain recumbent for at least 30
minutes. The FHR and uterine activity should be monitored continuously for a period of 30 minutes to 2 hours
after administration of the PGE2 gel (62). Uterine contractions usually are evident in the first hour and exhibit
peak activity in the first 4 hours (62, 63). The FHR
monitoring should be continued if regular uterine contractions persist; maternal vital signs also should be
recorded.
Are cervical ripening methods appropriate in

an outpatient setting?
Limited information is available on the safety of outpatient management of induction of labor. In a randomized,
double-blind, controlled trial comparing 2 mg of intravaginal PGE2 gel with placebo for 5 consecutive days as
1127
an outpatient procedure, it was noted that PGE2 gel was

effective and safe for initiation of labor in women at term
with a Bishop score of 6 or less (64). No significant differences in adverse outcomes were noted in another randomized trial of 300 women at term comparing the use
of controlled-release PGE2 in an outpatient versus inpatient setting (65). Larger controlled studies are needed to
establish an effective and safe dose and vehicle for PGE2
before use on an outpatient basis can be recommended.
However, outpatient use may be appropriate in carefully
selected patients. Mechanical methods may be particularly appropriate in the outpatient setting. A randomized
trial comparing the Foley catheter in an outpatient versus
inpatient setting for preinduction cervical ripening
demonstrated similar efficacy and safety with a reduction of hospital stay of 9.6 hours (66).
What are the potential complications of

various methods of induction?
The side effects of oxytocin use are principally dose
related; uterine tachysystole and Category II or III FHR
tracings are the most common side effects. Uterine tachysystole may result in abruptio placentae or uterine rupture.
Uterine rupture secondary to oxytocin use is rare even in
parous women (67). Water intoxication can occur with
high concentrations of oxytocin infused with large quantities of hypotonic solutions, but is rare in doses used for
labor induction.
Misoprostol appears to be safe and beneficial for
inducing labor in a woman with an unfavorable cervix.
Although the exact incidence of uterine tachysystole
with or without FHR changes is unknown and the criteria used to define this complication are not always clear
in the various reports, there are reports of uterine
tachysystole with or without FHR changes occurring
more frequently in women given misoprostol compared
with women given PGE2 (43, 45, 48, 68). There does not
appear to be a significant increase in adverse fetal outcomes from tachysystole without associated FHR decelerations (68, 69). The occurrence of complications does
appear to be dose-dependent (10, 48). Clinical trials have
shown that at an equivalent dosage, the vaginal route
produces greater clinical efficacy than the oral route
(53). Oral misoprostol administration is associated with
fewer abnormal FHR patterns and episodes of uterine
tachy-systole with associated FHR changes when compared with vaginal administration (70, 71).
The potential risks associated with amniotomy
include prolapse of the umbilical cord, chorioamnionitis,
significant umbilical cord compression, and rupture of
vasa previa. The physician should palpate for an umbilical cord and avoid dislodging the fetal head. The FHR
1128
should be assessed before and immediately after amniotomy. Amniotomy for induction of labor may be contraindicated in women known to have HIV infection
because duration of ruptured membranes has been identified as an independent risk factor for vertical transmission of HIV infection (29).
Stripping the amniotic membranes is associated with
bleeding from undiagnosed placenta previa or low-lying
placenta, and accidental amniotomy. Bilateral breast stimulation has been associated with uterine tachysystole with
associated FHR decelerations. In a systematic review,
breast stimulation was associated with an increased trend
in perinatal death (31). Until safety issues are studied further, this practice is not recommended in an unmonitored
setting.
is diluted 10 units in 1,000 mL of an isotonic solution for

an oxytocin concentration of 10 mU/mL. Oxytocin should
be administered by infusion using a pump that allows
precise control of the flow rate and permits accurate
minute-to-minute control. Bolus administration of oxytocin can be avoided by piggybacking the infusion into
the main intravenous line near the venipuncture site.
A numeric value for the maximum dose of oxytocin
has not been established. The FHR and uterine contractions should be monitored closely. Oxytocin should be
administered by trained personnel who are familiar with
its effects.
When oxytocin is used for induction of labor,

what dosage should be used and what precautions should be taken?
If uterine tachysystole with Category III FHR tracings

occur, prompt evaluation is required and intravenous
infusion of oxytocin should be decreased or discontinued to correct the pattern (32). Additional measures may
include turning the woman on her side and administering oxygen or more intravenous fluid. If uterine
tachysystole persists, use of terbutaline or other tocolytics may be considered. Hypotension may occur following a rapid intravenous injection of oxytocin; therefore,
it is imperative that a dilute oxytocin infusion be used
even in the immediate puerperium.
Any of the low- or high-dose oxytocin regimens outlined

in Table 2 are appropriate for labor induction (7278).
Low-dose regimens and less frequent increases in dose
are associated with decreased uterine tachysystole with
associated FHR changes (70). High-dose regimens and
more frequent dose increases are associated with shorter
labor and less frequent cases of chorioamnionitis and
cesarean delivery for dystocia, but increased rates of uterine tachysystole with associated FHR changes (74, 79).
Each hospitals obstetrics and gynecology department should develop guidelines for the preparation and
administration of oxytocin. Synthetic oxytocin generally
Table 2. Labor Stimulation with Oxytocin: Examples of Lowand High-Dose Oxytocin
Regimen
Starting
Dose
Incremental
Increase (mU/min)
Dosage
Interval (min)
Low-Dose
High-Dose
0.52
12
1540
36*
1540
*The incremental increase is reduced to 3 mU/min in presence of hyperstimulation and reduced to 1 mU/min with recurrent hyperstimulation.
Data from Hauth JC, Hankins GD, Gilstrap LC 3rd, Strickland DM, Vance P.
Uterine contraction pressures with oxytocin induction/augmentation. Obstet
Gynecol 1986;68:3059; Satin AJ, Leveno KJ, Sherman ML, Brewster DS,
Cunningham FG. High- versus low-dose oxytocin for labor stimulation. Obstet
Gynecol 1992;80:1116; Crane JM, Young DC. Meta-analysis of low-dose versus
high-dose oxytocin for labour induction. J SOGC 1998;20:121523; Cummiskey
KC, Dawood MY. Induction of labor with pulsatile oxytocin. Am J Obstet Gynecol
1990;163:186874; Blakemore KJ, Qin NG, Petrie RH, Paine LL. A prospective
comparison of hourly and quarter-hourly oxytocin dose increase intervals for the
induction of labor at term. Obstet Gynecol 1990;75:75761; Mercer B, Pilgrim
P, Sibai B. Labor induction with continuous low-dose oxytocin infusion: a randomized trial. Obstet Gynecol 1991;77:65963; and Muller PR, Stubbs TM,
Laurent SL. A prospective randomized clinical trial comparing two oxytocin
induction protocols. Am J Obstet Gynecol 1992;167:37380; discussion 3801.
How should complications associated with

oxytocin use be managed?
Are there special considerations that apply

for induction in a woman with ruptured
membranes?
The largest randomized study to date found that oxytocin induction reduced the time interval between premature rupture of membranes and delivery as well as the
frequencies of chorioamnionitis, postpartum febrile morbidity, and neonatal antibiotic treatments, without increasing cesarean deliveries or neonatal infections (80). These
data suggest that for women with premature rupture of
membranes at term, labor should be induced at the time of
presentation, generally with oxytocin infusion, to reduce
the risk of chorioamnionitis. An adequate time for the
latent phase of labor to progress should be allowed.
The same precautions should be exercised when
prostaglandins are used for induction of labor with ruptured membranes as for intact membranes. Intravaginal
PGE2 for induction of labor in women with premature
rupture of membranes appears to be safe and effective
(81). In a randomized study of labor induction in women
with premature rupture of membranes at term, only one
dose of intravaginal misoprostol was necessary for successful labor induction in 86% of the patients (67).
There is no evidence that use of either of these prostag-
PRACTICE BULLETINS
landins increases the risk of infection in women with

ruptured membranes (67, 81). There is insufficient evidence to guide the physician on use of mechanical dilators in women with ruptured membranes.
A meta-analysis that included 6,814 women with premature rupture of membranes at term compared induction
of labor with prostaglandins or oxytocin to expectant
management (82). A significant reduction in the risk of
women developing chorioamnionitis or endometritis and a
reduced number of neonates requiring admission to the
neonatal intensive care unit was noted in the women who
underwent induction of labor compared with expectant
management (82).
What methods can be used for induction of

labor with intrauterine fetal demise in the
late second or third trimester?
The method and timing of delivery after a fetal death
depends on the gestational age at which the death occurred, on the maternal history of a previous uterine scar, and
maternal preference. Although most patients will desire
prompt delivery, the timing of delivery is not critical;
coagulopathies are associated with prolonged fetal retention and are uncommon. In the second trimester, dilation
and evacuation can be offered if an experienced health
care provider is available, although patients should be
counseled that dilation and evacuation may limit efficacy
of autopsy for the detection of macroscopic fetal abnormalities.
Labor induction is appropriate at later gestational
ages, if second-trimester dilation and evacuation is unavailable, or based on patient preference. Much of the
data for management of fetal demise has been extrapolated from randomized trials of management of second
trimester pregnancy termination. Available evidence from
randomized trials supports the use of vaginal misoprostol as a medical treatment to terminate nonviable pregnancies before 24 weeks of gestation (83). Based on
limited data, the use of misoprostol between 24 to 28
weeks of gestation also appears to be safe and effective
(84, 85). Before 28 weeks of gestation, vaginal misoprostol appears to be the most efficient method of labor
induction, regardless of cervical Bishop score (84, 86),
although high-dose oxytocin infusion also is an acceptable choice (87, 88). Typical dosages for misoprostol use
are 200400 mcg vaginally every 412 hours. After 28
weeks of gestation, induction of labor should be managed
according to usual obstetric protocols. Cesarean delivery
for fetal demise should be reserved for unusual circumstances because it is associated with potential maternal
morbidity without any fetal benefit.
1129
Several studies have evaluated the use of misoprostol at a dosage of 400 mcg every 6 hours in women with
a stillbirth up to 28 weeks of gestation and a prior uterine scar (85, 89). There does not appear to be an increase
in complications in those women. Further research is
required to assess effectiveness and safety, optimal route
of administration, and dose.
In patients after 28 weeks of gestation, cervical ripening with a transcervical Foley catheter has been associated
with uterine rupture rates comparable to spontaneous
labor (90) and this may be a helpful adjunct in patients
with an unfavorable cervical assessment. Therefore, in
patients with a prior low transverse cesarean delivery, trial
of labor remains a favorable option. There are limited data
to guide clinical practice in a patient with a prior classical
cesarean delivery, and the delivery plan should be individualized.
Summary of
Recommendations and
Conclusions
Prostaglandin E analogues are effective for cervical
ripening and inducing labor.
Low- or high-dose oxytocin regimens are appropriate for women in whom induction of labor is indicated (Table 2).
Before 28 weeks of gestation, vaginal misoprostol
appears to be the most efficient method of labor
induction regardless of Bishop score, although highdose oxytocin infusion also is an acceptable choice.
Approximately 25 mcg of misoprostol should be
considered as the initial dose for cervical ripening
and labor induction. The frequency of administration should not be more than every 36 hours.
Intravaginal PGE2 for induction of labor in women
with premature rupture of membranes appears to be
safe and effective.
The use of misoprostol in women with prior cesarean
delivery or major uterine surgery has been associated
with an increase in uterine rupture and, therefore,
should be avoided in the third trimester.
The Foley catheter is a reasonable and effective
alternative for cervical ripening and inducing labor.
1130
The following recommendation is based on evidence that may be limited or inconsistent (Level B)
12. Blumenthal PD, Ramanauskas R. Randomized trial of

Dilapan and Laminaria as cervical ripening agents before
induction of labor. Obstet Gynecol 1990;75:3658. (Level I)
Misoprostol (50 mcg every 6 hours) to induce labor

may be appropriate in some situations, although
higher doses are associated with an increased risk of
complications, including uterine tachysystole with
FHR decelerations.
13. Chua S, Arulkumaran S, Vanaja K, Ratnam SS. Preinduction cervical ripening: prostaglandin E2 gel vs hygroscopic
mechanical dilator. J Obstet Gynaecol Res 1997;23:
1717. (Level I)
Measure
Percentage of patients in whom gestational age is established by clinical criteria when labor is being induced for
logistic or psychosocial indications
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85. Dickinson JE. Misoprostol for second-trimester pregnancy

termination in women with a prior cesarean delivery.
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89. Daskalakis GJ, Mesogitis SA, Papantoniou NE,
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1133

Task Force:
I

type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Induction of labor. ACOG Practice Bulletin No. 107. American College
38697.
1134
ACOG BULLETIN
EDUCATIONAL
Obstetric Aspects of Trauma

Management
This Educational Bulletin was developed

under the direction of the Committee on
Educational Bulletins of the American College of Obstetricians and Gynecologists as
an aid to obstetricians and gynecologists.
The College wishes to thank Mark
Pearlman, MD, and Cosmas van de Ven,
MD, for their assistance in the development
of this bulletin. This document is not to be
construed as establishing a standard of
practice or dictating an exclusive course of
treatment. Rather, it is intended as an educational tool that presents current information on obstetricgynecologic issues.
Reaffirmed 2006
Trauma has become one of the leading causes of morbidity and mortality of
women in the world, resulting in nearly one million deaths each year. It also has
become one of the leading causes of morbidity and mortality during pregnancy
(1, 2). It is estimated that physical trauma complicates approximately 1 in every
12 pregnancies, with motor vehicle crashes being the most significant contributor to fetal death due to trauma (3). Nearly 50,000 of the estimated 250 million
people in the United States die each year from motor vehicle crashes. This rate is
equivalent to approximately 20 deaths due to motor vehicle crashes for every
100,000 persons in the United States.
The incidence and severity of injuries can be lessened by the appropriate use
of automobile safety restraints. Physicians should counsel patients about such use
and reassure them of the safety of these devices during pregnancy. Despite these
precautions, injuries will occur during pregnancy and obstetriciangynecologists
should be equipped to handle them.
Optimum management of the seriously injured pregnant woman requires an
integrated effort of multiple specialties, starting with emergency medical technicians, emergency medicine physicians, trauma surgeons, and other specialists,
depending on the type of injury. Obstetricians play a central role in the management of injured pregnant women. Their knowledge and expertise are vital to
management decisions regarding both the woman and the fetus. The effects of
various drugs on uterine blood flow, potential teratogenic and mutagenic effects
of diagnostic radiation and medications, the effect of surgery on pregnancy, and
the assessment of gestational age are critical management issues. In addition,
complications of pregnancy unrelated to the trauma may be superimposed in the
injured gravida (eg, pregnancy-induced hypertension, placenta previa) and are
best managed by the obstetrician. The obstetrician may be consulted regarding
the condition of a pregnant trauma patient or, more commonly, may be the primary physician caring for the patient following trauma. In either case, the approach must be systematic, ensuring that the woman is medically stable prior to
evaluation of the fetus.
Obstetricians who are involved with the care of pregnant trauma patients
should seek consultation with experienced trauma surgeons. It also is helpful
for all physicians to be knowledgeable about advanced trauma life-support
measures.
Replaces Number 151, January 1991, and Number 161, November 1991
PRACTICE BULLETINS
Incidence
In industrialized nations, approximately two thirds of all
trauma during pregnancy results from motor vehicle
crashes. Other frequent causes of trauma during pregnancy are falls and direct assaults to the abdomen (3, 4).
According to the National Safety Council, female drivers
are more likely to be involved in automobile accidents
than male drivers (84 female drivers versus 73 male drivers per 10 million miles driven) (5).
Domestic violence has reached epidemic proportion
in the United States. It is estimated that approximately 2
million women per year are reported to have been assaulted by their male partners (6). Researchers have found a
prevalence of violence against pregnant women ranging
from 1% to 20% (7). Domestic violence and battery were
found to occur in 1 of every 12 pregnant women in an
inner-city setting (8). Among victims of physical abuse,
moderate or severe violence during pregnancy was
reported by 20% of women in the Baltimore area, 17% in
Houston, 7% in Galveston, and 7% in Toronto (9, 10).
Sixty percent of victims report two or more episodes of
physical assault during pregnancy (11). This latter statistic emphasizes the importance of early identification of
physical abuse during pregnancy and implementation of
effective intervention methods, which are discussed elsewhere (6).
Maternal Mortality
Trauma, either accidental (as in traffic accidents) or intentional (as in homicide or domestic violence), is a leading
cause of death in women of reproductive age (1). Trauma
also is the leading cause of nonobstetric maternal death
(12); for example, it accounted for an average of 22% of
all maternal deaths in Iowa and caused nearly one half of
95 maternal deaths from 1986 to 1989 in Cook County,
Illinois (2).
Fetal Mortality
Accurate statistics on the number of fetal losses due to
trauma each year are not available. Estimates extrapolated from published case series suggest that between 1,300
and 3,900 pregnancies are lost each year in the United
States as a result of trauma (13).
Life-threatening maternal trauma (eg, maternal
shock, head injury resulting in coma, emergency
laparotomy for maternal indications) is associated with a
4050% fetal loss rate, whereas minor or nonlife-threatening injuries resulted in a 15% pregnancy loss (14).
Because minor injuries are more common, most fetal
losses result from minor maternal injuries (4, 15, 16). It is
estimated that abruptio placentae is a complication in
4050% of pregnant women who sustain severe trauma,
compared with the 15% incidence in pregnant women
1135
who experience nonlife-threatening trauma (4, 1619).

Several series of fetal losses resulting from trauma indicate that more than 50% of fetal losses occur in association with seemingly minor or insignificant maternal trauma
(4, 15, 16, 18, 20).
Numerous retrospective studies have attempted to
predict fetal or neonatal outcome based on an injury
severity score. However, one study suggests that injury
severity scoring is not a good predictor of adverse fetal
outcome (21).
Types of Trauma
Blunt Abdominal Trauma
The evaluation and management of blunt abdominal
trauma during pregnancy involves several key issues.
Gestational age at the time of injury, extent and severity
of maternal injury, and mechanism of injury should be
considered.
The gestational age at the time of injury is valuable
in determining the need for fetal assessment as well as in
managing the mothers condition. The possibility of fetal
viability in an extrauterine environment (ie, beyond
2426 weeks of gestation) can significantly change management decisions if there is evidence of fetal compromise. Furthermore, enlargement of the uterus beyond
1820 weeks of gestation compresses both the inferior
vena cava and aorta in the supine position, increasing the
likelihood of hypotension and decreased uterine perfusion. Finally, the type of maternal and fetal injury patterns
may depend to a great extent on gestational age at the
time of injury. For example, direct injury to the uterus and
fetus prior to 13 weeks of gestation is extremely unlikely
because they are protected by the bony pelvis. Generally,
trauma in the first trimester does not cause pregnancy
loss, with the exception of profound hypotension and
associated hypoperfusion of the uterus and its contents.
Although it is not the highest priority in managing the
injured gravida, gestational age should be assessed as
soon as feasible.
Fetal loss resulting from blunt abdominal trauma
may result from abruptio placentae or other placental
injury, direct fetal injury, uterine rupture, maternal shock,
or death or some combination thereof. Several studies of
trauma and fetal loss show that at least 50% of fetal losses with known etiology were the result of abruptio placenta (4, 15, 16, 18). In one report of severe car crashes
involving pregnant women, maternal loss of life was the
most frequent cause of fetal death (17).
There are several potential mechanisms of abruptio
placentae due to trauma. Differences in tissue properties
between the elastic myometrium and the relatively inelas-
1136
tic placenta can result in a shearing at the tissue interface.

Because fluid is noncompressible, intrusion of the elastic
uterine wall will result in displacement of amniotic fluid
and distention of the other parts of the uterus. Therefore,
a shear force can occur regardless of placental location.
The risk of abruptio placentae appears to be independent
of the placental location (3).
Direct fetal injury (eg, skull fracture) complicates
less than 1% of all pregnancies in which trauma occurs.
Although case reports of fetal skull fractures have been
described following relatively minor trauma, most cases
result from significant maternal injury later in gestation
(22, 23).
Uterine rupture is an infrequent but life-threatening
complication of trauma. It occurs in only 0.6% of all
injuries during pregnancy and tends to complicate trauma
resulting from direct abdominal impact associated with
substantial force (24, 25). The extent of uterine injury can
be variable, and it may result in serosal hemorrhage or
abrasions; avulsion of the uterine vasculature with hemorrhage; complete disruption of the myometrial wall with
extrusion of the fetus, placenta, or umbilical cord into the
abdominal cavity; or complete uterine avulsion. Approximately 75% of reported cases of uterine rupture involve
the fundus. The presentation of uterine rupture can range
from subtle findings (eg, uterine tenderness, nonreassuring fetal heart rate patterns) without changes in maternal
vital signs, to rapid onset of maternal hypovolemic shock.
Signs of peritoneal irritation, such as distention, rebound
tenderness, guarding, and rigidity are frequently detected
upon examination but may be less pronounced during
pregnancy.
Pelvic Fractures
Pelvic fractures may result in significant retroperitoneal
bleeding, which is associated with substantial morbidity
and mortality. When combined with the possibility of intraperitoneal bleeding, pelvic fractures are frequently
associated with hypovolemic shock. Associated injuries
of the bladder or urethral disruption can result in hematuria and also may pose difficulty in placing a urinary
catheter.
Pelvic fracture is not a definite contraindication for
vaginal delivery. Even in the presence of a slightly displaced pelvic fracture, safe vaginal delivery can be accomplished. However, a severe, dislocated, or unstable
fracture or a large healing callus may preclude an attempt
at vaginal delivery.
Penetrating Trauma
Most penetrating abdominal trauma results from gunshot
wounds or stab wounds. Penetrating abdominal trauma
during pregnancy has a remarkably disparate prognosis
for the fetus and the woman (26, 27). Fetal loss due to
penetrating trauma usually occurs through direct injury or

by injury to the cord or placenta. Maternal outcome generally is more favorable because the maternal viscera are
shielded by the uterus and its contents, which absorbs
much of the projectile energy.
The extent and severity of maternal and fetal injury
due to gunshot wounds depends on a number of factors
including the size and velocity of the bullet; the anatomic region penetrated; the angle of entry; deflection of the
bullets trajectory by muscle, bone, or viscera; the gestational age of the fetus; and the distance from which the
bullet was fired. Frequently, more internal damage occurs
than that suggested by the appearance of the entrance
wound.
The enlarged uterus tends to protect the bowel from
injury when stab wounds penetrate the lower abdomen
because the bowel is displaced into the upper abdomen.
However, as a result of cephalad displacement of the
bowel by the enlarging uterus, stab wounds to the upper
abdomen can frequently result in more complex bowel
injury than in the nonpregnant woman.
Management
The primary goal and initial efforts in managing the
injured pregnant woman should be evaluation and stabilization of maternal vital signs. If attention is drawn to the
fetus before the woman is stabilized, serious or lifethreatening maternal injuries may be overlooked, or circumstances that can compromise fetal oxygenation (eg,
maternal hypoxemia, hypovolemia, or supine hypotension) may be ignored, lessening the likelihood of both
maternal and fetal survival.
A systematic approach begins with a primary survey
of the woman by securing and maintaining an airway, ensuring adequate breathing, and maintaining adequate circulatory volume. The placement of two large-bore (1416
gauge) intravenous lines is necessary in most seriously
injured trauma patients. Supplemental oxygen should be
administered by nasal cannula, mask, or endotracheal
intubation as required to maintain a hemoglobin saturation of 90% or greater. Crystalloid in the form of lactated
Ringers solution or normal saline should be given over
the first 3060 minutes of acute resuscitation as a 3:1 replacement based on blood loss. The use of vasopressors
to restore maternal blood pressure should be avoided until
appropriate volume replacement has been administered.
Although these agents may reduce uterine blood flow in
normovolemic patients, they should not be withheld if
needed in the resuscitation of the mother. Displacement
of the uterus off the inferior vena cava and abdominal
aorta with the patient in a supine position is helpful in
trauma patients beyond midpregnancy. This can be effected by having the patient lie in the lateral decubitus posi-
PRACTICE BULLETINS
tion. If the patient must remain supine (eg, if a spinal

injury is suspected or if cardiopulmonary resuscitation is
being administered), manual displacement of the uterus
laterally with a hand or placement of a wedge under a
backboard will accomplish this goal.
Following stabilization, a more detailed secondary
survey of the patient, including fetal evaluation, should
be performed. All body regions must be thoroughly examined. Pregnancy should not alter necessary treatment
and evaluation of the trauma patient. The abdomen is of
particular importance, because a substantial percentage of
serious injuries involve the uterus, intraperitoneal structures, and retroperitoneum. The uterus should be
examined for evidence of gross deformity, tenderness, or
contractions.
Computed tomography can be used to evaluate patients who have suffered significant trauma. Computed
tomographic scanning of the abdomen exposes the fetus
to approximately 3.5 rad, depending on the number and
thickness of the images and the equipment used. As with
any procedure involving ionizing radiation, scanning
closer to the uterus increases fetal exposure. Fetal exposure exceeding 20 rad may be sufficient to induce adverse
effects in early pregnancy (28).
Open peritoneal lavage can be effective in the diagnosis of intraperitoneal hemorrhage during pregnancy
(29). Open lavage with sharp dissection and opening of
the anterior abdominal peritoneum under direct vision,
usually periumbilically, is advocated over a blind needle
insertion to lessen the likelihood of injury to the uterus or
to other displaced intraabdominal organs. Peritoneal
lavage is unnecessary if clinically obvious intraperitoneal
bleeding is present. Following are some indications for
peritoneal lavage after trauma during pregnancy:
Abdominal signs or symptoms suggestive of intraperitoneal bleeding
Altered sensorium
Unexplained shock
Major thoracic injuries
Multiple major orthopedic injuries
Penetrating trauma requires the complete undressing
of the patient for careful inspection of all entrance and
exit wounds because occasionally victims are shot or
stabbed multiple times, and entrance and exit wounds of
high-velocity projectiles are unpredictable. Radiographs
of the area in multiple projections often are helpful to
localize a bullet if an exit wound is not seen. The uterus
and its contents can often stop the progression of a projectile, limiting the extent of maternal injury to the
abdominal wall and the uterus. Signs of peritoneal irritation are less reliable during pregnancy, however, and
changes in vital signs due to blood loss may occur relatively late because of the increase in blood volume related to pregnancy. The general approach to management of
1137
abdominal gunshot wounds involves exploratory laparotomy, although laparotomy can be used selectively (26).
Although stab wounds that do not appear to penetrate
beyond the abdominal wall have been managed nonoperatively, evidence of peritoneal penetration usually
requires exploratory laparotomy, particularly if there are
signs of intraperitoneal hemorrhage or bowel perforation
(30). The indications for tetanus prophylaxis do not
change in pregnancy, and appropriate candidates should
be vaccinated.
If adequate oxygenation and uterine perfusion are
maintained, the fetus usually tolerates surgery and anesthesia well. Intraoperative fetal heart rate monitoring
should be considered if the fetus is viable. A Doppler
device or ultrasound transducer wrapped in a sterile plastic bag may be used for this purpose. When the uterus has
been penetrated by an object or projectile, the fetus probably has been injured. If the fetus is alive, the decision to
perform cesarean delivery should be weighed against the
likelihood of fetal survival. Factors involved in this decision include gestational age, the condition of the fetus
based on any antenatal testing that may have been performed, the extent of injury to the uterus (ie, a cesarean
hysterectomy may be necessary with extensive injuries),
and whether the gravid uterus allows adequate exploration of the peritoneal cavity. These decisions often are
made jointly with the trauma surgeon. The need to
perform a laparotomy, by itself, is not an indication to
proceed with cesarean delivery. If the uterus has been
penetrated and delivery must proceed, a pediatric surgeon
and a neonatologist should be available if possible.
Fetal Assessment
The use of electronic fetal cardiac and uterine activity
monitoring in pregnant trauma victims beyond 20 weeks
of gestation may be predictive of abruptio placentae.
Placental abruption did not occur in trauma patients in
whom uterine contractions occurred at a frequency of less
than one every 10 minutes during 4 hours of monitoring
(16, 18). Of those women who had uterine contractions of
greater frequency, however, almost 20% had placental
abruption (16). Abnormal fetal heart tracings, including
tachycardia and late deceleration, were seen frequently in
cases of abruptio placentae.
Because abruption usually becomes apparent shortly
after injury, monitoring should be initiated as soon as the
woman is stabilized. Recommended minimum time of
posttrauma monitoring includes 4 hours (3, 18) and 26
hours (31). However, none of these times have been validated by large, prospective studies. Monitoring should be
continued and further evaluation carried out if uterine
contractions, a nonreassuring fetal heart rate pattern, vaginal bleeding, significant uterine tenderness or irritability,
serious maternal injury, or rupture of the amniotic mem-
1138
branes is present. If these findings are not present, the

patient may be discharged or transferred (20). Upon discharge, the patient should be instructed to return if she
develops vaginal bleeding, leakage of fluid, decreased
fetal movement, or severe abdominal pain.
The use of ultrasonography following trauma during
pregnancy does not appear to be as sensitive as cardiotocographic monitoring for diagnosing abruptio placentae
(4, 16, 18, 20). However, ultrasonography is useful in the
setting of trauma during pregnancy for establishing gestational age, locating the placenta, determining fetal wellbeing and extent of fetal injury or demise, and estimating
amniotic fluid volume. In the woman, ultrasonography
also may reveal the presence of intraabdominal fluid and
increase the index of suspicion for intraperitoneal hemorrhage.
FetalMaternal Hemorrhage
Complications of fetalmaternal hemorrhage in trauma
patients include fetal and neonatal anemia, fetal cardiac
arrhythmias, and fetal death. There is no evidence that
laboratory testing for fetalmaternal hemorrhage (eg,
KleihauerBetke test) can predict adverse immediate sequelae due to hemorrhage (32). Among women who
exhibit signs of fetalmaternal hemorrhage due to trauma,
the mean estimated blood volume of injected fetal blood
usually is less than 15 mL, and more than 90% of the
hemorrhages are less than 30 mL (4, 16). Therefore, administration of 300 g (one ampule) of D immune globulin would protect nearly all D-negative trauma victims
from D alloimmunization. The routine use of the
KleihauerBetke assay or other similar quantitative
assays of fetalmaternal hemorrhage may be useful in
identifying those few unsensitized, D-negative trauma
patients who are found to have more than 30 mL transfusion. Additional D immune globulin (300 g for every 30
mL of whole blood transfused) may be administered to
these patients. Administration of D immune globulin at
any time within the first 72 hours following fetal
maternal hemorrhage appears to provide protection from
alloimmunization. Consideration should be given to
administering D immune globulin to all unsensitized
D-negative pregnant patients who have experienced
abdominal trauma.
Special Considerations
Perimortem Cesarean Delivery
Although there are no clear guidelines regarding perimortem cesarean delivery, fetal survival is unlikely if
more than 1520 minutes have transpired since the loss of
maternal vital signs. There are insufficient data on which
to base conclusions regarding the appropriateness of
abdominal delivery when efforts at resuscitation have

failed. Based on isolated case reports, cesarean delivery
should be considered for both maternal and fetal benefit 4
minutes after a woman has experienced cardiopulmonary
arrest in the third trimester (33).
Safety Restraint Use During Pregnancy

There is substantial evidence that seat belt use during
pregnancy protects both the mother and the fetus (17, 34,
35). Nonetheless, many pregnant women do not wear seat
belts properly (13). Prenatal education on the use of seat
belts improves compliance of seat belt use as well as
improves knowledge of proper use (13). Current recommendations indicate that throughout pregnancy, safety
belts should be used with both the lap belt and shoulder
harness in place. The lap belt portion should be placed
under the pregnant womans abdomen, over both anterior
superior iliac spines and the pubic symphysis. The shoulder harness should be positioned between the breasts.
There should not be excessive slack in either belt, and
both the lap and shoulder restraints should be applied as
snugly as comfort will allow. Placement of the lap belt
over the dome of the uterus significantly increases pressure transmission to the uterus and has been associated
with significant uterine and fetal injury (36, 37). Based on
preliminary data using a crash dummy that simulates a
pregnant woman, there does not appear to be extraordinary force transmission to the pregnant uterus when seat
belts are properly placed (37).
Airbag deployment during pregnancy does not
appear to be associated with an increased risk for either
maternal or fetal injury. Based on limited existing information, it does not appear reasonable to recommend disabling airbags during pregnancy.
Summary
Trauma is one of the leading causes of death of young
people in this country; in many cases, it is preventable.
The appropriate use of safety restraint systems in automobiles, compliance with traffic laws, and early identification and intervention in suspected cases of domestic
violence are all preventive measures that may reduce the
likelihood of both maternal and fetal morbidity and mortality. The obstetriciangynecologist plays a central role
both in the education of pregnant women and in the early
identification of suspected abuse.
When trauma has occurred, an organized approach to
management is critically important to optimize outcome.
The first priority is treatment and stabilization of the
woman; only then should attention be directed to the
fetus. Electronic fetal and uterine monitoring is an important component of management beyond midtrimester
trauma.
PRACTICE BULLETINS
References
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Dorfman SF, Graham EH. Homicide and other injuries as
causes of maternal death in New York City, 1987 through
1991. Am J Obstet Gynecol 1995;172:15571564
2. Fildes J, Reed L, Jones N, Martin M, Barrett J. Trauma: the
leading cause of maternal death. J Trauma 1992;32:643
645
3. Pearlman MD, Tintinalli JE, Lorenz RP. A prospective controlled study of outcome after trauma during pregnancy.
Am J Obstet Gynecol 1990;162:15021510
4. Goodwin TM, Breen MT. Pregnancy outcome and fetomaternal hemorrhage after noncatastrophic trauma. Am J
5. National Safety Council. Accident facts. Chicago: National Safety Council, 1997
6. American College of Obstetricians and Gynecologists. Domestic violence. ACOG Technical Bulletin 209. Washington, DC: ACOG, 1995
7. Gazamararian JA, Lazorick S, Spitz AM, Ballard TJ,
Saltzman LE, Marks JS. Prevalence of violence against
pregnant women. JAMA 1996;275:19151920
8. Helton AS, McFarlane J, Anderson ET. Battered and pregnant: a prevalence study. Am J Public Health 1987;77:
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9. Berenson AB, Stiglich NJ, Wilkinson GS, Anderson GD.
Drug abuse and other risk factors for physical abuse in
pregnancy among white non-Hispanic, black, and Hispanic women. Am J Obstet Gynecol 1991;164:14911499
10. McFarlane J, Parker B, Soeken K, Bullock L. Assessing for
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11. Stewart DE, Cecutti A. Physical abuse in pregnancy. Can
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12. Varner MW. Maternal mortality in Iowa from 1952 to
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14. Pearlman MD, Tintinalli JE. Evaluation and treatment of
the gravida and fetus following trauma during pregnancy.
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15. Fries MH, Hankins GDV. Motor vehicle accident associated with minimal maternal trauma but subsequent fetal
demise. Ann Emerg Med 1989;18:301304
16. Pearlman MD, Tintinalli JE, Lorenz RP. Blunt trauma during pregnancy. N Engl J Med 1990;323:16091613
17. Crosby WM, Costiloe JP. Safety of lap-belt restraint for
pregnant victims of automobile collisions. N Engl J Med
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18. Dahmus MA, Sibai BM. Blunt abdominal trauma: are there
predictive factors for abruptio placentae or maternalfetal
distress? Am J Obstet Gynecol 1993;169:10541059
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19. Rothenberger D, Quattlebaum FW, Perry JF Jr, Zabel J,

Fischer RP. Blunt maternal trauma: a review of 103 cases.
J Trauma 1978;18:173179
20. Williams JK, McClain L, Rosemurgy AS, Colorado NM.
Evaluation of blunt abdominal trauma in the third trimester
of pregnancy: maternal and fetal considerations. Obstet
Gynecol 1990;75:3337
21. Biester EM, Tomich PG, Esposito TJ, Weber L. Trauma in
pregnancy: normal revised trauma score in relation to other
markers of maternofetal statusa preliminary study. Am J
22. Evrard JR, Sturner WQ, Murray EJ. Fetal skull fracture
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1989;10:232234
23. Hartl R, Ko K. In utero skull fracture: case report. J Trauma
1996;41:549552
24. Astarita DC, Feldman B. Seat belt placement resulting in
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25. Buchsbaum HJ. Accidental injury complicating pregnancy.
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26. Awwad JT, Azar GB, Seoud MA, Mroueh AM, Karam KS.
High-velocity penetrating wounds of the gravid uterus: review of 16 years of civil war. Obstet Gynecol 1994;83:
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27. Kissinger DP, Rozycki GS, Morris JA Jr, Knudson M,
Copes WS, Bass SM, et al. Trauma in pregnancy: predicting pregnancy outcome. Arch Surg 1991;126:10791086
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29. Esposito TJ, Gens DR, Smith LG, Scorpio R. Evaluation
of blunt abdominal trauma occurring during pregnancy. J
Trauma 1989;29:16281632
30. Grubb DK. Nonsurgical management of penetrating uterine trauma in pregnancy: a case report. Am J Obstet
Gynecol 1992;166:583584
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33. Katz VL, Dotters DJ, Droegemueller W. Perimortem cesarean delivery. Obstet Gynecol 1986;68:571576
34. Crosby WM, King AI, Stout LC. Fetal survival following
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35. Wolf ME, Alexander BH, Rivara FP, Hickok DE, Maier
RV, Starzyk PM. A retrospective cohort study of seatbelt
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PRACTICE BULLETINS
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PRACTICE BULLETINSGYNECOLOGY
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BULLETIN

Gynecology with the assistance
of Kamran S. Moghissi, MD
and Craig A. Winkel, MD. The
of practice.
Reaffirmed 2007
Medical Management of
Endometriosis
Endometriosis represents a significant health problem for women of reproductive age. Defined as the presence of endometrial-like glands and stroma in any
extrauterine site, endometriosis continues to defy our complete understanding
regarding etiology, the relationship between extent of disease and the degree of
symptoms, its relationship to fertility, and the most appropriate means of therapy. The purpose of this document is to present the evidence, including risks
and benefits, for the effectiveness of medical therapy for women who experience symptoms and problems believed to be secondary to endometriosis.
Background
Incidence
Endometriosis is a gynecologic condition that occurs in 710% of women in the
general population and up to 50% of premenopausal women (1), with a prevalence
of 38% (range, 2050%) (24) in infertile women, and in 7187% of women with
chronic pelvic pain (57). Contrary to much speculation, there are no data to support the view that the incidence of endometriosis is increasing, although improved
recognition of endometriosis lesions (8) may have led to an increase in the rate of
detection. There also appears to be no particular racial predisposition to endometriosis.
A familial association of endometriosis has been documented (9), and patients
with an affected first-degree relative have nearly a 10-fold increased risk of developing endometriosis. The proposed inheritance is characteristic of a polygenicmultifactorial mechanism.
Etiology
Although the pathogenesis of endometriosis remains unclear, leading theories
include retrograde menstruation, hematogenous or lymphatogenous transport,
1143
1144
and coelomic metaplasia. It has been suggested that virtually all women are potentially vulnerable to the development
of the lesions of endometriosis, but appropriate immunocompetency in most eradicates such lesions in a timely
fashion, preventing clinical sequelae (10). Menstrual flow
that produces a greater volume of retrograde menstruation
may increase the risk of developing endometriosis. Cervical
or vaginal atresia with outflow obstruction also is linked
with the development of endometriosis (11). Early menarche, regular cycles (especially without intervening pregnancy-induced amenorrhea), and a longer and heavier than
normal flow are associated with this disease (12). Because
endometriosis is an estrogen-dependent disease, factors that
reduce estrogen levels, such as exercise-induced menstrual
disorders, decreased body-fat content, and tobacco smoking, are associated with reduced risk of developing
endometriosis (12).
Clinical Manifestations
The clinical manifestations of endometriosis are variable
and unpredictable in both presentation and course. Dysmenorrhea, chronic pelvic pain, dyspareunia, uterosacral ligament nodularity, and adnexal mass (either symptomatic or
asymptomatic) are among the most well-recognized manifestations (1316). A significant number of women with
endometriosis remain asymptomatic.
The association between endometriosis and infertility
remains the subject of considerable debate. It is clear that
endometriosis may induce infertility as a result of anatomic
distortion secondary to invasive endometriosis and related
adhesions. Although it was previously believed that patients
with minimal and mild endometriosis displayed reduced
monthly fecundity rates (17), a cause-and-effect relationship
has not been proven, and more recent prospective controlled
trials suggest that minimal to mild endometriosis is not associated with reduced fecundity (18) and may not be a direct
cause of infertility (19).
Pelvic pain that is typical of endometriosis is characteristically described as secondary dysmenorrhea (with pain
frequently commencing prior to the onset of menses), deep
dyspareunia (exaggerated during menses), or sacral backache with menses. Endometriosis that involves specific
organs may result in pain or physiologic dysfunction of
those organs, such as perimenstrual tenesmus or diarrhea in
cases of bowel involvement or dysuria and hematuria in
cases of bladder involvement.
The pain associated with endometriosis has little relationship to the type or location of the lesions that are visible
at laparoscopy (20). Surgical assessment is complicated by
the varying, and subtle appearances of endometriosis (21,
22), and may be demonstrated histologically in a normal-
appearing peritoneum (23, 24). It has been shown that the

depth of infiltration of endometriosis lesions correlates
best with pain severity (6, 25, 26). Systematic analysis of
the source of pain in awake patients undergoing
laparoscopy (sometimes referred to as pain mapping)
demonstrates that pain arises from stimulation of adjacent
normal peritoneal surfaces that extend well beyond the
visible lesions of endometriosis. This suggests that painful
lesions are those involving peritoneal surfaces innervated
by peripheral spinal nerves, rather than those innervated
by the autonomic nervous system (20).
Diagnosis
Direct visualization confirmed by histologic examination,
especially of lesions with nonclassical appearance (21, 22,
27), remains the standard for diagnosing endometriosis.
The presence of two or more of the following histologic
features is used as the threshold criteria for the diagnosis
by a pathologist (28):
Endometrial epithelium
Endometrial glands
Endometrial stroma
Hemosiderin-laden macrophages
Visual inspection as the sole means for making the
diagnosis of endometriosis requires an experienced surgeon who is familiar with the protean appearances of
endometriosis. Experience is associated with increased
diagnostic accuracy (8, 21, 22), but the correlation
between visual inspection and histologic confirmation of
the presence of endometriosis in biopsy specimens is
imperfect (22). The finding of microscopic endometriosis
in normal-appearing peritoneum (23, 24) exemplifies the
inaccuracy of diagnosis by visualization alone. Peritoneal
biopsy may be used for diagnosing questionable peritoneal lesions (22).
Because tissue confirmation of the diagnosis of endometriosis requires a surgical procedure, investigators
have searched for a noninvasive alternative. The correlation between the presence of moderate and severe
endometriosis and an increased concentration of CA 125
in serum has been known for more than 10 years (29).
Although the specificity of CA 125 measurements had
been reported to be greater than 85%, with sensitivities
between 20% and 50% (3033), the clinical utility of
measuring CA 125 as a diagnostic marker for endometriosis appears to be limited. Determining the level of CA 125
in serum appears to be useful in detecting women with
severe endometriosis but is of questionable value in
detecting women with minimal or mild disease (34, 35).
PRACTICE BULLETINS
Measurement of peritoneal fluid levels, however, appears

to be better for detecting minimal and moderate disease
(34).
Concentrations of CA 125 in serum also have been
studied as a marker to determine the response to medical
therapy for endometriosis. Although CA 125 levels may
decrease during treatment when compared with pretreatment values (3638), posttreatment values that are normal
do not confirm the absence of endometriosis (36, 38), nor
are they useful for predicting disease recurrence (37).
Imaging studies, such as ultrasonography, magnetic
resonance imaging, and computed tomography, appear to
1145
be useful only in the presence of a pelvic or adnexal mass.

Ovarian endometriomas, visualized ultrasonographically,
typically appear as cysts that contain low-level, homogeneous internal echoes consistent with old blood. Imaging
studies alone appear to have greater predictive accuracy in
differentiating ovarian endometriomas from other adnexal
masses than when used in combination with measurement
of CA 125 levels in plasma (39). Magnetic resonance imaging may detect deeply infiltrating endometriosis that involves the uterosacral ligaments and the cul-de-sac, but
lacks sensitivity in detecting rectal involvement (40).

Revised Classification of Endometriosis
Patients name
Stage I (minimal)
Stage II (mild)
Stage III (moderate)
Stage IV (severe)
Date
15
615
1640
>40
Ovary
Peritoneum
Total
Ovary
Photography
Prognosis
Endometriosis
Superficial
Deep
R Superficial
Deep
L Superficial
Deep
Posterior
cul-de-sac
obliteration
Tube
Laparoscopy
Laparotomy
Recommended treatment
Adhesions
R Filmy
Dense
L Filmy
Dense
R Filmy
Dense
L Filmy
Dense
<1 cm
1
2
1
4
1
4
13 cm
2
4
2
16
2
16
>3 cm
4
6
4
20
4
20
Partial
Complete
40
<1/3 Enclosure
1
4
1
4
1
4*
1
4*
1/3 2/3
Enclosure
2
8
2
8
2
8*
2
8*
>2/3 Enclosure
4
16
4
16
4
16
4
16
*If the fimbriated end of the fallopian tube is completely enclosed, change the point assignment to 16.
Denote appearance of superficial implant types as red [(R), red, red-pink, flamelike, vesicular blobs,
clear vesicles], white [(W), opacifications, peritoneal defects, yellow-brown], or black [(B), black,
hemosiderin deposits, blue]. Denote percent of total described as R %, W %, and B %. Total
should equal 100%.
Figure 1. Modified from

the revised American
Fertility Society classification of endometriosis.
(Reprinted with permission from the American
Society for Reproductive
Medicine. Fertility and
Sterility 1996;67(5):819
820)
1146
Classification
Numerous classification schemas have been proposed to
describe endometriosis by anatomic location and severity of
disease. The American Society for Reproductive Medicine
(ASRM [formerly the American Fertility Society]) classification, which is the most commonly used system, was
revised for the third time in 1996 (41) (see Figure 1) but still
has limitations and inherent defects. The system is not a
good predictor of pregnancy following treatment despite
adjustments to the point scores and cut-points for disease
stage. The ASRM system does not correlate well with the
symptoms of pain and dyspareunia (6). The true value of
the ASRM 1996 revised system is in uniform recording
of operative findings and perhaps for comparing the results
of various therapies.

Recommendations
nodularity), ovarian suppression with a combination oral

contraceptive may be effective in reducing pain (50). The
efficacy of continuous administration of oral contraceptives compared with cyclic administration has not been
tested in a prospective fashion. Oral contraceptives probably should not be used for more than 3 months if the patient
experiences no relief of symptoms. Furthermore, there is
no reason to suspect that one oral contraceptive is better
than another for suppression of pain symptoms. If recurrent
symptoms do not respond to oral contraceptives, then therapy with medroxyprogesterone acetate (MPA), danazol, or
a GnRH agonist may be appropriate.
Danazol, when used in doses of 600800 mg per day
appears to as effective as GnRH agonists for pain relief in
most patients, but is associated with a significantly greater
incidence of side effects (51). The cost of treatment with
danazol is about one third less than treatment with a GnRH
agonist but nearly twice as costly as treatment with oral
contraceptives and oral or depot MPA.
In women with endometriosis-related pain

who desire future fertility, how does medical
therapy compare with no therapy for the treatment of pain and long-term preservation of
fertility potential?
Deeply infiltrating endometriosis, rather than surface noninfiltrating endometriosis, is commonly associated with pelvic
pain (6). At present, evidence suggests that pain associated
with endometriosis can be reduced with the use of a variety
of medications (progestins, danazol, oral contraceptives,
nonsteroidal antiinflammatory drugs, and gonadotropinreleasing hormone [GnRH] agonists) (4247). There is also
evidence that such medical therapies are likely to reduce the
size of endometriosis lesions and, thus, the stage of disease
(42, 48, 49). There are no data, however, showing that medical therapy eradicates the lesions. Although medical treatment may eliminate the symptoms associated with
endometriosis, there is no evidence that such treatment has
an impact on the future fertility of women with endometriosis. Because early-stage endometriosis is more likely to be
associated with pain symptoms without associated alterations in fecundity, it is unlikely that such data will be forthcoming. Furthermore, whereas infiltrating lesions of
endometriosis are associated with pain, studies are lacking
that suggest the absence of treatment is associated with a
progressive or future decline in fertility.
In a woman with normal or minor gynecologic findings suggesting mild disease (pelvic tenderness, uterosacral

who desire future fertility, how does medical
therapy compare with surgical therapy alone
for the management of pain and long-term
preservation of fertility potential?
The debate regarding medical treatment versus surgical

treatment for the management of pain related to endometriosis continues despite of the lack of substantive
data on either side of the argument. Surgical therapy for
women with endometriosis is associated with a significant
reduction in pain symptoms during the first 6 months following surgery (52). With continued follow-up, however, a
substantial portion (44%) of women experience recurrence
of symptoms within 1 year postoperatively (53). The
cumulative recurrence rate of pain symptoms during the
initial 5 years following discontinuation of therapy with a
GnRH agonist is 53% (54). No evidence exists regarding
the effectiveness of adjunctive treatment with danazol, oral
contraceptives, or progestins in comparison with surgical
treatment alone in the management of endometriosis-related pelvic pain. A major issue in considering comparisons
of surgical treatment with medical treatment is the experience and expertise of the surgeon.
Likewise, debate continues over the best means of surgical therapy. One opinion considers vaporization or
cautery of peritoneal implants adequate, whereas the other
recommends surgical excision as necessary for adequate
treatment (55). Currently, there are limited data to show
that one method is better than the other. Moreover, there are
PRACTICE BULLETINS
no data regarding whether surgical therapy influences

long term fertility. Also, no data exist to indicate whether
medical or surgical treatments result in the best fertility outcomes.
Following surgical diagnosis of endometriosis, what is the role of surgical destruction of

lesions, or medical therapy in conjunction
with surgery, for long-term pain relief in
patients with minimal to moderate endometriosis that has been completely resected?
GnRH agonists to extend the period of pain relief. In a randomized, controlled trial of an intranasal GnRH agonist,
31% of women who received the GnRH agonist following
laparoscopy needed additional medical treatment 18
months following surgery, whereas 57% of the women
who received placebo required additional medical suppression (59).
The efficacy of other hormonal therapy in conjunction
with surgery for treating women with endometriosis
remains unclear. Oral MPA has been shown to induce
regression of endometriosis lesions. One study has demonstrated that depot MPA is safe and effective in reducing pain
associated with endometriosis (45). Importantly, depot
MPA confers contraception during therapy while the use of
low-dose danazol (200400 mg) to reduce the dose-related
side effects may not prevent conception and thus exposes
the patient to the potential for teratogenesis. A combination
of low-dose danazol and oral contraceptives appears to offer
a similar degree of efficacy while providing effective contraception (45).
Few reports have examined the use of danazol as an
adjunct to surgical therapy. It appears that danazol treatment for 3 months following laparoscopic surgery for
women with Stage III and Stage IV endometriosis offers no
advantage over expectant management with regard to pain
recurrence (60).
It is probably impossible to completely resect all endometriosis lesions, if for no other reason than in up to 25%
of biopsies of normal-appearing peritoneum one will find
histologic evidence of endometriosis (23, 24). In addition,
even when experienced surgeons attempt to resect completely a deeply infiltrating lesion, histologic study often
reveals that the lesion is incompletely resected (26).
Operative laparoscopy for surgical treatment of pelvic
pain related to endometriosis appears to have numerous
advantages over laparotomy. These include more rapid
recovery, the potential to decrease postoperative adhesion
formation (56), and complication rates of 10% with laparoscopy (57). Although technical difficulties can be overcome partially through skill and experience, the efficacy of
surgical therapy still depends heavily on the surgeon. Regardless of the technique employedexcision, endocoagulation, electrocautery, or laser vaporizationno study
demonstrates the superiority of any one method, and recurrence rates average 19% (58). For successful surgical treatment, considering the varied appearances of endometriosis,
the challenge lies in the surgeons ability to recognize all
visible lesions.
The only prospective, double-blind, randomized, controlled trial designed to evaluate the effectiveness of laparoscopic surgery for women with pelvic pain was reported in
1994 (52). Of the women who underwent laser ablation of
endometriosis and laser uterosacral nerve ablation, 62%
experienced pain relief 6 months after surgery, compared
with 22% who underwent laparoscopic visualization only
(52). If one considers the results of this study and a number
of retrospective analyses, it appears that surgical treatment
alone will confer pain relief in approximately two thirds of
women for up to 1 year.
Postoperative medical treatment could be useful when
residual disease is expected, when pain is not relieved, or to
extend the pain-free interval following surgery. Although
not demonstrated on the basis of clinical studies available at
present, postoperative treatment should minimize the risk of
recurrence. Two studies support the use of postoperative
1147
Following surgical diagnosis of endometriosis, what is the role of surgical destruction of

lesions, or medical therapy in conjunction
with surgery, for long-term pain relief in
patients with severe endometriosis with residual disease present?
The recurrence rates for endometriosis appear to correlate

with severity of disease (54), with a recurrence rate over a
7-year period following medical treatment of 37% for
women with mild disease and 74% for women with severe
disease. Although one might conclude that postoperative
medical treatment would make sense for the woman with
severe endometriosis with residual disease, there are no data
documenting the efficacy of this therapy. In most cases,
studies of the efficacy of postoperative medical treatment
specifically address those patients with minimal to moderate disease, excluding those with severe endometriosis.
Treatment with a GnRH agonist prior to laparoscopic
surgery was associated with a higher fecundity rate within
the first year following surgery than with preoperative danazol or gestrinone (61). However, such therapy was not associated with a reduction in operating time or any decrease in
recurrence rate 1 year after surgery for ovarian endometri-
1148
In women receiving a 36-month regimen of

GnRH analog therapy for treatment of
endometriosis-related pelvic pain, what are the
advantages and disadvantages of an addback regimen?
Gonadotropin-releasing hormone agonists have been shown

to be efficacious and safe for treating women with endometriosis-related pelvic pain (47, 49, 6366). However,
because these agents create a state of relative estrogen deficiency, their use has been limited generally to a 6-month
course of therapy, particularly because of the potential
effects on bone density, as well as the side effects, most
notably vasomotor symptoms.
To minimize both the loss of bone and side effects,
add-back regimens (using either sex-steroid hormones or
other specific bone-sparing agents) have been advocated for
use in women undergoing long-term therapy (ie, >6
months). Such treatment strategies have included progestins
alone (6769), progestins and organic bisphosphonates
(70), low-dose progestins and estrogens (71,72), pulsatile
parathyroid hormone (73), and nasal calcitonin (74).
Although there are no published studies specifically
designed to compare the various add-back regimens, virtually all add-back regimens (except nasal calcitonin) have
considerable efficacy in reducing the loss of bone mineral
density associated with GnRH agonist treatment. Some regimens appear to reduce vasomotor symptoms better than
others; parathyroid hormone therapy has little effect on such
symptoms.
The potential advantages of add-back therapy for
women undergoing short-term (36 months) GnRH agonist
therapy are twofold. First, while it has been shown that the
bone loss after 3 months of treatment with a GnRH agonist
is less than that after 6 months of treatment (69, 70, 72),
add-back therapy does reduce the bone loss observed after
only 3 months of GnRH agonist therapy (72). Add-back
treatment does not diminish the efficacy of pain relief
observed during 3 months or 6 months of GnRH agonist
therapy. Second, add-back regimens that employ progestins
alone (6772) or in combination with estrogens (71, 72, 75)
reduce significantly the vasomotor symptoms associated
with GnRH agonist treatment. There appear to be no disadvantages to the use of an add-back regimen in combination
with a GnRH agonist other than the incremental cost associated with the additional medication.
omata (62). For women with severe endometriosis, with or

without suspected residual disease, the efficacy of either preoperative or postoperative medical therapy has yet to be
established.
In women who have had a good response to

GnRH therapy and who may benefit from an
extended duration of therapy with add-back
therapy (>6 months), what is the safety and
efficacy of such long-term treatment?
There are few data available on the use of GnRH agonists

for more than 6 months. The major concern with prolonged use of GnRH agonists is the loss of bone mineral
density that is observed during 6 months of therapy with
these drugs (76). The mean loss of bone mineral density
during a 6-month course of therapy with GnRH agonists
ranges from 5.9% to 15% and may depend on the dose,
route, and particular agonist being used (77). Marked individual differences in susceptibility to bone loss have been
noted. Bone loss during a 6-month course of intranasal
GnRH agonist was less than that observed with the intramuscular form (3% versus 5%) (78). Gonadotropin-releasing hormone agonists do not have adverse effects on
triglyceride or cholesterol metabolism (79), as may be seen
with danazol (80) or MPA (81).
A 12-month course of GnRH agonist therapy was
associated with approximately a 6% decrease in bone
density. The addition of norethindrone acetate alone or in
combination with conjugated equine estrogens had no
adverse impact on pain relief but did prevent bone mineral loss (44); there was also an associated increase in lowdensity lipoprotein cholesterol, a decrease in high-density
lipoprotein cholesterol, and an increase in triglycerides.
The clinical significance of these latter changes is
unclear. Currently, there are no data regarding extended
treatment with GnRH agonists beyond 1 year. Patients
receiving this treatment should be monitored regularly
for physical findings, bone density, and serum lipid parameters.
If the woman has previously undergone therapy with
a GnRH agonist, it appears safe to retreat with a GnRH
agonist alone provided there has been suitable time for
recovery of bone mineral density since the previous course
of treatment (82). If bone mineral density has not recovered fully, or if bone density has not been evaluated, the
use of either a potent progestin or danazol is recommended. No studies have been reported to evaluate bone density
after progestin administration following initial GnRH agonist therapy. Finally, a GnRH agonist in combination with
add-back treatment may be considered, especially if the
add-back regimen is commenced coincidentally with the
reinitiation of therapy with the GnRH agonist. The longterm effects of multiple courses of treatment with a GnRH
agonist have yet to be assessed.
PRACTICE BULLETINS
The need for laparoscopy (or any other surgical procedure)

for diagnosis or treatment of pelvic pain secondary to suspected endometriosis has been the subject of debate (83).
Arguments against the requirement to perform surgery to
definitively diagnose endometriosis include the imprecision of surgical diagnosis as well as the inherent risks of
surgery. Empiric therapy is used commonly in clinical
gynecology when the signs and symptoms support the particular diagnosis being entertained and the consequences
of an inaccurate diagnosis are likely to be minimal (eg,
mild cystitis, suspected pelvic infection, and bacterial
vaginosis).
In a woman with pelvic pain, diagnostic evaluation
should include a thorough history and physical examination to rule out other gynecologic causes of pain, such as
chronic pelvic inflammatory disease, leiomyomata uteri,
and ovarian cysts. Nongynecologic causes of pain, such as
gastrointestinal and urinary tract problems, may be ruled
out by appropriate testing. Consideration also should be
given to pelvic ultrasonography, complete blood count,
urinalysis, and endocervical sampling for gonococcal and
chlamydial infection if signs and symptoms warrant.
Based on a well-designed, prospective, randomized,
controlled, double-blind clinical trial, the following statement can be made (7). After an appropriate pretreatment
evaluation (to exclude other conditions) and failure of initial treatment with oral contraceptives and nonsteroidal
antiinflammatory drugs, empiric therapy with a 3-month
course of a GnRH agonist is appropriate. This approach is
associated with clinically and statistically significant
improvement in dysmenorrhea, pelvic pain, and pelvic
tenderness. Furthermore, if the diagnostic algorithm
described is employed prior to the initiation of empiric
GnRH therapy, the likelihood of endometriosis being present on posttreatment laparoscopy is 7887%. Thus, it
appears that empiric treatment with a GnRH agonist (ie,
without surgical diagnosis) is efficacious.
Comparing costs of empiric medical management
versus definitive surgical diagnosis is more difficult to
address. Although there are a lack of well-designed studies that compare the actual costs between the two
approaches, it has been estimated that the cost of 3 months
of empiric therapy is less than that of a laparoscopic procedure. No trials comparing primary medical and surgical
therapies have been reported, nor have data been reported

regarding the percentage of women who will still require
surgical therapy following satisfactory empiric treatment.
In a woman with symptoms consistent with

endometriosis, is empiric medical therapy
(without definitive surgical diagnosis) an
efficacious and cost-effective approach to
pain relief?
1149
In asymptomatic women in whom endometriosis is discovered incidentally, how does medical

therapy compare with no intervention for longterm pain relief and preservation of fertility?
The pathophysiology of endometriosis remains poorly

understood. Largely because of failure to identify a suitable
animal model, there is little systematic research regarding
either the progression of the disease or the prediction of clinical outcomes. The presence of endometriosis among
asymptomatic infertility patients varies between 20% and
50%, suggesting that it may not always be pathologic. In
biopsies of apparently normal peritoneum, one can demonstrate the presence of endometrial glands and stroma in 25%,
thus confirming the presence of endometriosis (23). In 50%
of cases, endometriosis regresses spontaneously or remains
constant (84). There are a number of obstacles, therefore, to
predicting what the presence of endometriosis holds for a
given woman. There are no data available regarding medical
therapy for prevention of disease progression or for prevention of future pain.
Although preliminary data suggest that the destruction
of all apparent lesions is associated with improved fecundity
during the next 36 months (85), there are no data available
on which to make a recommendation regarding medical therapy to prevent progression of disease or to prevent pain
symptoms.
Endometriosis frequently is associated with infertility,
although a cause-and-effect relationship between the two
remains controversial. Essential steps in the development of
endometriosis require a series of complex interactions
between peritoneal leukocytes and endometrial cells, but the
exact etiologic factor(s) remains unknown. In addition, both
specific and nonspecific immunologic alterations are likely
required. Whether these are the result or the cause of the disease also remains unclear. Although the pathophysiology of
infertility arising from endometriosis that results in distortion of normal anatomy is relatively easy to understand, the
mechanisms by which nonadhesive disease leads to infertility are still not clear.
There are no data to support the suggestion that medical
treatment to prevent the progression of the disease will result
in successful fertility in the future. It is not even clear
whether fertility can be predicted based on the presence of
endometriosis unless there is gross distortion of tubal and
ovarian anatomy.
1150

who have completed childbearing, how does
medical management compare with no therapy
for long-term pain relief?
In a woman with pelvic pain arising from

known endometriosis, does the presence of an
ovarian endometrioma on ultrasound influence the efficacy or safety of employing medical therapy for pain relief?
In patients with pain or bleeding arising from

known endometriosis affecting nonreproductive organs, what is the evidence for the efficacy of medical therapy for these symptoms?
Extrapelvic endometriosis has been reported in a variety of

sites, including the upper abdomen, the diaphragm, the
abdominal wall (particularly the umbilicus), the perineum
(episiotomy scar), and the thorax (89, 90). In addition,
endometriosis may invade the full thickness of the rectum,
large and small bowel, ureters, or bladder. The symptoms
that are associated with endometriosis at these sites vary
depending on location and depths of infiltration, including
women who experience cyclic episodes of gross hematuria, hematochezia, and hemoptysis. Although a number
of therapeutic approaches have been employed for women
with presumed extrapelvic endometriosis (91), the efficacy
of ovarian suppression with a GnRH agonist appears to
support it as the first line of therapy (92, 93). Based on current available evidence, medical treatment appears to be
efficacious for women with signs and symptoms of
extrapelvic endometriosis provided other, potentially serious diseases have been excluded.
The reliability of ultrasonography for diagnosing endometriosis depends on the nature of the lesions. The
endovaginal ultrasonographic approach appears to be superior to the transvesical approach for the evaluation of an
ovarian mass. For the diagnosis of ovarian endometriomas,
ultrasonography is reliable, with sensitivity up to 83% and
specificity of 98% (87). Scattered internal echoes that tend
to appear homogeneous are characteristic of endometriomas.
Gonadotropin-releasing hormone agonist treatment
resulted in a greater than 25% reduction in the diameter of
endometriomas for more than 80% of the women observed,
compared with 30% of those treated with danazol (61).
These authors did not report on the reduction in pain symptoms. Although it is theorized that preoperative medical
treatment of the woman with an ovarian endometrioma
might facilitate surgery by reducing inflammation and vascularity, there are no studies that address this practice. A
3-month preoperative course of a GnRH agonist has been
reported to produce decreased cyst wall thickness and
inflammation (88), but was not associated with either
reduced operating time or reduced incidence of recurrence
The rates for recurrence of pain symptoms following medical or surgical treatment for endometriosis do not differ
greatly. Following surgical therapy, about two thirds of
patients experience recurrence of pain symptoms within 2
years of surgery (52, 56). However, the recurrence of pain
symptoms may be delayed by the addition of 3 months of
treatment with a GnRH agonist (59).
Medical therapy alone is likely to result in a significant
pain-free interval following treatment with a GnRH agonist
(54, 86) in the absence of surgical treatment. In addition,
treatment with either oral contraceptives, danazol, or progestins has been shown to reduce, at least in the short term,
pain symptoms associated with endometriosis (43, 45, 46).
Currently, there are no follow-up data beyond 7 years after
medical treatment. The long-term impact of medical therapy on pain recurrence beyond this period remains unclear.
1 year later (62). There is only anecdotal information

regarding responses of suspected ovarian endometriomas
to therapy with oral contraceptives or MPA. When medical
treatment is used in a woman with an ovarian mass that is
assumed to be an endometrioma, the potential for missed
diagnosis or delay in diagnosis of a more serious condition
(such as a malignant or borderline tumor) must always be
kept in mind.
Because it is likely that the pain associated with endometriosis is most closely related to deeply infiltrating
peritoneal disease rather than the ovarian endometrioma,
medical therapy aimed at suppressing ovarian function is
likely to result in a similar reduction in pain symptoms,
whether or not there is a coincident ovarian endometrioma.
There are no studies, however, of the efficacy of medical
therapy for pain in the presence or absence of an
endometrioma.
In a woman who has undergone a total abdominal hysterectomy for definitive therapy
for endometriosis, what is the risk of symptomatic recurrence with estrogen replacement
therapy, and is there a role for suppressive
therapy after total abdominal hysterectomy
with bilateral salpingo-oophorectomy if there
is residual disease?
PRACTICE BULLETINS
which has led some to recommend the routine addition of a

progestin to the estrogen therapy, although there are no outcomes-based evidence to support this recommendation.
Although limited data indicate hormone replacement
therapy may stimulate the growth of residual ovarian or
endometrial tissue after total abdominal hysterectomy, the
overall benefits of hormone replacement (cardiovascular
benefits, reduced risk of osteoporosis, relief of vasomotor
symptoms) may outweigh these risks, and the decision
should be individualized.
Summary
For pain relief, treatment with a GnRH agonist for at

least 3 months or with danazol for at least 6 months
appears to be equally effective in most patients.
When relief of pain from treatment with a GnRH

agonist supports continued therapy, the addition of
add-back therapy reduces or eliminates GnRHinduced bone mineral loss without reducing the efficacy of pain relief.
Therapy with a GnRH agonist is an appropriate

approach to the management of the woman with
chronic pelvic pain, even in the absence of surgical
confirmation of endometriosis, provided that a
detailed initial evaluation fails to demonstrate some
other cause of pelvic pain.
For pain relief, oral contraceptives and oral or depot

MPA are effective in comparison with placebo and
may be equivalent to other more costly regimens.
Hormone replacement therapy with estrogen is not

contraindicated following hysterectomy and bilateral salpingo-oophorectomy for endometriosis.
For severe endometriosis, medical treatment alone

may not be sufficient.
The rates of recurrence of endometriosis after initial conservative surgery tend to vary based on stage or extent of
disease at the time of surgery. It is particularly difficult,
however, to distinguish between recurrence and persistence
of endometriosis. Recurrence rates range between 20% and
40% within 5 years after surgery for endometriosis (52, 53,
55, 94).
Hysterectomy, with or without bilateral oophorectomy,
is often regarded as definitive therapy for the treatment of
endometriosis associated with intractable pelvic pain,
adnexal masses, or multiple previous conservative surgical
procedures. Based on the results of a recently published retrospective analysis of women monitored for a mean duration of 58 months after hysterectomy, ovarian conservation
was associated with a 62% likelihood of recurrent symptoms and a 31% chance of requiring additional surgical
treatment (95). In women who underwent bilateral adnexectomy, there was a 10% chance of recurrence of symptoms
with only a 4% likelihood of additional surgery (95). The
relative risk for pain recurrence after total abdominal hysterectomy was found to be 6.1 (95% confidence interval:
2.514.6) with ovarian preservation when compared with
women who have their ovaries removed. The relative risk of
additional surgery was 8.1 (95% confidence interval:
2.131.3) with ovarian conservation (95).
Symptoms may recur in women even after hysterectomy and oophorectomy. Endometriosis may recur in up to
15% of women whether or not the patients are treated with
estrogen replacement therapy following bilateral oophorectomy (96). Although the true rate of recurrence is unknown,
among those patients in whom recurrent symptoms result in
an additional surgical procedure, endometriosis lesions may
be demonstrated. The most common site of recurrent lesions
is the large and small bowel. It is not clear whether such
lesions were present at the time of the oophorectomy and
were overlooked or were not visualized because they were
present only as microscopic disease in normal-appearing
peritoneum.
After total abdominal hysterectomy with bilateral salpingo-oophorectomy, delayed initiation of estrogen replacement therapy has been thought to decrease the risk of recurrent symptoms. Furthermore, the possibility does exist that
estrogen replacement therapy may support infiltration of
endometriosis lesions and result in continued progression of
the disease (97). Currently, there are limited data on which
to base a recommendation. It appears there is no advantage,
in terms of recurrence rate, in delaying introduction of estrogen treatment following surgery (96, 98). There is also a
concern about the possibility of estrogen induced malignant
transformation in residual endometriosis implants (99),
1151
Because endometriosis often is unpredictable and

may regress, expectant management may be appropriate in asymptomatic patients.
1152
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860864 (Level I)
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63. Dlugi AM, Miller JD, Knittle J, Lupron Depot (leuprolide
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64. Henzl MR, Corson SL, Moghissi K, Buttram VC, Berqvist
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65. Hornstein MD, Yuzpe AA, Burry KA, Heinrichs LR,
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with estrogen-progestin add-back therapy in the treatment
of endometriosis. Fertil Steril 1995;64:903908 (Level I)
72. Moghissi KS, Schlaff WD, Olive DL, Skinner MA, Yin H.
Goserelin acetate (Zoladex) with or without hormone
replacement therapy for the treatment of endometriosis.
Fertil Steril 1998;69:10561062 (Level I)
73. Finkelstein JS, Klibanski A, Schaefer EH, Hornstein MD,
Schiff I, Neer RM. Parathyroid hormone for the prevention
of bone loss induced by estrogen deficiency. N Engl J Med
1994;331:16181623 (Level I)
74. Roux C, Pelissier C, Listrat V, Kolta S, Simonetta C,
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75. Howell R, Edmonds DK, Dowsett M, Crook D, Lees B,
Stevenson JC. Gonadotropin-releasing hormone analogue
(goserelin) plus hormone replacement therapy for the
treatment of endometriosis: a randomized controlled trial.
76. Fogelman I. Gonadotropin-releasing hormone agonists
and the skeleton. Fertil Steril 1992;57:715724 (Level III)
77. Dawood MY. Hormonal therapies for endometriosis:
implications for bone metabolism. Acta Obstet Gynecol
Scand 1994;159:2234 (Level III)
78. Agarwal SK, Harmrang C, Henzl MR, Judd HL. Nafarelin
vs. leuprolide acetate depot for endometriosis. Changes in
bone mineral density and vasomotor symptoms. Nafarelin
Study Group. J Reprod Med 1997;42:413423 (Level I)
66. Tummon IS, Pepping ME, Binor Z, Radwanska E,

Dmowski WP. A randomized, prospective comparison of
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danazol for treatment of endometriosis. Fertil Steril
1989;51:390394 (Level I)
79. Lemay A, Brideau NA, Forest JC, Dodin S, Maheux R.

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80. Fahraeus L, Larsson-Cohn U, Ljungberg S, Wallentin L.

Profound alterations of the lipoprotein metabolism during
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68. Makarainen L, Ronnberg L, Kauppila A. Medroxyprogesterone acetate supplementation diminishes the hypoestrogenic side effects of gonadotropin-releasing hormone
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during treatment of pelvic endometriosis with medroxyprogesterone acetate. Fertil Steril 1986;45:503506 (Level
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and bone mineral density loss with combined norethindrone and long-acting gonadotropin-releasing hormone
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safety and bone mineral density. Fertil Steril 1997;
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83. Howard FM. The role of laparoscopy in chronic pelvic
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85. Marcoux S, Maheux R, Berube S. Laparoscopic surgery in
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88. Donnez J, Nisolle M, Clerckx F, Casanas-Roux F, Saussoy
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89. Shimizu I, Nakanishi R, Yoshino I, Yasumoto K. An
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endometriosis after amniocentesis. A case report. J Reprod
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91. Shek Y, De Lia JE, Pattillo RA. Endometriosis with a
pleural effusion and ascites. Report of a case treated
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92. Espaulella J, Armengol J, Bella F, Lain JM, Calaf J.
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93. Johnson WM 3d, Tyndal CM. Pulmonary endometriosis:
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94. Wheeler JH, Malinak LR. Recurrent endometriosis: incidence, management, and prognosis. Am J Obstet Gynecol
1983;146:247253 (Level III)
95. Namnoun AB, Hickman TN, Goodman SB, Gehlbach DL,
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96. Redwine DB. Endometriosis persisting after castration:
clinical characteristics and results of surgical management.
97. Lam AM, French M, Charnock FM. Bilateral ureteric
obstruction due to recurrent endometriosis associated with
hormone replacement therapy. Aust N Z J Obstet Gynaecol
1992;32:8384 (Level III)
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January 1985 and May 1999. The search was restricted to
articles published in the English language. Priority was
although review articles and commentaries also were
consulted. Abstracts of research presented at symposia and
scientific conferences were not considered adequate for inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of
Force:
I

committees.
98. Hickman TN, Namnoun AB, Hinton EL, Zacur HA, Rock
JA Timing of estrogen replacement therapy following hysterectomy with oophorectomy for endometriosis. Obstet
Copyright December 1999 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission
from the publisher.
99. Gucer F, Pieber D, Arikan MG. Malignancy arising in

extraovarian endometriosis during estrogen stimulation.
Eur J Gynaecol Oncol 1998;19:3941 (Level III)
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1156
ACOG
PRACTICE
BULLETIN

developed by the ACOG
Committee on Practice BulletinsGynecology with the
assistance of Dale Stovall,
MD. The information is designed to aid practitioners in
making decisions about appropriate obstetric and gynecologic care. These guidelines
treatment or procedure. Variations in practice may be warranted based on the needs
of the individual patient,
unique to the institution or
type of practice.
Reaffirmed 2009
Management of
Anovulatory Bleeding
Anovulatory bleeding, the most common form of noncyclic uterine bleeding, is
a condition for which women frequently seek gynecologic care and accounts for
considerable patient anxiety and inconvenience. Over the past decade, significant advances have been made in the evaluation and management of women
with anovulatory bleeding. The choice of treatment for anovulatory bleeding
depends on several factors, including the womans age, the severity of her
bleeding, and her desire for future fertility. The purpose of this document is to
provide management guidelines for the treatment of patients with menstrual
irregularities associated with anovulation based on the best available evidence.
Background
Definition and Nomenclature
The terms menses, menstrual flow, and menstruation will be used in this document interchangeably, and each of these terms simply refer to the presence of
menstrual effluent irrespective of whether the effluent is normal or abnormal.
Anovulatory uterine bleeding is defined as noncyclic menstrual blood flow that
may range from spotty to excessive, is derived from the uterine endometrium,
and is due to anovulatory sex steroid production specifically excluding an
anatomic lesion. Several terms have been used to describe anovulatory bleeding, including dysfunctional, irregular, and abnormal. In this bulletin, the term
anovulatory uterine bleeding will be used as the standard terminology to
describe menstrual bleeding arising from anovulation or oligo-ovulation.
Several descriptive terms also are used to describe menstrual bleeding patterns, including menorrhagia, metrorrhagia, polymenorrhea, and menometrorrhagia. Menorrhagia is defined as prolonged or excessive uterine bleeding that
occurs at regular intervals, or more strictly, the loss of 80 mL or more of blood
PRACTICE BULLETINS
per menstrual cycle or bleeding that lasts for more than 7

days (1). Metrorrhagia is defined as irregular menstrual
bleeding or bleeding between periods. Polymenorrhea is
defined as frequent menstrual bleeding or, more strictly,
menstrual bleeding that occurs every 21 days or less.
Menometrorrhagia is defined as frequent menstrual
bleeding that is excessive and irregular in amount and
duration.
Ovulatory Cycle
During a normal ovulatory cycleincluding follicular
development, ovulation, corpus luteal function, and luteolysisthe endometrium is sequentially exposed to ovarian
production of estrogen alone, followed by a combination
of estrogen and progesterone; the cycle is culminated by
estrogen and progesterone withdrawal. Ovulation is associated with a cyclic pattern of endometrial histology commencing with proliferation followed by secretion change,
desquamation, and repair. Normal ovarian steroid production is important for nidation and pregnancy. From a clinical perspective, the result is cyclic, predictable, and
relatively consistent menstrual blood loss (2).
Pathophysiology
With anovulation, a corpus luteum is not produced, and the
ovary fails to secrete progesterone, although estrogen production continues. This condition results in continual
endometrial proliferation without progesterone-induced
desquamation and bleeding. The clinical result is bleeding
that is noncyclic, unpredictable, and inconsistent in volume.
Continuous, unopposed estrogen stimulation of the
endometrium results in unsustainable endometrial
growth. The endometrium becomes excessively vascular
without sufficient stromal support and becomes fragile,
resulting in variable endometrial bleeding. Unlike the
uniform, synchronized endometrial sloughing and bleeding that occurs with normal cyclic estrogen and progesterone stimulation, endometrial loss during continuous
estrogen stimulation is irregular. As one area of bleeding
begins to heal, another area begins to slough, resulting in
irregular and prolonged menstrual flow.
Alterations in endometrial prostaglandin (PG)
synthesis and release appear to occur in women with
anovulatory uterine bleeding. In particular, lower concentrations of PGF2 have been found in the endometrium of women with anovulatory bleeding as compared
with women with ovulatory menstrual cycles (3).
Furthermore, these investigators found a reverse correlation between the endometrial PGF2/PGE2 ratio and the
amount of menstrual blood lost. Therefore, abnormal
vasoconstriction produced by altered endometrial
prostaglandins may enhance blood loss in women with
chronic anovulation.
1157
Establishing the Diagnosis

The diagnosis of anovulatory uterine bleeding is made
after the exclusion of anatomic pathology. Diagnostic
techniques to exclude anatomic pathology include physical examination supplemented by endometrial sampling,
transvaginal ultrasonography, sonohysterography, hysterosalpingography, hysteroscopy, curettage, endometrial
cultures, and timed tests for determining progesterone
levels in serum. Recognized causes of anovulation are
given in the box below and should be considered when
evaluating the medical history and results of the physical
examination. There are numerous other causes of noncyclic vaginal bleeding. The differential diagnosis of
abnormal bleeding is listed in the box on the next page.
In this document, recommendations are based on the
assumption that the diagnosis of anovulatory bleeding
has been firmly established.
The physical examination should include an assessment for obesity and hirsutism, because these findings
are associated with chronic anovulation (4, 5). Thyroid
disease may cause anovulation as well as hyperprolactinemia. Approximately one third of all women with
hyperprolactinemia will have galactorrhea (6). In women
of reproductive age with noncyclic uterine bleeding,
pregnancy must be ruled out. If medical therapy fails to
resolve bleeding thought to be the result of anovulation,
an anatomic cause, including a malignant or premalignant lesion or a coagulopathy, should be reconsidered
and the patient reevaluated.
Causes of Anovulation
Physiologic
Adolescence
Perimenopause
Lactation
Pregnancy
Pathologic
Hyperandrogenic anovulation (eg, polycystic ovary
syndrome, congenital adrenal hyperplasia, androgen-producing tumors)
Hypothalamic dysfunction (eg, secondary to anorexia nervosa)
Hyperprolactinemia
Hypothyroidism
Primary pituitary disease
Premature ovarian failure
Iatrogenic (eg, secondary to radiation or
chemotherapy)
1158
Differential Diagnosis of
Noncyclic Uterine Bleeding
Anovulation
Uterine leiomyoma
Endometrial polyp
Endometrial hyperplasia or carcinoma
Cervical or vaginal neoplasia
Endometritis
Adenomyosis
Bleeding associated with pregnancy
threatened or incomplete abortion
trophoblastic disease
ectopic pregnancy
Bleeding associated with the puerperium
retained products of conception
placental polyp
subinvolution of the uterus
Coagulopathies (von Willebrands disease, platelet
abnormalities, thrombocytopenic purpura)
Iatrogenic causes and medications
Systemic diseases
Age Considerations of Anovulatory

Bleeding
Adolescents (1318 Years)
Anovulatory bleeding is a normal physiologic process in
the perimenarchal years of the reproductive cycle.
Ovulatory menstrual cycles may not be established until
a year or more after menarche. This phenomenon is
attributed to the immaturity of the hypothalamicpituitary gonadal axis. Anovulatory bleeding at this age can
be excessive, resulting in anemia and requiring emergency care. Occasionally, adolescents with blood
dyscrasias, including von Willebrands disease and prothrombin deficiency, have heavy vaginal bleeding beginning at menarche. Disorders such as leukemia, idiopathic
thrombocytopenic purpura, and hypersplenism can all
produce platelet dysfunction and cause excessive bleeding. Studies have demonstrated a wide variation in the
prevalence of blood dyscrasias ranging from 5% to 20%
of hospitalized adolescents (7, 8). Because the prevalence
of blood dyscrasias in the adolescent population is significant, routine screening for coagulation disorders is
warranted in these patients, including a partial thromboplastin time, prothrombin time, and assessment of platelet
function. Physical examination should include an assessment for petechiae or ecchymoses.
Women of Reproductive Age (1939 Years)

Between 6% and 10% of women have hyperandrogenic
chronic anovulation (eg, polycystic ovary syndrome),
which includes noncyclic menstrual bleeding, hirsutism,
and obesity (body mass index 25 kg/m2). As many as
65% of hirsute, chronically anovulatory women are
obese (4). Numerous underlying biochemical abnormalities exist, including noncyclic estrogen production, elevated serum testosterone levels, hypersecretion of
luteinizing hormone, and hyperinsulinemia (9). A history
of rapidly progressing hirsutism accompanied by virilization suggests a tumor. In most cases, tumors can be
ruled out by testing testosterone and dehydroepiandrosterone sulfate levels in serum.
Although anovulation may be considered physiologic in adolescents, adult women of reproductive age who
have menorrhagia, metrorrhagia, or amenorrhea require
evaluation for a specific cause. The laboratory assessment of these women should include a pregnancy test, a
fasting serum prolactin level, and determination of levels
of thyroid-stimulating hormone (TSH). When the diagnosis of ovarian failure is suspected, levels of folliclestimulating hormone (FSH) also should be determined.
Anovulation was found to be the most common cause of
amenorrhea in a series of 262 women who experienced
adult-onset amenorrhea (10). Chronic anovulation that
results from hypothalamic dysfunction, as diagnosed by
a low FSH level, may be the result of excessive psychologic stress, exercise, or weight loss (10). Both hyperthyroidism and hypothyroidism can be excluded using the
sensitive TSH assay. In patients with amenorrhea who
have a negative pregnancy test result and normal FSH,
TSH, and prolactin levels, the diagnosis of anovulation
can be made.
Women of Later Reproductive Age

(40 Years to Menopause)
The incidence of anovulatory uterine bleeding increases
as women approach the end of their reproductive years.
In this regard, perimenopausal women are not unlike
their perimenarchal counterparts. In perimenopausal
women, the onset of anovulatory cycles represents a continuation of declining ovarian function. These patients
need to be educated regarding the specific health risks
associated with menopause so that an early proactive
approach toward the prevention of menopause-associated
conditions, such as osteoporosis, can be initiated. In addition to the use of hormone replacement therapy for cycle
control, important lifestyle changes include exercise,
dietary modification, and smoking cessation.
PRACTICE BULLETINS
In women of each age group with anovulatory

bleeding, when is endometrial evaluation indicated?
Adolescents (1318 Years). In 1995, the incidence of

endometrial cancer in women between the ages of 15 and
19 years was 0.1 per 100,000 (11). In one report of
endometrial carcinoma in adolescents, the patients experienced 23 years of anovulatory uterine bleeding (12).
One patient experienced precocious puberty, which
extended the number of years of unopposed estrogen
exposure for someone of her age. All of the adolescents
were obese. Because obesity is associated with conversion of androgens to estrogens and chronic anovulation,
obese patients may be at an increased risk for developing
endometrial hyperplasia and carcinoma. Therefore, one
should consider endometrial assessment particularly for
those adolescents who have a history of 23 years of
untreated anovulatory bleeding and especially for those
who are obese.
Women of Reproductive Age (1939 Years). The incidence of endometrial carcinoma increases with age.
However, the incidence of endometrial carcinoma is still
very low in women between the ages of 19 and 39 years,
reported as 9.5 per 100,000 in 1995 (11). However, there
is a distinct increase in the incidence of endometrial carcinoma from ages 3034 years (2.3/100,000 in 1995) to
ages 3539 years (6.1/100,000 in 1995) (11). Therefore,
based on age alone, endometrial assessment to exclude
cancer is indicated in any woman older than 35 years
who is suspected of having anovulatory uterine bleeding.
Although endometrial carcinoma is rare in women
younger than 35 years, patients between the ages of 19
and 35 years who do not respond to medical therapy or
have prolonged periods of unopposed estrogen stimulation secondary to chronic anovulation are candidates for
endometrial assessment.
Women of Later Reproductive Age (40 Years to
Menopause). The incidence of endometrial carcinoma in
women ages 4049 years was 36.2 per 100,000 in 1995
(11). Therefore, all women older than 40 years who present with suspected anovulatory uterine bleeding should
be evaluated with endometrial assessment (after pregnancy has been excluded).

Recommendations
1159
What medical therapies are most appropriate

for each age group?
Because anovulatory uterine bleeding is by definition an

endocrinologic abnormality, medical management is the
preferred method of therapy. The goals of medical treatment for anovulatory bleeding are to alleviate acute
bleeding, prevent future episodes of noncyclic bleeding,
decrease the patients risk of long-term complications
from anovulation, and improve the patients overall quality of life. To encourage compliance with medical therapy, it is important to counsel patients that treatment may
cause initial heavy menstrual bleeding secondary to
endometrial buildup, but will lighten over time (within
three cycles).
Adolescents (1318 Years). Most adolescents who experience anovulatory bleeding can be treated with medical
therapy. Occasionally, adolescents may have acute, profuse menstrual bleeding. High-dose estrogen therapy is
an appropriate treatment to control acute bleeding
episodes because it promotes rapid endometrial growth to
cover denuded endometrial surfaces. Patients with blood
dyscrasias need to be treated for their specific disease,
and leukemia needs to be ruled out in this population.
Conjugated equine estrogens can be administered orally
up to 10 mg/d in four divided doses or intravenously at 25
mg every 4 hours for up to 24 hours (13). In a retrospective study, most adolescent patients with acute bleeding
(93%) responded to medical therapy (8). After acute
bleeding has been treated, recurrent anovulatory bleeding
should be prevented with either a cyclic progestogen or
an oral contraceptive.
Women with chronic anovulation can be treated successfully using either a cyclic progestogen or an oral contraceptive. Oral contraceptives suppress both ovarian and
adrenal androgen production and increase sex hormone
binding globulin, further reducing bioavailable androgens (14, 15). They also may inhibit 5-reductase activity in the skin of adults (16). Treatment with a low-dose
combination oral contraceptive (35 g ethinyl estradiol)
is appropriate, and maintenance oral contraceptives are
the treatment of choice in women with chronic anovulation, especially if they are hyperandrogenic and hirsute
(17).
Women of Reproductive Age (1939 Years). Adult
women of reproductive age with anovulatory uterine
bleeding can be treated safely with either a cyclic
progestogen or oral contraceptives similar to those prescribed for adolescent patients. However, estrogen-con-
1160
Women of Later Reproductive Age (40 Years to

Menopause). Women who are older than 40 years and
who have anovulatory uterine bleeding can be treated with
cyclic progestogen, low-dose oral contraceptives, or
cyclic hormone replacement therapy. Not unlike younger
women, these patients usually have adequate estrogen
production. However, women older than 40 years with
oligomenorrhea may have reduced estrogen production.
Women with hot flashes secondary to declining estrogen
production can obtain symptomatic relief with estrogen
replacement therapy in combination with continuous or
cyclic progestogen. Up to 90% of perimenopausal women
receiving continuous estrogen and cyclic progestogen
therapy will respond with predictable progesterone withdrawal bleeding (19).
In patients who have completed childbearing,

what is the benefit of treating anovulatory
bleeding surgically rather than medically?
Currently, there are few randomized trials comparing

medical versus surgical therapy for anovulatory uterine
bleeding. One randomized trial that compared endometrial resection with medical management for women with
menorrhagia found that women who underwent medical
therapy were less likely to be satisfied with their therapy
(20). However, because of its reduced cost and risks, medical therapy should be offered before surgical intervention
unless it is otherwise contraindicated. Surgical therapy is
indicated for women with excessive anovulatory bleeding
in whom medical management has failed and who have
completed their childbearing. Avoidance of anemia,
reduction of excessively heavy bleeding, and increased,
though imperfect, predictability of bleeding are appropriate goals to attempt to achieve with medical therapy.
Success and failure of medical therapy should be defined
in partnership with the patient, to better achieve the therapeutic goal.
taining oral contraceptives are relatively contraindicated

in some women (eg, those with hypertension or diabetes).
Estrogen-containing oral contraceptives are contraindicated for women older than 35 years who smoke or have a
history of thromboembolic disease.
If pregnancy is desired, induction of ovulation with
clomiphene citrate is the initial treatment of choice (18).
Patients can have withdrawal bleeding induced with
progestogen followed by initiation of therapy with
clomiphene citrate, 50 mg/d for 5 days, beginning between days 3 and 5 of the menstrual cycle.
In women who have completed childbearing,

what is the evidence of efficacy among surgical techniques?
The surgical options include hysterectomy and endometrial ablation. Recent studies have reported morbidity
rates of 7% (21) and 15% (22) for women undergoing
hysterectomy for various indications. The overall mortality rate for hysterectomy is 12 deaths per 10,000 procedures, for all surgical indications (23). A surgical
alternative to hysterectomy is endometrial ablation.
Endometrial ablation can be performed with or without
the assistance of hysteroscopy.
Hysteroscopic-assisted endometrial ablation can be
performed with the resectoscope. Using the resectoscope, the endometrium can be removed or resected with
an electrocautery loop or ablated with the rollerball.
Endometrial ablation also can be accomplished with the
YAG laser. An alternative to hysteroscopic-assisted
endometrial ablation is thermal balloon ablation in which
the endometrium is ablated by heating saline inside an
intrauterine balloon to approximately 85C. The most
frequently reported complications of hysteroscopy are
uterine perforation, which occurs in approximately 14 per
1,000 procedures (24) and fluid overload, which occurs in
approximately 2 per 1,000 cases.
Studies evaluating the effectiveness of endometrial
ablation have been performed in a group of women who
were diagnosed with menorrhagia and who were not
necessarily anovulatory. However, women with anovulatory uterine bleeding are candidates for endometrial
ablation if they have failed medical therapy and have
completed their childbearing. The proportion of women
who are amenorrheic after undergoing an endometrial
resection using the resectoscope or endometrial laser
ablation is approximately 45%, and the percentage of
women at 12 months postoperatively who are satisfied
with their therapy approaches 90% (25, 26). This high
degree of satisfaction indicates that reduction of flow is
adequate symptom control for most women, and achievement of amenorrhea is not as important. Endometrial
ablation with the thermal balloon yields an amenorrhea
rate of approximately 15% and a 12-month postoperative satisfaction rate of approximately 90% (27, 28).
Patient satisfaction with hysterectomy and endometrial ablation performed for dysfunctional uterine bleeding has been compared. One study demonstrated a higher
satisfaction rate in women who underwent hysterectomy
as compared with women who underwent hysteroscop-
PRACTICE BULLETINS

The treatment of choice for anovulatory uterine
bleeding is medical therapy with oral contraceptives.
Cyclic progestins also are effective.
Women who have failed medical therapy and no
longer desire future childbearing are candidates for
endometrial ablation, which appears to be an efficient
and cost-effective alternative treatment to hysterectomy for anovulatory uterine bleeding. However,
endometrial ablation may not be definitive therapy.
An underlying coagulopathy, such as von Willebrands disease, should be considered in all patients
(particularly adolescents) with abnormal uterine bleeding, especially when bleeding is not otherwise easily
explained or does not respond to medical therapy.
Women who experience acute, profuse anovulatory

bleeding are candidates for estrogen therapy. In approximately 90% of cases, acute bleeding does not require
surgical intervention, but it can be treated with medical
therapy (8). In a large series of 61 adolescents (mean
age, 13.8 2.1 years) with acute anovulatory uterine
bleeding, only five (8.2%) failed medical therapy and
required dilation and curettage to stop their bleeding.
Conjugated equine estrogen therapy can be administered
intravenously (25 mg every 4 hours for 24 hours).
However, oral conjugated estrogen therapy at 1020 mg
per day in four divided doses can be substituted for intravenous estrogen administration. In a randomized trial of
intravenous conjugated equine estrogen therapy versus
placebo, conjugated estrogens were effective in stopping
vaginal bleeding in a significantly greater proportion of
women (72%) than those who received a placebo (38%)
Summary
What is the role of high-dose estrogen in acute

vaginal bleeding?
(13). Although this study included women with biopsyproven pathology, it is one of the few studies performed
to assess the efficacy of intravenous estrogen therapy for
the treatment of women with anovulatory uterine bleeding. Patients who do not respond to 12 doses of estrogen
with a significant decline in blood loss or are not hemodynamically stable should undergo dilation and curettage.
Furthermore, as high-dose estrogen therapy is commonly
associated with nausea, concomitant medical therapy with
antiemetics should be considered.
After the acute episode of bleeding has been controlled, amenorrhea should be maintained for several
weeks to allow for resolution of anemia. The best method
of therapy is a combination oral contraceptive. To extend
the interval before the next menses, continuous oral contraceptives (without the use of placebo pills) can be given
for several months; however, over time the patient will be
susceptible again to breakthrough bleeding. Once the
patients anemia has resolved, cyclic oral contraceptives
can be prescribed. All anemic patients should be given
iron therapy.
ic-assisted endometrial ablation (29). Furthermore, the

long-term satisfaction of women who have undergone
endometrial ablation has been questioned. In a 3-year follow-up study, 8.5% of women who had undergone
endometrial ablation later underwent repeat ablation, and
an additional 8.5% had undergone hysterectomy (30). In
a 5-year follow-up study, 34% of women who had undergone hysteroscopic ablation subsequently had a hysterectomy (31). Because women who undergo endometrial
ablation can have residual active endometrium, these
women should receive progestogen if they are prescribed
estrogen replacement therapy.
Numerous studies have compared costs and surgical
outcomes between endometrial resection or ablation and
hysterectomy. The evidence suggests that hysteroscopic
endometrial ablation results in less morbidity and shorter
recovery periods and is more cost-effective than hysterectomy (3237). However, if as many as one third of
women who undergo endometrial ablation undergo hysterectomy within the following 5 years, that would have a
significant impact on these cost analyses.
Evidence from randomized trials supports the use of
either a gonadotropin-releasing hormone agonist or danazol prior to endometrial ablation or resection with regard
to improved intrauterine operating environment and
short-term postoperative outcome (38). The choice of
agents should be based on cost, efficacy, and side effects.
There are insufficient data to assess the value of progestogen therapy prior to endometrial ablation.
1161
Although there is limited evidence evaluating the

efficacy of conjugated equine estrogen therapy in
anovulatory bleeding, it is effective in controlling
abnormal uterine bleeding.
1162
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9. Goudas VT, Dumesic DA. Polycystic ovary syndrome.
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10. Reindollar RH, Novak M, Tho SP, McDonough PG. Adultonset amenorrhea: a study of 262 patients. Am J Obstet
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12. Stovall DW, Anderson RJ, De Leon FD. Endometrial adenocarcinoma in teenagers. Adolesc Pediatr Gynecol 1989;
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16. Cassidenti DL, Paulson RJ, Serafini P, Stanczyk FZ, Lobo
RA. Effects of sex steroids on skin 5 alpha-reductase activity in vitro. Obstet Gynecol 1991;78:103107 (Level III)
17. Rittmaster RS. Clinical review 73: Medical treatment of

androgen-dependent hirsutism. J Clin Endocrinol Metab
1995;80:25592563 (Level III)
18. Hughes E, Collins J, Vandekerckhove P. Clomiphene citrate for unexplained subfertility in women (Cochrane
review). In: The Cochrane Library, Issue 4, 1999. Oxford:
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19. Strickland DM, Hammond TL. Postmenopausal estrogen
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Health 1988;2(1):2631 (Level III)
20. Cooper KG, Parkin DE, Garratt AM, Grant AM. Two-year
follow up of women randomised to medical management
or transcervical resection of the endometrium for heavy
menstrual loss: clinical and quality of life outcomes. Br J
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22. Summitt RL Jr, Stovall TG, Steege JF, Lipscomb GH. A
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24. Hulka JF, Peterson HA, Phillips JM, Surrey MW.
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27. Amso NN, Stabinsky SA, McFaul P, Blanc B, Pendley L,
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FD, Steege JF. Thermal balloon and rollerball ablation to
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DA, Russell IT, et al. Randomised trial of hysterectomy,
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resection for dysfunctional uterine bleeding. BMJ 1994;
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30. Chullapram T, Song JY, Fraser IS. Medium-term followup of women with menorrhagia treated by rollerball
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32. Gannon MJ, Holt EM, Fairbank J, Fitzgerald M, Milne
MA, Crystal AM, et al. A randomised trial comparing
endometrial resection and abdominal hysterectomy for the
treatment of menorrhagia. BMJ 1991;303:13621364
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33. Brooks PG, Clouse J, Morris LS. Hysterectomy vs. resectoscopic endometrial ablation for the control of abnormal
uterine bleeding. A cost-comparative study. J Reprod Med
1994;39:755760 (Level II-2)
34. Goldenberg M, Sivan E, Bider D, Mashiach S, Seidman
DS. Endometrial resection vs. abdominal hysterectomy for
menorrhagia. Correlated sample analysis. J Reprod Med
1996;41:333336 (Level II-2)
35. Cameron IM, Mollison J, Pinion SB, Atherton-Naji A,
Buckingham K, Torgerson D. A cost comparison of hysterectomy and hysteroscopic surgery for the treatment of
menorrhagia. Eur J Obstet Gynecol Reprod Biol
1996;70:8792 (Level I)
36. Vilos GA, Pispidikis JT, Botz CK. Economic evaluation of
hysteroscopic endometrial ablation versus vaginal hysterectomy for menorrhagia. Obstet Gynecol 1996;88:241
245 (Level II-2)
37. Brumsted JR, Blackman JA, Badger GJ, Riddick DH.
Hysteroscopy versus hysterectomy for the treatment of
abnormal uterine bleeding: a comparison of cost. Fertil
Steril 1996;65:310316 (Level II-2)
38. Fraser IS, Healy DL, Torode H, Song JY, Mamers P, Wilde
F. Depot goserelin and danazol pre-treatment before rollerball endometrial ablation for menorrhagia. Obstet Gynecol
1996;87:544550 (Level I)
1163

Force:
I
type of evidence.
committees.
Copyright March 2000 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this
Danvers, MA 01923, (978) 750-8400.
409 12th Street, SW
PO Box 96920
1164
ACOG
PRACTICE
BULLETIN
Premenstrual Syndrome
of Ann J. Davis, MD and Susan
R. Johnson, MD, MS. The information is designed to aid
of practice.
Reaffirmed 2008
Premenstrual syndrome (PMS) is a common problem for many women.

Determining the appropriate clinical management of this condition often creates frustration for both physicians and patients. Until recently, the difficulty in
managing PMS was largely attributed to imprecise diagnostic criteria, poorly
designed clinical trials, and the promotion of treatment options for which there
was no scientific support. In the mid-1980s, however, rigorous criteria for the
diagnosis of PMS were defined. Since then, most studies of pathophysiology
and treatment have met recognized standards of scientific design. This document will examine the evidence for commonly used approaches in the treatment
of PMS and identify those that are effective.
Background
Premenstrual syndrome has been defined as the cyclic occurrence of symptoms that are of sufficient severity to interfere with some aspects of life and that
appear with consistent and predictable relationship to the menses (1).
Although the symptoms themselves are not unique, the restriction of the symptoms to the luteal phase of the menstrual cycle is pathognomonic of PMS (2).
Epidemiology
Premenstrual symptoms are common and are considered a normal aspect of
ovulatory cycles. Most surveys have found that as many as 85% of menstruating women report one or more premenstrual symptoms. Severe symptoms that
meet the criteria for PMS, however, are much less common, with only 510%
of women reporting significant impairment in their lifestyles because of PMS
(3, 4).
Risk Factors
Advancing age often is cited as a risk factor for PMS, based on surveys that find
women are most likely to seek treatment after age 30 years. However, this syndrome can occur in menstruating women of any age. Genetics appears to play
PRACTICE BULLETINS
a role in PMS; the concordance rate of PMS is twice as

high among monozygotic twins as among dizygotic
twins (5, 6). Although women with PMS have a high rate
of affective disorders, a causal relationship has not yet
been demonstrated (7, 8).
There are no significant personality profile differences between women with PMS and asymptomatic
women (9). Furthermore, PMS is not more likely to be
diagnosed in women with higher levels of stress (10).
However, women who have PMS may not tolerate stress
as well as women who do not have PMS. Premenstrual
symptoms seem to affect women irrespective of culture
or socioeconomic status, although specific symptoms
may vary in frequency by culture (1113).
Etiology
The etiology of PMS is incompletely understood, but
considerable progress has been made in the past decade
in understanding some facets of the pathophysiology.
Circulating sex steroid levels (progesterone, estrogen,
and testosterone) are normal, although there may be an
underlying neurobiologic vulnerability to normal fluctuations of one or more of these hormones (14, 15). Most
likely, the biochemical changes involve central-nervoussystemmediated neurotransmitter interactions with sex
steroids. Serotoninergic dysregulation is currently the
most plausible theory. Among the several studies supporting this theory is a well-designed study in which
women with severe PMS responded better to selective
serotonin reuptake inhibitors (SSRIs) than to noradrenergic antidepressants such as maprotiline (16). Because not
all women with PMS respond to SSRIs, other etiologic
factors probably are involved.

Recommendations
Establishing evidenced-based recommendations for PMS
is difficult for many reasons. Definitions and inclusion
criteria for PMS vary significantly among studies. In
addition, the PMS patient populations studied in rigorous
trials also may be different from the patient population of
a given practitioner. For example, many recent PMS trials have properly included only women with the fullblown syndrome, including mood-related symptoms,
whereas many women seek care from their practitioners
for a less severe condition, with primarily somatic symptoms.
How is the diagnosis of PMS established?
The key elements of the diagnosis are a) symptoms consistent with PMS; b) restriction of these symptoms to the luteal
1165
phase of the menstrual cycle assessed prospectively; c)

impairment of some facet of the womans life; and d) exclusion of other diagnoses that may better explain the symptoms.
The National Institute of Mental Health criteria for
diagnosis are 1) a marked change of about 30% in the
intensity of symptoms measured instrumentally, from
cycle days 5 to 10 (as compared with those premenstrually), within the 6-day interval prior to menses and 2)
documentation of these changes for at least two consecutive cycles (17). Another definition of PMS developed for
research purposes by the University of California at San
Diego is based on womens prospective self-reports.
Their definition requires that patients have the cyclic
manifestation of at least 1 of 6 behavioral symptoms and
1 of 4 somatic symptoms (see the box). Dysfunction in
social or economic performance is included in this definition. Finally, the Diagnostic and Statistical Manual of
Mental Disorders, fourth edition, includes similar criteria
for the diagnosis of premenstrual dysphoric disorder,
which identifies women with PMS who have more severe
emotional symptoms (18).
The diagnosis of PMS should be based on prospective symptom diaries, because as many as half of the
Diagnostic Criteria for Premenstrual Syndrome
Premenstrual syndrome can be diagnosed if the patient
reports at least one of the following affective and somatic
symptoms during the 5 days before menses in each of
the three prior menstrual cycles*:
Affective
Depression
Angry outbursts
Irritability
Anxiety
Confusion
Social withdrawal
Somatic
Breast tenderness
Abdominal bloating
Headache
Swelling of extremities
*These symptoms are relieved within 4 days of the onset of menses,
without recurrence until at least cycle day 13. The symptoms are present
in the absence of any pharmacologic therapy, hormone ingestion, or
drug or alcohol use. The symptoms occur reproducibly during two
cycles of prospective recording. The patient suffers from identifiable dysfunction in social or economic performance.
Adapted from Mortola JF, Girton L, Yen SC. Depressive episodes in premenstrual syndrome. Am J Obstet Gynecol 1989;161:16821687
1166
women reporting a luteal phase pattern will be found to

have some other pattern when such diaries are examined.
Because some women experience cycle-to-cycle variability in symptoms, reviewing 23 months of prospective
charting is preferable to reviewing a single cycle (19).
In the clinical setting, a simple system in which the
woman records the dates of her menstrual periods and
notes her symptoms on a daily basis is usually sufficient
(20). However, a variety of standardized instruments and
diaries developed for research purposes are also available. The most commonly used are the Calendar of
Premenstrual Experiences (COPE) (21) and the Prospective Record of the Impact and Severity of Menstruation (PRISM) (22). Another type of instrument, the
Visual Analogue Scales (VAS), may be especially appropriate in non-English-reading populations (23).
A careful medical and psychologic history and physical examination in conjunction with the prospective
symptom diary usually will direct the clinician toward the
correct diagnosis. Laboratory testing should be restricted
to the identification of other disorders suggested by the
evaluation, such as measuring levels of thyroid-stimulating hormone when hypothyroidism is suspected. Routine
measurement of steroid hormones or gonadotropins is not
useful.
Which patients require therapeutic intervention for PMS?
Premenstrual syndrome, by definition, is associated with

symptoms that interfere with some part of the patients
normal life, but there are usually no medical sequelae if
the disorder is not treated. Therefore, the decision to treat
the disorder should be based on the patients desire for an
improvement in her symptoms. Furthermore, because
there is a wide range of symptom severity, the treatment
approach should match the patients needs.
Only a small portion of women presenting for evaluation

and treatment of PMS are likely to have PMS. For example, in a sample of women who responded to a newspaper recruitment for a PMS study, the most common
symptoms reported were consistent with PMS: irritability, depression, mood swings, anxiety, mastalgia, abdominal bloating, weight gain, fatigue, aggression, headache,
tension, muscle aches, food cravings, and breast swelling
(24). However, individuals who respond to such recruitment may not be representative of the general population.
In this study, after a complete evaluation, 60% of the
women also were found to have psychiatric disorders.
The phenomenon of menstrual magnification (sometimes called premenstrual or perimenstrual exacerbation)
helps explain this situation. Many medical and psychiatric conditions are exacerbated in the late luteal or menstrual phase of the cycle, leading a woman to believe that
she must be experiencing PMS. The underlying mechanism of this increase in symptoms is not understood.
The differential diagnosis of PMS therefore includes
any medical and psychiatric condition that either has
some of the many symptoms associated with PMS or is
subject to menstrual magnification. Depressive disorders,
which share a similar set of symptoms, are the most com-
How is PMS objectively differentiated from

similar conditions?
mon consideration (25). Depressive disorders also are

subject to the magnification effect, making the distinction
from PMS even more difficult. A key feature of depressive disorders, however, is that symptoms are almost
always present every day of the cycle. Other psychiatric
conditions that may be magnified are panic disorder and
generalized anxiety disorder.
The most common medical disorders subject to
menstrual magnification are migraines, seizure disorders,
irritable bowel syndrome, asthma, chronic fatigue syndrome, and allergies. Endocrine abnormalities such as
thyroid and adrenal disorders also should be considered.
The diagnosis of these conditions usually is straightforward because the key symptoms are not part of the typical PMS symptom set, and emotional symptoms are not
prominent, as they are in PMS.
Finally, women in the period of transition to
menopause may have symptoms typical of PMS, especially mood disturbance, fatigue, and hot flashes. Because
menstrual periods often are less predictable, these women
may be less aware of the relationship of the symptoms to
the menstrual cycle. The correct diagnosis usually can be
made by considering the patients age, a history of recent
menstrual cycle changes, and a symptom diary showing
sporadic or daily occurrence of symptoms.
What is the evidence supporting the effectiveness of the following common treatments for
PMS?
A wide variety of supportive, lifestyle, and dietary supplementation approaches to PMS have been recommended over the years, and a few of these have been demonstrated to have real benefit. Therefore, these strategies
can be recommended to women with mild to moderate
symptoms as a primary therapy and to women with
severe symptoms as adjunctive therapy.
Women with severe symptoms or with symptoms
resistant to nonmedical approaches should be considered
for drug therapy. Although no drugs currently are specifically approved by the U.S. Food and Drug Administration
PRACTICE BULLETINS
for the treatment of PMS, several available drugs have

been found to be effective for PMS and can be prescribed.
Supportive Therapy. Supportive therapy has been
employed as a central component in PMS management,
although it has not been studied rigorously. Reassurance
and informational counseling may relieve many anxieties
and increase the patients sense of control. Women anecdotally report relief when they are informed that PMS is
a common medical problem with a physiologic basis.
Supportive therapy may contribute in part to the high
response rate to placebos for virtually every form of
treatment used for PMS.
The value of more formal psychologic interventions
has not been conclusively demonstrated. The best evidence is for relaxation therapy. In one small comparative
study, relaxation therapy had its greatest effects in
women with the most severe symptoms (26). In a study
of cognitive behavior therapy, the comparison group who
received information about PMS, relaxation training, and
lifestyle and nutrition guidelines fared nearly as well as
the study group who received cognitive restructuring
training (27).
Aerobic Exercise. Aerobic exercise has been found in
epidemiologic studies to be associated with fewer reported PMS symptoms, and exercise has been found to
reduce symptoms among people with depressive disorders. Limited evidence supports a similar role for this
intervention in PMS. In a 3-month randomized trial of 23
women with prospectively diagnosed PMS, the group
taking regular moderate aerobic exercise reported more
improvement than the control group who did nonaerobic
exercise (28). In another small prospective but not randomized study, two groups of women who exercised aerobically reported fewer PMS symptoms at the end of a 6month trial than did a nonexercising comparison group
(29). Although the evidence base is modest at this time,
aerobic exercise can be recommended to all women with
PMS because of its numerous other health benefits.
Dietary Supplementation. Calcium and magnesium
have each been shown to be effective in the treatment of
PMS. However, most of these trials have tested small
numbers of patients and must be validated in larger trials
before strong evidence-based recommendations can be
made. One large well-designed multicenter trial of 466
women with PMS reported that 1,200 mg/d of calcium
carbonate was efficacious in reducing total symptom
scores (30). Two small trials have found that 200400 mg
of magnesium may be somewhat effective (31, 32).
Minimal data are available on the effectiveness of
vitamin E and the treatment of premenstrual syndrome.
Vitamin E has been recommended as a treatment for
1167
mastalgia. In one randomized, double-blind, controlled

study comparing vitamin E 400 IU/d during the luteal
phase with placebo, vitamin E was found to improve significantly affective and somatic symptoms in PMS
patients (33). Although effectiveness probably is minimal, no serious side effects are reported with vitamin E
400 IU/d, and as an antioxidant it has other beneficial
effects.
In one study, mood symptomatology and carbohydrate food cravings were shown to be improved by carbohydrate-rich beverages (34). This small, well-designed
study should be repeated with larger numbers of subjects
before evidence-based recommendations can be made.
One hypothesis to explain these benefits is that diets rich
in carbohydrates increase levels of tryptophan, the precursor to serotonin.
Well-designed scientific studies have not demonstrated that primrose oil is effective in the treatment of
PMS. However, it may be useful in treating breast tenderness (35).
On the basis of a recent systematic review of several
weak clinical studies, vitamin B6 is considered to be of
limited clinical benefit in the treatment of PMS (36).
Dosages in excess of 100 mg/d may cause medical harm,
including peripheral neuropathy (36).
Selective Serotonin Reuptake Inhibitors. The SSRIs are
the initial drugs of choice for severe PMS. Fluoxetine is
the most studied drug of this group. Its use has been studied in almost 1,000 women in rigorous trials. The largest,
a 6-month, multicenter trial, evaluated 313 women with
PMS who were prescribed dosages of 2060 mg/d (37).
Investigators observed 44% dropouts at dosages of 60
mg/d and 11% at dosages of 20 mg/d. This study, along
with several smaller, shorter-duration placebo-controlled
trials, have consistently reported the efficacy of fluoxetine. The dosage in these trials generally was 20 mg/d
throughout the menstrual cycle administered as a single
morning dose to avoid insomnia. One study reported efficacy in 64 women with PMS over a mean treatment time
of 18 months (38). In this 18-month study, symptoms
recurred in most of the women not taking fluoxetine and
resolved when treatment was restarted.
Other SSRI drugs that have had a beneficial effect
similar to that of fluoxetine are sertraline, paroxetine,
clomipramine, fluvoxamine, and nefazodone. In the
largest study of sertraline, in which there were 233 subjects, dosages ranged from 50 to 150 mg/d (39).
Intermittent therapy, with an SSRI given only during the symptomatic phase, also has been efficacious in
several small, randomized, double-blind, placebo-controlled trials (4042). This method of administration has
many advantages: it is less expensive, reduces the overall rate of side effects, and is more acceptable to many
1168
women. The drug is started between 7 and 14 days

before the next menstrual period, with the start day individualized to begin the medication at or just before the
expected onset of symptoms.
Side effects associated with fluoxetine include
headaches, nausea, and jitteriness. Insomnia often can be
avoided by early-morning dosing or, if appropriate, by
lowering the dosage. Decreased libido also is problematic in some patients. In cases in which improvement of
libido is not seen after dosage changes, alternative therapies may be considered (4).
Other Pharmacologic Approaches. Some placebocontrolled trials have shown alprazolam, an anxiolytic
medication, to be effective as a treatment for PMS
(4345), and some have not (46). There is a potential for
dependency and development of tolerance with this medication, especially if dosing is not limited to the luteal
phase. Sedation also can be a bothersome side effect in
some patients, and withdrawals can be problematic.
Alprazolam may potentially be useful for PMS patients
who are not relieved by other interventions. It may be
especially useful if agitation and anxiety are the primary
symptoms.
Because complaints of fluid retention are common
in the luteal phase, diuretic therapy has been advocated.
No evidence exists that thiazide diuretics are of benefit.
Spironolactone, an aldosterone antagonist with antiandrogenic properties, is the only diuretic that has been
shown to be of benefit in PMS. Several randomized,
double-blind, placebo-controlled trials have shown a significant reduction in somatic and affective complaints
(4751). Usual dosage in most studies is 100 mg/d in the
morning during the 14-day luteal phase. However, not
all reports evaluating spironolactone for PMS have
shown benefit.
Historically, natural progesterone has been one of the
most commonly employed therapies in women with PMS,
but careful scientific scrutiny has not supported an overall
benefit of this hormone when compared with placebo,
whether administered as a vaginal suppository (52) or as
oral micronized progesterone (45). Progesterone may be
helpful for specific symptoms, such as breast tenderness
and bloating, or specific psychologic symptoms, such as
worrying (53).
What is the role of hormonal suppression in

the treatment of PMS?
Oral Contraceptives. Although oral contraceptives are

widely prescribed for the treatment of PMS, few data
support their effectiveness. In one randomized trial, a
triphasic formulation reduced physical symptoms but not

mood alterations (54). In another study comparing triphasic and monophasic regimens, the monophasic formulation was less likely to cause mood alterations (55). Many
patients experience breast tenderness, nausea, mood alterations, and other side effects the first few months of oral
contraceptive use. The evidence suggests that oral contraceptives should be considered if symptoms are primarily
physical, but may not be effective if mood symptoms are
more prevalent.
Gonadotropin-Releasing Hormone Agonists. Improvement in PMS symptoms with gonadotropin-releasing hormone (GnRH) agonists has been reported in the majority
of well-designed studies (5657) but not in all of them
(58). The hypoestrogenic side effects and cost of GnRH
agonists limit the usefulness of this method except in
severe cases of PMS unresponsive to other treatment.
If this therapy is to be used for more than a few
months, bone loss becomes a concern. The most commonly used approach is add-back estrogen therapy (with
progestin if indicated). Add-back therapy also may result
in a return of symptoms, although studies are limited and
sometimes confusing. In a double-blind, placebo-controlled study of 10 women, both estrogen add-back therapy alone and progesterone therapy alone were associated
with a significant recurrence of symptoms (15). Another
small rigorous study evaluated eight women with PMS.
Administration of the GnRH agonist resulted in an
improvement of approximately 75% in luteal phase symptom scores. The addition of estrogen as well as progesterone was associated with worsening symptoms, but a
similar worsening also was seen with placebo (59). If hormone therapy results in a return of symptoms, alendronate
should be considered for osteoporosis prevention.
Bilateral Salpingo-Oophorectomy. Surgery for PMS is
controversial because it is irreversible, it is associated with
morbidity and mortality, and the resulting hypoestrogenemia must be addressed to prevent long-term complications. If employed, this approach should be reserved for
those severely affected patients who meet strict diagnostic
criteria and who do not respond to any potentially effective
therapy other than GnRH agonists (60). These limitations
are critical, because a major cause of therapeutic failure
with any of the described treatments is an incorrect diagnosis of PMS. It is advisable to perform a diagnostic trial
with an agonist for a minimum of 3 months to determine if
oophorectomy will be effective. An additional advantage to
an extended trial with an agonist is the opportunity to
assess the womans tolerance for estrogen replacement
therapy.
PRACTICE BULLETINS
Summary
The following recommendations are based on good and
Women in whom PMS has been diagnosed should

meet standard diagnostic criteria and should have the
timing of their symptoms confirmed using a
prospective symptom calendar.
Risk factors such as increased imposed stress and
specific personality profiles are not helpful in differentiating women with PMS from those without
PMS.
The SSRIs, particularly fluoxetine and sertraline,
have been shown to be effective in treating PMS.
The bulk of scientific evidence does not support the
usefulness of natural progesterone or primrose oil in
the treatment of PMS.
The following recommendations are based on limited or

The use of GnRH agonists and surgical oophorectomy

have been shown to be effective in PMS. However, the
side effects of GnRH agonists and oophorectomy
limit their usefulness in most patients.
Treatment with the anxiolytic alprazolam is effective
in some patients. Its side effects limit its use as a
first-line approach.
Carbohydrate-rich foods and beverages may
improve mood symptoms and food cravings in
women with PMS and are a reasonable first-line
approach in many patients.
Calcium supplements have been shown to be effective in the treatment of PMS.
Magnesium, vitamin B6, and vitamin E may have
minimal effectiveness in the treatment of PMS.
Oral contraceptives may improve physical symptoms of PMS.
The following recommendations are based primarily on

Supportive therapy is central to the management of

all PMS patients.
Aerobic exercise can be recommended to PMS
patients.
As an overall clinical approach, treatments should be
employed in increasing orders of complexity. Using
this principle, in most cases, the therapies should be
used in the following order:
Step 1. Supportive therapy, complex carbohydrate
diet, aerobic exercise, nutritional supplements (calcium, magnesium, vitamin E), spironolactone
1169
Step 2. The SSRIs (fluoxetine or sertraline as the initial choice); for women who do not respond, consider an anxiolytic for specific symptoms
Step 3. Hormonal ovulation suppression (oral contraceptives or GnRH agonists)
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Treatment of premenstrual syndrome by spironolactone: a
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50. Burnet RB, Radden HS, Easterbrook EG, McKinnon RA.
Premenstrual syndrome and spironolactone. Aust N Z J
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Ineffectiveness of progesterone suppository treatment for
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1171
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Efficacy of progesterone vaginal suppositories in alleviation of nervous symptoms in patients with premenstrual
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54. Graham CA. Sherwin BB. A prospective treatment study
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55. Backstrom T, Hansson-Malmstrom Y, Lindhe BA, CavilliBjorkman B, Nordenstrom S. Oral contraceptives in
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56. Johnson SR. Premenstrual syndrome therapy. Clin Obstet
57. Freeman EW, Sondheimer SJ, Rickels K. Gonadotropinreleasing hormone agonist in treatment of premenstrual
symptoms with and without ongoing dysphoria: a controlled study. Psychopharmacol Bull 1997;33:303309
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58. West CP, Hillier H. Ovarian suppression with the
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(Zoladex) in management of the premenstrual tension syndrome. Hum Reprod 1994;9:10581063 (Level I)
59. Mortola JF, Girton L, Fischer U. Successful treatment of
severe premenstrual syndrome by combined use of
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60. Casson P, Hahn PM, Van Vugt DA, Reid RL. Lasting
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(Level II-3)
1172

Force:
I
type of evidence.
committees.
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
PRACTICE BULLETINS
1173
ACOG
PRACTICE
BULLETIN

of Maida Taylor, MD. The information is designed to aid
of practice.
Reaffirmed 2008
Use of Botanicals for

Management of
Menopausal Symptoms
Lack of confidence in the espoused benefits of hormone replacement therapy
(HRT) coupled with a significant array of side effects of HRT, results in fewer
than 1 in 3 women choosing to take HRT. The use of alternatives to conventional HRT has become more accessible and acceptable to many women. As
more women choose these alternatives, physicians are confronted with the challenges of how to advise patients about alternative medicine and how to determine which therapies may be safe and effective. This document will examine
available scientific information on alternative therapies for treatment of
menopausal symptoms and provide recommendations on efficacy and potential
adverse consequences.
Background
Discontent with Current Pharmaceutical Regimens
Hormone replacement therapy is associated with various side effects and complications; 3040% of patients experience some degree of abnormal bleeding in
the first year of hormone use, which often results in discontinuation of use (1).
Initiating HRT also is viewed by some women as treating menopause as a medical disorder, which is seen by a large segment of the population as a natural,
normal part of the aging process. In addition, many women believe that estrogen therapy may increase the risk of breast cancer, and the fear of breast cancer is most often cited as the reason for lack of initiation (2).
1174
Complementary and Alternative

Medicine
Complementary medicine can be defined as those systems, practices, interventions, modalities, professions,
therapies, applications, theories, or claims that are currently not an integral part of the conventional medical
system (3). Alternatively, conventional medicine refers to
medicine as it is generally practiced and widely taught by
medical doctors, doctors of osteopathy, and their allied
health professionals (4). Alternative medicine encompasses a number of systematic medical practices based
on physical assessments that differ from physiology as it
is taught in Western medical institutions. The most
recognizable and widely employed alternatives are biologic-based therapies such as botanical medicines,
dietary supplements, vitamins, minerals, and orthomolecular medicine. In a 1998 survey, alternative medicine
visits exceeded visits to conventional primary care
providers, and 70% of such encounters were never discussed with the patients regular personal physician (5).
In addition, a national survey reported the highest rates of
use in the groups aged 3549 years (42%) and 5064
years (44%) (6). Three theories were proposed by the
investigator as tentative predictors of use of alternatives
therapies: 1) dissatisfaction with conventional medicine;
2) viewing alternatives as more empowering because of
their over-the-counter status; and 3) perceiving alternatives as more compatible with personal values or ethical
or religious belief systems. Predictors of alternative care
use were reported to include higher educational level,
poorer health status, holistic orientation to health, having
had a transformational experience changing ones world
view, and several chronic health conditions such as anxiety, back problems, chronic pain, and urinary tract problems. Only 4.4% of respondents relied primarily on alternative therapies.
In 1997, out-of-pocket expenditures for alternative
therapies were estimated at $27 billion, which was more
than the out-of-pocket expenditures for all physician services that year (7). Recently, third-party carriers have
started providing coverage for alternative therapies, sometimes assessing an extra premium for such expanded benefits.
Complementary and Alternative

Medicines Used in Menopause
The symptoms associated with perimenopause and
menopause stimulate a healthy concern about wellness
and motivate women to undertake appropriate interventions to lower health risks associated with menopause.
Interest in alternative medicine can be viewed simply as
a natural extension of interest in nutrition, exercise, and
other behavioral, nonpharmacologic interventions direct-
ed at maintaining well-being. Unfortunately, many of the

alternatives promoted and touted as substitutes for HRT
do not offer any substantiated health benefits.
According to the North American Menopause
Society, nonhormonal interventions commonly used for
menopause include a healthy diet, exercise, vitamins, and
calcium supplements. The North American Menopause
Society also indicates that more than 30% of women use
acupuncture, natural estrogen, herbal supplements, or socalled plant estrogens (8). Alternative therapies to conventional HRT include botanical products, vitamins and
minerals, unconventional hormones and steroids sold
over-the-counter as nutritional supplements or as cosmetics, and nonproprietary single and combination estrogen
and progestin preparations custom blended by compounding pharmacies.
Most studies of menopausal interventions, including
phase-III clinical trials of estrogenic drugs, show a
2030% response rate in placebo groups. Unconventional
interventions need to be studied in well-controlled trials
before their use can be supported. Documentation of efficacy is essential because these products should yield
effective results of a magnitude large enough to warrant
their costs, which are substantial.
Botanical Medicine
Up to one half of drugs commonly used today are either
plant products or phytochemicals that were initially isolated from botanical material but are now synthesized by
chemical processing techniques. Outside of pharmaceutical preparations, plants are used therapeutically in the
form of herbs, oils, pills, teas, or tinctures (see box). In
Therapeutic Forms of Botanical Preparations
Bulk herbs are raw or dried plants used in toto, as
pulvers or powders, or to make teas and tinctures.
The powders also can be put into capsules or compounded into tablet form.
Oils are concentrates of fat-soluble chemicals from
herbs, often highly concentrated, and usually used
externally. Many are highly toxic if ingested.
Tablets or capsules can be compounded for ease of
use and often with the intent of providing a fixed
metered dose.
Teas may be used to extract solubles in herbs by
adding hot water, and the potency is determined
by the steeping time. Teas are traditionally brewed
12 minutes, infusions for 2030 minutes, while
preparation of a decoction requires boiling the plant
material in water for 1020 minutes.
Tinctures are alcohol-extracted concentrates usually
added to water or placed directly into the mouth or
under the tongue.
PRACTICE BULLETINS
addition, currently used products include highly concentrated extracts of phytochemicals, synthetic derivatives,
and even steroids like dehydroepiandrosterone (DHEA)
and androstenedione, which are classified as food supplements because they are produced from plant precursor
sterols.
Dietary Plant Estrogen/Phytoestrogens

Plants do not make estrogens in the classic sense of the
term. Plants make sterol molecules, many of which exert
weak estrogenic activity in animals although their effects
increase when large quantities are ingested. These compounds, phytoestrogens, often possess structural similarities to more active human and animal estrogens. Plant
sterols are used as the precursors for the biosynthetic
production of mass-manufactured therapeutic pharmaceutical-grade steroids. A number of plants used to treat
symptoms of menopause have been identified in botanical
medicine texts as having estrogenic activity, but research
has contradicted these traditional assumptions (9).
Phytoestrogens are classified into three groups (10):
1. Isoflavones, particularly, genistein and daidzein, are
plant sterol molecules found in soy and garbanzo
beans and other legumes, which are most often consumed in products like tempeh, soy, miso, and tofu.
Generally, 1 g of soy protein yields 1.21.7 mg of
isoflavones, depending on the type of soybean used
as the source of the protein.
2. Lignins are a constituent of the cell wall of plants
and are bioavailable as a result of the effect of
intestinal bacteria on grains. The highest amounts
are found in the husk of seeds used to produce oils,
especially flaxseed. The whole seed added to salad
or cereal, or flaxseed meal or flour can be used as a
food additive.
3. Coumestans have steroidlike activity but are not a
significant source of phytoestrogens for most individuals. High concentrations are found in red clover,
sunflower seeds, and bean sprouts and are known to
have estrogenic effects when ingested by animals.
Asian diets are typically high in soy foods and contain an average of 4080 mg of active forms of
isoflavones per day, while American diets average less
than 3 mg per day. American and European diets tend to
elevate plasma levels of sex hormones and decrease sexhormone-binding-globulin concentrations, thus increasing the exposure of peripheral tissues to the effects of
circulating estrogens. High-soy diets act through several
mechanisms to lower effective circulating and tissue levels of steroids. High isoflavone intake may depress
luteinizing hormone (LH) levels and secondarily depresses estrogen production (11, 12).
1175
The plant lignan and isoflavonoid glycosides

become hormonelike compounds with weak estrogenic
and antioxidative activity through the action of intestinal
flora. Red clover is a rich source of isoflavones, as well
as coumestans, and is used commercially to make
isoflavone supplements. These compounds exert
detectable effects on circulating gonadotropins and sex
steroids, suggesting that they have biological activity
(12). They also can act on intracellular enzymes, protein
synthesis, growth factors, cellular proliferation, differentiation, and angiogenesis. Limited observational studies
on isolated populations in cross-cultural comparison suggest that the incidence of cancer and atherosclerotic disease decreases with increasing intake of bioflavonoids
and that diphenolic isoflavonoids and lignans are cancerprotective compounds (13). These protective effects have
accrued in populations over a lifetime. It is unclear that
changing ones intake of isoflavones or soy protein at age
50 years will significantly lower the lifetime risk of these
diseases. A directive advising lifelong adherence to a diet
rich in a variety of fruits and vegetables while limiting
the intake of animal protein and fat should apply to men
and women of all ages, not just those experiencing their
menopausal transition. Moreover, no single synthetic or
chemical derived from soy is thought to match the benefits derived from ingesting soy foods. The effectseither
beneficial or detrimentalof prolonged intake of supradietary levels of soy or isoflavone are unknown.
Bean products are rich sources of diphenols, which
are thought to lower cancer risk by modifying hormone
metabolism and production and limiting cancer cell
growth. Bean foods also provide large amounts of fiber,
and fiber modifies the level of sex hormones by increasing
gastrointestinal motility. Fiber alters bile acid metabolism
and partially interrupts the enterohepatic circulation
causing increased estrogen excretion by decreasing the
rate of estrogen reuptake in the enterohepatic system
(14).
Manufacturing and Regulating

Botanicals
The federal Dietary Supplement Health and Education
Act of 1994 (DSHEA) defined dietary supplements and
limited the claims that can be made on supplement labels
and in supporting literature. Manufacturers are responsible for ensuring the safety of their supplement products.
Supplements are neither foods nor drugs, so manufacturers
do not have to provide any evidence to support purported
benefits before marketing their products. The Food and
Drug Administration (FDA) oversees the industry, but the
Federal Trade Commission is responsible for identifying
inappropriate or unsubstantiated claims and enforcing
DSHEA regulations.
1176
In 1997, the FDA proposed a new dietary supplement rule allowing supplements to make structural or
functional claims, but not disease claims. Such language
as supports well-being or helps promote heart health
would be allowed, while statements like lowers cholesterol would not be permitted. Supplements that
expressly or implicitly claim to diagnose, treat, prevent, or cure a disease[would be] regarded as drugs
and have to meet the safety and effectiveness standards
for drugs (15). The American Botanical Council
objects to the FDA attempting to redefine the DSHEA,
while the American Medical Association supports the
refined definitions.
Botanicals are subject to a high degree of variation in
production. Plants grown in the field may have different
amounts of active constituents due to growing conditions.
Products coming out of production facilities may vary
greatly in the amount of active ingredients.
The botanical industry has set up voluntary guidelines, and some manufacturers have signed agreements in
kind affirming that they will produce products set to an
industry-defined standard. However, without mandatory
oversight, problems of adulteration, contamination, and
dose standardization will continue. Consequently, buyers
and their physicians need to beware.
Uses for Botanicals in

Menopausal Women
A brief description of several commonly used botanicals
follows. Also included are their suggested and advertised
uses.
Vasomotor Symptoms
Soy Products. The effects of soy protein found in whole
foods, soy protein isolates, and those of isoflavone isolates made into powders or pills may not all be the same.
Even soy foods are not necessarily reliable sources of
biologically active isoflavones. The alcohol processing
often used in the manufacture of tofu and soy milk
removes the biologically active forms, the aglyconic
isoflavones. Producers of soy foods recognize that the
public is interested in isoflavone supplements, and many
indicate in their product labeling the amounts and forms
of isoflavones found in the foodstuff. Although the mechanisms of action of soy and dietary isoflavones are not
fully understood, they appear to involve binding to the
estrogen receptor. For this reason, one should not assume
these dietary supplements are safe for women with estrogen-dependent cancers, most importantly breast cancer.
Black Cohosh. Black cohosh was the principle ingredient in Lydia Pinkhams Vegetable Compound, an ethanolic extract sold over-the-counter in the United States and
in Europe. A black cohosh extract is one of the leading

botanicals sold in Germany and is the countrys top selling
menopausal herbal remedy. The German Commission E
Monographs state that black cohosh has estrogenlike
action, suppresses LH, binds to estrogen receptors, has
no contraindications to its use, and that the only side
effect is occasional gastric discomfort (16).
Black cohosh has been found to reduce LH levels in
rats that had ovariectomies and to reduce LH levels in
postmenopausal women after 8 weeks of use (17).
Despite these LH effects, other studies in humans and
animals indicate that black cohosh has no estrogenic
effects on sex-steroid-dependent tissues. In one unpublished double-blind, randomized study, black cohosh did
not affect follicle-stimulating hormone, LH, estradiol,
estrone, prolactin, sex-hormone-binding globulin,
endometrial thickness, or vaginal maturation index (18).
No claims are made regarding cardiac or bone effects,
and black cohosh is suggested only for treatment of
menopausal symptoms such as hot flashes, sleep disorders, anxiety, and depression and for nonmenopausal
conditions like dysmenorrhea and premenstrual syndrome.
Evening Primrose. The evening primrose plant (also
called evening star) produces seeds rich in gamma
linolenic acid (GLA) and also contains several anticoagulant substances. Commercial preparations made from
fixed oil sources are generally 72% linolenic acid (LA)
and 14% GLA. Thus, each 500-mg capsule will contain
45 mg of GLA and 365 mg of LA plus lesser amounts of
oleic, palmitic, and stearic acid. Because GLA is elaborated by the placenta, and because high concentrations
are found in breast milk, it is suggested that GLA is the
nutritionally perfect fatty acid for humans. With respect
to the gynecologic uses of GLA, evening primrose is
commonly recommended for mastalgia and mastodynia,
premenstrual syndrome, menopausal symptoms, and
bladder symptoms.
Dong Quai. Dong Quai (also seen as Dang Gui and Tang
Kuei), a type of angelica, is the most commonly prescribed Chinese herbal medicine for female problems
(19). Dong Quai supposedly regulates and balances the
menstrual cycle and is said to strengthen the uterus. Dong
Quai is used in traditional Chinese medicine to nourish
and tonify blood. It also is said to exert estrogenic
activity. Most herbal practitioners seem to agree it is contraindicated during pregnancy and lactation.
Mood Disturbances
St. Johns Wort. Extracts of the flower hypericum
perforatum, known as St. Johns wort, have been used for
centuries to treat mild to moderate depression. The con-
PRACTICE BULLETINS
1177
stituents include hypericin, pseudohypericin, and

flavonoids. Several unconfirmed mechanisms of action
for the psychotropic effects of St. Johns wort have been
proposed, including monamine oxidase inhibition, suppression of corticotropin-releasing hormone, and serotonin receptor blockade. Hypericin does not appear to be
a monamine oxidase inhibitor (20).
Commercial preparations often contain generally recommended doses; one capsule three times a day provides
a cumulative dose equivalent to the upper limit of doses
found in the literature to date. Side effects are similar to,
but far less than, those of standard antidepressant medications, including dry mouth, dizziness, and constipation.
Ginseng. There are many types of ginseng (Panax ginseng)Siberian, Korean, American, White, and Red. All
are promoted as adaptogens, which help one cope with
stress and supposedly boost immunity. Ginseng also is
reputed to be an aphrodisiac, a claim that is unsubstantiated by medical evidence. It also is promoted as a means
of improving athletic performance and inducing weight
loss without the need for diet or exercise. There is evidence that ginseng does not improve athletic performance, despite claims made (23). Reports of antioxidant
effects and reduced rates of disease, particularly cancer
rates, are suspect because the products in general use have
been found to contain little or no active ingredients (24).
Valerian Root. Valerian root, the common valerian or

garden heliotrope, has been used traditionally as a tranquilizer and soporific. The active constituent has never
been identified but is thought to be a gamma aminobutyric acid (GABA) derivative. Note that a similar GABAlike compound has been found in chamomile, which is
also proffered as an herbal sleep aid. Before the advent of
benzodiazepines and barbiturates, many psychiatric disorders were treated with valerian. Although it has no
demonstrable toxicity and degrades rapidly, there have
been reports of dystonic reactions and visual disturbances,
perhaps mediated by other drugs used concomitantly.
Little is known about the actions, effects, or potential interactions of valerian with other drugs. After L-tryptophan
was taken off the market, valerian use became popular
again. Most botanical texts advise against its use during
pregnancy and lactation.
Menstrual Disorders/Menorrhagia
Loss of Libido/Vaginal Dryness/Dyspareunia

Recommendations
A limited body of scientific information about botanicals
is available in English. A few publications from Europe
and Asia are available in full text. Most of the literature
includes in vitro effects, animal models, and open, often
single-armed or nonrandomized studies. The amount and
sophistication of studies of most alternative therapies do
not meet the current standards for evidence-based recommendations.
Chasteberry. Chasteberry or vitex also is known as

Chaste tree, Monks pepper, agnus castus, Indian spice,
sage tree hemp, and tree wild pepper. It has been recommended by some for vaginal dryness at menopause and
also for depression. Vitex contains hormonelike substances, which competitively bind receptors and produce
antiandrogenic effects; it is often recommended to reduce
libido in males because of its proposed value as an antiaphrodisiac. Antithetically, vitex also is recommended by
some to enhance libido in menopausal women.
In vitro and animal studies have suggested that vitex
inhibits prolactin, and perhaps explains the purported
benefit of recommending vitex for mastalgia and premenstrual syndrome. A placebo-controlled, double-blind
clinical trial of 20 male subjects used 120-, 240-, and
480-mg extracts of vitex, which did not demonstrate any
effect on prolactin (21). Another single-armed study in
56 women with mastodynia showed a reduction in prolactin in the treatment group compared with controls
(22). Studies, the quality of which cannot be assessed,
claim that vitex corrects inadequate luteal phase, and that
it restores LH activity.
Wild Yam. Yam extracts, tablets, and creams claim to be

progesterone substitutes and also are touted as a natural
source of DHEA. Sterol structures from the plant are
used as precursors in the biosynthesis of progesterone,
DHEA, and other steroids, but do not have inherent biological activity. Claims are made that the plant sterol
dioscorea is converted into progesterone in the body and
alleviates estrogen dominance. There is no human biochemical pathway for bioconversion of dioscorea to
progesterone or DHEA in vivo. Mexican yam extract
more accurately is estrogenic, containing considerable
diosgenin, an estrogenlike substance found in plants.
Some estrogenic effects might be expected from eating
these species of yams, but only if large quantities of raw
yams are consumed (25). Yams from the grocery store
generally are not the varieties known to contain significant amounts of dioscorea or diosgenin. Yam extracts
also are purported to be effective for uterine cramps.
Are there useful nonpharmaceutical supplements or botanicals for treatment of vasomotor symptoms, including hot flashes, flushes,
and night sweats?
Soy/Isoflavone Isolates. In one study, women given a

soy protein supplement with 40 mg of protein and 76 mg
1178
Black Cohosh. Although a dozen studies of women taking black cohosh extracts show an apparent reduction in
symptomatology, the studies are largely unblinded, use
unvalidated tools to measure outcomes, and contain small
numbers of patients. Based on this limited evidence,
there appears to be a positive effect on sleep disorders,
mood disturbance, and hot flashes (28). There have been
no reports of black cohosh toxicity. No clinical studies
have reported efficacy or safety of black cohosh beyond
6 months of use. Black cohosh should not be confused
with blue cohosh, Caulophyllum thalictroides, which has
weak nicotine activity and toxic potential.
Evening Primrose. A meta-analysis of clinical trials of
evening primrose oil used to treat premenstrual syndrome
concluded that of the seven controlled trials, only five
were properly randomized (29). In the only one of the
five trials that was blinded, evening primrose was ineffective in treating premenstrual syndrome. To date, there
is only one randomized, double-blind, placebo-controlled
study of the use of GLA in the treatment of vasomotor
symptoms during menopause (30). Although the women
taking GLA had significant improvement... in the maximum number of night time flushes, GLA provided no
benefits beyond those seen with placebo.
Ginseng. Ginsana, the largest manufacturer of ginseng,

funded a study of 384 women to investigate the effects of
Are there alternative, nonpharmaceutical

supplements or botanicals that have demonstrated usefulness in the treatment of sleep,
mood and affective, cognitive, and other
behavioral disorders associated with
menopause syndrome?
St. Johns Wort. A meta-analysis of 15 controlled trials

encompassing 1,757 cases found that St. Johns wort
hypericin in doses less than 1.2 mg per day produced a
61% improvement in mild to moderate depression, while
doses up to 2.7 mg per day produced a 75% improvement
(34). Its efficacy in the treatment of severe depression is
not documented. Some have suggested that St. Johns
wort is helpful in treating seasonal affective disorder. No
clinical studies have reported results or safety parameters
beyond 2 years of use.
St. Johns wort is also potentially photosensitizing
(24), and concern has been raised about an increased rate
of cataracts. The issue of possible interactions between
St. Johns wort and selective serotonin reuptake
inhibitors or monamine oxidase inhibitors has been
raised. Some consultants advise against using St. Johns
wort for weeks to months after stopping these drugs.
Interaction with anesthetic agents has also been reported
(35).
Valerian Root. In 1998, the U.S. Pharmacopeia (USP)
stated in its monograph on valerian: Studies supporting
this use are not good enough to prove that it is effective.
Therefore, USP advisory panels do not support its use
(36). There is a case report of high-output congestive
heart failure, tachycardia, and delirium attributed to acute
withdrawal from valerian (37). Based on available data,
valerian appears not to be useful, and may be harmful.
Dong Quai. Kaiser Permanente conducted a doubleblind controlled clinical trial using a daily dose of 4.5 g
of dong quai (9). Dong quai and placebo both reported a
25% reduction in hot flashes. Critics of the study have
noted that the dose of dong quai was lower than that often
used in traditional Chinese medicine, and that dong quai
is never employed as an isolated intervention. The argument is made that the botanicals must be taken together
in a balanced formula and that the therapeutic outcome
requires that proper synergy take place between the components. However, its benefit cannot be substantiated
based on available evidence.
Dong quai is potentially toxic. It contains numerous
coumarinlike derivatives and may cause excessive bleeding or interactions with other anticoagulants (31). Dong
quai also contains psoralens and is potentially photosensitizing, which has led to concern about an increased risk
of sun-exposure-related skin cancers (32).
ginseng in menopausal women. No differences were

found between treatment subjects and placebo controls in
vasomotor symptoms, but significant improvements were
reported in quality of life measures, particularly depression, general health, and well-being scores (33).
of isoflavones had a 45% reduction in vasomotor symptoms compared with a 30% reduction in controls who
received a placebo (26). Other research demonstrated a
40% reduction in vasomotor symptoms when diet was
supplemented with soy flour, but the vaginal maturation
index did not improve (27). Based on these limited studies, the use of soy may have benefits.

supplements or botanicals that have been
shown to be useful for treatment of decreased
libido, vaginal dryness, or dyspareunia?
Soy/Isoflavones. Findings regarding the effects of soy

supplements on vaginal maturation index are inconsistent
with some showing improvements (11) and others showing
no change (12). Different isoflavones may have a differential impact on estrogen-sensitive tissues, so that various types of dietary soy may affect the lower genital tract
PRACTICE BULLETINS
Chasteberry or Vitex. Although vitexs supposed antihormonal activity serves as the basis for advising its use
in treating mastalgia, all claims of efficacy in women are
poorly documented. Although studies of vitex use in
menopause are limited, a recent randomized trial
assessed the effects of vitex in women with premenstrual
syndrome, which may apply to women with similar complaints in menopause. After three cycles of vitex, significant improvements in mood alteration, anger, headache,
and breast fullness were reported on a self assessment
screening tool. However, other menstrual symptoms, like
bloating, remained unchanged. Physician ratings of
patients conditions also indicated better effects than with
placebo (38).
Ginseng. No published studies have documented that
ginseng has an effect on libido in menopausal women.
Moreover, 54 ginseng products examined by the
American Botanical Council proved to have little ginseng
(60%) or no ginseng (25%), and many were heavily adulterated with caffeine (24). Other analyses have found significant variation in the active ingredient, ginsenosides,
as well as high levels of pesticides or lead. Ginseng may
hold some promise in the treatment of fatigue, depression, immunosuppression, and other health problems, but
it cannot be recommended as a treatment for menopause.
For its other indications, caution is advised given the
poor production standards and lack of quality evidence
for the claims made.
Wild and Mexican Yam. Based on the lack of bioavailability, the hormones in wild and Mexican yam would not
be expected to have any efficacy. Wild yam extracts are
neither estrogenic nor progestational, and although many
yam extract products contain no yam, some are laced with
progesterone. Perhaps some may even contain medroxyprogesterone. Oral ingestion does not produce serum levels.
There are no published reports demonstrating the efficacy
of wild yam cream. A 1-month supply costs more than
$25, while a month of commercially produced vaginal
estrogen cream costs less than $20 (39).
Are there useful alternative, nonpharmaceutical supplements or botanicals for the

prevention of coronary heart disease and
osteoporosis?
Soy/Isoflavone Isolates. There is some evidence to indicate that high isoflavone intake may favorably affect
lipid profile and is, by extension, thought to reduce cardiac disease risk. However, study results are conflicting.
A study in Finland found an inverse relationship
between isoflavone intake and coronary heart disease in
both women and men (40), but similar benefits have not
been demonstrated in the United States (41). A metaanalysis showed higher soy intake is associated with
significant improvement in lipid profiles (42). Soy
protein intake of approximately 47 g per day correlated
with a statistically significant 9.3% reduction in serum cholesterol, a 12.9% reduction in serum low-density
lipoprotein cholesterol, a 10.5% reduction in serum
triglycerides, and an insignificant 2.4% increase in
high- density lipoproteins. Isoflavone isolates containing
40 mg of isoflavone isolates have been shown to induce
a 23% increase in arterial compliance after 1 year of use,
an increase equal to that seen in women receiving conjugated equine estrogens (43).
Dietary soy or isolated isoflavone supplements may
have a salutary effect on bone mass. Ipriflavone, a synthetic version of genistein, slows bone reabsorption and
stimulates collagen synthesis in bone. Pharmaceutical
quality ipriflavone is approved in Europe and Japan for
treatment of osteoporosis using 600 mg per day.
Ipriflavone with supplemental calcium has been found to
decrease bone loss in natural menopause in some studies
(44, 45), but not others (46), to decrease bone loss after
surgically induced menopause (47), and in women with
gonadotropin-agonist-induced bone loss (48).

supplements or botanicals that are useful for
the treatment of menstrual disorders during
perimenopause and menopause?
with a significant degree of variability (12, 27).

Therefore, some soy products may be useful in the treatment of vaginal dryness and dyspareunia, although
sources of isoflavones and beneficial amounts have yet to
be clarified.
1179
Does the use of alternative therapies require

any special medical monitoring?
No published studies have investigated the role of clinical

monitoring in patients using alternative medicine therapies. However, alternative steroid products may pose a
risk for consequences of excessive steroid ingestion.
Androgens are associated with abnormal liver functions
as well as potential hyperandrogenicity. Estrogens compounded by an alternative therapy pharmacy may produce
varying serum estradiol levels in women or increased
estrogen bioactivity without detectable changes in circulating estradiol. Risks of excessive levels include hepatic
effects and increased risk of deep vein thrombosis.
Although most botanicals appear to be harmless,
products may be adulterated or contaminated. In addi-
1180
Counseling Patients About Complementary and

Alternative Medicine
Soy and isoflavones may be helpful in the short-term
(2 years) treatment of vasomotor symptoms. Given
the possibility that these compounds may interact
with estrogen, these agents should not be considered
free of potential harm in women with estrogendependent cancers.
St. Johns wort may be helpful in the short-term (2
years) treatment of mild to moderate depression in
women.
Black cohosh may be helpful in the short-term (6

months) treatment of women with vasomotor symptoms.
Modified from Cirigliano M, Sun A. Advising patients about herbal

therapies [letter]. JAMA 1998;280:15651566. Copyright 1998,
American Medical Association.
Given the general lack of standardization of products, the

relatively short duration of therapy and follow-up in the
available data, and the difficulty of interpreting the available clinical data, few recommendations can be made
with confidence. The following conclusions can be drawn
in reference to short-term ( 2 years) use of botanical and
alternative medicine for the management of menopause.
*For a complete listing of potentially dangerous drugherb interactions see Newall CA, Anderson LA, Phillipson JD. Herbal medicines: a
guide for health-care professionals. London: Pharmaceutical Press,
1996.
Summary of
Recommendations
All patients should be asked about their use of

herbal therapies and dietary supplements. Use of
these products should be documented in the
patients chart.
Natural is not an assurance of safety or efficacy.
Potentially dangerous drugherb interactions occur.*
Lack of standardization of botanicals may result in
variability of content and efficacy from batch to
batch, from a single manufacturer, or between manufacturers.
Lack of quality control and regulation may result in
contamination, adulteration, or potential misidentification of plant products.
Errors in compounding may result in toxic or lethal
outcomes in custom-blended herbal preparations.
Botanicals should not be used by women planning
to become pregnant in the near future or during
pregnancy or lactation without professional advice.
Botanicals should not be taken in larger than recommended doses or for longer than recommended
duration.
Several botanicals have known adverse effects and
toxicities.
Infants, children, and the elderly should not use
botanicals without professional advice.
Patients should be counseled in a rational, judicious,
and balanced manner about the relative risks and
benefits of conventional therapies and alternative
interventions.
Adverse events and outcomes should be documented in the chart, therapy discontinued, and reported
to the U.S. Food and Drug Administration.
Because the expected placebo response for
menopausal treatment ranges from 10% to 30%, a
small positive response to any treatment, conventional or alternative, may not necessarily represent a
pharmacologic effect. Anecdotal experience is not a
substitute for well-constructed clinical trials.
Nonetheless, the effect of support, counseling, and
empathetic care should not be discounted or dismissed.
tion, all menopausal women taking any pharmaceutical

or alternative preparation should have blood pressure
readings, mammograms, and Pap tests at recommended
intervals. Women using estrogen supplements who are
relying on unconventional estrogenic or progestational
therapies such as transdermal progesterone cosmetic
creams should be monitored according to standard guidelines for women taking unopposed estrogenthat is,
endometrial surveillance should be considered. In counseling patients, the risk of adverse effects from these therapies must be weighed against the costs associated with
any routine testing. Further guidelines for counseling
patients regarding the use of complementary and alternative medicine are shown in the box. Also, it is important
for clinicians to be aware of issues surrounding referral to
alternative care providers (3).
Soy and isoflavone intake over prolonged periods may

improve lipoprotein profiles and protect against osteoporosis. Soy in foodstuffs may differ in biological
activity from soy and isoflavones in supplements.
PRACTICE BULLETINS
References
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152156 (Level II-3)
2. Creasman WT. Is there an association between hormone
replacement therapy and breast cancer? J Womens Health
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4. National Center for Complementary and Alternative
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Van Rompay M, et al. Trends in alternative medicine use
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1181
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Nutrition 1997;13:535539 (Level II-3)
15. Mitka M. FDA never promised an herb gardenbut sellers and buyers eager to see one grow [news]. JAMA
1998;280:15541556 (Level III)
25. Mirkin G. Estrogen in yams. JAMA 1991;265:912 (Level

III)
26. Albertazzi P, Pansini F, Bonaccorsi G, Zanotti L, Forini E,
De Aloysio D. The effect of dietary soy supplementation
on hot flushes. Obstet Gynecol 1998;91:611 (Level II-1)
27. Murkies AL, Lombard C, Strauss BJ, Wilcox G, Burger
HG, Morton MS. Dietary flour supplementation decreases
post-menopausal hot flushes: effect of soy and wheat.
Maturitas 1995;21:189195 (Level I)
28. Warnecke G. Influence of a phytopharmaceutical on climacteric complaints. Die Medizinische Welt 1985;
36:871874 (German)
29. Budeiri D, Li Wan Po A, Dornan JC. Is evening primrose
oil of value in the treatment of premenstrual syndrome?
Control Clin Trials 1996;17:6068 (Level III)
30. Chenoy R, Hussain S, Tayob Y, OBrien PM, Moss MY,
Morse PF. Effect of oral gamolenic acid from evening
primrose oil on menopausal flushing. BMJ 1994;
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31. Fugh-Berman A. Herb-drug interactions. Lancet 2000;

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32. Tyler VE. The honest herbal: a sensible guide to the use of
herbs and related remedies. 3rd ed. Binghamton, New
York: Pharmaceutical Products Press, 1993 (Level III)
33. Wiklund IK, Mattsson LA, Lindgren R, Limoni C. Effects
of a standardized ginseng extract on quality of life and
physiological parameters in symptomatic postmenopausal
women: a double-blind, placebo-controlled trial. Swedish
Alternative Medicine Group. Int J Clin Pharmacol Res
1999;19:8999 (Level I)
34. Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer
W, Melchart D. St. Johns wort for depressionan
overview and meta-analysis of randomised clinical trials.
BMJ 1996;313:253258 (Meta-analysis)
35. Koupparis LS. Harmless herbs: a cause for concern [letter]? Anaesthesia 2000;55:101102 (Level III)
36. U.S. Pharmacopeia Botanical monograph series: information for the health care professional and consumer.
Rockville, Maryland: US Pharmacopeial Convention, Inc.,
1998 (Level III)
37. Garges HP, Varia I, Doraiswany PM. Cardiac complications and delirium associated with valerian root withdrawal [letter]. JAMA 1998;280:15661567 (Level III)
38. Schellenberg R. Treatment for the premenstrual syndrome
with agnus castus fruit extract: prospective, randomised,
placebo controlled study. BMJ 2001;322:134137 (Level I)
39. Gorski T. Wild yam cream threatens womens health. Nutr
Forum 1997;14:2324 (Level III)
40. Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid
intake and coronary mortality in Finland: a cohort study.
BMJ 1996;312:478481 (Level II-3)
41. Rimm EB, Katan MB, Ascherio A, Stampfer MJ, Willett
WC. Relation between intake of flavonoids and risk for
coronary heart disease in male health professionals. Ann
Intern Med 1996;125:384389 (Level II-3)
42. Anderson JW, Johnstone BM, Cook-Newell ME. Metaanalysis of the effects of soy protein intake on serum
lipids. N Engl J Med 1995;333:276282 (Meta-analysis)
43. Nestel PJ, Pomeroy S, Kay S, Komesaroff, Behrsing J,
Cameron JD, et al. Isoflavones from red clover improve
systemic arterial compliance but not plasma lipids in
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895898 [erratum J Clin Endocrinol Metab 1999;84:3647]
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44. Valente M, Bufalino L, Castiglione GN, DAngelo R,

Mancuso A, Galoppi P, et al. Effects of 1-year treatment
with ipriflavone on bone in postmenopausal women with
low bone mass. Calcif Tissue Int 1994;54:377380 (Level I)
45. Gambacciani M, Ciaponi M, Cappagli B, Piaggesi L,
Genazzani AR. Effects of combined low dose of the
isoflavone derivative ipriflavone and estrogen replacement
on bone mineral density and metabolism in postmenopausal women. Maturitas 1997;28:7581 (Level I)
46. Alexandersen P, Toussaint A, Christiansen C, Devogelaer
JP, Roux C, Fechtenbaum J, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA 2001;285:14821488 (Level I)
47. Gambacciani M, Spinetti A, Cappagli B, Taponeco F,
Felipetto R, Parrini D, et al. Effects of ipriflavone administration on bone mass and metabolism in ovariectomized
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48. Gambacciani M, Spinetti A, Piaggesi L, Cappagli B,
Taponeco F, Manetti P, et al. Ipriflavone prevents the bone
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Miner 1994;26:1926 (Level I)
Web Resources
The National Library of Medicine
(http://www.nlm.nih.gov/)
The National Center for Complementary and Alternative
Medicine (http://nccam.nih.gov)
The NIH Office of Dietary Supplements
(http://dietary-supplements.info.nih.gov)
The Richard and Hinda Rosenthal Center for
Complementary & Alternative Medicine
(http://cpmcnet.columbia.edu/dept/rosenthal/)
The American Botanical Council
(http://www.herbalgram.org)
Health World Online (http://www.healthy.net)
Quackwatch (http://www.quackwatch.com)
ConsumerLab (http://www.consumerlab.com)
PRACTICE BULLETINS

to conduct a literature search to locate relevant articles published between January 1985 and January 2001. Priority
was given to articles reporting results of original research,
although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of Health
Force:
I
type of evidence.
committees.
1183
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
409 12th Street, SW
PO Box 96920
1184
ACOG
PRACTICE
BULLETIN

of Robert Barbieri, MD. The
of practice.
Reaffirmed 2008
Management of
Infertility Caused by
Ovulatory Dysfunction
Approximately 20% of infertile women have ovulatory disorders (1, 2). In infertile women with ovulatory disorders, the cause of anovulation will guide the
selection of an appropriate treatment plan. Advances in reproductive
endocrinology allow the generalist obstetriciangynecologist to provide treatment that results in successful ovulatory stimulation and pregnancy in most
women with ovulatory disorders.
Background
Etiology
Ovulatory dysfunction is likely to be present in women with polymenorrhea or
oligomenorrhea and is almost always present in women with amenorrhea
(except in patients with uterine disease, such as uterine synechiae or
Ashermans syndrome). Regular menstrual cycles, with a cycle length between
22 and 35 days, and the presence of premenstrual bloating, dysmenorrhea, and
breast tenderness suggest the presence of ovulatory cycles.
Laboratory methods for determining ovulation include the basal body temperature chart, urine testing for the luteinizing hormone (LH) surge, properly
timed measurement of serum progesterone, and endometrial biopsy. Serial
pelvic ultrasonography also may be able to identify the growth and rupture of
a follicle, suggesting that ovulation has occurred. Basal body temperature
charts are inexpensive but may be a burden to the patient to complete and only
document ovulation retrospectively. The pulsatile ovarian secretion of progesterone in the luteal phase may decrease the sensitivity of a single measurement
of progesterone, but a serum progesterone level higher than 3 ng/mL is highly
specific for detecting ovulation. (These tests also can detect ovulation in
induced cycles.)
PRACTICE BULLETINS
If anovulation or clinically significant oligo-ovulation has been documented, a complete physical examination and selected laboratory testing are important to
identify the etiology of the ovulatory dysfunction.
The most common causes of ovulatory dysfunction are
1) polycystic ovary syndrome (PCOS) (approximately
70% of cases of ovulatory dysfunction) (3), 2) hypothalamic amenorrhea, also known as hypogonadotropic
hypogonadism (approximately 10% of cases), 3) hyperprolactinemia (approximately 10% of cases), and 4) premature ovarian failure, also known as hypergonadotropic
hypoestrogenic anovulation (approximately 10% of
cases) (4).
During the physical examination, the practitioner
should note the presence of galactorrhea, thyromegaly or
other evidence of hypothyroidism or hyperthyroidism,
acanthosis nigricans, hirsutism, acne, or signs of virilization. In addition, the patients body mass index (BMI)
should be calculated. A BMI less than 20 may indicate
hypothalamic ovulatory dysfunction (low gonadotropinreleasing hormone [GnRH] secretion, low LH and
follicle-stimulating hormone [FSH] secretion, low
endogenous estrogen secretion) (5). The combination of
amenorrhea and galactorrhea strongly correlates with
hyperprolactinemia. The presence of acanthosis nigricans
suggests the patient has a marked degree of insulin resistance.
In general, clinicians should first recommend the
least resource-intensive ovulation induction regimens
that are appropriate for each cause of ovulatory dysfunction. For example, for women with hypogonadotropic
hypogonadism and a BMI less than 20, weight gain may
be associated with the resumption of normal menses.

Polycystic ovary syndrome is defined as the presence of
oligomenorrhea or amenorrhea and hyperandrogenism in
the absence of other hyperandrogenic disorders, such as
androgen-secreting tumors or nonclassical adrenal hyperplasia. Clinical evidence of hyperandrogenism includes
hirsutism and acne. Laboratory evidence of hyperandrogenism includes an elevated total, bioavailable, or free
testosterone concentration. Elevated serum dehydroepiandrosterone sulfate (DHEAS) or androstenedione
levels also are evidence of hyperandrogenism. The morphologic characteristics of polycystic ovaries as
demonstrated on pelvic ultrasonography are not essential
for the diagnosis of PCOS but support the diagnosis. In
women of reproductive age, the prevalence of PCOS is
approximately 5%, making it one of the most common
reproductive disorders (3). Among women with ovulatory dysfunction, about 70% have PCOS (3).
1185
In women with PCOS, many therapies are available

to treat anovulatory infertility, including weight loss,
clomiphene, clomiphene plus metformin, clomiphene
plus glucocorticoid, gonadotropin injections, ovarian
surgery, and in vitro fertilization-embryo transfer (IVFET). Using the principle of progressing from the least
resource-intensive treatments to the most resource-intensive treatments, one potential strategy for organizing the
care of women with PCOS is presented in the box.
Hypothalamic Anovulation
Hypothalamic anovulation (hypogonadotropic hypogonadism) usually is associated with low levels of GnRH
secretion, low or normal levels of LH and FSH secretion,
and low levels of endogenous estrogen secretion.
Diseases associated with hypothalamic anovulation
include anorexia nervosa, Kallmanns syndrome, and
hypothalamic tumors and cysts. Factors associated with
hypogonadotropic hypogonadism include a low BMI
(<20); high-intensity exercise; certain dietary patterns,
including high-fiber, low-fat diets; and excessive stress.
One approach to treating this condition is to reverse the
lifestyle factors that contribute to the anovulation. For
example, in one study of 26 underweight women who
practiced strict dieting and were infertile, the subjects
were counseled by a dietitian and given physician-directed advice to increase their BMI (5). After the intervention, the women gained a mean 3.7 kg, and 73% of the
women became pregnant. Decreasing the intensity of
A Step-by-Step Approach to Ovulation Induction

in Women with PCOS
The least resource-intensive interventions are recommended in the early steps in the protocol, while the
most resource-intensive interventions are reserved for
later treatment.
Step 1. If the BMI is higher than 30, recommend
weight loss of at least 10% of body weight.
Step 2. Prescribe clomiphene to induce ovulation.
Step 3. If DHEAS is higher than 2 g/mL, consider
combining clomiphene with a glucocorticoid to
induce ovulation.
Step 4. If clomiphene does not result in ovulation,
consider a combination of metformin plus
clomiphene.
Step 5. Initiate low-dose FSH injections.
Step 6. Initiate low-dose FSH injections plus metformin.
Step 7. Consider laparoscopic ovarian surgery or in vitro
fertilization.
1186
exercise and stress also may help improve the rate of

ovulation in some of these women. However, no welldesigned clinical trials testing these recommendations
have been reported.
In the past, one option for ovulation induction for
hypogonadotropic hypogonadism was the parenteral
administration of GnRH in pulses using a portable programmable pump. It was associated with monofollicular
ovulation and a high rate of singleton pregnancy but the
pump is not commercially available in the United States
(6, 7).
Hyperprolactinemia
The most common causes of hyperprolactinemia are a
prolactin-secreting pituitary gland tumor and the use of
psychiatric medications. The presence of hyperprolactinemia should be confirmed if there is any question
about the timing of the blood test or the quality of the
assay; blood should be drawn after the patient has fasted
and preferably not after a breast examination or breast
stimulation (8). All women with hyperprolactinemia
should be tested for hypothyroidism (a thyroid-stimulating hormone screening or additional thyroid hormone
testing as clinically indicated) and pregnancy (9). An
imaging study (magnetic resonance imaging or computed tomography) of the central nervous system and the
pituitary gland should be obtained in all women with
hyperprolactinemia unless there is an obvious cause,
such as hypothyroidism, that makes a pituitary gland
tumor unlikely (10). If the imaging study reveals a
macroadenoma of the pituitary gland (tumor diameter
10 mm), the patient should be referred to a physician
with expertise in endocrinology or pituitary gland disease for consultation. Induction of ovulation in women
with large pituitary gland tumors is associated with a
high risk of neurosurgical complications during pregnancy (1113). In addition, women with large pituitary
gland tumors may have undiagnosed adrenal insufficiency, a condition that poses significant health risks. For
women with microadenomas (tumor diameter <10 mm)
that secrete prolactin, the risk of pituitary insufficiency
and neurosurgical complications during pregnancy is
very low (<1%) (1113). Observational studies indicate
that during 4 6 years of observation, 95% of microadenomas do not increase in size (14, 15).
Age-Related Ovulation Dysfunction and

Premature Ovarian Failure
As the ovarian follicular pool depletes with age, the
remaining follicles appear to be less capable of fertilization and establishing a successful pregnancy. Inhibin B
production by the small follicles decreases with age, the
inhibin suppression of FSH secretion decreases, and
pituitary gland secretion of FSH increases. An elevated

random FSH level in amenorrheic or severely oligomenorrheic women or an elevated day-3 FSH level in women
with menses is highly sensitive and specific for identifying women with a depleted ovarian follicular pool (16).
If initial attempts at ovulation induction do not result in
a pregnancy in women older than 37 years, consultation
with an infertility specialist may be advisable to develop
a plan for when assisted reproductive procedures, such
as IVF-ET or oocyte donation should be pursued.
Treatments proposed to induce ovulation in women
with premature ovarian failure include 1) oral contraceptive suppression of gonadotropins followed by discontinuation of the oral contraceptive to allow a rebound in
gonadotropin secretion and ovarian function, 2) GnRHagonist suppression of gonadotropin secretion followed
by high-dose gonadotropin injections, and 3) glucocorticoid suppression of the immune system. None of these
treatments has demonstrated efficacy in randomized
clinical trials for inducing ovulation in women with premature ovarian failure (17). Women with infertility, ovulatory dysfunction, and an elevated FSH level should be
referred to a physician with specialized expertise in
treating infertility.
Luteal Phase Deficiency

Luteal phase deficiency is a theoretical disorder in which
ovulation occurs, but there is insufficient progesterone
production by the corpus luteum to allow for successful
implantation. Luteal phase deficiency is thought to cause
recurrent pregnancy loss, especially in the first trimester,
and is believed to be responsible for a subset of cases of
infertility. Studies that have attempted to establish luteal
phase deficiency as a cause of infertility have not included control groups of fertile women. However, women
who have regular menstrual cycles may have luteal phase
abnormalities in as many as 31% of their cycles (18).
Methods to diagnose and treat luteal phase deficiencies,
therefore, are largely speculative. Because current infertility treatment often includes empiric treatment for
unexplained infertility, most women who have luteal
phase deficiencies and are infertile will receive treatment
that includes controlled ovarian hyperstimulation.
Therefore, a therapy specific to luteal phase deficiency is
not being aggressively pursued.
Treatment Options
Clomiphene Citrate
The precise mechanism of action of clomiphene citrate is
not completely understood. The administration of
clomiphene to anovulatory women with endogenous
PRACTICE BULLETINS
estrogen secretion often is followed by an increase in

both hypothalamic GnRH secretion and pituitary LH and
FSH secretion, which causes follicle growth, triggering
the LH surge and ovulation.
Clomiphene treatment is most effective in women
with normal FSH levels and adequate endogenous production of estrogen and is least effective in women with
hypothalamic amenorrhea or in women with an elevated
basal FSH concentration (19). In women with PCOS, the
presence of obesity, elevated testosterone concentration,
and severe insulin resistance decreases the efficacy of
clomiphene citrate (20). Most women with hypogonadotropic hypogonadism do not ovulate in response to
treatment with clomiphene.
Most clomiphene-induced pregnancies occur within
the first three menstrual cycles, and the vast majority occur
within 6 months. There is no benefit to increasing the
dosage once ovulation has occurred or to continuing
beyond 6 months of treatment (21). Clomiphene administration in anovulatory women differs from superovulation, or controlled ovarian hyperstimulation, which is
frequently attempted in couples with unexplained infertility. With clomiphene, monofolliculogenesis is the goal,
and adjunctive treatments, such as intensive follicle monitoring and intrauterine insemination, do not have a
defined role. With superovulation, women are already
ovulatory; clomiphene, if administered, is typically given
with human chorionic gonadotropin (hCG) to ensure ovulation, and intrauterine insemination also is appropriate.
Gonadotropin Injection
Gonadotropins can be administered using human urinary
menopausal gonadotropins, which contain both LH and
FSH, or by using recombinant FSH. Both types of
gonadotropins are effective in treating anovulation in
women with PCOS. The use of gonadotropin injections
to induce ovulation in women with PCOS is resource
intensive and is associated with a high risk of adverse
outcomes, such as ovarian hyperstimulation and highorder multiple pregnancy.
Gonadotropin injections are effective in the treatment of hypothalamic anovulation. Women with hypothalamic anovulation who have a baseline serum LH
level lower than 0.5 IU/L should be treated with both
FSH and LH because they have a deficiency in both
gonadotropins. Women with hypothalamic amenorrhea
and a baseline LH level higher than 0.5 IU/L can be successfully treated with FSH alone (22). In most circumstances, the use of FSH injections to induce ovulation
should be performed by physicians with advanced training in treating infertility.
1187
Metformin
Metformin is an oral biguanide antihyperglycemic agent
approved for the treatment of adult-onset diabetes mellitus. It is a category-B drug used by some clinicians to
treat diabetes mellitus in pregnant women. Metformin
decreases blood glucose levels by inhibiting hepatic glucose production and by enhancing peripheral glucose
uptake. Metformin increases insulin sensitivity at the
postreceptor level and stimulates insulin-mediated glucose disposal. Unlike sulfonylureas, metformin does not
cause hypoglycemia because it does not increase insulin
secretion. Unlike phenformin, metformin does not block
mitochondrial metabolism of lactate unless the patient
has renal failure (renal failure will cause lactate to accumulate to very high concentrations) or severe hypoxia
(mitochondrial dysfunction). Metformin is not approved
by the U.S. Food and Drug Administration (FDA) for
ovulation induction.
Dopamine Agonists
Dopamine-agonist drugs (bromocriptine, pergolide,
cabergoline) are the treatment of choice for ovulation
induction in women with hyperprolactinemia (23).
Dopamine-agonist drugs directly suppress prolactin production by the tumor and cause an increase in endogenous GnRH secretion, which stimulates pituitary gland
secretion of LH and FSH and consequently induces follicle development and ovulation. In addition, dopamine
agonists decrease the size of prolactin-secreting pituitary
gland tumors.
With dopamine-agonist therapy, a near-maximal
decrease in serum prolactin levels should be achieved
after 4 weeks of treatment. Serum prolactin levels should
be measured approximately 1 month after initiating therapy and about 1 month after a change in the dosage or
drug. Normalization of prolactin levels is the therapeutic
goal, as well as assuring that the tumor is responding to
the dopamine agonists. If the serum prolactin concentration is normal and no side effects have occurred, the initial dosage should be continued. If the serum prolactin
level has not decreased to normal and no side effects are
present, the dosage should be gradually increased. The
maximal dosage of bromocriptine is 5 mg twice daily;
pergolide, 0.25 mg once daily. Cabergoline is the newest
of these agents; it can be administered less frequently and
may induce nausea less often. However, as a result of
FDA approval, its use in pregnancy is extremely limited.
Women who do not tolerate the side effects of bromocriptine may need to be referred to a practitioner with additional expertise in the field to discuss in detail the risks
and benefits of newer therapies that have not been tested
as thoroughly.

Recommendations
How is the diagnosis of ovulatory dysfunction

established?
If the patient is amenorrheic, the minimal laboratory

evaluation should include measurement of serum levels
of FSH, thyroid-stimulating hormone, and prolactin. If
the patient has evidence of hyperandrogenism (eg, hirsutism, acne, signs of virilization), measurement of
testosterone and DHEAS may have clinical value if ovulation induction is planned. Clinical evaluation may be
used to determine if testing for Cushings syndrome or
Addisons disease should be performed. If the patient has
a BMI higher than 30, testing for diabetes mellitus may
be indicated before inducing ovulation (25). To decrease
the risk of congenital malformations, diabetes mellitus
should be treated before inducing pregnancy. In women
with irregular menses, attempting to obtain a luteal-phase
progesterone measurement may be cumbersome and
unnecessary if menses are relatively infrequent.
Documenting ovulation by basal body temperature evaluation or LH surge testing may be helpful. Women with
regular menses can be assessed for ovulatory status by
any of the techniques described previously.
Before using ovulation-inducing medications, it is

useful to consider evaluating the couple for male factor
infertility by performing a semen analysis. Routinely performing hysterosalpingography is unnecessary. However,
if the woman has a history of sexually transmitted diseases, pelvic inflammatory disease, appendicitis with
rupture, in utero exposure to diethylstilbestrol, or previous pelvic surgery, hysterosalpingography should be considered to establish tubal patency. Laparoscopy is not
routinely necessary before ovulation induction. The age
of the woman strongly influences the pregnancy rate with
ovulation induction (see Fig. 1). In older women, this
may lead to a greater sense of urgency and a rapid progression to more intensive treatments, with their greater
associated risks (26, 27).
If the serum prolactin level does not decrease to normal, switching to a different dopamine agonist may be
effective. If the patient cannot tolerate the dopamine agonist initially prescribed, a different dopamine agonist
may be associated with fewer side effects. If the patient
experiences side effects with all dopamine agonists, vaginal administration can be tried. If the patient cannot
tolerate any of the dopamine agonists, transsphenoidal
surgery may be effective in removing the tumor, returning prolactin secretion to normal, and causing the
resumption of ovulatory menses.
Following correction of hyperprolactinemia, about
80% of women will ovulate, and cumulative pregnancy
rates of 80% are commonly observed (24). Treatment
usually is discontinued once pregnancy is diagnosed.
However, in women with a macroprolactinoma, therapy
should be continued throughout pregnancy to decrease
the risk of tumor growth and neurosurgical complications, such as compression of the optic nerve.
In the small percentage of women with hyperprolactinemia who do not respond to dopamine-agonist
therapy, standard ovulation induction therapy with clomiphene citrate may be considered. In rare cases, gonadotropin therapy may be considered.
Does weight loss improve fertility in obese

women?
In women with a high BMI, abnormal hypothalamic

GnRH secretion, pituitary gland LH and FSH secretion,
insulin resistance, and anovulation are common (28).
Women with a BMI greater than 30 and oligo-ovulation
often have PCOS.
Epidemiologic studies have demonstrated that a
BMI greater than 27 is associated with an increased risk
of ovulatory infertility. For example, in one study of 597
cumulative pregnancy rate in women younger than 35 years

cumulative pregnancy rate in women older than 35 years
< 35 years
100
Cumulative pregnancy rate (%)
1188
80
60
35 years
40
20
0
2
4
Treatment cycles
Figure 1. Cumulative pregnancy rates for hypogonadotropic

anovulatory women treated with gonadotropins. (From
Lunenfeld B, Insler V. Human gonadotropins. In: Wallach EE,
Zacur HA, eds. Reproductive medicine and surgery. St. Louis:
Mosby-Year Book, 1995:617)
PRACTICE BULLETINS
women with ovulatory infertility and 1,695 controls, the

women with a BMI higher than 27 had a relative risk of
ovulatory infertility of 3.1 (95% confidence interval,
2.2 4.4) when compared with the control group with a
BMI of 2024.9 (29).
Many studies (most without a control group) have
demonstrated that in women who have PCOS and are
obese, weight loss often is associated with a decrease in
serum testosterone concentration, resumption of ovulation,
and, for infertile women, pregnancy. For example, in one
study, 18 obese women with PCOS were treated with a
hypocaloric diet (30). Before the diet, the mean weight of
the women was 77 kg; after the diet, it was 57 kg. The plasma testosterone concentration was 0.75 ng/mL before the
diet and 0.39 ng/mL after (P <0.001). Many of the women
resumed ovulation after weight loss. Another study evaluated the effects of weight loss on 20 obese women with
PCOS (31). Before the diet, the women had a mean BMI
of 32, amenorrhea for more than 3 months, and increased
plasma concentrations of androstenedione, testosterone, or
DHEAS. Following a hypocaloric diet of 1,0001,500
kcal per day, weight loss ranged from 4.8 kg to 15.2 kg.
After weight loss, significant reductions in the concentration of LH (45% decrease), fasting insulin (40% decrease),
and testosterone (35% decrease) were observed. After
weight loss, most of the women ovulated, and many of the
infertile women became pregnant.
In a small trial that examined the effect of weight
loss on reproductive function in 12 obese women with
PCOS, the women were randomized to either a weight
reduction program or a waiting list observation control
group (32). The six women randomized to the weight
reduction program had a mean weight decrease of 16 kg,
a significant decrease in circulating testosterone concentration, and a decrease in fasting insulin; four of the six
women resumed ovulating. The women randomized to
the observational control group had no weight change
during the study. All of the women in the control group
who were anovulatory before the study (five) remained
anovulatory during the study.
Weight reduction is best achieved by a combination
of diet and exercise. However, exercise at levels greater
than 60 minutes per day has been associated with an
increase in ovulatory infertility (33).
How is clomiphene citrate administered?
The FDA has approved clomiphene dosages of 50 mg or

100 mg daily for a maximum of 5 days per cycle. After
spontaneous menses or the induction of menses with a
progestin withdrawal, clomiphene is started on cycle day
3, 4, or 5 at 50 mg daily for 5 days. Starting clomiphene
on cycle day 3 or 5 does not appear to influence the preg-
1189
nancy rate (34). It is important to give clomiphene only

after menstrual bleeding to help ensure that the patient is
not pregnant. In properly selected women, approximately 50% will ovulate using the 50-mg daily dosage, and
another 25% will ovulate if the dosage is increased to
100 mg daily (35). If lower dosages are not successful in
inducing ovulation, many clinicians will prescribe
150 mg daily for 5 days; a few have used dosages as high
as 250 mg daily for 5 days. However, the pregnancy rates
associated with the use of clomiphene at dosages higher
than 150 mg daily for 5 days are very low (21). In general, if the 150-mg dosage is not successful, alternative
approaches to ovulation induction should be considered.
Of those women who ovulate while taking clomiphene,
between 40% and 80% will become pregnant. In one
study of 3,022 women taking clomiphene, the pregnancy
rate per ovulatory cycle was 20% (36). The pregnancy
rate decreases substantially after six cycles of clomiphene therapy (37).
Patients taking clomiphene should be monitored for
ovulation, pregnancy, and ovarian enlargement, as clinically indicated. Ovulation can be determined by measuring serum progesterone levels (about 14 days after the
last dose of clomiphene), basal body temperature charting, or properly timed endometrial biopsy. Detection of
an LH surge in the urine suggests a preovulatory follicle
has triggered the surge. Intense cycle monitoring with
frequent measurement of serum estradiol levels and pelvic ultrasonography is generally not necessary with the
use of clomiphene but is required for gonadotropin therapy. Clomiphene treatment can be associated with luteal
phase defects and the suboptimal production of cervical
mucus. Some clinicians recommend an endometrial biopsy in a test cycle of clomiphene treatment to assess
whether clomiphene-induced ovulation is associated with
luteal phase defect (38). A few authorities recommend a
postcoital test be performed during the first clomiphene
cycle to assess cervical mucus quality and quantity.
However, little evidence exists to support either practice.
Of clomiphene-induced pregnancies, 7% are twin
gestations and 0.3% are triplet gestations (39). The rate
of spontaneous abortion after clomiphene-induced pregnancy is approximately 15%. The incidence of birth
defects is similar to that seen in spontaneous pregnancy
(40). The most common symptoms experienced by
women taking clomiphene include vasomotor symptoms
(20%), adnexal tenderness (5%), nausea (3%), headache
(1%), and, rarely, blurring of vision or scotomata (21,
41). Many clinicians permanently discontinue clomiphene treatment in women with clomiphene-induced
visual changes. The main contraindications to the use of
clomiphene are pregnancy, hypersensitivity to the medication, and ovarian cysts.
1190
In women who do not ovulate using clomiphene alone, can the chances of ovulation be
improved by adding glucocorticoids?
In women who do not ovulate using clomiphene alone, can the chances of ovulation be
improved by adding an hCG injection?
In women who do not respond to clomiphene, does ovarian diathermy increase the
chances of ovulation more than FSH?
A number of surgical techniques have been described

that may increase the rate of ovulation in women with
PCOS. To date, no randomized, controlled clinical trial
has demonstrated the efficacy of surgery in this setting,
but case series totaling more than 1,000 subjects have
been published. Although ovarian wedge resection was
the initial surgical procedure reported to increase ovulation in women with PCOS, this procedure has been
replaced by laparoscopic techniques that use electrosurgical or laser energy. Overall, the case series report ovulation rates of 80% and pregnancy rates of 50% (45). For
women with PCOS, ovulation induction with FSH also is
associated with pregnancy rates of 50% (46). Injections
with FSH for ovulation induction are associated with a
high rate of multiple gestations (approximately 20%),
and it is not known if ovarian diathermy affects ovarian
reserve. Thus, treatment should be individualized.
The combination of clomiphene plus a single dose of

hCG may increase the efficacy of clomiphene induction
of ovulation when women fail to ovulate with standard
dosages of clomiphene (43). After the last dose of
clomiphene, pelvic ultrasonography can be used to monitor follicle size. When the mean diameter of the lead
follicle reaches 18 mm, a single dose of hCG can be
administered. Ovulation occurs approximately 3644
hours after the injection. There are no randomized controlled clinical trials that document the efficacy of this
approach.
It has been proposed that a regimen of 2 months of
oral contraceptives before ovulation induction with
clomiphene followed by an hCG injection when follicle
ripening has occurred may improve the rate of ovulation
and pregnancy. No randomized clinical trial supports this
approach. However, a clinical trial without controls
reported oral contraceptive treatment followed by
clomiphene therapy (100 mg daily for 5 days) plus an
Women with PCOS and a serum DHEAS concentration

higher than the middle of the normal range (>2 g/mL)
appear to have decreased ovulation and pregnancy rates
when they are treated with clomiphene. Some studies
suggest treatment with clomiphene plus a glucocorticoid
improves pregnancy rates in these women. One study
randomized 64 anovulatory infertile women to receive
either clomiphene, 50 mg daily on cycle days 59, or
clomiphene plus 0.5 mg dexamethasone daily (42). If
ovulation did not occur, the dosage of clomiphene was
increased by 50-mg increments up to 150 mg daily for
5 days each cycle. The investigators observed significantly higher rates of ovulation and conception in
women treated with clomiphene plus dexamethasone
than with clomiphene alone. The impact of combined
therapy was especially marked in the women with a
DHEAS concentration higher than 2 g/mL. Of the
women with a DHEAS concentration higher than
2 g/mL, 12 were randomized to receive clomiphene
alone, and 13 were randomized to receive clomiphene
plus dexamethasone. Among the 12 women receiving
clomiphene alone, six (50%) ovulated and four (33%)
became pregnant. Among the 13 women who received
clomiphene plus dexamethasone, 13 (100%) ovulated
and 11 (85%) became pregnant.
hCG injection was an inexpensive and potentially effective approach to treating women with PCOS who had
failed to ovulate and become pregnant with standard
clomiphene therapy (44). In that study, 38 infertile
women with PCOS who had failed to ovulate when treated with clomiphene (150 mg daily for 5 days) and who
had a DHEAS concentration lower than 2 g/mL took
oral contraceptives (ethinyl estradiol 0.03 mg, and desogestrel 0.15 mg daily) for 2 months followed by
clomiphene. Instead of the usual 7-day pill-free interval
between cycles, the investigators prescribed a regimen
with a 3-day pill-free interval. On cycle days 59 after
completion of the second month of oral contraceptives,
clomiphene (100 mg daily for 5 days) was prescribed.
Transvaginal ultrasonography was initiated on cycle day
12 and repeated every 12 days until hCG was administered. When the mean diameter of the lead follicle
reached 20 mm, hCG (10,000 units) was administered.
The 38 women completed 95 treatment cycles. Sixtynine of the 95 cycles were ovulatory (73%), and 29 of
the 38 women (76%) ovulated. Twenty-two pregnancies
occurred. Most of the pregnancies (82%) occurred in one
of the first three treatment cycles.
In women with hyperprolactinemia, which

medical treatments stimulate the resumption
of ovulation?
Bromocriptine has been used for more than 25 years to

induce ovulation in women with hyperprolactinemia. In
one study of 280 women with hyperprolactinemia,
PRACTICE BULLETINS
bromocriptine normalized the circulating prolactin level

in 82% of the women (47). The main side effects associated with bromocriptine are nausea, vomiting, and orthostatic hypotension. To minimize these potential side
effects, it is recommended that bromocriptine be initiated at a dosage of 1.25 mg at bedtime. After 1 week, the
dosage can be increased to 1.25 mg twice daily. The
dosage can then be increased to 2.5 mg twice daily, a
standard dosage that successfully decreases serum
prolactin levels in most women with hyperprolactinemia (47).
Pergolide, an ergot dopamine agonist, is approved
by the FDA for the treatment of Parkinsons disease but
is not approved for the treatment of hyperprolactinemia.
Unlike bromocriptine, pergolide can be given once per
day. Pergolide is the least expensive of the dopamine
agonists.
In women with PCOS, what is the role of

gonadotropins in inducing ovulation?
In one randomized clinical trial, low-dose FSH treatment

appeared to improve outcomes and decrease adverse
events when compared with standard-dose FSH treatment in women with PCOS (48). In this study, 50 infertile women with PCOS who had failed to conceive with
clomiphene therapy were randomized to receive either
conventional FSH treatment (75 IU daily, increasing by
75 IU every 56 days until follicular ripening occurred)
or low-dose FSH treatment (75 IU daily for 14 days of
treatment, increasing by 37.5 IU every 7 days thereafter
until follicular ripening was complete). Compared with
standard FSH treatment, women who received longterm, low-dose FSH treatment had more cycles with the
development of a single dominant follicle (74% versus
27%), fewer high-order multiple gestations, and a higher pregnancy rate (40% versus 24%).
When should metformin be added for the

treatment of ovulatory infertility?
Insulin sensitizers can be used alone or in combination

with clomiphene to induce ovulation in infertile women
with oligo-ovulation, hyperandrogenism, and insulin
resistance (49). To date, no large-scale clinical trials have
been published that demonstrate the impact of metformin on live birth rates in women with PCOS and
insulin resistance. A few small clinical trials have been
published demonstrating that in women with PCOS the
combination of clomiphene plus metformin is associated
with higher rates of ovulation and pregnancy than
clomiphene plus a placebo (50, 51). In one study, women
with PCOS who did not ovulate when treated with
clomiphene (150 mg daily for 5 days) were randomized
1191
to receive either metformin (1,500 mg daily) or placebo

for 7 weeks (51). During the initial 7-week treatment
period, one of the 12 women in the metformin group
ovulated, and none of the 15 women in the placebo
group ovulated. After this initial treatment period, all of
the women received clomiphene citrate, beginning at a
dosage of 50 mg daily for 5 days, with dosage escalation
if ovulation did not occur. Nine of the 12 women in the
metformin-plus-clomiphene group ovulated, compared
with four of the 15 women in the placebo-plusclomiphene group (P < 0 .02). Of the women who
completed the clinical trial, six (of 11) in the metforminplus-clomiphene group became pregnant, and one (of
14) in the placebo-plus-clomiphene group became pregnant (P <0.02). Of the six pregnancies in the metforminplus-clomiphene group, two resulted in spontaneous
abortion and four resulted in live singleton births. The
one pregnancy in the placebo-plus-clomiphene group
resulted in a live singleton birth.
A commonly used dosage of metformin is 500 mg
three times daily. The most common side effects of
metformin are gastrointestinal disturbances, including
diarrhea, nausea, vomiting, and abdominal bloating. To
minimize gastrointestinal side effects, many clinicians
recommend starting metformin at 500 mg daily for 1
week, increasing to 500 mg twice daily for 1 week, and
then increasing to 500 mg three times daily. Once the full
dosage is achieved, some clinicians switch to a dosing
regimen of 850 mg twice daily to improve patient compliance. Progesterone measurements can be periodically
obtained to determine whether ovulation has occurred, or
the patient can keep a basal body temperature chart. If
ovulation has not occurred after 48 weeks of metformin therapy, clomiphene (50 mg daily for 5 days) can
be administered after progestin-induced menstrual withdrawal bleeding. If the patient becomes pregnant, the
metformin therapy can be discontinued. Ovulation, if it
is going to occur, can be expected to occur within 68
weeks.
In rare cases, metformin therapy has caused fatal
lactic acidosis. In most of these cases, renal insufficiency or severe hypoxia (congestive heart failure, septic
shock) was present. Before treatment with metformin is
initiated, it is recommended that serum creatinine levels
be demonstrated to be lower than 1.4 mg/dL. Women
with liver dysfunction should not take metformin. Also,
metformin should be discontinued 48 hours beforeand
not restarted for 72 hours afterany radiologic test
involving intravenous contrast or before surgery.
Metformin appears to improve the ovulatory
response in women with PCOS treated with FSH injections. A trial randomized 20 infertile women with PCOS
and insulin resistance who had failed to ovulate when
1192
Is a postcoital test useful in a patient taking

clomiphene citrate?
The postcoital test has low reproducibility and low interobserver reliability and has not been proved to help
guide treatment recommendations (5355). In addition,
there is little consensus on what constitutes an abnormal
postcoital test result. Given these limitations, there is little scientific rationale for performing a postcoital test.
However, clinical experience suggests that clomiphene,
acting as an antiestrogen in the cervix, can cause cervical mucus production that is abnormal in quantity and
quality. Therefore, some clinicians recommend performing a postcoital test to assess the impact of clomiphene
on cervical mucus production.
Can the risk of multiple gestation be minimized?
Is the risk of ovarian cancer increased with

the use of induction agents, such as
clomiphene or gonadotropin injections?
The risk of ovarian cancer is increased in women who are

nulligravid (voluntarily and involuntarily) and women
with a strong family history of ovarian cancer. The risk of
ovarian cancer is decreased by pregnancy, use of oral contraceptives for more than 6 months, surgical tubal ligation,
and hysterectomy. Preliminary studies reported ovulationinducing medications may be associated with a small
increase in the risk of ovarian tumors (borderline tumors
and cancer) and that the risk may increase with the extended use of ovulation-inducing agents for many months (57,
58). In one of these studies, the strongest risk occurred
among 13 nulligravid women who had used infertility
drugs and had never become pregnant. In this subset, the
association was statistically significant, but the confidence
interval was wide, suggesting a great deal of variation, and
the sample size was small (n=13). Some practitioners
believe infertility (involuntary childlessness) is a more
powerful risk factor for ovarian tumors than treatment
with an ovulation-inducing medication. However, given
the low pregnancy rates observed after six cycles of ovulation induction with an induction agent (such as
clomiphene) and the potential (although low) risk that 12
or more cycles of clomiphene may be associated with an
increased risk of ovarian tumors, it is reasonable to limit
clomiphene treatment to fewer than 12 cycles. There are
no evidence-based guidelines about the appropriate duration of gonadotropin administration; however, given the
possibility that such agents can cause harm, it seems
appropriate to use them sparingly and only with clear-cut
indications.
Summary of
Recommendations
In obese women with PCOS, weight loss should be

considered because it is associated with a decrease
in circulating testosterone concentration, an
increase in the frequency of ovulation, and in some
women, pregnancy.
Multiple gestation is a growing problem. Public awareness is increasing about the hazards associated with
multiple births, as well as the long-term costs and consequences (56). Monofolliculogenesis is the goal of therapy in infertile patients.
To decrease the risk of multiple gestation, treatments associated with low rates of multiple gestation
should be used. For example, in women with PCOS,
ovulation induction with weight loss, clomiphene,
clomiphene plus metformin, clomiphene plus glucocorticoid, and ovarian surgery are associated with low rates
of triplet pregnancy. Gonadotropin injections and in vitro
fertilization are associated with higher rates of multiple
gestation (48). When using gonadotropin injections, the
use of low-dose regimens appears to be associated with
lower rates of multiple gestation than the use of standard
dose regimens. In addition, the risk of multiple gestation
with FSH injections can probably be decreased by withholding hCG and prescribing a barrier contraceptive
whenever more than three follicles greater than 15 mm in
diameter are detected with pelvic ultrasonography.
treated with clomiphene (150 mg daily for 5 days) to

receive either FSH injections alone or FSH injections plus
metformin (500 mg three times daily) (52). The mean
BMI of the subjects was approximately 27. Compared
with the women who received FSH alone, the women
who received both FSH and metformin had fewer dominant follicles (2.4 versus 4.5, P <0.01), a lower peak estradiol concentration (450 pg/mL versus 720 pg/mL,
P <0.001), and a lower cycle cancellation rate (0% versus
32%, P < 0.03). The investigators concluded a combination of FSH plus metformin is associated with an orderly
follicular response that probably decreases the risk for
ovarian hyperstimulation and multiple pregnancy.
In obese women with PCOS who did not ovulate

when treated with clomiphene, the combination of
clomiphene plus metformin may be considered
because the rate of ovulation is greater than it is with
clomiphene alone.
PRACTICE BULLETINS
In women with PCOS and a serum DHEAS level

higher than 2 g/mL, the combination of clomiphene plus glucocorticoid may be considered
because the rate of ovulation is greater than it is with
clomiphene alone.
In women with hypothalamic amenorrhea and a

BMI lower than 20, weight gain should be considered because it may be associated with the resumption of ovulation and pregnancy.
In women with PCOS receiving gonadotropin injections for ovulation induction, low-dose FSH may be
considered because it is associated with a higher
rate of cycles with the development of a single dominant follicle and fewer high-order multiple gestations.
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1195

Force:
I
type of evidence.
committees.
transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Management of infertility caused by ovulatory dysfunction. ACOG
Practice Bulletin No. 34. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2002;99:347358
1196
ACOG
PRACTICE
BULLETIN
NUMBER 35, MAY 2002

of Benjamin E. Greer, MD,
and Wui-Jin Koh, MD. The information is designed to aid
of practice.
Reaffirmed 2008
Diagnosis and Treatment

of Cervical Carcinomas
Invasive cervical carcinoma, once the most common reproductive-tract cancer
in the United States, has recently fallen to the rank of third most common.
Globally, cervical cancer is a major health problem, with a yearly incidence of
371,000 cases and an annual death rate of 190,000 (1). The International
Federation of Gynecology and Obstetrics (FIGO) recently revised its staging
criteria. In addition, new evidence has documented conclusively that survival
rates for women with cervical cancer improve when radiotherapy is combined
with cisplatin-based chemotherapy. This document will describe staging criteria and treatment for cervical carcinoma. For practical purposes, it will focus
on the squamous and adenocarcinoma histologies only.
Background
Prevalence
The American Cancer Society estimated that 12,900 new cases of cervical cancer would be diagnosed in the United States in 2001 and that 4,400 deaths from
cervical cancer would result (2). Cervical cancer comprises approximately 16%
of the estimated 80,300 cases of reproductive-tract cancers among women in
the United States. Seventy-eight percent of cases occur in developing countries
where cervical cancer is the second most frequent cause of cancer-related death
in women. The substantial decrease in incidence and mortality in developed
countries is thought to be a result of effective screening.
Risk Factors
Human papillomavirus is considered the most important factor contributing to the
development of cervical intraepithelial neoplasia and cervical cancer. Countries with
a high incidence of cervical cancer also have a high prevalence of human papillomavirus (1). Other epidemiologic risk factors associated with cervical intraepithelial
PRACTICE BULLETINS
neoplasia and cervical cancer include history of sexual intercourse at an early age, multiple sexual partners, sexually
transmitted diseases (including chlamydia), and smoking (3).
Additional risk factors include a male partner or partners
who have had multiple sexual partners; previous history of
squamous dysplasias of the cervix, vagina, or vulva; and
immunosuppression, such as after organ transplantation or
patients with acquired immunodeficiency syndrome.
Diagnosis
The signs and symptoms of early cervical carcinoma
include watery vaginal discharge, intermittent spotting, and
postcoital bleeding. Often the symptoms go unrecognized
by the patient. Because of the accessibility of the cervix,
accurate diagnosis often can be made with cytologic screening, colposcopically directed biopsy, or biopsy of a gross or
palpable lesion (4). In cases of suspected microinvasion and
early-stage cervical carcinoma, cone biopsy of the cervix is
indicated to evaluate the possibility of invasion or to define
the depth and extent of microinvasion. Cold knife cone biopsy provides the most accurate evaluation of the margins.
Histology
The two major histologic types of invasive cervical carcinomas are squamous cell carcinomas and adenocarcinomas. Squamous cell carcinomas comprise 80% of cases,
and adenocarcinoma or adenosquamous carcinoma comprise approximately 15%. The remaining cases are made
up of various rare histologies, which may have very different biologic behavior.
Management
Early carcinomas of the cervix usually can be managed by
surgical techniques or radiation therapy. The more
advanced carcinomas require primary treatment with radiation therapy. Many changes in radiation therapy techniques have occurred in the past decade. These include
incorporation of higher energy external beam equipment,
improved field design to cover anatomic regions at risk,
increased use of tomographic imaging, recognition of the
adverse impact of prolonged treatment, increased familiarity with high-dose-rate brachytherapy, and, more recently,
the use of chemotherapy concurrent with radiation therapy.

Recommendations
How are patients with cervical carcinoma

categorized or staged?
Staging of gynecologic cancers attempts to define the

anatomic extent of a given cancer. This allows for scien-
1197
tific comparison of treatment results from different centers or protocols. The three major staging systems are
those of FIGO, the American Joint Committee on Cancer,
and the International Union Against Cancer. Cancer registries approved by the American College of Surgeons
use the American Joint Committee on Cancers TNM
(tumor, nodes, metastasis) staging system. However, the
scientific literature reports gynecologic oncology statistics using the FIGO system. It is recommended that the
FIGO system be used to facilitate comparisons of international data.
Staging of invasive cervical cancer with the FIGO
system is achieved by clinical evaluation. Other gynecologic cancers are staged surgically. The current FIGO
nomenclature for cancer of the cervix was first adopted in
1994 (5) (see box, Carcinoma of the Cervix Uteri: FIGO
Nomenclature).
Careful clinical examination should be performed on
all patients. Examinations should be conducted by experienced examiners and may be performed under anesthesia.
Pretreatment evaluation of women with cervical carcinoma
often can be helpful if provided by an obstetriciangynecologist with advanced surgical training, experience, and
demonstrated competence, such as a gynecologic oncologist. The procedure may be scheduled to occur at the same
time the patient is undergoing another procedure requiring
anesthesia. Once established, the clinical stage must not be
revised because of subsequent findings, even if the cancer
recurs. The box, Guidelines for Clinical Staging of
Invasive Cervical Carcinoma, identifies key points in staging disease. These guidelines are made up of examinations
generally available throughout the world. Strict adherence
to the rules for staging provides the framework for making
valid scientific comparison of results.
Various optional examinations, such as ultrasonography, computed tomography (CT), magnetic resonance
imaging (MRI), lymphangiography, laparoscopy, and fineneedle aspiration, are valuable for treatment planning.
Surgical findings provide extremely accurate information
about the extent of disease and will guide treatment plans
but will not change the results of clinical staging. The
occasional hysterectomy specimen with unsuspected
extensive invasive cervical carcinoma cannot change the
previously documented clinical stage.
While not required as part of FIGO staging procedures, in the United States, various radiologic tests are
frequently undertaken to help define the extent of tumor
growth and guide therapy decisions, especially in
patients with locally advanced disease (ie, stage IIb or
more advanced). Computed tomography of the abdomen
and pelvis is the most widely used imaging study. Early
evaluation of the efficacy of CT scans in detecting
paraaortic adenopathy noted a very high specificity
1198
Carcinoma of the Cervix Uteri: FIGO Nomenclature

Stage 0 Carcinoma in situ, cervical intraepithelial neoplasia Grade III
Stage I The carcinoma is strictly confined to the cervix (extension to the corpus would be disregarded).
Ia
Invasive carcinoma that can be diagnosed only by microscopy. All macroscopically visible lesionseven with
superficial invasionare allotted to Stage Ib carcinomas. Invasion is limited to a measured stromal invasion with a
maximal depth of 5.0 mm and a horizontal extension of not more than 7.0 mm. Depth of invasion should not be
more than 5.0 mm taken from the base of the epithelium of the original tissuesuperficial or glandular.
The involvement of vascular spacesvenous or lymphaticshould not change the stage allotment.
Ia1 Measured stromal invasion of not more than 3.0 mm in depth and extension of not more than 7.0 mm
Ia2 Measured stromal invasion of more than 3.0 mm and not more than 5.0 mm with an extension of not
more than 7.0 mm
Ib
Clinically visible lesions limited to the cervix uteri or preclinical cancers greater than Stage Ia
Ib1 Clinically visible lesions not more than 4.0 cm
Ib2 Clinically visible lesions more than 4.0 cm
Stage II Cervical carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower third of the vagina
IIa
No obvious parametrial involvement
IIb
Obvious parametrial involvement
Stage III The carcinoma has extended to the pelvic wall. On rectal examination, there is no cancer-free space between
the tumor and the pelvic wall. The tumor involves the lower third of the vagina. All cases with hydronephrosis
or nonfunctioning kidney are included, unless they are known to be due to other causes.
IIIa Tumor involves lower third of the vagina, with no extension to the pelvic wall
IIIb Extension to the pelvic wall or hydronephrosis or nonfunctioning kidney
Stage IV The carcinoma has extended beyond the true pelvis, or has involved (biopsy proved) the mucosa of the bladder
or rectum. Bullous edema, as such, does not permit a case to be allotted to Stage IV.
IVa Spread of the growth to adjacent organs (bladder or rectum or both)
IVb Spread to distant organs
Benedet JL, Odicino F, Maisonneuve P, Beller U, Creasman WT, Heintz AP, et al. Carcinoma of the cervix uteri. J Epidemiol Biostat 2001;6:743
(96%) but low sensitivity (34%) (6). However, with technologic advancements leading to increased imaging resolution, accuracy of CT scanning has improved (7). Recent
experience has suggested MRI is as accurate as CT in
assessing nodal involvement and provides better definition of the extent of local tumors within the pelvis (7).
Some investigators have advocated the use of lymphangiography as the standard for noninvasive assessment
of retroperitoneal adenopathy, but a recent review has
shown that contemporary CT and MRI results are as
accurate as lymphangiography and are preferable given
that more information is provided on local tumor
infiltration (7). Early experience with a new imaging
modality, positron emission tomography (PET), shows
considerable promise in further increasing the accuracy
of noninvasive radiologic staging. The sensitivity of PET
has been reported to be 75%, and the specificity 92% (8).
Guidelines for Clinical Staging of Invasive

Cervical Carcinoma
Examinations should include inspection, palpation,
colposcopy, endocervical curettage, hysteroscopy,
cystoscopy, proctoscopy, intravenous pyelography,
and X-ray examination of lungs and skeleton.
Conization of the cervix is considered a clinical
examination.
Suspected bladder or rectal involvement should be
confirmed histologically.
If there is a question about the most appropriate
stage, the earlier stage should be assigned.
Data from Benedet JL, Odicino F, Maisonneuve P, Beller U, Creasman WT,
Heintz AP, et al. Carcinoma of the cervix uteri. J Epidemiol Biostat
2001;6:743
PRACTICE BULLETINS
How is stage Ib1 carcinoma distinguished

from stage Ib2?
Is surgical evaluation of cervical carcinoma

appropriate?
As discussed earlier, the results of surgical evaluation

should not influence the stage determined by using the
FIGO clinical staging system. However, it is well recognized that the presence of lymph node metastasis is the
most important adverse predictor of survival. Although
surgical evaluation of cervical cancer remains controversial, it is the best method of assessing nodal involvement.
Retroperitoneal surgical lymph node dissection of the
pelvic and paraaortic lymph nodes provides important
information about treatment planning and prognosis.
Patients with positive lymph nodes can have radiation
fields modified appropriately to cover areas at risk.
Resection of positive lymph nodes is thought to provide
therapeutic benefit (15, 16). Therefore, surgical evaluation allows individualization of therapy and may result in
better clinical outcomes.
In 1994, FIGO revised its staging criteria, subdividing

stage Ib carcinoma of the cervix into stage Ib1 (4 cm in
diameter) and stage Ib2 (>4 cm diameter). When the
tumor is confined to the cervix, the size of the primary
tumor has been shown to have a significant impact on
survival rates in stage Ib cervical cancer, regardless of
primary treatment modality (9, 10). A large, prospective
Gynecologic Oncology Group surgicalpathologic study
demonstrated that in stage Ib carcinoma of the cervix,
tumor size of 3 cm or more was an independent adverse
prognostic factor for decreased disease-free survival (11).
Other independent risk factors in this study were capillary-space involvement and depth of cervical stromal
invasion. A large study of patients treated by radiation
therapy or radiation therapy followed by hysterectomy
demonstrated significantly better survival rates for
patients with stage Ib tumors of less than 4 cm in diameter than for those with tumors greater than 4 cm (12).
Another study demonstrated the effect of tumor size on
outcomes in patients treated with radiation therapy alone
(ie, without surgery or chemotherapy). Five-year diseasefree survival rates for women with stage Ib cancer were
100% for lesions less than 1 cm in diameter, 93% for
those 11.9 cm, 98% for those 22.9 cm, 83% for those
33.9 cm, and 76% for lesions of 4 cm or more (13).
Retrospective analysis has evaluated patients who
had radical hysterectomies and lymph node dissections
for stage Ib1 and Ib2 cancers of the cervix (14). Patients
with stage Ib2 disease had a significantly worse 5-year
survival rate (72.8%) when compared with those who had
stage Ib1 tumors (90%). Also, in this study, in 38.7% of
cases of stage Ib1 disease and 72.9% of cases of stage Ib2
disease patients received postoperative radiation therapy
for high-risk indications such as positive lymph nodes,
parametrial disease, positive surgical margins, and deep
stromal invasion involving the outer third of the cervix.
The high percentage of postoperative radiation required
in patients with stage Ib2 disease suggests that primary
radiation should be considered for these patients and may
be supplemented by surgical or radiologic evaluation to
assess retroperitoneal nodal status.
1199
How is microinvasive cervical cancer diagnosed and treated?
The concept of microinvasive carcinoma of the cervix as

a distinct clinical entity was introduced by Mestwerdt in
1947 (17). The premise for this specific diagnosis was to
define a subset of patients with early carcinomas of the
cervix who had a favorable prognosis. It is important to
remember these lesions are defined microscopically and
cannot be visualized on gross inspection. The appropriate
definition of this entity has been debated for more than
50 years. The main issues affecting the definition are the
maximum depth of stromal invasion, the significance of
lymphatic-vascular space invasion, tumor volume, and
confluence of the invasion pattern as related to the frequency of pelvic node metastasis, vaginal recurrence, and
ultimate survival. These prognostic factors are important
determinants of treatment necessary for the best survival
with the lowest morbidity and, in certain circumstances,
may influence decisions regarding preservation of the
uterus for future pregnancy.
The definition of microinvasive carcinoma of the
cervix was modified by FIGO seven times between 1961
and 1994, indicating a lack of universal consensus. This
section will focus on the rationale for the 1994 definitions and the treatment options based on the best available scientific data.
During the 1970s, the concept of volumetric measurements for early small cancers, rather than just unidimensional consideration of penetration depth, was
being developed. Estimation of volume is most accurate
by using the three largest diameters of the lesions. The
rigorous technique for volumetric assessment requires
examining up to 100 sections per cone specimen. This
labor-intensive process was not well accepted. Bidimensional planar measurements were recommended
without testing. In 1988, FIGO changed the definition
of stage Ia2 tumor to include a specified maximal depth
of invasion of 5 mm and a maximal horizontal spread of
7 mm. This was based on the presumption that the overall volume of the microcarcinoma should not exceed
1200
7.8% rate of nodal metastasis and a death rate of 2.4%.

One study that included only lesions of less than 5 mm
depth found nodal metastasis when the lateral spread was
greater than 7 mm (23).
According to the FIGO criteria, patients with stage
Ia1 carcinoma could be treated with simple hysterectomy
without nodal dissection or conization in selected cases.
Those patients with invasion greater than 3 mm and no
greater than 5 mm (stage Ia2) should undergo radical
hysterectomy and pelvic lymphadenectomy (4, 22).
Although lymphatic-vascular invasion should not
alter the FIGO stage, it is an important factor in treatment
decisions. The risk of recurrence with lymphatic-vascular
involvement is 3.1% if the extent of invasion is 3 mm or
less and 15.7% if it is greater than 3 mm and no greater
than 5 mm (22). Therefore, the presence of lymphaticvascular invasion would suggest the need for more radical treatment to obtain the optimal outcome. Evaluation
in consultation with an obstetriciangynecologist with
advanced surgical training, experience, and demonstrated
competence, such as a gynecologic oncologist, often
helps to determine the extent of surgery needed and the
optimal use of adjunctive therapy.
Preservation of fertility has become increasingly
important as more women are delaying having families.
A treatment dilemma arises for women with cervical carcinoma who have not started or completed childbearing
but desire the option to become pregnant. For both ethical and medicallegal reasons, patients who opt for conservative management should fully understand the risks
involved. Recent reports have described the use of radical trachelectomy with or without lymph node dissection
(24, 25). This procedure should be considered experimental and may be carried out best in consultation with
an obstetriciangynecologist with advanced surgical
training, experience, and demonstrated competence, such
as a gynecologic oncologist.
Treatment of microinvasive squamous carcinoma of
the cervix deserves careful attention to details and individualization of therapy based on histologic evaluation.
The concept of microinvasive adenocarcinoma has not
been generally accepted.
350 mm3. One study concluded that a microcarcinoma

with a tumor volume of less than 500 mm3 generally was
not associated with metastasis (18).
The 1988 FIGO definition of 5 mm of depth for
stage Ia2 was in conflict with the Society of Gynecologic
Oncologists definition of 3 mm or less for microinvasive
disease, which had been used in the United States since
1974. In 1994, FIGO modified its definition of stage Ia1
to 3 mm or less of invasion. Currently, stage Ia1 is
defined as a depth of invasion no greater than 3 mm and
no wider than 7 mm, and stage Ia2 is defined as a depth
of invasion greater than 3 mm but no greater than 5 mm
and no wider than 7 mm. Lymphatic-vascular invasion
should not alter the stage.
Despite this background and these definitions, diagnosis of microinvasive squamous carcinoma of the cervix is
difficult. The FIGO staging guidelines presume the diagnosis will be made with a cone biopsy. Cold knife cone
biopsies may be more accurate than loop electrosurgical
excision procedure (LEEP) cones, because the margins are
very important. Cautery artifact, loss of tissue, and thermal
destruction account for the inaccuracy of information provided by LEEP specimens. In the United States, patients
with abnormal Pap test results undergo colposcopy and
biopsy for diagnosis. Colposcopic biopsies usually are performed before conization. The biopsy removes part of the
lesion and, therefore, alters the apparent depth of invasion
as seen on the cone specimen (19). Another potential problem in evaluation involves the accepted techniques of
pathologic study. After initial fixation in formalin, cone
biopsy specimens are divided into quadrants and stepsectioned. Maximal extent of horizontal spread could be
underestimated by this procedure. In addition, there are difficulties in interpretation of the histology by pathologists.
In two large studies that employed pathology re-review of
cases initially diagnosed as microinvasive cervical carcinomas, 4050% of the cases were excluded because they did
not meet the criteria for microinvasion (20, 21). In
2040%, no invasion was thought to be present, and in
67%, the depth of invasion was greater than 5 mm.
Understanding the concepts behind definition and
diagnosis of microinvasive carcinoma of the cervix is
important to understanding the biology and behavior of
the disease. A comprehensive review of the current literature found that nodal metastasis is the most consistent
and strongest predictor of survival for patients with early
invasive cervical cancers (22). There is a relationship
between depth of invasion and nodal metastasis.
Minimally invasive lesionsthose with invasion up
to 3 mmhave a lymph node metastatic risk rate of 1.2%
and a death rate of less than 1%. However, lesions greater
than 3 mm and no greater than 5 mm of invasion have a
How is early-stage (IbIIa) carcinoma treated?
Both treatment strategies for stage Ib and early-stage IIa

invasive carcinoma include 1) a primary surgical approach
with radical hysterectomy and pelvic lymphadenectomy or
2) primary radiation therapy with external beam radiation
and either high-dose-rate or low-dose-rate brachytherapy.
A review of collective observational experiences reported
in the literature demonstrates a 5-year survival rate of
8792% using either approach (26).
PRACTICE BULLETINS
What is the role of adjuvant therapy following

primary surgery in early-stage carcinoma?
The identification of various pathologic risk factors, such

as lymph node metastases, following primary surgical
management of early-stage cervical cancer portends a
higher rate of relapse and decreased survival rates (28).
Historically, attempts to improve outcome mainly
focused on the role of adjuvant pelvic radiation therapy,
with inconsistent results. More careful analysis of patterns of failure following radical hysterectomy has led to
better stratification of patients into risk groups and incorporated testing of systemic chemotherapy agents in those
considered at high risk of distant failure (28).
Two randomized clinical trials have greatly
advanced our understanding of the role of postoperative
therapy in cervical cancer (29, 30). Patients with histologically documented extracervical diseasespecifically
those with pelvic nodal involvement, positive margins, or
parametrial extensionare treated with concurrent
pelvic radiation therapy and cisplatin-based chemotherapy. The use of combined adjuvant chemotherapy
and radiation therapy in these high-risk patients following primary surgery significantly improves relapse-free
survival and overall survival rates when compared with
radiation therapy alone (29).
Following radical hysterectomy, a subset of nodenegative patients who have a constellation of primary risk
factors (large tumors, depth of stromal infiltration, and
lymphovascular space involvement) may be defined as
having intermediate risk for relapse. For these patients,
adjuvant pelvic radiation therapy provides clear therapeutic benefit, with significantly improved relapse-free
survival rates when compared with those who had no further therapy. However, observation of improvement in
overall survival favoring patients who had radiation therapy awaits further statistical confirmation following maturation of the data (30).
Until recently, there have been no prospective randomized studies comparing surgery and radiation therapy. An Italian randomized trial provides information
about primary surgery and radiation therapy but does not
include the addition of concurrent or neoadjuvant
chemotherapy (27). This study compared radical hysterectomy and primary radiotherapy with adjuvant radiation therapy in high-risk surgically treated patients.
Stratification for stage Ib and Ib2 was included.
Pathologic findings indicated identical 5-year overall and
disease-free survival rates in the radiation therapy group
and the surgical group with tailored postoperative radiation therapy. Severe morbidity occurred in 28% of patients
in the surgery and postoperative radiation therapy group
and in 12% of patients in the radiation therapyonly
group (P = 0.0004). In this study, adjuvant radiation therapy after primary surgery was used in 54% of patients
with tumors measuring 4 cm or less and in 84% of
patients with tumor diameters greater than 4 cm.
Significant prognostic factors included tumor diameter,
positive lymphangiography, and adenocarcinoma histology as identified on univariate and multivariate analyses.
Although the two modalities were found to be similarly effective in the randomized trials, the rate and types
of complications differ. The preference of treatment
depends on the situation, the physicians input, and the
patients age, health, and tumor characteristics.
Those who favor radical surgery point out that it
leaves the vagina in more functional condition, while
radiation therapy results in a reduction in length, caliber,
and lubrication of the vagina. In premenopausal women,
ovarian function can be preserved with surgery. The surgical approach also provides the opportunity for pelvic
and abdominal exploration and provides better clinical
and pathologic information with which to individualize
treatment. Surgery may be preferred over radiation therapy in women who have diverticular disease, tuboovarian
abscess, or appendiceal abscess; have had prior radiation
therapy; have congenital pelvic located kidney; or are
psychotic or noncompliant. Proponents of radiation therapy advocate primary radiation to avoid surgical morbidity or mortality, risk of blood loss and transfusion, and
excessive anesthesia time.
1201
How is late-stage carcinoma (IIb or later)

treated?
Historically, primary radiation therapy has been used to

treat patients with bulky or locally advanced cervical cancer. The approach generally consists of external beam
radiation to achieve primary tumor reduction and provide
coverage to the parametria and regional nodes at risk,
supplemented by brachytherapy to increase radiation
dose delivery to the central residual tumor. Earlier
attempts to improve outcome results from primary radiation therapy by the addition of agents such as hydroxyurea or hypoxic cell sensitizers met with mixed success.
Results from five randomized trials on cervical cancer have established the role of concurrent cisplatinbased chemotherapy and radiation therapy for high-risk
or locally advanced disease (29, 3134). The various
studies had different eligibility criteria, but in total
included a broad spectrum of clinical presentations: 1)
patients with locally advanced tumors for whom
chemoradiation represented primary therapy (three studies [31, 32, 34]); 2) bulky early-stage cancers in which
chemoradiation was delivered prior to adjuvant hysterec-
1202
tomy (one study [33]); and 3) postradical hysterectomy

cases with high-risk pathologic factors (positive lymph
nodes, positive parametria, positive margins) for whom
adjuvant chemoradiation was given (one study [29]). In
each of the five studies, a statistically significant survival
advantage was observed among patients who received
radiation therapy with a concurrent cisplatin-based regimen when compared with those who received radiation
alone or radiation combined with hydroxyurea. The dramatic 3050% reduction in the relative risk of death in
the five trials prompted a rare clinical announcement
from the National Cancer Institute stating that strong
consideration should be given to the incorporation of
concurrent cisplatin-based chemotherapy with radiation
therapy in women who require radiation therapy for
treatment of cervical cancer (35).
The five reported studies used cisplatin administered either weekly as a single agent or in combination
with infusion 5-fluorouracil every 34 weeks (29,
3134). Although the optimal cisplatin-based chemotherapeutic regimen has not yet been fully defined, many
are choosing to use weekly cisplatin because of its ease
of delivery and favorable toxicity profile (36). However,
it is clear that the previously controversial use of hydroxyurea can be abandoned. Furthermore, it should be
remembered that the advantages of chemoradiation are
obtained only in the setting of concurrent therapy.
Neoadjuvant chemotherapy prior to radiation therapy
has shown no benefit and has even been detrimental in
some cases.
The cumulative results from the recently reported
randomized trials represent a major advance in the management of women with cervical cancer and have established a new paradigm for therapy. At present, women
with locally advanced cervical cancer in North America
should receive cisplatin-based chemotherapy concurrent
with radiation therapy.
Should squamous cell cancer and adenocarcinoma be treated differently?
Underlying this question is the continuing debate regarding the independent prognostic implications of adenocarcinoma versus squamous cell histologies in cervical
cancer, especially in early-stage disease. Two large
reviews reflect the ongoing controversy. In an analysis of
813 patients with stage Ib cervical cancer entered into a
Gynecologic Oncology Group surgicalpathologic
study, excluding patients with positive paraaortic nodes
or gross extracervical disease, three specific cell types
were identified (645 squamous cell, 104 adenocarcinoma, and 64 adenosquamous). No significant differences
were found among the cell types with regard to the
patients age at presentation, performance status, pelvic

nodal metastases, depth of cervical invasion, uterine
extension, surgical margins, or parametrial infiltration.
Relapse-free survival rates were similar for all three histologies, but adenosquamous cell was associated with a
small, statistically significant reduction in overall survival, even after adjusting for associated pathologic risk
factors (37). In contrast, a retrospective review of 1,767
stage Ib cervical cancer patients who were clinically
staged and treated with primary radiation therapy identified adenocarcinoma histology (including adenosquamous cell types) as an independent risk factor for disease
recurrence and death, with distant metastases the primary site of failure (38, 39).
Despite the ongoing discussion regarding cell type
and prognosis, there is no evidence to support differences in treatment of invasive squamous cell cancer versus adenocarcinoma of the cervix. The only exception to
this is the management of microinvasive disease, where
guidelines have been developed for more conservative
management of patients with FIGO stage Ia1 squamous
cell cancer, corresponding with the Society of
Gynecologic Oncologists working definition for minimally invasive tumors discussed previously. It should be
emphasized that no definition for microinvasive adenocarcinoma of the cervix has been agreed upon; therefore,
treatment algorithms for such patients remain undefined.
For patients with frankly invasive disease, regardless of squamous cell or adenocarcinoma histology, the
primary options for treatment are radical hysterectomy
with lymphadenectomy or definitive radiation therapy.
In patients undergoing primary surgery who have positive nodes, positive margins, or parametrial infiltration,
adjuvant radiation concurrent with cisplatin-based
chemotherapy is indicated on the basis of positive results
from a randomized trial (29). In this trial, the addition of
chemotherapy to radiation appeared to overcome the
worse prognosis associated with adenocarcinoma cell
components, when compared with patients receiving
adjuvant radiation therapy only (29). For more advanced
disease in which primary radiation therapy is recommended, the addition of concurrent cisplatin-based
chemotherapy provides clear therapeutic benefit (35).
How should patients be monitored over the

long term?
Surveillance after primary therapy for invasive carcinoma of the cervix is universally recommended.
Approximately 35% of patients will have persistent or
recurrent disease. The main goal of surveillance is early
detection of recurrent disease so that patients can be
offered potentially curative salvage therapy. The average
PRACTICE BULLETINS
1-year survival for patients with recurrent cervical cancer is 1020% (39, 40). Surveillance schedules should
take into account the risk of recurrence, which is highest
in the first 2 years following treatment (41). The potential benefit of salvage therapy depends on the stage of
disease, type of treatment, and location of recurrence (ie,
local, regional, or distant). In general, radical radiation
therapy is used for recurrent cervical cancer after primary hysterectomy, while salvage surgery is required for
those who relapse after primary radiation therapy. In
selected patients with centralized pelvic recurrences, salvage may be achieved in about 50% of cases (42).
Few studies have specifically addressed the efficacy
of routine surveillance follow-up after definitive cervical
cancer therapy in asymptomatic and disease-free
patients, as opposed to symptom-based reassessment.
Schedules for posttherapy surveillance vary by practitioner and institution, although a common approach
includes examinations and Pap tests every 34 months
for the first 3 years, decreasing to twice yearly in the
fourth and fifth years (4).
Investigators recently attempted to develop an optimal surveillance program based on outcome analysis
following primary therapy for stage-Ib cervical cancer
(43). Detection of asymptomatic recurrences, whether
locally in the pelvis or with isolated pulmonary metastases, led to significantly better salvage options and survival when compared with detection only in patients
presenting with symptomatic recurrences. The authors
concluded this subset of patients may benefit from careful posttherapy surveillance and proposed a schedule
involving thrice-yearly follow-up visits for the first 2
years, and twice-yearly visits subsequently to year 5,
with Pap tests and chest X-rays on a yearly basis.
Posttreatment follow-up also is beneficial for reasons other than the diagnosis of recurrence. The psychologic support and reassurance of continued contact with
the treating team is vitally important. Annual health
maintenance visits for mammography, blood pressure,
and evaluation of other medical problems are important.
Many of these patients undergo bilateral salpingooophorectomy or radiation therapy, and hormone
replacement therapy should be considered in such
patients. Cervical adenocarcinoma is not a contraindication to hormone replacement therapy.
How should patients with invasive cancer

diagnosed during pregnancy be treated?
Between 2.7% and 3.5% of cases of cervical cancer

occur in pregnant women (44). The diagnosis of invasive
carcinoma during pregnancy presents a therapeutic
dilemma. Fortunately, cervical cancer rarely causes
1203
maternal mortality (45). The survival rate of patients

with stage I cervical cancer is excellent regardless of the
time of diagnosis during pregnancy, with recent reported
survival rates of 85% and 95% (46, 47). The overall survival rate for women who were pregnant and had invasive cervical cancer is 80% (48).
This clinical problem requires attention to the health
of the woman as well as the safety of the fetus. The
appropriate treatment is influenced by ethical concerns,
cultural and religious issues, and whether the patient
wishes to continue the pregnancy after being informed of
the potential risks and benefits of treatment. Optimal
counseling and therapy require an interdisciplinary
approach.
Therapeutic recommendations for a patient with
invasive cervical carcinoma are individualized according
to the patients presenting stage, lesion size, and desire to
continue the pregnancy. Pregnant women are 3.1 times
more likely than nonpregnant women to have diagnosed
Stage I disease, probably because of regular examinations (48). A summary of the current literature confirmed
that most patients with cervical cancer diagnosed during
pregnancy have stage I cancer (49). Seventy-six percent
have stage Ib, and 78% have squamous cell histology.
Pregnancy offers an ideal opportunity for cervical
cytologic screening. Figure 1 provides a general algorithm for the evaluation of abnormal cervical cytology in
pregnancy (50). A pregnant patient with carcinoma in
situ and microinvasive squamous carcinoma of 3 mm or
less can deliver vaginally and be reevaluated and treated
at 6 weeks postpartum.
Pregnant patients with invasive carcinoma of the
cervix may choose early termination or choose to continue the pregnancy. Those who have a mature fetus at the
time of diagnosis also may wish to delay treatment. If the
patient opts to continue the pregnancy, predelivery
assessment of fetal lung maturity by amniotic fluid analysis should be strongly considered, taking into account the
availability of neonatal support to optimize fetal outcome
and to avoid the potentially severe complications of prematurity, both in the neonatal period and in long-term
development (5154). Even those patients with earlystage disease should be aware that delaying treatment
carries an undefined, but likely small, risk of disease progression. However, delaying treatment to optimize fetal
maturity provides a major, quantifiable benefit for the
infant. All of the studies reporting outcome when treatment is intentionally delayed to optimize fetal outcome
suggest no measurable increased maternal risk (49). The
studies included 77 patients with early-stage cervical cancers who opted to delay treatment for 140 weeks. The
recurrence rate was 5% (4 of 77), which is similar to that
in nonpregnant patients.
1204
Abnormal cervical cytology

Colposcopy
Directed biopsy
No endocervical curettage
Cervical intraepithelial neoplasia
Microinvasive
squamous
carcinoma
Invasive carcinoma
Malignant
cytology
suggesting
invasion
Diagnostic
conization or
wedge biopsy
of cervix
Appropriate
therapy
Abnormal
cytology
without
suggesting
invasion
Papanicolaou test
and colposcopy
every 8 weeks
Microinvasion
3 mm
Anticipate vaginal delivery
Invasive
carcinoma
Figure 1. Evaluation of the

patient with abnormal cytology
during pregnancy. (Hannigan
EV. Cervical cancer in pregnancy.
Clin Obstet Gynecol 1990;33:
837845)
Appropriate
therapy
Reevaluate 6 weeks postpartum
The mode of delivery for those patients who choose

to delay treatment to allow fetal maturation remains controversial. Patients with small-volume, early-stage
lesions may be candidates for vaginal delivery. Whether
vaginal delivery promotes disease progression is not
clear. If possible, the patient should give birth by cesarean delivery at the time of planned radical surgery, and
vaginal delivery should be reserved for those patients
with preinvasive disease or stage Ia invasive disease with
planned postpartum fertility-sparing therapy. Intuitively,
it is prudent not to attempt vaginal delivery of women
with large or friable tumors, given the risk of obstructing
the progress of labor or the risk of bleeding with potentially life-threatening hemorrhage that might require
emergency hysterectomy under less than optimal circumstances.
The available literature includes reports of 10 cases
of implantation of malignancy at the episiotomy site
(5557). Posttreatment follow-up should include inspection and palpation of the episiotomy site. Treatment of
recurrent disease in the episiotomy consists of excision
followed by radiation.
For early-stage cervical cancer during pregnancy,
radical surgery and radiation therapy offer similar cure
rates. Radical hysterectomy with lymphadenectomy for
stage Ia2 to IIa cervical cancer during pregnancy has
demonstrated low associated morbidity, high survival
rates, and an opportunity for preservation of ovarian function (49). Gestational edema and more pronounced cleavage planes facilitate the dissection.
When radical cesarean hysterectomy is performed, a
classical uterine incision is preferred. Bilateral ovariopexy is a reasonable consideration at the time of surgery
in the event that adjuvant radiation might be indicated
for patients with high-risk histopathologic features.
Results of a casecontrol study comparing radical
surgery outcomes in pregnant and nonpregnant patients
demonstrated a higher blood loss in pregnant patients,
but this did not translate into a significant increase in
blood transfusion, operative morbidity, or major complication rates (58). Survival was 97% in the pregnant
patients and 90% in the controls, with mean follow-up
over 140 months.
Most pregnant patients who are candidates for radical surgery will benefit from surgery rather than radiation therapy, given the advantage of ovarian preservation
and the avoidance of radiation-associated vaginal fibrosis. Pregnant patients with stage IIb or more advanced
invasive cervical cancer and patients either not medically fit or not interested in primary surgical treatment
should undergo definitive radiation therapy. Patients
with advanced disease who elect to delay treatment
should have documented fetal pulmonary maturity prior
to classic cesarean delivery and should start their radia-
PRACTICE BULLETINS
The following recommendations are based primarily on expert opinion and consensus (Level
C):
Following treatment for cervical carcinoma, patients

should be monitored regularly, for example, with
thrice-yearly follow-up examinations for the first 2
years and twice-yearly visits subsequently to year 5,
with Pap tests annually and chest X-rays annually
for up to 5 years.
tion therapy postdelivery following uterine involution.

Pelvic and paraaortic lymph node dissection can be performed at the time of cesarean delivery to aid treatment
planning.
Planning radiation treatment for pregnant patients
with cervical cancer requires careful adaptation to adjust
for the anatomic distortion created by the gravid state.
Patients opting for primary radiation therapy with the
intent of pregnancy termination should begin with external-beam therapy. It is common for the pregnancy to
abort spontaneously when the woman is irradiated with
less than 4,000 cGy of external-beam radiation. In one
series, however, 27% of 45 patients did not abort and
required subsequent surgical uterine evacuation (58).
1205
Treatment for pregnant patients with invasive carcinoma of the cervix should be individualized on the
basis of evaluation of maternal and fetal risks.
References
Summary
For stage Ib and selected IIa carcinomas of the

cervix, either radical hysterectomy and lymph node
dissection or radiation therapy with cisplatin-based
chemotherapy should be considered. Adjuvant radiation therapy may be required in those treated surgically, based on pathologic risk factors, especially in
those with stage Ib2 carcinoma.
Stage IIb and greater should be treated with external-beam and brachytherapy radiation and concurrent cisplatin-based chemotherapy.
For stage Ia1 microinvasive squamous carcinoma of

the cervix, treatment with conization of the cervix or
simple extrafascial hysterectomy may be considered.
Stage Ia2 invasive squamous carcinoma of the

cervix should be treated with radical hysterectomy
with lymph node dissection or radiation therapy,
depending on clinical circumstances.
Stage Ib1 should be distinguished from stage Ib2

carcinoma of the cervix because the distinction predicts nodal involvement and overall survival and
may, therefore, affect treatment and outcome.
Patients with squamous cell cancers and those with

adenocarcinomas should be managed similarly,
except for those with microinvasive disease. Criteria
for microinvasive adenocarcinomas have not been
established.
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29:916 (Level II-3)
13. Grigsby PW. Primary radiotherapy for stage IB or IIA cervical cancer. J Natl Cancer Inst Monogr 1996;(21):6164
(Level III)
14. Finan MA, DeCesare S, Fiorica JV, Chambers R,
Hoffman MS, Kline RC, et al. Radical hysterectomy for
stage IB1 vs IB2 carcinoma of the cervix: does the new
staging system predict morbidity and survival? Gynecol
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15. Cosin JA, Fowler JM, Chen MD, Paley PJ, Carson LF,
Twiggs LB. Pretreatment surgical staging of patients with
cervical carcinoma: the case for lymph node debulking.
Cancer 1998;82:22412248 (Level II-2)
16. Goff BA, Muntz HG, Paley PJ, Tamimi HK, Koh WJ,
Greer BE. Impact of surgical staging in women with
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436442 (Level II-3)
17. Mestwerdt G. Probeexzision und Kolposkopie Frhdiagnose des Portiokarzinoms. Zentralb Gynaekol. 1947;69:
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alternative to radical hysterectomy for patients with stage

IA-B carcinoma of the cervix? Cancer 1999;86:
22732279 (Level II-2)
25. Dargent D, Martin X, Sacchetoni A, Mathevet P.
Laparoscopic vaginal radical trachelectomy: a treatment
to preserve the fertility of cervical carcinoma patients.
Cancer 2000;88:18771882 (Level II-3)
26. Averette HE, Method MW, Sevin B-U, Penalver MA.
Radical abdominal hysterectomy in the primary management of invasive cervical cancer. In: Rubin SC, Hoskins
WJ, eds. Cervical cancer and preinvasive neoplasia.
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27. Landoni F, Maneo A, Colombo A, Placa F, Milani R,
Perego P, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet
1997;350:535540 (Level I)
28. Koh WJ, Panwala K, Greer B. Adjuvant therapy for highrisk, early stage cervical cancer. Semin Radiat Oncol
2000;10:5160 (Level III)
29. Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk
BJ, Berek JS, et al. Concurrent chemotherapy and pelvic
radiation therapy compared with pelvic radiation therapy
alone as adjuvant therapy after radical surgery in high-risk
early-stage cancer of the cervix. J Clin Oncol 2000;
18:16061613 (Level I)
30. Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach
LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with
stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: a Gynecologic
Oncology Study Group Study. Gynecol Oncol 1999;73:
177183 (Level I)
18. Burghardt E, Holzer E. Diagnosis and treatment of

microinvasive carcinoma of the cervix uteri. Obstet
31. Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C,

Stevens RE, et al. Pelvic radiation with concurrent
chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med
1999;340:11371143 (Level I)
19. Greer BE, Figge DC, Timimi HK, Cain JC, Lee RB. Stage
IA2 squamous carcinoma of the cervix: difficult diagnosis
and therapeutic dilemma. Am J Obstet Gynecol
1990;162:14061409; discussion 14091411 (Level III)
32. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G,
Maiman MA, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999;340:11441153 (Level I)
20. Kolstad P. Follow-up study of 232 patients with stage

[Ia1] and 411 patients with stage Ia2 squamous cell carcinoma of the cervix (microinvasive carcinoma). Gynecol
Oncol 1989;33:265272 (Level III)
33. Keys HM, Bundy BN, Stehman FB, Muderspach LI,

Chafe WE, Suggs CL 3rd, et al. Cisplatin, radiation, and
adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.
21. Morgan PR, Anderson MC, Buckley CH, Murdoch JB,

Lopes A, Duncan ID, et al. The Royal College of
Obstetricians and Gynaecologists micro-invasive carcinoma of the cervix study: preliminary results. Br J Obstet
22. Benedet JL, Anderson GH. Stage IA carcinoma of the
cervix revisited. Obstet Gynecol 1996;87:10521059
(Level III)
23. Sevin BU, Nadji M, Averette HE, Hilsenbeck S, Smith D,
Lampe B. Microinvasive carcinoma of the cervix. Cancer
1992;70:21212128 (Level III)
24. Covens A, Shaw P, Murphy J, DePetrillo D, Lickrish G,
Laframboise S, et al. Is radical trachelectomy a safe
34. Whitney CW, Sause W, Bundy BN, Malfetano JH,

Hannigan EV, Fowler WC Jr, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an
adjunct to radiation therapy in stage IIB-IVA carcinoma of
the cervix with negative para-aortic lymph nodes: a
Gynecologic Oncology Group and Southwest Oncology
Group Study. J Clin Oncol 1999;17:13391348 (Level I)
35. National Cancer Institute. PDQ treatment summary for
health professionals. Cervical cancer. Bethesda, Maryland: National Institutes of Health, 2002. Available at
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=pdq&TYPE=search&SFMT=pdq_statement/1/0/0&Z20
8=208_00103H. Retrieved January 8, 2002 (Level III)
PRACTICE BULLETINS
36. Thomas GM. Improved treatment for cervical cancer

concurrent chemotherapy and radiotherapy. N Engl J Med
1999;340:11981200 (Level III)
37. Look KY, Brunetto VL, Clarke-Pearson DL, Averette HE,
Major FJ, Alvarez RD, et al. An analysis of cell type in
patients with surgically staged stage IB carcinoma of the
cervix: a Gynecologic Oncology Group study. Gynecol
Oncol 1996;63:304311 (Level II-3)
38. Eifel PJ, Burke TW, Morris M, Smith TL. Adenocarcinoma as an independent risk factor for disease recurrence in patients with stage IB cervical carcinoma.
Gynecol Oncol 1995;59:3844 (Level II-3)
39. Burke TW, Hoskins WJ, Heller PB, Shen MC, Weiser EB,
Park RC. Clinical patterns of tumor recurrence after radical hysterectomy in stage IB cervical carcinoma. Obstet
40. Adcock LL, Potish RA, Julian TM, Okagaki T, Prem KA,
Twiggs LB, et al. Carcinoma of the cervix, FIGO Stage
IB: treatment failures. Gynecol Oncol 1984;18:218225
(Level II-3)
41. Naumann RW, Shingleton HM. Posttreatment surveillance and patterns of recurrence. In: Rubin SC, Hoskins
WJ, eds. Cervical cancer and preinvasive neoplasia.
Philadelphia: LippincottRaven Publishers, 1996:361
369 (Level III)
42. Koh WJ, Paley PJ, Comsia ND, Greer BE. Radical management of recurrent cervical cancer. In: Eifel PJ,
Levenback C, eds. American Cancer Society atlas of clinical oncology: neoplasms of the female genital tract.
Hamilton, Ontario: BC Decker; 2001 (Level III)
1207
48. Zemlickis D, Lishner M, Degendorfer P, Panzarella T,

Sutcliffe SB, Koren G. Maternal and fetal outcome after
invasive cervical cancer in pregnancy. J Clin Oncol
1991;9:19561961 (Level II-2)
49. Goff BA, Paley PJ, Koh WJ, Petersdorf SH, Douglas JG,
Greer BE. Cancer in the pregnant patient. In: Hoskins WJ,
Perez CA, Young RC, eds. Principles and practice of gynecologic oncology. Philadelphia: Lippincott Williams &
Wilkins, 2000:501528 (Level III)
50. Hannigan EV. Cervical cancer in pregnancy. Clin Obstet
51. Greer BE, Easterling TR, McLennan DA, Benedetti TJ,
Cain JM, Figge DC, et al. Fetal and maternal considerations in the management of Stage I-B cervical cancer during pregnancy. Gynecol Oncol 1989;34:6165 (Level III)
52. Vohr BR, Garcia Coll CT. Neurodevelopmental and school
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(Level II-2)
53. Papile LA, Munsick-Bruno G, Schaefer A. Relationship
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54. Halsey CL, Collin MF, Anderson CL. Extremely low birth
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performance. Pediatrics 1993;91:807811 (Level II-2)
55. Cliby WA, Dodson MK, Podratz KC. Cervical cancer
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following vaginal delivery. Obstet Gynecol 1994;84:
179182 (Level III)
43. Bodurka-Bevers D, Morris M, Eifel PJ, Levenback C,

Bevers MW, Lucas KR, et al. Posttherapy surveillance of
women with cervical cancer: an outcomes analysis.
Gynecol Oncol 2000;78:187193 (Level II-3)
56. Copeland LJ, Saul PB, Sneige N. Cervical adenocarcinoma: tumor implantation in the episiotomy sites of two
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44. Donegan WL. Cancer and pregnancy. CA Cancer J Clin

1983;33:194214. Review (Level III)
57. Gordon AN, Jensen R, Jones HW 3rd. Squamous carcinoma of the cervix complicating pregnancy: recurrence
in episiotomy after vaginal delivery. Obstet Gynecol 1989;
73:850852 (Level III)
45. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin 1998;48:629 (Level II-3)
46. Hopkins MP, Morley GW. The prognosis and management of cervical cancer associated with pregnancy. Obstet
47. Monk BJ, Montz FJ. Invasive cervical cancer complicating intrauterine pregnancy: treatment with radical hysterectomy. Obstet Gynecol 1992;80:199203 (Level III)
58. Sood AK, Sorosky JI, Krogman S, Anderson B, Benda J,

Buller RE. Surgical management of cervical cancer complicating pregnancy: a case-control study. Gynecol Oncol
1996;63:294298 (Level II-2)
1208

to conduct a literature search to locate relevant articles published between January 1985 and December 2000. Priority
was given to articles reporting results of original research,
although review articles and commentaries also were consulted. Abstracts of research presented at symposia and
scientific conferences were not considered adequate for inclusion in this document. Guidelines published by organizations or institutions such as the National Institutes of
Force:
I
type of evidence.
committees.
transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior
Danvers, MA 01923, (978) 750-8400.
ISSN 1099-3630
Diagnosis and treatment of cervical carcinomas. ACOG Practice
Obstet Gynecol 2002;99:855-867
PRACTICE BULLETINS
1209
ACOG
PRACTICE
BULLETIN
Selective Estrogen
Receptor Modulators
Practice BulletinsGynecology
with the assistance of Steven R.
Goldstein, MD. The information
making decisions about appropriate obstetric and gynecologic care.
construed as dictating an exclusive course of treatment or procedure. Variations in practice may be
warranted based on the needs of
the individual patient, resources,
and limitations unique to the institution or type of practice.
Reaffirmed 2008
Selective estrogen receptor modulators (SERMs) are synthetic compounds that

bind estrogen receptors and produce agonistic activity in some tissues while
acting as estrogen antagonists in other tissues. Although referred to collectively, their effects in different organs (eg, endometrium, urinary tract) are far from
uniform. Much confusion exists about the indications for their use and the
effects of these compounds. The purpose of this document is to review the use
of SERMs for breast cancer risk reduction and skeletal protection as approved
by the U.S. Food and Drug Administration (FDA).
Background
A number of compounds that exhibit the properties of SERMs are either in clinical use or are in development. Four SERMs are approved for use in the United
States: 1) clomiphene, 2) tamoxifen, 3) toremifene, and 4) raloxifene. Clomiphene,
tamoxifen, and toremifene belong to the triphenylethylene family of SERMs,
whereas raloxifene is a benzothiophene.
Clomiphene is among the most widely prescribed drugs for the management of infertility in women (1). Tamoxifen, originally developed as a medical
therapy for the treatment of breast cancer, was found to have estrogenic activity on bone remodeling and in cholesterol metabolism. It also was found to have
estrogenic activity in the endometrium, resulting in an increase in the relative
risk of benign and malignant neoplasms. Tamoxifen has been approved by the
FDA for the treatment of breast cancer and to reduce the incidence of breast
cancer in healthy women at high risk of breast cancer. More studies comparing
tamoxifen with raloxifene for breast cancer prevention currently are underway.
Toremifene also is indicated for the treatment of estrogen-receptor-positive
breast cancer in postmenopausal women.
Raloxifene is approved for the prevention and treatment of osteoporosis in
postmenopausal women. In clinical trials for the treatment of osteoporosis,
1210
raloxifene was associated with a significant reduction in

new-onset cases of breast cancer when measured as a
secondary endpoint in low-risk women. Based on preclinical studies, raloxifene appears to be a pure estrogen
antagonist in the uterus. Short-term clinical studies in
small series of patients have not shown a stimulatory
effect on the uterus.
Tibolone has not yet received FDA approval.
However, it has been used in Europe for approximately
20 years for the treatment of menopausal symptoms and
the prevention of osteoporosis (2).
Other SERMs (idoxifene, droloxifene, and levormeloxifene) have shown adverse gynecologic, gastrointestinal, and genitourinary effects that resulted in the
suspension of phase three trials. Specifically, these
effects included uterine changes detected by ultrasonography that gave the impression of thickening of the
endometrium as well as an increased incidence of uterovaginal prolapse, urinary incontinence, and leukorrhea
(3, 4).
Bisphosphonates act as specific inhibitors of osteoclast mediated bone resorption. These agents reduce bone
turnover by reducing the number of sights at which bones
are remodeled. Thus, bone formation exceeds bone
resorption at these remodeling sights leading to progressive gains in bone mass.
Physiologic Effects
Bone Metabolism
Bone remodeling is a continuous process that involves
both resorption and formation. During menopause, bone
loss accelerates in women, leading to an increased risk
for osteoporosis. As antiresorptive agents, SERMs
decrease bone tissue resorption by osteoclasts and thereby inhibit bone loss. Rigorous clinical trial data on the
effects of SERMs on bone metabolism are limited primarily to raloxifene, although there also have been some
studies published about other SERMs. Clomiphene has
been shown to have some estrogen-agonist effects on
bone in ovariectomized rat models, but there is only limited clinical evidence for skeletal antiresorptive effects of
clomiphene (1). Studies of tamoxifen use in premenopausal women indicate that after initiation of therapy
there may be loss in bone mineral density for 3 years,
which stabilizes after this period (5). Studies in postmenopausal women taking tamoxifen for breast cancer
prevention demonstrated increases in bone mineral density of 12% per year (5). Similar results have been
observed in postmenopausal women taking tamoxifen to
treat breast cancer (6).
Breast Cancer Risk Reduction

One of the mechanisms of action of SERMs for breast
cancer risk reduction is mediated by competitive inhibition of estrogen binding to estrogen receptors. The rationale for the use of SERMs for breast cancer risk reduction
comes from clinical trials in breast cancer patients that
indicated tamoxifen reduced the incidence of contralateral breast cancer in women with invasive disease (7).
These results provided the rationale for testing the efficacy of tamoxifen in preventing breast cancer in women at
high risk for the disease.
Cardiovascular Effects
A number of intermediate markers of cardiovascular disease are altered favorably by raloxifene and tamoxifen,
while others show little change. Both agents have been
shown to reduce serum levels of total cholesterol and
low-density lipoproteins while having no effects on highdensity lipoproteins or triglycerides in postmenopausal
women (811). Raloxifene and tamoxifen significantly
decrease lipoprotein(a) levels (12, 13). Fibrinogen levels
are reduced with both tamoxifen and raloxifene therapy
(9, 10). Both raloxifene and tamoxifen also significantly
decrease serum concentrations of homocysteine (1417).
Raloxifene therapy is not associated with an increase in
C-reactive protein, whereas this marker was reduced significantly with tamoxifen (16, 18). The effect of raloxifene on plasminogen-activator inhibitor is neutral,
whereas tamoxifen therapy has been associated with
decreases in this marker (13, 16).
Although the effect on most surrogate markers for
cardiovascular disease usually is favorable or neutral
with the use of either raloxifene or tamoxifen, it is
unclear whether either compound will have an effect on
clinical outcomes of cardiovascular disease. In the
Multiple Outcomes of Raloxifene Evaluation (MORE)
trial, raloxifene therapy for 4 years was not associated
with a reduced risk for cardiovascular events in the
overall population (19). However, in a subpopulation of
1,035 women at increased risk for cardiovascular events,
raloxifene was associated with a statistically significant
40% reduction in the risk for cardiovascular events (19).
Neither raloxifene nor tamoxifen appears to be associated with an early increased risk for cardiovascular events
in randomized clinical trials of postmenopausal women
who have osteoporosis or are at increased risk for breast
cancer, respectively (19, 20).
Little data are available on the cardiovascular effects
of other SERMs. In comparative studies, the effects of
toremifene on lipid profiles have been comparable with
tamoxifen (21, 22). Likewise, droloxifene appears to
have a profile similar to tamoxifen (2325).
PRACTICE BULLETINS
Endometrial and Uterine Effects

In clinical trials of up to 3 years duration, raloxifene did
not cause increases in endometrial thickness or increase
the incidence of vaginal bleeding, endometrial hyperplasia, or uterine cancer (2628). In the MORE trial, fluid
in the endometrial cavity (observed by transvaginal
ultrasonography) was present in more women assigned
to raloxifene than those assigned to placebo. The clinical
significance of this finding is unknown. In contrast,
tamoxifen has been associated with endometrial thickening, endometrial polyps (29), endometrial cystic atrophy
(3032), endometrial hyperplasia (29, 33), a twofold to
fourfold increased risk for endometrial cancer in randomized, controlled clinical trials, and a small but
increased risk of uterine sarcoma (4, 34, 35). The uterine
effects of toremifene are not as well studied as those of
tamoxifen. The rates of vaginal bleeding and vaginal discharge are similar in randomized trials directly comparing tamoxifen and toremifene (36, 37). However, benign
uterine effects were less common with toremifene, and
to date it has not been associated with endometrial
hyperplasia or cancer. Levormeloxifene, idoxifene, and
droloxifene also have been associated with increased
endometrial thickness (3, 4).
Thromboembolic Events
Both raloxifene and tamoxifen are associated with an
increased risk for venous thromboembolism. In one
study, the relative risk of deep vein thrombosis or pulmonary embolism was 3.1 (95% confidence interval
[CI], 1.56.2) for women taking raloxifene, as compared
with placebo (38). The magnitude of this increased risk
is similar to that observed with tamoxifen (20). The risk
for venous thromboembolism with other SERMs is
unknown because of the small size of the clinical trials
and the rare nature of this event.
Genital Tract
nal atrophy, including vaginitis, leukorrhea, or dyspareunia (26).
Pelvic Floor Relaxation

Neither tamoxifen nor raloxifene has been associated
with pelvic floor relaxation. In a posthoc analysis based
on approximately 7,000 postmenopausal women who
had an intact uterus when they entered the study, 3 years
of raloxifene therapy was associated with a significant
reduction in the risk for pelvic floor surgery (50%) (41).
The mechanism by which SERMs might affect pelvic
floor relaxation is not clear. The presence of estrogen
receptors in pelvic floor tissues indicates this region is a
target for estrogen and may respond to SERMs. Similar
to their known effects on collagen metabolism in bone
tissue, SERMs also may affect tissue remodeling in the
pelvic floor.
Vasomotor Symptoms
In an integrated analysis of five randomized, placebocontrolled trials, younger, healthy postmenopausal
women receiving raloxifene had a significantly higher
incidence of hot flashes (25%) than those receiving
placebo (18%), but the trial excluded women with severe
vasomotor symptoms (26). However, there was no therapy difference for the severity of hot flashes or for the
discontinuation of therapy because of hot flashes. The
increased incidence of hot flashes in the raloxifene-treated group was observed only during the first 6 months of
therapy. In older, postmenopausal women with osteoporosis, the overall incidence of hot flashes was lower
but still significantly different between raloxifene (9.7%)
and placebo (6.4%) (38). A higher incidence of hot
flashes also has been associated with tamoxifen. Of
postmenopausal women taking tamoxifen, 16% sought
treatment for vasomotor symptoms (42). Extremely
bothersome hot flashes also were more common in the
tamoxifen-treated group of the NSABP Breast Cancer
Prevention Trial (NSABP P-1 trial) (20). Hot flashes also
have been associated with toremifene, idoxifene, and
droloxifene therapy (4345).

Recommendations
Several studies suggest tamoxifen has estrogenic effects

on the vagina. In a study comparing postmenopausal
women who had breast cancer with fit, age-matched controls, the vaginal pH in the tamoxifen-treated group was
significantly lower and was comparable with the pH levels in fertile women. Two thirds of tamoxifen-treated
women had well-estrogenized vaginal smears, compared
with none in the control group (39). In the National
Surgical Adjuvant Breast and Bowel Project (NSABP)
that studied cancer prevention, tamoxifen was associated
with an increase in vaginal discharge (20), as was
droloxifene (40). Although the effects of raloxifene on
the vaginal mucosa have not been studied directly, raloxifene has not been associated with events related to vagi-
1211
Are SERMs effective in reducing the risk of

breast cancer?
Tamoxifen is approved by the FDA for breast cancer risk

reduction on the basis of the results of the NSABP P-1
trial, in which it reduced the risk of both invasive and
1212
noninvasive breast cancer by approximately 50% (20,

46). The effects were primarily caused by a reduction in
the risk for estrogen-receptor-positive breast cancer. Two
other European trials failed to show similar efficacy (47,
48). These studies had smaller sample sizes, shorter follow-up, and allowed concomitant treatment with estrogen
replacement therapy or hormone replacement therapy.
Raloxifene also acts as an estrogen antagonist in
breast tissue. In the MORE trial, 4 years of raloxifene
therapy was associated with a 72% reduction in the risk
of invasive breast cancer (49). Similar to tamoxifen, the
risk reduction was attributable to a 90% reduction in the
risk of estrogen-receptor-positive breast cancer, with no
apparent decrease in the risk of estrogen-receptor-negative breast cancer.
Who are appropriate candidates for SERMs?
Nonmodifiable
Potentially Modifiable
Personal history of
fracture as an adult
Current cigarette smoking
History of fracture in
first-degree relative
Low body weight (<127 lb)
Caucasian race
Estrogen deficiency:
Early menopause (age <45 years) or bilateral ovariectomy
Prolonged premenopausal amenorrhea
(>1 year)
Advanced age
Low calcium intake
Female sex
Alcoholism
Dementia
Impaired eyesight despite adequate

correction
Poor health or frailty
Recurrent falls
Inadequate physical activity

Poor health or frailty
Reprinted with permission from Physicians guide to prevention and treatment of
osteoporosis. 1999, National Osteoporosis Foundation, Washington, DC 20037
Is raloxifene appropriate for breast cancer

patients who have completed a 5-year course
of tamoxifen?
No studies have investigated the use of raloxifene after a

5-year course of tamoxifen. Women previously treated
with tamoxifen may begin to lose bone mineral density
when they complete their course of therapy. Their status
and relative risk for osteoporosis should be evaluated and
choices for prevention or therapy made accordingly.
Because of the increase in thromboembolic events and

uterine malignancy seen in women older than 50 years
using tamoxifen, a delicate riskbenefit balance exists.
This issue appears to be of less concern for women
younger than 50 years because the NSABP P-1 trial did
not show any increase in uterine malignancy or thromboembolic events in this group. To warrant tamoxifen
therapy, women should be at high risk of developing
breast cancer (50). Those at high risk include women
with ductal carcinoma in situ and lobular carcinoma in
situ who do not choose surgical therapy, women with
ductal hyperplasia with atypia, and women with a high
risk on the basis of personal and family history. Chemoprophylaxis has been suggested for women at high risk of
developing breast cancer (46, 50).
Raloxifene is approved by the FDA for the prevention and treatment of osteoporosis. The National Osteoporosis Foundation recommends treatment for all women
in whom dual-energy X-ray absorptiometry elicits a T
score of 2 or, for those who have other risk factors, a T
score less than 1.5 (51). Significant risk factors are summarized in Table 1. Other appropriate candidates to consider for preventive therapy include postmenopausal
women who are currently taking hormone replacement
therapy for osteoporosis prevention but would like to
discontinue using it because of symptoms or fears associated with the use of hormone replacement therapy,
including breast tenderness, vaginal bleeding, and fear of
breast or uterine cancer. Raloxifene also is appropriate
for the prevention and treatment of osteoporosis in
women who have a family history of breast or endometrial cancer. Raloxifene is contraindicated in pregnant
women or those who may become pregnant and in
women with a current or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis.
Table 1. Risk Factors for Osteoporosis
Are SERMs effective in reducing bone loss?
In premenopausal women, tamoxifen may cause decreases in bone mineral density for 3 years after initiation of
therapy, which stabilizes after this period (5). Several
large, randomized clinical trials of raloxifene for the prevention and treatment of osteoporosis in postmenopausal
women have been published (8, 38, 5254). Increases in
bone mineral density of approximately 23% more than
placebo have been demonstrated for the spine and total
hip. Histomorphometry and bone turnover assessments
have been performed for women taking tamoxifen and
raloxifene, and both confirm the estrogenic actions of
these agents on bone tissue. Both raloxifene and tamoxifen reduce biochemical indices of bone turnover by
2050% (6, 8, 38, 55, 56). Histomorphometry studies
indicate bone morphology is normal in women receiving
raloxifene (57, 58).
PRACTICE BULLETINS
In patients using SERMs, are there beneficial

effects on vaginal dryness and hot flashes
with the addition of estrogen?
In patients using SERMs, are there benefits

with the addition of bisphosphonates?
Although the average increase in bone mineral density

with raloxifene in the first 24 months is 23%, some individuals actually lose bone mineral density. This also is
true of other antiresorptive agents. The addition of alendronate to raloxifene therapy significantly enhances the
antiresorptive efficacy beyond that of either agent independently (59, 60). The effect on actual fracture rates and
the long-term safety of such combinations of antiresorptive agents remain unknown.
How should women taking raloxifene be evaluated?
In terms of osteoporosis treatment, efficacy often is monitored with surrogate markers of clinical outcomes.
Because baseline bone mineral density is clearly predictive of future fracture risk, changes in bone mineral density in response to antiresorptive therapy traditionally
have been used as a surrogate marker of efficacy in terms
of osteoporosis. However, most antiresorptive agents are
associated with similar fracture risk reduction despite
wide variations in the magnitude of their bone mineral
density response (38, 6163). Effective treatments for
osteoporosis should not be discontinued or changed
because of early, treatment-associated decreases in bone
mineral density, especially because frequent bone mineral density monitoring may be misleading (64). Therefore,
although bone mineral density has been used in most
clinical studies to monitor the efficacy of treatment, the
frequency of bone mineral density testing for the screening and monitoring of therapy has not been standardized.
Based on limited studies, raloxifene does not appear
to induce proliferation, hyperplasia, or malignancy of the
endometrium (8, 28) nor does it cause polyps, as does
tamoxifen (65). Routine gynecologic care according to
established clinical principles seems to be appropriate for
patients taking raloxifene or tamoxifen. Specific or
heightened uterine surveillance is not routinely required
for patients taking SERMS. Vaginal bleeding should be
investigated. Nongynecologic surveillance (eg, lipid profiles, dual-energy X-ray absorptiometry, mammography)
should be based on individual patient history as well as
the established guidelines for those procedures.
With tamoxifen, many patients experience vaginal dryness. However, in the NSABP P-1 trial, 29% of patients
had leukorrhea described as moderately bothersome or
worse (20). No clinical trials adding vaginal estrogen to
systemic tamoxifen have been performed; therefore, efficacy and toxicity of this approach has not been evaluated.
Raloxifene does not differ from placebo with respect
to its association with vaginal dryness (26). Still, the lack
of a positive effect of raloxifene on urogenital atrophy
will cause many sexually active women to experience
vaginal discomfort. The addition of local estrogen therapy may improve such symptoms.
Twenty-five percent of younger postmenopausal
women taking raloxifene experienced hot flashes at some
point during the original clinical trials although only
1.7% discontinued therapy as a result (26). In the MORE
trial, a group of older women with osteoporosis experienced a 10.6% incidence of hot flashes (38). In the
NSABP P-1 trial, 68% of the women taking tamoxifen
reported hot flashes that were moderately bothersome or
worse, compared with 49% in the placebo group (20).
No published trials have studied the combination of
systemic estrogen and SERMs to reduce vasomotor
symptoms. Because the two compounds compete for the
same receptors, the effect of such co-administration on
other organ systems is unknown.
The MORE trial examined the effect of raloxifene on

fracture risk reduction in 7,705 postmenopausal women
with osteoporosis. This study demonstrated a significant
risk reduction of 3050% for vertebral fracture among
women treated for 3 years (38). In the NSABP P-1 trial,
tamoxifen was associated with a nonsignificant decrease
in the incidence of hip, vertebral, and Colles fractures
(20). However, tamoxifen has not been evaluated
prospectively in women with osteoporosis, and its effects
in the bone remain to be established.
1213
Does tamoxifen increase the risk of uterine

cancer?
Before the NSABP P-1 trial, only women who had breast
cancer were treated with tamoxifen. The NSABP P-1
trial showed a 50% reduction in preinvasive and invasive
breast cancer in women with a high risk of breast cancer
(20). An increase in endometrial cancer also was reported in these women. The overall relative risk of endometrial cancer with tamoxifen was 2.53 (95% CI,
1.354.97). In women older than 50 years, the relative
risk increased to 4.01 (95% CI, 1.7010.90), while in
women younger than 50 years, there was no statistically
significant difference (20). An increased risk of uterine
sarcoma has been observed in women taking tamoxifen
(35). This effect is small and similar to that of estrogen.
New data suggest it may be possible to identify
breast cancer patients at high and low risk for developing
atypical hyperplasia with tamoxifen therapy on the basis
of the presence or absence of benign endometrial polyps
1214
before beginning tamoxifen therapy (65). Among women

taking tamoxifen for up to 5 years, those who had polyps
that were removed before initiation of tamoxifen therapy
had an incidence of atypical hyperplasia 18 times greater
than those who had uterine cavities that were without
lesion (11.7% versus 0.7%).
The risk of endometrial cancer does not appear to
increase with raloxifene use. In a group of women with
osteoporosis receiving raloxifene, the relative risk of
endometrial carcinoma was 0.8 over a 3-year period of
follow-up (95% CI, 0.212.67) (25).
How should the risk of breast cancer be

assessed?
A womans decisions relating to her breast health

whether a program of intensive surveillance with mammography and ultrasonography, chemopreventive agents,
or possibly even prophylactic mastectomydepend on
her awareness of the medical options, her own personal
preferences, and, importantly, an individualized estimate
of the probability of her developing breast cancer over a
defined period. Such an estimate also is useful for
designing prevention trials in high-risk subsets of the
population. Such prevention trials differ from therapeutic
clinical trials because they expose asymptomatic, healthy
women to potentially toxic interventions for prolonged
periods to reduce their risk of developing breast cancer.
Risk estimates for various individual risk factors are
available (Table 2), but risk estimates for combinations of
risk factors (eg, the Gail model) (66) are clearly preferable. The usefulness of the Gail model is limited in
patients with second-degree relatives with breast cancer
(eg, paternal transmission) and is falsely increased in
patients with multiple breast biopsies.
Table 2. Factors That Increase the Relative Risk for Breast

Cancer in Women
Relative Risk
Factor
Relative risk >4
Certain inherited genetic mutations for breast

cancer
Two or more first-degree relatives with breast
cancer diagnosed at an early age
Personal history of breast cancer
Age (65 years vs <65 years, although risk
increases across all ages until age 80 years)
Relative risk 2.14
Nodular densities on mammogram (>75% of

breast volume)
Atypical hyperplasia
High-dose ionizing radiation to the chest
Ovaries not surgically removed (age <40 years)
Relative risk 1.12
Northern U.S. residence

Reproductive factors Early menarche (age <12 years)
Late menopause (age 55 years)
No term pregnancies (for breast cancer diagnosed at age 40 years)
Late age at first term pregnancy (30 years)
Never breastfed a child
Other factors
that affect
circulating
hormones
or genetic
susceptibility
Alcohol consumptio

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THE AMERICAN COLLEGE OF

OBSTETRICIANS AND GYNECOLOGISTS

The Compendium of Selected Publications CD-ROM contains all Committee Opinions,

A DOLESCENT H EALTH C ARE

Guidelines for Adolescent Health Research

Tubal Ligation with Cesarean Delivery

COMPENDIUM OF SELECTED PUBLICATIONS

Screening for TaySachs Disease

Statement on Surgical Assistants (Joint with Committee on Obstetric Practice)

COMPENDIUM OF SELECTED PUBLICATIONS

Partner Consent for Participation in Womens Reproductive Health Research

Misoprostol for Postabortion Care

O BSTETRIC P RACTICE (continued)

Induction of Labor for Vaginal Birth After Cesarean Delivery

ON PATIENT S AFETY AND

Partnering With Patients to Improve Safety

COMPENDIUM OF SELECTED PUBLICATIONS

P RACTICE B ULLETINS O BSTETRICS

P RACTICE B ULLETINS O BSTETRICS (continued)

Management of Herpes in Pregnancy

P RACTICE B ULLETINS G YNECOLOGY

Medical Management of Endometriosis

COMPENDIUM OF SELECTED PUBLICATIONS

P RACTICE B ULLETINS G YNECOLOGY (continued)

A PPENDIX C ONTENTS F ROM O THER C OLLEGE R ESOURCES

Practice Bulletins: Evidence-based guidelines developed to indicate a preferred method of diagnosis

COMPENDIUM OF SELECTED PUBLICATIONS

The Scope of Practice of

Code of Professional Ethics

COMPENDIUM OF SELECTED PUBLICATIONS

Societal responsibilities: The obstetriciangynecologist has a continuing responsibility to society as a

Physician Conduct and Practice

CODE OF PROFESSIONAL ETHICS

COMPENDIUM OF SELECTED PUBLICATIONS

The obstetriciangynecologist serving as an expert witness must accept neither disproportionate

ADOLESCENT HEALTH CARE

ADOLESCENT HEALTH CARE

The Committee wishes to thank

Guidelines for Adolescent Health

COMPENDIUM OF SELECTED PUBLICATIONS

or the participants legally authorized representative.

Four criteria set forth by 45 CFR Part 46 116(d)

COMPENDIUM OF SELECTED PUBLICATIONS

with respect to minors and review the guidelines

2. American College of Obstetricians and Gynecologists.

This document reflects emerging

Endometriosis in adolescents. ACOG

COMPENDIUM OF SELECTED PUBLICATIONS

toms decreases, the number of doctors having to be

Presentation and Characteristics

When evaluating an adolescent for suspected

apeutic laparoscopy can be initiated. An algorithm

ommended for diagnosing and treating presumed

Cyclic CHT and NSAIDs

Empiric GnRH agonist (if older than 18 years)

Endometriosis identified visually or by pathology

No endometriosisvisually and histologically negative

Gastrointestinal or urologic evaluation

Laparoscopy with resection of endometriosis

COMPENDIUM OF SELECTED PUBLICATIONS

patients in their cohort had Stage I disease (1),

of endometriosis. The goal of therapy for adolescent

progesterone acetate (0.625/2.5 mg per day) can