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Pregnancy and Asthma


Prof.Dr.Zeynep MISIRLIGL Ankara University School of Medicine Deparment of Pulmonary and Allergic Diseases

Prevalence of Asthma During Pregnancy

%3,7-8,4

Ann Epidemiol 2003;13:317

Acute Asthma During Pregnancy


At least one emergency department visit Pregnant women with acute severe asthma require hospitalization

18% 62 %

Crit Care Med 2005;33:5321

Effect of Pregnancy on Asthma


1/3 better 1/3 same 1/3 worse

%36 %41 %23

Women

with severe asthma tend to have worsening of their asthma

Juniper EF, Newhouse MT. Asthma and Immunological Diseases in Pregnancy and Early Infancy. NY, MD, 1993: 401-427

Asthma that is not adequately controlled during pregnancy can result in serious complications for both the mother and the fetus
Maternal Complications Preeclampsia Hypertension Toxemia Hyperemesis gravidorum Fetal Complications Perinatal mortality Intrauterine growth retardation Premature birth Low birth weight Neonatal hypoxia

Ann Allergy Asthma Immunol 2005;95;234-8

Acute Asthma During Pregnancy


At least one emergency department visit Pregnant women with acute severe asthma require hospitalization

18% 62 %

Crit Care Med 2005;33:5321

Maternal Asthma and Risk of Preterm Delivery

The study included women who delivered prior to the completion of 37 weeks gestation in a cohort population of 3253 pregnant women

OR:2.03; 95% Cl 1.01-4.09

Serensen et a l(2003)

Potential Mechanisms of Adverse Perinatal Outcomes in Asthma

Poor asthma control


Hypoxia Reduced uteroplacental blood flow due to hypocapnia, alkalosis, dehydration, hypertension Placental dysfanction

Asthma medications Other factors

Goals of Asthma Management in Pregnancy


Mothers should have Control of asthma symptoms Normal lung function Be able to go to work, school and exercise Avoid medication side effects Avoid attacks Deliver a healthy infant

To Achive Goals

Maternal lung function monitoring Symptoms Spirometry Peak flows Fetal monitoring Ultrasound monitoring Elektronic fetal hearts

Management of Asthma During Pregnancy


Smoking Allergen environmental control Non-immunologic triggers

Asthma and Pregnancy Choice of Medications


Human studies (when available) Animal studies (when available and


aplicable)

Drug efficacy Route of administration Duration of clinical exprience with the drug

FDA Pregnancy Categories


Category A B B C C D X Animal Studies Negative Negative Pozitive Pozitive Not done Irrelevant Irrelevant Human Studies Negative
Studies not done

Yarar/Risk Yes Yes Yes Yes Yes Yes NO

Negative
Studies not done Studies not done Studies and Rep.

Reports Pozitive
Studies and Reports Pozitive

Recommendations for pharmacologic tratment in asthma during pregnancy


Drugs

FDA Category
B B B B B B B C C C C C C

Budesonide Cromolyn Nedocromil Montelukast Zafirlukast Terbutaline Ipratropium Beclamethasone Fluticasone Albuterol Theophylline Salmeterol Formoterol

Selected Studies of Preagnancy Outcomes Associated with Theophylline Use


Investigators Stenius-Aarniala Et al.(1995) Desing Retrospevtive Cohort No.of subjects 212 exposed asthmatics 292 nonexposed 237 nonasthmatics controls Endpoints P value or OR ratio

Congenital anomalies NS Low birht weight Perinatal death Preterm delivery Preeclamsia NS NS NS NS NS NS NS NS

Shatz Et al 2004

Cohort

2123 asthmatics 273 exposed

Congenital anomolies Low birht weight Preterm delivery Preeclamsia/PIH

Perinatal project 1977 Michigan Medicold 2005

Cohort Database

55 000 Women 117 exposed 1240 exposed

Congenital anomolies NS Congenital anomalies NS

Bracken et al 2005

2379 enrolled 872 asthmatics 1333 controls 15 exposed

Low birth weigh Preterm delivery

NS

Immunol Allergy Clin N Am 2006;26:15

OR:1,1 (C1,1,1,011,1)

Long acting 2 agonist medications and Pregnancy


Investigators Desing No.of subject End Points % with event or p value
2%
8% 0%

Wilton et all 1995

Cohort

91 Salmetorol 65 exposed
1.trimester

Congenital anomolies spontaneous abortion


preterm delivery

Wilton Shakir 2002

Cohort

31 Farmoterol

Congenital anomalies spontaneous abortion

8%
10%

preterm delivery

20%

Brockenet al 2005

Cohort

2141 unexposed 112 exposed

Low birth delivery


preterm delivery

NS
20%

Immunol Allergy Clin Am 2006:26;18

Consensus Recommendations Regarding Leukotriene Antogonists During Pregnancy


Avoid Zileuton Consider montelukast or Zafirlukast for patients with recalcitrant asthma who have shown a uniquely favorable response prior to pregnancy

Consensus Recommendations Regarding Ipratropium During Pregnancy


Consider use in pregnant women presenting with acute asthma who do not improve substanstially with the first inhaled beta agonist treatment

Inhaled Corticosteroids During Pregnancy


(3 animal and 10 human studies included)

ICS associated with decreased exacerbation risk and increased FEV1 ICS no associated with congenital anomolies or perinatal outcomes Budesonide is preferred although no data indicate others are unsafe that other formulations may be continued in those who were well maintained on these agents prior to pregnancy.

RG Maureen, AAAAI, 2005

START study support the finding that treatment with low dose budesonide (400mcg) during the full course of pregnancy in individuals with mild to moderate persistent asthma had no adverse effects on the fetus or newborn Outcomes of the 313 pregnancies Analyzed
Budesonide n:196 %81 %19 Placebo n:117 %77 %23

Healthy children Adverse outcomes

Ann Allergy Asthma Immunol 2005;95:566-70

Adverse Associations with Oral Corticosteroids During Pregnancy


Oral

Clefts (3-6 fold Increased risk) Lower infant birth weight


(10 mg dally throughout pregnancy)

Preeclampsia

The Use Of Oral Corticosteroids During Pregnancy


deally, asthma would be controlled without oral corticosteroids When indicated for the management of severe asthma, risks of treatment are less than the potantial risks of severe uncontrolled asthma Maternal death Fetal death

Immunotherapy During Pregnancy


No advers effects on pregnancy outcomes Anapylaxix may a risk for mother and baby

Recommendations
Do not begin immunotherapy during pregnancy Carefully continue ongoing effective immunotherapy (avoid sistemic reactions)

Stepwise Approach for the Management of Chronic Asthma During Pregnancy


(National Asthma Education Program report of the working group on asthma during pregnancy update 2004)

Category Mild intermitant

Step Therapy
Inhaled 2 agonist as needed

Low dose inhaled corticosteroid Alternative: Cromolyn, leukotriene receptor antogonist or theophylline

Mild persistant

Moderate Persistent:

Low dose inhaled Corticosteroid and long acting agonist

Medium dose inhaled corticosteroid or (if neeeded) medium dose long acting agonist

Alternative: Low dose or (if needed) medium


dose inhaled corticosteroid and either theophylline or leukotriene receptor antagonist

Severe Persistent:

High dose inhaled corticosteroid and long acting agonist and if needed oral corticosteroid and theophylline

Alternative:High dose inhaled corticosteroid


and theophylline

Management of Acute Asthma in a Pregnant Women


Oxygen supplementation (SaO2>95%) ntravenous fluid hydration (if necessary) Inhale albuterol (every 20 mins up to three doses in the first hour) Ipratropium bromide (500g) (in severe cases) Systemic corticostreoids either intravenously or orally (in moderate/severe cases)

Obstetrical Management of Pregnant Patients With Asthma


Excellent Choice During Labor
Lumbar epidural analgesia Fentonyl (as a narcotic analgesic) Oxytocin and prostaglandin E2 supposituars (for labor induction) Pitocin, misoprostol and methylergonovine (for postportum hemorrhage)

Should be avoided Morphine Meperidine 15-methylprostaglandin F2

Asthma and Lactation


There is no effect of lactation on maternal asthma Prednisone, theophylline, antihistamines, ICS, SABAs, LABAs and cromolyn are not contrendicated. Theophylline may cause neonatal irritability, feeding difficulties.

Allergic Diseases Morbidity During Pregnancy

Allergic diseases effect 20 % of women in childbearing years Nasal symptoms occur in at least 20-30 % of pregnant women.

Pregnancy Rhinitis During Pregnancy

Allergic Rhinitis* Infectious Sinusitis Rhinitis medicamentosa Pregnancy rhinitis Eosinophilic nonallergic* rhinitis Nasal polyps* Structural nasal obstruction *History of some often precedes
pregnancy

Allergic Rhinitis During Pregnancy


15 % 34 % 45 % 6 % better worse same unknown

There was a sixfold increased risk of bacterial rhinosinusitis during pregnancy

Antihistamines
Oral and Intranasal

Tripelennamine Chlorpheniramine Loratadine Cetirisine Fexofenadine Azelastine Desloratadine Antezoline Azelastine Ketotifen Levocobastine Olopatodine Pheniramine

B B B B C C C C C C C C C

Ophtalmic Antihistamines

Medications to Treat Rhinitis During Pregnancy


Topical and oral decongestants

Phenylephrine Naphazoline Tetraphydrozolin Oxymetazoline Xylometazoline Pseudoephedrine

C C C C C C

Nasal Corticosteroids During Pregnancy


Budesonide Beklamatazon

Flutikazon
Mometazon

B C C C

Treatment of Allergic Rhinoconjunktivitis in Pregnancy

Allergen avoidance : All patients

Conjuntivitis: Optalmic cromolyn, supplemented by loratadine or cetirizine as needed

Allergic Rhinitis and Pregnacy


Intermitten rhinitis
(symtoms less than 4 days a week or for less than 4 weeks per year)

Mild:

Loratadine or cetirizine as needed

Modarate- severe
(mpairmen of sleep, daily activities, school or work or trouble some symptoms):

Intermitten intrasal budesonide, supplemented by loratadine or cetirizine as needed

Allergic Rhinitis and Pregnacy


Persistent Rhinitis
(symptoms more than 4 days per week and more than 4 weeks per year)

Mild:

Intranasal cromolyn supplemented by loratadine or cetirizine as needed

Moderate-Severe:

Regular intranasal budesonide, supplemented bye loratadine or cetirizine as needed; immunotherapy

Thank you..

Prof.Dr.Zeynep MISIRLIGL

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