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Introduction tic criteria, these percentages may be higher when diag-
nosis of a more mild form of nausea and vomiting are
The origins of “hyperemesis gravidarum” are difficult included.
to trace, as the term and the understanding of the disease
process have evolved greatly throughout medical history.
Although reports of maternal death from symptoms that Clinical Diagnosis
now appear attributed to hyperemesis date as far back as
religious documentation, historical medical literature cite According to the latest American College of Obstetri-
Antoine Dubois, a consultant surgeon and a head obste- cians and Gynecologists (ACOG) guidelines on Nausea
trician to Napoleon Bonaparte and his second wife and Vomiting during pregnancy (2015), there still is no
Empress Marie Louise, as a physician who first identified single accepted definition of hyperemesis gravidarum.
the condition in 1852. Dubois is thought to have first de- The most commonly cited criteria for diagnosis of hyper-
scribed the syndrome during his address before the emesis gravidarum include persistent vomiting not relat-
French Academy of Medicine when he spoke about the ed to other causes, an objective measure of acute starva-
finding of “pernicious vomiting of pregnancy” [1]. One tion (usually large ketonuria on urine analysis), electro-
of the first written original accounts of the term was in lyte abnormalities and acid-base disturbances, as well as
1897, when C.S. Bacon, an American physician, credited weight loss. Weight loss is often cited as at least 5% loss
the term of “hyperemesis gravidarum” and its “3-stage” of pre-pregnancy weight [4]. Serum electrolyte and acid-
classification to Dubois. This literature marks a milestone base abnormalities may include hypochloremic alkylosis,
of a change in the outlook upon this condition as a med- hypokalemia, and hyponatremia [7]. Other abnormalities
ical complication rather than a normal aspect of preg- such as mild elevation in amylase, lipase, and liver func-
nancy. After the original description, the literature of late tion enzymes are also associated with hyperemesis gravi-
19th and early 20th centuries flourished with suggestions darum [8]. Hyperemesis gravidarum may also present
of possible etiologies of disease including hypothesis such with signs and symptoms associated with severe dehydra-
as “irritation of the vomiting reflex from the stretching of tion including orthostatic hypotension, tachycardia, dry
the uterine fibers,” and “irritation of the cervix.” “Toxin- skin, mood changes, and lethargy.
emia” was named as another possibility and was interest- Recently, a classification system was created to catego-
ingly cited in association with hyperemesis gravidarum as rize hyperemesis gravidarum called the PUQE (pregnan-
well as eclampsia and “hysteria” [2, 3]. The etiology of cy-unique quantification of emesis and nausea) scoring
hyperemesis gravidarum has not been fully elucidated index. This index accounts for the daily number of vom-
and this is currently believed to reflect a multifactorial iting episodes, the length of nausea per day in hours, and
disease process. the number of retching episodes per day [9]. Clinical re-
search and medical practice have been yet to adopt a
universal system of hyperemesis gravidarum classifica-
Epidemiology tion the clinical diagnosis of exclusion, remains [4].
The lack of specific diagnostic criteria is one aspect of
The prevalence of hyperemesis gravidarum is approx- hyperemesis gravidarum, which makes it difficult to cross
imately 0.3–3% of pregnancies and varies on account of analyze clinical research studies. In this review of the top-
different diagnostic criteria and ethnic variation in study ic, we attempt to differentiate between studies on nausea
populations. Notwithstanding, most studies agree that and vomiting of pregnancy versus studies of the severe
hyperemesis gravidarum is more common among young, form, hyperemesis gravidarum.
primiparous mothers who are non-Caucasian and non- The differential diagnosis of patients with hyperemesis
smokers [4, 5]. Within the US population, there is lack of gravidarum is wide and includes infections, metabolic,
significant data on the difference in prevalence of hyper- gastrointestinal, neurologic, and iatrogenic causes [10].
emesis gravidarum between different ethnic backgrounds. Common diagnoses such as gastroenteritis, cholecystitis,
Worldwide, women of Asian and Middle Eastern ethnic- hepatitis and biliary tract diseases, drug abuse/misuse,
ities have been reported to have higher rates of preva- migraine headaches as well as more rare causes such as
lence, even as high as approximately 10% in a study re- diabetic ketoacidosis, intracranial lesions leading to in-
ported from a Chinese population [6]. It is important, creased intracranial pressure and intestinal obstruction,
however, to note that due to the lack of uniform diagnos- should also be considered. Hyperemesis gravidarum is of-
Icahn School of Medicine at Mount Sinai
146.203.151.55 - 6/29/2017 2:36:34 AM
Diclegis Antihistamine (H1 blocker) with vitamin Mainly in nausea/vomiting of pregnancy. FDA approved for N/V
B6 (cofactor in enzymatic reactions) May aid in pretreatment of HG of pregnancy
Pregnancy category A
Ondansetron Selective 5-HT3 receptor antagonist First-line treatment in HG Pregnancy category B
Metoclopramide Anti-HT3 antidopaminergic properties. First-line treatment in HG Pregnancy category B
Prokinetic agent
Clonidine Centrally acting alpha-agonist Pilot studies show benefit in refractory HG Pregnancy category C
Promethazine Weak antidopaminergic and antiserotonin Small-scale studies for refractory HG Pregnancy category C
receptor activity in CNS, antimuscarinic, show benefit of addition of promethazine to
long-lasting antihistamine action first-line treatment
Prednisone Multifactorial Small-scale studies show addition of Pregnancy category C
prednisone decreases daily episodes of emesis
Mirtazapine Multifactorial: adrenergic alpha2 Shows benefit in symptomatic relief in Pregnancy category C
antagonist, serotonin 5-HT2 and 5-HT3 small-scale studies of refractory HG Strong association of
antagonism with histaminergic and prednisone exposure and
muscarinic effects fetal oral cleft defects
emesis gravidarum. The main focus of disagreement is dansetron and metoclopramide, which appear to show
the effect of hyperemesis gravidarum on gestational similar efficacy and safety. Studies on therapeutics for
age at delivery and birth weight. The bulk of available refractory hyperemesis gravidarum are few in num-
research in the area is focused on therapeutic options ber, suggesting opportunities for further research in this
and studies of multiple first-line agents including on- arena.
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Icahn School of Medicine at Mount Sinai
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