High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals

Abstract

Objective

The goal of this study was to determine the prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of affected individuals.

Study design

Family history data were obtained on 1224 self-reported cases of hyperemesis gravidarum. Cases completed an online survey administered by the Hyperemesis Education and Research Foundation between 2003 and 2006.

Results

Approximately 28% of cases reported their mother had severe nausea and vomiting or hyperemesis gravidarum while pregnant with them. Of the 721 sisters with a pregnancy history, 137 (19%) had hyperemesis gravidarum. Among the most severe cases, those requiring total parenteral nutrition or nasogastric feeding tube, the proportion of affected sisters was even higher, 49/198 (25%). Nine percent of cases reported having at least two affected relatives including sister(s), mother, grandmother, daughters, aunt(s), and cousin(s).

Conclusion

There is a high prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of hyperemesis gravidarum cases in this study population. Because the incidence of hyperemesis gravidarum is most commonly reported to be 0.5%, this study provides strong but preliminary evidence for a genetic component to extreme nausea and vomiting of pregnancy.

Introduction

Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, hospitalizes more than 59,000 pregnant women in the U.S. annually, with most authors reporting an incidence of 0.5% [1], [2]. Estimates of severe nausea and vomiting of pregnancy vary greatly and range from 0.3% in a Swedish registry to as high as 10.8% in a Chinese registry of pregnant women [3], [4]. Recent large population studies support ethnic variation in the incidence of HG. A Norwegian study of the medical birth registry of Norway from 1967 to 2005, defined HG as persistent nausea and vomiting in pregnancy associated with ketosis and weight loss >5% of pre-pregnancy weight, and revealed an overall prevalence of 0.9%, but when broken down by ethnicity, found HG in 2.2% of 3927 Pakistani women and 1.9% of 1997 Turkish women, both more than twice the incidence of 0.9% in 798,311 Norwegian women [5]. A study of California birth and death certificates after 20 weeks gestation linked to neonatal hospital discharge data in 1999 with the primary diagnosis of hyperemesis found an incidence 0.5% (2466 cases out of 520,739 births), and women with HG were reportedly significantly less likely to be white or hispanic compared to non-whites or non-hispanics [6]. A Canadian study found HG in 1270 (0.8%) out of 156,091 of women with singleton deliveries between 1988 and 2002 [7]. This rate was confirmed in a second Canadian study during the same timeframe of the population-based Nova Scotia Atlee Perinatal Database of deliveries at 20 weeks gestation, that found 1301 (0.8%) out of 157,922 pregnancies [8]. Asian populations tend to have higher incidence rates. For example, a Malaysian study identified 192 recorded cases (3.9%) out of 4937 maternities [9]. Additionally, a study of 3350 singleton deliveries in an Eastern Asian population observed HG in 119 (3.6%) of the population [10]. As mentioned, a study of 1867 singleton live births revealed the highest rate of severe nausea and vomiting of pregnancy in Shanghai, China, from 1986 to 1987, with an incidence of 10.8%. However, unlike the other studies mentioned, this study was based on a clinical record of severe vomiting on prenatal care cards, rather than hospitalization for HG, did not limit itself to a primary diagnosis of HG and included, for example, women with chronic liver disease, chronic hypertension, chronic renal illness, and preeclampsia [4].

Hyperemesis gravidarum is the most common cause of hospitalization in the first half of pregnancy and is second only to preterm labor for pregnancy overall [11]. HG can be associated with serious maternal and fetal morbidity such as Wernicke's encephalopathy [12], fetal growth restriction, and even maternal and fetal death [6], [13].

A biologic component to the condition has been suggested from animal studies. Anorexia of early pregnancy has been observed in various mammals including monkeys [14]. In dogs, anorexia can be accompanied by vomiting and can be severe enough to require pregnancy termination [15].

Several lines of evidence support a genetic predisposition to nausea and vomiting in pregnancy (NVP). Firstly, in the only study of NVP in twins, concordance rates were more than twice as high for monozygotic compared to dizygotic twins [16]. Secondly, several investigators have noted that siblings and mothers of patients affected with NVP are more likely to be affected than siblings and mothers of unaffected individuals [17], [18]. Thirdly, the higher frequency of severe NVP in patients with certain genetically determined conditions such as defects in taste sensation [19], [20], glycoprotein hormone receptor defects [21], [22], [23], or latent disorders in fatty acid transport or mitochondrial oxidation [24], [25], suggests that some portion of HG cases may be related to discrete, genetically transmitted disease states that are unmasked or exacerbated in pregnancy. Overall, these data suggest that genetic predisposition may play a role in the development of nausea and vomiting of pregnancy.