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Familial Aggregation of Hyperemesis Gravidarum

Marlena Schoenberg Fejzo, Kimber MacGibbon, Frederic Schoenberg Paik
American Journal of Human Genetics, Volume 69 Number 4, October 2001

Nausea and vomiting in pregnancy, or “morning sickness,” occurs in 50-90% of all pregnant women. When the symptoms are so severe that individuals require hospitalization and/or therapeutic intervention, pregnant women are diagnosed with hyperemesis gravidarum (HG). HG occurs in approximately 0.3-2.0% of pregnant women, and is characterized by severe nausea and vomiting in early pregnancy that rapidly leads to at least a 5% weight loss. Symptoms of HG can include ketonemia, ketonuria, dehydration, electrolyte imbalance, ptyalism, gestational hyperthyroidism, and hepatic and renal damage.

Surprisingly, little is known about the etiology of this disease, which may be an abnormal toxic response to normal hormone levels during pregnancy, or conversely, may be a normal toxic response to abnormal hormone levels or abnormal metabolites during pregnancy. Currently approximately 70% of patients are prescribed antiemetic drugs of unknown safety and efficacy to treat the symptoms of HG.

In an attempt to learn more about HG, we wrote and collected surveys from over 260 affected individuals. Our study shows that the 3 most commonly prescribed antiemetics (phenergan, compazine, and tigan) are more strongly correlated with second trimester fetal demise than with having any positive therapeutic effect, suggesting a better understanding of the disease and new treatments is critical. To determine whether HG is amenable to genetic studies, we included a number of questions about family history. All patients were diagnosed by a medical professional to have hyperemesis gravidarum. Of the 260 respondents, 96 reported having at least one sister with a pregnancy history. Of the 96 sister pairs, 23 (24%) reported a sister with HG. In addition, 28 (11%) affected individuals reported having an affected mother, and 29 (11%) reported having an affected secondary relative. We have also identified 14 families with 3 or more affected individuals.

This study shows the frequency of HG in families is way above the reported 0.3-2.0% in the general population. This is the first evidence that there may be a genetic component to the severe form of morning sickness, hyperemesis gravidarum, which may make it amenable to genetic studies of complex disease. We hope that this will lead to a new field of study to identify the genetic basis for hyperemesis gravidarum and lead to development of targeted therapy.

Updated on: Apr. 18, 2013

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