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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