Hyperemesis gravidarum in relation to estradiol levels, pregnancy outcome, and other maternal factors: a seroepidemiologic study.

Two studies were conducted to assess factors associated with increased risk of hyperemesis gravidarum during pregnancy with data and serum samples collected from participants in the Collaborative Perinatal Study. In the case-control study, 419 pregnant women with hyperemesis gravidarum were matched on medical center, date of study registration, and race with 836 pregnant women who did not vomit during the index pregnancy. Younger age, nulliparity, and high body weight were significantly associated with increased risk of hyperemesis. Women with hyperemesis had significantly reduced risk of fetal loss; however, their infants had higher risk of central nervous system malformations. In the second study, first-trimester pregnancy hormones were measured in the serum of 35 women with hyperemesis and 35 control women who were individually matched to cases on age, parity, and medical center. After adjusting for length of gestation, mean levels of total estradiol were 26% higher and mean levels of sex hormone binding-globulin binding capacity were 37% higher in patients with hyperemesis gravidarum than in control subjects. These differences were statistically significant. Although human chorionic gonadotropin concentrations were higher in control pregnancies, the differences were not statistically significant. The average amount of estradiol that was nonprotein bound (adjusted for length of gestation) was also higher in patients than in control subjects. These results are consistent with the hypothesis that elevated estrogen levels are responsible for excessive vomiting in pregnancy.