Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3–2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complications. Two loci, chr19p13.11 and chr4q12, are genome-wide significant (p < 5 × 10−8) in both association scans and are replicated in an independent cohort. The genes implicated at these two loci are GDF15 and IGFBP7 respectively, both known to be involved in placentation, appetite, and cachexia. While proving the casual roles of GDF15 and IGFBP7 in nausea and vomiting of pregnancy requires further study, this GWAS provides insights into the genetic risk factors contributing to the disease.

Objective: To report the weight loss and associated symptoms experienced by a large cohort of women with hyperemesis gravidarum (HG). Methods: Data were obtained from an HG website registry, where women with HG were recruited on-line. Respondents were included if they experienced at least 1 live birth >27 weeks' gestation. Extreme weight loss was defined as a loss of >15% of prepregnancy weight. Results: Of the 819 women surveyed, 214 (26.1%) met criteria for extreme weight loss. These women were twice as likely to be Hispanic or nonwhite. Extreme weight loss ( p < 0.001) was associated with indicators of the severity of HG, such as hospitalization and use of parenteral nutrition, and with multiple symptoms during pregnancy, such as gallbladder and liver dysfunction, renal failure, and retinal hemorrhage. Among all women surveyed, 22.0% reported that symptoms lasted throughout pregnancy; this finding was nearly twice as likely among women with extreme weight Loss: 63 of 214 (29.4%) vs. 117 of 605 (19.3%) (OR ¼ 1.73, 95% CI 1.2-2.5, p ¼ 0.003). For some women, symptoms continued postpartum and included food aversions, muscle pain, nausea, and posttraumatic stress. Approximately 16% of babies were born prematurely, and 8% reportedly weighed <2500 g. Among women with extreme weight loss, 9.3% reported having a child with a behavioral disorder. Conclusions: Extreme weight loss is common among women with HG, suggesting that HG is a form of prolonged starvation in pregnancy and that the long-term effects of this condition on women and their offspring warrant further investigation.

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Objective: To describe the psychosocial burden of hyperemesis gravidarum (HG) in a large cohort of affected women, focusing on previously unreported problems. Result: Of the 808 participants, 626 (77.5%) were American. A large majority (82.8%) reported that HG caused negative psychosocial changes, consisting of (1) socioeconomic changes, for example, job loss or difficulties, (2) attitude changes including fear regarding future pregnancies and (3) psychiatric sequelae, for example, feelings of depression and anxiety, which for some continued postpartum. Women who reported that their health-care provider was uncaring or unaware of the severity of their symptoms were nearly twice as likely to report these psychiatric sequelae (odds ratio 1.86, 95% confidence interval 1.06 to 3.29, P ¼ 0.032).Conclusion: Over 80% of a large cohort of women with HG reported that HG caused a negative psychosocial impact.