Abstract
Objective Hyperemesis gravidarum, severe nausea and vomiting in pregnancy, occurs in up to 2% of pregnancies and leads to significant weight loss, dehydration, electrolyte imbalance, and ketonuria. It is associated with both maternal and fetal morbidity. Familial aggregation studies and twin studies suggest a genetic component. In a recent GWAS, we showed that placentation, appetite, and cachexia genes GDF15 and IGFBP7 are linked to hyperemesis gravidarum (HG). The purpose of this study is to determine whether GDF15 and IGFBP7 are upregulated in HG patients. Methods We compared serum levels of GDF15 and IGFBP7 at 12 and 24 weeksʼ gestation in women hospitalized for HG, and two control groups, women with nausea and vomiting of pregnancy (NVP), and women with no NVP. Results We show GDF15 and IGFBP7 serum levels are significantly increased in women with HG at 12 weeksʼ gestation. Serum levels of hCG are not significantly different between cases and controls. At 24 weeks gestation, when symptoms have largely resolved, there is no difference in GDF15 and IGFBP7 serum levels between cases and controls. Conclusion This study supports GDF15 and IGFBP7 in the pathogenesis of HG and may be useful for prediction and diagnosis. The GDF15-GFRAL brainstem-activated pathway was recently identified and therapies to treat conditions of abnormal appetite are under intense investigation. Based on our findings, HG should be included.
Highlights
Nausea and vomiting of pregnancy (NVP) affects 50–90 % of all pregnant women [1]
In a recent genome-wide association study (GWAS), we showed that placentation, appetite, and cachexia genes GDF15 and IGFBP7 are linked to hyperemesis gravidarum (HG)
Cases hospitalized for HG have significantly higher serum levels of GDF15 and IGFBP7, but not human chorionic gonadotropin (hCG) at 12 weeks gestation
Summary
Nausea and vomiting of pregnancy (NVP) affects 50–90 % of all pregnant women [1]. Hyperemesis gravidarum, the most severe form of NVP, occurs in 0.3–2 % of pregnancies and leads to significant weight loss, dehydration, electrolyte imbalance, and ketonuria [2, 3]. The proteins encoded by the genes identified in our GWAS (GDF15, IGFBP7) are upregulated in early pregnancy and cause loss of appetite in animal models [14, 15, 17, 21, 22]. We analyze these candidate genes/proteins linked to HG to provide further evidence that they may serve as biomarkers for prediction, diagnosis, and identification of novel treatments
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