Associations of vomiting and antiemetic use in pregnancy with levels of circulating GDF15 early in the second trimester: A nested case-control study

Abstract

Background: Although nausea and vomiting are very common in pregnancy, their pathogenesis is poorly understood. We tested the hypothesis that circulating growth and differentiation factor 15 (GDF15) concentrations in early pregnancy, whose gene is implicated in hyperemesis gravidarum, are associated with nausea and vomiting. Methods: Blood samples for the measurement of GDF15 and human chorionic gonadotrophin (hCG) concentrations were obtained early in the second trimester (median 15.1 (interquartile range 14.4-15.7) weeks) of pregnancy from 791 women from the Cambridge Baby Growth Study, a prospective pregnancy and birth cohort. During each trimester participants completed a questionnaire which included questions about nausea, vomiting and antiemetic use. Associations with pre-pregnancy body mass indexes (BMI) were validated in 231 pregnant NIPTeR Study participants. Results: Circulating GDF15 concentrations were higher in women reporting vomiting in the second trimester than in women reporting no pregnancy nausea or vomiting: 11,581 (10,977-12,219) (n=175) vs. 10,593 (10,066-11,147) (n=193) pg/mL, p=0.02). In women who took antiemetic drugs during pregnancy (n=11) the GDF15 levels were also raised 13,157 (10,558-16,394) pg/mL (p =0.04). Serum GFD15 concentrations were strongly positively correlated with hCG levels but were inversely correlated with maternal BMIs, a finding replicated in the NIPTeR Study. Conclusions: Week 15 serum GDF15 concentrations are positively associated with second trimester vomiting and maternal antiemetic use in pregnancy. Given GDF15's site of action in the chemoreceptor trigger zone of the brainstem and its genetic associations with hyperemesis gravidarum, these data support the concept that GDF15 may be playing a pathogenic role in pregnancy-associated vomiting.

Keywords: antiemetics; maternal-fetal relations; nausea; obesity; pregnancy.

Figure 1.. The relationship between week 15 maternal serum GDF15 concentrations and week 14 hCG MOMs.

( a) A scatter plot of untransformed GDF15 concentration and hCG MOM data from around weeks 14–15 of pregnancy in the Cambridge Baby Growth Study, ( b) a scatter plot of logarithmically-transformed data from the same cohort.

Figure 2.. The relationship between maternal serum GDF15 concentrations around week 15 of pregnancy and pre-pregnancy BMIs.

( a) A scatter plot of untransformed GDF15 concentrations from around week 15 of pregnancy and pre-pregnancy BMI data from the Cambridge Baby Growth Study, ( b) a scatter plot of transformed data from the same cohort, ( c) a scatter plot of untransformed GDF15 and BMI data from the NIPTeR Study and ( d) a scatter plot of transformed data from the same study.