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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.
Highlights
Nausea and vomiting in pregnancy (NVP) affects 70–90% of all pregnant women
As previous research has variably implicated human chorionic gonadotropin (hCG) in the pathogenesis of NVP24 we examined the relationships between hCG levels, NVP symptoms and Growth and Differentiation Factor 15 (GDF15) concentrations in those women in whom these measures were available
As there have been reports that low pre-pregnancy body mass index (BMI) predisposes to NVP9 we examined the relationship between pre-pregnancy BMI, GDF15 levels and NVP
Summary
Nausea and vomiting in pregnancy (NVP) affects 70–90% of all pregnant women. The most severe form of NVP, hyperemesis gravidarum (HG), leads to maternal dehydration and electrolyte imbalance and is the most common cause of hospital admission during early pregnancy[1]. Primiparity, younger maternal age, non-smoking[1] and being underweight[9,10,11] may be risk factors Reproductive hormones, such as human chorionic gonadotropin (hCG), progesterone and estrogen, have been implicated due to their rise in concentrations in the mother’s circulation contemporaneous with the manifestation of NVP12. 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. 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
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