Associations of vomiting and antiemetic use in pregnancy with levels of circulating GDF15 early in the second trimester: A nested case-control study.
Clive J Petry, Ken K Ong, Keith A Burling, Peter Barker, Sandra F Goodburn, John R B Perry, Carlo L Acerini, Ieuan A Hughes, Rebecca C Painter, Gijs B Afink, David B Dunger, Stephen O'Rahilly
Author Information
Clive J Petry: Department of Paediatrics, University of Cambridge Addenbrooke's Hospital Cambridge, Cambridge, CB2 0QQ, UK. ORCID
Ken K Ong: Department of Paediatrics, University of Cambridge Addenbrooke's Hospital Cambridge, Cambridge, CB2 0QQ, UK.
Keith A Burling: NIHR Biomedical Research Centre Core Biochemistry Assay Lab, University of Cambridge Addenbrooke's Hospital Cambridge, Cambridge, CB2 0QQ, UK.
Peter Barker: NIHR Biomedical Research Centre Core Biochemistry Assay Lab, University of Cambridge Addenbrooke's Hospital Cambridge, Cambridge, CB2 0QQ, UK.
Sandra F Goodburn: Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. ORCID
John R B Perry: Medical Research Council Epidemiology Unit, University of Cambridge Addenbrooke's Hospital Cambridge, Cambridge, CB2 0QQ, UK.
Carlo L Acerini: Department of Paediatrics, University of Cambridge Addenbrooke's Hospital Cambridge, Cambridge, CB2 0QQ, UK. ORCID
Ieuan A Hughes: Department of Paediatrics, University of Cambridge Addenbrooke's Hospital Cambridge, Cambridge, CB2 0QQ, UK.
Rebecca C Painter: Department of Gynaecology and Obstetrics, Academic Medical Center of the University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.
Gijs B Afink: Reproductive Biology Laboratory, Academic Medical Center of the University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands. ORCID
David B Dunger: Department of Paediatrics, University of Cambridge Addenbrooke's Hospital Cambridge, Cambridge, CB2 0QQ, UK. ORCID
Stephen O'Rahilly: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge Addenbrooke's Hospital Cambridge, Cambridge, CB2 0QQ, UK. ORCID
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. 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. 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. 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.
