Abstract
High maternal body-mass-index (BMI) is linked to adverse pregnancy outcomes, partly through impaired placental development. An inverse association between BMI and placental biomarkers has been described, however it is unclear whether this relationship is restricted to obesity or occurs across the full-BMI range. We assessed the relationship between maternal BMI and placental biomarkers across multiple cohorts. METHODS: We analysed three UK cohorts: ALSPAC (n = 994), CBGS (n = 1202) and POPS (n = 3869). Concentrations of growth-differentiation-factor15 (GDF15), beta-human chorionic gonadotropin (βhCG), pregnancy-associated plasma protein-A (PAPP-A), and alpha-fetoprotein (AFP) were measured at 8-16 weeks of gestation in maternal serum and expressed as gestational age-adjusted z-scores. Cohort-specific regression and individual-participant-data-meta-analyses (IPD-MA) were used. RESULTS: Across cohorts, each 1SD increase in maternal BMI was associated with significant reduction in: GDF15 (β: -0.16, 95%CI: -0.23 to -0.10; p<0.001), βhCG (β: -0.26, 95%CI: -0.28 to -0.23; p<0.001), PAPP-A (β: -0.38 95%CI: -0.41 to -0.36; p<0.001), and AFP (β: -0.21, 95%CI: -0.24 to -0.18; p<0.001). Associations were linear across the full BMI range, not driven solely by obesity. Biomarker levels correlated more strongly with early-pregnancy BMI than with estimated blood volume and associated directionally with the maternal polygenic-risk-scores (PRS) for BMI. CONCLUSIONS: Maternal BMI across its full range was inversely associated with biomarkers arising from, or transferred through, the placenta. We propose that the maternal caloric environment may regulate the development of the materno-fetal interface and its capacity for nutrient transfer, supporting similar rates of early fetal-growth in the face of substantial inter-individual variation in maternal body mass.