Environmental chemical exposures during pregnancy and women's cardio-metabolic health

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Project Summary While much research has been devoted to exploring the impact of environmental chemical exposures during pregnancy on infant and child health, relatively little attention has focused on the potential influence of these exposures on maternal health. Recent evidence suggests that pregnancy may be a sensitive period in the life course, during which chemical exposures may have long-lasting effects on cardio-metabolic disease risk among women. Using a well-characterized existing cohort study that enrolled 1,410 pregnant women in 2009- 2014, we propose the following aims: (1) quantify the relationship between environmental exposures during pregnancy and short-term maternal health outcomes including: postpartum weight retention, reduced breastfeeding initiation and duration, and incident diabetes; (2) quantify the relationship between environmental exposures during pregnancy and long-term maternal health outcomes: body composition, weight trajectories from pregnancy through ~10 years after parturition, hepatic fat, dysglycemia and incident diabetes, and cardiovascular disease; and (3) evaluate the potential role of maternal characteristics and behaviors during pregnancy, specifically obesity and diet quality, in modifying associations between environmental chemical exposures and outcomes. Exposures during pregnancy will include serum per- and polyfluoroalkyl substances (PFAS), urinary phthalate metabolites, phenols and parabens, metals, organophosphate flame retardants, and modeled air pollutants at the maternal residential address during pregnancy. We propose to recruit 700 of the original study participants to return for a follow-up visit at ~10 years postpartum. At this visit, participants will undergo a comprehensive metabolic health evaluation including body composition via air displacement plethysmography (BOD POD), dysglycemia via oral glucose tolerance test, and hepatic fat fraction via MRI. Medical records will be abstracted to document incident diabetes and cardiovascular disease, and to reconstruct body weight trajectories. We will estimate associations between exposures during pregnancy and maternal outcomes using covariate-adjusted multivariable regression models for continuous, binary, or time-to- event data, as appropriate. Exposures will be evaluated as single pollutants and as mixtures using advanced statistical methods including Bayesian Kernel Machine Regression and Bayesian hierarchical Cox survival models. We hypothesize that maternal body mass index prior to pregnancy and diet quality during pregnancy will modify the effects of environmental chemical exposures on cardio-metabolic outcomes, such that associations will be stronger among women with obesity entering pregnancy or with poor diet quality during pregnancy. The results of this study will inform public health interventions to identify women who may be especially susceptible to the effects of environmental chemical exposures during pregnancy, and to improve the environment of pregnancy to promote the long-term health of both the offspring and the mother.