Pregnancy and postpartum as vulnerable exposure windows: phthalates and maternal cardiometabolic health

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Pregnancy is a transformative period when multiple body systems radically adjust to protect and nurture the growing fetus. Increasingly, evidence shows that exposure to metabolism disrupting environmental chemicals such as phthalates, can dysregulate the body’s ability to adapt appropriately to the demands of pregnancy. Phthalates disrupt multiple nuclear receptor and hormone-mediated pathways and in cross-sectional research, they have been linked to obesity, diabetes, cardiovascular disease (CVD), and metabolic syndrome. Our research in multiple pregnancy cohorts demonstrates that elevated concentrations of certain phthalate metabolites are associated with adverse cardiometabolic outcomes including excessive gestational weight gain, gestational diabetes mellitus, and impaired glucose tolerance. In the postpartum, maternal physiology must readjust to the non-pregnant state, a physiological “reset” that may be a second critical period of heightened vulnerability to endocrine disruption. Dysregulation during this time is particularly important given the strong evidence that failure to appropriately adapt to the changing demands of pregnancy and postpartum may increase future risk of chronic disease (e.g. CVD, type 2 diabetes). The over-arching hypothesis of this research is that pregnancy and the postpartum are sensitive windows during which phthalates may dysregulate maternal physiology, leading to long-term cardiometabolic health risks. We propose that comprehensive characterization of cardiometabolic health in the first four years after childbirth will provide key insights into the effects of phthalate exposure during critical prenatal and postpartum windows. This proposal capitalizes on the infrastructure, rich data and biospecimen repositories of two ongoing pregnancy cohort studies, UPSIDE MOMS (UM; R01NR017602) & ERGO (R01ES026166), specifically designed to study maternal cardiometabolic health in pregnancy and postpartum. ERGO and UM had identical eligibility criteria, recruiting women in early pregnancy and following them through the postpartum, with extensive prenatal and postpartum bio-specimen collection, coupled with postpartum maternal cardiometabolic assessments. In the proposed combined UM- ERGO cohort (n=500) we capitalize on a larger sample size to measure maternal urinary phthalate concentrations at 6 time points (1st and 3rd trimesters, 1-3 years postpartum) and examine associations with body composition and cardiometabolic biomarkers at 1-4 years postpartum. Study aims include: (1) Determine associations between pregnancy and postpartum phthalate concentrations and maternal body composition at 1- 4 years postpartum; 2) Examine associations between pregnancy and postpartum phthalate concentrations and maternal cardiometabolic profiles at 1-4 years postpartum; and (3) Employ newer modeling approaches to identify sensitive windows in which phthalates may impact maternal obesity and cardiometabolic measures. Our study is a unique opportunity to examine phthalate exposure in pregnancy and the early postpartum in relation to maternal health over 4 years of intensive follow-up.