Project Summary/Abstract
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) that were specifically designed to study maternal cardio-
metabolic health in pregnancy and postpartum. Key complementary features of the 2 cohorts are first trimester
recruitment, extensive biospecimen collection across pregnancy, and postpartum maternal cardiometabolic
assessments. In the combined UM-ERGO cohort (n=500) we evaluate maternal urinary phthalate metabolite
concentrations at six time points (trimesters 1 & 3 in pregnancy; 1-4 years postpartum) and examine
associations with body composition and cardiometabolic biomarkers from 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 innovative modeling approaches to identify sensitive windows in which phthalates affect maternal
obesity and cardiometabolic measures. Our study presents a unique opportunity to examine phthalate
exposure in pregnancy and early postpartum in relation to maternal health over 4 years of intensive follow-up.