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.