Associations of Prenatal PFAS Mixtures With Adult Metabolic, Vascular, and Bone Health

ABSTRACT Per- and polyfluoroalkyl substances (PFAS) are toxic chemicals of significant public health concern due to their nearly indefinite persistence in the environment and widespread human exposures from contaminated drinking water, food, and consumer products. There is mounting evidence that PFAS exposures during gestation are associated with adverse health effects in childhood, including worse metabolic, vascular, and bone health. However, it is currently unknown whether these effects persist into adulthood. Further, as more communities discover historical PFAS exposures, there is an urgent need to identify interventions to mitigate adverse effects of PFAS exposures after they have already occurred. To address these critical knowledge gaps, the goals of this proposal are to estimate the impact of the effects of prenatal PFAS mixture burden on mid-adulthood health and to evaluate factors that may mitigate these effects. We will accomplish our aims using the New England Family Study (NEFS), a unique prospective cohort study of pregnancies in the 1960s with data collected from children annually from birth through age 7 years, and again in mid-adulthood (mean age=47 years, n=400). NEFS is an ideal cohort to address our aims, as it has amassed rich data from pregnancy through mid-adulthood including detailed adult health phenotyping. We will additionally measure concentrations of 44 PFAS in stored serum samples collected during pregnancy and adulthood. Using state-of- the-art analytical approaches to quantify PFAS mixture burden, we will determine whether prenatal PFAS burden is associated with worse metabolic function, vascular health, and bone mineral density in mid- adulthood, independent of concurrent PFAS burden (Aim 1) and assess whether adverse impacts are stronger among those with suboptimal diet quality and physical activity (Exploratory Aim). Our team of experts in exposure assessment, analytic chemistry, biostatistics, environmental epidemiology, and clinical medicine will be the first to examine long-term effects of PFAS mixture burden on multiple prevalent adult health outcomes, and to inform potential interventions to reduce the impact of prior exposures. Our findings will serve as the basis for a future follow-up of NEFS participants to elucidate the adult health impacts of early life PFAS exposures on metabolic, vascular, and bone health outcomes. Ultimately, this research will provide critical evidence on the long-term impacts of PFAS exposures to inform health screening guidance in PFAS-exposed communities, refine proposed PFAS drinking water regulations, and identify potential interventions to reduce the health impacts of historical PFAS exposures.