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.

Grant Number: 1R21ES036946-01
NIH Institute/Center: NIH
Principal Investigator: Joseph Braun