Prenatal PFAS Exposure and Adult Cardiometabolic Disease

Exposure to per- and polyfluoroalkyl substances (PFAS) is nearly universal in the United States (US) and has been associated with an array of adverse health outcomes in infants, children, and adults. Prior studies show that prenatal PFAS exposure may increase the risk of low birthweight, preterm birth, and altered childhood growth, which in turn are strong predictors of adult cardiometabolic disease. However, there are two critical gaps in our knowledge. First, no studies have determined if prenatal PFAS exposure increases the risk of adverse adult health outcomes, in large part because of the lack of prospective cohorts with the requisite biospecimens and long-term follow-up. Second, prior studies potentially underestimated the impacts of PFAS on neonatal, child, and adult health because they focused on a small number of PFAS and did not consider understudied PFAS or PFAS mixtures. We will address these gaps using a one-of-a-kind of resource, the New England Family Study (NEFS), a prospective cohort that recruited pregnant women in the 1960s and followed their children annually from birth through age 7 years, and again in mid-adulthood (mean age=47 years, n=751). We will conduct an unprecedented assessment of prenatal PFAS exposure, measuring 44 individual legacy and understudied PFAS, as well as total PFAS using extractable organic fluorine (EOF) in previously collected serum samples. Our team of experts in PFAS, analytic chemistry, exposure assessment, biostatistics, environmental epidemiology, and clinical medicine will apply sophisticated biostatistical methods to these biomarkers and previously collected health assessments to: 1) Estimate the impact of gestational PFAS mixtures and serum EOF on birth weight, gestational age, early adiposity rebound, and childhood BMI; 2) Estimate the impact of gestational and concurrent exposure to PFAS mixtures and EOF on risk of MetS and individual cardiometabolic components in mid-adulthood; and 3) Characterize the degree that birth weight, gestational age, postnatal growth, and childhood BMI mediates the association of prenatal PFAS with MetS and cardiometabolic components; and 4) Determine if mid-adulthood lifestyle factors mitigate the adverse effect of prenatal PFAS on risk of MetS and individual MetS components. Our study provides an unprecedented opportunity to be the first study to quantify the effects of prenatal PFAS exposure on early childhood and adult health. By conducted highly detailed measures of PFAS exposure during the susceptible prenatal period, we will inform risk assessments of PFAS mixtures and identify the most harmful components of this mixture. Moreover, our results will quantify the clinical impact of early-life PFAS exposure on infancy, early childhood, and adult cardiometabolic health, thus informing health screening guidance in exposed communities. Finally, using a solutions-oriented approach, we will identify behavioral or lifestyle factors that could ameliorate the effects of earlier life PFAS exposure, thus paving the way for targeted health interventions in historically exposed communities. Project Number: 1R01ES037335-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Environmental Health Sciences (NIEHS) | Principal Investigator: Joseph Braun | Institution: BROWN UNIVERSITY, PROVIDENCE, RI | Award Amount: $656,250 | Activity Code: R01 | Study Section: Social and Environmental Determinants of Health Study Section[SEDH] View on NIH RePORTER: https://reporter.nih.gov/project-details/11104938