Abstract 64: Prenatal Per- and Polyfluoroalkyl Substance (PFAS) Exposures, Individually and as a Mixture, Are Associated With Obesity Risk at 16-20 Years in the Project Viva Prospective Cohort: Implications for PFAS as Hazardous Substances for Developmental Health

Introduction: PFAS are obesogenic in adults, but findings on the associations between prenatal PFAS exposures and child obesity risk are inconsistent, and it is not clear if such associations extend up to mid- to late adolescence. We investigated the individual and joint associations of prenatal PFAS exposures with obesity risk at 16-20 years. Methods: In the prospective pre-birth cohort Project Viva, we measured PFAS in maternal plasma samples collected in the first trimester and child body mass index (BMI) at the mid-adolescent visit (median: 17.4y; range: 15.9-20.0y). We defined obesity as BMI ≥ 95 th percentile for age and sex based on the CDC Growth Charts. We used Poisson regression with robust variance estimates to examine associations of each PFAS, and Bayesian kernel machine regression (BKMR) to examine PFAS mixtures, with obesity. We adjusted for maternal age, education, pre-pregnancy BMI, race/ethnicity, parity, and smoking status during pregnancy. Results: Among 545 participants, 73 (13%) had a BMI in the obese range. Children with higher prenatal PFOS and PFNA exposures had a greater risk of obesity [relative risk = 1.59 (95% CI: 1.19, 2.11) per doubling of PFOS and 1.48 (95% CI: 1.11, 1.98) per doubling of PFNA] in multivariable-adjusted models. In BKMR models, PFOS and PFNA were similarly associated with greater risk of obesity when accounting for co-exposures of other PFAS (Panel A) . There was an interaction between PFOS and PFOA: the positive association between PFOS and obesity was stronger when PFOA levels were lower (Panel B) , while there was a negative association between PFOA and obesity when PFOS levels were higher (Panel C) . Children with higher concentrations of the mixture PFAS had greater obesity risk in a dose-dependent fashion (Panel D) . Conclusions: Prenatal PFAS exposures may have long-lasting, intergenerational obesogenic effects. Our findings support the U.S. Environmental Protection Agency’s recent designation of PFAS as hazardous substances for human health, including developmental health.