Perinatal PFAS Impact Children's Development: Examining the Roles of Placental Functional Multiomics and Protection by Maternal Exercise

PROJECT SUMMARY The perinatal period is well-recognized as a critical developmental window where organ systems are rapidly growing and tuning their functional programs. This is also a time when environmental exposures can have profound and long-term impacts on health if they disrupt these processes. Per- and polyfluoroalkyl substances (PFAS), a family of synthetic chemicals characterized by strong carbon-fluorine bonds, are of particular concern given their ubiquity in consumer products and their resistance to degradation. Exposures to PFAS prenatally are known to influence health outcomes, however the mechanisms that link prenatal PFAS to fetal and offspring outcomes are still unclear and likely includes perturbations to placental function. Similarly, while the first years of life are critical windows for growth and development, the effects of PFAS exposures postnatally are poorly understood due to the scarce literature, the lack of longitudinal studies and the difficulty in collecting biological samples from infants and children. Our team has gathered novel preliminary data and has thus far demonstrated that prenatal PFAS are associated with differences in the placental DNA methylome, with lower offspring body weight and fat mass during the first 6 months postnatally, and with poorer cognitive and language development at 12 months. Importantly, preliminary data also suggest that prenatal (maternal) physical activity is associated with a reduction in prenatal and umbilical cord serum PFAS concentrations. Taken together these results uniquely highlight that prenatal PFAS concentrations are associated with placental -omic responses and child health and suggest that physical activity may be an effective strategy to decrease PFAS burden. However, the placental mechanisms leading to such effects and postnatal PFAS exposures' contribution to these outcomes are not clear. Likewise, the contribution of postnatal PFAS exposure on children’s growth and development is understudied. Given that human exposures to PFAS will continue for decades, we plan to leverage three unique existing cohorts and a transdisciplinary team to address these gaps. This approach will allow for robust investigation of how prenatal PFAS exposures impact placental molecular regulation, and whether these perturbations are associated with growth and development, while also quantifying postnatal PFAS exposure (offspring serum at 6 months, 24 months, and 60 months) to examine the combined impact of pre- and postnatal PFAS on growth and development across the extensive longitudinal follow-up period (at least 5 visits between birth and 60 months of age). Lastly, we will leverage a randomized controlled trial of physical activity during pregnancy to test whether lifestyle changes can reduce prenatal PFAS burden or alleviate the risk for adverse effects on offspring outcomes.