Prenatal per- and polyfluoroalkyl substances (PFAS) exposure and associations with common childhood infections and allergies: A study of risks and resiliencies in the ECHO Program

Per-and polyfluoroalkyl substances (PFAS) are detected in virtually all people in the U.S. and the evidence of health effects at increasingly low levels of PFAS, is growing. Despite being used in manufacturing since the 1940s, there was little awareness or research on the health effects of PFAS until the last 15 years. A 2016 National Toxicology Program (NTP) systematic review concluded that PFOA and PFOS are a presumed immune hazard to humans. In particular, decreased antibody response has been identified as a critical endpoint for international, national, and state toxicity values and drinking water regulations. Despite the regulatory importance, research on the health consequences resulting from reduced immune function is not definitive. Common childhood infections and immune hypersensitivity outcomes such as allergies are useful measures for evaluating altered immune function in humans, and notably, no U.S. based cohort study has evaluated these outcomes. Combing pediatric birth cohorts with available prenatal PFAS serum concentrations from across the Environmental Influences on Child Health Outcomes cohort, we will evaluate associations with childhood infections (bronchiolitis, croup, pneumonia and bronchitis, ear infections) and allergies (allergy symptoms, and atopic dermatitis) at infancy and early childhood. PFAS will be evaluated individually in adjusted linear and logistic regression models and as mixtures using Bayesian Kernal Regression Models (BKMR). Potential effect modification by breastfeeding, child sex, child BMI, and other factors will be evaluated to understand differential impacts due to cumulative exposures. Dietary and demographic determinants of PFAS will be assessed with correlation analysis and multivariable linear regression across the ECHO-wide study and for each cohort to provide targets for further reduction of PFAS exposure in U.S. pregnant women. Positive and null findings, alike, from well conducted studies, will be important for understanding safe levels of exposure and guiding future regulations.