Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Blood Pressure Outcomes in Childhood and Adolescence: An ECHO Cohort Analysis

Per- and polyfluoroalkyl substances (PFAS) are widespread, persistent chemicals that cross the placenta and may affect fetal development. Animal studies suggest that prenatal PFAS exposure may increase offspring blood pressure (BP). However, epidemiologic evidence in children is limited and inconsistent. To address this gap, we aimed to examine the associations between prenatal PFAS exposure and childhood BP. In this prospective cohort study, 2421 children aged 3 to <13 years born from 1999–2020 participating in 13 U.S. recruitment sites of the Environmental influences on Child Health Outcomes (ECHO) Cohort were included. Exposures included concentrations of six PFAS (PFOA, PFOS, PFHxS, PFNA, PFDA, and MeFOSAA) in plasma or serum collected during pregnancy. Age-, sex-, and height-specific child BP percentiles according to the 2017 American Academy of Pediatrics Clinical Practice Guideline and elevated BP (systolic or diastolic BP [SBP or DBP] ≥90th percentile) were assessed. The children were 50% female; 21% were Hispanic, 24% non-Hispanic Black, 46% non-Hispanic White, and 9% other races. At a median age of 7.3 years (interquartile range [IQR], 4.9–10.3), 22% of children had elevated BP. Median SBP and DBP percentiles were 64 (IQR, 38–82) and 59 (IQR, 40–79), respectively. In adjusted analyses, each doubling of prenatal PFOA was associated with a 0.87 (95% CI, 0.13–1.60) higher DBP percentile and a 7% higher risk of elevated BP [relative risk 1.07 (95% CI, 1.01–1.14)]. Each doubling of prenatal PFDA was associated with a 0.78 (95% CI, 0.02–1.53) higher SBP percentile, and each doubling of prenatal PFNA was associated with a 0.77 (95% CI, 0.02–1.52) higher DBP percentile. However, none of these associations remained statistically significant after false discovery rate correction. Trimester-specific analyses revealed that PFAS–BP associations tended to be the strongest during the first trimester. Secondary effect modification analyses suggested that the positive PFOA–SBP association was stronger in males, while positive associations of PFOA and PFNA with DBP were stronger in females. However, interaction tests for these specific associations were not statistically significant. Though the observational design precludes causal inference, these findings suggest that prenatal exposure to PFOA, PFDA, and PFNA may be associated with higher childhood BP, reinforcing the importance of population-level prevention.