biostudies-literatureSchrott RNational Institute of Environmental Health SciencesU.S. Environmental Protection AgencyNIH Office of the DirectorNational Institutes of HealthOffice of the Director, National Institutes of Healthdvaf010https://www.ebi.ac.uk/biostudies/studies/S-EPMC12094075biostudies-literatureUnknown11(1)Gestation is a vulnerable window when exposure to per- and polyfluoroalkyl substances (PFAS) may impact child development and health. Epigenetic modification, including DNA methylation (DNAm), may be one mechanism linking prenatal PFAS exposure to offspring outcomes. We tested associations between prenatal PFAS and newborn DNAm in 1017 participants from 6 cohorts in the US Environmental influences on Child Health Outcomes consortium. Concentrations of PFAS [perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid] were measured in maternal serum or plasma. DNAm was quantified in newborn dried blood spot or umbilical cord blood leukocytes using the Infinium HumanMethylation450 (450K) or MethylationEPIC (EPIC) arrays. We tested associations between prenatal PFAS and neonatal blood DNAm on the 450K (<i>n</i> = 772) and EPIC (<i>n</i> = 245) arrays; results were meta-analysed across the platforms. Regional changes in DNAm were investigated, and findings were checked for replication in the Michigan Mother-Infant Pairs (MMIP) cohort (<i>n</i> = 140). Following correction for false discovery rate (<i>q</i> = 0.1 for meta-analyses), we identified an association between PFHxS and one cytosine-guanine (CpG) mapped to <i>CASC3</i> (<i>q</i> = 0.065) that replicated in MMIP (<i>P</i> = .006). PFOS was associated with six CpG sites, of which five were mapped to the genes <i>KIAA1841, ABR, LEP, SERPINA1</i>, and <i>LOXL1</i>. One differentially methylated region (DMR) was associated with prenatal PFOA exposure, and one DMR was associated with PFOS exposure. In this multicohort analysis including a diverse group from the USA, PFOA, PFOS, PFHxS, and PFNA exposures in pregnancy were associated with offspring DNAm, and the implications for children's health merit further exploration.Environmental epigeneticsPrenatal per- and polyfluoroalkyl substance exposures and DNA methylation among newborns in the Environmental influences on Child Health Outcomes program.PMC12094075RD83543601U2COD023375Schrott RYang IVLadd-Acosta CBarr DBDunlop ALHowerton EMZhu YFallin DMHivert MFOken EPadmanabhan VPetriello MCStarling APSmith AKDabelea DKnight AKCarignan CCBreton CVGoodrich JMPeterson AKRuden DCardenas ASchmidt RJfalsePrenatal per- and polyfluoroalkyl substance exposures and DNA methylation among newborns in the Environmental influences on Child Health Outcomes program.Gestation is a vulnerable window when exposure to per- and polyfluoroalkyl substances (PFAS) may impact child development and health. Epigenetic modification, including DNA methylation (DNAm), may be one mechanism linking prenatal PFAS exposure to offspring outcomes. We tested associations between prenatal PFAS and newborn DNAm in 1017 participants from 6 cohorts in the US Environmental influences on Child Health Outcomes consortium. Concentrations of PFAS [perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid] were measured in maternal serum or plasma. DNAm was quantified in newborn dried blood spot or umbilical cord blood leukocytes using the Infinium HumanMethylation450 (450K) or MethylationEPIC (EPIC) arrays. We tested associations between prenatal PFAS and neonatal blood DNAm on the 450K (<i>n</i> = 772) and EPIC (<i>n</i> = 245) arrays; results were meta-analysed across the platforms. Regional changes in DNAm were investigated, and findings were checked for replication in the Michigan Mother-Infant Pairs (MMIP) cohort (<i>n</i> = 140). Following correction for false discovery rate (<i>q</i> = 0.1 for meta-analyses), we identified an association between PFHxS and one cytosine-guanine (CpG) mapped to <i>CASC3</i> (<i>q</i> = 0.065) that replicated in MMIP (<i>P</i> = .006). PFOS was associated with six CpG sites, of which five were mapped to the genes <i>KIAA1841, ABR, LEP, SERPINA1</i>, and <i>LOXL1</i>. One differentially methylated region (DMR) was associated with prenatal PFOA exposure, and one DMR was associated with PFOS exposure. In this multicohort analysis including a diverse group from the USA, PFOA, PFOS, PFHxS, and PFNA exposures in pregnancy were associated with offspring DNAm, and the implications for children's health merit further exploration.2025-01-01T00:00:00Z20252026-05-14T03:21:57.777Z2026-05-14T03:12:50.241ZS-EPMC120940754040116810.1093/eep/dvaf010