Childhood exposure to per- and polyfluoroalkyl substances and neurodevelopment in the CHARGE case-control study

Background: Per-and polyfluoroalkyl substances (PFAS) are shown to have neurotoxic effects on animals, but epidemiological evidence for associations between childhood PFAS exposure and neurodevelopment is incon-clusive. We examined if childhood PFAS concentrations are associated with a diagnosis of autism spectrum disorder (ASD), developmental delay (DD), and other early concerns (OEC) in development.Methods: We included 551 children 2-5 years old from the CHildhood Autism Risks from Genetics and Envi-ronment (CHARGE) case-control study. Children were clinically diagnosed and classifled as having ASD, DD, OEC, and typical development (TD). Fourteen PFAS were quantifled in child serum samples collected when diagnostic assessments were performed. We used multinomial logistic regression models to investigate the cross-sectional associations of individual PFAS concentrations with neurodevelopmental outcomes and weighted quantile sum (WQS) regression models with repeated holdout validation to investigate the associations with PFAS mixtures.Results: Childhood perfluorooctanoic acid (PFOA) was associated with increased odds of ASD (odds ratio [OR] per ln ng/mL increase: 1.99, 95% confldence interval [CI]: 1.20, 3.29) and DD (OR: 2.16, 95% CI: 1.21, 3.84) versus TD. Perfluoroheptanoic acid (PFHpA) was associated with increased odds of ASD (OR: 1.61, 95% CI: 1.21, 2.13). However, perfluroundecanoic acid (PFUnDA) was associated with decreased odds of ASD (OR: 0.43, 95% CI: 0.26, 0.69). From mixture analyses, the WQS index was associated with increased odds of ASD (average OR: 1.57, 5th and 95th percentile: 1.16, 2.13). Child's sex and homeownership modifled associations of perfluorodecanoic acid (PFDA) with DD and ASD, respectively.Conclusions: In this case-control study, childhood PFOA, PFHpA, and a PFAS mixture was associated with increased odds of ASD, while PFUnDA was associated with decreased odds of ASD. Because we used concurrent measurements of PFAS, our results do not imply causal relationships and thus need to be interpreted with caution.

Automated summary

This case-control study found that childhood concentrations of PFOA and PFHpA were associated with increased odds of ASD and DD, while PFUnDA was associated with decreased odds of ASD. Mixture analysis showed that PFAS mixture was associated with increased odds of ASD.