Associations of childhood per- and polyfluoroalkyl substances with autistic traits and symptom severities among children with and without autism spectrum disorder

• We investigated the associations between childhood per- and polyfluoroalkyl substances and the risks of autism spectrum disorders (ASD) in Guangzhou, China. • This case-control study identified positive associations of total/linear PFHxS with the risks of ASD. • We observed positive associations of total/linear PFHxS with autistic traits among typical development children. • We observed positive associations of 8:2 Cl-PFESA with symptom severity among children with ASD. The associations of childhood legacy and alternatives per- and polyfluoroalkyl substances (PFASs) with autism spectrum disorder (ASD) -related outcomes were seldom discussed. In this case-control study conducted in Guangzhou, China, 6- to 9-year-old children underwent psychometric tests (autistic traits via Autism Spectrum Quotient-Children and symptom severities via Social Responsiveness Scale) who were clinically confirmed for ASD (case, n = 60) or typical development (TD, n = 180), and we tested their plasma concentrations of 16 legacy and alternative PFASs. We used conditional logistic regression models and generalized linear models to test the associations of PFASs exposure with ASD-related outcomes. Higher concentrations of total and linear PFHxS were associated with higher risk of ASD [OR = 2.44, 95% confidence interval (CI): 1.05-5.67; 2.73, 95CI: 1.17-6.38] and higher autistic traits among TD children (β = 0.45, 95%CI: 0.03-0.87; 0.44, 95CI: 0.01- 0.86). In addition, we observed a positive association between symptom severity with 8:2 Cl-PFESA, an alternative PFASs, among children with ASD (β =4.90, 95%CI: 0.07-9.72). We did not find joint associations between PFASs mixtures and the outcomes when using multiple-pollutant models. More studies are needed to confirm the PFASs-ASD associations, and the potential hazards of emerging PFASs should not be ignored.