ABSTRACT: BACKGROUND:Exposure to perfluoroalkyl substances (PFASs) may impact children's neurodevelopment. OBJECTIVE:To examine the association of prenatal and early childhood serum PFAS concentrations with children's reading skills at ages 5 and 8years. METHODS:We used data from 167 mother-child pairs recruited during pregnancy (2003-2006) in Cincinnati, OH, quantified prenatal serum PFAS concentrations at 16±3weeks of gestation and childhood sera at ages 3 and 8years. We assessed children's reading skills using Woodcock-Johnson Tests of Achievement III at age 5years and Wide Range Achievement Test-4 at age 8years. We used general linear regression to quantify the covariate-adjusted associations between natural log-transformed PFAS concentrations and reading skills, and used multiple informant model to identify the potential windows of susceptibility. RESULTS:Median serum PFASs concentrations were PFOS>PFOA>PFHxS>PFNA in prenatal, 3-year, and 8-year children. The covariate-adjusted general linear regression identified positive associations between serum PFOA, PFOS and PFNA concentrations and children's reading scores at ages 5 and 8years, but no association between any PFHxS concentration and reading skills. The multiple informant model showed: a) Prenatal PFOA was positively associated with higher children's scores in Reading Composite (?: 4.0, 95% CI: 0.6, 7.4 per a natural log unit increase in exposure) and Sentence Comprehension (?: 4.2, 95% CI: 0.5, 8.0) at age 8years; b) 3-year PFOA was positively associated with higher children's scores in Brief Reading (?: 7.3, 95% CI: 0.9, 13.8), Letter Word Identification (?: 6.6, 95% CI: 1.1, 12.0), and Passage Comprehension (?: 5.9, 95% CI: 1.5, 10.2) at age 5years; c) 8-year PFOA was positively associated with higher children's Word Reading scores (?: 5.8, 95% CI: 0.8, 10.7) at age 8years. Prenatal PFOS and PFNA were positively associated with children's reading abilities at age 5years, but not at age 8years; 3-year PFOS and PFNA were positively associated with reading scores at age 5years. But PFHxS concentrations, at any exposure windows, were not associated with reading skills. CONCLUSION:Prenatal and childhood serum PFOA, PFOS and PFNA concentrations were positively associated with better children's reading skills at ages 5 and 8years, but no association was found between serum PFHxS and reading skills.