Sensitive windows of per- and polyfluoroalkyl substances exposure and Children’s intelligence quotient

• This is a longitudinal study of PFAS and intelligence from prenatal to childhood. • Sex-specific associations are observed between PFAS and children’s intelligence. • Childhood is a sensitive window for PFAS-related visuospatial ability in boys. • Prenatal PFOA and PFHxS exposure is linked to higher verbal scores in girls. Accurate identification of critical windows of neurodevelopmental susceptibility to per- and polyfluoroalkyl substances (PFAS) exposure across the prenatal-to-childhood continuum carries significant public health implications. Although PFAS have been linked to neurodevelopmental impairments, the precise temporal windows of greatest susceptibility remain poorly defined. This longitudinal study followed 572 mother–child pairs and assessed PFAS exposure across five critical developmental periods, including maternal serum during early, mid, and late pregnancy; cord serum at birth; and child serum at 4–6 years of age. At the same follow-up visit, children’s intelligence quotient (IQ) was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV, CN). The associations between multiple PFAS exposures and IQ scores were then evaluated. Results indicate sex-specific neurocognitive effects. In boys, childhood exposure to specific PFAS correlated with reduced visuospatial reasoning and processing speed, identifying this period as a potential window of heightened sensitivity. In girls, higher maternal levels of perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) during mid-to-late pregnancy were associated with enhanced verbal comprehension. These findings indicate that the associations between PFAS exposure and cognitive functions differ by sex and by the timing of exposure, suggesting a greater sensitivity to childhood exposure in boys and to prenatal exposures in girls. Further research is imperative to elucidate the underlying biological mechanisms.