Impact of prenatal exposure to per- and polyfluoroalkyl substances on developmental delays in 4-year-old children: The Japan Environment and Children’s study

Although per- and polyfluoroalkyl substances (PFAS) have raised global concern due to their adverse effects on children's development, the association between prenatal exposure to PFAS and the achievement of developmental milestones in preschool children remains unclear. This study aimed to examine the individual and cumulative associations between prenatal PFAS and developmental delay in 4-year-old children. We used data from 15,131 mothers (15,175 children) in the Japan Environment and Children Study (JECS), an ongoing nationwide prospective birth cohort. Among 28 PFAS measured in maternal plasma, eight with detection frequencies ≥ 60 % were analyzed. Developmental delays were assessed using the Japanese version of the Ages and Stages Questionnaires third edition (JASQ-3), a self-administered screening tool, with suspicion of developmental delay indicated by total scores falling below the Japanese version cutoffs for the five JASQ-3 domains (communication, gross motor, fine motor, problem solving, and personal-social). Univariate and multivariable logistic regression analysis and quantile g-computation were applied. Findings revealed that these eight PFAS were not significantly associated with higher odds of developmental delay across any JASQ-3 domain, nor did their combined effects. However, the effects of PFAS substances not measured in this study and the impact of continued postnatal exposure to PFAS on developmental delays remain a concern. Continuous investigation of the effects of PFAS on development throughout the lifespan is necessary.