Associations between maternal exposure to per- and polyfluoroalkyl substances and childhood neurodevelopment up to age 4: The Japan environment and children's study

The link between maternal per- and polyfluoroalkyl substances (PFAS) exposure during pregnancy and child development is inconclusive. Addressing this requires better evaluation methods for mixed PFAS exposures and ensuring comparable outcomes. It is important to assess if PFAS mixtures affect developmental outcomes based on evaluation methods or timing.

The study included 4,585 participants from the Japan Environment and Children's Study sub-cohort. Maternal plasma PFAS exposure was assessed from the main cohort participants using liquid chromatography-tandem mass spectrometry. Of 28 PFAS compounds, eight detected in over 60 % of samples were selected. Single PFAS concentrations and an item response theory-based PFAS burden score were applied. Outcomes were assessed using the Kyoto Scale of Psychological Development (KSPD) at 2 and 4 years. Ages and Stages Questionnaires (ASQ-3) at eight-time points until 4 years, with trajectory groups formed growth mixture modeling from ASQ-3 data. Linear and multinomial logistic regression models adjusted for relevant covariates were used.

Positive associations were consistently observed between PFAS (e.g., PFAS burden score, PFNA, PFUnA, PFDoA, PFTrDA) and general and language development in KSPD at 2 and 4 years. Only one negative association was observed between PFHxS and gross motor development in KSPD at age 2. The ASQ-3 trajectory analysis maintained these trends but did not find any significance. No sex-specific differences were detected in KSPD and ASQ-3 trajectory analysis.

Prenatal PFAS exposure was associated with improved overall development and language-social scores at 2 and 4 years. Only one negative association was observed between PFHxS and gross motor development in KSPD at age 2.