Persistent pollutants and the developing brain: the role of PFAS in neurodevelopmental disorders

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of highly

persistent organofluorine compounds, and extensively used in industrial and

consumer application. Their environmental ubiquity and bioaccumulation in

humans have raised concerns about potential health impacts, particularly

on neurodevelopment. This mini-review synthesizes epidemiological and

experimental research published between 2020 and 2025 examining prenatal

PFAS exposure and neurodevelopmental outcomes in children. Prospective

birth cohort studies from Europe, North America, and Asia report subtle but

statistically significant associations between higher maternal PFAS levels and

a range of neurodevelopmental disorders (NDDs), including autism spectrum

disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), cognitive

delays (e.g., reduced IQ, language impairments), and behavioral dysregulation.

Mechanistic investigations reveal that PFAS can cross the placenta, alter

maternal–fetal thyroid and sex-steroid hormone homeostasis, activate

inflammatory pathways (e.g., AIM2 inflammasome), disrupt neurotransmitter

systems (notably dopaminergic and GABAergic signaling), modulate fetal

metabolomic profiles, and induce durable epigenetic modifications. Key

methodological challenges include heterogeneity of PFAS mixtures, reliance

on single-time-point exposure assessments, variable confounder control (e.g.,

socioeconomic status, maternal IQ, nutrition, breastfeeding), limited follow-up

into later childhood or adolescence, and sparse data on emerging short-

chain PFAS analogs. To strengthen causal inference and inform public health

interventions, future research should employ longitudinal designs with repeated

biomonitoring, standardized neuropsychological assessments, advanced

mixture-modeling approaches, comprehensive confounder adjustment,

inclusion of vulnerable populations, and focused evaluation of replacement

PFAS. Coordinated efforts bridging epidemiology, mechanistic science, and

regulatory policy are essential to mitigate PFAS exposure and safeguard

neurodevelopmental health in future generations.