MINI REVIEW article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
This article is part of the Research TopicNeurodevelopmental disorders: current research status and future challengesView all articles
Persistent Pollutants and the Developing Brain: The Role of PFAS in Neurodevelopmental Disorders
Provisionally accepted
- 1Italian National Research Council, Institute of Biophysics (IBF), Genova, Italy
- 2Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Alessandria, Italy
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
PPer- 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.
Keywords: Neuroinflammation, cognitive development, PFOS (perfluorooctane sulfonic acid), placental transfer, Epigenetic Modulation, Endocrine disruption activity, PFOA (perfluorooctanoate)
Received: 31 Aug 2025; Accepted: 04 Nov 2025.
Copyright: © 2025 Lagostena, Magnelli, ROTONDO and Dondero. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Francesco Dondero, francesco.dondero@uniupo.it
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.