Prenatal exposure to per- and polyfluoroalkyl substances and neurodevelopment trajectory: towards early warning via cohort- and metabolomics-based risk ranking

作者：Chang Gao, Ruonan Li, Hongyan Wu, Zhenzhen Xie, Weitian Tang, Yuanyuan Hou, Lin Tao, S. Zhang, Jia Lv, Tianrui Gao, Xiu‐Hong Meng, Maohua Miao, Wei Yuan, De‐Xiang Xu, Hong Liang, Yichao Huang · 发表于：BMJ Mental Health · 年份：2025 · DOI：10.1136/bmjment-2025-301912 · 被引用次数：4 · 研究领域：Per- and polyfluoroalkyl substances research、Fluorine in Organic Chemistry、Effects and risks of endocrine disrupting chemicals

Background Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may adversely affect neurodevelopment, but comparative risks and metabolic disruptions remain unclear. Objective To integrate various levels of evidence and illustrate the relationship between prenatal PFAS exposure and neurodevelopmental trajectories in children. Methods In the Shanghai-Minhang birth cohort, maternal PFAS were measured from plasma collected at 12–16 weeks’ gestation. Neurodevelopment was assessed at 6, 12 and 48 months using the Ages and Stages Questionnaire-3 and group-based trajectory modelling was performed. Associations between PFAS (co-)exposure and neurodevelopment were evaluated using logistic regression and mixture model effects. Metabolomic perturbations of PFAS with potential neurodevelopmental effects were analysed in PC12 neuronal cells. Findings Among 412 mother-child pairs, higher PFAS exposure was linked to suboptimal development in communication (highest vs lowest tertile: OR PFHxS =2.96, 95% CI 1.05 to 8.35, p trend =0.064; OR PFOS =3.45, 95% CI 1.27 to 9.43, p trend =0.012), personal-social (highest vs lowest tertile: OR PFNA =2.41, 95% CI 1.05 to 5.56, p trend =0.036), and total score (highest vs lowest tertile: OR PFOS =2.32, 95% CI 1.09 to 4.91, p trend =0.028) across early childhood. Metabolomic analysis revealed disrupted excitatory/inhibitory (E/I) neurotransmission. Integrated toxicological assessment, including exposure risk information, toxicogenomic signatu...