Choi Jeong Weon, Parenti Mariana, Slupsky Carolyn M, Tancredi Daniel J, Schmidt Rebecca J, Shin Hyeong-Moo
Department of Environmental Science, Baylor University, Waco, TX, USA.
Department of Nutrition, University of California, Davis, Davis, CA, USA.
Environ Pollut. 2025 Jul 9;383:126811. doi: 10.1016/j.envpol.2025.126811.
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to altered neurodevelopment in children, but the contribution of maternal metabolic disruption to this relationship remains unclear. We investigated associations between prenatal PFAS exposure, maternal metabolism, and child neurodevelopment. We analyzed 172 mother-child pairs from the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort. Nine PFAS were measured in maternal serum collected during pregnancy. Metabolites were quantified in third-trimester serum and placental tissue using proton nuclear magnetic resonance (H-NMR) spectroscopy. At age three, children were clinically classified as having autism spectrum disorder (ASD), typical development (TD), or non-typical development (non-TD), the latter including children with atypical developmental features who do not meet the criteria for ASD. Multiple linear regression assessed associations between individual PFAS and metabolites, and quantile-based g-computation evaluated PFAS mixture effects. Principal component analysis (PCA) summarized metabolomic profiles. One-way analysis of covariance (ANCOVA) and multinomial logistic regression examined associations between metabolites and child neurodevelopment. Correlation network analysis explored relationships among PFAS, serum, and placental metabolites. After multiple comparison correction, perfluorooctane sulfonate (PFOS) was significantly associated with serum 2-hydroxybutyrate (q < 0.10). Higher perfluorooctanoate (PFOA), PFOS, and PFAS mixture levels were associated with lower serum PC-2 scores. Higher serum PC-3 score, reflecting mitochondrial dysfunction, was associated with increased non-TD risk. Network analysis identified 2-hydroxybutyrate as a key serum metabolite potentially linked to PFAS and placental amino acids. Prenatal PFAS exposure was associated with maternal metabolic alterations; however, no clear linkage to child neurodevelopment were observed. These findings suggest the need to consider gene-environment interactions in studies of neurodevelopmental outcomes.
产前暴露于全氟和多氟烷基物质（PFAS）与儿童神经发育改变有关，但母体代谢紊乱对这种关系的影响尚不清楚。我们调查了产前PFAS暴露、母体代谢和儿童神经发育之间的关联。我们分析了来自MARBLES（婴儿自闭症风险标志物——早期学习迹象）队列的172对母婴。在孕期采集的母体血清中测量了9种PFAS。使用质子核磁共振（H-NMR）光谱对孕晚期血清和胎盘组织中的代谢物进行定量。在3岁时，儿童被临床分类为患有自闭症谱系障碍（ASD）、典型发育（TD）或非典型发育（非TD），后者包括具有非典型发育特征但不符合ASD标准的儿童。多元线性回归评估了个体PFAS与代谢物之间的关联，基于分位数的g计算评估了PFAS混合物的影响。主成分分析（PCA）总结了代谢组学特征。单因素协方差分析（ANCOVA）和多项逻辑回归检验了代谢物与儿童神经发育之间的关联。相关网络分析探索了PFAS、血清和胎盘代谢物之间的关系。经过多重比较校正后，全氟辛烷磺酸（PFOS）与血清2-羟基丁酸显著相关（q < 0.10）。较高的全氟辛酸（PFOA）、PFOS和PFAS混合物水平与较低的血清PC-2评分相关。反映线粒体功能障碍的较高血清PC-3评分与非TD风险增加相关。网络分析确定2-羟基丁酸是一种关键的血清代谢物，可能与PFAS和胎盘氨基酸有关。产前PFAS暴露与母体代谢改变有关；然而，未观察到与儿童神经发育的明确联系。这些发现表明在神经发育结局研究中需要考虑基因-环境相互作用。
