Maternal psychological distress modifies the association between prenatal exposure to per- and polyfluoroalkyl substances and infants' neurodevelopment.

Prenatal PFAS exposure and maternal psychological distress may adversely affect child neurodevelopment through shared biological pathways, such as hypothalamic-pituitary-adrenal (HPA) axis disruption and pro-inflammatory responses. However, whether psychological distress modifies PFAS-related neurodevelopmental risks remains unclear. Using data from the Shanghai Birth Cohort including 1779 mother-child pairs, we measured maternal PFAS levels during the first trimester and assessed maternal psychological distress (perceived stress, depression, and anxiety) during the second trimester. Child neurodevelopment was evaluated at 6 months of age using the Ages & Stages Questionnaires-Third Edition (ASQ-3). Multivariable regression models and quantile g-computation were conducted to evaluate the associations of ASQ-3 scores with individual and mixture PFAS. Stratified analyses were conducted between the psychological distress positive group (experienced any one type of stressor) and negative group (experienced no stressors). We found that 41 % of pregnant women experienced at least one type of psychological distress. Among the overall participants, maternal PFAS exposure was associated with reduced gross motor scores in children. Maternal psychological distress status modified the association between PFAS and gross motor scores. Specifically, the adverse associations of PFAS with gross motor development were only observed in the psychological distress positive group, while no association was found in the negative group. Significant interaction effects were observed between maternal psychological distress and most PFAS compounds (all P for interaction <0.1). Furthermore, the adverse associations of prenatal PFAS exposure with gross motor development intensified in women experiencing multiple types of psychological stressors. This study indicates that maternal psychological distress may increase the risk of PFAS-related adverse gross motor development in six-month-old children. Investigating maternal psychological distress could be crucial for identifying vulnerable populations and guiding intervention measures.