Per- and polyfluoroalkyl substances in breast milk and child growth trajectories during the first two years: A prospective birth cohort study in Nanjing, China.

Breast milk is a key source of infant per- and polyfluoroalkyl substances (PFAS) exposure, yet its influence on longitudinal child growth and the underlying mechanisms remain unclear. In this prospective study of 286 mother-child pairs from the Nanjing Birth Cohort (2021-2022), 23 PFASs were measured in breast milk. Child weight, length, and head circumference were assessed at 3, 6, 12, 18, and 24 months and converted to age-specific z-scores. Group-based trajectory modeling identified growth patterns, and their associations with PFAS were evaluated using multinomial logistic regression. A metabolome-wide association study (MWAS) with mediation analysis was performed to explore potential mechanisms. Fifteen PFASs were detected. Elevated levels were associated with a low-stable trajectory for weight-for-age z-score (WAZ) and a high-stable trajectory for length-for-age z-score (LAZ), a pattern supported by mixture analysis. For weight-for-length z-score (WLZ), perfluorocarboxylic acid (∑7PFCAs) was linked to a low-falling trajectory, while emerging PFASs showed an inverse association with a high-falling trajectory. Emerging PFASs were also associated with a low-stable trajectory for head-circumference-for-age z-score (HCZ). MWAS identified 123 metabolites associated with both PFAS exposure and growth trajectories. Enrichment analysis highlighted the "Biosynthesis of unsaturated fatty acids" pathway, which significantly mediated the effects of ∑7PFCAs and ∑15PFAS on the WLZ low-falling trajectory, accounting for 25.5% and 37.8% of the total effects, respectively. In conclusion, lactational PFAS exposure is associated with distinct growth trajectories, including lower weight, greater length, declining weight-for-length, and smaller head circumference. These effects appear partially mediated by breast milk metabolomic perturbations, providing novel mechanistic insights.