Associations of Prenatal Per- and Polyfluoroalkyl Substance Exposure with Neonatal Birth Weight z-Scores: The Potential Mediating Role of Maternal Glucose Homeostasis.

Abstract

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with impaired fetal growth, yet evidence regarding mixture effects and the potential mediating role of maternal glucose homeostasis remains limited. We examined these associations in 642 mother-infant pairs from a prospective birth cohort in Ma'anshan, China. Multivariable linear regression (MLR) was used to assess associations of individual PFAS with neonatal birth weight z-scores (BW-z) and maternal glucose homeostasis. Weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR) were applied to characterize cumulative mixture effects. Sex-stratified analyses were conducted to evaluate potential effect modification. PFNA, PFDA, PFOS, L-PFHxS, 6:2 Cl-PFESA, and 8:2 Cl-PFESA were negatively associated with BW-z, with stronger negative associations observed in female infants. Mixture analyses further supported an overall negative association between PFAS mixture exposure and BW-z. Several PFAS were positively associated with 1-h and 2-h glucose levels, whereas PFNA, PFDoA, and 8:2 Cl-PFESA were negatively associated with fasting plasma glucose (FPG); in turn, higher FPG was associated with increased BW-z. Mediation analyses suggested statistically significant indirect effects through FPG in the associations of 8:2 Cl-PFESA and PFNA with BW-z, although the mediation proportions were modest at 11.5% and 9.5%, respectively. These findings suggest that prenatal PFAS exposure is associated with reduced BW-z, particularly among female infants, and that altered fasting glucose may represent one possible, but not primary, pathway linking selected PFAS to fetal growth.