Prenatal exposure to per- and polyfluoroalkyl substances and child bone mineral density from the Shanghai Birth Cohort

Limited evidence is available for the association between prenatal per- and polyfluoroalkyl substances (PFAS) exposure and childhood bone mineral density (BMD). Among 755 mother-child pairs in the Shanghai Birth Cohort, ten PFAS were measured in first-trimester maternal plasma using high-performance liquid chromatography/tandem mass spectrometry, and childhood lumbar spine BMD was assessed using dual-energy X-ray absorptiometry. Multivariable linear regression, Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) were applied. In the overall analyses, PFHpA was suggestively associated with higher total BMD (β = 0.13; 95% CI: 0.00, 0.27). Sex-stratified analyses indicated possible differences by sex. Among girls, PFDA and PFDoA showed inverse associations with total BMD (β = -0.29; 95% CI: -0.57, 0.00 and β = -0.27; 95% CI: -0.50, -0.04, respectively). Among boys, PFHpA showed a positive association with total BMD (β = 0.20; 95% CI: 0.04, 0.37). BKMR analyses suggested that mixture effects tended to be inverse among girls and positive among boys at higher quantiles. In qgcomp models, the positive association was most evident for L3 BMD among boys (β = 0.23; 95% CI: 0.00, 0.45). Our findings provide preliminary evidence that prenatal PFAS exposure may be associated with childhood BMD, with possible sex-specific patterns.