Prospective studies examining early maternal exposure to trace metal (TM) mixtures and their effects on offspring remain limited. We analyzed data regarding maternal plasma trace metal concentrations and bone mineral density (BMD) for 220 children aged 3-6 years from the Guangxi Zhuang Birth Cohort. Inductively coupled plasma-mass spectrometry was used to measure 22 trace metal concentrations-Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Sb, Cs, Ba, W, Tl, Pb, and U-in maternal plasma samples collected before 13 weeks of gestation. BMD Z-scores in children were assessed using quantitative ultrasound. Generalized linear models, restricted cubic spline (RCS) models, principal component analysis, Bayesian kernel machine regression, and quantile-based g-computation (qgcomp) were used to evaluate the associations between maternal plasma metal levels and BMD Z-scores in the child. Higher maternal Fe concentration was correlated with lower child BMD Z-scores (β [95% confidence interval]: - 1.374 [- 2.426 to - 0.323], p = 0.011). Increased Pb exposure was correlated with higher Z-scores (β [95% CI]: 1.035 [0.150-1.920], p = 0.023), corroborated by the RCS model (p = 0.031). Ti levels exceeding the median were associated with increased BMD Z-scores (p = 0.027). Increased BMD in children was associated with higher levels of metal mixtures, including Mn, V, Ti, U, Ni, Zn, Sr, Pb, W, and Co. Pb appears to play a primary role in this effect. TM exposure during early pregnancy is associated with BMD in children
however, additional longitudinal and experimental studies are required to confirm this conclusion.