Dual-source heavy metal co-exposure impairs genetic growth potential in preschool children: a large population-based mixture analysis

Objective: Dual-source heavy metal exposure via diet and industrial take-home pathways impairs children’s growth, but population-based evidence on its independent impact on genetic growth potential remains limited. This study aimed to characterize dual-source metal mixtures, identify core toxic components, and examine whether selenium mitigates metal-related growth retardation in preschool children.

Methods: This cross-sectional study enrolled 10,242 children aged 0–7 years. Ten urinary metals (Pb, Cd, Hg, Se, Co, Mo, Cr, Mn, Cu, Ni) were quantified by ICP-MS, with creatinine standardization and Z-score transformation. Three dietary patterns were extracted via principal component analysis (PCA), and industrial/take-home exposure risk was stratified by residential distance to polluting factories and caregivers’ occupational hygiene. The primary outcome Adjusted-HAZ was defined as standardized residuals between observed and genetically predicted height-for-age Z-score (HAZ). We applied partial Spearman correlation, generalized linear models (GLM) and three mixture models (WQS, qgcomp, BKMR) to estimate mixture toxicity, with restricted cubic spline (RCS) for nonlinear thresholds, plus stratified and sensitivity analyses with full covariate adjustment and false discovery rate (FDR) correction.

Results: Source apportionment identified two distinct pathways: seafood diet correlated with elevated Hg and Se burdens, while high industrial/take-home exposure increased urinary Pb (β = 0.235, 95% CI: 0.056–0.414) and Co (β = 0.193, 95% CI: 0.046–0.340). Seven metals showed significant inverse associations with Adjusted-HAZ after FDR correction. Mixture models consistently revealed a robust overall growth-suppressing effect (WQS β = −0.320, P < 0.001), with Se, Hg, Cd, Cu and Pb as dominant contributors. Hg and Cu exhibited nonlinear inflection points, beyond which growth impairment accelerated sharply. High urinary selenium failed to counteract mixture toxicity, and all findings remained stable in sensitivity tests.

Conclusions: Dual-source heavy metal co-exposure significantly impairs children’s genetic growth potential. Selenium supplementation alone cannot alleviate growth damage; source-targeted interventions are critical to protect child growth.