Associations between Prenatal Heavy Metal Mixture Exposure and Child Growth Outcomes from Birth to 24 Months: Results from the Korean Children’s Environmental Health Study (Ko-CHENS)

Abstract

Objectives: During pregnancy, toxic heavy metals are encountered as mixtures in real-world environments; however, evidence regarding the effects of such mixed exposures on neonatal and early infant growth remains limited. This study aimed to evaluate the associations between prenatal heavy metal mixture exposure and child growth outcomes from birth to 24 months.Methods: We analyzed 4,978 mother–infant pairs from the Korean Children’s Environmental Health Study (Ko-CHENS). Prenatal blood concentrations of lead (Pb), mercury (Hg), and cadmium (Cd) were measured. Weight was assessed at birth and at 6, 12, and 24 months, whereas head circumference was assessed at 6, 12, and 24 months. Mixture effects were evaluated using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR).Results: Higher levels of prenatal heavy metal mixture exposure were associated with decreased birth weight, an effect primarily driven by cadmium. Head circumference showed consistent reductions at 6, 12, and 24 months, predominantly attributable to lead. Nonlinear patterns were observed in some exposure–response relationships. Even when the levels of other metals were held constant, cadmium consistently exhibited the strongest negative association with birth weight, while lead showed the greatest negative effect on head circumference. No significant interactions among the three metals were observed.Conclusions: Prenatal exposure to a mixture of heavy metals was associated with lower birth weight and smaller head circumference during infancy. These findings underscore the value of considering co-occurring metal exposures and multiple growth indicators across early-life time points when evaluating potential health implications of prenatal environmental exposures. Given the observational design, the findings should be interpreted as associations, and head circumference as an anthropometric growth indicator rather than a direct measure of brain growth or neurodevelopment.