Prenatal exposure to mixtures of heavy metals and neurodevelopment in infants at 6 months

Background: Exposure to mixture of neurotoxic metals such as lead, mercury and cadmium occurs at a specific point of time. When exposed to metal mixtures, one metal may act as an agonist or antagonist to another metal. Thus, it is important to study the effects of exposure to a combination of metals on children's development using advance statistical methods. Objectives: In this study, we explored the effects of prenatal metal exposure including lead, mercury and cadmium in early pregnancy (12-20 weeks), late pregnancy (> 28 weeks), and at birth on neurodevelopment of infants at 6 months of age. Methods: We included 523 eligible mother-child pairs from the mothers and children environmental health (MOCEH) study, a prospective birth cohort study in Korea. We used linear regression, Bayesian kernel machine regression (BKMR) and generalized additive models (GAM), to evaluate the effects of exposure to metal mixtures on neurodevelopment of infants aged 6 months. The Korean version of Bayley scale of infant and toddler development-II was used to measure the child's neurodevelopment. Results: Linear regression models showed a significant negative effect of lead exposure during late pregnancy on the mental development index (MDI) [beta = -2.51 (-4.92, -0.10)] scores of infants aged 6 months following co- exposure to mercury. Further, linear regression analysis showed a significant interaction between late pregnancy lead and mercury concentrations. BKMR analysis showed similar results as those obtained in linear regression models. These results were also replicated in the GAM. Stratification analysis showed that greater than 50 percentile concentration of mercury in late pregnancy potentiated the adverse effects of lead in late pregnancy on MDI [beta = -4.33 (-7.66, -1.00)] and psychomotor development index (PDI) [beta = -5.30 (-9.13, -1.46)] at 6 months of age. Prenatal cadmium exposure did not show a significant association with MDI and PDI at 6 months in the linear regression or BKMR analysis. Conclusion: Based on all the statistical methods used, we demonstrated the effect of combined exposure to metals on the neurodevelopment of infants aged 6 months, with significant interaction between lead and mercury.