Effects of Prenatal Essential and Toxic Metal Exposure on Children's Neurodevelopment: A Multi-Method Approach

The impact of prenatal exposure to trace metal mixtures on children's neurodevelopment remains debated. Many studies treat all trace metals as a single entity, overlooking the distinct biological roles of essential and toxic metals. This approach may highlight overall exposure but fails to capture their differential effects on neurodevelopment. This study aims to examine the associations between prenatal exposure to essential and toxic metals and children's cognitive development, focusing on their independent effects. A cohort of 201 mother-infant pairs was analyzed. Maternal urinary metal levels were measured at 12 weeks of gestation, and children's neurodevelopment was assessed at 4 years using the Wechsler Preschool and Primary Scale of Intelligence and the Developmental Neuropsychological Assessment. Generalized Additive Models (GAM), Restricted Cubic Spline (RCS), and Weighted Quantile Sum (WQS) regression were applied. GAM identified non-linear associations between essential metals (manganese and molybdenum) and cognitive outcomes, including verbal comprehension index (VCI), working memory index, full-scale IQ, and general ability index, which were confirmed by RCS. No non-linear relationships were observed for toxic metals. WQS showed negative associations between toxic metals and VCI (b = -1.07), processing speed index (b = -0.98), vocabulary acquisition index (b = -1.25), and verbal fluency (b = -0.23), mainly driven by cadmium (Cd) and antimony (Sb). Essential metal mixtures were not associated with cognitive outcomes. Prenatal exposure to toxic metals negatively affects children's cognitive and neuropsychological development. Reducing maternal exposure during pregnancy is essential for protecting offspring development.