Mixtures of Metals and Micronutrients in Early Pregnancy and Cognition in Early and Mid-Childhood: Findings from the Project Viva Cohort

The developing fetal brain is sensitive to many environmental exposures. However, the independent and joint effects of prenatal exposure to metals and micronutrients on child cognition are not well understood. Our aim was to evaluate associations of first-trimester ( wk) maternal erythrocyte concentrations of mixtures of nonessential and essential metals and micronutrients with early ( y) and mid-childhood ( y) cognitive test scores in Project Viva, a prebirth cohort in Boston, Massachusetts, USA. We measured concentrations of five essential metals (Cu, Mg, Mn, Se, Zn) and two micronutrients (vitamin B12 and folate), together termed the "nutrient mixture," as well as six nonessential metals (As, Ba, Cd, Cs, Hg, Pb), together termed the "neurotoxic mixture," in first-trimester ( wk) maternal erythrocytes (metals) or plasma (micronutrients). We assessed visual-motor function and receptive vocabulary in early childhood ( y), and visual-motor function, visual memory, and fluid and crystallized intelligence in mid-childhood ( y). We employed adjusted quantile g-computation and linear regression to estimate mixture and individual component associations, respectively. Analyses included 900 mother-child pairs (74% college graduates; 52% male children). In mixture analyses, a quartile increase in the nutrient mixture was associated with a mean difference in early childhood receptive vocabulary score of 1.58 points [95% confidence interval (CI): 0.06, 3.10], driven by Zn and Se. A quartile increase in the neurotoxic mixture was associated with a mean difference in mid-childhood visual-motor score of points (95% CI: , ), driven by Ba and Cs. Linear regressions supported quantile g-computation findings for mixture component contributions. Maternal circulating concentrations of several essential (Zn and Se) and nonessential (Ba and Cs) metals were associated with some domains of child cognition. In this folate-replete cohort, first-trimester circulating concentrations of known neurotoxic metals, such as Pb, were not associated with child cognition. https://doi.org/10.1289/EHP12016.