Prenatal metals and offspring cognitive development: Insights from a large-scale placental bioassay study

The developing foetus is particularly sensitive to neurotoxic metals. The placenta is considered an ideal tissue for biomonitoring prenatal cumulative metal exposure. Based on the Ma'anshan Birth Cohort study (MABC) in China, this study investigated associations of non-essential metals and essential metals in placenta, including arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), cobalt (Co), selenium (Se) and zinc (Zn), with cognitive development in children among 1586 mother-child pairs. Also, we explored potential interactions between the metals and modifying role of the sex. Children's cognitive development was tested at preschool age using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Analyses used multiple linear regression, Bayesian kernel machine regression (BKMR), the quantile g-computation (Qgcomp), interaction and marginal effects models, and restricted cubic spline in R and STATA. In this study, the geometric means [GMs (SD)] for placental metal concentrations were 8.10 (7.54) ng/g for As, 32.32 (29.20) ng/g for Cd, 11.89 (13.33) ng/g for Hg, 32.21 (28.24) ng/g for Pb, 15.05 (8.91) ng/g for Co, 508.82 (192.35) ng/g for Se, 18481.60 (14030.61) ng/g for Zn. In individual models, placental As levels were negatively associated with the Fluent Reasoning Index (FRI) in the overall sample. Cd levels were negatively associated with the full-scale intelligence quotient (FSIQ), the Verbal Comprehension Index (VCI) and the Visual Spatial Index (VSI). The four metal mixture (As, Cd, Hg and Pb) was negatively associated with FSIQ, VCI, VSI and FRI. Placental Cd and As were the largest contributors to the negative mixture association on the FSIQ. The negative associations of placental As, Cd and Hg with FSIQ in children were gradually attenuated with increasing Zn and Se. After stratifying by sex, the individual and mixture associations between elevated placental non-essential metal exposures and reduced cognitive scores were significant only in boys. Zn and Se were the major contributors to the positive mixture associations on the FSIQ. In summary, prenatal exposure to As, Cd and Hg has sex-specific adverse associations on children's cognitive development. A more accurate assessment of the necessity of prenatal supplementation of micronutrients including Zn and Se is needed.