Prenatal placental metal accumulation and its association with child attention deficit/hyperactivity disorder and autism spectrum disorder symptom at 3 years of age: The role of psychosocial-environmental support in infancy.

The placenta is recognized as a barrier to the passage of harmful substances and is an ideal biomonitoring sample for assessing cumulative prenatal exposure to metals. However, scientific knowledge is insufficient regarding the effects of cumulative prenatal exposure to metal mixtures on behavioral development in early life. This study included 2,154 mother-infant pairs from the Ma'anshan Birth Cohort study. Concentrations of eleven metals in the placenta were quantified, and attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) symptom were assessed in 3-year-old children. Thrive factor (T-factor) scores, derived from factors such as breastfeeding, sleep, parenting style, secondhand smoke exposure, family income, and parental absence, were calculated during infancy. It was found that elevated concentrations of cadmium (Cd) (OR: 1.36, 95% CI: 1.06, 1.75), manganese (Mn) (OR: 1.34, 95% CI: 1.02, 1.77), and copper (Cu) (OR: 1.53, 95% CI: 1.05, 2.23) in the placenta were associated with increased ADHD risk in children. Additionally, arsenic (As) showed a moderate association with ADHD risk (OR: 1.34, 95% CI: 0.99, 1.83). Results from the Bayesian Kernel Machine Regression (BKMR) model indicated significant positive associations between the mixture of placental metals and ADHD symptom risk when all eleven metal concentrations were elevated. The quantile-based g-computation (Qgcomp) approach also suggested a nearly significant association between the total mixture of eleven metals/elements and ADHD symptom risk (OR: 1.27, 95% CI: 0.97, 1.65). Among the metals, Cd was the largest contributor to the positive association, followed closely by Cu, cobalt (Co), Mn, mercury (Hg), As, and chromium (Cr). Conversely, zinc (Zn) was the largest contributor to the negative association, followed by selenium (Se) and lead (Pb). Further analysis revealed that a simultaneous increase in metal concentrations (Cd, Cu, Co, Mn, Hg, As, and Cr) by one quartile was significantly associated with ADHD symptom risk (OR: 1.31, 95% CI: 1.03, 1.69). Moreover, higher T-factor scores, composed of breastfeeding, sleep, parenting style, secondhand smoke exposure, household income, and parental absence, were significantly associated with decreased ADHD and ASD symptom risk at age 3. We observed a gradual attenuation or even disappearance of the associations of placental Cu and Mn with ADHD symptom as T-factor scores increased. Our findings suggest that Cd, Cu, and Mn are key metals associated with ADHD risk in early life, and that psychosocial environmental factors in infancy are potential modifiers of these associations.