Fetal and postnatal metal metabolism–related changes in brain function are associated with childhood behavioral deficits

Exposure to neurotoxic metals early in life can disrupt brain development and increase risk of later mental health problems, but vulnerable periods and underlying mechanisms remain unclear. We examined how early life exposures to mixtures of metals affect children's brain and behavior using naturally shed "baby" teeth as a biomarker of direct exposure. We studied 489 children aged 8 to 14 years and reconstructed weekly concentrations of nine metals from 20 weeks before birth to 40 weeks after birth. We assessed behavior using standardized questionnaires and measured brain structure and function with magnetic resonance imaging. Using lagged weighted quantile sum regression, we identified sensitive developmental windows during which higher exposure to metal mixtures was linked to more behavioral problems, smaller brain volume, reduced brain global efficiency, and weaker white matter integrity. Findings suggest that the developing brain is especially vulnerable to metals in early life, with lasting effects into adolescence.