Associations of perinatal metals and metalloid exposures with early child behavioral development over time in the New Hampshire Birth Cohort Study

Abstract Background Research on the neurodevelopmental effects of metal/metalloids has focused mainly on outcomes assessed at one time point, even though brain development progresses over time. We investigated biomarkers of perinatal exposure to metal/loids and changes in child behavior over time. Methods We followed 268 participants from the prospective New Hampshire Birth Cohort Study between birth and age five years. We measured arsenic (As), copper (Cu), manganese (Mn), lead (Pb), selenium (Se) and zinc (Zn) in toenails from 6-week-old infants. The Behavioral Symptoms Index (BSI), externalizing, and internalizing symptoms were assessed using the Behavior Assessment System for Children, 2nd edition (BASC-2) at ages 3 and 5 years. Multivariable linear regression was used to estimate associations of metal/loids with behavior change, calculated as the difference in symptom raw scores between 3 and 5 years, in addition to the associations for symptom scores at 3 and 5 years separately. Sex-specific associations were also explored using stratified models and a sex-metal interaction term. Results Adjusted associations of metal/loids and change in behavior varied by exposure and outcome. Each 1 µg/g increase in toenail Cu was associated with improved behavior between 3 and 5 years [BSI: β= -3.88 (95%CI: -7.12, -0.64); Externalizing problems: β = -2.20 (95%CI: -4.07, -0.33)]. Increasing Zn was associated with increased externalizing behavior over time (β = 3.42 (95%CI: 0.60, 6.25). Sex-stratified analyses suggested more pronounced associations among boys compared to girls. Conclusions Perinatal exposure to metal/loids may alter behavioral development between ages 3 and 5 years. Findings support the need for more research on associations between metal/loids and neurodevelopment over longer time periods.