Prenatal exposure to a mixture of elements and neurobehavioral outcomes in mid-childhood: Results from Project Viva

Background: Lead (Pb), manganese (Mn), selenium (Se) and methylmercury (MeHg) can be neurotoxic individually, despite Mn and Se also being essential elements. Little is known about the joint effects of essential and non-essential elements on neurobehavior, particularly for prenatal exposures. Objectives: To evaluate associations of prenatal exposure to multiple elements with executive function and neurobehavior in children. Methods: Participants included 1009 mother-child pairs from the Project Viva pre-birth cohort. We estimated maternal erythrocyte Pb, Mn, Se, and Hg concentrations prenatally. In 6-11-year old children (median 7.6 years), parents and teachers rated children's executive function-related behaviors using the Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite score and behavioral difficulties using the Strengths and Difficulties Questionnaire (SDQ) total difficulties score. We evaluated associations of element mixtures with neurobehavior using Bayesian kernel machine regression (BKMR), multivariable linear regression, and quantile g-computation. Results: Median erythrocyte Pb, Mn, Se, and Hg concentrations were 1.1 μg/dL, 33.1 μg/L, 204.5 ng/mL, and 3.1 ng/g, respectively. Findings from BKMR and quantile g-computation models both showed worse (higher) parent-rated BRIEF and SDQ z-scores with higher concentrations of the mixture, although estimates were imprecise. When remaining elements were set at their median within BKMR models, increases in Pb and Se from the 25th to 75th percentile of exposure distributions were associated with 0.08 (95% CI: 0.02, 0.19) and 0.07 (95% CI: 0.03, 0.16) standard deviation increases in parent-rated BRIEF scores, and 0.08 (95% CI: 0.02, 0.17) and 0.05 (95% CI: 0.03, 0.13) standard deviation increases in SDQ scores, respectively. There was no evidence of element interactions. Discussion: Although associations were small in magnitude, we found a trend of worsening neurobehavioral ratings with increasing prenatal exposure to an element mixture. However, we may be observing a limited range of dose-dependent impacts given the levels of exposure within our population.