Associations of metals and neurodevelopment: a review of recent evidence on susceptibility factors.

Purpose of review: Epidemiologic evidence exists that many metals are associated with adverse neurobehavioral effects in young children, including lead (Pb), methylmercury (meHg), manganese (Mn) and arsenic (As)^5-8. Importantly, chemical insult can vary depending on host factors and exposure circumstance. This systematic review summarizes the recent literature investigating modifying factors of the associations between metals and neurodevelopment, including immutable traits (sex or genetics) or exposure conditions (timing or co-exposures).

Recent findings: Of the 53 studies included in this review, the number investigating modification of exposure effects were: 30 for sex, 21 for co-exposures, 12 for timing of exposure, and six for genetic modifiers. Sex-specific effects of metal-neurobehavioral associations were inconclusive for all metals, likely due to the heterogeneity of outcome domains assessed and the exposure time points measured. Seven studies evaluated both sex and exposure timing as modifying factors using deciduous teeth or other biomarkers with repeated measures to characterize metals exposure over time. Only five studies used statistical methods for mixtures to evaluate associations of more than two metals with neurobehavioral domains.

Summary: Despite the expansion of research on susceptibility to the neurodevelopmental effects of metals exposure, considerable gaps remain. This work remains critical, as characterizing susceptible subpopulations can aid in identifying biological mechanisms and is fundamental for the protection of public health.