Early-life Exposure to Ferroalloy Metal Mixtures and Adolescent Cognition

About This Grant

ABSTRACT Moderate-to-severe neurodevelopmental disabilities affect 1 in 10 children and adolescents worldwide. Evidence suggests that environmental contaminants, including metals, pose a substantial risk for these disorders. Industrial emissions of ferroalloys, which are metal mixtures used primarily in steelmaking, contribute to elevated environmental exposure to neuroactive metals like manganese (Mn), lead (Pb), chromium (Cr), and copper (Cu), particularly in communities living near industries. Exposure to toxic ferroalloys during stages of rapid brain development—also known as critical windows of susceptibility—can profoundly impact child neurodevelopment, with life-long consequences. Currently, data on the cumulative and life stage- specific effects of metal exposure on neurodevelopment are limited, despite research suggesting the potential for complex interplay between mixture components at various stages of development. Early-life exposure to neuroactive chemicals can shape and constrain the ways in which later development unfolds, such that a neuropsychological deficit may not fully manifest until the relevant neural systems mature. Thus, it is imperative to investigate early-life exposure to toxic metals and neurodevelopment over multiple time points in development. Under the mentorship of an established, dedicated, multidisciplinary team of experts in environmental epidemiology, exposure science, lifespan neurodevelopment, and advanced statistical methods, this proposal will leverage rich exposure data and apply state-of-the-art statistical techniques to examine the impact of exposure to metal mixtures during early-life critical windows of susceptibility on early adolescent intelligence (Aim 1), as well as associations between metal mixtures and working memory trajectories from adolescence into early adulthood (Aim 2). The NIH-funded Public Health Impact of Metal Exposure (PHIME) study is an ideal data source to investigate the proposed aims given its fine-scale exposure data during early life for 201 children exposed to varying levels of ferroalloy emissions and its comprehensive set of neurobehavioral assessments including multiple validated tests of cognitive ability collected at different stages of development. This F31 proposal targets a NIEHS strategic goal of Advancing Environmental Health Science by evaluating critical windows of susceptibility in exposure timing and pollutant co-exposure. The results of this study will inform targeted public health interventions to prevent metal exposure in vulnerable communities, particularly children residing near metalworking facilities. This fellowship will provide critical training in neurodevelopment and advanced epidemiological and statistical methods necessary to prepare the applicant for a robust career in environmental epidemiology and children’s health.