Executive functions in urban Hispanic/Latino youth: exposure to mixture of arsenic and pesticides during childhood

点击翻译按钮获取中文摘要

Project Summary/Abstract Neurodevelopmental disabilities (NDD) are on the rise in the United States and worldwide but remain underdiagnosed among Hispanic/Latino children partly due to insufficient research on environmental risk factors. Inorganic arsenic (As) is a known neurotoxicant at higher exposure levels. Chronic levels of pesticides are also neurotoxic, affecting child cognition when exposure occurs in the prenatal period. But the relative contribution of lower levels of As and chronic common-use pesticide (chlorpyrifos and pyrethroids) exposure in urban Hispanic/Latino youth is unclear. It is also not well understood how childhood exposures affect executive function (EF) during adolescence, a critical window of susceptibility underpinned by the maturation of brain areas like the prefrontal cortex. As and pesticides accumulate mostly in EF-dominated brain regions. Combined effects produce more decreases in neurons and larger accumulations in brain regions than when examined individually. Deficits in domains of EF underlie NDDs. While there is a biological rationale and evidence of the proposed association, there are no longitudinal studies of the independent and mixture effects of childhood chlorpyrifos, pyrethroids, and low-level As, exposure on EF of urban Hispanic/Latino adolescents. This proposal will leverage a school cohort in Montevideo, a highly urban, South American city with exposure to many pollutants. The Salud Ambiental Montevideo (SAM) cohort provides an excellent opportunity to fulfill the proposed aims by providing biomarkers of exposure to As, chlorpyrifos and pyrethroids, multiple measures of EF (seven domains and three composite scores from the NIH Cognitive Toolbox), and rich contextual factors collected at the family and neighborhood levels on 421 participants aged 11-18 years. Aim 1 will estimate the association of As exposure in childhood and adolescence on adolescent EF. Aim 2 will estimate the association of chlorpyrifos and pyrethroids exposure in childhood and adolescence on adolescent EF. Aim 3 will investigate the association of the three exposures combined on EF during adolescence by employing novel statistical models of mixture effects. Accomplishing these aims will have a positive impact on urban Hispanic/Latino children from the US and Latin America by: (1) Laying a foundation of research on environmental risk factors for NDDs in disadvantaged urban communities, (2) A better recognition of the effects of real-world co-exposures to pollutants and (3) informing educational programs that will lead to better-informed caregivers, health and education systems to provide appropriate care, as well as preventive programs to lower exposure among communities that are both disproportionately exposed to and affected by environmental toxicants.