Exposure to metal mixtures in multiple critical periods of development and adolescent neuromotor function

在发育和青少年神经运动功能的多个关键时期接触金属混合物

• 批准号: 10464009
• 负责人: Alexa Friedman
• 金额: $ 1.99万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2022-10-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10464009
• 关键词: 14 year old; Academic achievement; Adolescence; Adolescent; Adverse effects; Affect; Age; Animals; Attention; Behavior; Biological; Biological Markers; Biology; Blood; Brain; Chemicals; Child; Childhood; Chromium; Cognition; Cognitive; Consensus; Copper; Data; Development; Elements; Emotional; Environmental Epidemiology; Environmental Hazards; Exposure to; Fellowship; Functional disorder; Funding; Goals; Hair; Hand; Health; Heterogeneity; Human; Individual; Industrial Waste; Industrialization; Industry; Intervention; Italy; Lead; Life; Link; Manganese; Measures; Mentorship; Metal exposure; Metals; Motor; Nail plate; National Institute of Environmental Health Sciences; Neuraxis; Neurodevelopmental Disorder; Neuropsychological Tests; Outcome; Performance; Personal Satisfaction; Posture; Predisposition; Pregnancy; Production; Productivity; Public Health; Quality of life; Reporting; Research; Role; Saliva; Social Development; Social Interaction; Societies; Soil; Speed; Statistical Methods; Time; Tooth structure; Toxic effect; Toxicology; Training; Tremor; United States National Institutes of Health; Urine; Work; aged; base; biomarker selection; career; cohort; community living; critical period; deciduous tooth; dexterity; early childhood; early life exposure; epidemiology study; girls; health goals; in utero; infancy; innovation; insight; metal poisoning; multidisciplinary; neurobehavioral; neurodevelopment; neurotoxicity; novel; pollutant; prenatal; prenatal exposure; secondary analysis; toxicant

Project Summary/Abstract Evidence for neurodevelopmental toxicity from exposure to environmental metals is mounting. Recent studies have found that neurotoxicity may depend on when during development the metal exposure occurs (e.g., in utero versus childhood) and that metals have synergistic adverse effects on children's neurodevelopment. Our study aims to elucidate the role of childhood environmental metal exposure on neuromotor function, a largely understudied neurodevelopmental outcome, by examining cumulative and interactive associations with a common industrial metal mixture. The proposed research in this F31 will use previously collected data from the Public Health Impact of Mixed Element exposure (PHIME) study, comprised of 720 children (ages 10-14 years) with varied airborne exposure to ferroalloy industry pollutants in Italy. Under the mentorship of a multidisciplinary team of experts in environmental epidemiology, neurobehavioral toxicology, exposure biology, statistical methods and chemical mixtures, Alexa Friedman (PI) proposes to estimate the associations of an industrially relevant metal mixture of manganese, copper, chromium and lead with neuromotor function in multiple critical periods of development. We will evaluate the relationship between metals, measured in multiple biomarkers (teeth, hair, nails, blood, saliva, urine) that represent exposure from the prenatal period through adolescence, and a battery of neuropsychological tests that evaluate motor function. We will use state- of-the-art statistical approaches, including Bayesian Kernel Machine Regression and quantile-based g- computation for metal mixtures, and hierarchical variable selection to examine biomarker selection. This research will inform our current understanding of metal associations with children's neuromotor function and provide insights for targeted interventions to reduce metals exposure. It also targets several NIEHS strategic goals including the study of co-exposures in communities living near environmental hazards and the innovative use of exposure data across critical developmental windows.

项目摘要/摘要 暴露于环境金属的神经发育毒性的证据正在固定。最近的研究 已经发现神经毒性可能取决于在发育过程中发生金属暴露时（例如，在 子宫与童年时期）和金属对儿童的神经发育有协同的不利影响。我们的 研究旨在阐明儿童环境金属暴露在神经运动功能上的作用，这在很大程度上 通过研究与A 常见的工业金属混合物。 F31中提出的研究将使用先前收集的数据 混合元素暴露（PHIME）研究的公共卫生影响，包括720名儿童（10-14岁） 在意大利，空降暴露于飞铁合金行业污染物中。在一个指导下 环境流行病学专家多学科团队，神经行为毒理学，暴露生物学， 统计方法和化学混合物，Alexa Friedman（PI）提议估计 锰，铜，铬和铅具有神经运动功能的工业相关金属混合物 在多个关键时期。我们将评估金属之间的关系，以 多种生物标志物（牙齿，头发，指甲，血液，唾液，尿液），代表从产前期间暴露 通过青春期以及评估运动功能的一系列神经心理学测试。我们将使用状态 - 艺术统计方法，包括贝叶斯内核机回归和基于分位数的G- 金属混合物的计算和分层变量选择以检查生物标志物选择。这 研究将为我们当前对金属关联与儿童的神经运动功能的了解和 提供针对性干预措施的见解，以减少金属暴露。它还针对几个NIEHS战略 目标包括研究生活在环境危害附近的社区和创新性的社区中 在关键发展窗口中使用曝光数据。