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.

项目概要/摘要 越来越多的证据表明暴露于环境金属会导致神经发育毒性。最近的研究 发现神经毒性可能取决于发育过程中金属暴露发生的时间（例如，在 子宫内与童年），并且金属对儿童的神经发育具有协同不利影响。我们的 研究旨在阐明儿童环境金属暴露对神经运动功能的影响，这在很大程度上是 通过检查与神经发育结果的累积和交互关联，对神经发育结果进行了充分研究 常见的工业金属混合物。 F31 中拟议的研究将使用之前从 混合元素暴露对公共卫生的影响 (PHIME) 研究由 720 名儿童（10-14 岁）组成 意大利铁合金工业污染物的空气暴露程度各不相同。在一个人的指导下 环境流行病学、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）建议估计 具有神经运动功能的工业相关的锰、铜、铬和铅金属混合物 处于发展的多个关键时期。我们将评估金属之间的关系，以 代表产前时期暴露的多种生物标志物（牙齿、头发、指甲、血液、唾液、尿液） 整个青春期，以及一系列评估运动功能的神经心理学测试。我们将使用状态- 最先进的统计方法，包括贝叶斯核机器回归和基于分位数的 g- 金属混合物的计算，以及用于检查生物标志物选择的分层变量选择。这 研究将有助于我们目前对金属与儿童神经运动功能关联的理解 为减少金属接触的有针对性的干预措施提供见解。它还针对一些 NIEHS 战略 目标包括研究生活在环境危害附近的社区的共同暴露以及创新 使用跨关键发育窗口的暴露数据。