Prenatal and Early Postnatal Lead Exposure on Childhood and Adolescent Brain, Cognitive and Behavioral Development

产前和产后早期铅暴露对儿童和青少年大脑、认知和行为发育的影响

• 批准号: 10240486
• 负责人: ELIZABETH R SOWELL
• 金额: $ 35.72万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-17 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10240486
• 关键词: Address; Adolescence; Adolescent; Adult; Affect; Archives; Area; Attention; Attenuated; Behavior; Behavioral; Biological Assay; Brain; Brain region; Child; Child Behavior Checklist; Child Health; Childhood; Cognition; Cognitive; Development; Dose; Education; Environment; Ethnic Origin; Exposure to; Family; Fetal Development; Funding; Future; Geographic Locations; Health; Home; Human; Impairment; Income; Individual; Intelligence; Language; Lead; Lead levels; Life; Literature; Maps; Measures; Mediating; Mediation; Metals; Neurotoxins; Outcome; Parents; Participant; Pathogenesis; Pattern; Perinatal; Problem behavior; Public Health; Race; Reporting; Research; Resources; Risk; Risk Factors; Sampling; Second Pregnancy Trimester; Sex Differences; Site; Socioeconomic Status; Structure; Testing; Third Pregnancy Trimester; Time; Tooth structure; Trees; United States National Institutes of Health; base; behavioral outcome; brain behavior; cognitive development; cohort; cost; deciduous tooth; deprivation; executive function; externalizing behavior; fetal; high risk; improved; in utero; indexing; lead concentration; lead exposure; low socioeconomic status; neighborhood safety; neurodevelopment; neuropsychiatric disorder; neurotoxic; novel; postnatal; prenatal; prenatal exposure; recruit; relating to nervous system; sex; socioeconomics; temporal measurement; toxicant; white matter

Children in the US are exposed to various neurotoxicants that can damage their developing brains. We have recently shown that the long-known negative impact of low SES on cognitive development is mediated by differences in brain structure. Specifically, the association between brain structure and SES is more pronounced in the poorest children, those who are often the most exposed to neurotoxic metals, such as lead (Pb). Here, we aim to better understand the impact of perinatal Pb exposure on brain, cognitive and behavioral development longitudinally using a novel tooth dentine assay. This novel measure allows quantification of prenatal and postnatal Pb exposure beginning with the 2nd trimester in utero and ultimately until the tooth is shed during later childhood; dentine develops over time, much like rings of a tree, trapping earlier exposures beneath the next “ring” of dentine to form, allowing temporal measurements of Pb in consecutive rings of dentine. The effects of Pb exposure may be exacerbated in the context of low SES, but this important aspect of brain development in the environmental setting has received little research attention. In this proposal, we will leverage substantial existing funding by investigating Pb exposure among a subset of ~500 participants of the Adolescent Brain Cognitive Development (ABCD) study who have donated shed deciduous (baby) teeth. We will also leverage recent funding from the Children's Health Exposure Analysis Resource (CHEAR: Project #2017-1920; now HHEAR) to cover the costs of tooth analysis at three distinct developmental periods: the 2nd trimester and 3rd trimester of fetal development and the 1st year of life. Notably, the ABCD cohort of over 11,800 participants varies considerably on race and ethnicity, geographic location, family income, and parent education, and nearly 4,000 participants have donated teeth. This will allow a strategic selection of participants who are matched by Pb risk measures (based on publicly available risk maps of Pb exposure geocoded to each participant's home address) while controlling for SES and race factors that could be confounded by risk of Pb exposure. Pb risk may increase the likelihood of exposure, but it is clear that some at high risk could have low exposure whereas some at low risk may have high exposure. While our preliminary studies show that Pb risk status is associated with brain, cognition, and behavior as a function of SES in the ABCD cohort, only by measuring endogenous Pb levels within groups of individuals matched on SES by risk status can we determine how and where to focus future efforts to reduce remediable Pb risk factors and improve the health of children in the US. In this proposal, we will assess (1) associations between dentine Pb levels on structural brain development during childhood and determine if associations vary as a function of level of exposure at 3 developmental time points, (2) associations between dentine Pb levels and cognitive and behavioral development along with sex differences on these associations, and (3) the moderating or mediating effects of SES on brain-cognitive-behavioral development in the context of perinatal Pb exposure.

美国的儿童暴露在各种神经毒物中，这些毒物可能会损害他们发育中的大脑。我们有 最近的研究表明，低SES对认知发展的负面影响是通过以下途径来实现的 大脑结构的差异。具体地说，大脑结构和SES之间的联系更多 在最贫穷的儿童中表现明显，他们往往是接触神经毒性金属最多的人，如铅 (Pb)。在这里，我们旨在更好地了解围产期铅暴露对大脑、认知和行为的影响 使用一种新的牙齿牙本质测试进行纵向开发。这一新的措施允许量化 出生前和出生后铅暴露，从怀孕中期开始，直到牙齿 在童年后期脱落；牙本质随着时间的推移而发展，很像树的年轮，捕捉早期的暴露 在下一个牙本质环下形成，允许在连续的牙本质环中对铅进行时间测量 牙本质。在低SES的情况下，铅暴露的影响可能会加剧，但这一重要方面 环境背景下的大脑发育几乎没有受到研究的关注。在这项提案中，我们将 通过调查约500名参与者中的铅暴露情况，利用大量现有资金 青少年大脑认知发展(ABCD)研究谁捐赠了脱落的乳牙(婴儿)。我们 还将利用儿童健康暴露分析资源(CHEAR：项目)最近提供的资金 #2017-1920；现在HHEAR)，以支付三个不同发育期的牙齿分析费用：第二个 胎儿发育的三个月和第三个月，以及生命的第一年。值得注意的是，超过 11,800名参与者在种族和民族、地理位置、家庭收入和父母方面存在很大差异 教育，近4,000名参与者捐赠了牙齿。这将允许对参与者进行战略性选择 谁与铅风险衡量标准相匹配(基于公开可用的铅暴露风险地图，地理编码为 每个参与者的家庭住址)，同时控制SES和种族因素，这可能会被 铅暴露。铅风险可能会增加暴露的可能性，但很明显，一些高风险的人可能已经 一些风险较低的人可能有较高的风险。而我们的初步研究表明，铅 在ABCD队列中，风险状态与大脑、认知和行为作为SES的功能相关，只有通过 根据风险状态测量与SES相匹配的个体组中的内源性铅水平是否可以确定 如何以及在哪里集中未来的努力，以减少可补救的铅危险因素，改善儿童的健康 在美国。在这项建议中，我们将评估(1)牙本质铅水平与结构脑之间的关系 并确定关联性是否随3岁时接触水平的不同而变化 发育时间点，(2)牙本质铅水平与认知和行为的关系 发展以及性别差异对这些联系的影响，以及(3) 围产期铅暴露对脑部认知行为发育的影响。