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: 10450156
• 负责人: ELIZABETH R SOWELL
• 金额: $ 69.27万
• 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/10450156
• 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; Income; Individual; Intellectual impairment; 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.

美国的儿童暴露于各种神经毒性，可能会损害其发育中的大脑。我们有 最近表明，低SES对认知发展的长期负面影响是由 大脑结构的差异。具体而言，大脑结构与SE之间的关联更多 在最贫穷的儿童中发音，那些通常是最容易暴露于神经毒性金属的孩子，例如铅 （PB）。在这里，我们旨在更好地了解围产期PB暴露对大脑，认知和行为的影响 使用新型牙齿牙本质测定法纵向开发。这种新颖的测量允许量化 产前和产后PB暴露于子宫内的第二学期，最终直到牙齿为直到牙齿 在童年后期棚子；随着时间的流逝，牙本质开发人员，就像树的戒指一样，捕获早期的暴露 在下一个牙本质的“环”下形成，允许在连续环中临时测量PB 牙本质。 PB暴露的影响可能会在低SES的背景下加剧，但是 环境环境中的大脑发育几乎没有得到研究的关注。在此提案中，我们将 通过调查约500名参与者的PB暴露来利用现有的资金 青少年脑认知发展（ABCD）研究，他们捐赠了落叶牙齿（婴儿）牙齿。我们 还将利用儿童健康暴露分析资源（Chear：Project）的最新资金 ＃2017-1920;现在hhear）在三个不同的发育时期内支付牙齿分析的成本：第二 胎儿发育和生命第一年的孕期和三个月。值得注意的是，ABCD队列 11,800名参与者在种族和种族，地理位置，家庭收入和父母方面仔细而轻松地变化 教育，近4,000名参与者捐赠了牙齿。这将允许参与者进行战略选择 由PB风险措施匹配的人（基于PB暴露的公开风险图，地理编码为 每个参与者的家庭住址）在控制SES和种族因素时可能会因风险而混淆 PB暴露。 PB风险可能会增加暴露的可能性，但是很明显，有些处于高风险的人可能有 低暴露量，而有些处于低风险可能会有很高的暴露。而我们的初步研究表明PB 风险状态与ABCD队列中SES的大脑，认知和行为有关，仅由 测量通过风险状态在SES上匹配的个体组中的内源性PB水平，我们可以确定 如何以及在何处集中未来的努力，以减少可补充的PB风险因素并改善儿童的健康状况 在美国。在此提案中，我们将评估（1）结构大脑上牙本质PB水平之间的关联 儿童期的发展，并确定关联是否因3时暴露水平而变化 发育时间点，（2）牙本质PB水平与认知和行为之间的关联 发展以及这些关联的性别差异，以及（3） 在围产期PB暴露的背景下，SES关于脑认知行为发育。