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.

美国儿童接触的各种神经毒物可能会损害他们正在发育的大脑。 最近表明，众所周知，低社会经济地位对认知发展的负面影响是由以下因素介导的： 具体来说，大脑结构与SES之间的关联性更大。 在最贫困的儿童中尤为明显，这些儿童往往最容易接触铅等神经毒性金属 (Pb)。在这里，我们的目标是更好地了解围产期铅暴露对大脑、认知和行为的影响。 使用新型牙齿牙本质测定纵向发育这种新颖的测量方法可以对牙齿牙本质进行量化。 产前和产后的铅暴露从子宫内的第二个三个月开始，最终直到牙齿长出 童年后期脱落；牙本质随着时间的推移而发展，就像树的年轮一样，捕获早期的暴露 在形成的下一个牙本质“环”下方，允许在连续环中对 Pb 进行时间测量 在低 SES 的情况下，铅暴露的影响可能会加剧，但这是一个重要的方面。 环境环境中的大脑发育很少受到研究关注。 通过调查约 500 名参与者的子集的铅暴露情况，利用大量现有资金 我们捐赠了乳牙（婴儿）的青少年大脑认知发展（ABCD）研究。 还将利用儿童健康暴露分析资源（CHEEAR：项目 #2017-1920；现在为 HHEAR）用于支付三个不同发育时期的牙齿分析费用：第二个时期 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，ABCD 队列超过。 11,800 名参与者在种族、民族、地理位置、家庭收入和父母方面差异很大 教育，近 4,000 名参与者捐赠了牙齿，这将有助于对参与者进行战略性选择。 谁与铅风险措施相匹配（基于公开的铅暴露风险地图，地理编码为 每个参与者的家庭住址），同时控制社会经济地位和种族因素，这些因素可能会因以下风险而混淆： 铅暴露可能会增加暴露的可能性，但很明显，一些高风险人群可能会出现铅暴露的情况。 低暴露，而一些低风险的人可能有高暴露。虽然我们的初步研究表明，铅暴露。 在 ABCD 队列中，风险状态与大脑、认知和行为相关，作为 SES 的函数，仅通过 通过测量按风险状态与 SES 匹配的个体组内的内源性 Pb 水平，我们可以确定 未来如何以及在哪里集中精力减少可补救的铅风险因素并改善儿童的健康 在美国，我们将评估 (1) 牙本质 Pb 水平与大脑结构之间的关联。 儿童时期的发育，并确定关联是否随暴露水平的函数而变化 3 发育时间点，(2) 牙本质 Pb 水平与认知和行为之间的关联 发展以及性别差异对这些关联的影响，以及（3）调节或中介作用 SES 对围产期铅暴露背景下大脑认知行为发展的影响。