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

美国的儿童暴露于各种神经毒素中，这些毒素会损害他们发育中的大脑。我们有 最近表明，低社会经济地位对认知发展的长期负面影响是由以下因素介导的： 大脑结构的差异。具体来说，大脑结构和SES之间的关联更多 在最贫穷的儿童中尤其明显，这些儿童通常最容易接触到神经毒性金属，如铅 （Pb）。在这里，我们的目的是更好地了解围产期铅暴露对大脑，认知和行为的影响 使用新的牙本质测定纵向发展。这种新的措施允许量化 出生前和出生后的铅暴露，从子宫内的第二个三个月开始，最终直到牙齿 在童年后期脱落;牙本质随着时间的推移而发展，就像树木的年轮，捕获早期的暴露 下一个“环”的牙本质形成，允许时间测量铅在连续的环， 牙质。在社会经济地位较低的情况下，铅暴露的影响可能会加剧，但铅暴露的这一重要方面 环境中的大脑发育很少受到研究关注。在本提案中，我们将 通过调查约500名参与者的铅暴露，利用大量现有资金， 青少年大脑认知发展（ABCD）研究谁捐赠脱落乳牙（婴儿）。我们 还将利用最近来自儿童健康暴露分析资源（CHINESE：项目）的资金 #2017-1920;现在的HHEAR），以支付三个不同发展时期的牙齿分析费用： 胎儿发育的三个月和第三个三个月以及生命的第一年。值得注意的是， 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 近4,000名参与者捐赠了牙齿。这将允许对参与者进行战略选择 通过铅风险度量（基于公开可用的铅暴露风险地图，地理编码为 每个参与者的家庭地址），同时控制SES和种族因素，这些因素可能会受到 铅暴露。铅风险可能会增加接触的可能性，但很明显，一些高风险的人可能会 低风险的人可能会有高风险。虽然我们的初步研究表明， 在ABCD队列中，风险状态与脑、认知和行为作为SES的函数相关，仅通过 通过测量与SES风险状态相匹配的个体组内的内源性铅水平，我们可以确定 如何以及在哪里集中未来的努力，以减少可补救的铅风险因素和改善儿童的健康 在美国.在这项建议中，我们将评估（1）牙本质铅水平之间的关联， 儿童时期的发育，并确定相关性是否随3岁时接触水平的变化而变化 发育时间点，（2）牙本质铅水平与认知和行为之间的关系 发展沿着性别差异对这些协会，（3）调节或中介作用 SES对围产期铅暴露背景下脑认知行为发育的影响

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.