Prenatal and Childhood Exposure to Fluoride and Neurodevelopment

描述(由申请人提供)：在这份新的R01中，我们将利用我们在墨西哥早期接触环境毒物(ELENT)计划的独特资源，这是一项获得1999年NIEHS进步和成就奖的分子环境流行病学出生队列研究，以对全人群暴露于氟对神经发育的潜在影响进行严格研究。这项工作涉及2007年美国国家研究委员会的一份报告，该报告的结论是，需要进行更多的研究，以解决全人群暴露的氟化物水平可能对神经行为构成重大威胁的可能性。Element的卓越数据和资源使我们的团队发表了40多篇关于产前和儿童暴露于铅和其他毒物对神经行为和身体发育的影响的论文。使用在我们的档案尿液、空腹血浆和脚趾甲样本中测量的氟化物水平，被广泛认为是氟化物暴露的最佳可用生物标志物的验证指标，我们建议利用4个元素队列中的3个，研究产前和儿童氟暴露对2至14岁时广泛使用和验证的神经行为指标的影响。我们使用严格和交叉验证的实验室方法对40对随机选择的母子对的存档尿液和血浆样本进行的初步研究表明，我们的元素受试者有一个氟化物水平分布，这将使我们能够实现我们的特定目标。此外，我们的试点数据显示，2岁(贝利智力发育量表)、4岁(麦卡锡儿童能力量表)和7-14岁(韦氏智力缩写量表)的产前暴露生物标志物与一般认知功能之间存在负相关关系的证据。我们的总体目标将是进行全面调查，以()解决关于出生前和出生后暴露于氟对整体神经行为功能测量的潜在影响的假说；(B)探索氟暴露对神经行为功能的特定领域的潜在影响、剂量-反应关系的形状、与暴露时间窗相关的不同易感性(产前与童年)，以及利用存档数据，与另一种广泛分布的神经毒物铅暴露的潜在相互作用；以及(C)对后代进行研究，以检查当前尿氟和趾甲氟水平的饮用水、饮食、牙膏、生活方式及其他决定因素。鉴于我们存档的资源和样本量的力量，我们将能够以一项新研究所需成本和时间的一小部分来完成这项研究。 公共卫生相关性：这项研究将直接解决以下问题：整个人群的产前和/或儿童氟暴露水平是否是某些形式的不良神经行为表现的重要风险因素。鉴于氟化物使用和暴露的广泛性质，以及在当前证据基础上对这一主题缺乏严格的流行病学研究，这项研究有望为氟化物风险评估和政策决策做出重大贡献。

DESCRIPTION (provided by applicant): In this new R01, we will capitalize on the unique resources of our Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) program, a molecular environmental epidemiology birth cohort study that won the 1999 NIEHS Progress and Achievement Award, to conduct a rigorous study of the potential impact of population-wide levels of exposure to fluoride on neurodevelopment. This effort addresses a 2007 US National Research Council report which concluded that more research is needed to address the possibility that population-wide levels of fluoride exposure may pose a significant threat to neurobehavior. The exceptional data and resources of ELEMENT has allowed our team to publish over 40 papers related to the impact of prenatal and childhood exposure to lead and other toxicants on neurobehavioral and physical development. Using levels of fluoride measured in our archived urine, fasting plasma and toenail specimens, validated measures widely recognized as being the best available biomarkers of fluoride exposure, we propose to study the impact of prenatal and childhood fluoride exposures on widely used and validated measures of neurobehavior at 2 to 14 years of age utilizing 3 of the 4 cohorts of ELEMENT. Our pilot research on archived urine and plasma samples from 40 randomly chosen mother-offspring pairs using rigorous and cross-validated laboratory methods indicates that our ELEMENT subjects have a distribution of fluoride levels that will enable us to pursue our specific aims. Further, our pilot data shows evidence of an inverse relationship between prenatal biomarkers of fluoride exposure and general cognitive function at 2 years (Bayley Scales of Mental Development), 4 years (McCarthy Scales of Children's Abilities) and 7-14 years (Wechsler Abbreviated Scales of Intelligence). Our overall goals will be to conduct a full investigation to () address hypotheses on the potential impact of pre- and postnatal exposures to fluoride on measures of overall neurobehavioral function; (B) explore the potential impacts of fluoride exposure on specific domains of neurobehavioral function, the shape of the dose-response relationships, differential susceptibility in relation to time windows of exposure (prenatal v. childhood), and, using archived data, potential interactions with lead exposure, another widely- distributed neurotoxicant; and (C) conduct a study of offspring to examine the drinking water, dietary, dentifrice, lifestyle, and other determinants of current urinary and toenail fluoride leves. Given the power of our archived resources and sample sizes, we will be able to accomplish this research at a small fraction of the cost and time required of a new study. PUBLIC HEALTH RELEVANCE: This research will directly address the issue as to whether population-wide levels of prenatal and/or childhood fluoride exposure is a significant risk factor for some forms of adverse neurobehavioral performance. Given the widespread nature of fluoride use and exposure and the lack of rigorous epidemiologic research on this topic of the current base of evidence, this research promises to make a major contribution to fluoride risk assessment and policy decision-making.