Prenatal and Childhood Exposure to Fluoride and Neurodevelopment

描述（由申请人提供）：在这个新的R01中，我们将利用我们在墨西哥早期生活暴露于环境毒物（ELEMENT）项目的独特资源，这是一项获得1999年NIEHS进展与成就奖的分子环境流行病学出生队列研究，对全人口暴露于氟化物水平对神经发育的潜在影响进行严格研究。这一努力回应了2007年美国国家研究委员会的一份报告，该报告得出的结论是，需要进行更多的研究，以解决全民接触氟化物水平可能对神经行为构成重大威胁的可能性。ELEMENT的特殊数据和资源使我们的团队能够发表40多篇有关产前和儿童接触铅和其他有毒物质对神经行为和身体发育影响的论文。利用我们存档的尿液、空腹血浆和脚趾甲标本中测量的氟化物水平（被广泛认为是氟化物暴露的最佳生物标志物），我们建议利用ELEMENT的4个队列中的3个队列，研究产前和儿童时期氟化物暴露对2至14岁时广泛使用和有效的神经行为测量的影响。我们使用严格和交叉验证的实验室方法，对40对随机选择的母亲-后代的尿液和血浆样本进行了试点研究，结果表明，ELEMENT研究对象的氟化物水平分布将使我们能够实现具体目标。此外，我们的试点数据显示，产前氟化物暴露生物标志物与2岁（贝利智力发展量表）、4岁（麦卡锡儿童能力量表）和7-14岁（韦氏简略智力量表）时的一般认知功能之间存在反比关系。我们的总体目标是进行一项全面的调查，以（）解决有关产前和产后接触氟化物对整体神经行为功能测量的潜在影响的假设；(B)探索氟暴露对神经行为功能特定领域的潜在影响，剂量-反应关系的形状，与暴露时间窗（产前与童年）相关的差异易感性，并利用存档数据，与铅暴露（另一种广泛分布的神经毒物）的潜在相互作用；(C)对后代进行研究，以检查饮用水、饮食、牙膏、生活方式和其他影响当前尿液和脚趾甲氟化物水平的决定因素。鉴于我们的存档资源和样本量的力量，我们将能够以一项新研究所需的成本和时间的一小部分完成这项研究。

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.