Prenatal and Childhood Exposure to Fluoride and Neurodevelopment

产前和儿童期接触氟化物与神经发育

• 批准号: 8271682
• 负责人: Karen Eileen Peterson
• 金额: $ 58.76万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8271682
• 关键词: 14 year old; 15 year old; 2 year old; 4 year old; Achievement; Address; Age; Archives; Award; Biological Markers; Birth; Child; Childhood; Cognition; Cognitive; Cohort Studies; Data; Decision Making; Dental Hygiene; Dentifrices; Development; Diet; Dietary intake; Dose; Environmental Epidemiology; Epidemiologic Studies; Exposure to; Fasting; Fluorides; Food; Goals; Influentials; Intelligence; Investigation; Knowledge; Laboratories; Lead; Life; Life Style; Maternal Exposure; Measures; Methods; Mexico; Modification; Molecular; Mothers; National Institute of Environmental Health Sciences; National Research Council; Nature; Neurotoxins; Outcome; Paper; Pattern; Performance; Plasma; Policies; Population; Predisposition; Pregnancy; Publishing; Reporting; Research; Resources; Risk Assessment; Risk Factors; Sample Size; Sampling; Shapes; Sodium Chloride; Specimen; Structure of nail of toe; Testing; Time; Toxic Environmental Substances; Urine; Variant; cognitive function; cohort; cost; drinking water; early life exposure; evidence base; indexing; lead exposure; lead fluoride; mental development; neurobehavior; neurobehavioral; neurodevelopment; offspring; postnatal; prenatal; prenatal exposure; programs; response; salt intake; toxicant; urinary

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.

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的生命早期暴露于环境毒物 (ELEMENT) 计划的独特资源，该计划是一项分子环境流行病学出生队列研究，荣获 1999 年 NIEHS 进步和成就奖，对全人群接触氟化物水平对神经发育的潜在影响进行严格研究。这项工作针对的是 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，需要进行更多研究来解决全民氟化物暴露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能够发表 40 多篇论文，涉及产前和儿童时期接触铅和其他有毒物质对神经行为和身体发育的影响。利用我们存档的尿液、空腹血浆和脚趾甲样本中测量的氟化物水平，以及被广泛认为是氟化物暴露的最佳可用生物标志物的经过验证的测量方法，我们建议研究产前和儿童期氟化物暴露对广泛使用和验证的神经行为测量方法的影响2 至 14 岁的儿童使用 4 组 ELEMENT 中的 3 组。我们使用严格且交叉验证的实验室方法对 40 个随机选择的母子对存档的尿液和血浆样本进行了初步研究，结果表明我们的 ELEMENT 受试者的氟化物水平分布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，氟化物暴露的产前生物标志物与 2 岁时（贝利智力发展量表）、4 岁时（麦卡锡儿童能力量表）和 7-14 岁时（韦克斯勒缩写量表）的一般认知功能之间存在负相关关系。情报）。我们的总体目标是进行全面调查，以 () 解决关于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) 探索氟化物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、与暴露时间窗口（产前与儿童期）相关的不同易感性，以及使用存档数据，潜在的相互作用接触铅（另一种广泛分布的神经毒物）； (C) 对后代进行一项研究，检查饮用水、饮食、牙粉、生活方式以及当前尿液和脚趾甲氟化物水平的其他决定因素。鉴于我们存档资源和样本量的力量，我们将能够以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：全人群的产前和/或儿童期氟化物暴露水平是否是某些形式的不良神经行为表现的重要危险因素。鉴于氟化物使用和接触的广泛性，以及目前证据基础上缺乏对该主题的严格流行病学研究，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。