Neurobehavioral effects of prevalent toxicants in children

常见毒物对儿童神经行为的影响

• 批准号: 6657529
• 负责人: BRUCE P LANPHEAR
• 金额: $ 17.91万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6657529
• 关键词: clinical chemistry; clinical research; embryo /fetus toxicology; environmental exposure; environmental toxicology; hearing tests; human subject; infant human (0-1 year); lead poisoning; longitudinal human study; neuropsychological tests; neurotoxins; pesticide biological effect; prenatal stress; preschool child (1-5)

DESCRIPTION (provided by applicant) Epidemiologic and experimental data have established the adverse neurobehavioral effects of exposure in utero and during early childhood to numerous environmental toxicants, including lead, alcohol, mercury, PCB s, and environmental tobacco smoke (ETS). Still, the ideal biomarker for measuring in utero exposure to specific toxicants has not been established and the adverse effects of many potential neurotoxicants have not been rigorously tested. Fetal exposure is typically measured with self-reported surveys, maternal blood and urine, or cord blood. In contrast, meconium is a non-invasive method to simultaneously test for chronic exposures to numerous toxicants, but it is as yet unclear whether conventional biomarkers or meconium are more predictive of the adverse effects linked with specific toxicants. For lead exposure, emerging data indicate that our efforts should emphasize primary prevention, but the safety and efficacy of lead hazard controls are uncertain, especially for children with low blood lead concentrations. The investigators propose to conduct a longitudinal cohort study of 400 children, followed from less than 16 weeks gestation to 36 months of age, to examine the dose-response of low-level exposures (pre- and postnatal) to prevalent neurotoxicants with neurobehavioral outcomes and development disorders, such as conduct disorder, cognitive deficits, hearing loss and behaviors consistent with ADHD. The investigators will also conduct a nested, randomized controlled trial to test the efficacy of lead hazard controls or the development of adverse neurobehavioral effects. In Project 1 of University of California's Center Grant, the investigators will test the following hypotheses: 1) In utero exposures as measured by survey (alcohol and ETS), maternal and cord blood (lead, mercury, pesticides and ETS), and urine (pesticides) are less predictive of in utero effects of prevalent toxicants, such as cognition, behavioral problems, growth and hearing, compared with the same toxicants in meconium. 2) Postnatal exposures to pesticides, ETS and lead (at blood levels below 10 ug/dl) are associated with adverse neurobehavioral effects, growth delay and hearing loss in early childhood. 3) Children in the Lead Reduction Group will have blood lead levels that are 2.7 ug/dl (30%) or lower, significantly higher cognitive scores, less hearing loss, greater growth velocity, and fewer behavioral problems than the Control Group at 36 months of age. If funded, this project, combined with the specific aim of Project 2, to validate meconium as a marker of in utero exposure, will serve as a model to evaluate the adverse effects of exposures to multiple prevalent toxicants, validate meconium as a measure of in utero exposures to numerous toxicants, provide exposure and risk assessment data for residential pesticides, test an intervention for the primary prevention of subclinical lead toxicity, and test the efficacy of a lead hazard control on children?s blood lead concentration and neurobehavioral functioning.

描述（由申请人提供） 流行病学和实验数据已经确定了不利的 子宫内和幼儿期暴露对神经行为的影响 许多环境毒物，包括铅、酒精、汞、多氯联苯， 环境烟草烟雾（ETS）。尽管如此，理想的生物标志物， 子宫内暴露于特定毒物尚未确定， 许多潜在的神经毒物的副作用还没有被严格地 测试.胎儿暴露通常通过自我报告的调查来测量， 母体血液和尿液或脐带血。相反，胎粪是一种非侵入性的 一种同时测试多种慢性暴露的方法 有毒物质，但目前还不清楚是否传统的生物标志物或 胎粪更能预测与特定的 有毒物质对于铅暴露，新出现的数据表明，我们的努力应该 强调一级预防，但铅危害的安全性和有效性 控制是不确定的，特别是对于低血铅儿童 浓度的研究人员建议进行一个纵向队列研究， 对400名儿童的研究，从妊娠不到16周到36个月 研究低水平照射（照射前和照射后）的剂量反应， 出生后）与神经行为结果的流行神经毒物， 发育障碍，如行为障碍、认知缺陷、听力障碍 注意力缺陷多动障碍的行为调查人员还将进行 一项巢式随机对照试验，以测试铅危害的有效性 控制或不良神经行为影响的发展。项目1 加州大学中心格兰特研究中心的研究人员将测试 以下假设：1）通过调查测量的子宫内暴露（酒精和 ETS）、母体和脐带血（铅、汞、杀虫剂和ETS）和尿液 （农药）对普遍毒物在子宫内的影响预测性较低， 如认知、行为问题、生长和听力， 胎粪中含有相同的有毒物质。2)产后接触杀虫剂、ETS和 铅（血液中铅含量低于10微克/分升）与 神经行为影响、生长延迟和儿童早期听力损失。第三章 减少铅摄入组的儿童血铅水平为2.7 ug/dl（30%）或更低，认知评分显著升高，听力降低 损失，更大的增长速度，和更少的行为问题比控制 36个月龄组。 如果得到资助，该项目与项目2的具体目标相结合， 验证胎粪作为子宫内暴露的标志物，将作为模型， 评估暴露于多种常见毒物的不良影响， 验证胎粪作为子宫内暴露于许多有毒物质的量度， 提供住宅杀虫剂的接触和风险评估数据，测试和 亚临床铅中毒的一级预防干预， 铅危害控制对儿童的有效性？血铅浓度 和神经行为功能。