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建立了不利的 子宫暴露的神经行为影响以及儿童早期 许多环境有毒物质，包括铅，酒精，汞，PCB S和 环境烟草烟雾（ETS）。不过，是测量的理想生物标志物 在子宫内尚未建立特定毒物，并且 许多潜在的神经毒性的不利影响尚未严格 测试。胎儿暴露通常通过自我报告的调查来测量 孕产妇的血液和尿液或脐带血。相比之下，胎粪是无创的 同时测试慢性暴露的方法 有毒物质，但尚不清楚常规生物标志物还是 胎粪更可预测与特定相关的不利影响 有毒物质。对于铅暴露，新兴数据表明我们的努力应该 强调主要预防，但铅危害的安全性和功效 控制措施不确定，特别是对于血液铅低的儿童 浓度。研究人员建议进行纵向队列 研究400名儿童，随后少于16周到36个月 年龄，检查低级暴露的剂量反应（前和 产后）至普遍的神经毒性，具有神经行为的结局和 发展障碍，例如行为障碍，认知缺陷，听力 损失和行为与多动症一致。调查人员还将进行 一项嵌套的随机对照试验，用于测试铅危害的功效 控制或发展不良神经行为效应。在项目1中 在加利福尼亚大学中心赠款中，调查人员将测试 以下假设：1）在子宫暴露中，如调查所测量的（酒精和 ETS），母体和脐带血（铅，汞，农药和ETS）和尿液 （农药）在普遍有毒物质的子宫效应中的预测较少， 与认知，行为问题，成长和听力相比 胎粪中相同的毒性。 2）产后暴露于农药，ET和 铅（以低于10 ug/dl的血液水平）与不利有关 幼儿期神经行为影响，生长延迟和听力损失。 3） 铅减少组的儿童的血液铅水平为2.7 UG/DL（30％）或更低，认知评分明显更高，听力较少 损失，更大的生长速度和比对照更少的行为问题 小组在36个月大。 如果资助，这个项目，加上项目2的具体目的， 验证胎粪作为子宫暴露的标志物，将作为模型 评估暴露对多种普遍有毒物质的不利影响， 验证胎粪作为子宫内暴露于众多有毒物质的量度， 提供住宅农药的暴露和风险评估数据，测试 主要预防亚临床铅毒性的干预措施和测试 铅危害控制儿童的血液铅浓度的功效 和神经行为功能。