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 宫内和儿童早期接触铅对神经行为的影响 多种环境毒物，包括铅、酒精、汞、多氯联苯S和 环境烟草烟雾(ETS)。尽管如此，理想的生物标记物 在子宫内暴露于特定毒物的情况尚未确定， 许多潜在的神经毒物的不良反应还没有得到严格的研究 测试过。胎儿暴露通常是通过自我报告的调查来衡量的， 母血和尿液，或脐带血。相比之下，胎粪是一种非侵入性的 一种同时检测长期接触大量 毒物，但目前尚不清楚常规生物标志物或 胎粪更能预测与特定疾病相关的不良反应 毒药。对于铅暴露，新出现的数据表明，我们的努力应该 强调初级预防，但铅危害的安全性和有效性 控制是不确定的，特别是对低血铅儿童 浓度。研究人员建议进行纵向队列研究 对400名儿童的研究，随访时间从怀孕不到16周到36个月 年龄，以检查低水平暴露的剂量反应(前和 出生后)对普遍存在的神经毒物有神经行为后果和 发育障碍，如品行障碍、认知障碍、听力障碍 损失和行为符合ADHD。调查人员还将进行 一项检验铅危害疗效的嵌套式随机对照试验 控制或发展不良的神经行为影响。在项目1中 加州大学中心助学金的研究人员将测试 以下假设：1)通过调查测量的子宫内暴露(酒精和 母血和脐带血(铅、汞、杀虫剂和ETS)和尿液 (杀虫剂)对普遍存在的毒物的宫内影响预测较少， 如认知、行为问题、成长和听力，与 胎粪中含有相同的毒物。2)出生后暴露于杀虫剂、ETS和 铅(血液水平低于10ug/dl)与不良反应有关 儿童早期的神经行为影响、生长迟缓和听力损失。3) 减铅组的儿童血铅水平将为2.7 Ug/dl(30%)或更低，认知分数显著较高，听力较差 损失、更快的增长速度和更少的行为问题 36月龄组。 如果得到资助，该项目结合项目2的具体目标，将 验证胎粪作为宫内暴露的标志，将作为一种模式 评估接触多种流行毒物的不良影响， 确认胎粪作为宫内暴露于多种毒物的量度， 提供住宅用杀虫剂的暴露和风险评估数据、测试和 亚临床铅中毒一级预防干预措施及试验 儿童铅危害控制的效果--S血铅浓度 和神经行为功能。