Neurodevelopment of Children Exposed to Anesthesia: A Population-Based Assessment

接受麻醉的儿童的神经发育：基于人群的评估

基本信息

批准号：
8431738
负责人：
Randall Paul Flick
金额：
$ 53.91万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8431738
关键词：
3 year old Academic achievement Achievement Adverse effects Affect Age Agonist Alcohols Anesthesia procedures Anesthetics Animal Model Animals Apoptotic Area Aspartate Behavior Behavioral Benefits and Risks Benzodiazepines Biological Markers Birth Brain Caring Cause of Death Child Childhood Childhood Injury Clinical Clinical Data Cognition Complement County Data Dose Drug usage Epidemiologic Studies Epidemiology Exposure to Frequencies GABA Antagonists General Anesthesia Glutamate Receptor Goals Human Imaging Techniques Incidence Infant Injury Ketamine Language Development Learning Learning Disabilities Life Macaca mulatta Measurement Measures Memory Methods Motor Nerve Degeneration Neurons Neuropsychological Tests Nitrous Oxide Observational Study Operative Surgical Procedures Parents Patients Performance Pharmaceutical Preparations Phenotype Population Primates Propofol Publishing Research Research Personnel Resources Rodent Safety Sedation procedure Speech Development Testing Time United States Work animal data clinically relevant clinically significant cohort executive function improved infant animal insight instrument juvenile animal learned behavior neurodevelopment neurotoxicity nonhuman primate population based pre-clinical prospective randomized trial sedative

项目摘要

DESCRIPTION (provided by applicant): Over one million young children are exposed to drugs used to induce and maintain general anesthesia each year in the United States. Mounting evidence shows that exposure of the developing brains of animals to alcohol, anesthetic and sedative medications may cause neurodegenerative changes with adverse effects on learning and behavior. These changes are associated with long-term changes in behavior, both in rodents and in non-human primates. The clinical significance of these observations is a topic of intense debate and concern, as there are very few human studies of how anesthetic exposure may affect neurodevelopment. Existing studies show that exposure to multiple, but not single, anesthetics at a young age is associated with an increased frequency of learning disabilities, but there are significant limitations of all existing human studies. The long term goal of this researc is to improve the safety of drugs that produce general anesthesia in young children. The overall objective of this application is to determine whether exposure of children to anesthesia is associated with neurodevelopmental abnormalities. The central hypothesis is that exposure to multiple anesthetics at a young age will impair later performance of children on detailed tests of neurodevelopmental performance. To achieve the objective, the Specific Aim of this proposal is to determine if exposure to anesthesia prior to age three is associated with neurodevelopmental abnormalities in children. Using a unique population-based resource, the Rochester Epidemiology Project, a cohort of children born in Olmsted County, MN between 1994 and 2007 and still currently resident in the area will be identified. From this cohort children exposed to anesthesia prior to age 3 will be propensity matched to children not exposed to anesthesia. Subjects (those exposed to anesthesia and those not exposed) will undergo detailed neuropsychological testing in the domains of intellectual ability, memory function, executive function, motor integrity, language and speech development, and academic achievement to test the hypothesis that multiple, but not single, exposures to anesthesia are associated with impaired performance in these domains. Children will also receive the Operant Test Battery from the National Toxicological Research Center. This will allow for comparison of results in children with published studies of how anesthetic exposure affects infant rhesus monkeys. Testing will be performed at ages 7-11 and 15-19 (in separate groups of children) to explore the persistence of any observed effects. The expected product of this research will be the first detailed phenotype of anesthetic- induced neurotoxicity in humans (if indeed evidence of neurotoxicity is found). More than one million children under the age of 3 years undergo anesthesia annually in the US so that the potential impact of this finding cannot be overstated. This phenotype would assist in interpreting the pre-clinical data, potentially devising strategies to mitigate anesthesia-induced injury, and assist patients and clinicians in making informed decisions.

描述（由申请人提供）：在美国，每年有超过一百万幼儿接触用于诱导和维持全身麻醉的药物。越来越多的证据表明，动物发育中的大脑接触酒精、麻醉剂和镇静药物可能会导致神经退行性变化，对学习和行为产生不利影响。这些变化与啮齿类动物和非人类灵长类动物的长期行为变化有关。这些观察结果的临床意义是一个激烈争论和关注的话题，因为关于麻醉剂暴露如何影响神经发育的人体研究很少。现有研究表明，年轻时接触多种而非单一麻醉剂与学习障碍发生率增加有关，但所有现有的人类研究都存在显着的局限性。这项研究的长期目标是提高幼儿全身麻醉药物的安全性。该应用的总体目标是确定儿童接受麻醉是否与神经发育异常相关。中心假设是，在年轻时接触多种麻醉剂会损害儿童以后在神经发育表现的详细测试中的表现。为了实现这一目标，该提案的具体目标是确定三岁之前接触麻醉是否与儿童神经发育异常相关。罗彻斯特流行病学项目将利用独特的基于人群的资源，识别 1994 年至 2007 年间出生于明尼苏达州奥姆斯特德县且目前仍居住在该地区的一组儿童。在该队列中，3 岁之前接触过麻醉的儿童的倾向将与未接触过麻醉的儿童相匹配。受试者（暴露于麻醉的和未暴露的）将在智力、记忆功能、执行功能、运动完整性、语言和言语发展以及学业成绩等领域接受详细的神经心理学测试，以检验多个而非单一的假设，麻醉暴露与这些领域的表现受损有关。孩子们还将收到国家毒理学研究中心提供的操作测试电池。这将有助于将儿童的结果与已发表的关于麻醉剂暴露如何影响幼年恒河猴的研究进行比较。测试将在 7-11 岁和 15-19 岁（在不同的儿童组中）进行，以探索任何观察到的影响的持续性。这项研究的预期产品将是第一个详细的麻醉剂引起的人类神经毒性表型（如果确实发现神经毒性的证据）。在美国，每年有超过 100 万 3 岁以下儿童接受麻醉，因此这一发现的潜在影响怎么强调都不为过。这种表型将有助于解释临床前数据，有可能制定减轻麻醉引起的损伤的策略，并帮助患者和临床医生做出明智的决定。