NEUROMATURATION DELAYS IN IRON DEFICIENT ANEMIC INFANTS

缺铁性贫血婴儿的神经成熟延迟

• 批准号: 2025726
• 负责人: BETSY LOZOFF
• 金额: $ 24.16万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-05 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2025726
• 关键词: child (0-11); child behavior; child physical development; clinical research; developmental neurobiology; developmental nutrition; disease /disorder model; evoked potentials; hearing tests; human subject; infant human (0-1 year); laboratory rat; longitudinal human study; malnutrition; microcytic /hypochromic anemia; myelinopathy; nutrition related tag; optic nerve; preschool child (1-5); psychomotor function; sleep; vagus nerve; visual perception

The proposed project will 1) test the hypothesis that changes in neuromaturation observed in iron-deficient anemic infants are due to hypomyelination and 2) test a model of mechanisms explaining why iron-deficiency anemia in infancy is associated with poorer developmental outcome. Given the important role of iron in myelin formation and maintenance, impaired myelination is a promising explanation for recent evidence of immature neuromaturation in 6- month-olds with iron-deficiency anemia (slower Central Conduction Time, decreased vagal tone). The hypomyelination hypothesis (Aim 1) will be tested directly in a developmental rat model by examining vagal/optic nerve and regional brain myelination and indirectly in the child using auditory and visual evoked potentials and vagal tone measures from sleep studies. Annual neurophysiology evaluations will be conducted until children are 5 years of age to determine if the findings to date represent irregular progressions or arrests in neuromaturation (n=226, half initially anemic or nonanemic). The proposed model of the effects of early iron-deficiency anemia (Aim 2) postulates that hypomyelination and impaired dopaminergic function contribute to altered behavior in anemic infants, which interferes with their learning from the physical and social environment (functional isolation~) and makes them more vulnerable to the effects of environmental stressors, leading to poorer intellectual and motor development and more internalizing behaviors. Causal modeling techniques will be used to evaluate this model (n=1000 for testing the overall model; n=350 for exploring underlying mechanisms related to neuromaturation, dopaminergic function, and specific behavioral alterations). The proposed integration of a developmental animal model, related measures of CNS functioning and behavior in the child, and an overall model of explanatory mechanisms promises to be a major advance in understanding poorer developmental and behavioral outcome in early iron deficiency anemia, which affects 20-25% of the world~s babies and many poor or minority infants in the U.S.

拟议的项目将1）检验以下假设。 在铁缺陷型贫血的婴儿中观察到的神经饱和是由于 低切率和2）测试一种机制模型，解释了为什么 婴儿期的铁缺乏症与较差有关 发展结果。 鉴于铁在髓鞘中的重要作用 形成和维护，髓鞘损害是一个有前途的 解释了6-的最新证据证据 具有铁缺陷贫血的月大（中央传导较慢） 时间，降低迷走神的语调）。 低切术假设（目标 1）将通过检查发育大鼠模型直接测试 迷走神经/视神经和区域大脑髓鞘，间接地 使用听觉和视觉诱发的潜力和迷走语气的孩子 睡眠研究的措施。 年度神经生理学评估将 进行直到儿童5岁，以确定是否是否 迄今为止的发现代表了不规则的进步或逮捕 神经饱和度（n = 226，最初贫血或非动态）。 这 提出的早期缺陷贫血作用的模型（AIM 2） 假设低monsyelin和多巴胺能功能受损 有助于贫血婴儿的行为改变，这会干扰 他们从身体和社会环境中学习（功能 隔离〜），使它们更容易受到影响 环境压力源，导致智力和运动较差 发展和更多内部化行为。 因果建模 技术将用于评估该模型（n = 1000用于测试 总体模型； n = 350用于探索与 神经饱和，多巴胺能和特定的行为 更改）。 提议的发展动物的整合 模型，CNS功能和行为的相关度量， 解释机制的总体模型有望成为 了解较差的发展和行为方面的重大进步 早期铁缺乏贫血的结果，影响20-25％ 在美国，世界的婴儿和许多贫穷或少数婴儿