Brain and Behavior in Iron deficient Infants

缺铁婴儿的大脑和行为

• 批准号: 7699676
• 负责人: BETSY LOZOFF
• 金额: $ 30.74万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7699676
• 关键词: Affect; Affective; Age; Anemia; Animal Model; Animals; Arts; Basal Ganglia; Behavior assessment; Behavioral; Birth; Blood Screening; Blood Tests; Brain; Brain region; Carrier Proteins; Child; China; Classification; Cognitive; Condition; Developed Countries; Developing Countries; Development; Dietary Iron; Disease; Ferritin; Functional disorder; Future; Genes; Health Policy; Hemoglobin; Hippocampus (Brain); Human; Immigrant; Infant; Investigation; Iron; Leukocytes; Link; Long-Term Effects; Malnutrition; Measures; Minority; Monkeys; Mothers; Motor; Neurotransmitters; Newborn Infant; Nutrient; Outcome; Perinatal; Placebos; Placenta; Pregnant Women; Process; Proteomics; Public Health; Randomized; Regulation; Relative (related person); Risk; Rodent; Role; Rural; Sensory; Severities; Structure; Symptoms; System; Testing; Thinking; Time; Toddler; Umbilical Cord Blood; Work; behavior measurement; brain behavior; cohort; design; fetal; human study; memory recognition; myelination; nonhuman primate; postnatal; prenatal; prevent; response; sensorimotor system; social; young mother

Project I (human infant) focuses on brain-behavior effects depending on the timing of iron deficiency (ID) and iron repletion in human infants. Iron deficiency (ID) is the world's most common single nutrient disorder, differentially affecting pregnant women and infants everywhere. Project I promises to be the first systematic investigation of brain and behavior effects of prenatal dietary iron deficiency in human infants (Aim 1). The design will support comparisons of brain/behavior effects depending on the timing and duration of ID (Aim 2). The study will assess reversibility of effects, depending on timing of ID and its treatment (Aim 3), and examine maternal vs. fetal iron regulatory mechanisms in placenta and white blood cells (Aim 4). State-ofthe- art neurophysiologic and behavioral measures will test specific hypotheses regarding effects of ID on sensory, motor, cognitive, affective-social and regulatory functions related to impaired myelination of sensory/motor systems and altered structure, neurotransmitter function and neurometabolism in targeted brain regions (basal ganglia and hippocampus). The study will be conducted in China, a rapidly developing country where ID often occurs among pregnant women and infants in the absence of generalized undernutrition. Cord blood hemoglobin (Hb) andferritin concentrations will be measured in 1122 rural fullterm infants, with iron status determined again at 9 and 18 mo. Brain-behavior assessments in the perinatal period will involve 359 infants ("newborn cohort"): 59 with low Hb ("low birth iron" group) will receive iron; 200 with marginal Hb or low cord ferritin ("marginal birth iron" group) will be randomly assigned at 6 wk, 50 to iron therapy and 150 to placebo; and 100 with normal cord Hb and ferritin levels ("normal birth iron" group) will receive placebo. The remaining 763 infants with cord blood testing will form the "blood screen cohort." At 9 and 18 mo, the newborn cohort will be reassessed, along with IDA infants from the blood screen cohort - about 58 at 9 mo ("early postnatal IDA") and 48 at 18 mo ("late postnatal IDA"). Approximately 39 marginalbirth- iron placebo-treated infants in the newborn cohort may also have IDA at 9 mo ("combined ID"). IDA infants will be treated with iron. Project I is tightly linked conceptually and methodologically with monkey and rodent projects in PPG2 and builds directly on findings in all projects in PPG1. Differential effects and/or reversibility depending on timing of ID or treatment could inform health policy and practice worldwide. However, the effects of prenatal iron deficiency have received very little study in human infants due in large part to previous thinking, no longer accepted, that the infant was protected. Up to 75% of pregnant women worldwide are anemic, with about half due to ID. An estimated 20-25% of 6- to 24-mo-old infants have IDA, and more have ID without anemia. Thus, the public health implications of study findings, especially in combination with Project II-IV animal models, could be profound.

项目 I（人类婴儿）侧重于根据缺铁 (ID) 的时间和时间对大脑行为的影响 人类婴儿的铁补充。缺铁（ID）是世界上最常见的单一营养障碍， 各地的孕妇和婴儿受到不同程度的影响。项目I有望成为第一个系统化的项目 调查人类婴儿产前膳食缺铁对大脑和行为的影响（目标 1）。这 设计将支持根据 ID 的时间和持续时间对大脑/行为影响进行比较（目标 2）。 该研究将评估影响的可逆性，具体取决于 ID 及其治疗的时间（目标 3），以及 检查胎盘和白细胞中母体与胎儿的铁调节机制（目标 4）。现状- 艺术神经生理学和行为测量将测试有关 ID 对影响的具体假设 与髓鞘形成受损相关的感觉、运动、认知、情感社会和调节功能 目标中的感觉/运动系统和改变的结构、神经递质功能和神经代谢 大脑区域（基底神经节和海马体）。该研究将在中国这个快速发展的国家进行 在缺乏普遍认识的情况下，孕妇和婴儿经常发生智力障碍的国家 营养不良。 1122名农村足月儿将测量脐带血血红蛋白（Hb）和铁蛋白浓度 婴儿，在 9 个月和 18 个月时再次测定铁含量。围产期大脑行为评估 期间将涉及 359 名婴儿（“新生儿队列”）：59 名低血红蛋白（“低出生铁”组）将接受铁剂； 200 具有边缘 Hb 或低脐带铁蛋白（“边缘出生铁”组）将在第 6 周随机分配 50 个铁剂组 治疗和 150 安慰剂； 100 名脐带血红蛋白和铁蛋白水平正常的人（“正常出生铁”组）将 接受安慰剂。其余 763 名接受脐带血检测的婴儿将组成“血筛队列”。 9点 18 个月后，新生儿队列以及血液筛查队列中的 IDA 婴儿将被重新评估 - 9 个月时约 58 例（“产后早期 IDA”），18 个月时约 48 例（“产后晚期 IDA”）。大约 39 边缘出生- 新生儿队列中接受铁剂安慰剂治疗的婴儿也可能在 9 个月时出现 IDA（“联合 ID”）。国际开发协会 婴儿将接受铁剂治疗。项目 I 在概念和方法上与猴子和 PPG2 中的啮齿动物项目，并直接基于 PPG1 中所有项目的发现。差异效应和/或 取决于 ID 或治疗时间的可逆性可以为全世界的卫生政策和实践提供信息。 然而，由于大量研究，产前缺铁对人类婴儿的影响研究甚少。 以前认为婴儿受到保护的想法已不再被接受。高达 75% 的孕妇 全世界都存在贫血症，其中大约一半是由于贫血引起的。据估计，6 至 24 个月大的婴儿中有 20-25% 患有 IDA， 更多的人患有ID但没有贫血。因此，研究结果对公共卫生的影响，特别是在 与 Project II-IV 动物模型相结合，可能会产生深远的影响。