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）的重点是脑行为的影响，这取决于缺铁（ID）的时间， 人类婴儿体内的铁元素缺铁（ID）是世界上最常见的单一营养素紊乱， 对各地孕妇和婴儿的影响各不相同。项目I有望成为第一个系统的 研究产前膳食铁缺乏对婴儿大脑和行为的影响（目的1）。的 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）。 该研究将根据ID的时间及其治疗（目标3）评估效应的可逆性，以及 检查胎盘和白色血细胞中母体与胎儿的铁调节机制（目标4）。国家 艺术神经生理学和行为测量将测试关于ID对 感觉、运动、认知、情感-社会和调节功能与髓鞘形成受损有关， 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）。这项研究将在中国进行，中国是一个发展迅速的国家， 在缺乏普遍的卫生保健的情况下，孕妇和婴儿经常发生ID的国家 营养不良本文对1122例农村足月新生儿脐血血红蛋白（Hb）和铁蛋白（Fe）进行了测定 婴儿，在9个月和18个月时再次测定铁状态。围产期脑行为评估 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; 200名 在6周时，将具有边缘血红蛋白或低脐带铁蛋白的婴儿（“边缘出生铁”组）随机分配至50个铁 治疗组和安慰剂组各150例; 100例脐带Hb和铁蛋白水平正常（“正常出生铁”组）， 接受安慰剂。其余763名接受脐带血检测的婴儿将组成“血液筛查队列”。“9点 18个月时，将重新评估新生儿队列，沿着血液筛查队列中的IDA婴儿- 9个月时约为58例（“出生后早期IDA”），18个月时约为48例（“出生后晚期IDA”）。大约39个边缘出生- 新生儿队列中铁安慰剂治疗的婴儿在9个月时也可能患有IDA（“联合ID”）。Ida 婴儿将接受铁治疗。项目I在概念上和方法上与猴子紧密相连， 啮齿动物项目在PPG 2和直接建立在所有项目的结果在PPG 1。差异效应和/或 取决于ID或治疗时间的可逆性可以为全球卫生政策和实践提供信息。 然而，产前缺铁的影响很少在人类婴儿中进行研究， 部分到以前的想法，不再接受，婴儿是保护。高达75%的孕妇 全世界范围内的婴儿都患有贫血，其中约一半是由于ID。估计20-25%的6- 24个月大的婴儿患有IDA， 而更多的人是没有贫血的ID。因此，研究结果的公共卫生意义，特别是在 结合II-IV项目动物模型，可能是深远的。