Brain and Behavior in Iron deficient Infants

项目I(人类婴儿)侧重于大脑行为的影响，取决于缺铁的时间(ID)和 人类婴儿体内的铁补充。缺铁(ID)是世界上最常见的单纯性营养障碍， 对各地孕妇和婴儿的影响不同。项目I有望成为第一个系统化的项目 产前膳食缺铁对婴幼儿大脑和行为影响的研究(目标1)这个 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)。 这项研究将评估效果的可逆性，这取决于ID及其治疗的时机(目标3)，以及 检查胎盘和白血球中母体和胎儿铁的调节机制(目标4)。国家-最新情况- ART神经生理学和行为测量将测试有关ID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 靶向感觉/运动系统与结构、神经递质功能和神经代谢的改变 大脑区域(基底节和海马体)。这项研究将在发展迅速的中国进行 在缺乏全身性免疫缺陷的情况下，孕妇和婴儿中经常发生艾滋病的国家 营养不良。1122名农村足月新生儿脐血血红蛋白和铁蛋白浓度测定 婴儿，在9个月和18个月时再次测定铁状态。围产期的脑行为评估 期间将涉及359名婴儿(“新生儿队列”)：59名低Hb婴儿(“低出生铁”组)将获得铁；200名 有边缘Hb或低脐带铁蛋白的人(“边缘出生铁组”)将在6周时随机分配到铁组，50周为铁组 其中150人接受治疗，150人服用安慰剂；100人脐带Hb和铁蛋白水平正常(“出生铁正常”组)。 服用安慰剂。剩下的763名接受脐带血检测的婴儿将组成“血液筛查队列”。在9点 和18个月，将重新评估新生儿队列，以及血液筛查队列中的IDA婴儿- 出生后9个月(“早期缺铁性贫血”)约为58例，18个月(“晚期缺铁性贫血”)约为48例。大约39个边缘出生- 接受铁安慰剂治疗的新生儿队列中的婴儿也可能在9个月时患上缺铁性贫血(“综合ID”)。艾达 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中所有项目的调查结果。差异效应和/或 可逆性取决于ID或治疗的时间，可以为世界各地的卫生政策和实践提供信息。 然而，产前缺铁的影响在人类婴儿中得到的研究很少，因为 这部分与以前的想法不再被接受，即婴儿受到保护。高达75%的孕妇 全世界都有贫血，其中大约一半是由于缺铁性贫血。据估计，6到24个月的婴儿中有20%-25%患有缺铁性贫血， 而且更多的人有身份证，没有贫血。因此，研究结果对公共卫生的影响，特别是在 与项目II-IV动物模型相结合，可能会产生深远的影响。

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.