Timing, Duration and Severity of Infant Iron Deficiency: Developmental Impacts

缺铁（ID）是世界上最常见的单一营养素紊乱，孕妇和 婴儿的风险最高。与先前研究中的长期差异，对发育中的大脑的影响， 婴儿的行为和发育是最令人担忧的问题之一。然而，基本问题 关于早期ID的因果关系、时间、持续时间和严重程度仍然没有答案。拟定的研究将 根据时间（目标1）和持续时间（目标2）确定预防ID的发育/行为效果 2)铁补充剂（即，出生前和/或出生后早期）。研究将结果与ID的严重程度相关 (Aim 3）并考虑铁剂治疗效果的可逆性，取决于时间（目的4）。我们预计 在大脑的不同阶段发生或预防/治疗ID时的不同神经行为效应 发展（扩散和增长阶段，主要是产前和区域多样化， 互联网在很大程度上处于婴儿期）。该项目需要2项随机对照试验（RCT）来支持 关于产前和/或产后早期预防ID的因果推断。该项目建立在一个大型CDC- 中国农村孕妇的研究。拟议RCT中的婴儿研究组 组合为a）产前和产后早期铁，B）产前铁，c）产后早期铁，和d）两者都没有（n = 10）。 500只/组，总计2000只，研究结束时）。铁状态与敏感的感觉、运动、认知、语言和 在出生时、6个月、12个月和24个月时评估社会情感结果。组B）与组c）的比较 相对于d），将确定预防出生前和出生后早期ID的不同效果（目标1，时机）。 比较组a）出生前和出生后的铁v. B）或c）将决定早期铁的持续时间是否 补充具有不同的行为/发育效应（目标2）。目标1和2的结果将 确定预防ID效应的最佳窗口，以及母乳喂养的婴儿在6岁之前是否受益于铁 密苏里州每个年龄段的婴儿铁状态测量将单独分析和组合分析，以确定 不同发育领域受到不利影响的ID水平（严重程度，目标3）。如果有不良影响 没有贫血的ID的记录，可能有重大的政策影响;筛查目前只是 治疗贫血检测或多或少的脆弱领域也可能指向其他干预措施， 铁疗法为了确定可逆性效应，根据治疗年龄（目标4），24个月时的结局将 比较婴儿1）从未缺铁，2）出生时铁状况差，并分配到产后铁，3） 母亲IDA（贫血）在妊娠早期或中期接受治疗，4）婴儿IDA在6个月时接受治疗，5）IDA接受治疗 这项研究比较了现有的方法--补充铁及其在乳房中的时机-- 喂养的婴儿，不同年龄的筛查和治疗-将使结果与全球实践高度相关 和有关ID的政策，这对各地的贫困和/或少数民族妇女和婴儿产生了不同的影响。

Iron deficiency (ID) is the most common single nutrient disorder in the world, and pregnant women and infants are at highest risk. With long-lasting differences in prior studies, effects on the developing brain and infant behavior and development are among the most worrisome concerns. However, fundamental questions about causality, timing, duration, and severity of early ID remain unanswered. The proposed study will determine developmental/ behavioral effects of preventing ID depending on timing (Aim 1) and duration (Aim 2) of iron supplementation (i.e., pre- and/or early postnatally). The study will relate outcomes to severity of ID (Aim 3) and consider reversibility of effects with iron therapy, depending on timing (Aim 4). We expect different neurobehavioral effects when ID occurs or is prevented/treated during different phases of brain development (proliferation and growth phase primarily prenatally and regional diversification and interconnection largely in infancy). The project entails 2 randomized controlled trials (RCTs) to support causal inferences about preventing ID pre- and/or early postnatally. The project builds on a large CDC- supported study involving pregnant women in rural China. Study groups of infants in the proposed RCTs combined are a) pre- and early postnatal iron, b) prenatal iron, c) early postnatal iron, and d) neither (n = 500/group, total 2000, at study end). Iron status and sensitive sensory, motor, cognitive, language, and social-emotional outcomes will be assessed at birth, 6,12, and 24 mo. Comparisons of groups b) v. c) relative to d) will identify differential effects of preventing ID pre- v. early postnatally (Aim 1, timing). Comparisons of groups a) pre- & postnatal iron v. b) or c) will determine whether the duration of early iron supplementation has differential behavioral/developmental effects (Aim 2). Results of Aims 1 & 2 will determine the best window to prevent ID effects and whether breast-fed infants benefit from iron before 6 mo. Infant iron status measures at each age will be analyzed individually and in combination to determine the level of ID at which different developmental domains are adversely affected (severity, Aim 3). If ill effects of ID without anemia are documented, there could be major policy implications; screening is currently only for anemia. Detecting more or less vulnerable domains may also point to other interventions in addition to iron therapy. To identify reversibile effects, depending on age of treatment (Aim 4), outcomes at 24 mo will be compared for infants 1) never iron-deficient, 2) poor iron status at birth and assigned to postnatal iron, 3) maternal IDA (anemia) treated in the 1st or 2nd trimester, 4) infant IDA treated at 6 mo, and 5) IDA treated at 12 mo.The study's comparisons of available approaches - iron supplementation and its timing in breast- fed infants, screening and treatment at different ages - will make the results highly relevant to global practice and policy regarding ID, which differentially affects poor and/or minority women and infants everywhere.