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

描述（由申请人提供）：缺铁（ID）是世界上最常见的单一营养素失调，孕妇和婴儿的风险最高。由于之前的研究存在长期差异，对发育中的大脑和婴儿行为和发育的影响是最令人担忧的问题之一。然而，关于早期ID的因果关系、时间、持续时间和严重程度等基本问题仍未得到解答。拟议的研究将根据补铁（即产前和/或产后早期）的时间（目标1）和持续时间（目标2）来确定预防缺铁的发育/行为影响。该研究将结果与ID的严重程度（Aim 3）联系起来，并考虑铁治疗效果的可逆性，取决于时间（Aim 4）。我们预计在大脑发育的不同阶段（主要是产前的增殖和生长阶段，主要是婴儿期的区域多样化和相互联系）发生或预防/治疗ID时，会产生不同的神经行为影响。该项目包括两项随机对照试验（rct），以支持产前和/或产后早期预防ID的因果推论。该项目建立在一项由美国疾病控制与预防中心支持的大型研究的基础上，该研究涉及中国农村的孕妇。所提出的随机对照试验中的婴儿研究组为a)产前和产后早期铁，b)产前铁，c)产后早期铁，d)两者都没有（n = 500/组，研究结束时共2000）。将在出生、6、12和24个月时评估铁状态和敏感感觉、运动、认知、语言和社会情绪结果。b)组与c)组相对于d)组的比较将确定产前和产后早期预防ID的不同效果（目的1，时间）。a)产前和产后铁与b)或c)组的比较将确定早期补铁的持续时间是否具有不同的行为/发育影响（目的2）。目标1和目标2的结果将确定预防缺铁效应的最佳窗口期，以及母乳喂养的婴儿是否在6个月前从铁中受益。每个年龄段的婴儿铁状态测量将单独分析，并结合分析，以确定不同发育领域受到不利影响的缺铁水平（严重性，目标3）。如果没有贫血的ID的不良影响被记录下来，可能会有重大的政策影响；筛查目前只针对贫血。检测更多或更少的脆弱区域也可能指向除了铁疗法之外的其他干预措施。为了确定根据治疗年龄的可逆性影响（目标4），将比较24月龄婴儿的结局：1)从不缺铁，2)出生时铁状态差并分配到产后铁，3)在妊娠1或2个月治疗的母体IDA（贫血），4)在6个月治疗的婴儿IDA，以及5)在12个月治疗的IDA。该研究比较了可用的方法-母乳喂养婴儿补充铁及其时机，在不同年龄进行筛查和治疗——将使结果与全球有关ID的实践和政策高度相关，ID对各地贫困和/或少数民族妇女和婴儿的影响不同。

DESCRIPTION (provided by applicant): 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.