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

缺铁(ID)是世界上最常见的单纯性营养障碍，孕妇和 婴儿的风险最高。由于先前研究的长期差异，对发育中的大脑和 婴儿的行为和发育是最令人担忧的问题之一。然而，根本问题是 关于早期ID的因果关系、时间、持续时间和严重性仍未得到回答。拟议的研究将 根据时机(目标1)和持续时间(目标1)确定预防ID的发育/行为影响 2)补充铁(即出生前和/或出生后早期)。这项研究将把结果与ID的严重性联系起来 (目标3)，并考虑铁剂治疗效果的可逆性，取决于时机(目标4)。我们预计 脑内不同阶段发生或防治ID对神经行为的不同影响 发展(扩散和生长阶段，主要是产前和区域多样化和 互联在很大程度上处于起步阶段)。该项目需要2个随机对照试验(RCT)来支持 关于出生前和/或产后早期预防糖尿病的因果推断。该项目建立在一个大型疾控中心- 支持农村中国孕妇参与的研究。拟议随机对照试验中的婴儿研究小组 包括：a)出生前和出生后早期的铁，b)产前的铁，c)出生后的早期铁，以及d)都不是(n= 每组500人，总数为2000人)。铁的状态和敏感的感觉、运动、认知、语言和 社会情绪结果将在出生时、6、12和24个月进行评估。B)v.c)组的比较 相对于d)将确定在出生前和出生后早期预防ID的不同效果(目标1，时机)。 A)产前和产后铁v.b)或c)组的比较将确定早期铁的持续时间 补充剂具有不同的行为/发育影响(目标2)。目标1和目标2的结果将 确定预防缺铁影响的最佳窗口，以及母乳喂养的婴儿是否在6岁之前从铁中受益 莫。将对每个年龄段的婴儿铁状况测量进行单独和组合分析，以确定 不同发展领域受到不利影响的ID水平(严重性，目标3)。如果有不良影响 没有贫血的ID被记录在案，可能会有重大的政策影响；目前只有筛查 治疗贫血症。检测到或多或少易受攻击的域还可能指向除 铁器疗法。为了确定可逆效应，取决于治疗的年龄(目标4)，24个月的结果将 与婴儿进行比较1)从不缺铁，2)出生时铁状况较差，并被分配给出生后铁，3) 孕妇缺铁性贫血(贫血)在怀孕第一或第二个月治疗，4)婴儿缺铁性贫血在6个月治疗，以及5)缺铁性贫血治疗 在中午12点。这项研究比较了可用方法--乳房补铁及其时机-- 喂养婴儿，在不同年龄进行筛查和治疗-将使结果与全球实践高度相关 以及关于身份证的政策，这对各地的贫困和/或少数族裔妇女和婴儿有不同的影响。

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.