Neuromaturational Delays in Iron Deficient Anemic Infants

描述(由申请人提供)：缺铁性贫血(IDA)在发育早期会对大脑和行为产生影响，可能会产生终生后果。动物模型显示了大脑结构、功能和相关行为的长期变化。在缺铁期间和多年后，婴儿的IDA与较差的运动、认知、社会情绪和神经生理结果有关。拟议的项目将确定婴儿期IDA的长期神经生物学效应(目标1)、与婴儿期预防IDA有关的成人功能结果(目标2)以及给铁充足的婴儿补铁的长期影响(目标3)。这是唯一一项对健康足月儿进行IDA及其预防的大型纵向研究。超过110名21岁的智利人在婴儿时期参加了铁缺乏项目的预防性试验和/或神经生物学方面的研究，并在4-5岁、10岁和16岁进行了随访。此外，研究人员还评估了与铁调节、神经递质功能和行为相关的功能性遗传多态。对于目标1，我们将继续进行最先进的神经生理学、神经成像(ERP)和行为测试，以确定早期IDA对神经认知和调节功能(睡眠-觉醒周期、神经内分泌)的长期影响及其与复杂行为的整合。这些复杂的神经生物学研究将在更大的队列中进行，包括90名21岁的婴儿期IDA患者和65名非贫血对照组。我们预测，前IDA组睡眠-觉醒周期的中断将扰乱与认知和情绪相关的系统。纵向分析将确定哪些影响是暂时的、持久的或在青春期出现的。我们假设，患有早期缺铁性贫血和易感基因的参与者在年轻时会表现出更多的不良后果。目的2继续我们的观察，观察婴儿时期更多的适应性行为，以及在婴儿时期随机服用铁剂的参与者中的10年适应性行为。在21岁时，我们预测婴儿期补充铁将有助于更好的功能结果，包括教育轨迹、工作潜力、心理健康和亲密关系(n~1028)。我们预计遗传交互作用-铁将更有益于那些与缺铁风险增加和/或精神健康或认知功能较差相关的基因型的个体。目标3涉及婴儿期普遍补铁和给铁充足的婴儿补铁的潜在风险。我们将比较258名婴儿时期随机服用高铁配方奶粉的受试者和230名随机服用低铁配方奶粉的受试者的成年功能。我们还将比较33名婴儿时期铁充足并接受至少6个月医用铁治疗的参与者和33名未接受治疗的参与者的非常敏感的神经生物学结果。这项研究仍然处于确定IDA对大脑和行为的长期影响、对健康的足月人类婴儿的预防以及向铁充足的婴儿提供铁的潜在风险的前沿。

DESCRIPTION (provided by applicant): Iron-deficiency anemia (IDA) during early development has brain and behavior effects that may have lifelong consequences. Animal models show long-lasting changes in brain architecture, function and associated behaviors. IDA in infants is associated with poorer motor, cognitive, social-emotional, and neurophysiologic outcomes during iron deficiency and years later. The proposed project will determine long-term neurobiological effects of IDA in infancy (Aim 1), adult functional outcomes related to preventing IDA in infancy (Aim 2), and long-term effects of giving iron to iron-sufficient infants (Aim 3). Itis the only large, longitudinal study of IDA and its prevention in healthy full-term infants. Over 110 Chileans, who will be 21 years old, participated in preventive trial and/or neurobiology aspects of an iron deficiency project as infants, with follow up at 4-5, 10, and 16 y. In addition, the cohrt has had assessment of functional genetic polymorphisms related to iron regulation, neurotransmitter function, and behavior. For Aim 1, we will continue state-of-art neurophysiologic, neuroimaging (ERP), and behavioral testing for hypotheses regarding long-lasting effects of early IDA on neurocognitive and regulatory functions (sleep-wake cycle, neuroendocrine) and their integration into complex behaviors. These sophisticated neurobiological studies will be conducted in a subset of the larger cohort, 90 21-year-olds with infancy IDA and 65 non-anemic controls. We predict that disruption in sleep-wake cycle in the former IDA group will disturb systems related to cognition and emotion. Longitudinal analysis will determine which effects are transient, persistent, or emergent through young adulthood. We hypothesize that participants with early IDA and vulnerable genotypes will show more adverse outcomes as young adults. Aim 2 pursues our observations of more adaptive behavior in infancy and 10 y among participants randomized to prophylactic iron in infancy. At 21 y, we predict that infancy iron supplementation will contribute to better functional outcomes, including educational trajectories, job potential, mental health, and close relationships (n ~ 1028). We expect genetic interactions-iron will be more beneficial for individuals with genotypes associated with increased risk for iron deficiency and/or poorer mental health or cognitive function. Aim 3 addresses universal iron supplementation in infancy and potential risks in giving iron to iron-sufficient infants. We will compare adulthood functioning in 258 individuals randomized to high-iron formula in infancy and 230 randomized to low- iron formula. We will also compare our very sensitive neurobiological outcomes in 33 participants who were iron-sufficient in infancy and treated with medicinal iron for at least 6 mo and 33 who were untreated. This study remains at the forefront of determining long-term brain and behavioral effects of IDA, its prevention in the healthy full-term human infant, and potential risks of providing iron to iron-sufficient infants.