Neuromaturational Delays in Iron Deficient Anemic Infants

描述（由申请人提供）：早期发育期间的缺铁性贫血（IDA）对大脑和行为有影响，可能造成终身后果。动物模型显示了大脑结构、功能和相关行为的长期变化。婴儿缺铁性贫血与缺铁期间和几年后的运动、认知、社会情感和神经生理结果较差相关。拟议的项目将确定婴儿期IDA的长期神经生物学影响（目标1），与预防婴儿期IDA相关的成人功能结局（目标2），以及给予铁充足婴儿铁的长期影响（目标3）。这是唯一一项在健康足月婴儿中进行的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预防性试验和/或缺铁项目的神经生物学方面，并在4 - 5岁，10岁和16岁时进行随访。此外，cohrt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性。对于目标1，我们将继续进行最先进的神经生理学、神经影像学（ERP）和行为学测试，以研究早期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较大队列的一个子集中进行，90名21岁的婴儿期IDA患者和65名非贫血对照。我们预测，在前IDA组中，睡眠-觉醒周期的中断将干扰与认知和情绪相关的系统。纵向分析将确定哪些影响是短暂的，持久的，或通过年轻的成年出现。我们假设早期IDA和易感基因型的参与者在年轻时会表现出更多的不良后果。目的2追求我们的观察，更多的适应行为在婴儿期和10岁的参与者随机预防铁在婴儿期。在21岁时，我们预测婴儿期补充铁将有助于改善功能结果，包括教育轨迹，工作潜力，心理健康和亲密关系（n~1028）。我们预计遗传相互作用-铁将更有利于与铁缺乏和/或较差的心理健康或认知功能的风险增加相关的基因型的个人。目标3针对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名婴儿期随机接受高铁配方奶粉的个体和230名婴儿期随机接受低铁配方奶粉的个体的成年期功能。我们还将比较我们非常敏感的神经生物学结果，其中33名参与者在婴儿期铁充足，并接受药用铁治疗至少6个月，33名未接受治疗。这项研究仍然处于确定IDA的长期大脑和行为影响的最前沿，它在健康足月人类婴儿中的预防，以及为铁充足的婴儿提供铁的潜在风险。 公共卫生相关性：缺铁性贫血（IDA）是一种全球性的健康问题，对孕妇和婴儿的影响不同，使发育中的大脑在出生前和/或出生后暴露于铁不足。缺铁性贫血很容易用铁治疗来纠正，但对大脑和行为的影响却不能。长期影响可能威胁到数百万成年人现在和未来的福祉。这项研究将在1100多名年轻人的样本中评估这种影响。

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. PUBLIC HEALTH RELEVANCE: Iron deficiency anemia (IDA) is a global health problem that differentially affects pregnant women and infants, exposing the developing brain to inadequate iron pre- and/or postnatally. IDA readily corrects with iron therapy, but effects on brain and behavior do not. Long-term effects may threaten well-being in millions of adults now and in the future. This study will assess such effects in a sample of over 1100 young adults.