Impaired Brain Development in a Premature Ex-utero Environment

过早的宫外环境中大脑发育受损

• 批准号: 9973941
• 负责人: ADRE Jacques DU PLESSIS
• 金额: $ 73.43万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-12 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9973941
• 关键词: Acute; Address; Age; Anatomy; Behavioral; Biological Markers; Bradycardia; Brain; Brain Injuries; Caring; Clinical Trials; Cognitive; Complex; Critical Illness; Data; Databases; Development; Dissociation; Early Intervention; Effectiveness; Ensure; Environment; Environmental Exposure; Event; Evolution; Exposure to; Fetus; Functional disorder; Future; Gestational Age; Goals; Growth; High Prevalence; Hypotension; Image; Impairment; Infant; Intervention; Investigation; Knowledge; Lead; Lesion; Link; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Measures; Metabolism; Nature; Neuropsychology; Outcome; Physiological; Play; Population; Pregnancy; Premature Birth; Premature Infant; Public Health; Readiness; Risk; Role; Services; Signal Transduction; Special Education; Structure; Survivors; System; Techniques; Time; aging brain; cost; data acquisition; data warehouse; disability; fetal; functional outcomes; impaired brain development; improved; in utero; magnetic resonance imaging biomarker; multimodal data; multimodality; neurodevelopment; neuroprotection; postnatal; premature; repository; social; societal costs; tool; trend

ABSTRACT Despite significant advances in survival and the decreased risk of major brain injury in premature infants, the persistent high prevalence of long-term remains a major public health problem, with enormous personal, familial, and societal costs. There is growing evidence that impaired structural brain development is detectable in premature infants before term corrected age, even without overt destructive brain injury. Together these observations suggest that brain dysmaturation in an artificial ex-utero environment disturbs neuropsychological development in prematurity survivors. In turn, this points to ongoing gaps between the effectiveness of current support/protection strategies for ex-utero preterm brain development, and that provided by the normal in-utero environment. Critical to closing this gap is identifying the disruptive interactions between the complex shifting landscape of brain maturation/vulnerability, and preterm ex-utero exposures, among which circulatory and oxygenation (C/O) exposures are considered a leading cause of neuropsychologic impairment. To approach this challenge the necessary steps are: to identify the earliest deviations of ex-utero brain maturation compared to normal in-utero brain maturation; to identify the temporal relationship between the onset of brain dysmaturation and preceding C/O exposures; and, to confirm that the early preterm maturational changes predict structural brain development at term-corrected age, and later functional outcome. To date, progress has been impeded by (i) the lack of reference data for normal in-utero brain development, (ii) the lack of serial measurements of ex-utero preterm brain development, and (iii) the lack concurrent biomarkers that capture continuous C/O exposures. Using our large repository of normal in-utero brain development and multimodal quantitative MRI, our preliminary studies show significant anatomic differences in brain development occurring in utero vs. ex utero, detectable well before term-equivalent age. We have developed systems for measuring and analyzing continuous physiological signals in sick preterm infants. In this proposal we combine serial 4- weekly MRI with concurrent exposure measurements in infants born <36 weeks gestation, to establish the relationship between disturbed early brain maturation, specific preterm C/O exposures, and their association with long-term neuropsychological impairment. These findings may inform future brain-oriented support of premature infants, identify specific targets for neuroprotection, and lead to improved neuropsychological outcomes.

抽象的 尽管生存率取得了重大进步和早产儿的重大脑损伤风险降低，但 长期持续持续的高流行仍然是一个重大的公共卫生问题，存在巨大的个人， 家族和社会成本。越来越多的证据表明结构性大脑发育受损 在学期校正年龄之前的过早婴儿中，即使没有明显的破坏性脑损伤。在一起 观察结果表明，人造前utero环境中的大脑不饱和肿瘤干扰神经心理学 早产幸存者的发展。反过来，这表明当前有效性之间持续的差距 前utero早产的支持/保护策略，并由正常UTERO提供 环境。缩小这一差距至关重要的是确定复杂变化之间的破坏性相互作用 大脑成熟/脆弱性的景观，以及早产前的暴露，其中循环和 氧合（C/O）暴露被认为是神经心理障碍的主要原因。接近 这项挑战必不可少的步骤是：确定比较前脑大脑成熟的最早偏差 正常脑内脑成熟；确定大脑发作之间的时间关系 不饱和和先前的C/O暴露；并且，确认早期早产的变化 预测期限校正时的结构性大脑发育，以及后来的功能结果。迄今为止，进步 （i）缺乏正常utero脑发育的参考证据所阻碍，（ii）缺乏序列 前 - Utero早产的测量，以及（iii）缺乏捕获的并发生物标志物 连续C/O暴露。使用我们正常utero脑发育和多模式的大型存储库 定量MRI，我们的初步研究表明，大脑发育发生了显着的解剖学差异 在子宫与前子宫内，可以在学期等年龄之前检测到。我们开发了用于测量的系统 并分析病人早产的连续生理信号。在此提案中，我们结合了串行4- 每周MRI，同时出生的婴儿的暴露测量<36周妊娠，以建立 干扰早期大脑成熟，特定早产C/O的关系及其关联之间 长期神经心理学障碍。这些发现可能会为未来的面向脑部的支持提供 早产儿，确定神经保护的特定靶标，并改善神经心理学 结果。