Project 2: RBC Irradiation and Anemia Trigger Gut Injury in Preterm Infants

项目 2：红细胞辐射和贫血引发早产儿肠道损伤

• 批准号: 8794966
• 负责人: CASSANDRA D JOSEPHSON
• 金额: $ 35.26万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8794966
• 关键词: Address; Age; Anemia; Arachidonic Acids; Biological Markers; Biometry; Birth; Blood; Cell physiology; Cessation of life; Characteristics; Clinical; Clinical Markers; Cohort Studies; Cytomegalovirus; Data; Defect; Development; Diagnostic tests; Disease; Encapsulated; Enrollment; Enteral Feeding; Erythrocyte Transfusion; Erythrocytes; Event; Exposure to; Extremely Low Birth Weight Infant; Functional disorder; Genetic Markers; Hemoglobin; Hospitals; Hour; Hypoxia; In Vitro; Infant; Inflammation; Inflammatory; Inflammatory disease of the intestine; Injury; Integration Host Factors; Intervention; Intestines; Investigation; Knowledge; Lipids; Low Birth Weight Infant; Measurement; Measures; Mediating; Mediator of activation protein; Mesentery; Metabolic; Metabolism; Methods; Near-Infrared Spectroscopy; Necrosis; Necrotizing Enterocolitis; Neonatal; Neonatal Mortality; Oxygen; Pathogenesis; Pathology; Pathway interactions; Patient Recruitments; Physiological; Population; Premature Infant; Prevention strategy; Prospective Studies; Public Health Schools; Publishing; Reperfusion Injury; Reporting; Research; Research Infrastructure; Risk; Risk Factors; Safety; Sampling; Testing; Time; Tissues; Transfusion; Vasodilation; Very Low Birth Weight Infant; Vulnerable Populations; cohort; design; hazard; high risk; in vivo; innovation; insight; irradiation; metabolomics; mortality; neonatal morbidity; neonate; prevent; prospective; repository; response; transmission process; vasoconstriction

Necrotizing enterocolitis (NEC), a disease characterized by rapid development of intestinal inflammation, often resulting in gut necrosis, is a leading cause of neonatal morbidity and mortality. NEC pathogenesis is poorly understood, and there are no diagnostic tests to predict which infants will develop NEC; furthermore, there are no effective prevention strategies. Recent studies have identified red blood cell (RBC) transfusion, a common therapy in extremely low birth weight (ELBW) infants, as an important risk factor and potential causative factor in the development of transfusion-related NEC (TR-NEC), defined as NEC developing within 48 hours of a RBC transfusion. However, biologic and clinical determinants of RBC TR-NEC remain poorly understood. Our proposed study will enroll 220 ELBW infants and be the first prospective, large, multicenter cohort study to investigate the pathophysiologic mechanisms that underlie the development of NEC following RBC transfusion. Our overarching hypothesis is that irradiation of RBC units followed by prolonged storage perturbs RBC metabolism/function, leading to paradoxical microvascular vasoconstriction, tissue hypoxia and TR-NEC in transfused infants with already impaired gut oxygenation due to significant anemia. Our three specific aims will test key aspects of this hypothesis. This study will utilize innovative methods to study TR-NEC, including metabolomics (Aims 1 and 2), near-infrared spectroscopy (NIRS) which is an in vivo non-invasive measure of mesenteric regional saturation of oxygen (MES-rSO2; Aims 1 and 3), and in vitro RBC functional studies (Aim 2). This proposed study will fill key knowledge gaps regarding the effects of RBC storage time and irradiation on neonatal gut injury. Further, these data will guide development of new interventions, such as using NIRS to identify susceptible infants, limiting IST of stored RBC products, and using metabolite biomarkers to predict RBC safety. This project addresses the P01 central theme since ELBW preterm infants are a population vulnerable to the development of TR-NEC with antecedent RBC transfusion(s). This project interacts with Projects 1, 3, and 4 by identifying metabolic biomarkers that are associated with adverse transfusion events. Additionally Core A (regulatory approvals, sample repository), Core B (metabolomics), and Core C (biostatistics) are utilized heavily in the proposed studies.

坏死性小肠结肠炎(NEC)是一种以肠道炎症迅速发展为特征的疾病， 通常导致肠道坏死，是新生儿发病率和死亡率的主要原因。NEC 发病机制尚不清楚，也没有诊断测试来预测哪些婴儿会发育。 NEC；此外，没有有效的预防战略。最近的研究发现了红血球 细胞(RBC)输注是极低出生体重(ELBW)婴儿的一种常见治疗方法，是一种重要的 输血相关NEC发生的危险因素和潜在致病因素， 定义为输注红细胞后48小时内发生的NEC。然而，生物学和临床 红细胞受体-NEC的决定因素仍然知之甚少。 我们建议的研究将招募220名极低出生体重儿，并成为第一个预期的、大型的多中心队列研究 探讨NEC继发的病理生理机制 红细胞输注。我们的主要假设是，照射RBC单位后延长 储存扰乱红细胞新陈代谢/功能，导致矛盾的微血管收缩，组织 输血后已存在明显肠道氧合损害的婴儿的缺氧和tr-NEC 贫血。我们的三个具体目标将检验这一假设的关键方面。本研究将利用创新的 研究方法包括代谢组学(AIMS 1和2)、近红外光谱(NIRS)。 这是一种体内无创性测量肠系膜局部氧饱和度(MES-rSO2；AIMS)的方法 1和3)，以及体外红细胞功能研究(目标2)。这项拟议的研究将填补关键的知识空白 探讨红细胞保存时间和照射对新生儿肠道损伤的影响。此外，这些数据将 指导制定新的干预措施，如使用近红外光谱识别易感婴儿，限制IST 并使用代谢物生物标志物来预测红细胞的安全性。 该项目涉及P01的中心主题，因为早产儿是一个群体 易患既往红细胞输注的TR-NEC(S)。此项目将与 项目1、3和4通过识别与不良反应相关的代谢生物标记物 输血事件。此外，核心A(监管审批、样本库)、核心B (代谢组学)和核心C(生物统计学)在拟议的研究中被大量使用。