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），这种疾病以肠道炎症的快速发展为特征 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 发病机理知之甚少，并且没有诊断性测试可以预测哪些婴儿会发育 NEC;此外，没有有效的预防策略。最近的研究发现了红血 细胞（RBC）输血，这是一种非常低的出生体重（ELBW）婴儿的常见疗法，很重要 与输血相关NEC（TR-NEC）的发展中的危险因素和潜在的病因因素， 定义为NEC在RBC输血后的48小时内发育。但是，生物学和临床 RBC TR-NEC的决定因素仍然很少理解。 我们提出的研究将招募220位ELBW婴儿，并成为第一个前瞻性，大，多中心队列 研究研究NEC发展的基础的病理生理机制 RBC输血。我们的总体假设是RBC单位的辐射，然后延长 存储Perturbs RBC代谢/功能，导致矛盾的微血管血管收缩，组织 由于明显的，患有已经受损的肠道氧合的输血婴儿中缺氧和TR-NEC 贫血。我们的三个具体目标将检验该假设的关键方面。这项研究将利用创新 研究TR-NEC的方法，包括代谢组学（目标1和2），近红外光谱（NIRS） 这是一种体内非侵入性测量的氧气肠道区域饱和度（Mes-rso2； Aims 1和3）和体外RBC功能研究（AIM 2）。这项拟议的研究将填补关键知识空白 关于RBC存储时间和辐照对新生儿肠道损伤的影响。此外，这些数据将 指导新干预措施的开发，例如使用NIR来识别易感婴儿，限制IST 存储的RBC产品，并使用代谢物生物标志物预测RBC安全。 该项目涉及P01中心主题，因为ELBW早产儿是人口 容易受到先进的RBC输血的开发。这个项目互动 通过识别与不利相关的代谢生物标志物，通过项目1、3和4 输血事件。此外，核心A（法规批准，样本存储库），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利用。