NEONATAL ANEMIA--PATHOPHYSIOLOGY AND TREATMENT

此申请是我们以前计划的竞争性更新 题为“新生儿贫血：病理生理学和 治疗“更新是基于从发现中发展出来的假设 原始PPG加上新生儿血液学中出现的新组织， 输血医学尽管最初PPG的所有目标都 已取得了进展（发表了512份手稿，7 已提交审查，15份正在编写），重要的是 继续在PPG环境下进行新生儿贫血研究，因为：1）医学 科学还没有达到一个全面的了解， 新生儿红细胞生成的生理学和 早产儿贫血; 2）严重的输血依赖性贫血 仍然是早产儿每天面临的一个问题， 疗效、毒性和最佳治疗方法尚未明确界定。 我们PPG的主题是优化新生儿贫血的管理- 特别是早产儿的严重贫血， 红细胞（RBC）输注。两个战略目标和八个具体目标将 由三个项目和一个核心来满足。为了优化重组 人促红细胞生成素（EPO）治疗新生儿贫血。项目#1将 继续研究生理学、药代动力学（PK）和 使用EPO的新方法的药效学（PD）， 生物素化EPO。研究铁（Fe）的有效性和 蛋白质营养与早产儿贫血的病理生理 并确定他们在治疗和可能的预防方面的要求 新生儿贫血，项目#2将研究蛋白质和 不同铁摄入量对红细胞生成的影响 输血和EPO对Fe治疗的影响，以及 静脉注射铁治疗。确定自体移植的益处 含有成熟RBC的胎盘输血， 造血/免疫祖细胞，项目#3将研究 延迟脐带钳夹或等效物的影响 胎盘血输注对新生儿血液及红细胞的维持作用 体积和造血/免疫发育。芯会 提供行政、统计和研究支助， 为所有项目提供生物素化实验室服务。完成这些 目标，更多的调查人员，在新的领域的专业知识，已 招募来补充我们建立的PPG正在进行的努力 组

This application is a competitive renewal of our previous Program Project Grant (PPG) entitled "Neonatal Anemia: Pathophysiology and Treatment." The renewal is based on hypotheses developed from findings of the original PPG plus new tissues arising in neonatal hematology and transfusion medicine. Although all objectives of the original PPG have been achieve with progress reported (512 manuscripts published, 7 submitted for review, and 15 in preparation), it is important to continue studies of neonatal anemia in a PPG setting because: 1) medical science has yet to achieve a comprehensive understanding of the physiology of neonatal erythropoiesis and the pathophysiology of the anemia of prematurity; and 2) severe, transfusion-dependent anemia continues to be a problem faced daily by preterm infants-for which the efficacy, toxicity and optimal use of therapies are not clearly defined. The theme of our PPG is to optimize management of neonatal anemia- particularly, severe anemia in preterm infants that requires red blood cell (RBC) transfusions. Two strategic goals and eight objectives will be met by three projects and a core. To optimize use of recombinant human erythropoietin (EPO) in treating neonatal anemia. Project #1 will continue to investigate the physiology, pharmacokinetics (PK) and pharmacodynamics (PD) of EPO-utilizing novel methods that employ biotinylated EPO. To investigate the role of iron (Fe) availability and protein nutrition in the pathophysiology of the anemia of prematurity and to define their requirements in treating and possibly preventing neonatal anemia, Project #2 will investigate the effect of protein and graded oral Fe intakes on erythropoiesis, the effects of RBC transfusions and EPO on Fe therapy, and the efficacy and safety of intravenous Fe therapy. To determine the benefits of autologous placental blood transfusions containing mature RBCs and hematopoietic/immunologic progenitor cells, Project #3 will study the effects of delayed umbilical cord clamping or the equivalent transfusions of placental blood on maintaining neonatal blood and RBC volumes and hematopoietic/immunological development. The Core will provide administrative, statistical and research support and biotinylation laboratory services to all projects. To accomplish these goals, additional investigators, with expertise in new areas, have been recruited to complement the ongoing efforts of our established PPG group.