NEONATAL ANEMIA:PATHOPHYSIOLOGY AND TREATMENT

这项申请是我们最初的名为“新生儿贫血：病理生理学和治疗”的项目资助(PPG)的竞争性更新。此次更新是基于我们之前的PPG研究结果提出的假设，它还解决了新生儿/婴儿血液学和输血医学中及时出现的新问题。虽然我们之前申请的目标已经基本实现(87篇已发表或正在印刷的手稿，7篇已提交的手稿，23篇正在进行的工作摘要)，但对新生儿的研究 贫血仍然很重要，因为：1)医学尚未全面了解新生儿红细胞生成的生理学和早产儿贫血的潜在病理生理学；2)至少75%的极早产儿和相当数量的较大婴儿仍然存在严重的输血依赖性贫血问题，其疗效、毒性(包括直接和间接的)和 治疗的长期)和最佳使用尚未明确确定。我们PPG的主题是确定机制并优化新生儿和婴儿贫血的管理，特别是需要输血红细胞(RBC)的早产儿的严重贫血。两个战略目标和九个目标将在三个项目和核心A中实现。为了优化不同来源的输血红细胞在治疗新生儿贫血中的使用，项目1将研究人类婴儿和新生羔羊输血后红细胞的恢复和存活率。为了确定与早产儿限制性或自由性输血标准相关的长期神经发育后果，项目2将在儿童参加先前的PPG随机研究12年后对他们进行跟踪研究。为了确定治疗新生儿贫血的最佳重组人促红细胞生成素疗法，项目3将继续 研究促红细胞生成素的生理、药代动力学和药效学。核心A将为所有项目提供研究人员以及行政、统计和实验室支持。为了实现我们的目标和目的，我们招募了更多在新领域具有专业知识的调查人员，以补充我们现有的PPG小组正在进行的努力。

This application is a competitive renewal of our original Program Project Grant (PPG) entitled "Neonatal Anemia: Pathophysiology and Treatment." The renewal is based on hypotheses developed from findings of our previous PPG, and it also addresses timely, new issues in neonatal/infant hematology and transfusion medicine. Although our previous application's objectives have mostly been achieved (87 manuscripts published or in press, 7 submitted manuscripts, and 23 abstracts of work in progress), the study of neonatal anemia remains important because: 1) medical science has yet to achieve a comprehensive understanding of the physiology of neonatal erythropoiesis and the underlying pathophysiology of the anemia of prematurity; and 2) severe, transfusion-dependent anemia continues to be a problem in at least 75% of very preterm infants and a significant number of larger infants, for which the efficacy, toxicity (both immediate and long-term) and optimal use of therapies have not been clearly identified. The theme of our PPG is to define mechanisms and to optimize the management of neonatal and infant anemia ¿ particularly, severe anemia in preterm infants that requires red blood cell (RBC) transfusions. Two strategic goals and nine objectives will be addressed in three projects and Core A. To optimize use of transfused RBCs from different sources in treating neonatal anemia, Project #1 will investigate post-transfusion RBC recovery and survival in human infants and newborn lambs. To determine the long-term neurodevelopmental consequences associated with either restrictive or liberal transfusion criteria in preterm infants, Project #2 will perform follow-up studies on children 12 years after they were enrolled in a previous PPG randomized study. To determine the optimal recombinant human erythropoietin therapy for treating neonatal anemia, Project #3 will continue to investigate the physiology, pharmacokinetics and pharmacodynamics of erythropoietin. Core A will provide research personnel and administrative, statistical, and laboratory support for all projects. To accomplish our goals and objectives, additional investigators with expertise in new areas have been recruited to complement the ongoing efforts of our established PPG group.