NEONATAL ANEMIA:PATHOPHYSIOLOGY AND TREATMENT

描述（由申请人提供）： 本申请是我们原来的计划项目补助金（PPG）的竞争性更新，题为“新生儿贫血：病理生理学和治疗。“更新是基于我们以前的PPG发现的假设，它还及时解决了新生儿/婴儿血液学和输血医学的新问题。虽然我们之前的应用程序的目标大多已经实现，（87篇已发表或正在出版的手稿，7篇已提交的手稿，23篇正在进行的工作摘要），新生儿贫血的研究仍然很重要，因为：1）医学科学尚未实现对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的全面理解;和2）严重的输血依赖性贫血在至少75%的极早产儿和相当数量的较大婴儿中仍然是一个问题，其疗效、毒性（立即和长期）和治疗的最佳使用尚未明确确定。我们PPG的主题是定义机制并优化新生儿和婴儿贫血的管理-特别是需要输注红细胞（RBC）的早产儿重度贫血。三个项目和核心A将涉及两个战略目标和九个具体目标。为了优化来自不同来源的输注RBC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的输注后RBC恢复和存活。为了确定早产儿中与限制性或自由输血标准相关的长期神经发育后果，项目2将对入组既往PPG随机研究后12年的儿童进行随访研究。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学、药代动力学和药效学。核心A将为所有项目提供研究人员和行政，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研究人员，以补充我们现有PPG团队的持续努力。这项研究与公共卫生的相关性：在美国，12%的婴儿早产，其中许多早产儿患有贫血症。这种贫血的原因以及预防或治疗它的最佳方法尚未得到很好的理解。本申请中提出的研究将有助于加深对这一问题的理解，并更好地了解如何预防和治疗这一问题。

DESCRIPTION (provided by applicant): 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. Relevance of this research to public health: Twelve percent of babies are born prematurely in the U.S. Many of these premature babies develop anemia. The reasons for this anemia and the best ways to prevent or treat it are not yet well understood. The research proposed in this application will result in improved understanding of this problem and better knowledge of how to prevent and treat this problem.