NEONATAL ANEMIA--PATHOPHYSIOLOGY AND TREATMENT

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The organizing theme of our Program is anemia in the neonatal patient, its etiology, manifestations, morbidities and treatments. We have two strategic goals: first, to reduce the number of homologous red blood cell (RBC) transfusions that neonatal patients receive; and second, to achieve the optimal benefit-to-risk ratio for unavoidable transfusions. We will address these goals by examining the physiological mechanisms that lead to neonatal anemia, by establishing sound scientific criteria for the detection of clinically significant anemia, by exploring therapy with recombinant human erythropoietin in an ovine model, by comparing the physiological effects of transfusions given at different levels of hematocrit, by modifying current blood banking techniques to permit long- term RBC support by a single blood donor, and by developing a nonradioactive method for safely measuring RBC volume and survival in neonates. Our Program integrates four projects that have inter-related aims, depend upon collaborative relations among the principal investigators, and share personnel and resources. Project #1, "Response to Anemia During Neonatal Period," uses an ovine model to focus on differences between anemic neonates and adults and on the differences in neonatal and adult responses to erythropoietin therapy. Project #2, "A Nonradioactive Method for RBC Volume and Survival," will develop and validate a biotin labeling method that will be applied to human infants. Project #3, "Red Blood Cell Transfusions for Anemia of Prematurity," will investigate the physiological effects of neonatal anemia and the infant's physiological responses to transfusion. Project #4, "Safety and Feasibility of Single- Donor Programs," will develop and test innovative blood banking techniques to establish whether RBCs, obtained from a single donor and stored for up to six weeks, can be safely transfused to infants. Investigators and consultants from Pediatrics, Pathology, Pharmacology, Radiology and Anatomy will collaborate in these projects. The theme of our Program is particularly important because neonates are among the most heavily transfused of all patient groups. Of the 38,000 premature neonates with birth weight <1500 g born annually in the United States, 80% will receive an average of ten RBC transfusions during early life--accounting for nearly 300,000 transfusions per year. Thus, information from our studies will be of immediate interest to the practice of neonatology and will provide a basis for continued research in perinatal hematopoiesis, hematology and transfusion medicine.