The unifying theme of this PPG renewal is understanding the pathophysiology, and establishing the optimal management, of two of the most serious and frequently encountered conditions among critically ill, premature infants: anemia and thrombocytopenia. Current treatment for these conditions relies largely on transfusion of red blood cells and platelets?therapies that remain controversial and incompletely investigated. Prior research by our PPG group and others has established that many aspects of the pathophysiology of the anemia and thrombocytopenia of prematurity are unique. However, our understanding is incomplete. Hence, the goals of our renewal are to further define the mechanisms that give rise to these pressing and related clinical conditions, to optimize their treatment per such mechanistic knowledge, and consequently, to reduce both short- and long-term disabilities associated with these conditions. Our 4 interrelated projects, whose objectives are directly relevant to our unifying theme, include: Project 1 """"""""Optimized erythropoietin treatment of neonatal anemia,"""""""" PL JA Widness (and P Veng-Pedersen);Project 2 """"""""Pathogenesis and treatment of neonatal thrombocytopenia,"""""""" PL M Sola-Visner;Project 3 """"""""Preterm transfusions: brain structure/function outcomes,"""""""" PL PC Nopoulos;and Project 4 """"""""The role of neonatal anemia In learning and memory,"""""""" PL MK Georgieff. Core A (""""""""Administrative, statistical, and research personnel"""""""") and Core B (""""""""Laboratory and database,"""""""" PL DM Mock) will provide support for all projects. To enhance effectiveness, our program has expanded to involve four (vs. two) performance sites, so that data can be shared among Projects 1, 2 and 3 (i.e. data from the same infants will be used In studies at multiple sites). Our history of success conducting multisite research will be invaluable in coordinating studies across the various performance sites. Because our Program rests on a highly-qualified, multidisciplinary group of new and experienced investigators, our renewal program consists of unique and collaborative research teams capable of accelerating the acquisition of knowledge vital to the fields of neonatal anemia and thrombocytopenia. Over the past 17 years, our productive PPG group (200 publications) has made a substantial impact on clinical practice and research in neonatal transfusion medicine and hematology. Our program embraces and exemplifies the synergistic P01 approach, which has and will enable us to make more rapid progress than any of us could individually. With this renewal, we are poised to continue to challenge paradigms and advance knowledge, as we build on prior results and maximize collaboration.

Public Health Relevance

The research proposed will enhance understanding of the pathophysiology of the 2 most important, common and costly hematological conditions encountered in the NICU: anemia and thrombocytopenia. It will do so by providing definitive answers to important, challenging, and timely clinical questions and by expanding potential treatment options to reduce costly short- and long-term consequences of these 2 challenging conditions. Results of our studies support the NIH's mission of reducing the burdens of illness and disability.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL046925-17
Application #
8491917
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Mondoro, Traci
Project Start
2000-04-01
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
17
Fiscal Year
2013
Total Cost
$1,878,101
Indirect Cost
$324,219
Name
University of Iowa
Department
Pediatrics
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Nalbant, Demet; Cancelas, José A; Mock, Donald M et al. (2017) In premature infants there is no decrease in 24-hour posttransfusion allogeneic red blood cell recovery after 42 days of storage. Transfusion :
Sparger, Katherine A; Ramsey, Haley; Lorenz, Viola et al. (2017) Developmental differences between newborn and adult mice in response to romiplostim. Platelets :1-8
Wallin, Diana J; Zamora, Tara G; Alexander, Michelle et al. (2017) Neonatal mouse hippocampus: phlebotomy-induced anemia diminishes and treatment with erythropoietin partially rescues mammalian target of rapamycin signaling. Pediatr Res 82:501-508
MacQueen, B C; Christensen, R D; Henry, E et al. (2017) The immature platelet fraction: creating neonatal reference intervals and using these to categorize neonatal thrombocytopenias. J Perinatol 37:834-838
Kuruvilla, Denison J; Widness, John A; Nalbant, Demet et al. (2017) Estimation of adult and neonatal RBC lifespans in anemic neonates using RBCs labeled at several discrete biotin densities. Pediatr Res 81:905-910
Bastian, T W; Duck, K A; Michalopoulos, G C et al. (2017) Eltrombopag, a thrombopoietin mimetic, crosses the blood-brain barrier and impairs iron-dependent hippocampal neuron dendrite development. J Thromb Haemost 15:565-574
Schmidt, Robert L; Mock, Donald M; Franco, Robert S et al. (2017) Antibodies to biotinylated red blood cells in adults and infants: improved detection, partial characterization, and dependence on red blood cell-biotin dose. Transfusion 57:1488-1496
Peters, Anna L; Beuger, Boukje; Mock, Donald M et al. (2016) Clearance of stored red blood cells is not increased compared with fresh red blood cells in a human endotoxemia model. Transfusion 56:1362-9
Ekhaguere, Osayame A; Morriss Jr, Frank H; Bell, Edward F et al. (2016) Predictive factors and practice trends in red blood cell transfusions for very-low-birth-weight infants. Pediatr Res 79:736-41
Brumbaugh, Jane E; Conrad, Amy L; Lee, Jessica K et al. (2016) Altered brain function, structure, and developmental trajectory in children born late preterm. Pediatr Res 80:197-203

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