The primary goal of Project #2 is to evaluate the long-term outcomes in brain function/structure of two? groups of VLBW infants (<1300 g) with anemia of prematurity, who were randomly assigned to either a? restrictive or liberal RBC transfusion protocol as part of a previous PPG project.
Our aim i s to determine? whether different RBC transfusion guidelines result in different long-term (at age 13)? neurodevelopmental outcomes. Our general hypotheses are: 1) Preterm groups will show structural? abnormalities of frontal, prefrontal, hippocampal, cerebellar and white matter brain regions, with the? restricted transfusion group showing greater abnormalities. 2) Neuropsychological deficits will be? identified in both preterm groups in functions governed by fronto-striatal circuits such as rapid naming,? verbal fluency, working memory, fine-motor dexterity, and attention. 3) There will be a relationship? between documented brain abnormalities and cognitive deficits. We will accomplish our goal by? comparing these two groups at age 13, as well as a matched healthy term control group, on? neuropsychological functions and brain structure (MRI). The hypotheses of Project #2 are based on the? concept that more restrictive transfusion criteria may decrease the oxygen available to the developing? brain and could result in more apnea and hypoxia or create iron depletion, either of which could result? in impaired neurodevelopment. The specific neuropsychological functions and brain structures that will? be addressed in this study have been selected as those most likely to be impaired by limited brain? oxygen delivery or brain iron depletion, either of which could be due to restrictive transfusion criteria or? to poorly understood adverse effects of multiple transfusions. This project allows the evaluation of? strategies for transfusion management of anemia, which is central to the overall PPG theme. Our? specific hypotheses are that more restrictive criteria for transfusion will lead to greater structural? abnormalities in specific regions of the brain including frontal-prefrontal cortex, basal ganglia, and? hippocampus and cerebellum. These abnormalities will affect functions such as rapid naming, verbal? fluency, memory, fine- and gross-motor dexterity, attention and executive functions. More restrictive? criteria will also lead to greater behavioral inhibition due to frontalstriatal deficits; but will not lead to? differences in more general functions such as language, visual-spatial skills, long-term memory,? intelligence, and academic achievement. The study proposed is timely because all of the children will? be 13 years old during this study period, allowing examination of long-term effects of the transfusion? practices. It is also timely in light of the continuing controversy regarding the most appropriate RBC? transfusion guidelines to be used to treat anemia of prematurity. The long-term neuropsychological and? brain imaging follow-up of premature anemic infants receiving different transfusion management criteria? has never before been examined. This study will provide important findings related to potential adverse? effects of transfusion practices on neurodevelopment.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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University of Iowa
Iowa City
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Benavides, Amanda; Metzger, Andrew; Tereshchenko, Alexander et al. (2018) Sex-specific alterations in preterm brain. Pediatr Res :
Mock, Donald M; Nalbant, Demet; Kyosseva, Svetlana V et al. (2018) Development, validation, and potential applications of biotinylated red blood cells for posttransfusion kinetics and other physiological studies: evidenced-based analysis and recommendations. Transfusion 58:2068-2081
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Teramo, Kari A; Klemetti, Miira M; Widness, John A (2018) Robust increases in erythropoietin production by the hypoxic fetus is a response to protect the brain and other vital organs. Pediatr Res :
Cakir, Bertan; Liegl, Raffael; Hellgren, Gunnel et al. (2018) Thrombocytopenia is associated with severe retinopathy of prematurity. JCI Insight 3:
Nalbant, Demet; Cancelas, José A; Mock, Donald M et al. (2018) In premature infants there is no decrease in 24-hour posttransfusion allogeneic red blood cell recovery after 42 days of storage. Transfusion 58:352-358
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
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
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

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