Red blood cell (RBC) transfusion management includes the criteria used to determine when transfusion should occur in preterm infants. There is controversy regarding whether more restrictive or more liberal criteria would best serve the goal of optimal brain development. Although some studies have indicated that liberal transfusions may be neuroprotective, our findings from the previous 4 years of this PPG indicate that liberal transfusions result in poor long-term brain development, and this is particularly true for females. The overall aim of Project #3 is to evaluate the neurodevelopmental outcomes of differential transfusion practices from a mechanistic viewpoint. We hypothesize that liberal transfusion will result in poorer neurodevelopmental outcomes compared to restrictive transfusion practices. Potential mechanisms explored for this phenomenon include inflammation and/or erythropoietin (Epo) suppression that result from liberal RBC transfusion. Cerebral white matter and sex effects will be of particular interest.
Specific Aim 1 will be to measure the relationships between serum biomarkers (average hematocrit (HCT), iron, ferritin, c-reactive proteins, cytokines and Epo), and brain structure (using MRI) in preterm infants that are randomized to either restricted or liberal transfusion. Biomarkers and MRI scan will be obtained during the NICU stay.
Specific Aim 2 will examine the effects of differential transfusion on brain development using a longitudinal assessment of the same infants at 12 months and 24 months. Follow-up assessments will include a comprehensive battery of cognitive and developmental measures as well as a follow-up MRI scan. The current proposal is designed to 'extend'an NICHD Neonatal Research Network trial to evaluate the relationship between neonatal transfusion approach and neurodevelopmental outcome. This study is called the Impact of a Liberal Red Blood Cell Transfusion Strategy on Neurologically-lntact Survival of Extremely- Low-Birth-Weight Infants: The Transfusion and Brain Injury (TABI) Trial. The TABI protocol will be the foundation for recruitment of subjects, our current proposal would extend the TABI by: 1) assessing transfusion status and neurodevelopmental impairment (NDI) as continuous measures rather than dichotomous measures;2) use additional assessments that more sensitively and more specifically quantify brain structure and function;and 3) explore specific proposed mechanisms by which differential transfusion may impact brain development (inflammation and Epo suppression).
Findings from the current proposal have a high likelihood of direct clinical impact: at a minimum, results that show liberal transfusion practice leads to poorer neurodevelopmental outcome will have a direct impact on clinical practice. Further, if we understand more about the roles of inflammation and/or the role of Epo, this could lead to further evaluation of potential treatments or interventions to minimize poor developmental outcomes when transfusions are required. This last point is of particular relevance in regard to the synergy of the PPG, as Project 1 is designed to evaluate the utility of Epo in the treatment of preterm anemia.
|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|
Showing the most recent 10 out of 190 publications