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).

Public Health Relevance

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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Iowa City
United States
Zip Code
Liu, Zhi-Jian; Hoffmeister, Karin M; Hu, Zhongbo et al. (2014) Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. Blood 123:3381-9
van 't Erve, Thomas J; Wagner, Brett A; Martin, Sean M et al. (2014) The heritability of metabolite concentrations in stored human red blood cells. Transfusion 54:2055-63
Mock, Donald M; Widness, John A; Veng-Pedersen, Peter et al. (2014) Measurement of posttransfusion red cell survival with the biotin label. Transfus Med Rev 28:114-25
Rosebraugh, Matthew R; Widness, John A; Nalbant, Demet et al. (2014) Pharmacodynamically optimized erythropoietin treatment combined with phlebotomy reduction predicted to eliminate blood transfusions in selected preterm infants. Pediatr Res 75:336-42
van 't Erve, Thomas J; Doskey, Claire M; Wagner, Brett A et al. (2014) Heritability of glutathione and related metabolites in stored red blood cells. Free Radic Biol Med 76:107-13
Josephson, Cassandra D; Mondoro, Traci Heath; Ambruso, Daniel R et al. (2014) One size will never fit all: the future of research in pediatric transfusion medicine. Pediatr Res 76:425-31
McCoy, Thomasin E; Conrad, Amy L; Richman, Lynn C et al. (2014) The relationship between brain structure and cognition in transfused preterm children at school age. Dev Neuropsychol 39:226-32
Kuruvilla, Denison J; Nalbant, Demet; Widness, John A et al. (2014) Mean remaining life span: a new clinically relevant parameter to assess the quality of transfused red blood cells. Transfusion 54:2724-9
Khan, Irfan; Zimmerman, Bridget; Brophy, Patrick et al. (2014) Masking of syndrome of inappropriate antidiuretic hormone secretion: the isonatremic syndrome. J Pediatr 165:722-6
Nalbant, Demet; Bhandary, Prasad; Matthews, Nell I et al. (2013) Comparison of multiple red cell volume methods performed concurrently in premature infants following allogeneic transfusion. Pediatr Res 74:592-600

Showing the most recent 10 out of 145 publications