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May 2, 2011

Long-term Outcome of Brain Structure in Premature Infants: Effects of Liberal vs Restricted Red Blood Cell Transfusions

Author Affiliations

Author Affiliations: Departments of Psychiatry (Drs Nopoulos and Conrad), Pediatrics (Drs Nopoulos, Bell, Strauss, Widness, Lindgren, and Richman), Neurology (Dr Nopoulos), Pathology (Dr Strauss), and Radiology (Dr Magnotta), Carver College of Medicine, and Department of Biostatistics, College of Public Health (Dr Zimmerman), University of Iowa, Iowa City; and Departments of Pediatrics and Child Psychology, University of Minnesota, Minneapolis (Dr Georgieff).

Arch Pediatr Adolesc Med. 2011;165(5):443-450. doi:10.1001/archpediatrics.2010.269

Advances in prenatal medicine and neonatal intensive care have resulted in improved survival for preterm infants, in particular for those infants with extremely low birth weight (<1000 g) and those born at the limits of viability (22-25 weeks' gestation). Despite improvements in survival, the incidence of disability in this population has not diminished accordingly.1 A major morbidity for this patient group is neurodevelopmental and behavioral abnormalities.2-8

Understanding the risk factors for abnormal neurodevelopmental outcomes is critical for implementing intervention strategies to improve the outcomes of premature infants. Some of the key risk factors for adverse outcome are biologic factors that are not modifiable following preterm birth: gestational age, birth weight, male sex, and multiple birth.9 However, there are factors with potential impact on developmental outcome that can be targeted for improvement. One important factor is management of the anemia of prematurity, particularly, optimal red blood cell (RBC) transfusion practices. Transfusion of packed red blood cells is a major component of neonatal care of the preterm infant. As many as 95% of extremely low-birth-weight infants will receive at least 1 RBC transfusion, as will up to 80% of preterm infants with birth weights less than 1500 g (very low birth weight), during the first few weeks of life.10-12 Red blood cell transfusions can be prescribed according to liberal or restricted guidelines (ie, with relatively high or low pretransfusion hematocrit values, respectively) with the possibility of undertransfusion or overtransfusion, either of which may have adverse effects.13

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    1 Comment for this article
    Limitations in measuring the effects of blood transfusion on long-term outcome in preterm infants.
    Niloufar Ashtiani, MD | VU University Medical Center,
    We acknowledge the importance of studies assessing long term follow- up of routine interventions in preterm infants. Nopoulos et al reported recently on the long term follow-up of liberal versus restricted red blood cell transfusions. The authors concluded that intracranial volume was substantially smaller in the liberal group compared with term controls, and that girls from the liberal group had significant more brain abnormalities. Although early interventions such as red blood cell transfusions may affect neurodevelopmental outcome, intracranial volume is not the best predictor of neurodevelopmental outcome, as it includes cerebrospinal fluid as well as total brain tissue.1 The authors also measured gray and white matter, but were not able to show differences between the liberal and restricted group. This is important since, differences in brain volume are related to changes in gray and white matter volume, rather than total brain volume in preterm compared to term infants.2 In a long term follow- up study of very low birth weight teenagers, white matter differences were related to perceptual, cognitive, mental health and motor impairments.3 Therefore, we have concerns regarding the conclusions of Nopoulos et al. Although the primary objective of this study was to compare long term outcome between infants in the liberal versus restricted group, these results (i.e. no differences in any of the brain volume measurements between both groups) are not reported in the conclusions. As may be foreseen, post hoc comparison with a term control group is hampered by methodological shortcomings. Furthermore, only 44% of the initial cohort was available for analysis, leading to important sex difference between the intervention (e.g. fewer females in the restricted group). Therefore, we believe that conclusions regarding the outcome of girls from any group are not possible. In our opinion, the conclusion of this study should be restricted to the results of the boys. Although the aim of this long term follow up study is important, the change of the study population over time hampers its conclusions.
    1. Peterson BS, Vohr B, Staib LH, Cannistraci CJ, Dolberg A, Schneider KC, Katz KH, Westerveld M, Sparrow S, Anderson AW, Duncan CC, Makuch RW, Gore JC, Ment LR. Regional brain volume abnormalities and long- term cognitive outcome in preterm infants. JAMA 2000;18;284(15):1939-47
    2. Ment LR, Kesler S, Vohr B, Katz KH, Baumgartner H, Schneider KC, Delancy S, Silbereis J, Duncan CC, Constable RT, Makuch RW, Reiss AL. Longitudinal brain volume changes in preterm and term control subjects during late childhood and adolescence. Pediatrics 2009;123;503-511
    3. Skranes J, Vangberg TR, Kulseng S, Indredavik MS, Evensen KA, Martinussen M, Dale AM, Haraldseth O, Brubakk AM. Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight. Brain 2007;130(Pt 3):654-66

    Conflict of Interest: None declared