Published online November 1, 2006
PEDIATRICS Vol. 118 No. 5 November 2006, pp. 2004-2013 (doi:10.1542/peds.2006-1113)

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ARTICLE

Effects of a Combined Therapy of Erythropoietin, Iron, Folate, and Vitamin B₁₂ on the Transfusion Requirements of Extremely Low Birth Weight Infants

Nadja Haiden, MD^a, Jens Schwindt, MD^a, Francesco Cardona, MD^a, Angelika Berger, MD^a, Katrin Klebermass, MD^a, Martin Wald, MD^a, Christina Kohlhauser-Vollmuth, MD^a, Bernd Jilma, MD^b and Arnold Pollak, MD^a

^a Division of Neonatology and Intensive Care, Department of Pediatrics
^b Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria

OBJECTIVES. Erythropoietin is frequently administered to premature infants to stimulate erythropoiesis. The primary goal of erythropoietin therapy is to reduce transfusions, but the efficacy of erythropoietin has not been convincingly demonstrated in this regard. The aim of this trial was to investigate whether combined administration of vitamin B₁₂, folic acid, iron, and erythropoietin could decrease transfusion requirements in extremely low birth weight infants.

PATIENTS AND METHODS. In a randomized, controlled trial, extremely low birth weight infants with a birth weight 800g and a gestational age 32 weeks were randomly assigned to a group receiving combination treatment or a control arm.

RESULTS. The treatment increased levels of folate in red blood cells, vitamin B₁₂, ferritin, transferrin receptor levels in plasma, and reticulocyte counts. The proportion of infants requiring no transfusions was lower in the treatment group (38%) as compared with controls (5%). The treatment group and the need for mechanical ventilation were independent predictors of the number of transfusions in multiple regression analysis. Cox regression analysis indicated that combined therapy resulted in a 79% risk reduction for any transfusion.

CONCLUSION. Combined treatment with erythropoietin, intravenous iron, folate, and vitamin B₁₂ during the first weeks reduces the need for transfusion in extremely low birth weight infants.

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Key Words: folate • vitamin B₁₂ • erythropoietin • iron • ELBW infant • transfusions

Abbreviations: RBC—red blood cell • GA—gestational age • ELBW—extremely low birth weight • TFR—transferrin receptor • CI—confidence interval • IRF—immature reticulocyte fraction • MCV—mean corpuscular volume • ROP—retinopathy of prematurity

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Accepted Jul 13, 2006.

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