The Effect of Epoetin Beta (Recombinant Human Erythropoietin) on the Need for Transfusion in Very-Low-Birth-Weight Infants
Rolf F. Maier, Michael Obladen, Paul Scigalla, Otwin Linderkamp, Gabriel Duc, Gertrud Hieronimi, Henry L. Halliday, Hans T. Versmold, Guy Moriette, Gerhard Jorch, Gaston Verellen, Ben A. Semmekrot, E. Ludwig Grauel, Barbara M. Holland, Charles Wardrop, for The European Multicentre Erythropoietin Study Group
Background Anemia of prematurity is characterized by low reticulocytecounts and inadequate erythropoietin response, for which manyvery-low-birth-weight infants receive multiple blood transfusions.We investigated whether early treatment of such infants withrecombinant human erythropoietin would reduce their need fortransfusions.
Methods We performed a controlled, blinded trial in 241 infantswith very low birth weights at 12 centers in six European countries.When three days old, the infants were randomly assigned eitherto the epoetin group or to the control group. Those in the epoetingroup received 250 IU of epoetin beta per kilogram of body weightsubcutaneously three times a week from day 3 to day 42 (fora total of 17 doses); those in the control group did not receivethis drug. Infants in both groups received oral iron (2 mg perday) from day 14 onward.
Results The control infants needed a mean of 1.25 transfusionseach, as compared with 0.87 transfusion for epoetin-treatedinfants (P = 0.013). The median cumulative volume of blood transfusedper kilogram per day was 0.41 ml in the control group (firstquartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetingroup (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044).The rate of success, defined as an absence of need for transfusionsand a hematocrit that never fell below 32 percent, was 4.1 percentin the control group and 27.5 percent in the epoetin group (P= 0.008). Epoetin was most beneficial in boys with birth weightsof 1200 g or more and a base-line hematocrit of 48 percent ormore. No toxic effects were observed in the epoetin group; ascompared with the control group, the epoetin group had an increasedincidence of septicemia (14 vs. 7 episodes, P not significant)and reduced weight gain (520 vs. 571 g, P = 0.02).
Conclusions Infants with very low birth weights have less needof transfusions if given epoetin beta during the first six weeksof life (250 IU per kilogram three times a week). We recommendearly epoetin treatment for all such infants, but further studiesof nutrition and iron supplementation during treatment are needed.
Source Information
From Universitatsklinikum Rudolf Virchow (R.F.M., M.O.) and Universitatsklinikum Steglitz (H.T.V.), Freie Universitat Berlin, Berlin, Germany; Boehringer-Mannheim, Mannheim, Germany (P.S.); Universitat Heidelberg, Heidelberg, Germany (O.L.); Universitat Zurich, Zurich, Switzerland (G.D.); Olgahospital, Stuttgart, Germany (G.H.); Royal Maternity Hospital, Belfast, United Kingdom (H.L.H.); Centre Hospitalier Universitaire Cochin Port-Royal, Paris (G.M.); Universitat Munster, Munster, Germany (G.J.); Universite Catholique de Louvain, Brussels, Belgium (G.V.); University Hospital Nijmegen, Nijmegen, the Netherlands (B.A.S.); Charite, Humboldt Universitat, Berlin (E.L.G.); Queen Mother's Hospital, University of Glasgow, Glasgow, United Kingdom (B.M.H.); and the Department of Hematology, University of Wales, Cardiff, United Kingdom (C.A.J.W.). The institutions and other coworkers of the European Multicentre Erythropoietin Study Group are listed in the Appendix.
Address reprint requests to Dr. Obladen at the Department of Neonatology, Universitatsklinikum Rudolf Virchow, Freie Universitat Berlin, Heubnerweg 6, D-14059 Berlin, Germany.
Recombinant Erythropoietin in Very-Low-Birth-Weight Infants
Beck D., Calame A., Masserey E., Carnielli V. P., Riol R. D., Montini G., van den Anker J. N., Montini G., Carnielli V. P., Maier R. F., Obladen M., Wardrop C. A.J.
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N Engl J Med 1994;
331:676-678, Sep 8, 1994.
Correspondence
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