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Volume 330:1173-1178 April 28, 1994 Number 17 Next

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ABSTRACT

Background Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions.

Methods We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward.

Results The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence 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 need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of 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.

Full Text of this Article

Related Letters:

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.
Extract | Full Text  
N Engl J Med 1994; 331:676-678, Sep 8, 1994. Correspondence

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