PEDIATRICS Vol. 95 No. 1 January 1995, pp. 1-8
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Recombinant Human Erythropoietin Stimulates Erythropoiesis and Reduces Erythrocyte Transfusions in Very Low Birth Weight Preterm Infants

Kevin M. Shannon MD1, Julian F. Keith III MD2, William C. Mentzer MD1, Richard A. Ehrenkranz MD3, Mark S. Brown MD4, John A. Widness MD5, Christine A. Gleason MD6, Ellen M. Bifano MD7, Dietra D. Millard MD8, Charles B. Davis MD2, David K. Stevenson MD9, Dale C. Alverson MD10, Charles F. Simmons MD11, Marlene Brim BS12, Robert I. Abels MD12, and Roderic H. Phibbs MD1

1 Departments of Pediatrics and Schools of Medicine, University of California, San Francisco, San Francisco, California
2 Departments of Pediatrics and Schools of Medicine, Naval Medical Center, San Diego, California
3 Departments of Pediatrics and Schools of Medicine, Yale University, New Haven, Connecticut
4 Departments of Pediatrics and Schools of Medicine, Presbyterian/St. Luke's Hospital, Denver, Colorado
5 Departments of Pediatrics and Schools of Medicine, University of Iowa, Iowa City, Iowa
6 Departments of Pediatrics and Schools of Medicine, Johns Hopkins University, Baltimore, Maryland
7 Departments of Pediatrics and Schools of Medicine, State University of New York, Syracuse, New York
8 Departments of Pediatrics and Schools of Medicine, Northwestern University, Chicago, Illinois
9 Departments of Pediatrics and Schools of Medicine, Stanford University, Palo Alto, California
10 Departments of Pediatrics and Schools of Medicine, University of New Mexico, Albuquerque, New Mexico
11 Departments of Pediatrics and Schools of Medicine, Harvard University, Boston, Massachusetts
12 Departments of Pediatrics and Schools of Medicine, R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey

Design and methods. We hypothesized that treatment with recombinant human erythropoietin (r-HuEPO) would stimulate erythropoiesis and would thereby reduce the need for erythrocyte transfusions in preterm infants. We treated 157 preterm infants born at 26.9 ± 1.6 weeks of gestation who weighed 924 ± 183 g at birth with either subcutaneous r-HuEPO (100 U/kg/d, 5 days per week) or placebo for 6 weeks in a randomized, double-blind, controlled clinical trial. All patients received oral iron and were managed according to uniform conservative transfusion guidelines.

Results. Treatment with r-HuEPO was associated with fewer erythrocyte transfusions (1.1 ± 1.5 per infant in the r-HuEPO group versus 1.6 ± 1.7 per infant in the placebo group; P = .046) and with a reduction in the volume of packed erythrocytes transfused (16.5 ± 23.0 mL versus 23.9 ± 25.7 mL per infant; P = .023). Overall, 43% of the infants in the r-HuEPO group and 31% of placebo-treated infants were transfusion-free during the study (P = .18). The volume of blood removed for laboratory tests and the need for respiratory support at the start of treatment had major effects on transfusion requirements independent of r-HuEPO. Reticulocyte counts were higher during treatment in the r-HuEPO group (P = .0001), and r-HuEPO-treated infants had higher hematocrit values at the end of the study (32% versus 27.3% in the placebo group; P = .0001). We found no differences in the incidence of major complications of prematurity between the treatment groups.

Conclusion. We conclude that treatment with r-HuEPO at a weekly dose of 500 U/kg stimulates erythropoiesis, moderates the course of anemia, is associated with a reduction in erythrocyte transfusions, and appears safe in very low birth weight preterm infants who are receiving iron supplements. Conservative transfusion criteria, minimization of phlebotomy losses, and treatment with r-HuEPO are complementary strategies to reduce erythrocyte transfusions in these infants.

Submitted on June 6, 1994
Accepted on September 28, 1994




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