Erythropoietin in Management of Infants

Erythroid burst-forming units are present in large numbers in infants with the anemia of prematurity. The erythroid progenitors respond normally in vitro to recombinant human erythropoietin (rHuEpo) (1). Although the mean hematocrit is considerably lower in premature infants than in adults, the mean serum erythropoietin concentration in the infants may not be any different from that in the adults (1). Subsequently, erythropoietin-sensitive progenitors have also been found in bone marrow samples obtained from preterm infants (Fig. 1) (2). The above-mentioned studies provide a physiologic basis for therapeutical trials of rHuEpo in infants with the anemia of prematurity. In an attempt to stimulate endogenous production of red blood cells and thus provide an alternative to red cell transfusions, Halperin et al. (3) have described their experience on the use of rHuEpo in the management of seven preterm infants with anemia of prematurity. The seven infants were free of common medical problems of prematurity, had a gestational age of between 30 and 33 weeks, and a birth weight of between 860 and 1800 g. The administration of rHuEpo was started at 2133 days of life; it was given subcutaneously three times a week for 4 weeks in amounts of 25-100 IU/kg body weight per dose. The treatment was followed by at least a twofold increase in the absolute number of reticulocytes in all patients (Fig. 2). The authors estimated that the peak reticulocyte count appeared at least 2 weeks earlier than in their historical reference group. In this experiment, the rHuEpo medication was discontinued at the age when one would expect to detect the physiologic stimulation of erythropoiesis and rise in reticulocyte count (4). The data on reticulocyte counts (Fig. 2) indicate that these events were diminished or even abolished in most of the infants. This finding may indicate that release of endogenous erythropoietin may not occur immediately (5), and that one should also study the effect of a more prolonged course of rHuEpo medication. Hemoglobin concentrations, at least in the larger prematures with birth weight over 1000 g, usually catch up to the values in term infants by the age of 4 months (6). On this basis, the age of 4 months might be the time when rHuEpo medication should be discontinued. Halperin et al. (3) further observed that the 4-week rHuEpo medication period resulted in the correction of the anemia of prematurity in four of the seven patients and an avoidance of red cell