Darbepoetin Administration in Term and Preterm Neonates

Abstract

Erythropoiesis-stimulating agents (ESAs) such as erythropoietin have been studied as red cell growth factors in preterm and term infants for more than 20 years. Recent studies have evaluated darbepoetin (Darbe, a long-acting ESA) for both erythropoietic effects and potential neuroprotection. We review clinical trials of Darbe in term and preterm infants, which have reported significant erythropoietic uses and neuroprotective effects. ESAs show great promise in decreasing or eliminating transfusions, and in preventing and treating brain injury in term and preterm infants.

Keywords: Anemia; Darbepoetin; Erythropoiesis-stimulating agents; Neurodevelopment; Neuroprotection; Transfusions.

Figure 1

Dose response curves for rHuEpo (open circles) and Darbe (solid circles). Progenitor cells isolated from 12 to 24 week gestation fetal marrow were cultured for 10–14 days in increasing concentrations of Darbe (0–500 ng/ml) or protein equivalent concentrations of rHuEpo. The number of BFU-E increased significantly (p<0.01, 10 vs. 50, 100, and 500 ng/mL Darbe, and p <0.01, 0.05 vs. 0.5, 1.0, and 2 U/mL rHuEpo).

Figure 2

Changes in reticulocyte count (panel A) and hematocrit (panel B) in preterm infants treated with 4 weekly Darbe doses (0 ≥g/kg [placebo]: open squares; 2.5 ≥g/kg: solid triangles; 5≥g/kg: solid squares; 10 ≥g/kg: solid circles). Reticulocyte counts increased by day 14 in infants receiving either 5 or 10 ≥g/kg dosing. Infants receiving 10 ≥g/kg had the greatest reticulocyte response (p=0.04 versus placebo). Hematocrits were greater by day 14 in infants receiving any Darbe (p=0.006 versus placebo).