Darbepoetin Reduces Transfusion Needs in Preterm Infants

Larry Hand

June 17, 2013

Injections of an erythropoiesis-stimulating agent (ESA), particularly darbepoetin alfa (Darbe), may eliminate or reduce the need for red blood cell transfusions in preterm infants, according to an article published online June 17 in Pediatrics.

Robin K. Ohls, MD, from the Department of Pediatrics, University of New Mexico, Albuquerque, and colleagues conducted a randomized trial involving 102 preterm infants at 4 high-altitude medical centers in New Mexico, Utah, and Colorado. Transfusion studies had not been conducted before at high-altitude centers, where oxygen use is generally increased, the researchers write.

To assess whether Darbe could decrease transfusions in preterm infants, the researchers randomly assigned (blind) the infants to 1 of 3 groups: erythropoietin (Epo), 400 U/kg, given subcutaneously 3 times a week; Darbe, 10 μg/kg, given subcutaneously once a week with sham dosing 2 other times a week; or placebo in 3 sham doses a week for 35 weeks. The infants were 48 hours old or younger, weighed between 125 and 500 g at birth, and were enrolled between July 2006 and May 2010.

The researchers based original doses of Darbe and Epo on study entry weight and adjusted weekly to give equivalent volumes (0.1 mL/kg body weight). The study drug was withheld under certain clinical conditions, such as a neutrophil count lower than 500/μL, and restarted on resolution, or was halted in cases of clinical seizures, thromboses diagnoses, or if hypertension or neutropenia occurred. All infants also received supplementations of iron, folate, and vitamin E.

Any transfusions were according to laboratory results and to a standardized, restrictive transfusion protocol used at the University of New Mexico.

Infants in the Darbe and Epo groups received significantly fewer transfusions (P = .015) and had significantly fewer donor exposures (P = .044) than infants in the placebo group (Darbe, 1.2 ± 2.4 transfusions and 0.7 ± 1.2 donors per infant; Epo, 1.2 ± 1.6 transfusions and 0.8 ± 1.0 donors per infant; placebo, 2.4 ±2.9 transfusions and 1.2 ± 1.3 donors per infant).

In addition, 59% of the Darbe-treated infants and 52% of the Epo-treated infants received no transfusions at all compared with 38% of infants in the placebo group. Darbe- and Epo-treated infants had significantly higher changes in absolute reticulocyte counts (P = .001) and hematocrits (P = .001) compared with infants in the placebo group.

Adverse effects were minimal and similar among groups. Morbidity and mortality (2 deaths in the Darbe group, 1 in the Epo group, 3 in the placebo group) were also similar among groups.

"This is the first prospective, randomized, masked, multicenter study of early Darbe administered to preterm infants," the researchers write, "and the first study of ESA administration to preterm infants that resulted in a significant decrease in both donor exposure and transfusion number."

Although transfusions have decreased in number during the last 20 years, extremely low birthweight babies still typically receive 3 to 5 transfusions, leaving them vulnerable to a "small but measurable risk of infection, transfusion reaction, or transfusion-associated morbidities," the authors write.

They conclude, "With increasing evidence of possible risks of transfusions, it was significant that more than 50% of the treated infants remained untransfused. Importantly, Darbe provides this effect with weekly dosing."

This research was supported by the Thrasher Research Fund, the University of Colorado Clinical and Translational Sciences Institute, the National Institutes of Health, and the University of New Mexico Clinical and Translational Science Center. The authors have disclosed no relevant financial relationships.

Pediatrics. Published online June 17, 2013.

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