Cognitive Outcomes of Preterm Infants Randomized to Darbepoetin, Erythropoietin, or Placebo

BACKGROUND: We previously reported decreased transfusions and donor exposures in preterm infants randomized to Darbepoetin (Darbe) or erythropoietin (Epo) compared with placebo. As these erythropoiesis-stimulating agents (ESAs) have shown promise as neuroprotective agents, we hypothesized improved neurodevelopmental outcomes at 18 to 22 months among infants randomized to receive ESAs. METHODS: We performed a randomized, masked, multicenter study comparing Darbe (10 mu g/kg, 1X/week subcutaneously), Epo (400 U/kg, 3X/week subcutaneously), and placebo (sham dosing 3X/week) given through 35 weeks' postconceptual age, with transfusions administered according to a standardized protocol. Surviving infants were evaluated at 18 to 22 months' corrected age using the Bayley Scales of Infant Development III. The primary outcome was composite cognitive score. Assessments of object permanence, anthropometrics, cerebral palsy, vision, and hearing were performed. RESULTS: Of the original 102 infants (946 +/- 196 g, 27.7 +/- 1.8 weeks' gestation), 80 (29 Epo, 27 Darbe, 24 placebo) returned for follow-up. The 3 groups were comparable for age at testing, birth weight, and gestational age. After adjustment for gender, analysis of covariance revealed significantly higher cognitive scores among Darbe (96.2 +/- 6 7.3; mean 6 SD) and Epo recipients (97.9 +/- 14.3) compared with placebo recipients (88.7 +/- 13.5; P =.01 vs ESA recipients) as was object permanence (P =.05). No ESA recipients had cerebral palsy, compared with 5 in the placebo group (P<.001). No differences among groups were found in visual or hearing impairment. CONCLUSIONS: Infants randomized to receive ESAs had better cognitive outcomes, compared with placebo recipients, at 18 to 22 months. Darbe and Epo may prove beneficial in improving long-term cognitive outcomes of preterm infants.