E.W. "Al" Thrasher
Status: Funded - Closed
A randomized, masked, placebo controlled study to assess the safety and efficacy of darbepoetin alfa administered to preterm infants
Robin Ohls, M.D.
BACKGROUND: We previously reported decreased transfusions and donor exposures in preterm infants randomized to darbepoetin or erythropoietin compared to placebo. As these erythropoiesis-stimulating agents (ESAs) have shown promise as neuroprotective agents, we hypothesized improved neurodevelopmental outcomes at 18-22 months among infants randomized to receive ESAs.
METHODS: We performed a randomized, masked, multicenter study comparing darbepoetin (10 μg/kg, 1x/week subcutaneously), erythropoietin (400 units/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 18-22 months corrected age using the Bayley Scales of Infant Development III (BSID III). The primary outcome was composite cognitive score. Assessments of object permanence (OP), anthropometrics, cerebral palsy (CP), vision and hearing were performed.
RESULTS: Of the original 102 infants (946±196 grams, 27.7±1.8 weeks gestation), 80 (29 Epo, 27 Darbe, 24 placebo) returned for follow-up. The three 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 (97±8; mean±SD) and Epo (98±12) compared to placebo recipients (89±14; p=0.02 vs ESA recipients) as was OP (p=0.01). None of the infants in the Darbe group had a composite cognitive score <85. No infants in the ESA groups had CP, compared with 5 in the placebo group (p=0.002). No differences between groups were found in visual or hearing impairment. Overall neurodevelopmental impairment (hearing or visual impairment, CP, or cognitive score <85) was significantly lower in the ESA recipients compared to placebo (p=0.001).
CONCLUSIONS: Infants randomized to receive ESAs had better cognitive outcomes, compared to placebo recipients, at 18-22 months. Darbepoetin and erythropoietin may prove beneficial in improving long term outcomes of preterm infants.
Anemia, Neuro-Cognitive Development, Treatment, Randomized Clinical Trial
University of New Mexico School of Medicine
Utah, Colorado, New Mexico