title: Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo.
abstract: 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 μg/kg, 1×/week subcutaneously), Epo (400 U/kg, 3×/week subcutaneously), and placebo (sham dosing 3×/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 ± 7.3; mean ± 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.
authors.affiliation: Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico; rohls@salud.unm.edu.
authors.forename: Robin K
authors.initials: RK
authors.lastname: Ohls
authors.affiliation: Cincinnati Children's Hospital, Cincinnati, Ohio;
authors.forename: Beena D
authors.initials: BD
authors.lastname: Kamath-Rayne
authors.affiliation: Intermountain Health Care, Salt Lake City, Utah;
authors.forename: Robert D
authors.initials: RD
authors.lastname: Christensen
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah;
authors.forename: Susan E
authors.initials: SE
authors.lastname: Wiedmeier
authors.affiliation: Department of Pediatrics, University of Colorado, Denver, Colorado;
authors.forename: Adam
authors.initials: A
authors.lastname: Rosenberg
authors.affiliation: Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico;
authors.forename: Janell
authors.initials: J
authors.lastname: Fuller
authors.affiliation: Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico;
authors.forename: Conra Backstrom
authors.initials: CB
authors.lastname: Lacy
authors.affiliation: Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico;
authors.forename: Mahshid
authors.initials: M
authors.lastname: Roohi
authors.affiliation: Intermountain Health Care, Salt Lake City, Utah;
authors.forename: Diane K
authors.initials: DK
authors.lastname: Lambert
authors.affiliation: Intermountain Medical Center, Salt Lake City, Utah; and.
authors.forename: Jill J
authors.initials: JJ
authors.lastname: Burnett
authors.affiliation: Department of Pediatrics, University of Colorado, Denver, Colorado;
authors.forename: Barbara
authors.initials: B
authors.lastname: Pruckler
authors.affiliation: Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico;
authors.forename: Hannah
authors.initials: H
authors.lastname: Peceny
authors.affiliation: Department of Medicine, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Cannon
authors.affiliation: Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico;
authors.forename: Jean R
authors.initials: JR
authors.lastname: Lowe
mesh_terms: D001803:Blood Transfusion; D003071:Cognition / Q000187:drug effects*; D003210:Concept Formation / Q000187:drug effects; D000068256:Darbepoetin alfa; D002658:Developmental Disabilities / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D007279:Injections, Subcutaneous; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009460:Neurologic Examination / Q000187:drug effects; D009483:Neuropsychological Tests; D011340:Problem Solving / Q000187:drug effects; D011446:Prospective Studies
chemical_list: D004921:Erythropoietin; D000068256:Darbepoetin alfa
keywords: cognitive outcome; darbepoetin; erythropoietin; prematurity