Journal article
Darbepoetin, Red Cell Mass, and Neuroprotection in Preterm Infants: A Randomized Clinical Trial
JAMA pediatrics, Vol.179(8), pp.836-845
08/01/2025
DOI: 10.1001/jamapediatrics.2025.0807
PMCID: PMC12070281
PMID: 40354084
Abstract
Previous studies suggest that administration of erythropoiesis-stimulating agents darbepoetin or erythropoietin to preterm infants results in fewer transfusions, fewer donor exposures, and improved neurodevelopmental outcome.
To determine if, compared with placebo, preterm infants randomized to weekly darbepoetin would have greater red cell mass during hospitalization and better neurocognitive outcome at 22 to 26 months' corrected age.
This randomized clinical trial was conducted between September 2017 and November 2019 for infants 23 0/7 to 28 6/7 weeks' gestation in 19 US Neonatal Research Network centers comprising 33 neonatal intensive care units. Follow-up occurred through January 2023. Infants were randomized by 36 hours after birth to weekly placebo or darbepoetin (10 μg/kg) through 35 weeks' postmenstrual age. Iron administration and transfusions were administered by protocol. Study data were analyzed from June to October 2023.
The primary outcome was the mean cognitive composite score on the Bayley Scales of Infant Development, third edition (Bayley-III) at 22 to 26 months' corrected age. The lowest possible score (54) was assigned to infants who died.
A total of 650 infants (322 darbepoetin; 328 placebo; mean [SD] gestational age, 26.2 [1.7] weeks; 328 female [50.5%]) were enrolled. Five hundred eighty-three infants (291 darbepoetin; 292 placebo) had the primary outcome determined (90% of those enrolled). Mean (SD) cognitive scores were similar between groups: 80.7 (19.5) darbepoetin vs 80.1 (18.7) placebo, adjusted mean difference, -0.23 (95% CI, -3.09 to 2.64). Compared with infants receiving placebo, more infants in the darbepoetin group were transfusion free (40% [127 of 319] vs 21% [70 of 327]; adjusted relative risk [RR], 1.3; 95% CI, 1.2-1.5), received fewer transfusions (mean [SD], 2.3 [3.1] vs 3.3 [3.5]), were exposed to fewer donors (mean [SD], 1.6 [2.3] vs 2.2 [2.3]), had higher red cell mass by week 2 of age (adjusted mean difference, 3.2; 95% CI, 1.7-4.7), and higher mean hematocrit by week 2 of age (adjusted mean difference, 2.8; 95% CI, 2.1-3.6), and were less likely to have bronchopulmonary dysplasia greater than grade 1 (35% [91 of 261] vs 46% [128 of 277]; RR, 0.78; 95% CI, 0.64-0.96). The incidence of retinopathy of prematurity stage greater than 2 was similar between groups, 13% (35 of 273) in the darbepoetin group vs 16% (45 of 279) in the placebo group. There were no differences in adverse effects between groups.
Results of this randomized clinical trial reveal that this dose and dosing schedule of darbepoetin did not improve cognitive scores of preterm infants at 22 to 26 months' corrected age. Darbepoetin significantly increased red cell mass resulting in higher hematocrit values, fewer transfusions, and fewer donor exposures.
ClinicalTrials.gov Identifier: NCT03169881.
Details
- Title: Subtitle
- Darbepoetin, Red Cell Mass, and Neuroprotection in Preterm Infants: A Randomized Clinical Trial
- Creators
- Robin K Ohls - University of UtahAbhik Das - RTI InternationalSylvia Tan - RTI InternationalJean R Lowe - University of New MexicoKurt Schibler - Cincinnati Children's Hospital Medical CenterSandra Sundquist Beauman - University of New MexicoEdward F Bell - University of IowaAbbot R Laptook - Women & Infants Hospital of Rhode IslandMariana Baserga - University of UtahRavi M Patel - Emory UniversityDavid P Carlton - Emory UniversityJohn Flibotte - University of PennsylvaniaCathy Grisby - Cincinnati Children's Hospital Medical CenterRosemary D Higgins - Florida Gulf Coast UniversitySeetha Shankaran - Wayne State UniversityKristi Watterberg - University of New MexicoAnna Maria Hibbs - Rainbow Babies & Children's HospitalWaldemar A Carlo - University of AlabamaTarah T Colaizy - University of IowaKrisa P Van Meurs - Stanford UniversityStephen D Kicklighter - WakeMedRyan Moore - East Carolina UniversityChristina Sollinger - University of RochesterLina F Chalak - Parkland Memorial HospitalSarvin Ghavam - Virtua Voorhees HospitalBrenda B Poindexter - Emory UniversityJon E Tyson - Memorial HermannC Michael Cotten - Duke UniversityMichelle L Baack - Sanford HealthOmid Fathi - The Ohio State UniversitySara B DeMauro - University of PennsylvaniaMatthew M Laughon - University of North Carolina at Chapel HillAnn Marie Reynolds - University at Buffalo, State University of New YorkAndrea F Duncan - Associate Editor, JAMA PediatricsSarah Winter - University of UtahDeanne E Wilson-Costello - Rainbow Babies & Children's HospitalMyriam Peralta-Carcelen - Stanford UniversityBetty R Vohr - Women & Infants Hospital of Rhode IslandHeidi M Harmon - University of IowaSusan R Hintz - Stanford UniversityBrenna Cavanaugh - University of RochesterRoy J Heyne - Parkland Memorial HospitalStephanie Merhar - Cincinnati Children's Hospital Medical CenterRicardo Mosquera - Memorial HermannElizabeth Sewell - Emory UniversityWilliam F Malcolm - Duke UniversityLaurie A Richards - Sanford HealthKristen L Benninger - The Ohio State UniversityAndrea Trembath - University of North Carolina at Chapel HillEunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
- Resource Type
- Journal article
- Publication Details
- JAMA pediatrics, Vol.179(8), pp.836-845
- DOI
- 10.1001/jamapediatrics.2025.0807
- PMID
- 40354084
- PMCID
- PMC12070281
- NLM abbreviation
- JAMA Pediatr
- ISSN
- 2168-6203
- eISSN
- 2168-6211
- Publisher
- AMER MEDICAL ASSOC; CHICAGO
- Grant note
- National Heart, Lung and Blood Institute: U01HL136318 National Institutes of HealthEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10HD21373, UG1 HD21364, UG1 HD21385, UG1HD27851, UG1 HD27853, UG1 HD27856, UG1HD27880, UG1 HD27904, UG1 HD34216, UG1HD36790, UG1 HD40492, UG1 HD40689, UG1HD53089, UG1 HD53109, UG1 HD68244, UG1HD68270, UG1HD68278, UG1 HD68263, UG1HD68284, UG1 HD87226, UL1 TR42, UL1 TR77, UL1 TR93, UL1 TR105, UL1 TR442, UL1TR454, UL1 TR1117
This work was supported by the National Heart, Lung and Blood Institute (U01HL136318), the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (U10HD21373, UG1 HD21364, UG1 HD21385, UG1HD27851, UG1 HD27853, UG1 HD27856, UG1HD27880,UG1 HD27904, UG1 HD34216, UG1HD36790, UG1 HD40492, UG1 HD40689, UG1HD53089, UG1 HD53109, UG1 HD68244, UG1HD68270, UG1HD68278, UG1 HD68263, UG1HD68284; UG1 HD87226, UG1 HD87229), and the National Center for Advancing Translational Sciences (NCATS) (UL1 TR6, UL1 TR41, UL1 TR42,UL1 TR77, UL1 TR93, UL1 TR105, UL1 TR442, UL1TR454, UL1 TR1117, provided grant support for the Neonatal Research Network, including for the followup study.
- Language
- English
- Electronic publication date
- 05/12/2025
- Date published
- 08/01/2025
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984822960502771
Metrics
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