An approach to using recombinant erythropoietin for neuroprotection in very preterm infants.
OBJECTIVE
Erythropoietin has been shown to be protective against hypoxic-ischemic and inflammatory injuries in cell culture, animal models of brain injury, and clinical trials of adult humans. The rationale for our study was that early administration of high-dose recombinant human erythropoietin may reduce perinatal brain injury (intraventricular hemorrhage and periventricular leukomalacia) in very preterm infants and improve neurodevelopmental outcome. We investigated whether administration of high-dose recombinant human erythropoietin to very preterm infants shortly after birth and subsequently during the first 2 days is safe in terms of short-term outcome.


METHODS
This was a randomized, double-masked, single-center trial with a 2:1 allocation in favor of recombinant human erythropoietin. Preterm infants (gestational age: 24 to 31 weeks) were given recombinant human erythropoietin or NaCl 0.9% intravenously 3, 12 to 18, and 36 to 42 hours after birth.


RESULTS
The percentage of infants who survived without brain injury or retinopathy was 53% in the recombinant human erythropoietin group and 60% in the placebo group. There were no relevant differences regarding short-term outcomes such as intraventricular hemorrhage, retinopathy, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. For 5 infants who were in the recombinant human erythropoietin group and had a gestational age of <26 weeks, withdrawal of intensive care was decided (3 of 5 with severe bilateral intraventricular hemorrhage, 2 of 5 with pulmonary insufficiency); no infant of the control group died. Recombinant human erythropoietin treatment did not result in significant differences in blood pressure, cerebral oxygenation, hemoglobin, leukocyte, and platelet count.


CONCLUSIONS
No significant adverse effects of early high-dose recombinant human erythropoietin treatment in very preterm infants were identified. These results enable us to embark on a large multicenter trial with the aim of determining whether early high-dose administration of recombinant human erythropoietin to very preterm infants improves neurodevelopmental outcome at 24 months' and 5 years' corrected age.
Fauchère
Jean-Claude
JC
Clinic of Neonatology, University Hospital Zurich, Zurich, Switzerland.
Dame
Christof
C
Vonthein
Reinhard
R
Koller
Brigitte
B
Arri
Sandra
S
Wolf
Martin
M
Bucher
Hans Ulrich
HU
D001034:Apgar Score; D001927:Brain Diseases / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D002543:Cerebral Hemorrhage / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D002658:Developmental Disabilities / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D019102:Infant, Very Low Birth Weight; D007363:Intensive Care Units, Neonatal; D008297:Male; D020714:Maximum Tolerated Dose; D011336:Probability; D011994:Recombinant Proteins; D012016:Reference Values; D012178:Retinopathy of Prematurity / Q000188:drug therapy / Q000517:prevention & control; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D011994:Recombinant Proteins; D004921:Erythropoietin