Neuroprotective Effect And Safety Of Early High-dose Recombinant Human Erythropoietin On Preterm Infants

Objective: To investigate the safety and short-term neuroprotective effect of high-dose recombinant human erythropoietin(rhEPO)on preterm infants in the early postnatal period.Methods: A prospective randomized clinical trial was performed on very preterm infants who were born between 28 and 32 weeks of gestation which were randomly divided into the rhEPO group(n = 37)and the placebo group(n = 47).The rhEPO group were given 1000u/Kg rhEPO intravenously within 48 hours after birth,then followed by another 4 doses every 48 hours.The placebo group was not given rhEPO.The changes of routine blood tests,liver and kidney functions,as well as the incidence of complications of preterm infants were monitored,and the neonatal behavioral neurological assessment(NBNA)was examed at 40-42 weeks of correct gestational age.Results: 32 preterm infants in the rhEPO group and 42 preterm infants in the placebo group were completed the regimen.1)Compared with the placebo group,leukocytes were significantly increased in the rhEPO groupat day 7-10(P<0.05),which were higher than the normal range,but decreased to normal range after discontinuation of the drug.Also found the significantly higher erythrocytes,hematocrit,hemoglobin and reticulocyte counts and lower platelets in the rhEPO group(P<0.05),but they were all within the normal range.2)There were no statistically significant differences in the incidences of increased alanine aminotransferase,blood urea nitrogen,creatinine,and hyperkalemia between the groups(P>0.05).3)The incidence of neonatal necrotizing enterocolitis(NEC)in the rhEPO group was lower than that in the placebo group(P<0.05).There were no statistically significant differences in the morbidity of other complications of premature infants such as bronchopulmonary dysplasia,retinopathy of prematurity,sepsis,anemia,etc between the groups(P>0.05).4)Stratified analysis based on gestational age and birth weight,mean NBNA score at40-42 weeks of gestational age was not statistically significantiy different between the rhEPO group and the placebo group(P>0.05).No differences were found between groups in the incidences of periventricular-intraventricular hemorrhage and abnormal amplitude integrated electroencephalogram(P>0.05).Conclusions: Early high-dose rhEPO administration to very preterm infantsin can influence the leukocytes,erythrocytes,hematocrit,reticulocyte,hemoglobin and platelets,but no obvious relevant clinical manifestations were found.It can reduce the incidence of NEC and has noobvious effects on liver and kidney functions as well as the morbidity of other complications of preterm infants.High-dose rhEPO does not significantly improve recent NBNA scores and cephalic ultrasound.In this study,there are no evidences for the neruoprotection effect of early high-dose rhEPO on preterm infants,requiring further study and follow-up for long-term neurological development,but early high-dose rhEPO administration to very preterm infants is safe and cause no excess major adverse events.