Objective To systematically review the clinical efficacy and safety of early use of recombinant human erythropoietin (rHu-EPO) for neuroprotection in premature infants.Method From establishment of the databases to November 2017,clinical randomized controlled trials (RCTs) of early use of rHu-EPO in premature infants were searched on English databases (PubMed,Embase,Cochrane Collaboration) and Chinese databases (CNKI,SinoMed,Wanfang,and VIP Database).Patients receiving conventional therapy were assigned into control group,and patients receiving both conventional therapy and rHu-EPO were assigned into rHu-EPO group.rHu-EPO group was subdivided into high-dose continuous group and low-dose intermittent group.We retrieved the related literatures,evaluated the quality,and then performed Meta-analysis using RevMan 5.3 software.Result A total of 2 588 patients in 17 studies were included and analyzed.Compared with the control group,Meta-analysis showed that early use of rHu-EPO was more effective in improving NBNA scores at 40 weeks of corrected gestational age (cGA) (MD=2.46,95％CI 1.58～3.33,P＜0.001),and high-dose continuous group was better than low-dose intermittent group (MD=3.19,95％CI 0.45～5.93,P=0.002;MD=2.22,95％CI 1.29～3.16,P＜0.001).Low-dose intermittent use of rHu-EPO significantly increased mental development index (MDI) (MD=6.66,95％CI 0.80～12.51,P=0.010) and psychomotor development index (PDI) (MD=5.77,95％CI 4.00～7.55,P＜0.001),and reduced the incidence of MDI＜70 at cGA 18～22 months (OR=0.42,95％CI 0.27～0.67,P＜0.001).As to the safety and side effects,treatment with rHu-EPO reduced the risk of necrotizing enterocolitis (OR=0.48,95％CI 0.31 ～0.72,P＜0.001) and periventricular leukomalacia (OR=0.52,95％CI 0.35～0.75,P＜0.001)without increasing the risk of bronchial dysplasia,patent ductus arteriosus,retinopathy in prematurity and intraventricular hemorrhage.Conclusion Current evidence shows that the early use of rHu-EPO in premature infants is relatively effective and safe,but multi-center RCTs are still needed.

Objective To evaluate the efficacy and safety of early use of high-dose rHu-EPO in the prevention of anemia in premature infants .Method Available data from clinical randomized controlled trials of early application of high-dose rHu-EPO to prevent premature infant anemia since database building till February 2017 were retrieved, which includes Pubmed, Embase, Cochrane Collaboration and CNKI , SinoMed, Wanfang, VIP.Premature infants less than gestational age of 37 weeks, with routine prevention of anemia as the control group and early combined use of high-dose rHu-EPO≥750 IU/( kg· w) as the treatment group.The relevant data from the literatures obtained were then screened and analyzed by the RevMan 5.3 software.Result A total of 1779 preterm infants from 21 articles including 898 cases of rHu-EPO treatment group and 881 cases in control group.Meta-analysis showed that rHu-EPO treatment group apparently increased the hemoglobin ( MD=27.42, 95%CI 20.01~34.84, P<0.001), hematocrit and reticulocyte count , reduced the blood transfusion. As to the risk of retinopathy of prematurity in rHu-EPO treatment group was significantly higher than that in the control group (RR=1.21, 95%CI 1.01~1.46, P=0.04), and reduced risks of bronchopulmonary dysplasia (RR=0.79, 95%CI 0.46 ~1.35, P =0.39) and patent ductus arteriosus ( RR =0.83, 95% CI 0.68 ~1.01, P=0.07) the difference, however, was not statistically significant, and there was no increasing risks of necrotizing enterocolitis , periventricular leukomalacia , intraventricular hemorrhage .Conclusion Early administration of high-dose of rHu-EPO can effectively prevent anemia in premature infants , but there is an increased risk of retinopathy of prematurity .