Abstract:

Objective To systematically evaluate the efficacy and safety of early use of erythropoietin(EPO) for neuroprotectionin premature infants. Methods PubMed, Embase, The Cochrane Library, CBM, CNKI, WanFang Data and VIP databases were searched through computers to collect randomized controlled trials(RCTs) on EPO for neuroprotection in premature infants, the searching time being from inception to December,2020.RevMan 5.3 software was used for Meta-analysis. Results A total of 16 RCTs involving 3 650 premature infants were included. The results of meta-analysis showed that low-dose EPO could increase the mental development index(MDI)［MD=7.26，95%CI(2.99，11.53)，P=0.000 9］ and the psychomotor development index(PDI)［MD=4.88，95%CI(1.76，7.99)，P=0.002］ in the infants at adjusted age of 12 to 24 months， and it could reduce the incidence of MDI<70［MD=0.41,95%CI(0.27, 0.64),P<0.000 1］, but the effect of high-dose EPO（≥1 000 U/kg） treatment showed no difference between treatment group and control group(P>0.05). Compared with the control group, the incidence of cerebral palsy, hearing impairment, visual impairment and other neurodevelopmental disorders in the EPO group were not statistically different(P>0.05). EPO could reduce the incidence of necrotizing enterocolitis, intraventricular hemorrhage（Ⅲ/Ⅳ） and periventricular leukomalacia, without increasing the risk of bronchopulmonary dysplasia and retinopathy in prematurity（≥Ⅲ）.Conclusion Low-dose EPO treatment at an early stage can improve the neurodevelopmental outcomes of premature infants and is safe, but the effect of high-dose EPO needs further study.Due to limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusions. 

Key words:

Neurodevelopment, Premature, Erythropoietin, Randomized controlled trial, Meta-analysis