A Meta-analysis of the Protective Effect of Recombinant Human Erythropoietin (rhEPO) for Neurodevelopment in Preterm Infants

The purpose of this study is to assess the efficacy and safety of recombinant human erythropoietin (rhEPO) for improving neurodevelopment outcomes in preterm infants. According to the requirements of Cochrane systematic review, a literature search was performed among PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Wan Fang Data, and VIP INFORMATION from the establishment of the database from January 1999 to December 2011. Quality assessments of clinical trials were carried out. Randomized controlled trials (RCTs) or quasi-RCTs with rhEPO in preterm infants were enrolled, and RevMan5.0 software was used for meta-analysis. Data extraction, quality assessment, and meta-analysis for the results of homogeneous studies were done by two reviewers. The trials were analyzed using weighted mean difference (WMD) for continuous data and odds ratio (OR) for dichotomous data, both kinds of data were expressed by 95 % CI. For homogenous data (P a parts per thousand yen 0.10), fixed effect model was calculated. Two RCTs and 3 quasi-RCTs including 233 preterm infants (119 of treatment group and 114 of control group) were included in the analysis. The results of quality assessment were that 1 study was A, 1 was B, and 3 were C. There was evidence of a significant effect of therapeutic rhEPO on the outcomes of MDI scores [WMD = 7.77, 95 % CI (3.49-12.06), P = 0.0004], PDI scores [WMD = 3.85, 95 % CI (0.62-7.09), P = 0.02] at 18-22 months and NBNA scores [WMD = 1.96, 95 % CI (1.56-2.37), P < 0.00001] at 40 weeks of corrected gestational age. However, rhEPO had no effect on MDI < 70 (OR = 0.70, 95 % CI 0.31-1.61), PDI < 70 (OR = 2. 46, 95 % CI 0.94-6.45), cerebral palsy (OR = 1.08, 95 % CI 0.39-2.99), blindness (OR = 0.34, 95 % CI 0.01-8.56), and hearing loss (OR = 1.04, 95 % CI 0.06-17.15). There were no differences between groups with respect to the percentage of preterm infants with severe retinopathy of prematurity of stage III or above (OR = 1.30, 95 % CI 0.50-3.43), severe intraventricular hemorrhage of stage III or above (OR = 2. 91, 95 % CI 0.64-13.23), necrotizing enterocolitis (OR = 0.57, 95 % CI 0.13-2.54), and borderline personality disorder (OR = 1. 06, 95 % CI 0.50-2.26). The rhEPO treatment has beneficial effect on the neurodevelopment outcomes without severe adverse side effect in preterm infants.