Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants

Hematocrit falls after birth in preterm infants due to physiological factors and blood letting. Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anemia. To assess the effectiveness and safety of late initiation of EPO (initiated at 8 days after birth or later) in reducing the use of red blood cell transfusions in preterm and/or low birth weight infants. Subgroup analyses of low (< 500 IU/kg/week) and high (> 500 IU/kg/week) doses of EPO and within these subgroups analyses of the use of low (< 5 mg/kg/day) and high (> 5 mg/kg/day) doses of supplemental iron, in reducing the use of red blood cell transfusions in these infants. MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings published in Pediatric Research and reference lists of identified trials and reviews were searched in November 2005/April 2006 and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2006). No language restrictions were applied. Randomised or quasi-randomized controlled trials of late initiation of EPO treatment (started at eight days of age or later) vs. placebo or no intervention in preterm (< 37 weeks) and/or low birth weight (< 2500 g) neonates. For inclusion the studies needed to provide information on at least one outcome of interest. Data were abstracted by the two authors on pre-tested data collection forms. Data were entered by one review author (AO) and checked for accuracy by the other (SA). Data were analysed using RevMan 4.2.8. The statistical methods included relative risk (RR), risk difference (RD), number needed to treat to benefit (NNTB), number needed to treat to harm (NNTH) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes reported with their 95% confidence intervals (CI). A fixed effects model was used for meta-analyses. Heterogeneity tests including the I squared (I(2)) statistic were performed to assess the appropriateness of pooling the data. Twenty-eight studies enrolling 1302 preterm infants in 21 countries were included. The quality of the trials varied. Most trials were of small sample size. Only one study clearly stated that infants were excluded if they had received red blood cell transfusion prior to study entry (Samanci 1996). A total of 19 studies including 912 infants reported on the primary outcome of "Use of one or more red cell transfusions". The meta-analysis showed a significant effect [typical RR