Early 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 early initiation of EPO (initiated before eight days after birth) in reducing 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 red blood cell transfusions in these infants. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings published in Pediatric Research and reference lists of identified trials and reviews were searched in November 2005. No language restrictions were applied. Randomised or quasi-randomized controlled trials of early initiation of EPO treatment (started before 8 days of age) 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 'typical' relative risk (RR), risk difference (RD), number needed to treat to benefit (NNTB) and 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-three studies enrolling 2074 preterm infants in 18 countries were included in the review. All studies except one applied transfusion guidelines. 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 (Arif 2005). A total of 16 studies, including 1825 infants reported on the primary outcome of "use of one or more red cell transfusions". The summary estimates were signific