Late erythropoiesis‐stimulating agents to prevent red blood cell transfusion in preterm or low birth weight infants

BACKGROUND: Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia. Darbepoetin (Darbe) and EPO are currently available ESAs. OBJECTIVES: To assess the effectiveness and safety of late initiation of ESAs, between eight and 28 days after birth, in reducing the use of red blood cell (RBC) transfusions in preterm or low birth weight infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE via PubMed (1966 to 5 June 2018), Embase (1980 to 5 June 2018), and CINAHL (1982 to 5 June 2018). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of late initiation of EPO treatment (started at >/= eight days of age) versus placebo or no intervention in preterm ( /= 3). The typical RR was 1.73 (95% CI 0.92 to 3.24) and the typical RD was 0.05 (95% CI -0.01 to 0.10). There was no heterogeneity for this outcome for RR (I(2) = 18%) but high heterogeneity for RD (I(2) = 79%). The quality of the evidence was very low.There were no significant differences in other clinical outcomes including mortality and necrotising enterocolitis. For the outcomes of mortality and necrotising enterocolitis, the quality of the evidence was moderate. Long-term neurodevelopmental outcomes were not reported. AUTHORS' CONCLUSIONS: Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant (< 1 transfusion per infant) but not the total volume (mL/kg) of RBCs transfused per infant. Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry. Late EPO does not significantly reduce or increase any clinically important adverse outcomes except for a trend in increased risk for ROP. Further research of the use of late EPO treatment, to prevent donor exposure, is not indicated. Research efforts should focus on limiting donor exposure during the first few days of life in sick neonates, when RBC requirements are most likely to be required and cannot be prevented by late EPO treatment. The use of satellite packs (dividing one unit of donor blood into many smaller aliquots) may reduce donor exposure.