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Cochrane Database Syst Rev. 2012 Sep 12;(9):CD004868. doi: 10.1002/14651858.CD004868.pub3.

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

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Neonatal Intensive Care Unit, Kilbil Hospital, Nashik, India.



Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia.


To assess the effectiveness and safety of late initiation of EPO (initiated at eight days after birth or later) in reducing the use of red blood cell (RBC) transfusions in preterm and/or low birth weight infants.


For this update MEDLINE, EMBASE, CINAHL, and The Cochrane Library were searched in March 2012. Additional searches included the Pediatric Academic Societies Annual Meetings from 2000 to 2012 (Abstracts2 View(TM)) and clinical trials registries (;; and


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 (< 37 weeks) and/or low birth weight (< 2500 g) neonates.


Data collection and analyses were performed in accordance with the methods of the Cochrane Neonatal Review Group.


In this 2012 update one new study for inclusion was identified. Twenty-eight studies enrolling 1361 preterm infants in 21 countries were included. Most trials were of small sample size. The meta-analysis showed a significant effect on the use of one or more RBC transfusions [typical risk ratio (RR); 0.66 (95% confidence interval (CI); 0.59 to 0.74); typical risk difference (RD) -0.21 (95% CI; -0.26 to -0.16); typical number needed to benefit (NNTB) of 5 (95% CI 4 to 6) 19 studies, 912 infants]. There was moderate heterogeneity for this outcome [for RR (P < 0.00001; I(2) = 74.0%); for RD (P = 0.0006; I(2) = 58.9%)]. Similar results were obtained in secondary analyses based on different combinations of high/low doses of EPO and iron supplementation. In this update there was no significant reduction in the total volume (mL/kg) of blood transfused per infant [typical MD -1.61mL/kg (95% CI -5.78 to 2.57); 5 studies, 197 infants] There was high heterogeneity for this outcome (P = 0.00001, I(2) = 92%). There was a significant reduction in the number of transfusions per infant (nine studies enrolling 567 infants); [typical MD -0.78 (-0.97 to -0.59)]. Three studies including 331 patients reported on retinopathy of prematurity (ROP) (all stages), with a typical RR 0.79 (95% CI 0.57 to 1.10) and a typical RD of -0.05 (95% CI -0.13 to 0.02). This outcome was not statistically significantly different between the groups. There was no heterogeneity for this outcome for either RR (P = 0.41; I(2) = 0%) or RD (P = 0.43; I(2) = 0%). Two trials enrolling 212 patients reported on severe ROP (stage 3 or greater). The typical RR was 0.83 (95% CI 0.23 to 2.98) and the typical RD was -0.01 (95% CI -0.06 to 0.05); neither were statistically significant. There was no heterogeneity for this outcome for either RR (P = 0.29; I(2) = 9.3%) or RD (P = 0.36; I(2) = 0%).There were no significant differences in other clinical outcomes. Long-term neurodevelopmental outcomes were not reported.


Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant but not the total volume 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. 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.

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