Cochrane review: Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants

Abstract Background Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia. Objectives To assess the effectiveness and safety of early initiation of EPO in reducing red blood cell (RBC) transfusions in preterm and/or low birth weight infants. Search strategy The Cochrane Central Register of Controlled Trials ( The Cochrane Library) , MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings published in Pediatric Research and reference lists of identified trials and reviews were searched through July 2009. Selection criteria Randomised or quasi‐randomised controlled trials of early (< 8 days of age) initiation of EPO treatment vs. placebo or no intervention in preterm and/or low birth weight neonates. Data collection and analysis Data collection and analysis were accomplished using the methods of the Neonatal Cochrane Review Group. Main results Update includes 27 studies that enrolled 2219 preterm infants. Early EPO reduced the risk of the "use of one or more RBC transfusions" [typical RR; 0.80 (95% CI 0.75, 0.86); 16 studies, 1825 infants]. Early EPO led to a significant reduction in the total volume (ml/kg) of blood transfused per infant and in the number of transfusions per infant. Two studies (n = 188) reported a significant reduction in the number of donors to whom the infant was exposed. There was a significant increase in the risk of stage ≥ 3 retinopathy of prematurity (ROP) in the early EPO group [typical RR; 1.65 (95% CI 1.12, 2.43); 8 studies, 984 infants]. The rates for mortality and other neonatal morbidities were not significantly changed by early EPO treatment nor were neurodevelopmental outcomes at 18 to 22 months in the small number of infants tested to‐date. Authors' conclusions Early administration of EPO reduces the use of RBC transfusions and the volume of RBCs transfused. These small reductions are of limited clinical importance. Donor exposure is probably not avoided since most studies included infants who had received RBC transfusions prior to trial entry. There was a significant increase in the rate of ROP (stage ≥ 3). Early EPO does not significantly decrease or increase any of the other important adverse outcomes. Ongoing research should deal with the issue of ROP and evaluate the current clinical practice that will limit donor exposure. Due to the limited benefits and the increased risk of ROP, early administration of EPO is not recommended. Evidence is lacking for the possible neuroprotective role of EPO in preterm infants. Plain Language Summary Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants In newborn infants, the number of red blood cells in the circulation decreases after birth. In infants born before term, this decrease is exaggerated by frequent withdrawal of blood, which may be necessary to monitor the infant's clinical condition. Therefore, infants born before term are likely to require transfusions of red blood cells. Low levels of erythropoietin (EPO), a substance in the blood that stimulates red blood cell production, in preterm infants provide a rationale for the use of EPO to prevent or treat anemia. EPO can be given "early" (before the infant reaches eight days of age) in order to prevent or decrease the use of red blood cell transfusions. More than 2200 infants born before term have been enrolled in 27 studies that used this approach. Early EPO treatment reduces the number of red blood cell transfusions and donor exposures following its use. However, the overall benefit of EPO may not be clinically important, as many of these infants had been exposed to red blood cell transfusions prior to entry into the trials. Treatment with early EPO did not have any important effects on mortality or common complications of preterm birth with the exception that EPO increased the risk for retinopathy of prematurity, a serious complication that may cause blindness in babies born before term. The addition of four new studies enrolling 145 infants did not change the conclusions. Based on our findings, EPO is not recommended for routine use in preterm infants.

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