PICO Summary: Does erythropoietin (EPO) inibated before 8 days after birth reduce red blood cell transfusions in preterm or low birth weight infants?

BackgroundRepeated blood drawing, shortened red blood cell survival, rapid growth, and attenuated EPO response all contribute to the anemia of prematurity. Anemia of prematurity is associated with clinical findings such as pallor, poor weight gain, decreased activity, tachypnea, tachycardia and feeding problems that prompt red blood cell transfusions. Although it is unknown how low hematocrit levels can fall before clinical signs of anemia of prematurity occur and what the acceptable minimal hematocrit level is in infants requiring supplemental oxygen (Ohls, 2002), transfusions to treat low haemoglobin or low hematocrit levels are frequently used. As many as 80% of VLBW infants and 95% of ELBW infants receive blood transfusions during their hospitalizations (Widness et al., 1996). EPO, with the addition of iron, effectively stimulate erythropoiesis. Plasma EPO levels in neonates are lower than those of older children and adults. The primary goal of EPO therapy is to reduce transfusions. Reducing the number of RBC transfusions reduces the risk of transmission of viral infections and may reduce costs. Frequent RBC transfusions may be associated with retinopathy of prematurity (Hesse et al., 1997) and bronchopulmonary dysplasia.
ParticipantsPreterm (<37 weeks gestation) and/or low birth weight (<2500 g) neonates less than 8 days of age.
InterventionEarly initiation of EPO (initiated before 8 days of age, using any dose, route, or duration of treatment).
ComparisonPlacebo or no intervention (standard care).
Outcome(s)The proportion of infants exposed to one or more red blood cell transfusions and other complications of prematurity.
StudiesRandomized or quasi-randomized controlled trials.
Study description and settingThe review of Ohlsson and coworkers (Ohlsson 2006) identified twenty-seven studies that enrolled 2219 preterm infants in the Neonatal Intensive Care Units in technically developed countries.
ResultsEarly EPO reduced the risk of the ‘use of one or more RBC transfusions’ (typical RR 0.80, 95% CI 0.75, 0.86; typical RD 95% CI; NNT 7(6–11); 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; typical RD 95% CI; NNH 20(12–100); eight 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.
Confidence in resultsHigh quality evidence for all primary outcomes reported.
Key figure(s)Thumbnail image of
Figure captionRetinopathy of prematurity (stage 3 or greater)
Search for eligible studiesCENTRAL, MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings published in Pediatric Research and reference lists of identified trials and reviews were searched through July 2009.
ConclusionEarly EPO reduced the risk of the ‘use of one or more RBC transfusions’ and reduced the total volume (ml/kg) of blood transfused per infant and the number of transfusions per infant. However, there was a significant increase in the risk of severe retinopathy of prematurity (ROP)(stage 3 or greater) in the early EPO group. The risk of severe ROP outweighs the benefits seen in decreased pRBC exposure.
CitationOhlsson A, Aher SM. Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004863. DOI: 10.1002/14651858.CD004863.pub2.
Date completed22 February 2010
People who helped prepare this Cochrane PICO:Roger Soll and Martin Offringa, editors