Review questions: Is early initiation of erythropoietin or darepoetin (initiated before eight days after birth) effective and safe in reducing red blood cell transfusions among preterm and/or low birth weight infants? Does early initiation of erythropoietin or darepoetin serve a neuro protective function? Do these agents protect against necrotising enterocolitis?

Background: 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 use of EPO to prevent or treat anaemia. EPO can be given ‘early’ (before the infant reaches eight days of age) to prevent or decrease the use of red blood cell transfusions. Increasing evidence suggests that EPO may protect against neurological damage and damage to the gut.

Study characteristics: We identified 34 studies that used this approach and enrolled a total of 3643 infants born before term. Studies of variable quality have been conducted in many different countries.

Key results: Early EPO treatment reduced the numbers 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 before trial entry. Early treatment with EPO does not alter the risk of death or retinopathy of prematurity and may decrease the risk of neurological damage and damage to the gut. It may also improve long-term outcomes.

Quality of evidence: According to GRADE, the quality of the main outcomes ranged from high to low.

Conclusions: On the basis of our findings, we do not currently recommend routine early use of erythropoietin in preterm infants. Ongoing studies might shed light on the possibility that erythropoietin may reduce risks of adverse neurodevelopmental outcomes and necrotising enterocolitis.