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

Chelsea and Westminster Hospital NHS Foundation Trust, Londinium, England, United Kingdom
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 07/2006; 2(3):CD004865. DOI: 10.1002/14651858.CD004865.pub2
Source: PubMed


The number of red blood cells falls after birth in preterm infants due to the natural breakdown of erythrocytes and blood letting. 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. A total of 262 infants born preterm have been enrolled in two studies of early vs. late administration of EPO to prevent blood transfusions. There were no demonstrable benefits of early vs. late administration of EPO with regards to reduction in the use of red blood cell transfusions, number of transfusions, the amount of red cells transfused or number of donor exposures per infant. However, the use of early EPO compared to late EPO administration increases the risk of retinopathy of prematurity, a serious complication in babies born before term. Currently, there is lack of evidence that either treatment confers any substantial benefits with regard to any donor blood exposure, as many infants enrolled in both studies were exposed to donor blood prior to study entry, and early EPO increases the risk of retinopathy of prematurity. Neither early nor late administration of EPO is recommended.

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    • "Clinical trials—Recent randomized controlled studies of small groups of very preterm (Fauchere et al., 2008) and extremely low-birth weight infants (Juul et al., 2008) have shown that there were no significant adverse effects with early high-dose recombinant EPO treatment, paving the way for larger trials. The initial concern about increased risk of thrombotic events reported for adults undergoing EPO therapy for chronic kidney failure has not been borne out for the neonate (Aher and Ohlsson, 2006). The first trial of EPO in full term neonates with moderate to severe hypoxia-ischemia demonstrated that it reduced death and disability at 18 months from 44% (controls) to 25% (EPO-treated) with no adverse effects (Zhu et al., 2009). "
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    ABSTRACT: A compromised intrauterine environment that delivers low levels of oxygen and/or nutrients, or is infected or inflammatory, can result in fetal brain injury, abnormal brain development and in cases of chronic compromise, intrauterine growth restriction. Preterm birth can also be associated with injury to the developing brain and affect the normal trajectory of brain growth. This review will focus on the effects that episodes of perinatal hypoxia (acute, chronic, associated with inflammation or as an antecedent of preterm birth) can have on the developing brain. In animal models of these conditions we have found that relatively brief (acute) periods of fetal hypoxemia can have significant effects on the fetal brain, for example death of susceptible neuronal populations (cerebellum, hippocampus, cortex) and cerebral white matter damage. Chronic placental insufficiency which includes fetal hypoxemia, nutrient restriction and altered endocrine status can result in fetal growth restriction and long-term deficits in neural connectivity in addition to altered postnatal function, for example in the auditory and visual systems. Maternal/fetal inflammation can result in fetal brain damage, particularly but not exclusively in the white matter; injury is more pronounced when associated with fetal hypoxemia. In the baboon, in which the normal trajectory of growth is affected by preterm birth, there is a direct correlation between a higher flux in oxygen saturation and a greater extent of neuropathological damage. Currently, the only established therapy for neonatal encephalopathy in full term neonates is moderate hypothermia although this only offers some protection to moderately but not severely affected brains. There is no accepted therapy for injured preterm brains. Consequently the search for more efficacious treatments continues; we discuss neuroprotective agents (erythropoietin, N-acetyl cysteine, melatonin, creatine, neurosteroids) which we have trialed in appropriate animal models. The possibility of combining hypothermia with such agents or growth factors is now being considered. A deeper understanding of causal pathways in brain injury is essential for the development of efficacious strategies for neuroprotection.
    Full-text · Article · Apr 2011 · International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience
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    Preview · Article · Jan 2006 · Cochrane database of systematic reviews (Online)
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    ABSTRACT: 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.
    Full-text · Article · Jul 2006 · Cochrane database of systematic reviews (Online)
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