ReviewNeuroprotection with erythropoietin in preterm and/or low birth weight infants
Introduction
Preterm birth rates have been reported to range from 5% to 7% of live births in some developed countries, but are estimated to be substantially higher in developing countries [1]. These figures appear to be rising [2]. Children who are born prematurely have a high risk of neurodevelopmental delay [3], [4]. Neurodevelopmental impairment (neurosensory abnormality including cerebral palsy, deafness, blindness, and/or Mental Developmental Index score of <70) is present in 36% to 48% of survivors [5], [6]. These deficits impart a significant burden to the children, their families, and society. Given the high incidence of survival with neurodevelopmental sequelae, physicians have been searching for effective strategies to prevent or minimize the long-term consequences of neonatal brain injury of prematurity.
Erythropoietin (EPO), which was originally identified for its role in erythropoiesis, has been used to treat a number of anemic states, including early and late anemia of prematurity [7], [8]. Surprisingly, neuroprotection with EPO has also been documented in spinal cord injury, traumatic brain injury, ischemic stroke, and perinatal asphyxia [9].
Successful pilot studies suggested that EPO was both feasible and broadly safe in neonates, supporting further randomized trials. The primary objective of this systematic review was to evaluate the efficacy and safety of EPO used for neuronal development protection, including results from recent trials.
Section snippets
Studies
For this review, both randomized and quasi-randomized (for example, randomization based on day, date, or hospital number) clinical trials of EPO used for neuronal development protection were included. Cohort studies, retrospective studies, case series, case reports, letters to editors that did not contain primary data, editorials, review articles and commentaries were not included, but were explored to identify potential new studies. Multiple reports of primary studies were reviewed to identify
Results
Twenty-one reports were evaluated for eligibility. Five retrospective studies, four case series, and five prospective cohort studies were excluded. Eight reports of seven clinical trials were selected for inclusion in this review.
Discussion
Preterm infants are at a high risk for brain injury and subsequent neurodevelopmental problems. This meta-analysis of seven eligible trials in infants confirms that EPO was associated with a reduced risk of the overall outcome of neurodevelopmental disability in infancy. There was no difference in the risk of morbidity, cerebral palsy, visual deficit, severe hearing deficit, necrotizing enterocolitis, intracranial hemorrhage and patent ductus arteriosus.
EPO is a 34 kD glycoprotein with four
Conclusion
The use of EPO is associated with reduction of neurodevelopmental disability in preterm infants to some extent. However it is still unclear what the proper dose and timing of administration of EPO should be. Continued assessment of long-term outcomes of patients enrolled in completed trials should be a key priority to confirm the long-term safety and efficacy of EPO in treating preterm infants.
Conflicts of Interest/Disclosures
The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.
Acknowledgements
This work was supported by a grant from Jiangsu Province’s Scientific and Technological Supporting Program (grant number BL2012058).
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