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Awaiting evidence of neuroprotective effects of recombinant erythropoietin in very preterm infants

Journal of Perinatology volume 33, page 411 (2013)Cite this article

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Reassuringly, the follow-up report from Juul and coworkers1 about their phase I/II trial (IND12656) on early high-dose recombinant erythropoietin (rEpo) for neuroprotection in extremely low birth weight (ELBW) infants indicates no adverse long-term outcomes up to 36 months of age. This extends their initial report on the safety and pharmacokinetics in this study.2 The assertion of the beneficial effects of rEpo, however, is apparently preliminary, likely because of incomplete data. Only 17 out of 25 survivors were examined, and the reason of the high drop-out rate (28%) remains unclear. Although infants in the study group were treated with different dosages of rEpo (3 × 500, 1000 or 1500 iU kg−1 per dose intravenously for the first 3 days, n=10 per group), analysis on the neurodevelopmental outcomes does not consider this aspect. Moreover, the number of examinations using the Bayley Scales of Infant Development at the age of 18 to 24 months was only 2 and 6 patients, respectively. A number of previous retrospective analyses point to better neurological outcomes in infants treated with rEpo (at dosages of ⩾750 iU kg−1 per week) for anemia of prematurity.3, 4, 5, 6 Such treatment is necessary to consider in outcomes analysis, but information on the dosage of rEpo for treatment of anemia of prematurity given to 8 out of the 17 patients and their allocation to the three subgroups with different rEpo dosages is not provided. Of note, infants suffering from intraventricular hemorrhage (IVH) do fare better if initially treated with high-dose rEpo. This is in line with recent follow-up outcome measures in ELBW infants suffering IVH, who were treated with rEpo for the anemia of prematurity and examined at the age of 10 years.6

Juul and coworkers2 propose a large placebo-controlled trial on the neuroprotective efficacy of high-dose rEpo in preterm infants. Such a trial has been initiated (NCT00413946). After completing the pilot trial including 30 very preterm infants,7 the study was extended to a multicenter trial within the Swiss Neonatal Network, recruiting a total number of 420 infants, treated with 3 × 3000 U kg−1 rEpo or placebo within 42 h after birth. Recruitment has been recently completed, but end-point neurodevelopmental outcomes measures (including Bayley Scales, magnetic resonance imaging) will last until the year 2014. One smaller phase II trial (NCT00589953; enrolling 22 preterm neonates, treated with 400, 800 or 1000 iU kg−1 per day for 7 days) has been completed, but not reported yet. There are two more trials in which recruitment has been either suspended (NCT00910234) or not started yet (PENUT, NCT013778273). Thus, evidence of neuroprotective effects of rEpo in very preterm infants is still pending.

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  1. Department of Neonatology, Universitätsmedizin Berlin, Berlin, Germany

    C Dame

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Dame, C. Awaiting evidence of neuroprotective effects of recombinant erythropoietin in very preterm infants. J Perinatol 33, 411 (2013). https://doi.org/10.1038/jp.2012.140

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