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  • Letter to the Editor
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Response to Dr C Dame

Journal of Perinatology volume 33, page 412 (2013)Cite this article

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We thank Dr Dame for his thoughtful comments on our paper.1, 2 We agree that the primary purpose of this work was to query the long-term safety of high-dose rEpo, as the study sample is clearly too small to establish efficacy, particularly with the three rEpo treatment doses used, giving a maximum of 10 subjects per group.3 The University of Washington is a referral center for the state of Washington, and so unless patients are prospectively followed in a study situation, long-term follow-up is frequently done at the referral sites. Despite this, we felt it was important to determine the long-term outcomes of as many patients who received high-dose Epo as possible, given that such use is still in its early stages. To date, there have been a limited number of clinical studies in preterm infants to test the safety and efficacy of early treatment with rEpo. The available studies are heterogeneous in their approach to rEpo treatment with variations in timing, duration and cumulative rEpo doses.4 As our report contains the only available long-term outcome data for extremely low birth weight infants treated with early high-dose rEpo, we consider it important to inform clinicians caring for preterm infants of these outcomes, recognizing that our study had limitations that preclude us from making recommendations about the most suitable rEpo-dosing strategy for effective neuroprotection in preterm neonates.

Epo shows great promise as a neuroprotective therapy, and happily, the transition from basic science to clinical trials is now underway. The optimal dose for Epo neuroprotection in preterm infants is not yet established, as is well illustrated by the variation in dosing strategies noted by Dr Dame. In rodent models of neonatal brain injury, repeated doses of 1000–5000 U kg per dose Epo result in sustained neuroprotection after acute brain injury, improving both short and long-term structure and function.5, 6 Preclinical data suggest that Epo neuroprotection has a U-shaped dosing curve, with too little or too much Epo resulting in diminished efficacy.6, 7 In extremely low birth weight infants, IV doses of 1000 U per kg Epo result in area under the curve measurements most similar to neuroprotective doses in neonatal rats.6, 8 The steady-state concentrations (mean=576 mU ml−1) produced by 1000 U kg−1 per dose is also thought to be neuroprotective.9

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References

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Authors and Affiliations

  1. Department of Pediatrics, Division of Neonatology, University of Washington, Seattle, WA, USA

    R M McAdams, R J McPherson & S E Juul

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  1. R M McAdams
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  2. R J McPherson
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  3. S E Juul
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Correspondence to S E Juul.

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McAdams, R., McPherson, R. & Juul, S. Response to Dr C Dame. J Perinatol 33, 412 (2013). https://doi.org/10.1038/jp.2012.141

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