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Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: a randomized placebo-controlled trial

Journal of Perinatology volume 37, pages 596–601 (2017)Cite this article

Subjects

Abstract

Objective:

Erythropoietin (EPO) is neuroprotective after asphyxia in animal studies. The efficacy and safety of EPO monotherapy in term neonates with hypoxic ischemic encephalopathy (HIE) is uncertain.

Study Design:

Hundred term neonates with moderate or severe HIE were randomized by random permuted block algorithm to receive either EPO 500 U kg−1 per dose in 2 ml saline intravenously (50 neonates) on alternate days for a total of five doses with the first dose given by 6 h of age (treatment group) or 2 ml of normal saline (50 neonates) similarly for a total of five doses (placebo group) in a double-blind study. No hypothermia was given. The primary outcome was combined end point of death or moderate or severe disability at mean age of 19 months (s.d., 0.61).

Results:

Death or moderate or severe disability occurred in 40% of neonates in the treatment group vs 70% in the placebo group (risk ratio, 0.57; 95% confidence interval (CI) 0.38 to 0.85; P=0.003). Death occurred in 16% of patients in both the groups (risk ratio, 1.0; 95% CI 0.33 to 2.9; P=0.61). The risk of cerebral palsy was lower among survivors in the treatment group (risk ratio, 0.52; 95% CI 0.25 to 1.03; P=0.04) and lesser number of babies were on anticonvulsants at assessment (risk ratio, 0.47; 95% CI 0.20 to 1.01; P=0.03). Neonatal brain magnetic resonance imaging showed more abnormalities in the placebo group (relative risk, 0.66; 95% CI 0.42 to 1.03; P=0.04)). Improvement in other neurological outcomes was not significant.

Conclusion:

EPO monotherapy reduces the risk of death or disability in term neonates with moderate or severe encephalopathy.

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Acknowledgements

We, Dr Rahid and Dr Mushtaq, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Author contributions

Dr Mushtaq conceptualized and designed the study, drafted the initial manuscript and approved the final manuscript as submitted. Drs Rahid, Rouf and Manzoor carried out the initial analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted. Dr Feroz coordinated and supervised data collection, critically reviewed the manuscript and approved the final manuscript as submitted.

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Authors and Affiliations

  1. Department of Paediatrics, Sheri Kashmir Institute of Medical Sciences, Srinagar, India

    R R Malla, M A Teli & M A Bhat

  2. Department of Neurology, Sheri Kashmir Institute of Medical Sciences, Srinagar, India

    R Asimi

  3. Department of Radiodiagnosis and Imaging, Sheri Kashmir Institute of Medical Sciences, Srinagar, India

    F Shaheen

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  1. R R Malla
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Correspondence to M A Bhat.

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Malla, R., Asimi, R., Teli, M. et al. Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: a randomized placebo-controlled trial. J Perinatol 37, 596–601 (2017). https://doi.org/10.1038/jp.2017.17

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