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

J Perinatol. 2017 May;37(5):596-601. doi: 10.1038/jp.2017.17. Epub 2017 Mar 9.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Asphyxia Neonatorum / drug therapy*
  • Asphyxia Neonatorum / mortality*
  • Brain / diagnostic imaging*
  • Cerebral Palsy / epidemiology
  • Double-Blind Method
  • Erythropoietin / administration & dosage*
  • Female
  • Humans
  • Hypoxia-Ischemia, Brain / complications*
  • India
  • Infant
  • Infant, Newborn
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Prospective Studies
  • Severity of Illness Index
  • Term Birth

Substances

  • Erythropoietin