Design: Phase 3 multicentre double-blind placebo-controlled randomised trial
Population: 313 infants ≥35 weeks with moderate or severe HIE receiving hypothermia
Primary outcome: Death or moderate-to-severe disability at 2 years
Effect: 34.1% vs 28.7%; RR 1.19 (95% CI 0.84 to 1.68)

PAEAN was a phase 3, double-blind, placebo-controlled trial in 24 neonatal units across Australia, New Zealand and Singapore. It randomised 313 infants of 35 weeks or more with moderate or severe hypoxic-ischaemic encephalopathy, all started on therapeutic hypothermia within six hours, to five doses of intravenous erythropoietin 1,000 IU/kg over the first week or placebo.

At two years, death or moderate-to-severe motor or cognitive disability occurred in 34.1% with erythropoietin and 28.7% with placebo (RR 1.19, 95% CI 0.84 to 1.68). Death, cerebral palsy, motor and cognitive deficits did not differ, and there were no safety concerns.

This agrees with the larger HEAL trial in the US, and together they make erythropoietin unlikely to be a useful add-on to cooling in term and near-term infants. Cooling, started early and done well, remains the treatment that works.

Do not add erythropoietin to therapeutic hypothermia for HIE outside a trial
Start cooling within six hours of birth in eligible infants with moderate or severe encephalopathy
Arrange early transfer to a cooling centre when encephalopathy is suspected after a difficult delivery
Plan structured neurodevelopmental follow-up to at least two years for every cooled infant

Why it matters

It closes a long-running question about the most studied adjunct to cooling.

The statistics, in plain English

A relative risk of 1.19 with an interval from 0.84 to 1.68 includes both modest harm and modest benefit, so the trial found no effect either way. The point estimate leaning slightly against erythropoietin is not evidence of harm.