Erythropoietin does not reduce deaths among infants with birth asphyxia

Key takeaways:

• High-dose erythropoietin did not improve outcomes for infants with hypoxic ischemic encephalopathy.
• Controlled cooling within 6 hours of birth remains the best treatment for birth asphyxia.

HONOLULU — Erythropoietin did not reduce the risk for death or severe disability among infants with hypoxic ischemic encephalopathy already being treated with hypothermia, according to the results of a phase 3 randomized controlled trial.

“Hypoxic ischemic encephalopathy (HIE) remains a feared complication when things go wrong during the birth of a baby, occurring in about one to three per 1,000 births in high-income countries,” Helen G. Liley, MBChB, FRACP, a professor at The University of Queensland in South Brisbane, Australia, told Healio.

Liley and colleagues conducted a phase 3 randomized controlled trial of 311 infants with HIE, also known as birth asphyxia, at 25 facilities in Australia, New Zealand and Singapore between 2016 and 2022. They assigned half of the infants to be treated with hypothermia alone — the standard of care for neonates with HIE — and the other half to be treated with hypothermia and five 1,000 units/kg doses of erythropoietin every other day for 9 days after birth. The primary outcome was death or severe disability up to age 2 years.

The researchers did not find a significant difference in the risk for death or disability between the erythropoietin group and the placebo group (35.3% vs. 29.4%; RR = 1.2; 95% CI, 0.85-1.7).

“Erythropoietin remains safe and highly valuable for promoting red cell production in certain kinds of anemia, but there is no evidence to use it to help babies who are receiving the current standard of treatment for HIE, which is a 3-day course of controlled cooling to around 33.5°C, started within 6 hours of birth,” said Liley, who presented the findings at PAS 2025.

The results supported findings from another trial published in The New England Journal of Medicine in 2022 that was conducted in the United States.

“Together, both trials provide greater certainty of evidence about this lack of benefit,” Liley said.

Some of the results were encouraging, though. Liley said the rates of death and disability were lower among babies in this trial compared with cooling trials from 20 years ago.

“We now have better information to give parents about outcomes, and they do have some room for hope,” she said.

Some other treatments for HIE are being tested, Liley said, including melatonin, neurohormones and stem cells.

She noted that the cause of HIE was known for about half of the infants in the study, including events like separation of the placenta, uterine rupture or the baby getting stuck during birth. She said researchers will need to find better ways to anticipate the risk for HIE and prevent it.

References:

• Liley HG, et al. Aiming to prevent adverse outcomes of neonatal hypoxic ischemic encephalopathy with erythropoietin — the PAEAN multicenter randomized controlled trial. Presented at: Pediatric Academic Societies Meeting; April 24-28, 2025; Honolulu.
• Study: Treatment ineffective for newborns with low oxygen or blood supply. Published April 25, 2025. Accessed April 25, 2025.

For more information:

Helen G. Liley, MBChB, FRACP, can be reached at pediatrics@healio.com.