Study: Treatment ineffective for newborns with low oxygen or blood supply

(Press-News.org) Erythropoietin, a treatment for newborns with critically low levels of oxygen or blood supply to the brain at birth, does not prevent death or disability, according to a new multinational study. The research will be presented at the Pediatric Academic Societies (PAS) 2025 Meeting, held April 24-28 in Honolulu. 

Researchers found that a high-dose treatment with erythropoietin, paired with standard cooling treatments, does not reduce death, rate of cerebral palsy, or physical or cognitive impairment for newborns with hypoxic-ischemic encephalopathy (HIE).

HIE, which leads to brain damage, is caused by labor and delivery problems, or problems with how the placenta is functioning just before or during birth.

The randomized trial (PAEAN) studied 311 babies born with HIE at or after 35 weeks in Australia, New Zealand, and Singapore. Researchers compared outcomes at age two between babies treated only with controlled cooling of the baby to a few degrees below normal, and those treated with both erythropoietin and cooling in the first days after birth.

“Our research supports the findings of the HEAL study, published by Dr. Yvonne Wu and her colleagues in 2022, which also indicated no benefit of erythropoietin for babies receiving cooling for HIE. The PAEAN study increases the certainty of evidence from HEAL, and together, they do not support prior studies showing erythropoietin could improve outcomes, which brought hope to lower-income countries where access to intensive treatment is not assured,” said Helen G. Liley, MBChB, FRACP, professor at the University of Queensland in Australia and presenting author. “Hypoxic-ischemic encephalopathy is a leading cause of death and disability among newborns, and the search for ways to prevent, detect, and treat it remains critical.”

Between one and five babies per 1,000 born in countries with high health care resources have HIE, while rates are significantly higher in countries with fewer resources for prenatal care and birth, according to researchers.

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EDITOR:
Helen G. Liley will present “Aiming to Prevent Adverse Outcomes of Neonatal Hypoxic lschemic Encephalopathy with Erythropoietin - the PAEAN Multicenter Randomized Controlled Trial” on Sat., April 26 from 2:00-2:15 p.m. ET. 
Reporters interested in an interview with Helen should contact Amber Fraley at amber.fraley@pasmeeting.org.
The PAS Meeting connects thousands of pediatricians and other health care providers worldwide. For more information about the PAS Meeting, please visit www.pas-meeting.org.

About the Pediatric Academic Societies Meeting
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Abstract: Aiming to Prevent Adverse Outcomes of Neonatal Hypoxic lschemic Encephalopathy with Erythropoietin - the PAEAN Multicenter Randomized Controlled Trial

Presenting Author: Helen G. Liley, MBChB, FRACP

Organization
The University of Queensland

Topic
Neonatal Clinical Trials

Background
Hypothermia is the standard of care to reduce mortality and disability following hypoxic-ischemic encephalopathy at birth. However, not all infants respond adequately, prompting research into adjunct "cooling plus" agents. Erythropoietin (Epo) has neuroprotective and reparative properties that may enhance the effects of hypothermia.

Objective
In infants with moderate to severe HIE, to assess whether hypothermia combined with five doses of Epo at 1000 U/kg IV on days one, three, five, seven, and nine after birth is superior to hypothermia alone in promoting normal neurodevelopmental outcomes and reducing mortality and disability (mild or moderate/severe) at two years of age.

Design/Methods
Phase III multicenter, double-blinded, placebo-controlled, randomized trial. Participants were recruited from Neonatal Intensive Care Units at 25 sites in Australia, New Zealand and Singapore. Eligible infants were born at ≥35 weeks' gestation, and were < 3 hours old, with: (i) perinatal depression (at least one of the following: Apgar score ~five at 10 minutes, need for prolonged resuscitation, or pH < 7.0 or base deficit  ≥12 on cord blood or within the first 60 minutes); (ii) moderate to severe encephalopathy (at least three of six or seizures plus two of six modified Samat criteria); and (iii) commenced hypothermia within six hours of birth. Consented eligible infants were randomly assigned to receive Epo + hypothermia or hypothermia alone. The primary outcome was a composite measure of death and moderate or severe disability (including assessment for cerebral palsy and using the Bayley Scales of lnfant Development) at two years. Secondary outcomes included death and disabilities alone and safety analysis.

Results
Between 2016-2022, 311 infants were randomized and treated (Epo n=156; Placebo n=157). Baseline characteristics were similar in the two groups. In the Epo group, protocol adherence was high for the first three of five doses (99%, 97%, 94%, 85%, and 56%). The composite primary outcome was 47/133 (35.3%) in the Epo group v. 40/136 (29.4%) for Placebo (relative risk 1.20 (95% CI 0.85 -1 .70) p=0.30. Among secondary outcomes, there were no significant differences for death [15.4% v. 12.2%, p=0.43]; rates of cerebral palsy [22 v. 21 infants]; motor deficit [13 v. 14]; or cognitive deficit [20 v. 16]. 

Conclusion(s)
Epo did not demonstrate any improved outcomes when added to hypothermia, ruling out clinically important reductions in death and disability.
 

END