Erythropoietin Fails to Stem Death, Neurodevelopmental Problems in Extreme Preemies

By Gene Emery

January 16, 2020

(Reuters Health) - The hope that giving high-dose erythropoietin to extremely preterm infants would prevent death and neurodevelopment impairment appears to have dimmed.

A new study of 941 infants born at 24 to just under 28 weeks of estimated gestation has shown no benefit to the treatment in that primary composite endpoint.

The combined rates of death or severe impairment were identical by age 2 - 26% - regardless of whether the newborn received the drug or placebo.

"I was disappointed in the results as we hoped it would provide a benefit to our target population," chief author Dr. Sandra Juul, who heads the division of neonatology at the University of Washington in Seattle, told Reuters Health in an email.

Doctors are looking for better ways to treat extremely preterm infants, because despite better survival, about 40% of babies born before 28 weeks still have major impairments such as deafness, blindness, cerebral palsy or intellectual disability.

The researchers focused on erythropoietin because of its importance in fetal brain development.

Four earlier phase 2 trials, included in a 2017 meta-analysis, collectively suggested significant improvement if erythropoietin is used.

About 7% of hospitals that treat extremely preterm infants already give erythropoietin to the majority of such babies, according to a 2019 study in the American Journal of Perinatology.

But the new study, known as PENUT and published January 15 online in The New England Journal of Medicine, showed no benefit of erythropoietin when given within 24 hours after birth to 32 weeks of postmenstrual age. Thirty U.S. hospitals participated in the study.

When the researchers looked at individual outcomes when the children were 22 to 26 months postmenstrual age, they also saw no benefit for erythropoietin therapy.

Death occurred in 13% of the babies who got the drug compared with 11% given placebo.

Rates of sepsis, retinopathy of prematurity, necrotizing enterocolitis, intracranial hemorrhage and bronchopulmonary dysplasia were also not significantly different between the two groups.

Eighty-eight percent in the erythropoietin group were discharged alive versus 90% in the control group. Median time to discharge was 101 days with the drug and 102 days with placebo.

But the drug therapy didn't produce troublesome side effects.

"We found no meaningful differences between groups in any serious adverse events, including those known to occur in adults who receive long-term erythropoietin treatments . . . or in common complications known to occur in extremely preterm infants," the researchers report.

It's not clear whether the results will prompt hospitals to throttle back on erythropoietin use in these babies.

"Each study only provides data regarding a specific treatment protocol, dose and dosing schedule and duration of treatment," said Dr. Juul.

"There are other ongoing studies of both Epo and its analog darbepoetin" and the drug did demonstrate some benefit, she said. "Transfusion number, volume and donor exposure were decreased using this protocol. That is a benefit to the babies. (And) we are also continuing to evaluate subpopulations in our study to try to understand why Epo was not effective in improving outcomes."

The research was financed by the National Institute of Neurological Disorders and Stroke.

SOURCE: The New England Journal of Medicine, online January 15, 2020.