What Effect Does High-Dose Erythropoietin Have on Preterm Infants With IVH?

Treatment with high-dose erythropoietin in preterm infants with intravascular hemorrhage (IVH) does not appear to affect brain injury scores on conventional magnetic resonance imaging (MRI) at term-equivalent age (TEA), according to study findings published in JAMA Network Open.

Recognizing that IVH is a major cause of neonatal morbidity and mortality among preterm infants, with no known specific medical treatment to date, researchers sought to evaluate the safety and short-term outcomes of high-dose erythropoietin in this patient population. Erythropoietin is a glycoprotein cytokine that is secreted mainly by the kidneys in response to cellular hypoxia and that stimulates red blood cell production in the bone marrow.

Between April 1, 2014, and August 3, 2018, the researchers conducted a multinational, prospective, randomized, double-blind, placebo-controlled trial, Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair; ClinicalTrials.gov Identifier: NCT02076373).

They enrolled a total of 121 preterm infants (gestational age less than 32 weeks or birth weight less than1500 g) aged 8 days or less with moderate to severe IVH who were identified via cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were conducted from October 1, 2019, through September 12, 2022.

The primary study outcome was the composite intelligence quotient at age 5 years, which will be reported following study completion in 2023. Secondary outcomes included a global brain abnormality score, as well as white and gray matter injury scores evaluated on T1- and T2-weighted MRI images at TEA on 3-T MRI systems at the various treatment sites.

Among the 121 study participants, 60 infants (48% male) were randomly assigned to receive erythropoietin and 61 infants (61% male) were randomly assigned to receive placebo. The median birth weight was 832 g (range, 687-990 g) in the erythropoietin   arm and 870 g (range, 680-1100 g) in the placebo arm. Median gestation was
26.1 weeks (range, 24.8-27.3 weeks) in the erythropoietin group vs 27.0 weeks (range, 24.9-28.1 weeks) in the placebo group. Baseline characteristics and morbidities were similar in both of the groups.

Up to TEA, 16.7% (10 of 60) of newborns in the erythropoietin group died vs 8.2% (5 of 61) of those in the placebo group (adjusted odds ratio, 2.24; 95% CI, 0.74-7.66; P =.15). Further, infants treated with erythropoietin had higher mean hematocrit levels. Conventional MRI scans at TEA in 100 infants revealed no significant differences in global or regional brain injury scores.

This preliminary report from the EpoRepair trial showed no evidence that treatment with high-dose erythropoietin in preterm infants with IVH impacts brain injury scores on conventional MRI at TEA.

Several limitations of the study warrant mention. Although the multicenter trial has the advantage of the results being more generalizable, it may have introduced more heterogeneity to this relatively small study. Further, since enrollment of multiples was not anticipated, accounting for them was not considered in the statistical analysis plan.

The researchers concluded that “Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials.”

Disclosure: One of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.