Early High-Dose Erythropoietin exibits no Long-Term Cognitive Benefits for Very Preterm Children: JAMA

Children born very preterm are at increased risk of experiencing long-term neurodevelopmental challenges. Erythropoietin, a hormone that stimulates red blood cell production, has been explored for its potential neuroprotective effects in very preterm infants—those born before 28 weeks of gestation. Given the high risk of developmental issues faced by these children, researchers hoped that early high-dose administration of rhEpo might enhance neurodevelopmental outcomes.

Against the above background, Flavia Maria Wehrle, Child Development Center, University Children’s Hospital Zurich, Zurich, Switzerland, and colleagues aimed to examine if early high-dose rhEpo is linked to improved executive functions and processing speed—cognitive abilities that develop later—in school-aged children born very preterm.

For this purpose, the researchers conducted a single-center cohort study, following up on a multicenter neonatal clinical trial. They focused on 365 children born very preterm (mean gestational age of 29.3 weeks; range, 26.0-31.9 weeks) who had been enrolled in the Swiss EPO Neuroprotection Trial at birth between 2005 and 2012. These children were included in the primary outcome analyses at two years of age and were subsequently recruited for the EpoKids study when they reached school age between 2017 and 2021. Term-born children were also recruited to serve as a control group. Data analysis was conducted between May and September 2022.

The study involved administering rhEpo (3000 IU/kg) or a placebo (saline, 0.9%) intravenously three times within the first two days of life as part of the Swiss EPO Neuroprotection Trial. To evaluate the impact of early high-dose rhEpo on cognitive development, the researchers used a comprehensive neuropsychological test battery to assess executive functions and processing speed. Additionally, parents provided reports on their child’s executive functions in everyday life. The aim was to determine if early high-dose rhEpo administration was associated with improved cognitive outcomes at school age.

The following were the key findings of the study:

• In the EpoKids study, 214 children born very preterm (58.6% of 365 children in the eligible cohort) were assessed at a mean age of 10.4 years; 54.7% were boys.
• There was no evidence that the 117 children who had received rhEpo differed from the 97 children who had received a placebo in any of the 15 executive function and processing speed tests, nor in parent-rated executive functions.
• Irrespective of rhEpo or placebo allocation, children born very preterm scored lower on 11 of 15 executive function and processing speed tests than term-born peers.

The study found no evidence linking prophylactic early high-dose rhEpo administration with improved long-term neurodevelopmental outcomes in children born very preterm.

"These findings indicate that a more comprehensive approach, integrating both pharmacological and non-pharmacological prevention and intervention strategies, is necessary to enhance neurodevelopmental outcomes for these children," the researchers concluded.

Reference:

Wehrle FM, Held U, Disselhoff V, et al. Early High-Dose Erythropoietin and Cognitive Functions of School-Aged Children Born Very Preterm. JAMA Netw Open. 2024;7(9):e2430043. doi:10.1001/jamanetworkopen.2024.30043