Researchers have completed preliminary clinical trials that indicate erythropoietin (EPO) may be useful in helping protect babies’ brains against damage caused by hypoxic-ischemic encephalopathy. The study looked at the efficacy of EPO when paired with hypothermia therapy (also known as brain cooling, head cooling, or whole-body cooling, depending on technique type). Their work, presented at the 45th Annual Meeting of the Child Neurology Society, is one potential method of helping minimize the long-term impairments associated with brain injuries at birth.
Babies who had both head cooling and erythropoietin treatment had a lower likelihood of developmental issues by one year of age. Although the study focuses on short-term development, it bolsters hope that the combination treatment can help babies’ long-term development after a hypoxic-ischemic injury. Newborns with moderate to severe hypoxic-ischemic encephalopathy (HIE) are at high risk for death or moderate-to-severe disabilities, and current standards of care involve inducing hypothermia within the first 6 hours after birth* in order to help the brain rewire itself as much as possible. The treatment, however, is not perfect – even with hypothermia therapy, mortality rates for HIE are still 44-55%. A subsequent cerebral palsy diagnosis still can occur for infants that receive the therapy.
This new research, part of the Neonatal Epo and Therapeutic Hypothermia Outcomes phase 2 trial, demonstrates that high-dose EPO treatment in conjunction with hypothermia therapy is safe for infants, paving the way for larger multicenter randomized controlled clinical trials for testing the efficacy of EPO and hypothermia therapy together on a much larger scale.
The randomized, double-blind placebo-controlled multicenter trial looked at a total of 50 newborns. 24 newborns received EPO and hypothermia therapy, while 26 received hypothermia and placebo saline. Babies treated with EPO had significantly lower global brain injury scores, lower incidence of moderate/severe brain injury, and lower incidence of subcortical and cerebellar injury.
Once the babies in the trial were one year old, researchers assessed the babies’ development using the Alberta Infant Motor Scale and the Warner Initial Developmental Evaluation. Babies treated with EPO and hypothermia therapy scored better than those treated with only hypothermia.
Of course, caution is necessary in generalizing the trial’s results. Because the trial was still fairly small, further study is needed to be able to truly prove the treatment’s effectiveness. Longer-term outcomes also were not examined in this study; further follow up of the children will be needed to determine the full usefulness of the therapy. Dr. Amy R. Brooks-Kayal (MD, FAAN, Chief and Ponzio Family Chair in Pediatric Neurology at Children’s Hospital Colorado; Professor of Pediatrics, Neurology and Pharmaceutical Sciences at the University of Colorado, Aurora) responded to the study’s results, saying: “These results do seem promising.”
*Research Update: Hypothermia Therapy May Be Effective 6-24 Hours After Birth
A recently-published study in the Journal of the American Medical Association (JAMA) suggests that hypothermia therapy may be effective 6-24 hours after birth. Laptook et al. (2017) conducted a randomized clinical trial of infants with moderate or severe HIE. 83 infants were given hypothermia therapy, while 85 were maintained at a normal body temperature (control group). The authors then followed up with these cohorts between 18 and 22 months of age. Their results were non-significant under traditional frequentist analysis, but they suggested that hypothermia therapy may still be helpful more than six hours after birth. Laptook et al. stress that further research is warranted, because an improved prognosis in even a small percentage of patients could be of clinical importance due to the severity of HIE-related brain damage. Moreover, they found “no evidence of commensurate harm” – in other words, the potential benefits of administering hypothermia therapy between 6-24 hours may outweigh the costs.
- Wu YW, Mathur AM, Chang T, et al. High-dose erythropoietin and hypothermia for hypoxic-ischemic encephalopathy: A phase II trial. Pediatrics 2016; 137(6). pii: e20160191.