Erythropoietin not beneficial for hypoxic-ischemic encephalopathy in newborns: NEJM

USA: In a new study conducted by Yvonne W. Wu and colleagues it has been found that, erythropoietin administration did not reduce the risk of mortality or neurodevelopmental damage in babies undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy, and it was also linked to a greater rate of major adverse events.

Putting it simplistically, adding erythropoietin to cooling therapy for term newborns with birth asphyxia has no benefit over cooling therapy alone.

The findings of the study were published in The New England Journal of Medicine.

In addition to being a significant cause of death, neonatal hypoxic-ischemic encephalopathy also leaves survivors with long-term disabilities. It has been speculated that erythropoietin may have neuroprotective benefits in newborns with hypoxic-ischemic encephalopathy, but it is uncertain if this treatment when combined with therapeutic hypothermia, may affect neurodevelopmental outcomes. This study was carried out in order to determine the impact of erythropoietin while jogging in conjunction with therapeutic hypothermia.

501 children were randomly allocated with moderate or severe hypoxic-ischemic encephalopathy born at 36 weeks or more gestation to receive erythropoietin or a placebo along with routine therapeutic hypothermia in a multicenter, randomized, double-blind, placebo-controlled study. Within 26 hours of delivery, as well as at 2, 3, and 4 days old, intravenous erythropoietin (1000 U per kilogram of body weight) or saline placebo was given.

At 22 to 36 months of age, the main result was either death or neurodevelopmental disability. Cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale from 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (corresponding to 0.67 SD below the mean) on the Bayley Scales of Infant and Toddler Development, were all considered to be signs of neurodevelopmental impairment. Higher scores indicated better performance.

The key findings of this study were as follows:

1. The modified intention-to-treat analysis included 500 babies, of which 257 got erythropoietin and 243 received a placebo.

2. In the erythropoietin group, there were 52.5% deaths or neurodevelopmental impairments, compared to 49.5% in the placebo group.

3. In comparison to the placebo group, there were more significant adverse events on average per kid in the erythropoietin group.

Reference:

Wu, Y. W., Comstock, B. A., Gonzalez, F. F., Mayock, D. E., Goodman, A. M., Maitre, N. L., Chang, T., Van Meurs, K. P., Lampland, A. L., Bendel-Stenzel, E., Mathur, A. M., Wu, T.-W., Riley, D., Yanowitz, T. D., … Juul, S. E. (2022). Trial of Erythropoietin for Hypoxic–Ischemic Encephalopathy in Newborns. New England Journal of Medicine, 387(2), 148–159. https://doi.org/10.1056/NEJMoa2119660