Effect of High-Dose Erythropoietin on Blood Transfusions in Extremely Low Gestational Age Neonates

Abstract

for the Preterm Erythropoietin Neuroprotection Trial Consortium IMPORTANCE Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure.OBJECTIVES To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions. DESIGN, SETTING, AND PARTICIPANTSThe Preterm Erythropoietin Neuroprotection Trial (PENUT) is a randomized, double-masked clinical trial with participants enrolled at 19 sites consisting of 30 neonatal intensive care units across the United States. Participants were born at a gestational age of 24 weeks (0-6 days) to 27 weeks (6-7 days). Exclusion criteria included conditions known to affect neurodevelopmental outcomes. Of 3266 patients screened, 2325 were excluded, and 941 were enrolled and randomized to erythropoietin (n = 477) or placebo (n = 464).

Anemia and Red Blood Cell Transfusions, Cerebral Oxygenation, Brain Injury and Development, and Neurodevelopmental Outcome in Preterm Infants: A Systematic Review

“…Endogenous erythropoietin is essential for the production of erythrocytes. Several studies have reported substantial neuroprotective properties of erythropoietin, functioning in the brain as both an important growth factor and a neuroprotective agent (65)(66)(67)(68). RBC transfusions during NICU admission may result in less endogenous erythropoietin production.…”

Neonatal red blood cell transfusion

“…A recent multicentre placebo‐controlled randomized trial in 941 infants born at less than 28 weeks of gestation (PENUT ClinicalTrials.gov number NCT01378273, 2020) evaluated the effect of EPO on neonatal brain injury and found no significant impact of EPO on mortality or severe neurodevelopmental impairment at 2 years of age and no effect on major neonatal morbidities including ROP, IVH, sepsis, NEC, BDP [112]. In a separately published post hoc analysis, the same authors also reported that the EPO dosing regimen used stimulated erythropoiesis, as evidenced by the lower number and volume of transfusions and the lower exposure to blood donors in the erythropoietin group [113]. All these studies on EPO use have been carried out in infants with varying degrees of prematurity and have evaluated its use with variable doses, timings and durations of treatment, as well as diverse concomitant therapies.…”

Erythropoietin Non-hematopoietic Tissue Response and Regulation of Metabolism During Diet Induced Obesity

“…Demonstration of EPO for neuroprotection in clinical trials for stroke ( Ehrenreich et al, 2002 ; Ehrenreich et al, 2009 ; Ehrenreich et al, 2011 ) or for very preterm infants ( Natalucci et al, 2020 ; Juul et al, 2020a ) remains elusive. High dose EPO in very preterm infants reduced the transfusion needs in this population, but at 2 years of age lower risk of severe neurodevelopment impairment was not observed ( Juul et al, 2020a ; Juul et al, 2020b ).…”