Erythropoietin Improves Poor Outcomes in Preterm Infants with Intraventricular Hemorrhage

Abstract

Background Intraventricular hemorrhage (IVH) is a common complication in preterm infants that has poor outcomes, especially in severe cases, and there are currently no widely accepted effective treatments. Erythropoietin has been shown to be neuroprotective in neonatal brain injury. Objective The objective of this study was to evaluate the protective effect of repeated low-dose recombinant human erythropoietin (rhEPO) in preterm infants with IVH. Methods This was a single-blinded prospective randomized controlled trial. Preterm infants ≤ 32 weeks gestational age who were diagnosed with IVH within 72 h after birth were randomized to receive rhEPO 500 IU/kg or placebo (equivalent volume of saline) every other day for 2 weeks. The primary outcome was death or neurological disability assessed at 18 months of corrected age. Results A total of 316 eligible infants were included in the study, with 157 in the rhEPO group and 159 in the placebo group. Although no significant differences in mortality ( p = 0.176) or incidence of neurological disability ( p = 0.055) separately at 18 months of corrected age were seen between the rhEPO and placebo groups, significantly fewer infants had poor outcomes (death and neurological disability) in the rhEPO group: 14.9 vs. 26.4%; odds ratio (OR) 0.398; 95% confidence interval (CI) 0.199–0.796; p = 0.009. In addition, the incidence of Mental Development Index scores of < 70 was lower in the rhEPO group than in the placebo group: 7.2 vs. 15.3%; OR 0.326; 95% CI 0.122–0.875; p = 0.026. Conclusions Treatment with repeated low-dose rhEPO improved outcomes in preterm infants with IVH. Trial Registration The study was retrospectively registered on ClinicalTrials.gov on 16 April 2019 (NCT03914690).

The Impact of Different Degrees of Intraventricular Hemorrhage on Mortality and Neurological Outcomes in Very Preterm Infants: A Prospective Cohort Study

“…However, there are currently no effective therapies for neonatal IVH. Fortunately, in the past few decades antenatal steroids ( 48 ), magnesium sulfate ( 49 ), mesenchymal stem cells ( 50 ), and erythropoietin ( 30 ) have shown promise as therapeutic agents for neuroprotection against death and neurological disability in preterm infants with severe IVH.…”

“…Sepsis is defined as a severe infection with positive blood culture ( 29 ). Severe anemia is defined based on different hemoglobin concentrations at different ages and respiratory status ( 30 ).…”

Pharmacological Management of Germinal Matrix-Intraventricular Hemorrhage

“…As the long-term neurodevelopmental outcomes of early rhEPO treatment still remain unclear, the authors do not recommend its routine use due to its limited benefits in preterm infants. However, a recent research study showed rhEPO has benefits in improving the mortality rate and neurodevelopmental outcomes, including atrophy and cognition 13,28) .…”

Free Radicals and Neonatal Brain Injury: From Underlying Pathophysiology to Antioxidant Treatment Perspectives

“…Moreover, in two randomized trials where preterm infants received high-dose rh-Epo versus placebo, significantly decreased white matter abnormalities, periventricular white matter loss and improved white matter development at term MRI were observed in the treated group [ 146 , 147 ]. In very preterm infants with IVH, rh-Epo administration following IVH diagnosis was associated with significantly lower rates of death, neurological disability and severe neurodevelopmental impairment at 18 months compared to placebo [ 148 ]; the results of a large double-blind, placebo-controlled trials, however, are expected to further confirm this data [ 149 ].…”