Erythropoietin Improves Poor Outcomes in Preterm Infants with Intraventricular Hemorrhage

Juan Song, Yong Wang, Falin Xu, Huiqing Sun, Xiaoli Zhang, Lei Xia, Shan Zhang, Kenan Li, Xirui Peng, Bingbing Li, Yaodong Zhang, Wenqing Kang, Xiaoyang Wang, Changlian Zhu, Juan Song, Yong Wang, Falin Xu, Huiqing Sun, Xiaoli Zhang, Lei Xia, Shan Zhang, Kenan Li, Xirui Peng, Bingbing Li, Yaodong Zhang, Wenqing Kang, Xiaoyang Wang, Changlian Zhu

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).

Conflict of interest statement

Juan Song, Yong Wang, Falin Xu, Huiqing Sun, Xiaoli Zhang, Lei Xia, Shan Zhang, Kenan Li, Xirui Peng, Bingbing Li, Yaodong Zhang, Wenqing Kang, Xiaoyang Wang, and Changlian Zhu have no conflicts of interest that are directly relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Study flow. Schematic flowchart showing the number of participants and the procedure of assigning patients to recombinant human erythropoietin or placebo and follow-up to 18 months of corrected age. Preterm infants with grade I–IV intraventricular hemorrhage were enrolled in the study. IVH intraventricular hemorrhage, rhEPO recombinant human erythropoietin

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