Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm inf
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Journal of Translational Medicine Open Access
RESEARCH
Effect of early prophylactic low‑dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants Huiqing Sun1†, Juan Song2†, Wenqing Kang1, Yong Wang2, Xiantao Sun3, Chongchen Zhou4, Hong Xiong1, Falin Xu2, Mingchao Li1, Xiaoli Zhang2, Zengyuan Yu1, Xirui Peng2, Bingbing Li2, Yiran Xu2, Shan Xing1, Xiaoyang Wang2,5 and Changlian Zhu2,6,7*
Abstract Background: Very preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants. Methods: A total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO (n = 950; 500 U/kg, rhEPO group) or saline (n = 948, control group) intravenously within 72 h of birth and then once every other day for 2 weeks. Results: The total incidence of ROP was not significantly different between the two groups (10.2% vs. 13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group (2.2% vs. 4.1%, RR 0.98; 95% CI 0.96–1.00; p = 0.021). Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys (1.8% vs. 4.3%, p = 0.021) and in those with a gestational age of 28–296/7 weeks (1.1% vs. 4.9%, p = 0.002) and birth weight of 1000–1499 g (1.2% vs. 4.2%, p = 0.002). There was a small increasing tendency for the incidence of ROP in infants with a gestational age of 28 weeks and birth weight > 1500 g. Trial registration The data of this study were retrieved from two clinical studies registered ClinicalTrials.gov (NCT 02036073) on January 14, 2014, https://clinicaltrials.gov/ct2/show/NCT02036073; and (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500. Keywords: Erythropoietin, Retinopathy of prematurity, Preterm infant
*Correspondence: [email protected] † Huiqing Sun and Juan Song contributed equally to this work 6 Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden Full list of author information is available at the end of the article
Background Anaemia of prematurity is common in preterm infants, especially in very preterm infants born at 14 days) [9]. If the parents wished to withdraw consent at any time, all study procedures would cease. rhEPO administration
Eligible infants received 500 U/kg rhEPO intravenously every other day for 2 weeks (a cumulative dose of 3500 U/kg for seven separate intravenous injections, regardless of gestational age; this dose was safe and resulted in improved neurologic outcomes). The first dose was administered within 72 h of birth. Infants in the control group received an equivale
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