The role of erythropoietin to prevent red blood cell transfusion in a 2018-2020 two-center cohort of preterm infants

Abstract

Background: Treatment with recombinant human erythropoietin (rHu-EPO) modestly prevented packed red blood cell transfusions (pRBCTs) in preterm infants in studies performed several years ago. In France, some neonatal units stopped using rHu-EPO, while others continued. The aim of this study was to explore the role of rHu-EPO in the prevention of pRBCTs in a recent cohort of preterm infants.

Materials and methods: Preterm infants who met rHu-EPO indications and were hospitalised between 2018 and 2020 in two neonatal units -one that did not use rHu-EPO and another that did- were eligible. Data about the neonatal history, rHu-EPO and iron treatments and pRBCT indications and volumes were collected. Infants exposed and not exposed to rHu-EPO were compared in univariate and multivariate analyses using backward logistic regression and Cox proportional hazards regression.

Results: A total of 257 patients exposed to rHu-EPO and 285 patients who were not exposed were included. Three profiles emerged. In the infants with a gestational age <28 weeks, the cumulative pRBCT volume/kg was similar regardless of rHu-EPO exposure (mean difference -2.8 mL, 95% confidence interval -16.1, 10.5, p=0.68). In the infants born between 28 and 30 weeks, a late pRBCT was prevented in the rHu-EPO group (single pRBCT: no rHu-EPO 22.1% vs rHu-EPO 8%, p=0.003). However, rHu-EPO was not independently associated with avoidance of this pRBCT. Finally, the need for pRBCT was low in the infants born after 30 weeks of gestation, making rHu-EPO treatment futile. In contrast, early iron supplementation was revealed to be critical in preventing pRBCT.

Discussion: No benefit of rHu-EPO in preventing pRBCT was observed in our cohort. The place of rHu-EPO in future requires careful consideration of the population concerned, adjustment of the therapeutic schedule and evolution of the indications for pRBCT.

Figure 1. Study flowchart

GA: gestational age; NICUs: neonatal intensive care units; RBC: red blood cell; rHu-EPO: recombinant human erythropoietin.

Figure 2. Repartition of infants according to gestational age, exposure to recombinant human erythropoietin (rHu-EPO) and number of packed red blood cell transfusions (pRBCTs) (i.e., none, one or multiple)

The empty bars correspond to the infants not exposed to rHu-EPO, and the dotted bars correspond to the infants treated with rHu-EPO. The white part of each bar corresponds to the infants who did not receive pRBCT, the light grey part corresponds to the infants who needed a single pRBCT during their neonatal course, and the dark grey part corresponds to the infants transfused with multiple pRBCTs. rHu-EPO: recombinant human erythropoietin, RBC: red blood cell.

Figure 3. Mean packed red blood cell (pRBC) volume (mL)/kg transfused to each infant according to postnatal week, exposure to recombinant human erythropoietin (rHu-EPO) and gestational age

The grey lines correspond to the infants not exposed to rHu-EPO, and the black lines correspond to the infants treated with rHu-EPO. The full lines correspond to the infants with a gestational age <28 weeks and the dotted lines correspond to the infants with a gestational age between 28 and 30 weeks. Statistical analysis: t-test for independent samples performed at each postnatal week, *p<0.05. GW: gestational week.