The effect of two red-cell transfusion strategies on outcomes and incidence of anemia after discharge in premature infants with extremely low birth weight

Premature newborns with extremely low birth weight are the main category of infants having to undergo one or more red-cell transfusions during the neonatal period in order to treat anemia. Presently, there are two major transfusion strategies: the liberal strategy aimed at maintaining higher hemoglobin levels, and the restrictive one when blood is transfused at lower hemoglobin levels. In our study, we aimed to compare outcomes and the incidence of anemia after discharge during the first 24 months of corrected age in infants with extremely low birth weight who had received red-cell transfusions according to the restrictive or liberal strategy. The study was approved by the Biomedical Research Ethics Committee (minutes No.12 of 17 November 2016) and the Scientific Council (minutes No.19 of 29 November 2016) of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russia. This was a single-center retrospective cohort study carried out at clinical departments of the Institute of Neonatology and Pediatrics of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russia. The included infants were divided into 2 groups: group 1 – infants who had received RBC transfusions following the liberal strategy; group 2 – infants in whom the restrictive transfusion strategy had been used. We looked at the incidence of such outcomes as retinopathy of prematurity (ROP) ≥ stage III, necrotizing enterocolitis (NEC) ≥ stage II, bronchopulmonary dysplasia (BPD), intraventricular hemorrhages (IVH) ≥ grade II, periventricular leukomalacia (PVL), anemia after discharge at a corrected age (CA) of 1, 3, 6, 12, 18 and 24 months. The gestational age of the newborns ranged from 24 to 28 weeks. The frequency of red-cell transfusions was 136/164 (82.9%) in group 1 versus 149/216 (68.9%) in group 2, with the median volume of transfusions of 29.3 mL/kg (IQR 17.5–51.8 mL/kg) in group 1 and 19.5 mL/kg (IQR 15.0–29.5 mL/kg) in group 2, p 0.05. There were no significant differences in the incidence of BPD, IVH ≥ grade II, PVL, ROP ≥ stage III between the study groups. The incidence of NEC ≥ stage II was 1.6 times higher in group 2 than in group 1. The incidence of anemia after discharge was lower in group 1 compared to group 2 at a CA of 1 and 3 months (32/72 (44.4%) vs. 106/166 (63.8%), p = 0.026 at 1 month, 28/72 (38.9%) vs. 90/166 (54.2%), p = 0.042 at 3 months). There were no reports of severe anemia after discharge in either of the groups. After 6 months CA there was no difference in the incidence of anemia between the groups. The use of the restrictive red-cell transfusion strategy did not lead to a clinically significant increase in the incidence of ROP ≥ stage III, BPD, PVL, IVH ≥ grade II or anemia after 6 months of CA. However, the risk of NEC ≥ stage II in the restrictive strategy group was 1.6 times higher than in the liberal one, which requires further analysis.