IMPORTANCE Red blood cell transfusions are commonly administered to infants weighing less than 1000 g at birth. Evidence-based transfusion thresholds have not been established. Previous studies have suggested higher rates of cognitive impairment with restrictive transfusion thresholds.OBJECTIVE To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted in 36 level III/IV neonatal intensive care units in Europe among 1013 infants with birth weights of 400 g to 999 g at less than 72 hours after birth; enrollment took place between July 14, 2011, and November 14, 2014, and follow-up was completed by January 15, 2018.INTERVENTIONS Infants were randomly assigned to liberal (n = 492) or restrictive (n = 521) red blood cell transfusion thresholds based on infants' postnatal age and current health state.
MAIN OUTCOME AND MEASURESThe primary outcome, measured at 24 months of corrected age, was death or disability, defined as any of cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Secondary outcome measures included individual components of the primary outcome, complications of prematurity, and growth. RESULTS Among 1013 patients who were randomized (median gestational age at birth, 26.3 [interquartile range {IQR}, 24.9-27.6] weeks; 509 [50.2%] females), 928 (91.6%) completed the trial. Among infants in the liberal vs restrictive transfusion thresholds groups, respectively, incidence of any transfusion was 400/492 (81.3%) vs 315/521 (60.5%); median volume transfused was 40 mL (IQR,16-73mL)vs19mL(IQR,0-46mL);andweeklymeanhematocritwas3percentagepointshigher withliberalthresholds.Theprimaryoutcomewasnotsignificantlydifferentbetweengroups,norwere the secondary outcomes of death, cognitive deficit, or cerebral palsy. In the liberal vs restrictive thresholds groups, respectively, necrotizing enterocolitis requiring surgical intervention occurred in 20/492 (4.1%) vs 28/518 (5.4%); bronchopulmonary dysplasia occurred in 130/458 (28.4%) vs 126/ 485 (26.0%); and treatment for retinopathy of prematurity was required in 41/472 (8.7%) vs 38/492 (7.7%). Growth at follow-up was also not significantly different between groups. Outcomes No./total (%) Absolute difference, % (95% CI) Odds ratio (95% CI) P value Liberal threshold Restrictive threshold Death or neurodevelopmental impairment by 24 mo 200/450 (44.4) 205/478 (42.9) 1.6 (−4.8 to 7.9) 1.05 (0.80-1.39) .72 Death by 24 mo 38/460 (8.3) 44/491 (9.0) −0.7 (−4.3 to 2.9) 0.91 (0.58-1.45) .70 Cognitive deficit 154/410 (37.6) 148/430 (34.4) 3.1 (−3.3 to 9.6) 1.12 (0.83-1.51) .47 Cerebral palsy 18/419 (4.3) 25/443 (5.6) −1.3 (−4.2 to 1.5) 0.75 (0.40-1.40) .37CONCLUSIONS AND RELEVANCE Among infants with birth weights of less than 1000 g, a strategy of liberal blood transfusions compared with restrictive transfusions did not reduce the likelihood of death or disability at 24 months of corrected age.