Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants
Authors: Axel R. Franz, Corinna Engel, Dirk Bassler, Mario Rüdiger, Ulrich H. Thome, Rolf F. Maier, Ingeborg Krägeloh-Mann, Martina Kron, Jochen Essers, Christoph Bührer, Georg Rellensmann, Rainer Rossi, Hans-Jörg Bittrich, Claudia Roll, Thomas Höhn, Harald Ehrhardt, Stefan Avenarius, Hans Thorsten Körner, Anja Stein, Horst Buxmann, Matthias Vochem, Christian F. Poets, Christian A. Maiwald, Gabriele von Oldershausen, Iris Bergmann, Michael Raubuch, Wolfgang Buchenau, Birgit Schuler, Silvia Sander, Hans-Ulrich Bucher, Heike Rabe, Josef Högel, Tamam Bakchoul, Sigrid Enkel, Reinhard Hopfner, Manuel B. Schmid, Steffen Ruess, Helmut D. Hummler, Maria Zernickel, Christof Dame, Christoph Czernik, Lars Garten, Florian Guthmann, Dieter Hüseman, Elisabeth Walch, Jessica Blank, Esther Rieger-Fackeldey, Claudius Werner, Katja Masjosthusmann, Julia Sandkötter, Isabell Hörnig-Franz, Thomas Kühn, Michael Emeis, Mikosch Wilke, Henriette Schönemann, Kathrin Roefke, Wolfgang Pielemeier, Patrizia Kutz, Laura Stüwe-Kunz, Klaus Lohmeier, Renate Richter-Werkle, Lars Klein, Dirk Faas, Rangmar Goelz, Jörg Arand, Ingo Müller-Hansen, Karen Kreutzer, Cornelia Wiechers, Christoph E. Schwarz, Irene Steiner-Wilke, Ralf Böttger, Claudia Jungbluth-Strauch, Janine Heindorf, Christoph Härtel, Levente Bejo, Britta M. Hüning, Rolf Schlößer, Doris Fischer, Antje Allendorf, Michael Zemlin, Pia Göbert, Susanne Kampmann, Silke Thomsen, Mirjam Wege, Franziska Heinz, Evelyn Grandmontagne, Martin Wagner, Ulrich Pohlmann, Patrick Neuberger, Thomas Strahleck, Marlene Westmeier, Zoubida El Hafid, Iris Kallenberg, Aurelia Giordano, Annett Bläser, Corinna Gebauer, Jürgen Seidenberg, Jeannette Dege, Birgitt Moed, Orsolya Genzel-Boroviczény, Stefanie Artmann, Rainer Burghard, Mechthild Hubert, Susanne Lüttchens, Bettina Bohnhorst, Corinna Peter, Christoph Jacobi, Barbara Seipolt, Violeta Cerda Ojinaga, Arite Koch, Beate Walter, Hugo Segerer, Annette Keller-Wackerbauer, Jochen Kittel, Norbert Teig, Susanne Wiegand, Almut Weitkämper, Dominique Singer, Sarah Kabisch, Monika Wolf, Mark Schoberer, Thorsten Orlikowsky, Sonja Trepels-Kottek, Victoria Rotering, Catherine Ley, Gernot Buheitel, Wilfried Schenk, Anne C. Garbe, Matthias Heckmann, Hagen Bahlmann, Stefan Schäfer, Holger Schiffmann, Bettina Behring, Tanja Bauer, Hans-Georg Topf, Patrick Morhart, Regina Trollmann, Michael Schroth, Angela Kribs, Sandra Zawatzki, Axel von der Wense, Peter Gudowius, Jes Reinholdt Petersen, Gitte Veiergang, Gorm Greisen, Ulla Christensen, Tine Brink Henriksen, Tuuli Metsvaht, Renáta Polácková
Journal: JAMA (2020)

<h3>Importance</h3> 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. <h3>Objective</h3> To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability. <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> 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. <h3>Main Outcome and Measures</h3> The 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. <h3>Results</h3> Among 1013 patients 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, 16-73 mL) vs 19 mL (IQR, 0-46 mL); and weekly mean hematocrit was 3 percentage points higher with liberal thresholds. Among infants in the liberal vs restrictive thresholds groups, the primary outcome occurred in 200/450 (44.4%) vs 205/478 (42.9%), respectively, for a difference of 1.6% (95% CI, −4.8% to 7.9%;<i>P</i> = .72). Death by 24 months occurred in 38/460 (8.3%) vs 44/491 (9.0%), for a difference of −0.7% (95% CI, −4.3% to 2.9%;<i>P</i> = .70), cognitive deficit was observed in 154/410 (37.6%) vs 148/430 (34.4%), for a difference of 3.2% (95% CI, −3.3% to 9.6%;<i>P</i> = .47), and cerebral palsy occurred in 18/419 (4.3%) vs 25/443 (5.6%), for a difference of −1.3% (95% CI, −4.2% to 1.5%;<i>P</i> = .37), in the liberal vs the restrictive thresholds groups, respectively. In the liberal vs restrictive thresholds groups, 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. <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01393496