Trials (Dec 2022)

BORN study: a multicenter randomized trial investigating cord blood red blood cell transfusions to reduce the severity of retinopathy of prematurity in extremely low gestational age neonates

  • Luciana Teofili,
  • Patrizia Papacci,
  • Nicoletta Orlando,
  • Maria Bianchi,
  • Tina Pasciuto,
  • Iolanda Mozzetta,
  • Fernando Palluzzi,
  • Luciano Giacò,
  • Carmen Giannantonio,
  • Giulia Remaschi,
  • Michela Santosuosso,
  • Enrico Beccastrini,
  • Marco Fabbri,
  • Caterina Giovanna Valentini,
  • Tiziana Bonfini,
  • Eleonora Cloclite,
  • Patrizia Accorsi,
  • Antonella Dragonetti,
  • Francesco Cresi,
  • Giulia Ansaldi,
  • Genny Raffaeli,
  • Stefania Villa,
  • Giulia Pucci,
  • Isabella Mondello,
  • Michele Santodirocco,
  • Stefano Ghirardello,
  • Giovanni Vento

DOI
https://doi.org/10.1186/s13063-022-06949-8
Journal volume & issue
Vol. 23, no. 1
pp. 1 – 10

Abstract

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Abstract Background Extremely low gestational age neonates (ELGANs, i.e., neonates born before 28 weeks of gestation) are at high risk of developing retinopathy of prematurity (ROP), with potential long-life visual impairment. Due to concomitant anemia, ELGANs need repeated red blood cell (RBC) transfusions. These produce a progressive replacement of fetal hemoglobin (HbF) by adult hemoglobin (HbA). Furthermore, a close association exists between low levels of HbF and severe ROP, suggesting that a perturbation of the HbF-mediated oxygen release may derange retinal angiogenesis and promote ROP. Methods/design BORN (umBilical blOod to tRansfuse preterm Neonates) is a multicenter double-blinded randomized controlled trial in ELGANs, to assess the effect of allogeneic cord blood RBC transfusions (CB-RBCs) on severe ROP development. Recruitment, consent, and randomization take place at 10 neonatology intensive care units (NICUs) of 8 Italian tertiary hospitals. ELGANs with gestational age at birth comprised between 24+0 and 27+6 weeks are randomly allocated into two groups: (1) standard RBC transfusions (adult-RBCs) (control arm) and (2) CB-RBCs (intervention arm). In case of transfusion need, enrolled patients receive transfusions according to the allocation arm, unless an ABO/RhD CB-RBC is unavailable. Nine Italian public CB banks cooperate to make available a suitable amount of CB-RBC units for all participating NICUs. The primary outcome is the incidence of severe ROP (stage 3 or higher) at discharge or 40 weeks of postmenstrual age, which occurs first. Discussion BORN is a groundbreaking trial, pioneering a new transfusion approach dedicated to ELGANs at high risk for severe ROP. In previous non-randomized trials, this transfusion approach was proven feasible and able to prevent the HbF decrease in patients requiring multiple transfusions. Should the BORN trial confirm the efficacy of CB-RBCs in reducing ROP severity, this transfusion strategy would become the preferential blood product to be used in severely preterm neonates. Trial registration ClinicalTrials.gov NCT05100212. Registered on October 29, 2021

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