Cord red blood cell transfusions for severe retinopathy in preterm neonates in Italy: a multicenter randomized controlled trial

Abstract

Background: Red blood cell (RBC) transfusions in preterm neonates are associated with retinopathy of prematurity (ROP).

Methods: BORN is a multicenter randomized trial investigating whether RBC transfusions from cord blood (CB-RBCs) instead of adult donors (A-RBCs) reduce ROP severity (NCT05100212). The study was conducted between December 2021 and November 2024 in 8 hospitals sited in 8 different Italian regions. Extremely low gestational age neonates (ELGANs) were randomized 1:1 to receive A-RBCs (control) or CB-RBCs (intervention) from birth to postmenstrual age (PMA) of 29 + 6 weeks. The main outcome was severe-ROP rate at 40 weeks PMA or discharge.

Findings: By intention-to-treat-analysis, 56 patients per arm were evaluated: 16 in the control arm and 14 in the intervention arm developed severe ROP (28·6% versus 25·0%, risk difference [RD] -0·03 [95% CI -0·21% to 0·14%]; P = 0·831). Twenty-four (42·8%) patients in the intervention arm received also A-RBCs. Per-protocol-analysis included those patients receiving exclusively the assigned treatment, consisting of 38 ELGANs in the control arm and 17 in the intervention arm, with comparable characteristics. Thirteen ELGANs in the control arm developed severe ROP, and 10 required ROP treatment whilst no patients in the intervention arm developed severe ROP or treatment-requiring ROP (34·2% versus 0%, RD -0·34 [95% CI -0·51% to -0·07%] for severe ROP, P = 0·005, and 26·3% versus 0%, RD -0·28 [95% CI -0·46% to -0·02%] for treatment-requiring ROP, P = 0·022). Twenty-four patients in the control arm and 5 in the intervention arm developed moderate/severe BPD (63·2% versus 29·4%, RD -0·33 [95% CI -0·56% to -0·02%], P = 0·039).

Interpretation: CB-RBCs may protect ELGANs from severe forms of ROP and BPD.

Funding: Funded by Fresenius HemoCare Italia SRL (Prot. N 0038762/21-04/11/2021; grant number 5800134-FPG).

Keywords: Extremely low gestational age neonates; Fetal hemoglobin; Randomized controlled trial; Retinopathy of prematurity; Transfusions; Umbilical blood.

Fig. 1

CONSORT diagram of the study. The diagram illustrates the number of patients included in the different sets of analysis planned in the study protocol: the intention-to-treat set, the per-protocol set, and the as-treated set. DAT indicates direct antiglobulin test.

Fig. 2

Area under the curve (AUC) of HbF at different postmenstrual ages (PMA) in BORN patients. The HbF AUC calculated from birth to 30 weeks PMA was adjusted for the number of postnatal days. Comparison between groups was made with Mann–Whitney's U test. a) HbF AUC of patients grouped according to the occurrence of severe ROP. Gray area refers to patients without severe ROP and red area to patients with severe ROP. ∗∗∗ denotes P < 0·001. b) HbF AUC in neonates developing or not moderate or severe BPD. Gray area indicates patients without moderate or severe BPD and red area those with moderate or severe BPD. ∗ indicates P = 0·037. c). HbF AUC of patients grouped according to arm allocation. Red area refers to control arm and gray area to the intervention arm. d) HbF AUC of patients grouped according to types of RBC products received before 30 weeks PMA. Gray area indicates non-transfused patients, red area neonates who received only A-RBCs, green area those who received only CB-RBCs, and blue area the neonates transfused with both A-RBCs and CB-RBCs. ∗∗∗ denotes P < 0·001 and ∗∗∗∗ denotes P < 0·0001 in comparison with non-transfused neonates.