Cord Blood Transfusions in Extremely Low Gestational Age Neonates in Italy: Results of a Prespecified Interim Analysis of the Randomized Born Trial.

Abstract Background Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels have been associated with ROP, but it is presently unknown if preventing the HbF decrease also reduces ROP. Case presentation: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of RBC units from adult donors (A-RBCS) reduces the incidence of severe ROP. Neonates born before 28 weeks of gestation are enrolled. Neonates are randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. The main outcome is the rate of severe ROP at 40 weeks of PMA or discharge. A prespecified interim analysis was scheduled after the first 58 patients were enrolled. Results in the intention-to-treat and per-protocol sets of analyses are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBC or A-RBC transfusions. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06–2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrements before the PMA of 30 weeks are critical for severe ROP development. Importantly subsequent CB-RBC transfusions do not lessen the ROP risk. Conclusions CB-RBC transfusions in preterm neonates are safe and, if early adopted, may help protect them from severe ROP. Trial registration: ClinicalTrials.gov Identifier: NCT05100212, Registered 29 October 2021