<scp>EBNEO</scp> Commentary: Cord Blood Red Cell Transfusions and Severe Retinopathy of Prematurity in Preterm Neonates

Teofili L, Papacci P, Pellegrino C, Molisso R, et al. Cord Red Blood Cell Transfusions for Severe Retinopathy in Preterm Neonates in Italy: A Multicenter Randomized Controlled Trial (BORN Trial). eClinicalMedicine 87 (2025): 103426. https://doi.org/10.1016/j.eclinm.2025.103426. This multicenter randomised trial [1] explores an innovative approach to transfusion in preterm neonates—preserving fetal haemoglobin (HbF) via cord blood–derived RBCs to mitigate oxidative complications such as ROP and BPD. The investigators deserve recognition for demonstrating both the feasibility and safety of cord blood transfusions in ELGANs, addressing a major logistical challenge in neonatal transfusion medicine. Methodologically, the study was robust—randomised, blinded, and multicenter—with clinically meaningful endpoints. The biological rationale is sound: HbF's high oxygen affinity may reduce retinal hyperoxia and free radical–mediated injury. The results are promising—no severe retinopathy of prematurity (ROP) or bronchopulmonary dysplasia (BPD) among infants who received only cord blood—but interpretation must remain cautious. Nearly half of the intervention group received mixed transfusions due to unit shortages, severely limiting statistical power in the ITT analysis. The striking benefit in the per-protocol subgroup, though compelling, was based on only 17 infants and is therefore hypothesis-generating rather than definitive. Additionally, logistical and cost barriers—cord collection, processing, and inventory constraints—would currently prevent large-scale adoption [2]. This trial aligns with previous observational data linking lower HbF levels to higher ROP and BPD risk [3, 4]. It adds randomised evidence supporting a potential causal mechanism but falls short of establishing clinical efficacy. Future studies should ensure adequate HbF exposure, standardised transfusion thresholds, and long-term visual and neurodevelopmental follow-up. The clinical message is that cord-derived transfusions may hold protective potential; however, the evidence remains preliminary. Neonatal units should continue to follow existing restrictive transfusion guidelines while further multicenter trials clarify the role of HbF-preserving strategies. URL LINK: https://ebneo.org/ebneo-commentary-cord-blood-red-cell-transfusions-and-rop Mahmud Benoune: writing – review and editing, conceptualization, writing – original draft, formal analysis. The author declares no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.