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Randomized Controlled Trial
. 2024 Aug 7;50(1):142.
doi: 10.1186/s13052-024-01714-w.

Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial

Luciana Teofili #  1   2 , Patrizia Papacci #  3   4 , Carlo Dani  5 , Francesco Cresi  6   7 , Giulia Remaschi  5 , Claudio Pellegrino  3   4 , Maria Bianchi  3 , Giulia Ansaldi  6 , Maria Francesca Campagnoli  7 , Barbara Vania  6 , Domenico Lepore  3   4 , Fabrizio Gaetano Saverio Franco  5 , Marco Fabbri  8 , Roberta Penta de Vera d' Aragona  9 , Anna Molisso  10 , Enrico Beccastrini  5 , Antonella Dragonetti  6 , Lorenzo Orazi  11 , Tina Pasciuto  3 , Iolanda Mozzetta  3 , Antonio Baldascino  3 , Emanuela Locatelli  6 , Caterina Giovanna Valentini  3 , Carmen Giannantonio  3 , Brigida Carducci  3 , Sabrina Gabbriellini  8 , Roberto Albiani  6 , Elena Ciabatti  8 , Nicola Nicolotti  3 , Silvia Baroni  3   4 , Alessandro Mazzoni  8 , Federico Genzano Besso  6 , Francesca Serrao  3 , Velia Purcaro  3 , Alessandra Coscia  6   7 , Roberta Pizzolo  6 , Genny Raffaeli  12   13 , Stefania Villa  12 , Isabella Mondello  14 , Alfonso Trimarchi  14 , Flavia Beccia  3   4 , Stefano Ghirardello  15 , Giovanni Vento  3   4
Affiliations
Randomized Controlled Trial

Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial

Luciana Teofili et al. Ital J Pediatr. .

Abstract

Background: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP.

Methods: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and 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. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions.

Results: Results in the intention-to-treat and per-protocol analysis 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-RBCs or A-RBCs. 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 decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk.

Conclusions: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP.

Trial registration: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.

Keywords: ELGAN; HbF; ROP; Randomized controlled trial; Transfusions; Umbilical blood.

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Conflict of interest statement

Carlo Dani is a member of the editorial board of Italian Journal of Pediatrics. The authors report no potential conflicts of interest, including relevant financial interests, activities, relationships, and affiliations.

Figures

Fig. 1
Fig. 1
Study population entering the interim analysis of safety of CB-RBC transfusions and of impact on the rate of severe ROP. (A) Flow-diagram of the study. (B) For the high rate of protocol deviations, a parallel analysis of safety and efficacy of CB-RBC transfusions was performed in the ”intention-to-treat” and “per protocol” settings
Fig. 2
Fig. 2
Area under the curve (AUC) of HbF and post-menstrual age (PMA). The lines represent median values of HbF. (A) HbF AUC of patients grouped according to the occurrence of severe ROP. (B) HbF AUC of patients grouped according to the types of RBC products received before 30 weeks of PMA
See this image and copyright information in PMC

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