Effects of Freshly Irradiated vs Irradiated and Stored Red Blood Cell Transfusion on Cerebral Oxygenation in Preterm Infants

Abstract

IMPORTANCE Gamma irradiation of leukoreduced red blood cells (RBCs) prevents transfusion-associated graft-vs-host disease but also exacerbates storage lesion formation in RBCs. It is unknown whether freshly irradiated RBCs are more efficacious than irradiated and stored RBCs in preterm infants with high transfusion requirements.OBJECTIVE To examine whether transfusion of freshly irradiated vs irradiated and stored RBC components improves cerebral oxygen delivery in preterm infants with anemia. DESIGN, SETTING, AND PARTICIPANTSThis single-center, double-blinded, proof-of-concept randomized clinical trial was conducted at the neonatal intensive care unit of Wellington Regional Hospital in Wellington, New Zealand, between December 1, 2017, and November 30, 2018. Participants were preterm infants (<34 weeks' gestation at birth) who were at least 14 days of age and had anemia. Participants underwent nonurgent transfusions, and these episodes were randomized to the intervention group (in which the infants received a transfusion of RBCs that were freshly irradiated on the day of transfusion) or control group (in which the infants received a transfusion of RBCs that were irradiated and stored for up to 14 days). Data were analyzed using the evaluable population approach.INTERVENTION Transfusion of freshly irradiated RBCs. MAIN OUTCOMES AND MEASURESThe prespecified primary outcome was the change in cerebral regional oxygen saturation (crSO 2 ) from baseline (immediately before) to immediately after the transfusion. The prespecified secondary outcomes were the change in cerebral fractional tissue oxygen extraction (cFTOE) at different time points (immediately after, 24 hours after, and 120 hours or 5 days after transfusion). Outcomes were measured by blinded clinicians using near-infrared spectroscopy. A covariate-adjusted linear mixed model was used to quantify mean treatment effects and account for multiple transfusions in some infants.RESULTS A total of 42 infants (mean [SD] gestational age, 26 [10] weeks and 3 days; 29 [69%] boys) were enrolled in the trial and underwent 64 transfusion episodes, which were randomized to the intervention (n = 31) or control (n = 33) group. Compared with infants in the control group, those in the intervention group showed a covariate-adjusted mean increase in crSO 2 (2.0 percentage points; 95% CI, 1.2-2.8 percentage points) and a mean decrease in cFTOE (0.02; 95% CI, 0.01-0.04) immediately after transfusion. These differences were sustained up to 120 hours or 5 days after transfusion. There were negligible mean changes in crSO 2 or cFTOE in infants in the control group at any of the follow-up time points.CONCLUSIONS AND RELEVANCE Results of this trial showed that transfusion of freshly irradiated RBCs conferred a small advantage in cerebral oxygenation for at least 5 days after transfusion compared with transfusion of irradiated and stored RBC components. On-demand irradiation of RBC components may be considered to optimize oxygen delivery in the recipient, but this physiological finding...

Current advances in 2022: A critical review of selected topics by the Association for the Advancement of Blood and Biotherapies (AABB) Clinical Transfusion Medicine Committee

“…A randomized trial in New Zealand of 42 preterm infants showed a small improvement in cerebral oxygenation by near‐infrared spectroscopy in infants receiving freshly irradiated RBCs versus irradiated and stored RBCs 67 . Although statistically significant, it is not clear whether the small differences are clinically significant and whether larger trials are needed.…”

Comparative efficacy and safety of restrictive versus liberal transfusion thresholds in anemic preterm infants: a meta-analysis of 12 randomized controlled trials

“…We excluded ineligible studies according to the exclusion criteria as follows: (1) ineligible study designs such as case series, narrative review, animal study, meta-analysis;…”

“…Preterm infants are at high risk for anemia due to immaturity, impaired erythropoiesis, and frequent blood sampling [ 1 , 2 ]. Therefore, preterm infants have one of the highest transfusion requirements within the hospital setting [ 3 ], especially very (VLBW) or extremely low birth weight (ELBW) infants [ 4 ].…”

Use of Irradiated Red Blood Cell Transfusions in Newborns to Improve Intracerebral Saturation

“…The physiological rationale that red blood cell (RBC) transfusion improved oxygen carrying capacity was a tantalizing prospect. In this issue of JAMA Pediatrics, Saito-Benz et al 1 renew such hopes in a novel proof-of-concept randomized clinical trial (RCT) of irradiating RBCs on the day of transfusion (which the authors termed fresh irradiation) to boost cerebral oxygen saturation. Their PICOT (population/ patient, intervention, comparison, outcome, and time) question was whether stable very low-birth-weight preterm infants requiring a top-up transfusion who received freshly irradiated RBCs showed an improvement in the noninvasively measured brain oxygenation compared to those who received routinely irradiated RBCs in a neonatal intensive care unit with high transfusion thresholds.…”

“…However, results of the ARIPI trial suggested that age is not important. 7 In assessing the potential benefits of freshly irradiated RBC for preterm transfusion, it is important to consider whether the surrogate primary outcome in the RCT by Saito-Benz et al 1 is robust. Does the short-term physiological surrogate outcome of crSO 2 (or related indexes) embody long-term outcomes?…”