Timing of RBC transfusions linked to necrotizing enterocolitis risk in premature infants, reveals JAMA study

The study, published in JAMA Network Open, suggests that compared with control periods, 72-hour hazard periods after exposure to RBC transfusions are not temporally associated with a higher NEC risk among extremely low-birthweight (ELBW) infants with the hemoglobin ranges outlined by the TOP trial.

"1690 ELBW infants experienced 4947 hazard periods of exposure to RBC transfusions and 5813 control periods of nonexposure," the researchers reported. "With 133 NEC cases, there was no significant difference in NEC frequency between posttransfusion hazard periods and pretransfusion control periods (11.9 vs 12.7 per 1000 periods, respectively)."

Necrotizing enterocolitis is a serious gastrointestinal disease that primarily affects premature infants, leading to significant morbidity and mortality. Among the various factors implicated in NEC development, the timing of RBC transfusions has garnered attention. Understanding the relationship between RBC transfusion timing and NEC occurrence is crucial for optimizing neonatal care protocols.

Against the above background, Ariel A. Salas, Department of Pediatrics, University of Alabama at Birmingham, and colleagues aimed to evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC among ELBW infants randomized to either lower or higher hemoglobin transfusion thresholds.

For this purpose, the researchers conducted a post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 and enrolled in the TOP randomized multicenter trial between 2012 and 2017.

The research team first examined the distribution of RBC transfusions and NEC occurrence up to postnatal day 60. Secondly, 72-hour posttransfusion periods were categorized as hazard periods and the pretransfusion periods of variable duration as control periods. Then, they compared the NEC risk in posttransfusion hazard periods with that in pretransfusion control periods, the risk was stratified based on the randomization group (higher or lower hemoglobin transfusion threshold group).

The primary outcome was NEC stage 2 or 3 incidence. Secondary outcomes included the incidence rates of NEC within five 10-day intervals, considering the number of days at risk.

Of 1824 ELBW infants randomized during the TOP trial, the analysis included 1690 infants (mean gestational age, 26.0 weeks; 53.2% were female). The key findings were as follows:

The study led to the following findings:

• After categorizing 4947 hazard periods and 5813 control periods, the researchers identified 133 NEC cases. 44.4% of these cases occurred during hazard periods.
• The baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods.
• NEC risk was 11.9 per 1000 posttransfusion hazard periods and 12.7 per 1000 control periods (adjusted risk ratio, 0.95). This risk did not differ significantly between randomization groups, but the incidence rate of NEC per 1000 days peaked between postnatal days 20 and 29 in the lower hemoglobin transfusion threshold group.

"The findings suggest that among ELBW infants with the hemoglobin ranges occurring in the TOP trial, exposure to RBC transfusions was not temporally associated with a higher NEC risk during 72-hour posttransfusion hazard periods," the researchers wrote.

"Given that the incidence rate of NEC peaked between postnatal days 20 and 29 among infants with lower hemoglobin values, a more in-depth examination of this at-risk period using larger data sets is warranted," they concluded.

Reference:

Salas AA, Gunn E, Carlo WA, et al. Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024;7(5):e249643. doi:10.1001/jamanetworkopen.2024.9643