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Updated: Jun 27, 2025
A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis
Published on: November 30, 2021
Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis: A Secondary Analysis of a
Ariel A Salas1, Elizabeth Gunn1, Waldemar A Carlo1
1Department of Pediatrics, University of Alabama at Birmingham.
Insights
Red blood cell (RBC) transfusions were not temporally linked to a higher risk of necrotizing enterocolitis (NEC) in extremely low-birthweight (ELBW) infants. Further research is needed for infants with lower hemoglobin values during specific postnatal periods.
Area of Science:
- Neonatal Medicine
- Pediatric Gastroenterology
- Hematology
Background:
- Observational studies suggest a link between anemia, red blood cell (RBC) transfusions, and necrotizing enterocolitis (NEC) in extremely low-birthweight (ELBW) infants.
- The temporal relationship between RBC transfusions and NEC risk in ELBW infants requires further investigation.
Purpose of the Study:
- To determine if there is a temporal association between RBC transfusions and NEC in ELBW infants.
- To compare the risk of NEC during posttransfusion periods versus pretransfusion periods.
Main Methods:
- A post hoc analysis of the Transfusion of Prematures (TOP) randomized multicenter trial involving 1690 ELBW infants.
- Categorized 72-hour posttransfusion periods as hazard periods and compared NEC risk with pretransfusion control periods.
- Stratified risk analysis based on randomization to higher or lower hemoglobin transfusion thresholds.
Main Results:
- No significant temporal association was found between RBC transfusions and an increased risk of NEC (adjusted risk ratio, 0.95; 95% CI, 0.68-1.32).
- NEC incidence peaked between postnatal days 20-29 in the lower hemoglobin transfusion threshold group.
- Infant characteristics did not differ between NEC cases occurring during hazard or control periods.
Conclusions:
- RBC transfusions were not temporally associated with a higher risk of NEC in ELBW infants within the hemoglobin ranges studied.
- Further investigation into the peak NEC incidence period (postnatal days 20-29) in infants with lower hemoglobin values is warranted.
- Findings suggest current transfusion thresholds may not increase NEC risk in ELBW infants.
Importance:
Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants.
Objective:
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 higher or lower hemoglobin transfusion thresholds.
Design, Setting, And Participants:
This post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 enrolled in the Transfusion of Prematures (TOP) randomized multicenter trial between December 1, 2012, and April 12, 2017, was performed between June 2021 and July 2023.
Exposures:
First, the distribution of RBC transfusions and the occurrence of NEC up to postnatal day 60 were examined. Second, 72-hour posttransfusion periods were categorized as hazard periods and the pretransfusion periods of variable duration as control periods. Then, the risk of NEC in posttransfusion hazard periods was compared with that in pretransfusion control periods, stratifying the risk based on randomization group (higher or lower hemoglobin transfusion threshold group).
Main Outcomes And Measures:
The primary outcome was incidence of NEC stage 2 or 3. Secondary outcomes included the incidence rates of NEC within five 10-day intervals, taking into account the number of days at risk.
Results:
Of 1824 ELBW infants randomized during the TOP trial, 1690 were included in the present analysis (mean [SD] gestational age, 26.0 [1.5] weeks; 899 infants [53.2%] were female). After categorizing 4947 hazard periods and 5813 control periods, we identified 133 NEC cases. Fifty-nine of these cases (44.4%) occurred during hazard periods. Baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods. The risk of NEC was 11.9 per 1000 posttransfusion hazard periods and 12.7 per 1000 control periods (adjusted risk ratio, 0.95; 95% CI, 0.68-1.32; P = .74). 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.
Conclusions And Relevance:
The findings of this post hoc analysis 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 risk of NEC during 72-hour posttransfusion hazard periods. 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.
Trial Registration:
ClinicalTrials.gov Identifier: NCT01702805.
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