Research AppraisalSystematic Review

Association between packed red blood cell transfusion and clinical deterioration in neonatal necrotizing enterocolitis: a systematic review and meta-analysis

Annals of medicineHuang, Jinglan, Gao, Qian, Xu, Ziqing et al.1 Dec 2026DOI

Clinical Snapshot

60CEBM
Evidence: WeakSystematic Review

PICO Framework

P — PopulationNeonates with necrotizing enterocolitis (NEC)
I — InterventionPacked red blood cell (pRBC) transfusion
C — ComparatorNo transfusion
O — OutcomesClinical deterioration or worsening of NEC

Bottom Line

This meta-analysis of 5 studies (971 neonates) suggests packed red blood cell transfusion is associated with a 6-fold increased odds of clinical deterioration in neonates with necrotizing enterocolitis. However, the evidence quality is low due to the small number of observational studies, lack of randomised trials, and potential confounding factors. The association may reflect confounding by indication rather than causation - sicker infants requiring transfusion may naturally have worse outcomes. While these findings warrant clinical caution when considering transfusion in NEC patients, they are insufficient to change established practice. Clinicians should continue individualised risk-benefit assessment for transfusion decisions in neonates with NEC, considering haemodynamic status, anaemia severity, and overall clinical condition. Large-scale prospective studies are needed to establish causality and inform evidence-based transfusion thresholds in this vulnerable population.

Evidence: Weak

Key Findings

  • P Value: Not reported

  • Effect Size: Odds ratio 6.05

  • Primary Outcome: Clinical deterioration of necrotizing enterocolitis

  • Nnt Or Sensitivity: Number needed to harm not calculable from available data

  • Confidence Interval: 95% CI: 3.02-12.14

Clinical Application

Results suggest caution with pRBC transfusion in NEC patients, but evidence insufficient for definitive practice change Relevant to Australian NICUs; aligns with existing conservative transfusion practices in neonates; may inform TGA blood product guidelines and ANZNN registry considerations Neonates with established NEC requiring blood transfusion decisions

Abstract

BACKGROUND: No systematic review has evaluated the existing evidence regarding the association between packed red blood cell (pRBC) transfusion and clinical worsening of necrotizing enterocolitis (NEC) in neonates. This systematic review and meta-analysis was conducted to address this knowledge gap. MATERIALS AND METHODS: We searched the Cochrane Library, EBSCO, Embase, Web of Science, Google Scholar, and PubMed for studies on pRBC transfusion and NEC published before May 10, 2025. Relevant articles were selected through title, abstract, and full-text screening. English-language case-control studies or cohort studies, or randomized controlled trials involving newborns with NEC that compared pRBC transfusion with no transfusion and reported changes in NEC clinical status were included. Review articles, systematic reviews, case reports, editorials, animal studies, duplicate publications, and studies with incomplete data were excluded. RESULTS: Five studies involving 971 neonates with NEC were included. The pooled analysis demonstrated a potential association between pRBC transfusion and clinical deterioration of NEC in neonates (odds ratio: 6.05, 95% confidence interval: 3.02-12.14). CONCLUSIONS: pRBC transfusion was associated with an exacerbation of NEC in neonates. However, these findings should be interpreted cautiously because of the small number of eligible studies included in this meta-analysis, and future large-scale, well-designed studies are needed to confirm the observed association. Published studies have identified an association between pRBC transfusion and NEC progression; however, whether this association is causal remains unclear.Despite consistent evidence from observational studies suggesting a potential association between pRBC transfusion and NEC progression, the overall quality of the evidence is low because of the lack of randomized controlled trials to determine causality.

References

  1. 1.Huang, J., Gao, Q., Xu, Z., & Wang, H. (2026). Association between packed red blood cell transfusion and clinical deterioration in neonatal necrotizing enterocolitis: a systematic review and meta-analysis. Annals of Medicine. https://doi.org/10.1080/07853890.2026.2675123
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