Current Understanding of Transfusion-associated Necrotizing Enterocolitis: Review of Clinical and Experimental Studies and a Call for More Definitive Evidence.

Introduction: The association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC), so-called transfusion-associated NEC (ta-NEC), was first described in 1987. However, further work is needed to confirm a causal relationship, elucidate underlying mechanisms, and develop possible strategies for prevention. We performed an extensive literature search in the databases PubMed, EMBASE, and Scopus. Areas covered: Although multiple retrospective human studies have strongly suggested an association between blood transfusions and subsequent occurrence of NEC, meta-analyses of randomized controlled trials (RCTs) testing RBC transfusion thresholds or the use of recombinant erythropoiesis-stimulating growth factors did not confirm an association of anemia with ta-NEC. These conflicting data necessitated the development of an animal model to elucidate mechanisms and causal factors. Data from this recent mouse model of ta-NEC highlighted the importance of sequential exposure to severe anemia followed by transfusion for development of ta-NEC. Expert opinion: This review summarizes current human and experimental data, highlights open questions, and suggests avenues for further research aimed at preventing ta-NEC in preterm infants. Further studies are required to delineate whether there is a tipping point, in terms of the level and duration of anemia, and to develop an effective strategy for blood management and the quality of RBC transfusions.

Effect of withholding feeds on transfusion-related acute gut injury in preterm infants: a pilot randomized controlled trial.

Background: Several retrospective studies have reported an increase in necrotizing enterocolitis (NEC) during the 48 h following red blood cell (RBC) transfusion. Whether withholding enteral feeding during transfusion decreases the risk of transfusion-associated acute gut injury (TRAGI) in preterm infants is unclear.Study design and methods: In this pilot study, 112 preterm infants with gestational age ≤32 weeks and/or birth weight ≤1500 g were randomly assigned to withholding (NPO) or continuance of feeding (FED) during RBC transfusion. Primary outcome measure was development of NEC (stage ≥ 2) within 72 h of a transfusion and the change in abdominal circumference.Results: One hundred fifty-four transfusion episodes (74 NPO and 80 FED) were analyzed. Demographic characteristics were found to be similar in both groups. There was no difference in rates of NEC (0 versus 3.4%; p = .49) between the NPO and FED groups. The incidence of feeding intolerance was higher in the FED group; however, it was statistically insignificant (1.9 versus 6.8%, p = .36). Abdominal circumference remained similar in both groups in all three consecutive days following transfusion (p>.05).Conclusion: This pilot study does not support withholding feedings during transfusion but is not adequately powered to test the hypothesis that NPO decreases NEC rates. Adequately powered well-designed multicenter trials are still required.