This is a repeat cohort study in which we sought to determine whether an association of necrotizing enterocolitis (NEC) <48 hours of a packed red blood cells (PRBC) transfusion was a prior sampling artifact.

All very low birth weight neonates with NEC Stage ≥IIB admitted over an 18-month period were categorized for NEC: (1) <48 hours after a PRBC transfusion; (2) unrelated to the timing of PRBCs; and (3) never transfused.

Eight hundred eighty-three admissions over 18 months were reviewed; 256 were very low birth weight that resulted in 36 NEC cases and 25% were associated with PRBC (n = 9). PRBC-associated cases had lower birth weight, hematocrit, and rapid onset of signs (<5 hours). The timing of association of PRBC transfusion and NEC differed from random, showing a distribution that was not uniform over time (χ² = 170.7, df = 40; P < .000001) consistent with the possibility of a causative relationship in certain cases of NEC. Current weight at onset of NEC did not differ; however, the more immature the neonate the later the onset of NEC creating a curious centering of occurrence at a median of 31 weeks postconceptual age.

We conclude that PRBC-related NEC exists. Transfusion-related acute gut injury is an acronym we propose to characterize a severe neonatal gastrointestinal reaction proximal to a transfusion of PRBCs for anemia. The convergence at 31 weeks postconceptual age approximates the age of presentation of other O₂ delivery and neovascularization syndromes, suggesting a link to a generalized systemic maturational mechanism.