The role of ischemia in necrotizing enterocolitis

Abstract Aim The role of ischemia in the pathogenesis of necrotizing enterocolitis (NEC) remains unclear. We used immunohistochemical markers of hypoxia to identify presence/absence of ischemia in NEC and spontaneous intestinal perforation (SIP) with clinical correlation. Methods Immunohistochemical staining was performed on 24 NEC and 13 SIP intestinal resection specimens using 2 hypoxia markers, hypoxia inducible factor 1α (HIF-1α) and glucose transporter 1 (GLUT1) and inflammatory markers, leukocyte common antigen (LCA) and myeloperoxidase. Ischemic score (0–6) from the sum of the HIF-1α and GLUT1 staining intensity grades was devised (positive ≥ 3). Inflammation was graded from the sum of LCA and myeloperoxidase grading. Relevant clinical information was obtained from hospital case records. Results Fourteen NEC specimens had positive ischemic score (4.6 ± 1.2). The remaining 10 NEC (ischemic score 0.7 ± 0.8) and all 13 SIP samples (ischemic score 0.5 ± 0.5) were ischemic-negative. The ischemic-positive cases had classic NEC with multiple areas of bowel necrosis; were associated with later onset, enteral feeding and pneumatosis. In contrast, all ischemic-negative NEC were short-segment NEC with perforation. Their clinical profile was similar to the SIP cases with younger gestational age at birth, early onset, association with ibuprofen/indomethacin usage but not with feeding and pneumatosis. Ischemic scores are correlated with inflammation scores in mucosa but not submucosa. Conclusions Ischemia as assessed with immunohistochemical markers HIF-1α and GLUT1, has a primary role in pathogenesis of classic NEC only, not in SIP or short-segment NEC with perforation. Better categorization of the different types of NEC can direct appropriate prevention and treatment strategies.