The role of ischemia in necrotizing enterocolitis

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.

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.

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.

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.