Mechanism of necrotizing enterocolitis in preterm infants through the hypoxia signaling pathway, neuronal-glial signaling pathway, and intestinal fatty acid signaling pathway

Abstract

The etiology of necrotizing enterocolitis (NEC) is influenced by many factors including hypoxia, intestinal immaturity, bacterial colonization, reactive oxidants, and imbalanced inflammatory response; therefore, the pathogenesis of NEC is considered multifactorial. However, the pathogenesis of NEC has not been fully elucidated and requires further investigation. This study aimed to analyze the association between hypoxia inducible factor-1alpha (HIF-1alpha), glial fibrillary acidic protein (GFAP), glial derived neutrophic factor (GDNF), fatty acid binding protein-2 (FABP-2), peroxime proliferator activated receptor-gamma (PPAR-gamma), interleukin-6 (IL-6), and interleukin-8 (IL-8) with the incidence of NEC in preterm infants. All preterm infants with birth weight <1500 grams or gestational age <34 weeks were included in this study. After the umbilical cord was removed, 1 mL of umbilical blood was taken for HIF-1alpha, GFAP, GDNF, FABP-2, PPAR-gamma, IL-6, and IL-8 examination. Examination of HIF-1alpha, GFAP, GDNF, FABP-2, PPAR-gamma, IL-6, and IL-8 was repeated in infants with NEC symptoms using peripheral venous blood specimen. Infants were observed for 2 weeks. NEC was diagnosed based on clinical symptoms and abnormal abdominal radiographs. Of the 30 infants, there were 9 (30%) infants who experienced NEC. Logistic regression analysis showed significant results on GFAP with Odds Ratio (OR)=15.629 (95% confidence interval=1.697-143.906) P=0.015 and FABP-2 with OR=1.008 (1.001-1.015) P=0.033. Multivariate analysis using Backward LR logistic regression model showed significant results on GFAP with adjusted OR=15.629 (1.697-143.906) with P=0.015. This study demonstrated that GFAP and FABP-2 were significantly associated with the incidence of NEC. This may explain the pathogenesis of NEC through a hypoxic mechanism.