O0029 ENTERAL ADMINISTRATION OF HB-EGF REDUCES THE INCIDENCE OF NECROTIZING ENTEROCOLITIS IN A RAT MODEL

Abstract

Introduction: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of prematurely born infants. The protective role of maternal milk against NEC has been reported, however the components of milk responsible for this protection have not been identified. Previously, we have shown that epidermal growth factor (EGF) reduces the incidence of NEC in a rat model (Dvorak et al., AJP 282:G156, 2002). Heparin-binding EGF-like growth factor (HB-EGF), another member of the EGF family, has been shown to be cytoprotective for intestinal epithelial cells. Recently, the presence of HB-EGF has been detected in human breast milk. The aim of this study was to examine the effect of enteral administration of HB-EGF on survival and the incidence and severity of NEC in a neonatal rat model. Methods: Neonatal rats delivered via abdominal incision on day 22 of gestation were artificially fed with rat milk substitute for 4 days. Four diets were used in this study: growth factor-free rat milk substitute (RMS) and RMS supplemented with 5, 50, and 500 ng/ml of HB-EGF (HB-5, HB-50, and HB-500, respectively). Experimental NEC was induced by daily exposure to asphyxia and cold stress. In addition, dam fed littermates were used as a control (DF). The development and severity of NEC was evaluated in the distal ileum using our histopathological scoring system. Results: In the NEC group, 91% of animals developed characteristic pathophysiological signs of NEC in the distal ileum. Supplementation of HB-EGF into milk formula significantly reduced the incidence of NEC and improved survival of the pups in a dose dependent manner.Table 1Conclusion: Milk-borne HB-EGF provides a protective effect on the development of neonatal NEC. The mechanism by which HB-EGF prevents NEC must be further investigated on the molecular level. However, supplementation of an optimized growth factor “cocktail” into infant formula for prematurely born babies might be a feasible strategy for the prevention of neonatal NEC. Supported by the NIH Grant HD-39657 (to B.D.).