Necrotizing Enterocolitis (NEC) is the most common acute gastrointestinal emergency in the neonatal period and is primarily found in preterm infants. As more preterm infants survive, the impact of NEC is more profound. Despite the significant effect of this disease on neonatal morbidity and mortality, the research directed in this area is relatively sparse. The single most important risk factor in the development of NEC is a premature gastrointestinal tract. Epidermal growth factor (EGF) is an established growth factor crucial to the development and maintenance of the gastrointestinal epithelium. Preliminary studies have revealed significantly reduced salivary EGF levels in infants following intestinal resection for NEC. This proposal will expand upon this observation and directly test the novel hypothesis that low salivary EGF levels are linked to the development of NEC. To test this hypothesis two specific aims are proposed.
Aim 1 - Determine the ontogeny of EGF expression in neonates. Since prematurity is the single most important risk factor for the development of NEC, this first aim tests the hypothesis that salivary EGF expression is directly related to gestational age. The developmental pattern of salivary EGF will be correlated with serum values and measured across different gestational ages, as well as longitudinally for each individual patient.
Aim 2 - Determine the predictive value of salivary EGF in the development of NEC.
This aim tests the hypothesis that the pattern of salivary EGF is predictive for the development of NEC. To test this hypothesis, the pattern of salivary EGF expression and its relationship to the development of NEC will be modeled, controlling for detailed clinical and demographic data on variables related to the development of NEC and expression of EGF. These experiments will provide essential original information regarding baseline serum and saliva EGF levels and their predictive value in the development of NEC. This information is requisite toward the development of innovative clinical trials using exogenous EGF as a new therapeutic modality in the treatment/prevention of NEC.
| Morrow, Ardythe L; Meinzen-Derr, Jareen; Huang, Pengwei et al. (2011) Fucosyltransferase 2 non-secretor and low secretor status predicts severe outcomes in premature infants. J Pediatr 158:745-51 |
| Warner, Barbara B; Ryan, Ann Ladd; Seeger, Kimberly et al. (2007) Ontogeny of salivary epidermal growth factor and necrotizing enterocolitis. J Pediatr 150:358-63 |
| Warner, Brad W; Warner, Barbara B (2005) Role of epidermal growth factor in the pathogenesis of neonatal necrotizing enterocolitis. Semin Pediatr Surg 14:175-80 |
