Prenatal administration of heparin-binding epidermal growth factor-like growth factor in an experimental model of necrotizing enterocolitis decreased both incidence and severity of the disease.

Background: Necrotizing enterocolitis (NEC) is the leading gastrointestinal cause of death in premature infants and causes long-term disabilities. Previously, enteral heparin-binding epidermal growth factor-like growth factor (HB-EGF) administered after birth demonstrated decreased incidence and severity of NEC in a neonatal animal model of NEC. We investigated the potential prophylactic strategy of preventing NEC using prenatally administered HB-EGF. Methods: An HB-EGF (800 µg/kg/dose) dose was injected into pregnant rats via tail vein or intraperitoneal route 2 hours prior to delivery. After cesarean section (C-section) at 21 days' gestation, the rat pups were subjected to the NEC protocol by inducing stressors: hypoxia, hypothermia, hypertonic feeds, and orogastric gavage of lipopolysaccharide (2 mg/kg). Postnatally, pups were monitored for 96 hours and assessed for the development of clinical and postmortem histological NEC. Results: The experimental NEC incidence in untreated, stressed rat pups was 66%. Compared with untreated pups, the maternal administration of HB-EGF correlated with a significant NEC incidence and severity decrease in rat pups. The strongest decrease was seen when HB-EGF was administered via the intraperitoneal route 2 hours prior to C-section (66% vs 31%, *p<0.05). Prenatal HB-EGF administration significantly increased pups' survival after NEC protocol exposure, with the greatest benefit observed in the group that received HB-EGF intraperitoneally 2 hours before delivery. Conclusions: Prenatal administration of HB-EGF decreases the incidence and severity of NEC, preserves gut barrier function and increases survival. This may represent a novel prophylactic clinical strategy for NEC offered to mothers at risk of delivering a premature infant.

Animal models of necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) is one of the leading causes of death in premature infants. To determine the factors present in the disease that lead to increased morbidity and mortality, manipulation of variables that are shown to have a positive response has been tested using various animal models. Testing and manipulation of these variables are unwarranted in humans due to regulatory health standards. Methods: The purpose of this review is to provide an update to previous summaries that determine the significance of animal models in studying the mechanisms of NEC. A large variety of animal models including rats, mice, rabbits, piglets, nonhuman primates, and quails have been described in literature. We reviewed the reported animal models of NEC and examined the pros and cons of the various models as well as the scientific question addressed. Results: The animals used in these experiments were subject to gavage feeding, hypoxia, hypothermia, oxygen perfusion, and other methods to induce the disease state. Each of these models has been utilized to show the effects of NEC on the premature, undeveloped gut in animals to find a correlation to the disease state present in humans. We found specific advantages and disadvantages for each model. Conclusions: Recent advances in our understanding of NEC and the ongoing therapeutic strategy developments underscore the importance of animal models for this disease.