This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pediatric surgeons often care for children with uncommon diseases. This is particularly true of major neonatal surgical disorders such as Necrotizing Enterocolitis. Even a major pediatric referral center will not see an adequate number of patients to meaningfully assess outcomes from the institution's treatment approach. For this reason, the scientific literature on the care of children with NEC is almost exclusively comprised of anecdotal case reports and single-institution case-series data. This study is sponsored by the Glaser Pediatric Research Network. The Glaser Research Network was established in 2001 to coordinate data collection between 6 institutions (Baylor, Harvard, University of San Francisco, Stanford, USC, UCLA). By combining data from these 6 institutions a more meaningful analysis can be carried out. Necrotizing Enterocolitis is a severe inflammatory disease of the intestine that occurs in premature and low birth weight infants. First described in the 1960s, NEC is now the most common surgical emergency in the newborn infant. The incidence of NEC is reported to be from 1% to 5% of neonatal intensive care unit (NICU) admissions or 1 to 3 cases per 1,000 live births. Based upon analysis of data from the National Center for Health Statistics and multi-center trials, there are about 10,000 cases of NEC per year in the United States. This results in approximately 2500 deaths per year. The incidence of NEC correlates strongly with the degree of prematurity. It is these very low birth weight babies which present the physician with the greatest clinical challenge. Since successful treatment of NEC typically results in the child being able to lead a healthy and fully productive life, improvements in care can produce a tremendous impact in terms of number of years of life saved. The clinical presentation of NEC can range from feeding intolerance to severe sepsis with cardiovascular collapse. No definitive treatment for NEC exists. Most cases respond to discontinuation of oral feedings with nasogastric decompression, fluid resuscitation, broad-spectrum antibiotics, and other supportive measures. Severe NEC can result in intestinal necrosis and perforation. When these conditions occur, surgical intervention is necessary. Identifying infants at particular risk for the development of NEC is an unsolved challenge. It is clear that the incidence of NEC correlates strongly with the degree of prematurity. Only a handful of patients with NEC were reported in the 1960's when very low birthweight (VLBW) infants did not survive long enough to acquire the disease. The routine use of both antenatal steroids and prophylactic surfactant has resulted in greater numbers of VLBW babies surviving. It is these extremely premature babies that present physicians the greatest challenge in the clinical management of NEC. Beyond prematurity, additional risk factors for NEC are less well defined. Enteral feeding has been implicated as a cause of NEC since 1978. For 25 years, neonatologists have argued for slow and cautious advancement of feeds in premature infants. This belief has led to the development of a myriad of different feeding practices, in the absence of reliable data. A recent randomized trial was not able to show a difference in the rate of NEC between babies receiving slow or rapid advancement of enteral feedings. The results of this small trial contrasts with other non-randomized data suggesting that slow advancement of feeds protects against NEC. A similar unsolved question is whether or not breast milk feeding reduces the incidence of NEC compared to formula feeding. Several small and uncontrolled studies have provided conflicting results.Other risk factors implicated in the pathogenesis of NEC include cyanotic congenital heart disease, patent ductus arteriosus, apnea and bradycardia, prior episodes of sepsis and a variety of other abnormalities. Numerous epidemiologic studies have failed to find consistent predictors of risk other than prematurity. Once the diagnosis of NEC is made, standard of practice is to institute bowel rest, gastric decompression, and broad spectrum antibiotics. Many patients respond well to this treatment and recover with no further intervention. Others deteriorate and develop intestinal necrosis or perforation requiring urgent operation. There is little available evidence to suggest what factors may help predict which infants are most likely to deteriorate. To date, no large prospective studies have followed infants diagnosed with NEC and determined their course. Identification of risk factors for deterioration could allow more intensive therapy to be focused on those most likely to benefit. In addition, such data could allow a more rapid return to enteral feeding and routine neonatal care for those not at high risk.
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