ObjectivesIntestinal failure (IF) is a condition whose treatment requires advanced knowledge and techniques and a multidisciplinary approach. Intestinal failure is the endpoint of many intestinal diseases and may result in full recovery, in life-long parenteral nutrition, or in the death of the child. The aim of this study was to evaluate the natural history of IF in children using a national network of resources.MethodsItalian centers of pediatric gastroenterology merged in a national network, developing a collaborative management approach for children with IF. A consensus definition of IF was achieved. A database was set up to investigate the cause, epidemiologic factors, and natural history of IF.ResultsOne hundred nine children were enrolled in 5 years. The cause of IF was: short bowel syndrome (n = 48), disorders of motility (n = 16), structural enterocyte defects (n = 14), multiple food intolerance (n = 10), autoimmune enteropathy (n = 7), and others or unknown (n = 14). The eventual outcome was closely related to the primary cause, ranging from full and permanent intestinal sufficiency in children with multiple food intolerance to high death rate or total dependance upon parenteral nutrition in those with structural enterocyte defects. Intermediate outcomes were observed for the other causes. Four children received intestinal transplantation.ConclusionsThe network approach for IF provides an effective model to optimize resources and to investigate prospectively the natural history of IF. Based on the work on this series, a European network for IF could be an effective model for fulfilling the diagnostic and management needs, including intestinal transplantation.