Intestinal failure (IF) in infants and children is a devastating condition that can be broadly defined as the inability of the intestinal tract to sustain life without supplemental parenteral nutrition (PN). Following injury or resection, the intestinal tract must adapt sufficiently to achieve independence from PN, or the patient is at risk for nutritional deficiencies, end-stage liver disease, vascular thrombosis, sepsis, and death. These complications are particularly prevalent in the pediatric population. The current medical literature is insufficient to determine factors that predict outcome in patients with IF as too few patients are seen at any one center in a short enough time that medical, nutritional, surgical, and transplant options are similar. Currently accepted therapies are based on anecdotal experience and reports of small uncontrolled studies, thus creating a sizeable knowledge gap in our understanding of optimal treatment strategies. A major obstacle to understanding outcomes is that there are no comprehensive, multi-center studies, nor large prospective studies in the field of pediatric IF. We propose to establish a consortium comprised of pediatric centers with a recognized interest in IF. Specific Aim #1 is to investigate the feasibility and plan a prospective, multi-center consortium that will collect, maintain, analyze, and report clinical, nutritional, surgical, epidemiological, and outcome data in children with IF, including information derived from serum, urine, tissue, and DNA specimens. The clinical data compiled by the to-be-established prospective registry will be used to develop a model to predict three critical outcomes in IF patients that include independence from PN, development of cholestasis, and death. We will propose to collect and store biological samples to be used by clinical and basic scientists, within and outside our consortium, to enhance our understanding of the physiological mechanisms that underlie pathophysiological conditions associated with IF such as intestinal adaptation, PN related cholestasis, nutritional deficiencies, and mucosal immunity. In conjunction with the prospective registry, we will propose to identify, conduct, and complete appropriately powered randomized, controlled treatment trials that will form the foundation of an evidence-based practice model in the care of these children with complicated clinical conditions. To ensure our ability to create a productive collaboration, we propose Specific Aim #2 which is to perform a multi-center, retrospective review of a contemporary cohort of infants and children with IF to determine the feasibility that such a study will be able to identify demographic, clinical, and nutritional risk factors that will predict the following critical outcomes: (1) need for long-term PN (>360 days), (2) discontinuation of PN, (3) development of cholestasis, (4) need for intestinal transplant, and (5) death. We will use the data collected and the experiences gained from the retrospective study to determine the feasibility of our consortium to conduct a multi-centered, prospective study of children with IF and to conduct randomized, controlled therapeutic trials. If successful, these data will be utilized for a future RO1 application. PUBLIC HEALTH RELEVANCE Intestinal failure (IF) in infants and children is a devastating condition that is defined as the inability of the intestinal tract to sustain life without supplemental nutrition that must be infused into a large vein, usually one located in the chest. Children with IF are at risk for developing nutritional deficiencies, cirrhosis, blood clots, blood infections, and death;yet the current medical literature is not sufficient to identify factors that that will allow doctors to predict whether the child will recover or need an intestinal transplant. To address the important problems related to children with IF, we propose to (1) establish an effective, collaborative relationship with a number of pediatric centers around the country who are recognized for their ability to care for these medically complicated children and (2) to look back over the last seven years to identify factors that will identify those children who are not likely to be removed from supplemental nutrition, who will likely require an intestinal transplant, or who is likely to die.