Pediatric intestinal failure (IF) is a rare condition that affects under 25,000 individuals in the United States. Children with IF require parenteral nutrition to provide enough calories at a critical period of life, for growth and development. IF is associated with high morbidity and mortality and transplant-free survival has been estimated to be 70% at 5 years. IF can be classified into two broad categories. In short bowel syndrome (SBS- IF), children have insufficient intestinal length to absorb enough nutrients for growth. The remaining functioning intestine may adapt over time to accommodate this diminished length, but only half of these children reach enteral autonomy, the state of no longer requiring any parenteral nutrition. To augment the adaptation process, hormonal therapy has been tried. The lone approved hormonal therapy carries a high cost with only a small fraction of children reaching enteral autonomy. The second category, functional IF, results from defects in either absorption of nutrients into enterocytes or intestinal motility. No medical therapy exists to treat functional IF disorders, resulting in lifelong parenteral nutrition dependence. The lack of adequate therapies in pediatric IF results in large part due to the extreme rarity of this condition and the associated dearth of available high-quality natural history data to be utilized in drug development and clinical trials. Moreover, study endpoints have focused on freedom from parenteral nutrition and survival without consideration of quality of life and additional meaningful disease specific outcome measures. This study will utilize the infrastructure of the existing International Intestinal Failure Registry (IIFR) to overcome these gaps and support new drug development in IF. The IIFR completed a successful pilot phase (N=204) in 2021 and currently prospectively follows nearly 400 children with IF. Participating study sites account for 170 current patients with an annual estimate of 183 new patients per year. In Aim 1, we will audit the ongoing prospective data collection on demographics, clinical characteristics, nutrition, genotype, and outcomes in children with both SBS-IF (Aim 1a) and functional IF (Aim 1b) to verify data quality. In Aim 2, in collaboration with our stakeholder team, we will incorporate a novel IF community-derived patient-reported outcome measure into the registry. In Aim 3, we will utilize an IF community-derived set of core outcomes to develop a classification method for risk stratification using machine learning methods. The result will be a longitudinal registry of high-quality patient data that can be used to support therapeutic development with built-in tools to assess patient-reported outcomes and risk stratify patients for future trials. In SBS-IF, this will provide the necessary standard of care comparison for several products currently being evaluated. In functional IF, this will provide novel genotype-phenotype correlation data to suppor...