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Although UC presents in children with varying severity, disease extent, and comorbidities, initial treatment is essentially uniform, consisting of 5-aminosalicylate drugs with corticosteroid induction for those with moderately to severely active disease. With the advent of anti-tumor necrosis factor (TNF) biologic therapy and several new biologics and small-molecule drugs for UC, precision medicine approaches to treatment are needed to more rapidly achieve sustained remission, restore quality of life, normalize development, and limit exposure to toxic corticosteroids in children with UC. Here, we review available data on clinical, biochemical, histopathologic, and molecular predictors of treatment response in UC. We also address known predictors and special treatment considerations in specific relevant scenarios such as very-early-onset UC, acute severe UC, ileal pouch anal anastomosis, and UC with concomitant primary sclerosing cholangitis. The review concludes with a prediction of how machine learning will integrate multimodal patient data to bring precision medicine to the bedside of children with UC in the future.<\/jats:p>","DOI":"10.3389\/fped.2021.634739","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T15:40:13Z","timestamp":1613749213000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Predicting Therapeutic Response in Pediatric Ulcerative Colitis\u2014A Journey Towards Precision Medicine"],"prefix":"10.3389","volume":"9","author":[{"given":"Ruben J.","family":"Colman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasbir","family":"Dhaliwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1038\/ajg.2017.208","article-title":"Rural and urban residence during early life is associated with risk of inflammatory bowel disease: a population-based inception and birth cohort study","volume":"112","author":"Benchimol","year":"2017","journal-title":"Am J Gastroenterol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1053\/j.gastro.2016.10.020","article-title":"Understanding and preventing the global increase of inflammatory bowel disease","volume":"152","author":"Kaplan","year":"2017","journal-title":"Gastroenterology."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1097\/MIB.0b013e318280b13e","article-title":"Incidence, clinical characteristics, and natural history of pediatric IBD in Wisconsin: a population-based epidemiological study","volume":"19","author":"Adamiak","year":"2013","journal-title":"Inflamm Bowel Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.3748\/wjg.v24.i25.2741","article-title":"Current global trends in the incidence of pediatric-onset inflammatory bowel disease","volume":"24","author":"S\u00fdkora","year":"2018","journal-title":"World J Gastroenterol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1111\/j.1440-1746.2012.07150.x","article-title":"Inflammatory bowel disease in Asia: a systematic review","volume":"27","author":"Prideaux","year":"2012","journal-title":"J. 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