Ulcerative Colitis in Children: Background, Epidemiology, Prognosis (original) (raw)

Overview

Background

Ulcerative colitis (UC) is a disease characterized by remitting and relapsing inflammation of the large intestine. UC, Crohn disease (CD) and indeterminate colitis account for the disorders that represent the inflammatory bowel diseases (IBDs).

Many patterns of presentation are possible within the pediatric age group. The hallmark symptoms of UC include abdominal cramping, diarrhea, and bloody stools, but physical symptoms vary with extent, duration, and severity of the disease. UC affects the rectum, with contiguous involvement that can include the entire large intestine. The disease phenotype can be characterized according to the Paris Classification, which divides the disease into isolated proctitis, left-sided colitis, extended colitis, and pancolitis. [1] Extraintestinal manifestations of UC, such as joint pain, ophthalmic conditions, and hepatobiliary disease may occur in some patients. See Presentation.

In the United States, 2 of every 100,000 children (age's 10-19 y) are affected, and 20-25% of all cases UC occur in persons aged 20 years or younger and the disease is increasing among young children (< 5 y). See Epidemiology.

Colonoscopy with biopsy is the most valuable procedure in evaluating patients with inflammatory bowel disease. Typical findings in someone with UC are inflammation that is first evident in the rectum and that proximally extends in a contiguous fashion. See Workup.

The therapeutic goal is to gain clinical and laboratory control of the disease with minimal adverse effects while permitting the patient to function as normally as possible. Approximately 5-10% of patients with UC require acute surgical intervention because of fulminant colitis refractory to medical therapy. Total proctocolectomy is often curative in patients with UC and removes the risk of colonic adenocarcinoma. See Treatment.

The mainstay of outpatient management is anti-inflammatory therapy with 5-aminosalicylic acid (5-ASA) preparations, such as sulfasalazine and mesalamine. Acute flares of UC in the pediatric population tend to respond well to corticosteroids, but numerous adverse effects prevent long-term use. Immunomodulatory agents and tumor necrosis factor inhibitors are also used to alleviate exacerbations of disease and increase patient comfort, as are newer therapies (eg, vedolizumab), and they can be a viable treatment option when the patient is steroid-dependent or steroid-refractory. See Medication.

For information on the general pathophysiology, etiology, and prognosis in patients with ulcerative colitis, see Ulcerative Colitis.

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Epidemiology

The incidence of pediatric-onset ulcerative colitis (UC) appears to be on the rise, often with a more severe disease presentation. [2] The prevalence of inflammatory bowel disease (IBD) overall increased in this population by 133% over a 9-year period (from 33.0/100,000 in 2007 to 77.0/100,000 in 2016). Among children, Crohn disease (CD) was twice as prevalent as UC (45.9 vs 21.6). Boys are affected more than girls for all forms of IBD. [2]

In the United States, 2-4 of every 100,000 children (age's 10-19 y) develop UC, and 20-30% of all cases occur in persons aged 20 years or younger. In most studies, UC incidence peaks between adolescence and early adulthood (ie, in people aged 15-30 y). A smaller peak occurs in patients aged 60-80 years. The incidence of inflammatory bowel disease among young children (< 5 y) has increased. These children often have disease that is limited to the colon; however, the disease can later progress to involve other parts of the intestine.

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Prognosis

Although many children with ulcerative colitis (UC) have a mild course and respond well to therapy, severe complications can arise in patients with UC during acute exacerbations of disease or as the disease progresses. Male sex and higher Pediatric Ulcerative Colitis Activity Index (PUCAI) score at diagnosis appear to be independent risk factors for colectomy in children with UC. [3]

A 2021 systematic review showed that at diagnosis, disease extent, PUCAI score (>65 points), hemoglobin and hematocrit levels, and white blood cell measurements (WBCs) may predict colectomy; PUCAI score >65 during the subsequent 3 months, family history of UC, and extraintestinal manifestations may predict colectomy. [4]

Factors predictive for the development of chronic pouchitis in pediatric ulcerative colitis are use of immunomodulators and the early occurrence of the first episode of pouchitis within 15 months after ileal pouch-anal anastomosis (IPAA). [5]

Toxic megacolon

Toxic megacolon is the most serious acute complication of UC and is reported to occur in up to 5% of patients; it is rare in young patients. Toxic megacolon is considered a medical and surgical emergency.

The pathogenesis of toxic megacolon is related to severe inflammation resulting in disordered intestinal motility. Compromised mucosal integrity then may allow bacteria to enter the submucosal tissues, leading to necrosis and peritonitis. Absorptive function is also impaired, resulting in increased luminal fluid volume and electrolyte losses.

Toxic megacolon usually occurs in the presence of severe pancolitis. Concurrent infection, such as Clostridium difficile colitis can lead to toxic megacolon; use of antidiarrheal agents or recent barium enema study or colonoscopy have also been implicated as causes. In addition, metabolic abnormalities (eg, hypokalemia, hypomagnesemia, hypoproteinemia), impaired epithelial integrity of the colon, and altered motor function and are frequently found in patients with toxic megacolon.

Toxic megacolon is associated with fever, abdominal distention, and tenderness. Abdominal series reveal dilatation of the colon with loss of normal haustral markings and signs of edema. Toxic megacolon places the patient at risk for colonic perforation, gram-negative sepsis, and massive hemorrhage.

Colonic malignancy

Colonic malignancy is a clinically significant complication in patients with UC. Disease duration and pancolitis are well-recognized risk factors for malignancy, with the cancer risk surpassing that of the general population after 10 years. Other less-characterized risk factors include sclerosing cholangitis, a bypassed and defunctionalized segment of bowel, and a low folate level.

Children who develop UC before age 14 years have a cumulative colorectal-cancer incidence of 5% at age 20 years and 40% at age 35 years. Patients aged 15-39 years who develop UC have a cumulative incidence of 5% at age 20 years and 30% at age 35 years. The risk for children with disease onset in the first decade of life is unknown, but these children should undergo colonoscopic screening for dysplasia beginning in adolescence.

Epithelial dysplasia generally precedes carcinoma; therefore, yearly screening with surveillance colonoscopy and biopsy should be performed. Dysplasia can be missed on surveillance biopsy; prophylactic colectomy should be considered for adults who developed UC during childhood. With this in mind, psychologically prepare adolescents and young adults by discussing surgical options before the need for surgery arises.

Extraintestinal manifestations

Extraintestinal manifestations are common in UC; approximately 25-35% of patients with inflammatory bowel disease (IBD) have at least one extraintestinal manifestation. Extraintestinal disease may be prognostically important because the rate of pouchitis increases after colectomy in patients with UC and extraintestinal manifestations.

Pyoderma gangrenosum occurs in 1% of UC patients. An indolent chronic ulcer may occur even when disease is in remission. Intralesional therapy with steroids is useful, and colectomy results in healing in approximately 50% of patients.

Ophthalmologic manifestations most frequently occur when the disease is active. The incidence in adults is 4% but is less in children. The most common findings are episcleritis and anterior uveitis. Uveitis is usually symptomatic, causing pain or decreased vision. Patients with IBD should likely undergo routine ophthalmologic examination.

Arthritis is the most common extraintestinal manifestation of IBD, occurring in 10-25% of adolescents. The arthritis is usually a transient, nondeforming synovitis that involves the large joints in an asymmetric distribution. In children, arthritis may precede gastrointestinal (GI) symptoms by years.

Hepatobiliary disease is another common extraintestinal manifestation of UC in children. Hepatobiliary complications may precede the onset of GI symptoms, they may accompany active disease, or they may develop after surgical resection. Chronic active hepatitis, granulomatous hepatitis, amyloidosis, fatty liver, and pericholangitis are some of the intrahepatic manifestations of IBD. Extrahepatic manifestations include cholelithiasis and primary sclerosing cholangitis (PSC).

Thromboembolic disease is considered to be the result of a hypercoagulable state that parallels disease activity and is manifested by thrombocytosis; elevated plasma fibrinogen, factor V, and factor VIII; and decreased plasma antithrombin III. The hypercoagulable state may lead to deep venous thrombosis, pulmonary emboli, and neurovascular disease. In an 11-year (2009-2020) population-based nested case-control study of Canadian children with IBD, 15 venous thromboembolic events (VTEs) (1.69%) occurred among 12 patients (12 with UC; 3 with Crohn disease). [6] Of children who developed VTE, females and those with with UC were disproportionately affected. Overall, the prognosis was good in those whose VTE were treated with anticoagulation therapy (there were no deaths or increased bleeding events reported). [6]

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Patient Education

Thorough education about the pathophysiology, medications, and short-term and long-term risks of ulcerative colitis (UC) is an essential part of any treatment program.

The Crohn's and Colitis Foundation of America and Crohn's and Colitis Canada are nonprofit organizations dedicated to the education and treatment of patients affected by Crohn disease and UC.

The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, in concert with the Children's Digestive Health and Nutrition Foundation, have developed educational resources for children and families affected by inflammatory bowel disease (IBD). These resources are available at GI Kids.

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  1. Levine A, Griffiths A, Markowitz J, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis. 2011 Jun. 17(6):1314-21. [QxMD MEDLINE Link].
  2. Ye Y, Manne S, Treem WR, Bennett D. Prevalence of inflammatory bowel disease in pediatric and adult populations: recent estimates from large national databases in the United States, 2007-2016. Inflamm Bowel Dis. 2020 Mar 4. 26(4):619-25. [QxMD MEDLINE Link]. [Full Text].
  3. Rinawi F, Assa A, Eliakim R, et al. Risk of colectomy in patients with pediatric-onset ulcerative colitis. J Pediatr Gastroenterol Nutr. 2017 Oct. 65(4):410-5. [QxMD MEDLINE Link]. [Full Text].
  4. [Guideline] Orlanski-Meyer E, Aardoom M, Ricciuto A, et al. Predicting outcomes in pediatric ulcerative colitis for management optimization: systematic review and consensus statements from the Pediatric Inflammatory Bowel Disease-Ahead Program. Gastroenterology. 2021 Jan. 160(1):378-402.e22. [QxMD MEDLINE Link]. [Full Text].
  5. Koike Y, Uchida K, Inoue M, et al. Early first episode of pouchitis after ileal pouch-anal anastomosis for pediatric ulcerative colitis is a risk factor for development of chronic pouchitis. J Pediatr Surg. 2019 Sep. 54(9):1788-93. [QxMD MEDLINE Link].
  6. Ding Z, Sherlock M, Chan AKC, Zachos M. Venous thromboembolism in pediatric inflammatory bowel disease: an 11-year population-based nested case-control study in Canada. Blood Coagul Fibrinolysis. 2022 Dec 1. 33 (8):449-56. [QxMD MEDLINE Link].
  7. [Guideline] Turner D, Ruemmele FM, Orlanski-Meyer E, et al. Management of paediatric ulcerative colitis, part 1: ambulatory care-an evidence-based guideline from European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Aug. 67(2):257-91. [QxMD MEDLINE Link]. [Full Text].
  8. Turner D, Otley AR, Mack D, et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology. 2007 Aug. 133(2):423-32. [QxMD MEDLINE Link].
  9. Deutsch DE, Olson AD. Colonoscopy or sigmoidoscopy as the initial evaluation of pediatric patients with colitis: a survey of physician behavior and a cost analysis. J Pediatr Gastroenterol Nutr. 1997 Jul. 25(1):26-31. [QxMD MEDLINE Link].
  10. Najarian RM, Ashworth LA, Wang HH, Bousvaros A, Goldsmith JD. Microscopic/"backwash" ileitis and its association with colonic disease in new onset pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr. 2019 Jun. 68(6):835-40. [QxMD MEDLINE Link].
  11. Torres J, Caprioli F, Katsanos KH, et al. Predicting outcomes to optimize disease management in inflammatory bowel diseases. J Crohns Colitis. 2016 Dec. 10(12):1385-94. [QxMD MEDLINE Link]. [Full Text].
  12. Vasiliauskas E. Serum immune markers in inflammatory bowel disease. Gastroenterology and Endoscopy News. [Full Text].
  13. Peeters M, Joossens S, Vermeire S, Vlietinck R, Bossuyt X, Rutgeerts P. Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease. Am J Gastroenterol. 2001 Mar. 96(3):730-4. [QxMD MEDLINE Link].
  14. Dubinsky MC, Ofman JJ, Urman M, Targan SR, Seidman EG. Clinical utility of serodiagnostic testing in suspected pediatric inflammatory bowel disease. Am J Gastroenterol. 2001 Mar. 96(3):758-65. [QxMD MEDLINE Link].
  15. Hoffenberg EJ, Fidanza S, Sauaia A. Serologic testing for inflammatory bowel disease. J Pediatr. 1999 Apr. 134(4):447-52. [QxMD MEDLINE Link].
  16. Kaditis AG, Perrault J, Sandborn WJ, Landers CJ, Zinsmeister AR, Targan SR. Antineutrophil cytoplasmic antibody subtypes in children and adolescents after ileal pouch-anal anastomosis for ulcerative colitis. J Pediatr Gastroenterol Nutr. 1998 Apr. 26(4):386-92. [QxMD MEDLINE Link].
  17. Yoon HM, Suh CH, Kim JR, et al. Diagnostic performance of magnetic resonance enterography for detection of active inflammation in children and adolescents with inflammatory bowel disease: a systematic review and diagnostic meta-analysis. JAMA Pediatr. 2017 Dec 1. 171(12):1208-16. [QxMD MEDLINE Link]. [Full Text].
  18. [Guideline] Levine A, Koletzko S, Turner D, et al, for the European Society of Pediatric Gastroenterology, Hepatology, et al. ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr. 2014 Jun. 58(6):795-806. [QxMD MEDLINE Link]. [Full Text].
  19. Eliakim R, Fischer D, Suissa A, et al. Wireless capsule video endoscopy is a superior diagnostic tool in comparison to barium follow-through and computerized tomography in patients with suspected Crohn's disease. Eur J Gastroenterol Hepatol. 2003 Apr. 15(4):363-7. [QxMD MEDLINE Link].
  20. Fell JM, Muhammed R, Spray C, Crook K, Russell RK, BSPGHAN IBD working group. Management of ulcerative colitis. Arch Dis Child. 2016 May. 101(5):469-74. [QxMD MEDLINE Link]. [Full Text].
  21. [Guideline] Cohen JL, Strong SA, Hyman NH, et al, for the Standards Practice Task Force American Society of Colon and Rectal Surgeons. Practice parameters for the surgical treatment of ulcerative colitis. Dis Colon Rectum. 2005 Nov. 48(11):1997-2009. [QxMD MEDLINE Link].
  22. Kam L. Ulcerative colitis in young adults. Complexities of diagnosis and management. Postgrad Med. 1998 Jan. 103(1):45-9, 53-6, 59. [QxMD MEDLINE Link].
  23. Sarigol S, Wyllie R, Gramlich T, et al. Incidence of dysplasia in pelvic pouches in pediatric patients after ileal pouch-anal anastomosis for ulcerative colitis. J Pediatr Gastroenterol Nutr. 1999 Apr. 28(4):429-34. [QxMD MEDLINE Link].
  24. Asacol (mesalamine) [package insert]. Rockaway, NJ: Warner Chilcott. 2013. Available at [Full Text].
  25. [Guideline] Turner D, Ruemmele FM, Orlanski-Meyer E, et al. Management of paediatric ulcerative colitis, part 2: acute severe colitis-an evidence-based consensus guideline from the European Crohn's and Colitis Organization and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Aug. 67(2):292-310. [QxMD MEDLINE Link]. [Full Text].
  26. Pini Prato A, Pio L, Leonelli L, et al. Morbidity and risk factors of laparoscopic-assisted ileostomies in children with ulcerative colitis. J Pediatr Gastroenterol Nutr. 2016 Jun. 62(6):858-62. [QxMD MEDLINE Link].
  27. Eidelwein AP, Cuffari C, Abadom V, Oliva-Hemker M. Infliximab efficacy in pediatric ulcerative colitis. Inflamm Bowel Dis. 2005 Mar. 11(3):213-8. [QxMD MEDLINE Link].
  28. Becker JM. Surgical therapy for ulcerative colitis and Crohn's disease. Gastroenterol Clin North Am. 1999 Jun. 28(2):371-90, viii-ix. [QxMD MEDLINE Link].
  29. Bismar N, Knod JL, Patel AS, Schindel DT. Outcomes following two-stage surgical approaches in the treatment of pediatric ulcerative colitis. J Pediatr Surg. 2019 Aug. 54(8):1601-3. [QxMD MEDLINE Link].
  30. [Guideline] Holubar SD, Lightner AL, Poylin V, et al, on behalf of the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons. The American Society of Colon and Rectal Surgeons Clinical practice guidelines for the surgical management of ulcerative colitis. Dis Colon Rectum. 2021 Jul 1. 64(7):783-804. [QxMD MEDLINE Link]. [Full Text].
  31. [Guideline] De Simone B, Davies J, Chouillard E, et al. WSES-AAST guidelines: management of inflammatory bowel disease in the emergency setting. World J Emerg Surg. 2021 May 11. 16(1):23. [QxMD MEDLINE Link]. [Full Text].
  32. [Guideline] Kucharzik T, Ellul P, Greuter T, et al. ECCO guidelines on the prevention, diagnosis, and management of infections in inflammatory bowel disease. J Crohns Colitis. 2021 Jun 22. 15(6):879-913. [QxMD MEDLINE Link]. [Full Text].
  33. [Guideline] Ko CW, Singh S, Feuerstein JD, et al, for the American Gastroenterological Association Institute Clinical Guidelines Committee. AGA clinical practice guidelines on the management of mild-to-moderate ulcerative colitis. Gastroenterology. 2019 Feb. 156(3):748-64. [QxMD MEDLINE Link]. [Full Text].
  34. American Gastroenterological Association. New guideline provides recommendations for the treatment of mild-to-moderate ulcerative colitis. January 9, 2019. Gastro.org. Available at https://www.gastro.org/press-release/new-guideline-provides-recommendations-for-the-treatment-of-mild-to-moderate-ulcerative-colitis. Accessed: March 20, 2019.
  35. [Guideline] Farraye FA, Melmed GY, Lichtenstein GR, Kane SV. ACG clinical guideline: preventive care in inflammatory bowel disease. Am J Gastroenterol. 2017 Feb. 112(2):241-58. [QxMD MEDLINE Link]. [Full Text].
  36. Salzmann M, von Graffenried T, Righini-Grunder F, et al, for the Swiss IBD Cohort Study Group. Drug-related adverse events necessitating treatment discontinuation in pediatric inflammatory bowel disease patients. J Pediatr Gastroenterol Nutr. 2022 Dec 1. 75 (6):731-6. [QxMD MEDLINE Link]. [Full Text].
  37. Miele E, Pascarella F, Giannetti E, Quaglietta L, Baldassano RN, Staiano A. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol. 2009 Feb. 104(2):437-43. [QxMD MEDLINE Link].
  38. Ziring DA, Wu SS, Mow WS, Martin MG, Mehra M, Ament ME. Oral tacrolimus for steroid-dependent and steroid-resistant ulcerative colitis in children. J Pediatr Gastroenterol Nutr. 2007 Sep. 45(3):306-11. [QxMD MEDLINE Link].
  39. Wiernicka A, Szymanska S, Cielecka-Kuszyk J, Dadalski M, Kierkus J. Histological healing after infliximab induction therapy in children with ulcerative colitis. World J Gastroenterol. 2015 Oct 7. 21(37):10654-61. [QxMD MEDLINE Link]. [Full Text].
  40. Mamula P, Markowitz JE, Brown KA, Hurd LB, Piccoli DA, Baldassano RN. Infliximab as a novel therapy for pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr. 2002 Mar. 34(3):307-11. [QxMD MEDLINE Link].
  41. Scarpato E, Russo M, Staiano A. Probiotics in pediatric gastroenterology: emerging indications: inflammatory bowel diseases. J Clin Gastroenterol. 2018 Nov/Dec. 52 suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017:S7-9. [QxMD MEDLINE Link].
  42. Tan Tanny SP, Yoo M, Hutson JM, Langer JC, King SK. Current surgical practice in pediatric ulcerative colitis: a systematic review. J Pediatr Surg. 2019 Jul. 54(7):1324-30. [QxMD MEDLINE Link].

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Author

Mutaz I Sultan, MD, MBChB Assistant Professor and Chief of Pediatrics, Al-Quds University Medical College; Pediatric Gastroenterologist and Hepatologist, Division of Pediatrics, Makassed Hospital, Palestine

Mutaz I Sultan, MD, MBChB is a member of the following medical societies: European Society for Paediatric Gastroenterology, Hepatology and Nutrition, Palestine Medical Council

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching. for: Abbott Nutritional, Abbvie, speakers' bureau.

Additional Contributors

Petar Mamula, MD Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine

Petar Mamula, MD is a member of the following medical societies: American Academy of Pediatrics, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Judith R Kelsen, MD Ann and Richard Frankel Chair in Gastroenterology Research, Director, Very Early-Onset Inflammatory Bowel Disease Program, Associate Professor of Pediatrics, Division of GI, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania

Judith R Kelsen, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Study of Liver Diseases, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Acknowledgements

Robert Baldassano, MD, Director, Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia; Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Pennsylvania School of Medicine

Robert Baldassano, MD is a member of the following medical societies:Alpha Omega Alpha, American Academy of Pediatrics, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Abbott Inc, Consulting fee, Consulting

Liz D Dancel, MD Intern, Department of Pediatrics, Greenville Hospital System University Medical Center

Disclosure: Nothing to disclose.

Jonathan Markowitz, MD Assistant Professor, Department of Pediatrics, Inpatient Gastroenterology, Division of Gastroenterology and Nutrition, University of Pennsylvania School of Medicine; Director, The Children's Hospital of Philadelphia.

Jonathan Markowitz is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

David A Piccoli, MD Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine

David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Jorge H Vargas, MD Professor of Pediatrics and Clinical Professor of Pediatric Gastroenterology, University of California, Los Angeles, David Geffen School of Medicine; Consulting Physician, Department of Pediatrics, University of California at Los Angeles Health System

Jorge H Vargas, MD is a member of the following medical societies: American Liver Foundation, American Society for Gastrointestinal Endoscopy, American Society for Parenteral and Enteral Nutrition, Latin American Society of Pediatric Gastroenterology, Hepatology & Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.