Increased Incidence of Inflammatory Bowel Disease After Hirschsprung Disease: A Population-based Cohort Study.

Supported by a Foundation Grant from the Canadian Institutes of Health Research (CIHR) and a CIHR Operating Grant Reference Number PJT 162393. C.B. is supported in part by the Bingham Chair in Gastroenterology. E.B. was supported by a New Investigator Award from the Canadian Institutes of Health Research, Canadian Association of Gastroenterology and Crohn's and Colitis Canada and by the Career Enhancement Program of the Canadian Child Health Clinician Scientist Program. M.K. was supported by a Mitacs Elevate Post-Doctoral Fellowship. The study sponsor (CIHR) had no role in any of (1) study design; (2) the collection, analysis, and interpretation of data; (3) the writing of the report; and (4) the decision to submit the paper for publication. C.B. has served on the advisory boards of Abbvie Canada, Janssen Canada, Pfizer Canada, Takeda Canada, Roche Canada; has served as a consultant for Takeda and Mylan Pharmaceuticals; has served on the speaker’s bureau for Abbvie Canada, Janssen Canada, Takeda Canada, and Medtronic Canada; has received unrestricted educational grants from Abbvie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada; and has done contract research with Abbvie, Janssen, Pfizer, Celgene, Boeringher Ingelheim, and Roche. W.E-M. served as an advisory board member of Abbvie Canada, Janssen Canada and Merck Canada and received honoraria for speaking from Abbvie Canada. H.S. has served on advisory boards or as a consultant for Amgen Canada, Sandoz Canada, Roche Canada, Takeda Canada, Pendopharm, Ferring Canada, Merck Canada, and Guardant Health, Inc; has received an educational grant from Ferring Canada; and research funding from Merck Canada for an independent investigator grant. G.K. has received honoraria for speaking or serving as a consultant for Abbvie, Janssen, Pfizer, and Takeda; has received research support from Ferring, Janssen, Abbvie, GlaxoSmith Kline, Merck, and Shire; has served as a consultant for Gilead; and shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. The other authors declare no conflicts of interest. Objective To determine the frequency with which inflammatory bowel disease (IBD) is diagnosed in persons with Hirschsprung disease (HD) in population-based datasets from three Canadian provinces. Study design: In Study I, Ontario data were used to assess the incidence of IBD in a birth cohort of children with HD relative to children without HD. In Study II, a case-control design was used in Alberta and Manitoba to determine the frequency of previously-diagnosed HD in persons with IBD, compared with the frequency of HD in matched controls. Validated algorithms for HD and IBD were applied to each provincial health registry. Results: Study I: Of 716 children diagnosed with HD in Ontario since 1991, 18 (2.5%) ultimately developed IBD (168.8 per 100,000 PYs), compared with 7109 of 3.377,394 children without HD (0.2%, 14.2 per 100,000 PYs). 77.8% of post-HD IBD were males. The incidence rate ratio was 11.9 (95%CI 7.5, 18.8). Study II: The odds ratio of having had HD prior to a diagnosis of IBD compared with controls was 74.9 (95%CI 17.1, 328.7) in Alberta and 23.8, (95%CI 4.6, 123) in Manitoba. Crohn’s disease was more common after HD than ulcerative colitis. Conclusions: IBD can emerge in over 2% of HD patients and, like HD itself, is more common in males. IBD is much more common after a diagnosis of HD than in the general population.