Identification of CD and UC: Details of confirmation process

In total, 1,680 (85%) of women in NHS and 1,413 (86%) of women in NHS II, who had self-reported CD or UC responded. After excluding subjects who subsequently denied the diagnosis of CD or UC on the supplemental questionnaire, (n= 706 in NHS; n= 594 in NHS II) or denied permission for record review (n= 235 in NHS; n= 218 in NHS II), we requested medical records from 739 women in NHS and 601women in NHS II. Among those from whom we requested medical records, we obtained 620 (84%) records in NHS and 557 (93%) records in NHS II with adequate information (clinical presentation and endoscopic, histopathologjc, radiologic or surgical specimen data) for review. All medical records were reviewed by two independent gastroenterologists and cases of CD and UC with date of diagnosis were confirmed according to strict diagnostic criteria for CD and UC (See below).1-5 The two reviewers were blinded to all exposure data. We confirmed the diagnosis of incidentcases of CD, UC, and chronic colitis (indeterminate colitis, microscopic colitis) in 485 NHS participants (June 1976 to June 2008) and 422 NHS II participants (June 1989 to June 2007) for a case confirmation rate of 78% in NHS and 76% in NHS II of the medical records reviewed. We excluded 139 cases of chronic colitis (83 in NHS; 56 in NHS II), leaving a total of 768 cases of CD (348) and UC (420). After baseline exclusions, which included 32 cases without data on smoking, body-mass index, use of oral contraceptives or hormones, or with a history of prior cancer, we had a total of 736 cases of CD (336) and UC (400) for analysis.

Diagnostic criteria for ulcerative colitis (UC):

Inclusion criteria-

Patient must meetthe following two criteria:

  1. Clinical presentation: typical history with hematochezia and/ or diarrhea for at least 4 weeks
  1. Diagnostic evaluation: macroscopic findings consistent with UC (may include the following):
  1. macroscopic appearance of UC by colonoscopy (or surgical specimen at colectomy) with continuous mucosal abnormalities (ex. diffusely granular or friable colonic mucosa, diffuse pinpoint ulcerations) affecting the rectum in continuity with some or all of the colon proximally (If biopsies are performed, microscopic features on biopsy must be consistent with UC)

OR

  1. barium enema x-ray consistent with chronic ulcerative colitis

AND

At least one of the following criteria of chronicity:

1.Pathology: Presence of architectural distortion in the setting of microscopic features consistent with UC on colonic biopsy

2.Colonoscopy: ( 2 ) abnormal colonoscopy examinations (macroscopic and/or microscopic) with features consistent with UC (at least 2 months apart)

3.Barium enema: ( 2 ) abnormal barium enema examinations with features consistent with UC (at least 2 months apart)

4.Clinical: Symptoms: recurrent, distinct episodes of constellation of symptoms, i.e. flares of disease

Exclusion criteria-

The following cases will be excluded:

1.Cases with another identifiable cause for colitis, such as infectious colitis, ischemic colitis, or diverticulitis

2.Cases consistent with Crohn’s disease according to the diagnostic criteria detailed below

Given that UC is confined to the colon by definition, inflammatory bowel disease with evidence of involvement outside of the colon noted on imaging studies or endoscopy (with the exception of ‘backwash ileitis’ and non-specific upper endoscopy findings) will be classified under Crohn’s disease.

Diagnostic criteria for Crohn’s disease (CD):

Inclusion criteria-

Patient must meet at least two of the three following criteria:

  1. Clinical presentation: typical history with abdominal pain and/or diarrhea, and/or hematochezia, and/or fever (+/- weight loss) for greater than 4 weeks
  1. Macroscopic findings consistent with CD (must include at least one of the

following)

  1. Endoscopy/ colonoscopy findings: segmental, discontinuous and/or patchy lesions with or without rectal involvement; discrete linear or aphthous ulcerations; fissuring and penetrating lesions; cobblestoning; strictures; or perianal disease. (If biopsies are performed, microscopic findings must be consistent with CD)
  2. Radiological findings: stenosis/ stricture, mucosal cobblestoning, or ulceration of the small bowel; segmental colitis or fistulae
  3. Surgical findings: segmental, discontinuous and/or patchy lesions with or without rectal involvement; discrete linear or aphthous ulcerations; fissuring and penetrating lesions; cobblestoning; strictures; fistulae; or perianal disease. (Microscopic findings must be consistent with CD)

3.Pathology findings of transmural inflammation on surgical specimen or presence of > 1 granuloma on biopsy

AND

At least one of the following criteria of chronicity:

1.Pathology: Presence of architectural distortion in the setting of microscopic features consistent with CD on colonic biopsy OR transmural inflammation/ fibrosis/ stricture on surgical specimen

2.Colonoscopy: ( 2 ) abnormal colonoscopy examinations (macroscopic and/or microscopic) with features consistent with CD (at least 2 months apart)

3.Imaging study: ( 2 ) abnormal examinations with features consistent with CD (at least 2 months apart)

4.Clinical symptoms: Recurrent, distinct episodes of constellation of symptoms, i.e. flares of disease

Exclusion criteria:

The following cases will be excluded:

Cases with another identifiable cause for findings such as for colitis, (infectious colitis, ischemic colitis, or diverticulitis) and for small bowel disease, (lymphoma, tuberculosis)

References:

1.Stowe S, Redmond S, Stormont Jet al. An epidemiologic study of inflammatory bowel disease in Rochester, New York. Hospital incidence. Gastroenterology 1990;98:104-110.

2.Moum B, Vatn M, Ekbom Aet al. Incidence of inflammatory bowel disease in southeastern Norway: evaluation of methods after 1 year of registration. Southeastern Norway IBD Study Group of Gastroenterologists. Digestion 1995;56:377- 381.

3.Fonager K, Sorensen H, Rasmussen Set al. Assessment of the diagnoses of Crohn's disease and ulcerative colitis in a Danish hospital information system. Scand J Gastroenterol 1996;31:154- 159.

4.Loftus EV, Silverstein MD, Sandborn WJet al. Crohn's disease in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gastroenterology 1998;114:1161-8.

5.Loftus EV, Silverstein MD, Sandborn WJet al. Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gut 2000;46:336-43.