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Timing, Frequency and Type of Physician-diagnosed Infections in Childhood and Risk for Crohn's Disease in Children and Young Adults

Springmann, Vicky MSc*,†; Brassard, Paul MD, MSc†,‡; Krupoves, Alfreda MD, PhD§; Amre, Devendra MBBS, PhD*,‖

doi: 10.1097/MIB.0000000000000098
Original Clinical Articles

Background: Recent experimental data show that exposure to microbes during early childhood can confer immunological tolerance and protect against Crohn's disease (CD). Epidemiological evidence for this link, however, remains controversial. Using prospective data, we examined the link between this hypothesis and risk for CD in children and young adults.

Methods: A case-control study design was used. CD cases (diagnosed before age 20 years) were recruited from a tertiary-care pediatric hospital in Montreal, and population-based controls matched for age, gender and, geographical location were selected. Infection data were ascertained from physician-billing records. These records, which use International Classification of Diseases, Ninth Revision diagnostic codes, were consulted retrospectively but provide prospectively collected diagnostic information. Conditional logistic regression analysis was used to study potential associations. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated.

Results: Four hundred nine cases and 1621 controls were included. Regression analysis adjusting for potential confounding variables suggested that any recorded infection before the diagnosis of CD was associated with reduced risk of CD (OR, 0.67; 95% CI, 0.48–0.93). The protective effect was restricted to infections occurring mainly before 5 years of age, with increasing number of infections resulting in greater protection (1–5 infections: OR, 0.74; ≥6 infections: OR, 0.61; P value for trend = 0.039). Infections affecting the oral and upper respiratory tracts, cellulitis, and, enteric infections seemed most protective.

Conclusions: Our study provides support for the hygiene hypothesis, whereby exposure to infections in early childhood could potentially reduce risks of CD.

Article first published online 25 June 2014.

*Department of Gastroenterology & Hepatology, Ste-Justine Hospital Research Centre, Montreal, QC, Canada;

Department of Social and Preventive Medicine, University of Montreal, Montreal, QC, Canada;

Department of Clinical Epidemiology and Community Studies, Jewish General Hospital, Montreal, QC, Canada;

§Division of Occupational & Environmental Health, Institut national de santé publique du Québec, Montreal, QC, Canada; and

Department of Pediatrics, University of Montreal, Montreal, QC, Canada.

Reprints: Devendra Amre, MBBS, PhD, Ste-Justine Hospital Research Centre, 3175 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1C5, Canada (e-mail:

Supported by the Crohn's and Colitis Foundation of Canada, the Canadian Institute for Health Research and the Fonds de Recherche du Québec-Santé. V. Springmann was supported by the Ste-Justine Hospital Research Foundation and the Faculty of Graduate and Post-doctoral Studies of the University of Montreal.

The authors have no conflicts of interest to disclose.

Received March 17, 2014

Accepted April 30, 2014

© Crohn's & Colitis Foundation of America, Inc.
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