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Rural and Urban Residence During Early Life is Associated with Risk of Inflammatory Bowel Disease: A Population-Based Inception and Birth Cohort Study

Benchimol, Eric I MD, PhD1,2,3,4,5; Kaplan, Gilaad G MD, MPH6,7; Otley, Anthony R MD, MSc8; Nguyen, Geoffrey C MD, PhD5,9; Underwood, Fox E MSc6,7; Guttmann, Astrid MDCM, MSc5,10; Jones, Jennifer L MD, MSc11; Potter, Beth K PhD4; Catley, Christina A PhD5; Nugent, Zoann J PhD12; Cui, Yunsong MSc11; Tanyingoh, Divine MSc6; Mojaverian, Nassim MSc5; Bitton, Alain MD13; Carroll, Matthew W BMed, MHSc14; deBruyn, Jennifer MD, MSc15; Dummer, Trevor J B BA, MSc, PhD16; El-Matary, Wael MD, MSc17; Griffiths, Anne M MD10; Jacobson, Kevan MBBCh18,19; Kuenzig, Ellen M PhD1,2,5; Leddin, Desmond MD11; Lix, Lisa M PhD20; Mack, David R MD1,2,3; Murthy, Sanjay K MD, MSc5,21; Sánchez, Juan Nicolás Peña MD, MPH, PhD22; Singh, Harminder MD, MPH12,23; Targownik, Laura E MD, MSHS12,23; Vutcovici, Maria MD, MSc13; Bernstein, Charles N MD12,23 on behalf of the Canadian Gastro-Intestinal Epidemiology Consortium

American Journal of Gastroenterology: September 2017 - Volume 112 - Issue 9 - p 1412–1422
doi: 10.1038/ajg.2017.208
ORIGINAL CONTRIBUTIONS: INFLAMMATORY BOWEL DISEASE
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Objectives: To determine the association between inflammatory bowel disease (IBD) and rural/urban household at the time of diagnosis, or within the first 5 years (y) of life.

Methods: Population-based cohorts of residents of four Canadian provinces were created using health administrative data. Rural/urban status was derived from postal codes based on population density and distance to metropolitan areas. Validated algorithms identified all incident IBD cases from administrative data (Alberta: 1999–2008, Manitoba and Ontario: 1999–2010, and Nova Scotia: 2000–2008). We determined sex-standardized incidence (per 100,000 patient-years) and incident rate ratios (IRR) using Poisson regression. A birth cohort was created of children in whom full administrative data were available from birth (Alberta 1996–2010, Manitoba 1988–2010, and Ontario 1991–2010). IRR was calculated for residents who lived continuously in rural/urban households during each of the first 5 years of life.

Results: There were 6,662 rural residents and 38,905 urban residents with IBD. Incidence of IBD per 100,000 was 33.16 (95% CI 27.24–39.08) in urban residents, and 30.72 (95% CI 23.81–37.64) in rural residents (IRR 0.90, 95% CI 0.81–0.99). The protective association was strongest in children <10 years (IRR 0.58, 95% CI 0.43–0.73) and 10–17.9 years (IRR 0.72, 95% CI 0.64–0.81). In the birth cohort, comprising 331 rural and 2,302 urban residents, rurality in the first 1–5 years of life was associated with lower risk of IBD (IRR 0.75–0.78).

Conclusions: People living in rural households had lower risk of developing IBD. This association is strongest in young children and adolescents, and in children exposed to the rural environment early in life.

1Children’s Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, Canada

2Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada

3Department of Pediatrics, University of Ottawa, Ottawa, Canada

4School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada

5Institute for Clinical Evaluative Sciences, Toronto, Canada

6Department of Medicine, University of Calgary, Calgary, Canada

7Department of Community Health Sciences, University of Calgary, Calgary, Canada

8Department of Pediatrics, Dalhousie University, Halifax, Canada

9Mount Sinai Hospital Centre for Inflammatory Bowel Disease, Department of Medicine, University of Toronto, Toronto, Canada

10Department of Paediatrics, University of Toronto, Toronto, Canada

11Department of Medicine, Dalhousie University, Halifax, Canada

12University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Canada

13McGill University Health Centre, Division of Gastroenterology, Montreal, Canada

14Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Canada

15Division of Gastroenterology, Department of Pediatrics, University of Calgary, Calgary, Canada

16School of Population and Public Health, University of British Columbia, Vancouver, Canada

17Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada

18Department of Pediatrics, University of British Columbia, Vancouver, Canada

19Child and Family Research Institute, University of British Columbia, Vancouver, Canada

20Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada

21The Ottawa Hospital IBD Centre, Department of Medicine, University of Ottawa, Ottawa, Canada

22Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Canada

23Department of Internal Medicine, University of Manitoba, Winnipeg, Canada

Correspondence: Eric I. Benchimol, MD, PhD, Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada. E-mail: ebenchimol@cheo.on.ca

SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/A561, http://links.lww.com/AJG/A563, http://links.lww.com/AJG/A565, http://links.lww.com/AJG/A566

Received 10 March 2017; accepted 16 June 2017

Guarantor of the article: Eric I. Benchimol, MD, PhD.

Specific author contributions: Eric I. Benchimol: study conception and design, analysis and interpretation of data, drafting of manuscript, statistical analysis, and obtained funding; Gilaad G. Kaplan: study conception and design, establishment of Alberta cohort, analysis and interpretation of data, critical revision of the manuscript, statistical analysis, and obtained funding; Anthony R. Otley: establishment of Nova Scotia cohort, analysis and interpretation of data, critical revision of the manuscript, and statistical analysis; Geoffrey C. Nguyen: study conception and design, analysis and interpretation of data, critical revision of the manuscript, statistical analysis, and obtained funding; Fox E. Underwood: health geography expertise, classification of rural/urban postal codes, analysis and interpretation of data, and critical revision of the manuscript; Astrid Guttmann: study conception and design, analysis and interpretation of data, critical revision of the manuscript, statistical analysis, and obtained funding; Jennifer L. Jones: establishment of Nova Scotia cohort, study conception and design, analysis and interpretation of data, critical revision of the manuscript, statistical analysis, and obtained funding; Beth K. Potter: study conception and design, analysis and interpretation of data, critical revision of the manuscript, statistical analysis, and obtained funding; Christina A. Catley: Ontario data methodologist/analyst, analysis and interpretation of results, statistical analysis, technical support, and critical revision of the manuscript; Zoann Nugent: Manitoba data methodologist/analyst, analysis and interpretation of results, statistical analysis, technical support, and critical revision of the manuscript; Yunsong Cui: Nova Scotia data methodologist/analyst, analysis and interpretation of results, statistical analysis, technical support, and critical revision of the manuscript. Divine Tanyingoh: Alberta data methodologist/analyst, analysis and interpretation of results, statistical analysis, technical support, and critical revision of the manuscript; Nassim Mojaverian: Ontario data methodologist/analyst, analysis and interpretation of results, statistical analysis, technical support, and critical revision of the manuscript; Alain Bitton: analysis and interpretation of data, and critical revision of the manuscript; Matthew W. Carroll: analysis and interpretation of data, and critical revision of the manuscript; Jennifer deBruyn: analysis and interpretation of data, and critical revision of the manuscript; Trevor J.B. Drummer: establishment of Nova Scotia Cohort, analysis and interpretation of data, and critical revision of the manuscript; Wael El-Matary: analysis and interpretation of data, and critical revision of the manuscript; Anne M. Griffiths: analysis and interpretation of data, and critical revision of the manuscript; Kevan Jacobson: analysis and interpretation of data, critical revision of the manuscript, and obtained funding; M. Ellen Kuenzig: analysis and interpretation of data, and critical revision of the manuscript; Desmond Leddin: analysis and interpretation of data, and critical revision of the manuscript; Lisa M. Lix: analysis and interpretation of data, and critical revision of the manuscript; David R. Mack: analysis and interpretation of data, and critical revision of the manuscript; Sanjay K. Murthy: analysis and interpretation of data, and critical revision of the manuscript. Juan Nicolás Peña Sánchez: analysis and interpretation of data; critical revision of the manuscript; Harminder Singh: analysis and interpretation of data, and critical revision of the manuscript; Laura E. Targownik: analysis and interpretation of data, and critical revision of the manuscript; Maria Vutcovici: analysis and interpretation of data, and critical revision of the manuscript; Charles N. Bernstein: study conception and design, establishment of Manitoba cohort, analysis and interpretation of data, critical revision of the manuscript, statistical analysis, and obtained funding.

Financial support: This research was funded by an independently administered, peer-reviewed operating grant from the Janssen Future Leaders in IBD Program. The grant sponsor had no role in the design, conduct, or interpretation of the research. CanGIEC is funded by the Canadian Institutes of Health Research (CIHR) Foundation Scheme. Eric Benchimol and Geoffrey Nguyen were supported by New Investigator Awards from CIHR, Crohn’s and Colitis Canada, and the Canadian Association of Gastroenterology. Eric Benchimol was also supported by a Career Development Award and the Career Enhancement Program from the Canadian Child Health Clinician Scientist Program. Gilaad Kaplan and Geoffrey Nguyen were CIHR Embedded Clinician Research Chairs. Astrid Guttmann was supported by a CIHR Applied Chair in Reproductive and Child Health Services and Policy Research. Trevor Dummer and the Nova Scotia team were supported by an Establishment Grant from the Nova Scotia Health Research Foundation. Charles Bernstein was supported in part by the Bingham Chair in Gastroenterology.

Potential competing interests: None.

© The American College of Gastroenterology 2017. All Rights Reserved.
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