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

Eric I Benchimol^{1

2

3

4

5}, Gilaad G Kaplan^{6

7}, Anthony R Otley⁸, Geoffrey C Nguyen^{5

9}, Fox E Underwood^{6

7}, Astrid Guttmann^{5

10}, Jennifer L Jones¹¹, Beth K Potter⁴, Christina A Catley⁵, Zoann J Nugent¹², Yunsong Cui¹¹, Divine Tanyingoh⁶, Nassim Mojaverian⁵, Alain Bitton¹³, Matthew W Carroll¹⁴, Jennifer deBruyn¹⁵, Trevor J B Dummer¹⁶, Wael El-Matary¹⁷, Anne M Griffiths¹⁰, Kevan Jacobson^{18

19}, M Ellen Kuenzig^{1

2

5}, Desmond Leddin¹¹, Lisa M Lix²⁰, David R Mack^{1

2

3}, Sanjay K Murthy^{5

21}, Juan Nicolás Peña Sánchez²², Harminder Singh^{12

23}, Laura E Targownik^{12

23}, Maria Vutcovici¹³, Charles N Bernstein^{12

23}

Affiliations

¹ Children's Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Canada.
² Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada.
³ Department of Pediatrics, University of Ottawa, Ottawa, Canada.
⁴ School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.
⁵ Institute for Clinical Evaluative Sciences, Toronto, Canada.
⁶ Department of Medicine, University of Calgary, Calgary, Canada.
⁷ Department of Community Health Sciences, University of Calgary, Calgary, Canada.
⁸ Department of Pediatrics, Dalhousie University, Halifax, Canada.
⁹ Mount Sinai Hospital Centre for Inflammatory Bowel Disease, Department of Medicine, University of Toronto, Toronto, Canada.
¹⁰ Department of Paediatrics, University of Toronto, Toronto, Canada.
¹¹ Department of Medicine, Dalhousie University, Halifax, Canada.
¹² University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Canada.
¹³ McGill University Health Centre, Division of Gastroenterology, Montreal, Canada.
¹⁴ Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Canada.
¹⁵ Division of Gastroenterology, Department of Pediatrics, University of Calgary, Calgary, Canada.
¹⁶ School of Population and Public Health, University of British Columbia, Vancouver, Canada.
¹⁷ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
¹⁸ Department of Pediatrics, University of British Columbia, Vancouver, Canada.
¹⁹ Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
²⁰ Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada.
²¹ The Ottawa Hospital IBD Centre, Department of Medicine, University of Ottawa, Ottawa, Canada.
²² Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Canada.
²³ Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.

PMID: 28741616
PMCID: PMC5596205
DOI: 10.1038/ajg.2017.208

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

Eric I Benchimol et al. Am J Gastroenterol. 2017 Sep.

. 2017 Sep;112(9):1412-1422.

doi: 10.1038/ajg.2017.208. Epub 2017 Jul 25.

Authors

Affiliations

¹ Children's Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Canada.
² Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada.
³ Department of Pediatrics, University of Ottawa, Ottawa, Canada.
⁴ School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.
⁵ Institute for Clinical Evaluative Sciences, Toronto, Canada.
⁶ Department of Medicine, University of Calgary, Calgary, Canada.
⁷ Department of Community Health Sciences, University of Calgary, Calgary, Canada.
⁸ Department of Pediatrics, Dalhousie University, Halifax, Canada.
⁹ Mount Sinai Hospital Centre for Inflammatory Bowel Disease, Department of Medicine, University of Toronto, Toronto, Canada.
¹⁰ Department of Paediatrics, University of Toronto, Toronto, Canada.
¹¹ Department of Medicine, Dalhousie University, Halifax, Canada.
¹² University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Canada.
¹³ McGill University Health Centre, Division of Gastroenterology, Montreal, Canada.
¹⁴ Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Canada.
¹⁵ Division of Gastroenterology, Department of Pediatrics, University of Calgary, Calgary, Canada.
¹⁶ School of Population and Public Health, University of British Columbia, Vancouver, Canada.
¹⁷ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
¹⁸ Department of Pediatrics, University of British Columbia, Vancouver, Canada.
¹⁹ Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
²⁰ Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada.
²¹ The Ottawa Hospital IBD Centre, Department of Medicine, University of Ottawa, Ottawa, Canada.
²² Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Canada.
²³ Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.

PMID: 28741616
PMCID: PMC5596205
DOI: 10.1038/ajg.2017.208

Erratum in

Corrigendum: Rural and Urban Residence During Early Life Is Associated with a Lower Risk of Inflammatory Bowel Disease: A Population-Based Inception and Birth Cohort Study.
Benchimol EI, Kaplan GG, Otley AR, Nguyen GC, Underwood FE, Guttmann A, Jones JL, Potter BK, Catley CA, Nugent ZJ, Cui Y, Tanyingoh D, Mojaverian N, Bitton A, Carroll MW, deBruyn J, Dummer TJB, El-Matary W, Griffiths AM, Jacobson K, Kuenzig ME, Leddin D, Lix LM, Mack DR, Murthy SK, Sánchez JNP, Singh H, Targownik LE, Vutcovici M, Bernstein CN. Benchimol EI, et al. Am J Gastroenterol. 2017 Sep;112(9):1485. doi: 10.1038/ajg.2017.271. Epub 2017 Aug 22. Am J Gastroenterol. 2017. PMID: 28874854 Free PMC article.

Abstract

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.

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Conflict of interest statement

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.

Figures

**Figure 1**
Incidence rate ratio for (a) IBD, (b) Crohn’s disease, and (c) ulcerative colitis based on rural/urban status at the time of diagnosis.

**Figure 2**
Incidence rate ratio for (a) IBD, (b) Crohn’s disease, and (c) ulcerative colitis based on rural/urban status at birth.

See this image and copyright information in PMC

References

1. Benchimol EI, Fortinsky KJ, Gozdyra P et al. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis 2011;17:423–439. - PubMed
1. Molodecky NA, Soon IS, Rabi DM et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012;142:46–54 e42. - PubMed
1. Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol 2015;12:720–727. - PubMed
1. Aujnarain A, Mack DR, Benchimol EI. The role of the environment in the development of pediatric inflammatory bowel disease. Curr Gastroenterol Rep 2013;15:326. - PubMed
1. Bernstein CN, Rawsthorne P, Cheang M et al. A population-based case control study of potential risk factors for IBD. Am J Gastroenterol 2006;101:993–1002. - PubMed

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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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

MeSH terms

LinkOut - more resources

Full Text Sources

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Medical