Inflammatory Bowel Disease Increases the Risk of Venous Thromboembolism in Children: A Population-Based Matched Cohort Study

Author:

Kuenzig M Ellen12ORCID,Bitton Alain3,Carroll Matthew W4,Kaplan Gilaad G5,Otley Anthony R6,Singh Harminder789,Nguyen Geoffrey C101112ORCID,Griffiths Anne M113,Stukel Therese A1012,Targownik Laura E11,Jones Jennifer L14,Murthy Sanjay K1015161718,McCurdy Jeffrey D151617,Bernstein Charles N78ORCID,Lix Lisa M1920,Peña-Sánchez Juan Nicolás21ORCID,Mack David R222324,Jacobson Kevan25ORCID,El-Matary Wael26ORCID,Dummer Trevor J B27,Fung Stephen G102324,Spruin Sarah10,Nugent Zoann7,Tanyingoh Divine5,Cui Yunsong14,Filliter Christopher28,Coward Stephanie5,Siddiq Shabnaz102324,Benchimol Eric I12101322ORCID

Affiliation:

1. SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada

2. Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada

3. McGill University Health Centre, Division of Gastroenterology and Hepatology, Montreal, Québec, Canada

4. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada

5. Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada

6. Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada

7. Univeristy of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada

8. Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

9. Research Institute at CancerCare Manitoba, Winnipeg, Manitoba, Canada

10. ICES, Toronto, Ontario, Canada

11. Mount Sinai Hospital Centre for Inflammatory Bowel Disease, Department of Medicine, University of Toronto, Toronto, Ontario, Canada

12. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada

13. Department of Paediatrics, and Institute of Health Policy, Management and Evaluation University of Toronto, Toronto, Ontario, Canada

14. Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada

15. Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada

16. Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

17. Division of Gastroenterology, The Ottawa Hospital IBD Centre, Ottawa, Ontario, Canada

18. School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada

19. Department of Community Health Sciences, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

20. George & Fay Yee Centre for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada

21. Department of Community Health & Epidemiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

22. Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada

23. CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, CHEO, Ottawa, Ontario, Canada

24. CHEO Research Institute, Ottawa, Ontario, Canada

25. Department of Pediatrics, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada

26. Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada

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

28. Lady Davis Institute of Medical Research, Jewish General Hospital, Montreal, Québec, Canada

Abstract

Abstract Background and Aims Although venous thromboembolism [VTE] is a well-known complication of inflammatory bowel disease [IBD] in adults, limited data exist on the risk in children. We report the incidence of VTE among children with and without IBD. Methods We conducted a matched cohort study within a distributed network of population-based Canadian provincial health administrative databases. Children <16 years diagnosed with IBD were identified using validated algorithms from administrative data in Alberta, Manitoba, Nova Scotia, Ontario and Québec and compared to age- and sex-matched children without IBD. Hospitalizations for VTE within 5 years of IBD diagnosis were identified. Generalized linear mixed-effects models were used to pool province-specific incidence rates and incidence rate ratios [IRR] with 95% confidence intervals [CI]. Hazard ratios [HR] from Cox proportional hazards models were pooled with fixed-effects meta-analysis. Results The 5-year incidence of VTE among 3593 children with IBD was 31.2 [95% CI 23.7–41.0] per 10 000 person-years [PY] compared to 0.8 [95% CI 0.4–1.7] per 10 000 PY among 16 289 children without IBD [unadjusted IRR 38.84, 95% CI 16.59–90.83; adjusted HR 22.91, 95% CI 11.50–45.63]. VTE was less common in Crohn’s disease than ulcerative colitis [unadjusted IRR 0.47, 95% CI 0.27–0.83; adjusted HR 0.52, 95% CI 0.29–0.94]. The findings were similar for deep vein thrombosis and pulmonary embolism when comparing children with and without IBD. Conclusions The risk of VTE is much higher in children with IBD than controls without IBD. While the absolute risk is low, we found a higher incidence rate than previously described in the pediatric literature. Conference Presentation: An abstract based on the data included in this paper was presented at Canadian Digestive Diseases Week [Montréal, Canada] in March 2020.

Funder

Crohn's and Colitis Canada

Canadian Institutes of Health Research

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,General Medicine

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