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Inflammatory Bowel Disease in Children of Manitoba: 30 Years’ Experience of a Tertiary Center

El-Matary, Wael*; Moroz, Stan P.*; Bernstein, Charles N.

Journal of Pediatric Gastroenterology and Nutrition: December 2014 - Volume 59 - Issue 6 - p 763–766
doi: 10.1097/MPG.0000000000000525
Original Articles: Gastroenterology

Objectives: The aim of this study was to describe the incidence and prevalence of inflammatory bowel disease (IBD) in children <17 years of age in 30 years from 1978 to 2007.

Methods: From January 1, 1978, to December 31, 2007, the sex- and age-adjusted annual incidence and prevalence of pediatric IBD per 100,000 population were calculated based on the pediatric IBD database of the only pediatric tertiary center in the province. The annual health statistics records for the Province of Manitoba were used to calculate population estimates for the participants. To ensure validity of data, the University of Manitoba IBD Epidemiology Database was analyzed for patients <17 years of age from 1989 to 2000.

Results: The sex- and age-adjusted incidence of pediatric Crohn disease has increased from 1.2/100,000 in 1978 to 4.68/100,000 in 2007 (P < 0.001). For ulcerative colitis, the incidence has increased from 0.47/100,000 in 1978 to 1.64/100,000 in 2007 (P < 0.001). During the same time period, the prevalence of Crohn disease has increased from 3.1 to 18.9/100,000 (P < 0.001) and from 0.7 to 12.7/100,000 for ulcerative colitis (P < 0.001). During the last 5 years of the study the average annual incidence of IBD in urban patients was 8.69/100,000 as compared with 4.75/100,000 for rural patients (P < 0.001).

Conclusions: The incidence and prevalence of pediatric IBD are increasing. The majority of patients were residents of urban Manitoba, confirming the important role of environmental factors in the etiopathogenesis of IBD.

*Section of Pediatric Gastroenterology and Manitoba Institute of Child Health, Departments of Pediatrics, Winnipeg, Manitoba, Canada

Section of Gastroenterology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

Address correspondence and reprint requests to Wael El-Matary MD, MSc, Section of Pediatric Gastroenterology, Department of Pediatrics, Manitoba Institute of Child Health, Faculty of Medicine, University of Manitoba, AE 408, Health Sciences Centre, 840 Sherbrook St, Winnipeg, Manitoba, Canada R3A 1S1 (e-mail: welmatary@hsc.mb.ca).

Received 23 January, 2014

Accepted 22 July, 2014

W.E.-M. is supported by a grant from the Manitoba Institute of Child Health and Children's Hospital Foundation, Winnipeg, Manitoba, Canada.

The authors report no conflicts of interest.

Inflammatory bowel disease (IBD) encompasses 2 related but distinct disorders: Crohn disease (CD) and ulcerative colitis (UC). CD is a chronic, idiopathic, transmural, patchy, inflammation of 1 or more segments of the digestive tract; UC is a chronic, idiopathic, diffuse mucosal inflammatory disease of the colon; and IBD type unclassified (IBD-U) is reserved for cases of colitis in which findings are not sufficient to allow differentiation between CD and UC (1). IBD is considered to be a disease of immune dysregulation, occurring in people with the appropriate genetic predisposition as a response to environmental triggers such as infection (2). UC and CD are diseases of young people, with a peak incidence in the second and third decades of life. Twenty-five percent of all cases usually present in childhood and adolescence.

The incidence of IBD appears to have risen in the last 20 years (1–3). Evidence from Europe and the United Kingdom has documented this increase (4–10). A systematic review of epidemiological studies of IBD concluded that the highest annual incidence of UC in Europe was 24.3/100,000 person-years with a prevalence of 505/100,000 people (3), and for CD, the highest annual incidence of was 12.7/100,000 person-years with a prevalence of 322/100,000 people. In North America, the highest annual incidence of UC was 19.2/100,000 person-years with a prevalence of 249/100,000 people (3), and for CD, the highest annual incidence of was 19.2/100,000 person-years with a prevalence of 319/100,000 people (3).

More data on the epidemiology of IBD in children from North America have become available (11). A study from Canada showed that Ontario has one of the highest incidence rates of pediatric-onset IBD (11.4/100,000) (12).

Our center has developed a population-based IBD database that dates back to 1984 (13). Although children were included in this administrative database, we had the opportunity to review a population-based clinical database that dates back to 1978.

We present herein our 30-year experience with pediatric IBD in the Winnipeg Children's Hospital (WCH), the only tertiary pediatric care facility in Manitoba, a central Canadian province. Our emphasis is on the epidemiological characteristics of our patient population and changes over time.

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METHODS

The records of all of the children and adolescents referred to the WCH from January 1, 1978 to December 31, 2007, who were diagnosed as having IBD, were reviewed. Accurate identification of all new cases diagnosed as having IBD from Manitoba was made. Although referrals were received from adjacent provinces of Saskatchewan and northern Ontario, and from the Nunavut region of the Northwest Territories, only Manitoba residents were considered in this study. Only Manitoba residents <17 years of age at diagnosis were included in the study because older children were mostly referred to adult gastroenterologists.

During most of the study period (January 1978–May 2003), 1 pediatric gastroenterologist (S.P.M.) served this referral area. Patients were assigned to 1 of 3 diagnostic categories: CD, UC, or IBD-U. The date of diagnosis was assigned as the date the diagnosis was considered definitive.

The diagnosis of IBD was made based on the combination of clinical picture, laboratory investigations, imaging studies and endoscopy with colonoscopy, and histopathology. Diagnostic imaging included barium series, white blood cell scan, computed tomography scan, and abdominal ultrasound. Laboratory investigations included blood and stool (negative infection screen) investigations. Blood tests included hemoglobin, white blood cell count with differential, serum albumin, erythrocyte sedimentation rate, and C-reactive protein. Serum anti-Saccharomyces cerevisiae antibodies and perinuclear anti-neutrophil cytoplasmic antibodies were included in the diagnostic assessment since January 2001.

Verification of diagnosis with data validation was ensured through reviewing the University of Manitoba IBD Epidemiology Database. This database is an administrative database that includes all people in Manitoba with IBD. Details on how this database was initiated and validated were previously published (13). For the sake of this study, data were analyzed for patients <17 years of age at diagnosis from January 1, 1989 December 31, 2000. For case verification, we accessed the University of Manitoba IBD Clinical and Research Centre clinic database (an adult clinic) to discern whether there were other cases diagnosed as children who may have been missed. We verified diagnoses of those children who were diagnosed at WCH and were studied in this adult clinic.

The sex- and age-adjusted annual incidence and prevalence per 100,000 population were determined from January 1, 1978 to December 31, 2007. Province of Manitoba annual health statistics were used to calculate population estimates for the participants (14). Statistics Canada definitions of urban and rural Manitoba (population and dwelling counts) were used to calculate the incidence of IBD in urban versus rural Manitoba (15,16).

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Statistical Analysis

Poisson regression analysis (using time of diagnosis as the predicting variable) was used to analyze incidence and prevalence to control for age group and sex. The Fisher exact test was used when appropriate to compare dichotomous variables (eg, sex). Log-linear modeling was used for comparing rural and urban incidence for the entire study period. All of the analyses were performed using SAS 9.1.3 (SAS Institute, Cary, NC).

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Ethical Considerations

The study protocol was approved by the health research ethics board of the University of Manitoba.

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RESULTS

During the 30-year study period, 397 patients with IBD, of whom 221 (56%) were boys, were studied at the WCH. A total of 233 (59%) had CD, 141 (35%) UC, and 23 (6%) IBD-U. The administrative population database did not identify other patients <17 years of age who were not included in our population from 1989 to 2000.

The median age at diagnosis was 13 years, range 2 to 16 (Fig. 1). Eighty-eight (22%) children were ≤10 years of age at diagnosis (P < 0.001), and 9 (2%) were ≤5 years.

FIGURE 1

FIGURE 1

Although UC was more common in children ≤10 years of age at diagnosis (early-onset IBD), CD was more common in older children (P = 0.018) (Fig. 2).

FIGURE 2

FIGURE 2

There was a male predominance in children with CD (P = 0.04), but not for UC or IBD-U. Table 1 summarizes the sex ratios by diagnosis for the entire study group and compares patients ≤10 years at diagnosis with the older patients. Of note is that male-to-female (M:F) sex ratio in Manitoban children <17 years remained constant at 1.05 during the study period (14).

TABLE 1

TABLE 1

The total number of newly diagnosed patients with IBD has constantly increased during the study period (Fig. 3). Although the number of new patients increased, the proportion of patients by diagnosis changed. CD comprised on average 70% of patients during the first 10 years but only 58% during the next 20 years.

FIGURE 3

FIGURE 3

The sex- and age-adjusted incidence of pediatric CD has increased from 1.2 (95% confidence interval [CI] 0.06–7.2)/100,000 in 1978 to 4.68 (95% CI 1.6–11.7)/100,000 in 2007 (P < 0.001) (Table 2). For UC, the incidence has increased from 0.47 (95% CI 0.07–2.8)/100,000 in 1978 to 1.64 (95% CI 0.06–5.80)/100,000 in 2007 (P < 0.001). During the same time period, the prevalence of CD has increased from 3.1 (95% CI 0.06–8.8) to 18.9 (95% CI 10.7–28.5)/100,000 (P < 0.001) and from 0.7 (95% CI 0.07–4.30) to 12.7 (95% CI 6.90–22.20)/100,000 for UC (P < 0.001) (Table 3).

TABLE 2

TABLE 2

TABLE 3

TABLE 3

Sixty-seven percent of patients lived in urban Manitoba, whereas the rest of the patients lived in rural regions of the province. During the last 5 years of the study, the average annual incidence of IBD in urban patients was 8.69/100,000 (95% CI 4.12–17.08) as compared with 4.75/100,000 (95% CI 1.62–11.67) for rural patients (P < 0.001). This difference was consistent during the entire study period.

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DISCUSSION

IBD is a chronic illness with remissions and relapses. Among major implications of the disease in pediatric age group is its effect on growth and development (17). Moreover, the disease has a major impact on health care use (18). Consequently, it is prudent to characterize the epidemiology of pediatric IBD, which should provide significant insight in health care planning. In 2012, the economic costs related to IBD in Canada were estimated to be $2.8 billion, with direct medical costs exceeding $1.2 billion per annum (18).

There has been consistent evidence indicating an increase in incidence and prevalence of pediatric IBD in many parts of the world (4–10). Our study provides additional evidence that pediatric IBD is also increasing in Canada. Nonetheless, other studies have shown a higher increase in incidence and prevalence of pediatric IBD. Researchers explored the population-based University of Manitoba IBD Epidemiology Database, which includes data on all Manitobans with IBD to 2010, and they reported increasing rates among children (19). This corroborates our findings. A study from Ontario, Canada, has reported an increase in pediatric IBD incidence and prevalence rates from 9.5 and 42.1/100,000 in 1994 to 11.4 and 56.3/100,000 in 2005, respectively (12). These numbers are higher than the numbers we are reporting. The Ontario study used data from a health administrative database.

Interestingly, although the incidence and prevalence of pediatric IBD in Canada are still on the rise, they seem to be relatively stable in the last 10 years in the midwestern US pediatric population (11). It is difficult to know whether this is related to a difference in the population demography or other unknown environmental factors. The median age of diagnosis of 13 years with 22% was ≤10 years at diagnosis and was concordant with the results from other studies (20,21).

Although pediatric incidence rates and prevalence of IBD from the University of Manitoba IBD Epidemiology (administrative) Database previously reported were higher than the present numbers in this study, the age stratification of the former study was 10 to 19 years (13), which may explain that difference.

More than 65% of children diagnosed as having IBD were living in urban Manitoba at the time of diagnosis. This finding is consistent with the conclusions of several studies during the last 4 decades (22,23). Environmental factors have been significantly embraced in the etiopathogenesis of IBD. A systematic review concluded that there is an increased risk for IBD for those who are living in an urban setting, with a pooled incidence rate ratio of 1.17 for UC and 1.42 for CD (24). Several factors have been implemented in explaining the increased risk associated with the urban setting, including lifestyle changes, environmental pollution, and exposure to some industrial agents (22,24,25).

Our study has several strengths. Manitoba has only 1 pediatric tertiary center for the assessment and treatment of children with chronic illness (WCH). All efforts were exhausted to capture all possible pediatric cases of IBD diagnosed during a span of 30 years. It is unlikely that children <17 years of age would have been referred to adult gastroenterologists in Manitoba or diagnosed by their general pediatricians or family physicians. There, however, remains a possibility that some incident cases especially in older pediatric age groups (≥16 years old) were missed and not captured, as suggested in Figure 1.

To validate our data, a review of the University of Manitoba IBD Epidemiology Database revealed that all of the patients diagnosed between 1989 and 2000 were captured. We also undertook a chart review of our cases and those within the University of Manitoba IBD Clinical and Research Centre, where most pediatric patients with IBD attend after their 18th birthday. We did not find adult cases diagnosed in childhood that were not included in our pediatric database.

Another strong point in our study is that the time period this study is covering (30 years) is one of the longest to date. On the contrary, with the long period of the study, there has been an evolution of diagnostic techniques and diagnostic criteria for IBD. This may have affected our results. Nonetheless, we validated our data through checking IBD diagnoses against another well-validated database (13).

In conclusion, we report the epidemiology of pediatric IBD in the central Canadian Province of Manitoba for 30 years. This is the longest duration reported for pediatric IBD thus far. The incidence and prevalence of pediatric IBD are increasing. This fact has extremely important implications for heath care policy decision making. The majority of our patients were residents of urban Manitoba, confirming the important role of environmental etiological factors.

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Acknowledgments

The authors thank Drs Janice Barkey, Pushpa Sathya, and Ray Postuma for their clinical care of children with IBD.

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Keywords:

children; colitis; Crohn; epidemiology; inflammatory bowel disease

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,