Globally rising incidence rates of paediatric-onset inflammatory bowel disease (IBD) have been observed in both developed and developing nations during the last 2 decades (1). The increasing incidence of paediatric IBD in most countries seems to be resulting from a rising incidence of Crohn disease (CD). The highest incidence rates of paediatric IBD have been observed in the Scandinavian countries and Canada (2–4).
The cause of IBD is incompletely understood. Twin studies have stressed the importance of genetic factors in the development of disease (5). Genome-wide association studies have discovered >160 susceptibility loci associated with IBD (6). The increasing incidence of paediatric IBD indicates that environmental risk factors are also involved in disease pathogenesis; however, genetic and environmental factors have failed to fully explain the reported differences in paediatric IBD incidence rates between and within different regions of the world (7,8).
Our group reported a sharp increase in paediatric IBD incidence in northern Stockholm County, Sweden, during 1990–2001 (2). We reported a shift in presentation from ulcerative colitis (UC) to CD. The incidence of paediatric IBD in northern Stockholm during 1999–2001 was higher than reported from any other region in the world. Here we present an update on the incidence of paediatric IBD in this catchment area during 2002–2007.
Background Area and Population
The catchment area for this general population–based study covered all residents younger than 16 years in northern Stockholm County (188,437 individuals younger than 16 years of age in 2005).
Data on the population in the catchment area during the study period were obtained from Statistics Sweden and the City of Stockholm. Calculated yearly incidence rates were standardised to the Swedish population standard for 2002 by sex and age.
Patients and Diagnosis
Astrid Lindgren Children's Hospital is the only paediatric gastroenterology unit in northern Stockholm County. Paediatric gastroenterology units in southern Stockholm County and in bordering counties were asked to report paediatric patients with IBD living in northern Stockholm during the study period.
The Swedish health care system recommends that children younger than 18 years should be treated by paediatricians. All adult gastroenterology departments within the catchment area were requested to report paediatric patients diagnosed as having IBD during 2002–2007. All of the 6 hospital inpatient and the 3 outpatient gastroenterology clinics responded and confirmed that no patient with IBD younger than 16 years had been treated at their units during the study period.
Prospectively recorded medical records of all patients ages 0 to 15 years diagnosed during 2002–2007 as having suspected paediatric IBD living in northern Stockholm, at time of diagnosis, were examined. Patients were diagnosed according to the criteria that were used in earlier incidence studies from Stockholm and Sweden (2,9). A diagnosis of IBD unclassified (IBDU) was recorded if histology and endoscopy or radiography compatible with IBD were observed, but these findings did not fulfill the criteria of UC or CD.
Endoscopic and histological findings were interpreted using the updated recommendations on how to differentiate childhood UC from CD (10).
The revision was undertaken by 2 experienced clinicians (H.H., P.M.), of whom 1 (H.H.) was also responsible for the diagnostic assessment in the earlier incidence study for northern Stockholm County in 1990–2001 (2). When the diagnosis was questioned, the gastrointestinal biopsies were examined by the same pathologist, specialised in gastrointestinal pathology, who was also the responsible pathologist and author in the earlier study.
After revision, 133 children fulfilled the criteria for IBD in northern Stockholm County during 2002–2007. Of the 133 children, 128 were diagnosed and followed at our unit. Among the 5 patients diagnosed elsewhere, 4 patients were diagnosed in non–hospital-based outpatient gastroenterology departments and then referred to our unit for follow-up. One patient who resided in Stockholm County was diagnosed and studied throughout the study period in a paediatric gastroenterology unit in a neighbouring county. Patients in the cohort were followed up for a median of 5.8 years (range 1.0–8.9 years). Ethical approval for the study was given by the regional ethical review board in Stockholm (Dnr 04–915/1 and Dnr 2009/1435–31/3).
A total of 132 patients were diagnosed using complete colonoscopy, whereas 1 patient was diagnosed using sigmoidoscopy only. The ileum was intubated in 111 (84%) patients at the diagnostic examination. Diagnostic gastroscopy was performed in all but 2 patients (98%). Structured biopsy sampling was performed at all endoscopies.
Of the 133 patients, 127 were re-endoscoped during follow-up. Of the 6 children (3 CD and 3 UC) that were not re-endoscoped, 3 underwent surgery (1 colectomy and 2 ileocaecal resections) and 2 moved abroad. At re-endoscopy, the ileum could be intubated in all of the patients whose small bowels were not inspected at the diagnostic endoscopy.
Of the 133 patients diagnosed as having paediatric IBD, 104 (78%) were examined with small bowel imaging within the first year from diagnosis. At the end of follow-up, 120 (90%) of the 133 patients had been examined with small bowel imaging (90 [75%] patients with barium follow-through and 30 [25%] with magnetic resonance tomography).
Date of first endoscopy or small bowel imaging demonstrating intestinal inflammation was defined as the date of diagnosis. In the 1 patient who presented with orofacial granulomatosis, the diagnostic date was set as the date of oral biopsy.
Patient phenotype was defined within the framework of the Paris classification (11) with 1 exception: paediatric IBD was defined as younger than 16 years because this was the criterion used in former incidence studies from Sweden and northern Stockholm.
Phenotyping for disease extension, localisation, and behaviour at diagnosis was based upon information acquired at diagnostic endoscopy and small bowel imaging. In the 2 patients who were not examined with upper endoscopy at diagnosis and the 4 patients who were neither ileum intubated at diagnostic endoscopy nor examined with small bowel imaging within the first year from diagnosis, disease localisation at diagnosis was estimated from results on re-endoscopy.
Data were analysed using SPSS (version 15.0, SPSS Inc, Chicago, IL). Continuous variables that were not normally distributed are presented as median and range. Categorical variables are presented as proportions and were compared using the χ 2 test or Fisher exact test for small sample sizes.
Incidence rates were age and sex standardised for the Swedish population standard of 2002. Confidence intervals were calculated assuming a Poisson distribution for incidence rate (12) and then weighted and scaled to give the interval for the directly standardised rate (13).
Trends in incidence rate were calculated using a Poisson regression model. For the study period 2002–2007, annual incidence rates were analysed. For comparison with our earlier study covering 1990–2001 (2), incidence rates for every 3-year period were used as the dependent variable. Sex and age (younger than 8 years, 8 years and older) were included in the model as categorical variables and calendar year as a continuous variable. Results from the model are presented as percent change in incidence rate per year. P values <0.05 were considered statistically significant.
Table 1 shows the characteristics of all 133 children diagnosed as having IBD in accordance with the Paris classification in northern Stockholm during 2002–2007. During the study period, 96 patients (72%) were diagnosed as having CD, 29 (22%) as having UC, and 8 (6%) as having IBDU. In patients with CD, isolated colonic disease (L2) was the most common disease location. Panenteric disease (L3 + L4) presentation was observed in 9% (9) of the children with CD. Pancolitis (E4) was the most common disease presentation in patients with UC.
Table 2 shows incidence figures of paediatric IBD in northern Stockholm during 2002–2007. The sex- and age-standardised incidence (per 105 person-years) of IBD was 12.8 (95% confidence interval [CI] 10.8–15.2), 9.2 (95% CI 7.5–11.2) for CD, and 2.8 (95% CI 1.9–4.0) for UC.
No significant temporal trend was observed for the incidence of IBD (3.2% [95% CI −6.6 to 14.0, P = 0.54]) during the study period. Although the CD rates started to decline at the end (2005–2007) of the study period, no statistically significant temporal trend in CD incidence (−8.8% [95% CI −18.6 to 3.0, P = 0.14]) was observed for the entire study period. An increasing incidence rate of UC (58.4% [95% CI 22.8–104.3, P < 0.01]) was observed during the study period.
A male predominance, although not statistically significant, was observed for IBD (sex ratio 1.3 [95% CI 0.9–1.8, P = 0.13]). A significant male predominance was observed for CD (sex ratio 1.5 [95% CI 1.0–2.3, P = 0.04]). The highest incidence was seen among children between 15 and 16 years of age for both CD and UC.
The initial diagnosis was changed in 7 of the 133 children after re-endoscopy. Five patients that were initially classified as having IBDU were considered to fulfill the criteria for CD (n = 4) or UC (n = 1). In one patient the diagnosis was changed from UC to CD, and in another patient the change was made in the opposite direction.
Comparison With Earlier Studies
Table 3 presents incidence rates with 95% CI for paediatric IBD in northern Stockholm County during 1990–2007 divided into 6-year periods (2). For comparison, incidence rates with corresponding CIs from some recent paediatric population–based studies are also presented in the table.
The incidence rate of IBD in northern Stockholm County during the study period (2002–2007) was significantly higher than during the previous 6-year period (1996–2001) (4.8% [95% CI 0.3–9.5, P < 0.05]). When the entire study period of 1990–2007 was analysed, we found significant statistically temporal trends for increasing incidence rates of both IBD (6.6% [95% CI 4.1–9.2, P < 0.01]) and CD (7.7% [95% CI 4.7–10.8, P < 0.01]). No significant temporal trend in the incidence rate of UC (3.3% [95% CI −1.4 to 8.1, P = 0.17]) was detected for the entire study period of 1990–2007. The incidence of paediatric IBD in northern Stockholm County between 1990 and 2007 is presented in Figure 1.
The incidence rate of paediatric IBD in northern Stockholm County, 2002–2007, was higher than reported from most other regions, although similar to rates observed in contemporary studies from Canada (4,14,15), Norway (16), and Finland (3). The predominance of CD over UC in northern Stockholm County is consistent with most population-based studies on paediatric IBD (1) but in contrast to the ratio observed in some contemporary Scandinavian studies (3,17,18) (Table 3).
In this study, we present an update of the incidence of paediatric IBD in northern Stockholm during 2002–2007. The incidence of paediatric IBD in northern Stockholm during 2002–2007 was significantly higher than that observed in our earlier study covering 1990–2001 (2). Equally high incidence rates of childhood-onset IBD have been reported from Canada (4,14,15), Norway (16), and Finland (3). Interestingly, significantly lower incidence rates have been observed in a contemporary paediatric population from neighbouring Denmark (19) (Table 3). This finding is perhaps surprising because the genetic, cultural, and socioeconomic differences between the 2 Scandinavian countries are small; however, different temporal trends in incidence rates have previously been observed in adult Scandinavian populations where the shift from low to high incidence of for both CD and UC seemed to develop approximately 15 years earlier in Sweden than in Denmark (20). The observed incidence rate of paediatric IBD in northern Stockholm during 2002–2007 was at least twice as high as the rate reported in the large studies from Great Britain (21) and northern France (22) that predate our study period (Table 3).
The incidence rate of childhood-onset CD in northern Stockholm during 2002–2007 was also significantly higher than that observed in our 1990–2001 study and higher than have been reported from most other regions in the world. The incidence of CD in our study for the subgroup of children ages 8 to 15 years (13.9/105 person-years (95% CI 11.1–17.2) equalled that observed among young adults (ages 16–30 years) in Stockholm County during the period 1990–2001 (12.3/105 person-years (95% CI 10.1–14.6) (23); however, toward the end of the study period, we observed a decrease in CD incidence indicating that the CD epidemic in northern Stockholm may have reached a peak. The observed plateauing incidence of CD in our study contrasts with most contemporary incidence reports, including those from the other Scandinavian countries that demonstrate persistent increasing incidence rates of paediatric CD (3,4,14,16,19,24–26). Future studies will establish whether we have observed a permanent shift from low to high incidence in the paediatric population in northern Stockholm.
The predominance of pure colonic disease observed among the children diagnosed as having CD in northern Stockholm is consistent with the results from our earlier incidence study (2); however, our findings contrast with most population-based studies from both Europe and North America, where intestinal inflammation restricted to colon is reported to be found in <40% of the patients at diagnosis (16,19,27,28). It is uncertain whether this could be explained through a patient population from a high incidence region or rather trough differences in phenotype classification. It should, however, be noted that this report is one of the first population-based childhood-onset IBD studies that have used the Paris classification system (11).
The distinctly higher incidence rate of CD than UC during the study period is consistent with our earlier results and some other epidemiological studies on paediatric IBD incidence during the last decade, from Norway, Scotland, and the United States (16,25,28); however, contemporary studies from Finland and Denmark report that UC is more frequently diagnosed than CD (3,17,18). Some studies in Canada have reported a dominance of CD (3) and others a dominance of UC (14), despite being contemporaneous. The inconsistent observations between and within countries suggest the possibility that diagnostic criteria may not be universal, although the reported variation between countries could reflect real differences. Misclassification could be expected to be more common within childhood-onset IBD because colitis is the most common disease presentation in children with CD and thus makes differentiation from UC more complicated.
Despite the predominance of CD, we observed an increasing incidence of UC during the study period that was statistically significant. An increasing incidence of UC has only been observed in a few studies during the last decade (3,24–26). It is possible that the updated recommendations on differentiation of childhood UC from CD (10) may have influenced the interpretation of endoscopic findings over time in our study; however, none of the patients with UC diagnosed during the late study period presented with findings (eg, caecal patch, relative rectal sparing) that formerly may have been considered as manifestations of CD. It is too early to conclude whether our observation is consistent with a true change in incidence pattern of UC because no trend for the incidence of UC could be detected when analysing our data since 1990. Further follow-up studies on the incidence of childhood-onset IBD in Stockholm are required to resolve this.
The strength of our study is that it presents the results from a relatively large general population-based cohort from a single centre with a long history of managing paediatric IBD. The organisation of the Swedish health care system makes it improbable that any patients younger than 16 years were diagnosed and followed at an adult gastroenterology department and therefore not identified by our study. Patients were followed for a median of 5.8 years after diagnosis, and all of the children were examined with gastroduodenoscopy and ileocolonoscopy at least once and in most cases twice during follow-up. The methods used to ascertain and confirm diagnoses ensured that the results were consistent with our earlier incidence study.
A weakness is the relatively small number of patients within the cohort, which limits the precision to detect smaller changes in incidence over time. Studies based on national registers or health administrative databases could gather much larger patient cohorts and thus provide statistical power to detect small and short-term changes in incidence rate; however, register studies could be less reliable because discrimination between IBD and other causes for enterocolitis, as well as between UC and CD, is often difficult.
It is possible that the reported differences in incidence rate of childhood-onset IBD and in the ratio of CD/UC between populations could be explained by differences in genetic or environmental factors; however, the Finnish findings indicate that differences in case ascertainment and validation methods when estimating incidence rates among adolescent patients with IBD (who may be treated by paediatric or adult gastroenterologists) may sometimes be important explanatory factors. Two studies covering the same time period and parts of the same population produced significantly different incidence rates: one a regional hospital-based study from southern Finland (18) and the other a national register-based study (3). The reported striking differences in CD/UC ratio within regions and between neighbouring countries, comparable in socioeconomic and genetic distributions, also imply that these may rather reflect variation in case ascertainment and classification rather than true differences in incidence. The creation of common diagnostic criteria for paediatric IBD would allow international comparisons to be made with greater certainty.
In this study, we conclude that the incidence of paediatric IBD in northern Stockholm during 2002–2007 was significantly higher than that observed in our earlier study covering 1990–2001. The rapid increase in CD incidence that we observed during 1990–2001 seems though to have levelled out, although the incidence rate during 2002–2007 was continuously higher than reported from most other areas in the world. Even though CD was still the predominant diagnosis, the observed increase in the incidence of UC during the study period is noteworthy and calls for further epidemiological studies in northern Stockholm.
1. Benchimol EI, Fortinsky KJ, Gozdyra P, et al. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis
2. Hildebrand H, Finkel Y, Grahnquist L, et al. Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 1990–2001. Gut
3. Lehtinen P, Ashorn M, Iltanen S, et al. Incidence trends of pediatric inflammatory bowel disease in Finland, 1987–2003, a nationwide study. Inflamm Bowel Dis
4. Benchimol EI, Guttmann A, Griffiths AM, et al. Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence from health administrative data. Gut
5. Halfvarson J, Bodin L, Tysk C, et al. Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. Gastroenterology
6. Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature
7. Henderson P, van Limbergen JE, Wilson DC, et al. Genetics of childhood-onset inflammatory bowel disease. Inflamm Bowel Dis
8. Ng SC, Bernstein CN, Vatn MH, et al. Geographical variability and environmental risk factors in inflammatory bowel disease. Gut
9. Hildebrand H, Brydolf M, Holmquist L, et al. Incidence and prevalence of inflammatory bowel disease in children in south-western Sweden. Acta Paediatr
10. Bousvaros A, Antonioli DA, Colletti RB, et al. Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America. J Pediatr Gastroenterol Nutr
11. Levine A, Griffiths A, Markowitz J, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis
12. Breslow NE, Day NE. Statistical Methods in Cancer Research. Volume II: The Design and Analysis of Cohort Studies. Lyon:International Agency for Research on Cancer, World Health Organization; 1987.
13. Dobson AJ, Kuulasmaa K, Eberle E, et al. Confidence intervals for weighted sums of Poisson parameters. Stat Med
14. Grieci T, Butter A. The incidence of inflammatory bowel disease in the pediatric population of Southwestern Ontario. J Pediatr Surg
15. Bernstein CN, Wajda A, Svenson LW, et al. The epidemiology of inflammatory bowel disease in Canada: a population-based study. Am J Gastroenterol
16. Perminow G, Brackmann S, Lyckander LG, et al. A characterization in childhood inflammatory bowel disease, a new population-based inception cohort from South-Eastern Norway, 2005–07, showing increased incidence in Crohn's disease. Scand J Gastroenterol
17. Jakobsen C, Wewer V, Urne F, et al. Incidence of ulcerative colitis and Crohn's disease in Danish children: still rising or levelling out? J Crohns Colitis
18. Turunen P, Kolho KL, Auvinen A, et al. Incidence of inflammatory bowel disease in Finnish children, 1987–2003. Inflamm Bowel Dis
19. Jakobsen C, Paerregaard A, Munkholm P, et al. Pediatric inflammatory bowel disease: increasing incidence, decreasing surgery rate, and compromised nutritional status: a prospective population-based cohort study 2007–2009. Inflamm Bowel Dis
20. Ekbom A. The epidemiology of IBD: a lot of data but little knowledge. How shall we proceed? Inflamm Bowel Dis
2004; 10 (suppl 1):S32–S34.
21. Sawczenko A, Sandhu BK, Logan RF, et al. Prospective survey of childhood inflammatory bowel disease in the British Isles. Lancet
22. Auvin S, Molinie F, Gower-Rousseau C, et al. Incidence, clinical presentation and location at diagnosis of pediatric inflammatory bowel disease: a prospective population-based study in northern France (1988–1999). J Pediatr Gastroenterol Nutr
23. Lapidus A. Crohn's disease in Stockholm County during 1990–2001: an epidemiological update. World J Gastroenterol
24. Orel R, Kamhi T, Vidmar G, et al. Epidemiology of pediatric chronic inflammatory bowel disease in central and western Slovenia, 1994–2005. J Pediatr Gastroenterol Nutr
25. Henderson P, Hansen R, Cameron FL, et al. Rising incidence of pediatric inflammatory bowel disease in Scotland. Inflamm Bowel Dis
26. Hope B, Shahdadpuri R, Dunne C, et al. Rapid rise in incidence of Irish paediatric inflammatory bowel disease. Arch Dis Child
27. Vernier-Massouille G, Balde M, Salleron J, et al. Natural history of pediatric Crohn's disease: a population-based cohort study. Gastroenterology
28. Kugathasan S, Judd RH, Hoffmann RG, et al. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. J Pediatr