Journal of Pediatric Gastroenterology & Nutrition:
Original Articles: Gastroenterology
Epidemiology of Inflammatory Bowel Disease: Is There a Shift Towards Onset at a Younger Age?
Braegger, Christian P.*; Ballabeni, Pierluigi†; Rogler, Daniela*; Vavricka, Stephan R.‡; Friedt, Michael*; Pittet, Valérie†; the Swiss IBD Cohort Study Group
*Division of Gastroenterology and Nutrition, University Children's Hospital Zurich
†Healthcare Evaluation Unit, Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne
‡Division of Gastroenterology, University Hospital Zurich, Switzerland.
Address correspondence and reprint requests to Prof Christian P. Braegger, Division of Gastroenterology and Nutrition, University Children's Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland (e-mail: firstname.lastname@example.org).
Received 12 May, 2010
Accepted 22 February, 2011
Members of the Swiss IBD Cohort Study Group: Pierluigi Ballabeni, Peter Bauerfeind, Christoph Beglinger, Stefan Begré, José Bengoa, Janek Binek, Daniel Boller, Jan Borovicka, Christian Braegger, Patrick Bühr, Patrick Brun, Bernard Burnand, Rafael Camara, Dominique Criblez, Philippe de Saussure, Lukas Degen, Joakim Delarive, Tobias Ehmann, Matthias Engelmann, Ali El Wafa, Christian Felley, Alain Frei, Remus Frei, Michael Fried, Michael Friedt, Florian Froehlich, Suzanne Gallot-Lavallée, Tilman Gerlach, Martin Geyer, Marc Girardin, Oliver Goetze, Horst Haack, Serger Hediger, Peter Hengstler, Klaas Heyland, Patrick Janiak, Pascal Juillerat, Vera Kessler Brondolo, Christoph Knoblauch, Gerd A. Kullak-Ublick, Michael Manz, Rémy Meier, Christa Meyenberger, Pierre Michetti, Christian Mottet, Christoph Müller, Beat Müllhaupt, Thierry Nicolet, Andreas Nydegger, Isabelle Pache, Franziska Piccoli, Julia Pilz, Valérie Pittet, Ronald Rentsch, Jean-Pierre Rey, Silvia Rihs, Daniela Rogler, Gerhard Rogler, Markus Sagmeister, Bernhard Sauter, Michela Schäppi, Niklaus Schaub, Susanne Schibli, Alain Schoepfer, Franck Seibold, Johannes Spalinger, Philippe Stadler, Michael Steuerwald, Alex Straumann, Michael Sulz, Joël Thorens, John-Paul Vader, Stefan Vavricka, Jürg Vögtlin, Roland Von Känel, Gert Wachter, Jürg Wermuth, Paul Wiesel.
This work was funded by a research grant from the Swiss National Science Foundation (grant no. 3347CO-108792 Swiss IBD Cohort). S.R.V. acknowledges additional research support from the Swiss National Science Foundation (320000-114009/1) and a grant from the Zurich Centre of Integrative Human Physiology.
The authors report no conflicts of interest.
Objectives: Increasing numbers of paediatric and adolescent patients with Crohn disease (CD) and ulcerative colitis (UC) are reported. To determine whether this observation is a consequence of a shift towards onset at a younger age, we analysed retrospective data from patients enrolled in the Swiss IBD Cohort Study (SIBDCS).
Patients and Methods: The SIBDCS is a disease-based cohort in Switzerland, which collects retrospective and prospective data on a large sample of patients with inflammatory bowel disease (IBD). Patients, diagnosed from 1980, were stratified according to diagnosis of CD and UC. Age at disease onset (age at first symptoms and age at diagnosis) was analysed in relation to calendar year of disease onset. Data were extracted from physician and patient questionnaires. Linear regressions of age at disease onset by calendar year of disease onset adjusted by sex, country of birth, and education were performed.
Results: Adjusted regression coefficients for CD and UC were significantly positive, that is, age at disease onset has increased with time. Male sex was associated with an increase in age at disease onset, and birth in Switzerland with a decrease. These associations were statistically significant.
Conclusions: The results from the SIBDCS do not support the hypothesis that disease onset of both CD and UC occur today at a younger age. On the contrary, our results show that there is a significant trend for age at disease onset occurring at an older age today as compared with recent decades. We conclude that the observation of increasing numbers of paediatric and adolescent patients with IBD is not caused by a trend towards disease onset at a younger age, but that this may rather be a consequence of the overall increasing incidence of these conditions.
See “Rising Incidence of Inflammatory Bowel Disease in Young Children: What Does the Future Hold?” by Kunde et al on page 128.
Epidemiological studies report a high and rising incidence of inflammatory bowel disease (IBD) in western and northern Europe and the United States (1–3). An increase in IBD incidence has also been observed recently in eastern and southern Europe as well as in Asia (4). Most data on the epidemiology of paediatric IBD have been published in Europe and the United States (5–7). The majority of these studies report on increasing numbers of paediatric and adolescent patients with Crohn disease (CD) and ulcerative colitis (UC) (8–12), although some studies did not observe any change in incidence (13,14).
To explore the hypothesis that increasing numbers of paediatric IBD are not only a consequence of rising incidence but also of a general shift towards a younger age at disease onset, we analysed data of paediatric and adult patients recruited in the Swiss IBD Cohort Study (SIBDCS).
PATIENTS AND METHODS
The SIBDCS is a disease-oriented cohort of patients with IBD in Switzerland, which is collecting retrospective and prospective data on a large sample of paediatric and adult patients with IBD throughout Switzerland by means of physician and patient questionnaires, starting in November 2006. The study is supported by the Swiss National Science Foundation and approved by local ethical committees (15). Patients are recruited by paediatric and adult gastroenterologists during a routine consultation. Inclusion criteria consist of a diagnosis based on the Lennard-Jones diagnostic criteria, confirmed by radiology, endoscopy, or surgery. Diagnosis must be established at least 4 months before enrollment.
A total of 1910 paediatric and adult patients were recruited between November 2006 and May 2010 in the SIBDCS. Fifty-nine cases were excluded because of missing data on sex, age, or diagnosis. Forty patients, diagnosed as having an indeterminate colitis, were not considered in the analyses. We focused our analyses on the group diagnosed during the past 30 years (1980–2010), excluding therefore another 123 patients. The number of patients included in the present analysis was 1688.
Sociodemographic data were collected at the time of inclusion in the study, both by physician questionnaires (age, sex, diagnosis, calendar year of diagnosis, calendar year at first symptoms) and by patient questionnaires (education, country of birth). All of the data collected for the SIBDCS were entered, controlled, and validated at the cohort data centre.
Calendar year at first symptoms and calendar year at diagnosis were collected both by physician questionnaires and patient questionnaires; no significant differences were observed between physician and patient information. This observation was taken as a quality indicator, showing the reliability of data collection for those 2 variables. Henceforth, we decided to rely on variables from physician questionnaires to perform our analyses. Country of birth was dichotomised into 2 categories: patients born in Switzerland and patients born outside Switzerland. The latter group comprised mainly patients born in countries situated south of the Swiss latitude. Education was grouped into 3 levels: primary level (no education or compulsory school only), secondary level (elementary professional formation, apprenticeship, training school, professional graduate school, diploma school, college or household school), and tertiary level (superior professional formation, technical school, superior professional school or university). This variable was taken as a proxy for the socioeconomic situation of the patients. For paediatric patients, the level was based on the highest level of education of the father or mother.
Patients were stratified according to diagnosis and analyses were performed separately for each diagnosis. Descriptive analyses were made to characterise the patient population studied. Linear regressions were performed between age at first symptoms and age at diagnosis in relation to the calendar year at first symptoms and calendar year at diagnosis, respectively. Crude regression coefficients were calculated and compared with age-, sex- and education-adjusted regression coefficients. Reference categories used for regression modeling were female sex, born outside Switzerland and primary level of education. Regression coefficients are given with 95% confidence intervals (CI). A P value <0.05 was considered statistically significant.
A total of 1688 patients were included in the study: 986 patients with CD, 702 patients with UC. About two-thirds of the patients were recruited at tertiary centres and one-third at a district hospital or a doctor's office/private practice. The sociodemographic characteristics of the study population are shown in Table 1. Nearly half of the patients were males and half were females, with a slightly higher proportion of males with UC and females with CD. Seventy-eight percent of the patients were born in Switzerland and 22% outside Switzerland. More than half of the patients who responded to the education level questions had a secondary education level, 12% had a primary education level, and 30% had a tertiary education level. Patients with CD had a mean age at first symptoms and at diagnosis of 27 and 29 years, respectively, and patients with UC of 31 and 32 years, respectively. Identical mean ages and standard deviations were reported in the patient questionnaire.
Figures 1 and 2 and associated tables show results from unadjusted and adjusted linear regressions for both CD and UC. Considering unadjusted regressions, the tables show that there was no evidence for a linear association either between log age at diagnosis and year of diagnosis or between log age at first symptoms and year of first symptoms.
The table associated with Figure 1A shows that there is evidence for a linear association between log age at diagnosis and year at diagnosis for CD, and that male sex and being born in Switzerland were also significantly associated with log age at diagnosis. Year of diagnosis (coefficient 0.011; 95% CI [0.007–0.015]) as well as male sex (coefficient 0.078; 95% CI [0.015–0.140]) are positively correlated with log age at diagnosis, whereas being born in Switzerland is negatively correlated with log age at diagnosis (coefficient −0.130; 95% CI [−0.201 to −0.050]). Education is not associated with log age at diagnosis, considering the linear model. The same observations were made for UC (Fig. 1B), except for male sex, which was not significantly associated with log age at diagnosis (coefficient 0.058; 95% CI [−0.010 to 0.126]). The low R2 values show that only 6% to 7% of the observed variation can be explained by a linear regression.
Adjusted linear regressions show significant association with the same variables, considering age at first symptoms and year of first symptoms (Fig. 2A and B). Additionally, however, male sex was significantly associated with a linear increase in log age at first symptoms both for CD and UC. The low R2 values again show that only 5% to 8% of the observed variation can be explained by the linear regression.
Table 2 shows that the proportion of patients with CD with first symptoms at younger than 18 years has increased in the 2000s (24.8%) compared with the 1980s (14.5%); no difference in proportion was observed for patients with first symptoms at older than 40 years (17.6% vs 17.4%); however, for UC, the proportion of patients with first symptoms at older than 40 years has increased from 14.3% in the 1980s to 27.0% in the 2000s (Table 3). An increased proportion was also observed for young patients with UC. Considering year at diagnosis, we observed an increase in the proportion of patients, with more than 40 diagnosed as having CD (12.3%–22.5%; Table 2), and an increase of patients, with both <18 (9.0–12.9%) or >40 (16.4–27.5%) diagnosed as having UC between the 1980s and the 2000s (Table 3). All of the observed associations were statistically significant.
Our data have been collected in the course of the large SIBDCS. The results of our analysis do not support the hypothesis that altogether first symptoms and diagnosis of both patients with CD and patients with UC in Switzerland occur today at a younger age. On the contrary, the results of the SIBDCS show, taking account of sex, country of birth, and education, that there is a slow but significant trend for both first symptoms and diagnosis occurring at an older age today compared with the last 3 decades. A linear relation between log age and year of event cannot explain most of the observed phenomena, which seem to be additionally complex.
The analysis of patient's age at first symptoms and diagnosis by decade revealed that in CD—despite the fact that altogether there is significant association for first symptoms and diagnosis occurring at an older age—the number of younger patients (younger than 18 years) has increased significantly from the 1980s to the 2000s. The same observation was made in UC; however, we also observed increasing numbers of patients with UC with first symptoms at an older age (older than 40 years). The trend for both first symptoms and diagnosis occurring at an older age today compared with the last 3 decades in IBD may therefore be caused by both a rise in the number of younger and older patients, with older patients having a stronger effect.
The limitations of our study include a potential sampling bias, caused by the late acquisition of data for patients diagnosed earlier in the 20th century. For example, the data of some of these patients diagnosed in the 1980s at an older age may not have been collected because some of the patients may already have died at the time of the start of data collection for the SIBDCS in the year 2006. Nevertheless, the regression analysis of our data shows that there is a significantly linear increase in log age with year. A further limitation includes a potential selection bias, caused by the fact that a majority of the patients in the SIBDCS were recruited in a tertiary referral centre. Therefore, patients with mild disease may not have been included in this study; however, there is no indication that patients with mild disease may be diagnosed at a younger age compared with patients with moderate-to-severe disease.
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Crohn disease; epidemiology; ulcerative colitis
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