Evolution of CD and UC Throughout the Study Period
There was an increase in the incidence of CD from 2.1 to 2.6 (+20% between 1988 to 1990 and 1997 to 1999) that did not reach statistical significance (P = 0.2) (Fig. 4). The UC incidence remained stable throughout the study period (P = 0.8). There was no change of location and type of investigations performed for CD and UC throughout the 12-year study. When the entire population with CD (n = 4013) was considered, the incidence of CD significantly increased from 5.2 to 6.4/105 (+23% between 1988-1990 and 1997-1999) (P < 0.0001). When the entire population with UC (n = 2665) was considered, the incidence of UC significantly decreased from 4.2 to 3.5/105 (−17% between 1988 to 1990 and 1997 to 1999) (P < 0.0001).
Our study shows that the incidence of pediatric CD in Northern France is comparable to previous reports from Brittany (1), Wales (2,3), Scotland (4), Great Brittain (5), Norway (6) and Sweden (7,8), where the incidence ranged from 1.2/105 to 4.9/105 (Fig. 5). Only the study from Denmark reported a much lower incidence of CD of 0.7/105 (9).
Although differing slightly among studies, the diagnostic criteria were very similar to ours, taking into account definite and probable CD and UC. The upper age limit at enrollment ranged from 14 years (9) to 15 years (2,5,6-8), 16 years (4,14,15) and 17 years in the present study and that of Brittany (1). Most studies used hospital-discharge-linked databases. It cannot be excluded that patients with mild or moderate CD or UC might not have been registered in a discharge diagnosis database. Few prospective studies have been published (1,5-8). A registration system was used only in our study and in the studies from Brittany and Great Brittain, with the collection of data made through interviewer practitioners at the gastroenterologist consulting room in our study and that of Brittany, and through a postal questionnaire in the study from Great Brittain (5).
In contrast to CD, the incidence of UC in our study was much lower than that reported in previous studies (Fig. 5), with the exceptions of Brittany (0.57/105) and Wales (0.71-0.75/105); the incidence of UC ranged from 1.56/105 in Scotland to 4.3/105 in Norway. It has been recently shown that the protective effect of appendectomy against UC only occurs when surgery is performed before the age of 20 years (16). The mean rate of appendectomy among French children and adolescents is known to be fourfold higher than that in the other countries of the European Union (17). This high rate of appendectomy among children and adolescents may play a role in the lower incidence of UC in Northern France and Brittany.
The lower incidence of UC compared with CD was observed in most pediatric studies, the CD/UC ratios being 0.1 in Denmark, 1.46 in Scotland, 1.82 in Wales, 2.3 in Stockholm-Sweden, 2.8 in Brittany, 3.09 in our study and 3.11 in Southwest Wales (1983-1993). In most epidemiologic studies of adult patients, the CD/UC ratio is less than 1.
Most reviews and texts indicate that the proportion of childhood cases among all IBD cases is 20% to 30% (18). Our study shows that the percentage of pediatric cases among IBD patients is lower than previously thought. To our knowledge, the only study giving similar information is that of Langholz et al. (9) in Denmark, in which IBD started before the age of 15 years in 6% of CD patients and 7% of UC patients. In our population, 91% of CD patients and 86% of UC patients were older than 10 years, showing that IBD mainly involves older children and adolescents.
It is known that the incidence of CD is higher among females than among males. The predominance of boys in pediatric CD observed in the present study has been reported in the Canadian province of Manitoba and in Great Brittain, Norway, Sweden and Scotland (5-8,15,16,19). This suggests that hormonal changes related to age could be involved in this phenomenon. However, other etiologic factors should be considered.
The question of an increased incidence of CD and UC in children over the last 10 to 20 years remains controversial. While the incidence of UC remained stable in our study, the incidence of CD increased from 2.1 in 1988-1990 to 2.6 in 1997-1999 (+20%), but this increase was not significant. A similar trend has been reported in Wales (1983-1993) (2), Scotland (1981-1992) (14) and Great Brittain (5). Only a Swedish study (1990-2001) found a significant increase of CD incidence that increased from 1.7 in 1990-1992 to 8.4 in 1999-2001 (P < 0.0001 for trend 1990-2001) (8). In our study, the absence of statistical significance is probably attributable to the lack of power related to the small population of CD pediatric patients. Indeed, the incidence of CD in the entire population (children and adults) of Northern France significantly increased (+23%) from 1988-1990 to 1997-1999, whereas the incidence of UC in the entire population significantly decreased (−17%) (20). Although not of statistical significance, the increased CD incidence in children from 1988-1990 to 1997-1999 suggests that factors influencing the frequency of the disease are still at work in this part of Europe. Tobacco consumption is a well-known factor influencing the occurrence of CD (21). However, tobacco consumption has not increased in French adolescents over the last 15 years (22). Case-control studies might give further insight into the possible factors involved in this increased incidence.
The authors thank the interviewer practitioners who collected the data: B. Lemaire, N. Guillon, M. Inglard, I. Rousseau, N. Wauquier, P. Fosse, M. Lecomte, D. Panis, L. Yzet, C. Dias, S. Richon. EPIMAD is organized under an agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), the Direction Générale de la Santé (DGS) and the Institut National de Veille Sanitaire (InVS), and is also supported by the François Aupetit Association, the Ferring Laboratories, IRMAD (ASTRA Company), the Observatoire Régional de la Santé du Nord-Pas-de-Calais, the Caisse Régionale d'Assurance Maladie de Nord Picardie and the Lille University Hospital.
The authors thank all the gastroenterologists and all specialists who participated to this study: J. M. André, M. Antonietti, A. Armand, I. Aroichane, J. P. Aubet, E. Auxenfants, B. Barbry, N. Bardoux, P. Baron, A. Baudet, B. Bazin, A. Bebahani, J. P. Becqwort, V. Benet, C. Benguigui, E. Ben Soussan, A. Bental, I. Berkelmans, J. Bernet, C. Bernou-Dron, P. Bertot, N. Biron, M. Bleuet, F. Blondel, F. Bohon, E. Boniface, P. Bonnière, E. Bonvarlet, P. Bonvarlet, A. Boruchowicz, R. Bostvironnois, B. Bouche, C. Boudaillez, C. Bourgeaux, A. Bourguet, A. Bourienne, G. Bray, F. Brazier, P. Breban, V. Brung-Lefebvre, P. Burgiere, J. Butel, J. Y. Canva, V. Canva-Delcambre, J. P. Capron, F. Cardot, P. Carpentier, E. Cartier, J. F. Cassar, J. F. Castex, L. Catteau, B. Caujolle, G. Cayron, M. Chantre, J. Charles, T. Charneau, J. F. Claerbout, P. Y. Clergue, G. Cohen, R. Collet, J. F. Crinquette, I. Dadamessi, V. Dapvril, T. Davion, J. Debas, F. Dehont, C. Delatre, R. Delcenserie, O. Delette, T. Delgrange, L. Delhoustal, J. S. Delmotte, G. Deregnaucourt, P. Descombes, J. P. Desechalliers, P. Desmet, G. Desseaux, P. Desurmont, A. Devienne, M. Devred, A. Devroux, A. Dewailly, R. Dubois, P. Ducatillon, J. Duclay, B. Ducrocq, F. Ducrot, P. Ducrotte, J. Dufilho, C. Duhamel, D. Dujardin, F. Dupont, Y. Duranton, M. C. Elie-Legrend, J. P. Evrard, B. Filoche, L. Finet, D. Foissey, M. C. Foutrein-Comes, P. Foutrein, T. Frere, P. Gallet, C. Gamblin, G. Geslin, Y. Gheyssens, T. Gilbert, P. Godard, J. M. Godchaux, R. Godchaux, O. Goria, F. Gottrand, P. Gower, B. Grandmaison, C. Guedon, J. F. Guillard, L. Guillem, F. Guillemot, D. Hanon, P. Heckestweiller, J. P. Hedde, H. Hellal, B. Heyman, M. Heraud, S. Herve, P. Hochain, P. Houcke, A. Ivanovic, E. Janicki, J. Jeu, C. Jonas, A. Kerleveo, A. Kiriakos, J. Kiriakos, O. Klein, R. Kornhauser, D. Koutsomanis, J. E. Laberenne, G. Laffineur, P. Lannoy, J. Lapchin, M. Laprand, D. Laude, P. Lecieux, N. Leclerc, C. Le Couteulx, J. Ledent, J. Lefebvre, A. Le Grix, P. Lelong, C. Lenaerts, A. Leplat, H. Leroi, M. Y. Leroy, J. P. Lesage, X. Lesage, J. Lesage, I. Lescanne-Darchis, J. Lescut, D. Lescut, B. Leurent, M. Lhermie, A. Lion, B. Lisambert, F. Loire, M. Luciani, D. Lucidarme, J. J. Lugand, O. Macaigne, D. Maetz, D. Maillard, H. Mancheron, R. Marti, F. Martin, G. Martin, E. Marzloff, C. Mathieu-Chandelier, J. Mauillon, V. Maunoury, J. L. Maupas, B. Mesnard, P. Metayer, B. Meurisse, F. Meurisse, L. Michaud, X. Mirmaran, T. Modaine, L. Morel, E. Moulin, O. Mouterde, J. Mudry, R. N'GuyenTack, B. Notteghem, A. Ostyn, D. Ouvry, N. Panien-Claudot, C. Paoletti, A. Papazian, B. Parent, J. C. Paris, P. Patrier, L. Paupart, B. Pauwels, M. Pauwels, R. Petit, M. Piat, S. Piotte, C. Plane, B. Plouvier, E. Pollet, P. Pommelet, G. Pouchain, P. Prades, A. Prevost, J. C. Prevost, A. M. Queuniet, J. F. Quinton, A. Rabache, P. Rabelle, V. Razemon, N. Reix, C. Richez, P. Robinson, J. Rodriguez, J. Roger, J. M. Roux, A. Rudelli, G. Savoye, P. Schlosseberg, M. Segrestin, A. Seryer, F. Sevenet, J. Silvie, V. Simon, C. Spyckerelle, N. Talbodec, J. L. Thelu, J. M. Thorel, J. Toisin, J. Tonnel, J. Y. Touchais, J. L. Tranvouez, C. Triplet, E. Vaillant, C. Valmage, D. Vanco, E. Vanderbecq, P. Vandermolen, P. Vandevenne, C. Vandewalle, J. P. Vanhoove, G. Verbiese, P. Vermelle, C. Verne, M. Vincendet, J. Viot, Y. M. Voiment, L. Waeghemaecker, J. Y. Wallez, M. Wantiez, J. Weber, J. L. Willocquet, E. Wolschies, A. Zellweger, C. Ziade.
1. Tourtelier Y, Dabadie A, Tron I, et al. Incidence of inflammatory bowel disease in children in Brittany (1994-1997). Breton association of study and research on digestive system diseases (Abermad) (1994-1997) [in French]. Arch Pediatr
2. Cosgrove M, Al-Atia RF, Jenkins HR. The epidemiology of paediatric inflammatory bowel disease. Arch Dis Child
3. Hassan K, Cowan FJ, Jenkins HR. The incidence of childhood inflammatory bowel disease in Wales. Eur J Pediatr
4. Barton JR, Gillon S, Ferguson A. Incidence of inflammatory bowel disease in Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-fold rise in Crohn's disease. Gut
5. Sawczenko A, Sandhu BK, Logan RFA, et al. Prospective survey of childhood inflammatory bowel disease in the British Isles. Lancet
6. Olafsdottir EJ, Fluge G, Haug K. Chronic inflammatory bowel disease in children in western Norway. J Pediatr Gastroenterol Nutr
7. Lindberg E, Lindquist B, Holmquist L, Hildebrand H. Inflammatory bowel disease in children and adolescents in Sweden (1984-1995). J Pediatr Gastroenterol Nutr
8. Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J. Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 1990-2001. Gut
9. Langholz E, Munkholm P, Krasilnikoff PA, Binder V. Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity and mortality in a regional cohort. Scand J Gastroenterol
10. Gower-Rousseau C, Salomez JL, Dupas JL, et al. Incidence of inflammatory bowel disease in northern France (1988-1990). Gut
11. Waterhouse J, Muire C, Correa P, Powel J. Cancer incidence in five continents. IARC Sci Publ
12. Breslow NE, Day NE. The design and analysis of cohort studies. In: Statistical Methods in Cancer Research
. Vol 2. Lyon: International Agency for Research on Cancer, 1987:48-79.
13. SAS/STAT user's guide
. Version 6, 4th ed. Cary, NC: SAS Institute INC, 1989.
14. Armitage E, Drummond H, Ghosh S, Ferguson A. Incidence of juvenile-onset Crohn's disease in Scotland. Lancet
15. Armitage E, Drummond H, Wilson DC, Ghosh S. Increasing incidence of both juvenile-onset Crohn's disease and ulcerative colitis in Scotland. Eur J Gastroenterol Hepatol
16. Andersson RE, Olaison G, Tysk C, Ekbom A. Appendectomy and protection against ulcerative colitis. N Engl J Med
17. Flamant Y, Zantain OL, Barge J. Questionable appendectomies [in French]. Rev Prat (Paris)
18. Griffiths AM, Hugot JP. Crohn's disease. In: Walker WA, Goulet O, Kleinman RE, et al., eds. Pediatric Gastrointestinal Disease
. 4th edition. Hamilton, Ontario: B. C. Decker, Inc. 2004:789-824.
19. Bernstein C, Blanchard J, Rawsthorne P, Wajda A. Epidemiology of Crohn's disease and ulcerative colitis in a central Canadian province: A population-based study. Am J Epidemiol
20. Molinié F, Gower-Rousseau C, Grandbastien B, et al. Opposite evolution in incidence of Crohn's disease and ulcerative colitis in Northern France (1988-1999). Gut
21. Bridger S, Lee JCW, Bjarnason I, Lennard Jones JE, Macpherson AJ. In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn's disease and non-smokers develop ulcerative colitis. Gut
22. Grizeau D, Baudier F, Janvrin MP. Epidemiology of tobacco smoking in France [in French]. Rev Prat (Paris)
Keywords:© 2005 Lippincott Williams & Wilkins, Inc.
Crohn disease; Ulcerative colitis; Children; Incidence; Epidemiology