Clinical predictors at diagnosis of disabling pediatric Crohn's disease.

BACKGROUND: Identification of children with Crohn's disease (CD) at high risk of disabling disease would be invaluable in guiding initial therapy. Our study aimed to identify predictors at diagnosis of a subsequent disabling course in a population-based cohort of patients with pediatric-onset CD. METHODS: Among 537 patients with pediatric CD diagnosed at <17 years of age, 309 (57%) with 5-year follow-up were included. Clinical and demographic factors associated with subsequent disabling CD were studied. Three definitions of disabling CD were used: Saint-Antoine and Liège Hospitals' definitions and a new pediatric definition based on the presence at maximal follow-up of: 1) growth delay defined by body mass index (BMI), weight or height lower than -2 SD Z score; and 2) at least one intestinal resection or two anal interventions. Predictors were determined using multivariate analyses and their accuracy using the kappa method considering a relevant value ≥ 0.6. RESULTS: According to the Saint-Antoine definition, the rate of disabling CD was 77% and predictors were complicated behavior and L1 location. According to the Liège definition, the rate was 37% and predictors included behavior, upper gastrointestinal disease, and extraintestinal manifestations. According to the pediatric definition, the rate of disabling CD was 15%, and predictors included complicated behavior, age <14, and growth delay at diagnosis. Kappa values for each combination of predictors were, respectively, 0.2, 0.3, and 0.2 and were nonrelevant. CONCLUSIONS: Clinical parameters at diagnosis are insufficient to predict a disabling course of pediatric CD. More complex models including serological and genetic biomarkers should be tested.

Nutritional status and growth in pediatric Crohn's disease: a population-based study.

OBJECTIVES: Growth retardation and malnutrition are major features of pediatric Crohn's disease (CD). We examined nutritional and growth parameters from diagnosis to maximal follow-up in a population-based pediatric cohort, and we determined predictive factors. METHODS: A total of 261 patients (156 boys, 105 girls) with onset of CD before the age of 17 were identified from 1988 to 2004 through the EPIMAD registry (Registre des Maladies Inflammatoires Chroniques de l'Intestin) in northern France. Median age at diagnosis was 13 years (11.2-15.4) and median follow-up was 73 months (46-114). Z-scores of height/age, weight/age, and body mass index (BMI)/age were determined. Multivariate stepwise regression analysis identified predictive factors for malnutrition and growth retardation at maximal follow-up. RESULTS: At diagnosis, 25 children (9.5%) showed height less than -2 s.d., 70 (27%) weight less than -2 s.d., and 84 (32%) BMI less than -2 s.d. At maximal follow-up, growth retardation was present in 18 children (6.9%), whereas 40 (15%) had malnutrition. Nutritional status was more severely impaired in children with stricturing disease. Growth and nutritional retardation at diagnosis, young age, male gender, and extraintestinal manifestations at diagnosis were indicators of poor prognosis. A significant compensation was observed for weight and BMI in both genders and for height in girls. No treatment was associated with height, weight, or BMI at maximal follow-up. CONCLUSIONS: In our pediatric population-based study, growth retardation and severe malnutrition were still present at maximal follow-up in 6.9 and 15% of CD children, respectively. Young boys with substantial inflammatory manifestations of CD have a higher risk of subsequent growth failure, especially when growth retardation is present at diagnosis.

Mapping of inflammatory bowel disease in northern France: spatial variations and relation to affluence.

BACKGROUND: Geographic variations in the incidence of inflammatory bowel disease (IBD) may reflect variations in the distribution of environmental etiologic factors. We assessed spatial variation in the incidence of IBD in northern France and analyzed its association with a deprivation index. METHODS: All cases of IBD included in the EPIMAD registry between 1990 and 2003 were extracted. The standardized incidence ratio (SIR) was calculated for each canton in the region. The association between incidence and deprivation was assessed using the Townsend deprivation index. RESULTS: The mean annual incidence rates of Crohn's disease (CD) and ulcerative colitis (UC) were 6.2 x 10(-5) and 3.8 x 10(-5), respectively. The mean cumulative numbers of cases by canton were 18.4 (1-183) for CD and 11.3 (0-148) for UC. For both CD and UC, mapping depicted spatial heterogeneity in the SIR with spatial autocorrelation. A high relative risk (RR) of CD was observed in mainly rural and periurban cantons of the region. For UC, a high RR was found in cantons of the south and the center of Pas-de-Calais. No significant correlation was observed between spatial variations in IBD and deprivation. CONCLUSIONS: The incidence of IBD is associated with spatial heterogeneity in northern France. The noteworthy predominance of CD in agricultural areas warrants further investigations.

The natural history of pediatric ulcerative colitis: a population-based cohort study.

OBJECTIVES: The natural history of ulcerative colitis (UC) has been poorly described in children. METHODS: In a geographically derived incidence cohort diagnosed from 1988 to 2002, we identified 113 UC patients (age 0-17 years at diagnosis) with a follow-up of at least 2 years. The cumulative risk of colectomy was estimated by the Kaplan-Meier method. Risk factors for disease extension were assessed with logistic regression models, and risk factors for colectomy with Cox hazards proportional models. RESULTS: Median follow-up time was 77 months (46-125). At diagnosis, 28% of patients had proctitis, 35% left-sided colitis, and 37% extensive colitis. Disease course was characterized by disease extension in 49% of patients. A delay in diagnosis of more than 6 months and a family history of inflammatory bowel disease were associated with an increased risk of disease extension, with odds ratios of 5.0 (1.2-21.5) and 11.8 (1.3-111.3), respectively. The cumulative rate of colectomy was 8% at 1 year, 15% at 3 years, and 20% at 5 years. The presence of extra-intestinal manifestations (EIMS) at diagnosis was associated with an increased risk of colectomy (hazard ratio (HR)=3.5 (1.2-10.5)). Among the patients with limited disease at diagnosis, the risk of colectomy was higher in those who experienced disease extension than in those who did not (HR=13.3 1.7-101.7). CONCLUSIONS: Pediatric UC was characterized by widespread localization at diagnosis and a high rate of disease extension. Twenty percent of children had their colon removed after 5 years. The colectomy rate was influenced by disease extension and was associated with the presence of EIMS at diagnosis.

Natural history of pediatric Crohn's disease: a population-based cohort study.

BACKGROUND & AIMS: The natural history of pediatric Crohn's disease and risk factors necessitating surgery have not been thoroughly described. METHODS: In a geographically derived incidence cohort diagnosed from 1988 to 2002, we identified 404 Crohn's disease patients (ages, 0-17 years at diagnosis) with a follow-up time >or=2 years. RESULTS: Median follow-up time was 84 months (range, 52-124 months). The most frequent disease location at diagnosis was the terminal ileum/colon (63%). Follow-up was characterized by disease extension in 31% of children. Complicated behavior was observed in 29% of children at diagnosis and 59% at follow-up. Kaplan-Meier survival estimates of the cumulative incidence of surgery were 20% at 3 years and 34% at 5 years from diagnosis. Multivariate Cox models showed that both structuring behavior at diagnosis (hazard ratio [HR], 2.54; 95% confidence interval [CI]: 1.58-4.01) and treatment with corticosteroids (HR, 2.98; 95% CI: 1.64-5.41) were associated with increased risk for surgery, whereas treatment with azathioprine (HR, 0.51; 95% CI: 0.33-0.78) was associated with decreased risk. Azathioprine was introduced earlier in the course of disease in patients not undergoing surgery than in patients requiring surgery. CONCLUSIONS: Pediatric Crohn's disease was characterized by frequent occurrence, with time, of a severe phenotype with extensive, complicated disease. Immunosuppressive therapy may improve the natural history of this disease and decrease the need for performing surgery.

Stressful life events as a risk factor for inflammatory bowel disease onset: A population-based case-control study.

BACKGROUND AND AIMS: Stress is often perceived by patients with inflammatory bowel disease (IBD) as the leading cause of their disease. The aim of this study was to assess whether stress, evaluated through life event (LE) occurrence, is associated with IBD onset. METHODS: Incident cases of IBD, including 167 patients with Crohn's disease (CD) and 74 with ulcerative colitis (UC), were compared with two control groups, one of 69 patients with acute self-limited colitis (ASLC) and another of 255 blood donors (BDs). Stress was assessed using Paykel's self-questionnaire of LEs. Only LEs occurring within 6 months before the onset of symptoms in IBD cases and ASLC controls and before blood donation in BD controls were registered. Anxiety and depression were assessed using Bate's and Beck's questionnaires, respectively. RESULTS: In univariate analysis, occurrence of LEs was more frequent in the 6-month period prior to diagnosis in CD cases than in UC cases or either control group. After adjustment for depression and anxiety scores as well as other characteristics such as smoking status and sociodemographic features, this association appeared no longer significant. No associations were noted between occurrence of LEs and onset of UC relative to controls. CONCLUSIONS: Despite its separate association with CD, LE occurrence does not appear to be an independent risk factor for IBD onset.

[Epidemiology and risk factors of inflammatory bowel diseases]. / Epidémiologie et facteurs de risque des maladies inflammatoires chroniques de l'intestin.

Inflammatory bowel diseases (IBD) are a public health problem in industrialized countries, where 1 in 1000 people are affected Most patients are young adults. The incidence of IBD has increased considerably in western countries since the second world war but is beginning to level off. On the other hand, the incidence is still rising in low-incidence areas such as Eastern Europe, Asia and developing countries. Differences in incidence rates across age, time, and geographic areas suggest that environmental factors are involved in IBD, but only cigarette smoking and appendectomy have consistently been identified as risk factors. An important role of genetic factors in IBD was first suggested by epidemiological studies showing familial aggregation of IBD and by twin studies. In 2001, the first CD susceptibility gene, NOD2/CARD15 on chromosome 16, was characterized. Other susceptibility genes have since been located. Their identification should help to understand the complex interaction between the environment and the intestinal immune system.

[Public health education in France: challenges and future perspectives]. / L'enseignement de la santé publique en France: objectifs et perspectives.

Public health difers from other fields of health education by its vast scope and by the diversity of its target populations. University training in public health is currently ensured in France by more than 300 permanent lecturers with significant research activity. Graduates find employment in hospitals and other public institutions. Public-sector managerial staff are educated by the National School of Public health. Currently, university training is poorly organized and coordinated in France. The creation of the Ecole des Hautes Etudes en Santo Publique provides an opportunity to reorganize the training infrastructure and calls for a reassessment of the place of universities in public health education.

[Epidemiology and risk factors of inflammatory bowel diseases]. / Epidémiologie et facteurs de risque des maladies inflammatoires chroniques de l'intestin.

Inflammatory bowel diseases (IBD) are a public health problem in developed countries as 1 per 1000 people suffers from these diseases. Most of affected people are young adults. The incidence of IBD has increased considerably in western countries since the Second World War and it is beginning to level off. On the other hand, incidence is still rising in low incidence areas such as Eastern Europe, Asia and developing countries. Differences in incidence across age, time, and geographic areas suggest that environmental factors are acting in IBD but so far cigarette smoking and appendectomy are the only risk factors which have been consistently demonstrated. An important role for genetic factors in IBD was first suggested by epidemiological studies showing familial aggregation of IBD and by twin studies. In 2001, the first CD susceptibility gene, NOD2/CARD15 on chromosome 16, has been characterized. Other susceptibility genes have been localized. Their identification should help to understand the complex interaction between the environment and the intestinal immune system from which IBD are originating.

Incidence, clinical presentation and location at diagnosis of pediatric inflammatory bowel disease: a prospective population-based study in northern France (1988-1999).

OBJECTIVE: To assess the incidence and location at diagnosis of inflammatory bowel disease in children and adolescents in northern France between 1988 and 1999. METHODS: A 12-year prospective population-based study was conducted by gastroenterologists and pediatric gastroenterologists of northern France (1,312,141 children <17 years of age). RESULTS: From 1988 to 1999, 509 cases of childhood inflammatory bowel disease were recorded (7.2% of all inflammatory bowel disease cases in Northern France): 367 Crohn disease, 122 ulcerative colitis and 20 indeterminate colitis. The mean standardized incidence was 3.1/10(5) for inflammatory bowel disease as a whole (2.3 for Crohn disease, 0.8 for ulcerative colitis and 0.12 for indeterminate colitis). Crohn disease location at diagnosis was: small bowel and colon (71%), colon only (10%) and small bowel only (19%). Location of initial ulcerative colitis was: proctitis (11%), left colitis (57%) and pancolitis (32%). Although ulcerative colitis incidence remained stable (0.8), Crohn disease incidence increased from 2.1 in 1988 to 1990 to 2.6 in 1997 to 1999 (P = 0.2). CONCLUSIONS: The incidence of Crohn disease in the children of northern France showed an increasing trend (20%; not significant) during the 12-year period while the incidence of ulcerative colitis remained stable. In the entire population(children and adults)the incidence of Crohn disease increased significantly (+23%; P < 0.001), while the incidence of ulcerative colitis decreased (-17%; P < 0.0001).