Eric Lerebours

Natural History of Pediatric Crohn's Disease: A Population-Based Cohort Study

BACKGROUND & AIMS The natural history of pediatric Crohns 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 Crohns 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 Crohns 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.

Opposite evolution in incidence of Crohn’s disease and ulcerative colitis in Northern France (1988–1999)

Background: Northern France was characterised by a high incidence of Crohn’s disease (CD) and a low incidence of ulcerative colitis (UC) according to the first inquiry undertaken in the late 1980s. Aims: To assess the trends in the incidence of inflammatory bowel disease (IBD) over a 12 year period (1988–1999) in the same area of Northern France. Patients: Patients living in Northern France (Nord, Pas-de-Calais, Somme, and Seine Maritime—total of 5 790 526 inhabitants) between 1988 and 1999 were included in the study. Case ascertainment was established according to methodology previously described. Methods: Trends in incidence were studied using a Poisson regression model in four three year periods (1988–90, 1991–93, 1994–96, and 1997–99) adjusted for age at diagnosis and sex. Incidence rates were standardised for age with the European standard population. Results: During 1988–99, 7066 cases of IBD were recorded (56.8% CD, 37.7% UC, and 5.5% indeterminate colitis). Mean annual incidence rate of CD increased from 5.2/100 000 inhabitants in 1988–90 to 6.4 in 1997–99 (adjusted p for trend <0.001). In contrast, the incidence of UC decreased from 4.2 to 3.5 (adjusted p for trend <0.001). The ileocolonic subtype of CD increased by 25% even though median age at diagnosis and frequency of digestive investigations were not different. Conclusions: Contrary to what has been reported in other countries in Northern Europe, the incidence of CD increased by 23% in 12 years in Northern France while that of UC decreased by 17% during the same period. This indicates that some factors which influence IBD frequency (in both directions) are still at work in this area of Europe, and that further studies aimed at identifying these should be performed. The rising incidence of CD could enhance the burden of this disease on the public health system in France.

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 3.1/105 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).

Environmental risk factors in paediatric inflammatory bowel diseases: a population based case control study

Background: Environmental exposures in early life have been implicated in the aetiology of inflammatory bowel disease. Objective: To examine environmental risk factors prior to the development of inflammatory bowel disease in a paediatric population based case control study. Methods: A total of 222 incident cases of Crohn’s disease and 60 incident cases of ulcerative colitis occurring before 17 years of age between January 1988 and December 1997 were matched with one control subject by sex, age, and geographical location. We recorded 140 study variables in a questionnaire that covered familial history of inflammatory bowel disease, events during the perinatal period, infant and child diet, vaccinations and childhood diseases, household amenities, and the family’s socioeconomic status. Results: In a multivariate model, familial history of inflammatory bowel disease (odds ratio (OR) 4.3 (95% confidence interval 2.3–8)), breast feeding (OR 2.1 (1.3–3.4)), bacille Calmette-Guerin vaccination (OR 3.6 (1.1–11.9)), and history of eczema (OR 2.1 (1–4.5)) were significant risk factors for Crohn’s disease whereas regular drinking of tap water was a protective factor (OR 0.56 (0.3–1)). Familial history of inflammatory bowel disease (OR 12.5 (2.2–71.4)), disease during pregnancy (OR 8.9 (1.5–52)), and bedroom sharing (OR 7.1 (1.9–27.4)) were risk factors for ulcerative colitis whereas appendicectomy was a protective factor (OR 0.06 (0.01–0.36)). Conclusions: While family history and appendicectomy are known risk factors, changes in risk based on domestic promiscuity, certain vaccinations, and dietary factors may provide new aetiological clues.

Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study

Background and aims Few studies have been conducted addressing the safety of thiopurine treatment in pregnant women with inflammatory bowel disease (IBD). The aim of this study was to evaluate the pregnancy outcome of women with IBD who have been exposed to thiopurines. Methods 215 pregnancies in 204 women were registered and documented in the CESAME cohort between May 2004 and October 2007. Physicians documented the following information from the women: last menstrual date, delivery term, details of pregnancy outcome, prematurity, birth weight and height, congenital abnormalities, medication history during each trimester, smoking history and alcohol ingestion. Data were compared between three groups: women exposed to thiopurines (group A), women receiving a drug other than thiopurines (group B) and women not receiving any medication (group C). Results Mean age at pregnancy was 28.3 years. 75.7% of the women had Crohns disease and 21.8% had ulcerative colitis, with a mean disease duration of 6.8 years at inclusion. Of the 215 pregnancies, there were 138 births (142 newborns), and the mean birth weight was 3135 g. There were 86 pregnancies in group A, 84 in group B and 45 in group C. Interrupted pregnancies occurred in 36% of patients enrolled in group A, 33% of patients enrolled in group B, and 40% of patients enrolled in group C; congenital abnormalities arose in 3.6% of group A cases and 7.1% of group B cases. No significant differences were found between the three groups in overall pregnancy outcome. Conclusions The results obtained from this cohort indicate that thiopurine use during pregnancy is not associated with increased risks, including congenital abnormalities.

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

OBJECTIVES:Growth retardation and malnutrition are major features of pediatric Crohns 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.

Costs of Crohn's Disease According to Severity States in France: A Prospective Observational Study and Statistical Modeling over 10 Years.

Background:To describe the medico–economic characteristics of Crohns disease (CD), we implemented a multicenter study in France. Methods:From 2004 to 2006, disease severity states, direct (hospital and extra hospital) and indirect costs were prospectively collected over 1 year in patients with CD naive from anti–tumor necrosis factor alpha (infliximab) at inclusion. Economic valorization was performed from the French Social Insurance perspective, and a statistical modeling over 10 years was performed. Results:In 341 patients, the mean total costs of management were &OV0556;6024 per year (&OV0556;4675 for direct costs). As compared to patients in remission, costs were 4 to 6 times higher in patients in an active period and 19 times higher for patients requiring surgery (SURG). The most important expense items were medical and surgical hospitalizations (56% of total costs), including cost of infliximab (36% of hospitalization costs, i.e., 20% of total costs), indirect costs (22%), and drugs (11%). The statistical modeling over 10 years showed that most of the clinical course was spent in drug-responsive state (54%) with 26% of costs or in remission (32%) with 11% of costs; time spent in a SURG state was small (3.2%) but generated 48% of total costs. Conclusions:Before the introduction of self-injectable anti–tumor necrosis factor alpha, the most important expenses were supported by hospitalizations, explaining why the most costly states were for patients requiring SURG or dependent on inhospital administrated drugs. Projected data show that most time is spent in a stabilized state with appropriate treatments or in remission, and that costs associated with SURG are high.