Clinical Remission and Psychological Management are Major Issues for the Quality of Life in Pediatric Crohn Disease.

OBJECTIVES: Crohn disease (CD) can affect patient's quality of life (QOL) with physical, social, and psychological impacts. This study aimed to investigate the QOL of children with CD and its relationship with patient and disease characteristics. METHODS: Children ages from 10 to 17 years with diagnosed CD for more than 6 months were eligible to this cross-sectional study conducted in 35 French pediatric centers. QOL was assessed by the IMPACT-III questionnaire. Patient and disease characteristics were collected. RESULTS: A total of 218 children (42% of girls) were included at a median age of 14 years (interquartile range [IQR]: 13--16). Median duration of CD was 3.2 years (IQR: 1.7-5.1) and 63% of children were in clinical remission assessed by wPCDAI. Total IMPACT-III score was 62.8 (±11.0). The lowest score was in "emotional functioning" subdomain (mean: 42.8 ±â€Š11.2). Clinical remission was the main independent factor associated with QOL of children with CD (5.74 points higher compared with those "with active disease", 95% confidence interval [CI] 2.77--8.70, P < 0.001). Age of patient at the evaluation was found negatively correlated with QOL (-0.76 per year, 95% CI: -1.47 to -0.06, P = 0.009). Presence of psychological disorders was associated with a lower QOL (-9.6 points lower to those without, 95% CI: -13.34 to -5.86, P < 0.0001). Total IMPACT-III and its subdomains scores were not related to sex, disease duration, or treatments. CONCLUSIONS: These results not only confirm that clinical remission is a major issue for the QOL of patients, but also highlights the importance of psychological care.

Efficacy and safety of adalimumab after infliximab failure in pediatric Crohn disease.

OBJECTIVES: The objective of the present study was to evaluate the effectiveness and safety of adalimumab (ADA) in children with Crohn disease (CD) who experienced infliximab (IFX) failure at the population level. METHODS: The present retrospective study included all of the children with CD from a pediatric-onset population-based cohort who received ADA before 18 years because of IFX failure or intolerance. Efficacy of ADA was evaluated using the physician's global assessment score, C-reactive protein and orosomucoid, and nutritional and growth indicators. RESULTS: A total of 27 children with CD received ADA. Median age at CD diagnosis and at ADA initiation was 11 years (Q1 = 9; Q3 = 12) and 15 years (12; 15), respectively. After a median follow-up of 16 (8; 26) months after ADA initiation, ADA had clinical benefit as measured by the physical global assessment score in 19 patients (70%). Cumulative probability of failure to ADA treatment was 38% at 6 months and 55% at 1 year. Eight patients had a primary failure (30%) and 5 of 19 (26%) a secondary failure to ADA. Furthermore, 11 patients (40%) experienced a total of 19 adverse effects. No serious adverse effects were observed and none resulted in ADA discontinuation. There was no significant change in growth and nutritional patterns during the study period, but we found a significant decrease in median C-reactive protein (15 mg/L [4; 44] vs 9 mg/L [3; 19]; P = 0.05) and orosomucoid (1.6 g/L [1.5; 2.6] vs 1.1 g/L [0.8; 1.9]; P = 0.001) from ADA initiation to maximal follow-up in patients responding to ADA. CONCLUSIONS: In the present population-based cohort of pediatric-onset CD with IFX failure, treatment with ADA was safe and effective in two-thirds of patients.

Mortality and cancer in pediatric-onset inflammatory bowel disease: a population-based study.

OBJECTIVES: Although the incidence of pediatric inflammatory bowel disease (IBD) continues to rise in Northern France, the risks of death and cancer in this population have not been characterized. METHODS: All patients <17 years, recorded in EPIMAD registry, and diagnosed between 1988 and 2004 with Crohn's disease (CD) or ulcerative colitis (UC) were included. The observed incidences of death and cancer were compared with those expected in the regional general population obtained by French Statistical Institute (INSEE) and the cancer Registry from Lille. Comparisons were performed using Fisher's exact test and were expressed using the standardized mortality ratios (SMRs) and standardized incidence ratios. RESULTS: A total of 698 patients (538 with CD and 160 with UC) were identified; 360 (52%) were men, the median age at IBD diagnosis was 14 years (12-16) and the median follow-up time was 11.5 years (7-15). During follow-up, the mortality rate was 0.84% (6/698) and did not differ from that in the reference population (SMR=1.4 (0.5-3.0); P=0.27). After a median follow-up of 15 years (10-17), 1.3% of patients (9/698) had a cancer: colon (n=2), biliary tract (cholangiocarcinoma; n=1), uterine cervix (n=1), prepuce (n=1), skin (basal cell carcinoma (n=2), hematological (acute leukemia; n=1), and small bowel carcinoid (n=1). There was a significantly increased risk of cancer regardless of gender and age (standardized incidence ratio=3.0 (1.3-5.9); P<0.02). Four out of nine patients who developed a cancer had received immunosuppressants or anti-tumor necrosis factor-α therapy (including combination therapy in three patients). CONCLUSIONS: In this large pediatric population-based IBD cohort, mortality did not differ from that of the general population but there was a significant threefold increased risk of neoplasia.

[Infant feeding, how to choose an infant milk?] / Alimentation du nourrisson : comment choisir un lait infantile ?

Infant feeding, how to choose an infant milk? The infant's nutrition is of particular concern, not only to assume a good nutritional status, an adequate growth and development, but also, to some extent, for his future health. Breast feeding remains the best choice but needs to be counseled in practice and in order to avoid deficiencies as well as chemical or in¬fectious contaminations. As a substitute to breast milk, none non modified mammalian milk fits the infant's nutritional needs. Similarly, no non-modified vegetal juice fits these needs, being able to provoke severe nutritional deficiencies. Out of the numerous available formulas, a choice criterion should be the presence of arachidonic acid in infant and follow-up formulae. No other ingredient can yet be counseled as inescapable for every healthy infant. Anti-reflux substitutes are useful for the spitting infants. The lac¬tose-free formulas should be used only in protracted or severe acute diarrheas. Extended hydrolysates of cow's milk proteins, or hydrolyzed rice formulas are prescribed in cow's milk allergy. In rare cases of allergy to these formulas, an amino-acid mixture-based formula is an alternative.

Alimentation du nourrisson : comment choisir un lait infantile ? L'alimentation du nourrisson revêt une importance cruciale non seulement pour assurer un bon état nutritionnel, un développement et une croissance optimaux mais aussi, dans une certaine mesure, pour sa santé ultérieure. L'allaitement maternel est à l'évidence le meilleur choix, mais il doit être accompagné, en termes de pratique et de prévention, des risques caren¬tiels, toxiques et infectieux. À titre de substitut du lait maternel, aucun lait brut de mammifère ne convient au nourrisson. Il en est de même des boissons végétales, non adaptées, qui font courir le risque de carences graves. Parmi les multiples préparations infantiles disponibles, le critère principal de choix pour l'enfant de moins de 1an en bonne santé serait la présence d'acide arachidonique, composé que la réglementation européenne n'a pas rendu obligatoire. Il ne se dégage actuellement aucun autre critère de choix dont l'intérêt soit totalement prouvé pour tous les nourrissons. Les laits antireflux ont un intérêt contre les régurgitations, les laits sans lactose en cas de diarrhée sévère ou prolongée. Les hydrolysats poussés et les préparations à base de riz sont utilisés en cas d'allergie au lait de vache, remplacés par des mélanges d'acides aminés en cas d'allergie à ces deux substituts.

Clinical features and risk factors for upper gastrointestinal bleeding in children: a case-crossover study.

OBJECTIVE: This population-based survey was conducted to provide a formal description of upper gastrointestinal bleeding (UGIB) in children on a nationwide basis and assess the contribution of risk factors, principally nonsteroidal anti-inflammatory drugs (NSAID). METHODS: A case-crossover study of UGIB patients aged between 2 months and 16 years was conducted in France. Medical data were collected by physicians, and personal risk factors and exposure to drugs during the month preceding the onset of the bleeding was ascertained by a standardised telephone interview with parents. The odds ratios for UGIB and NSAID was assessed by comparing exposure during the 7 days preceding the date of hospitalisation and the 21st to the 28th days before that date. RESULTS: A total of 177 children with UGIB were included over 2 years. Eighty-three children had taken at least one NSAID before the index date, among which 58 were ibuprofen, 26 aspirin and nine others. The adjusted odds ratio (OR) of exposure was 8.2 [95% confidence interval (CI) 2.6-26.0] for NSAIDs altogether, and this was 10.0 (95% CI 2.0-51.0) for ibuprofen and 7.3 (95% CI 0.9-59.4) for aspirin. There was no increased risk associated with NSAIDS for oesophageal lesion [OR = 1.0 [(5% CI:0.2-7.2)]. CONCLUSION: The study confirms that UGIB is rare but that some cases may be avoided, as one third of the cases was attributable to exposure to NSAID at doses used for analgesic or antipyretic purposes, which may be attained with alternative therapy. The findings from this study call for more caution in prescribing NSAIDS to children.

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.

Long-term outcome of pediatric-onset Crohn's disease: A population-based cohort study.

BACKGROUND: Pediatric-onset Crohn's disease (CD) may represent a more severe form of disease. The aim of this study was to describe long-term outcome and identify associated risk factors of complicated behavior in a large population-based pediatric-onset CD cohort. PATIENTS AND METHODS: Cases included all patients recorded in the EPIMAD registry diagnosed with definite or probable CD between January 1988 and December 2004, under the age of 17 years at the time of diagnosis, with at least two years of follow-up. RESULTS: Five hundred and thirty-five patients were included. Median follow-up was 11.1 years [IQR, 7.3-15.0]. At the end of follow-up, 8% (n = 44) of patients had pure ileal disease (L1), 8% (n = 44) had pure colonic disease (L2), and 83% (n = 439) had ileocolonic disease (L3). L4 disease and perianal disease were observed in 42% (n = 227) and 16% (n = 85) of patients, respectively. At the end of follow-up, 58% (n = 308) of patients presented complicated disease behavior (B2, 39% and B3, 19%), and 42% (n = 163) of patients with inflammatory behavior at diagnosis had evolved to complicated behavior. During follow-up, 86% of patients (n = 466) received at least one course of corticosteroids, 67% (n = 357) of patients had been exposed to immunosuppressants and 35% (n = 187) of patients received at least one anti-TNF agent. Forty-three percent (n = 230) of patients underwent at least one intestinal resection. The overall mortality rate was 0.93% and the SMR was 1.6 [0.5-3.8] (p = 0.20). Five cancers were reported with a crude cancer incidence rate of 1.1% and an SIR of 3.3 [1.2-7.0] (p = 0.01). In a multivariate Cox model, ileal (HR, 1.87 [1.09-3.21], p = 0.022) or ileocolonic (HR, 1.54 [1.01-2.34], p = 0.042) and perianal lesions at diagnosis (HR, 1.81 [1.13- 2.89], p = 0.013) were significantly associated with complicated behavior. CONCLUSION: About 80% of patients with pediatric-onset CD presented extensive ileocolonic disease during follow-up. The majority of patients evolved to complicated behavior. Surgery, cancer and mortality were observed in 43%, 0.9% and 0.9% of patients, respectively.

Incidence of autoimmune diseases in celiac disease: protective effect of the gluten-free diet.

BACKGROUND & AIMS: Celiac disease may be associated with autoimmune diseases. The aims of the present study were to determine in celiac patients which factors modulate the risk of autoimmune disease and to evaluate the effect of the gluten-free diet. METHODS: The occurrence of autoimmune disease and compliance to gluten-free diet were specified retrospectively in 924 celiac patients recruited from 27 French pediatric and adult gastroenterology centers. RESULTS: One or several autoimmune diseases had developed in 178 patients. The cumulative risk of autoimmune disease was 8.1% +/- 1% at age 15, and 15.7% +/- 1.5% at age 30. Factors associated with an increased risk were family history of autoimmunity (hazard ratio, 2.36; 95% confidence interval, 1.71-3.31) and diagnosis of celiac disease before 36 years of age (hazard ratio, 2.65; 95% confidence interval, 1.79-3.85). After diagnosis of celiac disease, 55 of 788 patients developed an autoimmune disease. The cumulative risk of subsequent autoimmune disease was lower in patients compliant to a gluten-free diet versus noncompliant patients (at 10 years, 6% +/- 2% vs 15.6% +/- 5.9%, respectively; P = .02). The incidence of autoimmune diseases was 5.4 per 1000 patient-years during adherence to a gluten-free diet versus 11.3 per 1000 patient-years during nonadherence to the diet (P = .002). Results were similar in both the pediatric and the adult populations. CONCLUSIONS: Celiac patients most at risk for autoimmune disease are those diagnosed early in life and having a family history of autoimmunity. The gluten-free diet has a protective effect.

Gene expression profiling in necrotizing enterocolitis reveals pathways common to those reported in Crohn's disease.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units. The challenge for neonatologists is to detect early clinical manifestations of NEC. One strategy would be to identify specific markers that could be used as early diagnostic tools to identify preterm infants most at risk of developing NEC or in the event of a diagnostic dilemma of suspected disease. As a first step in this direction, we sought to determine the specific gene expression profile of NEC. METHODS: Deep sequencing (RNA-Seq) was used to establish the gene expression profiles in ileal samples obtained from preterm infants diagnosed with NEC and non-NEC conditions. Data were analyzed with Ingenuity Pathway Analysis and ToppCluster softwares. RESULTS: Data analysis indicated that the most significant functional pathways over-represented in NEC neonates were associated with immune functions, such as altered T and B cell signaling, B cell development, and the role of pattern recognition receptors for bacteria and viruses. Among the genes that were strongly modulated in neonates with NEC, we observed a significant degree of similarity when compared with those reported in Crohn's disease, a chronic inflammatory bowel disease. CONCLUSIONS: Gene expression profile analysis revealed a predominantly altered immune response in the intestine of NEC neonates. Moreover, comparative analysis between NEC and Crohn's disease gene expression repertoires revealed a surprisingly high degree of similarity between these two conditions suggesting a new avenue for identifying NEC biomarkers.

Epidemiology of acute viral gastroenteritis in children hospitalized in Rouen, France.

This study assessed the epidemiologic characteristics of acute viral gastroenteritis in hospitalized children. A stool sample obtained from each child was analyzed for the presence of astrovirus, calicivirus, rotavirus, adenovirus, enterovirus, and digestive bacteria. Of the 438 stool samples obtained, 138 tested positive for > or =1 pathogen during the winters of 1997-1998 and 1998-1999 (P<.001). Virologic tests revealed rotavirus in 17.3% of samples, calicivirus in 7.3%, astrovirus in 6.8%, adenovirus in 0.7%, and > or =1 virus in 5.4%. Median age was higher for patients with rotavirus gastroenteritis than it was for those with astrovirus or calicivirus gastroenteritis (P=.014). Mean duration of hospitalization was statistically significantly lower for children with rotavirus gastroenteritis (P=.022), despite the more-frequent dehydration observed among children with rotavirus versus those with astrovirus or calicivirus gastroenteritis (P=.007). In contrast, enteral rehydration was more rapidly achieved in patients with gastroenteritis due to rotavirus.

A dose determination study of polyethylene glycol 4000 in constipated children: factors influencing the maintenance dose.

OBJECTIVES: To determine the doses of polyethylene glycol (PEG) 4000 without additional salts allowing normal bowel habits in childhood functional constipation. METHODS: This multicenter noncomparative study allocated children to 4 groups: 6-12 months, 13 months-3 years, 4-7 years, and 8-15 years. Constipation was defined as <1 stool/d for more than 1 month in children aged 6-12 months and <3 stools/w for more than 3 months in older children. Children randomly received either a nominal or a double starting dose. Treatment scheduled for 3 months could be adapted. Data were collected daily by the parents and rated at each visit by the investigator. RESULTS: In the 96 children included, the median (interquartile) effective daily doses were by groups; 3.75 (2.50-5.00) g, 6.00 (4.00-7.43) g, 11.71 (7.00-16.00) g, and 16.00 (16.00-24.00) g, respectively, i.e., around 0.50 g/day/kg with a potential increment of the maintenance dose with higher initial dosages. More children had a final dosage identical to the initial one when started on the nominal dose (73%) than with the double one (42%, P < 0.003). More than 90% of children recovered normal bowel habits. Fecal soiling ceased in >60% of children with this symptom at enrolment. Fecal mass in the rectum and abdominal pain were markedly reduced and appetite improved. CONCLUSIONS: A daily dose of PEG 4000 around 0.50 g/day/kg in children aged 6 months to 15 years is effective in more than 90% of constipated children and 60% of those with fecal soiling.