Petter Malmborg

Early-life exposures associated with antibiotic use and risk of subsequent Crohn's disease

Objective. An inappropriate immune response to normal bowel flora is implicated in the etiology of Crohns disease. Tolerance to bowel flora develops in infancy, so factors disrupting normal patterns of bowel colonization may increase the risk of Crohns disease. The aim of this study was to test the hypothesis that antibiotic therapy between birth and age 5 years may disrupt the pattern of bowel colonization and increase the risk of Crohns disease. Material and methods. Some 1098 patients with Crohns disease and 6550 controls matched by delivery unit, year of birth, sex, and born between 1973 and 1997 were identified through the Swedish population registers. Seven inpatient diagnoses between birth and age 5 years associated with antibiotic therapy were identified by prospectively recorded data. Results. Of the seven diagnoses, only pneumonia and otitis media were sufficiently common for use in the analyses. Pneumonia and otitis media were not independent of each other in their association with Crohns disease and the more important association was with pneumonia. Pneumonia by age 5 years was statistically significantly associated with both pediatric- and adult Crohns disease, with odds ratios (and 95% CI) of 2.74 (1.04–7.21) and 4.94 (1.83–13.23), respectively. Pneumonia after age 5 years was not statistically significantly associated with Crohns disease. Conclusions. Pneumonia prior to age 5 years, but not later, was associated with subsequent Crohns disease and this may represent either susceptibility or causation. The results are consistent with early exposures influencing immune function, such as through disruption of bowel colonization, and thus increasing the risk of Crohns disease.

Increasing incidence of paediatric inflammatory bowel disease in northern Stockholm County, 2002-2007.

Objectives: A sharp increase in paediatric (younger than 16 years) inflammatory bowel disease (IBD) incidence was observed in northern Stockholm County, Sweden, in 1990–2001. The increasing incidence was primarily explained by a rising incidence of Crohn disease (CD). Here, we present an update on the trends in incidence of paediatric IBD, 2002–2007. Method: Medical records of all children diagnosed as having suspected IBD in northern Stockholm County, 2002–2007, were scrutinised using defined diagnostic criteria. Disease extension, localisation, and behaviour at diagnosis were classified within the framework of the Paris classification. Result: A total of 133 children were diagnosed as having IBD 2002–2007 corresponding to a sex- and age-standardised incidence (per 105 person-years) for paediatric IBD of 12.8 (95% CI 10.8–15.2). The standardised incidence was 9.2 (95% CI 7.5–11.2) for CD and 2.8 (95% CI 1.9–4.0) for ulcerative colitis (UC). A significant increasing incidence of UC (P < 0.05) was observed during the study period. No temporal trend was observed for the incidence of CD. Conclusions: The incidence rate of paediatric IBD in northern Stockholm was significantly higher in 2002–2007 than that observed in our earlier study covering 1990–2001. The former sharp increase in incidence of paediatric CD seems, however, to have levelled out, although at a higher rate than reported from most other regions in the world. Although CD was still predominant, the observed increase in incidence of UC during the study period is notable.

Ganciclovir Treatment in Infants With Cytomegalovirus Infection and Cholestasis

ABSTRACTBackgroundThe authors have previously described an association between cytomegalovirus (CMV) infection and intrahepatic and extrahepatic forms of neonatal cholestasis. Pediatric use of the antiviral drug ganciclovir to treat patients with CMV infection has increased. In this study, infants w

Cesarean section and the risk of pediatric Crohn's disease.

Background: Crohns disease (CD) could involve an inappropriate immune response against normal bowel flora. Disrupted or atypical patterns of microbial bowel colonization may impair development of homeostasis between gut flora and the immune system. Perinatal microbial exposures may be particularly important in stimulating intestinal immune recognition. As birth by cesarean section is thought to represent an atypical pattern of early bowel colonization, we examined its association with pediatric CD. Methods: Some 1536 patients diagnosed with pediatric CD and 15,439 controls matched by delivery unit, week of birth, sex, and born between 1973 and 2006 were identified through Swedish registers. The association of birth by cesarean section with pediatric CD was examined using conditional logistic regression, with stratification by sex and adjustment for parental socioeconomic index and maternal infections during pregnancy. Results: Birth by cesarean section is associated with a modestly increased risk for pediatric CD among boys (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.01–1.54) but not girls, (OR = 0.99, 95% CI 0.76–1.29) and elective cesarean section is associated with a modest increased risk for the entire population (OR = 1.36, 95% CI 1.02–1.80). Conclusions: This study does not suggest that the delivery procedure should be altered, but the findings may be of etiological significance in CD, indicating a potential role for perinatal exposures associated with delivery mode. Although the sex difference may have arisen by chance, the modestly increased CD risk for boys delivered by cesarean section is consistent with sex‐specific differences in susceptibility to some exposures. (Inflamm Bowel Dis 2011;)

Presentation and progression of childhood-onset inflammatory bowel disease in Northern Stockholm County.

Background:Some studies have suggested that childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid progression to complications. Here, we report the presentation and progression of patients diagnosed with IBD during childhood in a population-based cohort from northern Stockholm County. Methods:Medical records for all 280 patients diagnosed in the period 1990–2007 with childhood-onset IBD in northern Stockholm County were followed until 2011 (median follow-up time, 8.8 yr). Disease phenotypes were classified according to the Paris pediatric IBD classification. Results:Among the 74 patients with ulcerative colitis, 72% presented with pancolitis. Among the 200 patients with Crohns disease (CD), 75% presented with colitis. Complicated disease behavior was observed in 18% of patients with CD by end of follow-up. Extension of the disease territory was observed in 22% of patients with ulcerative colitis and 15% of patients with CD. The cumulative risk of intra-abdominal surgery after 10 years was 8% (95% confidence interval, 4%–20%) for ulcerative colitis and 22% (95% confidence interval, 15%–28%) for patients with CD. Nonmucosal healing at 1 year was associated with a complicated disease course in patients with CD (hazard ratio = 14.56; 95% confidence interval, 1.79–118.68; P = 0.01). Conclusions:Patients with childhood-onset IBD were characterized by extensive colitis that was relatively stable over time and associated with a relatively low risk of complications and abdominal surgery. Our findings confirm the more extensive disease location in pediatric IBD but did not identify the proposed dynamic and aggressive nature of the childhood-onset phenotype. The association of nonmucosal healing with a complicated disease course suggests that endoscopy should guide treatment intensity in childhood-onset CD.

Childhood onset inflammatory bowel disease and risk of cancer: a Swedish nationwide cohort study 1964-2014

Objective To assess risk of cancer in patients with childhood onset inflammatory bowel disease in childhood and adulthood. Design Cohort study with matched general population reference individuals using multivariable Cox regression to estimate hazard ratios. Setting Swedish national patient register (both inpatient and non-primary outpatient care) 1964-2014. Participants Incident cases of childhood onset (<18 years) inflammatory bowel disease (n=9405: ulcerative colitis, n=4648; Crohn’s disease, n=3768; unclassified, n=989) compared with 92 870 comparators from the general population matched for sex, age, birth year, and county. Main outcome measures Any cancer and cancer types according to the Swedish Cancer Register. Results During follow-up through adulthood (median age at end of follow-up 27 years), 497 (3.3 per 1000 person years) people with childhood onset inflammatory bowel disease had first cancers, compared with 2256 (1.5 per 1000 person years) in the general population comparators (hazard ratio 2.2, 95% confidence interval 2.0 to 2.5). Hazard ratios for any cancer were 2.6 in ulcerative colitis (2.3 to 3.0) and 1.7 in Crohn’s disease (1.5 to 2.1). Patients also had an increased risk of cancer before their 18th birthday (2.7, 1.6 to 4.4; 20 cancers in 9405 patients, 0.6 per1000 person years). Gastrointestinal cancers had the highest relative risks, with a hazard ratio of 18.0 (14.4 to 22.7) corresponding to 202 cancers in patients with inflammatory bowel disease. The increased risk of cancer (before 25th birthday) was similar over time (1964-1989: 1.6, 1.0 to 2.4; 1990-2001: 2.3, 1.5 to 3.3); 2002-06: 2.9, 1.9 to 4.2; 2007-14: 2.2, 1.1 to 4.2). Conclusion Childhood onset inflammatory bowel disease is associated with an increased risk of any cancer, especially gastrointestinal cancers, both in childhood and later in life. The higher risk of cancer has not fallen over time.

Combining Rome III criteria with alarm symptoms provides high specificity but low sensitivity for functional gastrointestinal disorders in children

This study aimed to validate the Rome III criteria and alarm symptoms with regard to their ability to discriminate between organic and functional diagnoses in children with gastrointestinal complaints.

Surgical Treatment in Childhood-onset Inflammatory Bowel Disease–A Nationwide Register-based Study of 4695 Incident Patients in Sweden 2002-2014

Background and Aims The incidence of childhood-onset [< 18 years] inflammatory bowel disease [IBD] is increasing worldwide, and some studies suggest that it represents a more severe disease phenotype. Few nationwide, population-based studies have evaluated the surgical burden in patients with childhood-onset IBD, and whether the improved medical treatment has influenced the need for gastrointestinal surgery. The aim was to examine whether the surgical treatment at any age of patients with childhood-onset IBD has changed over time. Methods In a nationwide cohort study we identified 4695 children [< 18 years] diagnosed with incident IBD in 2002-2014 through the Swedish Patient Register [ulcerative colitis: n = 2295; Crohns disease: n = 2174; inflammatory bowel disease-unclassified: n = 226]. Abdominal [intestinal resections and colectomies] and perianal surgeries were identified through the Swedish Patient Register. The cumulative incidences of surgeries were calculated using the Kaplan-Meier method. Results In the cohort, 44% were females and 56% males. The median age at inflammatory bowel disease diagnosis was 15 years and the maximum age at end of follow-up was 31 years. The 3-year cumulative incidence of intestinal surgery was 5% in patients with ulcerative colitis and 7% in patients with Crohns disease, and lower in children aged < 6 years at inflammatory bowel disease diagnosis [3%] than in those aged 15-17 years at diagnosis [7%]. Calendar period of inflammatory bowel disease diagnosis was not associated with risk of surgery. Conclusion Over the past 13 years, the risk of surgery in childhood-onset inflammatory bowel disease has remained unchanged.

Reply about alarm symptoms in functional gastrointestinal disorders

We agree that the task of determining whether the cause of recurrent abdominal pain (RAP) in children is organic or functional, may be challenging. Abdominal pain-related functional gastrointestinal disorders are common and characterised by fluctuating symptoms, sometimes with long time symptom-free periods. In our study the diagnostic review was performed by two experienced paediatric gastroenterologists who had access to all patient records until at least 12 months after initial contact. A subgroup of children with RAP in the study by Gijsbers et. al. had positive tests for helicobacter pylori and intestinal parasites. This article is protected by copyright. All rights reserved.

OP024 Childhood-onset inflammatory bowel disease and risk of cancer – a Swedish nationwide cohort study 1964–2014

Childhood-onset inflammatory bowel disease and risk of cancer - a Swedish nationwide cohort study 1964-2014