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Background & Aims: In this nationwide study from the Israeli Inflammatory Bowel Disease Research Nucleus, we aimed to describe the incidence of very early onset inflammatory bowel diseases (VEOIBDs) with a focus on infantile-onset disease and to compare management and disease course with older children., Methods: Data were retrieved from the 4 Israeli Health Maintenance Organizations covering 98% of the population. Pediatric-onset IBD was categorized as follows: adolescent onset (10 to <18 y), early onset (6 to <10 y), VEOIBD (0 to <6 y), toddler onset (2 to <6 y), and infantile onset (<2 y)., Results: A total of 5243 children with 35,469 person-years of follow-up evaluation, were diagnosed with IBD during 2005 to 2020: 4444 (85%) with adolescent onset, 548 (10%) with early onset, and 251 (4.8%) with VEOIBD, of whom 81 (1.5%) had infantile onset. The incidence of pediatric-onset IBD increased from 10.8 per 100,000 in 2005 to 15.3 per 100,000 in 2019 (average annual percentage change, 2.8%; 95% CI, 2.2%-3.4%), but that of VEOIBD remained stable (average annual percentage change, 0%; 95% CI, -2.5% to 2.6%). The infantile-onset and toddler-onset groups were treated less often with biologics (36% and 35%, respectively) vs the early onset (57%) and adolescent-onset groups (53%; P < .001). The time to steroid dependency was shorter in infantile-onset (hazard ratio [HR], 2.1; 95% CI, 1.5-2.9) and toddler-onset disease (HR, 1.6; 95% CI, 1.2-2.0) vs early onset and adolescent-onset disease, but time to hospitalizations, time to surgery, and growth delay were worse only in infantile-onset disease. In a multivariable model, infantile-onset patients had a higher risk for surgery (HR, 1.4; 95% CI, 1.1-1.9) and hospitalization (HR, 1.7; 95% CI, 1.2-2.4) than the toddler-onset group., Conclusions: The incidence of VEOIBD remained stable. Infantile-onset IBD had worse outcomes than older children, while toddler onset had mostly similar outcomes, despite less frequent use of biologics., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Inflammatory bowel disease (IBD), including subtypes Crohn disease and ulcerative colitis is a chronic inflammatory disorder most often diagnosed in young adulthood. The incidence and prevalence of pediatric-onset IBD is increasing globally. IBD is likely caused by an interplay of multiple environmental factors resulting in a dysregulated mucosal response to the commensal intestinal microbiota in genetically predisposed individuals. This article provides an overview of pediatric IBD epidemiology and environmental risk factors associated with its development, such as the Hygiene Hypothesis, air pollution, greenspace and blue space, neonatal factors, antibiotics, and diet., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background & Aims: The timing of initiating biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC) is an area of ongoing controversy. In particular, there is concern that delaying the initiation of biologic therapy may lead to more treatment-resistant disease, which can result in more complications and hospitalizations., Methods: We used health administrative data from Manitoba, Canada to identify all persons with a new diagnosis of inflammatory bowel disease (IBD) between 2001 and 2018 who received tumor necrosis factor antagonists (anti-TNF) therapy and had at least 1 year of post anti-TNF initiation follow-up. We measured the rates of hospitalization, surgery, and outpatient visits, prior to and for up to 5 years following anti-TNF initiation. We compared the rates of these health care utilization outcomes between persons receiving anti-TNFs within 2 years following diagnosis and those receiving anti-TNFs more than 2 years following IBD diagnosis. We used inverse probability treatment weighting to adjust for baseline differences in risk between the 2 groups., Results: Among 742 persons with CD, early anti-TNF initiators had fewer IBD-specific and overall hospitalizations over the 5 years following the start of therapy. Incidence of resective surgery was also lower in earlier anti-TNF initiators with CD if the first year following initiation was excluded from the analysis. In 318 cases of UC, there was no impact of the timing of anti-TNF therapy on the rates of hospitalization and surgery., Conclusions: Earlier administration of anti-TNF therapy is associated with reduced downstream health care resource utilization in CD, though these impacts are not evident in UC., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Several studies have demonstrated higher rates of Clostridioides difficile infection (CDI) in adults with inflammatory bowel disease (IBD). We conducted a population-based study comparing the risk of hospitalization with CDI in children with and without IBD., Methods: Using health administrative data and validated algorithms, we identified all children (<16 years) diagnosed with IBD in 5 Canadian provinces, then age and sex matched to 5 children without IBD. Province-specific 5-year incidence rates of hospitalization with CDI were pooled and generalized linear mixed-effects models were used to estimate the crude incidence rate ratio (IRR) comparing (1) children with and without IBD and (2) children with Crohn disease and ulcerative colitis. Hazard ratios (HR) from Cox proportional hazards models adjusting for age, sex, rural/urban household, and income were pooled using fixed-effects models., Results: The incidence rate of CDI identified during hospitalization was 49.06 [95% confidence interval (CI), 39.40-61.08] per 10,000 person-years (PY) in 3593 children with IBD compared to 0.39 (95% CI, 0.13-1.21) per 10,000 PY in 16,284 children without IBD (crude IRR, 133.4, 95% CI, 42.1-422.7; adjusted HR, 68.2, 95% CI, 24.4-190.4). CDI was identified less often in children with Crohn disease than ulcerative colitis (crude IRR, 0.51, 95% CI, 0.32-0.82; adjusted HR, 0.69, 95% CI, 0.46-1.05)., Conclusions: Children with IBD have a markedly higher incidence of CDI identified during a hospitalization relative to children without IBD. Consequently, symptomatic children with IBD who are hospitalized should be screened for CDI., Competing Interests: E.I.B. has acted as a legal consultant for Hoffman La-Roche Limited and Peabody & Arnold LLP for matters unrelated to a medication used to treat inflammatory bowel disease or C. difficile infection. He has also acted as a consultant for McKesson Canada. G.G.K. has received honoraria for speaking or consultancy from Abbvie, Janssen, Pfizer, Amgen, and Takeda. He has received research support from Ferring, Janssen, Abbvie, GlaxoSmith Kline, Merck, and Shire. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent 62/ 555,397. A.R.O. has been on advisory boards of AbbVie Canada, Janssen Canada, and Nestle. He has received unrestricted educational grants from AbbVie Canada and Janssen Canada. His site is involved with clinical trials for AbbVie, Pfizer, Takeda, Eli Lily, and Celgene. A.M.G. has been a consultant for Abbvie, Amgen, BristolMyersSquibb, Janssen, Lilly, Pfizer, Roche; has received speaker fees from Abbvie, Janssen, Nestle, and investigator-initiated grant support from Abbvie. L.E.T. has received investigator initiated funding from Janssen Canada, and served on advisory boards for AbbVie Canada, Sandoz Canada, Takeda Canada, Merck Canada, Pfizer Canada, Janssen Canada, and Roche Canada. C.N.B. has been on the advisory boards of Abbvie Canada, Amgen Canada, Bristol Myers Squibb Canada, Janssen Canada, Pfizer Canada, Sandoz Canada, Takeda Canada, Roche Canada, and consulted to Takeda and Mylan Pharmaceuticals. He has been on the speaker’s bureau for Abbvie Canada, Janssen Canada, Takeda Canada and Medtronic Canada. He has received unrestricted educational grants from Abbvie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada and has done contract research with Abbvie, Janssen, Pfizer, Celgene, Boeringher Ingelheim, and Roche. K.J. has been on Advisory boards of Abbvie Canada, Janssen Canada, Merck Canada, and Mylan Pharmaceuticals. He has been on the speaker’s bureau of Abbvie Canada and Janssen Canada. He has received investigator-initiated research support from Abbvie Canada and Janssen Canada. W.E.M. has received honoraria for speaking or consultancy from Abbvie and MERCK. H.S. has consulted to Amgen Canada, Bristol-Myers Squibb Canada, Sandoz Canada, Roche Canada, Takeda Canada, and Guardant Health. The remaining authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background & Aims: The incidence of inflammatory bowel disease (IBD) is increasing internationally, particularly in nations with historically low rates. Previous reports of the epidemiology of pediatric-onset IBD identified a paucity of data. We systematically reviewed the global trends in incidence and prevalence of IBD diagnosed in individuals <21 years old over the first 2 decades of the 21st century., Methods: We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from January 2010 to February 2020 to identify population-based studies reporting the incidence and/or prevalence of IBD, Crohn's disease, ulcerative colitis, and/or IBD-unclassified. Data from studies published before 2000 were derived from a previously published systematic review. We described the geographic distribution and trends in children of all ages and limiting to very early onset (VEO) IBD., Results: A total of 131 studies from 48 countries were included. The incidence and prevalence of pediatric-onset IBD is highest in Northern Europe and North America and lowest in Southern Europe, Asia, and the Middle East. Among studies evaluating trends over time, most (31 of 37, 84%) studies reported significant increases in incidence and all (7 of 7) reported significant increases in prevalence. Data on the incidence and prevalence of VEO-IBD are limited to countries with historically high rates of IBD. Time trends in the incidence of VEO-IBD were visually heterogeneous., Conclusions: Rates of pediatric-onset IBD continue to rise around the world and data are emerging from regions where it was not previously reported; however, there remains a paucity of data on VEO-IBD and on pediatric IBD from developing and recently developed countries., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Environmental factors related to urbanization and industrialization are believed to be involved in inflammatory bowel disease (IBD) development, but no study has looked at the association between greenspace and IBD., Methods: We conducted a retrospective cohort study using linked population-based health administrative and environmental data sets. The study population comprised 2,715,318 mother-infant pairs from hospital births in Ontario, Canada, between April 1, 1991, and March 31, 2014. We measured the exposure to residential greenspace using the normalized difference vegetation index derived using remote-sensing methods. Average greenspace was estimated for the pregnancy and childhood periods. We used mixed-effects Cox proportional hazard models to assess potential associations between residential greenspace and the risk of developing IBD before 18 years while adjusting for covariates including sex, maternal IBD, rural/urban residence at birth, and neighborhood income., Results: There were 3,444 IBD diagnoses that occurred during follow-up. An increase in the interquartile range of residential greenspace during the childhood period was associated with a lower risk of developing pediatric-onset IBD (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.74-0.81). This relationship was significant for both ulcerative colitis (HR 0.72 95% CI 0.67-0.78) and Crohn's disease (HR 0.81, 95% CI 0.76-0.87). There was a linear dose response across increasing quartiles of greenspace (P < 0.0001). No consistent association was detected between maternal intrapartum greenspace exposure and pediatric-onset IBD., Discussion: Higher exposure to residential greenspace during childhood was associated with a reduced risk of IBD, suggesting a novel avenue to prevent IBD in children., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Inflammatory bowel disease (IBD) is associated with a high risk of venous thromboembolism (VTE) during hospitalization. It is unclear if this association persists after discharge. We aimed to assess the incidence of postdischarge VTE in IBD patients and to determine if IBD is associated with increased VTE risk., Methods: We performed a population-based cohort study between 2002 and 2016 using Ontario health administrative data sets. Hospitalized (≥72 hours) adults with IBD were stratified into nonsurgical and surgical cohorts and matched on propensity score to non-IBD controls. Time to postdischarge VTE was assessed by Kaplan-Meier methods, and VTE risk was assessed by Cox proportional hazard models., Results: A total of 81,900 IBD discharges (62,848 nonsurgical and 19,052 surgical) were matched to non-IBD controls. The cumulative incidence of VTE at 12 months after discharge was 2.3% for nonsurgical IBD patients and 1.6% for surgical IBD patients. The incidence increased in the nonsurgical IBD cohort by 4% per year (incidence rate ratio, 1.04; 95% CI, 1.02-1.05). In our propensity score-matched analysis, the risk of VTE at 1-month postdischarge was greater in nonsurgical IBD patients (hazard ratio [HR], 1.72; 95% CI, 1.51-1.96) and surgical patients with ulcerative colitis (HR, 1.68; 95% CI, 1.16-2.45) but not surgical patients with Crohn's disease. These trends persisted through 12 months., Conclusions: Nonsurgical IBD patients and surgical patients with ulcerative colitis are 1.7-fold more likely to develop postdischarge VTE than non-IBD patients. These findings support the need for increased vigilance and consideration of thromboprophylaxis in this population., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: The combination of infliximab and azathioprine is more efficacious than either therapy alone for Crohn's disease [CD] and ulcerative colitis [UC]. However, it is uncertain whether these benefits extend to real-world clinical practice and to other combinations of biologics and immunomodulators., Methods: We collected health administrative data from four Canadian provinces representing 78 413 patients with inflammatory bowel disease [IBD] of whom 11 244 were prescribed anti-tumour necrosis factor [anti-TNF] agents. The outcome of interest was the first occurrence of treatment failure: an unplanned IBD-related hospitalization, IBD-related resective surgery, new/recurrent corticosteroid use or anti-TNF switch. Multivariable Cox proportional hazards modelling was used to assess the association between the outcome of interest and receiving combination therapy vs anti-TNF monotherapy. Multivariable regression models were used to assess the impact of choice of immunomodulator or biologic on reaching the composite outcome, and random effects generic inverse variance meta-analysis of deterministically linked data was used to pool the results from the four provinces to obtain aggregate estimates of effect., Results: In comparison with anti-TNF monotherapy, combination therapy was associated with a significant decrease in treatment ineffectiveness for both CD and UC (CD: adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.66-0.90; UC: aHR 0.72, 95% CI 0.62-0.84). Combination therapy was equally effective for adalimumab and infliximab in CD. In UC azathioprine was superior to methotrexate as the immunomodulatory agent (aHR = 1.52 [95% CI 1.02-2.28]) but not CD (aHR = 1.22 [95% CI 0.96-1.54])., Conclusion: In an analysis of a database of real-world patients with IBD, combination therapy decreased the likelihood of treatment failure in both CD and UC., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The prevalence of inflammatory bowel disease (IBD) is increasing. The total direct costs of IBD have not been assessed on a population-wide level in the era of biologic therapy., Design: We identified all persons with IBD in Manitoba between 2005 and 2015, with each matched to 10 controls on age, sex, and area of residence. We enumerated all hospitalizations, outpatient visits and prescription medications including biologics, and their associated direct costs. Total and per capita annual IBD-attributable costs and health care utilization (HCU) were determined by taking the difference between the costs/HCU accrued by an IBD case and their controls. Generalized linear modeling was used to evaluate trends in direct costs and Poisson regression for trends in HCU., Results: The number of people with IBD in Manitoba increased from 6,323 to 7,603 between 2005 and 2015. The total per capita annual costs attributable to IBD rose from $3,354 in 2005 to $7,801 in 2015, primarily driven by an increase in per capita annual anti-tumor necrosis factor costs, which rose from $181 in 2005 to $5,270 in 2015. There was a significant decline in inpatient costs for CD ($99 ± 25/yr. P < 0.0001), but not for ulcerative colitis ($8 increase ±$18/yr, P = 0.63)., Discussion: The direct health care costs attributable to IBD have more than doubled over the 10 years between 2005 and 2015, driven mostly by increasing expenditures on biological medications. IBD-attributable hospitalization costs have declined modestly over time for persons with CD, although no change was seen for patients with ulcerative colitis.

Background: Inflammatory bowel diseases (IBD) and asthma share genetic and environmental risk factors. Consequently, several observational studies have explored an association between IBD and asthma. We systematically reviewed and summarized the literature on the co-occurrence of asthma and IBD., Methods: MEDLINE and EMBASE (to April 2017) were searched to identify observational studies on the association between asthma and IBD. Relative risks (RR) were pooled using random effects models. Heterogeneity was assessed using the I 2 and Cochran Q statistics. Meta-regression based on study design, source of patients (population-based vs. tertiary-care center) and study location was conducted to explain between-study heterogeneity., Results: Eighteen studies were identified (15 Crohn's disease, 15 ulcerative colitis (UC)). Asthma was associated with both Crohn's disease (pooled RR 1.30, 95% confidence interval (CI) 1.16-1.47, I 2  = 88%) and UC (RR 1.34, 95% CI 1.24-1.44, I 2  = 93%). The study design and source of patients and study location explained between-study heterogeneity in Crohn's disease, but not UC., Conclusion: Asthma is associated with both Crohn's disease and UC. Additional research is needed to determine if one disease influences the risk of developing the other or if the frequent co-occurrence of these diseases result from shared genetic, environmental, and microbial risk factors.

The incidence and prevalence of childhood-onset inflammatory bowel diseases (IBD), including subtypes Crohn's disease and ulcerative colitis, have risen dramatically in recent years, and have emerged globally as important pediatric chronic diseases. Therefore, health care providers are more frequently encountering very young children with IBD, a chronic and incurable condition requiring life-long therapy. These children are living long lives with IBD and therefore knowledge of long-term outcomes is increasingly important to better counsel families and determine the best course of treatment. This review summarizes the current knowledge and literature surrounding long-term outcomes of pediatric IBD, with emphasis on the following areas: need for surgery due to complicated disease behavior, risk of disease remission and recurrence, mental health and psychosocial well-being, educational outcomes, linear growth impairment, cancer risk, and mortality. In addition, we review recent research about predicting negative long-term outcomes in children with IBD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background & Aims: Asthma and the inflammatory bowel diseases (IBD) each arise through complex interactions between genetic and environmental factors, and share many environmental risk factors. We examined the association between asthma and Crohn's disease or ulcerative colitis., Methods: We performed a population-based case-control study using health administrative data from the province of Alberta, Canada. The odds of a diagnosis of asthma preceding the diagnosis of either Crohn's disease (N = 3087) or ulcerative colitis (N = 2377) were compared with the odds of diagnosis of asthma among persons without IBD (N = 402,800) using logistic regression. Effect measure modification by age at diagnosis of IBD (16 years or less, 17-40 years, or older than 40 years) was tested using a likelihood ratio test., Results: A diagnosis of asthma was associated with increased odds of incident Crohn's disease (adjusted odds ratio [OR], 1.45; 95% confidence interval [CI], 1.31-1.60). No effect measure modification was observed for age at diagnosis for Crohn's disease (P = .42). However, we observed effect measure modification by age at diagnosis for ulcerative colitis (P = .0103), with an adjusted OR of 1.49 (95% CI, 1.08-2.07) among individuals diagnosed at an age of 16 years or less (OR) and an adjusted OR of 1.57 (95% CI, 1.31-1.89) among individuals diagnosed at an age older than 40 years. However, there was no association between asthma and ulcerative colitis among individuals diagnosed between ages 17 and 40 (adjusted OR, 1.05; 95% CI, 0.86-1.26)., Conclusions: In a population-based case-control study, we associated asthma with Crohn's disease, and with early and late-onset ulcerative colitis., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Studies examining the association between smoking and the need for surgery in patients with Crohn's disease and ulcerative colitis have reached inconsistent conclusions. These studies often do not differentiate between patients undergoing early surgery and patients having surgery later in their disease course. Our study examined the association between smoking status and time to first bowel resection in patients with Crohn's disease and ulcerative colitis., Methods: We searched MEDLINE and EMBASE for studies (n = 12) reporting on the association between smoking status (current, former, and never) and surgery in IBD, and incorporated disease duration in the analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were pooled across studies using random effects models., Results: Current smokers with Crohn's disease were at increased risk of intestinal resection compared to never smokers (HR 1.27, 95% CI 1.08 to 1.49); however, there was no difference in the need for surgery when comparing former and never smokers (HR 1.11, 95% CI 0.95 to 1.30). In patients with ulcerative colitis, there was no difference in the need for colectomy when comparing current smokers to never smokers (HR 0.98, 95% CI 0.67 to 1.44). Former smokers with ulcerative colitis were at increased risk of colectomy (HR 1.38, 95% CI 1.04 to 1.83) compared to never smokers., Conclusions: Current smokers with Crohn's disease are at increased risk of surgery, while former smokers with ulcerative colitis have increased risk of colectomy.