Background Increased oxidative stress is well documented in patients with Crohn’s disease (CD). However, it remains unclear whether early redox-related alterations occur prior to diagnosis and whether they are correlated with early alterations in inflammatory responses. Aims We examined whether the serum cysteine sulfinic acid to cysteine ratio, as a redox-related marker indicative of sustained oxidative conditions, is associated with future CD risk and correlated with gut and systemic inflammation, proteomic, and metabolomic profiles. Methods In the Genetic, Environmental, and Microbial (GEM) Project, 79 healthy first-degree relatives (FDRs) who later developed CD (Pre-CD) were identified and matched by age, sex, geographic location, and time of recruitment with 311 FDRs who remained disease-free. Conditional logistic regression assessed the association between redox biomarkers and future CD risk. Partial Spearman correlation assessed correlations between the cysteine sulfinic acid to cysteine ratio and C-reactive protein (CRP), fecal calprotectin (FCP), serum metabolites (Metabolon®), and serum proteomic profiles (Olink®). Results An elevated serum cysteine sulfinic acid to cysteine ratio was positively associated with the risk of developing CD (odds ratio = 2.06, 95% CI: 1.42-3.00, p =0.00015) and showed a positive correlation with CRP (coefficient = 0.296; p = 3.04e-09) and FCP (coefficient = 0.123; p = 0.0198) levels. A total of 295 metabolites and 201 proteins were correlated with the cysteine sulfinic acid to cysteine ratio. Conclusion This study provides new evidence that redox-related alterations are present during the preclinical phase prior to CD onset.
BACKGROUND & AIMS:Single nucleotide polymorphisms in the interleukin23 receptor gene are associated with Crohn's disease, suggesting a role in pathogenesis, and several biologic agents targeting this pathway are now established therapies. Interleukin23 has been suggested to be involved in regulation of intestinal barrier function and may impact gut microbial composition. We investigated whether interleukin23 receptor genetic variants predict Crohn's disease risk and influence gut barrier function and microbiome composition in healthy first-degree relatives. METHODS:A total of 3055 healthy first-degree relatives with genotypic data from the Crohn's and Colitis Canada Genetic, Environmental, Microbial (CCC-GEM) cohort were included. A weighted interleukin23 receptor genetic risk score was generated from 7 Crohn's disease-associated interleukin23 receptor single nucleotide polymorphisms and dichotomized as high (top quintile) vs low interleukin23 receptor genetic risk score. A subset of this cohort was assessed for intestinal permeability (n = 1698) and microbiome profiling (n = 2523). Cox proportional hazards models evaluated Crohn's disease onset risk. RESULTS:High interleukin23 receptor genetic risk score was associated with increased Crohn's disease risk (hazard ratio, 1.67; 95% confidence interval, 1.01-2.75; P = .044). This association remained significant after adjusting for fecal calprotectin, indicating genetic risk independent of subclinical inflammation. High interleukin23 receptor genetic risk score was not associated with intestinal permeability (P = .84) but was associated with differences in 15 genera, including decreased Faecalibacterium and increased Akkermansia (q < 0.1). CONCLUSIONS:High interleukin23 receptor genetic risk score was associated with increased Crohn's disease risk in healthy first-degree relatives and was associated with microbial differences, but not with intestinal permeability. These findings suggest potential clinical applications for interleukin23 receptor genetic risk score in identifying high-risk individuals who may benefit from closer monitoring or future interleukin23 pathway-targeted preventive interventions.
Background:Ustekinumab dosing information for pediatric Crohn's disease (CD) is limited. Aims:To examine ustekinumab pharmacokinetic and effectiveness data in a largely bio-naïve cohort, focusing on early (week 8) levels. Methods:Children in the prospective Canadian Children IBD Network initiating intravenous (IV) ustekinumab for CD with a week 8 level were evaluated. Disease activity was assessed by corticosteroid-free clinical remission (CSFR), biochemical CSFR, and mucosal healing (MH) by colonoscopy or fecal calprotectin <150 µg/g beyond 16 weeks. We compared drug levels by weight group (</≥40kg) and outcome, using receiver-operating characteristic (ROC) curves to identify optimal week 8 levels. Results:Amongst 58 children (19 < 40 kg, 81% bio-naïve, median (interquartile range [IQR]) follow-up 11.5 [7.6-16.0] months), the IV loading dose for those <40kg (median 9.1 [8.6-10.2] mg/kg; 253 (239-268) mg/m2) was greater than for those ≥40kg (median 6.1 [5.4-6.5] mg/kg; 218 ([78-237] mg/m2, P < .001). However, week 8 levels were similar (P = .26). This was most striking in those with low albumin. Of 34/58 (59%) without escalation to 4 weekly dosing, 43%, 35%, and 19% exhibited CSFR, biochemical CSFR, and MH, respectively, during established maintenance. Median week 8 levels were roughly 5-6 µg/g vs 7-10 µg/g in patients not achieving vs achieving favorable outcomes, while ROC analysis indicated levels 8-9 µg/mL were associated with improved outcomes. Conclusions:Children <40 kg required more IV ustekinumab (median 9 mg/kg; 250 mg/m2) to achieve similar week 8 levels as children ≥40kg receiving conventional adult 6 mg/kg weight-tiered induction. Higher week 8 levels were associated with favorable later outcomes.
BACKGROUND:We aimed to build a serum proteomics-based model to predict primary nonresponse (PNR) to infliximab (IFX) in pediatric colonic inflammatory bowel disease, with early proactive therapeutic drug monitoring. METHODS:Children in the prospective Canadian Children IBD Network with ulcerative colitis (UC), inflammatory bowel disease unclassified (IBD-U), or colonic Crohn's disease (CD) with serum pre-IFX were eligible. We defined PNR as IFX cessation plus surgery/drug switch within 6 months. We compared clinical features between groups (Mann Whitney U, chi-square test). We measured serum proteins with Olink Inflammation/Immune Response panels. We built a regularized regression (generalized linear model [GLM]) machine learning model and compared its performance with other models with 10-fold cross-validation repeated 10 times (receiver-operating characteristic/precision-recall curves, predictive score separation). We ranked proteomic features by SHAP (SHapley Additive exPlanations) analysis. We hypothesized that treatment-naïve serum would be more informative than treatment-exposed serum. RESULTS:We included 96 patients: 71 UC/IBD-U (23 nonresponders), 42 treatment-naïve (12 nonresponders); and 25 CD, 19 treatment-naïve. Pre-third and pre-fourth dose serum infliximab levels were similar and robust (>10 µg/mL) in primary nonresponders and responders. Predictive performance was superior for diagnostic, treatment-naïve samples; the GLM showed good ability to separate primary nonresponders and responders. The GLM model on treatment-naïve serum (area under the curve ∼0.75) had better specificity to predict responders and included 21 proteins, with CSF1 and ITM2A top ranked. UC/IBD-U responders more often were steroid refractory and received infliximab as first maintenance. CONCLUSIONS:A serum proteomics linear model on treatment-naïve serum best predicted PNR. Findings require external validation but suggest that the diagnostic/pretreatment window may be key to understanding biology central to effective drug sequencing.
Lancefieldella parvula (previously known as Atopobium parvulum) has been associated with inflammatory bowel disease (IBD); however, prior in vivo studies relied on an oral-derived reference strain rather than intestinal clinical isolates, limiting interpretation of its role in gut inflammation. To address this gap, we isolated a clinical strain of L. parvula (designated L. parvula TI19E08) from a mucosal luminal aspirate of an ulcerative colitis (UC) participant. We developed a strain-specific quantitative PCR assay to quantify its abundance across anatomical sites in treatment-naïve pediatric IBD participant (UC and Crohn’s disease (CD)) and examined its relationship with site-specific endoscopic inflammation severity. We demonstrated that the relative abundance of L. parvula TI19E08 increased with increasing local inflammation severity. In UC, both strain-specific and total L. parvula levels were strongly correlated with inflammation severity, particularly in the proximal colon. In CD patients, strain-level associations were most pronounced in the terminal ileum, which is consistent with the disease distribution. This study characterizes an intestinal L. parvula isolate and demonstrates that strain-level expansion correlates with disease severity across IBD subtypes and anatomical regions. These findings identify L. parvula TI19E08 as a candidate mucosal marker of inflammation severity in IBD patients.
BACKGROUND & AIMS:Elevated antimicrobial antibodies have been reported up to 6 years before diagnosis of Crohn's disease (CD), but the specific antibody response is unclear. Here, we characterized the antimicrobial antibody responses before CD diagnosis in healthy first-degree relatives (FDRs) of patients with CD. METHODS:The CCC-GEM (Crohn's and Colitis Canada - Genetic, Environmental, Microbial) Project nested case-control cohort consisted of FDRs who later developed CD (N = 77), matched 1:4 by age, sex, follow-up duration, and geographical location with healthy FDRs (N = 304). Sera at enrollment were probed for antimicrobial reactivity using a microbiota antigen microarray and a flagellin peptide cytometric bead array. Conditional logistic regression was used to assess association with CD onset, and partial Spearman was used to correlate serologic responses with lactulose-to-mannitol ratio (LMR), C-reactive protein (CRP), and fecal calprotectin (FCP). False discovery rate was controlled using the Benjamini-Hochberg method (q < 0.05). RESULTS:Nineteen of 49 IgG antimicrobial antibody responses were significantly associated with the risk of CD; these antibodies were reactive to Lachnospiraceae family, particularly Roseburia-derived flagellins; 5 antibodies positively correlated with FCP, whereas 3 positively correlated with LMR. These IgG-seroreactive flagellins shared significant amino acid sequence homology, characterized by a conserved "hinge peptide" within D0-D1 domains of the amino-terminus. The cytometric bead array confirmed that elevated IgG seroreactivity to the hinge peptide is associated with future risk of CD independent of LMR and FCP. CONCLUSIONS:Increased antibody response in healthy FDRs towards Lachnospiraceae flagellins is associated with future risk of CD. Importantly, pre-CD subjects shared seroreactivity towards a conserved bacterial flagellin epitope, which may represent an early preclinical biomarker of CD.
Corticosteroids (CS) and exclusive enteral nutrition (EEN) are effective induction therapies for pediatric Crohn’s disease (CD), but comparative studies evaluating long-term outcomes in small bowel CD are lacking. Children (2–18 years) with newly diagnosed small bowel CD involving the ileum prospectively enrolled in the multicenter Canadian CIDsCaNN or European PIBD-SETQuality inception cohorts receiving CS or EEN induction treatment were evaluated longitudinally. The primary outcome was sustained steroid-free remission (SSFR) at 1 year. Secondary outcomes included changes in height z-scores, time-to-first-biologic and time-to-luminal-resection. Results were confirmed after propensity score matching (PSM). In total, 208 children (61
Fiber-based therapies focus on butyrate production, a process often dysregulated in inflammatory bowel disease (IBD), but seldomly examine other metabolites or functional pathways. Here, we systematically profiled ex vivo responses of 66 pediatric IBD microbiomes to nine resistant starches (RS), with extensive multi-omic characterization in a subset. Our study demonstrates that inter-individual variability dominates over RS-specific effects, yielding consistent yet highly personalized fermentation phenotypes, microbial compositional shifts, and metabolite outputs. Beyond butyrate, we identify previously unreported RS fermentation metabolites, revealing hidden functional pathways and cross-feeding interactions not captured by conventional short chain fatty acid-focused analyses. Metaproteomic profiling further revealed a coordinated shift from host mucin-degrading activity toward RS utilization. Together, these findings show that RS fermentation is shaped by both RS type and participant microbiome composition, and establish the RapidAIM ex vivo platform as a fiber personalization pipeline fit for interventions aimed at restoring microbial functions disrupted in human diseases.
Inflammatory bowel disease (IBD) represents a group of disorders with no known cure. IBD is impacted by biopsychosocial factors. The burden, psychosocial difficulties, and gene-environment interaction involved in the manifestation of IBD necessitate a fuller understanding of factors which worsen or ameliorate IBD. Case complexity (CC) captures current and historical biopsychosocial risks for individuals with IBD and holds promise for understanding variation in treatment response and individuals' experiences with IBD. The present study aimed to understand the relative contributions of: 1) historical vs. current factors impacting CC in predicting global health; and 2) biological, psychological, social, family, and health system factors on global health. Within a longitudinal design, 8-17-year-old youth (N = 83) completed the self-report Pediatric Global Health 7 + 2 at diagnosis (baseline) and 4- and 12 months post-diagnosis. The p-IBD-INTERMED, a clinical-decision support tool, which standardizes inter-professional assessment of biopsychosocial risks contributing to CC was completed by the healthcare provider team at the same timepoints. CC was associated with global health at all time points (T1r = -0.27; T2r = -0.42; T3r = -0.50). Hierarchical regression revealed that across time the relative contribution of historical CC was surpassed by current CC when predicting global health (at T1 βHCC=-0.13;βCCC = -0.17; at T3 βHCC = -0.04; βCCC = -0.48). In this cohort, at 4- and 12-months post diagnosis, psychological factors were the only domain of current CC to significantly predict global health, accounting for 29.1 % and 24.1 % of its variance respectively. Findings suggest that the global health of patients with IBD is not fixed by early life experiences. BACKGROUND:Inflammatory bowel disease (IBD) represents a prevalent group of disorders with no known cure. IBD is impacted by myriad biopsychosocial factors. The pervasive burden, pronounced psychosocial difficulties, and the potential gene-environment interaction involved in the manifestation of IBD necessitate a fuller understanding of factors which might worsen or ameliorate IBD. Case complexity (CC) captures current and historical biopsychosocial risks for individuals with IBD and holds promise for understanding variation in treatment response and individuals' experiences with this chronic illness. AIMS:We sought to understand the relative contributions of: 1) historical vs. current factors impacting CC in predicting global health (self-reported); and 2) biological, psychological, social, family, and health system factors on global health. METHODS:Within a longitudinal design, 8-17-year-old youth (N = 83) completed the self-report Pediatric Global Health 7 + 2 at diagnosis (baseline) and 4- and 12 months post-diagnosis. The p-IBD-INTERMED, an interview-based measure of CC, was completed by the healthcare provider team at the same timepoints. RESULTS:CC was associated with global health at all time points (T1r = -0.27; T2r = -0.42; T3r = -0.50). Hierarchical regression revealed that across time points the relative contribution of historical CC was surpassed by current CC when predicting global health (at T1 βHCC= - 0.13;βCCC= - 0.17; at T3 βHCC= - 0.04;βCCC= - 0.48). In this cohort of newly diagnosed children that had good medical response by one-year post diagnosis, at 4- and 12-months post diagnosis, psychological factors were the only domain of current CC to significantly predict global health, accounting for 29.1 % and 24.1 % of its variance respectively. DISCUSSION:Findings suggest that the global health of IBD patients is not fixed by early life experiences and shed light onto potential psychosocial treatment targets.
The mucosal virome is increasingly recognized for its potential role in shaping intestinal health and disease. Building on previous findings, we analyzed the mucosal virome from 51 individuals, including newly diagnosed treatment naïve participants with ulcerative colitis (UC), Crohn’s disease (CD), and non-inflammatory bowel disease (non-IBD) controls, incorporating longitudinal sampling for a subset of the participants. Viromes were highly individualized, with no shared or core components across participants. Unlike fecal virome studies, we observed no significant associations between mucosal virome diversity and mucosal inflammation, disease subtype, or sampling site. However, there was positive correlation between virome and bacteriome diversity, particularly in CD, suggesting the presence of dynamic interactions that influence microbial community structure. Crassvirales was abundant in the mucosa layer and, consistent with prior studies, Crassvirales abundance was reduced in IBD, irrespective of inflammation status or IBD subtype. These findings highlight their potential as biomarkers of virome health. Our data also revealed the potential presence of altered bacteriome-virome interactions and longitudinal sampling revealed a persistent subset of viruses, potentially shaping disease progression and remission dynamics. Our study underscores the importance of distinguishing microbial community dynamics across IBD subtypes and highlights Crassvirales as key players in mucosal immunity.
Abstract Background Antimicrobial serologies have been associated with Inflammatory Bowel Disease (IBD) type and Crohn’s disease (CD) progression. However, prospective pediatric data examining these associations while considering disease location are sparse. Aims 1) Describe rates of serology positivity by disease location; 2) Assess the ability of serologies to predict CD progression to stricturing (B2) /penetrating (B3) behaviour, while accounting for IBD location. Methods Children with CD enrolled in the prospective multicentre Canadian Children IBD Network (CIDsCaNN) were included. ASCA IgA and IgG, CBir1, OmpC and ANCA positivity were measured centrally at Cedars-Sinai. We assessed variables at diagnosis and last follow up. We used Pearson’s Chi-Squared test to compare proportions and Mann-Whitney U test to compare medians between groups. We used multivariable Cox regression to determine the association between serologies and progression to B2/B3 amongst CD patients with B1 at diagnosis, while accounting for L1 location. We calculated area under the ROC curve (AUC) to quantify predictive ability. Results There were 512 CD patients included: median age 13 y (IQR 10.8-14.9), follow up 3.3 y (IQR 1.9-5.0). There were 50/452 (11%) B1 CD patients who progressed (L1: 16/77 (21%); L2: 7/112 (6%); L3: 27/241 (11%)). ASCA+ was more frequent among patients with L1/L3 compared to L2 CD (28% vs 13%, p=0.009), while CBir1+ and OmpC+ rates did not differ by CD location (55% vs 48%, p=0.19 and 9% vs 9%, p=0.85). ANCA+ rate was higher among L2 CD compared to L1/L3 CD (30% vs 10%, p<0.001). In univariate survival analysis, CBir1+, ASCA+ and L1 were associated with progression to B2/B3 (Table 1). In multivariable analysis, only positivity for CBir1+ and L1 were associated with progression. CBir1 titre had only moderate ability to predict progression (AUC 0.65 (95%CI 0.57-0.72)). Conclusions While ASCA and CBir1 are associated with complicated CD in univariate analysis, this appears to be mediated by small bowel location for ASCA. While CBir1 was independently associated with B2/B3 disease, its predictive ability alone was limited. Table 1. Unadjusted and Adjusted Hazard Ratios for Progression to B2 or B3 Complications Funding Agencies CIHRCh.I.L.D Foundation
Background:The transition from pediatric to adult health care marks a complex and pivotal process for adolescents and young adults with inflammatory bowel disease (IBD). This group requires support regarding disease self-management, skill development, and system navigation in preparation for transition. Evidence-based interventions are needed to promote optimal health and psychosocial outcomes for adolescents and young adults with IBD during this period. Objective:A qualitative study embedded within a randomized controlled trial was conducted to evaluate the perceived impact of a biopsychosocial transition intervention on the transition experiences of adolescents and young adults, their views on the intervention, and recommendations for future care. Methods:This patient-oriented research study used a qualitative descriptive design. Virtual semistructured interviews were held with 21 adolescents and young adults with IBD (16-18 y) enrolled in the randomized controlled trial (intervention arm n=11 and control arm n=10). Interviews were audio-recorded, transcribed, and analyzed using an inductive approach to reflexive thematic analysis. Five members of a Youth Advisory Panel with lived experience of IBD collaborated throughout data analysis, interpretation, and the presentation of findings. Results:We constructed three themes through our analysis: (1) making meaning of transitions in care; (2) perceptions and impact of the biopsychosocial transition intervention; and (3) considerations for future transition care, including the importance of individualized support. Conclusions:Our findings illustrate the importance of relationships and the impact of a biopsychosocial intervention on adolescents' and young adults' confidence, knowledge, and self-management skills during transition. The results, which indicate the criticality of tailoring transition supports according to adolescents' and young adults' preferences and characteristics, will be used to refine the biopsychosocial intervention before it can be scaled and spread.
Host - microbiome interactions are central to Crohn'sdisease (CD) pathogenesis; yet the early metabolic alterations that precededisease onset remain poorly defined. To explore preclinical metabolicsignatures of CD, we analyzed baseline serum metabolomic profiles in a nestedcase-control study within the Crohn's and Colitis Canada - Genetics, Environment, Microbiome (CCC-GEM) Project, a prospective cohort of 5,122 healthyfirst-degree relatives (FDRs) of CD patients. We included 78 individuals wholater developed CD and 311 matched FDRs who remained disease-free. In an untargetedassessment of metabolomic data, we identified 63 metabolites significantlyassociated with future CD risk. Integrative analyses further identifiedmultiple associations between CD-related metabolites and proteomic markers, gutmicrobiome composition, antimicrobial antibody, fecal calprotectin andC-reactive protein. Quinolinate, a tryptophan catabolite, was elevated inindividuals who later developed CD and showed strong positive correlations withC-reactive protein, fecal calprotectin, and C-X-C motif chemokine ligand 9 (CXCL9).In contrast, higher levels of ascorbate and isocitrate were associated withreduced CD risk and were negatively correlated with C-reactive protein and CD-associated proteins.These findings identify several distinct molecular pathways that contribute toCD pathogenesis.
Purpose: The incidence of childhood -onset inflammatory bowel disease (IBD) is rising. We described variation in health services utilization and need for surgery among children with IBD between six and 60 months following IBD diagnosis across Canadian pediatric centers and evaluated the associations between care provided at diagnosis at each center and the variation in these outcomes. Patients and Methods: Using population -based deterministically -linked health administrative data from four Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario) we identified children diagnosed with IBD <16 years of age using validated algorithms. Children were assigned to a pediatric center of care using a hierarchical approach based on where they received their initial care. Outcomes included IBD-related hospitalizations, emergency department (ED) visits, and IBD-related abdominal surgery occurring between 6 and sixty months after diagnosis. Mixed -effects meta -analysis was used to pool results and examine the association between center -level care provision and outcomes. Results: We identified 3784 incident cases of pediatric IBD, of whom 2937 (77.6%) were treated at pediatric centers. Almost a third (31.4%) of children had >= 1 IBD-related hospitalization and there were 0.66 hospitalizations per person during follow-up. More than half (55.8%) of children had >= 1 ED visit and there were 1.64 ED visits per person. Between -center heterogeneity was high for both outcomes; centers where more children visited the ED at diagnosis had more IBD-related hospitalizations and more ED visits during follow-up. Between -center heterogeneity was high for intestinal resection in Crohn's disease but not colectomy in ulcerative colitis. Conclusion: There is variation in health services utilization among children with IBD and risk of undergoing intestinal resection in those with Crohn's disease, but not colectomy among children with ulcerative colitis, across Canadian pediatric tertiary -care centers. Improvements in clinical care pathways are needed to ensure all children have equitable and timely access to high quality care.
Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN. We analyzed prospectively recorded food frequency questionnaires (FFQs) for pre-diagnosis dietary patterns. Fecal microbiota were sequenced (16SrRNA) at baseline and through an 18-month follow-up period. Dietary patterns, Mediterranean diet adherence, and stool microbiota were associated with EEN treatment outcomes, disease flare, need for anti-tumor necrosis factor (TNF)-α therapy, and long-term clinical outcomes. Ninety-eight patients were included. Baseline disease severity and microbiota were associated with diet. Four dietary patterns were identified by FFQs; a “mature diet” high in fruits, vegetables, and fish was linked to increased baseline microbial diversity, which was associated with fewer disease flares (p < 0.05) and a trend towards a delayed need for anti-TNF therapy (p = 0.086). Baseline stool microbial taxa were increased (Blautia and Faecalibacterium) or decreased (Ruminococcus gnavus group) with the mature diet compared to other diets. Surprisingly, a “pre-packaged” dietary pattern (rich in processed foods) was associated with delayed flares in males (p < 0.05). Long-term pre-diagnosis diet was associated with outcomes of EEN therapy in pediatric CD; diet–microbiota and microbiota–outcome associations may mediate this relationship.
Background The incidence of pediatric-onset inflammatory bowel disease (IBD) and the costs of caring for individuals with IBD are both increasing. We calculated the direct healthcare costs of pediatric IBD in the first year after diagnosis and developed a model to predict children who would have high costs (top 25th percentile).Methods Using data from the Canadian Children IBD Network inception cohort (<= 16 years of age, diagnosed between 2013 and 2019) deterministically linked to health administrative data from Ontario, Canada, we estimated direct healthcare and medication costs accrued between 31 and 365 days after diagnosis. Candidate predictors included age at diagnosis, sex, rural/urban residence location, distance to pediatric center, neighborhood income quintile, IBD type, initial therapy, disease activity, diagnostic delay, health services utilization or surgery around diagnosis, regular primary care provider, and receipt of mental health care. Logistic regression with stepwise elimination was used for model building; 5-fold nested cross-validation optimized and improved model accuracy while limiting overfitting.Results The mean cost among 487 children with IBD was CA$15 168 +/- 15 305. Initial treatment (anti-tumor necrosis factor therapy, aminosalicylates, or systemic steroids), having a mental health care encounter, undergoing surgery, emergency department visit at diagnosis, sex, and age were predictors of increased costs, while having a regular primary care provider was a predictor of decreased costs. The C-statistic for our model was 0.71.Conclusions The cost of caring for children with IBD in the first year after diagnosis is immense and can be predicted based on characteristics at diagnosis. Efforts that mitigate rising costs without compromising quality of care are needed. Cost of caring for children with IBD is high-CA$15 168 between 31 and 365 days from diagnosis in 487 Canadian children. Predictors of high costs included anti-tumor necrosis factor therapy and mental health care, with lower costs in those with a primary-care provider.