Pediatric-onset Inflammatory Bowel Disease Research Articles

P655 Early life mebendazole exposure increases the risk of adult-onset ulcerative colitis: a population-based cohort study

Abstract Background According to the hygiene hypothesis, exposure to parasites may promote immune tolerance and protect against inflammatory bowel disease (IBD). The early life period, considered to extend from prenatal life to up to 5 years of age, is important towards immune maturation; exposures during this period are especially relevant towards IBD risk. We examined the impact of exposure to mebendazole, a broad-spectrum anthelminthic agent, during childhood and adolescence, on the risk of IBD, ulcerative colitis (UC) and Crohn’s disease (CD). Methods We used prospectively collected historical data of all individuals born in Denmark between 1995 and 2018 from national registers to conduct a population-based cohort study. Using the National Prescription Register, we identified mebendazole exposure at <18 years of age, as well as at <5 years of age. Using ICD8/10 codes in the cross-linked National Patient Register, we identified individuals who were subsequently diagnosed with UC or CD at <16 or ≥16 years of age. We performed adjusted Cox proportional hazards regression analyses to determine the risk of IBD, UC and CD with mebendazole exposure after adjusting for potential confounders, which included calendar period, number of siblings and half-siblings, antibiotic prescription, sex, socio-economic status, degree of urbanization and parental IBD status. Results Of 1,520,290 individuals in the cohort, 615,794 had childhood mebendazole exposure. 1,555 and 1,499 individuals were subsequently diagnosed with pediatric- and adult-onset IBD, respectively. On multivariable analysis, mebendazole exposure at <18 years of age did not impact pediatric- or adult-onset IBD risk (aHR 0.97, 95% CI 0.87, 1.07 and 1.08, 95% CI 0.97, 1.19, respectively) (Table). On limiting mebendazole exposure to age <5 years, while there was no association with pediatric-onset IBD (aHR 0.98, 95% CI 0.87, 1.11), adult-onset IBD risk was increased (aHR 1.17, 95% CI 1.04, 1.31). This increase in risk was driven by UC (aHR 1.32, 95% CI 1.12, 1.55), but not CD (1.03, 95% CI 0.87,1.22) (Figure) Table: Crude and adjusted estimates for outcome with exposure to mebendazole in early life (<5 years of age) Figure: Cumulative incidence curves for (a) ulcerative colitis and (b) Crohn’s disease Conclusion Early life, but not later in childhood or adolescence, mebendazole exposure is associated with increase in the risk of adult-onset UC. Mebendazole exposure does not impact pediatric-onset IBD risk or CD risk. These findings emphasize the importance of early-life exposures in shaping the risk of IBD later in life, may indicate differences between UC and CD risk factors and pathways, and may call for re-evaluation of risks and benefits of large-scale helminth eradication programs.

Twenty-first Century Trends in the Global Epidemiology of Pediatric-Onset Inflammatory Bowel Disease: Systematic Review

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. 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. 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. 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.

Vedolizumab Is Safe and Efficacious for the Treatment of Pediatric-Onset Inflammatory Bowel Disease Patients Who Fail a Primary Biologic Agent.

BackgroundVedolizumab (VDZ) is currently licensed for use in adults for the treatment of inflammatory bowel disease (IBD). We aimed to investigate the clinical course of pediatric-onset IBD following treatment with VDZ as more than a secondary biologic agent. We also evaluated factors associated with secondary loss of response (LOR) and durability of VDZ treatment.MethodsPediatric-onset IBD patients diagnosed at an age younger than 18 years who had received VDZ as more than a secondary biologic agent were included in this retrospective observational study conducted at the Department of Pediatrics of two centers in Korea. Comparative analysis was conducted between groups divided according to the development of secondary LOR during VDZ treatment.ResultsA total of 24 patients comprising 10 patients with Crohn’s disease and 14 with ulcerative colitis were included. Of these, 19 were male and 5 were female. The mean age at diagnosis was 14.6 ± 2.5 years. The mean age at initiation of VDZ was 20.5 ± 2.8 years. Nine patients (37.5%) had received two or more biologic agents before starting VDZ. During a median of 0.9 years follow-up from VDZ initiation, 9 patients (37.5%) experienced LOR requiring interval shortening and 4 patients (16.7%) were changed to a different biologic agent. According to multivariate Cox proportional hazard regression analysis, administration of two or more biologic agents before VDZ treatment was the only factor positively associated with LOR (hazard ratio [HR], 5.6; 95% confidence interval [CI], 1.026–30.56; P = 0.047), while LOR was the only factor negatively associated with VDZ durability (HR, 0.003; 95% CI, 0.00–0.08; P = 0.010). No adverse events were observed during treatment with VDZ.ConclusionVDZ is safe and efficacious for the treatment of pediatric-onset IBD patients failing a primary biologic agent. The durability of VDZ may be enhanced by introducing VDZ earlier in the disease course. Further prospective studies in children are required in the future to validate these findings.

Exploring Reproductive Health Decision Experiences and Preferences of Women With Pediatric-Onset Inflammatory Bowel Diseases.

Women with inflammatory bowel diseases (IBDs), such as Crohn's disease or ulcerative colitis, face several disease-specific concerns related to their reproductive health decisions. This study explored the reproductive health decision-making experiences and preferences of women with IBD to discover ways to improve this aspect of comprehensive care. We recruited women ages 18-44 years with IBD to participate in individual, semistructured interviews exploring their experiences and attitudes toward parenthood, pregnancy, contraception, and family planning care. Two independent coders performed analysis using an inductive and deductive coding approach and identified key themes. Twenty-one women with IBD participated in interviews (average age 24.7±5.9 years, range 18-43 years; average age of diagnosis 14.1±2.0 years). We identified 4 key themes: (1) Nulliparous women who do not currently desire pregnancy appear to lack reproductive health knowledge; (2) Women with IBD lack clarity regarding the role IBD plays in contraceptive choice; (3) Related to pregnancy, women are concerned about the heredity of IBD, antepartum disease activity, and the safety of their current medications; (4) Women with IBD typically default to their reproductive health provider for reproductive health care and counseling, but they expect their gastroenterologist to initiate relevant reproductive health discussions with them and to provide information in the context of their disease. Women have concerns about the effects of IBD on pregnancy, parenthood, and contraceptive choice; however, many have had limited or no discussion with their gastroenterologist about the topic.

P002 Psychiatric Comorbidity and Suicide in Childhood Onset Immune-Mediated Diseases -A Systematic Review and Meta-Analysis.

The course of paediatric onset immune mediated inflammatory diseases (IMID) is both physically and mentally challenging. Emotional distress with anxiety and depressive symptoms is commonly reported, however, data on diagnosed comorbid psychiatric disorders is scarce. The aim of this study was to provide a literature overview of psychiatric comorbidity, suicide rates, and their potential risk factors, in childhood onset IMID. This was a systematic review following the PRISMA guidelines. The protocol was registered at Prospero (ID: CRD42021233890). A literature search was made in the databases Pubmed, PsychINFO, and Embase. We included the following IMID: paediatric onset inflammatory bowel disease (pIBD), rheumatic diseases (RD) and autoimmune liver diseases. Studies that provided prevalence rates of diagnosed psychiatric disorders and/or suicide, were included. Pooled prevalence rates of psychiatric disorders (grouped according to ICD-10 criteria) reported by three or more studies, within the same IMID, were calculated using random-effects meta-analysis. Two authors independently evaluated risk of bias using the New-Castle Ottawa scale. Twenty-three studies met the inclusion criteria; 13 describing psychiatric disorders in pIBD and 10 in RD. No study reported on psychiatric disorders in autoimmune liver diseases. Compared to controls without somatic disease, IMID patients had an increased risk of psychiatric disorders, with anxiety and mood disorders being the most common. Prevalence rates for anxiety and mood disorders in pIBD were 6% (95% confidence interval (CI): 4%-9%) and 4% (95%CI: 2%-8%), respectively, in register-based studies, and 33% (95%CI: 25%-41%) and 18% (95%CI:12%-26%), respectively, in studies using psychiatric assessment. In RD pooled estimates were 13% (95%CI: 12%-15%) for anxiety disorders and 20% (95%CI: 15%-26%) for mood disorders. Based on single studies, risk of suicide was increased in pIBD, but not in juvenile idiopathic arthritis, the most common RD. In this systematic review, patients with childhood onset IMID had increased prevalence of psychiatric disorders compared to controls. However, only pooled estimates on emotional disorders were possible and studies investigating broad spectrum of psychiatric disorders are needed.

Colorectal Cancer associated with pediatric inflammatory bowel disease: a case series

BackgroundInflammatory bowel disease (IBD) is associated with an increased risk of Colorectal cancer (CRC), and its most important risk factors are the duration and extent of the disease. Pediatric-onset inflammatory bowel disease has a tendency for a more extensive, more severe, and longer predicted disease duration than adult-onset inflammatory bowel disease. This study aimed to identify the clinical characteristics of patients with CRC related to pediatric-onset IBD and consider the appropriateness of current surveillance endoscopy recommendations for the detection of premalignant lesions and early-stage CRC.MethodsWe searched a research platform based on the SUPREME electronic medical record data-mining system to identify cases of colorectal malignancy in patients with pediatric IBD that presented between 2000 and 2020.ResultsDuring the follow-up, 4 (1.29 per 1000 person years) out of 443 patients with PIBD was diagnosed with CRC. The median age at diagnosis of CRC was 18.5 (range: 15–24) years, and the median period from diagnosis of IBD to CRC was 9.42 (range: 0.44–11.96) years. The sigmoid colon was the most frequent location of CRC (in 3 of the 4 cases). Adenocarcinoma was the most common histological type (in 2 of the 4 cases).ConclusionsPatients with pediatric-onset IBD exhibited a much shorter disease duration than that of adult-onset IBD at the time of diagnosis of CRC, suggesting that surveillance endoscopy for the detection of precancerous lesions and early-stage cancer should be initiated earlier in pediatric patients than in adult patients.

The Incidence and Characteristics of Venous Thromboembolisms in Paediatric-Onset Inflammatory Bowel Disease: A Prospective International Cohort Study Based on the PIBD-SETQuality Safety Registry.

Background and AimsGuidelines regarding thromboprophylaxis for venous thromboembolisms [VTEs] in children with inflammatory bowel disease [IBD] are based on limited paediatric evidence. We aimed to prospectively assess the incidence of VTEs in paediatric-onset IBD [PIBD], characterize PIBD patients with a VTE and identify potential IBD-related risk factors.MethodsFrom October 2016 to September 2020, paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient <19 years with IBD. IBD details [type, Paris classification, clinical and biochemical disease activity, treatment] and VTE details [type, location, treatment, outcome] were collected. To estimate VTE incidence, participants annually reported the number of PIBD patients, data source and catchment area of their centre. A systematic literature review and meta-analysis was performed to calculate the VTE incidence in the general paediatric population.ResultsParticipation of 129 PIBD centres resulted in coverage of 24 802 PIBD patients. Twenty cases of VTE were identified [30% Crohn’s disease]. The incidence of VTEs was 3.72 (95% confidence interval [CI] 2.27–5.74) per 10 000 person-years, 14-fold higher than in the general paediatric population (0.27 [95% CI 0.18–0.38], p < 0.001). Cerebral sinus venous thrombosis was most frequently reported [50%]. All but one patient had active IBD, 45% were using steroids and 45% were hospitalized. No patient received thromboprophylaxis, whereas according to current PIBD guidelines, this was recommended in 4/20 patients.ConclusionThere is an increased risk of VTEs in the PIBD population compared to the general paediatric population. Awareness of VTE occurrence and prevention should be extended to all PIBD patients with active disease, especially those hospitalized.

Clinical Features and Long-Term Outcomes of Paediatric-Onset Inflammatory Bowel Disease in a Population-Based Cohort in the Songpa-Kangdong District of Seoul, Korea

The long-term outcomes of paediatric-onset inflammatory bowel disease [pIBD] in non-Caucasian populations are unknown. We therefore evaluated and compared the clinical features and long-term outcomes of pIBD with those of adult-onset IBD [aIBD] using a population-based cohort in the Songpa-Kangdong district of Seoul, Korea. Clinical characteristics and prognoses were compared between the two groups: pIBD [defined as <18 years of age at diagnosis] and aIBD [18-59 years of age at diagnosis]. We identified 131 patients with pIBD (48 ulcerative colitis [UC], 83 Crohn's disease [CD]) and 1192 patients with aIBD [866 UC, 326 CD] during 1986-2015. Extensive colitis at diagnosis was more prevalent in pUC than in aUC [45.8% vs 22.3%, p < 0.001], and the overall exposure to corticosteroids, thiopurines and anti-tumour necrosis factor agents was higher in pUC than in aUC [p < 0.001]. The cumulative risk of colectomy was higher in pUC than in aUC during a median follow-up of 125.0 and 112.1 months, respectively [8.9% vs 1.8% at 10 years after diagnosis, p = 0.030]. Ileocolonic location and inflammatory behaviour at diagnosis were more common in pCD than in aCD; however, patients with pCD and aCD did not differ regarding treatment or disease course during a median follow-up of 137.2 and 120.9 months, respectively. Our study showed clear differences between pIBD and aIBD, especially in UC. pUC presents with more extensive diseases and may have a more severe disease course, as suggested by an earlier time to administering medications and performing colectomy.

Tofacitinib Therapy in Children and Young Adults With Pediatric-onset Medically Refractory Inflammatory Bowel Disease.

Tofacitinib, a selective Janus kinase inhibitor, effectively induces and maintains remission in adults with inflammatory bowel disease (IBD), but data are limited in children. This study aimed to evaluate the efficacy and safety of tofacitinib for medically refractory pediatric-onset IBD. This single-center retrospective study included subjects ages 21 years and younger who started tofacitinib for medically refractory IBD. Clinical activity indices, clinical response, steroid-free remission, biochemical response, and adverse events (AEs) were evaluated over 52 weeks. Twenty-one subjects, 18 with ulcerative colitis or indeterminate IBD, received tofacitinib. At the end of the 12-week induction period, 9 out of 21 (42.9%) subjects showed clinical response and 7 out of 21 (33.3%) were in steroid-free remission. Of evaluable subjects at 52 weeks, 7 out of 17 (41.2%) showed clinical response and were in steroid-free remission. Of those remaining on tofacitinib at 1 year, none required concomitant systemic corticosteroids. Tofacitinib was discontinued in 8 subjects because of refractory disease, including 8 who ultimately underwent colectomy, and in 1 subject who developed a sterile intra-abdominal abscess. There were no instances of thrombi, zoster reactivation, or clinically significant hyperlipidemia, all of which were AEs of interest. There is limited experience with tofacitinib in pediatric IBD. In this cohort, tofacitinib induced rapid clinical response with sustained efficacy in nearly half of subjects. This study provides encouraging evidence for the efficacy and safety of tofacitinib as part of the treatment paradigm for young individuals with moderate-to-severe IBD. Larger, well-powered, prospective studies are warranted.

DOP71 Fungal and bacterial gut microbiota in paediatric onset Inflammatory Bowel Disease introduced to infliximab

Abstract Background Paediatric Inflammatory Bowel Disease (PIBD), including Crohn’s Disease (CD), Ulcerative Colitis (UC) and IBD undefined (IBDU) is increasing worldwide and is characterized by an onset inflammation in the gastrointestinal tract. The patients may present severe symptoms such as abdominal pain, diarrhoea and bloody stool. No defined pathogenesis has been established for PIBD, but an imbalanced intestinal microbiota is strongly associated to the disease. Anti-tumour necrosis factor alpha (TNF-α) is an effective drug to treat inflammation in IBD, but up to half of the patients do not have a long-term response to the drug. Presently, there are no methods available to predict the TNF-α response. Here we have investigated the biomarkers of the gut fungal and bacterial microbiota, which are largely unexplored in paediatric patients, particularly for the fungal microbiota, with the aim to find possible predictors of drug response. Methods The gut microbiota composition of 30 PIBD (25 CD, 2 UC and 3 IBDU) patients at the Children′s Hospital, University of Helsinki receiving the anti-TNF-α drug infliximab (IFX) was studied by MiSeq sequencing targeting the bacterial 16S rRNA gene and fungal ITS region separately from faecal samples collected before the start of treatment and two and six weeks after treatment initiation. The response to IFX was evaluated by a faecal calprotectin value below 100 µg/g at week six after treatment initiation. The fungal MiSeq sequencing data was processed by using the DADA2 pipeline, annotated to the BLAST database and analysed using the package mare. The bacterial MiSeq sequencing data was analysed using mare and annotated to the SILVA database. Results Both the fungal and bacterial microbiota differed significantly between responders compared to non-responders to IFX, further validated by high predictive power (area under curve &amp;gt; 0.8) for therapy response. This difference was characterized by an increase in short-chain fatty acid producing bacteria, such as bacteria in the class Clostridia in the responders at baseline. This was observed as elevated Faecalibacterium and Subdoligranulum genera in particular of responders at baseline. Additionally, Candida was increased while Saccharomyces was decreased in non-responders at the end of the study. Finally, we observed that the interkingdom correlations differed between response groups to IFX. Conclusion Our results strengthen the proposal that the gut microbiota composition of PIBD patients could predict the response to anti-TNF-α treatment in the future.

P012 Low frequencies of circulating inhibitory TIGIT+CD38+ effector T cells identify an immunologically distinct subgroup of pediatric patients with severe Crohn’s disease

Abstract Background Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a T cell driven intestinal inflammation. Current T cell suppressive therapeutic regimens are moderately successful due to a large clinical heterogeneity amongst patients. Detailed understanding of aberrant inflammatory and inhibitory T-cell responses in individual patients is lacking. Previously, we have shown that, in healthy individuals, 40% of peripheral blood CD38+ (CD62LnegCD4+) effector T cells, which are enriched for intestinal antigen specificity, express the inhibitory molecule T cell immunoglobulin and ITIM domain (TIGIT). TIGIT+CD38+ effector T cells have a regulatory function, produce IL-10 and express multiple co-inhibitory receptors. Conversely, TIGITnegCD38+ effector T cells are enriched in inflammatory IFN-γ producing cells. In a small cohort of pediatric-onset IBD patients, low frequencies of TIGIT+CD38+ effector T cells were associated with a reduced duration of clinical remission. We hypothesize that a subgroup of IBD patients has reduced frequencies of circulating inhibitory TIGIT+CD38+ effector T cells, reflecting a distinct pathogenesis associated with a more severe disease course. Methods In the Rotterdam PIBD-SETQuality cohort of newly diagnosed pediatric IBD patients (CD: n=37; UC: n=16), patients with suspicion of IBD but negative diagnosis (n=12) and age-matched healthy controls (n=22), we monitored TIGIT+ and TIGITnegCD38+ effector T cells in peripheral blood and collected plasma at diagnosis and during immunosuppressive therapy. Results At diagnosis, approximately 50% of CD patients had strongly reduced frequencies of inhibitory TIGIT+CD38+ effector T cells compared to UC patients and age-matched controls. CD patients with low frequencies of TIGIT+CD38+ effector T cells at diagnosis needed earlier anti-TNF treatment with 73% of patients receiving anti-TNF treatment within 1 year versus 38% for patients with normal frequencies of TIGIT+CD38+ effector T cells. Inflammatory TIGITnegCD38+ effector T cells were enriched in Ki67, reflecting recent proliferation, and expressed chemokine receptors associated with inflammatory non-classical T-helper-1 IFN-γ hiIL-17lo producing cells. High frequencies of TIGITnegCD38+ effector T cells correlated with high plasma IFN-γ concentrations. Conclusion These results demonstrate that reduced frequencies of circulating inhibitory TIGIT+CD38+ effector T cells discriminate a subgroup of pediatric CD patients with high frequencies of inflammatory IFN-γ hiIL-17lo producing cells, high plasma IFN-γ concentrations, and in need of early anti-TNF treatment, possibly indicative of a distinct pathogenesis with a more severe disease course.

Pediatric-onset Inflammatory Bowel Disease: What Are Different from Adult in the Treatment?

Pediatric-onset inflammatory bowel disease differs from adults in its epidemiological and clinical characteristics and courses. Since it is diagnosed at a young age, the duration of the disease is relatively longer than in adults. Therefore, it is necessary to select drugs in consideration of long-term risks and benefits, and efforts such as therapeutic drug monitoring to maximize the treatment effects and minimize side effects are required. In addition, special considerations for treating pediatric-onset inflammatory bowel disease include attention to the effects of the disease on growth and development, nutrition, and psychosocial problems. In children, more aggressive treatment is needed to avoid missing therapeutic window of opportunity during periods of rapid growth and development. Finally, efforts should be made to ensure that the therapeutic goals of mucosal healing are achieved, the quality of life is restored, and the transition to adult therapy is well carried out.

Early Life Greenspace and the Risk of Pediatric-Onset Inflammatory Bowel Disease: Insights into the Link Between Environmental and Human Health

Early Life Greenspace and the Risk of Pediatric-Onset Inflammatory Bowel Disease: Insights into the Link Between Environmental and Human Health

Novel CARMIL2 loss-of-function variants are associated with pediatric inflammatory bowel disease

CARMIL2 is required for CD28-mediated co-stimulation of NF-κB signaling in T cells and its deficiency has been associated with primary immunodeficiency and, recently, very early onset inflammatory bowel disease (IBD). Here we describe the identification of novel biallelic CARMIL2 variants in three patients presenting with pediatric-onset IBD and in one with autoimmune polyendocrine syndrome (APS). None manifested overt clinical signs of immunodeficiency before their diagnosis. The first patient presented with very early onset IBD. His brother was found homozygous for the same CARMIL2 null variant and diagnosed with APS. Two other IBD patients were found homozygous for a nonsense and a missense CARMIL2 variant, respectively, and they both experienced a complicated postoperative course marked by severe infections. Immunostaining of bowel biopsies showed reduced CARMIL2 expression in all the three patients with IBD. Western blot and immunofluorescence of transfected cells revealed an altered expression pattern of the missense variant. Our work expands the genotypic and phenotypic spectrum of CARMIL2 deficiency, which can present with either IBD or APS, aside from classic immunodeficiency manifestations. CARMIL2 should be included in the diagnostic work-up of patients with suspected monogenic IBD.

Mutation spectrum of NOD2 reveals recessive inheritance as a main driver of Early Onset Crohn\u2019s Disease

Inflammatory bowel disease (IBD), clinically defined as Crohn’s disease (CD), ulcerative colitis (UC), or IBD-unclassified, results in chronic inflammation of the gastrointestinal tract in genetically susceptible hosts. Pediatric onset IBD represents ≥ 25% of all IBD diagnoses and often presents with intestinal stricturing, perianal disease, and failed response to conventional treatments. NOD2 was the first and is the most replicated locus associated with adult IBD, to date. However, its role in pediatric onset IBD is not well understood. We performed whole-exome sequencing on a cohort of 1,183 patients with pediatric onset IBD (ages 0–18.5 years). We identified 92 probands with biallelic rare and low frequency NOD2 variants accounting for approximately 8% of our cohort, suggesting a Mendelian inheritance pattern of disease. Additionally, we investigated the contribution of recessive inheritance of NOD2 alleles in adult IBD patients from a large clinical population cohort. We found that recessive inheritance of NOD2 variants explains ~ 7% of cases in this adult IBD cohort, including ~ 10% of CD cases, confirming the observations from our pediatric IBD cohort. Exploration of EHR data showed that several of these adult IBD patients obtained their initial IBD diagnosis before 18 years of age, consistent with early onset disease. While it has been previously reported that carriers of more than one NOD2 risk alleles have increased susceptibility to Crohn’s Disease (CD), our data formally demonstrate that recessive inheritance of NOD2 alleles is a mechanistic driver of early onset IBD, specifically CD, likely due to loss of NOD2 protein function. Collectively, our findings show that recessive inheritance of rare and low frequency deleterious NOD2 variants account for 7–10% of CD cases and implicate NOD2 as a Mendelian disease gene for early onset Crohn’s Disease.

A81 BARRIERS AND FACILITATORS OF PEDIATRIC TO ADULT TRANSITION IN IBD: A PILOT STUDY EVALUATING THE STAKEHOLDER EXPERIENCE

Abstract Background Inflammatory bowel disease (IBD) is increasing in prevalence with up to 25% of IBD patients diagnosed before 18 years of age. These patients will require graduation from pediatric care to adult services. The transition of care from pediatric to adult gastroenterologists (GIs) is a purposeful transition that requires planning with involvement of all stakeholders to ensure proper transition and avoid interruption in care. Aims To identify the transition experiences of adult patients with pediatric diagnoses of IBD, their parents, pediatric and adult GIs and registered nurses (RNs) and identify barriers and facilitators to a successful transition. Methods Patients aged 18–25 diagnosed with pediatric-onset IBD were included. Semi-structured focus groups were held with 9 patients and separately with 4 parents. Questions focused on the patient transition experience, opportunities for improvement, and patient quality of life. Transition practices and expectations of 12 adult GIs, 7 pediatric GIs and 9 IBD nurses were also investigated in a series of provider specific focus groups. The groups were audio-recorded, transcribed and qualitative themes were noted. Results Patients: Facilitators included ease of access to adult providers outside of clinic time and parental presence in the early stages of transition. Barriers included abrupt transitions to adult care by age 18, lack of choice regarding adult GI and lack of adult nursing. Parents: Facilitators included an extended transition period, availability of support groups/resources. Barriers related to exclusion from the transition process and lack of input on adult GI choice. RNs: Facilitators include having champion IBD nurses on the pediatric and adult side during transition. Barriers included lack of educational tools for patients. Pediatric GIs: Facilitators included effective communication between adult and pediatric GIs, having an emergency assessment protocol, involving families in the transition process and access to multidisciplinary resources. Barriers included prolonged wait time for transfer and lack of adult access to multidisciplinary support. Adult GIs: Facilitators included succinct transfer summaries and formal transition programs for high risk patients. Barriers included a lack of multidisciplinary support, difficulty reaching rural areas, heavy case loads and prolonged wait time to transfer of care. Conclusions This study explores the stakeholder experience of pediatric to adult transition in IBD. Themes noted related to efficient communication between GIs, streamlining transfer summaries, ensuring a gradual transition process, involving parents and ensuring access to multidisciplinary resources. Identifying barriers and facilitators during the transition process can provide insight into creating a successful pediatric to adult transitions program in IBD. Funding Agencies None

A25 THE RISING GLOBAL INCIDENCE OF PEDIATRIC INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW OF POPULATION-BASED STUDIES

Abstract Background The incidence of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing internationally, particularly in developing nations where rates were historically low. Previous reports of the incidence and prevalence of pediatric-onset IBD have identified a paucity of population-based studies. Aims We reviewed the global trends in incidence of pediatric IBD using evidence from population-based studies. Methods (PROSPERO CRD42019125193) We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from 01/2010-02/2020 to identify population-based studies reporting the incidence of pediatric-onset IBD, CD, and UC. Included studies combined childhood and adolescent-onset IBD (onset &amp;lt;21y). Changes in incidence since 2000 were plotted by continent, with data from 2000–09 provided by our previous systematic review1. To depict trends, multiple times points reported in single studies were connected on graphs. When incidence was reported as an aggregated estimate over a range of years, data was plotted using the midpoint of the interval. Results Of 8096 abstracts screened, 74 studies described the incidence of IBD, CD, or UC in 33 countries (Figure panel A). The incidence of pediatric-onset IBD is highest in Northern Europe and North America, and lowest in Southern Europe, Asia, and the Middle East. This geographical distribution is similar in UC, while incidence of pediatric-onset CD is highest in North America and Northern Europe, followed by Australia. Trends in incidence over time, stratified by continent, are reported in Figure, panel B. Significantly increasing incidence of IBD, CD, and/or UC was reported in China, Bahrain, Canada, New Zealand, Australia, Singapore, Saudi Arabia, and most European countries. Very Early Onset (VEO) IBD significantly increased in Canada, however Saudi Arabia reported decreasing incidence of VEO-CD but stable incidence of VEO-UC. Conclusions Conclusion: Incidence of pediatric-onset IBD are highest in Northern Europe and North American and are increasing globally. There remains a paucity of studies from many parts of the world on the incidence pediatric IBD. Further research is needed to understand the pathogenesis of the rising incidence of pediatric IBD, including work to understand the genetic, environmental, immunological and microbiome alterations leading to the increasing rates in children.

Pediatric Inflammatory Bowel Disease

Inflammatory bowel disease is an important pediatric disease, with as many as 25% of cases presenting during childhood. In this article, we review the types, etiology epidemiology, presentation, diagnosis, and management of pediatric inflammatory bowel disease. We also highlight the unique aspects of pediatric-onset inflammatory bowel disease versus adult-onset and future directions in this field, such as the use of genetic studies and ultrasound for the management of pediatric patients with inflammatory bowel disease.

Pediatric-onset Inflammatory Bowel Disease Has Only a Modest Effect on Final Growth: A Report From the epi-IIRN.

The impact of pediatric-onset inflammatory bowel disease (IBD) on growth is debated. We aimed to investigate the effect of IBD on anthropometric measures at young adulthood. Children diagnosed with Crohn disease (CD) or ulcerative colitis (UC) (2005-2019) were identified in a national database along with matched non-IBD controls. Overall, 2229 IBD cases (68% CD) were matched to 4338 controls. Only females with CD differed in final height from controls (z scores: -0.37 ± 1.09 vs -0.25 ± 1.06, respectively; P = 0.01), corresponding to a mean difference of 0.7 ± 0.2 cm (all females) and 1.2 ± 0.3 cm in females diagnosed <14 years (P = 0.02). Final height was reduced in both sexes according to adjusted mean height difference analysis (-0.43 cm, 95% confidence interval -0.85 to -0.02; P = 0.04). This difference increased in patients with CD who underwent abdominal surgery (-0.91 cm, 95% confidence interval -1.39 to -0.42; P = 0.01). The proportion of patients with CD achieving final height z scores of -1 and zero differed significantly from controls for both males (71.1% and 34.8% vs 79.1% and 43.0%, respectively; P < 0.001) and females (67.7% and 30.4% vs 79.6%, and 43.3%, respectively; P < 0.001). Patients treated with anti-tumor necrosis factor agents during growth potential had similar height improvement to other regimens. Predominantly, patients with CD were leaner, with a greater proportion of subjects with underweight, compared with controls. In pediatric-onset IBD, absolute final height was modestly affected by females with CD. Nevertheless, greater proportions of both sexes with early diagnosis of CD failed to achieve normal final height, compared with controls.

EXPLORING THE REPRODUCTIVE HEALTH DECISION EXPERIENCES AND PREFERENCES OF WOMEN WITH INFLAMMATORY BOWEL DISEASES

Women with inflammatory bowel diseases (IBD), such as Crohn’s disease or ulcerative colitis, have normal fertility and can have healthy pregnancies and children. However, many have fewer children than the general population, with up to a third of women choosing “voluntary childlessness.” Given that IBD diagnoses can elicit reproductive concerns related to contraception choice, pregnancy, and parenthood, this study explored the reproductive health decision-making experiences and preferences of women with pediatric-onset IBD.