Comparison of endoscopic healing and durability between infliximab originator and CT-P13 in pediatric patients with inflammatory bowel disease.

Background and aims: Favourable clinical data were published on the efficacy of CT-P13, the first biosimilar of infliximab (IFX), in pediatric inflammatory bowel disease (IBD); however, few studies have compared the effect on endoscopic healing (EH) and drug retention rate between the IFX originator and CT-P13. Therefore, we aimed to compare EH and the drug retention rate between the IFX originator and CT-P13. Methods: Children with Crohn's disease (CD) and ulcerative colitis (UC)/IBD-unclassified (IBD-U) at 22 medical centers were enrolled, with a retrospective review conducted at 1-year and last follow-up. Clinical remission, EH and drug retention rate were evaluated. Results: We studied 416 pediatric patients with IBD: 77.4% had CD and 22.6% had UC/IBD-U. Among them, 255 (61.3%) received the IFX originator and 161 (38.7%) received CT-P13. No statistically significant differences were found between the IFX originator and CT-P13 in terms of corticosteroid-free remission and adverse events. At 1-year follow-up, EH rates were comparable between them (CD: P=0.902, UC: P=0.860). The estimated cumulative cessation rates were not significantly different between the two groups. In patients with CD, the drug retention rates were 66.1% in the IFX originator and 71.6% in the CT-P13 group at the maximum follow-up period (P >0.05). In patients with UC, the drug retention rates were 49.8% in the IFX originator and 56.3% in the CT-P13 group at the maximum follow-up period (P >0.05). Conclusions: The IFX originator and CT-P13 demonstrated comparable therapeutic response including EH, clinical remission, drug retention rate and safety in pediatric IBD.

First detection and characterization of hepatitis E virus (Rocahepevirus ratti) from urban Norway rats (Rattus norvegicus) in the Republic of Korea.

Hepatitis E virus (HEV), an emerging zoonotic pathogen, poses a significant public health concern worldwide. Recently, rat HEV (Rocahepevirus ratti genotype C1; HEV-C1) has been reported to cause zoonotic infections and hepatitis in humans. Human infections with HEV-C1 are considered to be underestimated worldwide due to limited knowledge of transmission routes, genome epidemiology, and the risk assessment of zoonosis associated with these viruses. A total of 186 wild Norway rats (Rattus norvegicus) were collected from the Republic of Korea (ROK) between 2011 and 2021. The prevalence of HEV-C1 RNA was 8 of 180 (4.4%) by reverse-transcription polymerase chain reaction. We first reported three nearly whole-genome sequences of HEV-C1 newly acquired from urban rats in the ROK. Phylogenetic analysis demonstrated that Korea-indigenous HEV-C1 formed an independent genetic group with those derived from R. norvegicus rats in other countries, indicating geographical and genetic diversity. Our findings provide critical insights into the molecular prevalence, genome epidemiology, and zoonotic potential of Rocahepevirus. This report raises awareness of the presence of Rocahepevirus-related hepatitis E among physicians in the ROK.

Gut Bacterial Dysbiosis in Irritable Bowel Syndrome: a Case-Control Study and a Cross-Cohort Analysis Using Publicly Available Data Sets.

Research on the gut microbiota in irritable bowel syndrome (IBS) shows discordant results due to inconsistent study designs or small sample sizes. This study aimed to characterize how gut microbiota in IBS patients differs from that in healthy controls by performing a case-control study and cross- and mega-cohort analysis. Multiple publicly shared data sets were examined by using a unified analytical approach. We performed 16S rRNA gene (V3-4) sequencing and taxonomic profiling of the gut bacterial communities. Fecal samples from children with IBS (n = 19) and age-matched healthy controls (n = 24) were used. Next, we analyzed 10 separate data sets using a unified data-processing and analytical approach. In total, 567 IBS patients and 487 healthy controls were examined. In our data sets, no significant differences existed in stool α-diversity between IBS patients and healthy controls. After combining all the data sets using a unified data-processing method, we found significantly lower α-diversity in IBS patients than in healthy controls. In addition, the relative abundance of 21 bacterial species differed between the IBS patients and healthy participants. Although the causal relationship is uncertain, gut bacterial dysbiosis is associated with IBS. Further functional studies are needed to assess whether the change in gut microorganisms contributes to the development of IBS. IMPORTANCE Research on the gut bacteria in irritable bowel syndrome (IBS) shows discordant results due to inconsistent study designs or small sample sizes. To overcome these issues, we analyzed microbiota of 567 IBS patients and 487 healthy people from 10 shared data sets using a unified method. We demonstrated that gut bacteria are less diverse in IBS patients than in healthy people. In addition, the abundance of 21 bacterial species is different between the two groups. Altered bacterial balance, called dysbiosis, has been reported in several disease states. Although the causal relationship is uncertain, gut bacterial dysbiosis also seems to be associated with IBS.

Gut microbiota affects brain development and behavior.

The gut covers a large surface area of the body and faces various external factors. The brain works in concert with commensal microbes in the gut to efficiently process the enormous amount of chemical signals that enter the gut every day. This review discusses: (1) evidence that gut bacteria can alter brain development and behavior, (2) mechanisms by which gut bacteria communicate with the brain, (3) preclinical and clinical studies demonstrating the impact of gut microbiota on autism spectrum disorder, and (4) variables worth consideration by future research on gut bacteria.

Treatment patterns of anti-tumour necrosis factor-alpha and prognosis of paediatric and adult-onset inflammatory bowel disease in Korea: a nationwide population-based study.

BACKGROUND: The global prevalence of inflammatory bowel disease (IBD) is increasing. However, population-level data are scarce for Asian populations. AIMS: To outline and compare paediatric and adult IBD incidence and prevalence data in Korea, describe prescription patterns, and analyse outcomes of anti-tumour necrosis factor (anti-TNF) use in a nationally representative cohort METHODS: IBD was identified based on the presence of Rare and Intractable Disease diagnosis codes for Crohn's disease (CD) and ulcerative colitis (UC). We calculated age-based prevalence and incidence, and examined prescription patterns. We used a Cox proportional hazard model to calculate the hazard ratio (HR) for undergoing surgery. RESULTS: The prevalence of CD increased between 2006 and 2015, particularly among those aged 10-19 years (12.7-35.5 patients per 100,000 people). The use of anti-TNF agents increased from 3.2% to 22.9% in paediatric CD patients. Early use of an anti-TNF agent increased 25-fold in CD patients. Further, CD patients aged 0-14 years were most likely to undergo fistulectomy (HR, 2.63; 95% confidence interval [CI], 1.73-3.97). Children with UC had a higher risk of undergoing surgery (HR, 3.01; 95% CI, 1.33-6.83) than adults. Early use of an anti-TNF agent in CD patients was associated with lower odds of surgery than late-stage use. CONCLUSION: The prevalence of IBD has increased over time, especially among paediatric patients. Given the magnitude of paediatric IBD disease burden, a multi-faceted approach is needed for early detection and vigilant monitoring to aim for better prognosis.

Saccharomyces boulardii and Lactulose for Childhood Functional Constipation: A Multicenter Randomized Controlled Trial.

Background/Aims: The effects of probiotics in children vary based on diseases and probiotic strains. We aim to investigate the effectiveness of Saccharomyces boulardii and lactulose for treating childhood functional constipation. Methods: This open-label randomized controlled trial was conducted at 10 university hospitals in Korea. Children who were diagnosed with functional constipation were allocated to 3 groups (lactulose monotherapy, combination therapy, and S. boulardii monotherapy). The primary outcome was treatment success rate that was accordingly defined as ≥ 3 bowel movements without incontinence at week 12. The cumulative successful maintenance and drug maintenance rates without drug changes were calculated throughout the study period. We compared stool frequency, incontinence, consistency, and painful defecation at week 2 among the 3 groups. Results: Overall, 187 children were assigned to the lactulose monotherapy (n = 69), combination therapy (n = 68), or S. boulardii monotherapy (n = 50) groups. The primary outcome was significantly higher in the lactulose monotherapy group (26.1%) or combination therapy group (41.2%) than in the S. boulardii monotherapy group (8.0%). The S. boulardii monotherapy group showed a significantly lower cumulative successful maintenance and drug maintenance rate than the other 2 groups. There were no significant intergroup differences in the frequency of defecation, incontinence, painful defecation, or stool consistency during the follow-up at week 2. Conclusion: S. boulardii monotherapy was not superior to lactulose monotherapy or combination therapy and showed a higher drug change rate, supporting the current recommendation of probiotics in the treatment of childhood functional constipation.

Clinical characteristics of neonatal cholestasis in a tertiary hospital and the development of a novel prediction model for mortality.

BACKGROUND: Few studies have described the aetiologies of neonatal cholestasis, and the overall neonatal cholestasis-related mortality (NCM) rate is unclear. We investigated the aetiology and outcome of neonatal cholestasis in a tertiary hospital and developed an NCM prediction model for these patients. METHODS: Patients aged <100 days with serum direct bilirubin (DB) levels of >1.0 mg/dL were retrospectively screened. Diagnostic and laboratory data during the 8-week follow-up period after enrolment between 2005 and 2020 were extracted digitally, and medical charts were reviewed manually by clinicians. Logistic regression was used to derive a prediction model for the 1-year mortality outcome of neonatal cholestasis, and performance evaluation and external validation were conducted for the NCM prediction model. FINDINGS: We enrolled 4028 neonates with DB of >1.0 mg/dL at least once. Prematurity and birth injury (35.4%), complex heart anomalies (18.6%), liver diseases (11.4%), and gastrointestinal anomalies (9.2%) were the most common aetiologies; 398 (9.9%) patients died before one year of age. The peak value of DB was positively correlated to the 1-year mortality rate. In the multivariate analysis, simple laboratory indices, including platelet, prothrombin time, aspartate aminotransferase, albumin, direct bilirubin, creatinine, and C-reactive protein, were independent predictors of 1-year mortality outcome of complete-case subjects. Using these laboratory indices, a logistic regression-based NCM prediction model was constructed. It showed acceptable performances on discrimination (area under the curve, 0.916), calibration (slope, 1.04) and Brier scoring (0.072). The external validation of the sample (n = 920) from two other centres also revealed similar performance profiles of the NCM model. INTERPRETATION: Various aetiologies of neonatal cholestasis were identified in a tertiary hospital, resulting in unfavourable outcomes of a large proportion. The NCM prediction model may have the potential to help clinicians to be aware of high-risk neonatal cholestasis. FUNDING: Ministry of Health & Welfare, Republic of Korea.

Impact of Social Distancing on Intussusception Incidence in Children.

Following nonpharmaceutical intervention (NPI) to mitigate coronavirus disease 2019 has led to drastic reduction in incidence of communicable disease. Intussusception is commonly preceded by infectious pathogens. Indirect effect from NPI implementation on incidence of intussusception has not been understood fully. We conducted a cohort study to estimate the impact of NPI on incidence of intussusception in Korean children. The net risk ratio of intussusception incidence for 2020 compared to 2010-2019 was 0.53 (95% confidence interval [CI], 0.43-0.64) for boys and 0.56 (95% CI, 0.44-0.71) for girls (P for difference = 0.017). Our study showed an association between NPI implementation and reduction of intussusception incidence, with more profound reduction in boys compared to girls.

Gut Bacterial Dysbiosis in Children with Intractable Epilepsy.

A few published clinical studies have evaluated the association between gut microbiota in intractable epilepsy, but with inconsistent results. We hypothesized that the factors associated with the gut bacterial composition, such as age and geography, contributed to the discrepancies. Therefore, we used a cohort that was designed to minimize the effects of possible confounding factors and compared the gut microbiota between children with intractable epilepsy and healthy controls. Eight children with intractable epilepsy aged 1 to 7 years and 32 age-matched healthy participants were included. We collected stool samples and questionnaires on their diet and bowel habits at two time points and analyzed the gut microbiota compositions. In the epilepsy group, the amount of Bacteroidetes was lower (Mann-Whitney test, false discovery rate (FDR) < 0.01) and the amount of Actinobacteria was higher (FDR < 0.01) than in the healthy group. The epilepsy subjects were 1.6- to 1.7-fold lower in microbiota richness indices (FDR < 0.01) and harbored a distinct species composition (p < 0.01) compared to the healthy controls. Species biomarkers for intractable epilepsy included the Enterococcus faecium group, Bifidobacterium longum group, and Eggerthella lenta, while the strongest functional biomarker was the ATP-binding cassette (ABC) transporter. Our study identified gut bacterial dysbiosis associated with intractable epilepsy within the cohort that was controlled for the factors that could affect the gut microbiota.

Percutaneous Endoscopic Gastrostomy and Nutritional Interventions by the Pediatric Nutritional Support Team Improve the Nutritional Status of Neurologically Impaired Children.

AIM: To evaluate the long-term effects of nutritional improvement following percutaneous endoscopic gastrostomy (PEG) tube feeding stratified by previous feeding method and to assess the impact of underlying muscle tone on the outcomes of the nutritional intervention. METHODS: Neurologically impaired children who underwent PEG tube insertion and nutritional intervention provided by a pediatric nutritional support team were enrolled. We measured anthropometric variables, laboratory parameters, and nutritional intake at baseline, 6 months after PEG insertion, and the last visit. We evaluated the percent ideal body weight (PIBW), body mass index (BMI)-for-age z-score, and percentiles and calculated the ratios of calorie intake compared to required requirement (CIR) and protein intake compared to recommended requirement (PIR). RESULTS: The PIBW and BMI-for-age z-score improved during the first 6 months (p = 0.003 and p = 0.005, respectively). The CIR (p = 0.015) and PIR (p = 0.004) increased during the study period. The baseline BMI and PIBW of the previous nasogastric tube feeding group were better than those of the oral feeding group (p = 0.02 and p = 0.03, respectively). The BMI-for-age z-score, PIBW, CIR, and PIR improved in the hypertonic group (p = 0.03, 0.02, 0.03, and 0.01, respectively). CONCLUSION: PEG tube feeding and active nutritional intervention improved the nutritional status of neurologically impaired children immediately after PEG insertion. The nutritional requirements might vary by the muscle tonicity.

Nationwide Multicenter Study of Eosinophilic Esophagitis in Korean Children.

PURPOSE: In East Asian countries, there are only a few epidemiologic studies of eosinophilic esophagitis (EoE) and no studies in children. We investigated the incidence and compared the clinical characteristics of EoE and eosinophilic gastroenteritis involving the esophagus (EGEIE) in Korean children. METHODS: A total of 910 children, who had symptoms of esophageal dysfunction, from 10 hospitals in Korea were included. EoE was diagnosed according to diagnostic guidelines and EGEIE was diagnosed when there were >15 eosinophils in the esophagus per high power field (HPF) and >20 eosinophils per HPF deposited in the stomach and duodenum with abnormal endoscopic findings. RESULTS: Of the 910 subjects, 14 (1.5%) were diagnosed with EoE and 12 (1.3%) were diagnosed with EGEIE. Vomiting was the most common symptom in 57.1% and 66.7% of patients with EoE and EGEIE, respectively. Only diarrhea was significantly different between EoE and EGEIE (p=0.033). In total, 61.5% of patients had allergic diseases. Exudates were the most common endoscopic findings in EoE and there were no esophageal strictures in both groups. The median age of patients with normal endoscopic findings was significantly younger at 3.2 years, compared to the median age of 11.1 years in those with abnormal endoscopic findings (p=0.004). CONCLUSION: The incidence of EoE in Korean children was lower than that of Western countries, while the incidence of EGEIE was similar to EoE. There were no clinical differences except for diarrhea and no differences in endoscopic findings between EoE and EGEIE.

Effect of nutritional supplement formula on catch-up growth in young children with nonorganic faltering growth: a prospective multicenter study.

BACKGROUND/OBJECTIVES: Inadequate nutrition in infants and young children affects physical growth and neurocognitive development. Therefore, early nutritional intervention is important to promote catch-up growth in young children with faltering growth. The aim of this study was to evaluate the effect of nutritional supplementation with a pediatric concentrated and balanced nutritional supplement formula on promoting growth and improving nutritional status in children with nonorganic faltering growth. SUBJECTS/METHODS: Children aged 12-36 months whose body weight-for-age was < 5th percentile on the Korean Growth Charts were enrolled. Children born premature or having organic diseases were excluded. Children were instructed to consume 400 mL of formula per day in addition to their regular diet for 6 months. Pediatricians and dietitians educated the parents and examined the subjects every 2 months. Anthropometric parameters were measured at baseline and at 2, 4, and 6 months, and laboratory tests were done at baseline and 6 months. The good consumption group included children who consumed ≥ 60% of the recommended dose of formula. RESULTS: Total 82 children completed the 6-month intervention. At baseline, there were no significant differences in all variables between the good consumption and poor consumption groups. Weight and weight z-scores were significantly improved in the good consumption group compared to the poor consumption group at the end of the intervention (P = 0.009, respectively). The good consumption group showed a significant trend for gaining weight (P < 0.05) and weight z-score (P < 0.05) compared to the poor consumption group during 6 months of formula intake. The concentration of blood urea nitrogen was significantly increased in the good consumption group (P = 0.001). CONCLUSIONS: Nutritional supplementation with a concentrated and balanced pediatric nutritional formula along with dietary education might be an effective approach to promote catch-up growth in children with nonorganic faltering growth.

A Novel VPS33B Variant Identified by Exome Sequencing in a Patient with Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome.

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare autosomal recessive multisystemic disease that is associated with the liver, kidney, skin, and central nervous and musculoskeletal systems. ARC occurs as a result of mutations in the VPS33B (Vacuolar protein sorting 33 homolog B) or VIPAR (VPS33B interacting protein, apical-basolateral polarity regulator) genes. A female infant presented with neonatal cholestasis with a severe clinical outcome. She was diagnosed with ARC syndrome using targeted exome sequencing (TES). Exome sequencing revealed compound heterozygous mutations, c.707A>T and c.239+5G>A, in VPS33B, where c.707A>T was a novel variant; the resultant functional protein defects were predicted via in silico analysis. c.239+5G>A, a pathogenic mutation that affects splicing, is found in less than 0.1% of the general population. Invasive techniques, such as liver biopsies, did not contribute to a differential diagnosis of ARC syndrome; thus, early TES together with clinical presentations constituted an apparently accurate diagnostic procedure.

Management of Acute Gastroenteritis in Children: A Survey among Members of the Korean Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

PURPOSE: No national survey has yet described the guidelines followed by Korean pediatricians to treat acute gastroenteritis (AGE). An online survey was performed to investigate the management of AGE followed by members of The Korean Society of Pediatric Gastroenterology, Hepatology, and Nutrition, and the results were compared between pediatric gastroenterologists (PG) and general pediatricians (GP). METHODS: Questionnaires were sent to pediatricians between June 2 and 4, 2018 regarding the type of hospital, indications for admission, antiemetic and antidiarrheal drugs and antibiotics prescribed, and dietary changes advised. RESULTS: Among the 400 pediatricians approached, 141 pediatricians (35.3%) responded to the survey. PG comprised 39% of the respondents and 72.7% worked at a tertiary hospital. Both PG and GP considered diarrhea or vomiting to be the primary symptom. The most common indication for hospitalization was severe dehydration (98.8%). Most pediatricians managed dehydration with intravenous fluid infusions (PG 98.2%, GP 92.9%). Antiemetics were prescribed by 87.3% of PG and 96.6% of GP. Probiotics to manage diarrhea were prescribed by 89.1% of PG and 100.0% of GP. Antibiotics were used in children with blood in diarrheal stool or high fever. Dietary changes were more commonly recommended by GP (59.3%) than by PG (27.3%) (p<0.05). Tests to identify etiological agents were performed primarily in hospitalized children. CONCLUSION: This survey assessing the management of pediatric AGE showed that the indications for admission and rehydration were similar between GP and PG. Drug prescriptions for diarrhea and dietary changes were slightly commonly recommended by GP than by PG.

Nationwide Survey for Application of ROME IV Criteria and Clinical Practice for Functional Constipation in Children.

BACKGROUND: This study aimed to investigate the awareness and application of ROME IV criteria for functional constipation (FC) in real-world practices and assessed differences between pediatric gastroenterologists (PGs) and general pediatricians. METHODS: A total of 239 (47.8%) out of 500 nationwide pediatricians answered a questionnaire for diagnosis and management of pediatric FC; 60 were PGs (75% of total PGs in Korea). RESULTS: A total of 16.6% of pediatricians were aware of the exact ROME IV criteria. Perianal examination and digital rectal examination were practiced less, with a higher tendency among PGs (P < 0.001). Treatment duration was longer among PGs for > 6 months (63.8%) than < 3 months among general pediatricians (59.2%, P < 0.001). Fecal disimpaction and rectal enema were practiced among 78.8% and 58.5% of pediatricians, respectively. High dose medication for initial treatment phase was prescribed by 70.7% of pediatricians, primarily within the first 2 weeks (48.3%). The most commonly prescribed medications in children aged > 1-year were lactulose (59.1%), followed by polyethylene glycol (PEG) 4000 (17.7%), and probiotics (11.8%). Prescription priority significantly differed between PGs and general pediatricians; lactulose or PEG 4000 were most commonly prescribed by PGs (89.7%), and lactulose or probiotics (75.7%) were prescribed by general pediatricians (P < 0.001). For patients aged < 1-year, lactulose (41.6%) and changing formula (31.7%) were commonly prescribed. Most participants recommended diet modification, and PGs more frequently used defecation diary (P = 0.002). CONCLUSION: Discrepancies between actual practice and Rome IV criteria and between PGs and general pediatricians were observed. This survey may help construct practice guidelines and educational programs for pediatric FC.

Association Between Vitamin D Deficiency and Suspected Nonalcoholic Fatty Liver Disease in an Adolescent Population.

PURPOSE: Vitamin D deficiency is a condition widespread throughout the world. Recent studies have suggested that vitamin D deficiency was associated with obesity and metabolic syndrome. The purpose of the study was to examine the relationship between vitamin D deficiency and nonalcoholic fatty liver disease (NAFLD) in adolescents. METHODS: The data were obtained from the Korean National Health and Nutrition Examination Survey from 2008-2014. A total of 3,878 adolescents were included in the study. Vitamin D deficiency was defined as a 25-hydroxyvitamin D concentration <20 ng/mL and suspected NAFLD was defined as an alanine transaminase concentration >30 U/L. RESULTS: Vitamin D deficiency was noted in 78.9% of the studied population. Age, body mass index, waist circumference, and blood pressure, glucose, cholesterol, and triglyceride levels were significantly higher in adolescents with suspected NAFLD than in adolescents without suspected NAFLD, while the mean vitamin D level was significantly lower in adolescents with suspected NAFLD. The multivariate-adjusted odds of suspected NAFLD were higher with increased age, male gender, obesity, and metabolic syndrome. Individuals with vitamin D deficiency were at higher risk of suspected NAFLD (odds ratio, 1.77; 95% confidence interval, 1.07-2.95) after adjusting for age, gender, obesity, and metabolic syndrome. CONCLUSION: Vitamin D deficiency was associated with suspected NAFLD, independent of obesity and metabolic syndrome, in adolescents.

Clinical Practice Guideline for the Diagnosis and Treatment of Pediatric Obesity: Recommendations from the Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology Hepatology and Nutrition.

The Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition newly developed the first Korean Guideline on the Diagnosis and Treatment of Obesity in Children and Adolescents to deliver an evidence-based systematic approach to childhood obesity in South Korea. The following areas were systematically reviewed, especially on the basis of all available references published in South Korea and worldwide, and new guidelines were established in each area with the strength of recommendations based on the levels of evidence: 1) definition and diagnosis of overweight and obesity in children and adolescents; 2) principles of treatment of pediatric obesity; 3) behavioral interventions for children and adolescents with obesity, including diet, exercise, lifestyle, and mental health; 4) pharmacotherapy; and 5) bariatric surgery.

Recent Advance in Very Early Onset Inflammatory Bowel Disease.

Recent studies on pediatric inflammatory bowel disease (IBD) have revealed that early-onset IBD has distinct phenotypic differences compared with adult-onset IBD. In particular, very early-onset IBD (VEO-IBD) differs in many aspects, including the disease type, location of the lesions, disease behavior, and genetically attributable risks. Several genetic defects that disturb intestinal epithelial barrier function or affect immune function have been noted in these patients from the young age groups. In incidence of pediatric IBD in Korea has been increasing since the early 2000s. Neonatal or infantile-onset IBD develops in less than 1% of pediatric patients. Children with "neonatal IBD" or "infantile-onset IBD" have higher rates of affected first-degree relatives, severe disease course, and a high rate of resistance to immunosuppressive treatment. The suspicion of a monogenic cause of VEO-IBD was first confirmed by the discovery of mutations in the genes encoding the interleukin 10 (IL-10) receptors that cause impaired IL-10 signaling. Patients with such mutations typically presented with perianal fistulae, shows a poor response to medical management, and require early surgical interventions in the first year of life. To date, 60 monogenic defects have been identified in children with IBD-like phenotypes. The majority of monogenic defects presents before 6 years of age, and many present before 1 year of age. Next generation sequencing could become an important diagnostic tool in children with suspected genetic defects especially in children with VEO-IBD with severe disease phenotypes. VEO-IBD is a phenotypically and genetically distinct disease entity from adult-onset or older pediatric IBD.