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Objective: We aimed to provide an evidence-supported approach to diagnose, monitor, and treat children with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC)., Methods: The core group formulated seven PICO-structured clinical questions. A systematic literature search from inception to December 2022 was conducted by a medical librarian using MEDLINE and EMBASE. Core messages from the literature were phrased as position statements and then circulated to a sounding board composed of international experts in pediatric gastroenterology and hepatology, histopathology, adult gastroenterology and hepatology, radiology, and surgery. Statements reaching at least 80% agreement were considered as final. The other statements were refined and then subjected to a second online vote or rejection., Results: Regular screening for gamma-glutamyltransferase (GGT) is essential for detecting possible biliary disease in children with IBD. MR cholangiopancreatography is the radiological modality of choice for establishing the diagnosis of PSC. Liver biopsy is relevant in the evaluation of small duct PSC or autoimmune hepatitis. Children who do not have known IBD at the time of PSC diagnosis should undergo initial screening with fecal calprotectin for asymptomatic colitis, and then at least once yearly thereafter. Children with a cholestatic liver enzyme profile can be considered for treatment with ursodeoxycholic acid and can continue if there is a meaningful reduction or normalization in GGT. Oral vancomycin may have a beneficial effect on GGT and intestinal inflammation, but judicious use is recommended due to the lack of long-term studies. Children with PSC-IBD combined with convincing features of autoimmune hepatitis may benefit from corticosteroids and antimetabolites., Conclusions: We present state-of-the-art guidance on the diagnostic criteria, follow-up strategies, and therapeutic strategies and point out research gaps in children and adolescents with PSC-IBD., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: We report disease outcomes of pediatric Crohn's disease (CD) affecting the proximal small bowel (SB) and detected through video capsule endoscopy (VCE)., Methods: We undertook a retrospective review of CD patients with VCE performed under age 18 between 2003 and 2017 and having received any biologics. We identified patients from our institutional registry., Results: Eligible patients (n = 118) had their first VCE performed after a median of 0.1 years after diagnostic endoscopies at a median age of 12.2 years. The proximal SB disease group (Paris classification L4b inclusive) comprised 70 patients with extensive SB lesions in 81% and deep ulcers in 79%. Patients with Paris L1-3 disease with no findings in VCE or disease restricted to the terminal ileum comprised the control group. At first VCE, levels of albumin (34 vs. 37 g/L) and hemoglobin (117 vs. 127 g/L) were lower in SB patients (p < 0.02). After the first VCE, 68% were introduced to biologics, while 10% already received them. Follow-up VCE was performed after a median of 2.4 years (SB group n = 42; controls n = 21). Proximal SB findings had disappeared in 40% of SB patients, and extensive lesions and deep ulcers had decreased to 26% and 29%, respectively (p = 0.001). In the control group, one had progressed to proximal disease. During the clinical follow-up of a median of 4.7 years, one patient with SB underwent surgery for a jejunal stricture., Conclusions: Proximal SB disease detected through capsule endoscopy abated in most patients with biological medication., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: The PRASCO trial reported the short-term superiority of an antibiotic cocktail plus intravenous corticosteroids (IVCS) over IVCS alone in children with acute severe colitis (ASC). Here, we report the extension of the PRASCO trial and the long-term outcomes of the antibiotic cocktail in ASC., Methods: This prospective follow-up of the PRASCO trial documented disease outcomes and treatments annually through 5 years. The primary outcome was colectomy, and the secondary outcome was escalation to biologics, analyzed descriptively., Results: A total of 26 children were included (12 receiving IVCS and 14 receiving IVCS + antibiotics), 19% of whom underwent colectomy during the follow-up period. The estimated probability of colectomy at 3, 6, and 12 months from admission were 7.1%, 7.1%, and 21% with IVCS + antibiotics and 0%, 8.3%, and 17% with IVCS. No children required colectomy after the first year of follow-up. The estimated probability of escalating to biologics were 66%, 77%, and 77% after 1, 2, and 3 years with IVCS + antibiotics and 42%, 51%, and 76% with IVCS. Clinical remission was higher in the IVCS + antibiotics group at each timepoint (e.g., 30% vs. 11% at 5-years). Delta of Pediatric Ulcerative Colitis Activity Index (PUCAI) score from baseline to day three of admission predicted future escalation to biologics (area under curves (AUC) 0.84 [95%CI 0.59-1.0])., Conclusion: While adding antibiotics to IVCS may provide better short-term outcomes, the long-term benefits were comparable to IVCS alone. At 5 years, about one-fifth of children had undergone colectomy, and almost four-fifths had escalated to biologics, particularly during the first year after admission., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Magnetic resonance cholangiopancreaticography (MRCP) has supplanted endoscopic retrograde cholangiopancreaticography (ERCP) as the preferred imaging modality for primary sclerosing cholangitis (PSC). However, data about the accuracy of MRCP in assessing disease severity are limited, particularly in children. We assessed the accuracy of MRCP in disease severity evaluation and investigated the correlation between imaging findings and biochemical parameters (including the multivariate risk index SCOPE) in patients with pediatric-onset PSC., Methods: We included 36 patients with PSC (median age: 16) who had MRCP and ERCP performed within 4-month intervals. Two experts, blinded to ERCP findings, evaluated the bile duct changes in consensus using the Modified Amsterdam PSC Score. The agreement between MRCP and ERCP evaluations was tested with weighted kappa statistics and the correlation between disease severity and biochemical parameters with Spearman's rank correlation., Results: The agreement between MRCP and ERCP was good for extrahepatic (weighted kappa 0.69; 95% confidence of interval [CI] 0.53-0.84) but fair for intrahepatic (weighted kappa 0.35; 95% CI 0.14-0.56) bile ducts. Intrahepatic and extrahepatic MRCP scores correlated with APRI (ρ = 0.42, p = 0.020 and ρ = 0.39, p = 0.033, respectively), while extrahepatic MRCP score also correlated with biliary neutrophils (ρ = 0.36, p = 0.035). We found a good correlation between the SCOPE index and intrahepatic MRCP score (ρ = 0.53, p = 0.004), and extrahepatic MRCP score (ρ = 0.57, p = 0.001)., Conclusions: MRCP is accurate at evaluating the severity of extrahepatic bile duct changes in pediatric-onset PSC but tends to underestimate intrahepatic changes. The SCOPE index's robust correlation with imaging scores supports its role as a comprehensive diagnostic tool, outperforming individual laboratory metrics., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Biological treatments (BTs) are essential in managing pediatric inflammatory bowel diseases (PIBDs). Elevated liver enzymes sometimes succeed BT, yet elucidating studies are scarce. We addressed liver biochemistry after introducing BT and searched for their determinants., Methods: We identified PIBD patients receiving infliximab, adalimumab, vedolizumab, or ustekinumab at the Children's Hospital, University of Helsinki, Finland, in 2000-2023, and followed their alanine transaminase (ALT) and γ-glutamyl transpeptidase (GT) levels for 24 months. ALT was categorized based on the age- and sex-specific upper limit of normal. We disregarded 46 patients with underlying primary sclerosing cholangitis with/without autoimmune hepatitis (AIH), pretreatment AIH diagnosis, and elevated liver enzymes at the beginning of BT from the analyses., Results: Of 618 BT episodes in 403 patients, 22.2% exhibited increased ALT or GT (ALT in 117, GT in 4, and both ALT/GT in 16 episodes). Of all ALT elevations (n = 133), 41.4% occurred within the first 3 months. ALT elevation was more common after infliximab (representing 59.5% of BTs) than other BTs (25.9% vs. 14.2%, adjusted odds ratio [OR]: 2.41, 95% confidence interval [CI]: 1.23-4.72). AIH followed 1.5% (n = 9) of BT episodes. Ninety-five percent of ALT elevations resolved within 6 months. Antibiotic exposure (particularly to metronidazole) was associated with ALT elevation in general (adjusted OR: 5.76, 95% CI: 2.40-13.9) and short disease duration before starting BT with notable ALT elevation (adjusted OR: 1.10, 95% CI: 1.01-1.22)., Conclusions: Benign ALT elevation is common within 3 months after starting BT (especially infliximab) and scarcely led to cessation of the treatment. AIH is a rare finding during the first year of BT., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Pediatric-onset inflammatory bowel disease (pIBD) increases the risk of developing several different cancer forms. In this case-control study, we aimed to assess the impact of medical treatment and disease activity on the risk of developing disease-associated cancer (DAC) and treatment-associated cancer (TAC)., Methods: In a previous study, we identified 27 cases of DAC (colorectal cancer, small bowel cancer, and cholangiocarcinoma) and 28 TAC (lymphoma and skin cancer) in 6689 patients with pIBD in Denmark and Finland during the period 1992-2015. In this study, the patient charts were reviewed manually. Cancer-free patients from another population-based pIBD cohort were included as controls. We recorded data on phenotype, medical treatment, surgery, and relapses. Logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) to estimate the relative risk., Results: We included 16 cases with DAC, 21 with TAC, and 331 controls. For DAC, lower frequencies of IBD-relapses were associated with an increased risk of cancer (OR 0.2 [95% CI: 0.04-0.8]). For TAC, we found an increased risk in patients receiving thiopurines at any point during the follow-up period (aOR: 11.7 [95% CI: 2.1-116.2]) and an association with proportion of follow-up time being exposed to thiopurines (aOR 5.6 [95% CI: 1.1-31.5])., Conclusions: In this nation-wide study, covering all pIBD patients from Denmark and Finland, we found that pIBD patients treated with thiopurines had an increased risk of TAC., Competing Interests: O.O. has been PI for projects (unrelated to the present paper) at Karolinska Institutet financed by grants from Janssen, Takeda, AbbVie, Ferring, and Pfizer. Karolinska Institutet has received fees for lectures (OO) and participation on advisory boards (OO) from Janssen, Ferring, Bristol Myers Squibb, Galapagos and Takeda. The remaining authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD., Methods: This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up., Results: Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation ( P = 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1-20.5) mg/L ( P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) µg/g ( P = 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported., Conclusions: Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation., Competing Interests: GPM has received speakers fees and congress support from Abbvie, Nestlé Health Science, Janssen and Nutricia. KLK has received consultancy fees from Abbvie, Biocodex, Ferring and Tillotts Pharma and funding for research from Pediatric Research Foundation and Helsinki University Hospital Research Fund. OH reports lectures/congress fees/consultancy (outside the submitted work): MSD, AbbVie, Takeda, Nutricia, Nestlé and Ferring. OH reports lectures/congress fees/consultancy (outside the submitted work): MSD, AbbVie, Takeda, Nutricia, Nestlé and Ferring. The remaining authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: The aim of the study was to evaluate the neurocognitive and motor development of biliary atresia (BA) patients in childhood and adolescence and to identify risk factors for impaired outcome., Methods: We invited all BA patients between ages 1 and 20 years followed up at Helsinki University Children's Hospital in Finland between 1 January 2019 to 31 January 2020 to participate. All participants underwent age-appropriate validated neurocognitive tests. Participants between 3.0 and 16.9 years of age were assessed with the Movement Assessment Battery for children, version 2. Guardians of participants between ages 5 and 17 years filled the Five-to-Fifteen-Revised (5-15R) parental questionnaire., Results: The mean (±standard deviation [SD]) total intelligence quotient (IQ) of the 39 participants was 91 ± 15, lower compared with test norms (mean IQ 100 ± 15, P < 0.01). Earlier clearance of jaundice (COJ) had a positive effect on mean (±SD) total IQ (COJ <3 months 96 ± 13 vs COJ ≥3 months post-portoenterostomy 84 ± 13, P < 0.05). Out of 30 participants assessed, 13 (43%) were either at risk or fulfilled the criteria for impaired motor development. Guardians reported elevated rates of functional difficulties affecting everyday life. There were no significant differences between native liver and liver transplanted (16/41%) groups., Conclusions: IQ is moderately, and motor scores markedly impaired in BA patients compared with normative data. Standardised cognitive and motor assessment before school-age for all BA patients is advisable to identify individuals in need of additional support., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children., Methods: A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors., Results: A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9., Conclusions: Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schönlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.

Anti-tumor necrosis factor-alpha (TNF-α) blockade is so far the most effective therapy for extensive pediatric Crohn disease (CD), but loss of response is frequently encountered. We describe here the use of golimumab (Simponi) in 6 pediatric CD patients with antibody formation/loss of response to infliximab and adalimumab. Most patients had undergone surgery but had poor disease control. After introduction of golimumab, the levels of inflammatory markers and fecal calprotectin declined at first, but the response was not sustained. Each patient needed dose escalation of golimumab from 4 to 2 week intervals, to maintain response and to increase trough levels. Importantly, most patients were able to attend school when undergoing golimumab therapy. As with other anti-TNFα drugs, follow-up of drug levels is advisable. Although golimumab therapy failed in most patients, it is an alternate treatment option in pediatric patients with severe CD. The therapeutic response, however, is suboptimal in anti-TNFα exposed patients.

Purpose: Major histocompatibility complex (MHC) genes have been widely studied in adult inflammatory bowel disease (IBD), but data on MHC genes are scarce in pediatric IBD. This study focused on MHC association of genes with pediatric-onset IBD and its different phenotypes., Methods: Blood samples of 103 patients with pediatric IBD (Crohn disease or ulcerative colitis) were collected at Children's Hospital, University of Helsinki, Finland. HLA-A, -B, -DRB1 alleles and complement C4A and C4B gene copy numbers were determined and constructed into haplotypes by a Bayesian algorithm (PHASE). A general population cohort (n = 149) served as a control. HLA-alleles and C4 deficiency frequencies were compared between patients and controls with χ-squared and Fisher exact test with Bonferroni correction (Pcorr)., Results: One MHC haplotype HLA-A03; HLA-B07; 1 C4A gene; 1 C4B gene; HLA-DRB115 was more common in Crohn disease and ulcerative colitis than in controls (7/61, 11.5%, 6/42, 14.3% and 1/149, 0.7%, respectively, odds ratio (OR) = 19.19, 95% CI 2.31-159.57, Pcorr = 0.004 for Crohn disease vs controls and OR = 24.67, 95% CI 2.88-211.36, Pcorr = 0.002 for ulcerative colitis vs controls). Two MHC markers were associated with clinical characteristics. HLA-DRB101 was more common in patients with milder disease course, that is, no need for anti-tumor necrosis factor (TNF)-α medication (18/32, 56.2% vs 19/71, 26.8% without and with anti-TNF-α medication, respectively, OR = 0.28, 95% CI 0.12-0.68, Pcorr = 0.032). C4B deficiency (<2 C4B genes) was associated with complicated recovery after surgery (12/16, 75.0% vs 4/16, 25.0%, respectively, OR = 9.00, 95% CI 1.82-44.59, Pcorr = 0.025)., Conclusions: One MHC haplotype is strongly linked with pediatric-onset IBD, whereas the need for immunomodulatory therapy and surgery outcome associates with other distinct MHC gene markers.

Objectives: The aim of this population-based observational case-control questionnaire study was to investigate the possible role of environmental risk factors associated with pediatric-onset autoimmune liver diseases., Methods: Seventy-one patients with autoimmune liver diseases (<16 years) received a questionnaire with 22 items, evaluating contact with environmental factors (eg, family manners, type of housing, pets) before the diagnosis. Two age- and sex-matched control groups were used: inflammatory bowel disease (IBD; n = 91) and healthy subjects (n = 716; matched also for place of residence at birth). Univariate analysis (odds ratio [OR] and 95% confidence interval) for all variables was calculated. Fisher exact test was performed to depict associations between variables and the multivariate logistic regression to test their interactions., Results: In the final analyses, the responses of 51 autoimmune liver diseases cases (n = 51/71, 72%), 59 IBD controls (n = 59/91, 65%), and 292 healthy controls (n = 292/716, 41%) were investigated. In univariate analysis only having a cat, a dog, and a cat or a dog were risk factors of autoimmune liver diseases (OR varying between 2.6-3.4); no other significant associations (eg, place of residence, number of siblings, family manners) were found. Multivariate logistic regression analyses showed that especially living with a cat in block of flats was a risk factor (OR 3.6, 1.2-10.8)., Conclusions: Living in a close contact with a pet (especially a cat) was a risk factor of autoimmune liver diseases. This finding may suggest an involvement of an unidentified agent (ie, toxin/microbe) among the triggers of these diseases.

Objectives: The diagnostic accuracy of faecal calprotectin (FC) concentration for paediatric inflammatory bowel disease (IBD) is well described at the population level, but not at the individual level. We reassessed the diagnostic accuracy of FC in children with suspected IBD and developed an individual risk prediction rule using individual patient data., Methods: MEDLINE, EMBASE, DARE, and MEDION databases were searched to identify cohort studies evaluating the diagnostic performance of FC in paediatric patients suspected of having IBD. A standard study-level meta-analysis was performed. In an individual patient data meta-analysis, we reanalysed the diagnostic accuracy on a merged patient dataset. Using logistic regression analysis we investigated whether and how the FC value and patient characteristics influence the diagnostic precision. A prediction rule was derived for use in clinical practice and implemented in a spreadsheet calculator., Results: According to the study-level meta-analysis (9 studies, describing 853 patients), FC has a high overall sensitivity of 0.97 (95% confidence interval [CI] 0.92-0.99) and a specificity of 0.70 (0.59-0.79) for diagnosing IBD. In the patient-level pooled analysis of 742 patients from 8 diagnostic accuracy studies, we calculated that at an FC cutoff level of 50 μg/g there would be 17% (95% CI 15-20) false-positive and 2% (1-3) false-negative results. The final logistic regression model was based on individual data of 545 patients and included both FC level and age. The area under the receiver operating characteristic curve of this derived prediction model was 0.92 (95% CI 0.89-0.94)., Conclusions: In high-prevalence circumstances, FC can be used as a noninvasive biomarker of paediatric IBD with only a small risk of missing cases. To quantify the individual patients' risk, we developed a simple prediction model based on FC concentration and age. Although the derived prediction rule cannot substitute the clinical diagnostic process, it can help in selecting patients for endoscopic evaluation.

Crohn disease (CD) may develop at any age, but is most typically diagnosed in late adolescence and early adulthood. To the best of our knowledge, there are no reports showing that congenital urological abnormalities may be associated to CD. We describe 5 pediatric patients who had ureteral/urethral abnormalities in their infancy and developed CD during subsequent years. The occurrence of CD in these patients constitutes a novel potential association.

Background: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete., Methods: We aimed to revise the original Porto criteria using an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm., Results: The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy., Conclusions: These revised Porto criteria for the diagnosis of PIBD have been developed to meet present challenges and developments in PIBD and provide up-to-date guidelines for the definition and diagnosis of the IBD spectrum.

Objective: The present understanding of inflammatory bowel disease pathogenesis mainly relies on studies of adult patients. Therefore, we studied the balance between T-effector and regulatory cells in pediatric inflammatory bowel disease., Methods: Quantitative polymerase chain reaction and immunohistochemistry served to quantify the expression of immunological markers in mucosal biopsies and flow cytometry analysis was used in peripheral blood mononuclear cells., Results: Colonic interleukin (IL)-17+, IL-22, and IL-6 mRNA upregulation and increase in the number of colonic IL-17 cells were demonstrated in both Crohn disease (CD) and ulcerative colitis (UC). Likewise, colonic forkhead box P3 (FOXP3+) mRNA expression and the number of colonic FOXP3 cells were increased both in CD and in UC and were accompanied in CD also with increased numbers of FOXP3+CD25 High CD4 cells in peripheral blood. Ileal relation of IL-17/CD4 cells was increased only in CD., Conclusions: We showed activation of colonic IL-17/IL-22 axis and upregulation of FOXP3 to occur both in pediatric CD and in UC, indicating shared immunological characteristics. Upregulation of IL-17 was restricted to colon in UC, but existed in the ileum and in the colon in active CD.

Objective: The aim of this study was to evaluate the suspicion of cow's-milk allergy in infants with unspecific gastrointestinal (GI) symptoms using the double-blind, placebo-controlled food challenge., Methods: A prospective cohort study, which recruited 57 consecutive children with gastrointestinally manifested symptoms suspected of cow's-milk allergy. All patients underwent a 5-day double-blind, placebo-controlled food challenge for cow's milk., Results: The median age of the patients was 8.7 months. None had measurable cow's-milk-specific IgE. The food challenge was positive in 18 (32%) cases, with symptoms manifesting within 48 hours in 17 of 18 cases. The only symptom that correlated with the positive challenge was loose stools, reported as a presenting symptom in 78% of challenge-positive and in 46% of challenge-negative children (P = 0.043). During active challenge, the respective proportions were 82% and 2% (P < 0.0001). No serious adverse effects were manifested during the challenges. In the challenge-negative group, significant placebo reactions occurred in 18 (46%) patients. In the challenge-negative children, adult-type hypolactasia genotype CC frequency was higher (31%, P = 0.033) than national prevalence of 18%., Conclusions: In an infant with unspecific GI symptoms suspected of cow's-milk allergy, this diagnosis is seldom confirmed. Other reasons for the troublesome GI symptoms should also be identified.

We identified a total of 595 Finnish children born in 1994-2008 and diagnosed as having inflammatory bowel disease (IBD) by October 2010 from the National Reimbursement Register (based on certificates including the diagnostic criteria) to determine whether the presence of cow's milk allergy (CMA) or asthma is associated with the risk of contracting IBD (altogether 2380 matched controls). A diagnosis of CMA in infancy was associated with Crohn disease (odds ratio [OR] 1.92, confidence interval [CI] 1.09-3.36, P < 0.05) and ulcerative colitis (OR 1.71, CI 1.04-2.83, P < 0.05), but childhood asthma only with Crohn disease (OR 2.33, CI 1.41-3.86, P = 0.001). Thus, CMA in infants is a risk factor for contracting pediatric IBD and accordingly, asthma for Crohn disease.

Objective: Of pediatric patients with Crohn disease, 20% to 30% undergo surgery within 10 years. Although disease relapses and reoperations are common, long-term functional outcomes and quality of life (QoL) are unclear., Methods: In 2010, we reviewed the hospital records of all pediatric patients with CD who had undergone intestinal resections during childhood in 2 major tertiary care hospitals between 1985 and 2008 and mailed out questionnaires that asked about health outcomes and QoL. We compared the QoL of the patients and a group of matched controls randomly chosen from the Population Register Centre., Results: In total, 36 children had undergone bowel resection a median of 10 years earlier and had at least 2 years of follow-up. Disease activation (verified at endoscopy) requiring medical or surgical treatment occurred in 94% (median 1.8 years after primary resection). At least 1 surgical complication occurred in 77%, and 54% underwent re-resection. The patients reported a median stool frequency of 3 stools during the day and zero at night, with 33% being totally continent. Overall, 96% were completely or moderately satisfied with the outcome of the surgery. The QoL was comparable between the patients and controls, but school or work absences diminished the QoL of the patients., Conclusions: Surgery for pediatric-onset CD is risky even under expert care. Disease relapses and bowel re-resections are common during the first decade after primary surgery. In the long term, however, bowel function is acceptable and the QoL is comparable between patients and their peers.

The recent development of easily applicable fecal surrogate markers of intestinal inflammation, such as fecal calprotectin (FC), has provided a new means for objectively assessing disease activity in patients with chronic inflammatory bowel disease. Because the use of these markers is about to emerge, it is important to be aware of the possible limitations of measurements. We assessed levels of FC during bowel cleansing. In patients with high FC levels at baseline, the values measured during bowel cleansing varied considerably, remaining high or even returning to normal. Thus, stool sampling for FC assessment is not recommended during bowel preparation for colonoscopy.

Background and Aims: Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)., Methods: A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature., Results: A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented., Conclusions: These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and monitoring of the disease course, while acknowledging that each patient is unique.

Glucocorticoid therapy is widely used in clinical practice. However, treatment with steroids carries the risk of side effects. We investigated changes in serum adiponectin and leptin in response to systemic glucocorticoid treatment in 18 pediatric patients with inflammatory bowel disease and contrasted these findings to circulating glucocorticoid bioactivity measured with a mammalian cell bioassay. Interestingly, serum adiponectin levels at 2 to 4 weeks of therapy were significantly higher in patients who experienced acute glucocorticoid-related side effects (22.9 +/- 2.6 microg/mL, n = 7) than in those who did not (16.0 +/- 2.1 microg/mL, n = 11, P < 0.05). Serum leptin was not associated with side effects. Circulating adiponectin may serve as an early and readily available endogenous biomarker for acute glucocorticoid-related side effects in pediatric patients.