Acute pancreatitis in children with inflammatory bowel disease: Risk factors, clinical course, and prognosis.

OBJECTIVES: To characterize the clinical course of acute pancreatitis (AP) in pediatric inflammatory bowel disease (IBD) patients compared to children with AP without IBD and to identify risk factors associated with AP among IBD patients. METHODS: This retrospective, single-center study compared clinical characteristics of children (<19 years) with AP with and without concomitant IBD who were hospitalized 2005-2019. We also conducted a risk factor analysis of AP development in pediatric IBD. RESULTS: Sixty-eight (54% males) patients with 120 episodes of AP were admitted at a median age of 15.3 years. Thirteen patients (14 episodes) had a co-diagnosis of IBD, representing 4% of our IBD patient population. The AP-IBD patients presented with lower amylase levels compared to the non-IBD patients (160 [interquartile range, IQR: 83-231] vs. 418 [IQR: 176-874] U/L, p > 0.01), all had a mild pancreatitis, and none required invasive intervention. The presumed etiology for AP in all IBD patients was IBD-related: IBD flare-up in five, side effects of medications in two, and undetermined in seven. The only risk factor for AP development among IBD patients was IBD-associated arthritis (23% vs. 3% for IBD-non-AP, p = 0.04), while extracolonic Crohn's disease and induction therapy with nutrition were negative risk factors (15% vs. 51%, p = 0.05, and 8% vs. 44%, p = 0.04, respectively). Other parameters, including disease type and medications, were nonsignificant. CONCLUSION: The clinical course of AP in pediatric IBD patients is mild. Only IBD-associated arthritis emerged as a risk factor for the development of AP, while, unexpectedly, IBD medication did not.

Juvenile polyposis syndrome in children: The impact of SMAD4 and BMPR1A mutations on clinical phenotype and polyp burden.

OBJECTIVE: A constitutional disease-causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%-60% of patients with juvenile polyposis syndrome (JPS). The aim of this study was to characterize the clinical course and polyp burden in children with DCV-positive JPS compared to DCV-negative JPS. METHODS: Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group. RESULTS: A total of 124 children with JPS were included: 69 (56%) DCV-negative and 55 (44%) DCV-positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range [IQR]) follow-up of 4 (2.8-6.4) years. DCV-positive children were diagnosed at an older age compared to DCV-negative children [12 (8-15.7) years vs. 5 (4-7) years, respectively, p < 0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs. 1.4%, p < 0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs. 5.8%, p < 0.001), and underwent more gastrointestinal surgeries (16.4% vs. 1.4%, p = 0.002). The incidence rate ratio for the development of new colonic polyps was 6.15 (95% confidence interval 3.93-9.63, p < 0.001) in the DCV-positive group compared to the DCV-negative group, with an average of 12.2 versus 2 new polyps for every year of follow-up. There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations. CONCLUSIONS: This largest international cohort of pediatric JPS revealed that DCV-positive and DCV-negative children exhibit distinct clinical phenotype. These findings suggest a potential need of differentiated surveillance strategies based upon mutation status.

Body composition in pediatric celiac disease and metabolic syndrome component risk-an observational study.

BACKGROUND: Celiac disease (CD) in children and adolescents has been linked with increased susceptibility for cardiometabolic disease in adulthood. We explored the interaction between body composition and metabolic syndrome (MetS) components in pediatric CD. METHODS: We conducted a retrospective observational study of patients with CD followed at our Pediatric Endocrine and Gastroenterology Units between 1/2018-1/2022. Data on sociodemographic, clinical, laboratory, and body composition parameters (bioelectrical impedance analysis, BIA) were collected. RESULTS: Forty-four patients with MetS components and 67 patients without them were enrolled. The cohort's mean age at BIA assessment was 11.5 ± 3.6 years. Individuals with MetS components were older (P = 0.045), had higher BMI z-scores (P < 0.001), higher total and truncal fat percentage levels (P < 0.001), lower muscle-to-fat ratio z-scores (P = 0.018), higher sarcopenic indices (P = 0.05), higher systolic blood pressure percentiles (P = 0.001), higher triglycerides levels (P = 0.009), and higher triglycerides/HDL-c ratios (P < 0.001) than those without MetS components. A sex- and age-adjusted model revealed that the diagnosis of MetS components was positively associated with fat percentage (odds ratio = 1.087, confidence interval [1.010-1.171], P = 0.027), but not with BMI z-scores (P = 0.138). CONCLUSIONS: We found that fat percentage but not weight status is associated with risk for MetS components in individuals with childhood-onset CD. Preventive interventions should target an improvement in body composition. IMPACT: The literature on cardiometabolic risk in pediatric patients with celiac disease (CD) is sparse. Our analysis revealed that at least one metabolic syndrome (MetS) component was present in two out of every five children and adolescents with CD. An increase in fat percentage but not in body mass index z-scores predicted the presence of MetS components in our cohort. These findings suggest that the weight status of children and adolescents with CD does not mirror their risk for MetS components. Body composition analysis should be considered as an integral part of the clinical evaluation in young patients with CD.

Thiopurines Maintenance Therapy in Children With Ulcerative Colitis: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Thiopurines are an established treatment for pediatric ulcerative colitis (UC). However, data regarding safety and efficacy are lacking. We aimed to determine short and long-term outcome following thiopurines use in children with UC. METHODS: We conducted a retrospective review of children (2-18 years) with UC treated with thiopurines between January 2008 and January 2019 at 7 medical centers in Israel. The primary outcome was corticosteroid (CS)-free clinical remission at week 52 following thiopurines initiation without the need for rescue therapy (infliximab, calcineurin inhibitors, or colectomy). RESULTS: A total of 133 children were included [median age at diagnosis of 12.4 (interquartile range 11.0-15.8) years, 30 (23%) left-sided colitis, 113 (85%) with moderate or severe disease at diagnosis]. At diagnosis 58 patients (44%) were treated with 5-aminosalicylates and 72 (54%) with CS. Sixty patients (45%) received thiopurines as 1st line maintenance therapy. Seventy-four patients (56%) had CS-free clinical remission at week 52 without rescue therapy. Predictors of clinical remission were not identified. In a sub-analysis among patients with steroid-responsive moderate to severe UC, 59 (55%) patients achieved this outcome. The likelihood of remaining free of rescue therapy among thiopurines-treated patients was 83%, 62%, 45%, and 37% at 1, 2, 3, and 4 years, respectively. CONCLUSION: More than half of children with UC starting thiopurines without previous or concomitant biologic therapy have CS-free clinical remission at 52 weeks later without the need for rescue therapy. Thiopurines are effective in pediatric UC and could be considered prior to biologics.

The Yield of Routine Tissue Sampling in Pediatric Gastrointestinal Endoscopy.

OBJECTIVES: Societies' guidelines suggest routine tissue sampling in all children undergoing esophagogastroduodenoscopy and ileocolonoscopy, even in the absence of visible endoscopy abnormalities. We aimed to determine the agreement between endoscopic and histopathological findings in pediatric endoscopy and to assess the yield of routine biopsies from all sites. METHODS: Since January 2019, our endoscopy institute protocol has included routine biopsies sampling from the esophagus, stomach, duodenum, ileum, and colon in all diagnostic procedures. Agreement between tests was done using the kappa coefficient ( κ ). The study included all endoscopies performed during 2019. RESULTS: In total, 541 diagnostic endoscopies were done during the study period with 434 (80%) esophagogastroduodenoscopy and 107 (20%) were ileocolonoscopy. Compared to histology, endoscopic findings performance were: esophagus-sensitivity 33%, specificity 98%; stomach-sensitivity 60%, specificity 89%; duodenum-sensitivity 50%, specificity 97%; duodenal bulb-sensitivity 47%, specificity 89%; terminal ileum-sensitivity 82%, specificity 100%; colon-sensitivity 84%, specificity 96%. Assessment of concordance between endoscopic and histopathologic findings reveals an overall low level of agreement in esophagogastroduodenoscopy ( κ of 0.39, 0.51, 0.53, and 0.24 for the esophagus, stomach, duodenal second part, and bulb, respectively), and good agreement in ileocolonoscopy ( κ of 0.88 and 0.81 for the ileum and colon, respectively). CONCLUSIONS: Endoscopy findings are highly specific for histologic pathology, whereas the absence of findings correlates poorly with histologic findings. Ileocolonoscopy shows better agreement than esophagogastroduodenoscopy. Our data support routine tissue sampling in pediatric endoscopy.

Pediatric feeding disorders among children with parental history of feeding disorders: a distinct group of patients with unique characteristics.

To investigate factors associated with pediatric feeding disorders (PFD) among children of parents that reported to have had feeding disorders during their own childhood compared to children with PFD with no history of parental PFD. We retrospectively reviewed the medical records of children diagnosed with PFD according to the recent WHO-based definition. The demographic and clinical characteristics of children with PFD with a parental history of PFD were compared to those of children with a PFD with no history of parental PFD. Included were 231 children with PFD (median [interquartile range] age 10 months [5.5-29] at diagnosis, 58% boys) of whom 133 children had parents without PFD and 98 children had parents with PFD. Unexpectedly, children of parents without PFD had a higher rate of low birth weight (28% vs. 19%, respectively, p = 0.007), more delivery complications (10% vs. 2%, p = 0.006), more hospitalizations (33% vs. 17%, p = 0.004), more prescription medications (27% vs. 18%, p = 0.05), and a higher percent of gastrostomy tube use (6% vs. 0, p = 0.02). Moreover, more parents with PFD had academic background compared with parents without PFD (72% vs. 59%, p = 0.05). There were no significant group differences in sex, history of breastfeeding, parental marital status, or type of the child's feeding disorder.  Conclusion: PFD among children with a parental history of PFD comprise a distinct group of patients with unique characteristics and outcomes. Since parental feeding history may explain their child's PFD in highly differing ways, such information may help in devising a specific family-based and multidisciplinary treatment plan for those children. What is Known: • Pediatric feeding disorder (PFD) is relatively common and its prevalence is increasing. • Information on an association between parental PFD and their child's feeding disorder is limited. What is New: • PFD among children with a parental history of PFD comprise a distinct group of patients with various characteristics and outcomes. • The parents' feeding history during childhood may provide important clues to their child's PFD.

Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (the Speed-up Study): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN.

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.

Clinical Features and Outcomes of Paediatric Patients With Isolated Colonic Crohn Disease.

OBJECTIVES: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-caecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2. METHODS: Retrospective data was collected through the Porto Inflammatory Bowel Disease group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on Paediatric patients with L2, L1 or UC at different time-points. Outcome measures included time to first flare, hospital admissions, initiation of anti-tumor necrosis factor-alpha (TNFα) drug, stricture and surgery. RESULTS: Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (P < 0.001 for all comparisons). Skip lesions were identified in 65% of patients with L2, and granulomas in 36%, similar to L1 patients. Rates of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic (pANCA) positivity significantly differed between the three groups: 25.4% and 16.7% for patients with L2, compared with 55.2% and 2.3%, and 1.8% and 52.9% for patients with L1 and UC, respectively. Response rates to exclusive enteral nutrition were comparable between L1 and L2 (78.3-82.4%), as was the response to oral steroids (70.4-76.5%) in the three groups. While times to first flare and admission were similar between groups, patients with L1 were commenced on anti-TNFα earlier. Moreover, stricturing phenotype and need for colectomy were very rare in patients with L2. CONCLUSIONS: Significant differences are observed in the clinical presentation and outcomes of Paediatric patients with L2, compared to patients with L1 and UC.

Elevated liver enzymes of newly diagnosed pediatric celiac patients-a prospective-observational study.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12 months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p < 0.01) and more commonly presented with diarrhea (32.3% vs. 14.9%, p = 0.03). Eighty percent of patients with elevated ALT levels normalized their ALT within 3 months and all within 1 year. Following gluten-free diet initiation, patients with elevated ALT had similar clinical course, growth, serology normalization rate, and laboratory results, compared to patients with normal ALT over a 1-year follow-up. A single patient was simultaneously co-diagnosed with celiac disease and autoimmune hepatitis.Conclusion: Clinically significant ALT abnormalities are rare among newly diagnosed pediatric celiac patients. Significant elevations failing to normalize on a gluten-free diet should raise concern of a concomitant primary liver disease and warrant further investigations. What is Known: • Elevated liver enzymes may be an extra-intestinal manifestation of celiac disease. • Reported prevalences of ALT elevations among children with a new diagnosis of celiac disease ranges between 5 and 40%. What is New: • ALT elevations are present in 25% of children with a new diagnosis of celiac disease. • Significant elevations (>3 × ULN) are rare (1.6%). • Elevated liver enzymes are associated with earlier age at diagnosis. • The natural history of patients with elevated liver enzymes at diagnosis is comparable to those without.

Increasing rate of a positive family history of inflammatory bowel disease (IBD) in pediatric IBD patients.

The role of a positive family history in pediatric inflammatory bowel disease (IBD) in the era of biologic therapy has not been elucidated. We retrospectively reviewed the medical records of children with IBD and retrieved demographic and clinical characteristics, including the presence of a positive family history of IBD, IBD phenotype, disease course, and therapy. Overall, 325 children (age range at diagnosis 11-15 years) were included, of whom 82 (25.2%) had a positive family history. Children diagnosed during 2016-2020 had a higher frequency of positive family history compared to those diagnosed during 2010-2015 (31.8% versus 20.7%, respectively, p = 0.024). Children with a positive family history had a higher risk for a stricturing phenotype than those with a negative family history (11.3% versus 2.8%, respectively, p = 0.052). They more often received nutritional therapy (53.7% versus 36.6%, p = 0.007) and less often received corticosteroids (36.6% versus 52.7%, p = 0.012). More children with a negative family history needed intensification of biologic therapy (p = 0.041).Conclusion: The rate of a positive family history of IBD in the pediatric IBD population is increasing. A positive family history may have some impact upon IBD phenotype but none on IBD outcome. What is Known: •Familial clustering of inflammatory bowel disease (IBD) has been reported in 5%-15% of IBD patients. •The investigation of the impact of a positive family history upon IBD characteristics and severity revealed conflicting results. What is New: •In this cohort of 325 children with IBD, 25.2% had a positive family history. •The rate of a positive family history of IBD in the pediatric IBD population is increasing. •A positive family history may have some impact upon IBD phenotype but none on IBD outcome.

Sarcopenia is a Predictor for Adverse Clinical Outcome in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Inflammatory bowel disease (IBD) has a high impact on nutritional status. Sarcopenia is related to higher risk of surgery and rescue therapy in adults with IBD; however, comparable data in pediatric populations are scarce. We evaluated muscle mass as a predictor of disease outcome in pediatric IBD. METHODS: All pediatric IBD patients who underwent magnetic resonance enterography (MRE) during 2008 to 2019 were included. Muscle mass was assessed by measuring the area of the psoas muscle at the upper level of L3 on MRE. The psoas area divided by the body surface area (BSA) yielded the psoas index. Clinical and radiological data, including disease location, activity, course, and medications were documented. The control group included non-IBD children who underwent an MR imaging study. RESULTS: We enrolled 101 IBD patients, 69 (68.3%) with Crohn disease (CD) and 32 (31.7%) with ulcerative colitis (UC) (mean age 15.03 ±â€Š3.27 years). The psoas index was significantly lower in the IBD patients compared with the 87 controls (326 vs 528, respectively, P < 0.001). Patients with a psoas index in the lowest quartile had significantly higher risk for biologic therapy (multivariate analysis, hazard ratio [HR] = 12.1, P = 0.046) and disease exacerbation (HR = 9, P = 0.047) independently of body mass index, compared with patients with a psoas index in the uppermost quartile. CONCLUSIONS: Sarcopenia correlates with the radiological severity of pediatric IBD and serves as a predictor for adverse clinical disease outcome. Muscle mass measurement in MRE studies may serve as a possible marker for disease outcome in this population.

Nutritional Therapy in Children With Spinal Muscular Atrophy in the Era of Nusinersen.

OBJECTIVES: Spinal muscular atrophy (SMA) is a genetic motor neuron disorder characterized by progressive muscle atrophy. Our aims were to evaluate the impact of nutritional intervention and nusinersen therapy on the nutritional status of SMA patients. STUDY DESIGN: This prospective study included all children and young adults (<24 years of age) with SMA who attended our multidisciplinary SMA clinic, during January 2017-July 2019. We documented demographic, clinical, anthropometric, and nutritional data at baseline and follow-up. A nutritional intervention was implemented according to standards of the 2018 Consensus Statement of SMA Management. RESULTS: The cohort included 51 SMA patients with a median age of 7.2 (interquartile range 2.1-15.3) years. Among them, 24 (47%) were SMA type 1, 16 (31.4%) SMA type 2, and 11 (21.6%) SMA type 3 patients. At baseline, 28 (54.9%) patients presented with malnutrition, 20 (71.4%) of whom with severe malnutrition. A decline in the frequency of severe malnutrition of SMA type 1 patients was observed at follow-up. The body mass index of patients who started nusinersen therapy after the nutritional intervention increased significantly compared with patients that started nusinersen therapy before the nutritional intervention (P = 0.042). There was also a significant increase in total energy and protein consumption in the former group (P = 0.043). CONCLUSIONS: Malnutrition is frequent among children with SMA, and the nutritional status of patients that started nusinersen therapy after implementation of a nutritional intervention underwent a more significant improvement. The importance of combining adequate nutritional management with disease-modifying treatment is highlighted.

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

OBJECTIVES: 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. METHODS: Children diagnosed with Crohn disease (CD) or ulcerative colitis (UC) (2005-2019) were identified in a national database along with matched non-IBD controls. RESULTS: 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 ±â€Š1.09 vs -0.25 ±â€Š1.06, respectively; P = 0.01), corresponding to a mean difference of 0.7 ±â€Š0.2 cm (all females) and 1.2 ±â€Š0.3 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. CONCLUSIONS: 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.

Monitoring Enables Progress: A Nationwide Quality Improvement Program in Children With Crohn Disease.

OBJECTIVES: In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation-wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country. METHODS: Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2-18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann-Kendall test, reporting τ (tau) values. RESULTS: The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ±â€Š3.1 years, median disease duration 1.8 years (interquartile range 0.69-4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti-tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 µg/mg (τ = 0.35; P = 0.015), and "resolution of inflammation" defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = -0.47; P = 0.001). CONCLUSIONS: Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators.

BMI in the lower and upper quartiles at diagnosis and at 1-year follow-up is significantly associated with higher risk of disease exacerbation in pediatric inflammatory bowel disease.

Inflammatory bowel disease (IBD) has been associated with underweight and malnutrition, but obesity may also serve as a negative prognostic factor. This study aimed to present the longitudinal course of height, weight, and body mass index (BMI) of children from IBD diagnosis to 18 months of follow-up, and to describe the impact of BMI on the clinical course of the disease. One hundred and fifty-two children were identified, of whom 85 had Crohn's disease (CD) and 67 had ulcerative colitis (UC). During a median (interquartile range) follow-up of 2.95 (1.73-4.5) years, weight and BMI Z-scores increased in the first 18 months since diagnosis in both the CD (P < 0.001) and UC (P < 0.028) groups. BMI in lower and upper quartiles at diagnosis was associated with higher risk of hospitalization (hazard ratio [HR] = 2.72, P = 0.021). In a multivariate analysis, BMI in the lower quartile at diagnosis and at 6, 12, and 18 months was associated with higher risk of disease exacerbation (HR = 2.36, 1.90, 1.98, and 2.43, respectively, P < 0.021), as was BMI in the upper quartile (HR = 2.59, 2.91, and 2.29, respectively, P < 0.013).Conclusion: BMI in the lower and upper quartiles at diagnosis and during follow-up was associated with a more severe disease course in children with IBD. What is Known: • Inflammatory bowel disease (IBD) has been associated with underweight and malnutrition. • The impacts of weight and body mass index (BMI) on the presentation and course of IBD have been mainly investigated in the adult population. What is New: • In the era of the obesity epidemic, this study identifies both low and high BMIs at diagnosis and at follow-up as a marker for poor outcome in pediatric IBD. • The results support using BMI as a predictor of IBD course and prognosis.

Biologic therapy is associated with a mild decrease in the rate of hospitalizations in pediatric IBD.

BACKGROUND: The effect of biologic therapy on the incidence of inflammatory bowel disease (IBD)-related hospitalizations is controversial. The high efficacy of biologic agents is weighted against potential therapy-related adverse events, however, there are no data on the effect of biologic therapy on the indications for hospitalization in IBD. We aimed to evaluate the impact of biologic therapy on the indications and rate of hospitalization in pediatric IBD. METHODS: This retrospective cohort study included all children (< 18 years of age) with IBD who were hospitalized in our medical center from January 2004 to December 2019. Data on demographics, disease characteristics and course, and therapy were collected, as were the indications for and course of hospitalizations. We evaluated the relationship between therapy with biologic agents, indications and rates of hospitalization. RESULTS: Included were 218 hospitalizations of 100 children, of whom 65 (65%) had Crohn's disease and 35 (35%) had ulcerative colitis. The indications for hospitalization were IBD exacerbations or complications in 194 (89%) and therapy-related adverse events in 24 (11%). The patients of 56 (25.7%) hospitalizations were receiving biologic therapy. In a multivariate analysis, no correlation between therapy and indication for hospitalization was found (p = 0.829). Among children under biologic therapy, a decrease in the rate of hospitalizations from 1.09 (0.11-3.33) to 0.27 (0-0.47) per year was observed for patients that were hospitalized during 2016-2019 (p = 0.043). CONCLUSION: Biologic therapy did not influence the indication for hospitalization, but were associated with a decrease in the rate of hospitalization during 2016-2019 in pediatric IBD.

Higher BMI predicts liver fibrosis among obese children and adolescents with NAFLD - an interventional pilot study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) can range from simple steatosis to steatohepatitis with or without fibrosis. The predictors for liver fibrosis and the effect of nutritional intervention on hepatic fibrosis in pediatric population are not well established. We aimed to investigate the predictors for liver fibrosis and the effects of short-term nutritional intervention on steatosis and fibrosis among obese adolescents with NAFLD. METHODS: Cross-sectional study among obese adolescents. Sociodemographic and clinical data were collected. Liver fibrosis was estimated by Shearwave elastography. All participants were recommended to consume a low carbohydrate diet and were followed biweekly. Blood tests and elastography were performed upon admission and repeated after 3 months. RESULTS: Fifty-seven pediatric patients were recruited (35 males, mean age 13.5±2.9 years, mean body mass index [BMI] 38.8±9.7). Liver fibrosis was diagnosed in 34 (60%) subjects, which was moderate/severe (F≥2) in 24 (70%). A higher BMI Z score and moderate/severe steatosis correlated with moderate/severe fibrosis (P < 0.05). Seventeen patients completed 3 months of follow-up and displayed a decrease in BMI Z score (from BMI Z score 2.6±0.5 before intervention to 2.4±0.5 after intervention), with a significant decrease in liver fibrosis (P = 0.001). CONCLUSION: Pediatric patients with high BMIs and severe liver steatosis are at risk for severe liver fibrosis. Nutritional intervention with minimal weight loss may improves hepatic fibrosis among the pediatric population. TRIAL REGISTRATION: TRN NCT04561804 (9/17/2020).

The effect of gluten-free diet on body mass index in paediatric celiac disease.

AIM: More normal weight and overweight children are currently diagnosed with celiac disease (CD). We aimed to describe the relation between body mass index (BMI) and the clinical characteristics of paediatric CD and to determine the effect of a gluten-free diet (GFD) on BMI. METHODS: Data on all children diagnosed with CD during 7/2010-7/2019 with documented anthropometric data at diagnosis were retrospectively analysed. The children were divided into three groups according to BMI status at diagnosis: underweight, normal weight and overweight (BMIs <5%, 5%-85% and >85%, respectively). RESULTS: Of the 236 children [median age 7.87 (4.91-11) years] included in the study, 24 (10.1%) were underweight at diagnosis and 32 (13.6%) were overweight. Diarrhoea as the presenting symptom was significantly more common in the overweight group (p = 0.012), while short stature was more common in the underweight group (p = 0.002). Following a GFD had no significant effect on the children's BMI during a median follow-up of 15.7 (0-85) months, but there was a significant shift of patients between the BMI categories (p < 0.001). CONCLUSION: Although a shift of patients between the BMI categories was observed, following a GFD did not significantly affect the overall BMI in children with CD.

Clock Gene Disruption Is an Initial Manifestation of Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Sleep disruption modifies the immune system and can trigger flares of inflammatory bowel diseases (IBD). Changes in expression of clock genes have been reported in patients with IBD. We investigated whether a change in the circadian clock is an early event in development of IBD. METHODS: We performed a prospective study of patients younger than 21 years old who underwent diagnostic endoscopies at the pediatric and adult gastroenterology units at the Tel Aviv Sourasky Medical Center from August 2016 through August 2017. Questionnaires were completed by 32 patients with IBD (8-21 years old) and 18 healthy individuals (controls) that provided data on demographics, sleep, disease activity scores. We also obtained data on endoscopic scores, anthropometric parameters, blood level of C-reactive protein (CRP), and fecal level of calprotectin. Peripheral blood and intestinal mucosa samples were analyzed for expression levels of clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1, and PER2). RESULTS: Levels of CRP and fecal calprotectin were significantly higher in patients with IBD compared with controls (P<.05). Expression levels of clock genes (CLOCK, CRY1, CRY2, PER1, and PER2) were significantly lower in inflamed intestinal mucosa from patients compared with intestinal mucosa from controls (P<.05). Expression levels of all clock genes except for PER2, were also significantly lower in non-inflamed intestinal mucosal tissues from patients compared with controls (P<.05). Expression levels of clock genes (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) were lower in white blood cells from patients with IBD compared with controls. This reduction was greater in white blood cells from patients with ulcerative colitis than in patients with Crohn's disease. CONCLUSION: Young, newly diagnosed, untreated patients with IBD have reduced expression of clock genes in inflamed and non-inflamed intestinal mucosal samples, and also in blood cells, compared with healthy individuals. Alterations in expression of clock genes might be an early event in IBD pathogenesis. ClinicalTrials.gov Identifier: NCT03662646.

Age and pain score before gastrointestinal endoscopies in children are predictors for post procedure pain.

BACKGROUND: Gastrointestinal endoscopy may be associated with pain and anxiety. Predictors for high pain scores after endoscopies in children are not known. The aim of our study was to identify risk factors for prolonged recovery and higher pain scores after gastrointestinal endoscopy in children. METHODS: All the children that were electively admitted for gastrointestinal endoscopies were included. We retrospectively collected demographic, clinical and endoscopic data as well as information on the recovery process. A numerical rating scale and the Faces, Legs, Activity, Cry, and Consolability Scale were used for pain scoring. RESULTS: During the study period (01/2016-10/2016), 284 children (median age 10.7 years, interquartile range 6.7-14.8) were recruited. In a univariate analysis, older age, higher pre-procedure pain scores, longer procedure durations, higher number of biopsies and longer recovery duration were associated with higher post-procedure pain scores. In a multivariate analysis higher pain scores before the procedure (OR 12.42, 95% CI 3.67-42, P < 0.001) and older age (OR 1.016, 95% CI 1.007-1.025, P < 0.001) were associated with higher pain scores after the procedure. Children with a higher pain score before the procedure also had a longer recovery period (OR 5.28, 95% CI (1.93-14.49), P = 0.001). CONCLUSION: Older age and higher pain score before the procedure were identified as predictors for higher pain score after pediatric gastrointestinal endoscopies. Children with these risk factors should be identified before the procedure in order to personalize their post-procedure management.