Role of Probiotics in the Treatment and Prevention of Common Gastrointestinal Conditions in Children.

Probiotics are live microorganisms that confer health benefits to the host when administered in adequate amounts. Although recommendations for probiotic use should be strain-specific, many systematic reviews, including recommendations from different societies, recommend probiotic use in general, providing no relevant information for healthcare professionals regarding which probiotic to recommend for which clinical indication, at what dose, and for how long. This narrative review aimed to present the available evidence on the use of probiotics in the prevention and treatment of common gastrointestinal diseases in children, considering the strain and dose used. Furthermore, this study summarizes the evidence on the possible side effects and quality of products containing probiotics.

The Frequency and Impact of Self-Imposed Elimination Diets on the Nutritional Status and Clinical Course of Disease in Children with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: From the patients' perspective, diet has a relevant role in triggering symptoms of inflammatory bowel disease (IBD). There is a lack of prospective studies regarding the diet of children with IBD. The aim of this study was to assess the frequency and impact of self-imposed elimination diets on the nutritional status and clinical course of disease in the pediatric population. METHODS: This was a prospective case-control study that included newly diagnosed patients with IBD and healthy controls (age/sex-matched peers and siblings) over a one-year period. The participants were examined in three categories: (1) anthropometric data and nutritional status; (2) dietary intake, as obtained by a Food Frequency Questionnaire (FFQ); and (3) dietary beliefs and elimination diets, as obtained by a structured questionnaire. RESULTS: Overall, one-hundred and thirty-seven participants were included (twenty-eight with Crohn's disease, sixteen with ulcerative colitis, three with IBD-unclassified, and seventy healthy controls). Only 15% of patients followed the self-imposed elimination diet upon the diagnosis, which increased to 47.6% by the end of the follow-up. The elimination diet did not influence the nutritional status and quality of the diet. Self-imposed elimination diets were not a risk factor for disease relapse. Most of the patients received nutritional counseling during the follow-up. CONCLUSIONS: The number of patients following self-imposed elimination diets had increased during the disease course but with no influence on nutritional status or relapse risk.

European expert recommendations on clinical investigation and evaluation of high-risk medical devices for children.

Several high-risk medical devices for children have become unavailable in the European Union (EU), since requirements and costs for device certification increased markedly due to the EU Medical Device Regulation. The EU-funded CORE-MD project held a workshop in January 2023 with experts from various child health specialties, representatives of European paediatric associations, a regulatory authority and the European Commission Directorate General Health and Food Safety. A virtual follow-up meeting took place in March 2023. We developed recommendations for investigation of high-risk medical devices for children building on participants' expertise and results of a scoping review of clinical trials on high-risk medical devices in children. Approaches for evaluating and certifying high-risk medical devices for market introduction are proposed.

Key Strategies for Optimizing Pediatric Perioperative Nutrition-Insight from a Multidisciplinary Expert Panel.

Adequate nutrition is an essential factor in healing and immune support in pediatric patients undergoing surgery, but its importance in this setting is not consistently recognized. Standardized institutional nutrition protocols are rarely available, and some clinicians may be unaware of the importance of assessing and optimizing nutritional status. Moreover, some clinicians may be unaware of updated recommendations that call for limited perioperative fasting. Enhanced recovery protocols have been used in adult patients undergoing surgery to ensure consistent attention to nutrition and other support strategies in adult patients before and after surgery, and these are now under evaluation for use in pediatric patients as well. To support better adoption of ideal nutrition delivery, a multidisciplinary panel of experts in the fields of pediatric anesthesiology, surgery, gastroenterology, cardiology, nutrition, and research have gathered and reviewed current evidence and best practices to support nutrition goals in this setting.

Gut Microbiota Composition Changes following Discontinuation of Exclusive Enteral Nutrition in Children with Crohn's Disease.

This study aims to determine changes in the intestinal microbiota of children with Crohn's disease (CD) before and during exclusive enteral nutrition (EEN) and after its discontinuation. A total of 14 newly diagnosed children with CD (median age 16.0 years; 43% female) were included in this study. Patients were initially treated with EEN and were followed for one year after EEN discontinuation. Stool samples were taken at the time of diagnosis (before EEN introduction), the second day of EEN, the last day of EEN, and every two months for one year after the discontinuation of EEN. A molecular approach targeting 16S ribosomal RNA was used for analysing the gut microbiota. No change was found in the Shannon diversity index before, during, and after EEN cessation (HhaI-digestion p = 0.82; MspI-digestion p = 0.87). According to the PCO, on the basis of the dissimilarity matrices of OTUs, a clear separation of patients at different time points, forming two clusters (before and during EEN as opposed to after EEN), was evident. No clear separation was noted between patients who achieved sustained remission as opposed to those who did not achieve sustained remission during EEN and at the follow-up. In conclusion, a distinct change in the microbiota composition already occurred after two months of EEN discontinuation and remained mostly unchanged over a year of follow-up.

Children with inflammatory bowel disease already have an altered arterial pulse wave.

Adults with inflammatory bowel disease (IBD) have an increased risk for vascular events. This study aims to evaluate arterial parameters in paediatric IBD. Carotid intima-media thickness (CIMT) was measured by ultrasound, and Arteriograph was used to assess aortic pulse wave velocity (PWVao), brachial and aortic augmentation indexes (AixBrach, AixAo), central systolic blood pressure (SBPao), and heart rate (HR). A total of 161 children were included; 55 (34%) children with newly diagnosed IBD (median age 14.35 (11.88-16.31) years, 53% males), 53(33%) in remission (median age 15.62 (13.46-16.70) years, 66% males), and 53 (33%) controls (median age 14.09 (11.18-14.09) years, 55% males) were recruited into a case-control study. Compared to controls, patients with active disease and those in clinical remission had significantly lower AixBrach and AixAo (P < 0.001, P = 0.009; P < 0.001, P = 0.003). PWVao and CIMT were still normal. HR was higher in both IBD groups than in controls (P < 0.001; P = 0.006). HR positively correlated with disease duration (P = 0.001). In the ordinary least squares regression models, anti-tumour necrosis factor (TNF) α treatment predicted lower peripheral and central systolic blood pressures, in contrast to aminosalicylates and methotrexate. Aminosalicylate treatment predicted increased HR.  Conclusion: Children with IBD have an increased heart rate, a lower augmentation index and, therefore, an altered pulse waveform. In paediatric IBD, arterial stiffness and CIMT are still normal, indicating the potential for adequate IBD treatment to preserve arterial health. What is Known: • Adult patients with inflammatory bowel disease (IBD) have increased carotid intima-media thickness and arterial stiffness, which positively correlates with cardiovascular risk and predicts mortality. Adequate treatment, especially anti-tumour necrosis factor (TNF) α medications, lower these risks. • Children with IBD have impaired endothelial function and reduced heart rate (HR) variability. What is New: • Children with IBD have impaired endothelial function and reduced heart rate (HR) variability. • Anti-TNFα treatment in children and adolescents with IBD lowers systolic pressure, whereas methotrexate and aminosalicylates have the opposite effect. Amiynosalyiciylate treatment also increases HR.

Impact of an exercise program in children with inflammatory bowel disease in remission.

BACKGROUND: The aim of our study was to investigate the impact of a structured exercise program on bone mineral density (BMD) and body composition parameters in children and adolescents with IBD in remission. METHODS: Patients were recruited to participate in a 6-month exercise program. Total body less head (TLBH) dual energy X-ray absorptiometry (DXA) was used to measure BMD. The same method was used to assess fat mass (FM) and lean body mass (LBM) at baseline and at the completion of the program. RESULTS: Based on the baseline and endpoint TBLH DXA measurements, a total of 42 study participants (25 boys; aged 15.3 ± 2.08 years) experienced an increase in BMD (from 0.959 ± 0.023 g/cm2 to 0.988 ± 0.025 g/cm2, p < 0.001) and LBM (from 37.12 ± 1.43 kg to 38.75 ± 1.61 kg, p = 0.012). Age- and sex-based BMD Z-score increased significantly (from -0.35 ± 0.15 to -0.28 ± 0.17, p = 0.020), whilst LBM Z-score did not significantly change (from -1.78 ± 0.23 to -1.71 ± 1.49, p = 0.908). CONCLUSIONS: There was a significant improvement in BMD, age- and sex-based BMD Z-score, and LBM amongst study participants. Subgroup analysis showed that patients with CD and male study participants experienced significant improvement in all parameters, whilst patients with UC and IBD-U and female patients experienced improvement solely in BMD. IMPACT STATEMENT: Children and adolescents with IBD, regardless of disease activity, are under increased risk of secondary osteoporosis and lean body mass deficits. A 6-month home-based structured exercise program leads to a significant improvement in bone mineral density and lean body mass. Exercise therapy should be explored as a potentially adjacent to standard treatment modalities.

Synbiotics in the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.

BACKGROUND: Synbiotics are a mixture comprising of live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There is an increasing number of studies investigating their role in different diseases and disorders. AIM: The purpose of this article is to provide recommendations for the use of synbiotics in the management of pediatric gastrointestinal disorders. The recommendations are developed by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications. METHODS: From existing literature databases, we searched and appraised all systematic reviews and/or meta-analyses, and subsequently published randomized controlled trials (RCTs) that compared the use of synbiotics, in all delivery vehicles and formulations, at any dose, compared to no synbiotics. Synbiotics which are part of infant formula were not assessed. The recommendations were formulated only if at least 2 RCTs that used a well-defined synbiotic were available. RESULTS: Based on the currently available evidence, no recommendation can be formulated in favor or against the use of evaluated synbiotic combination in the treatment of acute gastroenteritis, prevention of necrotizing enterocolitis, Helicobacter pylori infection, inflammatory bowel disease, functional gastrointestinal disorders, and allergy in infants and children. CONCLUSIONS: There is a need for more, well-designed RCTs on the role of synbiotics in gastrointestinal disorders with the same outcome measures to enable the inter-studies comparisons.

Prediction of thiopurine failure in pediatric Crohn's disease: pediatric IBD Porto group of ESPGHAN.

BACKGROUND: Maintaining of remission early in the disease course of Crohn's disease (CD) is essential and has major impact on the future prognosis. This study aimed to identify baseline predictors to develop model allowing stratification of patients who will not benefit from long-term azathioprine (AZA) treatment and will require more intensive therapy. METHODS: This study was designed to develop clinical prediction rule using retrospective data analysis of pediatric CD patients included in prospective inception cohort. Clinical relapse was defined as necessity of re-induction of remission. Sequence of Cox models was fitted to predict risk of relapse. RESULTS: Out of 1190 CD patients from 13 European centers, 441 were included, 50.3% patients did not experience clinical relapse within 2 years of AZA treatment initiation. Median time to relapse was 2.11 (CI 1.59-2.46) years. Of all the tested parameters available at diagnosis, six were significant in multivariate analyses: C-reactive protein (p = 0.038), body mass index Z-score >0.8 SD (p = 0.002), abnormal sigmoid imaging (p = 0.039), abnormal esophageal endoscopy (p = 0.005), ileocolonic localization (p = 0.023), AZA dose in specific age category (p = 0.031). CONCLUSIONS: Although the possibility of predicting relapse on AZA treatment appears limited, we developed predictive model based on six baseline parameters potentially helpful in clinical decision. IMPACT: The possibility of predicting relapse on AZA treatment appears to be possible but limited. We identified six independent predictors available at diagnosis of early AZA/6-MP treatment failure in pediatric CD patients. Using combination of these factors, a model applicable to clinical practice was created. A web-based tool, allowing estimation of individual relapse risk in pediatric CD patients on a particular therapeutic regimen, has been developed.

Diet and Pediatric Functional Gastrointestinal Disorders in Mediterranean Countries.

Background: The increased intake of FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyol) rich foods has been suggested as a possible trigger of functional gastrointestinal disorders (FGIDs). Despite the high FODMAP content, the Mediterranean diet (MD) appears to have beneficial effects on health. Our aim was to evaluate whether the prevalence of FGIDs in different Mediterranean countries may be influenced by FODMAP consumption and adherence to the MD. Methods: A school-based, cross-sectional, multicenter study was performed in six countries in the Mediterranean area: Croatia, Greece, Israel, Italy, Macedonia, and Serbia. Subjects 4-18 years were examined in relation to their eating habits and the presence of FGIDs, using Rome IV criteria, 3-day food diaries and Mediterranean Diet Quality Index in Children and Adolescents (KIDMED) questionnaires. Results: We enrolled 1972 subjects between 4 and 9 years old (Group A), and 2450 subjects between 10 and 18 years old (Group B). The overall prevalence of FGIDs was 16% in Group A and 26% in Group B. FODMAP intake was significantly different among countries for both age groups. In both groups, no significant association was found between FGIDs and FODMAPs. Adherence to the MD in all countries was intermediate, except for Serbia, where it was low. In both groups, we found a statistically significant association between FGIDs and the KIDMED score (Group A: OR = 0.83, p < 0.001; Group B: OR = 0.93, p = 0.005). Moreover, a significant association was found between the KIDMED score and functional constipation (Group A: OR = 0.89, p = 0.008; Group B: OR = 0.93, p = 0.010) and postprandial distress syndrome (Group A: OR = 0.86, p = 0.027; Group B: OR = 0.88, p = 0.004). Conclusions: Our data suggest that the prevalence of FGIDs in the Mediterranean area is not related to FODMAP consumption, whereas adherence to the MD seems to have a protective effect.

Chronic Intestinal Failure in Children: An International Multicenter Cross-Sectional Survey.

Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1−4 and 14−18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores < −2. One-third had %IVSE/REE > 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children.

Prediction Models for Celiac Disease Development in Children From High-Risk Families: Data From the PreventCD Cohort.

BACKGROUND & AIMS: Screening for celiac disease (CD) is recommended in children with affected first-degree relatives (FDR). However, the frequency of screening and at what age remain unknown. The aims of this study were to detect variables influencing the risk of CD development and develop and validate clinical prediction models to provide individualized screening advice. METHODS: We analyzed prospective data from the 10 years of follow-up of the PreventCD-birth cohort involving 944 genetically predisposed children with CD-FDR. Variables significantly influencing the CD risk were combined to determine a risk score. Landmark analyses were performed at different ages. Prediction models were created using multivariable Cox proportional hazards regression analyses, backward elimination, and Harrell's c-index for discrimination. Validation was done using data from the independent NeoCel cohort. RESULTS: In March 2019, the median follow-up was 8.3 years (22 days-12.0 years); 135/944 children developed CD (mean age, 4.3 years [range, 1.1-11.4]). CD developed significantly more often in girls (P = .005) and in Human Leukocyte Antigen (HLA)-DQ2 homozygous individuals (8-year cumulative incidence rate of 35.4% vs maximum of the other HLA-risk groups 18.2% [P < .001]). The effect of homozygosity DR3-DQ2/DR7-DQ2 on CD development was only present in girls (interaction P = .04). The prediction models showed good fit in the validation cohort (Cox regression 0.81 [0.54]). To calculate a personalized risk of CD development and provide screening advice, we designed the Prediction application https://hputter.shinyapps.io/preventcd/. CONCLUSION: Children with CD-FDR develop CD early in life, and their risk depends on gender, age and HLA-DQ, which are all factors that are important for sound screening advice. These children should be screened early in life, including HLA-DQ2/8-typing, and if genetically predisposed to CD, they should get further personalized screening advice using our Prediction application. TRIAL REGISTRATION NUMBER: ISRCTN74582487 (https://www.isrctn.com/search?q=ISRCTN74582487).

Functional Gastrointestinal Disorders in Mediterranean Countries According to Rome IV Criteria.

OBJECTIVES: The aim of this study was to assess the prevalence of functional gastrointestinal disorders (FGIDs) in children of Mediterranean area using Rome IV criteria and to compare the prevalence of FGIDs using Rome IV and Rome III criteria. METHODS: This was a cross-sectional study enrolling children and adolescents living in Croatia, Greece, Israel, Italy, Macedonia, and Serbia. Subjects were examined in relation to the presence of FGIDs, using the Rome IV criteria. Data were compared with the results of a previous study using Rome III data. RESULTS: We analyzed 1972 children ages 4 to 9 years (group A), and 2450 adolescents 10 to 18 years old (group B). The overall prevalence of FGIDs was 16% in group A and 26% in group B, with statistical differences among countries in both groups (P < 0.001). In group A, the prevalence of FGIDs and of functional constipation (FC) was significantly lower than in the previous study (P < 0.001), whereas in group B no significant difference was found. In both groups of age, the prevalence of abdominal migraine and irritable bowel syndrome decreased significantly (P < 0.001 and P < 0.001, respectively) using Rome IV versus Rome III criteria, conversely functional dyspepsia increased (P < 0.001). CONCLUSIONS: FGIDs are common in children and adolescents, their frequency increases with age, and there is a significant variation in the prevalence of some FGIDs among different European countries. The application of the Rome IV criteria resulted in a significantly lower prevalence of FGIDs in children compared with Rome III criteria.

Research priorities in pediatric parenteral nutrition: a consensus and perspective from ESPGHAN/ESPEN/ESPR/CSPEN.

Parenteral nutrition is used to treat children that cannot be fully fed by the enteral route. While the revised ESPGHAN/ESPEN/ESPR/CSPEN pediatric parenteral nutrition guidelines provide clear guidance on the use of parenteral nutrition in neonates, infants, and children based on current available evidence, they have helped to crystallize areas where research is lacking or more studies are needed in order to refine recommendations. This paper collates and discusses the research gaps identified by the authors of each section of the guidelines and considers each nutrient or group of nutrients in turn, together with aspects around delivery and organization. The 99 research priorities identified were then ranked in order of importance by clinicians and researchers working in the field using a survey methodology. The highest ranked priority was the need to understand the relationship between total energy intake, rapid catch-up growth, later metabolic function, and neurocognitive outcomes. Research into the optimal intakes of macronutrients needed in order to achieve optimal outcomes also featured prominently. Identifying research priorities in PN should enable research to be focussed on addressing key issues. Multicentre trials, better definition of exposure and outcome variables, and long-term metabolic and developmental follow-up will be key to achieving this. IMPACT: The recent ESPGHAN/ESPEN/ESPR/CSPEN guidelines for pediatric parenteral nutrition provided updated guidance for providing parenteral nutrition to infants and children, including recommendations for practice. However, in several areas there was a lack of evidence to guide practice, or research questions that remained unanswered. This paper summarizes the key priorities for research in pediatric parenteral nutrition, and ranks them in order of importance according to expert opinion.

Modified Crohn's disease exclusion diet is equally effective as exclusive enteral nutrition: Real-world data.

BACKGROUND: Data on the efficacy of the newly established dietetic treatment of Crohn's disease (CD), the CD exclusion diet (CDED), are scarce. The aim of this study was to provide real-world data on the efficacy of CDED in comparison with exclusive enteral nutrition (EEN) for remission induction. METHODS: A retrospective analysis of children diagnosed with CD who were treated with CDED + partial EN (PEN) or with EEN was performed. Eighty percent of the children assigned to CDED + PEN underwent 1-2 weeks of EEN prior to CDED + PEN. For all children, data from the medical charts were extracted before the introduction of diet therapy and at the end of EEN or CDED + PEN phase 1. RESULTS: A total of 61 patients (49.2% females; median age, 14.4 years [minimum: 6.7, maximum: 17.9]) were included in the study; 42 children (68.9%) achieved remission, 27 of 41 (65.9%) received EEN and 15 of 20 (75.0%) received CDED + PEN. There was no significant difference in the failure of nutrition therapy between the two groups (P = .469). Patients receiving CDED + PEN had significantly higher weight gain (P = .002) and increases in body mass index z-score (P = .001) compared with patients who received EEN alone. CONCLUSION: Treatment with CDED + PEN (with prior 1-2 weeks of EEN) has comparable efficacy to EEN therapy alone in inducing remission in children with CD, and it leads to better weight gain. Further studies are needed to confirm these results.

Moderate-to-Vigorous Physical Activity Is Associated With Higher Bone Mineral Density in Children With Inflammatory Bowel Disease.

OBJECTIVES: Decreased mineral bone density (BMD) and reduced lean body mass (LBM) are common amongst children with inflammatory bowel disease (IBD). The aim of our cross-sectional, observational study was to evaluate the relationship between BMD, body composition and physical activity (PA) in children with IBD in remission. METHODS: Total body less head (TLBH) dual energy X-ray absorptiometry (DXA) was used to measure BMD, fat mass (FM) and lean body mass (LBM). Triaxial accelerometer for five consecutive days was used to objectivize PA. RESULTS: Forty pediatric IBD patients in clinical remission (24 boys; age 15.3 ±â€Š0.4 years; Crohn disease [CD], n = 20, ulcerative colitis [UC], n = 18, inflammatory bowel disease-unclassified [IBD-U], n = 2) were recruited. Mean BMD was 0.940 g/cm2 and mean BMD z score was -0.42 ±â€Š0.14. Patients with CD had significantly lower BMD than UC counterparts (P < 0.001). Average time spent in PA was 247.24 ±â€Š16.71 min/day with 45.73 ±â€Š8.22 min/day spent in moderate-to-vigorous PA (MVPA). We observed a significant positive correlation between the time spent in MVPA and BMD z score (P = 0.003) and LBM z score (P = 0.026). Multivariate analysis confirmed that the positive correlation of MVPA and BMD z score. There was no significant correlation between daily protein intake and BMD. Cumulative glucocorticoid dose negatively correlated with LBM z score (P = 0.003), but not with BMD z score (P = 0.069). CONCLUSIONS: This study points to a strong positive relationship between MVPA, LBM and BMD. Longitudinal studies are required in order to elucidate the modifiable processes that determine body health and favorable body composition.

Point-of-Care Screening for Coeliac Disease in Schoolchildren Reveals Higher Disease Prevalence in Croatia.

Coeliac disease (CD) is an immune-mediated inflammatory disease triggered by dietary gluten and related proteins in genetically predisposed individuals. Point-of-care (POC) methods are non-invasive and easily performed tests, which could help to reduce the diagnostic delay of CD. The aim of our study was to determine the prevalence of CD using rapid POC test in first-grade schoolchildren in Zagreb, Croatia. A rapid qualitative immunoassay POC test designed for detection of immunoglobulin (Ig) A and IgG deamidated gliadin antibodies (DGP), as well as total IgA (to identify IgA deficient patients) in whole blood, was used to test healthy children on gluten containing diet. Out of 1404 tested children (51% female), 85 (6.05%) had a positive rapid POC test result and were referred to paediatric gastroenterologist. Finally, 7 children were diagnosed with CD (0.5%). There was no significant difference in children with CD and children with positive POC but negative serology in sex, BMI, or symptoms. However, children diagnosed with CD complained of abdominal pain significantly more often. The prevalence of CD in first-grade schoolchildren was 1:200 (0.5%), higher than in previous studies performed in Croatia. The results imply the possible benefit of IgA and IgG DGP-based POC tests in population screening.