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A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 0 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis, and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion, or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost, and quality of life.

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A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 1 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost and quality of life.

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OBJECTIVES: This study aimed to describe the impact of allogeneic/haploidentical hematopoietic stem cell transplantation on nutritional status and intake in a group of children aged 2 to 18 years. METHODS: In an observational study, data were collected prospectively. Patients were prescribed individual nutritional support by hospital routines. Anthropometrics were measured pre-transplant at hospital admission and weekly from the day of transplant (day 0) until day +28. z scores for weight, height, and BMI were calculated using Norwegian growth references to assess nutritional status. Pre-transplant diet was assessed on the day of hospitalization. Nutrient provision from enteral nutrition (EN = oral and tube) and parenteral nutrition (PN) was assessed by daily records from day +1 until day +28, or previous discharge, and compared with recommendations (RI) from the Nordic Nutrition Recommendations and ESPGHAN guidelines. Total energy intake was presented as the percentage (%) of basal metabolic rate (BMR) calculated by the Schofield equation. Macro- and micronutrient provisions were presented as medians (interquartile range) and the % of RI. RESULTS: Twenty-eight patients, mean age 10.3 years (range 3.5-16.6), were included. Two-thirds (n = 18) had malignant diseases. At admission, mean weight Z-score was -0.3, height z scores -0.7, and BMI Z-score 0.1. Eighteen percent (n = 5) were stunted and 25% (n = 7) had overweight. At admission, 25% (n = 7) had established tube feeding, and 7% (n = 2) also had PN. No significant changes in weight z scores were detected during the studied weeks ( P = 0.454). The median daily energy provision was 115% (110-123) of BMR and proteins 1.5 (1.3-1.8) g/kg. EN was provided during a median of 93% of the studied days and provided 21% of the energy. PN was given on a median of 96% of the studied days and provided 79% of energy. RI for vitamins, magnesium, and zinc was met. Provision of copper, iodine, selenium, calcium, and phosphate was below RI. CONCLUSIONS: Combined EN and PN providing 115% of BMR and 1.5 g/kg protein ensured stable weight by day +28 and covered RI, except for trace elements and minerals.

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OBJECTIVES: Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. METHODS: Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN).A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes.During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. RESULTS: A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. CONCLUSIONS: Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.

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BACKGROUND: Coeliac disease is one of the most prevalent immune-mediated gastrointestinal disorders in children. AIM: To review the incidence and prevalence of paediatric coeliac disease, and their trends, regionally across Europe, overall and according to age at diagnosis. METHODS: Systematic review and meta-analysis from January 1, 1950 to December 31, 2019, based on PubMed, CINAHL and the Cochrane Library, searches of grey literature and websites and hand searching of reference lists. A total of 127 eligible studies were included. RESULTS: The prevalence of previously undiagnosed coeliac disease from screening surveys (histology based) ranged from 0.10% to 3.03% (median = 0.70%), with a significantly increasing annual trend (P = 0.029). Prevalence since 2000 was significantly higher in northern Europe (1.60%) than in eastern (0.98%), southern (0.69%) and western (0.60%) Europe. Large increases in the incidence of diagnosed coeliac disease across Europe have reached 50 per 100 000 person-years in Scandinavia, Finland and Spain. The median age at diagnosis increased from 1.9 years before 1990 to 7.6 since 2000. Larger increases in incidence were found in older age groups than in infants and ages <5 years. CONCLUSIONS: Paediatric coeliac disease incidence and prevalence have risen across Europe and appear highest in Scandinavia, Finland and Spain. The most recent evidence shows large increases in incidence in most regions, but stabilisation in some (notably Sweden and Finland). Sharp increases in the age at diagnosis may reflect increases in milder and asymptomatic cases diagnosed since reliable serology testing became widely used, through endomysial antibodies after 1990 and tissue transglutaminase antibodies around 2000.

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OBJECTIVE: Accumulating evidence shows that patients with anorexia nervosa (AN) have globally reduced brain mass, including lower cortical volume and thickness, which largely normalizes following weight restoration. The underlying mechanisms for these processes are unknown, and how age and severity of emaciation are associated with brain morphology in AN is poorly understood. We investigated associations of age, body mass index (BMI) and biochemical parameters with brain morphology among patients in treatment. METHOD: We included 85 patients (94% female) aged 12-48 (mean = 23) years with quality controlled magnetic resonance imaging (MRI) data. T1-weighted MRI images, clinical characteristics and biochemical parameters were retrospectively collected from hospital records. Brain morphology was measured using FreeSurfer, and associations investigated using regression models and correlations. RESULTS: Controlling for BMI, age showed significant associations with brain morphology generally concordant with typical brain developmental patterns. Controlling for age, BMI showed significant positive associations with cortical volume and thickness. There were no significant interaction effects between age and BMI. None of the biochemical parameters correlated significantly with brain morphology. CONCLUSION: Our findings suggest the presence of typical neurodevelopmental patterns in AN. Importantly, we showed that severity of emaciation is related to brain morphology reductions, underscoring the importance of weight restoration.

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BACKGROUND & AIMS: Patients with intestinal failure (IF) are dependent on long-term home parenteral nutrition (HPN) to ensure growth and development. The primary aim of the present study was to assess bone mineral density (BMD) and vitamin D status in paediatric IF patients on HPN and a group of healthy children aged 2-18 years. Secondary aims were to assess growth, body composition, nutrient provision and physical activity. METHODS: An observational cross-sectional study was performed at Oslo University Hospital and at the Department of Nutrition, University of Oslo, from January to September 2017. Dual energy x-ray absorptiometry (DXA; Lunar Prodigy in IF patients and Lunar iDXA in healthy subjects) was performed to assess BMD and body composition. BMD z-score (BMDz) was calculated for total body and lumbar spine L2-L4 based on the integrated reference population in the software. Weight and height were measured for growth assessment. Nutrient provision was assessed by a 4-day food record. Blood samples were analysed for 25-hydroxy-vitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D). Physical activity was reported by a questionnaire. RESULTS: Nineteen IF patients and 50 healthy children were included. The mean age of participants was 10.0 years. The aetiology of IF patients was paediatric intestinal pseudo-obstruction (58%), short bowel syndrome (26%), and intestinal enteropathy (16%). Lower median BMDz for total body (-0.4 vs 1.1, P < 0.001) and lumbar spine L2-L4 (-0.9 vs 0.2, P = 0.01) were found in the IF group compared with the healthy children. Vitamin D provision was significantly higher in IF patients (17 µg/d vs 5.3 µg/d, P < 0.001). Both groups were sufficient in 25(OH)D (IF patients 71 nmol/L vs healthy 81 nmol/L). Nevertheless, IF patients had significantly lower 1,25(OH)2D than healthy children (71 pmol/L vs 138 pmol/L, P < 0.001). The IF group was significantly shorter (height for age z-score -1,5 vs 0,1, P = 0.001) and lighter (weight for age z-score -1,0 vs 0,1, P = 0.009) compared with the healthy subjects. BMIz did not differ; however, body fat percentage was significantly higher in IF patients compared with healthy children (34% vs 25%, P = 0.02). A lower frequency of physical activity was found in the IF group compared with the healthy group (P = 0.001). CONCLUSIONS: Paediatric IF patients on HPN had lower BMD, impaired growth, and higher body fat percentage in comparison with the healthy children. Despite a higher total supply of vitamin D in the IF group, the levels of 25(OH)D did not differ. Nevertheless, a significantly lower level of 1,25(OH)2D was found in IF patients. The results raise questions regarding differences between oral and parenteral vitamin D provision and whether intestinal function is important for the metabolism of vitamin D. TRIAL IDENTIFICATION NUMBER: Clinical Trials AEV2017/1. 2016/391/REK sør-øst B REVISION NUMBER: CLNESP-D-20-00022.

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Thiopurines, alone or in combination with other agents, have a pivotal role in the treatment of specific gastrointestinal and hepatological disorders. In inflammatory bowel disease and autoimmune hepatitis thiopurines have proven their value as steroid sparing agents for the maintenance of remission and may be considered for preventing postoperative Crohn disease recurrence where there is moderate risk of this occurring. Their use with infliximab therapy reduces antibody formation and increases biologic drug levels. The routine clinical use of thiopurines has, however, been questioned due to a number of potential adverse effects. The aim of this article is to provide information regarding the use, and in particular, safety of these agents in clinical practice in the light of such potentially severe, albeit rare, effects.

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BACKGROUND & AIMS: Children with intestinal failure (IF) receive parental nutrition to ensure adequate growth and development. The aim of this study was to assess micronutrient status in paediatric IF patients receiving home parenteral nutrition (HPN) in comparison to a group of healthy children. METHODS: An observational cross-sectional study was performed at Oslo University Hospital and at the Department of Nutrition, University of Oslo from January to September 2017. All children with IF, aged two to 18 years, were invited to participate. A reference group of healthy children was recruited through social media advertisement. Dietary intake was assessed by a four-day food record, and enteral and parenteral provision was recorded. Blood samples were analysed for vitamins, minerals and haematology to assess iron status. Two spot urine samples from each subject were analysed for iodine concentration (UIC) and creatinine. RESULTS: Nineteen children with IF and 50 healthy children were included. The mean age of the participants was 10.0 years. IF-patients received a median of 76% of their estimated energy requirements from parenteral nutrition (PN). Recommended intake (RI) for iodine from the diet was reached by 16% of IF patients and 28% of healthy children. In the IF group there was a significant positive correlation between UIC and the percentage of iodine intake from oral diet and enteral nutrition support (r = 0.57, p = 0.03). Although the IF patients had a median parenteral iodine supply of more than twice the ESPGHAN recommendation, the median UIC was 89 µg/L indicating insufficient iodine status. This may suggest that the ESPGHAN recommendation for iodine in paediatric parenteral nutrition is too low. The healthy children had sufficient iodine status according to the median UIC (133 µg/L). IF patients had significantly lower total provision of iron compared to the healthy children, 4,9 vs 8,4 mg/day (p = 0.01) with 21% of IF patients and 28% of healthy children reaching RI for iron. The prevalence of anaemia was higher in IF patients than in the healthy children (40 vs.10%, p = 0.016). CONCLUSION: The study indicates an insufficient iodine and iron status among paediatric IF patients. Iodine status was associated with enteral provision and patients had insufficient status even if they received the ESPGHAN recommendation of iodine. TRIAL IDENTIFICATION NUMBER: Clinical Trials AEV2017/1. 2016/391/REK sør-øst B.

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Acute diarrhoea is a leading cause of morbidity and mortality in the paediatric population. Racecadotril is an antisecretory drug recommended as an adjuvant antidiarrhoeal treatment.In the small bowel, the enzyme neutral endopeptidase (NEP) inhibits the action of enkephalins, which prevent water and electrolyte hypersecretion. By inhibiting NEP, racecadotril allows enkephalins to exhibit their antisecretory effects. Consequently, racecadotril reduces the secretion of water and electrolytes in the small intestine, without having an effect on intestinal motility. No serious adverse events related to racecadotril have been reported.Racecadotril has proven its efficacy as an adjuvant antidiarrhoeal drug with a good safety profile. Its addition to oral rehydration solution (ORS) appears clinically beneficial and potentially leads to health care savings.

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OBJECTIVES: To study micronutrient status and nutritional intake from complementary feeding in children on a cows' milk exclusion (CME) diet. METHODS: Fifty-seven children with cows' milk allergy, younger than 2 years, were included in a cross-sectional study. Blood was analyzed for micronutrient status. Complementary feeding was defined as all solids and liquids except of breast milk, and assessed by 3-day food diary. The results were analyzed according to 3 feeding patterns: mainly breast-fed (mBF), partially breast-fed, and no breast milk group (nBM). RESULTS: The children had a median age of 9 months and micronutrient status was within normal range for total homocysteine (p-tHcy), s-B12, s-folate, b-Hb, s-ferritin, s-zinc, and s-25(OH)D. There were no significant differences between feedings groups, except for B12-biomarkers. The mBF had higher p-tHcy (P < 0.000) and lower s-B12 (P = 0.002) compared nBM. Vitamin B12 deficiency (p-tHcy >6.5 µmol/L combined with s-B12 <250 pmol/L) was found in 12% of participants, most frequently among the mBF (36%) and none in nBM group (P = 0.009). Vitamin B12 intake from complementary feeding was negatively correlated with p-tHcy (r = -0.479, P = 0.001) and positively with s-B12 (r = 0.410, P = 0.003). Iron deficiency anemia was found in 5%. Iron intake correlated positively with b-Hb (r = 0.324, P = 0.02). Zinc deficiency was found in 7% and low 25(OH)D in 9%. Vitamin D intake was positively correlated with the use of supplements (r = 0.456, P = 0.001). CONCLUSION: The risk of B12 deficiency was high in mBF infants on CME diet, and complementary feeding was associated with better B12 status. Iron, zinc, and vitamin D deficiencies were present in all feeding groups. Complementary feeding should be introduced at 4 to 6 months of age. Vitamin D supplement is recommended to ensure adequate intake.

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OBJECTIVES: The aim of the present article was to investigate iodine status and growth in cow's milk protein allergic infants and to identify potential predictors of iodine status and growth. METHODS: Fifty-seven infants under 2 years of age were included in an observational cross-sectional study. Two spot urine samples were collected and analyzed for iodine, together with a 3-day food record and a food frequency questionnaire. Urine iodine concentrations were compared with the WHO cut-off values for iodine deficiency. Measurements of weight, length, and head circumference at birth and study inclusion were converted to standard deviation scores. Subgroup analyses were performed on different feeding patterns, according to weaning status. RESULTS: Median age was 9 months. Median urinary iodine concentration was 159 ug/L. One third of the children had urine iodine concentrations indicating iodine deficiency. Infants who were mainly breastfed were at highest risk and 58% were classified as deficient. Dietary factors positively associated with iodine excretion were intake of enriched baby cereals and meeting the dietary requirement for iodine. Stunting was present in 5%. Underweight and wasting was frequent at 11% and this was associated with food refusal and poor appetite, but not with iodine status. Growth failure was detected among boys. CONCLUSIONS: The present study suggests that cow's milk protein allergy children have high prevalence of iodine deficiency and poor growth, however the 2 conditions were not associated. The subgroup of mainly breastfed infants was at higher risk of iodine deficiency compared to weaned infants. Subjects with feeding problems had increased risk of malnutrition.

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