Reflections on treatment of IBD in children and adolescents.

Major pharmaceutical advancements in the field of inflammatory bowel diseases benefit to children and adolescents affected with this progressive chronic condition. Scientific organisations such as ESPGHAN and ECCO actively publish guidelines related to the many aspects of care from these patients. Clinical studies and long-term prospective registries in the appropriate age groups are crucial to support an evidence based strategy.

Gastric Emptying of Liquids in Children.

OBJECTIVES: The present study was performed to determine normal values for gastric half-emptying time (t1/2GE) of liquids in healthy children. METHODS: Gastric emptying (GE) of a standardized test milk-drink measured with technetium scintigraphy and the C-acetate breath test (C-ABT) was compared in 19 children ages between 4 and 15 years with upper gastrointestinal symptoms. The C-ABT was subsequently used to determine normal values for GE of the same liquid test meal in 133 healthy children ages between 1 and 17 years. RESULTS: In the group of children with upper gastrointestinal symptoms, the results showed a significant correlation (r = 0.604, P = 0.0006) between t1/2GE measured with both techniques. In the group of healthy children, the results of t1/2GE showed that there was no influence of age, sex, weight, height, and body mass index on GE. CONCLUSIONS: Normal values for GE of a standardized test milk-drink in healthy children were determined with the C-ABT. This technique is considered reliable and is well accepted by the patients.

Accuracy of Nutritional Screening Tools in Assessing the Risk of Undernutrition in Hospitalized Children.

OBJECTIVE: The aim of the present study was to evaluate the predictive accuracy of screening tools for assessing nutritional risk in hospitalized children in developed countries. METHODS: The study involved a systematic review of literature (MEDLINE, EMBASE, and Cochrane Central databases up to January 17, 2014) of studies on the diagnostic performance of pediatric nutritional screening tools. Methodological quality was assessed using a modified QUADAS tool. Sensitivity and specificity were calculated for each screening tool per validation method. A meta-analysis was performed to estimate the risk ratio of different screening result categories of being truly at nutritional risk. RESULTS: A total of 11 studies were included on ≥1 of the following screening tools: Pediatric Nutritional Risk Score, Screening Tool for the Assessment of Malnutrition in Paediatrics, Paediatric Yorkhill Malnutrition Score, and Screening Tool for Risk on Nutritional Status and Growth. Because of variation in reference standards, a direct comparison of the predictive accuracy of the screening tools was not possible. A meta-analysis was performed on 1629 children from 7 different studies. The risk ratio of being truly at nutritional risk was 0.349 (95% confidence interval [CI] 0.16-0.78) for children in the low versus moderate screening category and 0.292 (95% CI 0.19-0.44) in the moderate versus high screening category. CONCLUSIONS: There is insufficient evidence to choose 1 nutritional screening tool over another based on their predictive accuracy. The estimated risk of being at "true nutritional risk" increases with each category of screening test result. Each screening category should be linked to a specific course of action, although further research is needed.

Outcomes of endoscopy and novel pH-impedance parameters in children: is there a correlation?

OBJECTIVES: Discordance exists between outcomes of endoscopy, multichannel intraluminal impedance monitoring (pH-MII), MII baselines, and gastroesophageal reflux symptoms. The aim of the present study was to determine the association between endoscopy, pH-MII and MII baselines, in children with gastroesophageal reflux symptoms. METHODS: Endoscopies were graded for reflux esophagitis (RE). Biopsies of the distal esophagus were assessed for signs suggestive of esophagitis. Reflux index (RI), symptom association probability (SAP), number of reflux episodes, and mean baseline values were calculated. pH-MII was considered positive in children when RI was ≥ 3% and/or SAP was ≥ 95% and for infants when RI was ≥ 10% and/or SAP was ≥ 95%. Baselines were manually calculated and compared with an automated analysis. For MII baselines, patients were divided in 3 groups: normal endoscopy and negative overall pH-MII; normal endoscopy and an overall positive pH-MII; and RE. RESULTS: A total of 26 children and 14 infants were included, median age: 26.5 months (2 months-16.2 years). Thirteen (32.5%) had RE. A significant negative association was found for RI and MII baselines (P = 0.009) and between SAP and RE (P = 0.039, odds ratio 1.018). MII baseline values were predictive for neither conventional pH-MII parameters nor RE. Manual analysis and automated calculation of MII baselines showed a perfect correlation. Distal MII baselines were significantly lower in children with a positive overall pH-MII outcome compared with the proximal esophagus (P = 0.049). No significant changes were found in baselines among the different groups 1 to 3. CONCLUSIONS: Acid-related parameters are significantly related to MII baselines. A perfect correlation between manual- and automated analysis of MII baselines was found. Large prospective studies are needed to confirm the exact role of endoscopy and MII baselines.

Gastrointestinal manifestations of cow's milk protein allergy and gastrointestinal motility.

UNLABELLED: Cow's milk protein allergy (CMPA) may cause gastrointestinal motility disorders. Symptoms of both conditions overlap and diagnostic tests do not reliably differentiate between both. A decrease of symptoms with an extensive hydrolysate and relapse during challenge is not a proof of allergy, because hydrolysates enhance gastric emptying, a pathophysiologic mechanism of gastro-oesophageal reflux (GER). Thickened formula reduces regurgitation, and failure to do so suggests CMPA. A thickened extensive hydrolysate may induce more rapid improvement, but does not always differentiate between CMPA and GER. Different hypotheses are discussed: is the overlap between CMPA and functional disorders coincidence, or do both entities present with identical symptoms, or does the fact that symptoms are identical indicates that there is only one entity involved? Studies on the prevention of CMPA focused on 'at-risk families', and resulted in a decrease of CMPA and atopic dermatitis, but did not provide data on the incidence of GER. CONCLUSION: As long as there are no objective diagnostic tools to separate GER from CMPA, the physician has two options: first treat the most likely diagnosis, and switch if after 2-4 weeks there is no improvement, or treat both conditions with one intervention, what will not result in a diagnosis.

Soy infant formula: is it that bad?

UNLABELLED: The objective of this study is to review the indications of soy infant formula (SIF). Structured review of publications is made available through standard search engines (Pubmed,…). The medical indications for SIF are limited to galactosaemia and hereditary lactase deficiency. In the treatment of cow's milk allergy, SIF is used for economic reasons, as extensive hydrolysates are expensive. SIF is dissuaded mainly because of its phytooestrogen content. Isoflavone serum levels are much higher in SIF-fed infants than in breastfed or cow milk formula-fed infants. Administration of pure isoflavones to animals causes decreased fertility, but clinically relevant adverse effects of SIF in infants are not reported. CONCLUSION: Soy infant formula remains an option for feeding of term born infants if breastfeeding is not possible and if standard infant formula is not tolerated.

Intestinal Spirochetosis: A Case Series and Review of the Literature.

A clinical suspicion of intestinal spirochetosis is required when patients have long lasting complaints of abdominal pain, diarrhea, rectal bleeding, weight loss, and nausea. An endoscopy with biopsies needs to be performed to confirm the diagnosis of intestinal spirochetosis. The diagnosis of intestinal spirochetosis is based on histological appearance. Intestinal spirochetosis can also be associated with other intestinal infections and juvenile polyps (JPs). JPs seem to be more frequent in patients with intestinal spirochetosis than in patients without intestinal spirochetosis. Intestinal spirochetosis in children should be treated with antibiotics. Metronidazole is the preferred option. In this article, we describe 4 cases of intestinal spirochetosis in a pediatric population and provide a review of the literature over the last 20 years. Intestinal spirochetosis is a rare infection that can cause a variety of severe symptom. It is diagnosed based on histological appearance.

Chronic enteropathy and feeding in children: an update.

Enteropathy defines abnormalities of the small intestinal mucosa of various etiologies in which nutrition has a causal or a therapeutic role. Breast milk is the gold-standard feeding during infancy for optimal nutrition in health and the majority of diseases. Therapeutic formulae have decreased the need for enteral or parenteral support. Gastrointestinal infections are worldwide the most frequent cause of enteropathy by increasing mucosal permeability, local expression of costimulatory molecules allowing antigen penetration in the mucosa, and T-cell activation leading sometimes to disruption of oral tolerance. Concomitant malnutrition impairs not only the immunologic response but also the recovery of damaged mucosa with secondary intestinal and pancreatic enzymatic reductions. Optimal nutritional rehabilitation is the cornerstone of the management of persisting diarrhea. Celiac disease and cow's milk protein allergy are examples of chronic enteropathy. Multiple food allergies, even during breast-feeding, are increasingly reported due to an impaired development of oral tolerance. The dietary approach to allergic disease is currently evolving from passive allergen avoidance to active modulation of the immune system to (re)establish tolerance. The gastrointestinal flora provides maturational signals for the lymphoid tissue, improves balance of inflammatory cytokines, reduces bacterial invasiveness and dietary antigen load, and normalizes gut permeability. The clinical effects of nucleotides and zinc merit further clinical evaluation. Major attention has recently focused on the immune effects of dietary lipids in terms of possible prevention of allergic sensitization by downregulating inflammatory response and protecting the epithelial barrier and host-microbe interactions modifying the adherence of microbes to the mucosa.

Probiotics and zinc in acute infectious gastroenteritis in children: are they effective?

OBJECTIVE: Several studies in recent decades have assessed the effects of different probiotics in acute gastroenteritis, showing that specific strains of Lactobacilli (mainly Lactobacillus casei GG) and Saccharomyces boulardii may exert some beneficial therapeutic actions, mainly when used in rotavirus gastroenteritis, at a high dose, and in the early phase. The mechanisms of action of probiotics are not completely elucidated but seem to involve a complex interaction among epithelial, molecular, metabolic, and immune responses. Data on the prevention of community-acquired, nosocomial, and travelers' diarrhea are currently conflicting. Because each micro-organism has different properties, an accurate selection of the strain, dose, and patient should be cautiously considered. METHODS AND RESULTS: Several reports from developing countries have demonstrated that supplements of zinc also provide significant reduction in stool output and duration, persistency, and severity of diarrhea. In view of the published data and of the different actions of zinc (such as improvement of the immune status, intestinal permeability, epithelial and enzymatic function, and electrolyte transport), the use of zinc as adjunctive therapy to oral rehydration solution has the potential to improve the management of diarrhea and decrease complications in children worldwide. In contrast to probiotics, which most trials in the developed world have used, there has been no trial with zinc performed in developed countries. CONCLUSION: Data on the effect of a combined administration of zinc and probiotics in acute gastroenteritis are urgently needed.

Functional constipation in children: challenges and solutions.

This review intends to update what is known about and what is still a challenge in functional constipation (FC) in children regarding epidemiology, pathophysiology, diagnosis, and management. Although FC is a common childhood problem, its global burden remains unknown as data from parts of the world are missing. Another problem is that there is a large variation in prevalence due to differences in study methods and defining age groups. The pathophysiology of FC remains unclear to date but is probably multifactorial. Withholding behavior is likely to be the most important factor in toddlers and young children. Genetics may also play a role since many patients have positive family history, but mutations in genes associated with FC have not been found. Over the past years, different diagnostic criteria for FC in infants and children have been proposed. This year, Rome IV criteria have been released. Compared to Rome III, it eliminates two diagnostic criteria in children under the age of 4 who still wear diapers. Physical examination and taking a thorough medical history are recommended, but other investigations such as abdominal radiography, transabdominal recto-ultrasonography, colonic transit time, rectal biopsies, and colon manometry are not routinely recommended. Regarding treatment, guidelines recommend disimpaction and maintenance therapy with polyethylene glycol (PEG) with or without electrolytes. But experience shows that acceptability, adherence, and tolerance to PEG are still a challenge. Counseling of parents and children about causes of FC is often neglected. Recent studies suggest that behavior therapy added to laxative therapy improves the relief of symptoms. Further homogeneous studies, better-defined outcomes, and studies conducted in primary care are needed.

Development of a core outcome set for clinical trials in childhood constipation: a study using a Delphi technique.

OBJECTIVE: Patients, their parents and healthcare professionals (HCPs) have a different perception regarding the symptoms of functional constipation (FC). Consequently, a lack of agreement exists on definitions and outcomes used in therapeutic trials of FC. Therefore, our aim was to develop a core outcome set (COS) for FC for children aged 0-1 year and 1-18 years. DESIGN AND SETTING: Prospective study design: primary, secondary and tertiary care settings. METHODS: This COS was developed using a Delphi technique. First, HCPs, parents of children with FC and patients aged ≥12-18 years were asked to list up to five outcomes they considered relevant in the treatment of FC. Outcomes mentioned by >10% of participants were included in a shortlist. In the next phase, outcomes on this shortlist were rated and prioritised by HCPs, parents and patients. Outcomes with the highest scores were included in a draft COS. In a face-to-face expert meeting, the final COS was determined. RESULTS: The first phase was completed by 109 HCPs, 165 parents and 50 children. Fifty HCPs, 80 parents and 50 children completed the subsequent phase. The response rate was between 63% and 100% in both steps. The final COS for all ages consisted of: defecation frequency, stool consistency, painful defecation, quality of life, side effects of treatment, faecal incontinence, abdominal pain and school attendance. CONCLUSION: The use of this COS for FC will decrease study heterogeneity and improve comparability of studies. Therefore, researchers are recommended to use this COS in future therapeutic trials on childhood FC.

Treatment of Cow's Milk Protein Allergy.

The diagnosis and treatment of cow's milk protein allergy (CMPA) is still a challenge. A systematic literature search was performed using Embase, Medline, The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials for the diagnosis and treatment of cow's milk allergy (CMA). Since none of the symptoms of CMPA is specific and since there is no sensitive diagnostic test (except a challenge test), the diagnosis of CMPA remains difficult. A "symptom-based score" is useful in children with symptoms involving different organ systems. The recommended dietary treatment is an extensive cow milk based hydrolysate. Amino acid based formula is recommended in the most severe cases. However, soy infant formula and hydrolysates from other protein sources (rice) are gaining popularity, as they taste better and are cheaper than the extensive cow's milk based hydrolysates. Recent meta-analyses confirmed the safety of soy and estimate that not more than 10-15% of CMPA-infants become allergic to soy. An accurate diagnosis of CMA is still difficult. The revival of soy and the development of rice hydrolysates challenge the extensive cow's milk based extensive hydrolysates as first option and amino acid formula.

Nutritional status of children hospitalized for parapneumonic effusion.

BACKGROUND & AIMS: Among children hospitalized for pneumonia, those with parapneumonic effusion (PPE) are at particular risk for nutritional deterioration. This study aimed to 1) investigate the evolution of the nutritional status during hospitalization and at outpatient follow-up; 2) determine clinical risk factors for weight loss during hospitalization; 3) describe the nutritional interventions for these children. METHODS: Retrospective chart review (January '07 - September '12) of 56 children with pneumonia, complicated by PPE in two Belgian hospitals for data on body weight and height at admission (t0) and discharge (t1), and two weeks (t2) and one month (t3) after discharge. Length of hospitalization (LoS), length of stay in paediatric intensive care (LoSPICU) and maximal in-hospital weight loss (tmax) were calculated and nutritional interventions were recorded. RESULTS: The median (range) age was 3.5 (1.0-14.8) years. Weight or height was lacking in five (8.9%) children at t0 and in 28 (50%) at t1; 21.4% was weighed only once during hospitalization. At tmax, respectively 17/44 and 5/44 children lost ≥ 5% and ≥ 10% of their weight. Median (range) LoS and LoSPICU were 18.0 (10-41) and 4.0 (0-23) days. One-fourth received a nutritional intervention. Weight for height at admission (WFH(t0)) significantly predicted maximal weight loss (ß (95% CI) = -0.34 (-2.0--0.1); p = 0.03). At t2 and t3, 13/32 and 5/22 of the children with available follow-up data did not reach WFH(t0), whilst in 4/35 and 5/26 body weight remained ≥ 5% under the weight(t0). CONCLUSIONS: One-third of children with pneumonia complicated by PPE and monitored for weight and height, lost ≥ 5% of their body weight during hospitalization. One-fourth did not reach initial WFH one month after discharge. Those with a higher WFH at admission were at higher risk of weight loss. More attention for monitoring of weight loss and the nutritional policy during and after hospitalization is warranted.

Probiotics and IBD.

The pathophysiology of inflammatory bowel disease is still incompletely understood. While the development of the immune system and the establishment of the microflora take place during infancy young patients often have a more severe and extensive disease. The differences in composition and concentration of intestinal microbiota and aberrant immune responses towards the luminal bacteria prompted the concept of an 'ecological' approach to control the disease course. Probiotics, living, non pathogenic micro organisms with a beneficial effect on the host, and prebiotics, oligosaccharides promoting the growth of the beneficial microflora, have been studied to this effect. Results have so far been disappointing for Crohn's disease but encouraging for ulcerative colitis. An overview of studies using probiotics in adults or children and a perspective on specific pediatric issues is provided in this review.

Probiotics and prebiotics in pediatric diarrheal disorders.

INTRODUCTION: In pediatrics, prebiotics and/or probiotics are added to infant formula, mainly to prevent diseases such as diarrheal disorders. Probiotic food supplements and medication are frequently used in the treatment of diarrheal disorders. This paper reviews the recent published evidence on these topics. AREAS COVERED: Relevant literature published using PubMed and CINAHL was collected and reviewed. Recent review papers were give special attention. EXPERT OPINION: The addition of pre- and/or probiotics to infant formula seems not harmful, but the evidence for benefit is limited. Most probiotics are commercialized as food supplements, and therefore do not qualify for medication legislation. Worldwide, Saccharomyces boulardii is the only strain which is registered as "medication" in the majority of countries. Efficacy data can only be considered if performed with the commercialized product. Some products reduce the risk for antibiotic-associated diarrhea and reduced the duration of acute infectious diarrhea with about 24 h. Overall, data in the other indications (inflammatory bowel disease, irritable bowel syndrome) are disappointing, although there are some recent promising results. The use of food supplements as medication opens the discussion to create a category of "medical food."

The STRONG(kids) nutritional screening tool in hospitalized children: a validation study.

OBJECTIVE: The STRONGkids is a nutritional screening tool for hospitalized children, which was found to predict a negative weight for height (WFH) standard deviation score (SDS) and a prolonged hospital length of stay (LOS) in a Dutch population of hospitalized children. This study aimed to test the ease of use and reproducibility of the STRONGkids, and to confirm its concurrent and prospective validity in a Belgian population of hospitalized children. METHODS: Reproducibility was tested in a cohort of 29 hospitalized children in a tertiary center and validity was tested in 368 children (105 hospitalized in a tertiary and 263 in three secondary hospitals) ages between 0.08 and 16.95 y (median 2.2 y). RESULTS: Substantial intrarater (κ = 0.66) and interrater (κ = 0.61) reliabilities were found between observations. STRONGkids scores correlated negatively with WFH SDS of the patients (ρ = -0.23; P < 0.01; odds ratio [OR], 2.47; 95% confidence interval [CI], 1.11-5.49; P < 0.05). It had a sensitivity and negative predictive value (NPV) of respectively 71.9% and 94.8% to identify acutely undernourished children. STRONGkids did not correlate with weight loss during hospitalization, but correlated with LOS (ρ = 0.25; OR 1.96; 95% CI, 1.25-3.07; both P < 0.01) and the set-up of a nutritional intervention during hospitalization (OR, 18.93; 95% CI, 4.48-80.00; P < 0.01). The sensitivity and NPV to predict a LOS ≥ 4 d were respectively 62.6% and 72%, and respectively 94.6% and 98.9% to predict a nutritional intervention. CONCLUSIONS: STRONGkids is an easy-to-use screening tool. Children classified as "low risk" have a 5% probability of being acutely malnourished, with only a 1% probability of a nutritional intervention during hospitalization.