Symptoms and management of cow's milk allergy: perception and evidence.

Introduction: The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. Our aim was to compare the opinions of expert groups from the Middle East (n = 14) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n = 13). Methods: These Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Results: Overall, there was consensus amongst both groups of experts. Experts agreed that symptoms of crying, irritability and colic, as single manifestation, are not suggestive of CMA. They agreed that amino-acid based formula (AAF) should be reserved for severe cases (e.g., malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no unanimous consensus on the statement that a cow's milk based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role for hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle-East region. All ESPGHAN experts agreed that there is insufficient evidence that the addition of probiotics, prebiotics and synbiotics increase the efficacy of elimination diets regarding CMA symptoms (despite other benefits such as decrease of infections and antibiotic intake), whereas 3/14 of the Middle East group thought there was sufficient evidence. Discussion: Differences in voting are related to geographical, cultural and other conditions, such as cost and availability. This emphasizes the need to develop region-specific guidelines considering social and cultural conditions, and to perform further research in this area.

Why do clinical guidelines for probiotics differ?

Clinical guidelines are recommendations for healthcare providers regarding patients with specific conditions. These guidelines should be based on practice experience and the best available research evidence. However, guidelines developed by various health organisations worldwide often do not agree with each other. This is also true for the current guidelines for the clinical use of probiotics. This article aims to provide examples of conflicting clinical guidelines for probiotics, define reasons for this phenomenon, describe standard tools for improving their quality, and suggest ways to enhance the development and assessment of suitable clinical guidelines for the appropriate clinical use of probiotics in specific conditions.

Human milk mycobiota composition: relationship with gestational age, delivery mode, and birth weight.

Intestinal and human milk microbiota studies during infancy have shown variations according to geographical location, delivery mode, gestational age, and mother-related factors during pregnancy. In this study, we performed metagenomic mycobiota analyses of 44 transient and mature human milk among five different groups: mothers of normal spontaneous delivery-term (NS-T), caesarean delivery-term (CS-T), premature (PT), small for gestational age (SGA), and large for gestational age (LGA) infants. Fungi were detected in 80 out of the 88 samples. Regarding the number of observed fungal species, the NS-T group was more homogeneous (less variable) comparing the other groups (P<0.05). In the transient human milk samples, the most abundant species were Saccharomyces cerevisiae (33.3%) and Aspergillus glaucus (27.4%). While A. glaucus (33.7%) was second most abundant species in mature milk, S. cerevisiae disappeared (P<0.01) and Penicillium rubens became the most abundant species (35.5%) (P<0.05). Among the NS-T group, the most abundant species was Malassezia globosa in both transient and mature milk. In contrast, S. cerevisiae was the most abundant species in transient human milk (45.0%) in the CS-T group, but it disappeared in mature milk (P<0.01). In transient milk, M. globosa was only represented 6.0-9.0% of taxa in the PT, SGA, and LGA groups (P<0.05). In transient and mature milk in the PT, SGA and LGA groups, the most abundant species were A. glaucus and P. rubens. In mature milk samples, P. rubens is more abundant in CS-T group, PT group and LGA group, than the NS-T groups (P<0.05 for all). Although fungi constitute only a very small part of the human milk microbiome, we observed some changes that the human milk mycobiota composition varies in caesarean delivery, premature, SGA and LGA groups, comparing the normal spontaneous delivery, as well as differences between transient and mature human milk.

Mind the gut: probiotics in paediatric neurogastroenterology.

The gut-brain axis has recently emerged as a key modulator of human health and the intestinal microbiome has a well-recognised pivotal role in this strong connection. The aim of this narrative review is to update and summarise the effect and clinical applicability of probiotics in paediatric neurogastroenterology. The Cochrane Database and PubMed were searched using keywords relating to different subtypes of functional gastrointestinal disorders (FGIDs) and their symptoms, those relating to the CNS and related neurological or behavioural dysfunction as well as 'probiotic' OR 'probiotics'. Included papers were limited to those including children (aged 0-18 years) and using English language. Although significant effects of specific strains have been reported in infants with FGIDs, heterogeneity amongst the studies (different products and concentrations used and FGID subtypes), has limited the ability to draw an overall conclusion on the clinical value of probiotics. According to different meta-analyses of randomised controlled trials, the use of Lactobacillus reuteri (DSM 17938) was associated with a significant decrease in average crying time in infantile colic. There is moderate evidence for this strain and LGG and limited evidence (based on one study each) for the beneficial effect of VSL#3 and a three-strain bifidobacteria mix in abdominal pain FGIDs, particularly in the irritable bowel disease subgroup of children, but not in functional dyspepsia. There is currently no clear evidence of positive effects of oral probiotics in autistic spectrum disorder. Efficacy and safety of other strains or beneficial effects in other conditions still need to be proven, as probiotic properties are strain-specific, and data cannot be extrapolated to other brain-gut or mood diseases or to other probiotics of the same or different species. To transform the use of probiotics from a tempting suggestion to a promising treatment modality in neurogastroenterological disorders more accurate differentiation of the efficacy-proven strains, clarification of dose, duration, and outcome and a careful selection of the target patients are still necessary.

Economic evaluation of S. boulardii CNCM I-745 for prevention of antibioticassociated diarrhoea in hospitalized patients.

Interest in administration of probiotics to prevent antibiotic-associated diarrhoea (AAD) in hospitalized patients is increasing. We determined the cost of antibiotic-associated diarrhoea in hospital settings for non-complicated and Clostridium difficile (C.diff) complicated AAD, and performed a health-economic analysis of AAD prevention with S. boulardii CNCM I-745 (S. boulardii) from data collected in 1 university and 3 regional hospitals in Flanders. Using a decision tree analytic model, costs and effects of S. boulardii for AAD prevention are calculated. Incremental costs due to AAD, including increased length of hospitalization, were calculated using bottom-up and top-down costing approaches from a hospital, healthcare payer (HCP) and societal perspective. Model robustness was tested using sensitivity analyses. Additional costs per hospitalized patient range from € 277.4 (hospital) to € 2,150.3 (societal) for non-complicated and from € 588.8 (hospital) to € 2,239.1 (societal) for C. diff. complicated AAD. Using S. boulardii as AAD prevention results in cost savings between € 50.3 (bottom-up) and € 28.1 (topdown) per patient treated with antibiotics from the HCP perspective; and € 95.2 and € 14.7 per patient from the societal and hospital perspectives. Our analysis shows the potential for using S. boulardii as AAD prophylactic treatment in hospitalized patients. Based on 831,655 hospitalizations with antibiotic administration in 2014 and € 50.3 cost saving per patient on antibiotics, generalized use of S. boulardii could result in total annual savings up to € 41.8 million for the Belgian HCP.

Effectiveness of airway clearance techniques in children hospitalized with acute bronchiolitis.

OBJECTIVE: To evaluate the effectiveness of two airway clearance techniques (ACT's) in children <24 months hospitalized with mild to moderate bronchiolitis. DESIGN: One hundred and three children were randomly allocated to receive one 20-min session daily, either assisted autogenic drainage (AAD), intrapulmonary percussive ventilation (IPV), or bouncing (B) (control group), ninety-three finished the study. OUTCOME MEASURES: Mean time to recovery in days was our primary outcome measure. The impact of the treatment and the daily improvement was also assessed by a validated clinical and respiratory severity score (WANG score), heart rate (HR), and oxygen saturation (SaO2 ). RESULTS: Mean time to recovery was 4.5 ± 1.9 days for the control group, 3.6 ± 1.4 days, P < 0.05 for the AAD group and 3.5 ± 1.3 days, P = 0.03 for the IPV group. Wang scores improved significantly for both physiotherapy techniques compared to the control group. CONCLUSION: Both ACT's reduced significantly the length of hospital stay compared to no physiotherapy. Pediatr Pulmonol. 2017;52:225-231. © 2016 Wiley Periodicals, Inc.

[Management of Acute Gastroenteritis in Children]. / Traitement de la gastro-entérite aiguë chez L'Enfant.

Acute gastroenteritis remains one of the most frequent disorders in infants and children. The cornerstone of the treatment is oral rehydration, although the latter does not reduce the duration of the diarrhea, which is about four days. As a consequence, this quite benign condition of acute gastroenteritis in our countries still does have an important socio-economic impact. Therefore, recent European guidelines and recommendations consider the use of different medications and agents that reduce the duration of diarrhea.

Eosinophilic esophagitis that develops during therapy with proton pump inhibitors : case series and possible mechanisms.

Therapy with proton-pump inhibitors (PPIs) results in remission in at least one third of patients with esophageal eosinophilia, presumably because of both their acid-related and anti-inflammatory mechanisms of action. However, eosinophilic esophagitis (EoE) may also develop during therapy with PPIs. We present a case series of four children who were initially diagnosed with infectious esophagitis, gastroesophageal reflux disease or gastric ulcer, who had no eosinophilic infiltration of the esophagus, but subsequently developed symptoms, endoscopic features and histological picture of typical EoE. We discuss mechanisms of action of PPIs of likely relevance to an increased risk of development of EoE in some patients, such as their influence on mucosal barrier function, interference with pH-related protein digestion by pepsin, and antigen processing by immune cells.

Gastric emptying of solids in children: reference values for the (13) C-octanoic acid breath test.

BACKGROUND: (99m) Technetium scintigraphy ((99m) TS) is the 'gold standard' for measuring gastric emptying (GE), but it is associated with a radiation exposure. For this reason, the (13) C-octanoic acid breath test ((13) C-OBT) was developed for measuring GE of solids. The objective of this study was to determine normal values for gastric half-emptying time (t1/2 GE) of solids in healthy children. METHODS: Gastric emptying of a standardized solid test meal consisting of a pancake evaluated with (99m) TS and (13) C-OBT was compared in 22 children aged between 1 and 15 years with upper gastrointestinal symptoms. Subsequently, the (13) C-OBT was used to determine normal values for GE of the same solid test meal in 120 healthy children aged between 1 and 17 years. KEY RESULTS: The results showed a significant correlation (r = 0.748, p = 0.0001) between t1/2 GE measured with both techniques in the group of children with upper gastrointestinal symptoms. In the group of healthy children, mean t1/2 GE was 157.7 ± 54.0 min (range 71-415 min), but t1/2 GE decreased with age between 1 and 10 years and remained stable afterward. There was no influence of gender, weight, height, body mass index, and body surface area on t1/2 GE. CONCLUSIONS & INFERENCES: Normal values for GE of solids measured with the (13) C-OBT using a standardized methodology were determined in healthy children. We propose to use this method and corresponding reference ranges to study GE of solids in children with gastrointestinal problems.

Influence of intrapulmonary percussive ventilation in upright position on gastro-oesophageal reflux in infants.

OBJECTIVES: To determine the influence of physiotherapy using intrapulmonary percussive ventilation on gastro-oesophageal reflux (GOR) in infants <1 year. METHODS: In this controlled trial with intra-subject design, children were studied using multichannel intraluminal impedance pH (pH-MII) monitoring over 24 hr, during which they received one 20-min session of intrapulmonary percussive ventilation in upright position (IPVR ), 2 hr after their latest feeding. Two hours after each feeding, the number of reflux episodes (RE) over a 20-min period was registered for each infant and a mean per 20 min was calculated in order to obtain a baseline value. The number of RE during IPVR intervention was compared to baseline. RESULTS: Fifty infants with a median age of 133 days were recruited of whom 21 were diagnosed with pathological GOR. During IPVR , the incidence of RE in the entire group was significantly lower compared to baseline; median (inter-quartile range [IQR]) 0 (0-1) versus 0.71 (0-1.33) RE, respectively, P = 0.003. The subgroup with abnormal GOR showed also a significant decrease of RE during IPVR ; median (IQR) 0 (0-1) versus 1.17 (0.55-2.16) RE, respectively, P = 0.03. No difference was detected in the group with normal reflux; median (IQR) 0.6 (0-1) compared to 0 (0-1) RE, respectively, P = 0.34. CONCLUSION: IPVR does not induce, nor aggravate GOR in infants without and with pathological GOR, respectively, but on the contrary decreases the number of RE in patients with pathological reflux. Pediatr Pulmonol. 2016;51:1065-1071. © 2016 Wiley Periodicals, Inc.

Low mean impedance in 24-hour tracings and esophagitis in children: a strong connection.

Esophageal multiple intraluminal impedance baseline is an additional impedance parameter that was recently related to esophageal integrity. The aim of this study was to assess the relationship between mean esophageal impedance value and endoscopic findings in a large group of children. Children with symptoms of gastroesophageal reflux submitted to both endoscopy and impedance were included. Esophagitis was graded according to the Los Angeles classification. Mean impedance value was automatically calculated over 24-hour tracings. Data were adjusted for age through z-score transformation using percentiles normalized by the LMS (Lambda for the skew, Mu for the median, and Sigma for the generalized coefficient of variation) method. Nonparametric Mann-Whitney and Kruskal-Wallis tests, multiple, and stepwise regression were used. P-value <0.05 was considered as statistically significant. A total of 298 impedance tracings were analyzed. Endoscopic and histological esophagitis were detected in 30 and 29% patients, respectively. Median baseline z-score was significantly decreased both in proximal (P = 0.02) and distal (P = 0.01) esophagus in patients with endoscopic (but not histological) esophagitis. Patients with more severe esophagitis showed the lowest z-score. Bolus exposure index and the number of reflux episodes were the variables that were significantly associated with the baseline z-score. Impedance z-score is significantly decreased in infants and children with endoscopic esophagitis. Severity of esophagitis, bolus exposure index, and number of reflux episodes are factors influencing mean esophageal impedance.

Debates in allergy medicine: food intolerance does exist.

BACKGROUND: Health care professionals and patients mix and mingle (hyper)sensitivity, allergy and intolerance. The consequences are discrepancies which result in confusion. The following is a very personal point of view, intended to start a debate to come to consensus. OBJECTIVES: We aimed to clarify the proposed terminology for the primary health care professional from the point of view of the pediatric gastroenterologist. RESULTS: Many patients present with symptoms "related to food ingestion". We propose to use this wording if no underlying mechanism can be identified. Intolerance should be restricted to carbohydrate malabsorption causing symptoms. Allergy is restricted to IgE mediated allergy and non-IgE manifestations that can only be explained through an immune mediated mechanism, such as food induced atopic dermatitis and allergic colitis with blood in the stools. Unfortunately, primary heath care physicians have no diagnostic tools for non-IgE mediated allergy. A positive challenge test is a proof of a food-induced symptom, but does not proof that the immune system is involved. (Hyper)sensitivity suggests immune mediated mechanisms and should therefore not be used. The pathophysiologic mechanism of many food-related symptoms is unclear. The same symptom can be caused by allergy or be considered functional, such as infantile colic, gastro-esophageal reflux and constipation related to cow's milk ingestion in infants. In fact, "functional" is used if the pathophysiologic mechanism causing the symptom cannot be explained. Since the long term outcome of "allergy" differs substantially from "functional symptom", allergy should not be used inappropriate. CONCLUSION: "Food related symptom" should be used in each patient in which the pathophysiologic mechanism is not clear. Intolerance means a carbohydrate malabsorption that causes symptoms. Allergy should be used when the immune system is involved.

Effects of synbiotic on anthropometry, lipid profile and oxidative stress in obese children.

Recent studies have suggested some beneficial effects of probiotics and/or prebiotics on obesity in adults; such experience is limited in children and adolescents. This study was an open-label, randomised, controlled study including children with primary obesity. The first group was treated with a standard method with a reduced calorie intake and increased physical activity. The second group received add-on daily synbiotic supplementation during one month. The aim of this study was to evaluate potential effects of a synbiotic on anthropometric measurements, lipid profile and oxidative stress parameters. One month of supplementation of the synbiotic resulted in a significant reduction of weight (P<0.001) and body mass index (P<0.01). Changes (% reduction comparing to baseline) in anthropometric measurements, were significantly higher in the children receiving the additional synbiotic supplement (P<0.05). The percentage of children with weight loss was higher in the synbiotic group, but not statistically significant (71.4 vs 64.2%, P>0.05). At the 30(th) day of synbiotic intervention, serum total cholesterol, low density lipoprotein cholesterol and total oxidative stress levels significantly declined (P<0.05). Changes in serum lipid levels were significantly higher in the synbiotic group (P<0.05). Changes in serum total oxidative stress levels before and after the intervention period, were significant in synbiotic group (P<0.01). In our study, changes in weight, body mass index, and triceps skinfold thickness were higher in the group receiving the one month synbiotic supplement thin in the standard method group. The supplement tested also had a beneficial effect on lipid profile and total oxidative stress. To the best of our knowledge, this is the first study showing the effects of synbiotics on oxidative stress in obese patients with an additional effect on weight loss regarding to previous studies.

Saccharomyces boulardii CNCM I-745 reduces the duration of diarrhoea, length of emergency care and hospital stay in children with acute diarrhoea.

Evidence from the literature has shown that Saccharomyces boulardii provides a clinically significant benefit in the treatment of acute infectious diarrhoea in children. In this multicentre, randomised, prospective, controlled, single blind clinical trial performed in children with acute watery diarrhoea, we aimed to evaluate the impact of S. boulardii CNCM I-745 in hospitalised children, in children requiring emergency care unit (ECU) stay and in outpatient settings. The primary endpoint was the duration of diarrhoea (in hours). Secondary outcome measures were duration of hospitalisation and diarrhoea at the 3(rd) day of intervention. In the whole study group (363 children), the duration of diarrhoea was approximately 24 h shorter in the S. boulardii group (75.4±33.1 vs 99.8±32.5 h, P<0.001). The effect of S. boulardii (diarrhoea-free children) was observed starting at 48 h. After 72 h, only 27.3% of the children receiving probiotic still had watery diarrhoea, in contrast to 48.5% in the control group (P<0.001). The duration of diarrhoea was significantly reduced in the probiotic group in hospital, ECU and outpatient settings (P<0.001, P<0.01 and P<0.001, respectively). The percentage of diarrhoea-free children was significantly larger after 48 and 72 h in all settings. The mean length of hospital stay was shorter with more than 36 h difference in the S. boulardii group (4.60±1.72 vs 6.12±1.71 days, P<0.001). The mean length of ECU stay was shorter with more than 19 h difference in the probiotic group (1.20±0.4 vs 2.0±0.3 days, P<0.001). No adverse effects related to the probiotic were noted. Because treatment can shorten the duration of diarrhoea and reduce the length of ECU and hospital stay, there is likely a social and economic benefit of S. boulardii CNCM I-745 in adjunction to oral rehydration solution in acute infectious gastroenteritis in children.

Algorithms for managing infant constipation, colic, regurgitation and cow's milk allergy in formula-fed infants.

UNLABELLED: Gastrointestinal symptoms, such as constipation, regurgitation and infant colic, occur in about half of infants. These symptoms are often functional, but they may also be caused by cow's milk protein allergy. We developed three algorithms for formula-fed infants, which are consensus rather than evidence-based due to the limited research available in the existing literature. CONCLUSION: We believe that these algorithms will help primary healthcare practitioners to recognise and manage these frequent gastrointestinal manifestations in infants.

Healthy gut microbiota and long term health.

This review summarises how the composition of the gastro-intestinal microbiota depends on pre- and postnatal factors, and birth itself. The impact of method of delivery, feeding during infancy and medications, such as antibiotics and anti-acid medication, on the composition of the gastro-intestinal microbiota has clearly been shown. However, the duration of the impact of these factors is not well established. The gastro-intestinal microbiome composition is associated with many auto-immune mediated diseases. Although causality has not been obviously demonstrated, there is a strong tendency in this direction. Nevertheless, results of the manipulation of the gastro-intestinal microbiome composition in these conditions are often disappointing. A better understanding on factors determining the longterm composition of the gastro-intestinal microbiome and its health consequences are a priority research topic. A better understanding of the association between the microbiome and the immune system may have a tremendous impact on general health.

Updated algorithms for managing frequent gastro-intestinal symptoms in infants.

Regurgitation, constipation, excessive crying/fussiness, infantile colic and gassiness are frequent GI manifestations in young infants and result in numerous visits to paediatricians and in many cases in unnecessary change of formulas. The aim of this study was to offer paediatricians consensus based and simple algorithms for the management of the most frequent GI symptoms in infants. Paediatric gastroenterologists processed practical algorithms to assist general practitioners and general paediatricians. Four such practice recommendations were developed, based on the in 2013 published algorithms after an updated literature review. These algorithms cannot be considered as an 'evidence based guideline'. To date, these algorithms are the result of a consensus based on the available literature and the algorithms published in 2013.