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Pregnant and lactating women are continuously and ubiquitously exposed to numerous environmental pollutants from various sources including air, food, water, and occupational and household environments. The available evidence shows that pollutants are present in human milk and one of the emerging questions is what happens when the nursing infant is involuntarily exposed to contaminants through breastfeeding.The available literature does not currently provide a conclusive evidence of any consistent or clinically relevant health consequences in infants exposed to environment chemicals through breast milk. The available data strongly suggest that the benefits of breastfeeding outweigh the potential harmful effects of pollutants contained in human milk. The committee of nutrition of the French Pediatric Society strongly supports breastfeeding but also calls for public health actions to reduce the overall contamination level in the environment, to continue promoting breastfeeding, and to support research in this area.

International audience

It is well-established that food proteins, such as egg, soya, cow's milk and wheat, are detectable in breastmilk for many hours or days after ingestion. Exposure to these proteins is important to the process of developing tolerance but can also sometimes elicit IgE-mediated and non-IgE-mediated allergic symptoms in breastfed infants. Non-IgE-mediated allergy, outside of food protein-induced allergic proctocolitis and eosinophilic oesophagitis, is not well understood, leading to variations in the diagnosis and management thereof. A primary objective of the European Academy for Allergy and Clinical Immunology is to support breastfeeding in all infants, including those with food allergies. A Task Force was established, to explore the clinical spectrum of non-IgE-mediated allergies, and part of its objectives was to establish diagnosis and management of non-IgE-mediated allergies in breastfed infants. Eight questions were formulated using the Patient, Intervention, Comparison, Outcome (PICO) system and Scottish Intercollegiate Guideline Network (SIGN) criteria for data inclusion, and consensus was achieved on practice points through the Delphi method. This publication aims to provide a comprehensive overview on this topic with practice points for healthcare professionals.

This French multicenter, cross-sectional, observational study aimed to describe the family history of atopy in infants with cow's milk protein allergy (CMPA), and the related diagnostic approaches used by specialists in a real-life ambulatory setting.In total, 1674 infants with suspected CMPA [median age 4.5 months (range: 0.1-18.0), males 54%] were enrolled in the study by 466 private physicians (pediatricians: 97%). Family history of atopy was defined as a known history of atopy in at least one first- (father, mother, and/or sibling) and/or second-degree relative (grandparents, uncles, and aunts), as reported by parents to physicians.Atopy in a first-degree relative was more common among infants with documented or high probability of CMPA (in 84% and 80% of cases, respectively, vs. the other subgroups, P=0.005). Most infants experienced digestive (92%) and skin (61%) symptoms suggestive of CMPA. Delayed reactions were reported in 64% of infants. According to a post-classification based on the results of previous diagnostic tests and procedures, 1133 infants (68%) had highly probable (52%) or documented CMPA (16%). In these infants, a history of atopy was reported in first- and/or second-degree relative(s) in 86% of cases (81% in first-degree relatives). Whatever the family history of atopy, the characteristics of the infants were similar, except for fewer pets in the case of negative family atopy (14% vs. 25%, P0.001). Atopy in a parent was more frequent in infants who presented with the first signs suggestive of CMPA within the first 6 months of life vs. those with later first symptoms (75% vs. 65%, P=0.063).This French study confirms the high rate of family history of atopy in first-degree relatives of infants with probable or documented CMPA.

Purpose: The present study assessed the role of an amino acid-based formula (AAF) in the growth of infants with cow's milk protein allergy (CMPA). Methods: Non-breastfed, term infants aged 0-6 months with symptoms suggestive of CMPA were recruited from 10 pediatric centers in China. After enrollment, infants were started on AAF for two weeks, followed by an open food challenge (OFC) with cow's milk-based formula (CMF). Infants with confirmed CMPA remained on AAF until 9 months of age, in conjunction with a cow's milk protein-free complementary diet. Body weight, length, and head circumference were measured at enrollment and 9 months of age. Measurements were converted to weight-for-age, length-for-age, and head circumference-for-age Z scores (WAZ, LAZ, HCAZ), based on the World Health Organization growth reference. Results: Of 254 infants (median age 16.1 weeks, 50.9% male), 218 (85.8%) were diagnosed with non-IgE-mediated CMPA, 33 (13.0%) tolerated CMF, and 3 (1.2%) did not complete the OFC. The mean WAZ decreased from 0.119 to -0.029 between birth and enrollment (p=0.067), with significant catch-up growth to 0.178 at 9 months of age (p=0.012) while being fed the AAF. There were no significant changes in LAZ (0.400 vs. 0.552; p=0.214) or HCAZ (-0.356 vs. -0.284; p=0.705) from the time of enrollment to age 9 months, suggesting normal linear and head growth velocity. Conclusion: The amino acid-based study formula, in conjunction with a cow's milk protein-free complementary diet, supported normal growth till 9 months of age in a cohort of Chinese infants with challenge-confirmed non-IgE-mediated CMPA.

Exclusive breastfeeding ideally up to 6 months of life is the feed of choice for infants and should be promoted by healthcare professionals. However, when human milk is not sufficient or not available, infant formula, generally cow's milk-based, meeting strictly regulated nutritional and safety requirements, are recommended. Human breastmilk feeding has a positive health impact for both mother and child, but there is limited evidence that it has a long-term protective effect on the development of allergic disease. Some studies have found an association of an increased risk to develop cow's milk allergy with early exposure to cow's milk protein in formula milk. As a result, over the last 30 years, partially hydrolyzed formulas (pHF) have gained popularity and, more recently, become embroiled in a debate about their role in the primary prevention of allergic outcomes. Similar debates exist in regards to the potential preventative effects of pre-, pro- and synbiotics as well as nutritional factors, notably vitamin D and omega-3 fatty acids. This paper aims to critically address these aspects, drawing information from published data interpreted by an international expert group in paediatrics, allergy, gastro-intestinal diseases and nutrition. This group of experts emphasize that human milk is the optimal source of infant nutrition. With regards to pHFs, whilst no harm has been shown with their use and some studies have suggested potential benefit preventing atopic dermatitis in at risk infants, there is insufficient evidence for or against their routine recommendation for primary allergy prevention. The method of hydrolysation differs for every formula. There is insufficient evidence to recommend supplementation with vitamin D, omega-3 LCPUFA, specific prebiotic oligosaccharides or specific probiotic strains during pregnancy, lactation and early life to prevent the development of allergic disease in children. There remains a need for well-designed trials with the currently commercialised pHFs and supplements to allow for better clarity and evidence-based recommendations.

Functional constipation (FC) is a chronic constipation for which no physiological, anatomical or iatrogenic origin can be evidenced. This condition has a high impact on a patient’s quality of life and healthcare costs. Since FC is frequently associated with low physical activity and a diet low in fiber and/or water, first-line recommendations focus on sufficient activity, and sufficient fiber and water intake. In case of inefficacy of these measures, numerous drug treatments are available, either over the counter or on prescription. Magnesium sulfate has a long history in the treatment of FC, and magnesium sulfate-rich mineral waters have been used for centuries for their laxative properties. The laxative effect of magnesium and sulfate has since been widely demonstrated. Nevertheless, it appears that no clinical studies aiming at demonstrating their efficacy in FC had been conducted before the 21st century. In this paper, we reviewed the clinical data reporting the efficacy of magnesium sulfate-rich natural mineral waters. In view of their reported efficacy and safety, magnesium sulfate-rich natural mineral waters may represent a natural treatment for FC.

International audience; Due to transient gut immaturity, most very preterm infants receive parenteral nutrition (PN) in the first few weeks of life. Yet providing enough protein and energy to sustain optimal growth in such infants remains a challenge. Extrauterine growth restriction is frequently observed in very preterm infants at the time of discharge from hospital, and has been found to be associated with later impaired neurodevelopment. A few recent randomized trials suggest that intensified PN can improve early growth; whether or not such early PN improves long-term neurological outcome is still unclear. Several other questions regarding what is optimal PN for very preterm infants remain unanswered. Amino acid mixtures designed for infants contain large amounts of branched-chain amino acids and taurine, but there is no consensus on the need for some nonessential amino acids such as glutamine, arginine, and cysteine. Whether excess growth in the first few weeks of life, at a time when very preterm infants receive PN, has an imprinting effect, increasing the risk of metabolic or vascular disease at adulthood continues to be debated. Even though uncertainty remains regarding the long-term effect of early PN, it appears reasonable to propose intensified initial PN. The aim of the current position paper is to review the evidence supporting such a strategy with regards to the early phase of nutrition, which is mainly covered by parenteral nutrition. More randomized trials are, however, needed to further support this type of approach and to demonstrate that this strategy improves short- and long-term outcome.

Cow's milk is one of the most common foods responsible for allergic reactions in children. Cow's milk allergy (CMA) involves immunoglobulin E (IgE)- and non-IgE-mediated reactions, the latter being both variable and nonspecific. Guidelines thus emphasize the need for physicians to recognize the specific syndromes of CMA and to respect strict diagnostic modalities. Whatever the clinical pattern of CMA, the mainstay of treatment is the elimination from the diet of cow's milk proteins. The challenge is that both the disease and the elimination diet may result in insufficient height and weight gain and bone mineralization. If, during CMA, the mother is not able or willing to breastfeed, the child must be fed a formula adapted to CMA dietary management, during infancy and later, if the disease persists. This type of formula must be adequate in terms of allergic efficacy and nutritional safety. In older children, when CMA persists, the use of cow's milk baked or heated at a sufficient temperature, frequently tolerated by children with CMA, may help alleviate the stringency of the elimination diet. Guidance on the implementation of the elimination diet by qualified healthcare professionals is always necessary. This guidance should also include advice to ensure adequate bone growth, especially relating to calcium intake. Specific attention should be given to children presenting with several risk factors for weak bone mineral density, i.e., multiple food allergies, vitamin D deficiency, poor sun exposure, steroid use, or severe eczema. When CMA is outgrown, a prolonged elimination diet may negatively impact the quality of the diet over the long term.

Non-IgE-mediated, also labeled cell-mediated, allergic reactions to foods are more common than usually thought and probably account for approximately more than 40% of cases of cow’s milk allergy during infancy and young childhood. Food allergy is now described in the form of syndromes, among which food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP) are gaining increased recognition. FPIES occurs in infancy but may also occur in older children and in adults. The dominant symptom is emesis, repetitive in the chronic FPIES form and explosive in the acute form. Acute FPIES begins 1– 4 h following ingestion of the offending food. Diarrhea is frequent, between 5 and 10 h later, and may be accompanied by lethargy and dehydration, which both characterize severity. Cow’s milk is the most frequent food trigger, followed by soy. FPIES may develop up to 1 year of age, but may also occur in the newborn, and is possible in exclusively breastfed infants, in relation with the mother’s consumption of offending foods. FPIES may occur to solid foods (grains like rice or oat, meats, fish, egg, and vegetables). When starting during infancy, FPIES has a good prognosis and disappears grossly at 2 years of age. FPIES to fish or shellfish is more frequent in older children and adults and is long lasting. International consensus guidelines for the diagnosis and management of FPIES have been published recently. FPIAP starts in the first few months of life and is typically manifested with rectal bleeding in well-appearing breastfed infants during the first months of life in reaction to cow’s milk consumed by the mother. The condition is transient but represents one of the major causes of colitis during infancy.

Aim This French study assessed a quick, non-invasive, immuno-chromatographic, Helicobacter pylori (H. pylori) stool antigen test for detecting infections in children. Methods We enrolled 158 children, with a median age of 8.5 years (range eight months to 17 years), with digestive symptoms suggesting upper gastrointestinal tract disease. Upper digestive endoscopy was performed with gastric biopsy-specimens for histology, a rapid urease test, culture test and quantitative real-time polymerase chain reaction. The H. pylori stool antigen test was performed twice for each child and the results were compared to the reference method. Results The reference methods showed that 23 (14.6%) of the 158 children tested were H. pylori positive. The H. pylori stool antigen test showed 91.3% sensitivity, with a 95% confidence interval (95% CI) of 86.9-95.6 and 97% specificity (95% CI 94.3-99.6), 30.84 positive likelihood ratio and 0.09 negative likelihood ratio. The test accuracy was 96.2% (95% CI 93.2-99.1). The two blinded independent observers produced identical H. pylori stool antigen test results and the Kappa coefficient for the H. pylori stool antigen test was one. Conclusion The H. pylori stool antigen test was found to be a consistent, reliable, quick, and specific test for detecting the H. pylori infection in children. This article is protected by copyright. All rights reserved.

Background: Epicutaneous immunotherapy (EPIT®), currently investigated in the treatment of food allergy, needs the integrity of the skin to warrant safety and efficacy. Mutations in the gene encoding the key epidermal protein filaggrin (FLG) are risk factors for peanut allergy and disrupt the skin intergrity. We investigated the association between FLG deficiency and peanut EPIT® efficacy in a murine model. Methods: FLG mutant mice deficient in filaggrin (FLG-/-) or wild-type (WT) mice were sensitized with peanut protein extract (peanut protein) and cholera toxin. Sensitized mice received a patch per week during 8 weeks for EPIT®, using Viaskin®, and were then submitted to sustained peanut oral exposure. We assessed blood humoral and cellular responses and evaluated eosinophil infiltration in the gut mucosa. The different steps of allergen capture and transportation following deposition on the skin was also analyzed in sensitized mice. Results: Sensitization of mice was confirmed by a significant increase of specific Th2 biaised immunological responses. In sensitized mice, EPIT® significantly reduced IgE levels, splenocytes secretion of Th2 cytokines and recruitment of eosinophils in esophagus, compared to sensitized mice without epicutaneous immunotherapy. The allergen applied onto the skin of FLG-/- mice did not undergo passive skin passage or systemic delivery. Instead, the allergen was captured by skin CD205highDCs, which migrated to afferent lymph nodes, as already described in WT mice. Conclusions: EPIT® was efficient and safe in FLG-/- mice, suggesting that in Humans EPIT® keeps efficacy and safety in the presence of loss of function of FLG.

International audience; No abstract available

International audience; Avoidant/restrictive food intake disorder (ARFID) has recently been added to the DSM V (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) as a new class of eating disorders (EDs). ARFID is characterized by a lack of interest in eating or avoiding specific types of foods because of their sensory characteristics. This avoidance results in decreased nutritional intake, eventually causing nutritional deficiencies. In severe cases, ARFID can lead to dependence on oral nutritional supplements, which interferes with psychosocial functioning. The prevalence of ARFID can be as high as 3% in the general population, and it is often associated with gastrointestinal symptoms and mainly appears in children with anxiety disorders. Given the high prevalence of ARFID, a rapid and systematic nutrition survey should be conducted during every pediatric consultation. Its treatment should also be adapted depending on the severity of the nutritional problem and may involve hospitalization with multidisciplinary care (pediatrician, nutritional therapist, dietitian, psychologists, and speech therapists).

Objectives First-line recommendations for the management of functional constipation include nutritional-hygienic measures. We previously showed that a natural mineral water rich in sulphates and magnesium (Hepar) is efficient in the treatment of functional constipation. The aim of this study was to consolidate those first results and determine a precise time to respond to Hepar. Methods This multicenter, randomized, double-blind, controlled study of the effect of Hepar on stool consistency and frequency in functional constipation included 226 outpatients. After washout, patients used 1.5 L of water daily, including 1 L of Hepar or of low-mineral water, during 14 d. In addition to a daily reporting of stool consistency by the patient, an expert investigator blindly analyzed stool consistency (Bristol stool scale) based on photographs taken by the patient. Results The primary endpoint was met. Treatment response was more frequent in the Hepar arm than in the control group at day 14 (50% versus 29%, respectively; P = 0.001). Mean time to treatment response was shorter in the Hepar group (6.4 d) than in the control arm (7.3 d; P = 0.013). Concomitant stool scoring was available for 60% of the patients. Scores given to 79% of the stools were similar between the patient and the expert (differences ≤1). Safety analyses showed excellent results. Conclusion This study confirms the efficacy and safety of Hepar in the treatment of functional constipation and shows that it is associated with a response within 7 d. Hepar could be a safe response to the current absence of first-line medication in the treatment of functional constipation.

Introduction With advances in surgical and neonatal care, survival of patients with esophageal atresia (EA) has improved over time. While a number of conditions associated with EA may have an impact on feeding development (delayed primary anastomosis, anastomotic leaks, recurrent tracheoesophageal fistula, anastomotic stricture, gastroesophageal reflux, esophageal dysmotility, etc.) and although children with EA experience a number of oral aversive events in their first year of life, feeding disorders (FD) are poorly described and frequently unrecognized. The primary aim of this study was to describe FD in children born with EA, with a standardized scale. The secondary aim was to describe conditions associated with FD. Methods FEED-EASY is a multicentric French study. Parents of children born with EA between 2013 and 2016 in one of the 22 participating centers were asked to participate and received the French version of the standardized and reproductive ‘Montreal Children's Hospital Feeding Scale (MCH-FS)’. Results One hundred and forty-five children were included; 61 (42%) had FD according to the MCH-FS. These children were characterized by disinterest in food, oral hypersensitivity, difficulty in touching some textures and food avoidance, with an influence in quality of life. Nineteen (13%) were tube-fed between 1 and 4 years of age. Birth weight and chronic respiratory difficulties were associated with FD in children with EA. Anastomotic stricture (present in 31% of the included children) was not associated with FD. Conclusions FD is frequent and unrecognized in children with EA, and can influence growth and quality of life. MCH-FS allows pediatricians to identify FD in children with EA within a couple of minutes.

AIM: To summarise the results from four clinical trials assessing the efficacy and safety of a thickening complex in the management of regurgitation in infants. METHODS: Infants (n = 392) younger than 5 months presenting with at least five regurgitations per day were recruited in four open-label, interventional, single-group, multi-centric clinical trials sharing an identical design. The efficacy of four different formulae thickened with different thickening complexes of pectin, starch and locust bean gum, was evaluated on regurgitation at days 3, 14 and 90, and stools and growth at days 14 and 90. RESULTS: The daily number of regurgitation episodes was significantly reduced at days 3 and 14 vs baseline in all studies (P < .001), with the largest decrease with the formula having the highest pectin content (study 1; P < .001). In all studies, growth was within normal range. A trend towards stool normalisation for consistency was observed in three studies at day 90 vs baseline and was significant in study 1 (P < .001). Stool frequency was unchanged by the interventions. CONCLUSION: The four tested thickened formulae reduced regurgitation and were proven to be safe. The formula with the largest amount of pectin and lowest starch content showed the best efficacy.

Clinicians with expertise in managing children with gastrointestinal problems and/or atopic diseases attended a workshop in Brussels in September 2014 to review the literature and determine whether a clinical score derived from symptoms associated with the ingestion of cow's milk proteins could help primary healthcare providers. The Cow's Milk-related Symptom Score (CoMiSS), which considers general manifestations, dermatological, gastrointestinal and respiratory symptoms, was developed as an awareness tool for cow's milk-related symptoms. It can also be used to evaluate and quantify the evolution of symptoms during therapeutic interventions, but does not diagnose cow's milk protein allergy and does not replace a food challenge. Its usefulness needs to be evaluated by a prospective randomised study. Conclusion The CoMiSS provides primary healthcare clinicians with a simple, fast and easy-to-use awareness tool for cow's milk-related symptoms.

Background In 2010, the diagnosis and treatment of IgE-mediated CMA were systematized in a GRADE guideline.Objectives & methods After 6 years, the state of the knowledge in diagnosis and treatment of CMA has largely evolved. We summarize here the main advances, and exemplify indicating some specific points: studies aimed at better knowledge of the effects of breastfeeding and the production of new special formulae intended for the treatment of CMA. The literature (PubMed/MEDLINE) was searched using the following algorithms: (1) [milk allergy] AND diagnosis; (2) [milk allergy] AND [formul*] OR [breast*], setting the search engine [6-years] time and [human] limits. The authors drew on their collective clinical experience to restrict retrieved studies to those of relevance to a pediatric allergy practice.Results Several clinical studies did address the possibility to diagnose CMA using new tools in vitro and in vivo, or to diagnose it without any evaluation of sensitization. Some studies also addressed the clinical role of formulae based on milk hydrolysates, soy, or rice hydrolysates in the treatment of CMA. Many studies have elucidated the effects of selective nutrients in breastfed infants on their immunologic and neurologic characteristics.Conclusions Evidence-based diagnostic criteria should be identified for non-IgE-mediated CMA. Debate is ongoing about the best substitute for infants with CMA. In particular, Hydrolyzed Rice Formulae have been widely assessed in the last six years. In the substitute choice, clinicians should be aware of recent studies that can modify the interpretation of the current recommendations. New systematic reviews and metanalyses are needed to confirm or modify the current DRACMA recommendations. Keywords: Cow’s milk allergy, Infants, DRACMA guidelines

Background Epicutaneous immunotherapy (EPIT) is a promising method for treating food allergies. In animal models, EPIT induces sustained unresponsiveness and prevents further sensitization mediated by Tregs. Here, we elucidate the mechanisms underlying the therapeutic effect of EPIT, by characterizing the kinetics of DNA methylation changes in sorted cells from spleen and blood and by evaluating its persistence and bystander effect compared to oral immunotherapy (OIT). Methods BALB/c mice orally sensitized to peanut proteins (PPE) were treated by EPIT using a PPE‐patch or by PPE‐OIT. Another set of peanut‐sensitized mice treated by EPIT or OIT were sacrificed following a protocol of sensitization to OVA. DNA methylation was analyzed during immunotherapy and 8 weeks after the end of treatment in sorted cells from spleen and blood by pyrosequencing. Humoral and cellular responses were measured during and after immunotherapy. Results Analyses showed a significant hypermethylation of the Gata3 promoter detectable only in Th2 cells for EPIT from the 4th week and a significant hypomethylation of the Foxp3 promoter in CD62L+ Tregs, which was sustained only for EPIT. In addition, mice treated with EPIT were protected from subsequent sensitization and maintained the epigenetic signature characteristic for EPIT. Conclusions Our study demonstrates that EPIT leads to a unique and stable epigenetic signature in specific T‐cell compartments with downregulation of Th2 key regulators and upregulation of Treg transcription factors, likely explaining the sustainability of protection and the observed bystander effect.

INTRODUCTION: The symptoms of cow's milk protein allergy (CMPA) in infancy can be non-specific which may delay a correct diagnosis and cause adverse clinical outcomes. The diagnosis of non-IgE-mediated CMPA is particularly complex as it involves a 2 to 4 week elimination diet followed by oral food challenge (OFC). The Cow's Milk-related Symptom Score (CoMiSS) is a clinical resource for primary healthcare providers which aims to increase awareness of CMPA symptoms to facilitate an earlier diagnosis. The aim of the present study is to assess if the CoMiSS can be used as a potential diagnostic tool in infants with suspected CMPA.METHODS AND ANALYSIS: Exclusively formula-fed infants aged 0-6 months presenting with symptoms suggestive of CMPA will be included in this prospective, multicentre trial which will be conducted in 10 centres in China. All infants will commence a 2-week trial of an amino acid-based formula (AAF) while eliminating all cow milk protein from their diets. After the AAF treatment period, infants will undergo an open OFC in hospital with standard cow's milk formula, followed by an open home challenge for another 2 weeks. Clinical symptoms will be documented on standardised symptom scorecards. The CoMiSS will be determined at study entry (CoMiSS 1, before the start of the AAF), after 2 weeks (CoMiSS 2, before the OFC) and after a further period of 2 weeks or when symptoms suggestive of CMPA reappear (CoMiSS 3). Weight and length will be measured at each visit. The difference between CoMiSS 1 and 2 as a predictor of the OFC outcome will also be assessed. The diagnostic accuracy of the baseline CoMiSS will be calculated.ETHICS AND DISSEMINATION: The study was approved by the Hunan Children's Hospital Medical Ethics Committee, Hunan, China. The findings of this trial will be submitted for publication in a peer-reviewed journal in paediatric nutrition or gastroenterology. Abstracts will be submitted to the relevant national and international conferences.TRIAL REGISTRATION NUMBER: NCT03004729; Pre-results.

Epicutaneous immunotherapy is a developing technique, aiming at desensitizing patients with food allergy with less risks that oral ingestion or injection could generate. Several clinical trials have been performed and are currently running, in milk and peanut allergy, assessing the safety of the technique and its efficacy. Preclinical models indicate a major role in the mechanisms of desensitization, for example, Tregs and epigenetic modifications.

Amino acid-based formulas (AAFs) are recommended for children with cow's-milk allergy (CMA) failing to respond to extensively hydrolysed formulas (eHFs). We evaluated the effects of a new thickened AAF (TAAF, Novalac), containing a pectin-based thickener, and a reference AAF (RAAF, Neocate) on allergy symptoms and safety, through blood biochemistry analysis and growth.Infants (ages18 months) with CMA symptoms failing to respond to eHFs were randomised in a double-blind manner to receive TAAF or RAAF for 3 months. All of the infants were then fed TAAF for 3 additional months. Paediatric visits occurred at 1, 3, and 6 months. Blood samples were collected at inclusion and 3 months.Results at 1 month were previously described. The 75 infants with proven CMA and eHF intolerance tolerated their allocated formula. At 3 months, the dominant allergic symptom had disappeared in 76.2% of the infants with TAAF and in 51.5% of the infants with RAAF (P = 0.026). The Scoring Atopic Dermatitis Index significantly improved more with TAAF than with RAAF (-27.3 ± 2.3 vs -20.8 ± 2.2, P = 0.048). Of the infants, 92.9% had normal stools (soft or formed consistency) with TAAF vs 75.8% with RAAF (P = 0.051). More infants in TAAF group had better quality of nighttime sleep (P = 0.036) and low frequency of irritability signs (P 0.001). With both formulas, all of the biochemical parameters were within normal ranges. There were no differences between the 2 groups in any of the anthropometric z scores.The new TAAF was tolerated by all of the infants with CMA and intolerance to eHFs. Anthropometric and clinical data showed that both formulas were safe.

The aim of the study was to assess the usefulness of gastric biopsy-based quantitative real-time polymerase chain reaction (qPCR) for the detection of Helicobacter pylori infection and the identification of clarithromycin-resistant strains in children.A gastric biopsy-based qPCR for the detection of H pylori infection and the identification of clarithromycin-resistant strains in children was evaluated in 62 children with infection and 341 children without infection. H pylori infection was considered by the "reference method" when culture was positive for both histology and rapid urease test (RUT). Results were compared with those obtained using the qPCR.The reference method versus H pylori qPCR positivity showed 95% confidence interval sensitivity 100% versus 100%, specificity 93.2% (86.9-99.4) versus 100%, positive predictive value 59.7% (47.4-71.9) versus 100%, negative predictive value 100% versus 100%, and, finally, test accuracy of 59.6% (47.3-71.8) versus 100%. Sixty-two children were found to be H pylori positive, based on the qPCR results. Among those, 31 children had both positive qPCR and culture with concordant antimicrobial susceptibility testing results, whereas 31 children had negative culture and positive qPCR. The qPCR showed a bacterial load ≥10 copies per milliliter when culture, histology, and RUT were all positive (29/31 children) versus10 copies per milliliter when culture, histology, and RUT were all negative (25/31 children). Grades 2 and 3 histological gastritis were associated with a bacterial load ≥10 copies per milliliter for 28/35 of children versus 27/27 of grade 0 to 110 copies per milliliter.H pylori qPCR positivity is a more precise test than the routine culture, histology, RUT alone and allows detecting low bacterial loads.

Background: The 2010 Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow's milk allergy (CMA). They indicate oral food challenge (OFC) as the reference test for diagnosis, and suggest the choice of specific alternative formula in different clinical conditions. Their recommendations are flexible, both in diagnosis and in treatment. Objectives & methods: Using the Scopus citation records, we evaluated the influence of the DRACMA guidelines on milk allergy literature. We also reviewed their impact on successive food allergy and CMA guidelines at national and international level. We describe some economic consequences of their application. Results: DRACMA are the most cited CMA guidelines, and the second cited guidelines on food allergy. Many subsequent guidelines took stock of DRACMA's metanalyses adapting recommendations to the local context. Some of these chose not to consider OFC as an absolute requirement for the diagnosis of CMA. Studies on their implementation show that in this case, the treatment costs may increase and there is a risk of overdiagnosis. Interestingly, we observed a reduction in the cost of alternative formulas following the publication of the DRACMA guidelines. Conclusions: DRACMA reconciled international differences in the diagnosis and management of CMA. They promoted a cultural debate, improved clinician's knowledge of CMA, improved the quality of diagnosis and care, reduced inappropriate practices, fostered the efficient use of resources, empowered patients, and influenced some public policies. The accruing evidence on diagnosis and treatment of CMA necessitates their update in the near future.

International audience; Mutations in the desmoplakin (DSP) and desmoglein-1 (DSG1) genes have been implicated in patients with the inherited inflammatory skin disease known as severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome (MIM#603165, see Tables E1 and E2 in this article's Online Repository at www.jacionline.org).1, 2 The DSP and DSG1 genes encode desmosome components that are critical for the structure of intercellular junctions and maintenance of epithelial barrier integrity. DSP and DSG1 are also key regulators of signaling pathways involved in differentiation, epidermal homeostasis, and carcinogenesis. DSG1 promotes keratinocyte differentiation by inhibiting epidermal growth factor receptor/extracellular signal-regulated kinase signaling through ERBB2-interacting protein (ERBIN), a scaffolding and signaling protein.3 Through characterization of a new syndrome featuring severe allergic dermatitis and DSG1 deficiency, we highlighted the pivotal role of the functional DSG1/ERBIN interaction as an inhibitor of skin inflammation through the nuclear factor κB (NF-κB) signaling pathway.

CONTEXT: Lactobacillus reuteri DSM17938 has shown promise in managing colic, but conflicting study results have prevented a consensus on whether it is truly effective. OBJECTIVE: Through an individual participant data meta-analysis, we sought to definitively determine if L reuteri DSM17938 effectively reduces crying and/or fussing time in infants with colic and whether effects vary by feeding type. DATA SOURCES: We searched online databases (PubMed, Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, the Database of Abstracts of Reviews of Effects, and Cochrane), e-abstracts, and clinical trial registries. STUDY SELECTION: These were double-blind randomized controlled trials (published by June 2017) of L reuteri DSM17398 versus a placebo, delivered orally to infants with colic, with outcomes of infant crying and/or fussing duration and treatment success at 21 days. DATA EXTRACTION: We collected individual participant raw data from included studies modeled simultaneously in multilevel generalized linear mixed-effects regression models. RESULTS: Four double-blind trials involving 345 infants with colic (174 probiotic and 171 placebo) were included. The probiotic group averaged less crying and/or fussing time than the placebo group at all time points (day 21 adjusted mean difference in change from baseline [minutes] −25.4 [95% confidence interval (CI): −47.3 to −3.5]). The probiotic group was almost twice as likely as the placebo group to experience treatment success at all time points (day 21 adjusted incidence ratio 1.7 [95% CI: 1.4 to 2.2]). Intervention effects were dramatic in breastfed infants (number needed to treat for day 21 success 2.6 [95% CI: 2.0 to 3.6]) but were insignificant in formula-fed infants. LIMITATIONS: There were insufficient data to make conclusions for formula-fed infants with colic. CONCLUSIONS: L reuteri DSM17938 is effective and can be recommended for breastfed infants with colic. Its role in formula-fed infants with colic needs further research.

BACKGROUND AND AIMS: Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE in order to develop updated international consensus criteria for EoE diagnosis. METHODS: A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II. Pediatric and adult physicians and researchers from gastroenterology, allergy, and pathology subspecialties representing 14 countries utilized on-line communications, teleconferences, and a face-to-face meeting to review the literature and clinical experiences. RESULTS: Substantial evidence documented that PPIs reduce esophageal eosinophilia in children, adolescents and adults, with several mechanisms potentially explaining the treatment effect. Based on these findings, an updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement. CONCLUSIONS: EoE should be diagnosed when there are symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (or ~60 eosinophils per mm(2)) on esophageal biopsy, and after a comprehensive assessment of non-EoE disorders that could cause or potentially contribute to esophageal eosinophilia. The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.

Background Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy. However, its pathogenesis remains poorly understood and biomarkers are lacking. We aimed to perform in-depth characterization of humoral and cellular immune responses in children with cow’s milk (CM)-FPIES and investigated whether there is a FPIES metabolomic signature. Methods Children with CM-FPIES and control subjects with an IgE-mediated CM allergy (IgE-CMA), both avoiding CM, were recruited on the day of an oral food challenge. Blood samples were collected before the challenge. Total and specific levels of IgE, IgG1-4, IgA, IgM and IgD to various whey and casein allergens and to their gastroduodenal digestion products were measured in plasma, using plasma from CM-tolerant peanut allergic patients (IgE-PA, not avoiding CM) as additional controls. Cytokine secretion and cellular proliferation were analyzed after stimulation of PBMC with different CM allergens. Metabolomic profiles were obtained for plasma samples using liquid chromatography coupled to high-resolution mass spectrometry. Results Nine children with CM-FPIES and 12 control subjects (6 IgE-CMA and 6 IgE-PA) were included. In children with CM-FPIES, total Ig concentrations were lower than in control subjects, specific Ig against CM components were weak to undetectable, and no specific IgE against CM digestion products were detected. Moreover, in CM-FPIES patients, we did not find any Th cell proliferation or associated cytokine secretion after allergen reactivation, whereas such responses were clearly found in children with IgE-CMA. Plasma metabolic profiles were different between CM allergic patients, with significantly lower concentrations of various fatty acids and higher concentrations of primary metabolites such as amino acids in CM-FPIES compared to IgE-CMA patients. Conclusions In CM-FPIES, both humoral and cellular specific immune responses are weak or absent, and this is not related to CM avoidance. A metabolomic signature was identified in patients with CM-FPIES that may be useful for the diagnosis and management of this disease. Electronic supplementary material The online version of this article (10.1186/s13601-018-0224-9) contains supplementary material, which is available to authorized users.

Children with cows' milk protein allergy (CMPA) are at risk of insufficient length and weight gain, and the nutritional efficacy of hypo-allergenic formulas should be carefully assessed. In 2008, a trial assessed the impact of probiotic supplementation of an extensively hydrolysed casein-based formula (eHCF) on acquisition of tolerance in 119 infants with CMPA. First analysis of the study results showed that the studied formula allowed improvement of food-related symptoms. The scoring of atopic dermatitis (SCORAD) index was assessed at randomisation and after 6 months of feeding. A post hoc analysis was performed using WHO growth software's nutritional survey module (WHO Anthro version 3.2.2). All infants who were fed the study formula tolerated it well. The SCORAD index significantly improved from randomisation to 6 months of feeding with the study formula. Anthropometric data indicated a significant improvement in the weight-for-age, length-for-age and weight-for-length z scores, as well as in the restoration of normal BMI. The probiotic supplementation did not show any impact on these parameters. The present data showed that this eHCF was clinically tolerated and significantly improved the SCORAD index and growth indices.

IMPORTANCE: Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. OBJECTIVE: To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. DESIGN, SETTING, AND PARTICIPANTS: Phase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016). Patients (n = 221) had peanut sensitivity and positive double-blind, placebo-controlled food challenges to an eliciting dose of 300 mg or less of peanut protein. INTERVENTIONS: Randomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 μg (n = 53), 100 μg (n = 56), or 250 μg (n = 56) of peanut protein or a placebo patch (n = 56). Following daily patch application for 12 months, patients underwent a double-blind, placebo-controlled food challenge to establish changes in eliciting dose. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was percentage of treatment responders (eliciting dose: 10-times increase and/or reaching 1000 mg of peanut protein) in each group vs placebo patch after 12 months. Secondary end points included percentage of responders by age strata and treatment-emergent adverse events (TEAEs). RESULTS: Of 221 patients randomized (median age, 11 years [quartile 1, quartile 3: 8, 16]; 37.6% female), 93.7% completed the trial. A significant absolute difference in response rates was observed at month 12 between the 250-μg (n = 28; 50.0%) and placebo (n = 14; 25.0%) patches (difference, 25.0%; 95% CI, 7.7%-42.3%; P = .01). No significant difference was seen between the placebo patch vs the 100-μg patch. Because of statistical testing hierarchical rules, the 50-μg patch was not compared with placebo. Interaction by age group was only significant for the 250-μg patch (P = .04). In the 6- to 11-year stratum, the response rate difference between the 250-μg (n = 15; 53.6%) and placebo (n = 6; 19.4%) patches was 34.2% (95% CI, 11.1%-57.3%; P = .008); adolescents/adults showed no difference between the 250-μg (n = 13; 46.4%) and placebo (n = 8; 32.0%) patches: 14.4% (95% CI, −11.6% to 40.4%; P = .40). No dose-related serious AEs were observed. The percentage of patients with 1 or more TEAEs (largely local skin reactions) was similar across all groups in year 1: 50-μg patch = 100%, 100-μg patch = 98.2%, 250-μg patch = 100%, and placebo patch = 92.9%. The overall median adherence was 97.6% after 1 year; the dropout rate for treatment-related AEs was 0.9%. CONCLUSIONS AND RELEVANCE: In this dose-ranging trial of peanut-allergic patients, the 250-μg peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01675882.

Eosinophilic esophagitis (EoE) is a multifactorial esophageal inflammation, with a genetic predisposition, which combines a deficient esophageal mucosal barrier, an abnormal immune reaction to environmental allergens mediated by Th2 interleukins, immediate esophageal lesions and dysmotility, with secondary remodeling and fibrosis. Symptoms include reflux, abdominal pain, and food impaction, with a variation according to age. Fibroscopy shows major and minor endoscopic and histologic criteria, with a mucosal count≥15 eosinophils/high power field (Eo/hpf). A new entity has been defined, where gastroesophageal reflux disease (GERD) and EoE share responsibility: the PPIs-sensitive form of EoE (PPI-REE). Children with fibroscopy showing≥15 Eo/hpf need a second endoscopy following 8 weeks of PPI treatment. EoE has a strong association with other atopic disorders. Allergy testing (specific IgE blood test and skin prick tests [SPTs]) identifies patients at risk of anaphylaxis (14.8% of cases). The dietary therapy is based on a 4- to 12-week elimination test followed by endoscopy to check the disappearance of eosinophilic infiltration. The "dietary approaches are the amino acid-based formula, the allergy testing-based targeted diet, and the six-food elimination diet (empirical elimination of milk, wheat, soy, eggs, peanut/nuts, and fish/seafood). A recent first-line trial elimination of milk has been suggested, with wheat as a second elimination, if necessary. Dietary therapy allows remission and catch-up growth in 65% of cases. Swallowed topical steroids (budesonide in viscous gel or fluticasone propionate for nebulization) are an alternative, for which efficacy varies according to clinical and/or histological criteria and with relapses occurring at dosage tapering. Their use may be restricted by side effects, such as oral and/or esophageal candidiasis. The impact on long-term bone health and growth is unknown. Maintenance therapy is not standardized and is team-dependent, combining or not elimination diets and long-term steroids. The long-term risk of EoE is esophageal stenosis (25%) and endoscopic dilation may be repeated. Biotherapies have shown isolated histological improvement without significant clinical efficacy.

Treatment of eosinophilic gastritis by epicutaneous immunotherapy (EPIT) in peanut allergic piglets. Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology

Eosinophilic esophagitis (EoE) is a clinicopathologic disease that presents with a massive infiltration of the esophagus by eosinophils triggered by food antigen(s).To determine the impact of dietary therapy on nutritional parameters in patients who present with EoE.A convenience retrospective study analyzed patients with EoE after a 2-month dietary therapy (6-food elimination diet, avoidance of the 6 most common allergenic foods, plus avoidance of those eliciting positive skin testing, plus amino-acid formula as replacement for dairy products). Pre- and postdiet allergic and nutritional status were evaluated.Of 111 eligible patients, 59 patients, with a median age of 77.7 months (range, 9-189 months) were enrolled. Dietary therapy significantly increased the return to normal endoscopic appearance (47.4%, P.0009) and led to complete remission (5 eosinophils/esophageal HPF and disappearance of symptoms) in 59.3%. All symptoms improved, digestive (98.3%), cutaneous (80%), and respiratory (92.8%). The prediet median weight-for-height (WFH) z score was -0.75 (-3.00 to 5.69), and the postdiet WFH did not significantly differ, -0.51 (-3.09 to 5.00). The prediet WFH z score was less than -2 (moderate malnutrition) in 10.1%. Postdiet blood eosinophils counts decreased in absolute numbers and in counts ≥ 500 × 10(6)/L (P.0001). Evaluation after 1 year of progressive reintroduction of eliminated foods was available in 33 children: the median WFH z score did not significantly improve, from -0.89 (range, -3.00 to 0.67) at enrollment to -0.59 (range, -3.66 to 2.24).The nutritional status of children with EoE was mildly affected and not worsened by the 2-month dietary therapy.

IgE-mediated food allergy is a global health problem that affects millions of persons and affects every aspect of life for the patient. Developing effective treatment strategies to augment current practice standards of strict dietary avoidance of antigens and availability of self-injectable epinephrine has been a major focus of research teams, advocacy groups, funding agencies, and patients and their families. Significant progress has been made through the development of allergen-specific immunotherapy encompassing 3 major forms of treatment: oral, sublingual, and epicutaneous immunotherapy. These therapies are in various stages of clinical investigation, with some successes noted in clinical outcomes and modulation of immune mechanisms toward effective therapy. Here we review recent progress and areas of concern for the role of these forms of immunotherapy as an emerging treatment for food allergy.

During the nutritional vulnerable period of 1&ndash, 3 years of age, nutrient intake is often inadequate due to an unbalanced diet. Young child formula (YCF) has been proposed as a means of improving nutrition in this age group. We compared the food consumption and nutrient intake of 241 YCF consumers (YCF-C) to those of 206 non-consumers (YCF-NC), selected from among the children enrolled in the Nutri-B&eacute, b&eacute, survey, an observational cross-sectional survey, conducted from 3 January to 21 April 2013. Food consumption and nutrient intake were analyzed from a three-day dietary record. The YCF-C &lt, 2 years group had a protein (&ndash, 8 g/d, p &lt, 0.0001) and sodium (&ndash, 18%, p = 0.0003) intake that was lower than that of YCF-NC, but still above the respective EFSA (European Food Safety Authority) Average Requirement (AR) or Adequate Intake (AI). At all ages, the YCF-C group had higher intakes of essential fatty acids (p &lt, 0.0001), vitamins C (p &lt, 0.0001), A, D, and E (p &lt, 0.0001), all B vitamins (p &lt, 0.001) except B12, iron (9 vs. 5 mg/d, p &lt, 0.0001), reaching the Dietary Reference Values (DRVs, AR or AI), but similar DHA and ARA intakes. Getting closer to the reference values proposed by EFSA required at least 360 mL/d of YCF. The consumption of YCF may help infants and children at risk of nutrient deficiencies to meet their nutritional requirements. However, protein, sodium, and vitamin A intakes remained above the EFSA DRVs, and DHA, ARA, and vitamin D remained below.

Cow's milk protein allergy (CMPA) affect many organs, from mouth to gut, with, immediate and delayed reactions, including infantile colic, food protein induced enterocolitis syndrome, enteropathy, eosinophilic disorders, among which infantile proctocolitis, and "dysmotility" disturbances, gastro-esophageal reflux and constipation. Diagnosis follows usual steps, careful history taking and medical examination, before starting an elimination diet, for diagnosis and treatment. Beyond, laboratory tests may help, but definitive conclusion will arise from the oral food challenge. The double-blind-placebo-controlled-food challenge, the "gold standard", is needed in clinical research. The food challenge includes the progressive at-home reintroduction of milk, all the more needed since most cases of CMPA in infants are delayed: in clinical practice, diagnosing CMPA is more than saying if the child reacts to cow's milk. One has to define the syndrome the child is suffering from, the risk implied, the best replacement formula. When tolerance develops, a second diagnostic procedure allows seeing if the child has outgrown his disease and, if not, what is the expected outcome and which type of food is best adapted: small amounts of milk, or transformed forms, such as baked milk. Primary care practice is adapted to non-IgE mediated CMPA. When CMPA is part of multiple food allergies or of an eosinophilic disorder, referral centers will perform multiple allergy testing, endoscopic procedures and complex dietary guidance.

The prevalence of breastfeeding in France is one of the lowest in Europe: 65% of infants born in France in 2010 were breastfed when leaving the maternity ward. Exclusive breastfeeding allows normal growth until at least 6 months of age, and can be prolonged until the age of 2 years or more, provided that complementary feeding is started after 6 months. Breast milk contains hormones, growth factors, cytokines, immunocompetent cells, etc., and has many biological properties. The composition of breast milk is influenced by gestational and postnatal age, as well as by the moment of the feed. Breastfeeding is associated with slightly enhanced performance on tests of cognitive development. Exclusive breastfeeding for at least 3 months is associated with a lower incidence and severity of diarrhoea, otitis media and respiratory infection. Exclusive breastfeeding for at least 4 months is associated with a lower incidence of allergic disease (asthma, atopic dermatitis) during the first 2 to 3 years of life in at-risk infants (infants with at least one first-degree relative presenting with allergy). Breastfeeding is also associated with a lower incidence of obesity during childhood and adolescence, as well as with a lower blood pressure and cholesterolemia in adulthood. However, no beneficial effect of breastfeeding on cardiovascular morbidity and mortality has been shown. Maternal infection with hepatitis B and C virus is not a contraindication to breastfeeding, as opposed to HIV infection and galactosemia. A supplementation with vitamin D and K is necessary in the breastfed infant. Very few medications contraindicate breastfeeding. Premature babies can be breastfed and/or receive mother's milk and/or bank milk, provided they receive energy, protein and mineral supplements. Return to prepregnancy weight is earlier in breastfeeding mothers during the 6 months following delivery. Breastfeeding is also associated with a decreased risk of breast and ovarian cancer in the premenopausal period, and of osteoporosis in the postmenopausal period.

Gastroesophageal reflux (GER) is very common among preterm infants, but its real frequency is not well established. GER may be obvious, manifesting with regurgitations or emesis or more difficult to detect when associated with general symptoms such as apnea, bradycardia, pallor, oxygen desaturation, severe malaise, feeding difficulties with weight loss or poor growth (failure to thrive), crying, hematemesis, and melena. The origin probably resides in motor problems in some and in cow’s milk allergy in others. Diagnosis is difficult to make, in the absence of reference values. Impedancemetry coupled to a pH probe is interesting since reflux is frequently nonacid. The treatment should always be conservative and stepwise. None of the drugs used are licensed in this age range and some have severe adverse effect.

International audience; Vitamin A (retinol) fulfills multiple functions in vision, cell growth and differentiation, embryogenesis, the maintenance of epithelial barriers and immunity. A large number of enzymes, binding proteins and receptors facilitate its intestinal absorption, hepatic storage, secretion, and distribution to target cells. In addition to the preformed retinol of animal origin, some fruits and vegetables are rich in carotenoids with provitamin A precursors such as β-carotene: 6 μg of β-carotene corresponds to 1 μg retinol equivalent (RE). Carotenoids never cause hypervitaminosis A. Determination of liver retinol concentration, the most reliable marker of vitamin A status, cannot be used in practice. Despite its lack of sensitivity and specificity, the concentration of retinol in blood is used to assess vitamin A status. A blood vitamin A concentration below 0.70 μmol/L (200 μg/L) indicates insufficient intake. Levels above 1.05 μmol/L (300 μg/L) indicate an adequate vitamin A status. The recommended dietary intake increases from 250 μg RE/day between 7 and 36 months of age to 750 μg RE/day between 15 and 17 years of age, which is usually adequate in industrialized countries. However, intakes often exceed the recommended intake, or even the upper limit (600 μg/day), in some non-breastfed infants. The new European regulation on infant and follow-on formulas (2015) will likely limit this excessive intake. In some developing countries, vitamin A deficiency is one of the main causes of blindness and remains a major public health problem. The impact of vitamin A deficiency on mortality was not confirmed by the most recent studies. Periodic supplementation with high doses of vitamin A is currently questioned and food diversification, fortification or low-dose regular supplementation seem preferable.; La vitamine A (rétinol) a de multiples fonctions dans la vision, la croissance et la différenciation cellulaires, l’embryogenèse, l’entretien des barrières épithéliales, l’immunité, etc. De nombreux enzymes, protéines de liaison et récepteurs facilitent l’absorption digestive, le stockage hépatique, la sécrétion hépatocytaire et la distribution du rétinol aux cellules cibles. Hors le rétinol préformé d’origine animale, certains légumes et fruits sont riches en caroténoïdes à activité provitaminique A, comme le ß-carotène, dont 6 μg correspondent à 1 équivalent rétinol (ER). Les caroténoïdes n’entraînent jamais d’hypervitaminose A. La concentration hépatique, marqueur fiable du statut, étant, en pratique, inaccessible, on a recours, malgré son manque de sensibilité et de spécificité, à la rétinolémie. Une concentration inférieure à 0,7 μmole/L (200 μg/L) est un indicateur d’apports insuffisants. Une rétinolémie supérieure à 1,05 μmole/L (300 μg/L) reflète un statut satisfaisant. Les apports journaliers conseillés en ER vont de 250 μg à 7–36 mois jusqu’à 750 μg à 15–17 ans et sont satisfaits dans les pays industrialisés. Les apports dépassent les apports conseillés, voire les limites de sécurité (600 μg/j) chez certains nourrissons non allaités. La nouvelle réglementation européenne (2015) sur les préparations pour nourrissons et de suite, et la suppression des suppléments en rétinol non justifiés devraient en principe limiter cet excès d’apport. Dans certains pays en développement, la carence vitaminique A, cause majeure de cécité, reste d’actualité. Son impact sur la mortalité préscolaire n’apparaît plus dans des études récentes ; le recours aux charges semestrielles jusque-là recommandées est controversé, au profit d’une meilleure diversification alimentaire, voire d’aliments enrichis ou d’une supplémentation régulière à faible dose.

Protein energy malnutrition (PEM) occurs when energy and protein intake do not meet requirements. It has a functional and structural impact and increases both morbidity and mortality of a given disease. The Nutrition Committee of the French Pediatric Society recommends weighing and measuring any child when hospitalized or seen in consultation. The body mass index (BMI) must be calculated and analyzed according to references any time growth kinetics cannot be analyzed. Any child with a BMI below the third centile or -2 standard deviations for age and sex needs to be examined looking for clinical signs of malnutrition and signs orienting toward an etiology and requires having his BMI and height dynamics plotted on a chart. PEM warrants drawing up a nutritional strategy along with the overall care plan. A target weight needs to be determined as well as the quantitative and qualitative nutritional care including its implementation. This plan must be evaluated afterwards in order to adapt the nutritional therapy.

Background. The aim of this study was to compare the efficacy of epicutaneous immunotherapy (EPIT) to sublingual immunotherapy (SLIT) in a model of mice sensitized to Phleum pratense pollen. Methods. BALB/c mice were sensitized by sub-cutaneous route to pollen protein extract mixed treated for 8 weeks, using sham, EPIT, or SLIT. Measurements involved the serological response and cytokine profile from reactivated splenocytes, plethysmography after aerosol challenge to pollen, cell, and cytokine contents in the bronchoalveolar lavages (BALs). Results. After immunotherapy, sIgE was significantly decreased in the treated groups compared to sham (), whereas sIgG2a increased with EPIT and SLIT ( and versus sham). Reactivated splenocytes secreted higher levels of Th2 cytokines with sham (). Penh values were higher in sham than EPIT and SLIT. Eosinophil recruitment in BAL was significantly reduced only by EPIT (). Conclusion. In this model of mice sensitized to pollen, EPIT was at least as efficient as SLIT.

The aim of the study was to compare 2 different forceps designed to perform biopsies of the rectal mucosa, those of Noblett and Scheye, the latter having a similar design and differing by the disposable cutting system.This historical study compares biopsies obtained with the Noblett forceps in 13 girls and 20 boys (mean ± SD age, 13 ± 30 months) and biopsies obtained with the Scheye forceps in 19 girls and 21 boys (mean ± SD age, 8.5 ± 19 months).The thickness of the material obtained with the Scheye forceps was significantly greater for the specimens obtained with the Scheye forceps (total biopsy: 1.74 ± 0.46 mm vs 0.67 ± 0.2 mm, P.0001; submucosa: 1.12 ± 0.4 mm vs 0.14 ± 0.17 mm, P.001). The Scheye forceps considerably increased the yield of neuronal structures, both for submucosal plexus (P.003) and ganglia (P.0001). No complication occurred in either group.The Scheye disposable rectal biopsy system provides larger mucosal biopsy samples than the Noblett with increased recovery of neuronal structures.

New data on food allergy has recently changed the management of children with cow's milk protein allergy (CMPA). The diagnosis of CMPA first requires the elimination of cow's milk proteins and then an oral provocation test following a standard diagnostic procedure for food allergy, without which the elimination diet is unjustified and sometimes harmful. Once the diagnosis is made, the elimination diet is strict, at least until the age of 9-12 months. If the child is not breastfed or the mother cannot or no longer wishes to breastfeed, the first choice is a formula based on extensive hydrolyzate of cow's milk (eHF), provided that its effectiveness has been demonstrated. When eHF fails, a formula based on amino acids is warranted. eHF based on rice protein hydrolysates is an alternative to cow's milk eHF. Infant formulas based on soy protein can be used after the age of 6 months, after verification of good clinical tolerance to soy. Most commonly, CMPA disappears within 2 or 3 years of life. However, the age of recovery varies depending on the child and the type of CMPA, and whether or not it is IgE-mediated, the first being more sustainable. When the child grows, a hospital oral provocation test evaluates the development of tolerance and, if possible, authorizes continuing the reintroduction of milk proteins at home. Some children with CMPA will tolerate only a limited daily amount of cow's milk proteins. The current therapeutic options are designed to accelerate the acquisition of tolerance, which seems facilitated by regular exposure to cow's milk proteins.

Approximately 5% of young children and 3–4% of adults exhibit adverse immune responses to foods in westernized countries, with a tendency to increase. The pathophysiology of food allergy (FA) relies on immune reactions triggered by epitopes, i.e. small amino-acid sequences able to bind to antibodies or cells. Some food allergens share specific physicochemical characteristics that allow them to resist digestion, thus enhancing allergenicity. These allergens encounter specialized dendritic cell populations in the gut, which leads to T-cell priming. In case of IgE-mediated allergy, this process triggers the production of allergen-specific IgE by B cells. Tissue-resident reactive cells, including mast cells, then bind IgE, and allergic reactions are elicited when these cells, with adjacent IgE molecules bound to their surface, are re-exposed to allergen. Allergic reactions occurring in the absence of detectable IgE are labeled non-IgE mediated. The abrogation of oral tolerance which leads to FA is likely favored by genetic disposition and environmental factors (e.g. increased hygiene or enhanced allergenicity of some foods). For an accurate diagnosis, complete medical history, laboratory tests and, in most cases, an oral food challenge are needed. Noticeably, the detection of food-specific IgE (sensitization) does not necessarily indicate clinical allergy. Novel diagnostic methods currently under study focus on the immune responses to specific food proteins or epitopes of specific proteins. Food-induced allergic reactions represent a large array of symptoms involving the skin and gastrointestinal and respiratory systems. They can be attributed to IgE-mediated and non-IgE-mediated (cellular) mechanisms and thus differ in their nature, severity and outcome. Outcome also differs according to allergens.