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Background No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. Methods We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. Results Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P

Gastro-oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA-associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA-associated GORD and medical and dietary management. The task force (TF) on non-IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web-based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA-associated GORD.

Allergic diseases in children are increasing. Although maternal diet quality in pregnancy may be protective, it is unclear which measure of maternal diet best predicts offspring diseases.To examine the associations between multiple diet measures and allergy outcomes, and to compare the diagnostic accuracy of the measures for the prediction of allergy outcomes.Maternal diet during pregnancy was measured using a validated instrument, and scored using 5 measures: the maternal diet index (MDI), Healthy Eating Index, total diet diversity, healthy diet diversity, and unhealthy diet diversity. Unadjusted and adjusted logistic regression models assessed associations between maternal diet measures and offspring allergy outcomes up to age 4 years. The diagnostic accuracy of the diet measures was compared.There were significant associations between MDI (odds ratio [OR], 0.78; 95% CI, 0.70-0.87), Healthy Eating Index (OR, 0.98; 95% CI, 0.97-0.99), and healthy diet diversity scores (OR, 0.91; 95% CI, 0.85-0.98) during pregnancy and the primary combined outcome "any allergy excluding wheeze" in children up to age 4 years. Neither maternal total diet diversity (OR, 0.99; 95% CI, 0.95-1.03) nor unhealthy diet diversity scores (OR, 1.05; 95% CI, 0.98-1.13) were associated with the "any allergy excluding wheeze" outcome. For all outcomes studied, except for food allergy, there was a significant difference in the diagnostic accuracy between the 5 measures of maternal diet. The area under the curve for MDI was highest for every disease outcome, although not always significantly higher.Better quality and higher diversity of a woman's diet during pregnancy, measured in various ways, is associated with offspring allergy outcomes, with healthy foods associated with decreased risk, and unhealthy foods associated with a higher risk. The MDI, which appropriately weighted both healthy and unhealthy foods, best predicted childhood allergic disease.

The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) is a commonly used patient-reported outcome measure in food allergy (FA) research. It was developed before FA treatment clinical trials were commonplace and is used as a secondary outcome measure in pivotal FA treatment trials. We examined the psychometric properties of the FAQLQ-PF and its relevance to children with peanut allergy engaged in an epicutaneous immunotherapy (EPIT) clinical trial.Analysis was performed on 26 universally answered items of the FAQLQ-PF, from assessments undertaken during the phase 3 PEPITES study (baseline, Month 12), which examined the safety and efficacy of EPIT for children with peanut allergy aged 4-11 years. Item response theory (IRT) was used to assess psychometric parameters of the FAQLQ-PF (i.e., discrimination, difficulty, and information). Confirmatory factor analysis was also employed; reliability was assessed using McDonald's omega (ω) and Cronbach's alpha (α).A total of 23 of 26 items presented very high discrimination levels (1.7), and all 26 fell within the recommended difficulty threshold (between -1.5 and 1.5). The items contributed a reasonable information level for their respective factors/subdomains. The measure also presented a marginally acceptable model fit for the 3-factor structure (e.g., comparative fit index = 0.88, Tucker-Lewis index = 0.87) and good reliability levels across time points (ω and α 0.90).Herein, we present a novel reanalysis of the FAQLQ-PF items using IRT. The longitudinal performance of individual items and subscales was corroborated, and items with the highest discrimination were identified, showing that the tool is suitable for longitudinal measurements in FA treatment trials.

BackgroundFilaggrin (FLG) loss-of-function mutations in children and maternal diet in pregnancy have been implicated in child allergy outcomes. This paper studies the questions: “do FLG mutations modify the effect of maternal diet on the odds of development of allergic diseases?” and “which factor leads to the highest rate of diagnosis allergic diseases over time, maternal diet, or FLG mutations?”.MethodsExact logistic regressions studied effect modification. Cox proportional hazard models compared the rate of allergic disease development in three groups (N = 624): (1) children with FLG mutation, (2) children without FLG mutation whose mothers did not eat an allergy preventive diet, and (3) children without FLG mutation whose mothers ate an allergy preventive diet. Maternal diet was classified using a validated index.ResultsCox models showed the development of atopic dermatitis, asthma, and wheeze was significantly higher for children in group 1 versus 3 (HR = 2.40 [1.32, 4.37], HR = 2.29 [1.05, 4.97], and HR 2.10 [1.004, 4.38], respectively), but not significantly higher for children in group 1 versus 2 (HR = 1.30 [0.74, 2.29], HR = 1.27 [0.61, 2.63], and HR = 1.29 [0.65, 2.58], respectively). Development of allergic rhinitis was significantly higher for group 1 versus 2 and 3 (1 vs. 2: HR = 2.29 [1.10, 4.76]; 1 vs. 3: HR = 3.21 [1.46, 7.08]). There was no significant effect modification for any outcome.ConclusionChildren with FLG mutation had similar risk of atopic dermatitis, asthma, and wheeze as children without an FLG mutation whose mothers did not eat an allergy preventive diet during pregnancy. Child FLG mutation did not modify the effect of maternal diet. The results suggest that maternal diet in pregnancy, a modifiable risk factor, could be a target for preventive interventions.

Recent guideline recommendations have shifted from recommending prolonged avoidance of allergenic foods in the first 3 years of life to a primary prevention approach involving the deliberate early introduction to infants at risk of developing food allergy. Despite this, some infants, especially those with severe eczema who are at highest risk for developing peanut allergy, fail to receive the preventative benefits of early peanut introduction due to hesitancy and other factors. Difficulty adhering to regular ingestion after introduction further reduces the effectiveness of primary prevention. As emerging real-world evidence has demonstrated that performing peanut oral immunotherapy (OIT) among infants is effective and safe, peanut OIT could be a treatment option for infants with peanut allergy. This review discusses the benefits, risks, and barriers to offering peanut OIT to infants who fail primary prevention strategies. We propose the novel concept that infants with peanut allergy be offered peanut OIT as soon as possible after failed peanut introduction through a shared decision-making process with the family, where there is a preference for active management rather than avoidance.

The increase in food allergies worldwide has led to mounting concern among healthcare providers, families, schools, and the food industry. Of particular interest is the growing prevalence of peanut allergy. The Learning Early About Peanut Allergy (LEAP) study confirms that the early introduction of peanut significantly decreases the risk of developing peanut allergy among high-risk children. However, a number of issues, such as a unified definition of high risk and whether or not to screen patients before peanut introduction, remain. This article will review the LEAP findings and the new peanut allergy prevention guidelines, and then briefly discuss recommendations on the introduction of other allergenic foods based on results from other food allergy prevention randomised controlled trials.

Presently, hydrolyzed formulas (HF) are used primarily in infants that cannot be exclusively breastfed, those with cow's milk allergy and for primary prevention of allergic disease, but HFs are increasingly being used worldwide, begging the question if they may be recommended as the optimal choice for all standard-risk, full-term, non-exclusively breastfed infants. Data regarding the nutritional adequacy of modern-day HFs are scarce and lack long-term data suggesting that growth in infants fed HF versus an intact protein formula (IPF) is different. While human breast milk is the optimal source of nutrition for multiple reasons, a 2006 systematic review determined there were no comparable long-term studies regarding prolonged use of HFs versus breastfeeding. Meta-analyses of formula consumption and risk of atopic dermatitis (AD) have found that infants fed partially HF compared to IPF had a lower risk of AD, but there are significant limitations to these studies, making conclusions about the general use of HFs problematic. Costs should be considered in decision-making regarding the choice of the formula, but global comparison of this is difficult given large cost differences in different countries. Despite the issues raised here, the desire to provide concrete recommendations of widespread HF use needs to be balanced carefully in order not to overstate claims of benefit. Long-term studies are needed to investigate the feasibility of HF as a routine feeding option for healthy, standard-risk infants. Because of the paucity of data, routine use of HF as an equivalent option to breastfeeding or IPF cannot be supported at present based on available scientific evidence.

The purpose of this brief communication is to highlight emerging evidence regarding potential benefits of supporting early rather than delayed peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma, and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma, and Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.

Food allergies continue to increase in prevalence. Standard care is a strict elimination diet, but life-threatening reactions still occur. Allergen immunotherapy has the most potential in treating food allergy. Subcutaneous immunotherapy has not been adopted into food allergy therapy. Oral immunotherapy has a high rate of adverse reactions. Sublingual immunotherapy (SLIT) uses the tolerogenic environment of the oral mucosa and epicutaneous immunotherapy (EPIT) uses the immune cells of the epidermis to transport antigens to afferent lymph nodes to activate immune responses. SLIT and EPIT can successfully desensitize patients. More research is needed to define optimal doses and administration protocols.

There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes.Children aged 3 to 15 months were enrolled in an observational study with either (1) a convincing history of egg allergy, milk allergy, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis (AD) and a positive SPT response to milk or egg. Children enrolled with a clinical history of milk allergy were followed longitudinally, and resolution was established by means of successful ingestion.The cohort consists of 293 children, of whom 244 were given a diagnosis of milk allergy at baseline. Milk allergy has resolved in 154 (52.6%) subjects at a median age of 63 months and a median age at last follow-up of 66 months. Baseline characteristics that were most predictive of resolution included milk-specific IgE level, milk SPT wheal size, and AD severity (all P .001). Baseline milk-specific IgG4 level and milk IgE/IgG4 ratio were not predictive of resolution and neither was expression of cytokine-inducible SH2-containing protein, forkhead box protein 3, GATA3, IL-10, IL-4, IFN-γ, or T-bet by using real-time PCR in CD25-selected, casein-stimulated mononuclear cells. A calculator to estimate resolution probabilities using baseline milk IgE level, SPT response, and AD severity was devised for use in the clinical setting.In this cohort of infants with milk allergy, approximately one half had resolved over 66 months of follow-up. Baseline milk-specific IgE level, SPT wheal size, and AD severity were all important predictors of the likelihood of resolution.