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BACKGROUND: Peanut allergy affects 1% to 2% of European children. Early introduction of peanut into the diet reduces allergy in high-risk infants.OBJECTIVE: We aimed to determine the optimal target populations and timing of introduction of peanut products to prevent peanut allergy in the general population.METHODS: Data from the Enquiring About Tolerance (EAT; n = 1303; normal risk; 3-year follow-up; ISRCTN14254740) and Learning Early About Peanut Allergy study (LEAP; n = 640; high risk; 5-year follow-up; NCT00329784) randomized controlled trials plus the Peanut Allergy Sensitization (PAS; n = 194; low and very high risk; 5-year follow-up) observational study were used to model the intervention in a general population. Peanut allergy was defined by blinded peanut challenge or diagnostic skin prick test result.RESULTS: Targeting only the highest-risk infants with severe eczema reduced the population disease burden by only 4.6%. Greatest reductions in peanut allergy were seen when the intervention was targeted only to the larger but lower-risk groups. A 77% reduction in peanut allergy was estimated when peanut was introduced to the diet of all infants, at 4 months with eczema, and at 6 months without eczema. The estimated reduction in peanut allergy diminished with every month of delayed introduction. If introduction was delayed to 12 months, peanut allergy was only reduced by 33%.CONCLUSIONS: The preventive benefit of early introduction of peanut products into the diet decreases as age at introduction increases. In countries where peanut allergy is a public health concern, health care professionals should help parents introduce peanut products into their infants' diet at 4 to 6 months of life.

Background: The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH)-formerly AR101-has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy-related quality of life.Methods: We present a subset analysis of PALISADE-ARC004 participants (aged 4-17 years) who received 300 mg PTAH daily for a total of similar to 1.5 (Group A, n = 110) or similar to 2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double-blind, placebo-controlled food challenge (DBPCFC); skin prick testing; peanut-specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores.Results: Continued maintenance with PTAH increased participants' ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose-limiting symptoms. Immune biomarkers showed a pattern consistent with treatment-induced desensitization. Among PTAH-continuing participants, the overall and treatment-related exposure-adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life.Conclusions: These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response.

Background: The Learning Early About Peanut allergy (LEAP) study has shown the effectiveness of early peanut introduction in prevention of peanut allergy (PA). In the Enquiring About Tolerance (EAT) study, a statistically significant reduction in PA was present only in per-protocol (PP) analyses, which can be subject to bias. Objective: The aim of this study was to combine individual-level data from the LEAP and EAT trials and provide robust evidence on the bias-corrected, causal effect of early peanut introduction. Method: As part of the European Union-funded iFAAM project, this pooled analysis of individual pediatric patient data combines and compares effectiveness and efficacy estimates of oral tolerance induction among different risk strata and analysis methods. Results: An intention-to-treat (ITT) analysis of pooled data showed a 75% reduction in PA (p

Background Accurate diagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood test using the peanut bead-based epitope assay ("peanut BBEA") was developed utilizing the LEAP cohort and then validated using two independent cohorts. Methods The development of the peanut BBEA diagnostic test followed the National Academy of Medicine's established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 82 subjects from the CoFAR2 and 84 subjects from the POISED study. All samples were analyzed using the peanut BBEA methodology, which measures levels of IgE to two Ara h 2 sequential (linear) epitopes and compares their combination to a threshold pre-specified in the model development phase. When a patient has an inconclusive outcome by skin prick testing (or sIgE), IgE antibody levels to this combination of two epitopes can distinguish whether the patient is "Allergic" or "Not Allergic." Diagnoses of peanut allergy in all subjects were confirmed by double-blind placebo-controlled food challenge and subjects' ages were 7-55 years. Results In the validation using CoFAR2 and POISED cohorts, the peanut BBEA diagnostic test correctly diagnosed 93% of the subjects, with a sensitivity of 92%, specificity of 94%, a positive predictive value of 91%, and negative predictive value of 95%. Conclusions In validation of the peanut BBEA diagnostic test, the overall accuracy was found to be superior to existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE, and peanut component sIgE testing.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scare and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, pre-conception counseling, and health care provider education is crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.

Katy Gallop,1 Sarah Acaster,1 Jane de Vries,2 Richard Browne,2 Robert Ryan,2 Sarah Baker,3 George Du Toit4 1Acaster Lloyd Consulting Ltd, London, UK; 2Aimmune Therapeutics, London, UK; 3Anaphylaxis Campaign, Farnborough, UK; 4Department of Paediatric Allergy, Division of Asthma, Allergy and Lung Biology, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, Evelina London Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UKCorrespondence: Katy Gallop, Acaster Lloyd Consulting, 84 Theobalds Road, London, WC1X 8NL, UK, Tel +44 203 9781686, Email katy.gallop@acasterlloyd.com Robert Ryan, Aimmune Therapeutics, 10 Eastbourne Terrace, London, W2 6LG, UK, Email rryan@aimmune.comPurpose: This study aimed to estimate utility values for health states relating to oral immunotherapy (OIT) for peanut allergy (PA), for children with PA and their caregivers.Patients and Methods: Two methods were used: an online survey and structured interviews. Both methods assessed current utility/untreated PA (health-related quality of life, HRQoL) and HRQoL in different health states: “up-dosing phase of treatment”, “maintenance phase” and “able to tolerate 6– 8 peanuts if accidentally ingested”. The survey was conducted in individuals with and without experience of OIT; data collected included the EQ-5D-Y (child states) and EQ-5D-5L (caregiver states).Results: In total, 100 caregivers and 38 adolescents completed the treatment-naïve survey, a separate sample of 50 caregivers participated in structured interviews. Seven caregivers and two adolescents with experience of OIT for PA completed the survey. Data from the three samples were pooled, the mean utility values were untreated PA: 0.796 (child), 0.855 (caregiver); up-dosing: 0.711 (child), 0.806 (caregiver); maintenance: 0.821 (child), 0.849 (caregiver), tolerate 6– 8 peanuts: 0.859 (child), 0.884 (caregiver). The results show a gain in utility of 0.063 for children and 0.029 for caregivers between the untreated and tolerate 6– 8 peanuts health states.Conclusion: This study is the first to assess utilities relating to OIT for PA. The results show the potential benefit of OIT for individuals with PA and their caregivers and provide values for use in cost-effectiveness evaluation.Keywords: peanut allergy, oral immunotherapy, health-related quality of life, health state utilities, caregiver

Deleterious variation in the epidermal differentiation complex (EDC) on chromosome 1 is a well-known genetic determinant of atopic dermatitis (AD) and has been associated with risk of peanut allergy (PA) in population-based studies.Our aim was to determine the effect of genetic variation in the EDC on AD trajectory and risk of PA in early life.Genome sequencing was used to measure genetic variation in the EDC in the Learning Early about Peanut Allergy (LEAP) study participants. Association tests were done to identify gene- and variant-level predicted deleterious variation associated with AD severity by using the Scoring Atopic Dermatitis (SCORAD) tool (n = 559) at baseline and each follow-up visit, as well as PA and food allergy in peanut avoiders (n = 275). Predicted deleterious variants included missense variants that were frameshift insertions, frameshift deletions, stop-gain mutations, or stop-loss mutations. Associations between variant load, SCORAD score, and PA were tested by using linear and generalized linear regression models.The genes FLG, FLG2, HRNR, and TCHH1 harbored the most predicted deleterious variation (30, 6, 3, and 1 variant, respectively). FLG variants were associated with SCORAD score at all time points; 4 variants (R1798X, R501X, S126X, and S761fs) drove the association with SCORAD score at each time point, and higher variant load was associated with greater AD severity over time. There was an association between these variants and PA, which remained significant independent of baseline AD severity (odds ratio = 2.63 [95% CI = 1.11-6.01] [P = .02]).Variation in FLG predicted to be deleterious is associated with AD severity at baseline and longitudinally and has an association with PA independent of baseline severity.

Parents of children with food allergies (CwFA) experience reduced quality of life (QoL) and may have reduced access to in-person interventions in the COVID-19 pandemic. This trial developed and evaluated an online, self-help, information provision website, aimed at improving QoL in parents of CwFA.In a single-blinded, randomised controlled trial (RCT), participants were randomised to either receive access to the website or a waiting-list control. At baseline, post-intervention (week 4) and follow-up (week 8), measures of parental food allergy-related QoL, depression, anxiety, stress, intolerance of uncertainty (IU) and self-efficacy were obtained.A total of 205 participants were randomised; 97% were females, 91% white and 78% educated ≥ degree level, with a mean age of 38.95 years (SD = 6.89). 44.9% (n = 92) were retained at follow-up. The arms did not significantly differ on any outcome at any time point. For a sub-group of participants above the clinical cut-off for depression at baseline, the intervention may have improved QoL. Participants reported the website content as useful and accessible, but accessed it infrequently. In baseline data, IU and self-efficacy were significantly associated with QoL.While the COVID-19 pandemic has encouraged greater provision of online interventions, our RCT suggests this particular website is not suitable for this population in general, although future research could examine its efficacy for depressed parents of CwFA, to increase confidence that the sub-group finding was not a Type 1 error. The baseline data suggest IU and self-efficacy remain potential proximal targets for intervention.

Background Shared learnings from the early use of novel therapies can aid in their optimization. The recent introduction of peanut oral immunotherapy (peanut OIT; Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp]) for peanut allergy addresses a significant unmet need but also highlights the requirement for consideration of several factors by both prescribers and patients. Objective To provide guidance for prescribers of licenced peanut OIT to facilitate treatment delivery and improve outcomes. Methods Clinicians with experience of licenced peanut OIT (United States n = 6, United Kingdom n = 1) participated in a series of interviews and group discussions designed to elicit tips for successful implementation. Results Clinicians identified 8 tips that were considered the most relevant, practical, and impactful for prescribers of Peanut (Arachis hypogaea) Allergen Powder-dnfp: (1) preparing to provide treatment, (2) assessing the medical indication for treatment and (3) shared decision making, (4) staff education, (5) establishing office processes, (6) managing patient expectations and using anticipatory guidance, (7) optimising adherence and (8) maintaining flexibility throughout the treatment process. In addition, a range of supporting materials (e.g., checklists and action plans) are provided. Conclusion The introduction of a novel therapy often requires healthcare providers to modify or adopt practices to effectively employ the treatment. The provision of guidance based upon early real-world experiences of licenced peanut OIT may help inform clinical practice and improve treatment outcomes.

Atopic dermatitis (AD) typically develops in infancy and affects up to 20% of children in high-income countries (1). Immediate (IgE-mediated) food allergy (FA) affects around 3% of children (2). Children with AD are at higher risk of immediate-type FA (3, 4). Up to a third of children with moderate to severe AD have FA (3). A Danish population-based study, evaluating children from birth to 6 years, showed that 15% of all children with AD had concomitant FA and almost all children with FA had concomitant AD (4).

Oral Tolerance Induction (OTI) is the only RCT-proven effective intervention for preventing childhood food allergy.(1, 2) OTI to peanut is highly effective in a high-risk population with an 81% relative risk ration (RRR) to peanut allergy .(3) OTI also reduced egg allergy in the general population in a per protocol analysis.(1) These published RCT findings have changed practice and many governmental and allergy societies now recommend introducing peanut in infancy; some suggest that other foods, such as well-cooked egg, are also introduced. Only National Institute of Allergy and Infectious Diseases (NIAID) stratify their recommendations according to food allergy (FA) risk level.

BACKGROUND: More than 17 million people across Europe have allergies to food and the burden of food allergies is increasing. In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published guidelines for preventing food allergy. Important research has been published since then and it is essential to ensure the guidelines reflect the latest evidence. A systematic review will be undertaken to help prepare new guidelines due to be published in 2020.METHODS: Eleven bibliographic databases will be searched from inception to 31 October 2019 for randomized controlled trials about any intervention designed to prevent the development of new cases of immediate-type/IgE-mediated food allergy in infants, children and adults. There are few randomized controlled trials about the impact of breastfeeding on food allergy so prospective cohort studies about breastfeeding with at least 1000 participants at general risk or 200 at high risk of food allergy will also be eligible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to assess the certainty of the evidence and tabulate summary data. The risk of bias in individual trials will be assessed using the Cochrane risk of bias tool. All data extraction and quality appraisal will be undertaken independently by two reviewers in partnership with a taskforce of EAACI members.CONCLUSIONS: Preventing food allergy has the potential to improve personal well-being and reduce societal healthcare costs. It is important that forthcoming European guidelines take the latest research into account. Past reviews have tended to focus on single interventions or combined food allergy with other outcomes, making it difficult to draw robust conclusions about potential impacts for policy and practice.

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.

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of updating the guidelines on the diagnosis and management of food allergy. The existing guidelines are based on a systematic review of the literature until 30th September 2012. Therefore, a new systematic review must be undertaken to inform the new guidelines. This systematic review aims to assess the accuracy of index tests to support the diagnosis of IgE-mediated food allergy. Methods: The databases Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID) will be searched for diagnostic test accuracy studies from 1st October 2012 to 30th June 2021. Inclusion and exclusion criteria will be used to select appropriate studies. Data from these studies will be extracted and tabulated, and then reviewed for risk of bias and applicability using the QUADAS-2 tool. All evaluation will be done in duplicate. Studies with a high risk of bias and low applicability will be excluded. Meta-analysis will be performed if there are three or more studies of the same index test and food. Results: A protocol for the systematic review and meta-analyses is presented and was registered using Prospero prior to commencing the literature search. Discussion: Oral food challenges are the reference standard for diagnosis but involve considerable risks and resources. This protocol for systematic review aims to assess the accuracy of various tests to diagnose food allergy, which can be useful in both clinical and research settings.

BACKGROUND: This guideline from the European Academy of Allergy and Clinical Immunology (EAACI) recommends approaches to prevent the development of immediate-onset / IgE-mediated food allergy in infants and young children. It is an update of a 2014 EAACI guideline.METHODS: The guideline was developed using the AGREE II framework and the GRADE approach. An international Task Force with representatives from 11 countries and different disciplinary and clinical backgrounds systematically reviewed research and considered expert opinion. Recommendations were created by weighing up benefits and harms, considering the certainty of evidence and examining values, preferences and resource implications. The guideline was peer-reviewed by external experts and feedback was incorporated from public consultation.RESULTS: All of the recommendations about preventing food allergy relate to infants (up to one year) and young children (up to five years), regardless of risk of allergy. There was insufficient evidence about preventing food allergy in other age groups. The EAACI Task Force suggests avoiding the use of regular cow's milk formula as supplementary feed for breast fed infants in the first week of life. The EAACI Task Force suggests introducing well cooked, but not raw egg or uncooked pasteurised egg, into the infant diet as part of complementary feeding. In populations where there is a high prevalence of peanut allergy, the EAACI Task Force suggests introducing peanuts in an age-appropriate form as part of complementary feeding. According to the studies, it appears that the most effective age to introduce egg and peanut is from four to six months of life. The EAACI Task Force suggests against the following for preventing food allergy: (i) avoiding dietary food allergens during pregnancy or breastfeeding; and (ii) using soy protein formula in the first six months of life as a means of preventing food allergy. There is no recommendation for or against the following: use of vitamin supplements, fish oil, prebiotics, probiotics or synbiotics in pregnancy, when breastfeeding or in infancy; altering the duration of exclusive breastfeeding; hydrolysed infant formulas, regular cow's milk based infant formula after a week of age or use of emollients.CONCLUSIONS: Key changes from the 2014 guideline include suggesting (i) the introduction of peanut and well-cooked egg as part of complementary feeding (moderate certainty of evidence) and (ii) avoiding supplementation with regular cow's milk formula in the first week of life (low certainty of evidence). There remains uncertainty in how to prevent food allergy and further well-powered, multinational research using robust diagnostic criteria is needed.

International audience; Background: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited, and spontaneously resolve within days after drug discontinuation, sometime HR reactions to AEDs can be severe and life-threatening.Aim: This paper seeks to show examples on practical management of AED HRs in children starting from a review of what it is already known in literature.Results: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications, and genetic factors. The diagnostic workup consists of in vivo (intradermal testing and patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays, and granulysin (Grl) in flow cytometry. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids.Conclusion: Dealing with AED HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternative anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.

Fish allergy constitutes a severe problem worldwide. Its prevalence has been calculated as high as 7% in paediatric populations, and in many cases, it persists into adulthood with life-threatening signs and symptoms. The following review focuses on the epidemiology of Immunoglobulin E (IgE)-mediated fish allergy, its pathogenesis, clinical manifestations, and a thorough approach to diagnosis and management in the paediatric population. The traditional approach for managing fish allergy is avoidance and rescue medication for accidental exposures. Food avoidance poses many obstacles and is not easily maintained. In the specific case of fish, food is also not the only source of allergens; aerosolisation of fish proteins when cooking is a common source of highly allergenic parvalbumin, and elimination diets cannot prevent these contacts. Novel management approaches based on immunomodulation are a promising strategy for the future of these patients.

BACKGROUND: This systematic review of ways to prevent immediate-onset/IgE-mediated food allergy will inform guidelines by the European Academy of Allergy and Immunology (EAACI).METHODS: The GRADE approach was used. Eleven databases were searched from 1946 to October 2019 for randomized controlled trials (and large prospective cohort studies in the case of breastfeeding). The studies included heterogeneous interventions, populations, and outcomes and so were summarized narratively.RESULTS: Forty-six studies examined interventions to reduce the risk of food allergy in infancy (up to 1 year) or early childhood. The following interventions for pregnant or breastfeeding women and/or infants may have little to no effect on preventing food allergy, but the evidence is very uncertain: dietary avoidance of food allergens, vitamin supplements, fish oil, probiotics, prebiotics, synbiotics, and emollients. Breastfeeding, hydrolyzed formulas, and avoiding cow's milk formula may not reduce the risk of cow's milk protein allergy; however, temporary supplementation with cow's milk formula in the first week of life may increase the risk of cow's milk allergy. Introducing well-cooked egg, but not pasteurized raw egg, from 4 to 6 months probably reduces the risk of hen's egg allergy. Introducing regular peanut consumption into the diet of an infant at increased risk beginning from 4 to 11 months probably results in a large reduction in peanut allergy in countries with a high prevalence. These conclusions about introducing peanut are based on moderate certainty evidence, from single trials in high-income countries.CONCLUSIONS: Sixty percent of the included studies were published in the last 10 years, but much still remains to be understood about preventing food allergy. In particular, there is a need to validate the potential benefits of early introduction of food allergens in a wider range of populations.

Background Arachis hypogaea 2 (Ara h 2)-specific IgE is to date the best serologic marker to diagnose peanut allergy. Ara h 6 shares approximately 60% sequence identity and multiple epitopes with Ara h 2. Objective Our aim was to assess the diagnostic utility and relative importance of Ara h 2 and Ara h 6 in peanut allergy. Methods A cohort 100 of children was studied. The cohort included chidren who had peanut allergy, children who were sensitized to but tolerant of peanut, and children who were neither sensitized nor allergic to peanut. Levels of specific IgE to peanut and individual allergens were quantified by using ImmunoCAP. ImmunoCAP inhibition experiments and mast cell activation tests in response to both Ara h 2 and Ara h 6 were performed. Statistical analyses were done using SPSS version 14 and Prism version 7 software. Results Ara h 2–specific IgE and Ara h 6–specific IgE showed the greatest diagnostic accuracy for peanut allergy when compared with specific IgE to peanut and other peanut allergens. Most patients with peanut allergy were sensitized to both Ara h 2 and Ara h 6. Ara h 2 reduced Ara h 2–specific IgE binding more than Ara h 6 did (P < .001), whereas Ara h 6–specific IgE binding was inhibited to a similar degree by Ara h 2 and Ara h 6 (P = .432). In the mast cell activation test, Ara h 2 induced significantly greater maximal reactivity (P = .001) and a lower half maximal effective concentration (P = .002) than did Ara h 6 when testing cosensitized individuals. Conclusions Ara h 2–specific IgE and Ara h 6–specific IgE provide the greatest accuracy to diagnose peanut allergy. Ara h 2 is the dominant conglutin in peanut allergy in the United Kingdom, despite a degree of cross-reactivity with Ara h 6., Graphical abstract

Rationale: Allergic diseases are an increasing public health concern, and early life environment is critical to immune development. Maternal diet during pregnancy has been linked to offspring allergy risk. In turn, maternal diet is a potentially modifiable factor, which could be targeted as an allergy prevention strategy. In this systematic review, we focused on non-allergen-specific modifying factors of the maternal diet in pregnancy on allergy outcomes in their offspring. Methods: We undertook a systematic review of studies investigating the association between maternal diet during pregnancy and allergic outcomes (asthma/wheeze, hay fever/allergic rhinitis/seasonal allergies, eczema/atopic dermatitis (AD), food allergies, and allergic sensitization) in offspring. Studies evaluating the effect of food allergen intake were excluded. We searched three bibliographic databases (MEDLINE, EMBASE, and Web of Science) through February 26, 2019. Evidence was critically appraised using modified versions of the Cochrane Collaboration Risk of Bias tool for intervention trials and the National Institute for Clinical Excellence methodological checklist for cohort and case-control studies and meta-analysis performed from RCTs. Results: We identified 95 papers: 17 RCTs and 78 observational (case-control, cross-sectional, and cohort) studies. Observational studies varied in design and dietary intakes and often had contradictory findings. Based on our meta-analysis, RCTs showed that vitamin D supplementation (OR: 0.72; 95% CI: 0.56-0.92) is associated with a reduced risk of wheeze/asthma. A positive trend for omega-3 fatty acids was observed for asthma/wheeze, but this did not reach statistical significance (OR: 0.70; 95% CI: 0.45-1.08). Omega-3 supplementation was also associated with a non-significant decreased risk of allergic rhinitis (OR: 0.76; 95% CI: 0.56-1.04). Neither vitamin D nor omega-3 fatty acids were associated with an altered risk of AD or food allergy. Conclusions: Prenatal supplementation with vitamin D may have beneficial effects for prevention of asthma. Additional nutritional factors seem to be required for modulating the risk of skin and gastrointestinal outcomes. We found no consistent evidence regarding other dietary factors, perhaps due to differences in study design and host features that were not considered. While confirmatory studies are required, there is also a need for performing RCTs beyond single nutrients/foods.