How to Prevent Atopic Dermatitis (Eczema) in 2024: Theory and Evidence.

Atopic dermatitis (AD) or eczema is a chronic inflammatory skin disease characterized by dry, itchy, and inflamed skin. We review emerging concepts and clinical evidence addressing the pathogenesis and prevention of AD. We examine several interventions ranging from skin barrier enhancement strategies to probiotics, prebiotics, and synbiotics; and conversely, from antimicrobial exposure to vitamin D and omega fatty acid supplementation; breastfeeding and hydrolyzed formula; and house dust mite avoidance and immunotherapy. We appraise the available evidence base within the context of the Grades of Recommendation, Assessment, Development, and Evaluation approach. We also contextualize our findings in relation to concepts relating AD and individual-patient allergic life trajectories versus a linear concept of the atopic march and provide insights into future knowledge gaps and clinical trial design considerations that must be addressed in forthcoming research. Finally, we provide implementation considerations to detect population-level differences in AD risk. Major international efforts are required to provide definitive evidence regarding what works and what does not for preventing AD.

Longitudinal peanut and Ara h 2 specific-IgE, -IgG4, and -IgG4/-IgE ratios are associated with the natural resolution of peanut allergy in childhood.

BACKGROUND: There are no studies of longitudinal immunoglobulin measurements in a population-based cohort alongside challenge-confirmed peanut allergy outcomes. Little is known about biomarkers for identifying naturally resolving peanut allergy during childhood. OBJECTIVES: To measure longitudinal trends in whole peanut and component Ara h 2 sIgE and sIgG4 in the first 10 years of life, in a population cohort of children with challenge-confirmed peanut allergy, and to determine whether peanut-specific immunoglobulin levels or trends are associated with peanut allergy persistence or resolution by 10 years of age. METHODS: One-year-old infants with challenge-confirmed peanut allergy (n = 156) from the HealthNuts study (n = 5276) were prospectively followed at ages 4, 6, and 10 years with questionnaires, skin prick tests, oral food challenges, and plasma total-IgE, sIgE and sIgG4 to peanut and Ara h 2. RESULTS: Peanut allergy resolved in 33.9% (95% CI = 25.3%, 43.3%) of children by 10 years old with most resolving (97.4%, 95% CI = 86.5%, 99.9%) by 6 years old. Decreasing Ara h 2 sIgE (p = .01) and increasing peanut sIgG4 (p < .001), Ara h 2 sIgG4 (p = .01), peanut sIgG4/sIgE (p < .001) and Ara h 2 sIgG4/sIgE (p < .001) from 1 to 10 years of age were associated with peanut allergy resolution. Peanut sIgE measured at 1 year old had the greatest prognostic value (AUC = 0.75 [95% CI = 0.66, 0.82]); however, no single threshold produced both high sensitivity and specificity. CONCLUSION: One third of infant peanut allergy resolved by 10 years of age. Decreasing sIgE and sIgG4 to peanut and Ara h 2 over time were associated with natural resolution of peanut allergy. However, biomarker levels at diagnosis were not strongly associated with the natural history of peanut allergy.

Neonatal Vitamin D and Associations with Longitudinal Changes of Eczema up to 25 Years of Age.

BACKGROUND: Early-life vitamin D is a potentially modifiable risk factor for the development of eczema, but there is a lack of data on longitudinal associations. METHOD: We measured 25(OH)D3 levels from neonatal dried blood spots in 223 high-allergy-risk children. Latent class analysis was used to define longitudinal eczema phenotype up to 25 years (4 subclasses). Skin prick tests (SPTs) to 6 allergens and eczema outcomes at 6 time points were used to define eczema/sensitization phenotypes. Associations between 25(OH)D3 and prevalent eczema and eczema phenotypes were assessed using logistic regression models. RESULTS: Median 25(OH)D3 level was 32.5 nmol/L (P25-P75 = 23.1 nmol/L). Each 10 nmol/L increase in neonatal 25(OH)D3 was associated with a 26% reduced odds of early-onset persistent eczema (adjusted multinomial odds ratio (aMOR) = 0.74, 95% CI = 0.56-0.98) and 30% increased odds of early-onset-resolving eczema (aMOR = 1.30, 95% CI = 1.05-1.62) when compared to minimal/no eczema up to 12 years. Similar associations were seen for eczema phenotype up to 25 years. We did not see any strong evidence for the association between neonatal 25(OH)D3 and prevalent eczema or eczema/sensitization phenotype. CONCLUSIONS: Higher neonatal 25(OH)D3 levels, a reflection of maternal vitamin D levels in pregnancy, may reduce the risk of early-onset persistent eczema.

The Prevalence of IgE-Mediated Food Allergy and Other Allergic Diseases in the First 10 Years: The Population-Based, Longitudinal HealthNuts Study.

BACKGROUND: There are limited longitudinal data on the population prevalence of allergic conditions during childhood, and few studies have incorporated the reference standard oral food challenge to confirm food allergy. OBJECTIVE: To describe the population prevalence of IgE-mediated food allergy, eczema, asthma, and rhinitis at ages 6 and 10 years in Melbourne, Australia. METHODS: The HealthNuts study recruited 5,276 1-year-old infants in Melbourne, Australia, with repeat assessments at ages 6 and 10 years. At ages 6 and 10 years, carers completed a questionnaire on symptoms and doctor diagnosis of allergic conditions (International Study of Asthma and Allergies in Children). Children were invited to attend a clinic assessment including skin prick test, lung function tests, and oral food challenges when indicated. To minimize the impact of attrition bias, prevalence estimates among participants at ages 6 and 10 years were weighted to reflect characteristics of the whole cohort at recruitment. RESULTS: In total, 4,455 and 4,065 families participated at ages 6 and 10 years, respectively (84% and 77% of the original cohort). Of those, 73% and 55% of participants ages 6 and 10 years, respectively, completed clinical assessments. Overall, 36.5% (95% CI, 34.8-38.2) and 38.2% (95% CI, 36.5-40.1%) of 6- and 10-year-olds had at least one current allergic disease, and around one third of those had two or more allergic diseases. Food allergy occurred in 6.4% (95% CI, 5.6-7.2) of 6-year olds and 6.3% (95% CI, 5.5-7.2) of 10-year-olds. Among infants with challenge-confirmed food allergy in infancy, 45% had persistent disease at age 10 years. The prevalence of current diagnosed asthma at ages 6 and 10 years were 12.1% (95% CI, 10.9-13.3) and 13.1% (95% CI, 11.9-14.4), respectively, current eczema decreased slightly from 15.3% (95% CI, 14.1-19.7) at age 6 years to 12.9% (95% CI, 11.7-14.2) at age 10 years, and current rhinitis increased from 15.1% (95% CI, 13.9-16.5) at age 6 years to 25.0% (95% CI, 23.4-26.7) at age 10 years. CONCLUSIONS: Allergic diseases affect 40% of primary school-age children; one third have multiple allergic diagnoses. Challenge-confirmed food allergy prevalence remains high, and 45% of infants with food allergy have persistent disease to age 10 years.

Timing of complementary feeding for early childhood allergy prevention: An overview of systematic reviews.

OBJECTIVE: To summarise and critically appraise systematic review (SR) evidence on the effects of timing of complementary feeding (CF) on the occurrence of allergic sensitisation and disease. DESIGN: Overview of SRs. AMSTAR-2 and ROBIS were used to assess methodological quality and risk of bias (RoB) of SRs. RoB 2 Tool was used to assess RoB of primary randomised controlled trials (RCTs) (or extracted). The certainty of evidence (CoE) was assessed using GRADE. Findings were synthesised narratively. DATA SOURCES: MEDLINE (via PubMed and Ovid), the Cochrane Library and Web of Science Core Collection (2010 to 27 February 2023). ELIGIBILITY CRITERIA: SRs investigating the effects of timing of CF in infants or young children (0-3 years) on risk of developing food allergy (FA), allergic sensitisation, asthma, allergic rhinitis, atopic eczema and adverse events based on RCT evidence. RESULTS: Eleven SRs were included. Only two SRs had low RoB; common issues were failure to report on funding of primary studies and failure to provide a list of excluded trials. Common limitations of included trials were lack of blinding of outcome assessment or detailed trial preregistration, and inadequate handling of high loss to follow up. Primary study overlap was very high for specific FA and slight to moderate for FA in general and other primary outcomes. Introducing specific foods (peanut, cooked egg) early probably reduces the risk of specific FA. Evidence for other allergic outcomes was mostly very uncertain and based on few primary studies. Trials varied regarding timing of CF, nature of complementary foods and population risk, which limited comparability between SRs. CONCLUSIONS: For developing guidelines to support decision-making on the timing of CF as a preventive strategy, early introduction of specific foods (i.e. egg and peanut) seems promising and safe, whereas more extensive research is required regarding other allergic outcomes and potential adverse events.

Cashew Allergy Prevalence and Sensitization in 1-Year-Old Infants.

BACKGROUND: Cashew allergy is the most common tree nut allergy in Australia, but there are limited data on the population-level prevalence and risk factors. OBJECTIVE: Describe the prevalence of cashew sensitization and allergy in 12-month-old infants and identify risk factors. METHODS: Data were from the EarlyNuts cohort, a population-based sample of infants recruited in Melbourne, Australia. Families completed a questionnaire and infants underwent a skin prick test (SPT) to cashew. Infants with positive SPTs were offered food challenges. Questionnaires collected demographic data and allergy risk factors. Allergy outcomes were determined by challenge outcomes or a convincing history of an allergic reaction. We used weights to adjust estimated prevalence to reflect the distribution of risk factors among the combined sample of participants and nonparticipants. RESULTS: We recruited 1,933 participants and identified 1,414 cashew allergy outcomes. Of these, 1.96% (95% CI, 1.28-2.99) had an SPT result of 3 mm or greater and 1.49% (95% CI, 0.91-2.44) were allergic to cashew. Infants with eczema or peanut allergy in the first year of life were more likely to be allergic to cashew (adjusted odds ratio = 5.75; 95% CI, 2.08-15.88; P = .001; and adjusted odds ratio = 19.30; 95% CI, 5.44-68.43; P < .001, respectively). Twenty-five percent of participants had cashew introduced before 12 months (95% CI, 22.7-27.8). There was no association between the timing of cashew introduction and cashew allergy. CONCLUSIONS: To our knowledge, this is the first study describing the prevalence of and risk factors for cashew allergy in a population-based infant cohort. Eczema and peanut allergy were associated with an increased risk of cashew allergy. Few infants were introduced to cashew before age 12 months, which suggests that infant feeding guidelines have not yet translated to the earlier introduction of all allergens.

Australian Infant Food Allergy Emergency Presentations Following Updated Early Food Introduction Guidelines.

BACKGROUND: The Australasian Society of Clinical Immunology and Allergy food allergy prevention guidelines were updated in 2016 to recommend home introduction of allergenic foods actively in the first year of life, including to infants at high risk of allergy. An important consideration for parents and providers is whether this practice increases food allergy reactions or anaphylaxis. OBJECTIVE: We aimed to determine whether the 2016 update of food allergy prevention guidelines was associated with an increase in food allergy or anaphylaxis emergency department (ED) presentations. METHODS: We obtained hospital electronic medical records for infants aged 4 to 12 months who attended the Royal Children's Hospital Melbourne ED in 2015 or in 2018 with a presenting problem or an encounter diagnosis of food allergy or anaphylaxis. RESULTS: Emergency department presentations owing to food allergy increased from 1.0% (95% CI, 0.85-1.23) in 2015 to 1.4% (95% CI, 1.22-1.67) in 2018 (P = .006). There was no increase in the number of anaphylaxis presentations (28 in 2015 and 22 in 2018) or peanut anaphylaxis presentations (three in 2015 and three in 2018). Overall, the proportion of food allergy presentations attributed to IgE-mediated food allergy was similar (82.1% in 2015 and 84.1% in 2018), whereas peanut allergy presentations increased slightly, although not statically significantly, from 14.6% to 21.2% (P = .09). Food protein-induced enterocolitis syndrome ED presentations were five in 2015 (4.3%) and 12 in 2018(7.6%), although not statistically significant (P = .25). CONCLUSIONS: Changes to food allergy prevention guidelines recommending the earlier introduction of allergenic food may have led to a small increase in ED presentations for food allergy but not anaphylaxis.

Efficacy and safety of oral immunotherapy for peanut, cow's milk, and hen's egg allergy: A systematic review of randomized controlled trials.

BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for food allergies; however, safety is a concern. We synthesized evidence from the best randomized controlled trials (RCTs) on efficacy/safety of OIT for desensitization (DS) and remission (sustained unresponsiveness (SU)) in IgE mediated allergy to peanut, hen's eggs, and cow's milk. BODY: We searched Pubmed, EMBASE, and Cochrane databases (Until Oct 22) identifying 16 eligible RCTs published in English measuring food allergy by food challenge at the beginning and at the end of the study. The Cochrane Risk of Bias tool was used to assess study quality. We found 18 eligible studies. There was evidence of efficacy for DS for all allergens: peanut (RR 11.32; 95% CI 5.93, 21.60, I2 49%, 8 studies); hen's egg (RR 4.67; 2.66, 8.21, I2 0%, 5 studies); cow's milk (RR 13.98; 3.51, 55.65, I2 0%, 4 studies) and evidence for SU for peanut (RR 7.74; 2.90, 20.69, I2 0%, 3 studies) and hen's egg (RR 6.91; 1.67, 28.57, I2 0%, 2 studies). Allergic events were increased with intervention, and risk of adrenaline use increased for peanut RR 2.96; 1.63, 5.35, I2 0%, 8 studies; egg RR 1.71; 0.42, 6.92, I2 0%, 6 studies; and milk RR 8.45; 2.02, 35.27, I2 0%, 4 studies. CONCLUSION: We found strong evidence that peanut, hen's egg, and cow's milk OIT can induce DS and some evidence for remission. There was a high risk of allergic reactions. Generalizability to the entire food allergic population is not known.

Infant food allergy phenotypes and association with lung function deficits and asthma at age 6 years: a population-based, prospective cohort study in Australia.

BACKGROUND: Food allergy is considered a precursor to asthma in the context of the atopic march, but the relationship between infant food allergy phenotypes and lung function and asthma in childhood is unclear. We aimed to examine the association between food sensitisation and challenge-confirmed food allergy in infancy, as well as persistent and resolved food allergy up to age 6 years, and the risk of lung function deficits and asthma at age 6 years. METHODS: The longitudinal, population-based HealthNuts cohort study in Melbourne, VIC, Australia, recruited 5276 infants children aged 1 year who attended council-run immunisation sessions between Sept 28, 2007, and Aug 5, 2011. At age 1 year, all children completed skin prick testing to four food allergens (egg, peanut, sesame, and either shrimp or cow's milk) and an oral food challenge (egg, peanut, and sesame) at the Royal Children's Hospital in Melbourne. Parents completed questionnaires about their infant's allergy history, demographic characteristics, and environmental exposures. At age 6 years, children were invited for a health assessment that included skin prick testing for ten foods (milk, egg, peanut, wheat, sesame, soy, shrimp, cashew, almond, and hazelnut) and eight aeroallergens (alternaria, cladasporum, house dust mite, cat hair, dog hair, bermuda grass, rye grass, and birch mix), oral food challenges, and lung function testing by spirometry. Questionnaires completed by parents (different to those completed at age 1 year) captured the child's allergy and respiratory history and demographics. We investigated associations between food allergy phenotypes (food-sensitised tolerance or food allergy; and ever, transient, persistent, or late-onset food allergy), lung function spirometry measures (forced expiratory volume in 1 sec [FEV1] and forced vital capacity [FVC] z-scores, FEV1/FVC ratio, forced expiratory flow at 25% and 75% of the pulmonary volume [FEF25-75%], and bronchodilator responsiveness), and asthma using regression methods. Only children with complete data on the exposure, outcome, and confounders were included in models. Infants without food sensitisation or food allergy at age 1 year and 6 years served as the reference group. FINDINGS: Of 5276 participants, 3233 completed the health assessment at age 6 years and were included in this analysis. Food allergy, but not food-sensitised tolerance, at age 1 year was associated with reduced FEV1 and FVC (aß -0·19 [95% CI -0·32 to -0·06] and -0·17 [-0·31 to -0·04], respectively) at age 6 years. Transient egg allergy was associated with reduced FEV1 and FVC compared with never having egg allergy (-0·18 [95% CI -0·33 to -0·03] and -0·15 [-0·31 to 0·00], respectively), whereas persistent egg allergy was not (FEV1 -0·09 [-0·48 to 0·31]; FVC -0·20 [-0·62 to 0·21]). Transient peanut allergy was associated with reduced FEV1 and FVC (FEV1 aß -0·37 [-0·79 to 0·04] and FVC aß -0·55 [-0·98 to -0·12]), in addition to persistent peanut allergy (FEV1 aß -0·30 [-0·54 to -0·06] and FVC aß-0·30 [-0·55 to -0·05]), and late-onset peanut allergy (FEV1 aß -0·62 [-1·06 to -0·18] and FVC aß-0·49 [-0·96 to -0·03]). Estimates suggested that food-sensitised tolerance and food allergy were associated with reduced FEF25-75%, although some estimates were imprecise. Food allergy phenotypes were not associated with an FEV1/FVC ratio. Late-onset peanut allergy was the only allergy phenotype that was possibly associated with increased risk of bronchodilator responsiveness (2·95 [95% CI 0·77 to 11·38]). 430 (13·7%) of 3135 children were diagnosed with asthma before age 6 years (95% CI 12·5-15·0). Both food-sensitised tolerance and food allergy at age 1 year were associated with increased asthma risk at age 6 years (adjusted odds ratio 1·97 [95% CI 1·23 to 3·15] and 3·69 [2·81 to 4·85], respectively). Persistent and late-onset peanut allergy were associated with higher asthma risk (3·87 [2·39 to 6·26] and 5·06 [2·15 to 11·90], respectively). INTERPRETATION: Food allergy in infancy, whether it resolves or not, is associated with lung function deficits and asthma at age 6 years. Follow-up studies of interventions to prevent food allergy present an opportunity to examine whether preventing these food allergies improves respiratory health. FUNDING: National Health & Medical Research Council of Australia, Ilhan Food Allergy Foundation, AnaphylaxiStop, the Charles and Sylvia Viertel Medical Research Foundation, the Victorian Government's Operational Infrastructure Support Program.

The Burden of Self-Reported Antibiotic Allergies in Health Care and How to Address It: A Systematic Review of the Evidence.

BACKGROUND: Antibiotics are the first-line treatment for bacterial infections; however, overuse and inappropriate prescribing have made antibiotics less effective with increased antimicrobial resistance. Unconfirmed reported antibiotic allergy labels create a significant barrier to optimal antimicrobial stewardship in health care, with clinical and economic implications. OBJECTIVE: A systematic review was conducted to summarize the impact of patient-reported antibiotic allergy on clinical outcomes and various strategies that have been employed to effectively assess and remove these allergy labels, improving patient care. METHODS: The review was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A critical appraisal was conducted on all studies and a narrative synthesis was performed to identify themes. RESULTS: Four themes emerged: the prevalence of antibiotic allergy, impact of antibiotic allergy on antimicrobial prescribing, impact of antibiotic allergy on clinical outcomes, and delabeling strategies to improve clinical outcomes. Of the 32 studies, including 1,089,675 participants, the prevalence of reported antibiotic allergy was between 5% and 35%. Patients with a reported antibiotic allergy had poorer concordance with prescribing guidelines in 30% to 60% of cases, with a higher use of alternatives such as quinolone, tetracycline, macrolide, lincosamide, and carbapenem and lower use of beta-lactam antibiotics. Antibiotic allergy delabeling was identified as an intervention and recommendation to advance the state of the science. CONCLUSIONS: There is substantial evidence within the literature that antibiotic allergy labels significantly impact patient clinical outcomes and a consensus that systematic assessment of reported antibiotic allergies, commonly referred to as delabeling, improves the clinical management of patients.

Systematic Review of the Incidence and/or Prevalence of Eating Disorders in Individuals With Food Allergies.

BACKGROUND: Chronic diseases involving strict dietary adherence have been associated with an increased risk of eating disorders (EDs). This is the first systematic review investigating the rate of EDs among individuals with food allergies (FAs). OBJECTIVE: To report the incidence, prevalence, and types of EDs in individuals with FAs. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched 4 databases for studies published to January 2022 that reported the prevalence or incidence of EDs in samples with immunoglobulin E (IgE) or non-IgE-mediated allergy. Risk of bias was assessed and evidence qualitatively synthesized. RESULTS: From 1,180 papers identified, 9 met inclusion criteria. There were 4,161 adult and pediatric participants with IgE-mediated FAs or eosinophilic esophagitis. Avoidant/Restrictive Food Intake Disorder (ARFID) or anorexia nervosa/bulimia nervosa were the main EDs identified. The prevalence of EDs in samples with FA ranged from 0.8% to 62.9%. Among studies investigating IgE-mediated FA (n = 6), the prevalence of anorexia nervosa and/or bulimia nervosa ranged from 17.6 to 61%, ARFID was 62.9%, and unspecified EDs was 0.8% to 6%. Among samples with eosinophilic esophagitis (n = 3), ARFID prevalence ranged from 4.5% to 51%. Most studies were limited by small sample size, possible selection bias, and lack of diagnostic EDs tools validated for food allergic populations. CONCLUSIONS: Eating disorders appear prevalent in individuals with FA; however, prevalence estimates varied widely. Large studies with healthy control groups and validated measures to identify EDs in individuals with FA are needed to accurately determine the prevalence of EDs.

Managing Atopic Dermatitis in Patients With Skin of Color.

Managing atopic dermatitis (AD) in patients with skin of color presents unique challenges for the clinician. There is increasing evidence that AD has higher prevalence, persistence, and severity among skin of color populations. This is likely to be partly related to differences in living conditions and exposure to irritants and allergens, among other factors. Assessment of AD severity in patients with darker skin can be challenging, in particular the assessment of erythema, leading to the potential for underscoring AD severity. Variations in disease have also been described, with the potential for a greater risk of inflammation-induced nodularity and hyper- or hypopigmentation. Management challenges include variable adherence to treatment, potential disparities in access to health care, and differences in the metabolism of cyclosporine. Optimal management of AD in patients with skin of color requires a tailored approach. Here, we review approaches to diagnosing AD, evaluating extent and severity with subjective and objective measures, considering treatment options for patients with skin of color, and highlighting areas for improvement in AD care for skin of color populations.

TreEAT trial: Protocol for a randomized controlled trial investigating the efficacy and safety of early introduction of tree nuts for the prevention of tree nut allergy in infants with peanut allergy.

INTRODUCTION: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy; however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi-nut oral food challenge (OFC) compared with standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. METHODS AND ANALYSIS: TreEAT is a 2-armed, open-label, randomized, controlled trial (RCT). Infants (n = 212) aged 4-11 months with peanut allergy will be randomized 1:1 at peanut allergy diagnosis to either a hospital-based multi-tree nut (almond, cashew, hazelnut, and walnut) OFC using multi-nut butter or standard care (home introduction of individual tree nuts). All infants will be assessed at age 18 months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine the allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion, and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety, and allergy-related healthcare visits from randomization to 18 months of age. Analyses will be performed on an intention-to-treat basis. ETHICS AND DISSEMINATION: TreEAT was approved by the Royal Children's Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT04801823.

Early peanut introduction: To test or not to test?

OBJECTIVE: To review recent evidence and international guidelines on early peanut introduction for preventing peanut allergy and provide an update on the status of the debate around testing before early peanut introduction. DATA SOURCES: Review of published literature documenting: infant feeding guidelines; impact of early peanut introduction on peanut allergy; risk factors for peanut allergy; and impact of early peanut introduction guidelines on infant feeding practices and allergy. STUDY SELECTION: We used a narrative approach and present both pro and con arguments for testing before peanut introduction. Data from randomized controlled trials and post-hoc analyses of these trials and observational studies were included. RESULTS: Allergy prevention guidelines around the world now consistently recommend introducing peanut into an infant's diet before 12 months of age for countries with high peanut allergy prevalence. In the US, guidelines recently shifted away from recommending allergy testing before introduction for those at risk of peanut allergy. There is evidence primarily from Australia that recommending early introduction without prior testing is safe and effective in increasing early peanut introduction for both high and low-risk infants, although the subsequent reduction in peanut allergy prevalence at the population level was less than expected. CONCLUSION: Current evidence supports recommending early peanut introduction without routinely testing for peanut allergy. If testing is offered, this should be based on shared decision making between families and practitioners and only be undertaken where there is provision for rapid access to definitive diagnosis including oral food challenges.

Is antenatal or early-life vitamin D associated with eczema or food allergy in childhood? A systematic review.

OBJECTIVE: To summarise the associations between antenatal or early-life blood vitamin D and the development of eczema/food allergy in childhood. DESIGN: A systematic review and meta-analyses were conducted to synthesize the published literature. Two reviewers independently performed the study selection and data extraction on Covidence. We assessed the risk of bias for observational studies by using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool for clinical trials. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). DATA SOURCES: We systematically searched PubMed and Embase from inception and April 2022. ELIGIBILITY CRITERIA: Human studies that investigated prospective associations between antenatal or early-life blood vitamin D levels, dietary intake or supplementation and childhood eczema/food allergy. RESULTS: Forty-three articles including six randomised controlled trials (RCTs) were included. Four RCTs of vitamin D supplementation during pregnancy showed no evidence of an effect on the incidence of eczema (pooled odds ratio [OR] = 0.85; 0.67-1.08, I2  = 6.7%, n = 2074). Three RCTs reported null associations between supplementation in pregnancy/infancy and food allergy. From six cohort studies, increasing cord blood vitamin D levels were associated with reduced prevalence of eczema at/close to age one (OR per 10 nmol/L increase = 0.89; 0.84-0.94, I2  = 0%, 2025 participants). We found no evidence of an association between maternal antenatal or infant vitamin D level or dietary intake and the development of food allergy or eczema in offspring. CONCLUSIONS: We found an association between higher vitamin D levels in cord blood and reduced risk of eczema in cohort studies. Further trials with maternal and infant supplementation are needed to confirm if vitamin D supplementation can effectively prevent eczema or food allergy in childhood. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, No. CRD42013005559.

Complementary and Allergenic Food Introduction in Infants: An Umbrella Review.

BACKGROUND: Multiple systematic reviews examine the introduction of foods in relation to individual health outcomes, but the balance of harms and benefits has not been overviewed systematically. OBJECTIVES: We aimed to perform an overview of systematic reviews on age of introduction of complementary and allergenic foods to the infant diet and long and short-term health outcomes. DATA SOURCES: We searched Medline, Embase, Cochrane, and PubMed (July 25, 2022). STUDY SELECTION: Included systematic reviews examining the introduction of complementary or allergenic foods before age 1. Outcomes included allergic, autoimmune, and inflammatory diseases, neurodevelopment, nutrition, and weight. DATA EXTRACTION: Extraction and quality assessment were performed in duplicate (A Measurement Tool to Assess Systematic Reviews) and strength of evidence was assessed. RESULTS: We screened 4015 articles and included 32 systematic reviews. There was moderate evidence that peanut and egg should be introduced from 4 to 11 months to prevent food allergy (6 of 10 reviews). Complementary food introduction was not associated with food allergy. Moderate certainty evidence suggested age of complementary food introduction was not associated with eczema. Age at introduction of gluten was not associated with celiac disease (high certainty evidence; 3 of 4 reviews). Low certainty evidence indicated that introducing solids before 4 months may increase the risk of childhood obesity, but not growth. There was insufficient evidence regarding an association between any food introduction and bone health, gastrointestinal diseases, autoimmune disorders, asthma, or allergic rhinitis. LIMITATIONS: Gray literature was not included. CONCLUSIONS: Current evidence supports introducing complementary foods around 6 months and allergenic foods before 11 months.