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AIM: Adrenaline auto-injector (AAI) dispensing data, a community-based proxy for number of individuals at risk of anaphylaxis, provides complementary information on time trends of anaphylaxis risk in addition to hospital admission data. We examined trends of AAI dispensing over a 10-year period (from January 2005 to December 2014) in Australia. METHODS: Individuals with dispensed AAI were identified from a 10% random sample of Australian Pharmaceutical Benefits Scheme (PBS) data. PBS is the Australian national drug subsidy programme covering all Australians. Cumulative incidence and incidence rates of individuals with AAI were calculated. We assessed difference by age, sex, state and time trends. RESULTS: The cumulative incidence of individuals with AAI in 2005-2014 was 75.43/100 000 (95%CI 75.07-75.80/100 000). Incidence rate of individuals with AAI increased from 2005 to 2014 (from 71.47 to 82.07 per 100 000 person-years) although this varied by state. Over the time assessed, there was a shift to more prescriptions being provided by general practitioners (GP) rather than specialists. Children (0-19 years) were more likely to have been prescribed an AAI from a specialist and adults from a GP. CONCLUSION: Overall, an increase in dispensed AAI mirrored other evidence for a rising prevalence of allergy. This increase could also reflect changes in prescribing practices or increased awareness and education of health-care professionals on anaphylaxis and indications for prescribing AAI. The rising rate of AAI prescribed by GPs compared to decreasing rates by specialists suggests a changing response of the Australian health-care system to the increased burden of anaphylaxis.

Background and objective As the rise in prevalence of allergic diseases worldwide corresponds in time with increasing infant vaccination, it has been hypothesized that childhood vaccination may increase the risk of allergic disease. We aimed to synthesize the literature on the association between childhood vaccination and allergy. Design We searched the electronic databases PubMed and EMBASE (January 1946-January 2018) using vaccination and allergy terms. Methods Two authors selected papers according to the inclusion criteria. Pooled effects across studies were estimated using random-effects meta-analysis. Due to inadequate number of homogeneous publications on newer and underused vaccines, meta-analysis was limited to allergic outcomes following administration of (Bacillus Calmette-Guerin) BCG, measles or pertussis vaccination. The review was prospectively registered in the PROSPERO systematic review registry (NO: CRD42017071009). Results A total of 35 publications based on cohort studies and 7 publications based on randomized controlled trials (RCTs) met the inclusion criteria. RCTs: From 2 studies, early vaccination with BCG vaccine was associated with a reduced risk of eczema (RR = 0.83; 95% CI = 0.73-0.93; I2 = 0%) but not food allergy or asthma. No association was found between pertussis vaccine and any allergic outcome based on a single RCT. Cohort studies Childhood measles vaccination was associated with a reduced risk of eczema (RR = 0.65; 95% CI = 0.47-0.90, I2 = 0.0%), asthma (RR = 0.78; 95% CI = 0.62-0.98, I2 = 93.9%) and, with a similar, statistically non-significant reduction in sensitization (RR = 0.78; 95% CI = 0.61-1.01, I2 = 19.4%). Conclusions We found no evidence that childhood vaccination with commonly administered vaccines was associated with increased risk of later allergic disease. Our results from pooled analysis of both RCTs and cohort studies suggest that vaccination with BCG and measles vaccines were associated with a reduced risk of eczema.

Food allergy is a major public health issue with growing prevalence in the urbanized world and significant impact on the lives of allergic patients and their families. Research into the risk factors that have contributed to this increase and their underlying immune mechanisms could lead us to definitive ways for treatment and prevention of food allergy. For the time being, introduction of peanut and other allergenic foods in the diet at the time of weaning seems to be an effective way to prevent the development of food allergy. Improved diagnosis and appropriate management and support of food allergic patients are central to patient care with food immunotherapy and biologics making the transition to clinical practice. With the new available treatments, it is becoming increasingly important to include patients' and family preferences to provide a management plan tailored to their needs.

Background Few studies have investigated adverse food reactions among food-allergic children in a population-based sample, which is critical for the development of evidence-based management strategies. Objective We aimed to evaluate the frequency, characteristics, and risk factors for adverse food reactions, including anaphylaxis, among food-allergic 6-year-old-children using the population-based HealthNuts study. Methods The HealthNuts study of 5276 infants (1-year-old) followed them up at age 6 years (84.4% participated). A total of 260 children with IgE-mediated food allergy who completed a questionnaire detailing recent adverse food reactions were included in this analysis. Results Among food-allergic children, 44.6% (95% CI, 38.6%-50.8%) reported an adverse food reaction in the last 12 months and 10.8% (95% CI, 7.5%-15.2%) reported an anaphylactic reaction, although only half of these were recognized as anaphylaxis by parents. Adrenaline autoinjectors were used in 25% (4 of 16) of recognized anaphylaxis episodes. Nut allergy was associated with a reduced risk of having an adverse reaction (adjusted odds ratio, 0.3; 95% CI, 0.1-0.7). There were trends that adverse reactions were more likely in children with at least 1 parent born in Asia compared with both parents born in Australia (adjusted odds ratio, 1.9; 95% CI, 0.9-3.9), and in children with 3 or more food allergies compared with children with a single food allergy (adjusted odds ratio, 1.8; 95% CI, 0.9-3.5). Conclusions Adverse food reactions occurred in almost half of all food-allergic 6-year-old children and anaphylaxis occurred in 1 in 10 children over a 12-month period. Anaphylaxis was poorly recognized and adrenaline autoinjectors were not used appropriately. Improved regular education on the prevention, recognition, and management of adverse food reactions is urgently needed.

Background Environmental microbial exposure and human gut microbiota play a role in development of the immune system and susceptibility to food allergy. Pacifier use has been inconsistently associated with allergy, but the association between sanitization and food allergy is unknown. We investigated the association between infant pacifier use, with a consideration of sanitization, and food allergy at age 1 in the Barwon Infant Study (BIS). Methods Questionnaire data were collected prospectively from pregnant mothers from the Barwon region of south-east Australia at baseline and at infant ages 1, 6, and 12 months. Pacifier sanitization was defined as the joint exposure of a pacifier and cleaning methods (antiseptic, mouth, tap water, boiling). Challenge-proven food allergy was determined at age 1. Results Any pacifier use at 6 months was associated with food allergy (aOR, 1.94; 95% CI, 1.04-3.61), but not at other ages. This overall association was driven by the joint exposure pacifier-antiseptic use (aOR, 5.90; 95% CI, 2.18-15.97) compared to no pacifier use. Among pacifier users, pacifier-antiseptic was still associated with food allergy (aOR, 3.88; 95% CI, 1.55-9.72) when compared to pacifier-no antiseptic use. Further, increased use of pacifier-antiseptic at 0, 1 or 2 interviews over the first 6 months was associated with higher food allergy risk (ptrend=0.005). Conclusions Joint exposure to antiseptics and pacifiers at 6 months increased the odds of food allergy, showing a trend with increased use over time. Key messages This is the first report of pacifiers used with antiseptic being positively associated with challenge-proven food allergy.

Background Experimental challenge studies have shown that pollen can affect the lungs and airways. Here, we systematically reviewed community-based studies investigating outdoor pollen exposure, lung function and/or airway inflammation. Methods Four online databases were searched. The search strategy included terms relating to both exposure and outcomes. Inclusion criteria were studies published in English that were representative of the community. We only considered cross-sectional or short-term longitudinal studies which investigated pollen exposure by levels or season. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was conducted using random-effects models. Results We included 27 of 6,551 studies identified from the search. Qualitative synthesis indicated associations between pollen exposure and predominantly type-2 inflammation in both the upper and lower airways, but little evidence for lung function changes. People with ever asthma and/or seasonal allergic rhinitis (SAR) were at higher risk of such airway inflammation. Meta-analysis confirmed a positive relationship between pollen season and eosinophilic airway inflammation in people with ever SAR but the results between studies were highly variable. Heterogeneity was reduced after further subgrouping by age and the forest plots indicated that eosinophilic airway inflammation to outdoor pollen exposure increased with age. Conclusion Among people with ever asthma and ever SAR, exposure to increased ambient pollen triggers type-2 airway inflammation rather than a non-specific or innate inflammation. Key messages This review indicates pollen exposure influences predominantly type-2 airway inflammation, but little evidence on lung function.

Background and objectiveAs caesarean delivery and childhood allergy continue to rise, their inter-relationships may change. We examined whether caesarean delivery predicts allergic disease and impaired lung function in two contemporary harmonised population-based cohorts.MethodsParent-reported asthma and eczema data were drawn from two prospective Australian infant cohorts, HealthNuts (n=5276, born 2006–2010) and the Longitudinal Study of Australian Children (LSAC, n=5107, born 2003–2004) at age 6–7 years, and spirometric lung function from LSAC’s Child Health CheckPoint (n=1756) at age 11–12 years. Logistic regression estimated associations between delivery mode and current asthma and eczema at 6–7 years, and linear regression examined lung function at 11–12 years. Models were adjusted for potential confounding factors.ResultsComplete case analysis included 3135 HealthNuts and 3654 LSAC children (32.2% and 30.9% born by caesarean, respectively). An association was evident between caesarean delivery and asthma at age 6–7 years in HealthNuts (adjusted OR (aOR) 1.25, 95% CI 1.00 to 1.57) but not in LSAC (aOR 1.05, 95% CI 0.86 to 1.28), while neither study showed clear associations with eczema (HealthNuts: aOR 1.09, 95% CI 0.88 to 1.35; LSAC: aOR 0.89, 95% CI 0.69 to 1.15). Spirometric lung function parameters at age 11–12 years were similar by delivery mode. Associations were not modified by duration of breast feeding, maternal history of asthma/eczema, childcare attendance, number of older siblings or pet exposure.ConclusionsIn two unselected populations using harmonised protocols, the likely association of caesarean delivery with developing childhood allergy was small.

Background: Food allergies are a significant public health issue, and the only effective management option currently available is strict avoidance of all foods containing the allergen. In view of the practical impossibility of limiting risks to zero, quantitative allergen risk assessment and management strategies are needed. Objective: We sought to develop appropriate methods for informing population-based risk assessments and risk management programs to benefit all stakeholders but particularly patients with food allergy. Methods: Individual thresholds for food allergens (maximum tolerable doses and minimum eliciting doses) can ideally be established through double-blind, placebo-controlled food challenges. If double-blind, placebo-controlled food challenge data are not available, data from widely used open food challenges using predefined objective criteria can also provide useful data regarding minimum eliciting doses. For more than 20 years, the Netherlands Organisation for Applied Scientific Research and the Food Allergy Research and Resource Program at the University of Nebraska-Lincoln have been collecting individual maximum tolerable doses and minimum eliciting doses that produce objective symptoms from published and unpublished clinical data to better refine knowledge regarding the sensitivity of the population to food allergens. Results: In this article we provide in-depth insights into the methodology applied by the Netherlands Organisation for Applied Scientific Research and Food Allergy Research and Resource Program to derive individual maximum tolerable doses and minimum eliciting doses for objective symptoms from clinical food challenge data. More than 90 examples for determining individual allergic thresholds are presented. Conclusion: With the methodology presented in this article, we aim to stimulate harmonization and transparency in quantitative food allergen risk assessment and risk management programs, encouraging their wider adoption. © 2019 American Academy of Allergy, Asthma & Immunology

findings from systematic reviews into infant feeding and later adiposity are largely negative. World Health Organization (WHO) is auspicing Healthy Life Trajectories Initiative (HeLTI), a suite of trials aiming to prevent overweight/obesity in childhood. To inform planning, this narrative review sought to detail potentially effective components of nutrition-related interventions involving children aged 0 to 2 years. Systematic searches of PubMed and the Cochrane Library (2006-2016) identified 108 systematic reviews. These included 31 randomized trials in the age group of interest. Of these, 11 reported greater than or equal to 1 statistically significant (P

Background The genetic determinants of food allergy have not been systematically reviewed. We therefore systematically reviewed the literature on the genetic basis of food allergy, identifying areas for further investigation. Methods We searched three electronic databases (MEDLINE, EMBASE and PubMed) on 9 January 2018. Two authors screened retrieved articles for review according to inclusion criteria and extracted relevant information on study characteristics and measures of association. Eligible studies included those that reported an unaffected nonatopic control group, had genetic information and were carried out in children. Results Of the 2088 studies retrieved, 32 met our inclusion criteria. Five were genome-wide association studies, and the remaining were candidate gene studies. Twenty-two of the studies were carried out in a predominantly Caucasian population with the remaining 10 from Asian-specific populations or unspecified ethnicity. We found FLG, HLA, IL10, IL13, as well as some evidence for other variants (SPINK5, SERPINB and C11orf30) that are associated with food allergy. Conclusions Little genetic research has been carried out in food allergy, with FLG, HLA and IL13 being the most reproducible genes for an association with food allergy. Despite promising results, existing genetic studies on food allergy are inundated with issues such as inadequate sample size and absence of multiple testing correction. Few included replication analyses or population stratification measures. Studies addressing these limitations along with functional studies are therefore needed to unravel the mechanisms of action of the identified genes.

Diagnosis of peanut allergy presents a significant clinical challenge. Accurate diagnosis is critical for patient management and prevention of allergic reactions, whereas overdiagnosis or failure to diagnose tolerance in a previously allergic patient can lead to unnecessary dietary restrictions and impaired quality of life. Oral food challenges, the criterion standard for diagnosis, pose a risk of potentially severe allergic reactions, and are time- and resource- intensive. In this article, we review other currently available tests for peanut allergy and present the strengths and weaknesses of each to assist the clinician in determining which test might be appropriate for their patients, as well as highlighting emerging tests currently in development. Traditional tests for peanut-specific IgE (skin prick testing and specific IgE) remain useful as first-line tests-a negative test result is useful for excluding peanut allergy and a high positive result has a high specificity for peanut allergy. For those with an intermediate positive test result, Ara h 2 testing might be useful as a second step. Basophil activation tests and peanut protein epitope-specific IgE analyses appear promising in recent studies; however, further research is required into standardization, validation, and cost-effectiveness. Given the limitations of existing tests for peanut allergy, there remains a clear need for improvement. Finding a safe and affordable method for peanut allergy diagnosis that is both sensitive and specific remains an active area of research.

Background The home environment is the most important location in young children’s lives, yet few studies have examined the relationship between the outdoor home environment and child physical activity levels, and even fewer have used objectively measured exposures and outcomes. This study examined relationships between objectively assessed home yard size and greenness, and child physical activity and outdoor play. Methods Data were drawn from the HealthNuts study, a longitudinal study of 5276 children in Melbourne, Australia. We used cross-sectional data from a sample at Wave 3 (2013–2016) when participants were aged 6 years (n = 1648). A sub-sample of 391 children had valid accelerometer data collected from Tri-axial GENEActive accelerometers worn on their non-dominant wrist for 8 consecutive days. Yard area and greenness were calculated using geographic information systems. Objective outcome measures were minutes/day in sedentary, light, and moderate-vigorous physical activity (weekday and weekend separately). Parent-reported outcome measures were minutes/day playing outdoors (weekend and weekday combined). Multi-level regression models (adjusted for child’s sex, mother’s age at the birth of child, neighbourhood socioeconomic index, maternal education, and maternal ethnicity) estimated effects of yard size and greenness on physical activity. Results Data were available on outdoor play for 1648 children and usable accelerometer data for 391. Associations between yard size/greenness and components of physical activity were minimal. For example, during weekdays, yard size was not associated with daily minutes in sedentary behaviour (β: 2.4, 95% CI: − 6.2, 11.0), light physical activity (β: 1.4, 95% CI: − 5.7, 8.5) or MVPA (β: -2.4, 95% CI: − 6.5, 1.7), with similar patterns at weekends. There was no relationship between median annual yard greenness and physical activity or play. Conclusion In our study of young children residing in higher socio-economic areas of Melbourne yard characteristics did not appear to have a major impact on children’s physical activity. Larger studies with greater variation in yard characteristics and identification of activity location are needed to better understand the importance of home outdoor spaces and guide sustainable city planning.

Background Approximately 5% of adolescents have a food allergy, with peanut and tree nut allergies the most common. Having two or more food allergies in adolescence also doubles the risk of any adverse food reaction, and is associated with increased dietary and social burden. Investigations of immune function in persistently food allergic children are rare. Objective In the present study, we aimed to investigate the immune mechanisms that underlie food allergy in adolescence. Methods We used high-dimensional flow cytometry, unsupervised computational analysis and functional studies to comprehensively phenotype a range of non-antigen-specific immune parameters in a group of well-characterized adolescents with clinically defined single peanut allergy, multi-food allergy and aged-matched non-food allergic controls. Results We show that food allergic adolescents have higher circulating proportions of dendritic cells (p = .0084, FDR-adjusted p = .087, median in no FA: 0.63% live cells, in FA: 0.93%), and higher frequency of activated, memory-like Tregs relative to non-food allergic adolescents (p = .011, FDR-adjusted p = .087, median in no FA: 0.49% live cells, in FA: 0.65%). Cytokine profiling revealed that CD3/CD28 stimulated naive CD4 T cells from food allergic adolescents produced less IL-6 (p = .0020, FDR-adjusted p = .018, median log2 fold change [stimulated/unstimulated] in no FA: 3.03, in FA: 1.92) and TNFα (p = .0044, FDR-adjusted p = .020, median in no FA: 9.16, in FA: 8.64) and may secrete less IFNγ (p = .035, FDR-adjusted p = .11, median in no FA: 6.29, in FA: 5.67) than naive CD4 T cells from non-food allergic controls. No differences between clinical groups were observed for LPS-stimulated monocyte secretion of cytokines. Conclusions These results have important implications for understanding the evolution of the immune response in food allergy throughout childhood, revealing that dendritic cell and T-cell signatures previously identified in early life may persist through to adolescence.

Background: In Western countries, Asian children have higher food allergy risk than Caucasian children. The early-life environmental exposures for this discrepancy are unclear. We aimed to compare prevalence of food allergy and associated risk factors between Asian children in Singapore and Australia. Methods: We studied children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort (n = 878) and children of Asian ancestry in the HealthNuts cohort (n = 314). Food allergy was defined as a positive SPT ≥3 mm to egg or peanut AND either a convincing history of IgE-mediated reaction at 18 months (GUSTO) or a positive oral food challenge at 14-18 months (HealthNuts). Eczema was defined as parent-reported doctor diagnosis. Results: Food allergy prevalence was 1.1% in Singapore and 15.0% in Australia (P10 months) in Singapore (63.5%) than Australia (16.3%; P

Emerging research suggests environmental exposures before conception may adversely affect allergies and lung diseases in future generations. Most studies are limited as they have focused on single exposures, not considering that these diseases have a multifactorial origin in which environmental and lifestyle factors are likely to interact. Traditional exposure assessment methods fail to capture the interactions among environmental exposures and their impact on fundamental biological processes, as well as individual and temporal factors. A valid estimation of exposure preconception is difficult since the human reproductive cycle spans decades and the access to germ cells is limited. The exposome is defined as the cumulative measure of external exposures on an organism (external exposome), and the associated biological responses (endogenous exposome) throughout the lifespan, from conception and onwards. An exposome approach implies a targeted or agnostic analysis of the concurrent and temporal multiple exposures, and may, together with recent technological advances, improve the assessment of the environmental contributors to health and disease. This review describes the current knowledge on preconception environmental exposures as related to respiratory health outcomes in offspring. We discuss the usefulness and feasibility of using an exposome approach in this research, advocating for the preconception exposure window to become included in the exposome concept.

Several recent studies have reported a key role for innate cell hyper-responsiveness in food allergy. This has predominantly been observed in early life, with evidence that innate immune function may return to baseline if food allergy resolves in later childhood. Hallmarks of hyper-responsiveness include increased circulating frequency of monocytes and altered innate cell cytokine responses to in vitro exposure with bacterial endotoxin. These features mirror the defining signatures of trained innate immunity, seen in other complex diseases. In this study, detailed immune cell and cytokine profiling was performed on peripheral blood mononuclear cells at baseline from 27 1 year old infants in the HealthNuts cohort (n = 16 egg allergic and n = 11 non-allergic healthy controls) and following monocyte stimulation. We show that egg allergic infants have increased frequency of circulating monocytes, reduced numbers of regulatory CD4 T cells and increased monocyte: CD4 T cell ratios relative to healthy controls. Monocytes from both egg allergic and non-allergic infants responded to endotoxin stimulation with rapid cytokine production and downregulation of the surface receptor CD16, however monocytes from egg allergic infants were hyper-responsive, producing significantly more inflammatory cytokines (TNFα, IL-6, IL-1β, IL-8) and innate cell recruiting factors (MIP-1α) than healthy controls. This work indicates that monocytes of food allergic infants are programmed to a hyper-inflammatory phenotype and that the development of food allergy may be associated with trained immunity in early life.

Background: Previous research suggests that children who experience asthma may be less physically active, however results have been inconclusive. This study aimed to investigate whether the presence of asthma or wheeze is associated with lower physical activity levels in children, and whether sex, body mass index or earlier asthma or wheeze status modifies the association. Methods: This study was conducted in 391 HealthNuts participants in Melbourne, Australia. Asthma and wheeze data were collected via questionnaire at age 4 and 6 and physical activity was measured through accelerometry. Using adjusted linear regression models, the cross‐sectional and longitudinal associations were investigated. Results: There was no evidence of a difference in time spent in moderate‐to‐vigorous physical activity (MVPA) at age 6 years between children with and without asthma at age 4; children with asthma spent 8.3 minutes more time physically active per day (95%CI: ‐5.6, 22.1, p=0.24) than children without asthma. Similar results were seen for children with current wheeze (5.8 minutes per day more, 95%CI: ‐5.9, 17.5, p=0.33) or ever wheeze or asthma (7.7 min per day more, 95%CI: ‐4.8, 20.2, p=0.23) at age 4 years. Comparable null results were observed in the cross‐sectional analyses. Interaction with BMI could not be assessed, however, previous asthma or wheeze status and sex were not found to modify these associations. Conclusion: This analysis found no evidence of asthma hindering physical activity in these young children. These results are encouraging, as they indicate that the Australian asthma and physical activity public health campaigns are being effectively communicated and adopted by the public. Refereed/Peer-reviewed

Background Environmental microbial exposure plays a role in immune system development and susceptibility to food allergy. Objective We sought to investigate whether infant pacifier use during the first postnatal year, with further consideration of sanitization, alters the risk of food allergy by age 1 year. Methods The birth cohort recruited pregnant mothers at under 28 weeks’ gestation in southeast Australia, with 894 families followed up when infants turned 1 year. Infants were excluded if born under 32 weeks, with a serious illness, major congenital malformation, or genetic disease. Questionnaire data, collected at recruitment and infant ages 1, 6, and 12 months, included pacifier use and pacifier sanitization (defined as the joint exposure of a pacifier and cleaning methods). Challenge-proven food allergy was assessed at 12 months. Results Any pacifier use at 6 months was associated with food allergy (adjusted odds ratio, 1.94; 95% CI, 1.04-3.61), but not pacifier use at other ages. This overall association was driven by the joint exposure of pacifier-antiseptic use (adjusted odds ratio, 4.83; 95% CI, 1.10-21.18) compared with no pacifier use. Using pacifiers without antiseptic at 6 months was not associated with food allergy. Among pacifier users, antiseptic cleaning was still associated with food allergy (adjusted odds ratio, 3.56; 95% CI, 1.18-10.77) compared with no antiseptic use. Furthermore, persistent and repeated antiseptic use over the first 6 months was associated with higher food allergy risk (P = .029). Conclusions This is the first report of a pacifier-antiseptic combination being associated with a higher risk of subsequent food allergy. Future work should investigate underlying biological pathways.

In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella, a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort (n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal samples shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri. Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri., Incidence of food allergy in westernized populations is associated with low abundance of Prevotella. Here, the authors analyse the microbiome of a mother-infant prebirth cohort and find that maternal carriage, but not infant carriage, of P. copri during pregnancy predicts the absence of food allergy in the offspring.

IgE-mediated peanut allergic is common, often serious, and usually lifelong. Not all individuals who produce peanut-specific IgE will react upon consumption of peanut and can eat the food without adverse reactions, known as sensitized tolerance. Here, we employ high-dimensional mass cytometry to define the circulating immune cell signatures associated with sensitized tolerance and clinical allergy to peanut in the first year of life. Key features of clinical peanut allergic are increased frequency of activated B cells (CD19hiHLADRhi), overproduction of TNFα and increased frequency of peanut-specific memory CD4 T cells. Infants with sensitized tolerance display reduced frequency but hyper-responsive naive CD4 T cells and an increased frequency of plasmacytoid dendritic cells. This work demonstrates the utility and power of high-dimensional mass cytometry analysis to interrogate the cellular interactions that are associated with allergic sensitization and clinical food allergy in the first year of life., Food allergy is triggered by IgE, but some individuals are not allergic to peanuts despite making peanut-specific IgE, and are considered peanut-tolerant. Here, the authors identify differences in blood immune cell composition of peanut-allergic and tolerant infants using mass cytometry, which may help uncover the mechanism of allergic tolerance.

Background Asian children born in Australia have higher rates of eczema and nut allergy than non-Asian children. However, it is not known whether this country of birth differential exists for other allergies or anaphylaxis risk. Objective We investigated the influence of maternal and child's country of birth on the prevalence of parent-reported eczema, asthma, food allergy and being diagnosed by a doctor as being "at risk of anaphylaxis." Methods We assessed the relationship between mother and child country of birth and allergies using the 2010 School Entrant Health Questionnaire, completed for 57 005 5-year old children (85.8% response rate) in Victoria, Australia. Analyses were conducted using logistic regression with results presented as odds ratios (OR) with 95% confidence intervals (CIs). Results Children born in Australia to Asian-born mothers were more likely to have parent-reported food allergy (OR 2.33, 95%CI 1.96-2.77) and eczema (OR 2.04, 95%CI 1.73-2.41), but not more likely to have asthma (OR 0.87, 95% CI 0.74-1.02) than non-Asian children. By contrast, children born in Asia who subsequently migrated to Australia had a lower risk of food allergy (OR 0.33, 95%CI 0.20-0.55), eczema (OR 0.37, 95%CI 0.24-0.57) and asthma (OR 0.29, 95% CI 0.21-0.40). Patterns of anaphylaxis risk differed depending on the trigger. Compared with Australian-born non-Asian children, Australian-born Asian children were more likely to be diagnosed as being at risk of both food-induced and non-food-induced anaphylaxis. For children born in Asia, risk was lower for anaphylaxis to milk, peanut and tree nuts compared to non-Asian children, but higher for soy, wheat and non-food triggers. Conclusions and clinical relevance Patterns of allergy/anaphylaxis risk and their triggers differed according to both ethnicity and country of birth, suggesting a gene-environment factor is in play. The difference in patterns for asthma compared with other atopic diseases is surprising and warrants further exploration.

INTRODUCTION: Eczema is a common childhood ailment responsible for a considerable disease burden. Both timing of introduction to solid food and allergenic food are believed to be related to childhood eczema. Despite the growing body of evidence, the relationship between timing of any solid food introduction (allergenic and/or non-allergenic) and development of eczema has not previously been systematically reviewed. METHODS: PubMed and EMBASE databases were searched using food and eczema terms. Two authors selected papers according to the inclusion criteria and extracted information on study characteristics and measures of association. Meta-analyses were performed after grouping studies according to the age and type of exposure. RESULTS: A total of 17 papers met the inclusion criteria, reporting results from 16 study populations. Of these, 11 were cohort studies, two case controls, one cross sectional study and, 2 randomised controlled trials. Limited meta-analyses were performed due to heterogeneity between studies. Timing of solid food introduction was not associated with eczema. One randomized controlled trial provided weak evidence of an association between early allergenic (around 4 months) food introduction and reduced risk of eczema. CONCLUSIONS: The available evidence is currently insufficient to determine whether the timing of introduction of any solid food influences the risk of eczema. This article is protected by copyright. All rights reserved.

This review summarizes the current state of play with regard to food allergy prevention. Food allergy prevention strategies focused on promoting timely introduction of allergenic foods (predominantly peanut) into the infant diet have recently been introduced in several countries. Additional prevention strategies currently under investigation include optimizing infant vitamin D levels, modulating the gut microbiota through use of probiotics, and preventing eczema to reduce the risk of food sensitization through a damaged skin barrier.

CAPSULE SUMMARY: This study provides the first evidence that early dietary exposure to cashew by age 1 year is associated with reduced risk of cashew allergy in a population-based cohort.

In the past decade, food allergy has been increasingly recognized as an important public health issue. The role of maternal and infant diet in the development of food allergy has been a major focus of research throughout this period. Recently, research in this area has moved from observational studies to intervention trials, and the findings from these trials have started to influence infant feeding guidelines. In this article, we review recent studies of dietary interventions for preventing food allergy, summarize current knowledge and discuss future research directions.The latest result from an intervention trial shows that introduction of peanut in the first year of life reduces the risk of peanut allergy in high-risk infants. A systematic review and meta-analysis of intervention trials also suggests a protective effect of egg introduction from around 4 to 6 months of age for reducing the risk of egg allergy, with most studies conducted in high-risk infants. Despite several intervention trials involving modifications to the maternal diet, the effect of maternal diet during pregnancy and lactation in preventing food allergy remains unclear.Earlier introduction of allergenic foods is a promising intervention to reduce the risk of some food allergies in high-risk infants. Further work is needed to improve knowledge of how to prevent food allergy in the general population.

Background The precautionary allergen labelling (PAL) and Voluntary Incidental Trace Allergen Labelling (VITAL® ) tools were designed by industry to assist consumers with selecting safe foods for consumption. However, a sizeable proportion of food products bear no label, and it is unclear whether these products are free from allergens and therefore safe to consume or have simply not undergone a risk assessment and therefore remain unlabelled for that reason. Objective To assess the prevalence of unlabelled products that have undergone a risk assessment process and to examine the factors influencing industry's uptake of the VITAL® process. Methods A web-based questionnaire was distributed to Australasian food and grocery manufacturers. Results One hundred and thirty-seven Australasian manufacturers were contacted, and 59 questionnaires were returned (response rate: 43%). The respondents represented 454 different manufacturing sites. Manufacturers reported that 23% (95% CI 19-28) of products (n=102/434) that had been through the VITAL® risk assessment process had no PAL statement on the label. 34% (95% CI 30-38), (n=204/600) of products that had undergone another (non-VITAL® ) risk assessment process had no PAL statement. In examining the factors that influenced industry's uptake of the VITAL® process, 25 manufacturers reported on factors that influenced the uptake of the VITAL® process, 76% (CI 95% 55-91) reported that VITAL® was an effective tool because it was based on science; 52% (CI 95% 31-72) reported that it was too time-consuming and 36% (CI 95% 18-57) identified a concern with it not being endorsed by the government. Conclusion and clinical relevance Currently, we estimate that at least 30% of products may have been through a risk assessment process and yet bear no PAL statement on the label. Permissive labelling could be incorporated onto these products if they have been assessed to be safe for consumption.

Background: A defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions. Objective: To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy. Method: We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these individuals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent sample group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components. Results: SPINK5 variant rs9325071 (A(long rightwards arrow)G) was associated with challenge-proven food allergy in the discovery sample (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also. Conclusions: We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.

Background: Cashew is a common cause of tree nut allergy in children. To date there have been few studies of diagnostic tests for cashew allergy, and positive predictive values (PPVs) for cashew as well as other tree nuts are largely extrapolated from studies of peanut allergy. How relevant these cutoffs are for cashew has not been formally explored. Objective: We aimed to establish skin prick test (SPT) wheal sizes that correlated to 95% PPV for a positive food challenge for cashew. Methods: We included all cashew oral food challenges (OFCs) conducted as part of the HealthNuts (n = 108; age, 4-6 years) and SchoolNuts (n = 37; age, 10-14 years) studies, both recruited from the community (population cohort). A second cohort of all cashew OFCs conducted at the Royal Children's Hospital (RCH) allergy center (n = 343) (2011-2016) and a private allergy clinic based at RCH (n = 43) was included via electronic medical record review (clinic cohort). The 95% PPV for cashew SPT was calculated for both cohorts. Results: Among the population cohort (n = 145), 62% of cashew OFCs were positive compared with 20% of the clinic cohort (n = 386). The SPT cutoff for 95% PPV derived from the population cohort was 10 mm (95% confidence interval [CI], 7.5-12.0). For the clinic cohort, the 95% PPV was 14 mm (95% CI, 9.5-unknown). An SPT wheal size of 8 mm had a PPV of 89% (95% CI, 79-95) in the population cohort and 62% (95% CI, 45-78) in the clinic cohort. Conclusion: A higher SPT wheal size may be more appropriate than the commonly used 8 mm cutoff to guide clinical decisions around when to perform OFC for cashew.

Background Longer duration of breastfeeding may be protective against asthma. However, early manifestations of allergic disease, such as eczema, are risk factors for asthma and can influence the duration of breastfeeding, and hence, may bias observable associations. Objective To examine the relationship between breastfeeding ever and duration and the development of asthma and allergic asthma phenotypes, stratified by a diagnosis of eczema during or after the breastfeeding period. Methods A total of 3663 children participated in the 6-year-old follow-up of the HealthNuts study, a population-based, longitudinal study of allergic diseases in Australia. At age 1 year, breastfeeding and eczema data were collected and at age 6 years, information on wheeze, medication use, and parental report of doctor-diagnosed asthma were obtained, both via questionnaire. Skin prick test responses to food and aeroallergens at age 6 years further distinguished asthmatic children into allergic and nonallergic phenotypes. Results Breastfeeding initiation was not associated with current asthma at age 6 years (adjusted odds ratio, 0.76; 95% CI, 0.45-1.29) when compared with never breastfeeding. Results were similar for length of exclusiveness and overall duration of breastfeeding, and allergic and nonallergic asthma phenotypes. However, increased duration of breastfeeding among children without eczema in infancy was associated with reduced odds of asthma (per month increase, adjusted odds ratio, 0.98; 95% CI, 0.95-1.0; P = .05), which equates to 0.86 (95% CI, 0.74-1.0) reduced odds of asthma for a 6-month increase in breastfeeding. This association was not apparent in children who were diagnosed with eczema during breastfeeding (adjusted odds ratio, 1.03; 95% CI, 0.98-1.08; P = .3). Conclusions Longer duration of breastfeeding was associated with a reduced odds of asthma among children without eczema in the first year of life; this association was masked before stratification by eczema in infancy. Future studies examining breastfeeding practices and the risk of allergic outcomes in later childhood need to consider the presence of early-life allergic manifestations impacting on breastfeeding behavior.

Background: High folate status in pregnancy has been implicated in the increased prevalence of allergic disease, but there are no published data relating directly measured folate status in pregnancy to challenge‐proven food allergy among offspring. The study aim was to examine the association between red blood cell (RBC) folate status in trimester three of pregnancy and allergic disease among offspring. Methods: Red blood cell folate levels were measured at 28‐32 weeks’ gestation in a prospective birth cohort (n = 1074). Food allergy outcomes were assessed in 1‐year‐old infants by skin prick testing and subsequent food challenge. Eczema was assessed by questionnaire and clinical review. High trimester three RBC folate was defined as greater than (>) 1360 nmol/L. Binomial regression was used to examine associations between trimester three RBC folate and allergic outcomes, adjusting for potential confounders. Results: Red blood cell folate levels were measured in 88% (894/1064) of pregnant women. The mean concentration was 1695.6 nmol/L (standard deviation 415.4) with 82% (731/894) >1360 nmol/L. There was no evidence of either linear or non‐linear relationships between trimester three RBC folate and allergic outcomes, nor evidence of associations between high RBC folate and food allergy (adjusted risk ratio (aRR) 2.89, 95% CI 0.90‐9.35), food sensitization (aRR 1.72, 95% CI 0.85‐3.49), or eczema (aRR 0.97, 95% CI 0.67‐1.38). Conclusion: The majority of pregnant women in this study had high RBC folate levels. There was no evidence of associations between trimester three RBC folate and food allergy, food sensitization, or eczema among the offspring, although larger studies are required.

Given an apparent increase in food allergies worldwide, the focus on prevention strategies has intensified. Following the Learning Early About Peanut study, there is now a widespread acceptance that peanut should be introduced promptly into the diet of high-risk infants. However, most food allergies are caused by triggers other than peanut and additional prevention strategies are being evaluated. The appreciation of the role of an impaired skin barrier in the process of food sensitization and subsequent allergy has led to a spectrum of dermatologically orientated studies. Other prevention strategies address the role of the microbiome, dietary components, and other modifiable risk factors. With regard to early introduction of foods other than peanut, studies are heterogeneous in design and governmental and professional society response to the early introduction trials has varied, ranging from new guidelines confining advice specifically to peanut, to ones recommending prompt introduction of a broad spectrum of allergenic foods. Much remains to be determined with regard to the acceptability and uptake of the new guidelines and their impact on infant feeding behavior and food allergy outcomes. This review discusses the panoply of prevention approaches, their promise, and limitations.

Background The current millennium has seen an explosion in vitamin D testing with the overarching aim of requests to clinically stratify patients as replete or deficient in vitamin D. At a population level, dried blood spot (DBS) sampling offers a less invasive and more practical application for assessment of vitamin D status. We have therefore aimed to develop a sensitive and robust DBS vitamin D method that is traceable to serum for use in population-based studies. Methods Blood spots, calibrators and controls were prepared by punching a 3.2 mm DBS from filter paper and placed into a 96-well micro-plate. The DBS disk was eluted with a combination of water-methanol and internal standard (ISTD) solution followed by supported-liquid extraction and derivatisation. The extract was analysed by liquid-chromatography tandem-mass spectrometry in positive electrospray-ionisation mode with 732.5 > 673.4 and 738.4 > 679.4 m/z ion-transitions for derivatised vitamin D and the ISTD, respectively. Vitamin D results were made traceable to the National Institute of Standards and Technology reference material through the inclusion of Chromsystems vitamin D calibrators. Results 25-Hydroxy-vitamin D3 and its related ISTD were detected at a retention time of 7 min. The seven-point calibration-curve consistently demonstrated a coefficient of determination of 0.99 with an experimentally determined reportable range of 0.5–376 nmol/L. Method validation studies using DBS samples demonstrated 12.9% between-assay imprecision at 45 nmol/L, 84% average recovery and high correlation with plasma vitamin D (correlation coefficient = 0.86). Conclusions We have successfully developed an analytical method for vitamin D quantitation from DBSs which will be applied to our population-based vitamin D research study. This approach improves traceability of DBS results and potentially could be used broadly for other DBS measurands that require comparison to serum/plasma for their interpretation.

Background Randomized controlled trials demonstrate that timely introduction of peanut to infants reduces the risk of peanut allergy. However, much debate remains regarding how to best achieve earlier peanut introduction at the population level. Our previous study in 2007-2011 (HealthNuts, n = 5300) indicated that few infants were consuming peanut in the first year. Australian infant feeding guidelines were updated in 2016 to recommend introducing peanut before 12 months for all infants. There were no data available on the subsequent effect on peanut introduction or peanut reactions. Objective We sought to assess the consequences of a nonscreening approach to allergenic food introduction in a population-based sample of infants in their first year of life. Methods EarlyNuts is a population-based, cross-sectional study of 12-month-old infants in Melbourne, Australia, recruited by using an identical sampling frame and methods to HealthNuts (72% response rate vs 73% response rate in HealthNuts). We report here on the first 860 participants recruited between November 2016 and October 2018. Results Most infants (88.6%; 95% CI, 86.1% to 90.7%) had introduced peanut by 12 months (median age, 6 months), an increase from 28.4% (95% CI, 27.2% to 29.7%) in the HealthNuts study. By 12 months, the majority of these (76.4%) had consumed peanut more than 4 times, and 28% were eating peanut more than once per week. Preliminary results on parent-reported reactions show that 4.0% of those consuming peanut by 12 months had possible IgE-mediated reactions. Conclusions There has been a striking shift toward earlier peanut introduction, with a 3-fold increase in peanut introduction by age 1 year in 2018 compared with 2007-2011.

Background Food allergy is most accurately diagnosed by a formal oral food challenge (OFC); however, it is time and labor intensive, risks the individual to severe reaction, and access is often a limiting step in the diagnostic process. This is compounded for tree nut allergy diagnosis as several OFCs may be required to determine allergy status to each individual tree nut. Accurate diagnosis using minimally invasive diagnostic tests in predicting clinical tree nut allergy is important to correctly identify those with potentially life-threatening reactions and to efficiently and safely tailor nut avoidance to only those nuts deemed allergic to enable less restricted diets and increased food choices for food allergic individuals. Objective To conduct a systematic review on the diagnostic capacity of clinical tests (skin prick test, specific IgE, component-resolved diagnostics, and basophil activation test) to determine OFC-proven or clinical tree nut allergy. Methods We searched 4 electronic databases (OVID Medline, Embase, Cochrane library, and PubMed) until May 2020. Eligible studies were categorized by type of tree nut and diagnostic test. Results A total of 27 studies assessed diagnostic accuracy to a specific tree nut. Overall, the accuracy of diagnostic testing was only reasonable, with 95% positive predictive values established in a small number of tree nuts. Cashew has best diagnostic accuracy, with the cashew component Ana o 3 being most predictive. At the other end of the spectrum, diagnostic testing of almond is poor and of limited clinical use. Conclusion The systematic review highlights the limitations of our current diagnostic tools for tree nut allergy and highlights further areas for research. The unidirectionality of cross-reactivity between cashew/pistachio and walnut/pecan is described and can aid diagnosis. Using diagnostic algorithms such as those demonstrated for walnut/pecan and cashew/pistachio allergy, greater diagnostic accuracy and reduced number of OFCs may be achieved.

Background There is a substantial body of evidence on the epidemiology of allergic conditions, which has advanced the understanding of these conditions. We aimed to systematically identify systematic reviews and meta-analyses on the epidemiology of allergic diseases to assess what has been studied comprehensively and what areas might benefit from further research. Methods We searched PubMed and EMBASE up to 12/2014 for systematic reviews on epidemiological research on allergic diseases. We indexed diseases and topics covered and extracted data on the search characteristics of each systematic review. Results The search resulted in 3991 entries after removing duplicates, plus 20 other items found via references and conference abstracts; 421 systematic reviews were relevant and included in this overview. The majority contained some evidence on asthma (72.9%). Allergic rhinitis, atopic eczema and food hypersensitivity were covered in 15.7%, 24.5% and 9.0%, respectively. Commonly studied risk factors for atopic eczema included dietary and microbial factors, while for asthma, pollution and genetic factors were often investigated in systematic reviews. There was some indication of differing search characteristics across topics. Conclusion We present a comprehensive overview with an indexed database of published systematic reviews in allergy epidemiology. We believe that this clarifies where most research interest has focussed and which areas could benefit from further research. We propose that this effort is updated every few years to include the most recently published evidence and to extend the search to an even broader list of hypersensitivity/allergic disorders.

The past few years have seen an exponential increase in publications on the topic of IgE-mediated food allergy. Recent publications have greatly advanced our understanding of the global prevalence of food allergy, and have revealed new insights into risk factors for food allergy. In this article, we will review these recent developments, summarise the current state of knowledge of the epidemiology of IgE-mediated food allergy, and outline areas of ongoing research where gaps in evidence remain. Recent publications reveal substantial differences in food allergy prevalence between countries. Data show that the incidence of food-induced anaphylaxis in developed countries continues to rise, particularly in children, although it remains unclear to what extent this is due to an increase in food allergy prevalence, or an increase in severe reactions among allergic individuals, or both. There has been considerable progress in understanding risk factors for food allergy. In particular, there is now good evidence that delayed introduction of peanut increases the risk of developing peanut allergy in infants with pre-existing risk factors for peanut allergy. A shift towards earlier introduction of peanut in these infants, now starting to be recommended in allergy prevention guidelines, may help to prevent peanut allergy in future generations. Recent studies have defined the prevalence of food allergy in different regions of the world. These studies provide strong baseline data to measure the extent to which new food allergy prevention strategies, including recommending timely peanut introduction for high-risk infants, change the prevalence of childhood food allergy.

Precautionary allergen labelling (PAL) continues to be used by the food manufacturing industry to alert the food allergic consumer that cross-contact may have occurred during the supply chain for ingredients or the manufacturing process. This review will summarize recent evidence regarding use and interpretation of precautionary labels by industry, healthcare professionals, and food allergic consumers. Consumers find precautionary labels difficult to interpret and often distrust them as disclaimers of product liability. It is unclear from a clinician's perspective how healthcare professionals should advise their patients regarding these statements.Recent studies suggest that consumers do not always read food labels and that these labels are difficult to interpret and are often distrusted by consumers as disclaimers of liability. There is evidence to suggest that this behaviour occurs in all countries assessed that use PAL. The healthcare professional remains confused about the interpretation and value of the current PAL system as it is unclear whether foods that contain no advisory labels are safe to consume. There is a need for improvement in the value and use of precautionary labelling for allergen risk assessment for allergic consumers.New studies have shown the confusion that currently exists in regard to PAL for the healthcare professional and the consumer alike. The studies have also highlighted certain gaps in the literature that, once addressed, will improve the uniformity of PAL and provide the healthcare professional with appropriate advice which they can in turn relay to the allergic consumer. Because of the global supply of food products there is a need for an international approach in improving PAL.

Aim To determine whether infant-feeding practices, including duration of exclusive breastfeeding and use of partially hydrolysed formula, modify the risk of developing infant food allergy. Methods In an observational population-based study, 1 year olds were recruited from community immunisation clinics in Melbourne, Australia. Parent-reported data on infant-feeding practices and potential confounders were collected prior to infant skin prick testing for four food allergens. Sensitised infants attended hospital-based oral food challenges to establish food allergy status. Multiple logistic regression was used to investigate associations between breastfeeding and formula-feeding and infant food allergy adjusting for possible confounding variables. Results A total of 5276 (74% response) infants participated. Of the 4537 for whom food allergy status was determined, 515 (11.3%) were food allergic (challenge-proven in the context of skin prick testing positive (≥2 mm)). After adjusting for confounding variables, there was no association between duration of exclusive breastfeeding and food allergy. Use of partially hydrolysed formula did not reduce the risk of food allergy compared with cow's milk formula in the general population (adjusted odds ratios 1.03 (confidence interval 0.67-1.50)). Conclusion Duration of exclusive breastfeeding and use of partially hydrolysed formula were not associated with food allergy at 1 year of age in this large population-based study. These findings have implications for population-based infant-feeding guidelines and do not support the use of partially hydrolysed formula for food allergy prevention.

Background Asian infants born in Australia are 3 times more likely to develop nut allergy than non-Asian infants and rates of challenge-proven food allergy in infants have been found to be unexpectedly high in metropolitan Melbourne. To further investigate risk factors for nut allergy we assessed the whole of State prevalence distribution of parent-reported nut allergy in 5 year old children entering school. Methods Using the 2010 School Entrant Health Questionnaire administered to all 5 year old children in Victoria, Australia, we assessed the prevalence of parent-reported nut allergy (tree nut and peanut) and whether this was altered by region of residence, socioeconomic status, country of birth or history of migration. Prevalence was calculated as observed proportion with 95% confidence intervals (CI). Risk factors were evaluated using multivariable logistic regression and adjusted for appropriate confounders. Results Parent-reported nut allergy prevalence was 3.1% (95%CI 2.9-3.2) amongst a cohort of nearly 60,000 children. It was more common amongst children of mothers with higher education and socioeconomic index and less prevalent amongst children in regional Victoria than in Melbourne. While children born in Australia to Asian-born mothers (aOR 2.67 95%CI 2.28, 3.27) were more likely to have nut allergy than non-Asian children, children born in Asia who subsequently migrated to Australia were at decreased risk of nut allergy (aOR 0.1 95%CI 0.03, 0.31). Conclusion Migration from Asia after the early infant period appears protective for the development of nut allergy. Additionally, rural regions have lower rates of nut allergy than urban areas. This article is protected by copyright. All rights reserved.

Vitamin D is critical to children’s skeletal development and health. Despite this, the factors which determine vitamin D concentrations during infancy remain incompletely understood. This article reviews the literature assessing the factors which can affect vitamin D status in infancy, including antenatal and postnatal vitamin D supplementation. Observational data supports that dietary intake of vitamin D, UV exposure, and geographic factors contribute significantly to infants’ vitamin D status, but the relationship is unclear regarding genetic variation, ethnicity, and maternal vitamin D status. Randomised controlled trials have compared higher versus lower doses of infant vitamin D supplementation, but no studies have compared infant vitamin D supplementation to placebo and eliminated external sources of vitamin D to fully quantify its effect on vitamin D status. Knowledge gaps remain regarding the factors associated with optimal vitamin D concentrations in infants—including key factors such as ethnicity and genetic variation—and further studies are needed.

Introduction: Food allergy currently affects up to 10% of infants. Identification and implementation of effective food allergy prevention strategies is thus imperative. Areas covered: We focus on five food allergy risk factors/prevention strategies which have been or are currently being tested in randomized controlled trials: (1) timely introduction of allergenic foods into the infant diet; (2) maternal diet and consumption of allergenic foods during pregnancy and breastfeeding; (3) infant skin barrier and the role of moisturizers in early life; (4) infant Vitamin D levels and the role of Vitamin D supplementation; and (5) microbial exposure in early life. Expert commentary: Earlier introduction of allergenic foods, particularly peanut, in the infant diet has been shown to reduce food allergy. Novel intervention strategies, including infant vitamin D supplementation, maternal diet modifications, and moisturizing infants to improve skin barrier, are currently being tested in large-scale clinical trials. As results of these trials become available, we hope strategies that are both efficacious and cost-effective will be revealed and their implementation in the population, along with the timely introduction of allergenic foods, will reduce the burden of food allergy in future generations.