HealthNuts Study Research Articles

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

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. 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. 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. 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. 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.

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

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. To describe the population prevalence of IgE-mediated food allergy, eczema, asthma, and rhinitis at ages 6 and 10 years in Melbourne, Australia. 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. 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. 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.

Mass cytometry analysis of blood from peanut-sensitized tolerant and clinically allergic infants

IgE-mediated food allergies in infants are a significant health concern, with peanut allergy being of particular interest due to its prevalence and severity. Among individuals who produce peanut-specific IgE some experience no adverse reaction on peanut consumption. This asymptomatic phenotype is known as sensitized tolerance. To elucidate the immune environment of peanut sensitized tolerant and clinically allergic one-year-olds, high-dimensional mass cytometry was conducted as part of the HealthNuts study. The resulting data includes peripheral blood mononuclear cells from 36 participants encompassing non-allergic, peanut sensitized with tolerance, and clinically peanut allergic infants. The raw mass cytometry data is described here and freely available for reuse through the Immunology Database and Analysis Portal (ImmPort). Additional allergy information and serum vitamin D levels of the participants were measured and are also included in the data upload. These high-dimensional mass cytometry data, when combined with clinical information, offer a broad immune profile of peanut allergic and sensitized tolerant infants.

Characteristics of cow's milk allergy and sensitization in Chinese patients.

Characteristics of cow's milk allergy and sensitization in Chinese patients.

Out-of-hospital health care costs of childhood food allergy in Australia: A population-based longitudinal study.

Australia has one of the highest prevalence of childhood food allergy in the world, but there are no data on its economic burden in Australia. We used data from the HealthNuts study, a population-based longitudinal study undertaken in Melbourne, Australia. Infants were recruited at age 12 months between Sept 2007 and Aug 2011 with food allergy diagnosed using oral food challenges. Health care costs of out-of-hospital services were collected through data linkage to Australia's universal health insurance scheme Medicare. Two-part model was used to compare costs after controlling for potential confounders. 2919 children were included, and 390 (13.4%) had challenge-confirmed food allergy at age 1year. Compared with children without food allergy, children with food allergy had significantly higher costs for GP visits, specialist visits, tests, and prescriptions in the first four years of life. The total Medicare cost associated with food allergy from age 1 to 4 years was estimated to be AUD$889.7 (95% CI $566.1-$1188.3) or €411.0 (95% CI €261.5-€549.0) per child. This was projected into an annual Medicare cost of AUD$26.1 million (95% CI $20.1-$32.3 million) or €12.1 (95% CI €9.3-€14.9 million) based on population size in 2020. Childhood food allergy causes considerable Medicare costs for out-of-hospital services in the first four years after birth in Australia. These findings can help anticipate the financial impact on the health care system associated with childhood food allergy, act as a useful costing resource for future evaluations, and inform management of childhood food allergy internationally.

Infant feeding patterns before and after changes to food allergy prevention guidelines in Australia

Food allergy is an important public health problem in Australia. Randomised controlled trials have provided evidence that introducing infants to peanut and egg early reduces the risk of developing allergies to these foods.1 The Australian Infant Feeding Summit was therefore held in 2015 to review infant feeding recommendations.2 Based on a consensus among expert stakeholders (state and federal health care agencies, consumers, and experts in allergy, infant feeding, and population health), and with the aim of providing clear guideline advice to the public while balancing the need for food allergy prevention and other nutritional priorities, including the known benefits of breastfeeding, three recommendations were made: to introduce solid foods at about six months (but not before four months) of age; to introduce peanut and egg during the first twelve months of life; and to no longer use hydrolysed infant formula for preventing allergy.2 These recommendations were incorporated into the infant feeding guidelines of the Australasian Society of Clinical Immunology and Allergy in 2016.3 We have previously reported that introducing peanut during the first year of life increased in Melbourne after the new guidelines were introduced, from 28% of infants during 2007–11 to more than 88% during 2017–19.4 In this article, we report our assessment of breastfeeding rates, the introduction of solid foods, and the use of partially hydrolysed formula before and after the new Australian guidelines were published. We analysed data from two population-based studies we had undertaken using the same recruitment methods and sampling frame.4 Twelve-month-old infants were recruited at local council vaccination sessions in Melbourne, for the HealthNuts study during 2007–11, and for EarlyNuts during 2017–19. Their parents completed questionnaires including items on infant feeding practices (Box 1), with similar response rates (HealthNuts, 74%; EarlyNuts, 76%). The Royal Children’s Hospital Human Research Ethics Committee approved each study (HealthNuts, #27047; EarlyNuts, #36160). The proportion of infants breastfed for at least twelve months was larger during 2017–2019 than 2007–2011 (52.7%; 95% confidence interval [CI], 50.3–55.0% v 35.9%; 95% CI, 34.5–37.2%), and the proportion of those who received formula slightly smaller (76.0%; 95% CI, 74.0–77.9% v 80.1%; 95% CI, 79.0–81.2%); changes in the proportions of infants ever breastfed or who received partially hydrolysed formula were not statistically significant. The proportion of infants introduced to solid foods at four months increased (31.9%; 95% CI, 29.7–34.1% v 19.2%; 95% CI, 18.2–20.4%), but not that of those introduced very early (before four months) (Box 2). Breastfeeding rates were higher in the Melbourne EarlyNuts study than in the 2017–18 National Health Survey5 — breastfeeding ever, 95% v 93%; at least twelve months, 53% v 41% — but a smaller proportion had been introduced to solid food at six months or later (39% v 48%). As EarlyNuts was a food allergy study, rates of breastfeeding and the adoption of guideline recommendations among its participants may have been higher than for the general population. Our findings suggest that introducing common food allergens early is not associated with a decline in breastfeeding. They do not establish a causal relationship between the new allergy guidelines and changes in infant feeding outcomes, but it is reassuring that the proportion of breastfed infants did not decline after their publication. Timely introduction of allergens can be recommended without concern that it might curtail breastfeeding or increase extremely early introduction to solid foods. We recommend ongoing monitoring of breastfeeding, timing of the introduction of solid and allergenic foods, and the incidence of food allergy in Australia. The EarlyNuts study was supported by the National Health and Medical Research Council (NHMRC; GNT1146769) and the Murdoch Children's Research Institute. Research at the Murdoch Children's Research Institute is supported by the Victorian Government Operational Infrastructure Program. Victoria Soriano is supported by a PhD scholarship from the NHMRC-funded Centre for Food and Allergy Research (GNT1134812). Jennifer Koplin (GNT1158699), Merryn Netting (GNT1156518), and Rachel Peters (GNT1160779) are supported by NHMRC fellowships. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians. No relevant disclosures.

Mode of Birth Is Not Associated With Food Allergy Risk in Infants

The association between mode of delivery and the risk of food allergy remains unclear due to the absence of studies with both challenge-proven food allergy outcomes and detailed information on the type of caesarean delivery. We assessed whether emergency or elective caesarean, or caesarean delivery in the presence or absence of labor initiation, is associated with the risk of food allergy. The HealthNuts study recruited 5276 12-month-old infants who underwent skin prick testing and oral food challenge to ascertain food allergy status, and linked the child's study data to additional birth data from the Victorian Perinatal Data Collection. Parents of 3006 children consented to data linkage, and birth data were obtained on 2045. In this subgroup, 30% were born by caesarean and 13% had food allergy. Caesarean delivery, compared with vaginal birth, was not associated with the risk of food allergy (adjusted odds ratio [aOR]: 0.95, 95% confidence interval [CI]: 0.70, 1.30). Neither caesarean delivery before the onset of labor, nor after the onset of labor, was associated with the risk of food allergy (aOR: 0.83, 95% CI: 0.55-1.23 and aOR: 1.13, 95% CI: 0.75-1.72, respectively). Delivery by elective or emergency caesarean, compared with vaginal delivery, was not associated with risk of food allergy (aOR: 1.05, 95% CI: 0.71-1.55 and aOR: 0.86, 95% CI: 0.56-1.31). There was no evidence of effect modification by breastfeeding, older siblings, pet dog ownership, or maternal allergy. Caesarean delivery, either with or without labor, or elective or emergency, was not associated with the risk of food allergy in a population-based cohort of 12-month-old infants.

The association between environmental greenness and the risk of food allergy: A population-based study in Melbourne, Australia.

While exposure to environmental greenness in childhood has shown mixed associations with the development of allergic disease, the relationship with food allergy has not been explored. We investigated the association between exposure to environmental greenness and challenge-confirmed food allergy in a large population-based cohort. The HealthNuts study recruited 5276 12-month-old infants in Melbourne, Australia, who underwent skin prick testing to peanut, egg, and sesame; infants with a detectable wheal underwent food challenges to determine food allergy status. Environmental greenness was estimated using the normalized difference vegetation index (NDVI) for five buffer zones around the infant's home address: at the home, 100m, 500m, 800m, and 1600m radial distances. Environmental greenness was categorized into 3 tertiles and mixed effects logistic regression models quantified the association between greenness and the risk of food allergy, adjusting for confounding and accounting for clustering at the neighborhood level. NDVI data were available for n=5097. For most buffer zones, medium and high greenness, compared to low greenness, was associated with an increased risk of peanut allergy (eg, 100m tertile 2 aOR 1.89 95% CI 1.22-2.95, tertile 3 aOR 1.78 95% CI 1.13-2.82). For egg allergy, the effect sizes were smaller (100 m tertile 2 aOR 1.52 95% CI 1.16-1.97, tertile 3 aOR 1.38 95% CI 1.05-1.82). Socioeconomic status (SES) modified the association between greenness and peanut allergy, but not egg allergy; associations were apparent in the low SES group but not in the high SES group (p for interaction 0.08 at 100m). Air pollution (PM2.5) also modified the associations between environmental greenness and food allergy, with associations present in high air pollution areas but not low (p for interaction at 100m 0.05 for peanut and 0.06 for egg allergy.) CONCLUSION: Increased exposure to environmental greenness in the first year of life was associated with an increased risk of food allergy. Increased greenness may correlate with higher pollen levels which may trigger innate immune responses skewing the immune system to the Th2-dependent allergic phenotype; additionally, some pollen and food allergens are cross-reactive. Given the mixed data on greenness and other allergies, the relationship appears complex and may also be influenced by confounding variables outside those that were measured in this study.

Community-Based Adverse Food Reactions and Anaphylaxis in Children With IgE-Mediated Food Allergy at Age 6 Years: A Population-Based Study

To investigate the frequency, characteristics, and risk factors of community-based adverse food reactions, including anaphylaxis, among children with food allergies at 6 years of age in a population-based cohort: the HealthNuts study.The HealthNuts study is a longitudinal population-based study of childhood allergic disease in Melbourne, Australia in which researchers originally enrolled 5276 12-month old infants from community immunization clinics. In this report, 3233 children from this cohort are involved who, at 6 years of age, returned for an assessment. An additional 1222 only completed a questionnaire.All caregivers completed questionnaires, and children underwent skin-prick tests to milk, egg, peanut, soy, wheat, sesame, shellfish, cashew, almond, hazelnut and a panel of aeroallergens. Oral food challenges (OFCs) were performed for eligible children. Children were identified as definite or probable food allergy on the basis of skin tests and/or a history of food reactions or results of OFCs. A total of 413 children were eligible for an OFC.A total of 260 children were confirmed as having a food allergy. A total of 44.6% reported an adverse food reaction in the previous 12 months, nearly one-third having >1, with 73% likely immunoglobulin E–mediated. The most common symptoms were hives and vomiting. The most common foods were nuts and egg. One-half of the reactions occurred at home, with restaurants second (11.6%). A total of 28 children reported anaphylactic reactions; nearly one-half were not recognized as such by parents. Tree nuts (mostly cashew) and peanuts accounted for 65% of the anaphylactic reactions. Epinephrine autoinjectors were used in only 13.8% of all anaphylaxis episodes, only 25% of the parent-recognized anaphylaxis episodes, and none of the unrecognized anaphylaxis episodes. There were no risk factors identified for experiencing an adverse food reaction or anaphylaxis, but children with nut allergies were less likely to report an adverse food reaction compared with those without a nut allergy.A high-frequency of adverse food reactions and anaphylaxis in food-allergic children at the age of 6 years occurred in this population-based cohort study. Only one-half of the episodes of anaphylaxis were identified as such, and only 25% of those were treated with an Epinephrine autoinjector. Improved regular education on the prevention of adverse food reactions and recognition and management of anaphylaxis is needed.Pediatricians and other primary care practitioners need to review avoidance measures, possible symptoms or signs of anaphylaxis, and the importance of epinephrine as first-line therapy for anaphylaxis as part of their well-child care for patients with food allergies.

The Interplay Between Eczema and Breastfeeding Practices May Hide Breastfeeding’s Protective Effect on Childhood Asthma

Early allergic disease manifestations in infants may influence breastfeeding practices. In the current study, researchers sought to examine the relationship between breastfeeding duration and the development of asthma and allergic asthma phenotypes, stratified by a diagnosis of eczema during or after breastfeeding.Children who participated in the 6 year follow-up of the HealthNuts study, a population-based, longitudinal cohort study of allergic diseases in Australia.Children were enrolled between the ages of 11 and 15 months, and data regarding breastfeeding history, eczema diagnosis, environmental exposures, and family history of allergic disease were collected via questionnaire. At 6 years, information on wheeze, medication use, and parental report of physician-diagnosed asthma were obtained. Skin-prick testing to foods and aeroallergens at the age of 6 helped to stratify children with asthma into allergic and nonallergic phenotypes. From an original cohort of 5276 children, 3663 had completed questionnaires at 6 years, 3111 underwent skin testing, and 3632 had asthma data available for analysis. Children were characterized as never or ever breastfed. Of those breastfed, exclusive breastfeeding was categorized as never, <6 months, or >6 months. The overall duration of breastfeeding was treated as both a continuous (number of months) and categorical variable (<3 months, 3 to <6 months, 6 to <12 months, or >12 months).Children who did not participate in the full questionnaire at the age of 6 were more likely to be never breastfed, from a lower socioeconomic background, have one or both parents born outside of Australia, have no family history of allergic disease, and have had exposure to prenatal maternal or environmental smoking. Among children with asthma data, 96% were breastfed. At the age of 6, the prevalence of current asthma was 13%. Children with asthma were more likely to be male, have a parental history of asthma, have a family history of allergic disease, have been born preterm, have been born via cesarean delivery, and have been exposed to maternal smoking during pregnancy. Breastfeeding initiation was not associated with current asthma at the age of 6 years (adjusted odds ratio: 0.76) when compared with never breastfeeding. An increased duration of breastfeeding in children without eczema in infancy was associated with a reduced odds of asthma (per month increase; adjusted odds ratio: 0.98), which equates to a 0.86 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.A longer duration of breastfeeding was associated with a reduced odds of asthma at the age pf 6 years among children without history of eczema in the first year. This association was masked before stratification of patients by history of eczema in infancy.Breastfeeding is known to be beneficial for improving many health outcomes. However, previous studies have not clearly demonstrated protective effects for breastfeeding on asthma. In the current study, a modest protective association was observed between an increased duration of breastfeeding and asthma but only among children who were not diagnosed with eczema in their first year. This association is complex because infantile eczema is a known risk factor for asthma and has also been shown to influence breastfeeding choices. Additional study is needed on the interplay between breastfeeding practices, early allergic manifestations, and the risk of subsequent allergic outcomes.

Backyard benefits? A cross-sectional study of yard size and greenness and children\u2019s physical activity and outdoor play

BackgroundThe 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.MethodsData 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.ResultsData 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.ConclusionIn 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.

Earlier Ingestion of Peanut After Changes to Infant Feeding Guidelines: The EarlyNuts Study

VX Soriano, RL Peters, AL Ponsonby. J Allergy Clin Immunol. 2019;144(5):1327–1335.e5 In 2016, Australian feeding guidelines were updated to recommend early introduction of peanut (PN) and egg without screening high-risk infants beforehand. The aim of this study was to assess the consequences of that change on the rate of early introduction and the prevalence of PN and egg allergy as compared with the HealthNuts study ( J Allergy Clin Immunol 2014;133(2):476-484). This was a population-based, cross-sectional, observational study. The first 860 infants (11–15 months) who agreed to participate were recruited from immunization sessions in Melbourne. Feeding practices were compared with those identified after 2008 when Australian guidelines removed recommendations to avoid early introduction of allergenic foods. PN introduction was earlier …

The Interplay Between Eczema and Breastfeeding Practices May Hide Breastfeeding's Protective Effect on Childhood Asthma

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. 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. 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. 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). 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.

Community-Based Adverse Food Reactions and Anaphylaxis in Children with IgE-Mediated Food Allergy at Age 6 Years: A Population-Based Study

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. 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. 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. 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). 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.

Food Allergy Is an Important Risk Factor for Childhood Asthma, Irrespective of Whether It Resolves

To determine if food allergy at age 1 year is associated with an increased risk of asthma at age 4 years.The study population was drawn from the HealthNuts study, a population-based cohort study of allergic disease in Melbourne, Australia. The primary analysis in the current study includes 2789 participants (out of 5276 in the HealthNuts population) with complete data on exposure, outcome, and confounders of interest.The primary exposure was food allergy at age 1 year, and the primary outcome was asthma at age 4 years. At enrollment, all participants had skin prick tests to egg, peanut, sesame, and cow’s milk or shrimp. Children with positive skin prick test results (sensitized) were offered an oral food challenge to determine if they had food allergy. Children with food allergy were reassessed at age 4 years for resolution of allergy. The primary outcome of asthma was obtained by parental report of physician diagnosis when the children were 4 years old. Atopic dermatitis was also evaluated at baseline.Children with food allergy at age 1 year had a significantly increased risk of asthma at age 4 years compared with nonsensitized children (relative risk = 2.13; 95% confidence interval [CI]: 1.71–2.64). Sensitized children without food allergy also had a less-strong, borderline significant elevated risk of asthma. The authors observed a dose response: children who had 2 or more food allergies had a higher risk of asthma than children with 1 food allergy. There was no difference in asthma risk among children whose food allergy resolved by age 4 years compared with those with persistent food allergy. Although the risk of asthma was similarly elevated in those with either atopic dermatitis or food allergy at age 1 year, comorbid eczema and food allergy were associated with the highest risk of asthma (relative risk = 2.9; 95% CI: 2.22–3.70). Overall, preexisting wheeze and/or asthma did not explain the association between early food allergy and asthma.In this population-based study, children with food allergy in the first year of life had increased risk of asthma. The risk of asthma persisted regardless of whether there was resolution of food allergy. Allergy to multiple foods or comorbid atopic dermatitis at age 1 year were associated with an even higher risk of asthma.This large population-based study of average-risk children demonstrates that food allergy at age 1 year is a risk for subsequent asthma, even if the food allergy resolved. This early observation can be used to identify children at risk for asthma who may benefit from close monitoring and early intervention and may help provide insight into underlying mechanisms of atopy and asthma pathogenesis.

Patterns of Tree Nut Sensitization and Allergy in the First 6 Years of Life in a Population–Based Cohort

To determine the prevalence of tree nut allergy at age 6 years and investigate the relationship between egg and peanut allergy at age 1 year and tree nut allergy at age 6 years to guide testing and introduction advice.This study included infants recruited between 11 and 15 months for the longitudinal HealthNuts study in Melbourne, Australia.At entry, all subjects underwent skin prick testing (SPT) to egg, peanut, and sesame. At age 1 year, egg and peanut allergy were determined by oral food challenge. SPT to tree nuts (almond, cashew, hazelnut) was performed, and parental history of symptoms with tree nut ingestion was obtained. Those with negative SPT results were advised to introduce tree nuts at home; avoidance was recommended for those with positive SPT results. At age 6 years, a questionnaire was administered, SPT was performed, and tree nut allergy was assessed by food challenge.Five thousand two hundred seventy-sixchildren participated in the HealthNuts study at age 1. One thousand one hundred fourteen (21%) underwent additional evaluation, including SPT for tree nuts. At age 1 year, 6 parents (0.1%) reported a history consistent with tree nut allergy. Among those with challenge-confirmed egg or peanut allergy at age 1 year, 41% were already sensitized to 1 or more tree nuts, with an even higher rate in those with both allergies. At age 6, the prevalence of tree nut allergy was 3.3%, with cashew being the most common trigger, followed by hazelnut and almond. Forty-three percent of those with any tree nut allergy had peanut allergy. Of those with peanut allergy, 45% reacted to 1 or more tree nuts, most commonly cashew. In examining predictors of tree nut allergy, 14% of those with egg allergy at age 1 year, 27% of those with peanut allergy at age 1, and 37% of those with both egg and peanut allergy at age 1 had tree nut allergy at age 6 years.There is a low parent-reported rate of tree nut allergy at age 1 year, likely due to low tree nut consumption in the first year of life. However, 33% of those with peanut allergy and 41% of those with peanut or egg allergy are already sensitized to 1 or more tree nuts at age 1, with a higher rate in those with allergy to both foods. More than one-third of those with tree nut sensitization at age 1 are allergic to 1 or more tree nuts at age 6. Almost half of those with both peanut and egg allergy at age 1 have tree nut allergy at age 6. The prevalence of tree nut allergy at age 6 (3.3%) is similar to that of peanut allergy (2.8%), with cashew being the most common tree nut allergen.This study reports a high rate of tree nut sensitization and potential for allergy in those with egg and/or peanut allergy at age 1 and highlights the need to investigate the best approach to tree nut evaluation in those with known food allergy as well as strategies to prevent tree nut allergy in this at-risk population.

Earlier ingestion of peanut after changes to infant feeding guidelines: The EarlyNuts study

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 12months for all infants. There were no data available on the subsequent effect on peanut introduction or peanut reactions. 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. 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. Most infants (88.6%; 95% CI, 86.1% to 90.7%) had introduced peanut by 12months (median age, 6months), an increase from 28.4% (95% CI, 27.2% to 29.7%) in the HealthNuts study. By 12months, 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 12months had possible IgE-mediated reactions. There has been a striking shift toward earlier peanut introduction, with a 3-fold increase in peanut introduction by age 1year in 2018 compared with 2007-2011.

Severity and threshold of peanut reactivity during hospital-based open oral food challenges: An international multicenter survey.

Peanut allergy is classically managed by food avoidance. Immunotherapy programs are available at some academic centers for selected patients reacting to small amounts of peanut during food challenge. We aimed to determine and compare reaction thresholds and prevalence of anaphylaxis during peanut oral challenges at multiple specialist allergy centers. A retrospective, international survey of anonymized case records from seven specialist pediatric allergy centers from the UK and Ireland, as well as the Australian HealthNuts study. Demographic information, allergy test results, reaction severity and threshold during open oral peanut challenges were collated and analyzed. Of the 1634 children aged 1-18years old included, 525 (32%) failed their peanut challenge. Twenty-eight percent reacted to 25mg, while 38% only reacted after consuming 1g or more of whole peanut. Anaphylaxis (55 [11%]) was 3 times more common in teenagers than younger children and the likelihood increased at all ages as children consuming more peanut at the challenge. Children who developed anaphylaxis to 25-200mg of whole peanut were significantly older. Previous history of reaction did not predict reaction threshold or severity. More than a third of the children in this large international cohort tolerated the equivalent of one peanut in an oral challenge. Anaphylaxis, particularly to small amounts of peanut, was more common in older children. Tailored immunotherapy programs might be considered not only for children with low, but also higher reaction thresholds. Whether these programs could prevent heightened sensitivity and anaphylaxis to peanut with age also deserves further study.

The Prevalence of Food Sensitization Appears Not to Have Changed between 2 Melbourne Cohorts of High-Risk Infants Recruited 15 Years Apart

Although food allergy has probably risen over recent decades, recent reports suggest that the prevalence of food sensitization in the general population has not changed. However, this has not been analyzed in infants at high risk of food allergy. The objective of this study was to compare the prevalence of food sensitization in high-risk infants from 2 cohorts recruited 15 years apart in the same region. This study includes 620 high-risk infants with a family history of allergy (Melbourne Atopy Cohort Study [MACS]) born 1990-1994, and a subgroup of high-risk infants from the population-based HealthNuts study (n= 3,661/5,276), born 2006-2010. Both studies undertook skin prick tests (SPT) to peanut, egg, and milk at age 12 months. A logistic regression model generated adjusted prevalences to account for differences in sampling frame. SPT ≥ 95% positive predictive values (PPVs) for food allergy were used as proxies for food allergy. The adjusted prevalence of sensitization in MACS was similar to the observed prevalence of sensitization in the high-risk subgroup of HealthNuts: 7.9% (95% confidence interval 6.8-8.9) and 7.9% (7.0-8.8) respectively for peanut, 15.0% (13.4-16.6) and 14.5% (13.4-15.7) respectively for egg, and 2.4% (1.6-3.1) and 2.6% (2.0-3.4) respectively for cow's milk. The prevalence of SPT ≥ 95% PPVs was similar between the 2 studies. The prevalence of food sensitization among high-risk infants has remained stable in Australia since the 1990s, despite the reported increase in food-related anaphylaxis in the same period. This discrepancy could be due to increased food allergy in the low-risk population, increased conversion of food sensitization to allergy, or increased number of high-risk infants. Alternatively, increased awareness or severity of reactions may have led to an apparent increase in food allergy.

Genetic variation at the Th2 immune gene IL13 is associated with IgE-mediated paediatric food allergy.

Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells. Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy. We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed. IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE. We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.