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Background: There are limited longitudinal data on the population prevalence of allergic conditions during childhood, and few studies have incorporated the reference standard oral food challenge to confirm food allergy., Objective: To describe the population prevalence of IgE-mediated food allergy, eczema, asthma, and rhinitis at ages 6 and 10 years in Melbourne, Australia., Methods: The HealthNuts study recruited 5,276 1-year-old infants in Melbourne, Australia, with repeat assessments at ages 6 and 10 years. At ages 6 and 10 years, carers completed a questionnaire on symptoms and doctor diagnosis of allergic conditions (International Study of Asthma and Allergies in Children). Children were invited to attend a clinic assessment including skin prick test, lung function tests, and oral food challenges when indicated. To minimize the impact of attrition bias, prevalence estimates among participants at ages 6 and 10 years were weighted to reflect characteristics of the whole cohort at recruitment., Results: In total, 4,455 and 4,065 families participated at ages 6 and 10 years, respectively (84% and 77% of the original cohort). Of those, 73% and 55% of participants ages 6 and 10 years, respectively, completed clinical assessments. Overall, 36.5% (95% CI, 34.8-38.2) and 38.2% (95% CI, 36.5-40.1%) of 6- and 10-year-olds had at least one current allergic disease, and around one third of those had two or more allergic diseases. Food allergy occurred in 6.4% (95% CI, 5.6-7.2) of 6-year olds and 6.3% (95% CI, 5.5-7.2) of 10-year-olds. Among infants with challenge-confirmed food allergy in infancy, 45% had persistent disease at age 10 years. The prevalence of current diagnosed asthma at ages 6 and 10 years were 12.1% (95% CI, 10.9-13.3) and 13.1% (95% CI, 11.9-14.4), respectively, current eczema decreased slightly from 15.3% (95% CI, 14.1-19.7) at age 6 years to 12.9% (95% CI, 11.7-14.2) at age 10 years, and current rhinitis increased from 15.1% (95% CI, 13.9-16.5) at age 6 years to 25.0% (95% CI, 23.4-26.7) at age 10 years., Conclusions: Allergic diseases affect 40% of primary school-age children; one third have multiple allergic diagnoses. Challenge-confirmed food allergy prevalence remains high, and 45% of infants with food allergy have persistent disease to age 10 years., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Eczema is a common chronic debilitating skin condition in childhood. Data on the epidemiology and natural history of eczema across the life course are lacking. This analysis aimed to describe these epidemiological features in Australian children and adults., Methods: Data collected on eczema from four Australian cohort studies were analysed: namely HealthNuts, Melbourne Atopic Cohort Study (MACS), Tasmanian Longitudinal Health Study (TAHS) and the Australian arm of the European Community Respiratory Health Survey (ECRHS)., Results: Among children aged under 6 years, 28.8%-35.6% have ever-had eczema, and 16.7%-26.6% had 'current eczema'. Among those aged 6-12 years, 14.6%-24.7% had 'current eczema' with 12.0%-18.5% of those at ages of 6 and 10 years classified as having moderate-to-severe eczema according to the Scoring of Atopic Dermatitis (SCORAD) index. In adults, the prevalence of 'eczema ever' ranged between 13.8% and 48.4%. The 12-month period prevalence of eczema was 15.1% at age 18, while current eczema was 8.5% at an average age of 51, and 8.8% at an average age 53 years. Eczema was more common among young boys, but this difference became non-significant for older children and early adolescents. In contrast, eczema was more common for adult women than men., Conclusions: Eczema is common both in children and adults. The proportion of severe eczema in children was substantial., (© 2022 The Authors. Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Background: While the relationship between pollen and respiratory allergies is well-documented, the role of short-term pollen exposure in food allergy and eczema flares has not previously been explored. We aimed to investigate these associations in a population-based sample of children., Methods: We investigated 1- (n = 1108) and 6-year-old (n = 675) children in the grass pollen season from the HealthNuts cohort. Grass pollen concentrations were considered on the day of testing (lag 0), up to three days before (lag 1-lag 3) and cumulatively (lag 0-3). Associations between grass pollen and food skin-prick test reactivity (SPT ≥ 2 mm at age 1 year and ≥ 3 mm at age 6 years), eczema flares, challenge-confirmed food allergy, reaction threshold to oral food challenges (OFC), and serum food-specific IgE levels were analyzed using either logistic or quantile regression models. Atopy and family history of allergic disease were considered as potent effect modifiers., Results: Grass pollen at lag 0-3 (every 20 grains/m 3 increase) was associated with an up to 1.2-fold increased odds of food SPT reactivity and eczema flares in 6-year-olds. In 1-year-olds, the associations were only observed for peanut in those with a family history of food allergy. Increasing grass pollen concentrations were associated with a lower reaction threshold to OFC and higher serum IgE levels in peanut-allergic 1-year-olds only., Conclusion: Increasing grass pollen concentration was associated with increased risk of food SPT reactivity and eczema flares in children. The associations in peanut-allergic infants may be related to immune activation and/or peanut and grass pollen cross-reactivity leading to a lower reaction threshold., (© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Prospectively collected data on the natural history of food allergy are lacking., Objective: We examined the natural history of egg and peanut allergy in children from age 1 to 6 years and assessed whether a skin prick test (SPT) result or other clinical factors at diagnosis are associated with the persistence or resolution of food allergy in early childhood., Methods: The HealthNuts cohort consists of 5276 children who were recruited at age 1 year and have been followed prospectively. Children with food allergy at age 1 year (peanut [n = 156] or raw egg [n = 471] allergy ) and children who developed new sensitizations or food reactions after age 1 year were assessed for food sensitization and allergy (confirmed by oral food challenge when indicated) at the 6-year follow-up., Results: New-onset food allergy developed by age 6 years was more common for peanut (0.7% [95% CI = 0.5%-1.1%]) than egg (0.09% [95% CI = 0.03%-0.3%]). Egg allergy resolved more commonly (89% [95% CI = 85%-92%]) than peanut allergy (29% [95% CI = 22%-38%]) by age 6 years. The overall weighted prevalence of peanut allergy at age 6 years was 3.1% (95% CI = 2.6-3.7%) and that of egg allergy was 1.2% (95% = CI 0.9%-1.6%). The factors at age 1 year associated with persistence of peanut allergy were peanut SPT result of 8 mm or larger (odds ratio [OR] = 2.35 [95% CI 1.08-5.12]), sensitization to tree nuts (adjusted OR [aOR] = 2.51 [95% CI = 1.00-6.35]), and early-onset severe eczema (aOR = 3.23, [95% CI 1.17-8.88]). Factors at age 1 associated with persistence of egg allergy at age 6 were egg SPT result of 4 mm or larger (OR = 2.98 [95% CI 1.35-6.36]), other (peanut and/or sesame) food sensitizations (aOR = 2.80 [95% CI = 1.11-7.03]), baked egg allergy (aOR = 7.41 [95% CI = 2.16-25.3]), and early-onset severe eczema (aOR = 3.77 [95% CI = 1.35-10.52])., Conclusion: Most egg allergy and nearly one-third of peanut allergy resolves naturally by age 6 years. The prevalence of peanut allergy at age 6 years was similar to that observed at age 1 year, largely owing to new-onset food peanut allergy after age 1 year. Infants with early-onset eczema, larger SPT wheals, or multiple food sensitizations and/or allergies were less likely to acquire tolerance to either peanut or egg., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Grass pollen exposure is a risk factor for childhood asthma hospital attendances. However, its short-term influence on lung function, especially among those with other allergic conditions, has been less well-studied., Objective: To investigate this association in a population-based sample of children., Methods: Within the HealthNuts cohort, 641 children performed spirometry during the grass pollen season. Grass pollen concentration was considered on the day of testing (lag 0), up to 3 days before (lag 1-lag 3), and cumulatively (lag 0-3). We used linear regression to assess the relevant associations and examined potential interactions with current asthma, hay fever or eczema, and food allergy., Results: Associations were observed only in children with allergic disease (P value for interaction ≤ 0.1). In children with food allergy, grass pollen concentration was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV 1 /FVC) and lower mid-forced expiratory flows (FEF 25%-75% ) at all lags (eg, at lag 2, FEV 1 /FVC z-score = -0.50 [95% CI -0.80 to -0.20] and FEF 25%--75% z-score = -0.40 [-0.60 to -0.04] per 20 grains/m 3 pollen increase), and increased bronchodilator responsiveness (BDR) at lag 2 and lag 3 (eg, at lag 2, BDR = (31 [95% CI -0.005 to 62] mL). In children with current asthma, increasing grass pollen concentration was associated with lower FEF 25%-75% and increased BDR, whereas children with current hay fever or eczema had increased BDR only., Conclusions: A proactive approach needs to be enforced to manage susceptible children, especially those with food allergy, before high-grass pollen days., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Early life body mass index (BMI) trajectories influence the risk of asthma at 18 years of age. However, it is unclear if these are also associated with other allergic diseases., Objectives: We investigated the associations between BMI trajectories and subsequent allergic rhinitis, eczema and food sensitisation/allergies., Methods: Parent-reported anthropometric data were collected 18 times in the first two years of life from a cohort of 620 participants in a high-risk cohort. Group-based trajectory modelling was applied to develop BMI trajectories. Associations between trajectories and allergic rhinitis, eczema and food sensitisation at 6, 12 and 18 years of age were assessed using logistic regression models. Potential effect modifications by parental allergic disease, sex and allocated infant formula were assessed., Results: We identified five BMI trajectories: average, below average, persistently low, early low and catch up, and persistently high. None showed an association with allergic rhinitis. In participants with maternal allergic rhinitis, 'early-low and catch-up' (OR = 2.83;95%CI 1.34-5.96, P int  = 0.05) and 'below average' trajectories (OR = 2.39; 1.18-7.23, P int  = 0.02) were associated with allergic rhinitis at 18 years of age compared with the average trajectory. No associations were observed with eczema or food sensitisation., Conclusion: Infants with early-low and catch-up, or below average BMI growth, were at increased risk of allergic rhinitis at 18 years if they had a mother with allergic rhinitis. These results require replication, but suggest that interactions between poor intrauterine growth, failure to thrive and maternal allergies may influence the risk of allergic rhinitis., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

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 (P<0.001). Egg introduction was more often delayed (>10 months) in Singapore (63.5%) than Australia (16.3%; P<0.001). Prevalence of early-onset eczema (<6 months) was lower in Singapore (8.4%) than Australia (30.5%) (P<0.001). Children with early-onset eczema were more likely to have food allergy than those without eczema in Australia [aOR 5.11 (2.34-11.14); P<0.001] and Singapore [aOR4.00 (0.62-25.8); P = 0.145]., Conclusions: Among Asian children, prevalence of early-onset eczema and food allergy was higher in Australia than Singapore. Further research with larger sample sizes and harmonized definitions of food allergy between cohorts is required to confirm and extend these findings. Research on environmental factors influencing eczema onset in Australia and Singapore may aid understanding of food allergy pathogenesis in different parts of the world., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background and Objective: As 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., Methods: Parent-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., Results: Complete 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., Conclusions: In two unselected populations using harmonised protocols, the likely association of caesarean delivery with developing childhood allergy was small., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: We previously reported that infants with Asian-born parents are 3 times more likely to have IgE-mediated food allergy than those with Australian-born parents. It is unknown whether this translates to the increased risk of other allergic diseases later in childhood and whether ancestry interacts with other risk factors for allergic disease development., Objective: To compare prevalence and risk factors for allergic rhinitis, asthma, and aeroallergen sensitization at age 6 between children with East Asian-born and Caucasian-born parents., Methods: A total of 5276 1-year-old infants were recruited into a population-based longitudinal study of allergy. A total of 4455 children participated in age 6 follow-up (84.4%), including 3015 with Caucasian-born parents and 415 with East Asian-born parents. Children underwent skin prick tests to aeroallergens and questionnaires captured data on asthma, eczema, and allergic rhinitis., Results: Compared with children with Caucasian-born parents, children of East Asian-born parents had more allergic rhinitis (19.9% [95% confidence interval (CI) 14.9-26] vs 9.3% [95% CI 8-10.8], P < .001) and aeroallergen sensitization (64.3% [95% CI 57.5-70.5] vs 34.4% [95% CI 32.2-36.7], P < .001) at age 6. Asthma was similar in both groups (9.1% [95% CI 6.2-13.2] vs 11.7% [95% CI 10.4-13.1]), P = .21. Children with IgE-mediated food allergy and eczema in infancy were 3 times more likely to have asthma and 2 times more likely to have allergic rhinitis at age 6, irrespective of ancestry., Conclusions: Children of East Asian ancestry born in Australia have a higher burden of most allergic diseases in the first 6 years of life, whereas asthma may follow a different pattern. IgE-mediated food allergy and eczema at age 1 increase the risk of asthma and allergic rhinitis irrespective of ancestry., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Despite the rising rates of anaphylaxis in older children and adolescents, risk factors for food allergy among this age group are understudied., Objective: The objective of this study was to investigate the risk factors for current adolescent food allergy using a population-based sample., Methods: The SchoolNuts study was a questionnaire survey among 10- to 14-year-old adolescents and their parents, followed by clinic evaluation including oral food challenge when food allergy was suspected from questionnaire response. We investigated the association between food allergy and demographic and environmental factors among a total of 4,991 adolescents using multiple logistic regression., Results: Males and those with early-onset eczema had a higher risk of current food allergy in adolescence (adjusted odds ratio [aOR], 1.55; 95% confidence interval [CI], 1.12-2.15 and aOR, 14.08; 95% CI, 10.25-19.33). Those with Asian parents had increased risk compared with those with Caucasian parents (aOR, 2.82; 95% CI, 1.91-4.16), whereas being born in Asia compared with being born in Australia had decreased risk (aOR, 0.16; 95% CI, 0.04-0.67). Family history risk was higher for those with multiple members versus only 1 member (aOR, 4.62; 95% CI, 2.75-7.74 and aOR, 2.32; 95% CI, 1.36-3.97, respectively). Dog exposure during the first 5 years of life was associated with a decreased risk (aOR, 0.58; 95% CI, 0.38-0.91)., Conclusions: Early-onset eczema, Asian background, and family history of allergic disease were associated with an increased risk of food allergy, whereas dog exposure in early life reduced the risk in 10- to14-year-old adolescents. Factors predicting food allergy risk in an adolescent population-based cohort appear remarkably similar to those predicting early-onset food allergy in infancy., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The HealthNuts study previously reported interim prevalence data showing the highest prevalence of challenge-confirmed food allergy in infants internationally. However, population-derived prevalence data on challenge-confirmed food allergy and other allergic diseases in preschool-aged children remain sparse., Objective: This study aimed to report the updated prevalence of food allergy at age 1 year from the whole cohort, and to report the prevalence of food allergy, asthma, eczema, and allergic rhinitis at age 4 years., Methods: HealthNuts is a population-based cohort study with baseline recruitment of 5276 one-year-old children who underwent skin prick test (SPT) to 4 food allergens and those with detectable SPT results had formal food challenges. At age 4 years, parents completed a questionnaire (81.3% completed) and those who previously attended the HealthNuts clinic at age 1 year or reported symptoms of a new food allergy were invited for an assessment that included SPT and oral food challenges. Data on asthma, eczema, and allergic rhinitis were captured by validated International Study of Asthma and Allergies in Childhood questionnaires., Results: The prevalence of challenge-confirmed food allergy at age 1 and 4 years was 11.0% and 3.8%, respectively. At age 4 years, peanut allergy prevalence was 1.9% (95% CI, 1.6% to 2.3%), egg allergy was 1.2% (95% CI, 0.9% to 1.6%), and sesame allergy was 0.4% (95% CI, 0.3% to 0.6%). Late-onset peanut allergy at age 4 years was rare (0.2%). The prevalence of current asthma was 10.8% (95% CI, 9.7% to 12.1%), current eczema was 16.0% (95% CI, 14.7% to 17.4%), and current allergic rhinitis was 8.3% (95% CI, 7.2% to 9.4%). Forty percent to 50% of this population-based cohort experienced symptoms of an allergic disease in the first 4 years of their life., Conclusions: Although the prevalence of food allergy decreased between age 1 year and age 4 years in this population-based cohort, the prevalence of any allergic disease among 4-year-old children in Melbourne, Australia, is remarkably high., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: An altered compositional signature and reduced diversity of early gut microbiota are linked to development of allergic disease. We investigated the relationship between dominant Bifidobacterium species during the early post-natal period and subsequent development of allergic disease in the first year of life., Methods: Faecal samples were collected at age 1 week, 1 month and 3 months from 117 infants at high risk of allergic disease. Bifidobacterium species were analysed by quantitative PCR and terminal restriction fragment length polymorphism. Infants were examined at 3, 6 and 12 months, and skin prick test was performed at 12 months. Eczema was diagnosed according to the UK Working Party criteria., Results: The presence of B. catenulatum at 3 months was associated with a higher risk of developing eczema (OR adj = 4.5; 95% CI: 1.56-13.05, p adj = 0.005). Infants colonized with B. breve at 1 week (OR adj = 0.29; 95% CI: 0.09-0.95, p adj = 0.04) and 3 months (OR adj = 0.15; 95% CI: 0.05-0.44, p adj = 0.00001) had a reduced risk of developing eczema. Furthermore, the presence of B. breve at 3 months was associated with a lower risk of atopic sensitization at 12 months (OR adj = 0.38; 95% CI: 0.15-0.98, p adj = 0.05). B. breve colonization patterns were influenced by maternal allergic status, household pets and number of siblings., Conclusions: Temporal variations in Bifidobacterium colonization patterns early in life are associated with later development of eczema and/or atopic sensitization in infants at high risk of allergic disease. Modulation of the early microbiota may provide a means to prevent eczema in high-risk infants., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Postnatal vitamin D supplementation may be associated with a reduction in IgE-mediated food allergy, lower respiratory tract infections and improved bone health. Countries in the Northern hemisphere recommend universal infant vitamin D supplementation to optimise early vitamin D levels, despite the absence of large trials proving safety or efficacy for any disease outcome. With the aim of determining the clinical and cost-effectiveness of daily vitamin D supplementation in breastfed infants from age 6-8 weeks to 12 months of age, we have started a double-blind, randomised, placebo-controlled trial of daily 400 IU vitamin D supplementation during the first year of life, VITALITY., Methods Nd Analysis: Infants (n=3012) who are fully breastfed and not receiving vitamin D supplementation will be recruited at the time of their first immunisation, from council-led immunisation clinics throughout metropolitan Melbourne, Australia. The primary outcome is challenge-proven food allergy at 12 months of age. Secondary outcomes are food sensitisation (positive skin prick test), number of lower respiratory infections (through hospital linkage), moderately-severe and persistent eczema (by history and examination) and vitamin D deficiency (serum vitamin D <50 nmol/L) at age 12 months. The trial is underway and the first 130 participants have been recruited., Ethics and Dissemination: The VITALITY study is approved by the Royal Children's Hospital (RCH) Human Research Ethics Committee (#34168). Outcomes will be disseminated through publication and will be presented at scientific conferences., Trial Registration Numbers: ANZCTR12614000334606 and NCT02112734; pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

HealthNuts is a single-centre, multi-wave, population-based longitudinal study designed to assess prevalence, determinants, natural history and burden of allergy (particularly food allergy) in the early years of life. It is novel in the use of serial food challenge measures within its population frame to confirm food allergy. The cohort comprises 5276 children initially recruited at age 12 months from council-run immunization sessions across Melbourne, Australia. As well as parent-completed questionnaires and researcher-observed eczema status, all infants underwent skin-prick testing to egg, peanut, sesame and either cow's milk or shellfish, and those with detectable wheals underwent food challenges to determine clinical allergy. In wave 2, conducted at age 4 years, validated questionnaires collected data on asthma, allergic rhinitis (hay fever), eczema and food allergies. Food challenges were repeated in children previously identified as food allergic to determine resolution. In wave 3, all children (irrespective of food allergy status) were invited for clinical assessment at age 6 years, including lung function, physical measurements, skin-prick testing to foods and aeroallergens and food challenges if food sensitized. Biological specimens (blood, cheek swabs) were collected at each wave for ancillary immunological, genetic and epigenetic studies. Applications to access data and/or samples can be submitted to [katrina.allen@mcri.edu.au]., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Regulatory T cells (Treg) play an essential role in early immune programming and shaping the immune response towards a pro-allergic or tolerant state. We evaluated cord blood Treg and cytokine responses to microbial and non-microbial stimuli in infants at high risk of allergic disease and their associations with development of allergic disease in the first year., Methods: Cord blood mononuclear cells from 72 neonates were cultured with toll-like receptors (TLR2) ligands: lipoteichoic acid (LTA) and heat-killed Lactobacillus rhamnosus GG (HKL); TLR4 ligand: lipopolysaccharide (LPS); ovalbumin (OVA); anti-CD3; or media for 48 h. Treg numbers and Treg cytokines were assessed in relation to allergic disease outcomes during the first year of life (eczema and atopic sensitization)., Results: Infants with eczema (n = 24) had reduced percentages of FoxP3(hi)CD25(hi) Treg in LTA (p = 0.01, adj p = 0.005) and HKL (p = 0.04, adj p = 0.02) stimulated cultures as well as reduced IL-10 (p = 0.01) production following HKL stimulation compared to those without eczema (n = 48). No differences in Treg or cytokine responses to LPS, OVA or anti-CD3 were seen. Infants who developed sensitization had lower percentages of Treg following TLR2 stimulation (but not other stimuli) compared to non-sensitized infants., Conclusions: High-risk children who develop allergic disease in the first year of life have deficient Treg responses to microbial stimuli but not allergen from the time of birth, which may contribute to failure of immune tolerance development in infancy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The overall beneficial effects of breastfeeding for infants have been well documented, but its role in allergy prevention is controversial., Objective: We investigated the relationship between breast milk immunomodulatory factors and subsequent development of eczema and atopic sensitization in the first year of life., Methods: Day 7 and 28 breast milk samples were collected from mothers carrying infants at high risk of allergic disease. Aqueous-phase breast milk samples were assayed for TGF-β1, sCD14 and total IgA. Infants were assessed for the presence of eczema and atopic sensitization at 12 months of age. The levels of breast milk TGF-β1, sCD14 and total IgA were compared in infants who subsequently developed eczema and sensitization in the first year and those who did not., Results: The levels of breast milk sCD14, total IgA, and TGF-β1 at either day 7 or 28 were not associated with subsequent development of eczema or atopic sensitization during the first year of life., Conclusion: Levels of breast milk immune parameters were not associated with eczema outcomes or sensitization in infants at 12 months. This suggests that apparent immunological effects on breast milk immunomodulatory factors may not necessarily lead to clinical benefits, and these immune markers may not be critical determinants of allergic disease in infancy., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Background: Alterations in intestinal microflora have been linked to the development of allergic disease. Recent studies suggest that healthy infant immune development may depend on the establishment of a diverse gut microbiota rather than the presence or absence of specific microbial strains., Objectives: We investigated the relationship between diversity of gut microbiota in the early postnatal period and subsequent development of eczema and atopy in the first year of life., Methods: Fecal samples were collected 1 wk after birth from 98 infants at high risk of allergic disease, who were followed prospectively to age 12 months. Fecal microbial diversity was assessed by terminal restriction fragment length polymorphism (T-RFLP) using restriction enzymes Sau96I and AluI, with a greater number of peaks representing greater diversity of bacterial communities., Results: Microbial diversity at day 7 was significantly lower in infants with eczema at age 12 months as compared to infants without eczema (AluI mean number of peaks 13.1 vs. 15.5, p = 0.003, 95% CI for difference in means -3.9, -0.8; Sau96I 14.7 vs. 17.2, p = 0.03, 95% CI -4.9, -0.3). No differences were observed for atopic compared to non-atopic infants, or infants with two allergic parents compared to those with one or no allergic parent., Conclusions: A more diverse intestinal microbiota in the first week of life is associated with a reduced risk of subsequent eczema in infants at increased risk of allergic disease. Interventions that enhance microbial diversity in early life may provide an effective means for the prevention of eczema in high-risk infants., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Background and Objective: As 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.Methods: Parent-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.Results: Complete 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.Conclusions: In two unselected populations using harmonised protocols, the likely association of caesarean delivery with developing childhood allergy was small. [ABSTRACT FROM AUTHOR]

Background: Probiotic supplementation to mothers and/or their term‐born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants. Methods: This sub‐study was an a priori secondary outcome of the ProPrems multi‐center, double‐blind, placebo‐controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens. Results: There was no difference in eczema incidence between the probiotic and placebo groups (35[30%] of 118 infants vs 37[27%] of 137 infants, respectively, absolute difference 2.65%, 95% CI −8.45 to 13.75). Similarly, the incidence of atopic eczema (6[5%] of 118 vs 3[2%] of 137), food allergy (4[3%] of 124 vs 2[1%] of 154), wheeze (39[31%] of 127 vs 45[29%] of 154), and atopic sensitization (14[13%] of 106 vs 13[11%] of 123) were similar between the probiotic and placebo groups. Conclusion: This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction The overall beneficial effects of breastfeeding for infants have been well documented, but its role in allergy prevention is controversial. Objective We investigated the relationship between breast milk immunomodulatory factors and subsequent development of eczema and atopic sensitization in the first year of life. Methods Day 7 and 28 breast milk samples were collected from mothers carrying infants at high risk of allergic disease. Aqueous-phase breast milk samples were assayed for TGF-β1, sCD14 and total Ig A. Infants were assessed for the presence of eczema and atopic sensitization at 12 months of age. The levels of breast milk TGF-β1, sCD14 and total Ig A were compared in infants who subsequently developed eczema and sensitization in the first year and those who did not. Results The levels of breast milk sCD14, total Ig A, and TGF-β1 at either day 7 or 28 were not associated with subsequent development of eczema or atopic sensitization during the first year of life. Conclusion Levels of breast milk immune parameters were not associated with eczema outcomes or sensitization in infants at 12 months. This suggests that apparent immunological effects on breast milk immunomodulatory factors may not necessarily lead to clinical benefits, and these immune markers may not be critical determinants of allergic disease in infancy. [ABSTRACT FROM AUTHOR]

Hydrolyzed formulae are created by using enzymatic processes to break native proteins into smaller fragments. They may prevent development of allergic diseases by reducing exposure to intact allergens. Partially hydrolyzed whey formula (pHWF) is particularly promising for allergy prevention, as it is cheap to manufacture and palatable. Scientific organizations have recommended the use of hydrolyzed formula in the first 4-6 months of life for the prevention of allergic disease based on a limited number of trials. Three recent developments challenge these recommendations: our growing understanding of the importance of allergen exposure for induction of immune tolerance, recently published evidence that failed to identify a protective effect of pHWF, which the authors and other experts believe will necessitate updating of systematic reviews, and methodological limitations of available trials and systematic reviews on which these recommendations are based. Until more definitive evidence is obtained, the authors recommend continuing to advocate that 'breast is best', and caution against overstating the potential for pHWF to prevent allergic disease. INSET: Key issues. [ABSTRACT FROM AUTHOR]