Development of an intervention for reducing infant bathing frequency.

BACKGROUND: Bathing babies less frequently and intensively in the first six months of life may prevent eczema, but this has not yet been definitively tested in a randomised controlled trial. Such a trial would require evidence-based support to help parents engage with a minimal bathing routine. The present study reports the development of this support. METHODS: We adopted a four-stage design process: (i) Pregnant women and their families (n = 31) were interviewed to ascertain key barriers and facilitators towards following the minimal bathing intervention. (ii) These barriers and facilitators were mapped to behaviour change techniques, focussing on the intervention types of education, persuasion and environmental restructuring, alongside appropriate modes of delivery, and prototype intervention materials were developed. (iii) We iteratively refined these materials in a workshop with multidisciplinary experts and Patient and Public Involvement and Engagement (PPIE) representatives (n = 13) and an (iv) intervention walkthrough with families (n = 5). The design process was informed by the Behaviour Change Wheel, Theoretical framework of acceptability and the Template for intervention description and replication. RESULTS: Social influences and motivational factors are likely to influence both uptake and adherence to the intervention. Anticipated emotional reward from participating in research for the benefit of others was indicated to be a strong facilitator for intervention uptake. Alternatives to bathing, having fun with the baby and the night-time routine, alongside family support, were notable facilitators suggested to aid adherence to the intervention. Barriers included hygiene concerns and anticipated negative social appraisal. Barriers and facilitators were mapped to thirty-six behaviour change techniques, focussing on the intervention types of education, persuasion and environmental restructuring, all of which were embedded into the package of support. The prototype intervention materials received positive feedback from the expert workshop and study walkthrough with families. The final package of support comprises printed and digital prompts and cues, a study booklet, video, and digital tool for self-monitoring. CONCLUSIONS: The intervention design process incorporated the 'real world' views and experiences of families, experts and PPIE representatives, alongside criteria for designing behavioural interventions. The effectiveness of the package of support will be tested in a feasibility trial and embedded process evaluation.

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

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

Emollients for preventing atopic eczema: Cost-effectiveness analysis of the BEEP trial.

BACKGROUND: Recent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy. OBJECTIVE: To determine the cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children at 2 years from a health service perspective. We also considered a 5-year time horizon as a sensitivity analysis. METHODS: A within-trial economic evaluation using data on health resource use and quality of life captured as part of the BEEP trial alongside the trial data. Parents/carers of 1394 infants born to families at high risk of atopic disease were randomised 1:1 to the emollient group, which were advised to apply emollient (Doublebase Gel or Diprobase Cream) to their child at least once daily to the whole body during the first year of life or usual care. Both groups received advice on general skin care. The main economic outcomes were incremental cost-effectiveness ratio (ICER), defined as incremental cost per percentage decrease in risk of eczema in the primary cost-effectiveness analysis. Secondary analysis, undertaken as a cost-utility analysis, reports incremental cost per Quality-Adjusted Life Year (QALY) where child utility was elicited using the proxy CHU-9D at 2 years. RESULTS: At 2 years, the adjusted incremental cost was £87.45 (95% CI -54.31, 229.27) per participant, whilst the adjusted proportion without eczema was 0.0164 (95% CI -0.0329, 0.0656). The ICER was £5337 per percentage decrease in risk of eczema. Adjusted incremental QALYs were very slightly improved in the emollient group, 0.0010 (95% CI -0.0069, 0.0089). At 5 years, adjusted incremental costs were lower for the emollient group, -£106.89 (95% CI -354.66, 140.88) and the proportion without eczema was -0.0329 (95% CI -0.0659, 0.0002). The 5-year ICER was £3201 per percentage decrease in risk of eczema. However, when inpatient costs due to wheezing were excluded, incremental costs were lower and incremental effects greater in the usual care group. CONCLUSIONS: In line with effectiveness endpoints, advice given in the BEEP trial to apply daily emollient during infancy for eczema prevention in high-risk children does not appear cost-effective.

Timing of Allergenic Food Introduction and Risk of Immunoglobulin E-Mediated Food Allergy: A Systematic Review and Meta-analysis.

Importance: Earlier egg and peanut introduction probably reduces risk of egg and peanut allergy, respectively, but it is uncertain whether food allergy as a whole can be prevented using earlier allergenic food introduction. Objective: To investigate associations between timing of allergenic food introduction to the infant diet and risk of food allergy. Data Sources: In this systematic review and meta-analysis, Medline, Embase, and CENTRAL databases were searched for articles from database inception to December 29, 2022. Search terms included infant, randomized controlled trial, and terms for common allergenic foods and allergic outcomes. Study Selection: Randomized clinical trials evaluating age at allergenic food introduction (milk, egg, fish, shellfish, tree nuts, wheat, peanuts, and soya) during infancy and immunoglobulin E (IgE)-mediated food allergy from 1 to 5 years of age were included. Screening was conducted independently by multiple authors. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. Data were extracted in duplicate and synthesized using a random-effects model. The Grading of Recommendations, Assessment, Development, and Evaluation framework was used to assess certainty of evidence. Main Outcomes and Measures: Primary outcomes were risk of IgE-mediated allergy to any food from 1 to 5 years of age and withdrawal from the intervention. Secondary outcomes included allergy to specific foods. Results: Of 9283 titles screened, data were extracted from 23 eligible trials (56 articles, 13 794 randomized participants). There was moderate-certainty evidence from 4 trials (3295 participants) that introduction of multiple allergenic foods from 2 to 12 months of age (median age, 3-4 months) was associated with reduced risk of food allergy (risk ratio [RR], 0.49; 95% CI, 0.33-0.74; I2 = 49%). Absolute risk difference for a population with 5% incidence of food allergy was -26 cases (95% CI, -34 to -13 cases) per 1000 population. There was moderate-certainty evidence from 5 trials (4703 participants) that introduction of multiple allergenic foods from 2 to 12 months of age was associated with increased withdrawal from the intervention (RR, 2.29; 95% CI, 1.45-3.63; I2 = 89%). Absolute risk difference for a population with 20% withdrawal from the intervention was 258 cases (95% CI, 90-526 cases) per 1000 population. There was high-certainty evidence from 9 trials (4811 participants) that introduction of egg from 3 to 6 months of age was associated with reduced risk of egg allergy (RR, 0.60; 95% CI, 0.46-0.77; I2 = 0%) and high-certainty evidence from 4 trials (3796 participants) that introduction of peanut from 3 to 10 months of age was associated with reduced risk of peanut allergy (RR, 0.31; 95% CI, 0.19-0.51; I2 = 21%). Evidence for timing of introduction of cow's milk and risk of cow's milk allergy was very low certainty. Conclusions and Relevance: In this systematic review and meta-analysis, earlier introduction of multiple allergenic foods in the first year of life was associated with lower risk of developing food allergy but a high rate of withdrawal from the intervention. Further work is needed to develop allergenic food interventions that are safe and acceptable for infants and their families.

Varying Approaches to Management of IgE-Mediated Food Allergy in Children Around the World.

Food allergy is a chronic disease that affects individuals of all ages and is a significant public health problem globally. This narrative overview examines clinical management strategies for IgE-mediated food allergy in children around the world to understand variations in practice. Information was drawn from clinical practice guidelines, recent research, the websites of professional and governmental bodies with expertise in food allergy, and clinical experts from a broad cross-section of geographical regions. The structure and delivery of clinical services, allergen avoidance and food labeling, and resources to support the management of allergic reactions in the community are discussed in detail. The adoption of emerging food immunotherapies is also explored. Wide variations in clinical management of food allergy were apparent across the different countries. Common themes were continuing issues with access to specialist care and recognition of the need to balance risk reduction with dietary and social restrictions to avoid unnecessary detrimental impacts on the quality of life of food allergy sufferers. Findings highlight the need for standardized presentation of practice and priorities, and may assist clinicians and researchers when engaging with government and funding agencies to address gaps.

Early introduction of peanut reduces peanut allergy across risk groups in pooled and causal inference analyses.

BACKGROUND: The Learning Early About Peanut allergy (LEAP) study has shown the effectiveness of early peanut introduction in prevention of peanut allergy (PA). In the Enquiring About Tolerance (EAT) study, a statistically significant reduction in PA was present only in per-protocol (PP) analyses, which can be subject to bias. OBJECTIVE: The aim of this study was to combine individual-level data from the LEAP and EAT trials and provide robust evidence on the bias-corrected, causal effect of early peanut introduction. METHOD: As part of the European Union-funded iFAAM project, this pooled analysis of individual pediatric patient data combines and compares effectiveness and efficacy estimates of oral tolerance induction among different risk strata and analysis methods. RESULTS: An intention-to-treat (ITT) analysis of pooled data showed a 75% reduction in PA (p < .0001) among children randomized to consume peanut from early infancy. A protective effect was present across all eczema severity groups, irrespective of enrollment sensitization to peanut, and across different ethnicities. Earlier age of introduction was associated with improved effectiveness of the intervention. In the pooled PP analysis, peanut consumption reduced the risk of PA by 98% (p < .0001). A causal inference analysis confirmed the strong PP effect (89% average treatment effect relative risk reduction p < .0001). A multivariable causal inference analysis approach estimated a large (100%) reduction in PA in children without eczema (p = .004). CONCLUSION: We demonstrate a significant reduction in PA with early peanut introduction in a large group of pooled, randomized participants. This significant reduction was demonstrated across all risk subgroups, including children with no eczema. Furthermore, our results point to increased efficacy of the intervention with earlier age of introduction.

Emollients for prevention of atopic dermatitis: 5-year findings from the BEEP randomized trial.

BACKGROUND: The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years. METHODS: 1394 term infants with a family history of atopic disease were randomized (1:1) to daily emollient plus standard skin-care advice (693 emollient group) or standard skin-care advice alone (701 controls). Long-term follow-up at ages 3, 4 and 5 years was via parental questionnaires. Main outcomes were parental report of a clinical diagnosis of atopic dermatitis and food allergy. RESULTS: Parents reported more frequent moisturizer application in the emollient group through to 5 years. A clinical diagnosis of atopic dermatitis between 12 and 60 months was reported for 188/608 (31%) in the emollient group and 178/631 (28%) in the control group (adjusted relative risk 1.10, 95% confidence interval 0.93 to 1.30). Although more parents in the emollient group reported food reactions in the previous year at 3 and 4 years, cumulative incidence of doctor-diagnosed food allergy by 5 years was similar between groups (92/609 [15%] emollients and 87/632 [14%] controls, adjusted relative risk 1.11, 95% confidence interval 0.84 to 1.45). Findings were similar for cumulative incidence of asthma and hay fever. CONCLUSIONS: Daily emollient application during the first year of life does not prevent atopic dermatitis, food allergy, asthma or hay fever.

The hygiene hypothesis for allergy - conception and evolution.

In 1989, a short paper entitled "Hay fever, hygiene and household size" observed that British children from larger families were less likely to develop hay fever and suggested that this could be because early exposure to infection prevents allergy. This sibship size association for hay fever, since replicated many times in Britain and other affluent countries and confirmed by objective measures of atopy, prompted what has come to be known as the "hygiene hypothesis for allergy", although that term was not specifically used in the 1989 paper. The present paper reviews the historical roots of the "hygiene hypothesis" and charts its development over more than 30 years. Initial scepticism among immunologists turned to enthusiasm in the mid-1990s as the Th1/Th2 paradigm for allergic sensitisation emerged from animal experiments and the concept of "immunological old friends" became popular from the early 2000s. From the late 1990s, observations of reduced allergy risk among children of anthroposophic families and those brought up on farms suggested that the sibship size effects formed part of a broader range of "hygiene-related" determinants of allergy. Children from large families with farming exposure have approximately sixfold reduction in prevalence of hay fever, indicating the potential strength and epidemiological importance of these environmental determinants. During the 21st century, a wide range of specific microbial, environmental and lifestyle factors have been investigated as possible underlying mechanisms, but sadly none have emerged as robust explanations for the family size and farming effects. Thus, while the "hygiene hypothesis" led to a fundamental reappraisal of our relationship with our microbial environment and to the concept that early exposure, rather than avoidance, is beneficial for developing a healthy immune system, the underlying mechanism for variations in allergy prevalence with family size remains, in Churchillian terms, "a riddle wrapped in a mystery inside an enigma".

National Survey of United Kingdom Paediatric Allergy Services.

BACKGROUND: Comprehensive national assessments of paediatric allergy services are rarely undertaken, and have never been undertaken in the United Kingdom. A 2006 survey estimated national capacity at 30,000 adult or paediatric new allergy appointments per year and identified 58 hospital clinics offering a paediatric allergy service. OBJECTIVE: The UK Paediatric Allergy Services Survey was the first comprehensive assessment of UK paediatric allergy service provision. METHODS: All 450 UK hospitals responded to a survey. Paediatric allergy services are provided in 154 lead hospitals with 75 further linked hospitals. All 154 lead paediatric allergy services completed a detailed questionnaire between February 2019 and May 2020. RESULTS: The 154 paediatric allergy services self-define as secondary (126/154, 82%) or tertiary (28/154, 18%) level services. The annual capacity is 85,600 new and 111,400 follow-up appointments. Fifty-eight percent (85/146) of services offer ≤10 new appointments per week (no data provided from 8 services-2 no response, 6 unknown) and 50% (70/139) of the services undertaking challenges undertake ≤2 food or drug challenges per week (no data from 3 challenge services). Intramuscular adrenaline is rarely used during challenges-median annual frequency 0 in secondary services and 2 in tertiary services. Allergen-specific immunotherapy is offered in 39% (60/154) of services, with 71% (41/58) of these centres treating ≤10 patients per annum (no data from 2 immunotherapy services). The 12 largest services see 31% of all new paediatric allergy appointments, undertake 51% of new immunotherapy patient provision and 33% of food or drug challenges. Seventy percent (97/126) of secondary and all tertiary services are part of a regional paediatric allergy network. Only nine services offer immunotherapy for any food (3 for peanut), 10 drug desensitization and 18 insect venom immunotherapy. CONCLUSIONS: There has been a fourfold increase in paediatric allergy clinics and an approximately sevenfold increase in new patient appointment numbers in the United Kingdom over the past 15 years. Most services are small, with significant regional variation in availability of specific services such as allergen immunotherapy. Our findings emphasize the need for national standards, local networks and simulation training to ensure consistent and safe service provision.

Moving Complementary Feeding Forward: Report on a Workshop of the Federation of International Societies for Pediatric Gastroenterology, Hepatology and Nutrition (FISPGHAN) and the World Health Organization Regional Office for Europe.

The WHO Regional Office for Europe and the Federation of International Societies for Pediatric Gastroenterology, Hepatology, and Nutrition held a joint workshop, "Moving Complementary Feeding Forward" at the sixth World Congress Pediatric Gastroenterology, Hepatology, and Nutrition in 2021. Here we summarize workshop presentations and discussions. The workshop covered health implications of complementary feeding (CF) including allergies, challenges to meet dietary needs during the CF period, quality of commercial complementary foods (CFD) and respective marketing practices, national CF guidelines in Europe, a nutrient profiling system for CFD, and global policy perspectives on the standards and regulation of marketing for CFD. Adequate CF practices are of critical importance for short and long-term child health, prevention of nutrient deficiencies, normal growth and development, and reducing the risk of allergies. The workshop identified the need to improve feeding practices, harmonize evidence-based information and develop guidance jointly with various stakeholders, improve the composition and marketing practices of commercial CFD and their transparent labeling based on nutrient profiling. Renewed efforts for collaboration between scientists, public health experts, pediatric associations, national governments, and the WHO are necessary for advancing progress.

Detection and management of milk allergy: Delphi consensus study.

BACKGROUND: There is significant overdiagnosis of milk allergy in young children in some countries, leading to unnecessary use of specialized formula. This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and support carers of children with suspected milk allergy. METHODS: Delphi study involving two rounds of anonymous consensus building and an open meeting between January and July 2021. Seventeen experts in general practice, nutrition, midwifery, health visiting, lactation support and relevant areas of paediatrics participated, located in Europe, North America, Middle East, Africa, Australia and Asia. Five authors of previous milk allergy guidelines and seven parents provided feedback. FINDINGS: Participants agreed on 38 essential recommendations through consensus. Recommendations highlighted the importance of reproducibility and specificity for diagnosing milk allergy in children with acute or delayed symptoms temporally related to milk protein ingestion; and distinguished between children directly consuming milk protein and exclusively breastfed infants. Consensus was reached that maternal dietary restriction is not usually necessary to manage milk allergy, and that for exclusively breastfed infants with chronic symptoms, milk allergy diagnosis should only be considered in specific, rare circumstances. Consensus was reached that milk allergy diagnosis does not need to be considered for stool changes, aversive feeding or occasional spots of blood in stool, if there is no temporal relationship with milk protein ingestion. When compared with previous guidelines, these consensus recommendations resulted in more restrictive criteria for detecting milk allergy and a more limited role for maternal dietary exclusions and specialized formula. INTERPRETATION: These new milk allergy recommendations from non-conflicted, multidisciplinary experts advise narrower criteria, more prominent support for breastfeeding and less use of specialized formula, compared with current guidelines.

Food Proteins in Human Breast Milk and Probability of IgE-Mediated Allergic Reaction in Children During Breastfeeding: A Systematic Review.

BACKGROUND: Previous reports suggested that food proteins present in human milk (HM) may trigger symptoms in allergic children during breastfeeding, but existing evidence has never been reviewed systematically. OBJECTIVE: To assess the probability of food proteins in HM to trigger allergic reactions in infants with IgE-mediated food allergy. METHODS: Electronic bibliographic databases (MEDLINE, EMBASE) were systematically searched from inception to November 3, 2021. The data regarding the levels of food proteins detected in HM were extracted and compared with data from the Voluntary Incidental Trace Allergen Labelling (VITAL 3.0) guide to assess the probability of food-allergic individuals to experience immediate type allergic reactions on ingesting HM. RESULTS: A total of 32 studies were identified. Fourteen studies assessed excretion of cow's milk proteins into HM, 9 egg, 4 peanut, and 2 wheat; 3 measured levels of cow's milk and egg proteins simultaneously. We found that levels of all food proteins across the studies were much lower than the eliciting dose for 1% of allergic individuals (ED01) in most of the samples. The probability of an IgE-mediated allergic reaction in a food-allergic infant breastfed by a woman consuming the relevant food can be estimated as ≤1:1000 for cow's milk, egg, peanut, and wheat. CONCLUSIONS: To our knowledge, this is the first systematic review that assesses and summarizes evidence on food proteins in HM and potential for IgE-mediated allergic reactions. Our data suggest that the probability of IgE-mediated allergic reactions to food proteins in HM is low.

Frequency of guideline-defined cow's milk allergy symptoms in infants: Secondary analysis of EAT trial data.

BACKGROUND: Non-IgE-mediated Cow's Milk Allergy (CMA) has a prevalence of less than 1% in children. Guidelines developed to help non-specialists diagnose CMA may lead to misattribution of normal symptoms and contribute to overdiagnosis of CMA. We sought to establish the frequency of symptoms during infancy associated with non-IgE-mediated CMA, using the international Milk Allergy in Primary Care (iMAP) guideline as representative of CMA guidelines more generally. METHOD: Secondary analysis of the Enquiring About Tolerance (EAT) randomized controlled trial (ISRCTN 14254740; 1303 exclusively breastfed 3-month-old healthy infants). Key outcomes were ≥2 iMAP symptoms associated with 'mild-moderate' and 'severe' non-IgE-mediated CMA. RESULTS: Whilst breastfeeding and parental atopy rates were higher than the general population, participants were otherwise similar to the population of England and Wales. Two or more non-IgE CMA symptoms were reported by 25% families for mild-moderate and 1.4% for severe symptoms each month between ages 3 and 12 months, peaking at 38% with ≥2 mild-moderate and 4.3% ≥2 severe symptoms at three months, when participants were not directly consuming cow's milk. 74% of participants reported ≥2 mild-moderate symptoms and 9% ≥2 severe symptoms in at least one month during this period. At six months there was no evidence of difference in the proportion of children with ≥2 symptoms between those consuming (29.5% mild-moderate, 1.8% severe) and not consuming cow's milk (35.3% mild-moderate, 2.2% severe). Mean monthly reporting of ≥2 symptoms was also no different between those with (15.8% mild-moderate, 1.1% severe) or without eczema at baseline (16.7% mild-moderate, 1.3% severe). CONCLUSIONS: Guideline-defined symptoms of non-IgE-mediated CMA are very common in infants. Guidelines may promote milk allergy overdiagnosis by labelling normal infant symptoms as possible milk allergy.

Adherence to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist in articles published in EAACI Journals: A bibliographic study.

Research data derived from observational studies are accumulating quickly in the field of allergy and immunology and a large amount of observational studies are published every year. The aim of the present study was to evaluate the adherence to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist by papers published in the three European Academy of Allergy and Clinical Immunology journals, during the period 2009-2018. To this end, we conducted a bibliographic study of up to eight randomly selected papers per year per Journal. Our literature search resulted in 223 papers. Amongst those, 80, 80 and 63 records were from Paediatric Allergy and Immunology, Allergy and Clinical and Translational Allergy, respectively; the latter was published only from 2011 on. Prospective, case control and cross-sectional designs were described in 88, 43 and 92 papers, respectively. Full reporting of all STROBE items was present in 47.4%, 45.6% and 41.2% for the cohort, cross-sectional and case-control studies, respectively. Generally, no time trend in adherence of reporting STROBE items was observed, apart from reporting funding, which increased from 60% in 2009/2010 to more than 90% in 2018. We identified a cluster of STROBE items with low proportions of full reporting constituted by the items on reporting study design in the title and methods, variables types along with their measurement/assessment, bias and confounding, study size, and grouping of variables. It appears that the STROBE checklist is a suitable tool in observational allergy epidemiology. However, adherence to the STROBE checklist appeared suboptimal.