Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy.

BACKGROUND: Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. OBJECTIVES: This study tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive treatment to clinically affected skin only. METHODS: This was a multicenter, parallel-group, open-label, assessor-blind, randomized controlled trial (PACI [Prevention of Allergy via Cutaneous Intervention] study). This study enrolled infants 7-13 weeks old with atopic dermatitis and randomly assigned infants in a 1:1 ratio to enhanced early skin treatment or conventional reactive treatment using topical corticosteroids (TCSs). The primary outcome was the proportion of immediate hen's egg allergy confirmed by oral food challenge at 28 weeks of age. RESULTS: This study enrolled 650 infants and analyzed 640 infants (enhanced [n = 318] or conventional [n = 322] treatment). Enhanced treatment significantly reduced hen's egg allergy compared with the conventional treatment (31.4% vs 41.9%, P = .0028; risk difference: -10.5%, upper bound of a 1-sided CI: -3.0%), while it lowered body weight (mean difference: -422 g, 95% CI: -553 to -292 g) and height (mean difference: -0.8 cm, 95% CI: -1.22 to -0.33 cm) at 28 weeks of age. CONCLUSIONS: This study highlighted the potential of well-controlled atopic dermatitis management as a component of a hen's egg allergy prevention strategy. The enhanced treatment protocol of this trial should be modified before it can be considered as an approach to prevent hen's egg allergy in daily practice to avoid the adverse effects of TCSs. After remission induction by TCSs, maintenance therapy with lower potency TCSs or other topical therapies might be considered as alternative proactive treatments to overcome the safety concerns of TCSs.

[The advances on oral tolerance induction for prevention of egg allergy in infants].

The prevalence of food allergy is increasing worldwide and seriously affects the living quality of patients and their families. Egg allergy is one of the commonest forms of food allergy. The traditional regimen is to delay the introduction of eggs to infant complementary foods, which is not able to reduce the prevalence of egg allergies and causes negative effects on infants' physical and psychological conditions. Oral tolerance therapy is an approach to establish immune tolerance by the active suppression of specific immune responses to antigens in the gastrointestinal tract. The development of oral tolerance through early introduction of eggs to infant complementary has proven effective in randomized controlled trials, which has been incorporated into infant feeding guidelines in many countries. This article focuses on the mechanism, efficacy and safety of oral tolerance induction in the prevention of egg allergy.

Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL): a factorial, multicentre, cluster-randomised trial.

BACKGROUND: Primary prevention of food allergy by early introduction of allergenic foods seems promising. We aimed to determine whether early food introduction or the application of regular skin emollients in infants from a general population reduced the risk of food allergy. METHODS: This 2 × 2 factorial, cluster-randomised trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway, and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine 18-week ultrasound examination were cluster-randomised at birth to the following groups: (1) no intervention group; (2) the skin intervention group (skin emollients; bath additives and facial cream; from age 2 weeks to <9 months, both at least four times per week); (3) the food intervention group (early complementary feeding of peanut, cow's milk, wheat, and egg from age 3 months); or (4) combined intervention group (skin and food interventions). Participants were randomly assigned (1:1:1:1) using computer-generated randomisation based on clusters of 92 geographical areas and eight 3-month time blocks. Study personnel performing clinical assessments were masked to group allocation. The primary outcome was allergy to any interventional food at 36 months of age. The primary efficacy analysis was done by intention-to-treat analysis, which included all participants who were randomly assigned, apart from three individuals who withdrew their consent. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). This study is registered as ClinicalTrials.gov, NCT02449850. FINDINGS: We recruited 2697 women with 2701 pregnancies, from whom 2397 newborn infants were enrolled between April 14, 2015, and April 11, 2017. Of these infants, 597 were randomly assigned to the no intervention group, 575 to the skin intervention group, 642 to the food intervention group, and 583 to the combined intervention group. One participant in each of the no intervention, food intervention, and skin intervention groups withdrew consent and were therefore not included in any analyses. Food allergy was diagnosed in 44 children; 14 (2·3%) of 596 infants in the non-intervention group, 17 (3·0%) of 574 infants in the skin intervention group, six (0·9%) of 641 infants in the food intervention group, and seven (1·2%) of 583 infants in the combined intervention group. Peanut allergy was diagnosed in 32 children, egg allergy in 12 children, and milk allergy in four children. None had allergy to wheat. Prevalence of food allergy was reduced in the food intervention group compared with the no food intervention group (risk difference -1·6% [95% CI -2·7 to -0·5]; odds ratio [OR] 0·4 [95% CI 0·2 to 0·8]), but not compared with the skin intervention group (0·4% [95% CI -0·6 to 1· 5%]; OR 1·3 [0·7 to 2·3]), with no significant interaction effect (p=1·0). Preventing food allergy in one child required early exposure to allergenic foods in 63 children. No serious adverse events were observed. INTERPRETATION: Exposure to allergenic foods from 3 months of age reduced food allergy at 36 months in a general population. Our results support that early introduction of common allergenic foods is a safe and effective strategy to prevent food allergy. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).

Frequency of Infant Egg Consumption and Risk of Maternal-Reported Egg Allergy at 6 Years.

BACKGROUND: Recent research suggests that early egg introduction during infancy may help to prevent egg allergy development. However, the infant egg consumption frequency that is sufficient to induce this immune tolerance remains uncertain. OBJECTIVES: We examined the associations between the infant egg consumption frequency and maternal-reported child egg allergy at 6 y. METHODS: We analyzed data of 1252 children from the Infant Feeding Practices Study II (2005-2012). Mothers reported the frequency of infant egg consumption at 2, 3, 4, 5, 6, 7, 9, 10, and 12 mo old. Mothers reported the status of their child's egg allergy at the 6-y follow-up. We used Fisher exact test, Cochran-Armitage Trend Test, and log Poisson regression models to compare 6-y egg allergy risk by the frequency of infant egg consumption. RESULTS: The risk of maternal-reported egg allergy at 6 y significantly (P-trend = 0.004) decreased with infant egg consumption frequency at 12 mo: 2.05% (11/537) for infants not consuming eggs, 0.41% (1/244) for those consuming eggs <2 times per wk, and 0.21% (1/471) for those consuming eggs ≥2 times per wk. A similar but nonsignificant trend (P-trend=0.109) was observed for egg consumption at 10 mo (1.25%, 0.85%, and 0%, respectively). After adjusting for socioeconomic confounders, breastfeeding, complementary food introduction, and infant eczema, infants who consumed eggs ≥2 times per wk at 12 mo had a significantly lower RR of maternal-reported egg allergy at 6 y (confounder-adjusted RR: 0.11; 95% CI: 0.01, 0.88; P = 0.038), whereas those who consumed <2 times per wk (confounder-adjusted RR: 0.21; 95% CI: 0.03, 1.67; P = 0.141) did not have a significantly lower risk than those who did not consume eggs at all. CONCLUSIONS: Consumption of eggs ≥2 times per wk in late infancy is associated with a reduced risk of developing egg allergy later in childhood.

Delayed egg introduction beyond infancy and increased egg allergy risk in childhood.

AIM: Egg is a major food allergen in childhood. Recent studies suggest that early introduction of allergenic foods can decrease the risk of developing egg allergy. The impact of early egg introduction in the general population is unclear. We examined associations between age of infant egg introduction and childhood egg allergy outcomes in a general population. METHODS: The study population consisted of 1217 neonates from Project Viva, a longitudinal pre-birth cohort in eastern Massachusetts area, USA. Mothers reported age of infant egg introduction and child egg allergy using questionnaires and specific IgE to egg white was assayed. We estimated associations between age of infant egg introduction and egg allergy outcomes using Log-binomial regression models, adjusting for socio-demographics and health confounders. RESULTS: Egg allergy at 2 years was significantly higher (8.0% vs. 1.4%, P < 0.0001) in children who had delayed egg introduction beyond infancy, compared with children who were introduced to egg during infancy (adjusted relative risk or aRR 7.58; 95% CI 3.08, 18.61). At 12 years, the risk of egg allergy remained significantly higher (3.9% vs. 1.1%, P = 0.048) in children with delayed egg introduction compared with children introduced to egg during infancy (aRR 4.07; 95% CI 1.20, 13.87). CONCLUSIONS: Infants with delayed introduction of eggs after 12 months had increased risk of egg allergy in childhood (2 years) and the relationship persisted in early adolescence (12 years). Our findings suggest that introduction to eggs before 12 months could contribute to the prevention of egg allergy.

Early introduction of very small amounts of multiple foods to infants: A randomized trial.

BACKGROUND: We investigated whether multiple food allergies could be safely prevented by simultaneously administering very small amounts of multiple foods. METHODS: Infants 3-4 months old with atopic dermatitis from 14 primary care pediatric clinics in Japan were enrolled in this randomized, placebo-controlled trial. The infants were administered either mixed allergenic food powder (MP) containing egg, milk, wheat, soybean, buckwheat, and peanuts, or placebo powder (PP). The amount of powder was increased in a stepwise manner on weeks 2 and 4, and continued until week 12. The occurrence of food allergy episodes after powder intervention was assessed at 18 months old. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000027837). RESULTS: A total of 163 participants were randomly allocated to either the MP group (n = 83) or the PP group (n = 80). The incidence of food allergy episodes by 18 months was significantly different between the MP and PP groups (7/83 vs. 19/80, respectively; risk ratio 0.301 [95% CI 0.116-0.784]; P = 0.0066). Egg allergies were reduced in the MP group. In addition, food allergy episodes from any of the other five foods were significantly reduced, although the reductions in those due to individual foods were not significant. CONCLUSIONS: Gradually increasing the intake of very small amounts of multiple foods in early infancy can safely reduce the incidence of egg allergies. Other foods may also suppress food allergies, but no definitive conclusions could be reached.

Longitudinal egg-specific regulatory T- and B-cell development: Insights from primary prevention clinical trials examining the timing of egg introduction.

BACKGROUND: Egg allergy affects almost 1 in 10 Australian infants. Early egg introduction has been associated with a reduced risk in developing egg allergy; however, the immune mechanisms underlying this protection remain unclear. OBJECTIVE: To examine the role of regulatory immune cells in tolerance induction during early egg introduction. METHODS: Cryopreserved peripheral blood mononuclear cells (PBMC) were obtained from infants from 2 randomized controlled trials of early introduction of egg for the primary prevention of egg allergy; BEAT (at 12 months, n = 42) and STEP (at 5 months n = 82; 12 months n = 82) study cohorts. In vitro ovalbumin-stimulated PBMC were analyzed by flow cytometry for presence of ovalbumin-specific regulatory T cells, using activation markers, FoxP3, and IL-10 expression. Ovalbumin-specific regulatory B cells were identified by co-expression of fluorescence-conjugated ovalbumin and IL-10. RESULTS: Specific, age-dependent expansion of ovalbumin-specific regulatory T cells was only observed in infants who (a) had early egg introduction and (b) did not have egg allergy at 12 months. This expansion was blunted or impaired in children who did not undergo early egg introduction and in those with clinical egg allergy at 12 months. Infants with egg allergy at 12 months of age also had reduced frequency of ovalbumin-specific regulatory B cells compared to egg-tolerant infants. CONCLUSION: Early egg introduction and clinical tolerance to egg were associated with expansion of ovalbumin-specific T and B regulatory cells, which may be an important developmental process for tolerance acquisition to food allergens.

Evaluation of the introduction of allergen-containing foods: Feeding Infants and Toddlers Study 2016.

BACKGROUND: Guidelines on the early introduction of allergen-containing foods are evolving; however, little national data exist defining current allergen-feeding practices. OBJECTIVE: To investigate the consumption rates of foods containing egg and peanut among infants and toddlers before the guideline changes in 2017. METHODS: The Feeding Infants and Toddlers Study 2016 was conducted nationally among 3235 caregivers with a child under 4 years of age. The 24-hour dietary recalls were reviewed for peanut or egg ingredients. Participants were categorized as "consuming peanut or egg-containing foods" or "not consuming peanut or egg-containing foods." Data on physician-diagnosed food allergies and avoidance were collected. RESULTS: The consumption rates of peanut- and egg-containing foods were low. For the age group of 4 to 5.9 months, 0.3% reported peanut consumption and 2.4% reported egg consumption. For the age group of 6 to 8.9 months, 0.9% reported eating peanut-containing foods and 13.0% egg, and for the age group of 9 to 11.9 months, 5.5% were consuming peanut-containing foods and 33.2% egg-containing foods. Peanut or egg ingredients were identified in the diet of children whose caregivers reported avoidance. CONCLUSION: Before the publication of the 2017 Addendum Guidelines for the Prevention of Peanut Allergy, there were low rates of reported peanut consumption across the study population with less than 1% of any age group before 9 months of age and less than 6% in any age group before 12 months of age consuming peanut on the 24-hour recall day. In addition, reported egg consumption was low and increased with age. These results serve as an important baseline comparison for future studies evaluating the implementation and impact of early peanut and egg introduction.

Soybean and Lupine Addition in Hen Nutrition-Influence on Egg Immunoreactivity.

Modifying hen fodder is a common way of changing eggs composition today. However, there is no information on the effect of the source of protein in the fodder replacement on egg allergenicity. This research aimed to detect potential differences in the immunoreactivity and protein composition of eggs from hens fed with fodder containing legume. The aim of the first step of the study was to select the proper solvent for extracting allergenic proteins from hen eggs. Two of them (containing Tween 20 and Triton 100) were selected, based on protein profile and concentration analysis. Egg-white- and egg-yolk-proteins extracts prepared with them were checked for potential differences, using SDS-PAGE electrophoresis, and then the Western-blot method, using sera from children allergic to eggs and soy. Preliminary studies on the influence of fodder composition on the composition of egg proteins suggest that the addition of soy and lupine to fodder modifies the expression of egg proteins. The observed differences in the immunoreactivity of proteins contained in hen egg-white samples do not seem to be as significant as the appearance of protein with a molecular weight of ~13 kDa in the yolk of eggs obtained from soybean-fed hens. This protein may increase the immunoreactivity of eggs for children allergic solely to soy.

Preventing food allergy in infancy and childhood: Systematic review of randomised controlled trials.

BACKGROUND: This systematic review of ways to prevent immediate-onset/IgE-mediated food allergy will inform guidelines by the European Academy of Allergy and Immunology (EAACI). METHODS: The GRADE approach was used. Eleven databases were searched from 1946 to October 2019 for randomized controlled trials (and large prospective cohort studies in the case of breastfeeding). The studies included heterogeneous interventions, populations, and outcomes and so were summarized narratively. RESULTS: Forty-six studies examined interventions to reduce the risk of food allergy in infancy (up to 1 year) or early childhood. The following interventions for pregnant or breastfeeding women and/or infants may have little to no effect on preventing food allergy, but the evidence is very uncertain: dietary avoidance of food allergens, vitamin supplements, fish oil, probiotics, prebiotics, synbiotics, and emollients. Breastfeeding, hydrolyzed formulas, and avoiding cow's milk formula may not reduce the risk of cow's milk protein allergy; however, temporary supplementation with cow's milk formula in the first week of life may increase the risk of cow's milk allergy. Introducing well-cooked egg, but not pasteurized raw egg, from 4 to 6 months probably reduces the risk of hen's egg allergy. Introducing regular peanut consumption into the diet of an infant at increased risk beginning from 4 to 11 months probably results in a large reduction in peanut allergy in countries with a high prevalence. These conclusions about introducing peanut are based on moderate certainty evidence, from single trials in high-income countries. CONCLUSIONS: Sixty percent of the included studies were published in the last 10 years, but much still remains to be understood about preventing food allergy. In particular, there is a need to validate the potential benefits of early introduction of food allergens in a wider range of populations.

Efficacy of the Enquiring About Tolerance (EAT) study among infants at high risk of developing food allergy.

BACKGROUND: The Enquiring About Tolerance (EAT) study was a randomized trial of the early introduction of allergenic solids into the infant diet from 3 months of age. The intervention effect did not reach statistical significance in the intention-to-treat analysis of the primary outcome. OBJECTIVE: We sought to determine whether infants at high risk of developing a food allergy benefited from early introduction. METHODS: A secondary intention-to-treat analysis was performed of 3 groups: nonwhite infants; infants with visible eczema at enrollment, with severity determined by SCORAD; and infants with enrollment food sensitization (specific IgE ≥0.1 kU/L). RESULTS: Among infants with sensitization to 1 or more foods at enrollment (≥0.1 kU/L), early introduction group (EIG) infants developed significantly less food allergy to 1 or more foods than standard introduction group (SIG) infants (SIG, 34.2%; EIG, 19.2%; P = .03), and among infants with sensitization to egg at enrollment, EIG infants developed less egg allergy (SIG, 48.6%; EIG, 20.0%; P = .01). Similarly, among infants with moderate SCORAD (15-<40) at enrollment, EIG infants developed significantly less food allergy to 1 or more foods (SIG, 46.7%; EIG, 22.6%; P = .048) and less egg allergy (SIG, 43.3%; EIG, 16.1%; P = .02). CONCLUSION: Early introduction was effective in preventing the development of food allergy in specific groups of infants at high risk of developing food allergy: those sensitized to egg or to any food at enrollment and those with eczema of increasing severity at enrollment. This efficacy occurred despite low adherence to the early introduction regimen. This has significant implications for the new national infant feeding recommendations that are emerging around the world.

Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants.

BACKGROUND: The age at which allergenic foods should be introduced into the diet of breast-fed infants is uncertain. We evaluated whether the early introduction of allergenic foods in the diet of breast-fed infants would protect against the development of food allergy. METHODS: We recruited, from the general population, 1303 exclusively breast-fed infants who were 3 months of age and randomly assigned them to the early introduction of six allergenic foods (peanut, cooked egg, cow's milk, sesame, whitefish, and wheat; early-introduction group) or to the current practice recommended in the United Kingdom of exclusive breast-feeding to approximately 6 months of age (standard-introduction group). The primary outcome was food allergy to one or more of the six foods between 1 year and 3 years of age. RESULTS: In the intention-to-treat analysis, food allergy to one or more of the six intervention foods developed in 7.1% of the participants in the standard-introduction group (42 of 595 participants) and in 5.6% of those in the early-introduction group (32 of 567) (P=0.32). In the per-protocol analysis, the prevalence of any food allergy was significantly lower in the early-introduction group than in the standard-introduction group (2.4% vs. 7.3%, P=0.01), as was the prevalence of peanut allergy (0% vs. 2.5%, P=0.003) and egg allergy (1.4% vs. 5.5%, P=0.009); there were no significant effects with respect to milk, sesame, fish, or wheat. The consumption of 2 g per week of peanut or egg-white protein was associated with a significantly lower prevalence of these respective allergies than was less consumption. The early introduction of all six foods was not easily achieved but was safe. CONCLUSIONS: The trial did not show the efficacy of early introduction of allergenic foods in an intention-to-treat analysis. Further analysis raised the question of whether the prevention of food allergy by means of early introduction of multiple allergenic foods was dose-dependent. (Funded by the Food Standards Agency and others; EAT Current Controlled Trials number, ISRCTN14254740.).

Are both early egg introduction and eczema treatment necessary for primary prevention of egg allergy?

The Learning Early About Peanut Allergy (LEAP) study proved that early introduction of peanut significantly prevented the development of peanut allergy. However, in regard to similar attempts to prevent egg allergy through early egg introduction, the Prevention of Egg Allergy in High-risk Infants with Eczema (PETIT) study is the only randomized intervention trial to show a statistically significant effect. Meta-analysis of those studies indicated that neither the total amount nor pretreatment of egg showed any effect on egg allergy at the age of 12 months. However, raw egg powder resulted in a significantly higher prevalence of allergic reactions at initial introduction, whereas use of boiled egg was much safer. The prevalence of atopic dermatitis/eczema at introduction of egg correlated significantly with the subsequent prevalence of allergic reactions at initial introduction. In addition, the prevalence of egg allergy in the late introduction group correlated significantly with the prevalence of atopic dermatitis at introduction, even when the atopic dermatitis was proactively treated with a topical corticosteroid ointment. It is definitely true that the number of trials and number of participants in each trial are insufficient for drawing firm conclusions, especially regarding the optimal dose, raw versus boiled, when to start, and for whom to intervene. Therefore we propose various studies that should be performed to generate stronger data and conclusions. However, on the basis of the most recent results, we postulate that simultaneous intervention by both early boiled egg introduction and eczema treatment is probably indispensable for primary prevention of egg allergy.

Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Evidence is accumulating that early consumption is more beneficial than is delayed introduction as a strategy for primary prevention of food allergy. However, allergic reactions caused by early introduction of such solid foods have been a problematic issue. We investigated whether or not early stepwise introduction of eggs to infants with eczema combined with optimal eczema treatment would prevent egg allergy at 1 year of age. METHODS: In this randomised, double-blind, placebo-controlled trial, we enrolled infants 4-5 months of age with eczema from two centres in Japan. Exclusion criteria were being born before 37 weeks of gestational age, experience of ingestion of hen's eggs or egg products, history of immediate allergic reaction to hen's eggs, history of non-immediate allergic reaction to a particular type of food, and complications of any severe disease. Infants were randomly assigned (block size of four; stratified by institution and sex) to early introduction of egg or placebo (1:1). Participants in the egg group consumed orally 50 mg of heated egg powder per day from 6 months to 9 months of age and 250 mg per day thereafter until 12 months of age. We aggressively treated participants' eczema at entry and maintained control without exacerbations throughout the intervention period. Participants and physicians were masked to assignment, and allocation was concealed. The primary outcome was the proportion of participants with hen's egg allergy confirmed by open oral food challenges at 12 months of age, assessed blindly by standardised methods, in all randomly allocated participants who received the intervention. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000008673. FINDINGS: Between Sept 18, 2012, and Feb 13, 2015, we randomly allocated 147 participants (73 [50%] to the egg group and 74 [50%] to the placebo group). This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants, which showed a significant difference between the two groups (four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group; risk ratio 0·222 [95% CI 0·081-0·607]; p=0·0012). In the primary analysis population, five (8%) of 60 participants had an egg allergy in the egg group compared with 23 (38%) of 61 in the placebo group (risk ratio 0·221 [0·090-0·543]; p=0·0001). The only difference in adverse events between groups was admissions to hospital (six [10%] of 60 in the egg group vs none in the placebo group; p=0·022). 19 acute events occurred in nine (15%) participants in the egg group versus 14 events in 11 (18%) participants in the placebo group after intake of the trial powder. INTERPRETATION: Introduction of heated egg in a stepwise manner along with aggressive eczema treatment is a safe and efficacious way to prevent hen's egg allergy in high-risk infants. In this study, we developed a practical approach to overcome the second wave of the allergic epidemic caused by food allergy. FUNDING: Ministry of Health, Labour and Welfare, and National Centre for Child Health and Development, Japan.

The health and economic outcomes of early egg introduction strategies.

BACKGROUND: Studies suggest early egg introduction (EEI) in the first year of life is associated with reduced risk of developing egg allergy. No US recommendations exist regarding optimally implementing EEI. METHODS: Using simulation and Markov modelling over a 20-year horizon, we explored optimal EEI strategies applied to US, European and Canadian populations, comparing screening of high-risk infants (skin prick testing [SPT] or serum-specific IgE[sIgE]) before introducing cooked egg at 6 months of life vs egg introduction at home, without screening, for all infants. RESULTS: A no-screen approach dominated egg SPT screening of high-risk infants with early-onset eczema. Base model per-patient incremental costs of SPT were $6865 US dollars (USD), 6801 euros and $10 610 Canadian dollars (CAD). For egg sIgE screening in primary care settings, base model incremental costs were $16 722 USD, 18 072 euros and $28 193 CAD. As the simulation concluded 2.5% were egg allergic without screening vs 9.5%, 12% and 21.4% of children undergoing SPT, delayed introduction or sIgE screening. Incremental societal costs from screening reached $2 009 351 175 USD for SPT and $4 894 445 790 USD for sIgE testing. In sensitivity analyses, if the risk of reaction with initial egg ingestion was ≥22.5%, SPT before EEI became a preferred strategy. A no-screen approach dominated both EEI of raw pasteurized egg and delayed cooked egg introduction approaches. CONCLUSIONS: Assuming initial reaction rates < 22.5%, a no-screening EEI cooked egg approach has superior health and economic benefits in terms of number of egg allergy cases prevented and total healthcare costs vs screening testing.

Caregiver and expecting caregiver support for early peanut introduction guidelines.

BACKGROUND: Recent guidelines recommend early peanut introduction (EPI) beginning around 4 to 6 months of age in infants with severe eczema and/or egg allergy and around 6 months for all other infants. Caregiver preferences for such practices are unknown. OBJECTIVE: To determine levels of support for early allergenic solid food recommendations among new and expecting caregivers of infants at risk for peanut allergy. METHODS: We explored preferences for EPI and in-office allergy risk assessment (IRA) through a nationally representative survey of expecting (n = 1,000) and new caregivers of infants younger than 1 year (n = 1,000). RESULTS: Among a primarily female (99.7%), married (80.3%), and white (74.4%) sample, 29% had no or vague awareness of the new guidelines, 61% had no or minimal concern for their child developing food allergy, but 54% felt timing of food introduction has moderate to strong importance for developing food allergy. Only 31% expressed willingness for EPI before or around 6 months of age, with 40% reporting willingness to introduce peanut after 11 months of age, similar to tree nuts and seafood. However, 60% reported willingness to introduce egg before 8 months of age. A total of 51% and 56.8% were unwilling to allow IRA methods, such as skin testing and oral challenge, before 11 months of age, respectively. Odds of willingness to delay peanut introduction (odds ratio, 0.79; 95% confidence interval, 0.65-0.96) and undergo challenge (odds ratio, 0.67; 95% confidence interval, 0.54-0.82) after 6 months of age were lower among expecting caregivers. CONCLUSION: Among new and expecting caregivers, there is poor current willingness and questionable support for early allergenic solid food recommendations, including IRA before introduction. Willingness was better among expecting vs current caregivers. These trends underscore a need for broader formal implementation planning to facilitate early allergen introduction and maximize its preventive benefits.

A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy.

BACKGROUND: Epidemiologic evidence suggests delayed introduction of egg might not protect against egg allergy in infants at risk of allergic disease. OBJECTIVE: We sought to assess whether dietary introduction of egg between 4 and 6 months in infants at risk of allergy would reduce sensitization to egg. METHODS: We conducted a randomized controlled trial in infants with at least 1 first-degree relative with allergic disease. Infants with a skin prick test (SPT) response to egg white (EW) of less than 2 mm were randomized at age 4 months to receive whole-egg powder or placebo (rice powder) until 8 months of age, with all other dietary egg excluded. Diets were liberalized at 8 months in both groups. The primary outcome was an EW SPT response of 3 mm or greater at age 12 months. RESULTS: Three hundred nineteen infants were randomized: 165 to egg and 154 to placebo. Fourteen infants reacted to egg within 1 week of introduction (despite an EW SPT response <2 mm at entry) and were unsuitable for intervention. Two hundred fifty-four (83%) infants were assessed at 12 months of age. Loss to follow-up was similar between groups. Sensitization to EW at 12 months was 20% and 11% in infants randomized to placebo and egg, respectively (odds ratio, 0.46; 95% CI, 0.22-0.95; P = .03, χ2 test). The absolute risk reduction was 9.8% (95% CI, 8.2% to 18.9%), with a number needed to treat of 11 (95% CI, 6-122). Levels of IgG4 to egg proteins and IgG4/IgE ratios were higher in those randomized to egg (P < .0001 for each) at 12 months. There was no effect on the proportion of children with probable egg allergy (placebo, 13; egg, 8). CONCLUSIONS: Introduction of whole-egg powder into the diets of high-risk infants reduced sensitization to EW and induced egg-specific IgG4 levels. However, 8.5% of infants randomized to egg were not amenable to this primary prevention.

Randomized controlled trial of early regular egg intake to prevent egg allergy.

BACKGROUND: The ideal age to introduce egg into the infant diet has been debated for the past 2 decades in the context of rising rates of egg allergy. OBJECTIVE: We sought to determine whether regular consumption of egg protein from age 4 to 6 months reduces the risk of IgE-mediated egg allergy in infants with hereditary risk, but without eczema. METHODS: Infants aged 4 to 6 months were randomly allocated to receive daily pasteurized raw whole egg powder (n = 407) or a color-matched rice powder (n = 413) to age 10 months. All infants followed an egg-free diet and cooked egg was introduced to both groups at age 10 months. The primary outcome was IgE-mediated egg allergy defined by a positive pasteurized raw egg challenge and egg sensitization at age 12 months. RESULTS: There was no difference between groups in the percentage of infants with IgE-mediated egg allergy (egg 7.0% vs control 10.3%; adjusted relative risk, 0.75; 95% CI, 0.48-1.17; P = .20). A higher proportion of participants in the egg group stopped taking the study powder because of a confirmed allergic reaction (25 of 407 [6.1%] compared with 6 of 413 [1.5%]). Egg-specific IgG4 levels were substantially higher in the egg group at 12 months (median, 1.22 mgA/L vs control 0.07 mgA/L; P < .0001). CONCLUSIONS: We found no evidence that regular egg intake from age 4 to 6 months substantially alters the risk of egg allergy by age 1 year in infants who are at hereditary risk of allergic disease and had no eczema symptoms at study entry.

Randomized placebo-controlled trial of hen's egg consumption for primary prevention in infants.

BACKGROUND: Hen's egg is the most common cause of food allergy in early childhood. OBJECTIVE: We investigated the efficacy and safety of early hen's egg introduction at age 4 to 6 months to prevent hen's egg allergy in the general population. METHODS: This randomized, placebo-controlled trial included 4- to 6-month-old infants who were not sensitized against hen's egg, as determined based on specific serum antibodies (IgE). These infants were randomized to receive either verum (egg white powder) or placebo (rice powder) added to the first weaning food 3 times a week under a concurrent egg-free diet from age 4 to 6 until 12 months. The primary outcome was sensitization to hen's egg (increased specific serum IgE levels) by age 12 months. Hen's egg allergy (secondary outcome) was confirmed by double-blind, placebo-controlled food challenges. RESULTS: Among 406 screened infants, 23 (5.7%) had hen's egg-specific IgE before randomization. Seventeen of 23 underwent subsequent double-blind, placebo-controlled food challenges, and 16 were confirmed as allergic, including 11 with anaphylactic reactions. Of the 383 nonsensitized infants (56.7% male), 184 were randomized to verum and 199 to placebo. At 12 months of age, 5.6% of the children in the verum group were hen's egg sensitized versus 2.6% in the placebo group (primary outcome; relative risk, 2.20; 95% CI, 0.68-7.14; P = .24), and 2.1% were confirmed to have hen's egg allergy versus 0.6% in the placebo group (relative risk, 3.30; 95% CI, 0.35-31.32; P = .35). CONCLUSION: We found no evidence that consumption of hen's egg starting at 4 to 6 months of age prevents hen's egg sensitization or allergy. In contrast, it might result in frequent allergic reactions in the community considering that many 4- to 6-month-old infants were already allergic to hen's egg.