a randomized, double-blind, placebo-controlled trial

Hintergrund: Die Hühnereiallergie gehört zu den häufigsten Nahrungsmittelallergien im Kindesalter. Da es keine kausalen Therapiemöglichkeiten gibt, haben Präventions-maßnahmen einen hohen Stellenwert. Ergebnisse aus Beobachtungsstudien gaben Hinweise darauf, dass die frühe Einführung von potenten Nahrungsmittel-allergenen vor der Entwicklung von Nahrungsmittelallergien schützen könnte. Es war Ziel der randomisierten, placebokontrollierten Interventionsstudie zu untersuchen, ob die frühe Einführung von Hühnerei zwischen dem 4.-6. Lebensmonat in der Allgemeinbevölkerung ein sicherer und effektiver Weg zur Vorbeugung von Hühnereiallergien sein kann. Methoden: Die Kinder wurden bei Geburt rekrutiert und vor Beginn der Intervention auf eine vorbestehende Sensibilisierung auf Hühnerei getestet. Nicht sensibilisierte Säuglinge (Hu ̈hnerei-spezifische IgE-Antikörper im Serum < 0.35 kUA/l) wurden einer Verum- oder Placebo-Gruppe randomisiert zugeordnet und erhielten mit Beginn der Beikost ab dem 4.-6. Lebensmonat bis zum 12. Lebensmonat dreimal pro Woche pasteurisiertes Hühnereiweißpulver (Verum) oder Reispulver (Placebo) unter gleichzeitiger Hühnerei-freier Ernährung. Primärer Endpunkt war die Häufigkeit von Hühnerei-Sensibilisierungen im Alter von 12 Lebensmonaten. Die Häufigkeit von Hühnerei-Allergien wurde mit Hilfe der Durchführung von Nahrungsmittelprovokationen bestimmt. Die Studie wurde im Deutschen Register Klinischer Studien registriert (DRKS00005668). Ergebnisse: 406 Kinder wurden im Alter von 4-6 Lebensmonaten vor Beginn der Intervention auf eine vorbestehende Hühnereisensibilisierung gescreent. Bei 23/406 (5.7%) konnten bereits Hühnerei-spezifische Serum-IgE-Antikörper ≥ 0.35 kUA/l nachgewiesen werden. 17 der sensibilisierten Kinder erhielten eine doppelblinde, Placebo- kontrollierte Nahrungsmittelprovokation; hierbei wurden 16 Kinder als Hu ̈hnerei-allergisch getestet und 11 Kinder zeigten eine anaphylaktische Reaktion. Von den nicht-sensibilisierten Kindern (383/406) wurden 184 Kinder in die Verum- und 199 Kinder in die Placebo-Gruppe randomisiert. Im Alter von 12 Lebensmonaten waren 5.6% der Kinder in der Verum-Gruppe und 2.6% der Kinder in der Placebo-Gruppe Hühnerei-sensibilisiert (primärer Endpunkt; RR, 2.20; 95% KI, 0.68 bis 7.14; p=0.24). 2.1% in der Verum-Gruppe wurden als allergisch getestet im Vergleich zu 0.6% in der Placebo-Gruppe (RR, 3.30; 95% KI, 0.35 bis 31.32; p=0.35). Schlussfolgerung: Die frühe Einführung von pasteurisiertem Hühnerei ab dem 4.-6. Lebensmonat erwies sich in unserer Studie als nicht erfolgreich für die Prävention von Hühnerei-allergien. Stattdessen barg sie die Gefahr für allergische Reaktionen in der häuslichen Umgebung, da die Mehrzahl der Hühnerei-allergischen Kinder in unserer Studie bereits Hühnerei-sensibilisiert und Hühnerei-allergisch im Alter von 4-6 Lebensmonaten vor der Beikosteinführung waren.Background: Hen’s egg is the most common cause of food allergy in early childhood. Since there is no causal treatment, prevention strategies are sought keenly. Studies suggested that the early introduction of allergenic foods might reduce the risk of food allergy. The aim of this randomized placebo-controlled intervention study was to investigate whether the introduction of hen’s egg at 4-6 months of age can be a safe and effective measure to reduce hen’s egg allergy in a general population. Methods: All participating children were recruited at birth and screened for preexisting hen’s egg-specific serum IgE prior to intervention. Only children who were not sensitized against hen’s egg were randomized to receive either verum (pasteurized egg white powder) or placebo (rice powder) added to the first weaning food three times a week under concurrent egg-free diet from age 4-6 until 12 months. The primary outcome was sensitization to hen’s egg (hen’s egg-specific serum IgE ≥ 0.35 kUA/l) by age 12 months. Hen’s egg allergy (secondary outcome) was confirmed by food challenge tests. This study was registered in the German Clinical-Trials-Registry, number DRKS00005668. Results: Among 406 screened infants, 23 (5.7%) had hen’s egg-specific IgE ≥ 0.35 kUA/l prior to randomization. 17/23 underwent subsequent double-blind, placebo-controlled food challenges and 16 were confirmed as hen’s egg allergic including 11 with anaphylactic reactions. Of the 383 non-sensitized 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; RR, 2.20; 95% CI, 0.68 to 7.14; p=0.24), and 2.1% were confirmed to be hen’s egg allergic versus 0.6% in the placebo group, (RR, 3.30; 95% CI, 0.35 to 31.32; p=0.35). Conclusion: We found no evidence that the consumption of hen’s egg starting at 4-6 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 4-6 months old infants were already allergic to hen’s egg

Primary and pollen-associated hazelnut allergy in school-aged children in Germany: A birth cohort study

Background: Primary hazelnut allergy is a common cause of anaphylaxis in children, as compared to birch-pollen associated hazelnut allergy. Population-based data on hazelnut and concomitant birch-pollen allergy in children are lacking. We aimed to investigate the prevalence of primary and pollen-associated hazelnut allergy and sensitization profiles in school-aged children in Berlin, Germany. Methods: 1570 newborn children were recruited in Berlin in 2005–2009. The school-age follow-up (2014–2017) was based on a standardized web-based parental questionnaire and clinical evaluation by a physician including skin prick tests, allergen specific immunoglobulin E serum tests and placebo-controlled double-blind oral food challenges, if indicated. Results: 1004 children (63.9% response) participated in the school-age follow-up assessment (52.1% male). For 1.9% (n = 19, 95%-confidence interval 1.1%–2.9%) of children their parents reported hazelnut-allergic symptoms, for half of these to roasted hazelnut indicating primary hazelnut allergy. Symptoms of birch-pollen allergy were reported for 11.6% (n = 116 95%-CI 9.7%–13.7%) of the children. Both birch-pollen allergy and hazelnut allergy associated symptoms affected 0.6% (n = 6, 95%-CI 0.2%–1.3%) of children. Assessment of allergic sensitization was performed in 261 participants and showed that almost 20% of these children were sensitized to hazelnut, being the most frequent of all assessed food allergens, or birch-pollen, the majority to both. Conclusions: Based on parental reports hazelnut-allergic symptoms were far less common than sensitization to hazelnut. This needs to be considered by physicians to avoid unnecessary changes in diet due to sensitization profiles only, especially when there is a co-sensitization to hazelnut and birch-pollen.Peer Reviewe

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

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 &lt;.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 &lt;.0001). A causal inference analysis confirmed the strong PP effect (89% average treatment effect relative risk reduction p &lt;.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

Frequency of food allergy in school-aged children in eight European countries-The EuroPrevall-iFAAM birth cohort

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent-reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries. Methods: A follow-up assessment at age 6-10 years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double-blind, placebo-controlled oral food challenges (DBPCFC). Results: A total of 6105 children participated in this school-age follow-up (57.8% of 10 563 recruited at birth). For 982 of 6069 children (16.2%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face-to-face interviews and/or skin prick testing, 238 (10.4%) were eligible for a DBPCFC. Sixty-three foods were challenge-tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy-one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4% (88 related to all 6105 participants of this follow-up) and 3.8% (88 related to 2289 with completed eligibility assessment). Interpretation: In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons. Keywords: IgE; birth cohort study; epidemiology; food allergy; prevalence.European Commission Joint Research Centr

Prevalence and early-life risk factors of school age allergic multimorbidity - the EuroPrevall-iFAAM birth cohort

BACKGROUND: Coexistenceofchildhoodasthma,eczemaandallergicrhinitisishigherthancanbeexpectedbychance,suggestingacommonmechanism.Dataonallergicmultimorbidityfromapan-European,population-basedbirthcohortstudyhasbeenlacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children.METHODS: IntheprospectivemulticentreobservationalEuroPrevall/iFAAMbirthcohortstudyweusedstandardizedquestionnairesonsocio-demographics,medicalhistory,parentalallergiesandlifestyle,andenvironmentalexposuresatbirth,12and24months.Atprimaryschoolage,parentsansweredISAAC-basedquestionsoncurrentasthma,rhinitisandeczema.Allergicmultimorbiditywasdefinedasthecoexistenceofatleasttwoofthese.RESULTS: From10,563childrenrecruitedatbirthin8studycentres,weincludeddatafrom5,572children(meanage8.2years;51.8%boys).Prevalenceestimateswere:asthma8.1%,allergicrhinitis13.3%,eczema12.0%.Allergicmultimorbiditywasseenin7.0%ofthewholecohort,rangingfrom1.2%(Athens,Greece)to10.9%(Madrid,Spain). Riskfactorsforallergicmultimorbidity, identified with AICc,includedfamily-allergy-score, oddsratio(OR)1.50 (95% CI 1.32-1.70)perstandarddeviation;early-lifeallergysymptoms, OR2.72 (2.34-3.16)foreachsymptom;andcaesareanbirth, OR1.35 (1.04-1.76).Femalegender, OR0.72 (0.58-0.90);oldersiblings,OR0.79 (0.63-0.99);andday-care, OR0.81 (0.63-1.06)wereprotectivefactors.CONCLUSION: AllergicmultimorbidityshouldberegardedasanimportantchronicchildhooddiseaseinEurope.Someoftheassociatedearly-lifefactorsaremodifiableandmaybeconsideredforpreventionstrategies.</p

Similar occurrence of febrile episodes reported in non-atopic children at three to five years of age after prebiotics supplemented infant formula

This is a follow up study of a multicenter randomised placebo-controlled trial in seven centres in five West European countries. The RCT assessed the effect of infant formula supplemented with a mixture of prebiotics (with neutral short-chain and long-chain oligosaccharides and pectin-derived acidic oligosaccharides) during infancy in term-born children (n=1130). In the follow-up study 672 children (60% of the study population) participated: 232 (56%) from the prebiotics group (PG), 243 (58%) from the control group (CG), and 197 (66%) from the non-randomised breast-fed group (BG). The primary outcome was the occurrence of febrile episodes at three to five years of age prospectively documented by the parents: in the PG 1.17 (interquartile range 0.50-2.08) episodes per year versus 1.20 (0.52-2.57) in the CG; and 1.48 (0.65-2.60) in the BG. This specific prebiotics mixture given during infancy in healthy non-atopic subjects does not decrease febrile episodes and therefore seems not to prevent infection between their third and fifth birthday