EAACI guidelines on the diagnosis of IgE-mediated food allergy

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance. </p

Changes in food sensitization with changing allergy practice in Ireland

The CORAL cohort is a cohort of infants born in Ireland during the first  SARS-CoV-   2  mandated  lockdown  between  March  and  May 2020. We hypothesized that infants born during this time would have increased rates of allergy possibly mediated through changes in the infant social and physical environment during the lockdown. In this letter, we outline the unexpectedly low incidence of peanut and egg allergy at 2 years despite higher levels of atopic dermatitis (AD) (25.3% CORAL vs. 15.5% BASELINE p< .0001) and egg sensitization at 12 months.</p

Social communication skill attainment in babies born during the COVID-19 pandemic: a birth cohort study

Introduction: The SARS-CoV-2 (COVID-19) pandemic was managed with sustained mass lockdowns to prevent spread of COVID-19 infection. Babies born during the early stages of the pandemic missed the opportunity of meeting a normal social circle of people outside the family home. Methods: We compared 10 parentally reported developmental milestones at 12-month assessment in a cohort of 309 babies born at the onset of the pandemic (CORAL cohort) and 1629 babies from a historical birth cohort (BASELINE cohort recruited between 2008 and 2011). Results: Compared with a historical cohort, babies born into lockdown appeared to have some deficits in social communication. Fewer infants in the pandemic cohort had one definite and meaningful word (76.6% vs 89.3%), could point (83.8% vs 92.8%) or wave bye-bye (87.7% vs 94.4%) at 12-month assessment. Adjusted log-binomial regression analyses demonstrated significant differences in social communication in the CORAL cohort compared with the BASELINE cohort: one definite and meaningful word (relative risk (RR): 0.86 (95% CI: 0.80 to 0.92)), pointing (RR: 0.91 (95% CI: 0.86 to 0.96)) and waving bye-bye (RR: 0.94 (95% CI: 0.90 to 0.99)). Discussion: Parentally reported developmental outcomes in a birth cohort of babies born into lockdown during the COVID-19 pandemic may indicate some potential deficits in early life social communication. It must be noted that milestones are parentally reported and comparison is with a historical cohort with associated limitations. Further studies with standardised testing is required to validate these findings. Conclusion: Pandemic-associated social isolation may have impacted on the social communication skills in babies born during the pandemic compared with a historical cohort. Babies are resilient and inquisitive by nature, and it is hoped that with societal re-emergence and increase in social circles, their social communication skills will improve.</p

Atopic outcomes at 2 years in the CORAL cohort, born in COVID-19 lockdown

Introduction The CORAL study is a cohort of infants born during the first weeks of the first SARS-CoV-2 (COVID-19) lockdown. This cohort has had lower antibiotic exposure, higher breastfeeding rates and lower infection rates, especially in the first year of life. We hypothesized that the altered early-life environment of infants born during lockdown would change the incidence of allergic conditions. Methods This longitudinal, observational study followed 365 infants born between March and May 2020 from enrolment to the age of 2 years. Infants attended three research appointments at 6-, 12-, and 24-months and completed detailed questionnaires. At research appointments, children had skin prick testing, and atopic dermatitis (AD) assessment. Statistical analysis focused on changes within the group at different time points, the influence of specific environmental factors on allergic risk and compared the incidence of atopic conditions with a pre-pandemic Irish infant cohort, BASELINE. Results AD was more common in CORAL group at both 12 (26.5% vs. 15.5%; p p = .02) compared with pre-pandemic BASELINE cohort. Within the CORAL group, those with AD at both 12- and 24-month appointments had a more severe AD phenotype associated with a higher risk of allergic sensitization. There was less milk (0% vs. 1%; p = .09), peanut (0.6% vs. 1.8%; p = .3), and egg allergy (0% vs. 2.9%; p p p  Conclusions Despite higher AD incidence in the CORAL cohort, the incidence of food sensitization and allergy are lower than expected pre-pandemic rates possibly reflecting the early introduction and maintenance of dietary allergens enhanced by changes in infant infections, antibiotic use, and breastfeeding in the first 2 years of life in the group. These beneficial effects of the lockdown could be outweighing the expected risk of less early-life microbial encounters outlined by the hygiene hypothesis.</p

Parenting a newborn baby during the COVID-19 pandemic: a qualitative survey

Objective: The COVID-19 pandemic caused long periods of lockdown, social isolation and intense challenges for parents. This study examines parenting in an infant cohort born at the pandemic onset. Methods: The CORAL study is a prospective longitudinal observational study looking at allergy, immune function and neurodevelopmental outcome in babies born between March and May 2020. Demographic information was collected, babies were reviewed at 6-monthly intervals, and serology for COVID-19 infection was recorded. When babies were 12 months old, parents were asked for 3-5 words to describe raising a baby during the pandemic. Frequency of word usage was compared between first time parents and parents with other children, and parents of babies with and without a diagnosis of COVID-19 infection. Results: 354 babies were recruited to CORAL study. Social circles were small. At 6 months the median number of people (including parents) who had kissed the baby was 3, and by 12 months one-quarter of babies had never met another child of similar age. 304 parents completed the word choice. Commonly reported words were lonely (44.4%), isolating (31.9%) and strong bond (15.8%). 12 of those 304 babies had COVID-19 in their first year of life and there was no significant difference in reported negative or positive word number compared with parents of babies without a COVID-19 infection, or by first time parents or those who already had children. Conclusion: The lockdowns and social restrictions made raising an infant challenging for all parents in Ireland. It is important parents know this was a shared experience.</p

The impact of COVID-19 lockdown on infants’ coronavirus exposure and routine healthcare access in Ireland: the CORAL birth cohort study at 6 months.

The public health strategy during the SARS-CoV-2 (COVID-19) pandemic of 2020–2021 led to profound changes in social behaviour, affecting not only familial but also wider social interactions. These changes may have altered viral and bacterial interchange. A significantly decreased diversity of gut and skin microbiota has been demonstrated inallergic individuals compared to non-allergic subjects. The CORAL study is a longitudinal study of the impact of the Coronavirus Pandemic on allergic and autoimmune dysregulation of infants born from March –May 2020, during Ireland’s first lockdown (Ireland formally entered national lockdown on March 27th 2020, though severe restrictions had been gradually escalated for the 2 weeks prior to that date. The first release of lockdown was on June 8th 2020). CORAL will follow children initially until they are 2 years old, with stool sampling at 6,12 and 24 months for microbiome diversity analysis and allergy testing and blood RNA and epigenomic testing at 12 and 24 months</p

Developmental and behavioural outcomes at 2 years in babies born during the COVID-19 pandemic: communication concerns in a pandemic birth cohort

Introduction: The CORAL (Impact of Corona Virus Pandemic on Allergic and Autoimmune Dysregulation in Infants Born During Lockdown) study reported a reduction in social communication milestones in 12-month-old infants born into the COVID-19 pandemic. Aims: To look at 24-month developmental and behavioural outcomes in the CORAL cohort. Design: The CORAL study is a longitudinal prospective observational study of Irish infants born in the first 3 months of the pandemic. At 24 months of age, the Ages and Stages Developmental Questionnaire (ASQ24) and the Child Behaviour Checklist (CBCL) were completed and compared with prepandemic BASELINE (Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Impact) cohort. Results: 917 babies (312 CORAL infants and 605 BASELINE infants) were included. At 24 months of age, infants in the CORAL and BASELINE cohorts had similar developmental ASQ24 scores in fine motor, problem solving and personal and social domains but ASQ24 communication scores were significantly lower in the CORAL group compared with the BASELINE cohort (mean (SD) 49.5 (15.1) vs 53.7 (11.6), p Conclusion: 24-month-old pandemic-born infants had largely similar developmental and behavioural scores compared with their prepandemic counterparts. Concerns have been raised in the communication developmental domain.</p

Infants born during the Covid-19 pandemic have less interest in masked faces than unmasked faces

The COVID-19 pandemic was managed with lockdown, social distancing, mask-wearing and vaccination. Babies experienced societal isolation and encountered mask-wearing. There was speculation about whether COVID-19 mitigation measures, including mask-wearing, would impact child development. Deficits were identified in early communication skills among babies aged up to 24 months assessed during the pandemic. The CORAL Study is a longitudinal study of over 350 Irish infants born into the pandemic.4 We have previously demonstrated that CORAL infants had limited social circles and a reduction in social/communication skills relative to a historical cohort at 12 and 24 months of age.3 4 We used eye-tracking technology to determine where 18-month-old CORAL infants fixed their gaze when looking at unmasked and masked adults. </p

Association between gut microbiota development and allergy in infants born during pandemic-related social distancing restrictions

Background: Several hypotheses link reduced microbial exposure to increased prevalence of allergies. Here we capitalize on the opportunity to study a cohort of infants (CORAL), raised during COVID-19 associated social distancing measures, to identify the environmental exposures and dietary factors that contribute to early life microbiota development and to examine their associations with allergic outcomes. Methods: Fecal samples were sequenced from infants at 6 (n = 351) and repeated at 12 (n = 343) months, using 16S sequencing. Published 16S data from pre-pandemic cohorts were included for microbiota comparisons. Online questionnaires collected epidemiological information on home environment, healthcare utilization, infant health, allergic diseases, and diet. Skin prick testing (SPT) was performed at 12 (n = 343) and 24 (n = 320) months of age, accompanied by atopic dermatitis and food allergy assessments. Results: The relative abundance of bifidobacteria was higher, while environmentally transmitted bacteria such as Clostridia was lower in CORAL infants compared to previous cohorts. The abundance of multiple Clostridia taxa correlated with a microbial exposure index. Plant based foods during weaning positively impacted microbiota development. Bifidobacteria levels at 6 months of age, and relative abundance of butyrate producers at 12 months of age, were negatively associated with AD and SPT positivity. The prevalence of allergen sensitization, food allergy, and AD did not increase over pre-pandemic levels. Conclusions: Environmental exposures and dietary components significantly impact microbiota community assembly. Our results also suggest that vertically transmitted bacteria and appropriate dietary supports may be more important than exposure to environmental microbes alone for protection against allergic diseases in infancy.</p

Cow's milk and hen's egg anaphylaxis: a comprehensive data analysis from the European Anaphylaxis Registry

Background: Cow's milk (CM) and hen's egg (HE) are leading triggers of anaphylaxis in early childhood. The aim of this study was to identify clinical phenotypes and therapeutic measures for CM anaphylaxis (CMA) compared to HE anaphylaxis (HEA) in children up to 12 years of age, based on a large pan-European dataset from the European Anaphylaxis Registry. Methods: Data from 2007 to 2020 on clinical phenotypes and treatment from 10 European countries, as well as Brazil, were analysed. The two-step cluster analysis was used to identify the most frequent phenotypes. For each trigger, three clusters were extracted based on sex, age, and existence of symptoms in four vitally important systems. Results: Altogether 284 children with CMA and 200 children with HEA were identified. They were characterised as male (69% vs. 64%), infants (65% vs. 61%), with a most frequent grade III of Ring&Messmer classification (62% vs. 64%), in CMA versus HEA, respectively. Respiratory symptoms occurred more often in CMA (91% vs. 83%, p = 0.010), especially in infants (89% vs. 79%, p = 0.008). Cardiovascular symptoms were less frequent in CMA (30% vs. 44%, p = 0.002), in both infants (33% vs. 46%, p = 0.027), and older children (25% vs. 42%, p = 0.021). The clusters extracted in the CMA group were characterised as: (1) mild dermal infants with severe GI (40%), 2. severe dermal (35%), 3. respiratory (25%). While in HEA group: 1. infants with severe GI and/or reduction of alertness (40%), (2) conjunctival (16%), (3) mild GI without conjunctivitis (44%). The severity of the reaction was independent from the amount of ingested allergen protein, regardless of trigger. The first-line adrenaline application differed between the countries (0%-92%, as well as the reasons for not administering adrenaline, p Conclusions: Despite the similarity of their age, sex, and severity grade, the clinical profiles differed between the CMA and HEA children. Adrenaline was underused, and its administration was country dependent. Further studies are needed to assess to what extent the differences in the clinical profiles are related to matrix and/or absorption effects, and/or the allergen itself.</p