Introduction Diet diversity (DD) in infancy may be protective for early food allergy (FA) but there is limited knowledge about how DD incorporating consumption frequency influences FA risk. Methods Three measures of DD were investigated in 2060 infants at 6 and/or 9 months of age within the NorthPop Birth Cohort Study; a weighted DD score based on intake frequency, the number of introduced foods, and the number of introduced allergenic foods. In multivariable logistic regression models based on directed acyclic graphs, associations to parentally reported physician diagnosed FA at 9- and 18-months age were estimated, including sensitivity- and stratified analyses. Results High weighted DD scores (24-31p) at 9 months of age was associated with a 61% decreased FA risk at age 18 months [OR (95% CI) = 0.39 0.18-0.88] compared with infants with the lowest DD scores (0-17p). The association remained significant after exclusion of early FA cases. Having introduced 13-14 foods at age 9 months, independent of consumption frequency, was associated to a 45% decreased FA risk [OR (95% CI) = 0.55 (0.31-0.98)] compared to having introduced 0-10 foods. When stratifying, results remained only for children with no FA history in the family. No association was seen between reduced FA risk and DD measured at 6 months of age or having introduced more allergenic foods in infancy. Conclusion A diverse diet at 9 months of age may prevent FA at 18 months and results underscore the need for additional investigations on the impact of consumption frequency in infancy.

Clinical letter

Background Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE)-mediated food allergy that affects infants. It is characterized by massive and repetitive vomiting, lethargy, pallor, and watery diarrhea. Although FPIES can mimic acute gastrointestinal diseases, for which ultrasonography is useful, few studies on ultrasonographic findings in non-IgE-mediated food allergic disorders are available. We investigated the ultrasonographic features of patients with FPIES. Methods Patients who underwent an oral food challenge (OFC) test or were diagnosed with acute FPIES were enrolled. We divided the patients into the FPIES and non-FPIES groups. Ultrasonography was performed before and 6h after the OFC test. Patients in the FPIES group underwent ultrasonography 24 h after the OFC tests. We evaluated intestinal findings, including peristaltic movement, fluid accumulation, and wall thickness of the gastrointestinal tract. Results Fourteen patients in the FPIES group and 11 in the non-FPIES group were enrolled. Ultrasonography performed 6h after the OFC test showed that the number of patients with small intestinal fluid accumulation and hyperperistalsis was significantly higher in the FPIES group than in the non-FPIES group. In the FPIES group, jejunal wall thickness significantly increased 6h after the OFC test. Small bowel intussusception occurred in three patients with FPIES. Conclusions Small-intestinal wall thickening, fluid accumulation, and abnormal peristalsis on ultrasonography suggest its utility in diagnosing FPIES. In cases of small intestinal intussusception, FPIES should be considered in the differential diagnosis.

Background: Necrotizing enterocolitis (NEC) is a severe inflammatory gastrointestinal disease that affects premature neonates with high morbidity and mortality. We aimed to evaluate the potential of IgG anti-tissue transglutaminase antibodies (IgG tTG) as biomarkers for NEC and to explore their applicability in the early diagnosis, monitoring prognosis. Method: We conducted a prospective observational study on 60 neonates with abdominal distension, dividing into the NEC(n=30) and the control(n=30) groups according to the follow-up results. We collected plasma samples within 48 h of the onset of abdominal distension, and used the autoantigen microarray to screen for NEC-associated autoantibodies. Additionally, an Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the levels of IgG tTG in a validation study that included 43 neonates with NEC and 20 gestational age- and weight-matched controls. Results: The autoantibody microarray analysis indicated that plasma levels of IgG tTG were significantly higher in neonates with NEC compared to controls ( P< 0.001). ELISA confirmed the significant elevation of plasma IgG tTG in neonates with NEC ( P<0.001). Plasma IgG tTG were able to distinguish NEC from the control group, with an area under the curve (AUC) of 0.8674 (95% confidence interval (CI): 0.7794 - 0.9555, sensitivity of 72.09% and specificity of 95%). Encouragingly, IgG tTG levels were significantly higher in NEC stage I than in the controls ( P < 0.001). Furthermore, as neonates with NEC showed clinical improvement, the levels of IgG tTG decreased ( P=0.0159). Conclusion: IgG tTG may serve as a biomarker for diagnosis early NEC and predict its prognosis.

Letter to the EditorComment on: van der Rijst LP et al

Objective: To develop a multimodal artificial intelligence model based on medical health records, imaging information, and laboratory test indicators to assist in the diagnosis of Kawasaki disease. Methods: This study was conducted using the Kawasaki disease database from our hospital, retrospectively collecting medical information from a total of 500 children (both with Kawasaki disease and healthy). We designed a Chinese-BERT-Base module, a ResNet module, and a fully connected layer module to process medical records, image data, and laboratory test results, respectively. Subsequently, we utilized early fusion to concatenate the vectors and input them into a classifier for outputting classification results. We designed unimodal models and traditional machine learning models for comparative evaluation to assess the effectiveness of our model. We analyzed the attention of each module to the raw data to evaluate the interpretability of the model. Additionally, we collected data from another 100 children from a peer hospital as an external validation group. In a double-blind scenario, three senior doctors and the model performed classifications simultaneously for a human-machine comparison experiment. Results: The multimodal model developed in this study demonstrated significant improvements in accuracy (93%) and specificity (93%) compared to unimodal models and traditional machine learning models. Interpretability analysis showed that the attention of each module in the multimodal model largely aligned with the thought processes of human doctors. The human-machine comparison experiment indicated that the model’s classification performance (87%) still had a notable gap compared to that of the human doctors (98%). Conclusion: The multimodal model developed in this study effectively utilized clinical data, achieving good diagnostic performance and providing a relatively reliable tool to assist clinicians in diagnosing Kawasaki disease.

Background: It is necessary to evaluate the parental ability to achieve nutritional adequacy while avoiding allergens for children with food allergies (FA), yet this area is currently understudies. Our study aimed to develop and validate the Parental Self-Efficacy Scale for Dietary Management of Children with Food Allergies (PSED-FA). Methods: PSED-FA was developed through a literature review and semi-structured interviews, refined by a panel of five allergists and five dietitians, and validated using responses from caregivers of children with FA. The construction of the tool involved exploratory factor analysis (EFA), confirmatory factor analysis for model fit, and evaluation of internal consistency using Cronbach’s alpha. Convergent and divergent validity were assessed using the average variance extracted (AVE), maximum shared variance (MSV), and average shared variance (ASV). Results: Participants included nine focus interview groups, with 114 individuals in the validation group. Egg whites (55.2 %), tree nuts (35.2%), and peanuts (22.8%) were the most common allergens. The EFA identified three factors: preparing allergen-free meals, knowledge of nutrition management, and management of food restrictions. The goodness of fit of our model met all the criteria. The tool showed high internal consistency (overall Cronbach’s alpha: 0.902) and met the criteria for both convergent (AVE >0.5) and divergent validity (AVE >MSV and ASV). Conclusion: This study validated a reliable and effective tool for assessing parental self-efficacy in managing the dietary needs of children with FA. This tool can aid health professionals in evaluating parental confidence and identifying areas for improving dietary management in children with FA.

Background Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV-bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children < 6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. Methods In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV-bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. Results 234 patients were included. RSV was detected in 141/234(60.2%), being less common in the immunized group (37% vs 75%, p<0.001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral co-infections, the need for NIV/CMV or length of hospital stay. Conclusions This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-LRTI hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral co-infections nor differences in clinical severity once admitted.

THE IMPORTANCE OF FOLLOW-UP OF ESOPHAGEAL EOSINOPHILIA IN CHILDREN WITH SEVERE COW’S MILK ALLERGYTo the Editor:The current understanding of the intricate interplay between food allergy (FA) and eosinophilic esophagitis (EoE) remains incomplete, particularly in patients with severe manifestations of FA or those undergoing oral immunotherapy (OIT). EoE has been recognized as part of the atopic march1, as it shares type 2 inflammation and poses a risk of progression to other atopic diseases, including IgE-mediated food allergy (IgE-FA). However, the incidence of EoE even before food reintroduction2 raises doubts about whether this group represents a subtype of FA and how esophageal changes develop. In clinical practice, there are concerns about underdiagnosing EoE and its potential long-term complications, especially in children whose symptoms are often nonspecific and may be masked by adaptive behaviors3. The proposed longitudinal study aims to characterize esophageal eosinophilia (EE) in children with IgE-mediated cow’s milk allergy (IgE-CMA) and compare clinical and endoscopic findings between patients with and without esophageal symptoms over one year of follow-up.Patients aged 6 to 18 years were recruited from a Brazilian IgE-CMA reference center between 2019-2022. They underwent a standard routine, which included inquiries about esophageal symptoms, laboratory tests, and esophagogastroduodenoscopy (EGD) with biopsy. With the assistance of caregivers, patients verbally reported the frequency and intensity of esophageal symptoms over the last month. Adaptive eating behaviors were assessed using the IMPACT acronym4. Patients who confirmed the persistence of at least one esophageal symptom were classified as symptomatic. Caregivers completed the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) v2.05during the same visit. The specific IgEs for CM, α-lactalbumin, β-lactoglobulin, casein, egg, soy, wheat, peanut, Brazil nut, codfish, and shrimp were measured using the ImmunoCAP® method. Serum levels of eosinophils and total IgE were also collected.Subsequently, all patients underwent EGD, with at least 4-6 esophageal biopsies (proximal/mid and distal esophagus), along with gastric and duodenal biopsies. Macroscopic characteristics were described using the Endoscopic Reference Score (EREFS)6, completed by the same endoscopist. The histological evaluation included eosinophil count per high-power field (hpf) in each region. Biopsies were evaluated by a single pathologist trained in the EoE Histologic Scoring System (EoEHSS)7 for both proximal/mid and distal regions. The presence of ≥ 15 eos/hpf in the esophageal mucosa was designated as EE. After excluding other causes of EE, symptomatic patients were classified as EoE, while asymptomatic patients were classified as asymptomatic esophageal eosinophilia (aEE). EGD was repeated after at least 8 weeks of treatment for EoE or 1-year follow-up without intervention for aEE. See supplemental data for the detailed methodology.Thirty-three patients with IgE-CMA were assessed. Most were male (57.6%) with a median age of 8.75 years. 84.8% had other atopic conditions, with nearly all reporting prior CM anaphylaxis (87.8%), and 75.7% still reacted to baked milk. The frequency of EE was 45.4%, with 21.2% diagnosed with EoE and 24.2% with aEE. Regarding clinical data, statistically significant differences were not observed between the groups with and without EE (see Table 1). Laboratory tests showed higher results in the EE group but without statistical significance. The percentage of patients sensitized to other food allergens besides CM was similar between the two groups.Comparing patients with EoE and aEE, most of the clinical data did not differ statistically between the groups. A higher median age was found in those with EoE (10.3 vs 8.2 years, p=0.03), along with higher specific IgE values for CM and casein (p=0.02 and p=0.008, respectively). The percentage of patients sensitized to another food allergen was higher in the EoE group (85.7% vs 50%), but this difference did not reach statistical significance. The eosinophil count in the esophagus was statistically similar between the groups, with a predominance of non-diffuse distribution in both. None of the patients exhibited eosinophilia in the stomach or duodenum suggestive of other eosinophilic gastrointestinal diseases8.Table 2 illustrates the comparison of scores between the EoE and aEE groups. EoE patients had significantly higher median PEESS v2.0 total scores (p=0.01), particularly in domains associated with pain and dysphagia (p=0.02). Specifically, four questions were able to distinguish patients with EoE (1, 9, 11, and 12). EREFS scores were similar between the groups, although the frequency of abnormal macroscopy was higher in EoE patients (100% vs 37.5%, p=0.02). EoEHSS also showed no significant differences between the groups. During the follow-up period (see Table 3), most EoE patients achieved clinical and histological remission with omeprazole treatment, including the resolution of fibrosis. Among the 8 patients with aEE, 6 (75%) remained asymptomatic after one year. Of the 6 repeated EGDs, 3 revealed normal histology. The remaining 3 exhibited persistent fibrosis, involving 2 patients who maintained aEE and one who developed EoE.This is the first follow-up study in patients with IgE-CMA that evaluated EE beyond eosinophil counts, utilizing standardized EoE scores in childhood. A high frequency of EE was observed, particularly associated with severe cases of IgE-CMA, highlighting the importance of EoE screening among FA-IgE patients. Given the absence of reliable clinical markers for predicting EE, the challenge persists in identifying symptomatic patients who require EGD. While the use of PEESS contributed to EoE diagnosis in this study, we acknowledge the practical limitations of understanding sporadic complaints or oligosymptomatic patients. To grade PEESS questions or to assess the social impacts of symptoms could provide deeper insights into esophageal involvement. Another noteworthy finding of this study is the possibility of disease activity even before symptom onset, as endoscopic and histological features related to EE were similar between symptomatic and asymptomatic patients. However, since we still lack markers to define active EoE aside from clinical symptoms, debates continue regarding whether aEE should be considered a precursor to EoE or merely a transient phenomenon9.Diagnosing EoE is a relevant concern in IgE-FA patients, especially for those eligible for OIT. In this study, patients with EoE were distinguished from those with aEE by older age and higher levels of CM-specific IgE. However, due to the low incidence of EoE during this follow-up, predicting which aEE patients should be treated over time remains challenging. The phenotype definition could also contribute to understanding this progression. In both EE groups, our results suggest the predominance of a non-fibrostenotic phenotype with favorable outcomes over a period without changes in CM intake: (1) EREFS and EoESS features were mainly inflammatory, regardless of symptom presence, with most showing reversal of fibrosis during follow-up. (2) Histologic remission occurred spontaneously in asymptomatic patients or after omeprazole treatment in the majority of patients with EoE. As this is a small sample of pediatric patients followed for a short period, further follow-up studies will be necessary to confirm whether other IgE-FA groups exhibit a similar disease course.In line with previous research involving FA patients2,10, this study suggests that EoE originates from the sustained activity of inflammatory mediators, regardless of the presence of a food antigen in the esophagus. Especially in atopic individuals, characterized by type 2 immune dysregulation, further investigation is warranted to determine whether eosinophils play a protective or harmful role over time. Consequently, conducting additional research to elucidate the natural progression of EoE, including its underlying mechanisms and factors influencing its course, is essential. This deeper understanding not only promises to facilitate the development of more effective diagnostic and prognostic tools but also to pave the way for timely therapeutic interventions.Word count: 1999Keywords: eosinophilic esophagitis, esophageal eosinophilia, cow’s milk allergy, children, PEESS, EREFS, EoEHSS

Background: This study aims to investigate whether immune dysregulation and gut microbiome alteration are exacerbated in atopic dermatitis (AD) with food allergy (ADFA) and potential treatment strategies. Methods: Total 159 children with AD (tAD) were divided into two groups: AD without-food allergy (ADNFA) and with food allergy (ADFA); 100 children without AD were included as control. Eosinophil counts and total serum IgE levels were measured by routine methods, serum food-specific IgE levels by quantitative fluorescence immunoassay, and serum cytokine levels by multi-microsphere flow immunofluorescence. The intestinal microbiota was evaluated in fecal specimens using metagenomic sequencing. A novel ADFA mouse model was generated to evaluate whether probiotic candidates identified from human fecal samples contributed to the improvement in ADFA pathology. Results: The levels of eosinophils, IgE, IL-2, TNF-α, IL-4, IL-5, IL-6, IL-10, IL-17, IL-12P70 and IFN-α were elevated in tAD compared to normal controls. Compared with ADNFA, the levels of eosinophils, IgE and IL-5 were persistently increased, while IFN-γ was decreased, the species of Lactococcus lactis (L. lactis) was reduced in ADFA. Compared with AD, the ADFA model had more severe skin lesions on the back and significantly higher serum OVA-specific IgE, IL-4 and IL-5. Following oral administration of L. lactis ( L. lactis 1.1936+1.3992), skin lesions in ADFA mice was significantly improved. The levels of OVA-specific IgE, IL-4 and IL-5 decreased in a dose-dependent manner. Conclusions: Food allergy aggravates immune dysregulation and gut microbiome dysbiosis in children with AD. L. lactis could be a candidate probiotic for the treatment of ADFA.

A rare case of wheat-dependentexercise-induced anaphylaxis induced by exercise 5 hours after wheat ingestion.Tomoki Yaguchi1, Katsutoshi Nakano1, Tadayuki Kumagai1Department of Pediatrics, Yaizu City Hospital, Shizuoka, JapanCorresponding authorTomoki Yaguchi, 1000, Dobara, Yaizu-shi, Shizuoka 425-0055, Japan. Phone: +81-54-623-3111, Fax: +81-54-624-9103, E-mail: [email protected] Count for Main Text; 916The number of Table; 1, Figure; 0Keywords：wheat-dependent exercise-induced anaphylaxis, food allergy, aspirin, sensitization, anaphylaxis

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization and natural history review. Numerous factors that may affect disease activity and patient wellbeing need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even ‘real-time’, monitoring between visits. Following an approach that included needs assessment, evidence appraisal and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

Background – While the definition of anaphylaxis is clear, its grade of severity remains a subject of debate, especially since different published classifications provide different grading score, and the same reaction may not receive the same score from different classifications. The objective of this study was to evaluate the possible discrepancies in severity scoring system for anaphylaxis in patients with a positive food challenge (OFC), using the WHO for the 11 th version of the International Classification of Diseases (ICD-11) as the main reference. Methods – We conducted a retrospective observational study at the University Hospital of Montpellier, France, including patients with a positive OFC, between 2018 and 2022. We classified the severity of each reaction, as per the ICD-11 classification, but also as per four other widely used and validated classifications for grading anaphylaxis severity. Results – 235 patients presented a positive OFC between January 2018 and December 2022: 143 suffered from anaphylaxis, according to the ICD-11 classification. 76.2% of them were classified as grade 2 according to the ICD-11 classification, and 23.8% as grade 3. When comparing the different classifications, a complete concordance was recorded in 8 patients (5.6%) only. All classifications showed a good sensitivity (ranging from 99.3 to 100%), but different specificity (from 67.4 to 93.5%), and discrepancies between them were shown in most patients. Conclusion – Our work highlights the need to refine the different scoring systems, to accurately capture anaphylactic reactions and ensure appropriate management, and, in the end, to adopt a universal, intuitive, and easy-to-use classification, such as the ICD-11 one.

Background Due to changes in dietary habits tree nuts (TN) are consumed in many households and TN allergy appears to be increasing. One risk factor seems to be allergies to other food such as peanuts. The aim of our study was to investigate, how often peanut-sensitized infants and toddlers are co-sensitized to cashew, hazelnut and walnut and to determine the likelihood of its clinical relevance by their 2S albumin-specific (s)IgE. Methods Sera of 101 peanut-sensitized children, 5 to 24 months of age (median 16 months) were analyzed regarding sIgE to hazelnut, walnut and cashew and to their 2S-albumins Cor a 14, Jug r 1 and Ana o 3 as well as to Ara h 1 and 2, by using the NOVEOS TM immunoanalyzer system. Results 96% of the peanut-sensitized children were co-sensitized to at least one TN with 94.1% to hazelnut, 87.1% to walnut and 84.2% to cashew. More than half (58.4%) of the children were sensitized to at least one 2S albumin with similar rates for infants and toddlers, 26.7% to all three. Moreover, sensitization rates were similar in peanut allergic and tolerant children. Estimating the likelihood of clinical relevance, 15.8% of all peanut-sensitized children had an at least 90% probability to be hazelnut and/or cashew allergic. Conclusion TN sensitization seems to be common among peanut-sensitized infants and toddlers. Many had a high likelihood to be TN allergic. Therefore, it should be considered to determine TN-sIgE in peanut-sensitized children if TN are not consumed so far.

This review summarises recent advances in characterising the transcriptional pathways associated with outcomes following Oral Immunotherapy. Recent technological advances including single-cell sequencing are transforming the ways in which the transcriptional landscape is understood. The application of these technologies is still in its infancy in food allergy but here we summarise current understanding of gene expression changes following oral immunotherapy for food allergy and specific signatures underpinning the different clinical outcomes of desensitisation and remission (sustained unresponsiveness). T helper 2A cells have been identified as a cell type which correlates with disease activity and is modified by treatment. Molecular features at study entry may differentiate individuals who achieve more positive outcomes during OIT. Recent findings point to T cell anergy and Type 1 interferon pathways as potential mechanisms supporting redirection of the allergen-specific immune response away from allergy towards remission. Despite these developments in our understanding of immune mechanisms following OIT, there are still significant gaps. Additional studies examining immune signatures associated with long term and well-defined clinical outcomes are required to gain a more complete understanding of the pathways leading to remission of allergy, in order to optimise treatments and gain improved outcomes for patients.

Background Oral immunotherapy (OIT) is increasingly used for the treatment of childhood food allergies, with limited data available on cashew nut allergy OIT. This study investigated the safety and feasibility of cashew nut OIT, comparing it with peanut OIT. Methods We retrospectively analyzed cashew nut (n=24) and peanut (n=38) OIT cases initiated between 2018 and 2022. Two different starting protocols were used, and nut intake was then incrementally increased by 20-30% every two weeks to reach a maintenance dose of 1 g of nut protein. After consuming the maintenance dose regularly for 18-24 months, a second oral food challenge was performed. Patients who passed this challenge were considered desensitized. The safety of the therapy was evaluated based on the frequency and severity of adverse reactions during the up-dosing phase. Results Over the study period, 33% of cashew nut-allergic and 63% of peanut-allergic patients experienced mild to moderate side effects. Severe reactions occurred in five peanut-allergic children with high initial IgE levels. Six patients with peanut and none with cashew nut OIT, were discontinued due to side effects. The mean duration to reach the maintenance phase was longer for children with asthma or another food allergy. Among children undergoing the second challenge, desensitization was achieved in 88% of cashew nut and 69% of peanut-allergic patients. Conclusion Cashew nut OIT had a low frequency of adverse effects and was generally well tolerated. However, patient characteristics influenced side effect risk and treatment duration, emphasizing the need for individualized OIT plans.

Background Asthma during pregnancy is associated with a range of adverse perinatal outcomes. It is also linked to increased rates of neurodevelopmental conditions the offspring. We aimed to assess whether fractional exhaled nitric oxide (F ENO)-based asthma management during pregnancy improves child developmental and behavioural outcomes compared to usual care. Methods The Breathing for Life Trial was a randomised controlled trial that compared F ENO-based asthma management during pregnancy to usual care. Participants were invited to the developmental follow-up, the Breathing for Life Trial – Infant Development study, which followed up infants at 6 weeks, 6 months, and 12 months. The primary outcomes were measured in infants at 12-months using the Bayley-III: Cognitive, Language, and Motor composite scores. Secondary outcomes included Bayley-III social-emotional and adaptive behaviour scores, autism likelihood, and sensory and temperament outcomes. The exposure of interest was the randomised intervention group. Results 220 infants and their 217 participating mothers were recruited to the follow-up; 107 mothers were in the intervention group and 113 were in the control group. There was no evidence of an intervention effect for the primary outcomes: Bayley-III cognitive (Mean=108.9 control, 108.5 intervention, p=0.93), language (Mean=95.9 control, 95.6 intervention, p=0.87) and motor composite scores (Mean=97.2 control, 97.9 intervention, p=0.25). Mean scores for secondary outcomes were also similar among infants born to control and F ENO group mothers, with few results reaching p<0.05. Conclusion In this sample, F ENO-guided asthma treatment during pregnancy did not improve infant developmental outcomes in the first year of life.

Background: Accidental allergic reactions (AAR) in children are under-studied, especially with precise pediatrician-based exact diagnoses and follow-ups. This study aimed to assess the prevalence and risk factors for AAR in Japanese children with immediate-type food allergies. Methods: This single-center study included children with immediate-type hen’s egg (HE), cow’s milk (CM), wheat, or peanut allergy who had been followed-up regularly at a national center specialized for allergy in Japan. Low-dose reactivity was defined as allergic reactions to a low dose of ≤250, ≤102, ≤53, or ≤133 mg HE, CM, wheat, or peanut protein, respectively. From January to December 2020, pediatricians followed the AAR experience every 2–4 months. Risk factors for AAR were analyzed using multiple logistic regression. Results: Of the 1096 participants, 609, 457, 138, and 90 had HE, CM, wheat, and peanut allergies, respectively. In this cohort, the median age was 5.0 years, 39% had completely eliminated allergenic food, and 24% had low-dose reactivity. The annual AAR rate was 0.130 in all sub-cohorts. Moderate and severe symptoms occurred in 50% and 0.7%, respectively, of children who experienced AAR. Multiple logistic regression revealed that low-dose reactivity was a significant risk factor for AAR in the overall, HE, and CM cohorts, respectively ( p <0.001, p = 0.029 and 0.036). Conclusion: In Japanese children with immediate-type food allergies, the annualized rate of AAR was relatively low; however, half of the participants with AAR had moderate to severe symptoms. Children, especially those with low-dose reactivity, would require careful risk management of AAR.