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Introduction: Cow’s milk (CM) is one of the most common food allergens in Japan. The oral food challenge (OFC) of CM is important for the definite diagnosis of children with CM allergy, and it is recommended to be actively and safely performed in individuals with low CM-sIgE levels. This study aimed to investigate the safety of low-dose CM-OFC in individuals with low CM-sIgE levels and discuss the prognostic factors and appropriate approaches for assessing the starting doses of CM-OFC in these individuals. Methods: We retrospectively analyzed 6,929 OFC tests conducted between January 1, 2017, and December 31, 2021; of which, 1,390 were CM-OFC tests. The characteristics, OFC-positive rates, CM loading, and related factors were analyzed in 138 cases involving low CM-sIgE levels. Stepwise OFC tests were conducted according to the food allergies guidelines in Japan using an open and unblinded method. Results: Among 138 individuals with low CM-sIgE levels, 110 (79.7%) passed the OFC test without any symptoms. Among the cases with OFC-positive status, 50.0% (14/28) cases showed symptoms with low-dose OFC (30–105 mg CM protein). Moreover, complete CM elimination was associated with a significantly high OFC-positive rate, and 60.0% (12/20) of the cases involving complete CM elimination showed symptoms with low-dose OFC. Conclusion: Eighty percent of the patients with low CM-sIgE levels safely completed the OFC test. Nevertheless, careful observation is essential during low-dose OFC test in cases with low CM-sIgE levels, especially in the cases with complete elimination. The starting dose of the OFC test should be reevaluated, and modified using baked milk or a lower dose of CM to ensure safety and early outgrowth of CM allergy. [ABSTRACT FROM AUTHOR]

Background: Various guidelines for the diagnosis and management of cow's milk allergy (CMA) have been published. Purpose: This study aimed to compare voting outcomes of experts from Mexico, the Middle East, and the European Society of Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on statements regarding CMA Methods: The 3 expert groups voted on the same 10 statements. Each participant voted anonymously using a score of 0-9 (≥6 meant agreement; <5 reflected disagreement). If <75% of the participants agreed with the statement, it was rejected. None of the groups was aware of the voting outcomes of another group. Results: There was broad consensus amongst the 3 groups. Agreement was reached that infant colic as a single manifestation is not suggestive of CMA. All groups confirmed that an extensively hydrolysed formula is the preferred elimination diet in mild/moderate CMA cases; however, hydrolysed rice formula is an alternative. Amino acid-based formulas should be reserved for infants with severe symptoms. The discrepancy in voting outcomes regarding soy formulas highlights the differences in opinions. Two of 13 ESPGHAN experts (15%), 1 of 14 Middle East experts (7%), and 6 of 26 Mexican experts (23%) disagreed with the statement that soy formula should not be the first choice for the diagnostic elimination diet but can be considered in some cases for economic, cultural, and palatability reasons. All of the ESPGHAN and Mexican experts agreed that there was no added value of probiotics, prebiotics, or synbiotics to the efficacy of elimination diets on CMA, whereas 3 of 14 Middle East experts (21%) determined that there was sufficient evidence. Conclusion: Although all statements were accepted by the 3 groups, there were relevant differences illustrating variations according to geography, culture, cost, and formula availability. These findings emphasize the need for region-specific guidelines. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have identified associations between gastroesophageal reflux (GER) and cow's milk allergy (CMA) in infants. However, the role of GER in the development of CMA remains poorly understood. Our primary objectives were to develop a mouse model that suggests GER as a potential pathogenic mechanism for CMA and to elucidate the immunological mechanisms that connect lung innate immunity with CMA. Methods: Mice were exposed to cow's milk (CM) treated with hydrochloric acid through repeated aspiration into their airways. Subsequently, they were challenged by intraperitoneal injection of CM extract. The immunological mechanisms were investigated using comprehensive single-cell RNA sequencing (scRNA-seq) analysis of the lungs, combined with the use of genetically modified mice. Results: Mice exposed to CM mixed with hydrochloric acid via airway sensitization developed CMA, as evidenced by the production of antigen-specific IgE and IgG antibodies, and the induction of anaphylaxis upon systemic antigen administration. In contrast, aspiration of CM alone did not induce CMA. scRNA-seq analysis revealed potential roles of alveolar macrophages in response to hydrochloric acid. Mice lacking the TLR4 pathway were protected from developing CMA. Conclusions: We have developed a novel mouse model for CMA that utilizes the natural antigen and follows the physiological airway sensitization pathway, thus potentially resembling clinical scenarios. This model, named the acidified milk aspiration-induced allergy model, has the potential to shed light on the role of early innate immunity by analyzing a more physiological model.

Background Various guidelines for the diagnosis and management of cow's milk allergy (CMA) have been published. Purpose This study aimed to compare voting outcomes of experts from Mexico, the Middle East, and the European Society of Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on statements regarding CMA Methods The 3 expert groups voted on the same 10 statements. Each participant voted anonymously using a score of 0–9 (≥6 meant agreement;

Introduction. Despite active research into the mechanisms of food allergies (FA), the main approach to managing patients with this condition remains the complete exclusion of causative allergens from the diet for a certain period. At the same time, the question of timely reintroduction of excluded food triggers into the diet is frequently raised, which is important both for maintaining oral tolerance and reducing the negative effects of long-term elimination diets, such as nutritional and eating behavior disorders, as well as financial burdens on families. However, clear recommendations on the reintroduction of previously excluded foods have not existed until recently. Regarding cow’s milk protein allergy (CMPA), such recommendations were provided in 2023 in the consensus document of the World Allergy Organization (WAO) — DRACMA.Aim. The aim of this review is to present current approaches to the reintroduction of food allergens into the diets of patients with food allergies and to evaluate various reintroduction protocols, including those used for cow’s milk protein allergy (CMPA).Material and methods. This review provides a concise summary of current approaches to reintroducing food allergens into the diet, covering both IgE-mediated and non-IgE-mediated forms of food allergy. The advantages of different patient management protocols are discussed, with special attention given to CMPA as one of the most common manifestations of FA in children.Results. An analysis of modern approaches has demonstrated that modern recommendations regarding the reintroduction of allergens, including those presented in the document of the World Allergological Organization — DRACMA for allergy to cow’s milk proteins, allow for a more personalized and safe approach to the reintroduction of allergens, which helps reduce risks and maintain food tolerance.Conclusions. The introduction of new guidelines for the reintroduction of food allergens is an important step in managing patients with food allergies. These recommendations provide a more personalized approach to treating food-allergic patients, including those with cow’s milk protein allergy, reducing the risks associated with reintroducing allergens into the diet. They also help to mitigate the negative effects of elimination diets and maintain oral tolerance in patients, which is particularly important for children with FA.

Studies showed that complexation of polyphenols with milk allergens reduced their immunogenic potential. However, the relationship between structures of polyphenols and their hypoallergenic effects on milk allergens in association with physiological and conformational changes of the complexes remain unclear. In this study, polyphenols from eight botanical sources were extracted to prepare non-covalent complexes with β-lactoglobulin (β-LG), a major allergen in milk. The dominant phenolic compounds bound to β-LG with a diminished allergenicity were identified to investigate their respective role on the structural and allergenic properties of β-LG. Extracts from Vaccinium fruits and black soybeans were found to have great inhibitory effects on the IgE-and IgG-binding abilities of β-LG. Among the fourteen structure-related phenolic compounds, flavonoids and tannins with larger MWs and multi-hydroxyl substituents, notably rutin, EGCG, and ellagitannins were more potent to elicit changes on the conformational structures of β-LG to decrease the allergenicity of complexed β-LG. Correlation analysis further demonstrated that a destabilized secondary structure and protein depolymerization caused by polyphenol-binding were closely related to the allergenicity property of formed complexes. This study provides insights into the understanding of structure-allergenicity relationship of β-LG-polyphenol interactions and would benefit the development of polyphenol-fortified matrices with hypoallergenic potential.

The Cow's Milk-related Symptom Score (CoMiSS™) is a scoring system that reflects the appearance and intensity of symptoms possibly related to consumption of cow's milk. The original tool was recently updated by changing the cut-off, and the stool scale and by adding angioedema. There is no data available regarding the natural evolution of CoMiSS in infants with no cow's milk allergy (no-CMA) or a comparison between original and updated CoMiSS values. We determined the original and the updated CoMiSS in infants not diagnosed with cow's milk allergy. The evolution of CoMiSS during the first year of life was assessed repetitively during predefined check-ups at 1.5, 3, 4, 6, 8, 10, and 12 months. The original and updated scores were compared with the Wilcoxon Signed-Rank Test. We also tested the impact of feeding type, age, gender, and order in the family on the CoMiSS. One hundred and twenty-two infants were included. CoMiSS values during the first year of life showed an inverse relation to age. The difference in CoMiSS between the original and updated versions was significant at 6,8,10, and 12 months (p < 0.001), related to the switch from the Bristol Stool Form Scale to the Brussels Infants and Toddlers Stool Scale (BITSS). The difference between both versions of CoMiSS was not significantly different in infants < 6 months (p = 0.999 at 1.5 and 4 months, and p = 0.586 at 3 months, respectively). Conclusion: CoMiSS decreases with age during the first year of life. While there is no difference between the two CoMiSS versions in healthy infants under 6 months of age, the CoMiSS value in the updated version is lower than the original 1 in infants aged 6 to 12 months. What is known? • The Cow's Milk-related Symptom Score (CoMiSS) is a validated awareness tool for cow's milk allergy (CMA). • A CoMiSS of ≥ 10 indicates a risk for cow's milk allergy. What is new? • The natural evolution of CoMiSS in infants not diagnosed with CMA (no-CMA) shows an inverse relation to age. • There is no difference between the original and the updated CoMiSS versions in no-CMA-infants under six months of age, but the updated CoMiSS is lower in infants 6–12 months than the original one. [ABSTRACT FROM AUTHOR]

Copyright of Al-Azhar Journal of Pediatrics is the property of Al-Azhar Journal of Pediatrics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: The aim of our study was to investigate whether a 1-month-long milk-free diet results in a reduction in faecal calprotectin (FC) and faecal-zonulin-related proteins (FZRP) in children with milk-protein-induced allergic proctocolitis (MPIAP). Materials and methods: This is a single-centre, prospective, observational cohort study involving 86 infants with MPIAP, aged 1–3 months, and 30 healthy controls of the same age. The FC and FZRP were marked using the ELISA method (IDK® Calprotectin or Zonulin ELISA Kit, Immunodiagnostik AG, Bensheim, Germany). The diagnosis of MPIAP was confirmed with an open milk challenge test. Results: FFC and FZRP proved useful in evaluating MPIAP treatment with a milk-free diet, and the resolution of allergic symptoms and a significant (p = 0.0000) decrease in the concentrations of both biomarkers were observed after 4 weeks on the diet. The FC and FZRP concentrations were still higher than in the control group. A high variability of FC concentrations was found in all the study groups. An important limitation is the phenomenon of FZRP not being produced in all individuals, affecting one in five infants. Conclusions: FC and FZRP can be used to monitor the resolution of colitis in infants with MPIAP treated with a milk-free diet, indicating a slower resolution of allergic inflammation than of allergic symptoms. The diagnosis of MPIAP on the basis of FC concentrations is subject to considerable error, due to the high individual variability of this indicator. FZRP is a better parameter, but this needs further research, as these are the first determinations in infants with MPIAP. [ABSTRACT FROM AUTHOR]

Although gut dysbiosis is associated with cow's milk allergy (CMA), causality remains uncertain. This study aimed to identify specific bacterial signatures that influence the development and outcome of the disease. We also investigated the effect of hypoallergenic formula (HF) consumption on the gut microbiome of milk-allergic children. 16S rRNA amplicon sequencing was applied to characterize the gut microbiome of 32 milk-allergic children aged 5–12 years and 36 age-matched healthy controls. We showed that the gut microbiome of children with CMA differed significantly from that of healthy children, regardless of whether they consumed cow's milk. Compared to that of healthy cow's milk consumers, it was depleted in Bifidobacterium, Coprococcus catus, Monoglobus, and Lachnospiraceae GCA-900066575, while being enriched in Oscillibacter valericigenes, Negativibacillus massiliensis, and three genera of the Ruminococcaceae family. Of these, only the Ruminococcaceae taxa were also enriched in healthy children not consuming cow's milk. Furthermore, the gut microbiome of children who developed tolerance and had received an HF was similar to that of healthy children, whereas that of children who had not received an HF was significantly different. Our results demonstrate that specific gut microbiome signatures are associated with CMA, which differ from those of dietary milk elimination. Moreover, HF consumption affects the gut microbiome of children who develop tolerance. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Antigen‐specific memory B cells play a key role in the induction of desensitization and remission to food allergens in oral immunotherapy and in the development of natural tolerance (NT). Here, we characterized milk allergen Bos d 9‐specific B cells in oral allergen‐specific immunotherapy (OIT) and in children spontaneously outgrowing cow's milk allergy (CMA) due to NT.Samples from children with CMA who received oral OIT (before, during, and after), children who naturally outgrew CMA (NT), and healthy individuals were received from Stanford biobank. Bos d 9‐specific B cells were isolated by flow cytometry and RNA‐sequencing was performed. Protein profile of Bos d 9‐specific B cells was analyzed by proximity extension assay.Increased frequencies of circulating milk allergen Bos d 9‐specific B cells were observed after OIT and NT. Milk‐desensitized subjects showed the partial acquisition of phenotypic features of remission, suggesting that desensitization is an earlier stage of remission. Within these most significantly expressed genes, IL10RA and TGFB3 were highly expressed in desensitized OIT patients. In both the remission and desensitized groups, B cell activation‐, Breg cells‐, BCR‐signaling‐, and differentiation‐related genes were upregulated. In NT, pathways associated with innate immunity characteristics, development of marginal zone B cells, and a more established suppressor function of B cells prevail that may play a role in long‐term tolerance. The analyses of immunoglobulin heavy chain genes in specific B cells demonstrated that IgG2 in desensitization, IgG1, IgA1, IgA2, IgG4, and IgD in remission, and IgD in NT were predominating. Secreted proteins from allergen‐specific B cells revealed higher levels of regulatory cytokines, IL‐10, and TGF‐β after OIT and NT.Allergen‐specific B cells are essential elements in regulating food allergy towards remission in OIT‐received and naturally resolved individuals. [ABSTRACT FROM AUTHOR]

Background: The impact of alternative milk substitutes on the nutritional status of children with cow's milk allergy (CMA), the prevailing cause of food allergies, is unresolved. Methods: A cross‐sectional study was performed in children older than 2 years with IgE‐mediated CMA. Patients' clinical characteristics, anthropometric measurements, dietary intake (by 3‐day food diary), and biochemical markers of nutritional status were assessed. Results: One hundred two children with CMA (68.6% boys; median age, 3.7 years; 51% multiple food allergies) were evaluated. 44.1% of the children consumed plant‐based beverages (PBB), 19.6% therapeutic formula and 36.3% did not consume any milk substitutes. In all age groups, dietary calcium, riboflavin, and vitamin D intake of those who did not use milk substitutes were lower than those who consumed formula or PBB (p <.01). Also in the 2–3 years old age group, dietary zinc (p =.011) and iron intake (p =.004) of the formula‐fed group was higher. Formula‐fed patients had higher levels of 25‐OH vitamin D (μg/L) and serum vitamin B12 (ng/L) than PBB‐fed patients (respectively; p <.001, p =.005) and those who did not consume any milk substitute (p <.001). Patients of all ages who did not utilize a milk substitute failed to obtain an adequate amount of dietary calcium. Conclusion: The use of milk substitutes positively affects dietary calcium, riboflavin, and vitamin D intake in CMA, but their contribution is variable. Those who do not use milk substitutes are at greater risk inadequate of dietary calcium intake. Personalized nutritional advice, given the clinical diversity and the impact of individual differences, is required. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Chinese Institute of Food Science & Technology / Zhongguo Shipin Xuebao is the property of Journal of Chinese Institute of Food Science & Technology Periodical Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The purpose of this research was to assess the growth, tolerance, and compliance outcomes associated with the consumption of a hydrolyzed rice infant formula (HRF) enriched with 2′-Fucosyllactose (2′-FL) a Human Milk Oligosaccharide (HMO), and nucleotides in an intended population of infants. Methods: This was a non-randomized single-group, multicenter study. The study formula was a hypoallergenic HRF with 2′-FL, Docosahexaenoic acid (DHA), Arachidonic acid (ARA), and nucleotides. Infants 0–90 days of age who were formula fed and experiencing persistent feeding intolerance symptoms, symptoms of suspected food protein (milk and/or soy) allergy, or other conditions where an extensively hydrolyzed infant formula was deemed an appropriate feeding option were recruited by pediatricians from their local populations. The primary outcome was maintenance of weight-for-age z-score. Weight, length, head circumference, formula intake, tolerance measures, clinical symptoms and questionnaires were collected. Thirty-three infants were enrolled, and 27 completed the study, on study product. Results: Weight-for-age z-scores of infants showed a statistically significant improvement from Visit 1 to Visit 4 (p = 0.0331). There was an adequate daily volume intake of 762 ± 28 mL/day, average daily number of stools of 2.1 ± 0.3, and mean rank stool consistency of 2.38 ± 0.18. After 28 days of switching to a HRF, 86.8 ± 5.9% of the symptoms resolved or got better by Visit 4 as reported by parents. Conclusions: HRF with 2′-FL HMO was safe, well tolerated, and supported weight gain in infants with suspected cow's milk allergy or persistent feeding intolerance. [ABSTRACT FROM AUTHOR]

Background: Milk oral immunotherapy is the riskiest and most unpredictable form of oral immunotherapy. We aimed to produce a low allergenic product than conventional once baked‐cake/muffin, to develop indirect in‐house ELISA to check the tolerance status with milk products and evaluate IgE reactivity of patients' sera via western blotting (WB) and indirect in‐house ELISA. Method: A low allergenic product named biscotti‐twice baked‐cake was developed, and the total protein concentration was determined. The protein content was studied by SDS‐PAGE and proteomics. Milk‐specific IgE (sIgE) binding assays were performed by WB and indirect in‐house ELISA by using patients' sera. Results: Casein band intensity was observed to be lower in the biscotti‐twice baked‐cake than in the once baked‐cake (p =.014). Proteomics analysis and αS1‐casein measurement showed that the lowest intensity of casein was found in biscotti. The low binding capacity of milk sIgE to biscotti compared with once baked‐cake was shown by WB (p =.0012) and by indirect in‐house ELISA (p =.0001). In the ROC analysis, the area under the curve (AUC) of the in‐house ELISA IgE was comparable with Uni‐CAP milk and casein sIgE. The AUC of the in‐house ELISA IgE for cake (0.96) and biscotti (1) was slightly better than Uni‐CAP milk sIgE (0.94; 0.97) and casein sIgE (0.96; 0.97), respectively. Conclusion: The low allergenicity of the newly developed low allergenic product "biscotti‐twice baked‐cake" has been demonstrated by in vitro experiments. Biscotti could be a safe treatment option than once baked‐cake/muffin in patients who are reactive to once baked‐milk products. [ABSTRACT FROM AUTHOR]

The recognition of constipation as a possible non‐Immunoglobulin E (IgE)‐mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE‐mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non‐IgE‐Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review. [ABSTRACT FROM AUTHOR]

Introduction: The primary dietary approach for managing cow's milk allergy (CMA) is the elimination diet. We aimed to compare the growth patterns of children with CMA during and after the elimination diet with healthy peers and identify influencing factors. Methods: We compared 74 CMA children with age-matched healthy peers. Anthropometric data were collected during the third month of cow's milk elimination (CME) diet (T1), 3 months after diet cessation (T2), and after ≥3 months of normal diet (T3). Control group measurements coincided. Nutrient intake was assessed by a 3-day record, and patient laboratory results were noted at T3. Results: CMA children had consistently lower weight-for-age (WFA) and height-for-age (HFA) z-scores than controls. WtHt z-score of patients was lower than those of the healthy group at T2. HC z-scores of patients were lower than those of the healthy group at T0, T2, and T3. At T3, the HFA z-score of the CME group demonstrated a negative correlation with the duration of the elimination diet (p = 0.045). Inadequate intake of energy, vitamins A, E, B1, B6, C, folic acid, magnesium, and iron was significantly higher in CMA children (p < 0.05). T3 WFA z-score correlated positively with fiber, vitamin B1, magnesium, and iron intake (p < 0.05). T3 WtHt showed a positive moderate correlation with energy, protein, vitamin E, vitamin B1, vitamin B2, vitamin B6, calcium, magnesium, phosphor, iron intake (p < 0.05). Conclusions: Post-elimination diet, children with CMA need sustained monitoring and potentially micronutrient supplementation to match healthy peers' growth. [ABSTRACT FROM AUTHOR]

Milk is an essential source of protein for infants and young children. At the same time, cow's milk is also one of the most common allergenic foods causing food allergies in children. Recently, cow's milk allergy (CMA) has become a common public health issue worldwide. Modern food processing technologies have been developed to reduce the allergenicity of milk proteins and improve the quality of life of patients with CMA. In this review, we summarize the main allergens in cow's milk, and introduce the recent findings on CMA responses. Moreover, the reduced effects and underlying mechanisms of different food processing techniques (such as heating, high pressure, γ-ray irradiation, ultrasound irradiation, hydrolysis, glycosylation, etc.) on the allergenicity of cow's milk proteins, and the application of processed cow's milk in clinical studies, are discussed. In addition, we describe the changes of nutritional value in cow's milk treated by different food processing technologies. This review provides an in-depth understanding of the allergenicity reduction of cow's milk proteins by various food processing techniques. [ABSTRACT FROM AUTHOR]

Background: The basophil activation test is an emerging clinical tool in the diagnosis of cow's milk allergy (CMA). The aim was to assess the association between the basophil allergen threshold sensitivity to the major milk protein casein (casein‐specific CD‐sens), the levels of milk‐ and casein‐specific Immunoglobulin E antibodies (IgE‐ab), and the severity of allergic reactions at milk challenges. Methods: We enrolled 34 patients aged 5–15 (median 9) years who underwent a double‐blind placebo‐controlled milk‐challenge (DBPCMC) as screening before inclusion in an oral immunotherapy study for CMA. The severity of the allergic reaction at the DBPCMC was graded using Sampson's severity score. Venous blood was drawn before the DBPCMC. Milk‐ and casein‐specific IgE‐ab were analyzed. Following in vitro stimulation of basophils with casein, casein‐specific CD‐sens, was determined. Results: Thirty‐three patients completed the DBPCMC. There were strong correlations between casein‐specific CD‐sens and IgE‐ab to milk (rs = 0.682, p <.001), and between casein‐specific CD‐sens and IgE‐ab to casein (rs = 0.823, p <.001). There was a correlation between the severity of the allergic reaction and casein‐specific CD‐sens level (rs = 0.395, p =.041) and an inverse correlation between casein‐specific CD‐sens level and the cumulative dose of milk protein to which the patient reacted at the DBPCMC (rs = −0.418, p =.027). Among the 30 patients with an allergic reaction at the DBPCMC, 67% had positive casein‐specific CD‐sens, 23% had negative casein‐specific CD‐sens, and 10% were declared non‐responders. Conclusion: Two thirds of those reacting at the DBPMC had positive casein‐specific CD‐sens, but reactions also occurred despite negative casein‐specific CD‐sens. The association between casein‐specific CD‐sens and the severity of the allergic reaction and cumulative dose of milk protein, respectively, was moderate. [ABSTRACT FROM AUTHOR]

Background: Updated epidemiologic data are important for defining effective public health strategies for pediatric food allergy (FA). Objective: The Epidemiology of Paediatric Italian Food Allergy (EPIFA) study was designed to investigate the epidemiology of pediatric FA in one of the most heavily populated Italian regions. Methods: A retrospective cohort study was performed in collaboration with family pediatricians aimed at investigating the epidemiology of Italian pediatric FA during 2009 to 2021. Family pediatricians in the Campania region were invited to use the Google Forms platform for online compilation of data forms. Data forms were reviewed by experienced pediatric allergists at the coordinating center. Results: A total population of 105,151 subjects (aged 0-14 years) was screened during the study period. Data from 752 FA patients were evaluated. A progressive increase in FA incidence and prevalence was observed from 2009 to 2021, with a relative increase up to 34% and 113.6%, respectively, at the end of study period. The relative increase in FA prevalence was higher in the 0-3-year-old age group in the same study period (+120.8%). The most frequent allergens were cow’s milk, hen’s egg, and nuts. Conclusion: The results of the EPIFA study showed an increase in pediatric FA incidence and prevalence from 2009 to 2021 in Italy. These results underline the necessity of new effective strategies for preventing and managing these conditions.

Cow's milk allergy (CMA) is one of the most common presentations of food allergy in early childhood. Management of CMA involves individualized avoidance of cow's milk and other mammalian milk and foods containing these. Optimal elimination of cow's milk avoidance includes: label reading; information about safe and nutritious substitute foods; appropriate choice of infant formula or a plant-based food; establishing tolerance to baked milk and monitoring nutritional intake and growth. Substitute formulas are divided into soy formula (not hydrolyzed), milk-based extensively hydrolyzed formulas, rice based extensive, and partially hydrolyzed formulas and amino acid-based formulas. The use of other mammalian milks is not recommended for the management of cow's milk allergy due to a high level of cross-reactivity and nutritional concerns. For toddlers who are eating well, children, and adults, a suitable plant-based beverage may be a suitable alternative to a specialized formula, following careful nutritional considerations. Families need to be instructed on finding suitable nutritious foods and how to prepare suitable meals at home. Individuals with CMA also need to know how to identify and treat acute severe reactions.

Abstract Introduction Cow’s milk allergy (CMA) is the most common food allergy in infants. As this food allergy indicates a wide range of clinical syndromes due to immunological reactions to cow’s milk proteins, we aimed to evaluate the status of micronutrients in infants suffering from cow’s milk allergy. Methods In this historical cohort study, infants with CMA were divided into two equal groups: breastfeeding and diet formula feeding. Data were gathered by a form, including the micronutrients such as iron, selenium, calcium, phosphorus, zinc, and vitamin D. Groups were compared and data were analyzed by the IBM SPSS version 21. Results This study involved 60 six-month-old infants, and the findings revealed no significant difference between the two groups concerning magnesium, phosphorus, zinc, and vitamin D. However, infants in the formula-feeding group exhibited significantly elevated mean serum levels of iron and selenium, whereas breastfed infants displayed higher levels of calcium. Conclusion The findings of this research revealed a significant difference in calcium, selenium, and iron levels between formula-fed and breastfed infants, even though all variables were within the normal range for both groups. In light of these results, conducting further studies with a larger sample size and extended follow-up periods becomes imperative.

Background: IgE‐mediated cow's milk allergy (IgE‐CMA) is one of the first allergies to arise in early childhood and may result from exposure to various milk allergens, of which β‐lactoglobulin (BLG) and casein are the most important. Understanding the underlying mechanisms behind IgE‐CMA is imperative for the discovery of novel biomarkers and the design of innovative treatment and prevention strategies. Methods: We report a longitudinal in vivo murine model, in which two mice strains (BALB/c and C57Bl/6) were sensitized to BLG using either cholera toxin or an oil emulsion (n = 6 per group). After sensitization, mice were challenged orally, their clinical signs monitored, antibody (IgE and IgG1) and cytokine levels (IL‐4 and IFN‐γ) measured, and fecal samples subjected to metabolomics. The results of the murine models were further extrapolated to fecal microbiome‐metabolome data from our population of IgE‐CMA (n = 22) and healthy (n = 23) children (Trial: NCT04249973), on which polar metabolomics, lipidomics and 16S rRNA metasequencing were performed. In vitro gastrointestinal digestions and multi‐omics corroborated the microbial origin of proposed metabolic changes. Results: During mice sensitization, we observed multiple microbially derived metabolic alterations, most importantly bile acid, energy and tryptophan metabolites, that preceded allergic inflammation. We confirmed microbial dysbiosis, and its associated effect on metabolic alterations in our patient cohort, through in vitro digestions and multi‐omics, which was accompanied by metabolic signatures of low‐grade inflammation. Conclusion: Our results indicate that gut dysbiosis precedes allergic inflammation and nurtures a chronic low‐grade inflammation in children on elimination diets, opening important new opportunities for future prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose of Review: This narrative review explores food allergy prevalence and natural history stratified by life stages, especially in context of evolving knowledge over the last few decades. Recent Findings: The prevalence of food allergy remains highest in early childhood with common food triggers being cow's milk, soy, hen's egg, wheat, peanut, tree nuts, sesame, fish, and shellfish. This correlates with certain risk factors especially pertinent in the postnatal period which appear to predispose an individual to developing a food allergy. Some allergies (such as milk and egg) were previously thought to be easily outgrown in early life; however, recent studies suggest increasing rates of persistence of these allergies into young adulthood; the reason behind this is unknown. Despite this, there is also evidence demonstrating that food allergies can be outgrown in adolescents and adults. Summary: An understanding of the paradigm shifts in the natural history of food allergy allows clinicians to provide updated, age-appropriate, and tailored advice for patients on the management and prognosis of food allergy. [ABSTRACT FROM AUTHOR]

Food-protein-induced allergic proctocolitis (FPIAP) is an increasingly reported transient and benign form of colitis that occurs commonly in the first weeks of life in healthy breastfed or formula-fed infants. Distal colon mucosal inflammation is caused by a non-IgE immune reaction to food allergens, more commonly to cow's milk protein. Rectal bleeding possibly associated with mucus and loose stools is the clinical hallmark of FPIAP. To date, no specific biomarker is available, and investigations are reserved for severe cases. Disappearance of blood in the stool may occur within days or weeks from starting the maternal or infant elimination diet, and tolerance to the food allergen is typically acquired before one year of life in most patients. In some infants, no relapse of bleeding occurs when the presumed offending food is reassumed after a few weeks of the elimination diet. Many guidelines and expert consensus on cow's milk allergy have recently been published. However, the role of diet is still debated, and recommendations on the appropriateness and duration of allergen elimination in FPIAP are heterogeneous. This review summarizes and compares the different proposed nutritional management of infants suffering from FPIAP, highlighting the pros and cons according to the most recent literature data. [ABSTRACT FROM AUTHOR]

The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating cow's milk-related symptoms. Previous studies have focused on providing CoMiSS values for healthy and symptomatic infants aged 0–6 months. However, there is a notable gap in the literature concerning CoMiSS values for infants older than 6 months. This cross-sectional study aimed to determine CoMiSS values in presumed healthy infants who have completed 6 months and are up to 12 months old, hereafter referred to as 6 to 12 months old. Physicians from six European countries prospectively determined CoMiSS values in infants attending well-child clinics. Exclusion criteria included preterm delivery, acute or chronic disease, and the consumption of a therapeutic formula, dietary supplements (except vitamins), or medication. The following information was collected: gestational age, gender, age, type of feed (breast milk or infant formula), and complementary feeding. Descriptive statistics were summarized with mean and standard deviation for normally distributed continuous variables, median and IQR for non-normally distributed variables, and differences in CoMiSS values were analyzed with appropriate tests. Data from 609 infants were obtained. The overall median (Q1–Q3) CoMiSS values were 3 (1–5). Significant differences were found across age groups (p < 0.001), but not across groups based on gender (p = 0.551) or feeding type (p = 0.880). Conclusions: This study provided CoMiSS values in presumed healthy infants aged 6–12 months. Additional studies should be conducted to establish the use of CoMiSS to assess cow's milk-related symptoms in infants 6 months and older. What is Known: • The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating symptoms related to cow's milk. • CoMiSS values for presumed healthy infants aged 0-6 months infants are already available. What is New: • CoMiSS values in European infants aged 6-12 months are provided. • These CoMiSS values differed across various age groups but not across groups based on gender or feeding type. [ABSTRACT FROM AUTHOR]

The increasing prevalence of IgE‐mediated cow's milk allergy (CMA) in childhood is a worldwide health concern. There is a growing awareness that the gut microbiome (GM) might play an important role in CMA development. Therefore, treatment with probiotics and prebiotics has gained popularity. This systematic review provides an overview of the alterations of the GM, metabolome, and immune response in CMA children and animal models, including post‐treatment modifications. MEDLINE, PubMed, Scopus, and Web of Science were searched for studies on GM in CMA‐diagnosed children, published before 1 March 2023. A total of 21 articles (13 on children and 8 on animal models) were included. The studies suggest that the GM, characterized by an enrichment of the Clostridia class and reductions in the Lactobacillales order and Bifidobacterium genus, is associated with CMA in early life. Additionally, reduced levels of short‐chain fatty acids (SCFAs) and altered amino acid metabolism were reported in CMA children. Commonly used probiotic strains belong to the Bifidobacterium and Lactobacillus genera. However, only Bifidobacterium levels were consistently upregulated after the intervention, while alterations of other bacteria taxa remain inconclusive. These interventions appear to contribute to the restoration of SCFAs and amino acid metabolism balance. Mouse models indicate that these interventions tend to restore the Th2/Th1 balance, increase the Treg response, and/or silence the overall pro‐ and anti‐inflammatory cytokine response. Overall, this systematic review highlights the need for multi‐omics‐related research in CMA children to gain a mechanistic understanding of this disease and to develop effective treatments and preventive strategies. [ABSTRACT FROM AUTHOR]

IntroductionThe diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. Our aim was to compare the opinions of expert groups from the Middle East (n = 14) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n = 13).MethodsThese Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared.ResultsOverall, there was consensus amongst both groups of experts. Experts agreed that symptoms of crying, irritability and colic, as single manifestation, are not suggestive of CMA. They agreed that amino-acid based formula (AAF) should be reserved for severe cases (e.g., malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no unanimous consensus on the statement that a cow's milk based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role for hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle-East region. All ESPGHAN experts agreed that there is insufficient evidence that the addition of probiotics, prebiotics and synbiotics increase the efficacy of elimination diets regarding CMA symptoms (despite other benefits such as decrease of infections and antibiotic intake), whereas 3/14 of the Middle East group thought there was sufficient evidence.DiscussionDifferences in voting are related to geographical, cultural and other conditions, such as cost and availability. This emphasizes the need to develop region-specific guidelines considering social and cultural conditions, and to perform further research in this area.

Abstract Background The basophil activation test is an emerging clinical tool in the diagnosis of cow's milk allergy (CMA). The aim was to assess the association between the basophil allergen threshold sensitivity to the major milk protein casein (casein‐specific CD‐sens), the levels of milk‐ and casein‐specific Immunoglobulin E antibodies (IgE‐ab), and the severity of allergic reactions at milk challenges. Methods We enrolled 34 patients aged 5–15 (median 9) years who underwent a double‐blind placebo‐controlled milk‐challenge (DBPCMC) as screening before inclusion in an oral immunotherapy study for CMA. The severity of the allergic reaction at the DBPCMC was graded using Sampson's severity score. Venous blood was drawn before the DBPCMC. Milk‐ and casein‐specific IgE‐ab were analyzed. Following in vitro stimulation of basophils with casein, casein‐specific CD‐sens, was determined. Results Thirty‐three patients completed the DBPCMC. There were strong correlations between casein‐specific CD‐sens and IgE‐ab to milk (rs = 0.682, p

Milk fat globule membrane (MFGM), which contains abundant glycoproteins and phospholipids, exerts beneficial effects on intestinal health and immunomodulation. The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy (CMA) in a β-lactoglobulin (BLG)-induced allergic mice model. MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight. Results demonstrated that MFGM alleviated food allergy symptoms, decreased serum levels of lipopolysaccharide, pro-inflammatory cytokines, immunoglobulin (Ig) E, IgG1, and Th2 cytokines including interleukin (IL)-4, while increased serum levels of Th1 cytokines including interferon-γ and regulatory T cells (Tregs) cytokines including IL-10 and transforming growth factor-β. MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice, as evidenced by decreased relative abundance of Desulfobacterota, Rikenellaceae, Lachnospiraceae, and Desulfovibrionaceae, while increased relative abundance of Bacteroidetes, Lactobacillaceae and Muribaculaceae, and enhanced expressions of tight junction proteins including Occludin, Claudin-1 and zonula occludens-1. Furthermore, MFGM increased fecal short-chain fatty acids (SCFAs) levels, which elevated G protein-coupled receptor (GPR) 43 and GPR109A expressions. The increased expressions of GPR43 and GPR109A induced CD103+ dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent. In summary, MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation, which may be correlated with SCFAs-mediated activation of GPRs. These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Background: Oral immunotherapy (OIT) can ameliorate cow's milk allergy (CMA); however, the achievement of sustained unresponsiveness (SU) is challenging. Regarding the pathogenesis of CMA, recent studies have shown the importance of gut microbiota (Mb) and fecal water-soluble metabolites (WSMs), which prompted us to determine the change in clinical and gut environmental factors important for acquiring SU after OIT for CMA. Methods: We conducted an ancillary cohort study of a multicenter randomized, parallel-group, delayed-start design study on 32 school-age children with IgE-mediated CMA who underwent OIT for 13 months. We defined SU as the ability to consume cow's milk exceeding the target dose in a double-blind placebo-controlled food challenge after OIT followed by a 2-week-avoidance. We longitudinally collected 175 fecal specimens and clustered the microbiome and metabolome data into 29 Mb- and 12 WSM-modules. Results: During OIT, immunological factors improved in all participants. However, of the 32 participants, 4 withdrew because of adverse events, and only 7 were judged SU. Gut environmental factors shifted during OIT, but only in the beginning, and returned to the baseline at the end. Of these factors, milk- and casein-specific IgE and the Bifidobacterium-dominant module were associated with SU (milk- and casein-specific IgE; OR for 10 kUA/L increments, 0.67 and 0.66; 95%CI, 0.41–0.93 and 0.42–0.90; Bifidobacterium-dominant module; OR for 0.01 increments, 1.40; 95%CI, 1.10–2.03), and these associations were observed until the end of OIT. Conclusions: In this study, we identified the clinical and gut environmental factors associated with SU acquisition in CM-OIT.

Background. Using soy formulas in infant nutrition goes back more than 100 years. They have evolved from simple mixtures based on ground roasted beans to high-tech modern products based on soy protein isolate. Due to their high nutritional value, soy formulas remain a popular alternative when it comes to choosing a dairy-free diet. But there is still an ongoing debate about their safety, with particular attention being paid to the content and activity of phytoestrogens. In 2021, an international consensus of experts recognized soy formulae as safe for growth and development based on available scientific evidence. However, research continues, and with the growing popularity of plant-based diets, soy continues to be a focus of attention for scientists around the world. From the uncontrolled use of soy formulas in the past, the trend has long since shifted to using them as a specialized product for indications under medical supervision. Soy formulae are included in major international recommendations as second-line dietary therapy for cow's milk allergy. Allergy prevention with soy formulae, however, remains open and requires further research. Soy formulae are the product of choice for galactosemia and can also be used for diarrhea. They remain in the pediatrician's practice, but require certain prescribing guidelines. Objective. This article reviews the recommendations of leading experts and regulators on the use of soy protein isolate-based infant formulas.

Abstract Background Food ladders are tools designed to facilitate home-based dietary advancement in children with food allergies through stepwise exposures to increasingly allergenic forms of milk and egg. Several studies have now documented safety and efficacy of food ladders. In 2021, we published a Canadian adaptation of the previously existing milk and egg ladders originating in Europe using foods more readily available/consumed in Canada. Our study adds to the growing body of evidence supporting food ladder use and provides safety and effectiveness data for our Canadian adaptation of the milk and egg ladders. Methods Surveys were distributed to families of children using the Canadian Milk Ladder and/or the Canadian Egg Ladder at baseline, with follow up surveys at 3 months, 6 months, and 12 months. Data were analyzed using REDCap and descriptive and inferential statistics are presented. Results One hundred and nine participants were started on milk/egg ladders between September 2020 and June 2022. 53 participants responded to follow up surveys. Only 2 of 53 (3.8%) participants reported receiving epinephrine during the study. Severe grade 4 reactions (defined according to the modified World Allergy Organization grading system) were not reported by any participants. Minor cutaneous adverse reactions were common, with about 71% (n = 10/14) of respondents reporting cutaneous adverse reactions by 1 year of food ladder use. An increasing proportion of participants could tolerate most foods from steps 2–4 foods after 3, 6, and 12 months of the food ladder compared to baseline. Conclusion The Canadian food ladders are safe tools for children with cow’s milk and/or egg allergies, and participants tolerated a larger range of foods with food ladder use compared to baseline.

A single-arm study was conducted with 10 children aged 2–12 years with severe cow's milk allergy (CMA) requiring complete allergen elimination. Subjects were administered kestose, a prebiotic, at 1 or 2 g/day for 12 weeks. Results of a subsequent oral food challenge (OFC) showed a statistically significant increase in the total dose of cow's milk ingestion (1.6 ml vs. 2.7 ml, p = 0.041). However, the overall evaluation of the OFC results, TS/Pro (total score of Anaphylaxis Scoring Aichi (ASCA)/cumulative dose of protein), showed no statistically significant improvement, although the values were nominally improved in seven out of 10 subjects. The 16S rDNA analysis of fecal samples collected from the subjects revealed a statistically significant increase in the proportion of Faecalibacterium spp. (3.8 % vs. 6.8%, p = 0.013), a type of intestinal bacterium that has been reported to be associated with food allergy. However, no statistically significant correlation was found between Faecalibacterium spp. abundance and the results of the OFC.

Some infants and young children suffer from cow's milk allergy (CMA), and have always mainly used hypoallergenic infant formula as a substitute for breast milk, but some of these formulas can still cause allergic reactions. In recent years, it has been found that probiotic nutritional interventions can regulate CMA in children. Scientific and reasonable application of probiotics to hypoallergenic infant formula is the key research direction in the future. This paper discusses the mechanism and clinical symptoms of CMA in children. This review critically ex- amines the issue of how probiotics use intestinal flora as the main vector to combine with the immune system to exert physiological functions to intervene CMA in children, with a particular focus on four mechanisms: promoting the early establishment of intestinal microecological balance, regulating the body's immunity and alleviating allergic response, enhancing the intestinal mucosal barrier function, and destroying allergen epitopes. Additionally, it overviews the development process of hypoallergenic infant formula and the research progress of probiotics in hypoallergenic infant formula. The article also offers suggestions and outlines potential future research directions and ideas in this field.

Cow’s milk allergy (CMA) is one of the most common and complex presentations of allergy in early childhood. CMA can present as IgE and non-IgE mediated forms of food allergy. Non-IgE mediated CMA includes food protein-induced enterocolitis syndrome (FPIES), eosinophilic gastrointestinal disorders (EGIDs), and food protein-induced proctocolitis (FPIAP). There are recent guidelines addressing CMA diagnosis, management, and treatment. Each of these guidelines have their own strengths and limitations. To best manage CMA, individualized avoidance advice should be given. Cow’s milk (CM) can be replaced in the diet by using hypoallergenic formulas or plant-based milk, depending on factors such as the child’s age and their current food intake. Oral and epicutaneous immunotherapy is used to increase tolerance in children with CMA but is not without risk, and the long-term outcome of sustained unresponsiveness is still unclear. The allergenicity of CM proteins are affected differently by different forms of heating, leading to the use of baked milk or milk ladders in the management of CMA, most likely the most promising option for future management and treatment of CMA. Future management of children with CMA will also include discussion around the immunomodulatory potential of the child’s dietary intake.

Food allergy represents a failure of oral tolerance mechanisms to dietary antigens. Over the past few years, food allergies have become a growing public health problem worldwide. Gut microbiota is believed to have a significant impact on oral tolerance to food antigens and in initiation and maintenance of food allergies. Therefore, probiotics have also been proposed in this field as a possible strategy for modulating both the gut microbiota and the immune system. In recent years, results from preclinical and clinical studies suggest a promising role for probiotics in food allergy prevention and treatment. However, future studies are needed to better understand the mechanisms of action of probiotics in food allergies and to design comparable study protocols using specific probiotic strains, defined doses and exposure times, and longer follow-up periods. [ABSTRACT FROM AUTHOR]

Oral immunotherapy (OIT) can ameliorate cow's milk allergy (CMA); however, the achievement of sustained unresponsiveness (SU) is challenging. Regarding the pathogenesis of CMA, recent studies have shown the importance of gut microbiota (Mb) and fecal water-soluble metabolites (WSMs), which prompted us to determine the change in clinical and gut environmental factors important for acquiring SU after OIT for CMA. We conducted an ancillary cohort study of a multicenter randomized, parallel-group, delayed-start design study on 32 school-age children with IgE-mediated CMA who underwent OIT for 13 months. We defined SU as the ability to consume cow's milk exceeding the target dose in a double-blind placebo-controlled food challenge after OIT followed by a 2-week-avoidance. We longitudinally collected 175 fecal specimens and clustered the microbiome and metabolome data into 29 Mb- and 12 WSM-modules. During OIT, immunological factors improved in all participants. However, of the 32 participants, 4 withdrew because of adverse events, and only 7 were judged SU. Gut environmental factors shifted during OIT, but only in the beginning, and returned to the baseline at the end. Of these factors, milk- and casein-specific IgE and the Bifidobacterium -dominant module were associated with SU (milk- and casein-specific IgE; OR for 10 kU A /L increments, 0.67 and 0.66; 95%CI, 0.41–0.93 and 0.42–0.90; Bifidobacterium -dominant module; OR for 0.01 increments, 1.40; 95%CI, 1.10–2.03), and these associations were observed until the end of OIT. In this study, we identified the clinical and gut environmental factors associated with SU acquisition in CM-OIT. [ABSTRACT FROM AUTHOR]

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE cell mediated food allergy triggered by the ingestion of specific food proteins that may manifest in an acute or chronic form. We report a case of an infant with severe chronic FPIES presenting in the neonatal period that failed to respond to amino acid-based formulas. The patient remained on total parenteral nutrition for 4 weeks and after that he could tolerate amino acid formula. Our case suggests that bowel rest for extended periods may be necessary for severe cases of FPIES, while endoscopy may be helpful in the differential diagnosis and the therapeutic management of these cases. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate outcomes of oral food challenge (OFC) test to assess tolerance in infants with non-IgE-mediated cow's milk allergy (CMA) with gastrointestinal manifestations and explore clinical data predictive of these outcomes. Methods: Single-center retrospective study including infants (age < 12 months) who were referred for CMA between 2000 and 2018 and underwent OFC on follow-up. A univariate logistic regression test was performed to evaluate variables associated with the outcomes of the follow-up OFC test. Results: Eighty-two patients were included, 50% were male. Eighteen patients had a positive OFC test (22%). Most patients had presented with hematochezia (77%). The median age of symptom onset was 30 days. Two-thirds of the patients were on appropriate infant formula (extensively hydrolyzed or amino acid-based formula), exclusively or in association with breastfeeding. The median time on an elimination diet before the OFC test was 8 months (Q1 6 - Q3 11 months). All cases with positive follow-up OFC tests (n = 18) had been exposed to cow's milkbased formula before the first clinical manifestation of CMA. Five out of eight cases with Food Protein-Induced Enterocolitis Syndrome (FPIES) had positive OFC tests. Exposure to cow's milkbased formula before diagnosis, a history of other food allergies, hematochezia and diarrhea were predictors of a positive OFC test. Conclusions: In infants with non-IgE-mediated CMPA with gastrointestinal manifestations, the use of cow's milk-based formula, a history of other food allergies, and hematochezia and diarrhea upon initial presentation were associated factors for the later achievement of tolerance. [ABSTRACT FROM AUTHOR]

Background: Approximately 50%–90% of children with immediate‐type cow's milk allergy (CMA) acquire tolerance by pre‐school age. We aimed to investigate the acquisition rate of CMA tolerance in children aged 6–12 years. Methods: We included children with CMA who persisted until the age of 6. Tolerance was defined as passing an oral food challenge with 200 mL of unheated cow's milk (CM) or consuming 200 mL of CM without symptoms, whereas persistent CMA was defined as fulfilling neither of these criteria by 12 years old. Children receiving oral immunotherapy (OIT) were excluded from the primary analysis. Risk factors associated with persistent CMA were assessed using Cox regression analysis. Results: Of 80 included children, 30 (38%) had previous CM anaphylaxis, and 40 (50%) had eliminated CM completely from their diet. The median CM‐specific immunoglobulin E (sIgE) level at 6 years old was 12.0 kUA/L. Tolerance was acquired by 25 (31%) and 46 (58%) children by the age of 9 and 12 years, respectively. At baseline, persistent CMA was associated with higher CM‐sIgE levels (hazard ratio 2.29, 95% confidence interval 1.41–3.73, optimal cutoff level 12.7 kUA/L), previous CM anaphylaxis (2.07, 1.06–4.02), and complete CM elimination (3.12, 1.46–6.67). No children with CMA who had all three risk factors (n = 14) acquired tolerance. Conclusion: Except for OIT patients, more than half of children with CMA at 6 years old acquired tolerance by 12 years old. Children with CMA who have the risk factors are less likely to acquire tolerance. [ABSTRACT FROM AUTHOR]

Objective: Food protein-induced proctocolitis (BPIAP) is a food allergy that occurs frequently in apparently healthy infants and is characterized by bloody stools, usually in the first six months of life. In this study, we aimed to evaluate the clinical and laboratory findings of patients who presented to our clinic with bloody stools and were diagnosed with BPIAP, and to provide clinicians with more information about the typical presentation, nutritional management strategies and prognosis. Method: The records of 48 patients diagnosed with BPIAP who applied to the Pediatric Immunology and Allergy Clinic of Mersin University Faculty of Medicine with the complaint of bloody stool between January 2020 and January 2023 were retrospectively reviewed. Patients' age, gender, birth characteristics, age at diagnosis, symptoms, age at onset of symptoms, diet, nutritional history, accompanying allergic diseases, physical examination findings, presence of eosinophilia, total immunoglobulin E (IgE) level, skin prick test, atopy, food-specific IgE levels, oral food challenge test, food elimination applied, elimination diet duration, tolerance development time and age were recorded. Results: A total of 48 patients diagnosed with BPIAP were included in the study; 29 (60%) of which were males and 19 (40%) were females. The median ages at symptom onset and the diagnosis were three months (25-75 percentile: 2-4 months), and four months (25-75 percentile: 2.25-6 months) respectively. While 30 (62.5%) infants with symptoms were breastfed only, 12 (25%) received both breast milk and formula. The most common associated atopic disease was atopic dermatitis (n=8, 16.6%). While bloody stools were observed in all patients, six (12.5%) patients only had bloody stools and 22 patients (45.8%) had additional mucus. The most common cause was cow's milk (n=34, 70.8%) and it was the sole culprit in 29 patients (60.4%). The second most common trigger was eggs (n=15, 31.25%). Elimination of cow's milk protein was performed in 34 patients (70.8%). Six of these patients (17.6%) received a cow's milk elimination diet alone, whereas 18 patients (52.9%) received a highly hydrolyzed formula (eHF) in addition to the elimination diet, and 10 patients (29.4%) received an amino acid-based formula (AAF). Single elimination, was performed for eggs in 11 patients (23%), walnuts in one patient (2%), sesame in one patient (2%), and chicken meat in one patient (2%). In our study, tolerance developed in 39 patients (81.3%). The median age of tolerance development in patients was 12 months (25-75th percentile: 10-18 months). Conclusion: Although the prognosis of BPIAP is good, symptoms cause great concern among physicians and families, followed by unnecessary tests and invasive procedures. Milk and eggs are the most commonly responsible foods, however it should be kept in mind that different foods such as chicken, walnuts and sesame can cause BPIAP. Our study confirms the good clinical course of BPIAP. Although tolerance usually develops within the first year, symptoms may persist longer in some patients. Therefore, patients should be followed for a longer period. [ABSTRACT FROM AUTHOR]

Guidelines and recommendations for the diagnosis and management of cow's milk allergy (CMA) in childhood are based on scientific review of the available evidence. While this approach is the most rigorous, guidelines may not fully address all scenarios encountered by clinicians. Many symptoms of CMA overlap with other common childhood illnesses and are subjectively reported by the caregivers of the infant, as is the interpretation of the dietary interventions. Additionally, many healthcare professionals and caregivers do not follow the recommendations to perform an oral food challenge or reintroduction of cow's milk after a diagnostic elimination diet because (1) the infant is doing well and (2) the carer's fear of symptoms relapsing with this procedure. As a result, CMA in infants may be either under-diagnosed leading to reduced quality of life for families or over-diagnosed, resulting in unnecessary long-term elimination diets and increasing the risk for nutritional deficiencies. This paper discusses some of these controversial topics, focusing on misdiagnosis and mismanagement in clinical practice. The lack of objective diagnostic criteria can hamper the diagnosis and management of CMA in daily practice. [ABSTRACT FROM AUTHOR]

Background: Food ladders are tools designed to facilitate home-based dietary advancement in children with food allergies through stepwise exposures to increasingly allergenic forms of milk and egg. Several studies have now documented safety and efficacy of food ladders. In 2021, we published a Canadian adaptation of the previously existing milk and egg ladders originating in Europe using foods more readily available/consumed in Canada. Our study adds to the growing body of evidence supporting food ladder use and provides safety and effectiveness data for our Canadian adaptation of the milk and egg ladders. Methods: Surveys were distributed to families of children using the Canadian Milk Ladder and/or the Canadian Egg Ladder at baseline, with follow up surveys at 3 months, 6 months, and 12 months. Data were analyzed using REDCap and descriptive and inferential statistics are presented. Results: One hundred and nine participants were started on milk/egg ladders between September 2020 and June 2022. 53 participants responded to follow up surveys. Only 2 of 53 (3.8%) participants reported receiving epinephrine during the study. Severe grade 4 reactions (defined according to the modified World Allergy Organization grading system) were not reported by any participants. Minor cutaneous adverse reactions were common, with about 71% (n = 10/14) of respondents reporting cutaneous adverse reactions by 1 year of food ladder use. An increasing proportion of participants could tolerate most foods from steps 2–4 foods after 3, 6, and 12 months of the food ladder compared to baseline. Conclusion: The Canadian food ladders are safe tools for children with cow's milk and/or egg allergies, and participants tolerated a larger range of foods with food ladder use compared to baseline. [ABSTRACT FROM AUTHOR]

Food allergy has become a significant public health problem affecting a large number of people worldwide. Maternal obesity causes inflammation and alters the immune system of offspring, which may exacerbate their food allergy. The aim of this study was to determine whether offspring mice born to obese mothers would have more serve reactions to cow’s milk protein-induced food allergy, and further investigate the underlying mechanisms. Female offspring BALB/c mice of mothers with normal and high-fat diets were sensitized with β-lactoglobulin (BLG), respectively. Maternal obesity increased the serum immunoglobulin E and mouse mast cell protease levels, though did not have significant influence on anaphylactic symptom score, core temperature and diarrhea rate of offspring mice after BLG sensitization. Furthermore, maternal obesity led to a lower level of occludin mRNA expression in BLG -sensitized mice. The mice born to obese mothers exhibited increased mRNA expression levels of GATA-3, interleukin (IL)-4 and IL-10 in jejunum after BLG sensitization, indicating maternal obesity intensified Th2-type biased immune responses. In conclusion, maternal obesity exerted exacerbating effects on the responsiveness of their offspring to cow’s milk protein sensitization.

Cow’s milk allergy has been studied extensively in infants and young children and has public health importance around the globe. We describe the clinical and demographic characteristics of 3 cases of a rare presentation of adult-onset IgE-mediated cows' milk allergy.