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.

The globally dramatic increase in food allergy prevalence and severity is demanding effective preventive and therapeutic strategies. Food allergy derives from a defect of immune tolerance mechanisms. Immune tolerance is modulated by gut microbiome composition and function, and gut microbiome dysbiosis has been associated with the development of food allergy. Selected probiotic strains could regulate immune tolerance mechanisms. The mechanisms are multiple and are still not completely defined. Increasing evidence is providing useful information on the choice of optimal bacterial species/strains, dosage, and timing for intervention. The increased knowledge on the crucial role played by postbiotic gut microbiome-derived metabolites, such as butyrate, is also opening the way to a post- biotic approach in the stimulation of immune tolerance.

Cow\'s milk allergy (CMA) is a common childhood food allergy associated with a significant burden for those children who are affected and their families, including unintentional exposures that result in allergic reactions, severe allergic reactions, and anaphylaxis. In young children, cow\'s milk is one of the most frequent food triggers in anaphylactic episodes, and fatalities have also been described as a result of unintentional exposures, which reinforces the notion that milk allergy can be severe in some individuals. The natural history of CMA is favorable, with the allergy resolving over time in the majority of individuals, although some will have persistent allergy that does not resolve. The standard management approach for CMA consists of strict avoidance of milk and carriage of emergency medication for use in accidental exposures. Recently, a novel approach has emerged as an alternative option for management in patients with CMA in the form of oral immunotherapy (OIT). The aim of milk OIT is to protect patients from accidental exposures to milk-containing foods and allow patients to introduce larger amounts of milk into their diet. The goal of this article was to review the available evidence, discuss key studies that focused on milk OIT, and provide practical information and useful tips related to this novel treatment.

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.

UNASSIGNED: Updated epidemiologic data are important for defining effective public health strategies for pediatric food allergy (FA).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Casein (CN) is the primary allergenic protein in cow\'s milk, contributing to the worldwide escalating prevalence of food allergies. However, there remains limited knowledge regarding the effect of structural modifications on CN allergenicity. Herein, we prepared three modified CNs (mCN), including sodium dodecyl sulfate and dithiothreitol-induced linear CN (LCN), transglutaminase-cross-linked CN (TCN), and glucose-glycated CN (GCN). The electrophoresis results indicated widespread protein aggregation among mCN, causing variations in their molecular weights. The unique internal and external structural characteristics of mCN were substantiated by disparities in surface microstructure, alterations in the secondary structure, variations in free amino acid contents, and modifications in functional molecular groups. Despite the lower digestibility of TCN and GCN compared to LCN, they significantly suppressed IL-8 production in Caco-2 cells without significantly promoting their proliferation. Moreover, GCN showed the weakest capacity to induce LAD2 cell degranulation. Despite the therapeutic effect of TCN, GCN-treated mice displayed the most prominent attenuation of allergic reactions and a remarkably restored Th1/Th2 imbalance, while LCN administration resulted in severe allergic phenotypes and endotypes in both cellular and murine models. This study highlighted the detrimental effect of linear modifications and underscored the significance of glycation in relation to CN allergenicity.

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-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.

BACKGROUND: 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.

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.
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. 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.