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Objectives: To review the evidence pertaining to the association between cow’s milk protein allergy and recurrent acute otitis media and otitis media with effusion. Methods: The CENTRAL, Web of Science, EMBASE, MEDLINE, LILACS databases, and gray literature were searched. Results: Four studies were included, identifying the prevalence rates: 0.2% of delayed speech due to chronic otitis media with effusion in 382 children with cow’s milk protein allergy, 10.7% of cow’s milk protein allergy in 242 children who underwent ENT procedures, 40% of cow’s milk protein allergy in 25 children with recurrent otitis media with effusion and higher tendency to otitis media in children with cow’s milk protein allergy of 186 children (1.5 + 0.6 vs. 0.4 + 0.1; p

A large proportion of prescriptions for extensively hydrolyzed cow's milk protein (CMP) in newborns are not based on any scientific data justifying the indication. Many of these prescriptions are old habits or are based on incomplete data. The aim of this article is to analyze these practices and propose recommendations. The following points are covered: (a) indications for extensively hydrolyzed formula based on studies demonstrating their benefits in these situations-newborns with a proven allergy to CMP and occasional prescription of supplements to breastfeeding; (b) possible indications not based on a high level of evidence-re-initiation of feeding due to necrotizing enterocolitis, short bowel syndrome, re-initiation of feeding of newborns following intestinal surgery, and laparoschisis if neither the mother's own milk nor milk from a lactarium is available; (c) unjustified indications-newborns at risk of atopy, prematurity, severe neurological pathologies, newborns who are hemodynamically unstable and/or have congenital cardiopathy, neonatal hypoxic-ischemic encephalopathy treated with hypothermia, and newborns with esophageal atresia or diaphragmatic hernia. By following this classification, the prescriber will be guided to use the milk best suited to the pathology, bearing in mind that each situation must be adapted individually and the tolerance and effectiveness of the food reassessed from a nutritional and functional point of view., Competing Interests: Declaration of competing interest V. Rigourd, A. Heneau, A.L. Virlouvet, A. Basset, E. Herry, B. Jaquemet, A. Lapillonne, M. Bellaiche: no conflicts of interest; P. Tounian: Carrefour, Danone, Lactalis, Materna, Mead Johnson, Nestlé, Novalac, PédiAct, Sodilac., (Copyright © 2024 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: Low dose reactive cow's milk (CM) allergic children are at high risk of persistent CM allergy and a positive oral food challenge (OFC). The present study aimed to evaluate if the results of a very low dose (VL) OFC with these children contributes to better management of CM allergy. Methods: We retrospectively reviewed subjects with CM allergy who underwent a VL OFC with 3 mL heated CM and had a previous allergic reaction to

Cow's milk is one of the "big eight" most common allergenic foods, and β-lactoglobulin and α-Lactalbumin in whey protein are two major allergens of cow's milk protein. An effective strategy for reducing the allergenicity of whey protein is needed. In the present study, protein-EGCG complexes were obtained through non-covalent interactions between untreated or sonicated whey protein isolate (WPI) and epigallocatechin gallate (EGCG), and the allergenicity of complexes was assessed in vivo. The results showed that SWPI-EGCG complex possesses low allergenicity in BALB/c mice. As compared with untreated WPI, SWPI-EGCG complex had less effect on the body weight and organ indexes. Moreover, SWPI-EGCG complex could alleviate the WPI induced allergic reactions and intestinal damage of mice by decreasing the secretion of IgE, IgG, histamine, mMCP-1, modulating the balance of Th1/Th2 and Treg/Th17 response, and increasing the diversity of intestinal flora and the relative abundances of probiotic bacteria. These findings indicate that the interaction of sonicated WPI with EGCG could reduce the allergenicity of WPI, which could provide a new strategy for reducing food allergenicity., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

OBJETIVO: Avaliar a ingestão alimentar e o estado nutricional de crianças em dieta isenta de leite de vaca e derivados. MÉTODOS: Foram avaliadas 26 crianças, na primeira consulta realizada em ambulatório de gastroenterologia pediátrica, que vinham recebendo dieta isenta de leite de vaca e derivados (média de idade = 19,1 meses) e 30 crianças com dieta normal, isto é, sem nenhum tipo de restrição alimentar (média de idade = 16,8 meses). Empregou-se o método do dia alimentar habitual para a obtenção dos dados sobre consumo alimentar. A ingestão alimentar foi comparada entre os grupos e em relação às Dietary Reference Intakes (DRIs). O estado nutricional foi avaliado com base nos escores z de peso/idade, estatura/idade e peso/estatura. RESULTADOS: O grupo em dieta isenta de leite de vaca apresentou menor ingestão de energia (p = 0,005), proteínas (p < 0,001), lipídios (p < 0,001), cálcio (p < 0,001) e fósforo (p < 0,001) quando comparado ao grupo controle. Houve maior número de crianças no grupo em dieta isenta de leite de vaca com ingestão de energia, cálcio e fósforo inferior às DRIs em comparação ao grupo controle. As médias dos escores z dos grupos com dieta isenta de leite de vaca e controle, foram, respectivamente: estatura/idade -0,81±1,06 versus +0,42 ±1,25 (p < 0,001), peso/idade -1,03±1,21 versus +0,02 ±0,91 (p < 0,001) e peso/estatura -0,63 ±1,08 versus +0,30 ±1,11 (p = 0,004). CONCLUSÕES: Durante a terapêutica de exclusão do leite de vaca e seus derivados, deve ser realizado, periodicamente, monitoramento da ingestão alimentar qualitativa e quantitativamente, a fim de se prevenir prováveis inadequações no atendimento às necessidades nutricionais, bem como prejuízo ao crescimento e desenvolvimento dessas crianças.OBJECTIVE: To assess the food intake and the nutritional status of children on a cow's milk and cow's milk by-products free diet. METHODS: Twenty-six children receiving a cow's milk and cow's milk by-products free diet were assessed during their first visit to the Pediatric Gastroenterology Clinic (mean age = 19.1 months). Thirty children with no food restriction (mean age = 16.8 months) were also assessed. The usual daily food intake method was used to make the dietary assessment. The food intake was compared between the groups and in relation to the Dietary Reference Intakes (DRIs). The z-scores for weight/age, height/age and weight/height were used to evaluate the nutritional status. RESULTS: The cow's milk free diet group presented lower energy (p = 0.005), protein (p < 0.001), lipid (p < 0.001), calcium (p < 0.001) and phosphorous (p < 0.001) intake when compared to the control group. The number of children who had energy, calcium and phosphorous intake below the DRIs was higher in the cow's milk free diet group than in the control group. The z-score means for the cow's milk free diet and control groups were, respectively: height/age -0.81±1.06 vs +0.42±1.25 (p < 0.001), weight/age -1.03±1.21 vs +0.02+0.91 (p < 0.001), and weight/height -0.63+1.08 vs +0.30+1.11 (p = 0.004). CONCLUSIONS: During the cow's milk and cow's milk by-products exclusion therapy, qualitative and quantitative food intake monitoring must be carried out periodically, so as to prevent inadequacies in meeting nutritional requirements and impairment of growth and development.

Background: Soy-based infant formulas are increasingly popular, but data regarding their effects on neurodevelopmental outcomes during early childhood is scanty., Objective: This study investigated the effect of consuming soy-based infant formula at 9-12 mo after birth on the subsequent development of epilepsy, neurodevelopmental disorders, and developmental status., Methods: This nationwide retrospective administrative study used health screening examinations and linked insurance claims data of children born in Korea during 2008 and 2009. Infants who received soy formula were compared with those who received cow's milk formula using propensity score matching that considered birth history, economic status, clinical conditions, and drug prescription records. Exposure was defined as soy formula feeding determined from questionnaires completed by the parents when children were 9-12 mo old. Outcomes were epilepsy, attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental status. Children were followed until 31 December, 2017., Results: A total of 153,841 eligible participants were enrolled; 11,535 (7.5%) children received soy formula, while 142,864 (92.5%) received cow's milk formula. The incidence rate of epilepsy during the follow-up period was 29.8 per 100,000 person-years (95% CI: 19.48, 41.65) in the soy formula group and 22.6 per 100,000 person-years (95% CI: 31.97, 59.07) in the cow's milk formula group, with no significant difference (aHR: 1.318; 95% CI: 0.825, 2.106). The 2 groups also had no difference based on prespecified analysis using different definitions of epilepsy. Likewise, no significant associations of soy formula with ADHD (aHR: 1.26; 95% CI: 1.00, 1.60) or ASD (aHR: 0.99; 95% CI: 0.54, 1.83), or delays of developmental stages were observed., Conclusions: Feeding with soy formula rather than cow's milk formula had no apparent association with increased risks of epilepsy, ADHD, ASD, and developmental status, according to this cohort composed of a general pediatric population., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

A number of studies have reported comorbidity of food allergies with various neuropsychiatric disorders, such as anxiety, depression, attention-deficit hyperactivity disorder, and autism. However, inconsistent results across clinical studies have left the association between food allergy and behavioral disorders inconclusive. We postulated that the heterogeneities in genetic background among allergic cohorts affect symptom presentation and severity of food allergy, introducing bias in patient selection criteria toward individuals with overt physical reactions. To understand the influence of genetic background on food allergy symptoms and behavioral changes beyond anaphylaxis, we generated mouse models with mild cow's milk allergy by sensitizing male and female C57BL/6J and BALB/cJ mice to a bovine whey protein, β-lactoglobulin (BLG; Bos d 5). We compared strain- and sex-dependent differences in their immediate physical reactions to BLG challenge as well as anxiety-like behavior one day after the challenge. While reactions to the allergen challenge were either absent or mild for all groups, a greater number of BLG-sensitized BALB/cJ mice presented visible symptoms and hypothermia compared to C57BL/6J mice. Interestingly, male mice of both strains displayed anxiety-like behavior on an elevated zero maze without exhibiting cognitive impairment with the cross maze test. Further characterization of plasma cytokines/chemokines and fecal microbiota also differentiated strain- and sex-dependent effects of BLG sensitization on immune-mediator levels and bacterial populations, respectively. These results demonstrated that the genetic variables in mouse models of milk allergy influenced immediate physical reactions to the allergen, manifestation of anxiety-like behavior, levels of immune responses, and population shift in gut microbiota. Thus, stratification of allergic cohorts by their symptom presentations and severity may strengthen the link between food allergy and behavioral disorders and identify a population(s) with specific genetic background that have increased susceptibility to allergy-associated behavioral disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

β-Lactoglobulin (β-LG) is a member of lipocalin superfamily of transporters for small hydrophobic molecules. β-LG is also one of the major allergens in milk. Despite a lot of researches on decreasing of cow's milk allergenicity, the effects of the mutation of β-LG on its recognition by IgE from cow's milk allergy (CMA) patients have not been investigated. We described here the expression in the yeast Pichia pastoris of a mutant β-LG, in which Alanine 86 was changed into Glutamine (Ala86Gln; a mutation on one of the major epitopes of the protein). The purity and native like folded structure of the recombinant Ala86Gln have been demonstrated using circular dichroism, HPLC, SDS-PAGE and mass spectrometry. The effect of the mutation on the binding of IgE from CMA patients to mutant protein was evaluated by ELISA methods and the results showed that the mutation of Ala-86 was associated with weaker binding of IgE from CMA patients to Ala86Gln mutant protein. Subsequently, the binding of various ligands such as retinol, palmitic acid, resveratrol and serotonin, with native, recombinant wild type and Ala86Gln mutant β-LGs were investigated by fluorescence spectroscopy and an improvement on the binding affinity of the mutated protein to various ligands was observed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Low dose reactive cow's milk (CM) allergic children are at high risk of persistent CM allergy and a positive oral food challenge (OFC). The present study aimed to evaluate if the results of a very low dose (VL) OFC with these children contributes to better management of CM allergy., Methods: We retrospectively reviewed subjects with CM allergy who underwent a VL OFC with 3 mL heated CM and had a previous allergic reaction to <25 mL heated CM in the 2 years before the OFC. Subjects who passed the OFC were defined as VL tolerant, and subjects who failed were defined as VL reactive. VL tolerant subjects increased the dose to 25 mL heated CM either during an OFC in our hospital or gradually at home., Results: Of the 83 subjects (median age, 4.3 years; range, 1.0-12.9 years) who were included, 41 (49.4%) were VL tolerant, and 42 (51.6%) were VL reactive. Thirty-nine VL reactive subjects had skin and/or respiratory symptoms during the OFC. Most reactions could be treated with an antihistamine and/or a nebulized β2 agonist. The VL tolerant subjects consumed 3 mL heated CM or 10 g butter. Within the year following the OFC, 18 VL tolerant subjects (45.0%), but none of the VL reactive subjects, were able to consume 25 mL heated CM (p < 0.001)., Conclusions: A VL OFC allows the management of some low dose reactive CM allergic children to change from complete avoidance to partial intake of CM., (Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

This study describes two phases of a multi-phase project aiming to validate a mouse model for cow's milk allergy to assess the potential allergenicity of hydrolysed cow's milk based infant formulas (claim support EC-directive 2006/141/E). The transferability and the discriminatory power of this model was evaluated in 4 research centers. Mice were sensitized by oral gavage with whey or extensively hydrolysed whey (eWH) using cholera toxin as an adjuvant. Whey-specific antibodies, mMCP-1 levels, anaphylactic shock symptoms, body temperature and the acute allergic skin response were determined upon whey challenge. In phases I and II, all 4 centers detected elevated levels of whey-specific IgE/IgG1 in whey sensitized animals. Elevated levels of mMCP-1, anaphylactic symptoms, body temperature drop and acute allergic skin response were scored upon whey challenge in 3 out of 4 research centers. In contrast, none of the evaluated parameters were elevated in eWH orally exposed groups. The cow's milk allergy mouse model is capable to distinguish the sensitizing capacity of complete or hydrolysed cow's milk protein. The model uses straightforward parameters relevant to food allergic responses and can be effectively transferred between different laboratories. We propose this mouse model as a new strategy for the screening of new hypoallergenic cow's milk formulas., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Infants with cow milk allergy (CMA) are reported to have reduced growth and special nutritional needs., Objective: The aim of the present study was to compare nutrient intake, nutritional status, and growth in infants with CMA who were fed either a soy formula or an extensively hydrolyzed whey formula., Design: The study group comprised 168 double-blind challenge-proven infants with CMA. Eighty-four of the infants were fed a soy formula (mean starting age: 7.8 mo), and the other 84 infants were fed an extensively hydrolyzed whey formula (mean starting age: 7.5 mo)., Results: The length (SD score) of the infants was close to the mean Finnish reference growth by age 2 y in both groups. Weight-for-length measurements continued to reach the 50th percentile by age 4 y in both study groups. The mean nutrient intake followed the recommended intake in both groups, although most of the infants were supplemented with calcium and vitamin D. The observed serum transferrin receptor concentrations indicated a greater iron inadequacy in the tissue of infants in the soy formula group than in the hydrolyzed whey formula group (P = 0.08). However, there were no significant differences between the groups either in the percentages of abnormally low laboratory values (mean cell volume, hemoglobin, zinc, and ferritin) or in the percentages of high alkaline phosphatase activity, which indicates the comparable safety and effectiveness of the formulas studied., Conclusions: Both nutritional status and growth were well within reference values in the 2 groups, and the selection of a formula can largely be made on the basis of infant tolerance to the formulas.

The ability of inflammatory bowel disease (IBD) patients to tolerate dairy products and the guidance they receive from physicians and nutritionists on this subject are important considerations in the management of their IBD. Although most affected persons are able to consume a glass of milk daily without discomfort, additional consideration must be given to specific factors that can be relevant to certain individuals. The declaration by patients that they are "dairy sensitive" may be related to lactose intolerance or malabsorption, the long-chain triacylglycerol content of milk, allergy to milk proteins, as well as psychologic factors and the misconception that dairy products can be detrimental to their health. The prevalence of lactose malabsorption is significantly greater in patients with Crohn disease involving the small bowel than it is in patients with Crohn disease involving the colon or ulcerative colitis. In the latter colonic conditions the prevalence of lactose malabsorption is mainly determined by ethnic risk, which is based on genetic factors. In addition, lactose malabsorption in Crohn disease of the small bowel may be determined by factors other than lactase enzyme activity, such as bacterial overgrowth and/or small bowel transit time. Physicians differ widely in the advice they give their patients: some dogmatically advise avoidance of dairy products when the diagnosis is made whereas others discount the possible role of dairy in the management of IBD. IBD patients avoid dairy products more than they would need to based on the prevalence of lactose malabsorption and/or milk intolerance, probably partly because of incorrect patient perceptions and arbitrary advice from physicians and authors of popular diet books. Adequate scientific and clinical information is now available to permit recommendations about the intake of dairy products for each IBD patient.