Milk Allergy Research Articles

Metabolomics in Children Cow’s Milk Protein Allergy: Possible Contribution from a System Biology Approach?

One of the most frequent triggers of food anaphylaxis in pediatric age but also among the most common, early, and complex causes of childhood food allergy is cow’s milk protein allergy (CMPA). The diagnostic course and management of this allergy is defined in a complex clinical picture due to several factors. First of all, the epidemiological data are not uniform, mainly as a consequence of the diagnostic methodology used in the various studies and the different age ranges covered. In addition, there is the complexity of terminology, since although CMPA traditionally refers to immune-mediated reactions to cow’s milk, it is a term encompassing numerous clinical features with different symptoms and the requirement for specific treatments. Moreover, the differential diagnosis with other very frequent diseases, especially in the first year of life, such as gastro-esophageal reflux disease or colic, is still complex. This can result in misdiagnosis and incorrect treatment, with harmful health consequences and significant economic repercussions. In this context, the combination of several omics sciences together, which have already proved useful in clarifying the allergenicity of cow’s milk proteins with greater precision, could improve the diagnostic tests currently in use through the identification of new, more specific, and precise biomarkers that make it possible to improve diagnostic accuracy and predict the patient’s response to the various available treatments for the recovery of tolerance.

Children's food allergy: Effects of environmental influences and antibiotic use across critical developmental windows

BackgroundIncreasing studies linked outdoor air pollution (OAP), indoor environmental factors (IEFs), and antibiotics use (AU) with the first wave of allergies (i.e., asthma, allergic rhinitis, and eczema), yet the role of their exposures on children’s second wave of allergy (i.e., food allergy) are unknown. ObjectivesTo investigate the association between exposure to OAP and IEFs and childhood doctor-diagnosed food allergy (DFA) during the pre-pregnancy, prenatal, early postnatal, and current periods, and to further explore the effect of OAP and IEFs on DFA in children co-exposed to antibiotics. MethodsA retrospective cohort study involving 8689 preschoolers was carried out in Changsha, China. Data on the health outcomes, antibiotic use, and home environment of each child were collected through a questionnaire. Temperature and air pollutants data were obtained from 8 and 10 monitoring stations in Changsha, respectively. Exposure levels to temperature and air pollutants at individual home addresses were calculated by the inverse distance weighted (IDW) method. Multiple logistic regression models were employed to assess the associations of childhood DFA with exposure to OAP, IEF, and AU. ResultsChildhood ever doctor-diagnosed food allergy (DFA) was linked to postnatal PM10 exposure with OR (95% CI) of 1.18 (1.03–1.36), especially for CO and O3 exposure during the first year with ORs (95% CI) = 1.08 (1.00–1.16) and 1.07 (1.00–1.14), as well as SO2 exposure during the previous year with OR (95% CI) of 1.13 (1.02–1.25). The role of postnatal air pollution is more important for the risk of egg, milk and other food allergies. Renovation-related IAP (new furniture) and dampness-related indoor allergens exposures throughout all time windows significantly increased the risk of childhood DFA, with ORs ranging from 1.23 (1.03–1.46) to 1.54 (1.29–1.83). Furthermore, smoke-related IAP (environmental tobacco smoke [ETS], parental and grandparental smoking) exposure during pregnancy, first year, and previous year was related to DFA. Additionally, exposure to pet-related indoor allergens (cats) during first year and total plant-related allergens (particularly nonflowering plants) during previous year were associated with DFA. Moreover, exposure to plant-related allergy during first and previous year was specifically associated with milk allergy, while keeping cats during first year increased the risk of fruits/vegetables allergy. Life-time and early-life AU was associated with the increased risk of childhood DFA with ORs (95% CI) = 1.57 (1.32–1.87) and 1.46 (1.27–1.67), including different types food allergies except fruit/vegetable allergy. ConclusionsPostnatal OAP, life-time and early-life IEFs and AU exposure played a vital role in the development of DFA, supporting the "fetal origin of childhood FA" hypothesis.

Knowledge and Attitude of Community Pharmacists Toward Cow Milk Protein Allergy Complications and Treatment in Children: A Cross-Sectional Study in Sudan.

Cow's milk protein allergy is the most frequent type of food allergy in newborns and young children. It affects numerous body systems. A community pharmacist possessing adequate knowledge and appropriate practices is crucial for the management of the disease. : This study aimed to assess the knowledge and attitude of community pharmacists toward the complications and treatment of cow milk protein allergy. A descriptive cross-sectional study was conducted among 332 randomly selected community pharmacists in the Capital of Sudan (Khartoum state). Data were collected using a validated and internally consistent (Cronbach Alpha = 0.712) self-administered questionnaire Descriptive statistics and Chi-square analysis were conducted using Statistical Package for the Social Sciences version 25. The response rate was 95.8%, and about 47.8% of the population had 1-5 years of experience as community pharmacists, and 37.4% of them had a post-graduate degree. Only 30.8% of respondents had good knowledge, while 40.6% had poor knowledge, and 28.6% had scored as having fair knowledge of complications of Cow's milk protein allergy. Regarding knowledge toward treatment, 65.1% of respondents had a poor knowledge, 24.5% had fair knowledge, and only 10.4% had good knowledge. Overall, 39.62% of participants had a positive attitude, and 60.38% had a negative attitude toward this disease. Data analysis showed no significant association between the sociodemographic characteristics of respondents and their knowledge and attitude. Community pharmacists in Khartoum State had inadequate knowledge and attitude about the complications and treatment of cow milk protein allergy. As a result, we recommend the implementation of strategies to raise pharmacists' knowledge and attitude.

Basophil allergen threshold sensitivity to casein (casein-specific CD-sens) predicts allergic reactions at a milk challenge in most but not all patients.

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. 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. 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. 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.

Dietary Advancement Therapy using milk and egg ladders among children with a history of anaphylaxis

BackgroundAnaphylaxis is increasing in recent years, with common triggers in infants being milk and eggs. Currently the mainstay of treatment for milk and/or egg allergy is strict avoidance. Recently new therapies have emerged including stepwise introduction of allergens via a ladder approach. The suitability of infants for the ladders is debated. ObjectiveThis study aims to focus on the use of food ladders in children with anaphylaxis to egg or milk. MethodsRetrospective review of paediatric patients diagnosed with IgE-mediated milk and/or egg allergy between 2011-2021. Inclusion and exclusion criteria applied. Anaphylaxis defined as per the World Allergy Organisation amended criteria 2020. Data analysis utilised SPSS Version 28. Results1552 patient charts reviewed, 1094 excluded (n=458). 70 infants had anaphylaxis at diagnosis (milk n=36, egg n=34). 77.8%-85.2% with anaphylaxis successfully completed the ladder, 88.9-92.9% without anaphylaxis were successful. Children who successfully completed the ladder did so at similar rates. 20.6-50% children presenting with anaphylaxis at diagnosis experienced allergic symptoms during treatment, compared to 17.3-40.7% without anaphylaxis. Reactions were mild, mostly cutaneous and not requiring medical attention. Patients experiencing allergic symptoms while on the ladder were less likely to successfully complete treatment. ConclusionMilk and egg ladders are a safe and effective way of inducing tolerance in infants, including those with a history of anaphylaxis at diagnosis. There are no obvious predictors for who will experience allergic reactions while on the ladder, however these children are less likely to complete the ladder so parents should be educated in management of mild allergic reactions at home.

Oral Immunotherapy With Extensively Hydrolyzed Milk for a 12-Year-Old Child With Persistent, Severe Cow’s Milk Allergy

Oral Immunotherapy With Extensively Hydrolyzed Milk for a 12-Year-Old Child With Persistent, Severe Cow’s Milk Allergy

Changing clinical characteristics of pediatric inpatients with pneumonia during COVID-19 pandamic: a retrospective study

BackgroundThe COVID-19 pandemic have impacts on the prevalence of other pathogens and people’s social lifestyle. This study aimed to compare the pathogen, allergen and micronutrient characteristics of pediatric inpatients with pneumonia prior to and during the COVID-19 pandemic in a large tertiary hospital in Shanghai, China.MethodsPatients with pneumonia admitted to the Department of Pediatric Pulmonology of Xinhua Hospital between March-August 2019 and March-August 2020 were recruited. And clinical characteristics of the patients in 2019 were compared with those in 2020.ResultsHospitalizations for pneumonia decreased by 74% after the COVID-19 pandemic. For pathogens, virus, mycoplasma pneumoniae (MP) and mixed infection rates were all much lower in 2020 than those in 2019 (P < 0.01). Regarding allergens, compared with 2019, the positive rates of house dust mite, shrimp and crab were significantly higher in 2020 (P < 0.01). And for micronutrients, the levels of vitamin B2, B6, C and 25-hydroxyvitamin D (25(OH)D) in 2020 were observed to be significantly lower than those in 2019 (P < 0.05). For all the study participants, longer hospital stay (OR = 1.521, P = 0.000), milk allergy (OR = 6.552, P = 0.033) and calcium (Ca) insufficiency (OR = 12.048, P = 0.019) were identified as high-risk factors for severe pneumonia by multivariate analysis.ConclusionsThe number of children hospitalized with pneumonia and incidence of common pathogen infections were both reduced, and that allergy and micronutrient status in children were also changed after the outbreak of the COVID-19 pandemic.

Evaluation of Streptococcus mutans biofilm formation and acidogenicity of infant milk formulas for treating cow milk allergy: An in vitro study.

When infants cannot consume breast milk, the most commonly available alternative milk formula is cow milk-based. Due to a rise in the prevalence of cow milk protein allergy (CMPA) among children, this study aimed to assess the biofilm formation and acidogenicity of cow milk-based formulas as well as milk formulas suggested for children with CMPA. Cow milk-based formulas with 0%, 10%, or 18% sucrose added, partially hydrolyzed formula (pHF), extensively hydrolyzed formula (eHF), amino acid-based formula (AAF), and soy-based formulas with 0%, or 11% sucrose added were evaluated. Streptococcus mutans was used as a representative microorganism associated with caries. The acidogenicity after 24-h incubation was assessed by the pH of the formed biofilm and lactic acid formation. Biofilm formation was quantified using crystal violet staining. Additionally, the biofilm characteristics were determined using confocal laser scanning microscopy (CLSM). Comparisons were made among formulas without added sucrose to observe protein-based differences. Furthermore, formulas with different sucrose percentages were compared to explore the impact of sucrose content. When comparing the formulas without added sucrose, the biofilm formation in the cow milk-based formula and pHF were significantly greater than the soy-based formula, eHF, and AAF. In the presence of S. mutans, all formulas reduced the biofilm pH below the critical enamel pH. The cow milk-based formula and AAF showed a significantly lower biofilm pH than the pHF, soy-based, and eHF groups, while the lactic acid production was markedly higher in the cow milk-based formula, pHF and AAF, compared with the eHF and soy-based formula. Adding sucrose into the cow milk-based and soy-based formulas substantially increased biofilm mass. The biofilm pH of the cow milk-based formulas, with or without sucrose, was significantly lower than that of the soy-based formulas. The CLSM indicated distinct biofilm characteristics among the different protein-based formulas, with sucrose supplementation promoting S. mutans aggregation in cow milk-based formula biofilm and increased density and intact biofilm in the soy-based formula. All assessed milk formulas had caries-inducing factors, including those without supplemental sucrose. Among them, the eHF demonstrated the least caries-inducing factors, attributed to its minimal biofilm formation and the highest biofilm pH.

Assessing and Comparing Potential Allergenicity of Two Partially Hydrolyzed Whey-Based Formulas for Infants: A Population-Based Study in China.

In cases where breast milk is unavailable or inadequate, hydrolyzed infant formula is recommended as the primary alternative. The aim of this study is to assess and compare the allergenicity of two partially hydrolyzed whey-based formulas (PHF-Ws) using serum samples from patients with cow's milk allergy (CMA). LC-MS/MS technology is used to investigate the peptide distribution in both samples. The immunoreactivity of two PHF-Ws in 27 serum samples from 50 Chinese infants (02 years) with CMA is analyzed. The results demonstrate that even with a similar a degree of hydrolysis (DH), primary protein sources, peptides with molecular weights <5 kDa, and differences in the number of residual allergenic epitopes in the hydrolyzed peptide segments can lead to varying immune responses. The two PHF-Ws have notably high intolerance rates, exceeding 10% among infants with CMA. Therefore, suggesting that PHF-Ws may not be suitable for infants and children with CMA in China.

Out-of-pocket expenses and parent reported quality of life in children with cow's milk protein allergyin Bogotá, Colombia.

To identify the out-of-pocket expenses and parent-reported quality of life (QoL) of children with a diagnosis of cow's milk protein allergy (CMPA)between the ages of 0 and 5 using the Food Allergy Quality of Life Questionnaire - Parent Form. A cross-sectional study was conducted in two tertiary care centers in Bogotá. Demographic, medical information, and QoL scores were collected by parental interview. We carried out a cost-of-illness analysis based on self-reported out-of-pocket expenses attributed to the treatment as a whole and the family's monthly income. Exploratory analyses used the QoL scores and the percentage of out-of-pocket expenses attributable to treatment as outcomes. 122 families were analyzed. Median subject age was 17 months (Q1-Q3: 11-26.75 months) and female subjects made up 71% of the sample. The median QoL score was 3.21 points (Q1-Q3: 2.43-4.34) and only differed by age groups and personal history of other food allergies. The median out-of-pocket treatment related costs was 300,000 Colombian pesos (COP) (Q1-Q3: 280,000-340,000 COP). About 17% of the families had to pay over 15% of their monthly income to purchase food and dietary products. Out-of-pocket treatment related costs differed depending on whether the treatment included formulas (Mann-Whitney test p < 0.001). Out-of-pocket treatment expenses were uncorrelated with the QoL scores. Food allergy related QoL scores were not associated with out-of-pocket expenses as a whole or as a fraction of monthly income but were higher in children with additional food allergies and in older age groups, suggesting a lower QoL.

Goat milk exerts anxiolytic and anti-depressive effects through modulating JAK/STAT3 and p-Akt/CREB signaling pathways in chronic unpredictable mild stress mice

Anxiety and depression are the second major diseases in the world. Current antidepressants are not universally effective and always cause numerous side effects and strong dependence. Cow milk, as a daily nutritional supplement, can assist in the treatment to improve anxiety and depression symptoms. Whereas, cow milk allergy and lactose intolerance are present in a sizable portion of the population. Compared with cow milk, goat milk has higher nutritional value, easier digestion, lower allergy and better tolerance. However, the anxiolytic and anti-depressive effects of goat milk are still pending, and the related mechanisms are not confirmed. Therefore, in the present study, cow milk as a control, the anxiolytic and anti-depressive effects of goat milk were investigated in chronic unpredictable mild stress mice, and the corresponding mechanism was explored. Our data suggested that goat milk elevated monoamine neurotransmitters, reduced pro-inflammatory cytokines release, increased anti-inflammatory cytokine concentration, inhibited the expression of NSE, STAT3, and NF-κB, and increased the expression of p/Akt and CREB. We concluded that goat milk exerted anxiolytic and anti-depressive effects by increasing neurotransmitters and reducing inflammatory mediators via modulating hippocampal JAK/STAT3 and p-Akt/CREB signaling pathways. No significant difference in the anti-depressive effect between cow and goat milk was observed. This study firstly demonstrates that goat milk has a similar effect as cow milk in improving anxiety and depression symptoms and goat milk might be expected as an ideal nutritional supplement for people suffering from anxiety and depression who are allergic or lactose intolerant to cow milk.

Clinical guideline highlights for the hospitalist: Evaluation, management, and prevention of cow's milk allergy.

An ESPGHAN position paper on the diagnosis, management and prevention of cow's milk allergy RELEASE DATE: Journal of Pediatric Gastroenterology and Nutrition, July 26, 2023 PRIOR VERSION: 2012 DEVELOPER: ESPGHAN (European Society of Paediatric Gastroenterology, Hepatology and Nutrition), NASPGHAN (North American Society of Pediatric Gastroenterology, Hepatology and Nutrition) FUNDING SOURCE: ESPGHAN TARGET POPULATION: Infants and young children with suspected cow's milk allergy.

Clinical characteristics, laboratory findings, and tolerance acquisition in infants with cow's milk protein allergy in a private center in Lima, Peru for the period 2021-2022.

Cow's milk protein allergy (CMPA) remains relatively understudied in Latin America. In this observational study, we enrolled 64 patients with a median age of 3 months, of whom 60% were male. Patients included had a history of IgE-mediated reactions with IgE sensitization or non-IgE-mediated reactions or symptoms following exposure to cow's milk. They underwent skin prick test, ImmunoCAP, fecal calprotectin (FC), and fecal eosinophil-derived neurotoxin (EDN), in addition to double-blinded placebo-controlled oral food challenges (DBPCFC), with clinical evolution and tolerance acquisition observed over 1 year. Malnutrition was present in 78.1% of patients, and 87.5% had a family history of atopy, with 51.6% receiving exclusive breastfeeding. Gastrointestinal manifestations were prevalent in 90.6% of patients, followed by dermatological manifestations (10.9%), with only 2 experiencing anaphylaxis. IgE-mediated CMPA was observed in only six patients. In those with non-IgE-mediated CMPA, FC had a median of 284 mg/dL (IQR: 138.5-415.5), while EDN had a median of 508.5 mg/dL (IQR: 160.25-868). One year after diagnosis, median FC significantly decreased (p < 0.0001), and malnutrition prevalence reduced to 17.1%. Moreover, 81% of patients acquired tolerance following DBPCFC, with 52% utilizing nutritional replacement formulas at diagnosis. Notably, 94% of those extensively hydrolyzed casein-based formulas achieved tolerance (p = 0.08). Our findings provide a foundational framework for future investigations into CMPA diagnosis, tolerance acquisition, and the utilization of hypoallergenic formulas tailored to the unique characteristics of our region.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XII – Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA

BackgroundCow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. ObjectiveThese evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. MethodsWAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. ResultsAfter reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as “conditional” following the GRADE approach due to the very low certainty about the health effects based on the available evidence. ConclusionsIf breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers’ values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

Consumption of cow's milk formula in the nursery and the development of milk allergy.

The effect of the amount of transient cow's milk formula (CMF) consumed during the first days of life on IgE-cow's milk allergy (IgE-CMA) is unknown. A cohort of 58 patients with IgE-CMA was identified from a large scale population-based study of 13,019 infants followed from birth. A group of 116 infants matched for sex and breastfeeding only duration (beyond the nursery period), and another random group of 259 healthy infants were used as controls. Parents were interviewed and the infants' medical records were searched to assess CMF consumption in the nursery. While 96% of the mothers of the 174 infants (58 with Cow's milk allergy and 116 controls) reported on exclusive breastfeeding during the stay in the nursery, CMF consumption was documented in 96 (55%) of the infants. Of those, most (57; 59%) received one to three feedings, 20 (21%) received four to nine feedings, and 19 (20%) received ≥10 feedings. Fewer formula feeds (1-3) were significantly more common in the allergic group than ≥4 feeds (p=0.0003) and no feeds at all (p=0.02) compared to controls (n=116). Of those exclusively breastfed in the nursery, 13/23 allergic infants (57%) introduced CMF at age 105-194days (the period with highest-risk for IgE-CMA) compared to 33/98 (34%) from the random control group (n=259) (p=0.04). Most infants end up receiving few CMF feeds in the nursery. Transient CMF in the nursery is associated with increased risk of IgE-CMA.

Selenium in plant-based beverages: How can in vitro bioaccessibility contribute to an accurate daily intake?

BackgroundLactose intolerance, cow milk protein allergy, and environmental and ethical concerns drive the global market for plant-based beverages (PPBs). Despite this, data on the occurrence of selenium (Se) in these beverages are scarce. ObjectiveThe objectives of this study were to assess total selenium and determine the bioaccessible fractions in plant-based beverages (PBBs) from cereals, oilseeds, and pumpkin seeds, using an in vitro static method to simulate human digestion; and estimate the contribution these beverages have to the reference daily intake (RDI) for children and adults. MethodologyThe study involved beverages made under laboratory conditions. Samples and extracts were submitted to acid digestion (ultrasonic and block digester); total and bioaccessible Se levels were determined by ICP-MS. In vitro bioaccessibility was assessed using the INFOGEST protocol. ResultsThe results revealed a wide variation in Se content in the studied plant-based beverages from 10.3 µg kg−1 (sunflower seeds) to 3509 µg kg−1 (Brazil nuts). The bioaccessibility of Se was found only in PBBs made from oilseeds with macadamia, cashew and Brazil nut, with a variation in values from 86 to 96 %. The Se content and its bioaccessible fraction of Brazil nut PBB may contribute to 1276 % and 1218 % of the RDI for children and adults, respectively. ConclusionsThe Se content varied among samples of cereals, oilseeds and pumpkin seeds, reflecting the diversity in the studied PBBs. Only PBBs containing oilseeds (macadamia, cashews, and Brazil nuts) exhibited measurable amounts of bioaccessible Se, indicating an association with the raw material. However, the consumption of the PBB containing Brazil nuts may pose a risk of adverse effects, due to its high contribution to the RDI in both children and adults.

The age-specific microbiome of children with milk, egg, and peanut allergy

BackgroundImmune regulation by gut microbiota is affected by dysbiosis and may precede food allergy onset. Prior studies lacked comparisons stratified by age and clinical phenotype. ObjectiveTo assess the microbiome of children with food allergy (<3 years, 3-18 years) compared with similar aged children without food allergy. MethodsA real-world prospective cross-sectional study performed from 2014 to 2019 recruited children highly likely to have milk, egg, or peanut allergy defined by history and serum IgE or confirmed by food challenge. 16S ribosomal RNA sequencing identified stool microbial DNA. Alpha and beta diversity was compared between groups with food allergy and healthy controls stratified by age. Differential abundance for non a priori taxa was accepted at absolute fold-change greater than 2 and q value less than 0.05. ResultsA total of 70 patients were included (56 with food allergy and 14 healthy controls). Groups were not significantly different in age, gender at birth, race, mode of delivery, breastfeeding duration, or antibiotic exposure. Younger children with food allergy had similar alpha diversity compared with controls. Beta diversity was significantly different by age (P = .001). There was differential abundance of several a priori (P < .05) taxa (including Clostridia) only in younger children. Both a priori (including Coprococcus and Clostridia) and non a priori (q < 0.05) Acidobacteria_Gp15, Aestuariispira, Tindallia, and Desulfitispora were significant in older children with food allergy, especially with peanut allergy. ConclusionDysbiosis associates with food allergy, most prominent in older children with peanut allergy. Younger children with and without food allergy have fewer differences in gut microbiota. This correlates with clinical observations of persistence of peanut allergy and improved efficacy and safety of oral immunotherapy in younger children. Age younger than 3 years should be considered when initiating therapeutic interventions.

Continuous cow’s milk protein ingestion during infancy may promote casein-specific IgG4 production

BackgroundEarly supplementation and subsequent discontinuation of cow’s milk formula (CMF) may increase the risk of cow’s milk allergy in breastfed infants, but little is known about the relationship between continuous CMF ingestion and cow’s milk protein-specific immunoglobulin production. ObjectiveThis study aimed to clarify this relationship in cow’s milk-sensitized infants. MethodsUsing data from a randomized controlled trial of a Japanese birth cohort, we performed a subgroup analysis of participants who had ingested CMF in the first 3 days of life and exhibited a positive skin prick test response to cow’s milk at 6 months of age. We compared the differences in median titers of cow’s milk-specific IgE, casein-specific IgE, and casein-specific IgG4 between participants who continued daily or intermittent CMF ingestion up to 6 months of age (“continuous group”) and participants who discontinued CMF ingestion before 6 months of age (“discontinued group”). ResultsFrom 462 trial participants, 49 (10.6%) were included in this study (continuous group: 21, discontinued group: 28). The median titer of cow’s milk-specific IgE was 0.17 kUA/L (interquartile range: <0.10-0.57) in the continuous group and 0.66 kUA/L (0.49-1.18) in the discontinued group (P=.0008). The median titer of casein-specific IgE was <0.10 kUA/L (<0.10-0.15) in the continuous group and <0.10 kUA/L (<0.10-0.37) in the discontinued group (P=.51). The median titer of casein-specific IgG4 was 2.58 mgA/L (0.77-6.73) in the continuous group and 0.09 mgA/L (0.07-0.13) in the discontinued group (P<.0001). ConclusionContinuous CMF ingestion may promote casein-specific IgG4 production in cow’s milk-sensitized infants.

Development of IgE-mediated food allergies in children with history of food protein-induced allergic proctocolitis: a series of five cases.

Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated allergic condition that presents with hematochezia in otherwise healthy infants. It is most commonly induced by cow's milk protein via breast milk or formula. The prognosis for FPIAP is generally considered favorable with most infants achieving symptomatic resolution after diet modification. Most infants go on to tolerate the offending foods by 1-3 years of age. Over 8 years at our institution, five patients were identified and noted to have FPIAP to cow's milk during infancy with subsequent development of IgE-mediated allergic reaction to cow's milk and other foods. All five cases developed other atopic disorders (atopic dermatitis in four cases). IgE-mediated cow's milk allergy has persisted beyond the preschool years in at least two patients (currently 8 and 16 years old). For three of the patients, the IgE-mediated reaction to cow's milk was severe with development of anaphylaxis or angioedema. In addition, three patients experienced anaphylaxis or angioedema to allergens other than milk. While FPIAP is a non-IgE-mediated process traditionally thought not to progress past the first year of life, some infants with FPIAP develop severe, persistent IgE-mediated cow's milk allergy. To our knowledge, this is the first detailed clinical description of such patients.

Regular consumption following early introduction of allergenic foods and aggressive treatment of eczema are necessary for preventing the development of food allergy in children.

Over the past two decades, food allergy prevention strategies have shifted from 'delayed introduction' to 'no delayed introduction' to 'early introduction' of allergenic foods. This article reviews important research in this field published in the early 2020s to support future strategies for food allergy prevention. Recent randomized controlled trials (RCTs), systematic reviews, meta-analyses, and real-world studies have reported that early allergenic food introduction, especially peanut and egg, are effective for preventing food allergies. However, there are also reports that food-induced anaphylaxis admission rates in infants are increasing. Early allergenic food introduction by itself is not sufficient to prevent the development of food allergies. Recent RCTs (SPADE study and COMEET study) have demonstrated that continued regular cow's milk consumption after early introduction is important for preventing the onset of cow's milk allergy. Furthermore, an RCT (PACI study) reported that early and aggressive anti-inflammatory topical therapy for eczema can contribute to the prevention of egg allergy by suppressing percutaneous sensitization. Food allergies may be prevented through a combination of early food introduction, regular consumption, and active eczema treatment. Further research is needed to develop well tolerated, effective, and practical strategies to prevent food allergies.