BACKGROUND: Cow\'s milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA overdiagnosis and identify individual-level and primary care practice-level risk factors.
METHODS: We analysed data from 1394 children born in England in 2014-2016 (BEEP trial, ISRCTN21528841). Participants underwent formal CMA diagnosis at ≤2 years. CMA overdiagnosis was defined in three separate ways: parent-reported milk reaction; primary care record of milk hypersensitivity symptoms; and primary care record of low-allergy formula prescription.
RESULTS: CMA was formally diagnosed in 19 (1.4%) participants. CMA overdiagnosis was common: 16.1% had parent-reported cow\'s milk hypersensitivity, 11.3% primary care recorded milk hypersensitivity and 8.7% had low-allergy formula prescription. Symptoms attributed to cow\'s milk hypersensitivity in participants without CMA were commonly gastrointestinal and reported from a median age of 49 days. Low-allergy formula prescriptions in participants without CMA lasted a median of 10 months (interquartile range 1, 16); the estimated volume consumed was a median of 272 litres (26, 448). Risk factors for CMA overdiagnosis were high practice-based low-allergy formula prescribing in the previous year and maternal report of antibiotic prescription during pregnancy. Exclusive formula feeding from birth was associated with increased low-allergy formula prescription. There was no evidence that practice prescribing of paediatric adrenaline auto-injectors or anti-reflux medications, or maternal features such as anxiety, age, parity and socioeconomic status were associated with CMA overdiagnosis.
CONCLUSIONS: CMA overdiagnosis is common in early infancy. Risk factors include high primary care practice-based low-allergy formula prescribing and maternal report of antibiotic prescription during pregnancy.

Infant formulas based on hydrolysed cow\'s milk proteins are used when breastfeeding is not feasible in cow\'s milk allergic infants. Camel milk has been shown to be well-tolerated by the majority of children with cow\'s milk allergy (CMA) and may be a substitute in management of CMA. Here we aimed to evaluate the impact of processing on immunogenicity, sensitising, antibody-binding and cross-reactive capacity of cow\'s and camel milk. Cow\'s and camel milk were processed by means of enzyme hydrolysis or heat treatment. Brown Norway rats were immunised with PBS, non-processed, enzyme hydrolysed or heat-treated cow\'s or camel milk. In vivo tests were performed for evaluation of clinical signs. Blood and faecal samples were analysed for levels and specificity of antibody responses. Cow\'s and camel milk showed similar sensitising capacity. Processing decreased the sensitising capacity of cow\'s milk, yet only enzyme hydrolysis but not heat treatment decreased the sensitising capacity of camel milk. Processing affected the specificity of antibodies raised in the rats, though the effect differed between cow\'s and camel milk. The study showed a low cross-reactivity between cow\'s and camel milk, which was decreased with processing, suggesting that processing of camel milk may improve its usefulness in CMA management.

METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.

The objective of the present study is to assess the rates of acquired tolerance to cow\'s milk (CM) after 36 months in subjects who consumed amino acid-based formula with synbiotics (AAF-S) or amino acid-based formula without synbiotics (AAF) during a 1-year intervention period in early life as part of the PRESTO study (Netherlands Trial Register number NTR3725). Differences in CM tolerance development between groups were analysed using a logistic regression model. Results show that the proportion of subjects (mean [±SD] age, 3.8 ± 0.27 years) who developed CM tolerance after 36 months was similar in the group receiving AAF-S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p = 0.253), that is, figures comparable to natural outgrowth of CM allergy. Our data suggest that the consumption of AAF and absence of exposure to CM peptides do not slow down CM tolerance acquisition.

UNASSIGNED: Cow\'s milk protein allergy (CMPA) is the most frequent food allergy in early childhood. For those infants requiring breastmilk substitutes, formulas with extensively hydrolyzed proteins (EHF), should be the treatment of choice. As there are limited data showing the progression of initial symptoms in infants newly diagnosed with CMPA who are treated with EHF with added synbiotics, the main objective of this study was to evaluate the resolution of symptoms in said infants after 4 weeks of treatment. As a secondary objective this study aimed to assess the impact of the treatment on the family\'s quality of life.
UNASSIGNED: observational, longitudinal, prospective, and multicentric real-world evidence study. The intervention phase (EHF with synbiotics) lasted 28 days and was completed by 65 patients. Treating physicians registered child´s anthropometry, Infant Gastrointestinal Symptoms Questionnaire (IGSQ-13) and CoMiSS (Cow´s Milk Allergy Symptoms Score) both at baseline and after 28 days of treatment. During treatment, caregivers reported child´s regurgitation and stools, PO-SCORAD (Patient Oriented Scoring of Atopic Dermatitis) and FAQL-PB (Family Quality of Life-Parental Burden). Data were collected using Google Forms and analyzed through the STATA program.
UNASSIGNED: 95.4% of the patients showed an improvement or disappearance of the overall initial symptoms after 4 weeks of treatment. Gastrointestinal symptoms improved or disappeared in 92% of patients (p < 0.05) while dermatological symptoms improved or disappeared in 87.5% of patients (p < 0.05). The median CoMiSS at baseline was 9, with 21 patients exceeding the cut-off point of 12. After 4 weeks of treatment, the median dropped to 3, and no patient exceeded the 12-cut-off point (p = 0.000). At baseline, patients had a PO-SCORAD of 11.5 (interquartile range 1-23) that went to 1.0 (interquartile range 1-6) at day 28 (p = 0.000). The treatment diminished stool frequency (p < 0.05), improved stool consistency (p = 0.004) and decreased the frequency of regurgitation in infants with CMPA (p = 0.01). The percentage of patients who no longer had any episode of regurgitation increased from 11% to 31% on day 28 (p = 0.003). At baseline, 13% of patients cried more than 3 h per day, while at day 28 that percentage dropped to 3% (p = 0.03). An improvement in the infants\' sleep pattern was also appreciated with the treatment. At study onset, 56% of the families reported feeling very overwhelmed, a percentage that dropped to 17% after 28 days of treatment (p < 0.05). The small percentage of families who did not feel overwhelmed at study onset (17%), grew to 43% on day 28 (p < 0.05).
UNASSIGNED: The use of an EHF with synbiotics for the management of infants diagnosed with or suspected to have CMPA suggested a good safety profile, an adequate infant growth, and improvement of overall, gastrointestinal, and dermatological symptoms. It also suggested a lower daily frequency of regurgitations and stools, and an improvement in stool consistency, sleeping pattern, and quality of life of the infant and his family.

Cow\'s milk allergy (CMA) is one of the most common food allergies world-wide. The emergence of online CMA symptom questionnaires, aimed at parents and/or healthcare professionals (HCP), may raise awareness about the possible diagnosis of CMA, but also increases the risk for overdiagnosis leading to unnecessary dietary restriction impacting on growth and nutrition. This publication sets out to establish the availability of these CMA symptom questionnaires and critically assesses the development and validity.
Thirteen HCP working in the field of CMA, from different countries, were recruited to participate. A combination of a Pubmed and CINAHL literature and online review using the Google search engine in English language was used. Symptoms in the questionnaires were assessed, using the European Academy for Allergy and Clinical Immunology guidelines for food allergy. Following the assessment of both the questionnaires and literature, the authors followed the modified Delphi approach to generate consensus statements.
Six hundred and fifty-one publications were identified, of which 29 were suitable for inclusion, with 26 being associated with the Cow\'s Milk-Related Symptoms Score. The online search yielded 10 available questionnaires: 7/10 were sponsored by formula milk companies and 7/10 were aimed at parents and three at HCP. Following the assessment of data, 19 statements were generated in two rounds of anonymous voting reaching 100% agreement.
Online CMA questionnaires, available to parents and HCP\'s, are varied in symptoms, and most were not validated. The overarching consensus generated from authors is that these questionnaires should not be used without the involvement of HCP.

METHODS: Currently there are no specific recommendations for the use of any particular infant formula in the prevention of cow\'s milk allergy (CMA). Recently, there has been an increasing interest in alternative infant formulas based on milk proteins from other sources than the cow, including milk from other mammalians such as goat, sheep, donkey, horse, and camel. Whereas these have been studied for their usability in CMA management, there are no studies of their CMA preventive capacity. Thus, the aim of this study is to evaluate whether camel milk can prevent CMA and vice versa.
RESULTS: The capacity of camel milk in preventing CMA and vice versa is evaluated in a well-established prophylactic Brown Norway rat model. IgG1, IgE, and IgA responses, allergy elicitation, intestinal and mLN gene expression, and protein uptake are analyzed. The study demonstrates that camel and cow\'s milk in general has an insignificant cross-preventive capacity. Yet, whereas cow\'s milk is shown to have a low transient capacity to prevent sensitization and clinically active camel milk allergy, camel milk does not show this effect for CMA.
CONCLUSIONS: This study suggests that due to lack of cross-tolerance camel milk cannot be used for CMA prevention.

BACKGROUND: Cow\'s milk allergy (CMA) is one of the most common food allergies among children. Whilst avoidance of cow\'s milk protein is the cornerstone of management, further treatment of symptoms including those affecting the gastrointestinal, skin and respiratory systems plus other allergic comorbidities, maybe required. This study aimed to quantify the wider economic impact of CMA and its management in the United Kingdom (UK).
METHODS: We conducted a retrospective matched cohort study on children with CMA (diagnosis read code and/or hypoallergenic formula prescription for ≥3 months) examining healthcare data (medication prescriptions and healthcare professional contacts) from case records within The Health Improvement Network (A Cegedim Proprietary Database) in the UK. A comparative cost analysis was calculated based on healthcare tariff and unit costs in the UK.
RESULTS: 6998 children (54% male; mean observation period 4.2 years) were included (n = 3499 with CMA, mean age at diagnosis 4.04 months; n = 3499 matched controls without CMA). Compared to those without CMA, medications were prescribed to significantly more children with CMA (p < 0.001) at a higher rate (p < 0.001). Children with CMA also required significantly more healthcare contacts (p < 0.001) at higher rate (p < 0.001) compared to those without CMA. CMA was associated with additional potential healthcare costs of £1381.53 per person per year.
CONCLUSIONS: The findings of this large cohort study suggest that CMA and its associated co-morbidities presents a significant additional healthcare burden with economic impact due to higher prescribing of additional medications. Further research into management approaches that may impact these clinical and economic outcomes of CMA is warranted.

BACKGROUND: Cow\'s milk allergy is a common type of allergy in infants that is caused by the immune response to proteins in cow\'s milk. Digestive manifestations, atopic dermatitis, and respiratory discomfort are some of the clinical manifestations that appear; however, none of them are objective criteria to confirm the diagnosis, which may result in misdiagnosis, treatment hindrance, and parental concerns. Therefore, new methodologies for an accurate and immediate diagnosis is essential.
METHODS: In this descriptive study, infants referred to the pediatric health center in Sulaymaniah were selected during a period of 1 year. The data were collected using a demographic questionnaire and the Cow\'s Milk Related Symptom Score (CoMiSS). Chi-squared and independent t tests were used to analyze the data.
RESULTS: The findings of the present study indicated that among 250 infants (117 boys, 133 girls), with a mean ±  SD age of 2.9 ± 1.6 years, 21% were breastfed, 39% were fed both cow\'s milk and breast milk, and 60% were fed only cow\'s milk. The contingency of cow\'s milk allergy was positive in 35% of infants. According to this questionnaire, 18% of the participants got a score of 0-5, 47% scored 6-11, and 35% scored ≥ 12. A significant relationship was found between cow\'s milk allergy and the participants\' diet (p < 0.001). A significant association was also found between age-dependent growth index (weight p = 0.04, height p = 0.01, and head circumstance p = 0.02) and cow\'s milk allergy.
CONCLUSIONS: Although common problems in infancy such as colic and reflux may interfere with an accurate diagnosis of cow\'s milk allergy, give false-positive results, and decrease the reliability of CoMiSS; there is a need for non-invasive and easy methods for early diagnosis and improving awareness to encourage parents to take preventive measures.

There is significant overdiagnosis of milk allergy in young children in some countries, leading to unnecessary use of specialized formula. This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and support carers of children with suspected milk allergy.
Delphi study involving two rounds of anonymous consensus building and an open meeting between January and July 2021. Seventeen experts in general practice, nutrition, midwifery, health visiting, lactation support and relevant areas of paediatrics participated, located in Europe, North America, Middle East, Africa, Australia and Asia. Five authors of previous milk allergy guidelines and seven parents provided feedback.
Participants agreed on 38 essential recommendations through consensus. Recommendations highlighted the importance of reproducibility and specificity for diagnosing milk allergy in children with acute or delayed symptoms temporally related to milk protein ingestion; and distinguished between children directly consuming milk protein and exclusively breastfed infants. Consensus was reached that maternal dietary restriction is not usually necessary to manage milk allergy, and that for exclusively breastfed infants with chronic symptoms, milk allergy diagnosis should only be considered in specific, rare circumstances. Consensus was reached that milk allergy diagnosis does not need to be considered for stool changes, aversive feeding or occasional spots of blood in stool, if there is no temporal relationship with milk protein ingestion. When compared with previous guidelines, these consensus recommendations resulted in more restrictive criteria for detecting milk allergy and a more limited role for maternal dietary exclusions and specialized formula.
These new milk allergy recommendations from non-conflicted, multidisciplinary experts advise narrower criteria, more prominent support for breastfeeding and less use of specialized formula, compared with current guidelines.