An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy.

A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 0 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis, and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion, or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost, and quality of life.

Diagnosis and management of food allergy-associated gastroesophageal reflux disease in young children-EAACI position paper.

Gastro-oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA-associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA-associated GORD and medical and dietary management. The task force (TF) on non-IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web-based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA-associated GORD.

Introduction of soy-free plant-based pediatric formula in infants with FPIES: A case report.

Background: Standard practice for management of food protein-induced enterocolitis syndrome (FPIES) frequently requires the use of hypoallergenic semi-elemental or elemental formulas. For some patients, there is poor tolerance of these formulas and no improvement of gastrointestinal symptoms. For others, especially those over 4 months of age, the introduction of these formulas is difficult due to their scientifically demonstrated poor palatability. Case presentation: This case report features an 18-month-old child diagnosed with FPIES at 4 months who failed to tolerate standard hypoallergenic semi-elemental and elemental formulas to supplement maternal breast milk feedings resulting in suboptimal growth. After failing to tolerate all standard options, the patient was introduced off-label to a plant-based pediatric formula, Else Toddler, at 6 months-of-age. Outcomes and implications: In this case, Else Toddler was tolerated as a source of supplemental nutrition without triggering FPIES symptoms. Recommendations: This case demonstrates the successful use of Else Toddler, a pediatric formula sourced from almond butter, buckwheat flour, and tapioca maltodextrin, as a possible alternative to the standard use of hydrolysate or elemental amino-acid formulas. It is free of some of the most common FPIES triggers - dairy, soy, rice, and pea proteins and there for a possible acceptable alternative approach to FPIES management.

The use of extensively hydrolysed and amino acid feeds beyond cow's milk allergy: a national survey.

BACKGROUND: Extensively hydrolysed formulas (EHFs) and amino acid formulas (AAFs) with proven hypoallergenicity are used for children suffering from cow's milk allergy, when breast milk is not available. However, these feeds are often used in other medical conditions where tolerance and absorption of whole protein is affected, frequently without assessment of efficacy. This practice survey assessed the use of these feeds in paediatric conditions other than cow's milk allergy; aiming to describe the population, growth parameters and micronutrient status. METHODS: Four National Health Service tertiary paediatric centres participated in this practice survey. Inclusion: children between 0 and 18 years, consuming >25% of their estimated energy requirements of an EHF/AAF for any condition other than allergic disease. Anonymised data were collected: (i) descriptive information; (ii) indications; (iii) type and route of feeding; (iv) growth status and nutritional deficiencies; and (v) medication and vitamin and mineral supplementation. RESULTS: One hundred-and-ninety-one children were included with a median age of 19 months (interquartile range 4-63]. Seventeen percent (33/191) were on AAFs and 83% (158/191) were on EHFs. The feeds were commonly used in cancer for 26% and in critical illness for 31%. The majority (73%) of children had enteral feeds via a nasogastric tube. Nutritional biomarkers were performed in 29% of children and 83% were on a vitamin or mineral supplement. CONCLUSIONS: This practice survey found that EHFs and AAFs were used in a variety of medical conditions. Indications for feed choice varied, and evidence-based research supporting the use was scarce. Awaiting further research, children on these types of feeds should have regular nutritional monitoring.

Biotin and carnitine deficiency due to hypoallergenic formula nutrition in infants with milk allergy.

Amino acid formulas and hydrolyzed formulas given to infants in Japan with milk allergies theoretically contain little, if any, biotin and carnitine. We assessed biotin and carnitine insufficiency in six infants with milk allergy who were fed amino acid formulas and/or hydrolyzed formulas, by measuring urine 3-hydroxyisovaleric acid (3-HIA) and serum free carnitine (C0), respectively. All patients presented with elevated urine 3-HIA and lowered serum C0 compared with post-menstrual age-matched infants who were fed breast milk or standard infant formulas. Supplementation with biotin and L-carnitine immediately improved the insufficiency. Care should be taken to avoid biotin and carnitine deficiency in allergic infants fed amino acid or hydrolyzed formulas.

Amino acid formula induces microbiota dysbiosis and depressive-like behavior in mice.

Amino acid formula (AAF) is increasingly consumed in infants with cow's milk protein allergy; however, the long-term influences on health are less described. In this study, we established a mouse model by subjecting neonatal mice to an amino acid diet (AAD) to mimic the feeding regimen of infants on AAF. Surprisingly, AAD-fed mice exhibited dysbiotic microbiota and increased neuronal activity in both the intestine and brain, as well as gastrointestinal peristalsis disorders and depressive-like behavior. Furthermore, fecal microbiota transplantation from AAD-fed mice or AAF-fed infants to recipient mice led to elevated neuronal activations and exacerbated depressive-like behaviors compared to that from normal chow-fed mice or cow's-milk-formula-fed infants, respectively. Our findings highlight the necessity to avoid the excessive use of AAF, which may influence the neuronal development and mental health of children.

Symptoms and management of cow's milk allergy: perception and evidence.

Introduction: The 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). Methods: These Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Results: Overall, 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. Discussion: Differences 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.

Impact of the 2022 national formula shortage on clinical decision-making of healthcare providers in switching amino acid formulas for infants with cow's milk protein allergy: a survey-based study.

Background: In 2022, the United States experienced a national shortage of infant formula due to a global supply chain crisis and a large-scale domestic formula recall. The existing literature on healthcare providers' (HCPs) clinical decision-making during formula shortages is limited. This study aims to analyze the factors influencing pediatric HCP clinical decision-making when switching between amino acid formulas (AAF) for managing cow's milk protein allergy (CMPA) in infants under 24 months of age during an unprecedented national formula shortage. Methods: The study included pediatric HCPs with experience managing CMPA in infants and toddlers under 24 months during the formula shortage from January 2022 to November 2022. A de-identified survey comprising 26 questions examining driving factors used in clinical decision-making was administered to pediatric HCPs using a real-time mobile data collection tool. Results: Among the surveyed pediatric HCPs (n = 75), the factors most frequently considered as "extremely important" when switching to another AAF included safety (85%), tolerability (73%), and efficacy (83%). No statistically significant differences were found in HCP ratings among the listed examined factors of the four AAFs. The availability of specific formulas was the only factor that exhibited a statistically significant difference in perceived performance among pediatric HCPs when comparing the four AAFs (p < 0.05). Discussion: This study elucidates the crucial aspects that influenced pediatric HCPs' selection of AAFs for CMPA management during the 2022 formula shortage. The findings highlight the significance of safety, tolerability, efficacy, and availability in the pediatric HCP decision-making processes.

Managing cow's milk protein allergy during the 2022 formula shortage: decision-making among pediatric healthcare providers.

Introduction: Cow's milk protein allergy (CMPA) affects 2%-7% of infants and is managed with hypoallergenic formulas. The 2022 recalls of infant formulas due to factors including contamination led to specialty formula shortages, highlighting CMPA management challenges. Understanding healthcare providers' (HCPs) decision-making in transitioning to alternative formulas during shortages is crucial. Limited attention has been given to how pediatric physicians make these choices. Methods: This study utilized US HCPs' de-identified survey data to assess driving factors when switching extensively hydrolyzed formulas during shortages. Results: 104 eligible HCPs participated, including general pediatrics, pediatric allergy/immunology, and pediatric gastroenterology specialists. Safety, tolerability, and efficacy were identified as top factors for switching formulas. Formula 1 was considered well-tolerated, patient-accepted, and safe by all HCPs. Most expressed strong belief in Formula 1's safety and effectiveness. Discussion: Findings inform CMPA management during shortages, offering guidance to HCPs for suitable formula selection and enhanced infant care.

Corrigendum: Navigating formula shortages: associations of parental perspectives on transitioning to alternative infant formulas for cow's milk protein allergy during the 2022 national formula shortage.

[This corrects the article DOI: 10.3389/falgy.2023.1333570.].

Impact of Dietary Protein on the Management of Pediatric Short Bowel Syndrome.

Essential amino acids (AAs) play a key role in stimulating intestinal adaptation after massive small gut resection. The nutritional effect of dietary amino acids during intestinal regrowth has received considerable attention in recent years. This review explores the significance of dietary amino acids in the nutritional management of infants and children with intestinal failure and short bowel syndrome (SBS) as reported in the medical literature over the last three decades. A literature search was conducted using electronic databases. Breast milk emerged as the first-line enteral regimen recommended for infants with SBS. Hydrolyzed formulas (HFs) or amino acid formulas (AAFs) are recommended when breast milk is not available or if the infant cannot tolerate whole protein milk. The superiority of AAFs over HFs has never been demonstrated. Although glutamine (GLN) is the main fuel for enterocytes, GLN supplementation in infants with SBS showed no difference in the child's dependence upon parenteral nutrition (PN). Circulating citrulline is considered a major determinant of survival and nutritional prognosis of SBS patients. Early enteral nutrition and dietary supplementation of AAs following bowel resection in children are essential for the development of intestinal adaptation, thereby eliminating the need for PN.

Short-term symptom improvement in infants with suspected cow's milk protein allergy using amino acid formula: a prospective cohort analysis.

Background: Cow's milk protein allergy (CMPA) occurs commonly in infants. While the long-term efficacy of amino acid formulas for managing CMPA is well-established, there is limited data on the short-term symptom improvement of using amino acid formula (AAF). Objective: This study aimed to determine the short-term effects of managing suspected CMPA in infants aged 6 months and under using a commercial AAF. Methods: Healthcare providers who treated infants with suspected CMPA aged 6 months or younger (n = 104) provided de-identified survey data in this prospective study. Healthcare providers scored symptoms for severity from 0 to 3 (none, low, moderate, severe) before using a commercial AAF at Visit 1 and at Visit 2 (3-6 weeks later). Results: Gastrointestinal (94%), skin (87%), respiratory (86%), and uncategorized symptoms (89%) improved from AAF initiation, and these findings were consistent across different follow-up visit durations. Conclusion: This study is the most extensive prospective analysis conducted in the United States examining the short-term change in suspected CMPA symptoms using an AAF. These findings suggest that AAF may decrease the severity of suspected CMPA symptoms in infants 6 months or younger, often by the next follow-up visit. Further randomized controlled trials are required to confirm these initial findings.

The use of amino acid formulas in pediatric patients with allergy to cow's milk proteins: Recommendations from a group of experts.

One of the most common food allergies in children is cow's milk allergy (CMA). In breast-fed infants with CMA, the mother is encouraged to avoid dairy products. If this is not possible, or in formula fed infants, use of hypoallergenic replacement formulas such as extensively hydrolyzed formulas (EHF) is recommended. However, in ∼5% of patients EHFs are not tolerated and/or allergy symptoms can persist. When EHFs are ineffective and in severe forms of CMA, amino acid-based formulas (AAF) should be considered. Six pediatric gastroenterologists with extensive experience in food allergy management reviewed scientific publications and international clinical practice guidelines to provide practical recommendations on AAF. The guidelines reviewed had discrepancies and ambiguities around the specific indications for using formulas as a milk substitute. The panel recommends AAFs as the first therapeutic option in anaphylaxis due to CMA, in acute and chronic severe food protein-induced enterocolitis syndrome, in CMA associated with multiple food allergy, and in cases of eosinophilic esophagitis not responding to an extended exclusion diet or not eating solids. The main benefit of AAF is its absence of residual allergenicity, making it a safe treatment option in severe CMA patients who do not tolerate or respond to an EHF.

Navigating formula shortages: associations of parental perspectives on transitioning to alternative infant formulas for cow's milk protein allergy during the 2022 national formula shortage.

The COVID-19 pandemic led to supply chain disruptions causing a severe shortage of infant formula. The shortage impacted parents of infants with cow's milk protein allergy (CMPA) who rely on specialized formulas. However, research on parent perspectives during formula shortages is limited. We aimed to understand the factors guiding parents' decisions when transitioning to alternative amino acid formula (AAF) or extensively hydrolyzed formula (eHF) during the national formula shortage. We conducted a survey using the ZSMoments platform and found that before the shortage, parents valued safety (83%), tolerability (78%), and reputability (78%) as primary factors in selecting eHFs and AAFs. Post-shortage, formula tolerability (86%), assurance (84%), and safety (80%) gained more importance. Among those switching eHF (n = 54), health care provider recommendations (81%), reputability (78%), taste (78%), and tolerability (78%) were rated as "extremely important." Among those switching AAF (n = 26), top factors included tolerability (77%), assurance (73%), safety (73%), cost-effectiveness (73%), and formula trustworthiness (73%). These data suggest that parents carefully weigh various factors when managing their child's CMPA and transitioning to different AAF or eHF options.

The Remaining Challenge to Diagnose and Manage Cow's Milk Allergy: An Opinion Paper to Daily Clinical Practice.

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.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guideline update - VII - Milk elimination and reintroduction in the diagnostic process of cow's milk allergy.

The diagnosis of cow's milk allergy (CMA) in infants and young children remains a challenge because many of the presenting symptoms are similar to those experienced in other diagnoses. Both over- and under-diagnosis occur frequently. Misdiagnosis carries allergic and nutritional risks, including acute reactions, growth faltering, micronutrient deficiencies and a diminished quality of life for infants and caregivers. An inappropriate diagnosis may also add a financial burden on families and on the healthcare system. Elimination and reintroduction of cow's milk (CM) and its derivatives is essential for diagnosing CMA as well as inducing tolerance to CM. In non-IgE mediated CMA, the diagnostic elimination diet typically requires 2-4 weeks before reintroduction, while for IgE mediated allergy the time window may be shorter (1-2 weeks). An oral food challenge (OFC) under medical supervision remains the most reliable diagnostic method for IgE mediated and more severe types of non-IgE mediated CMA such as food protein induced enterocolitis syndrome (FPIES). Conversely, for other forms of non-IgE mediated CMA, reintroduction can be performed at home. The OFC cannot be replaced by the milk ladder after a diagnostic elimination diet. The duration of the therapeutic elimination diet, once a diagnosis was confirmed, can only be established through testing changes in sensitization status, OFCs or home reintroduction, which are directed by local protocols and services' availability. Prior non-evidence-based recommendations suggest that the first therapeutic elimination diet should last for at least 6 months or up to the age of 9-12 months, whichever is reached first. After a therapeutic elimination diet, a milk-ladder approach can be used for non-IgE mediated allergies to determine tolerance. Whilst some centers use the milk ladder also for IgE mediated allergies, there are concerns about the risk of having immediate-type reactions at home. Milk ladders have been adapted to local dietary habits, and typically start with small amounts of baked milk which then step up in the ladder to less heated and fermented foods, increasing the allergenicity. This publication aims to narratively review the risks associated with under- and over-diagnosis of CMA, therefore stressing the necessity of an appropriate diagnosis and management.

Budget Impact of Early Introduction of Amino Acid Formula in Managing Infants with Cow Milk Protein Allergy: Arabian Gulf Countries' Experience.

Objective: This study estimates the budgetary impact of the introduction of amino-acid formula (AAF) as first-line management in the elimination diet of infants with suspected cow milk protein allergy (CMPA) in the Kingdom of Saudi Arabia (KSA), Kuwait, and the United Arab Emirates (UAE) from a health-care payer's perspective. Methods: A global decision tree model was adapted to compare estimated costs in current practice (extensively hydrolyzed formula [eHF] or soy formula [SF] with the proposed approach of early introduction of AAF as first-line treatment of CMPA in non-breast-fed infants). Model inputs were derived from explorative literature reviews and medical experts' opinions. All costs were reported in local currency, ie, Saudi Riyal (SAR) for KSA, Kuwaiti Dinar (KWD) for Kuwait, and United Arab Emirates Dirham (AED) for the UAE. Results: Cost savings with the early introduction of AAF were 10% (SAR 15102542) in KSA, 10% (KWD 306565) in Kuwait, 17% (AED 1842018) in the UAE government sector and 13% (AED 4232932) in the UAE private sector. The highest cost reduction was observed in the cost of soy formula (SF), with a 58% reduction both in KSA (SAR 4204540) and UAE public sector (AED 110331). A significant cost reduction in medication costs in Kuwait (37%; KWD 5630) and medical examination costs in the UAE private sector (50%; AED 1508918) was observed. Conclusion: Results indicated that the introduction of AAF as the first line in the management of CMPA is a cost-saving strategy for the Gulf Cooperation Council (GCC) countries-KSA, Kuwait, and UAE- from a health-care payer's perspective.

When Supplemental Formula Is Essential: Overcoming Barriers to Hypoallergenic Formula Access for Patients With Food Allergies.

For food-allergic patients, hypoallergenic formulas (HFs) are medically indicated, often a primary component of the diet and essential for patient safety, health, nutrition, and overall well-being. Yet, food allergy is not included among the conditions mandated for coverage under federal health programs and private health insurance. The 2022 infant formula crisis has affected many North American families and has particularly influenced patients with food allergies who rely on a limited number of safe HF brands to safely meet their nutritional needs for growth and development. The current formula shortage further highlights the longstanding difficulties faced by families with food allergies in accessing HF. Within this context, this article focuses on chronic barriers faced by patients with food allergies in accessing HF and proposes potential solutions. Legislation is desperately needed to address HF affordability through changes in insurance reimbursement and disparities in access to HF among individuals with food allergy.

The Use of an Amino Acid Formula Containing Synbiotics in Infants with Cow's Milk Protein Allergy-Effect on Clinical Outcomes.

Cow's milk protein allergy (CMPA) is common and costly. Clinical trials of infants with CMPA have shown that the use of an amino acid formula containing pre- and probiotics (synbiotics) (AAF-Syn) may lead to significant reductions in infections, medication prescriptions and hospital admissions, compared to AAF without synbiotics. These effects have not yet been confirmed in real-world practice. This retrospective matched cohort study examined clinical and healthcare data from The Health Improvement Network database, from 148 infants with CMPA (54% male, mean age at diagnosis 4.69 months), prescribed either AAF-Syn (probiotic Bifidobacterium breve M16-V and prebiotics, including chicory-derived oligo-fructose and long-chain inulin) or AAF. AAF-Syn was associated with fewer symptoms (-37%, p < 0.001), infections (-35%, p < 0.001), medication prescriptions (-19%, p < 0.001) and healthcare contacts (-18%, p = 0.15) vs. AAF. Infants prescribed AAF-Syn had a significantly higher probability of achieving asymptomatic management without hypoallergenic formula (HAF) (adjusted HR 3.70, 95% CI 1.97-6.95, p < 0.001), with a shorter clinical course of symptoms (median time to asymptomatic management without HAF 1.35 years vs. 1.95 years). AAF-Syn was associated with potential cost-savings of £452.18 per infant over the clinical course of symptoms. These findings may be attributable to the effect of the specific synbiotic on the gut microbiome. Further research is warranted to explore this. This real-world study provides evidence consistent with clinical trials that AAF-Syn may produce clinical and healthcare benefits with potential economic impact.

How Are Infants Suspected to Have Cow's Milk Allergy Managed? A Real World Study Report.

The purpose of this study was to evaluate the diagnosis and management of infants presenting with symptoms attributable to cow's milk allergy (CMA) in a real life setting and to test how the Cow's Milk-related Symptom Score (CoMiSS®) can be used to support the awareness to diagnose cow's milk protein allergy in primary care practice. The CoMiSS is an awareness tool based on various symptoms such as crying, gastrointestinal symptoms, dermatological and respiratory symptoms. The study was conducted on 268 infants from four countries (Belgium, Czech Republic, Germany, UK) aged 0 to 18 months consulting for CMA related symptoms. The analysis was based on two visits of these subjects. The results show an average CoMiSS of 11 at the first visit. After a therapeutic dietary intervention, the score at the second visit, which happened 3 weeks ± 5 days after the first one, dropped to an average value of 4. A satisfaction questionnaire completed by the primary care practitioners suggested an overall high level of satisfaction with the application of the CoMiSS tool in routine practice. These data highlight a huge discrepancy in the diagnosis and management of infants suspected of CMA in the different countries. The findings suggest that the CoMISS questionnaire is an effective tool in aiding awareness of CMPA in primary health care.