Efficacy of donkey's milk in treating highly problematic cow's milk allergic children: An in vivo and in vitro study

Successful therapy in cow's milk protein allergy rests on completely eliminating cow's milk proteins from the child's diet: it is thus necessary to provide a replacement food. This prospective study investigated tolerance of donkey's milk in a population of 46 selected children with cow's milk protein allergy, for whom it was not possible to use any cow's milk substitute. Thirty-eight children (82.6%) liked and tolerated donkey's milk at the challenge and for the entire duration of follow-up. Catch-up growth was observed in all subjects with growth deficit during cow's milk proteins challenge. The degree of cross-reactivity of immunoglobulin E (IgE) with donkey's milk proteins was very weak and aspecific. Donkey's milk was found to be a valid alternative to both IgE-mediated and non-IgE-mediated cow's milk proteins allergy, including in terms of palatability and weight-height gain.     

Skin prick test predictive value on the outcome of a first known egg exposure in milk-allergic children

Children with milk allergy have higher incidence of other food allergies, especially egg allergy. The objective of this study was to ascertain the accuracy of the prick test in children with IgE-mediated milk allergy for diagnosing egg allergy. Children under the age of 1 yr who came consecutively to Allergy Department 2003–05, and were diagnosed with IgE-mediated milk allergy were selected for this study. Egg introduction was completely avoided until the age of 14 months when clinical history, skin prick tests (SPT), specific-IgE antibodies determination and egg challenge test were performed. One hundred and four milk-allergic children were included. At least one positive prick test to any egg allergen was found in 65 out of the 104 (62.5%). Thirty-eight (36.5%) were allergic to egg proteins as well. Prick tests with egg white and ovomucoid (OVM) had the best diagnostic performances showing the largest areas under the receiver operating characteristic curve. The optimal diagnosis cut-off point was 6 mm for egg white and 5 mm for OVM. The positive likelihood ratios for these cut-off points were: 2.95 (95% CI: 1.74–4.99) for egg white prick test, and 20 (95% CI: 2.9–143.7) for OVM prick test. Children with specific IgE-mediated cow's milk allergy must be closely followed as a risk group for egg allergy. Early diagnosis is necessary and the SPT has shown itself to be a very useful tool for diagnosing immediate IgE reactions to egg on first known exposure.     

Allergenicity of milk protein hydrolysate formulae in children with cow's milk allergy

Cow's milk protein hydrolysate formulae have been developed to lower or eliminate the allergenicity of cow's milk proteins, and to reduce the antigenic load and the risk of sensitization. Cross-reactivity between different hydrolysate formulae and cow's milk proteins has been demonstrated. We have studied 20 children (median age 31 months, range 15–76 months) with a history of IgE-mediated cow's milk allergy. All the children had immediate allergic respiratory and/or cutaneous and/or gastro-intestinal reactions to cow's milk ingestion. In addition, the children had positive prick skin tests and positive RAST to cow's milk. Prick skin test, RAST, and double-blind placebo controlled food challenges were performed with three different hydrolysate formulae: a casein hydrolysate formula and two whey formulae, one partially and one extensively hydrolyzed. All 20 children had immediate allergic reactions after the challenge test with cow's milk. Only 2/20 children had a positive challenge test with a casein hydrolysate formula (Alimentum): one developed asthma and one urticaria. Two of the 15 children challenged with an extensively hydrolysed whey formula (Profylac) developed perioral erythema. Nine out of 20 children had a positive challenge test with a partially hydrolysed whey formula (Nidina H.A.): four developed asthma, three urticaria and two lip oedema. All children had positive prick skin tests to cow's milk proteins (casein and/or lactalbumin); 9 to Nidina H.A.; 3 to Profylac, and 3 to Alimentum. Specific IgE antibodies to cow's milk were present in all children; in 13 to Nidina H.A., in 4 to Profylac, and in 3 to Alimentum.     

The spectrum of cow''s milk allergy

Childhood cow's milk allergy is a diagnosis encompassing various syndromes. Antigen-immunoglobulin E (IgE) antibody interaction is classically involved in mast cell degranulation in IgE-mediated food allergy, while non-IgE mediated cow's milk allergy is mostly mediated by cellular mechanisms. The diagnosis of cow's milk allergy largely relies on a good knowledge of the clinical expression of the disease. In this educational review series, we describe three cases of cow's milk allergy, first a 7-yr-old girl with persisting IgE-mediated cow's milk allergy, second a 8-month-old boy with cow's milk induced flares of atopic dermatitis, and third a 6-yr-old boy with sheep and goat milk allergy, in the absence of cow's milk allergy. The cases are discussed and summarized with more general recommendations for the clinical management of cow's milk allergy.     

Neutral oligosaccharides in colostrum in relation to maternal allergy and allergy development in children up to 18 months of age

Several recent studies have demonstrated a relationship between the composition of the gut microbiota in infancy and subsequent development of allergic disease. Human milk is the major food in infancy and may thus profoundly influence the composition of the gut flora. Oligosaccharides in breast milk survive the passage through the stomach and are utilized by the gut microbiota. As the relationship between breast feeding and childhood allergy is controversial we hypothesized that the composition of oligosaccharides in breast milk might explain the controversy. Nine of the most abundant neutral oligosaccharides in human milk were analysed in colostrum samples from allergic and non-allergic women and related to subsequent development of allergy in their children. The carbohydrate fraction of the colostrum was separated by gel permeation chromatography and neutral oligosaccharides, tri- to hexasaccharides were collected. Neutral oligosaccharides were analysed with high-performance liquid chromatography. There was a large variation in the concentration of neutral oligosaccharides in colostrum, which could not be explained by the allergic status of the women. Allergic children consumed higher amounts of neutral oligosaccharides in total, although not significantly (p = 0.12). When different oligosaccharides were analysed separately, there was no significant difference in consumption between the infants who developed atopic allergy later (n = 9) and infants who did not (n = 11). Thus, the amount of neutral oligosaccharides in colostrum does not directly correlate with maternal allergy, nor with allergy development in children up to 18 months of age.     

A new model for low-dose food challenge in children with allergy to milk or egg

Background: Atopic eczema and food allergy are common in early childhood. Children seem to gradually develop tolerance to milk and egg, and it is a relief for families when their child can tolerate small amounts of these basic foods, even if larger doses may still cause symptoms. Aim: To develop a model for low-dose oral food challenge, facilitating re-/introduction of milk or egg. Methods: In 39 children sensitized to milk and/or egg, we performed 52 challenges using a new standardized model for low-dose oral food challenge. The recipes were validated for blinding with sensorial tests. Results: Four children challenged to milk had a positive challenge outcome. There were no significant differences with respect to family history, associated atopic manifestations, nutritional supply, eczema severity, or skin-prick test compared with the non-reacting children, but total and specific IgE values were significantly higher. All but two of the non-reacting children were able to introduce milk and egg into their diet without problems.
Conclusion: We report recipes and a protocol to be used for standardized open and double-blind placebo-controlled low-dose food challenge in young children, enabling the introduction of small amounts of egg and milk into the diet during tolerance development.     

Frequency of food allergy in a pediatric population from Spain

We evaluated the prevalence and characteristics of the principal foods implicated in 355 children diagnosed with IgE-mediated food allergy. Diagnosis was established on the basis of positive clinical history for the offending food, positive specific IgE by skin prick test and RAST, and open food challenge. Our results showed the principal foods involved in allergic reactions are: eggs, fish, and cow's milk. These are followed in frequency by fruits (peaches, hazelnuts and walnuts), legumes (lentils, peanuts and chick peas) and other vegetables (mainly sunflower seeds). The legumes demonstrated the highest degree of clinical cross-reactivity. Most patients with food allergy reacted to one or two foods (86.7%). Only 13.3% of patients reacted to 3 or more foods, mostly to legumes and fruits. We found that food allergy begins most frequently in the first (48.8%) and second (20.4%) years of life. Allergy to proteins of cow's milk, egg, and fish begins predominantly before the second year, demonstrating a clear relationship with the introduction of these foods into the child's diet. Allergy to foods of vegetable origin (fruits, legumes and other vegetables) begins predominantly after the second year.;     

Oral desensitization in children with immunoglobulin E-mediated cow's milk allergy – follow-up at 4 yr and 8 months

Until now, the basic treatment for food allergy has been to avoid the offending item. This approach is difficult in the case of common foods and in the case where there is a risk of severe reaction after consuming the offending food, even inadvertently. This is the follow‐up of a previous study aimed at desensitizing 21 children with immunoglobulin E (IgE)‐mediated cow’s milk (CM) allergy. This protocol was totally or partially successful in 85% of cases, but failed in the remaining 15%. Our aims were to study the long‐term effectiveness and safety of oral CM desensitization, and the prognostic value of Skin Prick Test (SPT) and specific serum CM IgE. The 21 children were called back (one dropped out). The allergic history and other information on CM intake over the last 4–5 yr were recorded. Children underwent SPT, and end‐point SPT, with casein and α‐lactoalbumin. Specific CM IgE was also measured. At follow‐up, 14/20 children totally (n = 13, 65%) or partially (n = 1, 5%) tolerated CM. None of the recalled children reported use of emergency care. SPT positivity to casein and/or α‐lactoalbumin decreased significantly (p < 0.01), and all the negative SPT referred to the tolerant children. Cutaneous sensitivity to both casein and α‐lactoalbumin (end‐point SPT) significantly decreased after the 6‐month desensitization period of the previous study (p < 0.001), but did not decrease significantly at follow‐up. A significant reduction of serum‐specific CM IgE was also observed (p < 0.05). Clinical tolerance induced by oral CM desensitization persists in time. Negativization of SPT and reduction of specific CM IgE could be considered prognostic indicators of CM tolerance. Oral CM desensitization seems to be a promising method to treat CM food allergy. This protocol is time‐consuming but offers the advantage that it can be performed at home. This methodology must only be used by trained staff.     

Anaphylaxis to sheep's milk cheese in a child unaffected by cow's milk protein allergy

A 5-year-old atopic boy unaffected by cow's milk protein allergy experienced several anaphylactic reactions after eating food containing “pecorino” cheese made from sheep's milk. Prick-prick tests were strongly positive to sheep's buttermilk curd and `pecorino' sheep's cheese. Skin prick tests to fresh sheep's milk and to goat's milk were also positive, whereas they were negative to all cow's milk proteins, to whole pasteurized cow's milk and to cheese made from cow's milk. Specific IgE antibodies were negative to all cow's milk proteins. Conclusion Sheep's milk and cheese derived from sheep's milk may cause severe allergic reactions in children affected and, as we report, in children not affected by cow's milk protein allergy. Received: 14 January 1997 and in revised form: 20 June 1997 / Accepted: 8 July 1997     

Lessons from the clinical course of IgE-mediated cow milk allergy in Israel

Cow milk and milk products are the most common food products consumed in Israel; rates of allergy to cow milk exceed those of peanuts in infants and children. The aim of the present study was to evaluate retrospectively the clinical features and natural course of immunoglobulin (Ig) E-mediated cow milk allergy (CMA) in Israel. Data of children diagnosed with CMA from 1995 to 2003, were collected regarding age at first and most recent reactions, symptoms and signs, family history of atopy, other allergic diseases, emergency department visits, hospitalizations, and treatment. Patients with transient CMA were compared to those with persistent CMA (> or =3 yr old). The study group consisted of 105 patients, 43 with transient CMA (age range: 0.48-11 yr). The remaining 62 patients (age range: 3-16.5 yr) did not achieve tolerance to cow milk during the follow-up period. No differences were found between the groups in mean age and symptoms and signs at the first allergic reaction and family history of atopy. Patients with persistent CMA had a higher rate of asthma than patients with transient CMA (61.2% vs. 18.6%, p < 0.001). Fifty patients with persistent CMA had 137 subsequent allergic reactions after diagnosis, 25% of the reactions were due to oral milk challenge at the clinic and 75% due to accidental exposure, of which 13% required an emergency department visit and 8%, hospitalization. Only 19% of the reactions were treated with epinephrine injection. In conclusion, in our experience, less than half of the children diagnosed with IgE-mediated CMA during 9 yr, outgrew it. The patients with persistent CMA have a higher prevalence of asthma compared with the general population or to children with transient CMA. The high number of recurrent allergic reactions due to accidental exposure and the low rate of epinephrine usage in these patients point to a need for better education of patients and their families.     

Correlation of allergen‐specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies

Scott‐Taylor TH, Hourihane J, Strobel S. Correlation of allergen‐specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies.
Pediatr Allergy Immunol 2010: 21: 935–944.
© 2010 John Wiley & Sons A/S Cytokines can affect the quantity and class of allergen‐specific immunoglobulins through the T cell polarization that accompanies atopy. Antigen‐specific IgG subclasses and IgE antibodies were compared with intracellular T cell cytokine changes to sensitizing antigens in 23 children with multiple food allergies and 20 healthy controls. Allergic children showed higher levels of total and food‐specific IgE, IgG1 and IgG4 to peanut, milk and egg than non‐atopic children or adults, coinciding with a TH2 cytokine response to sensitizing antigens. IgG1 and IgG4 antibodies specific to milk and egg and peanut protein were elevated relative to age‐matched healthy children (p ≤ 0.05) and, in milk‐ and egg‐sensitized children, correlated with cytokine responses (p < 0.05). Peanut‐sensitized children additionally had elevated levels of IgG2 and IgG3 also which correlated inversely (p < 0.003 and p < 0.04, respectively) with IFNγ production. Elevated allergen‐specific IgG subclass antibodies in sensitized children correlated with total IgE levels (p ≤ 0.05) in all three food allergen groups. The ratio of specific IgG1 to IgG4 was highest in those with high IgE, inverted with resolution of allergy, and correlated with total IgE levels (p ≤ 0.01) in milk‐ and egg‐sensitized children. The correlation of TH2 responses with allergen‐specific antibodies would implicate polarized T cells in food allergic children in IgE hypersensitivity and overproduction of particular IgG subclasses alike. IgG1:IgG4 ratio declines with allergy sensitization and may denote emerging tolerance.     

Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants

The relationship between breast-feeding, IgA production and development of atopic disease in children is a matter of controversy. Some of this controversy might be due to individual differences in the composition of breast milk. The aim of this study was to relate the levels of cytokines, chemokines and secretory (S)-IgA antibodies in breast milk to the development of atopic manifestation and salivary IgA production in infants. Cytokine, chemokine and SIgA levels, as measured with enzyme-linked immunosorbent assay (ELISA), in colostrum and mature milk were analyzed in relation to the development of positive skin-prick tests (SPT), allergic symptoms and salivary IgA antibody production during the first 2 years of life in 53 infants. There was no association between levels of IL-4, -5, -6, -8, -10, -13, -16, IFN-γ, TGF-β1, -β2, RANTES, eotaxin or SIgA levels in the breast milk with either SPT-positivity, development of allergic symptoms or salivary IgA levels during the first 2 years of life in the infants. Thus, differences in the composition of cytokines, chemokines and SIgA in breast milk did not, to any major degree, affect the development of a positive SPT, atopic symptoms, nor salivary IgA antibody production during the first 2 years of life.     

Prevention and management of food allergy

The phenotypic expression and natural history of food allergy vary widely according to the patient's age, disease presentation and type of offending food. Prevention of food allergy might be achieved by altering the dietary factors responsible for the sensitization and phenotypic expression of the disease. Owing to the peculiarity of the atopic status, a minute amount of allergens can trigger both sensitization and symptoms in atopic individuals. The oral dose of β-lactoglobulin causing sensitization can be estimated to be between 1 ng and several milligrams. In food allergy, sensitization and treatment are allergen specific; therefore, for primary prevention (avoiding sensitization) and secondary prevention of food allergy (avoiding symptoms in an already sensitized subject), a product without immunogenic and allergenic epitopes should be given in each case. Babies of atopic parents are particularly prone to develop food allergy and for this reason they are called high-risk babies. Cow's milk is the most commonly offending food in both gastrointestinal and cutaneous manifestations. Cow's milk proteins are potent allergens and around 2.5% of infants experience cow's milk allergy in the first years of life. The major risk factors for cow's milk allergy are positive family history of atopy and early exposure to cow's milk proteins. Hydrolysate formulae have been developed for the purpose of reducing the allergenicity of cow's milk proteins. More recently, partially and extensively hydrolysed formulae have also been used for feeding babies with a high risk of atopy for the prevention of cow's milk allergy. However, according to the results of a recent randomized controlled study, only an extensively hydrolysated formula, and not a partially hydrolysated formula, significantly decreased the prevalence of cow's milk allergy.     

Safety of a new, ultrafiltrated whey hydrolysate formula in children with cow milk allergy: a clinical investigation

The purpose of this study was to determine whether a new ultrafiltrated whey hydrolysate infant formula, Profylac®, could be administered safely to children with cow milk protein allergy/intolerance. Profylac has a stated molecular weight of < 8 kD and at least 30, 000 times reduced antigenicity which is controlled by a combination of ELISA-techniques and immunochemical methods. The study comprised 66 children with cow milk protein allergy/intolerance diagnosed by controlled elimination/ challenge procedures. The children were aged 1 month-14. 5 years, median 1% years and 15 were below 1 year. Thirty-five of these children had proven IgE-mediated reactions (cow milk protein allergy). Sixty-one of the children had at least two different symptoms and 31 had concomitant allergies to other foods and/or inhalants. All 66 children underwent and tolerated open, controlled challenges with Profylac. A total of 64 children continued having Profylac daily for at least 3 months and 58 for at least 6 months after challenge. Nine of the children older than 1 year did not like the taste and only had Profylac in minor amounts. No side effects were registered. Fifteen of the infants were below 1 year of age, and this group was compared with an age matched group of 16 infants challenged with and fed an extensively hydrolysed casein hydrolysate, Nutramigen®. All the infants in these two groups accepted and tolerated Profylac and Nutramigen, respectively, and no side effects were registered. Among the 35 patients with IgE-mediated reactions 6% (2/35) had positive skin prick tests and 11% (3/28) had specific IgE class 2 against Profylac, 2 of the latter before intake of Profylac. None of the patients with non-IgE-mediated reactions had a positive skin prick test or specific IgE against Profylac. The study provides 95% confidence that this product is tolerated by at least 95% of children with cow milk protein allergy/intolerance and by 90% with IgE-mediated reactions. We conclude, that this ultrafiltrated whey hydrolysate is generally safe to feed to children with verified adverse reactions to cow milk protein, including children with IgE-mediated reactions. The taste of the product was widely accepted, also by older children.     

Dietary insulin as an immunogen and tolerogen

We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin-specific immune response in infants. Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3-7 days and/or 3 months after delivery. After exclusive breast-feeding, the children received either CM formula or casein hydrolysate during the first 6-8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta-cell autoimmunity when compared with autoantibody-negative children (p = 0.030); this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast-fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI. However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance.     

High levels of IgG4 antibodies to foods during infancy are associated with tolerance to corresponding foods later in life

Children with eczema and sensitization to foods are recommended skin care and, if food allergy is proven by challenge, an elimination diet. For most children the diet period is transient, but the process behind tolerance development and the influence of decreased allergen exposure is not fully known. The aim of the study was to investigate the effect of elimination diet on serum and salivary antibodies and to identify immunological parameters related to the ability to tolerate foods. Eighty‐nine children, below 2 yr of age, with eczema and suspected food allergy were included. Recommended treatment was skin care to all children, and 60 children had a period of elimination diet. At 4½ yr of age, the children were divided into two groups, based on if they had been able to introduce the eliminated foods, or not. Serum and salivary antibodies were analyzed with enzyme‐linked immunosorbent assay and UniCAP^® before and after a 6‐wk treatment period and at 4½ yr of age. Children sensitized to egg and/or milk that could eat and drink the offending foods at 4½ yr of age, had higher levels of Immunoglobulin G₄ antibodies to ovalbumin and β‐lactoglobulin and also higher IgG₄/Immunoglobulin E ratios on inclusion in the study, than those who had to eliminate egg and/or milk from their diet, beyond 4½ yr of age. The highest IgG₄/IgE ratios were found in children with circulating IgE antibodies to egg and/or milk but negative skin prick test on inclusion. The 6‐wk treatment period did not significantly affect the levels of serum and salivary antibodies. In conclusion, eczematous, food sensitized infants with high levels of IgG₄ and high ratios of IgG₄/IgE antibodies to food allergens are more likely to consume these foods at 4½ yr than infants with low levels and ratios.     

Prevalence of food allergy among preschool children in northern Thailand

Background: The epidemiology and clinical spectrum of food allergies (FA) confirmed by oral food challenge tests (OFC) in the Southeast Asian countries are limited. The aim of the present study was to examine the prevalence and characteristics of FA among preschool children in northern Thailand. Methods: Five hundred and forty‐six children aged 3–7 years living in Chiang Mai, Thailand participated in this study. A cross‐sectional parent questionnaire survey was conducted. Families with children reporting FA were invited to undergo further investigations with skin prick testing, serum specific IgE, and OFC. Results: A total of 452 out of 546 questionnaires (82.8%) were returned. Forty‐two children (9.3%) were reported to have FA. The five leading allergic foods reported were shrimp, cow's milk, fish, chicken eggs, and ant eggs. The most commonly reported symptom was a skin rash (78.0%), followed by abdominal pain and vomiting (31.1%). Anaphylaxis was found in two children (3.4%), from ant eggs allergy. Eighteen children underwent OFC; five of them were positive to shrimp, fish, and crab. Either skin prick test or serum‐specific IgE was positive in these children. Factors associated with parent‐reported FA included personal and family history of atopic dermatitis. Conclusions: The prevalence of IgE‐mediated FA confirmed on OFC was ≥1.11% (95% confidence interval: 0.41–2.98%). The most common causative food was shrimp. Ant eggs were a unique food allergen causing severe reactions in preschool children in northern Thailand.     

Dietary prevention of allergic diseases in infants and small children

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cow's milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.     

Dietary prevention of allergic diseases in infants and small children

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light into this issue, a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. In this paper, the immunology of the fetus and newborn is reviewed as well as the post-natal development of the immune system. The influence of post-natal environment and breastfeeding on tolerance induction and sensitization are examined. Allergic diseases result from a strong relationship between genetic and environmental factors. Sensitization to food allergens occurs in the first year of life and cow's milk allergy is the first food allergy to appear in the susceptible infants. Hypoallergenicity of food formulas to be used is a critical issue both for treatment of cow's milk-allergic children and for prevention. Methods to document hypoallergenicity are discussed and evaluated in the preclinical and clinical steps.     

Predictive factors for the persistence of cow’s milk allergy

Santos A, Dias A, Pinheiro JA. Predictive factors for the persistence of cow’s milk allergy.
Pediatr Allergy Immunol 2010: 21: 1127–1134.
© 2010 John Wiley & Sons A/S Cow’s milk allergy (CMA) is usually transient, but recent studies have shown a later acquisition of tolerance to CM. Our aims were to characterize a population of Portuguese children with CMA and to identify predictive factors for the persistence of this food allergy. Children with CMA observed in our Paediatric Allergy Clinic between 1997 and 2006 were selected. Demographic and clinical data were collected from medical records. The group of children who tolerated CM before the age of 2 was compared with the group of children who tolerated CM beyond that age or persisted with CMA until the end of the study. Multivariate logistic regression analysis was used to investigate independent predictive factors for the persistence of CMA beyond the age of 2. In the subgroup of children with IgE‐mediated CMA, the acquisition of tolerance was analysed using Cox regression. In this population of 139 children, the majority presented more than one symptom (73%) affecting more than one organ (51%), with cutaneous (81%), gastrointestinal (55%), respiratory (16%) manifestations and/or anaphylaxis (3%). Thirty‐two per cent developed asthma, 20% atopic eczema, 20% rhinoconjunctivitis and 19% other food allergies over time. The acquisition of tolerance was different in the whole population versus the subgroup with IgE‐mediated CMA: 34%versus 0% at the age of 2, 55%versus 22% at the age of 5 and 68%versus 43% at the age of 10. Immediate allergic symptoms, asthma and other food allergies were independent factors for the persistence of CMA beyond the age of 2. Higher maximum weal diameter on skin prick test to CM and higher maximum level of specific IgE to CM were associated with reduced likelihood of acquiring tolerance in the subgroup of children with IgE‐mediated CMA. In conclusion, children with IgE‐mediated CMA acquire tolerance to CM at older age. Clinical parameters and allergy tests may be helpful in defining prognosis. CM‐allergic children tend to develop other atopic conditions and need specialized follow‐up in the long term.