Baked Milk Research Articles

Long-Term Follow-Up After Baked Milk Introduction

Clinical trials of baked milk (BM) introduction have demonstrated accelerated resolution of milk allergy. Long-term data regarding real-world introduction of BM are lacking. We sought to characterize our experience of BM introduction. We performed a retrospective chart review of consecutive BM oral food challenges performed in our clinicfrom 2009 to 2014, with a minimum follow-up of 24months. Of the 206 patients challenged, 99 (48%) passed and 187 were sent home with detailed instructions to incorporate BM into their diets. After a median of 49 months of follow-up, 43% of the 187 had progressed to direct milk, 20% to less-cooked forms of milk, 10% remained ingesting BM, and 28% were strictly avoiding milk. Higher milk IgE levels were associated with decreased odds of passing a BM challenge and advancing to less-cooked forms of milk. Predictors of progressing to less-cooked forms of milk were passing the challenge and younger age. There were 79 reported milk reactions involving 68 patients (33% of total) during follow-up. Of these, 78% were classified as mild, 14% severe, and 6 patients developed eosinophilic esophagitis. Of 11 severe reactions, 4 were accidental exposures, 3 were planned escalations, and 4 occurred with previously tolerated doses. The majority of patients who underwent a BM challenge, including those who failed their challenge, were able to progress to direct or less-cooked forms of milk. However, adverse reactions were common, and even a successful BM challenge does not guarantee future tolerance of BM or preclude later reactions, even to previously tolerated doses.

Increased Tolerance to Less Extensively Heat-Denatured (Baked) Milk Products in Milk-Allergic Children

Most milk-allergic children tolerate baked milk. To investigate the effect of more frequent versus less frequent introduction of higher doses of more allergenic (less heat-denatured) forms of milk (MAFM) on progression to tolerance. Milk-allergic children were challenged with increasing doses of MAFM; baked foods were incorporated into the diet; challenges were repeated at 6- or 12-month intervals over 36 months. A total of 136 children (70% males) were enrolled in the active group (median age, 7 years). At baseline, 41 (30%) reacted to muffin, 31 (23%) to pizza, 11 (8%) to rice pudding, 43 (32%) to non-baked milk; and 10 (7%) tolerated non-baked milk. Children who tolerated baked milk but reacted to non-baked liquid milk were randomized to MAFM challenges every 6 months (n= 41) or 12 months (n= 44). At month 36, 61% children in the 6-month and 73% in the 12-month escalation groups tolerated MAFM. Overall, 41 (48%) children who ingested baked-milk diet became tolerant to non-baked milk; no difference was seen between 6- and 12- month escalations. Among children who reacted to muffin at baseline and continued avoidance, 20% developed tolerance to baked milk and 0% tolerated non-baked milk. None of the 34 children who qualified for inclusion but chose not to take part in the active study became tolerant to any form of milk by history. Majority of children tolerated baked milk at baseline. Baked-milk diets were associated with progressive immunomodulation. Most children who incorporated baked milk into their diet progressed to tolerating MAFM, but there was no advantage to more frequent attempts to escalate to MAFM, per intention-to-treat analysis.

Safety and allergic reaction profiles of children undergoing baked milk and egg challenges: a 6-year experience from a pediatric tertiary referral center

Safety and allergic reaction profiles of children undergoing baked milk and egg challenges: a 6-year experience from a pediatric tertiary referral center

Immunothérapie orale au lait : cru ou cuit ?

Avoidance is currently the only accepted form of management for children with cow's milk allergy. Oral immunotherapy has emerged as a promising alternative but carries the potential risk of anaphylactic adverse reaction. Baked milk seems to be safer than raw milk in most cases. However, severe adverse events continue to pose a real threat even in oral immunotherapy programs using baked milk. While many patients undergo successful oral immunotherapy without major safety issues, this is not the case for all patients. The benefits of oral immunotherapy with baked milk in speeding up recovery in children with a severe phenotype of cow's milk allergy should be carefully evaluated at specialized centers equipped to manage highly sensitive patients.

Safety and Efficacy Balance of Baked Milk and Egg Oral Immunotherapy

Purpose of review There is a subgroup of individuals with egg or cow’s milk (CM) allergy that can tolerate heated egg or CM. Thermal processing has been shown to affect antigen allergenicity either directly by denaturation of significant epitopes, or indirectly by synergistically altering their susceptibility to the digestion process under specific pH conditions. CM and egg proteins have heat labile molecules that become hypoallergenic after thermal treatment. The allergenicity may be further reduced when the CM and egg allergens are interacting with wheat proteins, and in particular gluten, in an interplay that teleologically affects solubility and therefore bioavailability. This phenomenon is known as the food matrix effect. By exploiting these observations, it has been suggested that diets containing extensively heated CM and egg might comprise an oral immunotherapeutic approach that could alter the expected natural allergy resolution or immunomodulate to tolerance the cases with persistent allergy. Recent findings There is evidence suggesting that most of the baked-tolerant patients can be benefited from baked CM or egg oral immunotherapy (OIT). Following this approach, these patients can be desensitized, can be promoted to a transition from baked CM/egg OIT-induced tolerance to unheated CM and egg OIT-induced tolerance, or may acquire sustained tolerance. Summary Baked CM or egg OIT may accelerate CM or egg allergy resolution and therefore may be a new therapeutic option to etiologically and not just symptomatically treating CM and egg allergy. It remains to be appropriately studied which are the phenotypic characteristics of these patients and which will be the appropriate immunotherapeutic protocol so that OIT can be easily and safely be offered to them.

Contribution of Molecular Allergen Analysis in Diagnosis of Milk Allergy.

We sought to describe the available evidence supporting the utilization of the molecular allergen analysis (MAA) for diagnosis and management of cow milk protein allergy (CMPA). Cow milk proteins are among the most common food allergens in IgE- and non-IgE-mediated food allergic disorders in children. Most individuals with CMPA are sensitized to both caseins and whey proteins. Caseins are more resistant to high temperatures compared to whey proteins. MAA is not superior to the conventional diagnostic tests based on the whole allergen extracts for diagnosis of CMPA. However, MAA can be useful in diagnosing tolerance to extensively heated milk proteins in baked foods. Children with CMPA and high levels of casein IgE are less likely to tolerate baked milk compared to children with low levels of casein IgE. Specific IgE-binding patterns to casein and betalactoglobulin peptides may predict the natural course of CMPA and differentiate subjects who are more likely to develop CMPA at a younger age versus those with a more persistent CMPA. Specific IgE-binding patterns to casein and beta-lactoglobulin peptides may also predict response to milk OITand identify patientsmost likely to benefit fromOIT.

Long-term outcomes following baked milk–containing diet for IgE-mediated milk allergy

Long-term outcomes following baked milk–containing diet for IgE-mediated milk allergy

Baked milk tolerant patient: Is there any special feature?

BackgroundDetermining whether patients with cow's milk allergy (CMA) can tolerate foods produced with baked milk could provide a better quality of life, a better prognosis, and an option for desensitization. ObjectivesThe aim of this study was to identify which patients over four years of age with persistent CMA could tolerate baked milk, to compare the clinical and laboratory characteristics of reactive and non-reactive groups and to describe their clinical evolution. Materials and methodsA cross-sectional study was conducted (January/13 to November/14) that included all the patients followed at a food allergy center who met the inclusion criteria. The patients underwent an oral food challenge (OFC) with a muffin (2.8g of cow's milk protein). To exclude cow's milk (CM) tolerance, the patients were subsequently challenged with unheated CM. ResultsThirty patients met all the inclusion criteria. Fourteen patients (46.7%) were considered non-reactive to baked milk and reactive to unheated CM. When the groups that were reactive and non-reactive to baked milk were compared, no statistically significant differences in clinical features were found. The prick test for α-lactalbumin (p=0.01) and casein (p=0.004) and the serum specific IgE for casein (p=0.05) presented statistical differences. After one year, none of the patients who were reactive to baked milk were ingesting CM, while 28% of the tolerant patients were consuming fresh CM (p=0.037). ConclusionsBaked milk can be tolerated by patients with CMA, especially those with lower levels of casein and α-lactalbumin. This option can improve quality of life and accelerate tolerance.

Prospective evaluation of testing with baked milk to predict safe ingestion of baked milk in unheated milk-allergic children.

BackgroundCow’s milk allergy is one of the most common food allergies affecting young children. A subset of milk-allergic individuals can eat baked milk without allergic symptoms which is beneficial in terms of prognostication and liberalization of the diet. A retrospective study suggested that skin prick testing (SPT) with a baked milk (muffin) slurry may provide a sensitive means of predicting the outcome of a medically supervised baked milk oral food challenge. We evaluated the predictive value of SPT with baked milk to identify unheated milk-allergic children who are able to safely eat baked milk.MethodsChildren aged 2–16 years with a prior history of reaction to milk and a milk extract SPT of 8–14 mm were recruited. Investigator-blinded SPT to muffin slurry and powdered milk in triplicate and specific IgE (sIgE) to casein and milk were performed. Graded oral challenge to egg-free baked milk muffins (total 2.6 gm milk protein) was performed in the hospital. Reliability of tests was analyzed for intraclass correlation. Statistical significance for clinical characteristics of population and muffin testing versus baked milk reactivity was calculated with Fisher exact test for dichotomous and t-test for continuous variables. Wilcoxon rank sum test was used to compare immunological characteristics between individuals who tolerated or reacted to baked milk. Fitted predicted probability curves and ROC curves were generated.ResultsThirty-eight children were consented and 30 met study criteria. The muffin SPT and casein sIgE were significantly different in those who passed versus failed baked milk challenge. Negative (<3 mm) baked milk tests were found in 8/30 children (27 %) and were associated with non-reactivity to baked milk (p = 0.01) with a sensitivity of 1 (0.70–1.00). All children with negative SPT for baked milk passed the oral challenge. Specificity was 0.41 (0.19–0.67). The optimal decision point for the muffin SPT was 4 mm and the casein sIgE was 6 kU/L. The powdered milk test was not helpful.ConclusionsSkin prick testing with a baked milk (muffin) slurry may have a role in clinical practice to identify baked milk tolerance in milk-allergic patients.

Baked Egg and Milk Exposure as Immunotherapy in Food Allergy.

Baked milk and egg have the potential to act as a form of oral immunotherapy (OIT). Clinical studies have shown that a majority of milk- and egg-allergic children can tolerate these allergens modified in baked form, and immunologic changes reported in subjects ingesting baked milk and egg mirror those seen in food allergy OIT trials. In addition, several studies have indicated that resolution of milk and egg allergies occur sooner in populations regularly ingesting baked milk and egg. Oral food challenges remain the best method for determining tolerability of baked milk and egg since baseline characteristics and diagnostic testing have not been reliable predictors. In this review, we explore the tolerability of baked milk and egg and their potential as OIT treatment for milk and egg allergy.

Practice of the Treatment of Milk Allergy in the UK: A National Audit

Background: The management of cow's milk allergy (CMA) includes initial dairy exclusion with suitable dietary substitution, diagnostic challenges where indicated, and supervised re-introduction as the condition resolves. Information on clinician practice is limited. We audited the current practice of clinicians in the UK to evaluate adherence to international guidelines. Methods: An online questionnaire was sent to all clinicians whose practice included children identified on the national allergy society website. One hundred and sixty questionnaires were sent and 116 (73%) responded. Results: Skin prick tests were more commonly used than serum-specific IgE as diagnostic tests. Respective proportions selecting amino acid formulas (AAF) or extensively hydrolysed formulas (EHF) in severe versus mild/moderate presentations were 78 and 40% versus 20 and 88%; soya formula was the first choice in 8.6 and 24%. The criteria for selection of AAF as the first choice were predominantly severe IgE-mediated and non-IgE-mediated reactions, failure to thrive and if infants refused EHF. Oral challenges might be used to diagnose CMA in 69%, whereas nearly 90% performed challenges to assess tolerance. Most of these were open challenges, more commonly with fresh milk (90%) than baked milk (60%). Home baked milk challenges were frequently considered (70%), although only after consideration of the clinical scenario. Practice did not vary with experience. Conclusions: Current practice amongst UK clinicians of the management of CMA is broadly in line with current guidance, particularly the positioning of hypoallergenic milks as substitute milk choices. A notable deviation was the use of home baked milk challenges or re-introduction.

Outcomes of 109 Consecutive Open Food Challenges to Extensively-Heated (baked) Milk

Outcomes of 109 Consecutive Open Food Challenges to Extensively-Heated (baked) Milk

Debates in allergy medicine: baked milk and egg ingestion accelerates resolution of milk and egg allergy

Cow’s milk and hen’s egg are ubiquitous in diets around the world and can be important sources of protein in young children. Unfortunately, milk and egg allergies are also some of the most common food allergies in childhood. Less allergenic forms of milk and egg due to heating and interactions with a food matrix, as in baked goods, are tolerated by a majority of milk- and egg-allergic patients. Adding baked milk and egg into the diets of milk- and egg-allergic children can broaden diets, increase nutrition, and improve quality of life. Most important, regular ingestion of baked milk and egg can help children outgrow their allergies to milk and egg. This article will review our current understanding of baked milk and egg tolerance and outline how these baked forms accelerates tolerance to regular milk and egg.

Powder milk: a user-friendly and safe product for heated-milk food challenge?

BackgroundPrevious studies have reported that up to 75 % of milk allergic subjects tolerate heated milk products. However, the food used for heated milk challenge is often prepared in a non-standardized manner by the parents at home, which may prove inconvenient and even sometimes raise concerns with regards to test validity. Instant skim milk powder is made by a food process that involves heating skim milk to up to 250 °C (390 °F) for up to 30 min which ought to be sufficient to denature thermo-labile proteins.ObjectiveTo appraise the use of instant skim milk for the purpose of heated milk food challenge.MethodsWe reviewed all oral food challenges to instant skim milk powder performed at Sainte-Justine University Hospital Center in Montreal, Canada between November 2008 and January 2013 (cumulative dose of 4 g proteins).ResultsDuring the study period, 39 children underwent an open food challenge to instant skim milk powder. Thirty patients (76.9 %) passed the challenge without clinical reaction, of which 26 successfully introduced heated milk products at home. The remaining four children reported intermittent mild reactions to specific forms of heated milk goods while they tolerated others. Subjects’ clinical and paraclinical characteristics were comparable to previous cohorts evaluating baked milk challenge, which reported similar rates of heated milk positive challenges, ranging from 17 to 28 %.ConclusionChallenge with instant skim milk powder could be a safe, convenient and easily standardizable alternative to home baked food for heated milk challenge. Further controlled studies are needed before this can be implemented to practice.

Cow's Milk Allergy: the Relevance of IgE.

Cow's milk allergy (CMA) accounts for most diagnosed food allergies, mainly in the first year of life.1 CMA can cause severe anaphylaxis.2 CMA management is based on strict avoidance and the prescription of rescue medication. Cow's milk (CM) contains more than 40 proteins, including casein (Bos d 8), -lactalbumin (Bos d 4), and -lactoglobulin (Bos d 5), identified as major milk allergens.1 Serum specific IgE (sIgE) to casein characterized patients with persistent CMA,3 CM tolerance,4 and reactivity to baked milk.5 Oral immunotherapy (OIT) for CMA has been used with interesting outcomes as it may induce immunologic tolerance.1,2 However, a safety perspective represents a relevant concern, because reactions to OIT are frequent1,2 It has been demonstrated that sIgE to raw CM >50 kUA/L predicted not-tolerated OIT.6 Molecular-based allergy diagnostics have now become recently available in clinical practice. This method allows for defining and characterizing the sensitization profile that identifies potentially dangerous proteins and suggests a more precise prognosis. In this regard, Cingolani and colleagues reported that component resolved diagnosis had a good ability to define 2 phenotypes of CMA children: high-anaphylaxis and milder-risk.7 In particular, these phenotypes can be differentiated through measuring the level of sIgE to Bos d 8. We now report our experience concerning a retrospective cohort. This observational and retrospective experience evaluated the usefulness of ImmunoCAP and ISAC (please describe company, city, country) to detect anaphylaxis after CM ingestion. We evaluated children with CMA diagnosis who consecutively visited the Istituto Gaslini (a third tier children's hospital) in the last year. CMA diagnosis was performed on suggestive history consistent with CM sensitization (i.e. symptom occurrence after milk ingestion), documented milk sensitization, and a positive food challenge test. Anaphylaxis was defined according to validated criteria: briefly, suggestive history (sudden occurrence of symptoms, involving at least two systems, such as gastrointestinal and/or cutaneous and/or respiratory and/or cardiovascular after milk ingestion) consistent with documented CM sensitization.1 Serum sIgE to: raw CM allergen, Bos d 4, 5, and 8 were measured by the quantitative ImmunoCAP method and the semi-quantitative microarray-ISAC method (Thermo Fisher Italy). We Evaluated 53 patients (20 with anaphylaxis and 33 with CMA). Children with anaphylaxis presented: skin symptoms (89%), respiratory complaints (77%), gastrointestinal features (57%), and cardiovascular symptoms (11%). Children with CMA presented: skin symptoms (71%), gastrointestinal features (65%, mainly vomiting), and respiratory complaints (58%). The Table shows the clinical and immunologic characteristics of the 2 groups. The significant prevalence for male gender in anaphylaxis was consistent with that of Cingolani's study. The age was significantly lower in the anaphylaxis group, it conflicted with the findings of that study (surprisingly the age was particularly old in regards to CMA). Serum sIgE levels to raw CM allergen were significantly higher in the anaphylaxis group; however, there was no significant difference between the two groups for all molecular components as measured by both the ImmunoCAP and ISAC method. Table Clinical and imunological characteristics of patients Receiver operating characteristic (ROC) analysis showed that raw CM ImmunoCAP had a good specificity (86.7%), but weak sensitivity (52.9%), fair positive (69.2%), and negative (76.5%) predictive value, with Diagnostic Odds Ratio (ORDiagn) 7.3. The assessment of molecular components by ImmunoCAP was unsatisfactory in regards to area under the ROC curve (AUC), sensitivity, and specificity, despite the fair positive and negative values. The micro-assay ISAC method was also unreliable in our setting. We believe that the diagnostic work-up for CMA should consider a molecular-based allergy diagnostic as well as a raw allergen assessment to obtain more useful information for the management and possible identification of risk factors.

Efficacy of baked milk oral immunotherapy in baked milk–reactive allergic patients

Patients with IgE-mediated cow's milk allergy who are nonreactive to baked milk (BM) can be desensitized with BM to promote tolerance to unheated milk (UM). We sought to test whether patients who are BM reactive can progress in BM oral immunotherapy (OIT) and become desensitized to UM as well. Fifteen patients (>4 years) who previously failed to complete our milk OIT program were enrolled into the BM OIT protocol. A dose of BM (180 °C for 30 minutes) which was less than the eliciting dose was increased 50% monthly while under medical supervision until the primary outcome dose of 1.3 g/d BM protein was achieved. Basophil reactivity and milk protein-specific IgE binding were analyzed at the first round of BM OIT therapy (T0) and at 12 months of BM treatment. In terms of the primary outcome, only 3 (21%) of 14 patients tolerated the 1.3 g/d BM dose. Although some patients initially progressed in BM OIT, 8 of 11 failed because of IgE-mediated reactions. Three did not complete the program because of non-IgE-mediated factors. An increase in challenge threshold to UM was noted in patients continuing until 12 months (P = .003), including those among whom reactions precluded continuation in the program. Patients (n = 3) who successfully reached maintenance had decreased milk-specific IgE reactivity. Furthermore, the mean difference at T0 between induced HM and UM percentages of CD203c expression was significantly lower in patients who successfully completed BM OIT than in those who did not (-11% vs 4.4%, P = .0002), which is consistent with their decreased clinical reactivity to BM. Although use of hypoallergenic BM in OIT is a promising therapy, care must be taken before its administration in BM-reactive patients because of the risk for anaphylaxis and only limited increase in challenge threshold attained.

Safety and effectiveness of specific oral tolerance induction to cow's milk

Results In 23 patients we started a standard cluster protocol using unheated CM (UCM) oral ingestion of increasing doses, always in a hospital setting, until reaching the target dose of 200 mL/day. In 2 cases, SOTI was performed with baked milk (BM). Among 23 who started SOTI with UCM, 12 completed the protocol successfully, 7 are still ongoing, 2 were changed to BM and in 3 patients SOTI failed to improve the condition, for a variety of reasons, including unresponsive gastric pain (2) and de novo diagnosis of eosinophilic esophagitis (1). Of the 4 patients who started or were changed to BM, 2 ended the protocol with (complete or partial) success, one is still ongoing and the last one was not able to progress beyond 0.5 mL. In summary, SOTI were completed with success in 14 patients (56%) 12 with UCM and 2 with BM, and failed to improve the condition in 4 cases 3 with UCM and 1 with BM. In 7 patients the protocol is still ongoing 6 with UCM and 1 with BM. There were adverse reactions in 80% of cases, 3 of which with severe reactions (anaphylaxis), always in the induction phase.

Use of baked milk challenges in clinical practice: a worldwide survey

Results Of 113 participants 51(45.1%) were dietitians, 31(27.4%) Paediatric Allergists and Paediatricians, 15(13.3%) Allergists/Clinical Immunologists, 2(1.9%) General Practitioners, and 14(12.4%) other health scientists. 14 (12.7%) of participants reported that they use baked milk challenges to confirm the diagnosis in CMA and 82(73.2%) to determine tolerance to milk. 52(46%) perform baked milk challenges in IgE mediated CMA in hospital, 8(7.1%) suggest home and 33(29.2%) in both places. In non-IgE mediated CMA, 8(7.1%) conduct these challenges in hospital, 51(45.1%) at home and 27 (23.9%) at both places. 17(15%) of responders stated that they use graded introduction of milk containing foods (Milk Ladder) to diagnose CMA and 80(70.8%) to determine tolerance. 19(16.8%) carry out the Milk Ladder in IgE CMA in hospital, 22(19.5%) use it at home and 27(23.9%) in both places. 3(2.7%) perform graded milk introduction in non-IgE mediated CMA in hospital, 56(49.6%) suggest home, and 18(15.9%) in both places.

Sensory profiles and consumer acceptability of a range of sugar-reduced products on the UK market

Current UK intake of non-milk extrinsic sugars (NMES) is above recommendations. Reducing the sugar content of processed high sugar foods through reformulation is one option for reducing consumption of NMES at a population level. However, reformulation can alter the sensory attributes of food products and influence consumer liking. This study evaluated consumer acceptance of a selection of products that are commercially-available in the UK; these included regular and sugar-reduced baked beans, strawberry jam, milk chocolate, cola and cranberry & raspberry juice. Sweeteners were present in the reformulated chocolate (maltitol), cola (aspartame and acesulfame-K) and juice (sucralose) samples. Healthy, non-smoking consumers (n=116; 55 men, 61 women, age: 33±9years; BMI: 25.7±4.6kg/m2) rated the products for overall liking and on liking of appearance, flavor and texture using a nine-point hedonic scale. There were significant differences between standard and reduced sugar products in consumers' overall liking and on liking of each modality (appearance, flavor and texture; all P<0.0001). For overall liking, only the regular beans and cola were significantly more liked than their reformulated counterparts (P<0.0001). Cluster analysis identified three consumer clusters that were representative of different patterns of consumer liking. For the largest cluster (cluster 3: 45%), there was a significant difference in mean liking scores across all products, except jam. Differences in liking were predominantly driven by sweet taste in 2 out of 3 clusters. The current research has demonstrated that a high proportion of consumers prefer conventional products over sugar-reduced products across a wide range of product types (45%) or across selected products (27%), when tasted unbranded, and so there is room for further optimization of commercial reduced sugar products that were evaluated in the current study. Future work should evaluate strategies to facilitate compliance to dietary recommendations on NMES and free sugars, such as the impact of sugar-reduced food exposure on their acceptance.

Increasing Tolerance to Less Extensively Heat-Denatured (baked) Milk Products in Milk-Allergic Children

To determine whether consumption of progressively less heated forms of baked milk products would be an effective form of oral immunotherapy for children with cow’s milk allergy (CMA). CMA-children were challenged with increasing amounts of more allergenic forms of milk (MAFM) at baseline. Tolerated baked foods were incorporated into the diet and challenges repeated at 6-month (6M) or 12-month (12M) intervals with introduction of MAFM into the diet as tolerated. Children avoiding milk were included as controls. 136 children (70% males) were enrolled (median age: 7 years; inter-quartile range, 5-9 years) in the active group. Forty-one (30%) reacted to muffin, 31 (23%) to pizza, 11 (8%) to rice pudding, 43 (32%) to fresh milk; and 10 (7%) tolerated fresh milk. Children who tolerated baked-milk but not unheated-milk were randomized into 6M (n=41) and 12M (n=44) dose escalation. At 36-months, 61% children in 6M and 73% in 12M progressed to tolerating MAFM; 49% in 6M and 39% in 12M tolerated unheated-milk. Unheated-milk tolerance at 36 months was unrelated to the baked food tolerated at baseline (muffin vs pizza vs rice pudding), P=0.27. None of the muffin-reactors became tolerant to unheated-milk; however, 20% progressed to tolerating MAFM; P<0.01 versus randomized subjects. None of the control subjects (n=34) became tolerant to unheated-milk; P<0.01 versus randomized subjects. Baked-milk diet is associated with accelerated acquisition of tolerance to unheated-milk. Among baked milk-tolerant children, introducing MAFM every 6-months compared to every 12-months did not accelerate the progression to tolerating MAFM or unheated- milk at 36 months.