An extensively hydrolysed casein-based formula for infants with cows' milk protein allergy: tolerance/hypo-allergenicity and growth catch-up. The prevalence and natural course of food protein-induced enterocolitis syndrome to cow's milk: a large-scale, prospective population-based study. Safety and efficacy of a new extensively hydrolyzed formula for infants with cow's milk protein allergy. Markers of gut mucosal inflammation and cow’s milk specific immunoglobulins in non-IgE cow’s milk allergy Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy. The acquisition of tolerance toward cow's milk through probiotic supplementation: a randomized, controlled trial. Allergenicity of goat's milk in children with cow's milk allergy. Specific oral tolerance induction in children with very severe cow's milk-induced reactions. Clinical course of cow's milk protein allergy/intolerance and atopic diseases in childhood. Hypoallergenicity and efficacy of an amino acid-based formula in children with cow's milk and multiple food hypersensitivities. Breast-feeding and the development of cows' milk protein allergy. Importance of the first meal on the development of cow's milk allergy and intolerance. Synbiotics in Children with Cow's Milk Allergy: A Randomized Controlled Trial A Prospective Study of Cow's Milk Allergy in Exclusively Breast‐Fed Infants [Incidence and symptoms of cow's milk protein intolerance following acute gastroenteritis in young infants. Effect of a hypoallergenic diet]. Specific IgE levels in the diagnosis of immediate hypersensitivity to cows' milk protein in the infant. Specific antibodies to cow’s milk proteins in infants: effect of early feeding and diagnosis of cow’s milk allergy
Children with cows ' milk protein allergy ( CMPA ) are at risk of insufficient length and weight gain , and the nutritional efficacy of hypo-allergenic formulas should be carefully assessed . In 2008 , a trial assessed the impact of probiotic supplementation of an extensively hydrolysed casein-based formula ( eHCF ) on acquisition of tolerance in 119 infants with CMPA . First analysis of the study results showed that the studied formula allowed improvement of food-related symptoms . The scoring of atopic dermatitis ( SCORAD ) index was assessed at r and omisation and after 6 months of feeding . A post hoc analysis was performed using WHO growth software 's nutritional survey module ( WHO Anthro version 3.2.2 ) . All infants who were fed the study formula tolerated it well . The SCORAD index significantly improved from r and omisation to 6 months of feeding with the study formula . Anthropometric data indicated a significant improvement in the weight-for-age , length-for-age and weight-for-length z scores , as well as in the restoration of normal BMI . The probiotic supplementation did not show any impact on these parameters . The present data showed that this eHCF was clinical ly tolerated and significantly improved the SCORAD index and growth indices BACKGROUND The prevalence and natural history for food protein-induced enterocolitis syndrome ( FPIES ) have not been determined . OBJECTIVE We sought to determine the prevalence , clinical manifestations , and rate of recovery for FPIES in a large-scale , population -based prospect i ve study . METHODS In a prospect i ve study the feeding history of 13,019 infants was obtained . Infants with probable adverse reactions to cow 's milk protein ( CMP )  were clinical ly examined , skin prick tested , and challenged orally . Diagnostic criteria for CMP-induced FPIES included age less than 9 months , delayed recurrent vomiting ( usually with nausea ) , and lethargy after exposure to CMP in the absence of other IgE-mediated symptoms , such as rash , urticaria , and respiratory symptoms . In addition , a positive challenge response to milk result ed in the above-mentioned gastrointestinal symptoms , removal of milk from the diet result ed in the resolution of those symptoms , or both . RESULTS Ninety-eight percent of the cohort participated in the study . The cumulative incidence for FPIES was 0.34 % ( 44/13,019 patients ) . The most common symptoms were recurrent vomiting ( 100 % ) , lethargy ( 77 % ) diarrhea ( 25 % ) , pallor ( 14 % ) , and bloody diarrhea ( 4.5 % ) . All patients had FPIES  within the first 6 months of life . By the age of 3 years , 90 % of the patients had recovered . We did not detect any concomitant reaction to soy . Eight patients with FPIES had IgE-mediated cow 's milk allergy ( IgE-CMA ) . CONCLUSIONS The prevalence of FPIES is significant , and its clinical presentation is distinct from that of IgE-CMA . Most patients with FPIES recover , although a proportion might convert to IgE-CMA . The likelihood for a cross-reactivity to soy in this population was less than previously estimated Cow 's milk protein allergy ( CMPA ) is best treated by complete elimination of cow 's milk from the diet . For infants with CMPA who can not be breast-fed , formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow 's milk-based formulas . In this study , we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose ( eHF ) with those who were fed an amino acid formula ( AAF ) . This was a prospect i ve , multi-center , r and omized , reference-controlled study . Seventy-seven infants < 12 months old with suspected CMPA were enrolled . In 66 of these , CMPA was confirmed by oral challenge in a double-blind , placebo-controlled food challenge ( DBPCFC ) or by a medical history of severe allergic reaction to cow 's milk and a positive skin prick test . These infants were then tested for their reaction to eHF and AAF in a DBPCFC . All infants tolerated both formulas and were r and omized to receive either eHF ( n = 34 ) or AAF ( n = 32 ) for 180 days . Growth ( weight , length , and head circumference ) and tolerance [ skin , gastro-intestinal , and respiratory tract symptoms of allergy ] were evaluated after 30 , 60 , 90 , and 180 days . There were no significant differences between the two groups in any of the growth measurements . Length and head circumference were similar to Euro-growth st and ards , but weight was slightly lower . Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups . However , whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF , there was a slight decrease in those fed AAF . Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools . The new eHF is safe and well tolerated in infants diagnosed with CMPA Background Allergy to cow ’s milk protein ( CMP ) may cause gastrointestinal ( GI ) symptoms in the absence of CMP specific IgE. The immunological mechanisms involved in such disease are not fully understood . Therefore we examined markers of gut mucosal inflammation and the immunoglobulin profiles in children with Gl symptoms suspected of cow ’s milk protein allergy ( CMPA ) . Patients and methods We prospect ively recruited infants and young children ( n = 57 ; median age 8.7 months ) with gastrointestinal complaints suspected of CMPA . The diagnosis of CMPA was made using the double-blind , placebo-controlled food challenge . Serum and stool sample s were collected during CMP-free diet and after both placebo and active challenges . We analyzed the stool sample s for calprotectin , human β-defensin 2 and IgA. In serum , we analyzed the levels of β-lactoglobulin and α-casein specific IgA , and IgG antibodies ( total IgG and subclasses IgG1 and IgG4 ) . Control group included children with e.g. dermatological or pulmonary problems , consuming normal diets .  Results Fecal calprotectin levels were higher in the challenge positive group ( n = 18 ) than in the negative ( n = 37 ) , with respective geometric means 55 μg/g [ 95 % confidence interval 38–81 ] and 29 [ 24–36 ] μg/g ( p = 0.0039 ) , during cow ’s milk free diet . There were no significant inter-group differences in the fecal β-defensin and IgA levels . The CMP specific IgG and IgA were not elevated in patients with CMPA , but the levels of β-lactoglobulin-IgG4 ( p = 0.0118 ) and α-casein-IgG4 ( p = 0.0044 ) , and total α-casein-IgG ( p = 0.0054 ) and -IgA ( p = 0.0050 ) in all patient sample s ( regardless of CMPA diagnosis ) were significantly lower compared to the control group using dairy products . Conclusions Despite cow ’s milk elimination in children intolerant to cow ’s milk there might be ongoing low- grade inflammation in the gut mucosa . CMP specific IgG or IgA should not be used to diagnose non-IgE CMPA . The observed frequency of impaired CMP specific total IgA , IgG and IgG4 production in patients following cow ’s milk free diet warrants further studies BACKGROUND The diversity in the perceived prevalence , recovery , and risk factors for cow 's milk allergy ( CMA ) necessitated a large-scale , population -based prospect i ve study . OBJECTIVE We sought to determine the prevalence , cross-reactivity with soy allergy , and risk factors for the development of CMA . METHODS In a prospect i ve study the feeding history of 13,019 infants was obtained by means of telephone interview ( 95.8 % ) or question naire ( 4.2 % ) . Infants with probable adverse reactions to milk were examined , skin prick tested , and challenged orally . RESULTS Ninety-eight percent of the cohort participated in the study . The cumulative incidence for IgE-mediated CMA was 0.5 % ( 66/13,019 patients ) . The mean age of cow 's milk protein ( CMP ) introduction was significantly different ( P < .001 ) between the healthy infants ( 61.6 + /- 92.5 days ) and those with IgE-mediated CMA ( 116.1 + /- 64.9 days ) . Only 0.05 % of the infants who were started on regular CMP formula within the first 14 days versus 1.75 % who were started on formula between the ages of 105 and 194 days had IgE-mediated CMA ( P < .001 ) . The odds ratio was 19.3 ( 95 % CI , 6.0 - 62.1 ) for development of IgE-mediated CMA among infants with exposure to CMP at the age of 15 days or more ( P < .001 ) . Sixty-four patients with IgE-mediated CMA tolerated soy , and none had a proved allergy to soy . CONCLUSIONS IgE-mediated CMA is much less common than generally reported . Early exposure to CMP as a supplement to breast-feeding might promote tolerance . Finally , soy is a reasonable feeding alternative in patients with IgE-mediated CMA BACKGROUND Cow 's milk allergy ( CMA ) is the most frequently diagnosed food allergy in infancy . In general , patients have a good prognosis because the majority acquire tolerance within the first years . Interventions have been proposed to accelerate tolerance and reduce morbidity . Probiotic supplementation could be effective through modulation of the immune system . OBJECTIVE We sought to determine whether supplementation with a combination of probiotics ( Lactobacillus casei CRL431 and Bifidobacterium lactis Bb-12 ) accelerates tolerance to cow 's milk ( CM ) in infants with CMA . METHODS We performed a double-blind , r and omized , placebo-controlled trial in 119 infants with CMA . Infants received CRL431 and Bb-12 supplemented to their st and ard treatment of extensively hydrolyzed formula for 12 months . Primary outcome was clinical tolerance to CM at 6 and 12 months of treatment . Furthermore , we analyzed T- and B-lymphocyte subsets ( CD3(+ ) , CD3(+)CD4(+ ) , CD3(+)CD8(+ ) , and CD20(+ ) ) in peripheral blood at r and omization and at 12 months with flow cytometry and examined the presence of viable probiotic strains in fecal sample s. RESULTS The cumulative percentage of tolerance to CM at 6 and 12 months was similar in both groups : 56 ( 77 % ) in the probiotics group versus 54 ( 81 % ) in the placebo group . Infants in the placebo group had higher percentages of CD3(+ ) and CD3(+)CD4(+ ) lymphocytes compared with those seen in probiotic-treated infants . Probiotic intake was confirmed because probiotics were isolated from feces more often in treated infants than in the placebo group . CONCLUSION Supplementation of CRL431 and Bb-12 to extensively hydrolyzed formula does not accelerate CM tolerance in infants with CMA BACKGROUND Cow 's milk allergy ( CMA ) is a common disease of infancy and childhood . An appropriate cow 's milk ( CM ) substitute is necessary for feeding babies with CMA .  CM substitutes are soy formulas and casein- or whey-based extensively hydrolyzed formulas . In several countries , including Italy , goat 's milk ( GM ) formulas are available , and some physicians recommend them for feeding babies with CMA . OBJECTIVE We sought to investigate , in vitro and in vivo , the allergenicity of GM in 26 children with proven IgE-mediated CMA . METHODS All the children underwent skin tests with CM and GM ; detection of specific serum IgE to CM and GM ; and double-blind , placebo-controlled , oral food challenges ( DBPCOFCs ) with fresh CM , GM , and , as placebo , a soy formula ( Isomil , Abbott , Italy ) . CAP inhibition and immunoblotting inhibition assays were also carried out in 1 of 26 and 4 of 26 children with positive RAST results to both CM and GM , respectively . RESULTS All the children had positive skin test responses and CAP results to both CM and GM , all had positive DBPCOFC results to CM , and 24 of 26 had positive DBPCOFCs to GM . In CAP inhibition tests , preincubation of serum with CM or GM strongly inhibited IgE either to CM or to GM . In immunoblotting inhibition assays , preincubation with CM completely extinguished reactivity to GM , whereas GM partially inhibited reactivity to CM . CONCLUSIONS These data strongly indicate that GM is not an appropriate CM substitute for children with IgE-mediated CMA . A warning on the lack of safety of GM for children with CMA should be on the label of GM formulas to prevent severe allergic reactions in babies with CMA BACKGROUND Some children allergic to cow 's milk proteins ( CMPs ) experience exceptionally severe reactions after ingesting only trace amounts of antigen . Avoiding the food and carrying self-injectable epinephrine are the current strategies for their management . OBJECTIVE The aim of this study was to evaluate the safety and efficacy of specific oral tolerance induction ( SOTI ) for children with severe CMP-induced systemic reactions . METHODS Ninety-seven children aged 5 years or older with a history of severe allergic reactions and very high CMP-specific IgE levels were selected for a double-blind , placebo-controlled food challenge .  Sixty had positive test results to very small amounts of milk and were r and omly divided in 2 different groups . Thirty children ( group A ) immediately began SOTI , whereas the remaining 30 ( group B ) were kept on a milk-free diet and followed for 1 year . RESULTS After 1 year , 11 ( 36 % ) of 30 children in group A had become completely tolerant , 16 ( 54 % ) could take limited amounts of milk ( 5 - 150 mL ) , and 3 ( 10 % ) were not able to complete the protocol because of persistent respiratory or abdominal complaints . In group B the result of the double-blind , placebo-controlled food challenge performed after a year was positive in all 30 cases ( P < .001 ) . CONCLUSIONS In this study SOTI was effective in a significant percentage of cases A cohort of 1,749 newborns from the municipality of Odense , born during 1995 at the Odense University Hospital , were followed up prospect ively for the development of cow 's milk protein allergy/intolerance ( CMPA/I ) during the first year of life . Once a diagnosis of CMPA/I was confirmed , a milk-free diet was continued until a new milk challenge had shown development of tolerance . All infants with CMPA/I were rechallenged at 12 months of age and , in the event of continued clinical sensitivity to cow 's milk protein , controlled rechallenges were performed every 6 months up to 3 years of age ; and thereafter every 12 months until the age of 15 years . From the same birth cohort , 276 infants were r and omly selected at birth for prospect i ve non-interventional follow-up in order to investigate the natural course of sensitization and development of atopic disease during childhood . St and ardized question naires on atopic heredity , environmental factors and presence of atopic symptoms were answered at 0 , 6 , 12 and 18 months and at 5 , 10 and 15 years of age . Interviews on atopic history and environmental factors as well as physical examination were carried out at 18 months , 5 , 10 and 15 years of age . Skin prick test and specific sIgE ( Pharmacia CAP ) testing were performed at 18 months , 5 , 10 and 15 years of age against a panel of inhalant allergens ( birch , grass , mugwort , dog , cat , horse , Dermatophagoidespteronyssinus , Dermatophagoides farinae , alternaria and cladosporium herbarum ) . Furthermore , lung function measurements were performed in children when 10 and 15 years of age . Based on controlled milk elimination and challenge procedures , the diagnosis of CMPA/I was confirmed in 39 out of 117 infants , with symptoms suggestive of CMPA/I , thus result ing in a 1-year incidence of CMPA/I of 2.2 % . The overall prognosis of CMPA/I was good , with a total recovery of 56 % at 1 year , 77 % at 2 years , 87 % at 3 years , 92 % at 5 and 10 years and 97 % at 15 years of age . In children younger than 10 years of age , 41 % developed asthma and 31 % rhinoconjunctivitis . Children with non-IgE-mediated CMPI had a good prognosis , whereas children with IgE-mediated CMPA in early childhood had a significantly increased risk for persistent CMPA , development of other food allergies , asthma and rhinoconjunctivitis . During early infancy , recurrent wheezing was the most prevalent disease ( 20 % ) , followed by atopic dermatitis ( 14 % ) and food allergy ( 7 % ) at 18 months of age . Physician diagnosed asthma increased from 2 % at 1.5 years of age to 9 % at 10 years of age .  Rhinoconjunctivitis  increased from < 1 % at 1.5 years of age to 9 % at 10 years of age . Overall , the current prevalence of any atopic disease was 20 % at 1.5 years of age , declining to 14 % at 5 years of age and followed by an increase to 25 % at 10 years of age . Sensitization to inhalant and /or food allergens ( specific IgE of > or = class 2 ; CAP RAST ) showed a low rate of sensitization among asymptomatics ( 3 % , 10 % and 12 % ) compared with higher rates of sensitization of 8 % , 39 % and 30 % among symptomatic atopics at 1.5 , 5 and 10 years of age respectively . The highest rate of sensitization ( 53 % ) was found among children with current asthma at 10 years of age OBJECTIVE To determine the hypoallergenicity and efficacy of a pediatric amino acid-based formula ( AAF ) , EleCare , for children with cow 's milk allergy ( CMA ) and multiple food allergies ( MFA ) . STUDY DESIGN Hypoallergenicity was determined by performing blinded oral food challenges in 31 consecutive children with documented CMA .  Growth , tolerance , and biochemical response were evaluated during a nonr and omized feeding study with each child serving as his or her own control . RESULTS Thirty-one children ( median age , 23.3 months ; range , 6 months to 17.5 years ) were recruited ; 29 had MFA , 17 had acute reactions and cow 's milk-specific IgE antibody , and 14 had allergic eosinophilic gastroenteritis . At study entry , 23 were receiving another AAF ;  13 had not tolerated extensively hydrolyzed formula .  Eighteen subjects with allergic eosinophilic gastroenteritis and /or MFA were followed up while receiving AAF for a median of 21 months ( range , 7 to 40 months ) , with biochemical analysis performed at 4 months . No statistically significant differences were observed in the change in weight or height National Center for Health Statistics z scores from entry ; the percent of expected growth exceeded 90 % . There was a small decline in percent eosinophils and increase in hemoglobin , hematocrit , and serum ferritin level ( P < .05 ) . Except for small increases in plasma leucine and valine levels ( P < or = .006 ) , the remaining biochemical markers were unchanged . CONCLUSIONS The AAF was hypoallergenic and effective in maintaining normal growth for children with CMA and MFA Early feeding with cows ' milk ( CM ) may cause cows ' milk allergy ( CMA )  . Breast milk contains many immune factors which compensate for the undeveloped defence mechanisms of the gut of the newborn infant . We studied the effect of supplementary CM feeding at the maternity hospital on the subsequent incidence of CMA , the effects of formula and breast feeding on the subsequent immunologic types of CMA , and the importance of immune factors present in colostrum in the immune responses of infants with CMA . In a cohort of 6209 infants , 824 were exclusively breast-fed and 87 % required supplementary milk while in the maternity hospital : 1789 received CM formula , 1859 pasteurized human milk , and 1737 whey hydrolysate formula . The cumulative incidence of CMA , verified by a CM elimination-challenge test , was 2.4 % in the CM , 1.7 % in the pasteurized human milk and 1.5 % in the whey hydrolysate group . Among these infants , exposure to CM at hospital and a positive atopic heredity increased the risk of CMA . Of the exclusively breast-fed infants , 2.1 % had CMA . Risk factors for the development of IgE-mediated CMA were : exposure to CM at hospital , breast-feeding during the first 8 weeks at home either exclusively or combined with infrequent exposure to small amounts of CM and long breast-feeding . The content of transforming growth factor-beta1 ( TGF-beta1 ) in colostrum from mothers of infants with IgE-mediated CMA was lower than from mothers of infants with non-IgE-mediated CMA . In infants with CMA , TGF-beta1 in colostrum negatively correlated with the result of skin prick test and the stimulation of peripheral blood mononuclear cells to CM , but positively with infants ' IgA and IgG antibodies to CM proteins . Feeding of CM formula at maternity hospital increases the risk of CMA , but exclusive breast-feeding does not eliminate the risk . Prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of CM during the first 8 weeks induces the development of IgE-mediated CMA . Colostral TGF-beta1 may inhibit IgE- and cell mediated reactions and promote IgG-IgA antibody production to CM in infants prone to developing CMA A cohort of 1749 newborns from the municipality of Odense born during 1985 in the University Hospital of Odense were followed prospect ively for the development of cow 's milk allergy (CMA)/cow 's milk protein intolerance ( CMI ) during their first year . The diagnosis of CMA/CMI was based on elimination/open milk challenge procedures according to generally accepted criteria . Thirty nine infants ( 2.2 % ) developed CMA/CMI .  Infants with CMA/CMI were fed cow 's milk formula daily during the first month of life significantly more often than infants in the study population ( p less than .001 ) . All 39 infants with CMA/CMI had ingested cow 's milk formula ( 40 - 830 mL ) neonatally , whereas none of the 210 neonates without supplements of cow 's milk formula  developed CMA/CMI ( p less than .05 ) . Based on a positive skin-prick test ( 2 + or more ) and /or specific serum IgE antibody to cow 's milk ( AL-RAST class 2 or more ) 16 infants were classified as having CMA . In infants solely breast-fed for greater than 1 month CMA was as frequent ( 1 % [ 14/1414 ] as in cow 's milk formula fed infant ( 0.6 % [ 2/335 ] ) . In infants with CMI , a significant majority ( 3.9 % [ 13/335 ] versus 0.7 % [ 10/1414 ] , p less than .001 ) had been cow 's milk formula fed during the first month . These data indicate an association between early cow 's milk formula feeding and development of reproducible adverse reactions to cow 's milk protein . Early neonatal intake of cow 's milk protein is probably a condition of sensitization and later adverse reactions to cow 's milk protein Objective : Cow`s milk protein allergy usually occurs in infants within the first months of life . It can affect several organs , but gastrointestinal symptoms are the most clinical symptoms observed . The most effective treatment is restricting the cow ` s milk protein in mother and infant`s diet . Lactobacillus GG supplementation in infant could be effective through modulation of the immune system and the gut microflora . Methods : Thirty two breastfed infants with cow`s milk protein allergy were enrolled in a double-blinded r and omized controlled trial in which they received Synbiotic ( n=16 ) or placebo ( n=16 ) once a day for one month , simultaneously with cow`s milk protein restriction in mother and infant`s diet . Clinical gastrointestinal symptoms ( vomiting , colic , rectal bleeding and diarrhea ) , head circumference , body length and weight were recorded at the beginning , the end of the first and third month of study . Findings : Percentage of increment in head circumference and weight were statistically more in synbiotic group compared with placebo group at the end of the first and third month of study . There was no significant difference in resolution of clinical gastrointestinal symptoms ( vomiting , colic , rectal bleeding or diarrhea ) and percentage of increment in body length . Conclusion : Synbiotic supplementation in infants may improve increment of head circumference and weight gain , but has no effect on resolution of clinical symptoms ABSTRACT . A cohort of 1749 newborns in the municipality of Odense were followed prospect ively for the development of  cow 's milk allergy ( CMA )  during their first year of life . Altogether 39 fulfilled the criteria for CMA ( 2.2 % ) . Out of the 39 infants , 17 developed symptoms of CMA during breast‐feeding , in all cases before the age of 3 months . Nine of these were solely breast‐fed at the time of diagnosis , giving a one year incidence of CMA in exclusively breastfed infants of 0.5 % ( 9/1 749 ) in a study population with a frequency of exclusive breast‐feeding of 52 % at 3 months of age . None of the infants had signs of CMA in the neonatal period . Review of records from the newborn nursery revealed that all 9 infants had been exposed to cow 's milk formula in amounts corresponding to approximately 0.4‐3.0 g of Beta‐lactoglobulin ( BLG ) during the first three days of life . Human milk sample s were analyzed by enzyme‐linked immunosorbent assay ( ELISA ) for the content of bovine BLG . Detectable amounts ( 0.5–45 ng/ml ) were found in 3/9 sample s of human milk against which the infants reacted clinical ly . Analysis of the size distribution by high pressure liquid gel permeation chromatography in combination with ELISA indicated a molecular weight of BLG corresponding to that of monomeric BLG ( 18 kD ) . Possibly early inadvertent and occasional exposure to cow 's milk proteins may initiate sensitization in predisposed neonates . Subsequent exposure to minute amounts of bovine milk proteins in human milk may act as booster doses eliciting allergic reactions In a prospect i ve r and omized study we investigated in 28 mainly bottle-fed infants younger than 60 days whether in acute gastroenteritis a hypoallergenic formula could prevent the development of cow 's milk protein intolerance . Group 1 ( 14 infants ) was fed with a formula adapted to human milk , Group 2 ( 14 infants ) got a semi-elementary formula ( Alfaré ) . After 3 months group II was exposed to cow 's milk protein with a st and ardized challenge and the incidence of CMPI in both groups was calculated . All cases with the acute form of CMPI occurred in group II ( 5/12 ) whereas in group I only one infant suffered from the protracted mild form of the disease . Inspite of the relatively small number of prob and s we conclude from our results that in infants who are not totally breast-fed in the post-enteritic period feeding with a formula adapted to human milk is preferable to hypoallergenic semi-elementary preparations . An allergen free period of 3 months seems to induce symptoms of cow 's milk intolerance , probably as a booster-effect to early sensibilisation BACKGROUND A milk-free diet with substitute formula should be established when immediate symptomatic hypersensitivity to cows ' milk protein ( CMP ) is diagnosed , and therefore an accurate diagnosis is very important . OBJECTIVE This study aims to find the optimal cutoff values for specific IgE antibody levels that discriminate between allergic and tolerant infants by using cows ' milk and its principal proteins as allergens . METHODS A prospect i ve study was carried out on 170 patients under 1 year old ( mean , 4.8 months ) . These patients were seen consecutively over a 4-year period in our outpatient clinic and for the first time because of a reaction suggesting immediate hypersensitivity after ingestion of cows ' milk formula . A clinical history , prick test with cows ' milk and its proteins ( alpha-lact-albumin , beta-lactoglobulin , and casein ) , determination of specific IgE antibodies with the CAP system FEIA for the same allergens as for the prick test , and a challenge test according to the diagnostic protocol were performed in all of the children . A study of validity of the prick test ( cutoff point , 3 mm ) and CAP system by using different cutoff points in the specific IgE values for cows ' milk and its proteins were also analyzed . RESULTS Prevalence of immediate symptomatic hypersensitivity to CMP in this study was 44 % . When both the whole milk and its principal milk proteins were used in the prick test , the negative predictive value was very high , and a negative value excluded allergy in 97 % of the patients . When the different cutoff points of the specific IgE for milk were analyzed , 2.5 KU(A)/L had a positive predictive value of 90 % and 5 KU(A)/L had a positive predictive value of 95 % . CONCLUSIONS When diagnosing immediate hypersensitivity to CMP in infants , negative skin test responses exclude allergy in most of the patients . If the prick test response is positive , specific IgE levels for cows ' milk may be helpful . If these values are 2.5 KU(A)/L or greater , the challenge test should not be performed because of its high positive predictive value ( 90 % ) Purpose To investigate whether specific IgA , IgG , IgG1 and IgG4 responses to cow ’s milk proteins differ between infants with cow ’s milk allergy and infants with cow ’s milk related symptoms ( control subjects ) , and whether early feeding affects these responses as well as specific IgE. Methods A cohort of 6,209 healthy , full-term infants in a double-blind r and omized trial received , as supplementary feeding at maternity hospitals ( mean duration 4 days ) , either cow ’s milk formula , extensively hydrolyzed whey formula or donor breast milk .  Infants who developed cow ’s milk associated symptoms ( n = 223 ) underwent an open oral cow ’s milk challenge ( mean age 7 months ) , which confirmed cow ’s milk allergy in 111 and was negative in 112 . We measured in sera cow ’s milk specific IgE levels with UniCAP ( Phadia , Uppsala , Sweden ) , and β-lactoglobulin and α-casein specific IgA , IgG1 , IgG4 and IgG levels with enzyme-linked immunosorbent assay . Results Infants with IgE-mediated cow ’s milk allergy had lower β-lactoglobulin and α-casein specific IgG1 , IgG4 and IgG levels ( p < 0.05 ) than infants with non-IgE-mediated cow ’s milk allergy or control subjects . Within the group of infants with cow ’s milk allergy , exposure to cow ’s milk during the first few days after birth led to higher β-lactoglobulin and α-casein specific IgG4 levels ( p < 0.005 ) compared to infants fed with either breast milk or extensively hydrolyzed formula . Conclusions Subdued IgG class responses to cow ’s milk proteins characterized IgE-mediated cow ’s milk allergy . In infants who developed cow ’s milk allergy early exposure to cow ’s milk result ed in a heightened specific IgG4 response
Conclusion : Limited low- quality evidence indicates that probiotic supplementation may be associated with earlier acquisition of tolerance to CMP in children with CMPA .
CMPA is associated with significant socioeconomic burden.• Elimination diet and extensively hydrolyzed formula is the mainstay of the management of CMPA.What is New:• This first systematic review of r and omized controlled trials shows that probiotics as an adjuvant can lead to earlier acquisition of tolerance to CMP  in children at 36 months of age .
However , the evidence is low quality and influenced by data from one large study .• Probiotic supplementation was not associated with earlier resolution of hematochezia
Cow ’s milk protein allergy ( CMPA ) is the commonest food allergy in infancy and is associated with significant health burden .
Given their immune modulatory properties , probiotics have been proposed as a strategy for management of CMPA .
We aim ed to systematic ally review efficacy and safety of probiotics in the management of CMPA .
Large well- design ed trials are essential to confirm these findings .What is Known:• Cow ’s milk protein allergy ( CMPA ) is one of the commonest food allergies in children .