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 .
Clinical course of cow's milk protein allergy/intolerance and atopic diseases in childhood.
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
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 .