The effect of different formulas in children with cow ' s milk allergy on the occurrence of other allergic manifestations and the time of immune tolerance acquisition: The atopic march II study

Background : Recent data suggest that the use of extensively hydrolyzed casein formula containing the probiotic L.rhamnosus GG (LGG) (EHCF+LGG) reduces the incidence of other AMs and hastens the development of immune tolerance in children with IgE- mediated cow ' s milk allergy (CMA). To see whether formula choice for CMA treatment could impact the occurrence of other AMs and the time of immune tolerance acquisition. Method : Prospective open non- randomized trial on a cohort of children with a diagnosis of IgE- mediated CMA in the first year of life, already in follow- up. The patients were treated with one of the following formulas: EHCF+LGG, rice hydrolyzed formula (RHF), soy formula (SF), extensively hydrolyzed whey formula (EHWF) or amino- acid based formula (AAF). All subjects were evaluated during a 36 months follow- up. The occurence of AMs (atopic eczema, allergic urticaria, asthma and oculorhinitis) was diagnosed Immune tolerance acquisition was evaluated every 12 month by the result of oral food challenge. Results : A total of 365 subjects completed the study, 73 per group. All children were from families of middle socio- economic status and lived in urban areas. At enrollment, all subjects were in stable clinical conditions without symptoms related to CMA. Demographic and anamnestic features were similar comparing the study cohorts at enrolment. Binomial regression revealed that the estimates of the incidence of the AMs are: EHCF+LGG: 0.22 (Bonferroni corrected 95%CI: 0.09 to 0.34); RHF: 0.52 (Bonferroni corrected 95%CI: 0.37 to 0.67); SF: 0.58 (Bonferroni corrected 95%CI: 0.43 to 0.72); EHWF : 0.51 (Bonferroni corrected 95%CI: 0.36 to 0.66); AAF: 0.77 (Bonferroni corrected 95%CI: 0.64 to 0.89). The incidence of the main outcome in the RHF, SF, EHWF and AAF groups vs the EHCF+LGG group was always higher than the pre- specified absolute difference of 0.25 and significantly higher at the pre- specified alphalevel of 0.0125 ( P - value <= 0.001 in all cases). The acquisition of immune tolerance was significantly higher in the EHCF+LGG group comparing to the other groups. The rate of immune tolerance acquisition for EHCF+LGG groups was (95%CI): at 12 months = 0.41 (0.30 to 0.52); at 24 months = 0.64 (0.53 to 0.75); at 36 months = 0.81 (0.72 to 0.90). Conclusion : The results of the study suggest that EHCF+LGG is superior to other formulas for the prevention of AMs and for the acquisition of immune tolerance in children with CMA.