Introduction: Cow’s milk allergy (CMA) is a common diagnosis in infants, requiring the exclusion of cow’s milk until tolerance is recovered. In the present study, we aim to determine which factors are associated with the development of tolerance. Methods: Retrospective, observational study of subjects who underwent the same clinical follow-up methodology. We studied 245 cases of CMA (125 IgE-mediated and 120 non-IgE-mediated). The following variables were analysed: age at diagnosis, gender, type of delivery, type of feeding received, feeding during the first months of life, clinical features, and type of feed received as treatment: casein hydrolysates or casein hydrolysates with Lactobacillus rhamnosus GG (LGG). Results: Factors associated with earlier tolerance were non-IgE-mediated CMA (HR = 2.92; 95% CI: 2.20–3.88) and patients receiving casein hydrolysate with LGG (HR = 1.79; 95% CI: 1.33–2.42). Later tolerance was associated with caesarean delivery (HR = 0.78; 95% CI: 0.58–1.05) and breastfeeding for a period of at least 3 days (HR = 0.64; 95% CI: 0.44–0.93). The multivariate study shows that the type of formula (HR = 1.61; 95% CI: 1.19–2.18) and the type of CMA (HR = 2.82; 95% CI: 2.12–3.85) have an effect on the recovery time. Casein hydrolysates with LGG reduces the recovery time in IgE-mediated (HR = 1.88; 95% CI: 1.17–3.01) and non-IgE-mediated CMA (HR = 1.46; 95% CI: 0.98–2.17). Conclusions: Tolerance acquisition is faster in non-IgE-mediated CMA subjects and in those who received casein hydrolysate with LGG.

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