Abstract Background Cow’s milk protein allergy (CMPA) is a major health concern; its prevalence is between 1.9% and 4.9% in the first year of life. Tolerance to cow’s milk is tested after at least 6 months of elimination diet through two common approaches which are the milk ladder method and direct milk administration. Aim To compare tolerance frequency between those who had milk products reintroduced via milk ladder to those who were directly exposed to pure milk antigen after 6 months of elimination diet, and to assess the factors affecting the overall tolerance frequency of cow’s milk after 6 months elimination diet. Methods A randomized controlled clinical trial involving 116 children recruited from the Pediatric Gastroenterology Clinic, Children’s Hospital, in Shams University, diagnosed as non-IgE mediated cow’s milk protein allergy proven by elimination re-challenge test and followed six months of elimination diet. The included children were randomly assigned into 2 groups, where one group had milk products reintroduced via 6 steps milk ladder, and the second group had direct milk antigen administration in gradual increments. They were followed up for 2 months after the introduction of milk or milk containing products to confirm resolution of allergy. Results The overall tolerance rate after 6 months elimination diet was 81% with no significant difference between the two approaches (Direct milk 84.5%, and milk ladder 77.6%), in addition, the regression analysis showed that weight was a significant factor influencing the resolution of CMPA patients, with normal weight patients having higher chance of resolution than underweight patients (odds ratio=3.73). Conclusion Non-IgE medicated CMPA has high rate of resolution after 6 months elimination diet. Both approaches of introduction were equivalent.
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