The Efficacy and Safety of Stepwise Oral Food Challenge in Children with Cow’s Milk Allergy.

\n<bold><italic>Introduction:</italic></bold> Stepwise oral food challenge (OFC) tests begin with low doses of allergens and progress to full doses. We previously reported the safety and efficacy of stepwise OFC for reintroducing hen eggs. In this study, we discuss its application for cow’s milk (CM) allergy. <bold><italic>Methods:</italic></bold> We included 927 children (median age, 3.2 years) who underwent CM-OFC between 2017 and 2021. The target challenge dose was classified as low (<10 mL), middle (≥10 mL but <100 mL), or full. When participants reacted to the low dose, they underwent a very low-dose OFC using baked milk or <1 mL of CM. <bold><italic>Results:</italic></bold> Positive reactions occurred in 210 cases (22.7%), including 69 anaphylactic reactions (7.4%). A lower target dose resulted in more positive OFC results (<italic>p</italic> < 0.001) and anaphylaxis (<italic>p</italic> = 0.001). The lower dose group included more children with complete elimination of CM (<italic>p</italic> < 0.001), with numerous histories of anaphylaxis induced by CM (<italic>p</italic> < 0.001), and higher levels of total IgE (<italic>p</italic> = 0.033) and CM-sIgE (<italic>p</italic> < 0.001). A multivariate analysis indicated that in the low-dose-OFC group, higher CM-sIgE levels (<italic>p</italic> = 0.034), younger age (<italic>p</italic> = 0.005), and complete elimination of CM (<italic>p</italic> = 0.002) were associated with positive OFC results. <bold><italic>Conclusion:</italic></bold> The stepwise OFC could reintroduce small amounts of CM, even in cases with high CM-sIgE levels or a history of anaphylaxis. Performing CM-OFC at younger ages, specifically from infancy, with very low doses, might facilitate the safe reintroduction of CM. Stepwise oral food challenge (OFC) tests begin with low doses of allergens, progressing to full doses. This is one of the strategies used to avoid anaphylactic reactions to the reintroduction of allergens. We previously reported the safety and efficacy of hen egg OFC. In this study, we discuss it for cow’s milk (CM) allergy. We included 927 children (median age, 3.2 years) who underwent CM-OFC between 2017 and 2021. The target challenge dose was classified as low (<10 mL), middle (≥10 mL but <100 mL), or full. When the participants reacted to low doses, they underwent very low-dose OFC using baked milk or <1 mL of CM. Positive reactions developed in 210 cases (22.7%), including 69 anaphylactic reactions (7.4%). A lower target dose resulted in more positive OFC results and anaphylaxis. Multivariate analysis indicated that only in low-dose OFCs, higher CM-specific IgE (CM-sIgE) levels, younger age, and complete CM elimination were associated with positive OFC results. Food ladders, an approach to reintroduce allergens, are becoming increasingly popular. Although we believe that OFC is a safer strategy to reintroduce CM to children with CM allergy, our CM-OFCs appeared to develop more anaphylactic reactions than milk ladders. The stepwise OFC reintroduced small amounts of CM, even in cases with high CM-sIgE levels or a history of anaphylaxis. Performing CM-OFC at a younger age, preferably from infancy, with very low doses, similar to milk ladders, may facilitate the safe reintroduction of CM. [ABSTRACT FROM AUTHOR]