Included studies
Our electronic searches resulted in 2741 records, after removing duplications, screening titles and abstracts, remained 274 records were screened again for eligibility by two reviewers independently. Discrepancies were resolved through discussion. After applying the inclusion and exclusion criteria, we selected 11 studies[11-21] for this meta-analysis (Figure 1). The characteristics of the included studies are summarized in Table 1.
These 11 studies were published between 2007 and 2021, a total of 469 children (242 OIT, 227 control) were included, of which 234 patients (126 OIT, 108 controls) were older than 3 years old, and a subgroup analysis was conducted for these patients. IMCMA was confirmed by a DBPCFC in eight of the studies[12-18, 21], and by a simple-blind placebo-controlled food challenge in two studies[11, 20]. But in the study of Esmaeilzadeh et al[19], IMCMA was diagnosed by a history of immediate onset of symptoms after ingesting cow’s milk and positive SPT and/or IgE antibodies to cow milk. Eight studies used continued elimination diet as a control[11, 12, 15, 17-21], whereas the other two studies used a placebo control[13, 16], and Pajno et al used soy milk as a control. Most of the included studies used raw cow milk for OIT, but Esmaeilzadeh et al,used baked milk for OIT and Takahashi et al combined OIT with OMB as the treatment group. The efficacy of desensitization was evaluated by identifying the maximum tolerated dose of milk in the individual studies, as follows: 240ml[19]; 200 mL[11, 14-18, 20]; 150 mL[12]; 100ml[21] and 500 mg[13]. Four studies included patients younger than three years old[11, 15, 17-18], and two studies included only children with a history of severe anaphylaxis to milk[12, 18], while other three studies excluded such patients[13, 15, 21], and the rest studies included patients with any degree of reaction. The OIT protocol was different in each study, most of them involved a build-up phase in an institution (hospital, clinic, or research center) followed by periodic up-dosing (either in a clinic or at home) and maintenance at home, but Salmivesi et al conducted OIT trial in the outpatient clinic, and Takahashi et al didn’t illustrate this point.