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.