3 | Results
Our search strategy generated 3949 citations from 2 databases. 3773
articles were removed after exclusion of duplicates and screening of
titles and abstracts. Of the remaining 176 studies, 163 studies were
excluded after reviewing the full text. In total, 13 articles including
260,029 participants met the inclusion criteria and were included in the
meta-analysis.11,24-35 The flow diagram of trial
identification and selection is shown in fig 1. Descriptions and
baseline characteristics of included studies are detailed in Table 1. No
problems were encountered with participant data deficiency during the
data integrity check.
Two cohorts were conducted in Americas, five in Europe and two in Asia.
Two Cross-sectional studies were conducted in Europe, one was in Asia
and one in America. One cohort study was conducted in Africa. None of
the included studies were at low risk of bias (rated A) as all trials
had an element of pragmatism in using different methods. Nine included
studies, including 87% participants, were deemed to be at moderate risk
of bias (rated B). We judged four studies including only 13%
participants to have high risk of bias (rated C) in the field of study
participation or statistical reporting.
3.1 | Association of BCG Vaccination in Childhood
with Incidence of Allergic Disease
In the pooled analysis, we found that participants received BCG in
childhood associated with a lower risk of allergic disease than that of
non-BCG group (OR=0.86, 95%CI 0.75 to 0.97; fig 2).
12 studies involving 139035 participants reported the relationship
between BCG vaccination and the risk of asthma. Compared with non-BCG
group, received BCG in early childhood was associated with a
significantly reduced risk of asthma (OR=0.74, 95%CI 0.61 to 0.91; fig
2).
8 studies including 58,825 participants reported the association between
rhinitis and BCG vaccine and 9 studies including 61,109 participants
studied eczema and BCG vaccine. Compared with the control group, use of
BCG vaccine showed no significant effect in preventing eczema and
rhinitis (OR=0.87 and 1.03, 95%CI 0.68 to 1.11 and 0.87 to1.22,
respectively; fig 2).
3.2 | Association between BCG Vaccination and
Demographics Factors on the Risk of Allergic
Disease
We evaluated the association between BCG vaccination and participants
demographics on the preventative effect of allergic disease.
Participants from Europe and America were associated with a
significantly lower risk of developing asthma when administered BCG
vaccine in early childhood (pooled OR=0.59 and 0.90, 95%CI 0.40 to 0.88
and 0.82 to
0.98,
respectively; fig 3). However, in Asia and Africa, participants who
received BCG vaccine in early childhood were not associated with a
significant reduced risk of allergic disease
(pooled OR=0.97 and 1.16, 95%CI 0.51
to 1.87 and 0.68 to 1.97, respectively; fig 3).
Use of BCG vaccine was not associated with the risk of eczema in the
subgroup analysis of different continents (fig 4). Similar results were
obtained in participants with rhinitis (fig 5). The results from our
study did not observe an association of BCG vaccination with reduction
in risk of eczema or rhinitis in Europe, America, Asia or Africa.
3.3 | Publication Bias
The total publication bias is outlined in the funnel plot (fig 6). From
visual inspections of the funnel plots and by Egger’s
test36, it is suggested that publication bias did not
impact our estimates. (bias coefficient for the main analysis 1.18,
95%CI 0.38 to 2.75, P=0.13)