Study Selection
Figure 1 shows the study selection procedure, and the reasons for the excluded studies are also shown. A total of 598 studies were retrieved from PubMed (n=302), Embase (n=265), and Cochrane (n=31). After removing the duplicates, 432 articles were examined. Ten articles were excluded because of being notes/reports, 109 articles were excluded because they were conference abstracts, 25 articles were excluded because of being reviews, and 15 articles were excluded because of the language. Then, 273 articles were left for full-text screening and 264 were excluded because of being not accessible (n=10), study aim/design (n=54), population (n=100), outcome (n=28), intervention (n=63), and animal (n=9). No additional records were identified through other sources. Hence, nine observational studies entered our final model [10, 12, 16, 21-26].
Characteristics of the included studies
Table 1 presents the included studies [10, 12, 16, 21-26]. There were four prospective cohort studies [7,18-20], four retrospective cohort studies [12, 16, 24, 25] and one case-control study [26]. Most included studies were from Europe [10, 12, 16, 21, 23, 26], and the others were from America [22, 24, 25]. These studies included 982,942 patients. The included studies investigated different exposures, including depression, anxiety, depression or anxiety, mental health service use, prenatal distress, and negative life events. Studies were grouped into the categories according to their outcomes: five for asthma [10, 12, 16, 21, 24], three for AD [22, 23, 26], and one for asthma and AD [25]. To ensure the reliability and quality control of this meta-analysis, we scored each study using the NOS criteria, and studies with more than 5 stars were included in the meta-analysis. After evaluation, six studies scored 9 stars [10, 12, 21, 23, 25, 26], and three studies scored 8 stars [16, 22, 24] (Supplementary Table 1a). Letourneau et al. [22] was examined infants of only 18 months of age, and Liu et al. [16] examined children when they were 0-6 years of age; both studies examined their population before the usual onset age for asthma and AD, possibly explaining their lower quality, at least in part. Radhakrishnan et al. defined exposure as any use of mental health service, which may include a wide variety of mental illnesses besides anxiety and depression [24].
Effect of prenatal depression on childhood asthma
Six studies (eight datasets) [10, 12, 16, 21, 24, 25] could be included for the meta-analysis of prenatal depression on childhood asthma. Compared with the control group (maternal without depression), the results showed that prenatal depression influenced childhood asthma (ES=1.146, 95%CI: 1.054-1.245, P=0.001; I2=93.5%, Pheterogeneity<0.001) (Figure 2A and Table 2a).
Effect of prenatal depression on childhood AD
Four studies (eight datasets) [22, 23, 25, 26] could be included for the meta-analysis of prenatal depression on childhood AD. The result indicated that there was no statistically significant difference between the control and treatment groups, which means that prenatal depression may not influence childhood AD (ES=1.211, 95%CI: 0.982-1.494, P=0.073; I2=78.5%, Pheterogeneity<0.001) (Figure 2B and Table 2b).
Subgroup analyses of childhood asthma
Only one study [10] examined the association between prenatal anxiety and childhood asthma (ES=1.03, 95%CI: 0.86-1.23, P=0.746). Another study examined prenatal depression and childhood asthma [21] and reported a significant association (ES=1.17, 95%CI: 1.06-1.29, P=0.002). Four studies considered prenatal depression or anxiety [12, 16, 24, 25] and there was a significant association was observed (ES=1.16, 95%CI: 1.05-1.27, P=0.003; I2=95.3%, Pheterogeneity<0.001) (Figure 3A and Table 2a).
There were two prospective studies [10, 21] (ES=1.123, 95%CI: 1.000-1.262, P=0.051; I2=33.2, Pheterogeneity=0.221) that a borderline possible association between prenatal mental disorder and childhood asthma, whereas four retrospective studies [12, 16, 24, 25] indicated that childhood asthma was associated with prenatal mental disorder (ES=1.157, 95%CI: 1.050-1.275, P=0.003; I2=95.3, Pheterogeneity<0.001) (Figure 3B and Table 2a). Four studies from Europe [10, 12, 16, 21] showed that childhood asthma was associated with prenatal mental disorder (ES=1.106, 95%CI: 1.001-1.221, P=0.047; I2=93.5, Pheterogeneity<0.001), but two studies from North America [24, 25] suggested the opposite conclusion (ES=1.328, 95%CI: 0.989-1.784, P=0.059; I2=88.7, Pheterogeneity=0.003) (Figure 3C and Table 2a).
Subgroup analyses of childhood AD
Two studies [22, 23] indicated no association between prenatal anxiety and childhood AD (ES=1.31, 95%CI: 0.58-2.96, P=0.523; I2=68, Pheterogeneity=0.044). Two other studies [23, 26] demonstrated that there was no significant association between prenatal depression and childhood AD (ES=1.14, 95%CI: 0.85-1.53, P=0.391; I2=84.3, Pheterogeneity<0.001). One study [25] showed that childhood AD was associated with prenatal depression or anxiety (ES=1.27, 95%CI: 1.11-1.46, P=0.001) (Figure 3D and Table 2b).
Two prospective studies [22, 23] (ES=1.329, 95%CI: 0.816-2.164, P=0.253; I2=72.1, Pheterogeneity=0.006) and one case-control study [26] (ES=1.010, 95%CI: 0.824-1.237, P=0.927; I2=75.5, Pheterogeneity=0.043) showed a negative association between prenatal mental disorder and childhood AD, whereas only one retrospective cohort study [25] showed the opposite (ES=1.27, 95%CI: 1.11-1.46, P=0.391; I2=84.3, Pheterogeneity<0.001) (Figure 3E and Table 2b).
Two studies from Europe [23, 26] (ES=1.144, 95%CI: 0.876-1.494, P=0.322; I2=80.3, Pheterogeneity<0.001) and two studies from North America [22, 25] (ES=1.607, 95%CI: 0.795-3.248, P=0.187; I2=58.4, Pheterogeneity=0.121) suggested that there was no correlation between childhood AD and prenatal mental disorder (Figure 3F and Table 2a).
Sensitivity analyses
The sensitivity analyses indicated that publication bias was not significant since there was no individual study that affected the observed result for childhood asthma (Supplementary Figure 1A) and childhood AD (Supplementary Figure 1B).