Exposure to Nitrogen Oxide in the First Trimester and Risk of Cardiovascular-Related Malformations: A Dose-Response Meta-Analysis of Observational Studies
Table 2
Summary risk estimates of the associations between NO2 and cardiovascular-related malformation, ASD, and VSD.
Cardiovascular-related malformation
ASD
VSD
Number of studies
SOR (95% CI)
(%)
Number of studies
SOR (95% CI)
(%)
Number of studies
SOR (95% CI)
(%)
Overall
8
0.99 (0.95–1.04)
37.8
0.13
8
0.99 (0.93–1.06)
0
0.71
8
1.01 (0.95–1.08)
11.7
0.34
Study design
0.91
0.80
0.27
Cohort study
2
1.01 (0.94–1.07)
0
0.66
2
1.04 (0.77–1.39)
55.6
0.13
2
1.07 (0.95–1.21)
5.8
0.35
Case-control study
6
1.02 (0.99–1.05)
10.4
0.29
6
1.00 (0.93–1.07)
0
0.82
6
1.01 (0.95–1.07)
0
0.60
Geographic location
0.01
0.31
0.14
US
3
1.05 (1.02–1.08)
0
0.48
3
1.01 (0.91–1.13)
26.9
0.26
3
1.05 (0.99–1.12)
0
0.43
Others
5
0.95 (0.89–1.00)
0
0.93
5
0.94 (0.84–1.06)
0
0.96
5
0.95 (0.86–1.05)
0
0.95
Adjustment for confounders
Maternal age
0.61
0.91
0.57
Yes
4
1.02 (0.98–1.06)
28.1
0.13
4
1.00 (0.93–1.07)
0
0.59
4
1.04 (0.97–1.10)
0
0.58
No
4
1.00 (0.94–1.05)
0
0.79
4
0.98 (0.85–1.13)
0
0.46
4
0.99 (0.89–1.10)
0
0.44
Socioeconomic status
0.96
0.94
0.83
Yes
5
1.01 (0.97–1.05)
32.6
0.09
5
1.00 (0.93–1.07)
0
0.75
5
1.02 (0.96–1.09)
0
0.48
No
3
1.01 (0.95–1.07)
0
0.82
3
1.02 (0.82–1.28)
23
0.27
3
1.02 (0.91–1.15)
0
0.44
Conception season
0.01
0.27
0.14
Yes
4
0.94 (0.89–1.00)
0
0.96
4
0.94 (0.83–1.05)
0
0.98
4
0.95 (0.86–1.06)
0
0.89
No
4
1.05 (1.02–1.08)
0
0.54
4
1.02 (0.95–1.10)
0
0.40
4
1.05 (0.99–1.12)
0
0.53
Year of birth
0.44
0.92
0.89
Yes
4
1.02 (0.98–1.07)
43.9
0.05
4
1.00 (0.93–1.07)
0
0.59
4
1.03 (0.97–1.09)
0
0.41
No
4
0.99 (0.94–1.05)
0
0.85
4
0.98 (0.86–1.12)
0
0.46
4
1.01 (0.90–1.12)
0
0.51
Infant sex
0.35
0.43
0.76
Yes
2
0.97 (0.89–1.05)
0
0.80
2
0.94 (0.81–1.09)
0
0.52
2
0.99 (0.84–1.15)
0
0.71
No
6
1.03 (1.00–1.06)
6.9
0.34
6
1.01 (0.94–1.08)
0
0.63
6
1.03 (0.97–1.09)
0
0.44
Gestational age
N/A
N/A
N/A
Yes
1
0.92 (0.81–1.05)
N/A
0.70
1
0.98 (0.74–1.30)
N/A
N/A
1
0.91 (0.68–1.22)
N/A
N/A
No
7
1.03 (1.00–1.06)
2.3
0.43
7
1.00 (0.93–1.06)
0
0.60
7
1.03 (0.97–1.09)
0
0.57
Educational level
0.07
0.54
0.83
Yes
2
1.04 (1.01–1.08)
10.5
0.32
2
1.00 (0.91–1.10)
25.7
0.25
2
1.03 (0.96–1.11)
1.9
0.38
No
6
0.98 (0.93–1.03)
0
0.79
6
0.97 (0.86–1.08)
0
0.73
6
1.00 (0.92–1.09)
0
0.56
value for heterogeneity within each subgroup; value for heterogeneity between subgroups with meta-regression analysis. ASD, atrial septal defect; CI: confidence interval; SOR, summary odds ratio; VSD, ventricular septal defect.
