Exposure to Nitrogen Oxide in the First Trimester and Risk of Cardiovascular-Related Malformations: A Dose-Response Meta-Analysis of Observational Studies
Table 1
Summary risk estimates of the associations between NO 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
9
1.01 (0.98–1.04)
38.6
0.09
8
1.01 (0.96–1.06)
0
0.70
9
1.03 (0.97–1.10)
67.0
<0.01
Study design
0.86
0.55
0.59
Cohort study
3
1.01 (0.99–1.03)
0
0.73
2
1.04 (0.77–1.39)
55.6
0.13
3
1.02 (1.00–1.05)
0
0.44
Case-control study
6
1.03 (1.01–1.05)
0
0.57
6
1.02 (0.96–1.08)
0
0.81
6
1.01 (0.93–1.09)
57
0.01
Geographic location
0.27
0.79
0.88
US
3
1.03 (1.01–1.06)
0
0.73
3
1.02 (0.95–1.08)
0
0.43
3
1.04 (0.98–1.1)
0
0.53
Others
6
1.01 (0.99–1.03)
0
0.50
5
1.00 (0.91–1.10)
0
0.61
6
1.03 (0.93–1.13)
76
<0.01
Adjustment for confounders
Maternal age
0.51
0.59
0.63
Yes
5
1.02 (0.99–1.06)
30.7
0.10
4
1.00 (0.93–1.07)
0
0.59
5
1.02 (1.00–1.05)
0
0.71
No
4
1.02 (0.99–1.05)
0
0.92
4
1.03 (0.95–1.11)
0
0.52
4
1.03 (0.93–1.14)
56.8
0.01
Socioeconomic status
0.06
0.78
0.51
Yes
5
1.02 (0.99–1.06)
32.0
0.09
5
1.02 (0.95–1.08)
0
0.61
5
1.04 (0.94–1.15)
69.3
<0.01
No
4
1.01 (0.99–1.03)
0
0.98
3
1.00 (0.91–1.10)
0
0.44
4
1.02 (1.00–1.04)
0
0.71
Conception season
0.26
0.75
0.72
Yes
5
1.01 (0.98–1.03)
4.1
0.41
4
1.00 (0.91–1.09)
0
0.51
5
1.03 (0.93–1.13)
79.8
<0.01
No
4
1.03 (1.01–1.06)
0
0.76
4
1.02 (0.96–1.08)
0
0.57
4
1.04 (0.98–1.10)
0
0.61
Year of birth
0.02
0.72
0.33
Yes
4
1.03 (0.99–1.07)
41.3
0.06
4
1.02 (0.95–1.08)
0
0.47
4
1.05 (0.95–1.16)
72.6
0.01
No
5
1.01 (0.99–1.02)
0
0.98
4
1.00 (0.91–1.09)
0
0.61
5
1.02 (0.99–1.04)
0
0.74
Infant sex
0.44
0.6
0.72
Yes
3
1.01 (0.99–1.03)
0
0.78
2
0.94 (0.81–1.09)
0
0.52
3
1.02 (1.00–1.04)
0
0.86
No
6
1.03 (1.01–1.05)
0
0.61
6
1.02 (0.97–1.08)
0
0.68
6
1.03 (0.96–1.11)
54
0.01
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
8
1.02 (1.01–1.03)
0
0.65
7
1.01 (0.96–1.07)
0
0.61
8
1.04 (0.98–1.10)
57.1
<0.01
Educational level
0.56
0.95
0.29
Yes
3
1.02 (1.00–1.03)
0
0.63
2
1.01 (0.95–1.08)
0
0.51
3
1.02 (1.00–1.04)
0
0.69
No
6
1.02 (0.98–1.06)
0
0.53
6
1.01 (0.93–1.11)
0
0.54
6
1.05 (0.95–1.17)
55.2
0.03
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.
