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Nitrogen oxide (NO  x  ) is produced during combustion at high temperature, which is a major constituent of air pollutants. Recent studies suggested inconsistent results on the association between NO  x   exposure and cardiovascular-related malformations. We aimed to assess aforementioned association in pregnant women in the first trimester and cardiovascular-related malformations of infants. A systematic literature review identified studies for observational studies about NO  x   exposure and cardiovascular-related malformation in PubMed. Random-effect models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned association. Finally, nine studies met the inclusion criteria. Overall, the SOR of cardiovascular-related malformation per 10 ppb increment in NO  x   and NO 2  concentration was 1.01 (95% CI: 0.98–1.04;  I  2  = 38.6%,  P  = 0.09) and 0.99 (95% CI: 0.95–1.04;  I  2  = 37.8%,  P  = 0.13), respectively. Stratifying by study design, geographic locations, and confounded adjustments, the majority of strata showed negative results, which were consistent with the main findings. However, we found that exposure to NO  x   and NO 2  in the first trimester increased the risk of coarctation of the aorta (COA) malformation by 13% and 19%, respectively. Our study provided limited evidence regarding the association between NO  x   exposure in the first trimester and cardiovascular-related malformations in infants.

biomed research international

Exposure to Nitrogen Oxide in the First Trimester and Risk of Cardiovascular-Related Malformations: A Dose-Response Meta-Analysis of Observational Studies