Maternal air pollution exposure and congenital heart defects in offspring: A systematic review and meta-analysis

Congenital heart defects (CHDs) has a multifactorial causation with a strong genetic component and many environmental triggers. Emerging body of empirical studies suggest that air pollution is an important contributor to the development of CHDs, however, there still remains some controversy over the current evidence, and to the authors' knowledge, no studies have reviewed the most recent evidence. We performed a systematic review and meta-analysis of epidemiological literature to investigate the relationship between maternal air pollution exposure and CHDs risk in offspring. The presence of heterogeneity and publication bias across available studies were also examined. An extensive literature search of epidemiological studies pertaining to air pollution and CHDs, published in English language, until August 1, 2019 was conducted. Summary risk estimates of pollution–outcome combinations were calculated for i) risk per specific increment of concentration and ii) risk at high versus low exposure level in each study using fixed-effect model or random-effects model. A total of 26 studies were finally included. In the meta-analyses, high versus low carbon monoxide (CO) exposure was associated with an increased risk of tetralogy of Fallot [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.04–1.41], yet particulate matter ≤ 5 μm (PM2.5) exposure was marginally associated with it. Increased risk of atrial septal defects (ASDs) was found for each 10 μg/m3 and 10 ppb increment in particulate matter ≤ 10 μm (PM10) and ozone (O3) exposure, respectively (OR = 1.04, 95% CI: 1.00–1.09; OR = 1.09, 95% CI: 1.02–1.17). Categorical nitrogen dioxide (NO2) exposure was associated with an increased risk of coarctation of the aorta (OR for high versus low = 1.14, 95% CI: 1.02–1.26). Analyses for other combinations yielded none statistically significant associations. Sensitive analyses showed similar findings. The summary effect estimates from this study suggest statistically significant associations between increased risk of specific CHDs subtypes and PM2.5, PM10, NO2, CO, and O3 exposures. Further studies, especially conducted in developing countries, with improvements in exposure assessing, outcome harmonizing, and mechanistic understanding are needed to elaborate the suggestive associations.