Ambient Air Pollution and Congenital Heart Disease: Updated Evidence and Future Challenges.

Congenital heart disease (CHD) represents the major cause of infant mortality related to congenital anomalies globally. The etiology of CHD is mostly multifactorial, with environmental determinants, including maternal exposure to ambient air pollutants, assumed to contribute to CHD development. While particulate matter (PM) is responsible for millions of premature deaths every year, overall ambient air pollutants (PM, nitrogen and sulfur dioxide, ozone, and carbon monoxide) are known to increase the risk of adverse pregnancy outcomes. In this literature review, we provide an overview regarding the updated evidence related to the association between maternal exposure to outdoor air pollutants and CHD occurrence, also exploring the underlying biological mechanisms from human and experimental studies. With the exception of PM, for which there is currently moderate evidence of its positive association with overall CHD risk following exposure during the periconception and throughout pregnancy, and for ozone which shows a signal of association with increased risk of pooled CHD and certain CHD subtypes in the periconceptional period, for the other pollutants, the data are inconsistent, and no conclusion can be drawn about their role in CHD onset. Future epidemiological cohort studies in countries with different degree of air pollution and experimental research on animal models are warranted to gain a comprehensive picture of the possible involvement of ambient air pollutants in CHD etiopathogenesis. While on the one hand this information could also be useful for timely intervention to reduce the risk of CHD, on the other hand, it is mandatory to scale up the use of technologies for pollutant monitoring, as well as the use of Artificial Intelligence for data analysis to identify the non-linear relationships that will eventually exist between environmental and clinical variables.