Parental alcohol consumption and the risk of congenital heart diseases in offspring: An updated systematic review and meta-analysis

Objective The aim of this study was to provide updated evidence to assess the association between parental alcohol consumption and the risk of total congenital heart diseases (CHDs) and specific CHD phenotypes in offspring, and explore the possible dose-response pattern. Methods PubMed, Embase and Chinese databases were searched with an end-date parameter of July 24, 2019 to identify studies meeting pre-stated inclusion criteria. A random-effects model was used to calculate the overall combined risk estimates. A meta-analysis of the dose-response relationship was performed. Subgroup analysis, sensitivity analysis, and Galbraith plot were conducted to explore potential heterogeneity moderators. Results A total of 55 studies involving 41,747 CHD cases and 297,587 controls were identified. Overall, both maternal (odds ratio (OR) = 1.16; 95% confidence interval (CI): 1.05-1.27) and paternal (OR = 1.44; 95% CI: 1.19-1.74) alcohol exposures were significantly associated with risk of total CHDs in offspring. Additionally, a nonlinear dose-response relationship between parental alcohol exposure and risk of total CHDs was observed. With an increase in parental alcohol consumption, the risk of total CHDs in offspring also gradually increases. For specific CHD phenotypes, a statistically significant association was found between maternal alcohol consumption and risk of tetralogy of fallot (OR = 1.20; 95% CI: 1.08-1.33). Relevant heterogeneity moderators have been identified by subgroup analysis, and sensitivity analysis yielded consistent results. Conclusions Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, our review indicates that parental alcohol exposures are significantly associated with the risk of CHDs in offspring, which highlights the necessity of improving health awareness to prevent alcohol exposure during preconception and conception periods.