Maternal Viral Infection and Risk of Fetal Congenital Heart Diseases: A Meta-Analysis of Observational Studies

Background At present, the association between maternal viral infection and risk of congenital heart diseases ( CHD ) in offspring is uncertain; additionally, a complete overview is missing. A meta-analysis of observational studies was performed to address the question of whether women who had a history of viral infection in early pregnancy were at an increased risk of CHD in offspring, compared with mothers without viral infection. Methods and Results Unrestricted searches were conducted, with an end date parameter of July 15, 2018, of PubMed, Embase, Google Scholar, Cochrane Libraries, and Chinese databases, to identify studies that met prestated inclusion criteria. Seventeen case-control studies involving 67 233 women were included for analysis. Both fixed-effects models (odds ratio [OR], 1.83; 95% CI , 1.58-2.12; P<0.0001) and random-effects models ( OR , 2.28; 95% CI , 1.54-3.36; P<0.0001) suggested that mothers who had a history of viral infection in early pregnancy experienced a significantly increased risk of developing CHD in offspring. For specific viral infections, the risk of developing CHD in offspring was significantly increased among mothers with rubella virus (OR, 3.49, 95% CI, 2.39-5.11 in fixed-effects models; and OR, 3.54; 95% CI, 1.75-7.15 in random-effects models) and cytomegalovirus (OR, 3.95; 95% CI, 1.87-8.36 in fixed-effects models) in early pregnancy; however, other maternal viral infections in early pregnancy were not significantly associated with risk of CHD in offspring. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed. Conclusions Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that maternal viral infection is significantly associated with risk of CHD in offspring.