Maternal psychological stress during pregnancy and risk of congenital heart disease in offspring: A systematic review and meta-analysis

Background The relationship between maternal psychological stress during pregnancy and risk of congenital heart disease (CHD) in offspring is still unclear. We conducted a meta-analysis to quantitatively evaluate the association. Methods Literature search was performed through May 2020 using PubMed and Web of Science databases. Observational studies evaluating the associations of maternal psychological stress including stress, stress life events, anxiety and depression with CHD risk in offspring were eligible for the study. Results Ten case-control studies with 16,382 CHD cases and 1,812,999 non-CHD controls were included in the meta-analysis. Four studies assessed the association between maternal stress during pregnancy and CHD risk in offspring. The pooled odds ratio (OR) was 2.11 (95%CI: 1.62, 2.74) for those mothers with stress during pregnancy. Six studies assessed the association between maternal stressful life events during pregnancy and CHD risk in offspring. The pooled OR was 1.86 (95%CI: 1.29, 2.68) for those mothers exposed to stressful life events during pregnancy. Maternal anxiety and depression may not be associated with CHD risk in offspring. The pooled ORs were 1.42 (95%CI: 0.53, 3.77) and 2.10 (95%CI: 0.46, 9.59) for the maternal anxiety and depression during pregnancy, respectively. Limitations Residual confounding, heterogeneity and publication bias may exist, which may limit the interpretation of the results. Conclusion Maternal stress and stressful life events during pregnancy may be associated with higher risk of CHD in offspring, but such association was not observed for other mental health exposures such as anxiety and depression.