Associations of maternal upper respiratory tract infection/influenza during early pregnancy with congenital heart disease in offspring: evidence from a case-control study and meta-analysis

Background Evidences regarding the associations between maternal upper respiratory tract infection/influenza during pregnancy and the risk of congenital heart disease (CHD) is still controversial. This study was specifically designed to examine the associations by a case-control study and a meta-analysis of the published evidences and our finding. Methods A hospital-based case-control study involving 262 children with simple CHD and 262 children with complex CHD, along with 262 control children, was conducted through June, 2016 to December, 2017. All children were aged 0-2 years old. Furthermore, a meta-analysis based on both previously published studies and our case-control study was performed. Results In the case-control study, after adjusting for possible confounders, maternal upper respiratory tract infection/influenza during early pregnancy was found to be related to an increased risk of CHD (OR = 3.40 and 95% CI: 2.05-5.62 for simple CHD; OR = 2.39 and 95% CI: 1.47-3.88 for complex CHD). After a meta-analysis, the adverse impact was still kept significant (OR = 1.47 and 95% CI: 1.28-1.67 for simple CHD; OR = 1.44 and 95% CI: 1.14-1.75 for complex CHD). The very similar associations were also observed among single type of CHD, herein, ventricular septal defects (VSD) and tetralogy of fallot (TOF) in the case-control study. In the subsequent meta-analysis, however, the significant association only existed in VSD. Conclusions Although there is still conflicting in TOF, the results are overall consistent, which provide new enforced evidence that maternal upper respiratory tract infection/influenza during early pregnancy, in general, play an important role in the occurrence of CHD.