Association of maternal disease and medication use with the risk of congenital heart defects in offspring: a case-control study using logistic regression with a random-effects model

Objective: To examine the association between maternal diseases and congenital heart defects (CHDs) and to evaluate whether those associations vary with corresponding medication use. Methods: A multi-hospital case-control study conducted from February 2010 to December 2014 analysed 916 controls and 1236 cases. Participating mothers were asked whether they suffered from influenza, common cold, herpes and threatened abortion or had used corresponding medication during the periconception period or the early pregnancy period. We used a random-effects logistic regression model to compute the odds ratios (ORs), adjusted odds ratios (AORs) and 95% confidence intervals (CIs) while controlling for potential confounders. Results: Compared with the results for mothers with no exposure, there were significant associations between maternal diseases with medication non-use and CHDs in the aggregate, including influenza (AOR, 1.83; 95% CI, 1.13-2.95), common cold (AOR, 2.05; 95% CI, 1.60-2.64) and herpes (AOR, 7.00; 95% CI, 2.15-22.84). There was no significant association between medication users and offspring with any subtype of CHDs, except that maternal common cold with medication use slightly increased the risk of the specific subtype, namely, isolated cardiac defects. However, an association was observed between maternal threatened abortion and medication and isolated cardiac defects (AOR, 1.33; 95% CI, 1.01-1.75). Conclusion: Maternal influenza, common cold, herpes and threatened abortion from 3 months before pregnancy through the first trimester were associated with an increased risk of congenital heart disease in offspring. The teratogenic effect of these conditions may be attenuated by medication use, except for threatened abortion.