Congenital anomalies associated with the use of cardiovascular drugs during pregnancy: a large-scale data analysis from the FAERS database

Abstract

Background: Cardiovascular drugs can cross the placenta during pregnancy, potentially exposing the fetus to teratogenic effects. However, ethical constraints on clinical trials with pregnant women limit safety data and result in inadequate drug labeling.

Research design and methods: Using the FAERS database (2004-2023), we conducted a retrospective pharmacovigilance study analyzing adverse event reports involving congenital anomalies in newborns (<28 days). Signal detection methods included Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Our analysis concentrated on the systems or organs involved in the signals, particularly those with higher report counts or signal values, to explore the association between drugs and congenital abnormalities.

Results: Among 6,208 cases of congenital anomalies in newborns, 387 were linked to cardiovascular drugs, generating 97 signals for 16 drugs. Strong signals included sartans (renal failure, skeletal deformity), metoprolol (hypospadias, large-for-dates baby), amlodipine (gastrointestinal malformations), and statins, furosemide, and spironolactone (dysmorphism).

Conclusions: Enhanced monitoring is recommended for fetal malformations in women exposed to these drugs before or during pregnancy. While our findings suggest associations, they do not establish causality, highlighting the need for further research to ensure medication safety during pregnancy.

Keywords: Cardiovascular drug; congenital anomaly; pharmacovigilance; pregnancy; signal detection.