Association between zidovudine and adverse pregnancy outcomes/congenital malformations: A pharmacovigilance study using FAERS data

BackgroundZidovudine (AZT), a key antiretroviral drug used for HIV treatment and preventing mother-to-child transmission, has insufficient post-marketing pharmacovigilance regarding pregnancy outcomes and congenital disorders. MethodsThis pharmacovigilance study analyzed adverse event (AE) reports associated with zidovudine from the U.S. FDA Adverse Event Reporting System (FAERS) database (Q1 2004-Q4 2024) to assess its safety in pregnancy. Four statistical methods were used: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). ResultsA total of 2,931 case reports (12,586 adverse events) involving zidovudine as the primary suspect drug were analyzed, with 802 cases reported from pregnant individuals. Disproportionality analysis revealed significant associations with blood and lymphatic disorders, pregnancy and perinatal complications, congenital and genetic disorders, as well as hepatobiliary conditions. Notable signals included preterm birth [ROR(95% CI) = 32.61 (28.36, 37.49)], low birth weight [ROR(95% CI) = 20.44 (14.51, 28.78)], and congenital anomalies [ROR(95% CI) = 26.54 (19.58, 35.96)]. Additionally, new unlabeled signals, such as acquired lipodystrophy and atrial septal defects, were identified. ConclusionThe findings from this pharmacovigilance study enhance the post-marketing safety monitoring of zidovudine, inform clinical decisions in pregnant populations, and highlight the need for targeted surveillance and risk-benefit assessment. Future research should validate novel signals and compare different antiretroviral regimens in pregnancy.