Pregnancy related adverse events and congenital disorders associated with fluoroquinolones: A real-world pharmacovigilance study of the FDA adverse event reporting system (FAERS)

Abstract

Background: Fluoroquinolones, including ciprofloxacin, levofloxacin, and moxifloxacin, are extensively employed as broad-spectrum antibacterial agents. However, their use is discouraged during pregnancy due to potential adverse events (AEs). The aim of this study is to systematically investigate the association between fluoroquinolones (specifically ciprofloxacin, levofloxacin, and moxifloxacin) and AEs related to pregnancy, as well as their potential impact on congenital disorders.

Methods: A disproportionality analysis was conducted utilizing FDA Adverse Event Reporting System (FAERS) data spanning from the first quarter of 2004 to September 2023. The objective was to identify potential AEs signatures associated with fluoroquinolones through conducting reporting odds ratios (RORs) and Bayesian confidence propagation neural networks (BCPNN). Assessing the potential risk of pregnancy-associated AEs involved comparing each fluoroquinolone with all other medications. Additionally, in-depth comparative analyses were carried out between various fluoroquinolones and a reference drug (azithromycin).

Results: A total of 1159 cases were identified, involving AEs related to pregnancy and congenital disorders. Obvious disproportionate association of abortion spontaneous and other nine AEs was identified for fluoroquinolone during gestation. Upon comparison with all the other drugs, ciprofloxacin exhibited an elevated risk of spontaneous abortion, non-site specific bone disorders congenital and 10 other significant signals. Levofloxacin demonstrated an increased risk of congenital tongue disorders and three other significant signals. Moxifloxacin displayed a noteworthy signal indicating multiple congenital cardiac abnormalities.

Conclusions: We present compelling evidence regarding pregnancy-related AEs and congenital disorders linked to fluoroquinolones. Considering perinatal and genotoxicity aspects, we explore whether levofloxacin or moxifloxacin might be preferable when fluoroquinolones are deemed necessary to balance the benefits of pregnant women and fetuses.

Keywords: Congenital disorders; Disproportionality analysis; FAERS; Fluoroquinolone; Pharmacovigilance; Spontaneous abortion.

Fig. 1

The flow diagram of selecting Fluoroquinolone-related AEs from FAERS database.

Fig. 2

Disproportionality analysis of pregnancy-related AEs for specific fluoroquinolone at the High Level Terms (HLTs) level, compared with all the other fluoroquinolones. Emerging findings of specific fluoroquinolone associated AEs from FAERS database. The figure shows data with the number of cases (N) greater than or equal to 3 (N ≥ 3). * Indicates statistically significant signals in algorithm. ROR, reporting odds ratio; CI, confidence interval; IC025, the lower end of 95 % CI of the information component.

Fig. 3

Disproportionality analysis of pregnancy-related AEs for fluoroquinolone at the High Level Terms (HLTs) level, compared with azithromycin. Emerging findings of specific fluoroquinolone associated AEs from FAERS database. The figure shows data with the number of cases (N) greater than or equal to 3 (N ≥ 3).* Indicates statistically significant signals in algorithm. ROR, reporting odds ratio; CI, confidence interval; IC025, the lower end of 95 % CI of the information component.