Investigating drug-induced optic nerve hypoplasia and septo-optic dysplasia from the FDA adverse events database.

OBJECTIVE: To identify potential teratogenic medication associated with optic nerve hypoplasia (ONH) and/or septo-optic dysplasia (SOD), by screening the Food and Drug Administration Adverse Events Reporting System (FAERS) database.

DESIGN: Retrospective pharmacovigilance study using disproportionality signal detection methods.

PARTICIPANTS: Adverse event reports submitted to FAERS between Q1 2004 and Q3 2024. Reports were included if ONH or SOD was listed as an adverse event and drug exposure occurred in utero.

METHODS: A qualitative assessment evaluated patient demographics, and a disproportionality analysis covered pharmacovigilance signal detection and drug-event reporting frequencies. Pharmacovigilance algorithms that were applied to determine the statistical significance of signals included the proportional reporting ratio (PRR), chi-squared with Yates' correction (χ2), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC).

RESULTS: A total of 103 adverse event reports for ONH and/or SOD were identified. The 75 cases reporting prenatal medication exposure were included. Twenty-three reports were of male patients, 13 reports of female patients, and 39 of unspecified gender. Thirty drugs were implicated as primary suspect drugs. Diazepam was the most reported primary suspect medication (n = 15; 20%) followed by methadone and citalopram (n = 8; 11%). The disproportionality analysis showed a positive signal with one medication: diazepam (n = 15; PRR = 82.24; χ2 = 1008.66, ROR 95% CI: 102.55 [56.75-185.33], EBGM [EBGM05]: 48.45 [28.16], IC [IC05]: 4.46 [3.67]).

CONCLUSIONS: A possible association was found between prenatal diazepam exposure and ONH/SOD. Further investigation is required to confirm this relationship and drug safety profiles.