Pregabalin Safety in Pregnancy: A Disproportionality Analysis of VigiBase Spontaneous Reporting System.

Abstract

Background/Objectives: Some product information on pregabalin suggests a potential risk for congenital anomalies (CAs), although evidence remains inconsistent and lacks clear patterns. This study aimed to provide additional safety information on pregabalin use in pregnancy by analyzing VigiBase, the World Health Organization's global pharmacovigilance database of individual case safety reports (ICSRs). Methods: The analysis included de-duplicated ICSRs related to pregabalin exposure in pregnancy, collected up to 16 January 2024. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated for CA categories reported in at least 10 ICSRs, with a statistical threshold defined as a 95% CI lower bound > 1. Results: Among 410 ICSRs, the majority originated from Europe (64.8%) and North America (26.5%). Of these, 59 (14.4%) ICSRs documented only pregabalin exposure in pregnancy, while 351 (85.6%) also reported adverse events in pregnancy. CAs occurred in 82 ICSRs (23.3%), most commonly involving heart defects (30), nervous system anomalies (18), and limb anomalies (12). No signals of disproportionate reporting were identified for these categories compared to the full database (heart defects: ROR 0.587, 95% CI 0.410-0.839; nervous system anomalies: ROR 0.588, 95% CI 0.370-0.933; limb anomalies: ROR 0.671, 95% CI 0.381-1.183). Conclusions: Future disproportionality analyses, along with pharmacovigilance and pharmacoepidemiological studies using patient registries and large-scale collaborative projects, are essential for the ongoing monitoring of pregabalin safety in pregnancy.