Assessing medical product safety during pregnancy using parameterizable tools in the sentinel distributed database

Area of Science:

• Pharmacovigilance
• Reproductive Epidemiology
• Pediatric Safety

Background:

• The Sentinel System is a US FDA initiative for medical product safety monitoring.
• It utilizes parameterizable analytic tools to assess drug safety in pregnant individuals and their infants.
• Routine monitoring of drug utilization and safety during pregnancy is crucial.

Purpose of the Study:

• To evaluate the feasibility of using the Sentinel System's data and tools.
• To assess the known association between first-trimester topiramate exposure and oral clefts in infants.
• To demonstrate the Sentinel System's capability in real-world drug safety assessments.

Main Methods:

• Identified mother-infant pairs from six Sentinel data partners (2000-2015).
• Compared first-trimester topiramate-exposed pairs with unexposed and lamotrigine-exposed pairs.
• Used propensity score stratification to estimate adjusted risk ratios for oral clefts.

Main Results:

• The study included over 1 million mother-infant pairs.
• An increased odds ratio for oral clefts was observed in topiramate-exposed infants (OR 2.92 vs. unexposed; OR 2.72 vs. lamotrigine-exposed).
• The findings align with previous research on topiramate and oral clefts.

Conclusions:

• First-trimester topiramate exposure is associated with an increased risk of oral clefts.
• The Sentinel System's data and tools can efficiently assess medical product safety in mother-infant cohorts.
• This study validates the Sentinel System's utility for timely pharmacovigilance.