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Evaluation Video

Oral Presentation

Session: EmBRACEing Collaborations for Benefit-Risk Decision Making

Risk of Prenatal Exposure to Teratogenic Medications: Development of Evidence for the Teratogenic Risk Impact and Mitigation (TRIM) Tool

Monday, August 26, 2024
2:00 PM – 2:15 PM CEST
Location: Room III
Background: Risk of prenatal exposure is an important factor in considering teratogenic medications for risk mitigation programs, and one of the criteria used for the Teratogenic Risk Impact and Mitigation (TRIM) Tool.

Objectives: To quantify the overall risk of prenatal exposure to teratogenic medications and rank medications based on these risk estimates for inclusion in the TRIM score.

Methods: We used a retrospective cohort design to estimate the risk of prenatal exposure to teratogenic medications using Medicaid (MC) (2013 – 2014) and Merative MarketScan® (MS) Commercial Databases (2014 – 2018). We included females aged 12 to 55 years who used ≥1 medication with known teratogenic risk (n = 142 drugs) to create treatment episodes. Eligible exposure time was from start of treatment to the earliest of the end of treatment or 300 days before the end of continuous healthcare coverage. Pregnancy episodes with estimated gestational age and known outcomes were identified using validated algorithms. Prenatal exposure rate was estimated as the number of pregnancies overlapping with treatment episodes per at-risk exposure time (i.e., 1,000 exposed years) considering trimester-specific medication risk profile. The rate calculation considered two scenarios: treatment initiation during pregnancy and conception during treatment.

Results: During the study period, 130 and 136 of 142 medications had eligible treatment episodes from MC and MS, respectively; and 94 medications with ≥ 10,000 at-risk exposure days. Mean prenatal exposure rate across both populations, ranged from 0 for several cancer medications to 1,668 per 1,000 exposed years (tertile: 5.0; 15.0) for fluconazole. Fingolimod and isotretinoin were in the first tertile with an overall rate of 21.0 (MC: 34.3 vs. MS: 7.6) and 16.1 (MC: 27.5 vs. MS: 4.7) per 1,000 exposed years. Other medications at high risk for prenatal exposure include antiepileptic medications (topiramate: 31.9, carbamazepine: 26.5, valproic acid: 22.4), sulfamethoxazole/trimethoprim (338.3), and vedolizumab (481.1) and are not subject to additional risk mitigation programs. Of the 66 medications with ≥ 10,000 at-risk exposure days in both populations, the exposure rate in the MC population was higher for 50 medications, with prenatal exposure rates up to 2,512 per 1,000 exposed years (tertile: 8.3; 22.6), compared to 824 (tertile: 3.5; 8.6) in the MS population.

Conclusions: Several medications with known teratogenic effects and no current risk mitigation program exhibited larger prenatal exposure risks compared to medications with active program. The MC population faced a higher prenatal exposure risk compared to persons with private insurance. Data will be used to derive TRIM scores to consider medications for risk mitigation considerations.