Common teratogenic medication exposures—a population-based study of pregnancies in the United States

Abstract

BackgroundRisk mitigation for most teratogenic medications relies on risk communication via drug label, and prenatal exposures remain common. Information on the types of and risk factors for prenatal exposures to medications with teratogenic risk can guide strategies to reduce exposures. ObjectivesTo identify medications with known or potential teratogenic risk commonly used during pregnancy among privately insured persons. Study DesignWe used MarketScan® Commercial Claims and Encounters Data to identify pregnancy episodes with live or non-live (ectopic pregnancies, spontaneous and elective abortions, stillbirths) outcomes among persons aged 12 to 55 years during 2011-2018. Start/end dates of medication exposure and pregnancy outcomes were identified via an adapted algorithm based on validation studies. We required continuous health plan enrollment from 90 days before conception until 30 days after pregnancy end date. Medications with known or potential teratogenic risk were selected from the Teratogen Information System (TERIS) and drug monographs based on the level of risk and quality of evidence (138 with known and 60 with potential risk). We defined prenatal exposure based on ≥1 outpatient pharmacy claim or medical encounter for drug administration during target pregnancy periods considering drug risk profiles (e.g., risk only in the first trimester or at a certain dose threshold). Sex hormones and hormone analogs, abortion and post-partum/abortion hemorrhage treatments were not considered as teratogenic medications because of challenges to separate pregnancy-related indications, nor were opioids (due to complex risk-benefit) or anti-obesity drugs if their only teratogenic mechanism was weight loss. ResultsAmong all pregnancies, the 10 medications with known teratogenic risk and with the highest prenatal exposures were sulfamethoxazole/trimethoprim (SMX/TMP) (1,988 per 100,000 pregnancy years), high-dose fluconazole (1248), topiramate (351), lisinopril (144), warfarin (57), losartan (56), carbamazepine (50), valproate (49), vedolizumab (28 since 2015), and valsartan (25). Exposure prevalence to SMX/TMP decreased from 2,346 to 1,453 per 100,000 pregnancy years during 2011 – 2018, but exposure prevalence to vedolizumab increased sixfold since its approval in 2015. Prenatal exposures in the first trimester among non-live pregnancies were higher compared to live-birth pregnancies, with the largest difference for warfarin (non-live 370 vs. live-birth 78), followed by valproate (258 vs. 86) and topiramate (1,728 vs. 674). Prenatal exposures to medications with potential teratogenic risk were most prevalent for low-dose fluconazole (6,495), metoprolol (1,325) and atenolol (448). The largest first-trimester exposure differences between non-live and live-birth pregnancies were for lithum (242 vs. 89), gabapentin (1,639 vs. 653), and duloxetine (1,914 vs. 860). Steady increases in hydralazine and gabapentin exposures were seen during study years, while atenolol exposures decreased (561 to 280). ConclusionsSeveral medications with teratogenic risk for which there are potentially safer alternatives continue to be used during pregnancy. The fluctuating rates of prenatal exposure observed in select teratogenic medications suggest regular reevaluation of risk mitigation strategies is needed. Future research focusing on understanding the clinical context of medication use is necessary to develop effective strategies for reducing exposures to medications with teratogenic risk during pregnancy.