(12) Targets for Quality Improvement? Top 10 Teratogenic Drugs Used During Pregnancy in the US

Publication Number: 343

Background: Risk mitigation for most teratogenic (TEX) drugs relies on drug label information and prenatal exposure remains common. Evidence on the types and etiologies of prenatal exposures to TEX drugs can guide quality improvement.

Objectives: To identify the top 10 TEX drugs with exposure among privately insured pregnant persons.

Methods: We used MarketScan® Commercial Claims and Encounters Data to identify pregnancy episodes with live or non-live outcomes (ectopic, abortions, stillbirths) among persons aged 12 to 55 years during 2010-2018. Pregnancy outcome and start/end dates were identified via a previously validated algorithm. We required continuous health plan enrollment from 90 days before conception until 30 days after pregnancy end date. TEX drugs were selected from the Teratogen Information System and drug monographs based on the level of risk and quality of evidence (140 with definite 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 because of challenges to separate pregnancy-related indications, nor were opioids (due to complex risk-benefit) and anti-obesity drugs if their TEX mechanism was only weight loss.

Results: Among all pregnancies, the 10 definite TEX drugs with the highest prenatal exposures were sulfamethoxazole/trimethoprim (SMX/TMP) (1,153 per 100,000 pregnancies), ≥450mg fluconazole (671), topiramate (199), lisinopril (54), warfarin (33), carbamazepine (31), valproate (29), losartan (19), vedolizumab (16 since 2015), and valsartan (10). Exposure prevalences to SMX/TMP decreased from 1,399 to 809 per 100,000 pregnancies during 2010 – 2018, while those for vedolizumab increased sixfold since 2015 (approval). When evaluating non-live pregnancies only, lisinopril, losartan, and valsartan were not in the top 10, but isotretinoin and mycophenolate, both with FDA-required risk mitigation programs, took the 8th and 9th place. Phenytoin was the #10. Among potential teratogens, prenatal exposure was most prevalent for low-dose fluconazole (3,592), followed by metoprolol (259) and duloxetine (235).

Conclusions: Several drugs commonly used by women of child-bearing age are also commonly used during pregnancy. Changing prevalences over time emphasize that risk mitigation needs may warrant reevaluation. Future research is needed to understand the context of clinical use to elucidate approaches for quality improvement.