Exposure to Known or Suspected Teratogenic Drugs Prior to Conception in a Commercially Insured Population of Pregnant Women

Background: In studies of drug safety in pregnancy, identifying pregnancies with exposure to non-study drugs with potentially teratogenic or other adverse effects is essential. These pregnancy episodes may be excluded from the eligible study population or otherwise accounted for during analyses. This may have considerable impact on sample size. There are no recent studies describing the prevalence and timing of teratogenic drug exposures as a whole in the months prior to the start of pregnancy.

Objectives: To describe the exposure prevalence of suspected teratogenic drugs in the 180 days prior to the start of pregnancy.

Methods: This study used data from Optum's Dynamic Assessment of Pregnancies and Infants (DAPI), a proprietary pregnancy database within the Optum Research Database, a health insurance claims data source. The estimated date of last menstrual period (LMP) was used as the start of pregnancy, and was identified via International Classification of Diseases, 10th revision (ICD-10) Z3A codes (indicating weeks of gestation) or pregnancy outcomes codes. All pregnancies were required to have 180 days of continuous enrollment prior to LMP. Known or suspected teratogenic drugs, compiled through a review of published literature, were identified through the presence of drug or procedure codes in the 180 days prior to and including the date of LMP.

Results: Among 536,470 pregnancy episodes with LMP between 01 January 2017 and 31 October 2021, prevalence of exposure to any teratogenic drug rose from 2.9% (n = 15,573) in the 30 days prior to LMP to 8.8% (n = 47,171) in the 180 days prior to LMP. The most commonly observed drug classes in the 180 days were antifungals (4.9%, n = 26,339), antineoplastics (2.5%, n = 13,219) and anticonvulsants (0.6%, n = 3,234). In the 30 days prior to LMP, antineoplastics were the most commonly observed drug class (1.2%, n = 6,617) followed by antifungals (1.0%, n = 5,493). Exposed pregnancies were more likely to be older (27.2% of exposed pregnancies were over the age of 35 as compared to 21.9% of pregnancies overall) due largely to antineoplastic agents, angiotensin receptor blockers, and angiotensin-converting-enzyme inhibitors.

Conclusions: Few pregnancy episodes had evidence of teratogenic drug exposures in the 30 days prior to LMP, but the number rose to near 10% when the full 180 days prior to LMP was assessed. The most common exposures were to antifungals and antineoplastic agents, though their relative prevalence switched during the 180 days, with antineoplastic agents more common in the time nearer to LMP. This information is useful for public health surveillance efforts and has implications for sample size in studies of pregnancy safety.