Pregnancy and Medication Safety

Pregnancy and Medication Safety
Bobby LeDuff, PharmD, Essentia Health

Background:  Medication use, both prescription and over-the-counter, is quite common in pregnancy with studies estimating that 95-97% of women use at least one medication during their pregnancy. However, the data behind the safety of medication use in pregnancy is limited. Questions surrounding the state of the United States Food and Drug Administration’s (FDA) pregnancy and lactation labeling have become more frequent lately, especially with the shift away from letter drug categories and the 2015 implementation of the Pregnancy and Lactation Labeling Rule (PLLR). There are concerns among researchers and clinicians regarding the number of new and pre-existing FDA drug labels that have not yet transitioned to the new PLLR format, which leads to uncertainty around the quality of data that exists for pregnancy, lactation, and reproductive impacts. Moreover, further studies are needed to assess the safety of common medications used before, during, and after pregnancy. 

Evidence: A recent cross-sectional study completed by Byrne et al. reviewed the labeling data for 290 newly approved FDA therapeutic products between 2010 and 2019. Within the 10 years of the study, researchers found that a significant amount of FDA drug labels were in compliance with the new PLLR format, especially ones that were submitted for approval after 2015 (P<0.001); however, 32.6% of drug labels submitted between 2010 and 2015 were not in compliance with the new PLLR format by June 2019. Upon review, there were only 31 drugs with data from human studies, whereas most of the approved drugs only have data from animal studies. In a prospective cohort study conducted by Haas et al., medication use was documented throughout the length of pregnancy for the cohort of women. Medications were categorized based on classification and reason for use. The data from this cohort study found that 97% of women took at least one medication during pregnancy and 30.5% of women took five or more medications during pregnancy, meeting the study’s definition for polypharmacy. Findings in this study were congruent with previous studies that indicated the high rates of medication use in pregnancy. Despite this finding, researchers failed to classify medication data by either the FDA’s PLLR system or the previous pregnancy category letter system.  

Clinical Impact and Discussion:  As the pregnant population in the United States continues to grow in medical complexity, there is an increasing need for evidence-based medicine and research. While studies have shown that most new therapeutic products are compliant with the new PLLR rules, more than one-third of labels are not compliant, and human data on pregnancy and lactation is unavailable for more than 20% of new drug labels. Clinicians who care for pregnant patients should be familiar with available resources such as Drugs in Pregnancy and Lactation, TERIS (Teratogen Information System), LactMed, and Mother’s Milk to help guide clinical and shared decision making throughout pregnancy. 


  1. Dude, C, & Jamieson, DJ. Assessment of the safety of common medications used during pregnancy. JAMA. 2020;326(23):2421–2422. doi:10.1001/jama.2021.20191
  2. U.S. Food and Drug Administration. An evolution of labeling information for pregnant women: PLLR history and background. Published March 5, 2018. Accessed January 27, 2022.
  3. Byrne, JJ, Saucedo, AM, & Spong, CY. Evaluation of drug labels following the 2015 pregnancy and lactation labeling rule. JAMA Netw Open. 2020;3(8):e2015094. doi:10.1001/jamanetworkopen.2020.15094
  4. Haas, DM, Marsh, DJ, Dang, DT, et al. Prescription and other medication use in pregnancy. Obstet Gynecol., 2018;131(5):789–798. doi:10.1097/AOG.0000000000002579