Prescription medication use during pregnancy in the United States from 2011 to 2020: trends and safety evidence

Abstract

Background: Medication use during pregnancy has increased in the United States despite the lack of safety data for many medications.

Objective: This study aimed to inform research priorities by examining trends in medication use during pregnancy and identifying gaps in safety information on the most commonly prescribed medications.

Study design: We identified population-based cohorts of commercially (MarketScan 2011-2020) and publicly (Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files 2011-2018) insured pregnancies ending in live birth from 2 health care utilization databases. Medication use was based on filled prescriptions between the date of last menstrual period through delivery, as well as the period before the last menstrual period and during specific trimesters. We also included a cross-sectional representative sample of pregnancies ascertained by the National Health and Nutrition Examination Survey (2011-2020), with information on prescription medication use during the preceding month obtained through maternal interviews. Teratogen Information System was used to classify the available evidence on teratogenic risk.

Results: Among over 3 million pregnancies, the medications most commonly dispensed at any time during pregnancy were analgesics, antibiotics, and antiemetics. The top medications were ondansetron (16.8%), amoxicillin (13.5%), and azithromycin (12.4%) in MarketScan, nitrofurantoin (22.2%), acetaminophen (21.3%; mostly as part of acetaminophen-hydrocodone products), and ondansetron (19.5%) in Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files, and levothyroxine (5.0%), sertraline (2.9%), and insulin (2.9%) in the National Health and Nutrition Examination Survey group. The most commonly dispensed suspected teratogens during the first trimester were antithyroid medications. The use of antidiabetic and psychotropic medications has continued to increase in the United States during the last decade, opioid dispensation has decreased by half, and antibiotics and antiemetics continue to be common. For one-quarter of medications, there is insufficient evidence available to characterize their safety profile in pregnancy.

Conclusion: There is a need for more drug research in pregnant patients. Future research should focus on anti-infectives with high utilization and limited level of evidence on safety for use during pregnancy. Although lack of evidence is not evidence of safety concerns, it does not indicate risk either. In many instances, the benefits outweigh the risks when these medications are used clinically, and some of the medications with no proven safety may be necessary to treat patients.

Keywords: TERIS; gestation; perinatal; pharmacoepidemiology; teratogens; utilization.

Figure 1.

Utilization of antiemetics at any time during pregnancy by LMP year in MarketScan (2011–2020) and MAX/TAF (2011–2017). LMP: last menstrual period

Figure 2.

Utilization of antidiabetics at any time during pregnancy by LMP year in MarketScan (2011–2020) and MAX/TAF (2011–2017). LMP: last menstrual period Antidiabetics with <100 exposures were not included: thiazolidinediones, alpha-glucosidase inhibitors (AGIs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, meglitinides, and pramlintide acetate.

Figure 3.

Utilization of psychotropics at any time during pregnancy by LMP year in MarketScan (2011–2020) and MAX/TAF (2011–2017). LMP: last menstrual period ADHD: attention-deficit/hyperactivity disorder

Figure 4.

Utilization of analgesics and antimigraine medications at any time during pregnancy by LMP year in MarketScan (2011–2020) and MAX/TAF (2011–2017). LMP: last menstrual period NSAIDs: nonsteroidal anti-inflammatory drugs. * Opioids exclude antitussives/expectorants.