NCHR Comments on FDA’s Guidance on Post-Approval Pregnancy Safety Studies

National Center for Health Research, June 28, 2019

National Center for Health Research’s Comments on
FDA’s Post-approval Pregnancy Safety Studies – Guidance for Industry


Thank you for the opportunity to express our views on the FDA’s Post-approval Pregnancy Safety Studies – Guidance for Industry.  The National Center for Health Research is a nonprofit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety.  We do not accept funding from companies that make products that are the subject of our work.

Currently, 9 in 10 women take at least one medication during their pregnancy, and 7 in 10 women take at least one prescription medication during their pregnancy.1 It is therefore vital to develop safety profiles of drugs used during any stage of pregnancy.  Those studies must be subject to rigorous methodology and surveillance.

Post-market pregnancy safety surveillance studies provide important safety information which helps to improve drug labeling and to enable healthcare providers to better inform women about potential risks of prescription drug use during pregnancy.

Currently, pregnancy exposure registries tend to be too small and often do not include sufficient numbers of racial and ethnic minorities to provide useful information about them.2 In addition to patient recruitment methodologies put forth in the FDA guidance document, there should be an emphasis on collecting information relevant to different racial and ethnic subgroups. For example, African American women have higher rates of pregnancy-related complications such as preeclampsia or hypertension, which requires management with medication.3,4 In contrast, white women have higher rates of antidepressant use.5,6 The data collected need to include sufficient diversity to establish safety profile for drugs use in various subgroups during pregnancy.

Medication outcomes also have the potential to be dose related. As mentioned in the FDA guidance document, nearly half of all pregnancies in the US are unintended, and that inevitably results in unintended exposure to certain drugs. It is therefore important to actively recruit these women for retrospective data collection to study the effects of certain drugs on the early stages of fetal development.

In addition to capturing information on medication use across various subgroups, registries should aim to capture women with different insurance coverage. According to the Pregnancy Risk Assessment Monitoring System (PRAMS) data from 2017, nearly 36% of pregnant women seeking prenatal care were uninsured, and 64% were insured through Medicaid. These women can have different health risks and medications use than privately insured women. For example, the PRAMS data show women on Medicaid are more likely than those on private insurance to be diagnosed with diabetes and hypertension. They are also more likely to have preterm labor, low birth-weight babies or both.7 Registries should develop methods to include doctors and facilities that treat patients insured with Medicaid, as well as those who are uninsured who seek care from community centers and organizations such as Planned Parenthood.

Finally, the FDA should require pregnancy registries for all newly marketed drugs used by women of childbearing age. As we have mentioned in our previous comments to the FDA; registries following this guidance should also be required for some older products that are commonly used during pregnancy but have limited or no data about their effects.

For questions or more information, please contact National Center for Health Research at or at (202) 223-4000.

  1. Mitchell AA, Gilboa SM, Werler MM, et al. Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. American Journal of Obstetrics and Gynecology. 2011;205(1):51.e1-8.
  2. Doamekpor L, National Center for Health Research. NCHR Testimony at the FDA Pregnancy Registries Meeting. May 2014.
  3. Ghosh G, Grewal J, Männistö T, et al. Racial/ethnic differences in pregnancy-related hypertensive disease in nulliparous women. Ethnicity & Disease. 2014;24(3):283–289.
  4. U.S. Preventive Services Task Force. Final Update Summary: Preeclampsia: Screening. April 2017.
  5. Cooper WO, Willy ME, Pont SJ, Wayne, Ray WA. Increasing use of antidepressants in pregnancy. American Journal of Obstetrics and Gynecology. 2007;196(6):544.e1-5.
  6. Yamamoto A, McCormick MC, Burris HH. Disparities in antidepressant use in pregnancy. Journal of Perinatology. 2015;35(4):246–251.
  7. Medicaid and CHIP Payment and Access Commission. Advising Congress on Medicaid and CHIP Policy., November 2018.