Risk of major malformations in infants after first-trimester exposure to benzodiazepines: Results from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications

Depress Anxiety. 2022 Dec;39(12):751-759. doi: 10.1002/da.23280. Epub 2022 Jul 31.


Background: Perinatal anxiety affects 20% of women, and untreated maternal mental illness can cause deleterious effects for women and their children. Benzodiazepines are commonly used to treat anxiety disorders. The reported risk of congenital malformations after in utero benzodiazepine exposure has been inconsistent.

Methods: The Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications prospectively enrolls pregnant women with psychiatric illness who take one or more psychiatric medications. Participants are interviewed twice during pregnancy and at 12 weeks postpartum. Women taking any benzodiazepine during the first trimester of pregnancy were compared with a group of women taking psychiatric medication(s) other than benzodiazepines during pregnancy.

Results: A total of 1053 women were eligible for this analysis; N = 151 women who had taken a benzodiazepine during the first trimester, and the comparison group was N = 902 women. There were 5 (3.21%) major malformations in the exposure group and 32 (3.46%) in the comparison group (odds ratio 0.92; 95% confidence interval 0.35-2.41).

Conclusion: This ongoing pregnancy registry offers reassurance that benzodiazepines do not appear to have major teratogenic effects. The precision of relative risk estimate will improve as the number of participants increases. This and other pregnancy registries will better inform the reproductive safety of benzodiazepines.

Trial registration: ClinicalTrials.gov NCT01246765.

Keywords: anxiety; pharmacotherapy; pregnancy and postpartum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzodiazepines* / adverse effects
  • Child
  • Female
  • Hospitals, General
  • Humans
  • Infant
  • Pregnancy
  • Pregnancy Complications* / drug therapy
  • Pregnancy Complications* / epidemiology
  • Pregnancy Trimester, First
  • Registries


  • Benzodiazepines

Associated data

  • ClinicalTrials.gov/NCT01246765