Pregnancy and benzodiazepines

• benzodiazepines cross the placenta - there is a risk of adverse effects in the fetus
  • during late pregnancy, or during labour, high doses may result in neonatal hypotonia and/or hypothermia. A mild neonatal respiratory distress may occur.
  • physical dependence may occur in infants born to mothers who take benzodiazepines chronically
    
• use of both benzodiazepine anxiolytics and anxiety in pregnancy is associated with preterm delivery and low birth weight (2)
  • short-term neonatal effects of hypotonia, depression, and withdrawal are described
  • benzodiazepines are associated with physical dependence and withdrawal symptoms which can be serious

A case-time-control study, benzodiazepine use during pregnancy was associated with an increased risk of miscarriage, even after accounting for unmeasured confounders, including those related to genetics and the family environment (3):

• use of benzodiazepines during pregnancy was associated with an increased risk of miscarriage (OR 1.69, 95%CI 1.52-1.87)
  • for individual agents, ORs ranged from 1.39 (alprazolam) to 2.52 (fludiazepam
• the study authors stated that:
  • observation of an increased risk of miscarriage associated with benzodiazepine use during pregnancy suggests that benzodiazepines should only be used after a thorough evaluation of the potential benefits and risks for both the mother and child

A Korean study (n=5949 exposed, 55,015 controls) found prenatal benzodiazepine (BZD) receptor agonist exposure increased long‑term neurodevelopmental disorder risk (13.9% vs 11.4%; OR 1.25, 95% CI 1.16- 1.35) (4)

• risk was higher with 2nd/3rd‑trimester exposure and with BZDs vs Z drugs
  • class-specific analyses showed stronger associations for benzodiazepines only (odds ratio 1.19, 95% CI: 1.15–1.23) than for Z-drugs only (odds ratio 1.06, 95% CI: 1.04–1.08)

Reference

1. CSM (1997), 23, 10.
2. Shyken JM, Babbar S, Babbar S, Forinash A. Benzodiazepines in Pregnancy. Clin Obstet Gynecol. 2019 Mar;62(1):156-167
3. Meng L, Lin C, Chuang H, Chen L, Hsiao F. Benzodiazepine Use During Pregnancy and Risk of Miscarriage. JAMA Psychiatry. Published online December 27, 2023. doi:10.1001/jamapsychiatry.2023.4912
4. Oh TK, Song I-A. Prenatal exposure to benzodiazepines, Z-drugs and long-term risk of neurodevelopmental disorders in offspring: nationwide cohort study. The British Journal of Psychiatry. Published online 2025:1-7.