[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 18.204.227.250. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Views 3,708
Citations 0
Original Investigation
May 15, 2019

Association Between Incident Exposure to Benzodiazepines in Early Pregnancy and Risk of Spontaneous Abortion

Author Affiliations
  • 1Research Center, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
  • 2Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada
JAMA Psychiatry. 2019;76(9):948-957. doi:10.1001/jamapsychiatry.2019.0963
Key Points

Question  Which type of benzodiazepine places women in early pregnancy at increased risk of spontaneous abortion?

Findings  In this nested case-control study of the 442 066 pregnancies included in the Quebec Pregnancy Cohort, an association between benzodiazepine exposure during early pregnancy and risk of spontaneous abortion was observed in all 3 independent models that quantified benzodiazepine use by drug class, duration of action, and specific benzodiazepine agents.

Meaning  The findings suggest that any benzodiazepine use during early pregnancy is associated with spontaneous abortion and that health care clinicians should carefully evaluate the risk-benefit ratio of benzodiazepine use for the treatment of mood and anxiety disorders or insomnia during early pregnancy.

Abstract

Importance  Benzodiazepine use in early pregnancy is associated with spontaneous abortion (SA). However, to date, the association between specific benzodiazepine agent exposure and the risk of SA has not been examined.

Objective  To quantify the risk of SA associated with gestational benzodiazepine incident use by drug class, duration of action, and specific benzodiazepine agent.

Design, Setting, and Participants  This nested case-control study within the Quebec Pregnancy Cohort, Montreal, Quebec, Canada, includes all pregnancies covered by the Quebec Prescription Drug Insurance Plan from January 1, 1998, through December 31, 2015. Each case was randomly matched with up to 5 controls. Statistical analysis was performed from January 1, 1998, through December 31, 2015.

Exposures  Benzodiazepine exposure was defined as 1 or more filled prescriptions between the first day of the last menstrual period and the index date (the calendar date of the SA diagnosis). Benzodiazepine exposure was categorized by overall use, long- or short-acting benzodiazepine, and specific benzodiazepine agents.

Main Outcomes and Measures  Spontaneous abortion defined as a pregnancy loss between the beginning of the sixth week of gestation and the 19th completed week of gestation. Conditional logistic regression models were used to calculate odds ratios (OR) and 95% CIs.

Results  Of the 442 066 pregnancies included in the Quebec Pregnancy Cohort, 27 149 (6.1%) ended with SA, with a mean (SD) maternal age of 24.2 (6.5) years. Among pregnancies ending with SA, 375 (1.4%) were among women exposed to benzodiazepines in early pregnancy compared with 788 (0.6%) of the 134 305 matched control pregnancies (crude OR, 2.39; 95% CI, 2.10-2.73). Adjusting for potential confounders, including maternal mood and anxiety disorders before pregnancy, and compared with nonuse, benzodiazepine exposure in early pregnancy was associated with an increased risk of SA (adjusted OR, 1.85; 95% CI, 1.61-2.12). The risk was similar among pregnancies exposed to short-acting (284 exposed cases; adjusted OR, 1.81; 95% CI, 1.55-2.12) and long-acting (98 exposed cases; adjusted OR, 1.73; 95% CI, 1.31-2.28) benzodiazepines during early pregnancy. All benzodiazepine agents were independently associated with an increased risk of SA (range of adjusted ORs, 1.13-3.43).

Conclusions and Relevance  An increased risk of SA was observed among early pregnancies with incident exposure to short- and long-acting benzodiazepines and all specific benzodiazepine agents during early pregnancy. Insomnia, anxiety, and mood disorders are prevalent during pregnancy; clinicians should carefully evaluate the risk-benefit ratio of prescribing benzodiazepines in early pregnancy since alternative nonpharmacologic treatments exist.

×