Benzodiazepine Use During Pregnancy Associated With Spontaneous Abortion

An increased risk for spontaneous abortion in early pregnancy was linked to incident exposure to short- and long-acting benzodiazepines.

Benzodiazepine use during early pregnancy is associated with spontaneous abortion (SA), according to research results published in JAMA Psychiatry. In order to determine what type of benzodiazepine exposure increases the risk for SA during early pregnancy, researchers assessed outcomes through drug class, duration of action, and specific benzodiazepine agent.

In a nested case-control study within the Quebec Pregnancy Cohort, researchers evaluated 442,066 pregnancies covered by the Quebec Prescription Drug Insurance Plan, each of which was randomly matched with up to 5 controls. Researchers defined benzodiazepine exposure as 1 or more filled benzodiazepine prescriptions between last period and SA diagnosis. The exposure was then categorized by overall use, long- or short-acting benzodiazepine, and specific benzodiazepine agents. SA was described as pregnancy loss between the 6th and 19th gestational weeks. The odds ratios were calculated using conditional logistic regression models.

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The prevalence of SA in the 262,070 eligible pregnancies was 7.0%, and 27,149 pregnancies with SA met inclusion criteria. The mean (SD) age of the case pregnancies was 24.2 (6.5) years, while the mean (SD) gestational age was 16.7 (3.1) weeks. Of the included cases, 375 of the pregnancies that ended with SA (1.4%) were associated with women exposed to benzodiazepines in early pregnancy vs 788 of the 134,305 matched control pregnancies. When adjusting for potential confounders, benzodiazepine exposure in early pregnancy was associated with an increased risk for SA compared with non-use. This risk was similar in pregnancies exposed to both short- and long-acting benzodiazepines. All benzodiazepine agents were independently associated with SA.

The study was limited by the lack of information about potentially significant confounders like tobacco and alcohol use. In addition, there was no available data on assisted reproduction.

“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,” the researchers wrote. They added that if benzodiazepines are needed, prescribing them for short durations is preferable.


Sheehy O, Zhao J, Bérard A. Association between incident exposure to benzodiazepines in early pregnancy and risk of spontaneous abortion [published online May 15, 2019]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.0963