According to the results of a recently published nested case-control study, exposure to any benzodiazepine in early pregnancy may increase the risk of spontaneous abortion (SA).

In order to quantify the risk of SA associated with benzodiazepine use during early pregnancy, the study authors collected data from the Quebec Pregnancy Cohort (QPC) and matched each case randomly with up to 5 controls. Risk was assessed for the medication class overall as well as by duration of action, and specific benzodiazepine used.  

“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),” the study authors explained. They added, “Benzodiazepine exposure was categorized by overall use, long- or short-acting benzodiazepine, and specific benzodiazepine agents.” The main outcome of the study was SA, which was defined as the loss of pregnancy between the start of week 6 and the end of week 19 of gestation.

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The QPC included data on a total of 442,066 pregnancies, of which, 6.1% (N=27,149) ended in SA (mean [SD] maternal age: 24.2 [6.5] years). The study authors reported that 1.4% (N=375) of the pregnancies that ended in SA were in women exposed to benzodiazepines in early pregnancy while 0.6% (788/134,305) of the matched control pregnancies experienced SA (crude odds ratio [OR]: 2.39; 95% CI: 2.10, 2.73). Moreover, an increased risk of SA in women exposed to benzodiazepines in early pregnancy was observed even after adjusting for potential confounders (maternal mood and anxiety disorders before pregnancy) (adjusted OR: 1.85; 95% CI: 1.61, 2.12).

With regard to the type of benzodiazepine used, no significant difference was noted in SA risk in women exposed to short acting vs long acting benzodiazepines in early pregnancy (adjusted OR: 1.81; 95% CI: 1.55, 2.12; N=284 vs adjusted OR: 1.73; 95% CI: 1.31, 2.28; N=98, respectively); each benzodiazepine medication was independently associated with an elevated risk of SA (adjusted OR range: 1.13, 3.43).

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“The findings suggest that health care clinicians should carefully evaluate the risk-benefit ratio of benzodiazepines for the treatment of insomnia and mood or anxiety disorders in early pregnancy,” the authors concluded.

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This article originally appeared on MPR