Previous studies have shown that benzodiazepine use in early pregnancy is associated with spontaneous abortion (SA). The association between specific benzodiazepines and the risk of SA, however, has not been investigated. In this nested case-control study based in Montreal, Quebec, Canada, cases defined as any pregnancy loss between the beginning of the sixth week of gestation and the 19th completed week of pregnancy were matched to controls by gestational age and calendar year (1998-2015) to quantify the risk of SA associated with gestational incident benzodiazepine use by drug class, duration of action, and specific benzodiazepine agent. Of the 442,066 pregnancies included in the Quebec Pregnancy Cohort, 27,149 (6.1%) ended with SA. Of these pregnancies, 1.4% occurred in women exposed to benzodiazepines in early pregnancy; this was compared to 0.6% amongst matched controls (OR 2.39, 95% CI 2.10 to 2.73). This association persisted after adjustment for maternal mood and anxiety disorders before pregnancy (OR 1.85, 95% CI 1.61 to 2.12). Interestingly, the risk conferred with benzodiazepine use was comparable in women that used either short- (OR 1.81, 95% CI 1.55 to 2.12) or long-acting (OR 1.73, 95% CI 1.31 to 2.28) benzodiazepines. This study therefore shows that incident benzodiazepine use in early pregnancy may be associated with an increased risk of SA.
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