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TITLE: Incident Exposure to Benzodiazepine in early Pregnancy and the Risk of Spontaneous AbortionABSTRACT IMPORTANCE Benzodiazepine use in early pregnancy is associated with spontaneous abortion (SA). However, no one has examined the association between specific benzodiazepine agent exposure and the risk of SA.OBJECTIVE To quantify the risk of SA associated with gestational benzodiazepine incident use as a class as well as by duration of action, and by specific benzodiazepine agents.DESIGN AND SETTING We conducted a nested case-control study within the Quebec Pregnancy Cohort (QPC), which includes all pregnancies covered by the Quebec Prescription Drug plan from 01/01/1998 to 31/12/2015. Conditional logistic regression models were used to calculate odds ratios (OR), and 95% confidence intervals (CI).MAIN OUTCOME AND PARTICIPANTS SA was defined as a pregnancy loss before the 19th completed week of gestation. Each case of SA was randomly matched with up to five controls.EXPOSURE Benzodiazepine exposure was defined as u2265one filled prescription between the first day of the last menstrual period and the index date. Benzodiazepine exposure was categorized as 1) overall use, 2) long- or short-acting, and 3) by specific benzodiazepine agents RESULTS Of the 442,066 pregnancies who were included in the QPC, a total of 27,147 (6.1%) ending with a SA, with a mean (SD) maternal age of 24.2 (6.5) years. Among pregnancies ending with a SA 375 (1.4%) were exposed to benzodiazepine in early pregnancy, as compared to 788 (0.6%) of the 134,305 matched controls (crude OR, 2.39; 95%CI, 2.10-2.73). Adjusting for potential confounders including maternal mood and anxiety disorders before pregnancy, and compared to non-use, early pregnancy benzodiazepine exposure was associated with an increased risk of SA (aOR, 1.85; 95%CI, 1.61-2.12). The risk of SA was similar among pregnancies exposed to short-acting (aOR 1.81, 95%CI 1.55-2.12; 284 exposed cases) and long-acting benzodiazepines (aOR 1.73, 95%CI 1.31-2.28; 98 exposed cases). Specific benzodiazepine agents were all independently associated with an increased risk of SA (aOR from 3.43 to 1.13). CONCLUSIONS AND RELEVANCE An increased risk of SA was observed among early pregnancies with incident exposure to short and long-acting benzodiazepines, as well as all specific benzodiazepine agents.
03 - INDIVIDUAL BENZODIAZEPINE EXPOSURE DURING EARLY PREGNANCY AND THE RISK OF SPONTANEOUS ABORTION
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