That is according to a new case-time-control study from National Taiwan University. Researchers found that benzodiazepine use during pregnancy was linked to an increased risk of miscarriage, even after taking into account confounders including genetics and the family environment.
A report in the Journal of the American Medical Association Psychiatry noted that benzodiazepine use during pregnancy is concerning because of potential harmful effects of the drug class on neonates. In response, the study team conducted a nationwide, population-based case-time-control study using Taiwan’s National Birth Certificate Application and the National Health Insurance databases.
The researchers matched 1:1 pregnancies resulting in miscarriage between 2004 and 2018 with a control group. Data were analyzed from August 2022 to March 2023. Their focus was on discordant exposures to benzodiazepines during the risk period (1-28 days before miscarriage) and two reference periods (31-58 days and 181-208 days before the last menstrual period). For the purposes of the study, miscarriage was defined as any pregnancy loss occurring between the first prenatal care visit (usually 8 weeks) and the 19th completed week of pregnancy.
The research included more than 3 million pregnancies among nearly 2 million women, of which 4.4% resulted in miscarriage. The mean (SD) age of the study population was 30.61 (5.91) years.
The results indicated that the use of benzodiazepines during pregnancy was associated with an increased risk of miscarriage (odds ratio [OR], 1.69; 95% CI, 1.52-1.87), and the researchers explained that “consistent findings were observed across multiple sensitivity analyses considering different time windows and accounting for misclassification.”
In subgroup analyses, the authors reported that an increased risk of miscarriage was associated with each commonly used individual benzodiazepine, ranging from case-time-control ORs of 1.39 (95% CI, 1.17-1.66) for alprazolam to 2.52 (95% CI, 1.89-3.36) for fludiazepam.
“These findings underscore the necessity for healthcare professionals to meticulously balance the risk-benefit ratio when considering the use of benzodiazepines to treat psychiatric and sleep disorders during pregnancy,” the researchers emphasized.
Because psychiatric and sleep disorders are common during pregnancy, benzodiazepines, which have anxiolytic and hypnotic properties, are often prescribed to pregnant women for the treatment of anxiety and insomnia. The study suggested that approximately 1.7% of pregnant women are prescribed benzodiazepines during the first trimester and that the use of the drugs has been increasing in recent years.
“When used during pregnancy, benzodiazepines can readily cross the placental barrier and accumulate substantially in embryo and fetal tissues,” the authors point out. “Given their potential role in cell proliferation and differentiation processes, it is plausible that benzodiazepines may cause fetal developmental abnormalities, ultimately leading to miscarriage.”
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