Benzodiazepine use during pregnancy and risk of miscarriage

In this case-time-control study, benzodiazepine use during pregnancy was associated with an increased risk of miscarriage, even after accounting for unmeasured confounders, including those related to genetics and the family environment. The study is published in JAMA Psychiatry.

Benzodiazepine use during pregnancy has raised significant concerns due to the potential harmful effects of this drug class on neonates. Studies on the association between benzodiazepine use and the risk of miscarriage are limited.

This was a nationwide, population-based case-time-control study using Taiwan’s National Birth Certificate Application database and the National Health Insurance database. Pregnancies resulting in miscarriage between 2004 and 2018 were included in the case group and were 1:1 matched with exposure time-trend control individuals using disease risk score, considering demographic characteristics and prepregnancy comorbidities. Data were analyzed from August 2022 to March 2023.

This study comprised a total of 3 067 122 pregnancies among 1 957 601 women, 136 134 of which (4.4%) resulted in miscarriage. The mean (SD) age of the study population was 30.61 years. The use of benzodiazepines during pregnancy was associated with an increased risk of miscarriage, and consistent findings were observed across multiple sensitivity analyses considering different time windows and accounting for misclassification. In subgroup analyses, an increased risk of miscarriage was associated with each commonly used individual benzodiazepine, ranging from case-time-control ORs of 1.39 (for alprazolam to 2.52 for fludiazepam.

This nationwide case-time-control study revealed an increased risk of miscarriage associated with benzodiazepine use during pregnancy after accounting for measurable confounders, and results were unlikely to be due to unmeasured confounding. These findings underscore the necessity for health care professionals to meticulously balance the risk-benefit ratio when considering the use of benzodiazepines to treat psychiatric and sleep disorders during pregnancy.

Reference: Meng L, Lin C, Chuang H, Chen L, Hsiao F. Benzodiazepine Use During Pregnancy and Risk of Miscarriage. JAMA Psychiatry. Published online December 27, 2023. DOI:10.1001/jamapsychiatry.2023.4912.