Benzodiazepine treatment during pregnancy is associated with a significantly elevated risk for miscarriage.
Benzodiazepine use during pregnancy is associated with an increased risk for miscarriage, according to new research published in JAMA Psychiatry. Health care professionals should carefully consider the risk-benefit ratio when considering benzodiazepine treatment for pregnant individuals.
Although benzodiazepines can cross the placental barrier and may potentially impact fetal development, they are still used to treat psychiatric and sleep disorders in pregnancy. Studying the effect of benzodiazepines on pregnancy outcomes is challenging as pregnant women are often precluded from randomized clinical trials and confounding factors can bias results in observational studies. The current study aimed to quantify the risk for miscarriage associated with benzodiazepine use during pregnancy, using a case-time-control design that accounts for confounders.
This nationwide, population-based study was conducted in Taiwan using pregnancy data from the National Health Insurance (NHI) database from 2002 to 2019 and the National Birth Certificate Application (BCA) database from 2004 to 2018. Researchers employed a case-time-control design to investigate the association between benzodiazepine use during pregnancy and the risk for miscarriage, comprising 2 analyses: a case-crossover analysis and an exposure time-trend control crossover analysis. The researchers used a conditional logistic model to estimate the odds ratios (ORs) of miscarriage.
Overall, the study included 3,067,122 pregnancies among 1,957,601 women (mean age=30.61; SD, 5.91). Of those pregnancies, 136,134 (4.4%) resulted in miscarriage. The researchers then matched the case group of individuals who experienced miscarriage with controls (based on age, psychiatric medical conditions, lifestyle factors, chronic comorbidities, medication use, and health care utilization), resulting in 134,864 pairs of pregnant women.
Among the cases cohort, 1502 pregnant women were exposed to benzodiazepines during the risk period only (1 to 28 days before miscarriage), and 2806 were exposed during the reference period only (181 to 208 days before the last menstrual period). Case-time-control ORs confirmed that exposure to benzodiazepines was associated with an increased risk for miscarriage (OR, 1.69; 95% CI, 1.52-1.87). Further, subgroup analyses revealed a dose-response association between benzodiazepine exposure and miscarriage, with the OR increasing from 1.61 (95% CI, 1.43-1.82) for low-dose exposure to 1.86 (95% CI, 1.53-2.25) for high-dose exposure.
This nationwide case-time-control study revealed that benzodiazepine use during pregnancy was associated with an approximately 70% increased risk for miscarriage, even after accounting for measurable confounders. Study authors concluded, “Prescribing benzodiazepines should only be considered following a comprehensive evaluation of the potential benefits and risks for both the mother and the child.”
The primary limitation of the study is the potential bias resulting from the use of birth certificate-based and claims-based databases for pregnancy and benzodiazepine exposure measures.
This article originally appeared on Psychiatry Advisor