The safety of benzodiazepines and related drugs during pregnancy: an updated meta-analysis of cohort studies.

ABSTRACT

PURPOSE: The prevalence of benzodiazepines and related drugs (BZRDs) use during pregnancy increased sharply in recent years. Thus, there are concerns regarding the pregnancy outcomes following exposure to BZRDs. METHODS: Two electronic databases were thoroughly searched to identify related clinical studies published from inception until June 2023. English-language cohort studies with high-quality comparing antenatal BZRDs exposure to an unexposed group on any delivery outcome were included. RESULTS: Ten cohort studies that estimated adverse neonatal outcomes associated with exposure to BZRDs during pregnancy were included. Exposure to BZRDs during pregnancy was associated with an increased risk of congenital malformation [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.05-1.13, p < 0.001], heart malformation (OR 1.13, 95% CI 1.04-1.22, p = 0.003), preterm birth (OR 1.45, 95% CI 1.23-1.7, p < 0.001), SGA (OR 1.18, 95% CI 1.08-1.29, P < 0.001), LBW (OR 1.42, 95% CI 1.25-1.6, p = 0.001) or low Apgar score (OR 1.42, 95% CI 1.08-1.87, p = 0.011),compared with no exposure. Further analyses limited to the first trimester exposure yielded consistent results. CONCLUSIONS: Exposure to BZRDs during pregnancy may be associated with several adverse neonatal outcomes. However, we could not rule out the potential indication confounding factor, further studies with high-quality that control for important confounders are still needed to verify our findings.