Maternal use of benzodiazepines and non-benzodiazepine hypnotics is not associated with increased risk of psychiatric

1. Maternal use of benzodiazepines or non-benzodiazepine hypnotics (Z-hypnotics) during pregnancy was not associated with an increased risk of psychiatric disorders in offspring after controlling for shared familial factors.

Evidence Rating Level: 2 (Good)

Benzodiazepines and non-benzodiazepine hypnotics (Z-hypnotics) are frequently prescribed drugs among pregnant women who commonly experience psychiatric conditions such as anxiety and insomnia. Although previous studies have not found benzodiazepine or Z-hypnotic exposure during pregnancy to increase risk of congenital malformations, the risk of neurodevelopmental consequences remains uncertain. This study thus examined the associations between prenatal exposure to benzodiazepines and Z-hypnotics and the risk of psychiatric disorders in offspring. This population-based cohort study used data from the National Health Information Database (NHID) and included all liveborn children between 2010 and 2022 who were followed until 2023. Children were classified into three cohorts: those exposed to benzodiazepines or Z-hypnotics during pregnancy, unexposed, and those whose mothers used benzodiazepines or Z-hypnotics before pregnancy (past users). Sibling-controlled analysis was conducted to account for shared familial factors by only including children with at least one sibling with a discordant exposure status. The main outcomes were overall and 12 specific psychiatric disorders in offspring. Among the 3,809,949 liveborn children included in the study, 94,482 (2.5%) were exposed to benzodiazepines or Z-hypnotics during pregnancy, 3,715,467 were unexposed, and 147,307 were born to past users. Offspring exposed to benzodiazepines or Z-hypnotics had a higher risk of any psychiatric disorders compared with those unexposed (hazard ratio [HR] 1.15, 95% CI 1.13 to 1.18) and offspring of past users (HR 1.12, 95% CI 1.09 to 1.15); however, this association was no longer significant in the sibling-controlled analysis (HR 0.99, 95% CI 0.94 to 1.04). No significant associations were observed between offspring exposed to benzodiazepines or Z-hypnotics and risk of individual psychiatric disorders. Modestly elevated but non-significant hazard ratios were observed during the second half of pregnancy and both first and second half of pregnancy with benzodiazepine or Z-hypnotic exposure, and with 30 or more days of Z-hypnotic exposure. Overall, this study found that maternal use of benzodiazepines or Z-hypnotics during pregnancy was not associated with an increased risk of psychiatric disorders in offspring after controlling for shared familial factors. However, modest elevations in point estimates in subgroup analyses cannot rule out the potential for slightly increased risk.

Click here to read this study in the BMJ

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