Findings offer reassurance to clinicians and pregnant women, say researchers
A large South Korean study published by The BMJ today finds no increased risk of psychiatric or neurodevelopmental disorders, such as ADHD and autism, in children whose mothers used sedative drugs (benzodiazepines or Z-hypnotics) during pregnancy.
Benzodiazepines and Z-hypnotics are used to alleviate anxiety and insomnia, which are among the most common conditions during pregnancy.
Previous studies have examined the short term safety of benzodiazepine and Z-hypnotic use in pregnancy, but evidence on their psychiatric and neurodevelopment effects in children remains scarce.
To fill this evidence gap, researchers used South Korea's National Health Information Database to track nearly 3.8 million children born between 2010 and 2022.
Pregnancies exposed to benzodiazepines or Z-hypnotics were compared with unexposed pregnancies and with women who had used these drugs before but not during pregnancy (past users).
Twelve specific neurodevelopmental and general psychiatric disorders were assessed, including substance use disorder, schizophrenia, personality disorder, intellectual disability, autism, ADHD, and behavioural disorder.
Factors, such as mother's age, income, underlying conditions and other medication use were also taken into account.
Among the 3,809,949 children, 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.
During the tracking period of up to 14 years, a total of 10,060, 311,997, and 15,645 events occurred in the exposed, unexposed, and past user groups, respectively.
Overall, rates of psychiatric disorders were slightly higher (19.2%) in exposed children compared with 13.8% in unexposed children and 16.5% in the past user group.
However, these associations were no longer significant when the researchers used sibling analysis to disentangle drug effects from shared family, genetic, and environmental factors, and no increased risk was found for individual psychiatric disorders.
Further analyses were generally consistent with the main findings, although some estimates, such as exposure in early and late pregnancy, and longer durations of Z-hypnotic use specifically, remained modestly elevated in certain groups.
This is an observational study, so can't establish cause and effect, and the researchers acknowledge that a prescription may not always reflect actual ingestion and their follow-up period may be insufficient to capture late onset conditions such as schizophrenia or personality disorders. What's more, this study was not designed to assess the overall safety of these drugs but specific psychiatric outcomes in children.
However, use of a large, nationally representative database and rigorous methods to overcome confounding suggest the results withstand scrutiny.
As such, they say this study suggests "no substantial evidence that prenatal exposure to benzodiazepines or Z-hypnotics increases the risk of psychiatric disorders in children."
Although these findings provide reassurance about neuropsychiatric safety, further research is needed to clarify the modest elevations seen in some analyses and help inform discussions when considering sedative therapy in pregnancy, they add.
In a linked editorial, researchers agree that this evidence is reassuring, but this does not mean that sedatives should be prescribed without caution.
Clinicians should be mindful of signals around prolonged use and late pregnancy exposure, while also balancing the risks of untreated maternal psychiatric illness, they write.
However, they conclude that this study "offers a compelling example of how observational research can generate reliable estimates of prenatal drug safety.
