Study finds no mental risk from prenatal sedatives

A large South Korean study published by bmj Today no increased risk of psychiatric or neurodevelopmental disorders, such as ADHD and autism, has been found in children whose mothers used sedative drugs (benzodiazepines or z-hypnotics) during pregnancy.

Benzodiazepines and Z-hypnotics are used to reduce anxiety and insomnia, which are one of 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 neurodevelopmental effects in children is 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 pregnancies without exposure and women who had previously used these drugs, but not during pregnancy (previous users).

Twelve specific neurodevelopmental and common mental disorders were evaluated, including substance use disorders, schizophrenia, personality disorders, intellectual disability, autism, ADHD, and conduct disorders.

Factors such as the mother’s age, income, underlying conditions and use of other medications were also taken into account.

Of the 3,809,949 children, 94,482 (2.5%) were exposed to benzodiazepines or Z-hypnotics during pregnancy, 3,715,467 were not exposed, and 147,307 were born to previous 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 previous user groups, respectively.

Overall, the rate of mental disorders was slightly higher (19.2%) in exposed children, compared to 13.8% in exposed children and 16.5% in the previous user group.

However, these associations were no longer significant when researchers used sibling analysis to separate the effects of the drug from shared family, genetic and environmental factors, and no increased risk for individual mental disorders was found.

Further analyzes were generally consistent with the main findings, although some estimates, such as risks in early and late pregnancy, and particularly longer duration of Z-hypnotic use, remained modestly elevated in some groups.

This is an observational study, so cannot establish cause and effect, and the researchers acknowledge that a prescription may not always reflect actual ingestions and that their follow-up period may be insufficient to capture late-onset conditions such as schizophrenia or personality disorders. Furthermore, this study was not designed to assess the overall safety of these medications but to assess specific psychiatric outcomes in children.

However, the use of a large, nationally representative database and rigorous methods to rule out confounding suggest that the results are worth investigating.

Thus, they state that this study suggests that “there is no strong evidence that prenatal exposure to benzodiazepines or Z-hypnotics increases the risk of psychiatric disorders in children.”

Although these findings provide reassurance regarding neuropsychiatric safety, further research is needed to explain the modest increases observed in some analyzes and to help inform the discussion when considering sedative therapy in pregnancy.

In a linked editorial, the researchers agree that this evidence is reassuring, but it does not mean that sedative drugs should be prescribed without caution.

Clinicians must be alert to signs of long-term use and late pregnancy risk, they write, while also balancing the risks of untreated maternal mental illness.

However, they concluded that this study “offers a striking example of how observational research can generate reliable estimates of prenatal drug safety.