Pregnant people who take benzodiazepines may be at an increased risk for miscarriage, according to a study published in JAMA Psychiatry.
Despite considering factors that could increase miscarriage risk such as age, psychiatric history, medical conditions, medication use, and other lifestyle factors, researchers found that women who took benzodiazepines before 19 completed weeks of gestation had a roughly 70% higher risk for miscarriage.
Alternative approaches to treating anxiety or sleep disorders, like "psychotherapy and medications such as SSRIs may be reasonable alternatives to benzodiazepines in pregnancy," said Rachel Zhuk, MD, assistant clinical professor in the department of psychiatry at Mount Sinai Health System in New York City. Zhuk was not affiliated with the study.
Experts say the detailed findings from this study underscore the importance of understanding the specific medications and doses involved when considering the potential risks for expectant parents.
"The decision to prescribe benzodiazepines should involve a thorough evaluation of the potential risks to the fetus and benefits to the mother and their offspring," said Fei-Yuan Sharon Hsiao, PhD, director of the Graduate Institute of Clinical Pharmacy at National Taiwan University's College of Medicine, and a coauthor of the study.
Hsiao and her colleagues analyzed information from two large databases containing health and birth information for the majority of the population in Taiwan. By combining these databases, researchers aimed to understand whether using benzodiazepines, a type of medication often prescribed for anxiety, might be linked to a higher risk for miscarriage.
The study included more than 3 million pregnancies among 1,957,601 women, with 136,134 (4.4%) resulting in miscarriage. Scientists focused on pregnancies that ended in miscarriage before the 20th week of gestation, comparing women who had taken benzodiazepines with those who had not.
"This is an impressive study, and it begins to address a major problem in previous studies of risk of miscarriage with benzodiazepine use," said Zhuk said.
The challenge in previous research has been delineating if the drugs contribute the most to a patient's risk, given that the underlying anxiety or depression for which the drugs are prescribed also contribute to the risk for miscarriage, according to Zhuk.
The study examined various benzodiazepines commonly prescribed for anxiety. The study found a 42% (95% CI, 1.13-1.79) increased risk for miscarriage for lorazepam, 39% (1.17-1.66) for alprazolam, 69% (1.31-2.19) for diazepam, and 54% (1.27-1.86) for oxazolam. Fludiazepam was associated with a 252% increased risk (1.89-3.36) for miscarriage. Fludiazepam is not approved by the FDA but is available by prescription in Taiwan.
The findings are consistent with those of a 2019 study published in the same journal that examined more than 400,000 pregnancies in Canada and found an increased risk for pregnancy loss among women taking both short- and long-acting benzodiazepines.
In the current study, researchers observed a dose-dependent relationship, indicating that higher doses of benzodiazepines during early pregnancy were associated with a greater risk for miscarriage.
"Even if there is an association between benzodiazepine use and miscarriage, it's difficult to say how it might change practice: Among medications we might prescribe for acute anxiety or insomnia in pregnancy, lorazepam still has the largest body of reassuring safety data," said Zhuk. Lorazepam has been shown in previous studies to be among the safest benzodiazepines to take if needed during pregnancy, Zhuk said.
While anxiety medications can be helpful, the potential risk for miscarriage should be considered, Hsiao said.
"We may not want to go straight to suggest recommending one type of benzodiazepine over another as the selection of individual benzodiazepine could be considered after a thorough individual risk-to-benefit evaluation," she said.
Zhuk also suggested alternative approaches to treating anxiety or sleep disorders among patients who are considering pregnancy or who become pregnant.
"Psychotherapy and medications like SSRIs may be reasonable alternatives to benzodiazepines in pregnancy," Zhuk said, adding the importance of considering these options before pregnancy if possible.
This study was funded by the National Science and Technology Council. The study authors report no conflicts of interest.
Rachel Zhuk, MD, also reports no relevant conflicts of interest.
Lara Salahi is a freelance journalist.
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