Benzodiazepines in early pregnancy tied to heightened risk of miscarriage

Pregnant women who take a class of drugs that’s often prescribed for anxiety or insomnia may run a higher risk of miscarriage, a new study suggests.

Canadian researchers looked at the outcomes from more than 160,000 early pregnancies and found that women taking benzodiazepines, such as Alprazolam (Xanax), Diazepam (Valium) and Clonazepam (Klonopin), were nearly twice as likely to miscarry, according to the results in JAMA Psychiatry.

“Anxiety and mood disorders need to be treated during pregnancy,” said the study’s lead author, Anick Berard, a professor and research chair on medications, pregnancy and lactation, at the University of Montreal. “Given the high prevalence of anxiety and mood disorders during pregnancy, physicians need to evaluate the risk and benefits of using benzodiazepines given that alternative nonpharmacologic treatments exist.”

The benzodiazepine class of drugs has already been shown to pass into the placenta, and to be associated with certain birth defects, Berard’s team notes. Past studies have also linked the drugs to miscarriage risk, but it wasn’t clear if all versions of these medications carry the same risk.

To look at the impact on pregnancy of specific benzodiazepines, and different forms of the drug that are long- or short-acting, Berard and her colleagues turned to the Quebec Pregnancy Cohort, which included information on 442,066 pregnancies. Included in their analysis were 161,454 women, 27,149 of whom had suffered a miscarriage and 134,305, the control group, had given birth.

The researchers excluded women who had epilepsy, previous benzodiazepine use and/or exposure to substances known to be toxic to fetuses. Also excluded were women whose pregnancy loss occurred before six weeks or after 19 weeks.

Among those who suffered a miscarriage, 375, or 1.4 percent, had used benzodiazepines in early pregnancy. Among the women who successfully delivered, 788, or 0.6 percent, had used benzodiazepines.

After accounting for factors such as mood and anxiety disorders diagnosed before pregnancy, exposure to antidepressants and antipsychotic medications, the researchers found that women who used benzodiazepines early in pregnancy were 1.85 times more likely than those who did not take the drugs to have a miscarriage.

Every form of the drug carried an increased risk of miscarriage. The increase varied by the particular benzodiazepine used, ranging from a low of 1.13 times that of nonusers for flurazepam, to 3.43 times that of nonusers for diazepam. Most of the women only used the drugs for about two weeks, the authors note.

How could these drugs be harming pregnancies?

“Benzodiazepines are anxiolytics and signaling molecules,” Berard said in an email. “It is believed that they disrupt binding and implantation when used in early pregnancy.”

The new study was carefully done and because of this it is “persuasive,” said Catherine Monk, director of the women’s mental health program in obstetrics and gynecology at NewYork-Presbyterian/Columbia University Irving Medical Center in New York City.

“Far too often, primary care providers or obstetricians prescribe benzodiazepines to pregnant women rather than referring her to a mental health provider for a thorough evaluation and engagement in the myriad of non-medicine tools that have strong evidence in treating anxiety and insomnia,” Monk said in an email.

Dr. Priya Gopalan welcomed the new study. “The literature on benzodiazepines in pregnancy is fairly limited compared to the antidepressant literature,” said Gopalan, chief of psychiatry at Magee-Womens Hospital at the University of Pittsburgh Medical Center.

And while there may be possible limitations to the study because of possible confounding factors, it’s one we should “pay attention to,” Gopalan said.

It suggests that physicians should first try other treatment options, such as psychotherapy, Gopalan said.

SOURCE: JAMA Psychiatry, online May 15, 2019.