In the Journals

Benzodiazepine use early in pregnancy may boost risk of spontaneous abortion

Exposure to any benzodiazepine agent in early pregnancy was associated with a higher risk for spontaneous abortion, according to data published in JAMA Psychiatry.

“Spontaneous abortion is the most common complication in early pregnancy and occurs in 12% to 15% of clinically recognized pregnancies,” Odile Sheehy, MSc, from the Centre Hospitalier Universitaire Sainte-Justine, Montreal, and colleagues wrote. “A population-based study from the United Kingdom found that women exposed to benzodiazepines during pregnancy had a 60% higher risk of spontaneous abortion compared with women with unmedicated depression or anxiety during the first trimester.”

In a nested case-control study, researchers examined the risk for spontaneous abortion linked to gestational benzodiazepine incident use by drug class, duration of action and specific benzodiazepine agent using data on all pregnancies covered by the Quebec Prescription Drug Insurance Plan from 1998 through 2015. They matched each case randomly with up to five controls.

Spontaneous abortion was defined as a pregnancy loss between the start of the sixth week of gestation and the 19th completed week of gestation, and benzodiazepine exposure was categorized by overall use, long- or short-acting benzodiazepine and specific benzodiazepine agents.

Of 442,066 pregnancies in the cohort, 27,149 (6.1%) ended with spontaneous pregnancy (mean maternal age, 24.2 years).

Overall, 375 (1.4%) of the pregnancies that ended with spontaneous abortion were among women exposed to benzodiazepines during early pregnancy compared with 788 (0.6%) of the 134,305 matched control pregnancies (crude OR = 2.39; 95% CI, 2.1-2.73), according to the results.

After adjusting for possible confounders (ie, maternal mood and anxiety disorders before pregnancy), benzodiazepine use in early pregnancy was linked to a higher risk for spontaneous abortion (adjusted OR = 1.85; 95% CI, 1.61-2.12) compared with nonuse.

Sheehy and colleagues found that all benzodiazepine agents were independently tied to an increased risk for spontaneous abortion. The risk for spontaneous abortion was similar among women exposed to short-acting (n = 284; adjusted OR = 1.81; 95% CI, 1.55-2.12) and long-acting (n = 98; adjusted OR = 1.73; 95% CI, 1.31-2.28) benzodiazepines during early pregnancy. In addition, link between benzodiazepines and spontaneous abortion strengthened as the diazepam-equivalent daily dose increased.

“The findings suggest that health care clinicians should carefully evaluate the risk-benefit ratio of benzodiazepines for the treatment of insomnia and mood or anxiety disorders in early pregnancy,” the researchers wrote. “Alternative nonpharmacologic treatments exist and are recommended, but if benzodiazepines are needed, they should be prescribed for short durations.” – by Savannah Demko

Disclosure: Sheehy reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Exposure to any benzodiazepine agent in early pregnancy was associated with a higher risk for spontaneous abortion, according to data published in JAMA Psychiatry.

“Spontaneous abortion is the most common complication in early pregnancy and occurs in 12% to 15% of clinically recognized pregnancies,” Odile Sheehy, MSc, from the Centre Hospitalier Universitaire Sainte-Justine, Montreal, and colleagues wrote. “A population-based study from the United Kingdom found that women exposed to benzodiazepines during pregnancy had a 60% higher risk of spontaneous abortion compared with women with unmedicated depression or anxiety during the first trimester.”

In a nested case-control study, researchers examined the risk for spontaneous abortion linked to gestational benzodiazepine incident use by drug class, duration of action and specific benzodiazepine agent using data on all pregnancies covered by the Quebec Prescription Drug Insurance Plan from 1998 through 2015. They matched each case randomly with up to five controls.

Spontaneous abortion was defined as a pregnancy loss between the start of the sixth week of gestation and the 19th completed week of gestation, and benzodiazepine exposure was categorized by overall use, long- or short-acting benzodiazepine and specific benzodiazepine agents.

Of 442,066 pregnancies in the cohort, 27,149 (6.1%) ended with spontaneous pregnancy (mean maternal age, 24.2 years).

Overall, 375 (1.4%) of the pregnancies that ended with spontaneous abortion were among women exposed to benzodiazepines during early pregnancy compared with 788 (0.6%) of the 134,305 matched control pregnancies (crude OR = 2.39; 95% CI, 2.1-2.73), according to the results.

After adjusting for possible confounders (ie, maternal mood and anxiety disorders before pregnancy), benzodiazepine use in early pregnancy was linked to a higher risk for spontaneous abortion (adjusted OR = 1.85; 95% CI, 1.61-2.12) compared with nonuse.

Sheehy and colleagues found that all benzodiazepine agents were independently tied to an increased risk for spontaneous abortion. The risk for spontaneous abortion was similar among women exposed to short-acting (n = 284; adjusted OR = 1.81; 95% CI, 1.55-2.12) and long-acting (n = 98; adjusted OR = 1.73; 95% CI, 1.31-2.28) benzodiazepines during early pregnancy. In addition, link between benzodiazepines and spontaneous abortion strengthened as the diazepam-equivalent daily dose increased.

“The findings suggest that health care clinicians should carefully evaluate the risk-benefit ratio of benzodiazepines for the treatment of insomnia and mood or anxiety disorders in early pregnancy,” the researchers wrote. “Alternative nonpharmacologic treatments exist and are recommended, but if benzodiazepines are needed, they should be prescribed for short durations.” – by Savannah Demko

Disclosure: Sheehy reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.