In the past few decades, using benzodiazepine has increased substantially in the USA. It is commonly prescribed for indications such as anxiety disorder, insomnia, acute alcohol withdrawal, and seizures. Benzodiazepines include alprazolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, oxazepam, quazepam, temazepam and triazolam.
Women who use benzodiazepines before becoming pregnant are at greater risk of ectopic pregnancies because it could affect muscle contraction in the fallopian tube.
Fig: Various sites and frequency of ectopic pregnancies
Ectopic pregnancies occur in 1 to 2% of pregnancies each year and are a serious health emergency for women. They are responsible for 6-13% of pregnancy-related deaths, and deaths from hemorrhaging are the leading cause of pregnancy-related death in the first trimester of pregnancy. Nearly 95 percent of ectopic pregnancies are implanted in the various segments of the fallopian tube and give rise to fimbrial, ampullary, isthmic, or interstitial tubal pregnancies. The remaining 5 percent of nontubal ectopic pregnancies implant in the ovary, peritoneal cavity, cervix, or prior cesarean scar.
Researchers using data from US commercial insurance claims performed a cohort study of 1,691,366 pregnancies between 1 November 2008 and 30 September 2015. Our study included 1,691,366 pregnancies, of which 30,046 (1.78%) were ectopic and 17,990 (1.06%) were to women who had a benzodiazepine prescription before conception.
Although pelvic infections, use of reproductive technology, intrauterine devices, smoking, and increased age are known to be risk factors for ectopic pregnancies, approximately half of women who have an ectopic pregnancy do not have a known risk factor. This study found that women who have a benzodiazepine prescription before conception are at an increased risk of ectopic pregnancy. This information can help women, and their healthcare providers make more fully informed decisions about benzodiazepine use in their reproductive years.
The researchers suggest that healthcare providers could consider carrying out early pelvic ultrasounds for women who have used benzodiazepines before conception, particularly if they have other risk factors for the condition. However, many women do not know they have an ectopic pregnancy until they start experiencing pain or other complications.
Ectopic pregnancy. Reproduced with permission from Cunningham FG, Leveno KJ, Bloom SL (eds). In Williams Obstetrics, 24th ed. New York, McGraw-Hill Education, 2014.
Elizabeth Wall-Wieler, Thalia K. Robakis, Deirdre J. Lyell, Reem Masarwa, Robert W. Platt, and Suzan L. Carmichael. Benzodiazepine use before conception and risk of ectopic pregnancy. Human Reproduction, Vol.35, No.7, pp. 1685–1692, 2020.