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Can Valium and Xanax Cause Increase the Risk of Ectopic Pregnancy?

According to the findings of a recent study, taking benzodiazepines such as Xanax or Valium during pregnancy could significantly raise a woman’s risk of having an ectopic pregnancy. In this study, published by Stanford University in the journal Human Reproduction, scholars found that pregnant women taking these drugs to reduce anxiety or induce sleep have a 50% increased chance of developing life-threatening complications.

Normal Pregnancies vs. Ectopic Pregnancies

In a normal pregnancy, a fertilized egg will attach itself to the lining of the uterus in order to begin the growing process. However, an ectopic pregnancy will occur if the fertilized egg implants and grows outside of the main cavity of the uterus.

zanax-and-ectopicIt most commonly occurs in one of the fallopian tubes, but occasionally an ectopic pregnancy will occur in other areas as well, such as in one of the ovaries, the abdominal cavity, or the cervix. In the case of an ectopic pregnancy, the mother is at a much higher risk of having complications that can result in a birth injury.

Benzodiazepines and Ectopic Pregnancies

In the Stanford study, researchers asked whether women who fill a benzodiazepine prescription before conception are at an increased risk of ectopic pregnancy. Using data from U.S. commercial insurance claims, researchers began a cohort study involving over 1.6 million pregnancies from November 2008 to September 2015. To identify ectopic pregnancies in women that were prescribed benzodiazepines in the 90 days before conception, they used diagnosis and procedure codes.

Benzodiazepines

Benzodiazepines are a class of drugs commonly known as tranquilizers, which are prescribed by doctors to treat anxiety, insomnia, and seizures. Brand names include Xanax, Valium, and Klonopin.

Of the 1,691,366 pregnancies, approximately 1% (almost 18,000) of the women involved had filled at least 2 benzodiazepine prescriptions before conception. There was an excess of 80 ectopic pregnancies per 10,000 pregnancies, and their IPT-weighted risk of ectopic pregnancies was 1.47 times greater for women who took benzodiazepine before conception.

Parting Thoughts

Ultimately, the findings showed that women who took benzodiazepines like Valium or Xanax before conception had a 50% increased risk of having an ectopic pregnancy. Additionally, these women were also at a higher risk of miscarriage, birth injuries, and the child was more likely to have developmental issues.

This study was very important because the information that is produced can be used to help women and their healthcare providers make more fully informed decisions about what drugs they are taking during their reproductive years.

More Relevant Studies of Interest

  1. Prevalence of benzodiazepines and benzodiazepine-related drugs exposure before, during, and after pregnancy: A systematic review and meta-analysis” by Babette Bais, et al., Journal of Affective Disorders, 2020.

Because the maternal use of benzodiazepines during pregnancy is considered fairly common, this study reviews and analyzes the use of these drugs before, during, and after pregnancy to estimate the true prevalence of the use of this drug in pregnant women. The study confirmed that the use of benzodiazepines was common in pregnant women and that the potential risks for both the mother and baby are a major concern. The study concluded that due to the commonality of benzodiazepine prescriptions for pregnant women and the potential risks of taking them, further research is necessary to ensure the short- and long-term maternal safety and explore other non-pharmacological alternative treatments.

  1. Obstetrical and neonatal outcomes after benzodiazepine exposure during pregnancy: Results from a prospective registry of women with psychiatric disorders” by Marlene P. Freeman, et al., General Hospital Psychiatry, 2018.

The goal of this study was to examine the effects of benzodiazepine use during pregnancy on both the mother and unborn baby. There were 794 women that were followed throughout their pregnancy, with data taken from maternal reports and medical records to track maternal outcomes (cesarean sections and preeclampsia) and neonatal outcomes (birth weight, difficulty breathing, difficulty feeding, prematurity, etc…). Results showed that infants exposed to benzodiazepines in utero were more likely to be admitted to the NICU, as well as more likely to have a smaller head circumference, as opposed to unexposed infants. The study also found adverse effects on the infant, such as respiratory and muscular issues.

  1. Association of Maternal Use of Benzodiazepines and Z-Hypnotics During Pregnancy With Motor and Communication Skills and Attention-Deficit/Hyperactivity Disorder Symptoms in Preschoolers” by Angela Lupattelli, Ph.D., et al., JAMA Network, 2019.

A study meant to examine the reproductive safety of maternal benzodiazepine use, and the potential long-term developmental risks it might have on children that have been exposed to it. Researchers hoped to quantify the association between the use of this drug by mothers of preschool-aged children that exhibit symptoms of motor and communication deficits, and attention-deficit hyperactivity disorder. Results showed that there was no increased risk for greater ADHD symptoms or motor deficits following intrauterine exposure to benzodiazepines at different points. However, children born to mothers that were taking these drugs late in their pregnancy did show an increased instance of greater motor and communication deficits than unexposed children.

  1. Use of benzodiazepine medications during pregnancy and potential risk for birth defects, National Birth Defects Prevention Study, 1997-2011” by Sarah C. Tinker, et al., Birth Defects Research, 2019.

This study is meant to look at the conflicting results for the association between benzodiazepine use during pregnancy and birth defects. Researchers analyzed data from the National Birth Defects Prevention Study between the years of 1997-2011 in order to assess the prevalence of factors associated with benzodiazepine use during pregnancy among mothers of infants without any birth defects. Results showed that exposure to benzodiazepines during pregnancy was rare, but may be associated with risks for certain birth defects. However, researchers did also conclude that these results should be interpreted cautiously, as they would need to be replicated to make them more concrete.

  1. Benzodiazepine Intoxication in a Neonate by Maternal Use in Pregnancy” by Bittmann S. Villalon G, Weissenstein A, and Luchter E, Journal of Clinical Cases and Reports, 2019.

This study looks at how the abuse of benzodiazepines by pregnant women can cause intoxication in the fetus. They do this because benzodiazepines can diffuse across the placenta to the fetus due to their high lipid solubility. When the placenta loses its cytotrophoblast following the 6th month of pregnancy, the transport of benzodiazepines is further facilitated. The study looks at a newborn delivered in the 36th week of pregnancy to a mother that used benzodiazepines, which was born “floppy, drowsy, and pulmonary impaired.”

  1. Benzodiazepines in Pregnancy” by Jaye M. Shyken, et al., Clinical Observations and Gynecology, 2019.

A study that looks at the short-term neonatal effects of maternal use of benzodiazepine to treat anxiety. Both anxiety and benzodiazepine use are both associated with low birth weight and preterm delivery, while long-term effects include hypotonia, depression, and withdrawal. These long-term effects are still poorly understood. To avoid withdrawal, the study suggests that these medications be gradually tapered off. Additionally, the study looks at the pharmacology, pregnancy implications, tapering schedules, and alternative treatment strategies for anxiety.

2023 Thoughts

So there is still limited research on the relationship between benzodiazepine use and the risk of ectopic pregnancy. Yes, some studies suggest that the use of benzodiazepines, such as Valium and Xanax, during early pregnancy may increase the risk of ectopic pregnancy. The exact mechanisms by which benzodiazepines might increase the risk of ectopic pregnancy are not fully understood and more research is needed to clarify the relationship.  But more research is needed to confirm these findings.   Has that happened since these studies came out?  No.

So what do you do now?  The key is talking to your doctor and making a choice after considering all of the known potential risks and benefits.