Benzodiazepine Use During Pregnancy May Be Associated With Miscarriage

Women who use benzodiazepines during pregnancy may be more likely to experience miscarriage, according to a report in JAMA Psychiatry.

This finding underscores “the necessity for health care professionals to meticulously balance the risk-benefit ratio when considering the use of benzodiazepines to treat psychiatric and sleep disorders during pregnancy,” wrote lead author Fei-Yuan Hsiao, Ph.D., M.S., of the National Taiwan University College of Medicine and colleagues.

The population-based study in Taiwan used two national data sources to investigate the association between benzodiazepine use during pregnancy and the risk of miscarriage: the National Health Insurance database and the National Birth Certificate Application database. A total of 134, 864 pregnancies resulting in miscarriage between 2004 and 2018 were matched to an equal number of pregnancies carried to term, adjusted for demographic characteristics and pre-pregnancy comorbidities. Miscarriage was defined as any pregnancy loss occurring between the first prenatal care visit (usually 8 weeks) and the 19th completed week of pregnancy. Included in the analysis were 13 long-acting and 12 short-acting benzodiazepines.

For each pregnancy, benzodiazepine exposure occurring 1 to 28 days before miscarriage was considered the risk period. To account for potential variables like genetics and family environment, the women’s benzodiazepine use and other medical and lifestyle data during the risk period were compared with those from two reference periods: 31 to 58 days and 181 to 208 days before the last menstrual period.

Of the pregnancies resulting in miscarriage, 1,502 had been exposed to benzodiazepines during the risk period only, while among pregnancies carried to term, 753 had been exposed during the risk period only. After factoring in differences between the groups as well as differences during the reference periods, the researchers calculated that exposure to benzodiazepines was associated with a 69% higher risk of miscarriage.

In addition, each benzodiazepine in the study was associated with an increased risk of miscarriage, ranging from 39% for alprazolam to 152% for fludiazepam. Additionally, a dose-response association was observed between benzodiazepine exposure and miscarriage, with the risk increasing from 61% for low-dose exposure to 86% for high-dose exposure.

“These findings suggest that caution is warranted when using benzodiazepines during early pregnancy,” the authors wrote. “Prescribing benzodiazepines should only be considered following a comprehensive evaluation of the potential benefits and risks for both the mother and the child.”

For related information, see the Psychiatric News article “Perinatal Treatment Requires Careful Risks, Benefit Consideration.”

(Image: Getty Images/iStock/damircudic)

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Prescribing Lithium During Pregnancy Requires Careful Balancing of Benefits, Risks

The risk of giving birth to a child with birth defects may be slightly higher in women with bipolar disorder who take lithium compared with those who do not take lithium, suggests a meta-analysis in AJP in Advance. However, these slight risks may be outweighed by the dangers to mother and child of relapse of illness episodes (either depressive or manic), the authors of the analysis caution.

“Pregnancy should not be considered an absolute contraindication to lithium prescription, given the relatively small increase in risk for any malformation or cardiac malformations, and given that such events, fortunately, remain rare,” wrote Michele Fornaro, M.D., Ph.D., of the University of Naples Federico II School of Medicine and colleagues. In comparison, women with bipolar disorder who are not in treatment may experience frequent relapse of mood episodes during pregnancy and the postpartum period. These episodes themselves can harm the health of the mother and the fetus or newborn.

Fornaro and colleagues compiled data from 29 studies that assessed the efficacy and safety outcomes of lithium treatment during pregnancy and the postpartum period. They found that lithium exposure was not associated with any risk of preterm birth or low birth weight. Compared with women who were not prescribed lithium, however, those who took lithium any time during pregnancy had 1.81 times greater odds of giving birth to a child with a congenital defect and 1.86 times greater odds of giving birth to a child with a cardiac birth defect; these risks were slightly higher for women who started taking lithium in the first trimester (1.81 times for any congenital defect and 1.96 times for a cardiac defect). Women who took lithium in the first trimester also had 3.77 times greater odds of a miscarriage. When the comparisons were limited to women with bipolar disorder, however, women who took lithium did not have any increased risk of miscarriage compared with those who did not, and no increased risk of cardiac birth defects when lithium was taken in the second and/or third trimester.

Women with bipolar disorder who took lithium were 84% less likely to relapse during the postpartum period than women with bipolar disorder who did not take lithium during pregnancy.

To read more on this topic, see the Psychiatric News article “How to Manage Meds Before, During, and After Pregnancy.”

(Image: iStock/serezniy)

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