Anxiety Medications Tied to Adverse Pregnancy Outcomes

While the effects of depression and antidepressant use on birth outcomes have been extensively researched—and reported by the media—fewer studies have looked at pregnancy outcomes in women with anxiety.

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A study that tracked outcomes in 2,654 women from Connecticut and Massachusetts through their pregnancies and the postpartum period found that neither panic disorder nor generalized anxiety disorder (GAD) was associated with adverse birth outcomes. Benzodiazepines and serotonin reuptake inhibitors (SRIs)—the two most common anxiety medications—were, however, associated with several adverse outcomes, including low-birth-weight infants and the need for a caesarean delivery.

This study was led by Kimberly Yonkers, M.D., a professor of psychiatry, epidemiology, obstetrics/gynecology, and reproductive sciences at Yale University and editor of APA’s new journal Psychiatric Research and Clinical Practice. She noted that this study had a unique element in that all 2,654 participants had face-to-face interviews with clinicians prior to their 17th week of pregnancy and follow-up phone interviews at 28 weeks and again eight weeks after delivery. Large population studies typically rely on data in health registries or insurance records, which are useful but can have incomplete or inaccurate diagnostic information, she said.

Of the 2,654 women in the study, 252 were diagnosed with GAD and 98 with panic disorder. The authors required only a minimum of one month of symptoms for a GAD diagnosis, whereas DSM-5 guidelines require six months. (The time was shortened in part due to the limited length of the study, but Yonkers said that her team’s prior research has found that even one month of anxiety symptoms is enough to cause significant disability.)

A total of 293 women reported taking an SRI (which includes selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors) during pregnancy, and 67 reported taking benzodiazepines during pregnancy.

The researchers examined the following maternal outcomes: preterm birth (<37 weeks), caesarean delivery, and hypertensive diseases of pregnancy (gestational hypertension or preeclampsia); and neonatal outcomes: low birth weight (less than 2.5 kg), use of minor respiratory interventions (such as oxygen administration or suctioning mucous), and use of ventilatory support. Other outcomes that have been linked with these medications, such as cleft palate and other physical malformations, were not examined due to the sample size.

Regarding medication use, benzodiazepines were associated with increased odds of a caesarean delivery, low-birth-weight infant, and use of neonatal ventilatory support for the newborn. SRIs were associated with increased odds of a preterm birth, use of minor neonatal respiratory interventions, and gestational hypertension or preeclampsia.

While some of the risks are potentially serious, Yonkers and colleagues provided additional context to illustrate what these odds mean in practice: SRI use was estimated to lead to 43 additional preterm births for every 1,000; the absolute difference in the duration of gestation among women who were or were not treated with an SRI was only 1.8 days. Exposure to SRIs was also estimated to result in 53 additional cases of hypertensive disease per 1,000 births and 152 additional newborns per 1,000 in need of minor respiratory support.

Exposure to benzodiazepines was estimated to result in 200 additional caesarean deliveries per 1,000 births, 117 additional low-birth-weight infants per 1,000 births, and 61 additional newborns needing ventilatory support per 1,000 births, the authors reported.

Yonkers said that she hopes that these results, especially the lack of association between the anxiety disorders and adverse outcomes, will be reassuring to women, who can be reluctant to take medications during pregnancy. Still, she emphasized, the findings should not discount the potential severity of anxiety disorders.

“Often, mothers have the clearest sense of their risk of relapse if medication is discontinued, and this relapse bears on her well-being and that of her offspring,” Yonkers and colleagues wrote. “Clinicians and patients need to consider both maternal illness and treatment needs in addition to risks associated with offspring when making treatment decisions in pregnancy.”

This study was published September 13 in JAMA Psychiatry. The research was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ■