Association of Panic Disorder, Generalized Anxiety Disorder, and Benzodiazepine Treatment During Pregnancy With Risk of Adverse Birth Outcomes

Kimberly Ann Yonkers, Kathryn Gilstad-Hayden, Ariadna Forray, Heather S Lipkind
JAMA Psychiatry 2017 November 1, 74 (11): 1145-1152

Importance: Registry data show that maternal panic disorder, or anxiety disorders in general, increase the risk for adverse pregnancy outcomes. However, diagnoses from registries may be imprecise and may not consider potential confounding factors, such as treatment with medication and maternal substance use.

Objective: To determine whether panic disorder or generalized anxiety disorder (GAD) in pregnancy, or medications used to treat these conditions, are associated with adverse maternal or neonatal pregnancy outcomes.

Design, Setting, and Participants: This cohort study conducted between July 1, 2005, and July 14, 2009, recruited women at 137 obstetric practices in Connecticut and Massachusetts before 17 weeks of pregnancy and reassessed them at 28 (±4) weeks of pregnancy and 8 (±4) weeks postpartum. Psychiatric diagnoses were determined by answers to the World Mental Health Composite International Diagnostic Interview. Assessments also gathered information on treatment with medications and confounding factors, such as substance use, previous adverse birth outcomes, and demographic factors.

Exposure: Panic disorder, GAD, or use of benzodiazepines or serotonin reuptake inhibitors.

Main Outcomes and Measures: Among mothers: preterm birth, cesarean delivery, and hypertensive diseases of pregnancy. Among neonates: low birth weight, use of minor respiratory interventions, and use of ventilatory support.

Results: Of the 2654 women in the final analysis (mean [SD] age, 31.0 [5.7] years), most were non-Hispanic white (1957 [73.7%]), 98 had panic disorder, 252 had GAD, 67 were treated with a benzodiazepine, and 293 were treated with a serotonin reuptake inhibitor during pregnancy. In adjusted models, neither panic disorder nor GAD was associated with maternal or neonatal complications of interest. Most medication exposures occurred early in pregnancy. Maternal benzodiazepine use was associated with cesarean delivery (odds ratio [OR], 2.45; 95% CI, 1.36-4.40), low birth weight (OR, 3.41; 95% CI, 1.61-7.26), and use of ventilatory support for the newborn (OR, 2.85; 95% CI, 1.2-6.9). Maternal serotonin reuptake inhibitor use was associated with hypertensive diseases of pregnancy (OR, 2.82; 95% CI, 1.58-5.04), preterm birth (OR, 1.56; 95% CI, 1.02-2.38), and use of minor respiratory interventions (OR, 1.81; 95% CI, 1.39-2.37). With maternal benzodiazepine treatment, rates of ventilatory support increased by 61 of 1000 neonates and duration of gestation was shortened by 3.6 days; with maternal serotonin reuptake inhibitor use, gestation was shortened by 1.8 days, 152 of 1000 additional newborns required minor respiratory interventions, and 53 of 1000 additional women experienced hypertensive diseases of pregnancy.

Conclusions and Relevance: Panic disorder and GAD do not contribute to adverse pregnancy complications. Women may require treatment with medications during pregnancy, which can shorten the duration of gestation slightly. Maternal treatment with a serotonin reuptake inhibitor is also associated with hypertensive disease of pregnancy and cesarean delivery.


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