Psychiatric disorders during pregnancy, including panic disorder and generalized anxiety disorder (GAD), with or without major depressive episode (MDE), are not associated with maternal or neonatal complications, new research suggests.
However, investigators did find an association between treatment for these conditions and adverse outcomes.
The cohort study, which assessed more than 2600 women, showed that pregnant women who used of benzodiazepines were at increased risk for cesarean delivery, as well as a low birth weight and ventilatory support for the newborn, compared with pregnant women who did not use the drugs.
Use of a selective serotonin reuptake inhibitor (SRI) was associated with maternal hypertension in pregnancy and minor respiratory interventions for the newborn.
Use of both types of drugs was also associated with an increased risk for preterm birth, shortening gestation by 3.6 and 1.8 days, respectively. But, “this is actually not a lot of time,” lead author Kimberly Ann Yonkers, MD, professor of psychiatry at Yale School of Medicine, and director of the Center for Wellbeing of Women and Mothers, New Haven, Connecticut, told Medscape Medical News.
“There’s often this sense that treatment for psychiatric disorders is somehow optional, but it isn’t. These are serious conditions, and without treatment, many women would find it impossible to carry a pregnancy to term,” said Dr Yonkers.
“So, just like those with diabetes or epilepsy, these women have a right to treatment. We just have to do our due diligence and understand what some of the risks and benefits are.”
She added that the main take-away for the study is optimistic: “It’s that women are not harming their babies if they have one of these psychiatric conditions.”
The findings were published online September 13 in JAMA Psychiatry.
“Imprecise Data”
The investigators note that although previous research suggests an association between maternal anxiety disorders and adverse pregnancy outcomes, those reports relied on registry data, which can be “imprecise and may not consider potential confounding factors, such as treatment with medication and maternal substance abuse.”
“Registry data can be a little bit anemic,” said Dr Yonkers. “Part of the reason is that panic disorder is not as easy to capture as something like depression. A diagnostic interview is better [in order] to make sure patients have the requisite symptoms.” She added that GAD is also not captured well in registry data.
“So we were concerned about the accuracy of some of the data that might be available in a registry,” she said. “Also, while there has been a lot of attention paid to possible associations between adverse maternal or neonatal outcomes and depression or major depressive episode or their treatments, there hasn’t been a lot on anxiety disorders, which can be quite debilitating especially during pregnancy.”
The parent study of the current cohort analysis was conducted between July 2005 and July 2009 and included 137 obstetric practices in Connecticut and Massachusetts.
Inclusion criteria included being 18 years of age or older and not having reached 17 weeks’ pregnancy at baseline. Exclusion criteria included receiving insulin for diabetes.
In-home interview assessments were conducted at baseline, and telephone interviews were conducted at about 28 weeks of pregnancy and at about 8 weeks after delivery. Version 2.1 of the World Mental Health Composite International Diagnostic Interview was administered at each visit.
In addition, the Edinburgh Postnatal Depression Scale, which includes an anxiety subscale, was administered and the Mini-International Neuropsychiatric Interview was used to assess posttraumatic stress disorder.
Of the 2654 participants (mean age, 31.0 years) included in the current analysis, 252 had GAD and 98 had panic disorder. Also, 293 received SRI treatment some time during pregnancy, and 67 received benzodiazepines.
For adverse outcomes, medical record data were used to determine birth weight and delivery mode; low birth weight was defined as less than 2500 g; and incident hypertension after 20 weeks of pregnancy or preeclampsia made up “hypertensive diseases of pregnancy.”
Delee or tracheal suction and oxygen administration were classified as “minor neonatal respiratory interventions.”
Anxiety Not a Risk Factor
After adjusting for possible confounders, such as age, race, educational level, smoking or heavy drinking status, and use of illicit drugs, none of the maternal or neonatal complications studied were significantly associated with GAD or panic disorder. Comorbid MDEs for those with these conditions did not increase risk.
The lack of association with adverse outcomes was a bit surprising, said Dr Yonkers. “We did think we’d find a potential association, especially between panic and preterm birth, but we did not,” she said.
“There’s a lot of reasons to think that other factors may account for some of the associations found in other research.”
As shown in the following table, treatments for GAD or panic disorder were linked to some adverse outcomes.
Table. Adjusted Risk for Adverse Outcomes by Treatment
| Outcome | Benzodiazepine Use (Odds Ratio; 95% CI*) | SRI Use (Odds Ratio; 95% CI*) |
|---|---|---|
| Maternal | ||
| Cesarean delivery | 2.45; 1.36 – 4.40 | 0.91; 0.66 -1.20 |
| Preterm birth | 1.98; 0.97 – 4.04 | 1.56; 1.02 – 2.38 |
| Hypertensive diseases of pregnancy | 1.49; 0.53 – 4.18 | 2.82; 1.58 – 5.04 |
| Neonatal | ||
| Low birth weight | 3.41; 1.61 – 7.26 | 1.10; 0.63 – 1.93 |
| Ventilatory support | 2.85; 1.17 – 6.94 | 0.61; 0.30 – 1.24 |
| Minor respiratory intervention | 1.35; 0.80 – 2.30 | 1.81; 1.39 – 2.37 |
| *95% CI, 95% confidence interval | ||
“Estimated probabilities translate to 200 additional cesarean deliveries per 1000 births” for exposure to benzodiazepines (95% CI, 96 – 138) and to 61 additional newborns per 1000 births needing ventilatory support (95% CI, 46 – 76), report the investigators.
For SRI use, the probabilities translated to 43 additional preterm births per 1000 births (95% CI, 35 – 51), 152 additional cases per 1000 of minor respiratory interventions needed (95% CI, 47 – 158), and 53 additional women per 1000 experiencing hypertensive diseases of pregnancy (95% CI, 46 – 60).
Battling “Alarmist” Literature
Although the researchers note that including only 98 women with panic disorder may have limited the power for finding an association with adverse outcomes, Dr Yonkers pointed out that “98 is not that small a number.
“That’s the thing ― you either have very large numbers and perhaps don’t have the detail or ability to control for a variety of factors, or you have fewer women but are able to control for a number of factors,” she said.
Overall, “there can be a lot of alarmism is the literature, and so women worry if their illness is going to have an effect on their baby,” said Dr Yonkers. “I just want to reassure them that just because they have an illness they didn’t ask for, it doesn’t mean they’re contributing to problems in their pregnancy and in their offspring’s well-being.”
As for potential risks associated with treatment, “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,” write the investigators. They add that clinicians and patients should discuss specific risk-benefit ratios for treatment.
The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr Yonkers reports receiving consulting fees from Juniper and Marinus Pharmaceuticals and royalties for a chapter written for UpToDate. The remaining study authors have reported no relevant financial relationships.
JAMA Psychiatry. Published online September 13, 2017. Abstract
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