Antidepressant Use in Pregnancy and Heart Defects: No Link

Nancy A. Melville

February 17, 2016

Women treated with antidepressants during pregnancy show no increased risk of having children with congenital heart anomalies. However, the risk is significantly higher among women with many characteristics often associated with antidepressant use, new research shows.

"Women who were prescribed SSRIs [selective serotonin reuptake inhibitors] in pregnancy...were found not to be at greater risk of giving birth to a child with a congenital heart anomaly than other women," the authors, led by Irene Petersen, PhD, of the University College of London's Department of Primary Care and Population, in the United Kingdom, write. "Neither did women who were prescribed non-SSRI antidepressants in pregnancy experience a higher risk," they write.

"The finding persisted after adjustment for sociodemographic status, lifestyle characteristics, and other psychotropic medication," they add.

Previous research that examined the risk for heart defects in children of mothers who used antidepressants during pregnancy has yielded conflicting results.

However, studies often fail to control for the variety of important risk factors that can be associated with antidepressant use or depression, the authors emphasize.

"It is amazing how many studies that have been published where [the authors] did not account for the most common risk factors," Dr Petersen told Medscape Medical News.

"Often the databases or population registries studies do not have information on diabetes, alcohol, obesity, and illicit drug use available."

The study was published in the January issue of the Journal of Clinical Psychiatry.

Info on Potential Confounders

For the study, the researchers evaluated data from the Health Improvement Network primary care database in the United Kingdom. Their study included 5154 women who were treated with SSRIs before pregnancy, 2776 who received the drugs during pregnancy, and 992 who received antidepressants other than SSRIs during pregnancy.

The cohorts were compared with 200,213 women who were not treated with antidepressants before or during pregnancy.

Among all of the groups combined, fewer than 1% of children had a record of congenital heart anomalies during the first 5 years after birth.

There were no significant differences in rates of the heart defects between women who were and those who were not prescribed SSRI or non-SSRI antidepressants. The findings were consistent after adjusting for factors that included sociodemographic status, lifestyle characteristics, and use of other psychotropic medication.

Other factors, however, that were associated with an increased risk of having a child with congenital heart anomalies included diabetes (odds ratio [OR] = 2.23; 95% confidence interval [CI], 1.79 - 2.77), increasing age (OR = 1.01; 95% CI, 1.00 - 1.02), having a problem with the use of alcohol (OR = 2.58; 95% CI, 1.55 - 4.29), illicit drug use (OR = 1.89; 95% CI, 1.09 - 3.25), and having a body mass index (BMI) greater than 30 (OR = 1.38; 95% CI, 1.13 - 1.69).

Importantly, the rates of all of those risk factors were higher among women taking antidepressants, including SSRIs and non-SSRIs, before and during pregnancy, compared with those not taking the medications: Approximately one third of the women prescribed antidepressants before or during pregnancy were smokers, compared with 19% of those not prescribed the drugs; about 8% to 10% were obese vs 4.9% of the women not receiving antidepressants; diabetes was present in 3.5% to 4.8% of the women prescribed any antidepressants, compared with 2.6%; 1.8% to 6.5% had records of illicit drug use, and 1.6% to 4.1% had records of alcohol problems, compared with 0.4% of both measures in the group that did not receive antidepressants.

"Although the absolute number of individuals with entries of alcohol problems and illicit drug use was small, such use was up to 16 times more common among women who continued antidepressants in pregnancy," the authors note.

Other findings included the fact that among women treated with non-SSRI antidepressants, the rate of births before 37 weeks (15%) was twice that in comparison with women who were not treated with antidepressants (15% vs 7.5%). The rate among SSRI-treated patients ranged from 8.6% to 10.7%, which is consistent with previous research.

The most commonly used SSRIs included fluoxetine, citalopram, paroxetine, sertraline, and escitalopram, and the most common non-SSRIs were venlafaxine, amitriptyline, dosulepin, lofepramine, and clomipramine.

Other research, including a meta-analysis published last month, as reported by Medscape Medical News, suggested a risk for congenital heart defects in association with use of the SSRI paroxetine. In addition, it has been suggested that serotonin's role as a signaling molecule may influence heart development during embryogenesis.

As with other previous research, it was speculated that residual confounding may have played a role in the results.

With depression in pregnancy having been shown to be associated with important risks to the mother and fetus alike, the authors call for careful consideration in the use of antidepressants in pregnancy on a case-by-case basis.

"For some women, pregnancy may be the right time to discontinue treatment, whereas for others, it may not," Dr Petersen said.

"It is important to recognize that the proportion of women with diabetes, a history of alcohol and illicit drug problems is higher among women who are treated with antidepressants, and that these are independent risk factors for congenital heart problems.

"Likewise, it is important to consider the negative impact of depression on the health and well-being of both mother and child," she added.

Important Contribution

The findings shed important light on the factors surrounding depression in pregnancy that may or may not present a risk to the fetus, said Krista F. Huybrechts, PhD, assistant professor of medicine at Harvard Medical School and epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital, in Boston, Massachusetts.

"This study adds to the growing body of evidence that SSRI exposure early in pregnancy does not appear to significantly increase the risk of congenital cardiac malformations," she told Medscape Medical News.

Dr Huybrechts and her team found similar results in a study of theirs published in 2014 in the New England Journal of Medicine.

That study, which compared rates of cardiac malformations among offspring of women treated with SSRIs in the first trimester with those who were not exposed, similarly showed an increased risk in the SSRI group that was attenuated after adjustment for confounders.

Considering the new study's findings on the role of risk factors with antidepressant use, Dr Huybrechts recommended that clinicians weigh all factors carefully in treating depression during pregnancy.

"There are multiple factors involved in a clinician's decision about whether to continue or discontinue treatment with antidepressants during pregnancy, including evidence suggesting a possible increase in the risk of preterm birth and neonatal withdrawal and the safety issues that can result from withholding a needed treatment in pregnant women with severe depression that requires medication," she said.

"The accumulated evidence from well-controlled studies suggests that the risk of cardiac malformations should not be an important consideration."

The authors and Dr Huybrechts have disclosed no relevant financial relationships.

J Clin Psychiatry. 2016;77:e36–e42. Abstract

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