Maternal Antidepressant Use Linked to Some Specific Birth Defects

Associations between maternal antidepressant use and specific birth defects exist, particularly among mothers taking venlafaxine, according to a recent case-control study published in JAMA Psychiatry.

However, these results need confirmation due to the lack of published literature on venlafaxine use during pregnancy and the associated risk for birth defects. The researchers added that studies to assess birth defect risk among women taking antidepressants should also account for underlying conditions. This is clinically relevant, as “findings from such analyses can support work to identify medications with the highest and lowest birth defect risks independent of the underlying condition.”

Depressive and anxiety disorders disproportionately affect reproductive-aged women in the United States, with first-line treatments for these disorders including antidepressants and evidence-supported psychotherapies.

“Approximately 10% to 15% of US reproductive-aged women are prescribed antidepressants annually,” the researchers wrote. “These disorders are prevalent among pregnant women, with 6% to 8% of US pregnant women reporting being prescribed or using an antidepressant.”

Although previous research has looked into the overall effect of antidepressant use on birth defects, fewer studies have assessed associations between specific birth defects and individual antidepressants. As such, “the clinical usefulness of prior research is limited by the inability to account for associations between the underlying condition and birth defects, which may confound associations between early pregnancy antidepressant use and birth defect risk and possibly yield inaccurate risk estimates,” the authors wrote.

Using data from the National Birth Defects Prevention Study (NBDPS), a US population-based study, researchers used multivariable logistic regression to calculate adjusted odds ratios (aORs). NBDPS took place between 1997 and 2011 in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah. The study was designed to examine risk factors for major structural birth defects.

Controls comprised randomly sampled live-born infants without major birth defects from the same birth months and state as those with defects. Overall, the study population included 30,630 case mothers of infants with birth defects and 11,478 control mothers; all were ages 12 to 53 years.

In phone interviews, mothers were asked about their use of citalopram, fluoxetine, paroxetine, sertraline, venlafaxine, and bupropion during the 3 months before conception or during pregnancy (ie, early pregnancy). Additional antidepressants could be reported when mothers were asked to report any medications used during the same time period.

The study population was found to use the following drug classes: selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants and other norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, and other antidepressants. In total, early pregnancy antidepressant use was reported by 1562 case mothers (5.1%) and 467 control mothers (4.1%).

Analyses revealed:

• In the control mothers, elevated aORs were observed for individual SSRIs and selected congenital heart defects (CHDs) (fluoxetine and anomalous pulmonary venous return: aOR, 2.56; 95% CI, 1.10-5.93). This association was attenuated after partially accounting for underlying conditions (aOR, 1.89; 95% CI, 0.56-6.42)
• Associations between SSRIs and non-CHD birth defects often persisted or strengthened after partially accounting for underlying conditions (citalopram and diaphragmatic hernia: aOR, 5.11; 95% CI, 1.29-20.24)
• Mothers who used paroxetine or fluoxetine in early pregnancy had the highest proportion of elevated aORs with specific birth defects among the SSRIs examined, followed by citalopram and sertraline
• After accounting for the underlying condition, the elevated venlafaxine aORs persisted for most defects; in some instances, the association strength increased (anencephaly and craniorachischisis: aOR, 9.14; 95% CI, 1.91-43.83)
• After accounting for the underlying condition, researchers observed an elevated aOR for bupropion and diaphragmatic hernia (aOR, 6.50; 95% CI, 1.85-22.88)
• Escitalopram had no elevated aORs

“In our analysis, associations between the SSRIs and specific heart defects were largely attenuated when compared with women who took antidepressants only outside of early pregnancy,” the researchers wrote. “Our findings suggest that the elevated associations between heart defects and antidepressants may be confounded by the underlying condition.”

Differences in disease severity, relapse risk, or other clinical differences among women who select specific antidepressants were not assessed, marking a limitation to the study. Due to the retrospective nature of data collection, recall bias may also have been present

“Depressive and anxiety disorder treatment during pregnancy remains clinically challenging, in part because of the competing reproductive safety risks of poorly treated mental health disorders and potential safety concerns regarding antidepressant treatment during pregnancy,” researchers conclude.

For pregnant patients with depression or anxiety, “fully informed decision-making requires balancing the risks and benefits of any proposed intervention against the maternal and fetal risks of untreated depression or anxiety, mindful that with every pregnancy an underlying risk of a birth defect exists regardless of antidepressant treatment.”

Reference

Anderson KN, Lind JN, Simeone RM, et al. Maternal use of specific antidepressant medications during early pregnancy and the risk of selected birth defects. JAMA Psychiatry. Published online August 5, 2020. doi:10.1001/jamapsychiatry.2020.2453