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August 12, 2020
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Researchers find more evidence for role of maternal antidepressant use in birth defects

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Certain antidepressants appeared associated with specific birth defects, according to study results published in JAMA Psychiatry.

“We know little about the effects of taking most medications in pregnancy on developing babies because pregnant women are often excluded from studies that determine the safety of new medications,” Jennita Reefhuis, PhD, branch chief of the Birth Defects Monitoring and Research Branch at CDC’s National Center on Birth Defects and Developmental Disabilities, told Healio Psychiatry. “As a result, women and health care providers have limited information about the safety of most medications, especially newer medications, in pregnancy.

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Source: Adobe Stock

“We also know that antidepressants are commonly prescribed to women of reproductive age,” Reefhuis added. “Some previous studies indicated that taking certain antidepressants, such as venlafaxine and selective serotonin reuptake inhibitors, may increase the risk for some birth defects. With this research, we wanted to look at individual medications and their link with individual birth defects, while also trying to separate the effect of medication use from that of the underlying health condition.”

Jennita Reefhuis

Reefhuis and colleagues analyzed data of 30,630 case mothers of infants with birth defects and 11,478 control mothers, obtaining data from the population-based, multicenter case-control National Birth Defects Prevention Study. Control and case mothers provided interview answers after the expected delivery date. The investigators coded self-reported antidepressant exposure to indicate monotherapy antidepressant exposure. Further, they compared women exposed to antidepressants during early pregnancy with those who were not exposed to antidepressants, and they partially accounted for confounding by underlying maternal conditions by comparing the former group with those exposed to antidepressants outside of the critical period for birth defect development.

Results showed 1,562 case mothers (5.1%) and 467 control mothers (4.1%) reported early pregnancy antidepressant use. These participants exhibited elevated adjusted odds ratios for SSRIs and selected congenital heart defects (CHDs) (aOR = 2.56; 95% CI, 1.1-5.93). After partially accounting for underlying conditions, this association was attenuated (aOR = 1.89; 95% CI, 0.56-6.42). The researchers observed this pattern for numerous SSRI-CHD combinations. They noted that associations between SSRIs and non-CHD birth defects tended to persist or strengthen after partially accounting for underlying conditions. Venlafaxine use exhibited elevated associations with multiple defects that persisted after partially accounting for underlying conditions.

“This study provides more information about the potential risk for birth defects, which is one factor that helps inform the larger conversation about antidepressant use during pregnancy,” Reefhuis told Healio Psychiatry. “With every pregnancy, a woman starts out with a 3% chance of having a baby with a birth defect, regardless of underlying health conditions or medication use. Health care providers play an important role in reviewing safety information and making shared decisions with women about treatments before, during and after pregnancy. Fully informed, shared decision-making requires balancing the risks and benefits of medical treatment with the potential risks to women and their developing babies of untreated depression or anxiety.”

In a related editorial, Katherine L. Wisner, MD, MS, of Northwestern University School of Medicine’s Asher Center for the Study and Treatment of Depressive Disorders, and colleagues provided a focus for future efforts in this research area.

“Looking ahead, we must direct our research to advance the sophistication of treatment decision-making,” they wrote. “How do we optimally treat women across pregnancy given the progressive changes in maternal physiology and altered hepatic cytochrome P450 enzymes, which may alter plasma drug concentrations (maternal and fetal)? If maternal depression is treated to remission with SSRI, are reproductive outcomes improved compared with exposed women who remain symptomatic?

“[SSRIs] are prescribed with the expectation of benefit to mothers and their offspring,” they added. “Is it now time to turn from focusing on identifying risks to discovering potential maternal fetal benefits of pharmacotherapy? Only when we effectively define and communicate scientific evidence of benefit-risk tradeoffs to pregnant women and clinicians will we improve outcomes for this vulnerable population.”