Certain antidepressants linked to very specific birth defects

Mothers who took certain antidepressants in early pregnancy had a high risk of having children with birth defects, according to a case-control study.

Compared to other selective serotonin reuptake inhibitors (SSRIs), paroxetine (Paxil) and fluoxetine (Prozac) had the highest number of associations with specific birth defects, reported Kayla Anderson, PhD, of the National Center on Birth Defects and Developmental Disabilities at the CDC in Atlanta, and colleagues from JAMA Psychiatry.

For example, fluoxetine use in early pregnancy was associated with more than twice the risk of abnormal pulmonary venous return in infants compared to unexposed pregnancies (aOR 2.56, 95% CI 1.10-5, 93), although the risk was mitigated by taking into account underlying mental disorders. health problems (aOR 1.89, 95% CI 0.56-6.42).

Venlafaxine (Effexor), a selective norepinephrine reuptake inhibitor (SNRI), had the highest proportion of elevated risks of birth defects and was associated with heart and neural tube defects, gastroschisis, and birth defects. the mouth cleft.

Between 6 and 8 percent of pregnant women in the United States reported being prescribed or using an antidepressant, according to the study, and the risk of antidepressant use during pregnancy is not well defined, with limited evidence on specific drugs.

In an email to MedPage todayco-author Jennita Reefhuis, PhD, said this research clarified previous findings, showing that SSRIs like sertraline (Zoloft), fluoxetine, paroxetine, and citalopram (Celexa), were each associated with a small number of birth defects.

“We were surprised to find that the small number of associations between specific SSRIs and non-cardiac birth defects remained even after partially accounting for underlying mental health status,” Reefhuis said. She added that this may suggest that the defects are due to the drugs themselves, but more research is needed.

In an accompaniment editorialKatherine Wisner, MD, of Northwestern University School of Medicine in Chicago, and her colleagues pointed out that distinguishing between the adverse effects of psychiatric illnesses and the effects of drugs on the risk of birth defects is a major challenge in observational research.

Missing information about psychiatric diagnosis, unaccounted for residual confounders and recall bias are all possibilities that can skew these results, the editorial writers wrote. They added that the multiple risks of venlafaxine affect a small proportion of this patient population because it is not a first-line drug for pregnant women.

“The evidence accumulating over the past 2 decades indicates that the risk (if any) of birth defects associated with antidepressants is acceptable relative to the risks of untreated or undertreated maternal depression, Wisner and colleagues wrote. “Only when we effectively define and communicate the scientific evidence of benefit-risk trade-offs to pregnant women and clinicians will we improve outcomes for this vulnerable population.”

Reefhuis said this study could inform broader conversations about the use of antidepressants during pregnancy.

Health care providers play an important role in reviewing safety information and making shared decisions with women about treatments before, during and after pregnancy,” she said. “Fully informed and shared decision-making requires balancing the risks and benefits of medical treatment with the potential risks to women and their babies developing untreated depression or anxiety.”

Study details

Anderson and his colleagues obtained data from the National Birth Defect Prevention Studya population-based multisite case-control study in the United States, and included pregnancies from 1997 to 2011.

The researchers compared mothers of infants with a birth defect to those whose infants did not. The mothers were interviewed via computer-assisted technology, from 6 weeks to 2 years after their estimated due date. Participants self-reported start and end dates, frequency, and duration of antidepressant use in the 3 months before conception and during pregnancy.

All infants with known genetic disorders or chromosomal abnormalities were excluded from the study, as were mothers with incomplete drug history, diabetes during pregnancy, or use of teratogenic drugs before or during pregnancy.

The researchers conducted two birth defect analyses. The first compared women exposed to antidepressants in early pregnancy to those who were not exposed to them at all. This analysis was adjusted for maternal race and ethnicity, pre-pregnancy body mass index (BMI), education, and early smoking and alcohol consumption. of pregnancy.

After that, the group compared women exposed to antidepressants in early pregnancy to those who were exposed outside of that time, to account for underlying conditions that indicated drug use. They adjusted this model for kindergarten education.

There were 30,630 mothers of infants who had a birth defect and 11,478 in the control group. About 5% of those whose babies had a birth defect and 4% of control mothers reported using antidepressants in early pregnancy. The most common antidepressants used by the control group were sertraline, fluoxetine, paroxetine, citalopram, escitalopram, venlafaxine, and bupropion.

Mothers exposed to antidepressants in early pregnancy were more likely to be older, non-Hispanic Caucasian, to have had a previous live birth, and to report alcohol or tobacco use during pregnancy. They also had higher levels of education and pre-pregnancy BMI.

The risks were mitigated when the underlying conditions were taken into account, and no elevated risk of birth defects was observed with the use of escitalopram.

Anderson and colleagues did not confirm mental health diagnoses associated with specific drug treatment, which limited their ability to fully explain the underlying conditions. They also did not account for differences in antidepressant half-lives, which may have resulted in periods of use classified as non-exposures.

  • Amanda D’Ambrosio is a reporter on the business and investigative team at MedPage Today. She covers obstetrics and gynecology and other clinical news, and writes about the US healthcare system. To follow


The study was supported by the CDC.

The study co-authors revealed relationships with UpToDate, the National Institute of Mental Health, the Agency for Healthcare Research and Quality, the Mayo Foundation for Medical Education and Research and the Massachusetts Department of Public Health.

Wisner and colleagues reported funds from grants to Eli Lilly’s Brigham and Women’s Hospital and support from the Center for Obstetric and Fetal Pharmacology Research.

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