Between 6% and 8% of United States (US) pregnant women are prescribed antidepressants (ADs). However, concerns remain about the adverse effects of ADs on fetal and infant health, including birth defect risk after early pregnancy exposure. The current study addresses this concern by examining the final data from the National Birth Defects Prevention Study, a case-control study conducted in multiple sites across the US. Cases with selected birth defects (N=30,630) were identified from medical records of pregnancies. Controls (N=11,478) were randomly sampled live-born infants without major birth defects from the same birth month and state (or county). AD use was determined by maternal retrospective report. Early pregnancy exposure was defined as using 1 or more ADs in any dose, duration, or frequency from the month before conception through the third pregnancy month. Controls included unexposed women and women exposed solely during the 2-3 months before conception and/or pregnancy months 4 to 9. Comparison of cases with the latter group was conducted to account partially for confounding by the underlying condition. Underlying condition described the condition necessitating treatment with an antidepressant as well as social and environmental factors associated with the condition; however, maternal psychiatric diagnoses were not obtained.
Early pregnancy AD use was reported by 1,562 cases (5.1%) and 467 controls (4.1%). Compared to unexposed controls, early pregnancy exposure to paroxetine (adjusted odds ratios [aORs]=2.10-4.76) or fluoxetine (aORs=2.04-4.08) had the highest proportion of elevated aORs with specific birth defects, followed by citalopram (aORs=2.09-3.01) and sertraline (aORs=2.79-3.32). Mothers who used venlafaxine had elevated aORs for most examined defects (aORs=3.34-5.26). Compared to women exposed outside of early pregnancy, early pregnancy exposure to ADs was not associated with as many defects, and aORs were generally attenuated. Moreover, there were elevated aORs for non-heart defects with early pregnancy exposure to sertraline, fluoxetine, paroxetine and citalopram, as well as venlafaxine (in some instances the association strengthened), compared to exposure outside of early pregnancy. Overall, this study showed that venlafaxine had the highest proportion of elevated aORs with specific birth defects, while escitalopram had the lowest proportion (none). However, many birth defects are extremely rare, and it is unclear how the relative risks described in this study correspond to absolute risk. An important limitation of this study is the lack of diagnostic equivalence between AD exposed groups. Psychiatric diagnosis impacts illness severity, comorbid conditions, and concomitant drug exposure, which may be associated with increased risk of birth defects. Additional research accounting for psychiatric diagnoses and addressing the trade-off between the risks and benefits of treating maternal psychiatric illness with pharmacotherapy is needed to guide treatment decision-making.
Anderson KN et al. JAMA Psychiatry 2020;e202453. Abstract
Wisner KL, Oberlander TF, Huybrechts KF. JAMA Psychiatry 2020; Epub ahead of print Abstract
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