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Antidepressant Use During Pregnancy and the Risk of Preterm Delivery and Fetal Growth Restriction

Toh, Sengwee ScD*; Mitchell, Allen A. MD; Louik, Carol ScD; Werler, Martha M. ScD; Chambers, Christina D. PhD, MPH; Hernández-Díaz, Sonia MD, DrPH*†

Journal of Clinical Psychopharmacology: December 2009 - Volume 29 - Issue 6 - p 555-560
doi: 10.1097/JCP.0b013e3181bf344c
Original Contributions

Objective: The associations between prenatal exposure to antidepressants and preterm delivery and fetal growth restriction are controversial and poorly understood. We studied the relation between antidepressant use and these outcomes.

Methods: Analysis included women with nonmalformed infants interviewed in the Slone Epidemiology Center Birth Defects Study between 1998 and 2008. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for premature and small-for-gestational age (SGA) offsprings, adjusting for sociodemographic, lifestyle, medical, and reproductive factors.

Results: The frequencies of preterm delivery were 7.3% among the 5710 nonusers (reference), 8.9% among the 192 selective serotonin reuptake inhibitor (SSRI) users (OR, 1.1; 95% CI, 0.6-2.0), and 15.3% among the 59 non-SSRI antidepressant users (OR, 2.2; 95% CI, 1.0-4.9); the respective frequencies of delivering an SGA offspring were 7.2%, 10.9% (OR, 1.7; 95% CI, 1.0-2.7), and 13.6% (OR, 2.2; 95% CI, 1.0-4.9). Compared with nonusers, the frequencies of preterm delivery (7.6%) and SGA offspring (5.7%) were not increased among the 106 women who discontinued SSRIs before the end of the first trimester. Among women who continued SSRIs beyond the first trimester, 10.5% delivered a preterm infant (OR, 1.3; 95% CI, 0.6-2.8) and 17.4% had an SGA offspring (OR, 3.0; 95% CI, 1.7-5.5).

Conclusions: Women treated with SSRIs late in pregnancy had a higher frequency of delivering SGA infants, and women receiving non-SSRI antidepressants were more likely to deliver premature and SGA offsprings. The findings suggest an effect of underlying mood disorder or an effect common to both drug classes. In any case, prenatal antidepressant use may help identify women at elevated risks of delivering preterm and SGA infants.

From the *Department of Epidemiology, Harvard School of Public Health; †Slone Epidemiology Center at Boston University, Boston, MA; and ‡Department of Pediatrics, University of California San Diego, La Jolla, CA.

Received March 10, 2009; accepted after revision August 31, 2009.

Reprints: Sengwee Darren Toh, ScD, Department of Population Medicine, Harvard Medical School / Harvard Pilgrim Health Care Institute, 133 Brookline Ave 6th Floor, Boston, MA 02215 (e-mail:

The study was not directly financed by any organization. Drs Mitchell, Louik, Werler, and Hernández-Díaz were partially supported by grant R01 HD046595 from the National Institute of Child and Human Development (NICHD).

© 2009 Lippincott Williams & Wilkins, Inc.