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Depression and Serotonin Reuptake Inhibitor Treatment as Risk Factors for Preterm Birth

Yonkers, Kimberly A.a,b,c; Norwitz, Errol R.d; Smith, Megan V.a,e; Lockwood, Charles J.f; Gotman, Nathana; Luchansky, Edwardg; Lin, Haiqunc; Belanger, Kathleenc

doi: 10.1097/EDE.0b013e31825838e9
In-Utero Exposures

Background: Major depressive disorder and the use of serotonin reuptake inhibitors (SRIs) in pregnancy have been associated with preterm birth. Studies that have attempted to separate effects of illness from treatment have been inconclusive. We sought to explore the separate effects of SRI use and major depressive episodes in pregnancy on risk of preterm birth.

Methods: We conducted a prospective cohort study of 2793 pregnant women, oversampled for a recent episode of major depression or use of an SRI. We extracted data on birth outcomes from hospital charts and used binary logistic regression to model preterm birth (<37 weeks' gestation). We used ordered logistic regression to model early (<34 weeks' gestation) or late (34–36 weeks) preterm birth, and we used nominal logistic regression to model preterm birth antecedents (spontaneous preterm labor/preterm premature rupture of membranes/preterm for medical indications/term).

Results: Use of an SRI, both with (odds ratio = 2.1 [95% confidence interval = 1.0–4.6]) and without (1.6 [1.0–2.5]) a major depressive episode, was associated with preterm birth. A major depressive episode without SRI use (1.2 [0.68–2.1]) had no clear effect on preterm birth risk. None of these exposures was associated with early preterm birth. Use of SRIs in pregnancy was associated with increases in spontaneous but not medically indicated preterm birth.

Conclusions: SRI use increased risk of preterm birth. Although the effect of a major depressive episode alone was unclear, symptomatic women undergoing antidepressant treatment had elevated risk.

From the Departments of aPsychiatry, bObstetrics, Gynecology and Reproductive Sciences, and cEpidemiology and Public Health, Yale University School of Medicine, New Haven, CT; dDepartment of Obstetrics and Gynecology, Tufts University School of Medicine, Boston, MA; eDepartment of Child Study, Yale University School of Medicine, New Haven, CT; fDepartment of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH; and gDepartment of Obstetrics and Gynecology, Bridgeport Hospital, Bridgeport, CT.

Submitted 15 November 2011; accepted 21 February 2012; posted 23 May 2012.

Supported by National Institute of Child Health and Human Development Grant R01 HD045735. Dr. Smith was supported by K12 DA031050 from the National Institute on Drug Abuse, National Institute on Alcohol Abuse and Alcoholism, and Office of Research on Women's Health. Dr. Yonkers is the lead author and discloses royalties from Up To Date and support from Pfizer via study medication for an NIMH trial. Drs. Norwitz and Lockwood also have received royalties from Up To Date. The authors reported no other financial interests related to this research.

Editors' note: A commentary on this article appears on page 686.

Correspondence: Kimberly A. Yonkers, 142 Temple St, Suite 301, New Haven, CT 06510. E-mail:

© 2012 Lippincott Williams & Wilkins, Inc.