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

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.