To the Editor: I would like to congratulate Katherine L. Wisner, M.D., et al. for their important study, published in the May 2009 issue of the Journal, on depression and antidepressant treatment in pregnant women (1). However, I have several concerns with the article.

The study appears to show that depressed pregnant women with either continuous depression or continuous selective serotonin reuptake inhibitor (SSRI) use have preterm birth rates >20%. However, these two groups are very different, and it seems that the authors did not adequately control for group differences. The group with continuous depression (no SSRI exposure) was more likely to be young, African American, obese, unmarried, and of lower educational attainment. This group was also more likely to be using alcohol while pregnant and more severely depressed compared with the continuous SSRI exposure group. Perhaps most importantly, of the 14 women in the continuous depression group, there were four prior preterm births, while there were only six prior preterm births among the 48 women with continuous SSRI exposure.

Many of these differences between the two groups (e.g., African American race, low socioeconomic status, prior preterm birth) are risk factors for preterm birth, which must be controlled for. In the article, it does not appear that this was the case. Even without controlling for all of these factors, based on Table 4, it seems that only the continuous SSRI group had a statistically significant increase in the rate of preterm birth (a rate ratio of 5.43), with a confidence interval that did not cross 1.00.

These results are dramatic and join the accumulating evidence that now links SSRI use to preterm birth (2, 3). Pregnant women and their providers should be made aware of the growing evidence that supports an association between SSRI use and preterm birth.

1. Wisner KL, Sit DKY, Hanusa BH, Moses-Kolko EL, Bogen DL, Hunker DF, Perel JM, Jones-Ivy S, Bodnar LM, Singer LT: Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Am J Psychiatry 2009; 166:557–5662. Suri R, Altshuler L, Hellemann G, Burt VK, Aquino A, Mintz J: Effects of antenatal depression and antidepressant treatment on gestational age at birth and risk of preterm birth. Am J Psychiatry 2007; 164:1206–12133. Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL: Birth outcomes in pregnant women taking fluoxetine. N Engl J Med 1996; 335:1010–1015

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