SSRI Use in Depressed Moms Does Not Change Odds of Preterm Birth

Janis Kelly

March 19, 2009

March 19, 2009 — Pregnant women with major depression have a 1-in-5 risk of preterm delivery, regardless of whether they are taking continuous serotonin-reuptake inhibitors (SSRIs) or receive no treatment for depression.

In a prospective study published online March 16 in the American Journal of Psychiatry, Katherine L. Wisner, MD, from the University of Pittsburgh Medical Center, in Pennsylvania, report that women who took SSRIs throughout gestation had a preterm birth risk of 21%. Those with continuous untreated depression during pregnancy had a preterm birth risk of 23%. The comparison group of women with neither depression nor SSRI exposure had a preterm birth rate of 6%.

"If a woman is concerned about preterm birth being associated with SSRI treatment during pregnancy, our data suggest that opting to remain untreated, which risks relapse into depression, may result in the same risk for preterm birth," Dr. Wisner told Medscape Psychiatry.

Important Contribution

Dr. Wisner said that these data suggest some characteristic of the underlying depressive disorder affects preterm birth, whether it is treated or not, or that SSRIs affect preterm birth in a manner that differs from untreated depression, but with a similar magnitude of impact.

Christina Chambers, PhD, from the University of California, San Diego, whose 1996 report in the New England Journal of Medicine first raised the alarm about adverse birth outcomes in pregnant women taking fluoxetine (Chambers C et al. N Engl J Med. 1996;335:1010-1015), said the current study is noteworthy.

"This is a carefully conducted study that contributes importantly to the literature by virtue of having a comparison group of continuous depression/no treatment and assessment of multiple confounding factors. The main finding regarding preterm delivery is important," Dr. Chambers told Medscape Psychiatry.

The study also showed that partial depression exposure, defined as depression during part of pregnancy but no depression for at least 1 trimester, was associated with a 9% rate of preterm birth.

Partial SSRI use, defined as use at some point during gestation but at least 1 full trimester without exposure, was associated with a 4% preterm birth rate. These rates were not significantly different from those in the no-depression/no-SSRI comparison group.

Supportive of Current Guidelines

Compared with mothers with no SSRI exposure and no depression (adjusted for maternal age and race), women with continuous SSRI exposure throughout gestation were 5.43 times as likely to have preterm births.

Those with continuous depression but no SSRI exposure were 3.71 times more likely and those with either partial SSRI exposure or partial depression were not significantly more or less likely to have preterm births.

Preterm births were twice as likely in African American mothers, regardless of depression and treatment history, and 3.48 times as likely in women younger than 31 years.

Dr. Chambers said that the Wisner study supports current clinical guidelines that if a woman has severe enough depression to need continued treatment, at least in terms of preterm delivery as an outcome, "the clinical decision to treat or not treat would not be strongly influenced by fear of this 1 adverse outcome."

The researchers were surprised to find that, despite the increased risk for preterm birth, children of the SSRI-exposed mothers had no increased rates of minor physical anomalies, no major physical anomalies, no greater risk of entering a neonatal intensive care unit, and no other differences apart from slightly worse 5-minute Apgar scores.

"I expected that the SSRI-treated mothers would have infants with more neonatal signs," Dr. Wisner said.

Study Too Small to Address Major Fetal Abnormalities

However, Dr. Chambers said the study was too small to address concerns about major fetal abnormalities. These, especially the risk for cardiac malformations, were behind 2005 warnings from the Canadian Medical Association and from the US Food and Drug Administration regarding small risks associated with paroxetine in pregnancy.

Dr. Chambers said that it is possible that SSRI exposure was mainly a marker for underlying depression. "That's why the comparison group was important with a measure of disease severity. As the discussion states, the results could be interpreted several ways — for example, that SSRIs themselves cause preterm delivery and that untreated depression also does so independently, or that some underlying feature of the disease that leads some women to continue treatment with SSRIs or not to be treated at all is associated with preterm delivery in both cases.

"One does wonder what other unmeasured differences there are between women with severe depression who are not treated during any part of pregnancy and women with severe depression who are continuously treated," she said.

Gregory E. Simon, MD, a psychiatrist and researcher at the Group Health Center for Health Studies in Seattle, Washington, commented, "Additional research may help us to define more exactly the risk associated with depression and the risk associated with untreated depression.

"Additional studies are needed to determine whether risk of medication exposures differs across medications. But, in the end, we will be left with some uncertainty, and the best we can do is to share our uncertainty with our patients and allow each woman to make a decision consistent with her values and preferences."

Dr. Wisner discloses she has received research support from the American Society for Bariatric Surgery, the Heinz Foundation, the New York Mid-Atlantic Consortium for Genetics and Newborn Screening Services, the National Institute of Mental Health, Novogyne, Pfizer, the Stanley Medical Research Foundation, and the State of Pennsylvania. She serves on the speaker's bureau for GlaxoSmithKline.

Am J Psychiatry. Published online March 16, 2009. Abstract

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