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Untreated major depression, as well as the use of antidepressant medications, may increase the risk for premature (preterm) birth, but the risk of other problems in fetuses such as breathing, gastrointestinal, or motor problems, may not be increased, according to a study of pregnant women published online ahead of print March 15, 2009, in the American Journal of Psychiatry.

Use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), is common among women of childbearing age. Although there is some concern regarding the use of SSRIs during pregnancy and their effects on the growing fetus, research results have been mixed. Overall, it appears the risk for major birth defects is very low, but the risk for other complications, such as minor physical anomalies—a specific type of birth defect—or preterm birth (before 37 weeks gestation), has not been consistently established.
Katherine L. Wisner, M.D., of the University of Pittsburgh, and colleagues aimed to determine whether the use of SSRIs or the existence of major depression during pregnancy was associated with minor physical anomalies in the baby, low infant birth weight, preterm birth or other issues. In this observational study, the researchers categorized 238 pregnant women in Cleveland, Ohio, and Pittsburgh, Pa., into one of three groups:
· no use of SSRIs and no major depression during pregnancy (131 women);
· use of SSRIs either at some point (23 women) or throughout the pregnancy (48 women);
· those who had major depression—either at some point (22 women) or throughout the pregnancy (14 women)—but who remained unmedicated.
The researchers gave general advice to the women about managing major depression and use of SSRIs, but they did not interfere in treatment decisions made by the women and their doctors. Wisner and colleagues examined various outcomes, such as maternal weight gain, pregnancy duration, minor physical anomalies in the infant, infant birth weight, and other infant characteristics.

Results of the Study
Wisner and colleagues found that for both pregnant women with untreated major depression and for those who were taking SSRIs throughout their pregnancy, more than 20 percent of infants were delivered preterm. In comparison, only 4 percent of infants partially exposed to SSRIs during gestation and 6 percent not exposed at all to SSRIs or depression during gestation were delivered pre-term.
Neither the use of SSRIs nor major depression was associated with an increase in minor physical anomalies; short-term medication-associated issues like breathing, gastrointestinal or motor problems; or reduced weight gain among the women during pregnancy. Birth weight of infants also did not differ across groups.

The results support other studies that have found a link between continuous SSRI treatment and an increase in risk of preterm birth, but they are not consistent with studies that have found an increased risk of drug-associated issues in infants exposed to SSRIs while in the womb. However, the researchers note that untreated depression among pregnant women may present the same risk to infants as SSRI use, reiterating the need for doctors to work with individual patients to balance the risks and benefits of SSRI use and the treatment of major depression during pregnancy.

What's Next
More research is needed to better determine whether women with major depression who are treated with SSRIs and experience remission during pregnancy have more favorable outcomes compared to unmedicated depressed women. In addition, larger studies may be able to determine differences in outcomes among SSRIs. Finally, more research into non-medication interventions for treating depression during pregnancy, including psychotherapy and other approaches, is also needed.


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