SSRIs Don’t Show Link to Stillbirths, Neonatal Deaths

In a major new study, researchers found that use of SSRI antidepressants during pregnancy was not associated with stillbirths, neonatal deaths, or postneonatal deaths.

This finding on a topic that has generated considerable controversy in recent years comes from a large Scandinavian study published in the January 2 Journal of the American Medical Association (JAMA). The lead researcher was Olof Stephansson, M.D., Ph.D., an associate professor and senior consultant in obstetrics and gynecology at the Karolinska Institute in Stockholm, Sweden.

The study included more than 1.6 million women and the births of their single children in Denmark, Finland, Iceland, Norway, or Sweden from 1996 to 2007. Such a large-scale study was feasible because of the national registry systems in those countries, where residents are assigned a unique identification number.

The researchers used patient, birth, and prescription registries to obtain information about the women, their health, and their health behaviors—for example, whether they had high blood pressure or diabetes, smoked, or had been hospitalized for a psychiatric illness.

The researchers used prescription registries to determine whether any of the women had filled prescriptions for an SSRI antidepressant from three months before the start of a pregnancy until giving birth. They found that some 29,000 (2 percent) had. Compared with the rest of the study population, those women were more likely to be older and smokers and have high blood pressure and/or diabetes and a history of psychiatric hospitalization.

This finding didn’t surprise him, Stephansson told Psychiatric News. “It is known that women with depression tend to use alcohol and smoke more during pregnancy, and the likelihood of getting depression and medication for depression increases with age. However, the association with hypertensive disease and diabetes was less known to me.”

The researchers then evaluated three outcomes: stillbirth (intrauterine death after 22 or more weeks of gestation), neonatal death (death within 0 to 27 days following birth), and postneonatal death (death from 28 to 364 days after birth). Information on stillbirths was obtained from the medical birth registries in each country and on neonatal and postneonatal deaths from the causes-of-death registries, which contain information on the date and causes of death for all individuals who resided in those countries at the time of their death. There were 6,054 stillbirths, 3,609 neonatal deaths, and 1,578 postneonatal deaths.

Finally the researchers assessed whether children of women who had used an SSRI antidepressant during pregnancy had more stillbirths, neonatal deaths, or postneonatal deaths than children of women who had not used one of these drugs during pregnancy.

Confounds Change the Outcome

Compared with women who had been unexposed to SSRIs during pregnancy, those who had taken these medications experienced significantly more stillbirths and postneonatal deaths, but not neonatal deaths, the researchers found. However, when possibly confounding factors such as maternal psychiatric illness, maternal cigarette smoking, and advanced maternal age were considered, there were no longer any significant differences between the exposed and unexposed women for stillbirths, neonatal deaths, or postneonatal deaths.

Thus “the present study of more than 1.6 million births suggests that SSRI use during pregnancy was not associated with increased risks of stillbirth, neonatal death, or postneonatal death,” the researchers concluded. “The increased rates of stillbirth and postneonatal mortality among infants exposed to an SSRI during pregnancy were explained by the severity of the underlying maternal psychiatric disease and unfavorable distribution of maternal characteristics such as cigarette smoking and advanced maternal age.”

“I am glad that these researchers have been able to do what no one has yet done, and the study is a needed addition to the literature,” psychiatrist Harold Koplewicz, M.D., president of the Child Mind Institute in New York City, told Psychiatric News. “Though there are a few criticisms one could make of the design, I believe that the authors convincingly demonstrate through the multivariate analysis that their observations are valid. . . . I would never urge anything less than caution when treating a pregnant woman with any medication. But this study is helpful in reminding us to be as concerned with the effects of the disease as we are about the treatment. Unfortunately, the idea is still radical to many people.”

The study was funded by the Swedish Society of Medicine and the Swedish Pharmacy Company. The researchers reported that the latter was not involved in the study’s design, implementation, or data interpretation.

Other Studies Address Related Issues

This study is one of the latest to explore the impact of SSRI use during pregnancy on fetal outcome. Two studies that appeared in the June 28, 2007, New England Journal of Medicine suggested that if a woman takes SSRIs during the first trimester of pregnancy, it may raise the risk of certain birth defects in her offspring. The researchers in that study emphasized, however, that the overall risk is small and that untreated depression can also be deleterious to the fetus (Psychiatric News, July 20, 2007).

In a study published March 16, 2009, in AJP in Advance, researchers found that pregnant women with continuous untreated depression and those with continuous exposure to SSRIs had similarly elevated rates of more than 20 percent for preterm delivery (Psychiatric News, April 3, 2009). And in a study published January 2, 2009, in AJP in Advance, researchers found a link between SSRI exposure in late pregnancy and a significantly higher risk for gestational hypertension and preeclampsia (Psychiatric News, April 3, 2009). ■