No significant link between SSRI use during pregnancy and risk of stillbirth, neonatal death

In a study that included nearly 30,000 women from Nordic countries who had filled a selective serotonin reuptake inhibitor (SSRI) prescription during pregnancy, researchers found no significant association between use of these medications during pregnancy and risk of stillbirth, neonatal death, or postneonatal death, after accounting for factors including maternal psychiatric disease, according to a study in the January 2 issue of JAMA.

"Depression during pregnancy is common with prevalences ranging between 7 percent and 19 percent in economically developed countries. Maternal depression is associated with poorer pregnancy outcomes, including increased risk of preterm delivery, which in turn may cause neonatal morbidity and mortality," according to background information in the article. "Use of selective serotonin reuptake inhibitors during pregnancy has been associated with congenital anomalies, neonatal withdrawal syndrome, and persistent pulmonary hypertension of the newborn. However, the risk of stillbirth and infant mortality when accounting for previous maternal psychiatric disease remains unknown."

Olof Stephansson, M.D., Ph.D., of the Karolinska Institutet, Stockholm, Sweden and colleagues conducted a study to examine whether SSRI exposure during pregnancy was associated with increased risks of stillbirth, neonatal death, and postneonatal death. The study included women with single births from all Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at different periods from 1996 through 2007. The researchers obtained information on maternal use of SSRIs from prescription registries; maternal characteristics, pregnancy, and neonatal outcomes were obtained from patient and medical birth registries. The authors estimated relative risks of stillbirth, neonatal death, and postneonatal death associated with SSRI use during pregnancy taking into account maternal characteristics and previous psychiatric hospitalization.

Among 1,633,877 singleton births in the study, there were 6,054 stillbirths; 3,609 neonatal deaths; and 1,578 postneonatal deaths. A total of 29,228 (1.79 percent) of mothers had filled a prescription for an SSRI during pregnancy. The researchers found that women exposed to an SSRI had higher rates of stillbirth (4.62 vs. 3.69 per 1000) and postneonatal death (1.38 vs. 0.96 per 1000) than those who did not. The rate of neonatal death was similar between groups (2.54 vs. 2.21 per 1000). "Yet in multivariate models, SSRI use was not associated with stillbirth, neonatal death, or postneonatal death. Estimates were further attenuated when stratified by previous hospitalization for psychiatric disease," the authors write.

"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 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."

"However, decisions regarding use of SSRIs during pregnancy must take into account other perinatal outcomes and the risks associated with maternal mental illness," the researchers conclude.