No link found between SSRIs and stillbirth

Maternal use of selective serotonin reuptake inhibitors during pregnancy showed no association with stillbirth, neonatal mortality, or infant death up to 1 year of age in a large epidemiologic study reported in the Jan. 2 issue of JAMA.

An unadjusted preliminary analysis of the data, which covered 1.6 million recent singleton births in five Nordic countries, showed an association between SSRI use and both stillbirth and 1-year mortality. But that association disappeared once the data were adjusted to account for the severity of the mother’s underlying psychiatric disease and other maternal factors such as advanced age and smoking status, said Dr. Olof Stephansson of the Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, and his associates.

Creatas Images

"To our knowledge, only two studies have specifically addressed the risk of stillbirth or infant death after prenatal SSRI exposure," and neither one accounted for underlying maternal psychiatric disease. The findings of these two studies were somewhat equivocal.

Dr. Stephansson and his colleagues examined the issue using information in national registries of the entire populations of Denmark, Finland, Iceland, Norway, and Sweden. They analyzed prospectively collected data regarding 1,633,877 singleton births during several time periods between 1996 and 2007. In 29,228 (2%) of these cases, the mother had filled prescriptions for SSRIs during pregnancy.

The most frequently used SSRI was citalopram (6.49 prescriptions per 1,000 population), followed by fluoxetine (4.66/1,000) and sertraline (3.93/1,000). Paroxetine, fluvoxamine, and escitalopram also were included in the study.

There were 135 stillbirths, 74 neonatal deaths, and 40 postneonatal deaths among women who took SSRIs during pregnancy.

In a preliminary analysis, rates of stillbirth and postneonatal death were higher among women who took the antidepressants than among women who didn’t. However, in the final analysis that accounted for maternal characteristics including previous psychiatric hospitalizations, SSRI exposure was no longer associated with stillbirth or postneonatal death.

A sensitivity analysis produced essentially the same results, the investigators said (JAMA 2013;309:48-54).

In a further analysis of SSRI exposure by trimester, the risk of stillbirth appeared to be slightly elevated if exposure occurred during the first trimester, while the risks of neonatal and postneonatal death were not affected by trimester of exposure. However, this finding must be interpreted with caution because of the small number of study subjects in each category of exposure, the researchers said.

This study also was limited in that it did not include information on several variables that could affect rates of stillbirth, neonatal mortality, and infant mortality, such as the mothers’ alcohol intake or use of illegal drugs during pregnancy, their use of medications other than SSRIs, and the dosage levels of their SSRIs, Dr. Stephansson and his associates added.

This study was funded by the Swedish Pharmacy Co. and the investigators’ affiliated organizations. No financial conflicts of interest were reported.

Maternal use of selective serotonin reuptake inhibitors during pregnancy showed no association with stillbirth, neonatal mortality, or infant death up to 1 year of age in a large epidemiologic study reported in the Jan. 2 issue of JAMA.

An unadjusted preliminary analysis of the data, which covered 1.6 million recent singleton births in five Nordic countries, showed an association between SSRI use and both stillbirth and 1-year mortality. But that association disappeared once the data were adjusted to account for the severity of the mother’s underlying psychiatric disease and other maternal factors such as advanced age and smoking status, said Dr. Olof Stephansson of the Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, and his associates.

Creatas Images

"To our knowledge, only two studies have specifically addressed the risk of stillbirth or infant death after prenatal SSRI exposure," and neither one accounted for underlying maternal psychiatric disease. The findings of these two studies were somewhat equivocal.

Dr. Stephansson and his colleagues examined the issue using information in national registries of the entire populations of Denmark, Finland, Iceland, Norway, and Sweden. They analyzed prospectively collected data regarding 1,633,877 singleton births during several time periods between 1996 and 2007. In 29,228 (2%) of these cases, the mother had filled prescriptions for SSRIs during pregnancy.

The most frequently used SSRI was citalopram (6.49 prescriptions per 1,000 population), followed by fluoxetine (4.66/1,000) and sertraline (3.93/1,000). Paroxetine, fluvoxamine, and escitalopram also were included in the study.

There were 135 stillbirths, 74 neonatal deaths, and 40 postneonatal deaths among women who took SSRIs during pregnancy.

In a preliminary analysis, rates of stillbirth and postneonatal death were higher among women who took the antidepressants than among women who didn’t. However, in the final analysis that accounted for maternal characteristics including previous psychiatric hospitalizations, SSRI exposure was no longer associated with stillbirth or postneonatal death.

A sensitivity analysis produced essentially the same results, the investigators said (JAMA 2013;309:48-54).

In a further analysis of SSRI exposure by trimester, the risk of stillbirth appeared to be slightly elevated if exposure occurred during the first trimester, while the risks of neonatal and postneonatal death were not affected by trimester of exposure. However, this finding must be interpreted with caution because of the small number of study subjects in each category of exposure, the researchers said.

This study also was limited in that it did not include information on several variables that could affect rates of stillbirth, neonatal mortality, and infant mortality, such as the mothers’ alcohol intake or use of illegal drugs during pregnancy, their use of medications other than SSRIs, and the dosage levels of their SSRIs, Dr. Stephansson and his associates added.

This study was funded by the Swedish Pharmacy Co. and the investigators’ affiliated organizations. No financial conflicts of interest were reported.

Maternal use of selective serotonin reuptake inhibitors during pregnancy showed no association with stillbirth, neonatal mortality, or infant death up to 1 year of age in a large epidemiologic study reported in the Jan. 2 issue of JAMA.

An unadjusted preliminary analysis of the data, which covered 1.6 million recent singleton births in five Nordic countries, showed an association between SSRI use and both stillbirth and 1-year mortality. But that association disappeared once the data were adjusted to account for the severity of the mother’s underlying psychiatric disease and other maternal factors such as advanced age and smoking status, said Dr. Olof Stephansson of the Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, and his associates.

Creatas Images

"To our knowledge, only two studies have specifically addressed the risk of stillbirth or infant death after prenatal SSRI exposure," and neither one accounted for underlying maternal psychiatric disease. The findings of these two studies were somewhat equivocal.

Dr. Stephansson and his colleagues examined the issue using information in national registries of the entire populations of Denmark, Finland, Iceland, Norway, and Sweden. They analyzed prospectively collected data regarding 1,633,877 singleton births during several time periods between 1996 and 2007. In 29,228 (2%) of these cases, the mother had filled prescriptions for SSRIs during pregnancy.

The most frequently used SSRI was citalopram (6.49 prescriptions per 1,000 population), followed by fluoxetine (4.66/1,000) and sertraline (3.93/1,000). Paroxetine, fluvoxamine, and escitalopram also were included in the study.

There were 135 stillbirths, 74 neonatal deaths, and 40 postneonatal deaths among women who took SSRIs during pregnancy.

In a preliminary analysis, rates of stillbirth and postneonatal death were higher among women who took the antidepressants than among women who didn’t. However, in the final analysis that accounted for maternal characteristics including previous psychiatric hospitalizations, SSRI exposure was no longer associated with stillbirth or postneonatal death.

A sensitivity analysis produced essentially the same results, the investigators said (JAMA 2013;309:48-54).

In a further analysis of SSRI exposure by trimester, the risk of stillbirth appeared to be slightly elevated if exposure occurred during the first trimester, while the risks of neonatal and postneonatal death were not affected by trimester of exposure. However, this finding must be interpreted with caution because of the small number of study subjects in each category of exposure, the researchers said.

This study also was limited in that it did not include information on several variables that could affect rates of stillbirth, neonatal mortality, and infant mortality, such as the mothers’ alcohol intake or use of illegal drugs during pregnancy, their use of medications other than SSRIs, and the dosage levels of their SSRIs, Dr. Stephansson and his associates added.

This study was funded by the Swedish Pharmacy Co. and the investigators’ affiliated organizations. No financial conflicts of interest were reported.