Faculty of Medicine

BACKGROUND:
Information regarding the safety of selective serotonin-reuptake inhibitors (SSRIs) in human pregnancy is sparse. Concern has been raised about the risk of congenital heart defects associated with the use of SSRIs in pregnancy.

METHODS:
We obtained data on 9622 case infants with major birth defects and 4092 control infants born from 1997 through 2002 from the National Birth Defects Prevention Study. Case infants were ascertained through birth-defects surveillance systems in eight U.S. states; controls were selected randomly from the same geographic areas. Mothers completed a standardized telephone interview regarding exposure to potential risk factors, including medications, before and during pregnancy. Exposure to SSRIs was defined as treatment with any SSRI from 1 month before to 3 months after conception. Birth defects were assigned to 26 categories and subcategories.

RESULTS:
There were no significant associations between maternal use of SSRIs overall during early pregnancy and congenital heart defects or most other categories or subcategories of birth defects. Maternal SSRI use was associated with anencephaly (214 infants, 9 exposed; adjusted odds ratio, 2.4; 95% confidence interval [CI], 1.1 to 5.1), craniosynostosis (432 infants, 24 exposed; adjusted odds ratio, 2.5; 95% CI, 1.5 to 4.0), and omphalocele (181 infants, 11 exposed; adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.7).

CONCLUSIONS:
Maternal use of SSRIs during early pregnancy was not associated with significantly increased risks of congenital heart defects or of most other categories of birth defects. Associations were observed between SSRI use and three types of birth defects, but the absolute risks were small, and these observations require confirmation by other studies.

Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly used medications, with a prescription frequency of 2.3% in pregnant women. Although most babies born to women who take SSRIs during pregnancy are normal, there is accumulating evidence that maternal SSRI treatment during pregnancy may cause adverse reproductive outcomes. Maternal SSRI treatment during the first trimester has been implicated in increased risks of birth defects, specifically cardiac abnormalities, in the infant, whereas third-trimester treatment has been linked to various neonatal complications, including symptoms of neonatal withdrawal and toxicity, prematurity, low birth weight and persistent pulmonary hypertension of the newborn. Although data on neurobehavioural and long-term cognitive problems among children of women who were treated with SSRIs during pregnancy remain limited, the possibility of such functional abnormalities is an additional concern. On the other hand, untreated maternal depression also carries serious risks for both the mother and the baby, and SSRIs are one of the best available treatments. Thus, pregnant women who require treatment for depression and their physicians often face a difficult choice regarding the use of SSRIs.

OBJECTIVE:
We sought to determine if maternal bupropion treatment in early pregnancy is associated with congenital heart defects in the infant.

STUDY DESIGN:
We conducted a retrospective case-control study of birth defects risk factors. Data on 6853 infants with major heart defects were compared with 5869 control infants born in 1997-2004. Bupropion exposure was defined as any reported use between 1 month before and 3 months after conception.

RESULTS:
Mothers of infants with left outflow tract heart defects were more likely to have reported taking bupropion than mothers of control infants (adjusted odds ratio, 2.6; 95% confidence interval, 1.2-5.7; P = .01).

CONCLUSION:
We identified a positive association between early pregnancy bupropion use and left outflow tract heart defects; however, the magnitude of the observed increased risk was small. Nevertheless, further studies are needed to confirm these results.

This article describes the pattern of reported antidepressant use around the time of pregnancy in a population-based sample of women who delivered live-born babies without birth defects. Data were used from the National Birth Defects Prevention Study, an ongoing case-control study of risk factors for birth defects covering 10 US states. Mothers of live-born infants without birth defects (controls) born between 1998 and 2005 were randomly selected from each site. Information on the mother's characteristics and exposure to antidepressants was collected via a standardized telephone interview. Among 6582 mothers included in the study, 298 (4.5%) reported use of an antidepressant in the period of 3 months before through the end of pregnancy. Use of selective serotonin-reuptake inhibitors was reported most often (3.8%), followed by bupropion (0.7%). A statistically significant decline was observed, from 3.1% to 2.3% (P < .001), in reported use of antidepressants between the first and second month after conception. The frequency of reported antidepressant use at any time during pregnancy increased from 2.5% in 1998 to 8.1% in 2005 (P < .001) in 4 states. The findings show an increase in reported antidepressant use over a 9-year period and a substantial decrease in use around the usual time of pregnancy recognition.