Pharm.D. (six years)


Kristina E. Ward

Advisor Department

Pharmacy Practice (PHP)




pharmacy; SSRI; pregnancy; CHD; selective serotonin reuptake inhibitors; congenital heart defects; meta-analysis; population based cohort studies

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.


The American College of Obstetricians and Gynecologists estimate that 10-23% of pregnant women in the US face depression at some point during their pregnancy. However, no clear recommendations regarding the treatment of depression in pregnancy are available. Antidepressants are commonly used during pregnancy without clear evidence of their safety. A study of 1,106,757 women in 47 states found that 89,980 (8.1%) had taken an antidepressant at some point during their pregnancy. The Centers for Disease Control and Prevention (CDC) found that 298 (4.5%) of 6582 women in 10 states between the years of 1998 and 2005 had taken an antidepressant at some time during a pregnancy or up to three months before pregnancy. Of the women, 250 (3.8%) used a selective serotonin reuptake inhibitor (SSRI) making them the most commonly used type of antidepressant in pregnancy. A major concern with SSRI use during pregnancy is the potential risk for congenital malformations, including congenital heart defects (CHD).

Therefore, the study purpose is to determine if risk of CHD is associated with the use of SSRIs during pregnancy. After an extensive review of the biomedical literature and extraction of data from existing studies of CHD risk with SSRI using during pregnancy, a meta-analysis will be completed. Few meta-analyses examine the effects of the SSRI class on CHDs; existing meta-analyses focus on paroxetine. The goal of this meta-analysis is to pool data from studies meeting inclusion criteria to examine a possible connection between the use of SSRIs during pregnancy and CHD. An extensive data search was performed using three databases: PubMed, EMBASE, and Cochrane Databases. From all searches, a total of 1,417 results were found, including duplicates. Studies were narrowed based on topic relevance, medications studied, and study type. Eight studies were selected for further analysis based on several criteria. Studies included in the analysis were all population-based cohort studies with specific data including: number of women exposed and unexposed to SSRIs, and number of CHDs in both exposed and unexposed women. Studies were excluded if they included women exposed to antidepressants other than SSRIs. From the eight studies included in the analysis a total of 65,710 women were exposed to SSRIs during pregnancy and 719 reports of CHD were reported. Of the 2,960,492 women who were not exposed to an SSRI during their pregnancy, 27,405 CHD outcomes were reported. The studies included in the analysis show mixed results individually. Three of the studies found no association between SSRI use and CHD (Huybrechts et al, Margulis et al, Winchman et al). Five studies found an association between SSRI use and CHD (Berard et al, Kundsen et al, Jimenez-Solem et al, Malm et al, Pedersen et al). Even within the studies variation is found. For example, in Berard et al., cardiac malformations were not significant with SSRI use; however, when further analyzed by type of malformation, ventricular and atrial septal defects were associated with SSRI use.

Based on the lack of knowledge about the effect of SSRIs on CHD, this meta-analysis will help to clarify this much-debated topic. The results will help women and their providers make an educated assessment regarding the potential risks from SSRI use during pregnancy and balance that knowledge with the risks of not treating depression during pregnancy.