Use of selective serotonin-reuptake inhibitors in the first trimester and risk of cardiovascular-related malformations: a meta-analysis of cohort studies

The relationship between selective serotonin-reuptake inhibitors (SSRIs) use during first trimester and cardiovascular-related malformations of infants is still uncertain. Therefore, we conducted this systematic review and meta-analysis to assess the aforementioned association. A systematic literature review identified studies for cohort studies about SSRIs use and cardiovascular-related malformations in PubMed and Web of Science. We summarized relative risk (RRs) and 95% confidence intervals (CIs) of cardiovascular-related malformations using random-effects model, and heterogeneity and publication-bias analyses were conducted. Eighteen studies met the inclusion criteria. Pregnant women who were exposed to SSRIs at any point during the first trimester had a statistically significant increased risk of infant cardiovascular-related malformations (RR = 1.26, 95%CI = 1.13-1.39), with moderate heterogeneity (I2 = 53.6). The corresponding RR of atrial septal defects (ASD), ventricular septal defects (VSD), ASD and/or VSD was 2.06 (95%CI = 1.40-3.03, I2 = 57.8), 1.15 (95%CI = 0.97-1.36; I2 = 30.3), and 1.27 (95%CI = 1.14-1.42; I2 = 40.0), respectively. No evidence of publication bias and significant heterogeneity between subgroups was detected by meta-regression analyses. In conclusion, SSRIs use of pregnant women during first trimester is associated with an increased risk of cardiovascular-related malformations of infants including septal defects. The safety of SSRIs use during first trimester should be discussed to pregnant women with depression.