Increasing the risk of spontaneous abortion and major malformations in newborns following use of serotonin reuptake inhibitors during pregnancy: A systematic review and updated meta-analysis

Evidences show that there is an increase in psychiatric disorders particularly depression and anxiety during pregnancy [1,2]. Although the pathogenesis is unknown, hormonal dysregulation, abnormalities in hypothalamic-pituitary-adrenal axis activity, and the contributions of genetics and epigenetics seems playing key roles in the development of perinatal mood disorders [3]. Women with depression during pregnancy are at increased risk for premature delivery, low birth weight, and postpartum depression [4,5].The estimate is that up to 13% of all pregnant women use an at least one antidepressant during pregnancy. Selective serotonin reuptake inhibitors (SSRIs) are the first-line, most frequently used antidepressants among pregnant women [3]. However, some studies demonstrated adverse pregnancy outcome following exposure to SSRIs. Results from our recent meta-analysis published in 2006 revealed that SSRIs do not increase the risk of major cardiovascular and minor malformations but do increase the risk of spontaneous abortion [6]. In the present study we have updated our previous meta-analysis by including more studies published in the recent 6 years about the effects of SSRIs on pregnancy outcomes.Scopus, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CCRCT) were searched for studies that investigated the effect of SSRIs on pregnancy outcomes of depressive women. Data were collected for the years 1990 to 2012 (up to March). The search terms were “serotonin reuptake inhibitors” and “pregnancy”, “birth outcome”, or “obstetrical outcome”. For PubMed, all relevant MeSH terms were used. For Web of Science and CCRCT, the same entry terms including their abbreviations were applied. The final queries were validated by manual review and matching results. The reference lists from retrieved articles were manually reviewed for finding additional applicable studies.All controlled studies that investigated the effect of SSRIs on pregnancy outcomes were co