Selective serotonin reuptake inhibitors and the risk of congenital anomalies anomalies: a systematic review of current meta-analyses

Objective:A review of current meta-analyses examining the relationship between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and congenital anomalies. Methods:PubMed was searched for meta-analyses published in English language between January 2010 and April 2020 by using the following combinations of key words:meta-analysis, pregnancy, antidepressant, SSRI, citalopram, escitalopram, fuloxetine, paroxetine, sertraline, fluvoxamine, neonatal outcome, birth outcome, congenital malformation, congenital anomaly, birth defect, cardiac malformation and heart defect. Results:A total of 15 meta-analyses met the search criteria. These meta-analyses consistently suggested a significant positive association between the use of SSRIs in general and paroxetine and fluoxetine in particular and the risk of major congenital anomalies. The data also showed a consistency in increased cardiovascular defects in infants due to maternal use of paroxetine. The risk of cardiovascular defects in infants of women using SSRIs in general and fluoxetine and sertraline in particular was controversial. Conclusion:Further large-scale prospective observational studies and meta-analyses on the effects of individual SSRIs other than paroxetine, especially escitalopram and fluvoxamine, are required to reach definitive conclusions.