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Open Access Review article

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

Shekoufeh Nikfar12, Roja Rahimi34, Narjes Hendoiee5 and Mohammad Abdollahi3*

Author Affiliations

1 Food and Drug Laboratory Research Center, Food and Drug Organisation, Tehran, Iran

2 Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Traditional Pharmacy, Faculty of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

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DARU Journal of Pharmaceutical Sciences 2012, 20:75  doi:10.1186/2008-2231-20-75

Published: 1 November 2012

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are the most frequently used antidepressants during pregnancy. There are conflicting results about their influence on pregnancy outcomes. The goal of this study was to update our previous meta-analysis about pregnancy outcomes following exposure to SSRIs. For this purpose, all relevant databases were searched from 1990 to March 2012 for studies investigating the pregnancy outcomes following exposure to any therapeutic dosage of any SSRI (fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine) during pregnancy. Types of outcome investigated were spontaneous abortion, major malformations, cardiovascular malformations, and minor malformations. A total of 25 studies met our criteria and were included in the meta-analysis. The odds ratio (OD) values are 1.87 (95% CI: 1.5 to 2.33, P< 0.0001) for spontaneous abortion, 1.272 (95% CI: 1.098 to 1.474, P = 0.0014) for major malformations, 1.192 (95% CI: 0.39 to 3.644, P= 0.7578) for cardiovascular malformations, and 1.36 (95% CI: 0.61 to 3.04, P= 0.4498) for minor malformations. The results demonstrated that SSRIs increase the risk of spontaneous abortion and major malformations during pregnancy while they don’t increase the risk of cardiovascular malformations and minor malformations. Our previous meta-analysis only showed an increase in the risk of spontaneous abortion following the use of SSRIs during pregnancy. This might be due to increase in the number of studies included or addition of two new SSRIs (citalopram and escitalopram). The message to researchers is to try considering SSRIs individually during pregnancy to reduce heterogeneity, although all are aware of inevitable limitations to study on pregnant mothers.

Keywords:
Selective serotonin reuptake inhibitors (SSRIs); Pregnancy outcome; Meta-analysis; Evidence-based medicine; Malformation; Systematic review