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Int. J. Mol. Sci. 2016, 17(8), 1333; doi:10.3390/ijms17081333

The Risk of Congenital Heart Anomalies Following Prenatal Exposure to Serotonin Reuptake Inhibitors—Is Pharmacogenetics the Key?

1
Department of Pharmacy, Unit of PharmacoTherapy, -Epidemiology and -Economics, University of Groningen, 9713AV Groningen, The Netherlands
2
School of Pharmaceutical Sciences, Discipline of Clinical Pharmacy, Universiti Sains Malaysia, 11800 Penang, Malaysia
3
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713AV Groningen, The Netherlands
4
Department of Epidemiology, University Medical Centre Groningen, University of Groningen, 9713AV Groningen, The Netherlands
5
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713AV Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editors: Sabrina Angelini and Gloria Ravegnini
Received: 1 June 2016 / Revised: 27 July 2016 / Accepted: 27 July 2016 / Published: 13 August 2016
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine 2016)
View Full-Text   |   Download PDF [700 KB, uploaded 13 August 2016]   |  

Abstract

Serotonin reuptake inhibitors (SRIs) are often prescribed during pregnancy. Previous studies that found an increased risk of congenital anomalies, particularly congenital heart anomalies (CHA), with SRI use during pregnancy have created concern among pregnant women and healthcare professionals about the safety of these drugs. However, subsequent studies have reported conflicting results on the association between CHA and SRI use during pregnancy. These discrepancies in the risk estimates can potentially be explained by genetic differences among exposed individuals. In this review, we explore the potential pharmacogenetic predictors involved in the pharmacokinetics and mechanism of action of SRIs, and their relation to the risk of CHA. In general, the risk is dependent on the maternal concentration of SRIs and the foetal serotonin level/effect, which can be modulated by the alteration in the expression and/or function of the metabolic enzymes, transporter proteins and serotonin receptors involved in the serotonin signalling of the foetal heart development. Pharmacogenetics might be the key to understanding why some children exposed to SRIs develop a congenital heart anomaly and others do not. View Full-Text
Keywords: congenital heart defects; heart abnormalities; antidepressive agents; teratogenesis; serotonin reuptake inhibitors; drug-induced birth defects congenital heart defects; heart abnormalities; antidepressive agents; teratogenesis; serotonin reuptake inhibitors; drug-induced birth defects
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MDPI and ACS Style

Daud, A.N.A.; Bergman, J.E.H.; Kerstjens-Frederikse, W.S.; Groen, H.; Wilffert, B. The Risk of Congenital Heart Anomalies Following Prenatal Exposure to Serotonin Reuptake Inhibitors—Is Pharmacogenetics the Key? Int. J. Mol. Sci. 2016, 17, 1333.

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