title: The Risk of Congenital Heart Anomalies Following Prenatal Exposure to Serotonin Reuptake Inhibitors-Is Pharmacogenetics the Key?
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.
authors.affiliation: Department of Pharmacy, Unit of PharmacoTherapy, -Epidemiology and -Economics, University of Groningen, 9713AV Groningen, The Netherlands. n.a.a.daud@rug.nl.|School of Pharmaceutical Sciences, Discipline of Clinical Pharmacy, Universiti Sains Malaysia, 11800 Penang, Malaysia. n.a.a.daud@rug.nl.
authors.forename: Aizati N A
authors.initials: AN
authors.lastname: Daud
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, 9713AV Groningen, The Netherlands. j.e.h.van.kammen@umcg.nl.
authors.forename: Jorieke E H
authors.initials: JE
authors.lastname: Bergman
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, 9713AV Groningen, The Netherlands. w.s.kerstjens@umcg.nl.
authors.forename: Wilhelmina S
authors.initials: WS
authors.lastname: Kerstjens-Frederikse
authors.affiliation: Department of Epidemiology, University Medical Centre Groningen, University of Groningen, 9713AV Groningen, The Netherlands. h.groen01@umcg.nl.
authors.forename: Henk
authors.initials: H
authors.lastname: Groen
authors.affiliation: Department of Pharmacy, Unit of PharmacoTherapy, -Epidemiology and -Economics, University of Groningen, 9713AV Groningen, The Netherlands. b.wilffert@rug.nl.|Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713AV Groningen, The Netherlands. b.wilffert@rug.nl.
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
mesh_terms: D005260:Female; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000502:physiology; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics*; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors
keywords: antidepressive agents; congenital heart defects; drug-induced birth defects; heart abnormalities; serotonin reuptake inhibitors; teratogenesis