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

Aizati N. A. Daud*, Jorieke E. H. Bergman, Wilhelmina S. Kerstjens-Frederikse, Henk Groen, Bob Wilffert

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

8 Citations (Scopus)
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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.

Original languageEnglish
Article number1333
Number of pages20
JournalInternational Journal of Molecular Sciences
Volume17
Issue number8
DOIs
Publication statusPublished - 13-Aug-2016

Keywords

  • congenital heart defects
  • heart abnormalities
  • antidepressive agents
  • teratogenesis
  • serotonin reuptake inhibitors
  • drug-induced birth defects
  • POPULATION-BASED COHORT
  • MAJOR DEPRESSIVE DISORDER
  • CYP1A2 GENETIC POLYMORPHISMS
  • P-GLYCOPROTEIN EXPRESSION
  • TERM TREATMENT RESPONSE
  • EARLY-PREGNANCY
  • HUMAN PLACENTA
  • ANTIDEPRESSANT RESPONSE
  • PLASMA-CONCENTRATIONS
  • BIRTH-DEFECTS

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