First-Trimester Use of Paroxetine and Congenital Heart Defects: A Population-Based Case-Control Study

Eurocat Northern Netherlands, Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Birth Defects Research Part A Clinical and Molecular Teratology (Impact Factor: 2.09). 11/2009; 88(2):94-100. DOI: 10.1002/bdra.20641
Source: PubMed


There is a need for case-control studies of the effect of paroxetine on the occurrence of specific heart defects.
We performed a case-control study with data from a population-based birth defects registry in the Netherlands. All the children born between 1997 and 2006 were selected. Cases were defined as fetuses and children with isolated heart defects, and the controls were fetuses and children with a genetic disorder with no heart defect. We excluded children for whom there was no information on maternal medication use and deceased children and fetuses who were not examined postmortem. First-trimester exposure to paroxetine was compared between cases and controls by calculating adjusted odds ratios (AOR).
We included 678 cases with isolated heart defects and 615 controls. The first trimester exposure rate was 1.5% for cases and 1.0% for controls. After excluding mothers who used paroxetine outside the first trimester, or who had used another SSRI, we found no significantly increased risk for heart defects overall (10 exposed cases; AOR, 1.5; 95% confidence interval [CI], 0.5-4.0), but we did find a significantly increased risk for atrium septum defects (three exposed cases; AOR, 5.7; 95% CI, 1.4-23.7).
Our results suggest that the use of paroxetine in early pregnancy is associated with an increased risk of atrium septum defects. The results stress the importance of studying possible teratogenic effects of a drug, preferably in regard to well-specified malformations.

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Available from: Wilhelmina S Kerstjens-Frederikse
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    • "Some reviewers have concluded that there is no increased risk in first-trimester exposure [25] [26] [27], some that the evidence is conflicting [28], some that paroxetine is teratogenic and that other SSRIs are not [29], and others that there may be poor neonatal outcomes [30]. In a case-control study first-trimester exposure to paroxetine was associated with a significantly increased risk of atrial septal defects (adjusted OR ¼ 5.7; 95% CI ¼ 1.4, 24) [31]. However, in contrast, in one study there was a possible association between cardiovascular anomalies and first-trimester exposure to fluoxetine but not paroxetine [32] and in another a greater risk of septal heart defects with sertraline and citalopram but not paroxetine or fluoxetine [33]; this illustrates the confusion that can arise from such studies. "
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