The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis

Abstract

Aims: The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into account indication, study design and reference category.

Method: A systematic review of studies published between 1966 and November 2015 was conducted using embase and MEDLINE. Studies reporting major malformations with first trimester exposure to paroxetine were included. Potentially relevant articles were assessed and relevant data extracted to calculate risk estimates. Outcomes included any major malformations and major cardiac malformations. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models.

Results: Twenty-three studies were included. Compared with non-exposure to paroxetine, first trimester use of paroxetine was associated with an increased risk of any major congenital malformations combined (pooled OR 1.23, 95% CI 1.10, 1.38; n = 15 studies), major cardiac malformations (pooled OR 1.28, 95% CI 1.11, 1.47; n = 18 studies), specifically bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n = 8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n = 4 studies) and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n = 4 studies). Although the estimates varied depending on the comparator group, study design and malformation detection period, a trend towards increased risk was observed.

Conclusions: Paroxetine use during the first trimester of pregnancy is associated with an increased risk of any major congenital malformations and cardiac malformations. The increase in risk is not dependent on the study method or population.

Keywords: cardiac malformations; major malformations; meta-analysis; paroxetine; pregnancy.

Figure 1

Flow diagram of study selection in the systematic review and meta‐analysis of the effect of paroxetine use during pregnancy on the risk of major malformations and cardiac malformations. [Indexed from 1966 to November 10th, 2015].

Figure 2

Forest plots and pooled measures of risks for overall malformation and cardiac malformation according to the comparator group. (A) Major malformations, comparison: unexposed to paroxetine, (B) major malformations, comparison: unexposed to SSRIs, (C) major malformations, comparison: unexposed to any antidepressants, (D) cardiac malformations, Comparison: unexposed to paroxetine, (E) cardiac malformations, comparison: unexposed to SSRIs, (F) cardiac malformations, comparison: unexposed to any antidepressants.