Maternal depression, antidepressant prescriptions, and congenital anomaly risk in offspring: a population-based cohort study

ObjectiveTo estimate risks of major congenital anomaly (MCA) among children of mothers prescribed antidepressants during early pregnancy or diagnosed with depression but without antidepressant prescriptions. DesignPopulation-based cohort study. SettingLinked UK maternal-child primary care records. PopulationA total of 349127 singletons liveborn between 1990 and 2009. MethodsOdds ratios adjusted for maternal sociodemographics and comorbidities (aORs) were calculated for MCAs, comparing women with first-trimester selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) and women with diagnosed but unmedicated depression, or women without diagnosed depression. Main outcome measuresFourteen system-specific MCA groups classified according to the European Surveillance of Congenital Anomalies and five specific heart anomaly groups. ResultsAbsolute risks of MCA were 2.7% (95% confidence interval, 95%CI, 2.6-2.8%) in children of mothers without diagnosed depression, 2.8% (95%CI 2.5-3.2%) in children of mothers with unmedicated depression, and 2.7% (95%CI 2.2-3.2%) and 3.1% (95%CI 2.2-4.1%) in children of mothers with SSRIs or TCAs, respectively. Compared with women without depression, MCA overall was not associated with unmedicated depression (aOR1.07, 95%CI 0.96-1.18), SSRIs (aOR1.01, 95%CI 0.88-1.17), or TCAs (aOR1.09, 95%CI 0.87-1.38). Paroxetine was associated with increased heart anomalies (absolute risk 1.4% in the exposed group compared with 0.8% in women without depression; aOR1.78, 95%CI 1.09-2.88), which decreased marginally when compared with women with diagnosed but unmedicated depression (aOR1.67, 95%CI 1.00-2.80). ConclusionsOverall MCA risk did not increase with maternal depression or with antidepressant prescriptions. Paroxetine was associated with increases of heart anomalies, although this could represent a chance finding from a large number of comparisons undertaken.