Abstract

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 349 127 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 (aOR 1.07, 95% CI 0.96–1.18), SSRIs (aOR 1.01, 95% CI 0.88–1.17), or TCAs (aOR 1.09, 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; aOR 1.78, 95% CI 1.09–2.88), which decreased marginally when compared with women with diagnosed but unmedicated depression (aOR 1.67, 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.

Highlights

  • Antenatal depression is estimated to affect 8–11% of women in high-income countries,[1] and the proportion of pregnant women prescribed antidepressants has increased dramatically in the last two decades.[2]

  • BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists

  • Multiple comparisons are often inevitable in congenital anomaly research; for all adjusted odds ratios (ORs) we described the exact numbers of exposed cases available, and for associations where 95% confidence intervals (95% CIs) did not cross 1.00, we presented exact P values to three decimal places in consideration that we would expect smaller values of P < 0.01 to be less likely as a result of chance alone

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Summary

Introduction

Antenatal depression is estimated to affect 8–11% of women in high-income countries,[1] and the proportion of pregnant women prescribed antidepressants has increased dramatically in the last two decades.[2] Whereas it is important to manage antenatal depression, as it may confer harmful effects if left untreated,[3,4] there is conflicting evidence for the safety of antidepressant use during early pregnancy, for congenital anomaly risks.[5,6]. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

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