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

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.

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study

“…Recent studies have suggested that the association between SSRI and CHD may be explained by confounding [23,33,59]. A Danish healthcare database study of livebirths found a higher risk of CHD both among women exposed to SSRI in the first trimester, and those who paused SSRI use during pregnancy, suggesting confounding by underlying depression or factors Wemakor associated with depression [33].…”

“…for women with unmedicated depression, and for individual SSRIs found a significantly elevated risk only for paroxetine when compared to unmedicated depression [23]. A US health insurance database study found that in an analysis restricted to women with a diagnosis of depression, controlling for co-exposures to other medications attenuated the CHD risks [59].…”

“…It has been suggested that the apparent excess risk of less severe CHDs might reflect ascertainment bias due to greater likelihood of exposed babies receiving special neonatal care [48,[57][58]. Other studies have focused on confounding by indication or co-exposures including co-medications [23,33,59] finding evidence of attenuation of CHD risk.…”

“…Prior to 2005, SSRIs were regarded to be safe in pregnancy, based mostly on prospective cohort studies with limited sample sizes [17][18][19][20][21]. Thereafter, starting with paroxetine [22], the SSRIs have come under scrutiny particularly in relation to congenital heart defects (CHD) [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Although not all studies have supported this association [38][39][40][41][42][43][44][45], meta-analyses have found positive overall evidence [46][47][48][49][50].…”

Effect of antidepressants use in pregnancy on foetus development and adverse effects in newborns

“…Renal dysplasia was more common in children born to mothers on fluoxetine, and hypospadias was most strongly correlated with citalopram. Congenital lower limb deformity was associated with exposure to paroxetine, sertraline and escitalopram [27].…”