Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of congenital anomalies: A European register-based study in 12 European countries

Objective / Background The Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants are widely prescribed in pregnancy, but there is evidence that they may cause congenital anomalies, particularly congenital heart defects (CHD). Objective: To determine the specificity of association between first trimester pregnancy exposure to individual SSRI and specific congenital anomalies (CAs). Methods Population-based case-malformed control study covering 3.3 million births from 12 EUROCAT registries 1995-2009. CAs included non-syndromic live births, fetal deaths and terminations of pregnancy for fetal anomaly (n=42,839). Three groups of CA were studied: CHD (n=12,828), 15 non-CHD "signals" derived from the literature (n=12,460), and other subgroups of CA not previously associated with SSRIs (controls, n=17,046). First trimester SSRI exposure was compared to no SSRI use. Odds ratios (OR) and 95% confidence intervals (CI) were calculated adjusted for registry. Results SSRI use in first trimester pregnancy was associated with CHD overall (OR 1.38, 95 % CI 1.05-1.82, n=109); and with severe CHDs (OR 1.56, 95 % CI 1.03-2.38, n=29). Specific associations between SSRI and Tetralogy of Fallot (OR 3.36, 95 % CI 1.67-6.75, n=9), and Ebstein's anomaly (OR 8.23, 95 % CI 2.91-23.28, n=4) were detected. Statistically significant associations between SSRI and four of the 15 non- CHDsignals (anorectal atresia and stenosis, gastroschisis, renal dysplasia, clubfoot) were found. In all the statistically significant associations identified there was little evidence of specificity in relation to SSRI type. Conclusion / Discussion These data support the previously reported association between SSRIs and CHDs and a number of other CAs, but do not suggest specificity of action in relation to SSRI type. This may indicate confounding or a common mechanism of teratogenic effect among SSRIs, the specificity of CA supporting the latter explanation. Preconceptional and pregnancy care for women should include weighing the benefits of SSRIs against the growing evidence of risk when assessing treatment options.