A multicountry (Denmark, Finland, Iceland, Norway, and Sweden) population based cohort study 2, including sibling controlled design assessed the risk of birth defects associated with use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy.The full study cohort included women giving birth to 2.3 million live singletons. The sibling cohort included 2288 singleton live births. The sibling controlled analyses included sibling pairs who were discordant for exposure to SSRIs or venlafaxine and birth defects.Among 36 772 infants exposed to any SSRI in early pregnancy, 3.7% (n=1357) had a birth defect compared with 3.1% of 2,266,875 unexposed infants, yielding a covariate adjusted odds ratio of 1.13 (95% CI 1.06 to 1.20). In the sibling controlled analysis the adjusted odds ratio decreased to 1.06 (0.91 to 1.24). The odds ratios for any cardiac birth defect with use of any SSRI or venlafaxine were 1.15 (95% CI 1.05 to 1.26) in the covariate adjusted analysis and 0.92 (0.72 to 1.17) in the sibling controlled analysis. For atrial and ventricular septal defects the covariate adjusted odds ratio was 1.17 (1.05 to 1.31). Exposure to any SSRI or venlafaxine increased the prevalence of right ventricular outflow tract obstruction defects, with a covariate adjusted odds ratio of 1.48 (1.15 to 1.89). In the sibling controlled analysis the adjusted odds ratio decreased to 0.56 (0.21 to 1.49) for any exposure to SSRIs or venlafaxine and right ventricular outflow tract obstruction defects.
In a case-control study 1, the associations between first-trimester maternal use of selective serotonin-reuptake inhibitors (SSRIs) and the risk of birth defects were examined among 9849 infants with and 5860 infants without birth defects. In analyses of defects previously associated with SSRI use (involving 42 comparisons), overall use of SSRIs was not associated with significantly increased risks of craniosynostosis (OR 0.8, 95% CI 0.2 to 3.5; 115 subjects, 2 exposed to SSRIs), omphalocele (OR 1.4, 95% CI 0.4 to 4.5; 127 subjects, 3 exposed), or heart defects overall (OR 1.2, 95% CI 0.9 to 1.6; 3724 subjects, 100 exposed). Analyses of the associations between individual SSRIs and specific defects showed significant associations between the use of sertraline and omphalocele (OR 5.7, 95% CI, 1.6 to 20.7; 3 exposed subjects) and septal defects (OR 2.0, 95% CI 1.2 to 4.0; 13 exposed subjects) and between the use of paroxetine and right ventricular outflow tract obstruction defects (OR 3.3, 95% CI 1.3 to 8.8; 6 exposed subjects). The risks were not appreciably or significantly increased for other defects or other SSRIs or non-SSRI antidepressants. Exploratory analyses involving 66 comparisons showed possible associations of paroxetine and sertraline with other specific defects.
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