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Thomas R Einarson
Deborah Kennedy
Adrienne Einarson


Antidepressants, pregnancy, malformations, research design



Many studies examining the teratogenic potential of antidepressants have been published. A variety of observational designs have been used with apparent conflicting results, although odds ratios were rarely >2.



To examine whether these apparent differences were associated with research methods such as model, comparison groups, data source, data collection procedures, definition of malformations, outcome ascertainment or management of confounders.



Medline and Embase were searched using terms: pregnancy, antidepressants, serotonin uptake inhibitors OR SSRI, AND embryonic structures OR congenital malformations OR fetal development for observational studies with original data. Data were analyzed using a structured approach and narrative review. Designs that were compared, included prospective cohort, retrospective cohort, and case-control studies. Rates of major malformations and cardiac malformations were combined by study type using random effects meta-analytic models.



We identified 150 papers; 127 were rejected, 23 were analyzed: 9 prospective cohort, 8 retrospective cohort, and 6 case-control studies. Sample sizes were large (1,818 exposed in case-control and 16,824 in cohort studies), providing relatively robust findings. Overall Odds Ratio’s for major malformations ranged from 1.03-1.24 and 0.81-1.32 for cardiac malformations. No discrepancies among research designs were identified.



Diverse observational models with differing strengths and weaknesses produced remarkably similar nonsignificant results. Perceived conflicting results may be due to subsequent dissemination of results with attention given to small statistically differences with negligible clinical importance. Improved methods of knowledge transfer and translation are required to provide sound evidence-based information to assist in decision-making surrounding the use of antidepressants in pregnancy.

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