Which antidepressants used by pregnant women are associated with specific birth defects and do associations between antidepressants and specific birth defects remain after partially accounting for the underlying condition?

In a case-control study of 30 ,630 mothers of infants with birth defects and 11, 478 control mothers, there were previous and new associations between individual selective serotonin reuptake inhibitors,  , and bupropion and specific birth defects. Many selective serotonin reuptake inhibitor and birth defect (particularly heart defect) associations attenuated after partially accounting for the underlying condition; most venlafaxine associations remained.

This study included 30 630 case mothers of infants with birth defects and 11 478 control mothers (aged 12–53 years). Early pregnancy antidepressant use was reported by 1562 case mothers (5.1%) and 467 control mothers (4.1%), for whom elevated aORs were observed for individual selective serotonin reuptake inhibitors (SSRIs) and selected congenital heart defects (CHD) (eg, fluoxetine and anomalous pulmonary venous return: aOR, 2.56; 95% CI, 1.10-5.93; this association was attenuated after partially accounting for underlying conditions: aOR, 1.89; 95% CI, 0.56-6.42). This pattern was observed for many SSRI-CHD combinations. Associations between SSRIs and non-CHD birth defects often persisted or strengthened after partially accounting for underlying conditions (eg, citalopram and diaphragmatic hernia: aOR, 5.11; 95% CI, 1.29-20.24). Venlafaxine had elevated associations with multiple defects that persisted after partially accounting for underlying conditions (eg, anencephaly and craniorachischisis: aOR, 9.14; 95% CI, 1.91-43.83).

Conclusions: Venlafaxine was associated with the highest number of defects, which needs confirmation given the limited literature on venlafaxine use during pregnancy and risk for birth defects. Our results suggest confounding by underlying conditions should be considered when assessing risk. Fully informed treatment decision-making requires balancing the risks and benefits of proposed interventions against those of untreated depression or anxiety.