Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects

Key PointsQuestionWhich 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? FindingsIn this case-control study of 30630 mothers of infants with birth defects and 11478 control mothers, there were previous and new associations between individual selective serotonin reuptake inhibitors, venlafaxine, 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. MeaningVenlafaxine was associated with more birth defects than other antidepressants, which needs confirmation; studies to assess birth defect risk among women taking antidepressants should account for the underlying condition. ImportanceAntidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks. ObjectiveTo examine associations between individual antidepressants and specific birth defects with and without attempts to partially account for potential confounding by underlying conditions. Design, Setting, and ParticipantsThe population-based, multicenter case-control National Birth Defects Prevention Study (October 1997-December 2011) included cases with selected birth defects who were identified from surveillance systems; controls were randomly sampled live-born infants without major birth defects. Mothers of cases and controls participated in an interview after the expected delivery date. The data were analyzed after the completion of the National Birth Defects Prevent Study's data collection. ExposuresSelf-reported antidepressant exposure was coded to indicate monotherapy exposure to antidepressants. Main Outcomes and MeasuresWe used multivariable logistic regression to calculate adjusted odds ratios (aORs) and 95% confidence intervals for associations between maternal antidepressant use and birth defects. We compared early pregnancy antidepressant-exposed women with those without antidepressant exposure and, to partially account for confounding by underlying maternal conditions, those exposed to antidepressants outside of the birth defect development critical period. ResultsThis study included 30630 case mothers of infants with birth defects and 11478 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 and RelevanceWe found some associations between maternal antidepressant use and specific birth defects. 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. This case-control study examines associations between individual antidepressants and specific birth defects for women who used antidepressants during early pregnancy.