Antidepressant use in pregnancy and severe cardiac malformations: Danish
Objective Studies restricted to live births may underestimate
severe teratogenic effects. We address the limitation by including data
from both prenatal and postnatal diagnoses of cardiac malformations.
Design Register-based study. Setting Denmark.
Population 364,012 singleton pregnancies from 2007 to 2014.
Methods We used data from five nationwide registries. Exposure
to antidepressants was measured using redeemed prescriptions.
Main Outcome Measures Pregnancies with cardiac malformations
that end in miscarriage, termination, stillbirth, postnatal death or
cardiac surgery <1 year of birth were classified as severe
cardiac malformations (SCM). Propensity scores with adjusted prevalence
ratios (PRs) were calculated. Results SCM were reported in 972
/ 364 012 pregnancies overall and in 16 / 4105 exposed. PRs for SCM were
1.09 (95%CI: 0.52-2.30) for selective serotonin reuptake inhibitors
(SSRIs) and 2.13 (95%CI: 0.89-5.13) for venlafaxine. Among the
venlafaxine-exposed pregnancies, there was a cluster of hypoplastic left
heart syndromes (HLHS) (crude PR 17.4 (95%CI: 6.41-47.2)) of which none
ended in a live birth. For HLHS, the absolute risk increase was 4.4 per
1000, the number needed to harm (NNH) was 225. PRs for cardiac
malformations not classified as SCM were 1.38 (95%CI: 1.00-1.92) for
SSRIs, and 1.73 (95%CI: 1.08-2.77) for venlafaxine.
Conclusions Pregnancy exposure to venlafaxine, but not SSRIs,
is associated with an increased risk of SCM but with a low absolute
risk. Potential mechanisms include direct effects or confounding by
indication. Venlafaxine exposure is a marker for risk pregnancies for
which fetal echocardiography may be considered. Keywords
pregnancy, antidepressants, SSRI, venlafaxine, prenatal ultrasound,