TY - JOUR

T1 - Antidepressant use in pregnancy and severe cardiac malformations

T2 - Danish register-based study

AU - Kolding, L.

AU - Ehrenstein, V.

AU - Pedersen, L.

AU - Sandager, P.

AU - Petersen, O. B.

AU - Uldbjerg, N.

AU - Pedersen, L. H.

N1 - Publisher Copyright: © 2021 John Wiley & Sons Ltd.

PY - 2021

Y1 - 2021

N2 - 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 of 364 012 pregnancies overall and in 16 of 4105 exposed. For venlafaxine, the PR for SCM was 2.13 (95% confidence interval [CI] 0.89–5.13), 1.73 (95% CI 1.08–2.77) for other cardiac malformations, and there was a cluster of hypoplastic left heart syndromes (HLHS) (crude PR 17.4 [95% CI 6.41–47.2]), none of which ended in a live birth. For HLHS, the absolute risk increase was 4.4/1000 and the number needed to harm was 225. For selective serotonin reuptake inhibitors, the PRs were 1.09 (95% CI 0.52–2.30) and 1.38 (95% CI 1.00–1.92) for SCM and other cardiac malformations, respectively. Conclusions: Pregnancy exposure to venlafaxine is associated with an increased risk of severe cardiac malformations 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. Tweetable abstract: Exposure to venlafaxine is associated with an increased risk of cardiac malformations but with a low absolute risk. Tweetable abstract.

AB - 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 of 364 012 pregnancies overall and in 16 of 4105 exposed. For venlafaxine, the PR for SCM was 2.13 (95% confidence interval [CI] 0.89–5.13), 1.73 (95% CI 1.08–2.77) for other cardiac malformations, and there was a cluster of hypoplastic left heart syndromes (HLHS) (crude PR 17.4 [95% CI 6.41–47.2]), none of which ended in a live birth. For HLHS, the absolute risk increase was 4.4/1000 and the number needed to harm was 225. For selective serotonin reuptake inhibitors, the PRs were 1.09 (95% CI 0.52–2.30) and 1.38 (95% CI 1.00–1.92) for SCM and other cardiac malformations, respectively. Conclusions: Pregnancy exposure to venlafaxine is associated with an increased risk of severe cardiac malformations 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. Tweetable abstract: Exposure to venlafaxine is associated with an increased risk of cardiac malformations but with a low absolute risk. Tweetable abstract.

KW - Antidepressants

KW - pregnancy

KW - prenatal ultrasound

KW - selection bias

KW - SSRI

KW - venlafaxine

U2 - 10.1111/1471-0528.16772

DO - 10.1111/1471-0528.16772

M3 - Journal article

C2 - 34036715

AN - SCOPUS:85108248720

VL - 128

SP - 1949

EP - 1957

JO - BJOG: An International Journal of Obstetrics and Gynaecology

JF - BJOG: An International Journal of Obstetrics and Gynaecology

SN - 0140-7686

IS - 12

ER -