Obstetric care for women that use antidepressants in pregnancyLine Kolding, MD, PhDVera Ehrenstein, MPH, DSc, ProfessorLars Pedersen, MSc, PhD, ProfessorPuk Sandager, MD, PhD, Associate ProfessorOlav B. Petersen, MD, PhD, ProfessorNiels Uldbjerg, MD, DMSc, ProfessorLars H. Pedersen, MD, PhD, ProfessorCorresponding:Lars Henning PedersenAarhus University Hospital / Aarhus UniversityPalle Juul-Jensens Blvd. 99, 8200 Aarhus N, DenmarkEmail: firstname.lastname@example.orgPhone: +45 50526512We are grateful to Drs. Braillon and Bewley for their interest in our recent paper in the BJOG 1 and would like to elaborate on some of the important points they raise.We agree with Braillon and Bewley on the urgent need for improved pharmacovigilance of medication in pregnancy in general, and for antidepressants in particular. There are excellent international collaborations (e.g., the EuroCat) and local initiatives (e.g., the Swedish JanusInfo), but clinically we’re often forced to rely on very limited information indeed. Systematic international recording as suggested by Braillon and Bewley would represent an important step forward.On a smaller scale, we are establishing an automated surveillance system based on curated data that include information on both pre- and postnatally diagnosed malformations. We have, however, faced substantial legal and bureaucratic challenges, and have been forced to use data from the Central Denmark Region only, instead of national data. The surveillance system is consequently based on information on approx. 75,000 pregnancies, and even though it has the potential to aide clinical management, it is a drop in the ocean of the huge potential of for instance a comparable European collaboration.In our study, we used ≥2 redeemed prescriptions to define exposure with a prevalence 1.1%.1 The prevalence of pregnant women that redeemed ≥1 prescription was 3.2% (p. 3/ Table S1), and even though this is likely an overestimation due to non-adherence, the estimates are in line with previously reported prevalences in Scandinavia.2Braillon and Bewley emphasise the need to also consider non-pharmacological treatment of some pregnant women with depression and, further, to provide evidence-based and individualised treatment of women in the reproductive ages. Optimal individualised care will definitely result in non-pharmacological treatment of some pregnant women but, reversely, will cause yet other women to continue or initiate pharmacological treatment. This is in line with what is almost a truism in this field, that the potential harmful foetal effects must be balanced against the potential benefits of a pharmacological treatment, but it is no easy task. Pregnant women might overestimate the foetal risks associated with use of medication3 and discontinue important treatment, on the other hand some may use medication when there may be a better alternative for them. Regardless, we need to provide optimal obstetric care for the pregnant women that choose treatment with antidepressants. If our results are correct, prenatal follow-up of pregnant women treated with venlafaxine may include targeted foetal heart scans, even though the underlying causal explanation for the observed association with cardiac malformations is undetermined.1. Kolding L, Ehrenstein V, Pedersen L, Sandager P, Petersen OB, Uldbjerg N, et al. Antidepressant use in pregnancy and severe cardiac malformations: Danish register-based study. BJOG. 2021 May 25.2. Zoega H, Kieler H, Norgaard M, Furu K, Valdimarsdottir U, Brandt L, et al. Use of SSRI and SNRI Antidepressants during Pregnancy: A Population-Based Study from Denmark, Iceland, Norway and Sweden. PLoS One. 2015;10(12):e0144474.3. Wolgast E, Lindh-Åstrand L, Lilliecreutz C. Women’s perceptions of medication use during pregnancy and breastfeeding—A Swedish cross-sectional questionnaire study. Acta Obstetricia et Gynecologica Scandinavica. 2019;98(7):856-64.
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, selection bias