Fetal cardiac safety of sertraline use during pregnancy

ABSTRACT

Introduction

Fetal cardiac safety of sertraline is controversial even though it is among the most frequently used antidepressants in pregnancy. Sertraline could theoretically affect the fetal heart resulting in malformations or more subtle changes, but studies evaluating fetal cardiac safety are prone to a number of systematic and random errors.

Areas covered

The objective of this review is to evaluate the fetal cardiac safety profile of sertraline in pregnancy. A literature review included articles until November 2022 in Medline with no time or language limitations.

Expert Opinion

Sertraline is associated with septal heart malformations, but not with more severe heart malformations. The association may be causal or at least partly related to systematic errors, including confounding by indication. Regardless of the causal mechanism, the association should not limit well-indicated treatments of maternal depression. The few available studies on fetal heart function is reassuring. There are no human data on the long-term effects on offspring cardiac function, but the teratogenic and fetal heart function studies do not imply risks of any major cardiac problems later in life. Interactions with other medication may, however, alter the risks associated with any medication in pregnancy, and information and surveilence systems taking this into account is much needed.

KEYWORDS:

• Antidepressants
• drug safety
• cardiac function
• cardiac malformations
• pregnancy
• sertraline
• SSRI
• teratology

Article highlights

• Sertraline could theoretically influence cardiac function and cause cardiac malformations.

• The observed increased risk of cardiac malformations after sertraline exposure is likely limited to less severe malformations (i.e. malformations that did not result in terminations, miscarriages, stillbirths, or cardiac surgery).

• Ventricular changes after prenatal sertraline exposure have been observed in experimental animal studies and in neonates, but the few available data suggest no effect on fetal cardiac function in humans.

• Comprehensive data, including prenatal diagnoses, may be needed in analyses on outcomes prone to selection (e.g. severe cardiac malformations)

• Care for pregnant women with depression should ideally be based on the most updated information available, and currated survailence and information systems are promising

Declaration of interest

JN Henriksen has received speaker honoraria fees from Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

LHP conceived of the presented idea. All authors contributed to the final manuscript

Additional information

Funding

This paper was funded by Health Research Foundation of the Central Denmark Region and Borregaard Clinical Ascending Investigator Grant from the Novo Nordisk Foundation (NNF18OC0054457).