Second-generation antipsychotic use during pregnancy and risk of congenital malformations

Maarit K. Leinonen,Maria Ellfolk,Sonja Kiuru-Kuhlefelt,Heli Malm,Mika Gissler,Leena Saastamoinen

doi:10.1007/s00228-021-03169-y

Abstract

PurposeTo study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM).MethodsA population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996–2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models.ResultsUse of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72–1.19) or to F-GA users (OR 0.82; 95% CI 0.56–1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19–3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35–10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results.ConclusionsOlanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.

Highlights

Maternal well-being is important for a successful pregnancy outcome, and psychiatric illness must be treated adequately during pregnancy
We evaluated the risk of overall major congenital malformations (MCM) and organ specific MCMs in offspring exposed to second-generation antipsychotic (S-GA) in early pregnancy using national register data
S-GA users were more likely to be overweight than first-generation antipsychotics (F-GAs) users or unexposed and S-GA and F-GA users were more likely to smoke tobacco than women in the unexposed group

Summary

Introduction

Maternal well-being is important for a successful pregnancy outcome, and psychiatric illness must be treated adequately during pregnancy. European Journal of Clinical Pharmacology (2021) 77:1737–1745 antidepressants [1]. Off-label use includes use in anxiety disorders, obsessive–compulsive disorders (OCD), post-traumatic stress disorder (PTSD) and insomnia [2]. The use of S-GA has been steadily increasing among pregnant women since year 2000; a recent study from ten countries reported that up to 2% of pregnant women use S-GAs, while there are differences across countries [3]. The use of first generation antipsychotics (F-GA) has waned [3, 4]. The increasing use of S-GAs may be at least partly explained by the increasing off-label use of quetiapine for insomnia [2, 5]

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