Second-generation antipsychotics and pregnancy complications

Maria Ellfolk,Marja-Leena Nurminen,Maarit K. Leinonen,Heli Malm,Leena Saastamoinen,Anna-Maria Lahesmaa-Korpinen,Mika Gissler

doi:10.1007/s00228-019-02769-z

Abstract

PurposeTo study if second-generation antipsychotic (S-GA) use during pregnancy is associated with an increased risk of pregnancy and neonatal complications.MethodsA population-based birth cohort study using national register data extracted from the “Drugs and Pregnancy” database in Finland, years 1996–2016. The sampling frame included 1,181,090 pregnant women and their singleton births. Women were categorized into three groups: exposed to S-GAs during pregnancy (n = 4225), exposed to first-generation antipsychotics (F-GAs) during pregnancy (n = 1576), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 21,125). Pregnancy outcomes in S-GA users were compared with those in the two comparison groups using multiple logistic regression models.ResultsComparing S-GA users with unexposed ones, the risk was increased for gestational diabetes (adjusted odds ratio, OR 1.43; 95% CI 1.25–1.65), cesarean section (OR 1.35; 95% CI 1.18–1.53), being born large for gestational age (LGA) (OR 1.57; 95% CI 1.14–2.16), and preterm birth (OR 1.29; 95% CI 1.03–1.62). The risk for these outcomes increased further with continuous S-GA use. Infants in the S-GA group were also more likely to suffer from neonatal complications. Comparing S-GA users with the F-GA group, the risk of cesarean section and LGA was higher (OR 1.25, 95% CI 1.03–1.51; and OR 1.89, 95% CI 1.20–2.99, respectively). Neonatal complications did not differ between the S-GA and F-GA groups.ConclusionsPrenatal exposure to S-GAs is associated with an increased risk of pregnancy complications related to impaired glucose metabolism. Neonatal problems are common and occur similarly in S-GA and F-GA users.

Highlights

Use of the second-generation antipsychotics (S-GAs) has increased during the last decades
Because of the increasing use of S-GAs among pregnant women and conflicting data on their safety, we investigated the association between S-GA use during pregnancy and pregnancy and neonatal complications using nationwide register data
Compared with that in the first-generation antipsychotics (F-GAs) group, the risk of gestational diabetes was not increased, while the risk of cesarean section was 25% higher and large for gestational age (LGA) was close to twice as high in the small for gestational age (SGA) group (Table 2)

Summary

Introduction

Use of the second-generation antipsychotics (S-GAs) has increased during the last decades. This tendency is evident on population level and within the pregnant population. In the USA, the prevalence of use of S-GAs during pregnancy increased from 0.4 to 1.3% in 2001–2010, while the use of first-generation antipsychotics (F-GAs) remained stable at around 0.1% [1]. The increased use of S-GAs may be related to the argued, but not uniformly proven, better tolerability or a more favorable side-effect profile when compared with that of F-GAs [2]. Off-label use, including use as hypnotics and sedatives, may play a role. There are no published data on use of antipsychotics during pregnancy in Finland

Methods

Results

Conclusion