Antipsychotic drug use in pregnancy: A multinational study from ten countries

Reutfors, Johan; Cesta, Carolyn E.; Cohen, Jack; Bateman, Brian T.; Brauer, Ruth; Einarsdóttir, Kristjana; Engeland, Anders; Furu, Kari; Gissler, Mika; Havard, Alys; Hernández–Dı́az, Sonia; Huybrechts, Krista F.; Karlstad, Øystein; Leinonen, Maarit K.; Li, Jiong; Man, Kenneth K C; Pazzagli, Laura; Schaffer, Andrea L; Schink, Tania; Wang, Zixuan; Yu, Yongfu; Zoëga, Helga; Bröms, Gabriella

doi:10.1016/j.schres.2020.03.048

Cited by 40 publications

(33 citation statements)

References 42 publications

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“…Of the individual S-GAs, olanzapine use was associated with a twofold increased risk of overall malformations, and specifically, a nearly fourfold increased risk of musculoskeletal malformations when compared to unexposed. Use of S-GAs has been increasing among the pregnant population [3,4] and indications for S-GA use have expanded during the last decade to include also illnesses outside psychotic disorders [3,5]. S-GAs are used increasingly in treating bipolar disorder and as augmentation treatment in unipolar depression [15].…”

Section: Discussionmentioning

confidence: 99%

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

Ellfolk

Leinonen

Gissler

et al. 2021

Eur J Clin Pharmacol

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Purpose To 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). Methods A 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. Results Use 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. Conclusions Olanzapine 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.

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Section: Discussionmentioning

confidence: 99%

“…S-GAs are used increasingly in treating bipolar disorder and as augmentation treatment in unipolar depression [15]. Further, S-GAs may be preferred during pregnancy because of safety concerns related to antiepileptic drugs as mood stabilizers [3]. Antipsychotic augmentation may also be effective in treatment-refractory OCD [16].…”

Section: Discussionmentioning

confidence: 99%

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

Ellfolk

Leinonen

Gissler

et al. 2021

Eur J Clin Pharmacol

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“…An increasing trend of antipsychotic use, in particular atypical antipsychotics, in pregnancies has been observed in the last 3 decades. [9][10][11] It is therefore important to investigate the safety of these medications.…”

Section: Introductionmentioning

confidence: 99%

Prenatal exposure to antipsychotic agents and the risk of congenital malformations in children: A systematic review and meta‐analysis

Wang¹,

Brauer²,

Man

et al. 2021

Brit J Clinical Pharma

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Study selection: Of 38 reports initially identified as being of potential interest, 13 studies met our inclusion criteria: English observational studies that examined the association between gestational antipsychotic use and congenital malformations in children.Data extraction: Data were extracted independently by 2 investigators including the publication year, study site, study period, data source, study design, sample size, medication exposure, exposure period and pregnancy definition, exposure as well as outcome ascertainment, selection of study and comparison group, confounding adjustment, statistical analysis, and method of linkage between mother and children.Risk estimates were pooled using a random-effect model and the I 2 statistic was used to evaluate the degree of heterogeneity.Results: Thirteen studies met our systematic review inclusion criteria. Six studies with a total of 2 515 272 pregnancy episodes were included in our meta-analysis, which provided a pooled adjusted risk ratio of 1.23, 95% confidence interval: 0.96-1.58. The I 2 result showed moderate heterogeneity between studies (I 2 = 35.2%, P = .173). Conclusion:We did not find strong evidence of an association between prenatal exposure to antipsychotic medications and the risk of congenital malformations in children. We recommend further studies investigate this association, focusing on Abbreviations: aRR, adjusted risk ratio; CI, confidence interval; FGA, first-generation antipsychotic; NOS, Newcastle-Ottawa Scale; OR, odds ratio; PS, propensity score; RR, risk ratio; SGA, second-generation antipsychotic.

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“…The recent studies carried out within our collaboration before we had individually pooled and harmonized data were based on sharing aggregated data tables Reutfors et al, 2020. This approach was labor intensive, requiring the analysis to be run in each country with a unique program adapted to the local data structure.…”

Section: Discussionmentioning

confidence: 99%

A common data model for harmonization in the Nordic Pregnancy Drug Safety Studies (NorPreSS)

et al. 2021

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It is necessary to carry out large observational studies to generate robust evidence about the safety of drugs used during pregnancy. In the Nordic countries, nationwide population-based health registers that document all births and dispensed prescribed drugs are valuable resources for such studies. A common data model (CDM) is a data harmonization and structuring tool that enables a unified and streamlined analytic approach for studies including data from multiple countries or databases. We describe a CDM developed for the Nordic Pregnancy Drug Safety Studies (NorPreSS), including details on data sources and structure of the data tables. We also provide an overview of the advantages and disadvantages of the approach (e.g. sharing of data analysis programs versus extra initial work to create CDM datasets from raw data).

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Antipsychotic drug use in pregnancy: A multinational study from ten countries

Cited by 40 publications

References 42 publications

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

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

Prenatal exposure to antipsychotic agents and the risk of congenital malformations in children: A systematic review and meta‐analysis

A common data model for harmonization in the Nordic Pregnancy Drug Safety Studies (NorPreSS)

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