Antipsychotic use during pregnancy and risk of specific neurodevelopmental disorders and learning difficulties in children: a multinational cohort study

Claudia Bruno; Carolyn E Cesta; Vidar Hjellvik; Sinna Pilgaard Ulrichsen; Marte-Helene Bjørk; Buket Öztürk Esen; Malcolm B Gillies; Mika Gissler; Alys Havard; Øystein Karlstad; Maarit K Leinonen; Mette Nørgaard; Sallie-Anne Pearson; Johan Reutfors; Kari Furu; Jacqueline M Cohen; Helga Zoega

doi:10.1016/j.eclinm.2024.102531

Antipsychotic use during pregnancy and risk of specific neurodevelopmental disorders and learning difficulties in children: a multinational cohort study

EClinicalMedicine. 2024 Mar 17:70:102531. doi: 10.1016/j.eclinm.2024.102531. eCollection 2024 Apr.

Authors

Claudia Bruno^{1

2}, Carolyn E Cesta³, Vidar Hjellvik², Sinna Pilgaard Ulrichsen⁴, Marte-Helene Bjørk^{5

6}, Buket Öztürk Esen⁴, Malcolm B Gillies¹, Mika Gissler^{7

8

9}, Alys Havard^{1

10}, Øystein Karlstad², Maarit K Leinonen⁷, Mette Nørgaard⁴, Sallie-Anne Pearson¹, Johan Reutfors³, Kari Furu^{2

11}, Jacqueline M Cohen^{2

11}, Helga Zoega^{1

12}

Affiliations

¹ School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
² Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway.
³ Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
⁴ Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark.
⁵ Department of Clinical Medicine, University of Bergen, Bergen, Norway.
⁶ Department of Neurology, Haukeland University Hospital, Bergen, Norway.
⁷ Knowledge Brokers, Finnish Institute for Health and Welfare, Helsinki, Finland.
⁸ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁹ Research Centre for Child Psychiatry, University of Turku, Turku, Finland.
¹⁰ National Drug and Alcohol Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
¹¹ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
¹² Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Abstract

Background: Antipsychotics are commonly prescribed to treat a range of psychiatric conditions in women of reproductive age and during pregnancy, including schizophrenia, bipolar disorder, anxiety, depression, autism spectrum disorder, and insomnia. This study aimed to evaluate whether children exposed to antipsychotic medication prenatally are at increased risk of specific neurodevelopmental disorders and learning difficulties.

Methods: Our population-based cohort study used nationwide register data (1 January 2000-31 December 2020) on pregnant women diagnosed with a psychiatric disorder and their live-born singletons from Denmark, Finland, Iceland, Norway, and Sweden. Cox proportional hazard regression yielded propensity score-weighted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of intellectual-, speech or language-, learning-developmental disorders, and a composite outcome of the listed disorders. We defined poor performance as scoring within the lowest quartile on national school tests in mathematics and language arts. We estimated propensity score-weighted risk ratios (aRRs) using Poisson regression. We analysed data from Denmark separately and pooled results using random effects meta-analysis.

Findings: Among 213,302 children (median follow-up: 6.7 years), 11 626 (5.5%) were exposed to antipsychotics prenatally. Adjusted risk estimates did not suggest an increased risk of neurodevelopmental disorders: aHR of 1.06 (95% CI 0.94-1.20) for the composite outcome, or for poor academic performance: aRR of 1.04 (95% CI 0.91-1.18) in mathematics, and of 1.00 (95% CI 0.87-1.15) in language arts. Results were generally consistent across individual medications, trimesters of exposure, sibling- and sensitivity analyses.

Interpretation: The findings of this large multinational cohort study suggest there is little to no increased risk of child neurodevelopmental disorders or learning difficulties after prenatal exposure to antipsychotics. Our findings can assist clinicians and women managing mental illness during pregnancy.

Funding: This study was funded by the NordForsk Nordic Program on Health and Welfare (Nordic Pregnancy Drug Safety Studies, project No. 83539), by the Research Council of Norway (International Pregnancy Drug Safety Studies, project No. 273366) and by the Research Council of Norway through its Centres of Excellence funding scheme (project No. 262700), and UNSW Scientia Programme Awards (PS46019, PS46019-A).

Keywords: Academic performance; Antipsychotics; Children; Neurodevelopmental disorders; Nordic health registers; Pregnancy.