Association between exposure to atypical antipsychotics during pregnancy and risk of miscarriage

Author:

Ishikawa Tomofumi1ORCID,Sakai Takamasa2,Iwama Noriyuki34,Obara Ryo4,Morishita Kei4,Adomi Motohiko5,Noda Aoi467,Ishikuro Mami46,Kikuchi Saya8,Kobayashi Natsuko8,Tomita Hiroaki8,Saito Masatoshi3,Nishigori Hidekazu9,Kuriyama Shinichi4610,Mano Nariyasu17,Obara Taku467

Affiliation:

1. Laboratory of Biomolecule and Pathophysiological Chemistry, Graduate School of Pharmaceutical Sciences Tohoku University Sendai Japan

2. Drug Informatics, Faculty of Pharmacy Meijo University Nagoya Japan

3. Department of Obstetrics and Gynecology, Graduate School of Medicine Tohoku University Sendai Japan

4. Division of Molecular Epidemiology, Graduate School of Medicine Tohoku University Sendai Japan

5. Department of Epidemiology Harvard T.H. Chan School of Public Health Boston Massachusetts USA

6. Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization Tohoku University Sendai Japan

7. Department of Pharmaceutical Sciences Tohoku University Hospital Sendai Japan

8. Department of Psychiatry, Graduate School of Medicine Tohoku University Sendai Japan

9. Department of Development and Environmental Medicine, Fukushima Medical Center for Children and Women, Graduate School of Medicine Fukushima Medical University Fukushima Japan

10. International Research Institute of Disaster Science Tohoku University Sendai Japan

Abstract

AbstractObjectiveTo evaluate the association between exposure to atypical antipsychotics during pregnancy and risk of miscarriage.Material and MethodsThis nested case–control study used a large Japanese administrative database. Pregnancy onset and outcomes were estimated using previously reported algorithms, classifying cases as women becoming pregnant between 2013 and 2022 and ending in a miscarriage. Controls were randomly selected from the entire pregnancy cohort by risk‐set sampling with replacement and were individually matched to the cases (3:1). The association between exposure to atypical antipsychotics and risk of miscarriage was assessed using conditional logistic regression adjusted for confounders. The association between benzodiazepine exposure and the risk of miscarriage was assessed as a positive control.ResultsIn the cohort, 44,118 patients were matched with 132,317 controls. The mean ages (standard deviations) of the case and control groups were 33.3 (5.7) and 33.2 (5.5) years, respectively. The prevalence of atypical antipsychotics was 0.5% in both groups. Aripiprazole is an individual antipsychotic with the highest prescription prevalence. The adjusted odds ratios (aOR) for miscarriage were 0.966 (95% confidence interval [CI], 0.796–1.173) for atypical antipsychotics and 0.998 (0.784–1.269) for aripiprazole. A higher aOR (1.431, 95% CI 1.303–1.573) suggested an association with benzodiazepines. A sensitivity analysis that limited the population to women diagnosed with schizophrenia alone did not suggest an association between atypical antipsychotics and the risk of miscarriage.ConclusionsThe results of this study do not suggest an association between exposure to atypical antipsychotics during pregnancy and the risk of miscarriage.

Funder

Ministry of Health, Labour and Welfare

Japan Society for the Promotion of Science

Publisher

Wiley

Reference39 articles.

1. Japanese Society of Neuropsychopharmacology Japanese Society of Clinical Neuropsychopharmacology.Guideline for pharmacological therapy of schizophrenia 2022 (in Japanese). Available:https://www.jsnp‐org.jp/csrinfo/img/togo_guideline2022.pdf(Accessed on February 20 2024)

2. The American Psychiatric Association.Practice guideline for the treatment of patients with schizophrenia third edition 2021. doi:10.1176/appi.books.9780890424841(Accessed on February 20 2024).

3. Japanese Society of Perinatal Mental Health.Perinatal mental health consensus guideline 2023 (in Japanese). Available:http://pmhguideline.com/consensus_guide2023/consensus_guide2023.html(Accessed on February 20 2024)

4. Antipsychotic Medication Use Among Publicly Insured Pregnant Women in the United States

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

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