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Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations : A Multinational Study

Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations : A Multinational Study


Title: Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations : A Multinational Study
Author: Bröms, Gabriella
Hernandez-Diaz, Sonia
Huybrechts, Krista F.
Bateman, Brian T.
Kristiansen, Eskild Bendix
Einarsdóttir, Kristjana
Engeland, Anders
Furu, Kari
Gissler, Mika
Karlsson, Pär
... 8 more authors Show all authors
Date: 2023-01-16
Language: English
Scope: 601953
Department: Faculty of Medicine
Series: The Journal of clinical psychiatry; 84(1)
ISSN: 0160-6689
DOI: 10.4088/JCP.22m14430
Subject: Pregnancy; Infant, Newborn; Female; Humans; Atomoxetine Hydrochloride/adverse effects; Cohort Studies; Prevalence; Abnormalities, Drug-Induced/epidemiology; Pregnancy Trimester, First; Heart Defects, Congenital/chemically induced; Psychiatry and Mental Health
URI: https://hdl.handle.net/20.500.11815/4386

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Citation:

Bröms , G , Hernandez-Diaz , S , Huybrechts , K F , Bateman , B T , Kristiansen , E B , Einarsdóttir , K , Engeland , A , Furu , K , Gissler , M , Karlsson , P , Klungsøyr , K , Lahesmaa-Korpinen , A M , Mogun , H , Nørgaard , M , Reutfors , J , Sørensen , H T , Zoega , H & Kieler , H 2023 , ' Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations : A Multinational Study ' , The Journal of clinical psychiatry , vol. 84 , no. 1 . https://doi.org/10.4088/JCP.22m14430

Abstract:

Objective: Most research on safety of attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy concerns central nervous system stimulants, while little is known about the safety of atomoxetine, a primary treatment alternative. We assessed the prevalence of major congenital malformations overall, and cardiac malformations and limb malformations specifically, after first-trimester exposure. Methods: In this cohort study, we included all approximately 2.4 million pregnancies ending in live births recorded in the population-based nationwide health registers of Denmark, Iceland, Norway, and Sweden (2003-2017) and approximately 1.8 million publicly insured pregnancies ending in live births recorded in the US Medicaid Analytic eXtract (MAX, 2001-2013) health care claims database. We compared the prevalence of major congenital malformations in the newborn among pregnancies exposed and unexposed to atomoxetine. For each country, we calculated prevalence ratios (PRs), crude and stratified by propensity scores (PSs). We pooled the country-specific PS strata to obtain a PR adjusted for potential confounding factors. Results: We identified 368 pregnancies exposed to atomoxetine during the first trimester in the 4 Nordic countries and 622 in the US. The pooled crude PR for any major congenital malformation was 1.18 (95% CI, 0.88-1.60), and the adjusted PR was 0.99 (95% CI, 0.74-1.34). For cardiac malformations, the adjusted PR was 1.34 (95% CI, 0.86-2.09). For limb malformations, the adjusted PR was 0.90 (95% CI, 0.38-2.16). Conclusions: After atomoxetine exposure in early pregnancy, we observed no increase in major congenital malformations overall and, although with some uncertainty due to sample size, no statistically increased risk estimates for cardiac malformations and limb malformations.

Description:

Funding Information: Submitted: February 18, 2022; accepted September 20, 2022. Published online: January 16, 2023. Relevant financial relationships: Dr Bröms has been a speaker for Takeda and has been involved in projects at Centre for Pharmacoepidemiology, Karolinska Institutet, partly financed by Janssen, Pfizer, and UCB, all unrelated to this project. Dr Hernandez-Diaz is an investigator on grants to her institution from Takeda for unrelated studies, has received personal consulting fees from UCB and Roche outside the submitted work, and has served as an epidemiologist with the North America AED pregnancy registry and as a scientific advisor for the National Pregnancy Registry for Psychiatric Medication and for Pregistry, which are funded by multiple companies. Dr Huybrechts reports being an investigator on research grants to her institution from Takeda and UCB for unrelated studies. Mr Karlsson is employed at the Centre for Pharmacoepidemiology, Karolinska Institutet, which receives grants from several entities (pharmaceutical companies, regulatory authorities, and contract research organizations) for performance of drug safety and drug utilization studies, with no relation to the work reported in this article. Dr Nørgaard is employed at the Department of Clinical Epidemiology, Aarhus University Hospital, which receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of these studies has any relation to the present study. Dr Reutfors is employed at the Centre for Pharmacoepidemiology, Karolinska Institutet, which receives grants from several entities (pharmaceutical companies, regulatory authorities, and contract research organizations) for performance of drug safety and drug utilization studies, with no relation to the work reported in this article. Dr Sørensen is employed at the Department of Clinical Epidemiology, Aarhus University Hospital, which receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of these studies have any relation to the present study. Dr Zoega is employed at the Centre for Big Data Research in Health, UNSW Sydney, which received funding from AbbVie Australia in 2020 to conduct research, unrelated to this study. AbbVie did not have any knowledge of, or involvement in, this study. Dr Kieler is employed at the Centre for Pharmacoepidemiology, Karolinska Institutet, which receives grants from several entities (pharmaceutical companies, regulatory authorities, and contract research organizations) for performance of drug safety and drug utilization studies, with no relation to the work reported in this article. Drs Bateman, Einarsdóttir, Engeland, Furu, Gissler, Klungsøyr, and Lahesmaa-Korpinen; Mr Kristiansen; and Ms Mogun report no conflicts of interest. Funding/support: This study was supported by the Söderström-König Foundation (SLS-664411); the Swedish Society of Medicine (SLS-689141); and the Stockholm Region (clinical postdoc appointment SLL-20170670); partly supported by the Research Council of Norway through its Centres of Excellence funding scheme (Project# 262700); NordForsk as part of the Nordic Pregnancy Drug Safety Studies (NorPreSS; Project# 83539); the Research Council of Norway as part of the International Pregnancy Drug Safety Studies (InPreSS; Project# 273366); UNSW Scientia Award (to H.Z.); The Drugs and Pregnancy project, funded by the Finnish Institute for Health and Welfare (THL), the Finnish Medicines Agency (FIMEA), and the Social Insurance Institution of Finland (Kela); the National Institute of Child Health and Human Development (R21 HD092879); and the National Institute of Mental Health (R01 MH116194). Role of the sponsor: The funding sources had no role in the design and conduct of the study or in the decision to publish. Previous presentation: An oral presentation of this work (title: ADHD Drugs During Pregnancy and the Risk of Congenital Malformations: A Study from the International Pregnancy Safety Study [InPreSS] Consortium) was made at the International Conference of Pharmacoepidemiology and Drug Safety; Montreal, Canada; August 26-30 2017. Ethical approval: The study was approved by the Regional Ethical Review Board in Stockholm, Sweden (2015/1826-31/2); the National Bioethics Committee in Iceland (VSNb201860017/03.01); the Steering Committee of the Drugs and Pregnancy Project; the Norwegian Data Inspectorate and the Regional Ethics Committee for Medical Research of South/East Norway); and the Danish Data Protection Agency (2015-57-0002). The use of the US data was approved by the Institutional Review Board of Brigham and Women’s Hospital, which granted a waiver of informed consent. Additional information: The data in this study were obtained from national health registers in Denmark, Iceland, Norway, and Sweden and the US Medicaid Analytic eXtract and cannot be made publicly available in their entirety due to national laws and data privacy. ORCID: Gabriella Bröms: https://orcid.org/0000-0002-2423-1968; Johan Reutfors: https://orcid. org/0000-0003-1372-4262; Mika Gissler: https:// orcid.org/0000-0001-8254-7525; Kari Klungsøyr: https://orcid.org/0000-0003-2482-1690; Mette Nørgaard: https://orcid.org/0000-0001-6110-5891; Anders Engeland: https://orcid.org/0000-0001-5620-9207; Anna-Maria Lahesmaa-Korpinen: https://orcid.org/0000-0003-1062-2893; Krista Huybrechts: https://orcid.org/0000-0001-5805-8430; Kari Furu: https://orcid.org/0000-0003-2245-0179; Kristjana Einarsdóttir: https://orcid.org/0000-0003-4931-7650; Henrik Toft Sørensen: https:// orcid.org/0000-0003-4299-7040; Helga Zoega: https://orcid.org/0000-0003-0761-9028 Supplementary material: Available at Psychiatrist.com. Publisher Copyright: © 2023 The Authors. Published by Physicians Postgraduate Press, Inc.

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