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In utero exposure to ADHD medication and long-term offspring outcomes

Molecular Psychiatry (2023)Cite this article

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Abstract

Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.

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Fig. 1

Code availability

Statistical analyses were performed in Stata 15.1 (StataCorp, College Station, TX, USA) and code to perform analyses can be made available by request.

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Acknowledgements

KBM and TMO receive funding from Sygeforsikring “danmark” (Journalnr. 2021-0139). This study was also funded by the National Institute of Mental Health (NIMH) (R01MH122869). JWD reports funding from the Independent Research Fund Denmark (1133-00026B). The funding agencies had no role in the design, data collection, analysis, interpretation, writing the manuscript, or the decision to submit the manuscript for publication. The corresponding author had full access to the data and had final responsibility for data integrity and data analysis.

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Author notes

  1. These authors contributed equally: Trine Munk-Olsen, Veerle Bergink.

Authors and Affiliations

  1. NCRR - National Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Aarhus, Denmark

    Kathrine Bang Madsen, Xiaoqin Liu, Natalie Momen, Julie Werenberg Dreier & Trine Munk-Olsen

  2. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Thalia K. Robakis, Jeffrey H. Newcorn & Veerle Bergink

  3. School of Medical Sciences, Örebro University, Örebro, Sweden

    Henrik Larsson

  4. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Henrik Larsson

  5. Department of Clinical Medicine, University of Bergen, Bergen, Norway

    Julie Werenberg Dreier

  6. Hans Christian Andersen’s Children’s Hospital, Odense University Hospital, Odense, Denmark

    Helene Kildegaard

  7. Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark, Odense, Denmark

    Helene Kildegaard

  8. Department of Otorhinolaryngology and Audiology, Zealand University Hospital, Universty of Copenhagen, Køge, Denmark

    Jane Bjerg Groth

  9. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Per Hove Thomsen

  10. Research Center at the Department for Child‐ and Adolescent Psychiatry, Aarhus University Hospital, Skejby, Denmark

    Per Hove Thomsen

  11. Research Unit of Psychiatry, Institute for Clinical Research, University of Southern Denmark, Odense, Denmark

    Trine Munk-Olsen

  12. Department of Psychiatry, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands

    Veerle Bergink

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Contributions

KBM, TKR, XL, NM, TMO, and VB designed the study. KBM, NM, and XL conducted the analysis and KBM wrote the first draft of the manuscript. TKR, XL, NM, HL, JWD, HK, JBG, JHN, PHT, TMO, and VB made significant contributions to the interpretation of the analysis and writing of the study. All authors have revised the article critically and all share responsibility for the content of the manuscript. All authors have approved the manuscript.

Corresponding author

Correspondence to Kathrine Bang Madsen.

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Competing interests

HL reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Medice, Shire/Takeda Pharmaceuticals, and Evolan Pharma AB; and sponsorship for a conference on attention-deficit/hyperactivity disorder from Shire/Takeda Pharmaceuticals and Evolan Pharma AB, all outside the submitted work. HL is editor-in-chief of JCPP Advances. JHN reports the following disclosures (all unrelated to this work): consultant/advisory board for Adlon Therapeutics, Arbor, Corium, Lumos, Medice, Myriad, NLS, OnDosis, Rhodes, and Supernus; research support from Adlon, Otsuka, Shire, Supernus; honoraria for disease state lectures from Otsuka and Takeda, and served as a consultant for the US National Football League. PHT has received speakers fees from MEDICE and Takeda within the last 3 years. All other authors have nothing to declare.

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Bang Madsen, K., Robakis, T.K., Liu, X. et al. In utero exposure to ADHD medication and long-term offspring outcomes. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-01992-6

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