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In utero exposure to methylphenidate, amphetamines and atomoxetine and offspring neurodevelopmental disorders: a population-based cohort study and meta-analysis
Department of Clinical Research, University of Southern Denmark, Odense, Denmark; NCRR- National Centre for Register-based Research, Department of Public Health, Aarhus University, Aarhus, Denmark; CIRRAU - Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID iD: 0000-0002-6851-3297
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
NCRR- National Centre for Register-based Research, Department of Public Health, Aarhus University, Aarhus, Denmark; CIRRAU - Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
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2025 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 30, no 9, p. 3885-3894Article in journal (Refereed) Published
Abstract [en]

The use of Attention-Deficit/Hyperactivity Disorder (ADHD) medications during pregnancy is increasing, raising concerns about potential long-term effects on offspring. This study investigates in utero exposure to methylphenidate, amphetamines and atomoxetine and risk of offspring neurodevelopmental disorders (NDDs). The population-based cohort study identified from Swedish registers included 861,650 children born by 572,731 mothers from 2008-2017. We categorized exposure based on redeemed medication during pregnancy and compared exposed children to those whose mothers discontinued medication before conception. Main outcomes were any NDD, including ADHD and autism spectrum disorder (ASD). Cox proportional hazards regression estimated hazard ratios (HRs), adjusting for maternal psychiatric and sociodemographic factors. Sensitivity analyses included stratifications by medication type, timing, and duration of exposure, and sibling comparisons. We also performed a meta-analysis combining data from the present study with those from a previous Danish study. Results showed no increased risk for any NDD (HRadjusted 0.95, 95% CI 0.82-1.11), ADHD (HRadjusted 0.92, 95% CI 0.78-1.08), or ASD (HRadjusted 0.86, 95% CI 0.63-1.18). Sensitivity analyses showed consistent patterns of no increased risks across different exposure durations, medication types and between siblings. Meta-analyses further supported the findings (pooled HR for any NDD 1.00, 95% CI 0.83;1.20). Our study provides evidence that in utero exposure to ADHD medications does not increase the risk of long-term NDDs in offspring. This study replicates safety data for methylphenidate and extends it with new safety data on amphetamines and atomoxetine. These findings are crucial for informing clinical guidelines and helping healthcare providers and expectant mothers make informed decisions.

Place, publisher, year, edition, pages
Springer Nature, 2025. Vol. 30, no 9, p. 3885-3894
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Psychiatry
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URN: urn:nbn:se:oru:diva-120337DOI: 10.1038/s41380-025-02968-4ISI: 001454859900001PubMedID: 40148550Scopus ID: 2-s2.0-105001130351OAI: oai:DiVA.org:oru-120337DiVA, id: diva2:1948533
Note

Funding Agency:

Open access funding provided by University of Southern Denmark.

Available from: 2025-03-31 Created: 2025-03-31 Last updated: 2025-08-25Bibliographically approved

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Larsson, HenrikGarcia-Argibay, Miguel

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