In utero exposure to methylphenidate, amphetamines and atomoxetine and offspring neurodevelopmental disorders: a population-based cohort study and meta-analysisDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Erasmus Medical Centre Rotterdam, Rotterdam, the Netherlands.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Solent NHS Trust, Southampton, UK; Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York City, NY, USA; DiMePRe-J-Department of Precision and Regenerative Medicine-Jonic Area, University of Bari "Aldo Moro", Bari, Italy.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
Research Center at the Department for Child- and Adolescent Psychiatry, Aarhus University Hospital, Skejby, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Division of Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Biomedicine, 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
National Category
Psychiatry
Identifiers
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.
2025-03-312025-03-312025-08-25Bibliographically approved