ArticlemedRxiv : the preprint server for health sciences2024
Antidepressant use during pregnancy and birth outcomes: analysis of electronic health data from the UK, Norway, and Sweden.
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Florence Z MartinMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0002-6804-008X
Viktor H AhlqvistMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0003-1383-3194
Paul Madley-DowdMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0003-2932-9486
Michael LundbergMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.
Jacqueline M CohenMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0002-7300-0488
Kari FuruMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0003-2245-0179
Dheeraj RaiMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0002-7239-3523
Harriet ForbesMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0001-6888-2212
Kayleigh EaseyMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0002-3718-2915
Siri E HåbergMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0002-2199-5225
Gemma C SharpMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0003-2906-4035
Cecilia MagnussonMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0002-8567-6725
Maria C MagnusMRC Integrative Epidemiology Unit, Oakfield House, University of Bristol, BS8 2BN Florence Z Martin PhD student Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark Viktor H Ahlqvist postdoctoral fellow MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Paul Madley-Dowd research fellow Solnavägen 1 E, 11365 Stockholm Michael Lundberg statistician Marcus Thranes gate 6, 0473 Oslo Jacqueline M Cohen senior researcher Marcus Thranes gate 6, 0473 Oslo Kari Furu research professor Centre for Academic Mental Health, Canynge Hall, University of Bristol, BS8 2PN Dheeraj Rai professor of neurodevelopmental psychiatry Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT Harriet Forbes assistant professor School of Psychological Science, University of Bristol, BS8 1TU Kayleigh E Easey senior lecturer Myrens verksted 2, 0473 Oslo Siri E Håberg centre director School of Psychology, University of Exeter, EX4 4QG Gemma C Sharp associate professor of epidemiology Solnavägen 1 E, 11365 Stockholm Cecilia Magnusson adjunct professor Myrens verksted 2, 0473 Oslo Maria C Magnus researcher.ORCID 0000-0002-0568-3774
Funding
Maternal epilepsy, antiepileptic drug use during pregnancy, and risk of autismR01NS107607 · NINDS · DREXEL UNIVERSITY · PI LEE, BRIAN KANE, MAGNUSSON, CECILIA · 2019 to 2022
$1.7MNINDS NIH HHS R01 NS107607Wellcome Trust
Abstract
Objectives: To explore the association between antidepressant use during pregnancy and birth outcomes. Design: Cohort study. Setting: Electronic health record data. Participants: 2 528 916 singleton births from the UK's Clinical Practice Research Datalink (1996-2018), Norway's Medical Birth Registry (2009-2020), and Sweden's Medical Birth Register (2006-2020). Main outcome measures: Stillbirth, neonatal death, pre- and post-term delivery, small and large for gestational age, and low Apgar score five minutes post-delivery. Results: A total of 120 209 (4.8%) deliveries were exposed to maternal antidepressant use during pregnancy. Maternal antidepressant use during pregnancy was associated with increased odds of stillbirth (adjusted pooled OR (aOR) 1.16, 95% CI 1.05 to 1.28), preterm delivery (aOR 1.26, 95% CI 1.23 to 1.30), and Apgar score < 7 at 5 minutes (aOR 1.83, 95% CI 1.75 to 1.91). These findings persisted in the discordant sibling analysis, but with higher uncertainty. The adjusted predicted absolute risk for stillbirth was 0.34% (95% CI 0.33 to 0.35) among the unexposed and 0.40% (95% CI 0.36 to 0.44) in the antidepressant exposed. Restricting to women with depression or anxiety, the association between antidepressant exposure and stillbirth attenuated (aOR 1.07, 95% CI 0.94 to 1.21). Paternal antidepressant use was modestly associated with preterm delivery and low Apgar score. Most antidepressants were associated with preterm delivery (except paroxetine) and Apgar score (except mirtazapine and amitriptyline). Conclusions: Maternal antidepressant use during pregnancy may increase the risk of stillbirth, preterm delivery, and low Apgar score, although the absolute risks remained low. Confounding by severity of indication cannot be ruled out, as the severity of symptoms was not available. The modest association between paternal antidepressant use and both preterm delivery and low Apgar score suggests that residual confounding by familial environment cannot be ruled out.
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