First-trimester use of antiseizure medications and the risk of miscarriage: a population-based cohort study.

CLINICAL NEUROLOGY OBSTETRICS PSYCHIATRY

Journal

Journal of neurology, neurosurgery, and psychiatry
ISSN: 1468-330X
Titre abrégé: J Neurol Neurosurg Psychiatry
Pays: England
ID NLM: 2985191R

Informations de publication

Date de publication:
22 May 2024
Historique:
received: 05 01 2024
accepted: 27 04 2024
medline: 23 5 2024
pubmed: 23 5 2024
entrez: 22 5 2024
Statut: aheadofprint

Résumé

Antiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage. We carried out a population-based cohort study using routinely collected healthcare data from the UK, 1995-2018. Pregnancies were identified in the Clinical Practice Research Datalink and we estimated the HR of miscarriage associated with prescriptions of ASMs during the first trimester of pregnancy, using Cox regression, adjusting for potential confounders, including ASM indications. ASMs were prescribed during the first trimester in 7832 (0.8%) of 1 023 787 included pregnancies. 14.5% of pregnancies with first-trimester exposure to ASMs ended in miscarriage, while 12.2% without ASM exposure in the first trimester ended in miscarriage; after adjustment, there was a 1.06-fold relative hazard of miscarriage (95% CI 1.00 to 1.13) in women with first-trimester ASM use. After restricting to women with specific ASM indications, this association was not evident in women with epilepsy (adjusted HR 0.98, 95% CI 0.89 to 1.08), but was observed in women with bipolar or other psychiatric conditions (1.08, 95% CI 1.00 to 1.16) although CIs overlapped. Compared with discontinuation of ASMs prior to pregnancy, there was no evidence of increased risk of miscarriage for first-trimester ASM use in women with bipolar or other psychiatric conditions (1.02, 95% CI 0.87 to 1.20). We found no clear evidence to suggest that first-trimester ASM use increased the risk of miscarriage. Taken together, our analyses suggest that apparent associations between first-trimester ASM use and miscarriage may be the result of confounding by the presence of a bipolar disorder or associated unmeasured variables.

Sections du résumé

BACKGROUND BACKGROUND
Antiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage.
METHODS METHODS
We carried out a population-based cohort study using routinely collected healthcare data from the UK, 1995-2018. Pregnancies were identified in the Clinical Practice Research Datalink and we estimated the HR of miscarriage associated with prescriptions of ASMs during the first trimester of pregnancy, using Cox regression, adjusting for potential confounders, including ASM indications.
RESULTS RESULTS
ASMs were prescribed during the first trimester in 7832 (0.8%) of 1 023 787 included pregnancies. 14.5% of pregnancies with first-trimester exposure to ASMs ended in miscarriage, while 12.2% without ASM exposure in the first trimester ended in miscarriage; after adjustment, there was a 1.06-fold relative hazard of miscarriage (95% CI 1.00 to 1.13) in women with first-trimester ASM use. After restricting to women with specific ASM indications, this association was not evident in women with epilepsy (adjusted HR 0.98, 95% CI 0.89 to 1.08), but was observed in women with bipolar or other psychiatric conditions (1.08, 95% CI 1.00 to 1.16) although CIs overlapped. Compared with discontinuation of ASMs prior to pregnancy, there was no evidence of increased risk of miscarriage for first-trimester ASM use in women with bipolar or other psychiatric conditions (1.02, 95% CI 0.87 to 1.20).
CONCLUSION CONCLUSIONS
We found no clear evidence to suggest that first-trimester ASM use increased the risk of miscarriage. Taken together, our analyses suggest that apparent associations between first-trimester ASM use and miscarriage may be the result of confounding by the presence of a bipolar disorder or associated unmeasured variables.

Identifiants

DOI: 10.1136/jnnp-2023-333149 PMID: 38777577
pubmed: 38777577
pii: jnnp-2023-333149
doi: 10.1136/jnnp-2023-333149
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Harriet Forbes (H)

Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK Harriet.Forbes@lshtm.ac.uk.
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
ORCID: 0000-0001-6888-2212

Paul Madley-Dowd (P)

Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Viktor Ahlqvist (V)

Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Department of Global Public Health, Karolinska Institute, Stockholm, Sweden.
ORCID: 0000-0003-1383-3194

Jennifer Campbell (J)

Clinical Practice Research Datalink, Medicines and Healthcare Products Regulatory Agency, London, UK.

Neil M Davies (NM)

Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Division of Psychiatry, University College London, London, UK.
K.G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway.

Rachel Liebling (R)

Department of Obstetrics, University Hospitals Bristol and Weston, National Health Service England, Redditch, UK.

Kristen Lyall (K)

Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, Pennsylvania, USA.

Craig Newschaffer (C)

College of Health and Human Development, The Pennsylvania State University, Pennsylvania, Texas, USA.

Jessica Rast (J)

Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, Pennsylvania, USA.
A.J. Drexel Autism Institute, Philadelphia, Pennsylvania, USA.

Torbjörn Tomson (T)

Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.

Caichen Zhong (C)

Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, Pennsylvania, USA.

Cecilia Magnusson (C)

Department of Global Public Health, Karolinska Institute, Stockholm, Sweden.
Centre for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden.

Dheeraj Rai (D)

Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Avon and Wiltshire Partnership NHS Mental Health Trust, Bristol, UK.

Brian K Lee (BK)

Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Department of Global Public Health, Karolinska Institute, Stockholm, Sweden.
Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, Pennsylvania, USA.
A.J. Drexel Autism Institute, Philadelphia, Pennsylvania, USA.

Classifications MeSH