The prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs
Open accessAbstract
The aim of this study was to compare the prevalence of diagnosed neurodevelopmental disorders in children exposed, in utero, to different antiepileptic drug treatments. A prospective cohort of women with epilepsy and a control group of women without epilepsy were recruited from antenatal clinics. The children of this cohort were followed longitudinally until 6 years of age (n=415). Diagnosis of a neurodevelopmental disorder was made independently of the research team. Multiple logistic regression analysis revealed an increase in risk of neurodevelopmental disorders in children exposed to monotherapy sodium valproate (VPA) (6/50, 12.0%; aOR 6.05, 95%CI 1.65 to 24.53, p=0.007) and in those exposed to polytherapy with sodium VPA (3/20, 15.0%; aOR 9.97, 95% CI 1.82 to 49.40, p=0.005) compared with control children (4/214; 1.87%). Autistic spectrum disorder was the most frequent diagnosis. No significant increase was found among children exposed to carbamazepine (1/50) or lamotrigine (2/30). An accumulation of evidence demonstrates that the risks associated with prenatal sodium VPA exposure include an increased prevalence of neurodevelopmental disorders. Whether such disorders are discrete or represent the severe end of a continuum of altered neurodevelopmental functioning requires further investigation. Replication and extension of this research is required to investigate the mechanism(s) underpinning the relationship. Finally, the increased likelihood of neurodevelopmental disorders should be communicated to women for whom sodium VPA is a treatment option.
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A rare consistent association with AD is in utero exposure to two known teratogenic medications, thalidomide and valproate, or the abortifactant misoprostol.
“In addition, concerning the prenatal risk factors for AD, a rare consistent association with AD is in utero exposure to two known teratogenic medications, thalidomide, and valproate (valproate is a broad-spectrum anticonvulsant drug used in seizures, bipolar disorder, or migraine headache), or the abortifactant misoprostol (7, 61–63).”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [62]
Children exposed to valproate in utero were seven times more likely to develop autism than those not exposed to antiepileptic drugs.
“Thus, children exposed to valproate in utero were seven times more likely to develop autism than those not exposed to antiepileptic drugs (61, 62).”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [62]
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- Authors
- Bromley, R. L., Mawer, G. E., Briggs, M., Cheyne, C., Clayton-Smith, J., Garcia-Finana, M., Kneen, R., Lucas, S. B., Shallcross, R., Baker, G. A., On Behalf of the Liverpool and Manchester Neurodevelopment Group, Baker, G., Briggs, M., Bromley, R., Clayton-Smith, J., Dixon, P., Fryer, A., Gummery, A., Kneen, R., Kerr, L., Lucas, S., Mawer, G., & Shallcross, R.
- Affiliations
- University of Liverpool (GB)
- Manchester Academic Health Science Centre (GB)
- ORCID
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2013-01-31
- Volume
- 84
- Issue
- 6
- Pages
- 637-643
- ISSN
- 0022-3050 (ISSN-L)
- PMC
- PMC4115188
- OpenAlex
- W2143309726
- Cited by
- 367
- References
- 42
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 29 · 2023: 23 · 2022: 31 · 2021: 33 · 2020: 31 · 2019: 27 · 2018: 33 · 2017: 31 · 2016: 31 · 2015: 25 · 2014: 24 · 2013: 16
- FWCI
- 29.81
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Funders
- Sanofi
- Epilepsy Research UK
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS038455, R01NS038455, U01NS038455)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- neurodevelopmental disorders, valproic acid, women with epilepsy, autism spectrum disorder, carbamazepine, lamotrigine, polypharmacy, children
- MeSH terms
- Lamotrigine, Adult, Anticonvulsants, Carbamazepine, Child, Developmental Disabilities, Child Development Disorders, Pervasive, Child, Preschool, Female, Humans, Infant, Pregnancy, Prenatal Exposure Delayed Effects, Prospective Studies, Risk Factors, Triazines, Valproic Acid, Prevalence, Logistic Models, Case-Control Studies
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