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Published on: May 16, 2019
Antiseizure medication use during pregnancy and children's neurodevelopmental outcomes
Paul Madley-Dowd1,2,3, Viktor H Ahlqvist4,5, Harriet Forbes6,7
1Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. p.madley-dowd@bristol.ac.uk.
Insights
Valproate and other antiseizure medications (ASMs) during pregnancy may increase risks for neurodevelopmental disorders in children. Lamotrigine showed less evidence of risk, suggesting potential safer alternatives for pregnant individuals.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Pharmacology
Background:
- The teratogenicity of valproate during pregnancy is known.
- Limited data exists on the long-term safety of other antiseizure medications (ASMs) in pregnancy.
- Understanding risks associated with ASMs is crucial for maternal and child health.
Purpose of the Study:
- To investigate the association between prenatal exposure to various ASMs and neurodevelopmental diagnoses in children.
- To compare the risks of autism, intellectual disability, and ADHD following exposure to different ASMs.
Main Methods:
- Utilized UK primary care data and Swedish national registries.
- Created a large cohort of over 3 million children, including nearly 17,500 exposed to ASMs prenatally.
- Employed robust statistical analysis to compare neurodevelopmental outcomes between exposed and unexposed groups.
Main Results:
- Prenatal valproate exposure was linked to higher rates of autism, intellectual disability, and ADHD.
- Topiramate exposure increased the likelihood of intellectual disability by 2.5 times.
- Carbamazepine exposure was associated with a 1.25-fold increased risk of autism and a 1.30-fold increased risk of intellectual disability.
- Lamotrigine exposure showed minimal association with increased neurodevelopmental diagnoses.
Conclusions:
- Valproate, topiramate, and carbamazepine use during pregnancy may be associated with increased risks of neurodevelopmental disorders.
- Lamotrigine appears to have a comparatively better safety profile regarding these outcomes.
- Consideration of alternative, safer ASMs before conception is warranted when clinically feasible.
Abstract:
The teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.5 times more likely to be diagnosed with intellectual disability (95% CI: 1.23-4.98), and those exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05-1.48) and 1.30 times more likely to be diagnosed with intellectual disability (95% CI: 1.01-1.69). There was little evidence that children exposed to lamotrigine in pregnancy were more likely to receive neurodevelopmental diagnoses. While further research is needed, these findings may support considering safer treatment alternatives well before conception when clinically appropriate.
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