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Research paper
The prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs
  1. Rebecca Louise Bromley1,
  2. George E Mawer2,
  3. Maria Briggs2,
  4. Christopher Cheyne3,
  5. Jill Clayton-Smith2,
  6. Marta García-Fiñana3,
  7. Rachel Kneen4,5,
  8. Sam B Lucas2,
  9. Rebekah Shallcross6,
  10. Gus A Baker1,
  11. On Behalf of the Liverpool and Manchester Neurodevelopment Group
  1. 1Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
  2. 2Genetic Medicine, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
  3. 3Department of Biostatistics, University of Liverpool, Liverpool, UK
  4. 4Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK
  5. 5Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
  6. 6Department of Clinical Psychology, University of Liverpool, Liverpool, UK
  1. Correspondence to Dr Rebecca Louise Bromley, Department of Molecular and Clinical Pharmacology, Clinical Sciences Centre for Research and Education, Lower Lane, Liverpool L9 7LJ, UK; r.l.bromley{at}liv.ac.uk

Abstract

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.

  • Epilepsy
  • Neuropsychology
  • Neurotoxicology
  • Paediatric
  • Obstetrics

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