The prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs.
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.
Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK. r.l.bromley@liv.ac.uk
Rebecca Louise
RL
Bromley
George E
GE
Mawer
Maria
M
Briggs
Christopher
C
Cheyne
Jill
J
Clayton-Smith
Marta
M
García-Fiñana
Rachel
R
Kneen
Sam B
SB
Lucas
Rebekah
R
Shallcross
Gus A
GA
Baker
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects; D016022:Case-Control Studies; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000139:chemically induced / Q000453:epidemiology; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D000077213:Lamotrigine; D016015:Logistic Models; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D014227:Triazines / Q000009:adverse effects; D014635:Valproic Acid / Q000009:adverse effects
D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D014635:Valproic Acid; D000077213:Lamotrigine
Epilepsy; Neuropsychology; Neurotoxicology; Obstetrics; Paediatric