Foetal Antiepileptic Drug Exposure and Verbal versus Non-Verbal Abilities at Three Years of Age

We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-c...

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Bibliographic Details
Published in:	Brain (London, England : 1878) England : 1878), 2011-02, Vol.134 (2), p.396-404
Main Authors:	Meador, Kimford J, Baker, Gus A, Browning, Nancy, Cohen, Morris J, Clayton-Smith, Jill, Kalayjian, Laura A, Kanner, Andres, Liporace, Joyce D, Pennell, Page B, Privitera, Michael, Loring, David W
Format:	Article
Language:	eng
Subjects:	Adult Age Anticonvulsants - adverse effects Anticonvulsants. Antiepileptics. Antiparkinson agents Antiepileptic agents Biological and medical sciences Carbamazepine Child, Preschool Children Cognition Disorders - chemically induced Cognition Disorders - complications Cognition Disorders - prevention & control Cognition Disorders - psychology Cognitive ability Comparative Analysis Correlation Developmental Tests of Visual Motor Association Dose-Response Relationship, Drug Drug Therapy Drugs Epilepsy Epilepsy - complications Epilepsy - drug therapy Female Females Folic acid Folic Acid - therapeutic use Foreign Countries Hemispheric laterality Humans Integration Intelligence Intelligence Quotient Intelligence Tests lamotrigine Language Lateral Dominance Measures (Individuals) Medical sciences Neonates Neurology Neuropharmacology Nonverbal Ability Original Peabody Picture Vocabulary Test Pharmacology. Drug treatments Phenytoin Pregnancy Prenatal Exposure Delayed Effects - psychology Preschool Children Prospective Studies Psychomotor Performance - drug effects Psychomotor Skills Risk Seizures United Kingdom United States Valproic acid Verbal Ability Verbal Behavior - drug effects
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Summary:	We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled pregnant females with epilepsy on monotherapy from 1999 to 2004. The study seeks to determine if differential long-term neurodevelopmental effects exist across four commonly used drugs (carbamazepine, lamotrigine, phenytoin and valproate). This report compares verbal versus non-verbal cognitive outcomes in 216 children who completed testing at the age of three years. Verbal and non-verbal index scores were calculated from the Differential Ability Scales, Preschool Language Scale, Peabody Picture Vocabulary Test and Developmental Test of Visual-Motor Integration. Verbal abilities were lower than non-verbal in children exposed in utero to each drug. Preconceptional folate use was associated with higher verbal outcomes. Valproate was associated with poorer cognitive outcomes. Performance was negatively associated with valproate dose for both verbal and non-verbal domains and negatively associated with carbamazepine dose for verbal performance. No dose effects were seen for lamotrigine and phenytoin. Since foetal antiepileptic drug exposure is associated with lower verbal than non-verbal abilities, language may be particularly susceptible to foetal exposure. We hypothesize that foetal drug exposure may alter normal cerebral lateralization. Further, a dose-dependent relationship is present for both lower verbal and non-verbal abilities with valproate and for lower verbal abilities with carbamazepine. Preconceptional folate may improve cognitive outcomes. Additional research is needed to confirm these findings, extend the study to other drugs, define the risks associated with drug treatment for seizures in the neonates, and understand the underlying mechanisms.
ISSN:	0006-8950 1460-2156