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Prenatal exposure to sodium valproate and levetiracetam: consequences for neurodevelopmental outcomes?
[Thesis]. Manchester, UK: The University of Manchester; 2012.
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Abstract
Prenatal exposure to sodium valproate and levetiracetam: consequences for neurodevelopmental outcomes? Rebecca L. Bromley, PhD. For the award: Doctorate of Clinical Psychology. Submitted to the University of Manchester June 2012.Research has demonstrated that prenatal exposure to antiepileptic drugs is associated with an increased risk of physical malformations. The potential risk such exposure conveys to the developing brain and therefore the later cognitive functioning of the child is now the focus of both national and international research. This thesis investigated the relationship between prenatal exposure to antiepileptic drugs and child cognitive functioning. This investigation was undertaken in three phases: a systematic review of the published literature; an original research piece investigating prenatal exposure to sodium valproate and levetiracetam and finally a critical review of the research undertaken as part of this thesis and in the wider published literature.The systematic review identified 30 studies which had investigated the cognitive abilities of children with a history of prenatal exposure to antiepileptic drugs. Methodological quality of the studies was considered against the criteria of the Newcastle Ottawa Scale. Differential findings were noted across the antiepileptic drug types, with the largest number of studies documenting increased risks associated with prenatal exposure to sodium valproate. A lack of high quality research across all antiepileptic drugs, and in particular the more recently licensed antiepileptic drugs is highlighted. In the research paper presented here children aged between five and nine years of age exposed to either levetiracetam (n=37), sodium valproate (n=40) or who were born to women with epilepsy but did not require medication (n=43) were recruited from throughout the UK. Demographic and health information was collected from prospective records and supplemented with maternal interview. Formal standardised neuropsychological assessments were undertaken to inform on the child’s current level of intellectual, memory, language, attentional and executive functioning. Following adjustment for variables likely to influence child cognitive ability, prenatal exposure to sodium valproate was found to be associated with poorer intellectual and language functioning in a dose dependent manner. When stratified by dose, 57.9% of children exposed to doses of sodium valproate above 800mg daily scored below the average range for their global intellectual ability. Prenatal exposure to levetiracetam was not found to be associated with poorer cognitive functioning. The critical review highlighted a number of methodological strengths of this research, despite time and resource implications. However, consideration should be given to the retrospective nature of this cohort and the potential for recruitment bias.This thesis concludes that women who require continuation of their treatment during pregnancy to control their seizures should be counselled regarding the risks and the benefits of their treatment to allow them to make informed decisions.
Layman's Abstract
Prenatal exposure to sodium valproate and levetiracetam: consequences for neurodevelopmental outcomes? Rebecca L. Bromley, PhD. For the award: Doctorate of Clinical Psychology. Submitted to the University of Manchester June 2012.Research has demonstrated that prenatal exposure to antiepileptic drugs is associated with an increased risk of physical malformations. The potential risk such exposure conveys to the developing brain and therefore the later cognitive functioning of the child is now the focus of both national and international research. This thesis investigated the relationship between prenatal exposure to antiepileptic drugs and child cognitive functioning. This investigation was undertaken in three phases: a systematic review of the published literature; an original research piece investigating prenatal exposure to sodium valproate and levetiracetam and finally a critical review of the research undertaken as part of this thesis and in the wider published literature.The systematic review identified 30 studies which had investigated the cognitive abilities of children with a history of prenatal exposure to antiepileptic drugs. Methodological quality of the studies was considered against the criteria of the Newcastle Ottawa Scale. Differential findings were noted across the antiepileptic drug types, with the largest number of studies documenting increased risks associated with prenatal exposure to sodium valproate. A lack of high quality research across all antiepileptic drugs, and in particular the more recently licensed antiepileptic drugs is highlighted. In the research paper presented here children aged between five and nine years of age exposed to either levetiracetam (n=37), sodium valproate (n=40) or who were born to women with epilepsy but did not require medication (n=43) were recruited from throughout the UK. Demographic and health information was collected from prospective records and supplemented with maternal interview. Formal standardised neuropsychological assessments were undertaken to inform on the child’s current level of intellectual, memory, language, attentional and executive functioning. Following adjustment for variables likely to influence child cognitive ability, prenatal exposure to sodium valproate was found to be associated with poorer intellectual and language functioning in a dose dependent manner. When stratified by dose, 57.9% of children exposed to doses of sodium valproate above 800mg daily scored below the average range for their global intellectual ability. Prenatal exposure to levetiracetam was not found to be associated with poorer cognitive functioning. The critical review highlighted a number of methodological strengths of this research, despite time and resource implications. However, consideration should be given to the retrospective nature of this cohort and the potential for recruitment bias.This thesis concludes that women who require continuation of their treatment during pregnancy to control their seizures should be counselled regarding the risks and the benefits of their treatment to allow them to make informed decisions.