Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6years

Abstract

The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study is a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on adaptive and emotional/behavioral functioning at 6 years of age in 195 children (including three sets of twins) whose parent (in most cases, the mother) completed at least one of the rating scales. Adjusted mean scores for the four AED groups were in the low average to average range for parent ratings of adaptive functioning on the Adaptive Behavior Assessment System—Second Edition (ABAS-II) and for parent and teacher ratings of emotional/behavioral functioning on the Behavior Assessment System for Children (BASC). However, children whose mothers took valproate during pregnancy had significantly lower General Adaptive Composite scores than the lamotrigine and phenytoin groups. Further, a significant dose-related performance decline in parental ratings of adaptive functioning was seen for both valproate and phenytoin. Children whose mothers took valproate were also rated by their parents as exhibiting significantly more atypical behaviors and inattention than those in the lamotrigine and phenytoin groups. Based upon BASC parent and teacher ratings of attention span and hyperactivity, children of mothers who took valproate during their pregnancy were at a significantly greater risk for a diagnosis of ADHD. The increased likelihood of difficulty with adaptive functioning and ADHD with fetal valproate exposure should be communicated to women with epilepsy who require antiepileptic medication. Finally, additional research is needed to confirm these findings in larger prospective study samples, examine potential risks associated with other AEDs, better define the risks to the neonate that are associated with AEDs for treatment of seizures, and understand the underlying mechanisms of adverse AED effects on the immature brain.

Using the Norwegian Mother and Child Cohort Study to determine risk factors for delayed development and neuropsychiatric

“…In utero AED exposure has been linked to lower IQ, delayed motor, verbal and social development, and neuropsychiatric disease such as autistic disorders and attention deficit hyperactive disorder (ADHD) (6)(7)(8). However, three major methodological challenges render the interpretation of these findings difficult.…”

Congenital Malformations in Newborns of Mothers Affected by Epilepsy

“…The elderly population is also prone to multiple comorbid conditions relevant to the etiology of epilepsy, such as stroke, cerebrovascular diseases, central nervous system tumors, and neurodegenerative diseases [4]. It has been estimated that 60% of incident epilepsy cases in the elderly population for which the etiology was identified were associated with cerebrovascular diseases, whereas approximately 20% were related to neurodegenerative diseases [4].…”

“…It has been estimated that 60% of incident epilepsy cases in the elderly population for which the etiology was identified were associated with cerebrovascular diseases, whereas approximately 20% were related to neurodegenerative diseases [4].…”

“…Recommendation that during the last month of pregnancy the mother with vitamin K (10 mg daily) for prevention of hemorrhagic disease in a child [3][4][5].…”

Algorithms of using valproic acid drugs in women

“…Отдельные публикации позволя-ют предполагать, что у детей, рожденных от матерей, при-нимавших препараты ВК, развиваются симптомы дефи-цита внимания и гиперактивпости [10][11][12]. Также пока-зана определенная зависимость между приемом препара-тов ВК и женским здоровьем, хотя данные факты доста-точно противоречивы [13][14][15].…”