Prenatal and family risks of children born to mothers with epilepsy: Effects on cognitive development

Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Germany.
Developmental Medicine & Child Neurology (Impact Factor: 3.51). 03/2008; 50(2):117-22. DOI: 10.1111/j.1469-8749.2007.02020.x
Source: PubMed


The offspring of mothers with epilepsy are considered to be at developmental risk during pregnancy from: (1) generalized maternal seizures (hypoxia); (2) teratogenicity of antiepileptic drugs (AEDs); and (3) adverse socio-familial conditions associated with having a chronically sick mother. Sixty-seven children of mothers with epilepsy and 49 children from non-affected mothers, matched for control variables, were followed from birth to adolescence (53 males, 63 females; mean age 14y 2mo, range 10-20y). Prediction of intellectual performance of these children during adolescence was calculated from the following variables: maternal generalized seizures, prenatal exposure to AEDs, and quality of family stimulation (HOME Inventory) assessed in children at 2 years of age. Children who were prenatally exposed to AEDs achieved lower IQs than control children at adolescence. This effect was moderately significant for children who had been exposed to monotherapy (6 IQ points lower), but was considerable in those exposed to polytherapy (12 IQ points lower). Generalized seizures during pregnancy, observed in half the mothers, did not exacerbate this effect. Relative to prenatal risk status, the quality of the family environment had varied effects on intellectual development. Children with prenatal risks appeared to be more vulnerable to environmental disadvantage than control children, but they also showed longer-lasting effects of environmental support.

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Available from: Hellgard Rauh, Sep 27, 2014
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    • "The relationship between AED variables and seizure occurrence should be considered, as the effect of seizures may be confounded by a particular AED, polytherapy treatment , or dose. This was highlighted in the research by Titze et al. (2008). "
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    ABSTRACT: In this prospective study the early cognitive development of children born to women with epilepsy (n = 198) was assessed and compared to a group of children representative of the general population (n = 230). The children were assessed when younger than the age of 2 years using the Griffiths Mental Development Scales, either in their local participating hospital or in their home. The assessments were completed by an assessor who was blinded to whether the child's mother had epilepsy and to antiepileptic drug type. Children exposed to sodium valproate had a statistically significant increased risk of delayed early development in comparison to the control children. Linear regression analysis showed a statistically significant effect of sodium valproate exposure on the child's overall developmental level that was not accounted for by confounding variables. Delayed early development is also noted for children within an ad hoc group of less commonly utilized antiepileptic drugs, although conclusions cannot be drawn due to the size of this group (n = 13). Children exposed to either carbamazepine or lamotrigine in utero did not differ significantly in their overall developmental ability. Differences noted in specific developmental areas for these two groups were not statistically significant after the control for confounders such as socioeconomic status and maternal IQ. Women with epilepsy should be informed of the risks posed to their potential offspring prior to pregnancy to allow for informed decisions regarding treatment. Children exposed in utero to antiepileptic drugs should be monitored throughout childhood to allow for early intervention when necessary.
    Epilepsia 10/2010; 51(10):2058-65. DOI:10.1111/j.1528-1167.2010.02668.x · 4.57 Impact Factor
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    • "However, developmental anomalies were also observed after application of newly synthesized AEDs ('newer AEDs'), i.e. lamotrigine, topiramate or gabapentin [15] [16] [17] [18] [19]. There is a two-fold higher risk for congenital malformations in the offspring of epileptic mothers taking AEDs during pregnancy than in the offspring of non-epileptic mothers, respectively, 4–8% vs 2–4% [18] [20] [21]. Table 1 Doses of AEDs applied to pregnant women in the study. "
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    ABSTRACT: Epidemiological data indicate that pregnancies of epileptic women constitute about 1% of all pregnancies. Newborns of mothers exposed to anti-epileptic drugs (AEDs) are at increased risk for major congenital malformations, cognitive impairment and fetal death. Cord-blood lymphocytes of the newborns whose mothers received long-term AEDs therapy during pregnancy were used in this study. There were 37 newborns (Group A), divided into two subgroups, i.e. from mothers receiving mono-therapy (A1) and from those receiving poly-therapy (A2). The major drugs given to the pregnant women with epilepsy in mono-therapy were valproic acid (VPA) and carbamazepine (CBZ) analogues. In poly-therapy, besides VPA and CBZ derivatives also phenyltriazine, sulphanamide, benzodiazepines and gamma-aminobutyric acid (GABA) derivatives were administered. Three kinds of in vitro cytogenetic test were applied: the chromosome aberration (CA) assay, the sister chromatid exchange (SCE) assay, and the cytokinesis-block micronucleus assay (CBMN). In addition, the mitotic index (MI), the replication index (RI) and the nuclear division index (NDI) were determined. The mean number of CA/cell (excluding gaps) for group A did not differ statistically significantly from the negative controls (p>0.1), nor did the mean MI value (p>0.1). In group A, the mean number of SCE/cell was statistically significantly higher compared with the negative control (p<0.05). The mean RI value for group A did not demonstrate statistically significant differences (p>0.1). The mean MN number for group A was higher than in the negative control, but this difference was on the border of statistical significance (p=0.07). The value of NDI for group A did not differ significantly from the value in the negative control (p>0.1). The anti-epileptic drugs given to epileptic women in mono- and poly-therapy during pregnancy evoked potentially clastogenic and genotoxic effects in cord-blood lymphocytes. These drugs did not exert a cytotoxic effect, neither did they inhibit the cell-division kinetics of cord-blood lymphocytes.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 05/2010; 701(2):111-7. DOI:10.1016/j.mrgentox.2010.05.003 · 3.68 Impact Factor
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    • "Cognitive function in children exposed in utero to AEDs has also been investigated. Several studies are reporting that in utero exposure to AEDs increases the risk of cognitive dysfunction later in life (Marsh et al., 2006; Meador et al., 2007; Nicolai et al., 2008; Titze et al., 2008; Vinten et al., 2005). "
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    ABSTRACT: Epilepsy, the most common neurological disorder in young humans, has its highest incidence during the first year of life. Antiepileptic drugs (AEDs) which are used to treat seizures in infants, children and pregnant women target ion channels, neurotransmitters and second messenger systems in the brain. The same targets regulate brain processes essential both for propagation of seizures and for brain development, learning, memory and emotional behavior. Here we review adverse effects of AEDs in the developing mammalian brain. In addition, we discuss mechanisms explaining adverse effects of AEDs in the developing mammalian brain including interference with cell proliferation and migration, neurogenesis, axonal arborization, synaptogenesis, synaptic plasticity and physiological apoptotic cell death.
    Epilepsy research 10/2009; 88(1):11-22. DOI:10.1016/j.eplepsyres.2009.09.019 · 2.02 Impact Factor
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