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

Abstract

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.

Neurodevelopmental effects of prenatal exposure to psychotropic medications

“…Such reassuring results were confirmed in a recent, well-designed study [50] performed on 3-year-old children and replicated in older children [51] (this study, however, did not provide standardized instruments for assessing child neurodevelopment), as well as in adolescents. [52] The neutral effect of intrauterine exposure to CBZ on the later cognitive performances was also corroborated by two small population-based studies. [53,54] On the other hand, it must be stressed that concerns regarding the impact of in utero exposure to CBZ on the infant cognitive and motor development were reported by studies that lumped together data coming from different AEDs [55,56] and studies that analyzed the potential neurobehavioral toxicity of single AEDs.…”

“…[65,66] The detrimental effects of VPA on neurocognitive performances were also detectable in young adults, [52] being particularly severe in the case of environmentally disadvantaged conditions. [52] Conversely, a population based study [53] failed to demonstrate any relationship between in utero exposure to VPA and neurocognitive dysfunctions later in the life.…”

“…Titze et al [52] (N 5 Eriksson et al [53] (N 5 Wide et al [54] (N 5 Katz et al [55] (N 5 Arulmozhi et al [56] (N 5…”

“…[66] In fact, the need for additional educational support shown by these children has been demonstrated in more than a few studies. [64,65,67] Although it has been correctly reported that such studies are observational and, thus, women who had taken AEDs were not randomized to different monotherapies (as a consequence, the results might be susceptible to the effects of uncontrolled confounding factors, e.g., head circumference at birth and paternal IQ [94] ), the finding that neurocognitive dysfunctions in subjects prenatally exposed to VPA are still detectable at adult age [52] remains of particular concern.…”

Effect of in utero Exposure to Antiepileptic Drugs on Cognitive Function in Children

“…Today, many antiepileptic drugs (AEDs) are widely available for treating different forms of epilepsy, thereby reducing the recurrence of epileptic episodes. Although AEDs possess a wide array of advantages, long-term use of AEDs can adversely affect cognitive function by suppressing neuronal excitability or enhancing inhibitory neurotransmission [1,2]. Cavanna et al [3] describes cognition as a subset of behaviors that in turn incorporate attention, speed of intellectual functioning, linguistic and arithmetic skills, learning, memory, and coordination.…”