Fetal antiepileptic drug exposure: Motor, adaptive, and emotional/behavioral functioning at age 3years (original) (raw)

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

Epilepsy & Behavior, 2013

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

Motor and mental development of infants exposed to antiepileptic drugs in utero

Epilepsy & Behavior, 2008

We prospectively evaluated the mental (MeDQ) and motor (MoDQ) developmental quotients of 395 (67.5% of the eligible) infants of mothers with epilepsy (IME) (mean age: 15 months) enrolled in the Kerala Registry of Epilepsy and Pregnancy between 1998 and 2004. The same developmental pediatricians, blinded to antiepileptic drug (AED) exposure, evaluated the children using the Indian adaptation of the Bayley Scale of Infant Development: Their mean MeDQ was 89.1 ± 29.9 and mean MoDQ was 90.7 ± 26.9. The MeDQ and MoDQ were impaired (<84) for 150 (37.6%) and 133 (33.5%) IME, respectively. Maternal age, type of epilepsy, seizure frequency, or use of folic acid did not correlate with the mean MeDQ or MoDQ. Maternal education was significantly correlated with the MoDQ, but not with the MeDQ, of the infants. Infants not exposed to AEDs (n = 32) had a higher MeDQ (mean: 92.3, 95% CI: 81.4-103.2) and MoDQ (mean 94.7; 95% CI 84.9-104.5) than those exposed to AEDs (MeDQ-mean: 88.6, 95% CI: 85.5-91.6; MoDQ-mean: 90.0, 95% CI: 87.3-92.8). Those exposed to polytherapy had significantly lower developmental quotients than those exposed to monotherapy. Cumulative AED scores during pregnancy had an inverse relationship with developmental quotients. On multiple regression analysis, polytherapy was a stronger predictor of lower developmental quotients than dosage. Compared with carbamazepine monotherapy, valproate monotherapy was associated with significantly lower MeDQ and MoDQ in IME (93.1 and 95 vs 86.9 and 86.1), but the differences between other AEDs were not significant for IME exposed to valproate monotherapy. A limitation of the study is that the influence of maternal intelligence on developmental quotients was not evaluated.

Differential effects of antiepileptic drugs on neonatal outcomes

Epilepsy & Behavior, 2012

Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. WWE on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and 12-months-old, but normalized by age 24-months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1 minute, but scores were near normal in all groups at 5 minutes. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks amongst the AEDs can help inform decisions about AED selection for women during childbearing years.

Neurodevelopmental effects of antiepileptic drugs

Current neurology and neuroscience reports, 2002

Although the vast majority of children born to women with epilepsy are normal, these children are at increased risk for both anatomic and cognitive impairments. Current evidence suggests that the defects are the result of in utero antiepileptic drug (AED) exposure combined with a genetic predispositon. However, the exact mechanisms underlying these effects remain to be delineated. AED polytherapy increases the risk, but it remains uncertain if specific AEDs pose an overall greater threat. Most women with epilepsy cannot avoid AEDs during pregnancy because of the greater risks posed by seizures to the mother and fetus. Therefore, current recommendations emphasize definitive diagnosis and the use of AED monotherapy at the lowest effective dose if treatment is indicated. Prenatal folate and multivitamins should also be given routinely to women of childbearing age who require AED therapy.

Exposure to antiepileptic drugs in utero and child development: A prospective population-based study

Epilepsia, 2013

Purpose: Antiepileptic drugs may cause congenital malformations. Less is known about the effect on development in infancy and childhood. The aim of this study was to examine whether exposure to antiepileptic drugs during pregnancy has an effect on early child development. Methods: From mid-1999 through December 2008, children of mothers recruited at 13-17 weeks of pregnancy were studied in the ongoing prospective Norwegian Mother and Child Cohort Study. Information on birth outcomes were obtained from the Medical Birth Registry (108,264 children), and mothers reported on their child's motor development, language, social skills, and autistic traits using items from standardized screening tools at 18 months (61,351 children) and 36 months (44,147 children) of age. The relative risk of adverse outcomes in children according to maternal or paternal epilepsy with and without prenatal exposure to antiepileptic drugs was estimated as odds ratios (ORs), using logistic regression with adjustment for maternal age, parity, education, smoking, depression/anxiety, folate supplementation, and child congenital malformation or low birth weight. Key Findings: A total of 333 children were exposed to antiepileptic drugs in utero. At 18 months, the exposed children had increased risk of abnormal scores for gross motor skills (7.1% vs. 2.9%; OR 2.0, 95% confidence interval [CI] 1.1-3.7) and autistic traits (3.5% vs. 0.9%; OR 2.7, CI 1.1-6.7) compared to children of parents without epilepsy. At 36 months, the exposed children had increased risk of abnormal score for gross motor skills (7.5% vs. 3.3%; OR 2.2, CI 1.1-4.2), sentence skills (11.2% vs. 4.8%; OR 2.1, CI 1.2-3.6), and autistic traits (6.0% vs. 1.5%; OR 3.4, CI 1.6-7.0). The drug-exposed children also had increased risk of congenital malformations (6.1% vs. 2.9%; OR 2.1, CI 1.4-3.4), but exclusion of congenital malformations did not affect the risk of adverse development. Children born to women with epilepsy who did not use antiepileptic drugs had no increased risks. Children of fathers with epilepsy generally scored within the normal range. Significance: Exposure to antiepileptic drugs during pregnancy is associated with adverse development at 18 and 36 months of age, measured as low scores within key developmental domains rated by mothers. Exposures to valproate, lamotrigine, carbamazepine, or multiple antiepileptic drugs were associated with adverse outcome within different developmental domains.