Abstracts

Rationale: An increased risk of major congenital malformations for some AEDs and politherapy during pregnancy was demonstrated. Differently, there are insufficient data regarding the long-term effects of fetal exposure to AEDs on cognitive and behavioral functioning in exposed children. Methods: Between 1998 and 2003 a group of 23 pregnant women (mean age 26.4, ranged from 22 to 34 years) with Juvenile Myoclonic Epilepsy (JME), receiving AEDs (valproate (VPA)-6, lamotrigine (LTG) -10 or a combination of LTG and VPA- 7) were enrolled in a prospective, observational one-center study. All women received folic acid in pre-conceptional dose of 4-5 mg. VPA doses ranged from 750-1500 mg/day, LTG doses were from 150 to 300/day. No alcohol abuse was noted. Children (14 male, 9 female) who had been exposed to AEDs in utero and their parents were assessed by Wechsler Intelligence Scale for Children (WISC) or for Adults (WAIS). Maternal IQs was measured in all cases, while paternal IQs were obtained in 12 non-epileptic fathers (unable or unwilling to participate). Results: Congenital, unilateral sensory-neural deafness was diagnosed in two children (exposed to LTG and VPA) and mild left kidney malformation (polycystic kidney and uretherocoele) in one child exposed to LTG in utero. At 6 years of age, the children exposed to LTG scored IQv -100.5 and IQm -102.8, while those exposed to VPA achieved mean IQv of 95.2 and IQm of 98.4. Children exposed to LTG during the first trimester and to LTG+VPA during the 2nd and 3rd trimester scored IQv of 91.8 (significantly lower in comparison with LTG subgroup) and IQm of 96.3. Children exposed to politherapy performed lower than those whom mothers received VPA monotherapy. Mean maternal IQ were IQv-100.5 (range 92-112), IQm-102.3 (range 93-114), while paternal scores were IQv-99.4 and IQm-103.4. Four mothers (LTG -1, VPA -1, LTG+VPA -2) had 1-2 generalized tonic-clonic seizures during pregnancy. Their children scored IQv 102, IQm 104 (LTG), IQv 95, IQm 98 (VPA) and IQv 90/91, IQm 95/97 (LTG+VPA). Parental socio-economic class (high in 8, middle in 15) had no significant influence in IQ scores. The number of patients in subgroup is small for more detailed statistical analysis. Conclusions: In utero exposure to VPA in combination with LTG seems associated with an increased risk of lower verbal IQ at 6 years of age. No parental IQs, AED doses, rare generalized tonic-clonic seizures and socio-economic class significantly contributed to results.