Developmental Effects On Children Of Women Who Take Antiepileptic Drugs During Pregnancy

• Executive Functioning,Tower-NEPSY [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
• Linguistic Functioning via Expressive one word vocabulary test and NEPSY subscales [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
• Visual-Spatial Motor Functioning via NEPSY subscale and Visual-Motor Integration Scale [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
• Memory via Children's Memory Scale [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
• Motor Functioning via Grooved Pegboard [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
• Academic Functioning via Wide Range Achievement Test [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
• Adaptive Functioning via Adaptive Behavior System -2nd Edition [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
• Behavior via Behavior Assessment for Children & Parent Stress Index [ Time Frame: 6 Years ] [ Designated as safety issue: No ]

The purpose of this study is to determine if antiepileptic drugs (AEDs) differ in their neurodevelopmental effects. Specifically, do the children of the women with epilepsy differ in their behavioral and cognitive development depending on which AED their mother takes during pregnancy?

This is a prospective investigation enrolling 285 to 380 women with epilepsy during the first two trimesters of their pregnancies. There are 25 clinical centers as well as the database center. The women will be taking one of the following AEDs: carbamazepine, phenytoin, valproate, or lamotrigine. Cognitive and behavioral testing of the child will be done up to the age of 6 years. The study does not change the woman's doctor and does not interfere with the care of the treating physician.

Mothers and their child(ren) who were exposed to one of the following monotherapies in utero- Lamotrigine, Carbamazepine, Phenytoin, or Valproate. Fathers of the children and a first degree materal relative of the mother are also invited to have IQ testing and medical history

• Epilepsy
• Seizure
• Cognition Disorders

• Behavioral: Differential Abilities Scale
  IQ measurement at 3, 4.5 and 6 years of age
  Other Name: DAS
• Behavioral: Neuropsychological Testing
  Tests of memory, attention, and behavior administered at 2,3, 4.5 and 6 Years of age
  Other Names:

  • (Toni-3) Test of Nonverbal Intelligence
  • (WAIS) - Wechslers Adult Intelligence Scale -revised
  • Beck Depression Inventory
  • Bayley Scales of Infant Development,
  • NEPSY
  • Trails Preschool
  • Preschool Language Scale-4
  • Expressive One-Word Vocabulary TEst
  • Peabody Picture Vocabulary Test
  • Developmental Test of Visual-Motor Integration
  • Children's Memory Scale
  • Grooved Pegboard
  • Bracken Basic Concepts Scale
  • Wide Range Achievement TEst
  • Adaptive Behavior Assessment Scale
  • Behavioral Assessment for Children
  • Parenting Stress Index

• Carbamazepine
  Children and their mothers exposed to Carbamazepine monotherapy in utero
  Interventions:

  • Behavioral: Differential Abilities Scale
  • Behavioral: Neuropsychological Testing
• Phenytoin
  Children and their mothers exposed to phenytoin in utero
  Interventions:

  • Behavioral: Differential Abilities Scale
  • Behavioral: Neuropsychological Testing
• Lamotrigine
  Children and their mothers exposed to Lamotrigine in utero
  Interventions:

  • Behavioral: Differential Abilities Scale
  • Behavioral: Neuropsychological Testing
• Valproate
  Children and their mothers exposed to Valproate in utero
  Interventions:

  • Behavioral: Differential Abilities Scale
  • Behavioral: Neuropsychological Testing

• Meador KJ, Chadwick D, Clayton-Smith J, Pennell P, Liporace J, Kalayian L, and NEAD Study Group. Antiepileptic drugs in pregnancy: Differences in U.K. and U.S.A. Epilepsia, 2003;44 (Suppl. 9):289.
• Meador KJ, Page P, Liporace J, Kalayjian L, NEAD Study Group. Antiepileptic Drugs in Pregnancy. Neurology 2004;62 (Suppl 5):A311.
• Meador KJ, Baker GA, Clayton Smith J, Pennell P, Liporace J, Kalayjian L, Kini U, NEAD Study Group. Differential Effects of Antiepileptic Drugs on Serious Adverse Outcomes in Children Exposed In Utero. Epilepsia 2004;45 (Suppl 3):58
• Meador KM, Loring DW, Baker G, Smith JC, Pennell P, Liporace J, Kalayjian L, Kini U, NEAD Study Group. Differential and dose dependent effects of in utero antiepileptic drugs. Neurology 2005;64 (Suppl 1):A427
• Meador KJ, Baker GA, Finnell RH, Kalayjian LA, Liporace JD, Loring DW, Mawer G, Pennell PB, Smith JC, Wolff MC; NEAD Study Group. In utero antiepileptic drug exposure: fetal death and malformations. Neurology. 2006 Aug 8;67(3):407-12.
• Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW; NEAD Study Group. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol. 2013 Mar;12(3):244-52. doi: 10.1016/S1474-4422(12)70323-X. Epub 2013 Jan 23.

• Subject must be diagnosed with partial seizures and/or secondary generalization or primary generalized seizures (absence, atonic, myoclonic, and generalized tonic-clonic seizures)
• Subjects must be on either carbamazepine, lamotrigine, phenytoin, or valproate monotherapy.
• Mothers must not have a history of drug abuse (including alcohol) in the last year and have no sequelae of drug abuse.
• Mothers must be able to maintain an accurate seizure diary of major motor seizures
• Subjects must have an IQ greater than or equal to 70 points.
• Subjects must have a history of a negative RPR and HIV.
• Subjects must not have progressive cerebral disease or presence of other major medical illness
• Subjects must not have exposure to known teratogens during pregnancy, except AEDs.
• Subjects must not have poor compliance with prenatal care.
• Subjects must have adequate reading skills to perform the cognitive tests.