title: Effects of fetal antiepileptic drug exposure: outcomes at age 4.5 years.
abstract: OBJECTIVE
  To examine outcomes at age 4.5 years and compare to earlier ages in children with fetal antiepileptic drug (AED) exposure.
  
  
  METHODS
  The NEAD Study is an ongoing prospective observational multicenter study, which enrolled pregnant women with epilepsy on AED monotherapy (1999-2004) to determine if differential long-term neurodevelopmental effects exist across 4 commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate). The primary outcome is IQ at 6 years of age. Planned analyses were conducted using Bayley Scales of Infant Development (BSID at age 2) and Differential Ability Scale (IQ at ages 3 and 4.5).
  
  
  RESULTS
  Multivariate intent-to-treat (n = 310) and completer (n = 209) analyses of age 4.5 IQ revealed significant effects for AED group. IQ for children exposed to valproate was lower than each other AED. Adjusted means (95% confidence intervals) were carbamazepine 106 (102-109), lamotrigine 106 (102-109), phenytoin 105 (102-109), valproate 96 (91-100). IQ was negatively associated with valproate dose, but not other AEDs. Maternal IQ correlated with child IQ for children exposed to the other AEDs, but not valproate. Age 4.5 IQ correlated with age 2 BSID and age 3 IQ. Frequency of marked intellectual impairment diminished with age except for valproate (10% with IQ <70 at 4.5 years). Verbal abilities were impaired for all 4 AED groups compared to nonverbal skills.
  
  
  CONCLUSIONS
  Adverse cognitive effects of fetal valproate exposure persist to 4.5 years and are related to performances at earlier ages. Verbal abilities may be impaired by commonly used AEDs. Additional research is needed.
authors.affiliation: Neurology & Pediatrics, Emory University, Atlanta, GA, USA. kimford.meador@emory.edu
authors.forename: K J
authors.initials: KJ
authors.lastname: Meador
authors.forename: G A
authors.initials: GA
authors.lastname: Baker
authors.forename: N
authors.initials: N
authors.lastname: Browning
authors.forename: M J
authors.initials: MJ
authors.lastname: Cohen
authors.forename: R L
authors.initials: RL
authors.lastname: Bromley
authors.forename: J
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: L A
authors.initials: LA
authors.lastname: Kalayjian
authors.forename: A
authors.initials: A
authors.lastname: Kanner
authors.forename: J D
authors.initials: JD
authors.lastname: Liporace
authors.forename: P B
authors.initials: PB
authors.lastname: Pennell
authors.forename: M
authors.initials: M
authors.lastname: Privitera
authors.forename: D W
authors.initials: DW
authors.lastname: Loring
mesh_terms: D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000009:adverse effects*; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007360:Intelligence / Q000187:drug effects*; D007361:Intelligence Tests / Q000706:statistics & numerical data; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D011446:Prospective Studies; D014705:Verbal Behavior / Q000187:drug effects
chemical_list: D000927:Anticonvulsants