Effects of fetal antiepileptic drug exposure: Outcomes at age 4.5 years

K. J. Meador, G. A. Baker, N. Browning, M. J. Cohen, R. L. Bromley, J. Clayton-Smith, L. A. Kalayjian, Andres M Kanner, J. D. Liporace, P. B. Pennell, M. Privitera, D. W. Loring

Research output: Contribution to journalArticle

85 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1207-1214
Number of pages8
JournalNeurology
Volume78
Issue number16
DOIs
StatePublished - Apr 17 2012
Externally publishedYes

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Valproic Acid
Anticonvulsants
Aptitude
Carbamazepine
Phenytoin
Child Development
Drugs
Multicenter Studies
Observational Studies
Pregnant Women
Epilepsy
Mothers
Confidence Intervals
Research

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Meador, K. J., Baker, G. A., Browning, N., Cohen, M. J., Bromley, R. L., Clayton-Smith, J., ... Loring, D. W. (2012). Effects of fetal antiepileptic drug exposure: Outcomes at age 4.5 years. Neurology, 78(16), 1207-1214. https://doi.org/10.1212/WNL.0b013e318250d824

Effects of fetal antiepileptic drug exposure : Outcomes at age 4.5 years. / Meador, K. J.; Baker, G. A.; Browning, N.; Cohen, M. J.; Bromley, R. L.; Clayton-Smith, J.; Kalayjian, L. A.; Kanner, Andres M; Liporace, J. D.; Pennell, P. B.; Privitera, M.; Loring, D. W.

In: Neurology, Vol. 78, No. 16, 17.04.2012, p. 1207-1214.

Research output: Contribution to journalArticle

Meador, KJ, Baker, GA, Browning, N, Cohen, MJ, Bromley, RL, Clayton-Smith, J, Kalayjian, LA, Kanner, AM, Liporace, JD, Pennell, PB, Privitera, M & Loring, DW 2012, 'Effects of fetal antiepileptic drug exposure: Outcomes at age 4.5 years', Neurology, vol. 78, no. 16, pp. 1207-1214. https://doi.org/10.1212/WNL.0b013e318250d824
Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J et al. Effects of fetal antiepileptic drug exposure: Outcomes at age 4.5 years. Neurology. 2012 Apr 17;78(16):1207-1214. https://doi.org/10.1212/WNL.0b013e318250d824
Meador, K. J. ; Baker, G. A. ; Browning, N. ; Cohen, M. J. ; Bromley, R. L. ; Clayton-Smith, J. ; Kalayjian, L. A. ; Kanner, Andres M ; Liporace, J. D. ; Pennell, P. B. ; Privitera, M. ; Loring, D. W. / Effects of fetal antiepileptic drug exposure : Outcomes at age 4.5 years. In: Neurology. 2012 ; Vol. 78, No. 16. pp. 1207-1214.
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AU - Clayton-Smith, J.

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