Antiepileptic Drugs and Neurodevelopment: An Update
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
In utero exposure to some antiepileptic drugs (AEDs) is associated with an increased risk of impaired cognitive development. Specifically, valproate and polytherapy exposure are each associated with an increased risk of cognitive impairment in children compared with other antiepileptic medications. The data regarding the risk to neurocognitive development imposed by maternal use of other AEDs are conflicting or insufficient at this time to draw definitive conclusions. Behavioral dysfunction including autistic spectrum disorder is also associated with maternal use of AEDs during pregnancy. Whether treatment with AEDs during childhood permanently affects cognitive neurodevelopment is yet to be determined.
- Meadow SR. Anticonvulsant drugs and congenital abnormalities. Lancet. 1968;292:1296. CrossRef
- Meador K, Reynolds MW, Crean S, et al. Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res. 2008;81:1–13. CrossRef
- Hill RM, Verniaud WM, Horning MG, et al. Infants exposed in utero to antiepileptic drugs. Am J Dis Child. 1974;127:645–53.
- Hanson JW, Myrianthopoulos NC, Harvey MA, et al. Risks to offspring of women treated with hydantoin anticonvulsants, with emphasis on the fetal hydantoin syndrome. J Pediatr. 1976;89:662–8. CrossRef
- Leavitt AM, Yerby MS, Robinson N, et al. Epilepsy in pregnancy: developmental outcome of offspring at 12 months. Neurology. 1992;42 suppl 5:141–3.
- Losche G, Steinhausen, Koch S, et al. The psychological development of children of epileptic parents. II. The differential impact of intrauterine exposure to anticonvulsant drugs and further influential factors. Acta Paediatr. 1994;83:961–6. CrossRef
- Granstrom ML, Gaily E. Psychomotor development in children of mothers with epilepsy. Neurology. 1992;42:144–8.
- Reinisch JM, Sanders SA, Mortensen EL, et al. In utero exposure to phenobarbital and intelligence deficits in adult men. JAMA. 1995;274:1518–25. CrossRef
- Majewski F, Steger M, Richter B, et al. The teratogenicity of hydantoins and barbiturates in humans, with considerations on the etiology of malformations and cerebral disturbances in the children of epileptic parents. Int J Biol Res Pregnancy. 1981;2:37–45.
- Wide K, Henning E, Tomson T, et al. Psychomotor development in preschool children exposed to antiepileptic drugs in utero. Acta Paediatr. 2002;91:409–14. CrossRef
- Koch S, Titze K, Zimmermann RB, et al. Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents. Epilepsia. 1999;40:1237–43. CrossRef
- • Nicolai J, Vles JSH, Aldenkamp AP. Neurodevelopmental delay in children exposed to antiepileptic drugs in utero: a critical review directed at structural study-bias. J Neurol Sci. 2008;271:1–14. In this literature review, studies of the cognitive effects of in utero exposure are summarized and critically reviewed. Methodologies that should limit interpretation of study results are highlighted. CrossRef
- Adab N, Tudur Smith C, Vinten J, et al. Common antiepileptic drugs in pregnancy in women with epilepsy (Review). Cochrane Database of Systematic Reviews 2010, Issue 1.
- •• Meador KJ, Baker GA, Browning N, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. NEJM. 2009;360:1597–605. This is the first prospective study of the long-term cognitive effects of in utero exposure to AEDs. It is also one of the few studies of this subject that analyzes factors that could confound the data. CrossRef
- Bromley RL, Mawer G, Love J, et al. Early cognitive development in children born to women with epilepsy: a prospective report. Epilepsia. 2010;51:2058–65. CrossRef
- Gaily E, Kantola-Sorsa MA, Hiilesmaa V, et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology. 2004;62:28–32.
- Adab N, Kini U, Vinten J, et al. The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry. 2004;75:1575–83. CrossRef
- Thomas SV, Ajaykumar B, Sindhu K, et al. Motor and mental development of infants exposed to antiepileptic drugs in utero. Epilepsy Behav. 2008;13:229–36. CrossRef
- Titze K, Koch S, Helge H, et al. Prenatal and family risks of children born to mothers with epilepsy: effects on cognitive development. Dev Med Child Neurol. 2008;50:117–22. CrossRef
- •• Vinten J, Bromley RL, Taylor J, et al. The behavioral consequences of exposure to antiepileptic drugs in utero. Epilepsy Behav. 2009;14:197–2001. This study examines long-term behavior consequences of in utero exposure to AEDs. The cognitive tools used are scales that evaluate life skills and parental stress. CrossRef
- Dean JCS, Hailey H, Moore SJ, et al. Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth. J Med Genet. 2002;39:251–9. CrossRef
- Viinikainen K, Eriksson K, Monkkonen A, et al. The effects of valproate exposure in utero on behavior and the need for educational support in school-aged children. Epilepsy Behav. 2006;9:636–40. CrossRef
- Rasalam AD, Hailey H, Williams JHG, et al. Characteristics of fetal anticonvulsant syndrome associated autistic disorder. Dev Med Child Neurol. 2005;47:551–5. CrossRef
- Bromley RL, Mawer G, Clayton-Smith J, et al. Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology. 2008;71:1923–4. CrossRef
- Stefovska VG, Uckermann O, Czuczwar M, et al. Sedative and anticonvulsant drugs suppress postnatal neurogenesis. Ann Neurol. 2008;64:434–45. CrossRef
- Manent JB, Jorquera I, Mazzucchelli I, et al. Fetal exposure to GABA-acting antiepileptic drugs generates hippocampal and cortical dysplasias. Epilepsia. 2007;48:684–93. CrossRef
- Ogura H, Yasuda M, Nakamura S, et al. Neurotoxic damage of granule cells in the dentate gyrus and the cerebellum and cognitive deficit following neonatal administration of phenytoin in mice. J Neuropathol Exp Neurol. 2002;61:956–67.
- Wong WT, Wong RO. Changing specificity of neurotransmitter regulation of rapid dendritic remodeling during synaptogenesis. Nat Neurosci. 2001;4:351–2. CrossRef
- Bittagau P, Sifringer M, Ikonomidou C. Antiepileptic drugs and apoptosis in the developing brain. Ann NY Acad Sci. 2003;993:103–14. CrossRef
- Katz I, Kim J, Gale KN, et al. Effects of lamotrigine alone and in combination with MK-801, phenobarbital, or phenytoin on cell death in the neonatal rat brain. J Pharmacol Exp Ther. 2007;322:494–500. CrossRef
- Kim J, Kondratyev A, Gale K. Antiepileptic drug-induced neuronal cell death in the immature brain: effects of carbamazepine, topiramate, and levetiracetam as monotherapy vs polytherapy. J Pharmacol Exp Ther. 2007;323:165–73. CrossRef
- Farwell JR, Lee YJ, Hirtz DG, et al. Phenobarbital for febrile seizures-effects on intelligence and on seizure recurrence. NEJM. 1990;322:364–9. CrossRef
- Vining EPG, Mellits ED, Dorsen MM, et al. Psychologic and behavioral effects of antiepileptic drugs in children: a double-blind comparison between phenobarbital and valproic acid. Pediatrics. 1987;80:165–74.
- Calandre EP, Dominguez-Granados R, Gomez-Rubio M, et al. Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Acta Neurol Scand. 1990;81:504–6. CrossRef
- Stores G, Hart J. Reading skills of children with generalized or focal epilepsy attending ordinary school. Dev Med Child Neurol. 1976;18:705–16. CrossRef
- Forsythe I, Butler R, Berg I, et al. Cognitive impairment in new cases of epilepsy randomly assigned to carbamazepine, phenytoin and sodium valproate. Dev Med Child Neurol. 1991;33:524–43. CrossRef
- Aman WG, Werry JS, Paxton JW, et al. Effects of carbamazepine on psychomotor performance in children as a function of dose, concentration, seizure type, and time of medication. Epilepsia. 1990;31:51–60. CrossRef
- Bailet LL, Turk WR. The impact of childhood epilepsy on neurocognitive and behavioral performance. Epilepsia. 2000;41:426–31. CrossRef
- Donati F, Gobbi G, Campistol J, et al. The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures. Seizure. 2007;16:670–9. CrossRef
- Pressler RM, Binnie CD, Coleshill SG, et al. Effect of lamotrigine on cognition in children with epilepsy. Neurology. 2006;66:1495–9. CrossRef
- Mandelbaum DE, Bunch M, Kugler SL, et al. Efficacy of levetiracetam at 12 months in children classified by seizure type, cognitive status, and previous anticonvulsant drug us. J Child Neurol. 2005;20:590–4.
- Levisohn PM, Mintz M, Hunter SJ, et al. Neurocognitive effects of adjunctive levetiracetam in children with partial-onset seizures: a randomized, double-blind, placebo-controlled, noninferiority trial. Epilepsia. 2009;50:2377–89. CrossRef
- Kang H-C, Eun B-L, Lee CW, et al. The effects of cognitive function and behavioral problems of topiramate compared to carbamazepine as monotherapy for children with Benign Rolandic Epilepsy. Epilepsia. 2007;48:1716–23. CrossRef
- Coppola G, Verrotti A, Resicato G, et al. Topiramate in children and adolescents with epilepsy and mental retardation: a prospective study on behavior and cognitive effects. Epilepsy Behav. 2008;12:253–6. CrossRef
- Aarsen FK, van den Akker ELT, Drop SLS, et al. Effect of topiramate on cognition in obese children. Neurology. 2006;67:1307–8. CrossRef
- Sulzbacher S, Farwell JR, Temkin N, et al. Late cognitive effects of early treatment with phenobarbital. Clin Pediatr. 1999;38:387–95. CrossRef
- Vazquez B, Gibson P, Kustra R. Epilepsy and women’s health issues: unmet needs-survey results from women with epilepsy. Epilepsy Behav. 2007;10:163–9. CrossRef
- Antiepileptic Drugs and Neurodevelopment: An Update
Current Neurology and Neuroscience Reports
Volume 11, Issue 4 , pp 423-427
- Cover Date
- Print ISSN
- Online ISSN
- Current Science Inc.
- Additional Links
- Antiepileptic drugs
- Industry Sectors