CC BY-NC-ND 4.0 · International Journal of Epilepsy 2017; 04(01): 094-097
DOI: 10.1016/j.ijep.2016.11.001
Case report
Thieme Medical and Scientific Publishers Private Ltd.

Valproic acid during pregnancy: Case report of a child with congenital malformations due to fetal valproate syndrome, and a high unbound serum level of valproic acid at birth

Shirley Sparla
a   Department of Clinical Pharmacy, Meander Medical Centre, Maatweg 3, 3813 TZ Amersfoort, The Netherlands
,
Paul Hogeman
b   Department of Pediatrics, Meander Medical Centre, Maatweg 3, 3813 TZ Amersfoort, The Netherlands
,
Maarten van Gemert
c   Department of Neurology, Meander Medical Centre, Maatweg 3, 3813 TZ Amersfoort, The Netherlands
,
Eleonora Swart
d   Department of Clinical Pharmacology and Pharmacy, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
,
Mirte Malingre
a   Department of Clinical Pharmacy, Meander Medical Centre, Maatweg 3, 3813 TZ Amersfoort, The Netherlands
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Publikationsverlauf

Received: 01. Juli 2016

Accepted: 11. November 2016

Publikationsdatum:
06. Mai 2018 (online)

Abstract

We present a child in utero exposed to valproic acid with congenital malformations due to fetal valproate syndrome and with toxic effects. Directly postnatal, a high-unbound serum level of valproic acid was measured. The total serum level of valproic acid was in the therapeutic range. Measuring unbound serum levels during pregnancy and postnatal period in the child provides more information about real-time exposure than measuring total serum levels.

 
  • References

  • 1 Marson AG, Al-Kharusi AM, Alwaidh M. et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalized and unclassifiable epilepsy: an unblended randomized controlled trial. Lancet 369 2007; 1016-1026
  • 2 Bonnett LJ, Tudur Smith C, Smith D, Williamson PR, Chadwick D, Marson AG. Time to 12-month remission and treatment failure for generalized and unclassified epilepsy. J Neurol Neurosurg Psychiatry 85 2014; 603-610
  • 3 Craig JJ, Hunt SJ. Treating women with juvenile myoclonic epilepsy. Pract Neurol 9 2009; 268-277
  • 4 Thisted E, Ebbesen F. Malformations, withdrawal manifestations, and hypoglycemia after exposure to valproate in utero. Arch Dis Child 69 1993; 288-291
  • 5 Tomson T, Marson A, Boon P. et al. Valproate in the treatment of epilepsy in girls and women of childbearing potential. Epilepsia 56 (07) 2015; 1006-1019
  • 6 Teramo K, Hiilesmaa V. Pregnancy and Fetal Complications in Epileptic Pregnancies, Epilepsy, Pregnancy and the Child. 1982. Raven Press; New York: 53-59
  • 7 Wlodarczyk BJ. Antiepileptic drugs and pregnancy outcomes. Am J Med Genet A 158A (08) 2012; 2071-2090
  • 8 Valproic Acid, monography, Micromedex, visited 15-01-2016.
  • 9 Monography valproic acid, www.tdm-monografie.org Dutch guidelines for TDM, viewed on 6-11-2015
  • 10 Schaefer C, Peters P, Miller PK. Drugs During Pregnancy and Lactation. 2nd ed.. 2007. Elsevier; 12-13 269–273
  • 11 Santis De M, Luca De C, Mappa I, Cesari W, Quattrocchi T. Antiepileptic drugs during pregnancy: pharmacokinetics and transplacental transfer. Curr Pharm Biotechnol 12 2011; 781-788
  • 12 Deligiannidis KM, Byatt N, Freeman MP. Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol 34 (02) 2014; 244-255
  • 13 Tomson T, Battino S, Bonizzoni E. et al. Dose-dependent teratogenicity of Valproate in mono- and polytherapy: an observational study. Neurology 85 2015; 8
  • 14 Kaneko S, Battino D, Andermann E. et al. Congenital malformations due to antiepileptic drugs. Epilepsy Res 33 (02) (03) 1999; 145-158
  • 15 Patsalos PN, Berry DJ, Bourgeois BF. et al. Anti-epileptic drugs-best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE commission on Therapeutic Strategies. Epilepsia 49 (07) 2008; 1239-1276
  • 16 Tomson T, Dahl ML, Kimland E. Therapeutic monitoring of antiepileptic drugs for epilepsy (review). Cochrane Database Syst Rev 2010; CD002216
  • 17 Touw DJ, Neef C, Thomson AH, Vinks AA. Cost-effectiveness of therapeutic drug monitoring: a systematic review. Ther Drug Monit 27 l 2005; 10-15
  • 18 Deligiannidis KM, Byatt NDO, Freeman MP. Pharmacotherapy for mood disorders in Pregnancy: a review of pharmokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol 34 (02) 2014; 244-255
  • 19 Brodtkorb E, Reimers A. Seizure control and pharmacokinetics of antiepileptic drugs in pregnant women with epilepsy. Seizure 17 2008; 160-165
  • 20 Adab N. Therapeutic monitoring of antiepileptic drugs during pregnancy and in the postpartum period: is it useful?. CNS Drugs 20 (10) 2006; 791-800
  • 21 Krishnamurthy KB. Managing epilepsy during pregnancy: assessing risk and optimizing care. Curr Treat Options Neurol 14 2012; 348-355
  • 22 Dutch Society Neurologist, guideline epilepsia, pregnancy and hormones, update 28 June 2016.