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1508 Spectrum of Neural Tube Defects after Prenatal Antiepileptic Drug Exposure: Extensive Case Series
  1. MH van Dijk1,
  2. S Bulk2,
  3. ACC van Oppen3,
  4. ACG Egberts1,4,
  5. ER Heerdink1,4,
  6. D Lindhout2,5
  1. 1Department of Clinical Pharmacy
  2. 2Department of Medical Genetics
  3. 3Department of Obstetrics and Perinatology, University Medical Center Utrecht
  4. 4Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences
  5. 5SEIN - Epilepsy Institute, Utrecht, The Netherlands


Background Most pregnant women with chronic active epilepsy need to use antiepileptic drugs (AEDs) during pregnancy to prevent epileptic seizures that may threaten maternal and fetal well-being. Valproic acid (VPA) and carbamazepine (CBZ) have been associated with an increased risk of neural tube defects (NTDs) in the exposed fetus.

Aim To investigate the spectrum of neural tube defects and associated central nervous system (CNS) and non-CNS malformations after prenatal exposure to CBZ and/or VPA.

Methods NTDs in pregnancies in which CBZ and/or VPA were used during the first trimester were collected from 1970–2012 in the Netherlands. Type and location of the NTDs, associated CNS and non-CNS major malformations and relevant patient characteristics were analysed.

Results 87 pregnancies were included. NTDs after exposure to CBZ or VPA were mostly caudally located, whereas a combination of CBZ and VPA was associated with a location shift of the NTD to the rostral side (Figure 1). There were no differences between CBZ and VPA in the percentage of associated CNS malformations and non-CNS malformations circa 75% and 45%.

Abstract 1508 Figure 1

Antiepileptic drugs versus type and location of NTDs

Conclusions The combination of VPA and CBZ shows a tendency towards a more rostral location (lumbar) which may have more severe functional consequences. Current findings confirm that NTDs associated fetal exposure to VPA and/or CBZ are serious and frequently accompanied by other CNS and non-CNS malformations.

Funding Netherlands Epilepsy Foundation (NEF) grant nr 03.18, University Medical Center Utrecht [NL] - institutional Genvlag grant.

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