Journal of Neurology

, Volume 261, Issue 3, pp 579–588 | Cite as

Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy

  • Gyri Veiby
  • Anne Kjersti Daltveit
  • Bernt A. Engelsen
  • Nils Erik Gilhus
Original Communication


The primary aim of this study was to assess the risks of fetal growth restriction and birth defects in children exposed prenatally to newer and older antiepileptic drugs, using an unselected epilepsy cohort. Deliveries recorded in the compulsory Medical Birth Registry of Norway 1999–2011 formed the study population. All 2,600 children exposed to antiepileptic drugs during pregnancy were compared to all 771,412 unexposed children born to women without epilepsy. Children of untreated mothers with epilepsy served as an internal control group. The main outcomes were small for gestational age birth weight and head circumference, and major congenital malformations. Children exposed to antiepileptic drugs had a moderate risk of growth restriction. Infants exposed to topiramate had a considerable risk of microcephaly (11.4 vs. 2.4 %; OR 4.8; CI 2.5–9.3) and small for gestational age birth weight (24.4 vs. 8.9 %; OR 3.1; 95 % CI 1.9–5.3). Carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, gabapentin, and pregabalin had low malformation rates, whereas topiramate tended to have an elevated malformation rate. Valproate monotherapy was associated with a significant risk of birth defects (6.3 vs. 2.9 %; OR 2.5; CI 1.6–3.8), and specifically with septal heart defects and hypospadias. For mothers using valproate, the presence of major birth defect in one child was associated with a markedly increased risk for the siblings (42.9 vs. 6.7 %; OR 10.4; CI 2.3–46.7). Children of untreated mothers with epilepsy had malformation risk similar to the reference group. In conclusion, topiramate was associated with a substantial risk of fetal growth restriction, and possibly an increased malformation rate. Other newer-generation antiepileptic drugs had a low malformation rate. Valproate monotherapy had a significant malformation risk, especially in repeated pregnancies.


Antiepileptic drugs Pregnancy Birth defects Microcephaly Birth weight 


Conflicts of interest

Dr Veiby has received travel support from UCB Pharma and lecture fees from GlaxoSmithKline. Dr Engelsen has received travel support from GlaxoSmithKline and lecture fees from Lundbeck. Authors Gilhus and Daltveit have no conflicts of interest.

Supplementary material

415_2013_7239_MOESM1_ESM.pdf (433 kb)
Supplementary material 1 (PDF 433 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Gyri Veiby
    • 1
    • 2
  • Anne Kjersti Daltveit
    • 3
    • 4
  • Bernt A. Engelsen
    • 1
    • 2
  • Nils Erik Gilhus
    • 1
    • 2
  1. 1.Department of Clinical Medicine, Section for NeurologyUniversity of BergenBergenNorway
  2. 2.Department of NeurologyHaukeland University HospitalBergenNorway
  3. 3.Department of Global Health and Primary CareUniversity of BergenBergenNorway
  4. 4.Medical Birth Registry of Norway, Division of EpidemiologyNorwegian Institute of Public HealthBergenNorway

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