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

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Abstract

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.

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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.

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Authors and Affiliations

  1. Department of Clinical Medicine, Section for Neurology, University of Bergen, Bergen, Norway

    Gyri Veiby, Bernt A. Engelsen & Nils Erik Gilhus

  2. Department of Neurology, Haukeland University Hospital, 5021, Bergen, Norway

    Gyri Veiby, Bernt A. Engelsen & Nils Erik Gilhus

  3. Department of Global Health and Primary Care, University of Bergen, Bergen, Norway

    Anne Kjersti Daltveit

  4. Medical Birth Registry of Norway, Division of Epidemiology, Norwegian Institute of Public Health, Bergen, Norway

    Anne Kjersti Daltveit

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  1. Gyri Veiby
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  2. Anne Kjersti Daltveit
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  3. Bernt A. Engelsen
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  4. Nils Erik Gilhus
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Correspondence to Gyri Veiby.

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Veiby, G., Daltveit, A.K., Engelsen, B.A. et al. Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy. J Neurol 261, 579–588 (2014). https://doi.org/10.1007/s00415-013-7239-x

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  • DOI: https://doi.org/10.1007/s00415-013-7239-x

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