Exposure to antiepileptic drugs in utero and child development: A prospective population-based study

Authors

  • Gyri Veiby,

    Corresponding author
    1. Department of Clinical Medicine, Section for Neurology, University of Bergen, Bergen, Norway
    2. Department of Neurology, Haukeland University Hospital, Bergen, Norway
    • Address correspondence to Gyri Veiby, Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway. E-mail: gyri.veiby@hotmail.com

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  • Anne K. Daltveit,

    1. Department of Public Health and Primary Health Care, University of Bergen, Norway
    2. Medical Birth Registry of Norway, Division of Epidemiology, Norwegian Institute of Public Health, Bergen, Norway
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  • Synnve Schjølberg,

    1. The Norwegian Institute of Public Health, Oslo, Norway
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  • Camilla Stoltenberg,

    1. Department of Public Health and Primary Health Care, University of Bergen, Norway
    2. The Norwegian Institute of Public Health, Oslo, Norway
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  • Anne-Siri Øyen,

    1. The Norwegian Institute of Public Health, Oslo, Norway
    2. Nic Waals Institute, Lovisenberg Hospital, Oslo, Norway
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  • Stein E. Vollset,

    1. Department of Public Health and Primary Health Care, University of Bergen, Norway
    2. The Norwegian Institute of Public Health, Oslo, Norway
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  • Bernt A. Engelsen,

    1. Department of Clinical Medicine, Section for Neurology, University of Bergen, Bergen, Norway
    2. Department of Neurology, Haukeland University Hospital, Bergen, Norway
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  • Nils E. Gilhus

    1. Department of Clinical Medicine, Section for Neurology, University of Bergen, Bergen, Norway
    2. Department of Neurology, Haukeland University Hospital, Bergen, Norway
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Summary

Purpose

Antiepileptic drugs may cause congenital malformations. Less is known about the effect on development in infancy and childhood. The aim of this study was to examine whether exposure to antiepileptic drugs during pregnancy has an effect on early child development.

Methods

From mid-1999 through December 2008, children of mothers recruited at 13–17 weeks of pregnancy were studied in the ongoing prospective Norwegian Mother and Child Cohort Study. Information on birth outcomes were obtained from the Medical Birth Registry (108,264 children), and mothers reported on their child's motor development, language, social skills, and autistic traits using items from standardized screening tools at 18 months (61,351 children) and 36 months (44,147 children) of age. The relative risk of adverse outcomes in children according to maternal or paternal epilepsy with and without prenatal exposure to antiepileptic drugs was estimated as odds ratios (ORs), using logistic regression with adjustment for maternal age, parity, education, smoking, depression/anxiety, folate supplementation, and child congenital malformation or low birth weight.

Key Findings

A total of 333 children were exposed to antiepileptic drugs in utero. At 18 months, the exposed children had increased risk of abnormal scores for gross motor skills (7.1% vs. 2.9%; OR 2.0, 95% confidence interval [CI] 1.1–3.7) and autistic traits (3.5% vs. 0.9%; OR 2.7, CI 1.1–6.7) compared to children of parents without epilepsy. At 36 months, the exposed children had increased risk of abnormal score for gross motor skills (7.5% vs. 3.3%; OR 2.2, CI 1.1–4.2), sentence skills (11.2% vs. 4.8%; OR 2.1, CI 1.2–3.6), and autistic traits (6.0% vs. 1.5%; OR 3.4, CI 1.6–7.0). The drug-exposed children also had increased risk of congenital malformations (6.1% vs. 2.9%; OR 2.1, CI 1.4–3.4), but exclusion of congenital malformations did not affect the risk of adverse development. Children born to women with epilepsy who did not use antiepileptic drugs had no increased risks. Children of fathers with epilepsy generally scored within the normal range.

Significance

Exposure to antiepileptic drugs during pregnancy is associated with adverse development at 18 and 36 months of age, measured as low scores within key developmental domains rated by mothers. Exposures to valproate, lamotrigine, carbamazepine, or multiple antiepileptic drugs were associated with adverse outcome within different developmental domains.

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