ORIGINAL ARTICLE

Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth

J C S Dean¹, H Hailey¹, S J Moore², D J Lloyd³, P D Turnpenny⁴, J Little⁵

¹ Department of Medical Genetics, Medical School, Foresterhill, Aberdeen AB25 2ZD, UK
² Medical Genetics Program, Memorial University of Newfoundland, St John's, Newfoundland A1B 3V6, Canada
³ Department of Neonatal Medicine, Aberdeen Maternity Hospital, Aberdeen, UK
⁴ Department of Clinical Genetics, Royal Devon and Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK
⁵ Epidemiology Group, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK

Correspondence to:
Correspondence to:
Dr J C S Dean, Department of Medical Genetics, Medical School, Foresterhill, Aberdeen AB25 2ZD, UK;
j.dean{at}abdn.ac.uk

Objective: To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero.

Design: Retrospective population based study.

Setting: Population of the Grampian region of Scotland.

Participants: Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed.

Main outcome measures: Frequencies of neonatal withdrawal, congenital malformations, childhood onset medical problems, developmental delay, and behaviour disorders.

Results: Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs. Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of non-exposed sibs, and developmental delay in 24% of exposed children, compared with 11% of non-exposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of non-exposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of non-exposed sibs), and 20% had behaviour disorders (5% of non-exposed).

Conclusion: Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation.

Keywords: epilepsy; anticonvulsants; malformation; neurodevelopment

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