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From the Hospital for Children and Adolescents (Drs. Gaily and Granström, E. Kantola-Sorsa and M. Isoaho), Department of Obstetrics and Gynecology (Drs. Hiilesmaa and Matila), and Department of Neurology (Dr. Kotila), Helsinki University Central Hospital; Haaga Neurological Research Center (Dr. Nylund), Helsinki; National Agency for Medicines (Dr. Bardy), Helsinki; and Division of Pharmacology and Toxicology, Department of Pharmacy (E. Kaaja), University of Helsinki, Finland.
Address correspondence and reprint requests to Dr. Eija Gaily, P.O. Box 280, Hospital for Children and Adolescents, 00029 HUS, Finland; e-mail: eija.gaily{at}hus.fi
Objective: To investigate the effect of antiepileptic drugs, especially carbamazepine and valproate, on intelligence in prenatally exposed children of mothers with epilepsy.
Methods: Intelligence of 182 children of mothers with epilepsy (study group) and 141 control children was tested in a blinded setting at preschool or school age using Wechsler Preschool and Primary Scale of Intelligence–Revised or Wechsler Intelligence Scale for Children–Revised. Data on maternal antiepileptic treatment and seizures during pregnancy were gathered prospectively. The study group represented approximately 50% of the children born to mothers with epilepsy in Uusimaa province during 1989 through1994. One hundred seven children were exposed to antiepileptic monotherapy: 86 to carbamazepine and 13 to valproate. Thirty children were exposed to polytherapy: 23 combinations included carbamazepine, and 17 included valproate. The median maternal doses and blood levels during the second half of pregnancy were 600 mg and 26 µmol/L for carbamazepine and 950 mg and 300 µmol/L for valproate.
Results: The mean verbal and nonverbal IQ scores in the children exposed in utero to carbamazepine monotherapy were 96 (95% CI, 93–100) and 103 (95% CI, 100–106). They did not differ from control subjects, whose mean verbal and nonverbal IQ scores were 95 (95% CI, 92–97) and 102 (95% CI, CI, 100–105). Significantly reduced verbal IQ scores were found in children exposed to valproate (mean, 82; 95% CI, 78–87) and to polytherapy (mean, 85; 95% CI, 80–90) compared with the other study group children and control subjects.
Conclusions: Carbamazepine monotherapy with maternal serum levels within the reference range does not impair intelligence in prenatally exposed offspring. Exposures to polytherapy and to valproate during pregnancy were associated with significantly reduced verbal intelligence. The independent effects of valproate remain unconfirmed because the results were confounded by low maternal education and polytherapy.
Received April 11, 2003. Accepted in final form October 31, 2003.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the January 13 issue to find the title link for this article.
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