Normal intelligence in children with prenatal exposure to carbamazepine.
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 through 1994. 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 micro mol/L for carbamazepine and 950 mg and 300 micro mol/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.
Gaily
E
E
Hospital for Children and Adolescents, 00029 HUS, Finland. eija.gaily@hus.fi
Kantola-Sorsa
E
E
Hiilesmaa
V
V
Isoaho
M
M
Matila
R
R
Kotila
M
M
Nylund
T
T
Bardy
A
A
Kaaja
E
E
Granström
M-L
ML
D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008607:Intellectual Disability / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D007360:Intelligence / Q000187:drug effects*; D009035:Mothers / Q000706:statistics & numerical data; D009483:Neuropsychological Tests; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects; D012016:Reference Values; D014635:Valproic Acid / Q000009:adverse effects*; D014705:Verbal Behavior / Q000187:drug effects; D014888:Wechsler Scales / Q000706:statistics & numerical data
D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid