Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents.
OBJECTIVE
Antiepileptic drugs (AEDs) are potential teratogenic agents. The purpose of this study was to examine the long-term effects of intrauterine AED exposure on neurologic and psychological functioning.


METHODS
Of a prospective study, "Epilepsy, pregnancy, and child development," children could be retraced at school age and adolescence. Sixty-seven were born to mothers with epilepsy [no drugs during pregnancy (n = 13), monotherapy (n = 31), polytherapy (n = 23)]; 49 were nonafflicted control children. Assessments included an intelligence test (Wechsler), a neurologic examination (Touwen), and an EEG. Data analyses were performed, controlling for parental social status, type of maternal drug therapy and drug dosage, type of epilepsy, frequency of seizures during pregnancy, the original subgroups, and specific drug effects.


RESULTS
Type of maternal epilepsy and type and kind of AED therapy, but not maternal seizures during pregnancy correlated with an increase in abnormal EEG patterns. Minor neurologic dysfunction was diagnosed, with increased frequency from the control to the risk/no drug or monotherapy to the polytherapy group. The compromised intelligence score of the polytherapy group was primarily due to those children who had been exposed to primidone (PRM). Level of IQ was negatively associated with PRM dosage.


CONCLUSIONS
Maternal epilepsy and AED therapy during pregnancy appear to have long-term effects on the offspring well into adolescence, as evinced in EEG patterns, minor neurologic dysfunction, and intellectual performance. Severity of effects increased from control group to epilepsy/no-drug group to monotherapy group and was most marked in the polytherapy group. These group differences are assumed to reflect differential neural vulnerability to social and family factors.
Koch
S
S
Department of Pediatrics, Humboldt University, Berlin, Germany.
Titze
K
K
Zimmermann
R B
RB
Schröder
M
M
Lehmkuhl
U
U
Rauh
H
H
D000293:Adolescent; D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D002648:Child; D002658:Developmental Disabilities / Q000139:chemically induced / Q000209:etiology; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000706:statistics & numerical data; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D008431:Maternal-Fetal Exchange; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis* / Q000453:epidemiology; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000453:epidemiology; D011324:Primidone / Q000009:adverse effects; D011446:Prospective Studies
D000927:Anticonvulsants; D011324:Primidone