Normal intelligence in children with prenatal exposure to carbamazepine
Normal intelligence in children with prenatal exposure to carbamazepine
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DOI：
10.1212/wnl.62.1.28
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发表时间：
2004-01-13
期刊：
影响因子：
9.9
通讯作者：
Granström, ML
中科院分区：
文献类型：
--
作者：
Gaily, E;Kantola-Sorsa, E;Granström, ML
目的：探讨抗癫痫药物特别是卡马西平和丙戊酸对癫痫母亲产前暴露儿童智力的影响。方法：采用《韦氏学前及小学智力量表》或《韦氏儿童智力量表》对182名癫痫母亲的幼儿（研究组）和141名对照儿童进行盲法智力测试。前瞻性地收集孕妇抗癫痫治疗和妊娠期间癫痫发作的数据。该研究组约占1989年至1994年乌西马省癫痫母亲所生儿童的50%。107名儿童接受抗癫痫单药治疗：86名接受卡马西平治疗，13名接受丙戊酸治疗。30名儿童接受多种治疗：23种组合包括卡马西平，17种组合包括丙戊酸。妊娠后半期产妇的中位剂量和血液水平卡马西平为600毫克和26 μ mol/L，丙戊酸为950毫克和300 μ mol/L。结果：在子宫内接受卡马西平单药治疗的儿童的平均言语和非言语智商得分分别为96 （95% CI, 93-100）和103 （95% CI, 100-106）。他们与对照组没有差异，后者的平均言语和非言语智商得分分别为95 （95% CI, 92-97）和102 （95% CI， CI, 100-105）。与其他研究组儿童和对照组相比，暴露于丙戊酸盐（平均82；95% CI, 78-87）和多重治疗（平均85；95% CI, 80-90）的儿童的言语智商得分显著降低。结论：卡马西平单药治疗在母体血清水平在参考范围内不会损害产前暴露子代的智力。怀孕期间暴露于多种疗法和丙戊酸盐与语言智力显著降低有关。丙戊酸的独立作用仍未得到证实，因为结果与母亲教育程度低和综合治疗相混淆。
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 mumol/L for carbamazepine and 950 mg and 300 mumol/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.