Congenital malformations due to antiepileptic drugs
Congenital malformations due to antiepileptic drugs
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DOI：
10.1016/s0920-1211(98)00084-9
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发表时间：
1999-02-01
影响因子：
2.2
通讯作者：
Teranishi, T
中科院分区：
文献类型：
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作者：
Kaneko, S;Battino, D;Teranishi, T
为了确定孕期使用抗癫痫药物(AEDs)治疗癫痫的母亲的后代中先天性畸形发生率增加的主要危险因素，并确定AEDs的相对致畸风险，我们前瞻性地分析了983名出生在日本、意大利和加拿大的子女。未接触毒品的子代先天畸形发生率为3.1%，而接触毒品的子代先天畸形发生率为9.0%。暴露于单一AED的子代发病率最高的是扑米酮(PRM；14.3%)，其次是丙戊酸盐(VPA；11.1%)、苯妥英(PHT；9.1%)、卡马西平(CBZ；5.7%)和苯巴比妥(PBI)(5.1%)。VPA剂量和水平与畸形发生率呈正相关。为了避免畸形的发生，本研究首次确定了VPA剂量和水平的临界值，分别为1000 mg/d和70µg/ml。随着药物数量的增加和每日总剂量的增加，畸形的发生率也会增加。抗癫痫药物的特定组合，如VPA+CBZ和PHT+PRM+PB会产生更高的先天性畸形发生率。除兄弟姐妹中存在畸形外，畸形的发生率与所研究的任何背景因素无关。这些结果表明，先天畸形发生率的增加主要是由AEDs引起的，这表明在治疗育龄癫痫妇女时，通过改进药物治疗方案，避免使用多药和高水平的VPA(>70微克/毫升)，可以预防畸形的发生。(C)1999 Elsevier Science B.V.保留所有权利。
To identify the major risk factors for the increased incidence of congenital malformations in offspring of mothers being treated for epilepsy with antiepileptic drugs (AEDs) during pregnancy and, to determine the relative teratogenic risk of AEDs, we prospectively analyzed 983 offspring born in Japan, Italy, and Canada. The incidence of congenital malformations in offspring without drug exposure was 3.1%, versus an incidence with drug exposure of 9.0%. The highest incidence in offspring exposed to a single AED occurred with primidone (PRM; 14.3%), which was followed by valproate (VPA; 11.1%), phenytoin (PHT; 9.1%), carbamazepine (CBZ; 5.7%), and phenobarbital(PBI 5.1%). The VPA dose and level positively correlated with the incidence of malformations. This study first determined a cut-off value of VPA dose and level at 1000 mg/day and 70 mu g/ml, respectively, to avoid the occurrence of malformations. The incidence of malformations increases as the number of drugs increases, and as the total daily dose increases. Specific combinations of AEDs such as VPA+ CBZ and PHT+PRM +PB produced a higher incidence of congenital malformations. The incidence of malformations was not associated with any background factors studied except for the presence of malformations in siblings. These results indicate that the increased incidence of congenital malformations was caused primarily by AEDs, suggesting that malformations can be prevented by improvements in drug regimen, and by avoiding polypharmacy and high levels of VPA (more than 70 mu g/ml) in the treatment of epileptic women of childbearimg age. (C) 1999 Elsevier Science B.V. All rights reserved.