Neuroteratogens in man: An overview with special emphasis on the teratogenicity of antiepileptic drugs in pregnancy
Neuroteratogens in man: An overview with special emphasis on the teratogenicity of antiepileptic drugs in pregnancy
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DOI：
10.1016/j.reprotox.2006.03.014
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发表时间：
2006-08-01
影响因子：
3.3
通讯作者：
Ornoy, Asher
中科院分区：
文献类型：
--
作者：
Ornoy, Asher
人类大脑和小脑最活跃的生长和发育发生在怀孕后半段和出生后第一年。因此，许多致畸剂也可能影响发育，导致轻微、中度甚至严重的脑损伤，这并不奇怪。 “经典”抗癫痫药物（AED）丙戊酸（VPA）、苯妥英、苯巴比妥、扑米酮和卡马西平都被认为具有致畸性。它们可能会增加主要先天性异常的发生率，包括神经管缺陷（NTD），导致特定的面部和其他畸形特征——“抗癫痫药物综合症”（AEDS），并且通常会导致某种程度的精神障碍。在这些 AED 中，致畸性最强的似乎是丙戊酸，它导致约 2% 的 NTD，并导致主要先天性异常增加 4-8%。苯妥英也会增加各种异常的发生率，但显然不会增加 NTD 的发生率。苯巴比妥扑米酮和卡马西平也会致畸并损害智力功能，但程度比 VPA 和苯妥英要轻。患有 AEDS 的儿童的认知能力主要受到损害。这种损伤是轻微到中度的，受影响的儿童智力接近边缘。妊娠期拉莫三嗪单药治疗似乎相对安全。一般来说，联合疗法比单一疗法对胎儿更危险，至少对于VPA和拉莫三嗪来说，似乎存在“阈值效应”。 (c) 2006 Elsevier Inc. 保留所有权利。
The most active growth and development of the human cerebrum and cerebellum occurs in the second half of pregnancy and in the first year of life. It is therefore not surprising that many teratogens may also affect development causing slight, moderate or even severe brain damage. The "classical" antiepileptic drugs (AEDs) valproic acid (VPA), phenytoin, phenobarbital, primidone and carbamazepine are all considered to be teratogenic. They may increase the rate of major congenital anomalies including neural tube defects (NTD), cause specific facial and other dysmorphic features-the "Anti Epileptic Drug Syndrome" (AEDS) and often some degree of mental impairment. Of these AEDs, the most teratogenic seems to be valproic acid, causing about 2% of NTD and an additional increase of 4-8% in major congenital anomalies. Phenytoin also increases the rate of various anomalies, but apparently not of NTD. Phenobarbital primidone and carbamazepine are also teratogenic and impair intellectual function but to a lesser extent than VPA and phenytoin. Cognition is mainly impaired in the children that also exhibit the AEDS. The impairment is slight to moderate, leaving the affected children with a close to borderline intelligence. Lamotrigine monotherapy in pregnancy seems to be relatively safe. In general, polytherapy is more dangerous to the fetus than monotherapy and, at least for VPA and lamotrigine, there seems to be a "treshold effect". (c) 2006 Elsevier Inc. All rights reserved.