Teratogenicity of sodium valproate.
Teratogenicity of sodium valproate.
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DOI：
10.1517/14740338.4.2.345
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发表时间：
2005-03-01
影响因子：
3.1
通讯作者：
Wyszynski, Diego F
中科院分区：
文献类型：
--
作者：
Alsdorf, Rachel;Wyszynski, Diego F
广泛流行的抗癫痫药物（AED）和情绪稳定剂丙戊酸钠（也称为丙戊酸钠，VPA）的致畸性已被先前的研究证明；然而，这些发现往往受到受感染妇女的小群体样本和回顾性研究设计的限制。许多因素导致VPA的致畸性。这些因素包括共同给药的药物数量、药物剂量、母亲和/或婴儿的代谢差异、暴露时胎儿的胎龄以及遗传易感性。VPA与各种大小畸形有关，包括神经管缺陷、唇腭裂、心血管异常、泌尿生殖系统缺陷、发育迟缓、内分泌紊乱、肢体缺陷和自闭症的发病率增加20倍。有研究表明，对癫痫孕妇进行综合治疗会增加其后代致畸的风险。此外，VPA剂量与不良后果之间存在确定的关系。大剂量的单次VPA可能导致胎儿血清中的峰值水平，从而产生有害影响。目前，为了更好地确定抗癫痫药物的致畸作用，正在建立的国家和国际妊娠登记处的数量有所增加。这些努力希望通过解决过去研究的局限性，提高我们对aed及其相关风险的理解。
The teratogenicity of the widely popular antiepileptic drug (AED) and mood stabiliser sodium valproate (also known as valproate, VPA) has been evidenced by previous research; however, these findings have often been limited by a small population sample of exposed women and a retrospective study design. Many factors contribute to the teratogenicity of VPA. These include the number of drugs that are co-administered, drug dosage, differences in maternal and/or infant metabolism, the gestational age of the fetus at exposure, and hereditary susceptibility. VPA has been associated with a variety of major and minor malformations, including a 20-fold increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrinological disorders, limb defects, and autism. It has been suggested that polytherapy treatment in epileptic pregnant women increases the risk of teratogenicity in offspring. Furthermore, there is an established relationship between VPA dose and adverse outcome. Large single doses of VPA potentially cause high peak levels in the fetal serum resulting in deleterious effects. Currently there is an increase in the number of national and international pregnancy registries being formed in an effort to better identify the teratogenic effects of AEDs. These efforts hope to enhance our understanding of AEDs and their associated risks by addressing past study limitations.