Inoyama Katherine, Meador Kimford J
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Epilepsy Res. 2015 Aug;114:89-97. doi: 10.1016/j.eplepsyres.2015.04.016. Epub 2015 May 2.
Antiepileptic drugs (AEDs) have been known to have teratogenic effects for a little over 50 years. While early reports focused on fetal malformations, there has been an increasing amount of data over the last few decades exploring the cognitive outcomes of offspring exposed to AEDs in utero. Although the challenges of confounding factors and varied methodologies have led to inconsistent results, the negative impact of some of the agents, such as valproate, have become clear. Further studies are needed to evaluate the cognitive effects of prenatal exposure to many AEDs which have not been tested, to clarify the effects of existing AEDs which have yielded mixed results, and to better understand the effects of polytherapy. Research in animal models is warranted to screen AEDs for their effects on cognition in exposed offspring and to further our understanding of the underlying mechanisms by which AEDs exert their harmful effects on the developing brain. And finally, new AEDs without these harmful effects and agents which can prevent or reverse the negative consequences imparted by AED therapy on cognition should be sought.
抗癫痫药物(AEDs)具有致畸作用已有50多年的时间了。早期报告主要关注胎儿畸形,而在过去几十年里,越来越多的数据开始探索子宫内接触AEDs的后代的认知结局。尽管混杂因素和多样的方法带来了挑战,导致结果不一致,但某些药物(如丙戊酸盐)的负面影响已变得清晰。需要进一步开展研究,以评估产前接触许多未经测试的AEDs的认知影响,阐明那些结果不一的现有AEDs的影响,并更好地理解联合治疗的影响。有必要在动物模型中开展研究,以筛查AEDs对暴露后代认知的影响,并进一步了解AEDs对发育中大脑产生有害影响的潜在机制。最后,应寻找没有这些有害影响的新型AEDs以及能够预防或逆转AED治疗对认知造成的负面后果的药物。