Pennell Page B
Department of Neurology, Division of Epilepsy, Division of Women's Health, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Neurotherapeutics. 2016 Oct;13(4):811-820. doi: 10.1007/s13311-016-0464-0.
Although prenatal exposure to antiepileptic drugs (AEDs) is known to impart relatively higher risks of major congenital malformations, prospective studies have provided refined data that allow us to differentiate the risks of different types and doses of AEDs. As the number of AED prescriptions has dramatically increased in reproductive-aged women with a variety of neuropsychiatric indications, the evolving concepts learned from studies in women with epilepsy can be applied to a much larger group of pregnant women to improve child outcomes while maintaining maternal disease control. In addition to careful selection of the type of medication, the amount of fetal exposure at conception and in the first trimester probably matters across all AEDs. Some AED polytherapy regimens are not associated with a higher risk of malformations, although other outcomes have not yet been formally studied. The individual woman's drug target concentration should be established preconception and maintained during pregnancy, to prevent seizure worsening. Substantial pharmacokinetic changes occur with many of the medications during pregnancy and postpartum, and interindividual variability supports the use of therapeutic drug monitoring for most AEDs. During pregnancy, vigilance and close monitoring should also include intrauterine fetal growth, obstetric complications, and neonatal complications. Breastfeeding can provide additional neurodevelopmental benefit and should be an option for women on AEDs. Knowledge of these key principles enhances our ability to make treatment recommendations with resultant improved maternal and child outcomes. Additional prospective studies are needed to further define the risk-benefit ratio across a variety of medications, dosing strategies, and neuropsychiatric disorders.
尽管已知产前暴露于抗癫痫药物(AEDs)会带来相对较高的重大先天性畸形风险,但前瞻性研究已提供了精确数据,使我们能够区分不同类型和剂量AEDs的风险。随着有各种神经精神疾病指征的育龄妇女中AED处方数量急剧增加,从癫痫女性研究中学到的不断演变的概念可应用于更大群体的孕妇,以在维持母亲疾病控制的同时改善儿童结局。除了仔细选择药物类型外,受孕时和孕早期胎儿暴露的量可能对所有AEDs都很重要。一些AED联合治疗方案与较高的畸形风险无关,尽管其他结局尚未进行正式研究。应在孕前确定个体女性的药物目标浓度,并在孕期维持,以防止癫痫发作恶化。孕期和产后许多药物会发生显著的药代动力学变化,个体差异支持对大多数AEDs进行治疗药物监测。孕期,警惕和密切监测还应包括宫内胎儿生长、产科并发症和新生儿并发症。母乳喂养可提供额外的神经发育益处,对于服用AEDs的女性应是一种选择。了解这些关键原则可增强我们做出治疗建议的能力,从而改善母婴结局。需要更多的前瞻性研究来进一步确定各种药物、给药策略和神经精神疾病的风险效益比。