Nucera Bruna, Brigo Francesco, Trinka Eugen, Kalss Gudrun
Department of Neurology, Hospital of Merano (SABES-ASDAA), Merano-Meran, Italy.
Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Centre for Cognitive Neuroscience, Member of the ERN EpiCARE, Salzburg, Austria.
Ther Adv Neurol Disord. 2022 Jun 11;15:17562864221101687. doi: 10.1177/17562864221101687. eCollection 2022.
Women with epilepsy (WWE) wishing for a child represent a highly relevant subgroup of epilepsy patients. The treating epileptologist needs to delineate the epilepsy syndrome and choose the appropriate anti-seizure medication (ASM) considering the main goal of seizure freedom, teratogenic risks, changes in drug metabolism during pregnancy and postpartum, demanding for up-titration during and down-titration after pregnancy. Folic acid or vitamin K supplements and breastfeeding are also discussed in this review. Lamotrigine and levetiracetam have the lowest teratogenic potential. Data on teratogenic risks are also favorable for oxcarbazepine, whereas topiramate tends to have an unfavorable profile. Valproate needs special emphasis. It is most effective in generalized seizures but should be avoided whenever possible due to its teratogenic effects and the negative impact on neuropsychological development of exposed children. Valproate still has its justification in patients not achieving seizure freedom with other ASMs or if a woman decides to or cannot become pregnant for any reason. When valproate is the most appropriate treatment option, the patient and caregiver must be fully informed of the risks associated with its use during pregnancies. Folate supplementation is recommended to reduce the risk of major congenital malformations. However, there is insufficient information to address the optimal dose and it is unclear whether higher doses offer greater protection. There is currently no general recommendation for a peripartum vitamin K prophylaxis. During pregnancy most ASMs (e.g. lamotrigine, oxcarbazepine, and levetiracetam) need to be increased to compensate for the decline in serum levels; exceptions are valproate and carbamazepine. Postpartum, baseline levels are reached relatively fast, and down-titration is performed empirically. Many ASMs in monotherapy are (moderately) safe for breastfeeding and women should be encouraged to do so. This review provides a practically oriented overview of the complex management of WWE before, during, and after pregnancy.
希望生育的癫痫女性（WWE）是癫痫患者中一个高度相关的亚组。治疗癫痫的专家需要明确癫痫综合征，并选择合适的抗癫痫药物（ASM），同时要考虑癫痫发作控制这一主要目标、致畸风险、孕期及产后药物代谢的变化，以及孕期加量和产后减量的需求。本综述还讨论了叶酸或维生素K补充剂以及母乳喂养的问题。拉莫三嗪和左乙拉西坦的致畸潜力最低。关于奥卡西平的致畸风险数据也较为有利，而托吡酯的情况往往不太乐观。丙戊酸盐需要特别强调。它对全身性癫痫发作最为有效，但由于其致畸作用以及对暴露儿童神经心理发育的负面影响，应尽可能避免使用。对于使用其他ASM仍无法控制癫痫发作的患者，或者因任何原因决定不怀孕或无法怀孕的女性，丙戊酸盐仍有其合理性。当丙戊酸盐是最合适的治疗选择时，必须让患者和护理人员充分了解孕期使用该药的相关风险。建议补充叶酸以降低重大先天性畸形的风险。然而，关于最佳剂量的信息不足，尚不清楚更高剂量是否能提供更大的保护。目前对于围产期维生素K预防没有普遍建议。孕期大多数ASM（如拉莫三嗪、奥卡西平、左乙拉西坦）需要增加剂量以补偿血清水平的下降；丙戊酸盐和卡马西平除外。产后，相对较快就能达到基线水平，减量是根据经验进行的。许多单药治疗的ASM对母乳喂养（中度）安全，应鼓励女性进行母乳喂养。本综述提供了一个以实际应用为导向的关于癫痫女性孕前、孕期及产后复杂管理的概述。
