Tomson T, Danielsson B R, Winbladh B
Neurologiska kliniken, Karolinska sjukhuset, Stockholm.
Lakartidningen. 1997 Aug 20;94(34):2827-32, 2835.
Pregnancy may be especially problematic for the epileptic woman, obstetric complications tend to be more frequent, and seizure control and the pharmacokinetics of anticonvulsants may be affected. The risk of seizures is particularly high during labour and delivery-almost 10-fold higher than at other times during pregnancy. As uncontrolled generalised tonic-clonic seizures may be hazardous to both gravida and fetus, the use of anticonvulsants to prevent their occurrence is to be recommended during pregnancy even though all anticonvulsant drugs are potential teratogens. There is a 2- to 3-fold increase in the risk of birth defects in conjunction with fetal exposure to these drugs. Although the mechanisms mediating the teratogenic effects have not been identified, interference with folate metabolism, formation of toxic metabolites and drug-induced fetal hypoxia have been suggested. Despite the incompleteness of our knowledge, some recommendations can be made for the management of pregnant women with epilepsy. Pre-pregnancy counselling is important. Epileptic women contemplating pregnancy need to be informed of the pros and cons, and any major change in anticonvulsant therapy should be made before conception. Monotherapy is preferable, using the drug appropriate to seizure type and epilepsy syndrome at the lowest dosage and serum level that protects against tonic-clonic seizure. The clinical situation needs to be assessed and drug levels need to be monitored more frequently during pregnancy than otherwise. Patients on anticonvulsant treatment during pregnancy also need to be informed of the possibility of antenatal diagnosis. The use of new anticonvulsant drugs during pregnancy represents a particular challenge, since available clinical data may be insufficient to indicate their teratogenic potential Such a drug should be used in pregnancy only if essential to obtain seizure control. Moreover, the outcome of all such pregnancies needs to be carefully documented.
怀孕对于癫痫女性来说可能尤其成问题,产科并发症往往更为常见,而且癫痫发作的控制以及抗惊厥药的药代动力学可能会受到影响。分娩期间癫痫发作的风险特别高——几乎比孕期其他时间高10倍。由于未得到控制的全身性强直阵挛发作可能对孕妇和胎儿都有危险,因此即使所有抗惊厥药物都是潜在的致畸剂,在孕期也建议使用抗惊厥药来预防发作。胎儿接触这些药物会使出生缺陷的风险增加2至3倍。尽管介导致畸作用的机制尚未明确,但有人提出可能与干扰叶酸代谢、形成有毒代谢产物以及药物引起的胎儿缺氧有关。尽管我们的认识并不全面,但对于癫痫孕妇的管理仍可提出一些建议。孕前咨询很重要。打算怀孕的癫痫女性需要了解利弊,并且在受孕前应对抗惊厥治疗方案进行任何重大调整。单药治疗更佳,应根据癫痫发作类型和癫痫综合征选用合适的药物,以最低剂量和血清水平来预防强直阵挛发作。孕期需要比平时更频繁地评估临床情况并监测药物水平。孕期接受抗惊厥治疗的患者还需要了解产前诊断的可能性。孕期使用新型抗惊厥药物是一个特殊的挑战,因为现有的临床数据可能不足以表明其致畸潜力。只有在控制癫痫发作必不可少时,才应在孕期使用此类药物。此外,所有此类妊娠的结局都需要仔细记录。