The risk of spina bifida aperta after first-trimester exposure to valproate in a prenatal cohort.
The risk of spina bifida aperta after first-trimester exposure to valproate in a prenatal cohort.
复制标题
产前队列中妊娠早期接触丙戊酸后发生脊柱裂的风险。
作者：
J. Omtzigt;F. Los;D. Grobbee;L. Pijpers;M. Jahoda;H. Brandenburg;P. Stewart;H. L. Gaillard;E. Sachs;J. Wladimiroff
怀孕期间使用抗癫痫药物（AED）会增加先天性畸形的风险。脊柱裂与丙戊酸 (VPA) 特别相关（估计风险为 1% 至 2%）。实际风险、VPA 与脊柱裂而不是无脑畸形的唯一关联以及确切的因果关系仍然是讨论的问题。对接受 AED 治疗并在妊娠 22 周前转诊进行产前诊断的癫痫孕妇进行了一项前瞻性队列研究，并随访至出生后 3 个月。对 261 名女性的怀孕情况（291 名单胎和 6 名双胞胎）进行了评估。接触任何 AED 后出现异常的发生率为 6.9%。对于暴露于 VPA 的胎儿，患病率为 9.4%，其中 6 例脊柱裂，其中 2 例为同卵双胞胎（患病率为 6.3%，如果双胞胎算作 1 则为 5.4%）。与正常妊娠的妊娠相比，脊柱裂与 VPA 的平均每日剂量显着较高相关（1.640 +/- 136 mg/d vs 941 +/- 48 mg/d，p = 0.0001）。未观察到脊柱裂的发生与母亲癫痫发作或癫痫类型、癫痫或神经管缺陷家族史或病史之间存在关系。根据这些结果，我们建议，当怀孕期间无法避免使用 VPA 时，可以通过减少每日剂量来降低致畸风险。
Use of antiepileptic drugs (AEDs) during pregnancy is associated with an increased risk of congenital malformations. Spina bifida aperta has been linked specifically to valproic acid (VPA) (estimated risk, 1 to 2%). The actual risk, the exclusive association of VPA with spina bifida and not anencephaly, and the precise causative relation remain matters of discussion. A prospective cohort study of pregnant women with epilepsy receiving AEDs and referred for prenatal diagnosis before week 22 of gestation was conducted, with follow-up to 3 months after birth. Pregnancies (291 singleton and 6 twin) in 261 women were evaluated. The prevalence of anomalies after exposure to any AED was 6.9%. For fetuses exposed to VPA, the prevalence was 9.4%, including six cases of spina bifida, two of which were in monozygotic twins (giving a prevalence rate of 6.3%, or 5.4%, if twins counted as one). Spina bifida was associated with a significantly higher average daily dose of VPA as compared with pregnancies with normal outcome (1.640 +/- 136 mg/d vs 941 +/- 48 mg/d, p = 0.0001). No relation was observed between the occurrence of spina bifida and type of maternal seizure or epilepsy, family history of epilepsy or neural-tube defects, or medical history. From these results we suggest that when the use of VPA during pregnancy cannot be avoided, the teratogenic risk might be diminished by reduction of the daily dose.