妊娠早期停用抗癫痫发作药物癫痫女性患者的临床特征和结局

Clinical features and outcomes of women with epilepsy who withdraw anti-seizure medications in early pregnancy

目的探讨妊娠早期停用抗癫痫发作药物(ASM)的妊娠癫痫女性(PWWE)患者停药前的ASM治疗模式、癫痫发作情况、孕产期结局和后代结局。方法对2009年1月至2022年10月在四川大学华西医院登记的PWWE数据库中妊娠早期停药及全程维持ASM治疗的患者进行回顾性分析。妊娠早期停药的定义为妊娠0~3个月停用ASM。最终纳入65例妊娠早期停用ASM治疗的PWWE患者(停药组),并按照1∶2的比例匹配130例同期在华西医院就诊的全程维持ASM治疗的PWWE患者(维持治疗组)。比较两组患者的人口学特征、ASM使用情况、癫痫发作情况、孕产期及后代1岁内结局。在亚组分析中,将停药组患者根据妊娠中晚期是否恢复用药分为全程停药组(n=53)和恢复用药组(n=12),对两组患者进行分层比较。结果停药组本科以下学历[72.3%(47/65)比54.6%(71/130),χ^(2)=5.68,P=0.017]、家庭人均月收入低于5000元[44.6%(29/65)比18.5%(24/130),χ^(2)=14.98,P<0.001]、伴有癫痫家族史[12.3%(8/65)比3.1%(4/130),χ^(2)=4.90,P=0.027]及再次妊娠的患者比例[43.1%(28/65)比26.2%(34/130),χ^(2)=5.72,P=0.017]均高于维持治疗组。妊娠前停药组较维持治疗组接受多种ASM治疗的患者比例更低[16.9%(11/65)比38.5%(50/130),χ^(2)=9.35,P=0.002]。停药组孕期伴有强直阵挛的癫痫发作[50.8%(33/65)比31.5%(41/130),χ^(2)=6.81,P=0.009]和孕期癫痫发作加重的比例[32.3%(21/65)比9.2%(12/130),χ^(2)=16.41,P<0.001]均明显高于维持治疗组。停药组后代早产率低于维持治疗组[4.6%(3/65)比19.2%(25/130),χ^(2)=101.70,P<0.001]。与妊娠期全程停药组相比,中晚期恢复用药组的孕期癫痫发作加重的比例稍高[7/12比26.4%(14/53),χ^(2)=3.22,P=0.073]。结论有癫痫家族史、再次妊娠的PWWE更可能在妊娠期停药,停药后妊娠期癫痫发作明显加重,但后代早产率相对降低。

Objective To explore anti-seizure medication(ASM)treatment patterns,seizures,maternal and fetal outcomes and offspring outcomes of pregnant women with epilepsy(PWWE)who withdraw ASM in the first trimester of pregnancy.Methods A retrospective analysis was performed on the PWWE database registered in West China Hospital,Sichuan University from January 2009 to October 2022.Patients who withdrew ASM therapy in the first trimester and those who maintained ASM therapy throughout pregnancy were included.Withdrawal in the first trimester was defined as discontinuation of ASM between 0 and 3 months of pregnancy.Sixty-five PWWE(withdrawal group)who withdraw ASM in the first trimester were included,and 130 PWWE(maintained-therapy group)who took ASM throughout pregnancy in West China Hospital during the same period were matched 1∶2.Demographic characteristics,ASM,seizures,maternal and fetal outcomes within 1 year were compared between the 2 groups.In the subgroup analysis,the withdrawal group was divided into a full withdrawal group(n=53)and a resumption group(n=12)according to whether the ASM was resumed in the second and third trimesters of pregnancy,and the 2 groups were stratified and compared.Results In the withdrawal group,the proportion of patients with bachelor degree below[72.3%(47/65)vs 54.6%(71/130),χ^(2)=5.68,P=0.017],family income less than 5000 yuan per capita[44.6%(29/65)vs 18.5%(24/130),χ^(2)=14.98,P<0.001],a family history of epilepsy[12.3%(8/65)vs 3.1%(4/130),χ^(2)=4.90,P=0.027],and a second pregnancy[43.1%(28/65)vs 26.2%(34/130),χ^(2)=5.72,P=0.017]was higher than in the maintained-therapy group.The proportion of patients who received multiple ASM was lower in the withdrawal group than in the maintained-therapy group[16.9%(11/65)vs 38.5%(50/130),χ^(2)=9.35,P=0.002].In the withdrawal group,the rate of seizures with tonic-clonic seizures during pregnancy[50.8%(33/65)vs 31.5%(41/130),χ^(2)=6.81,P=0.009]and seizure exacerbation during pregnancy[32.3%(21/65)vs 9.2%(12/130),χ^(2)=16.41,P<0.001]was higher.The preterm birth rate in the withdrawal group was lower than that in the maintained-therapy group[4.6%(3/65)vs 19.2%(25/130),χ^(2)=101.70,P<0.001].The rate of seizure exacerbation during pregnancy was higher in the resumption group than in the full withdrawal group[7/12vs 26.4%(14/53),χ^(2)=3.22,P=0.073].Conclusion sPWWE with a family history of epilepsy and a second pregnancy were more likely to withdraw ASM during pregnancy.After withdrawal,the seizures during pregnancy were significantly worse,but the preterm birth rate of offspring was relatively reduced.