癫痫妇女妊娠期间癫痫发作及服用抗癫痫药物对胎儿影响的研究
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摘要
目的本研究探讨女性癫痫患者妊娠期间癫痫发作以及服用抗癫痫药物对胎儿的影响。方法收集2003年3月5日至2016年7月15日在中国人民解放军总医院和首都医科大学附属北京天坛医院癫痫门诊就诊的育龄期癫痫妇女50例作为研究对象,对患者妊娠前准备、妊娠期间发作/服药情况、产后哺乳、婴幼儿健康状况等进行跟踪调查,随访至2017年12月31日,评估癫痫发作次数、服用抗癫痫药物对胎儿健康的影响。结果在观察期内共收集到50例妊娠癫痫妇女,采集患者所有临床资料,截止到随访结束时,所生婴幼儿平均年龄为4.5±4岁(6个月~13岁)。妊娠期间服药患者共26例,在上述26例患者所生27个婴幼儿中(其中1例有二胎),有1例服用丙戊酸(VPA)联合拉莫三嗪的患者所生孩子为脑瘫、脊柱裂、并指等发育畸形,另有一例怀孕期间服用卡马西平,第10周胎儿停止发育、人工流产,其余婴幼儿均体健,发育较同龄人无明显差别。怀孕期间未服药的患者共24例,在怀孕期间复杂部分性发作4例,继发全面性发作11例,既有复杂部分性发作又有继发全面性发作3例,一直无发作6例。1例患者所生孩子为脑瘫外,其余婴幼儿均体健,发育较同龄人无明显差别。在这些患者中哺乳期仍坚持服药的患者共11例,所有服药哺乳的婴幼儿均健康。结论妊娠期间癫痫发作多数情况下不影响胎儿发育,但需警惕全面性发作造成的不良影响。现有数据不足以得出癫痫妇女妊娠期间服用奥卡西平是安全的,这尚有待于更多的研究证实。
Objective To investigate the influence of seizure attack and safety of anti-epileptic drug during pregnancy. Method This study collected 50 cases of women with epilepsy at childbearing age in Chinese PLA General Hospital and Beijing Tiantan Hospital from March 5, 2003 to July 15, 2016. A survey was made about the patient preparation before pregnancy, seizure attack and medication prescription during pregnancy, postpartum lactation, infant health, and we assessed the seizure frequency and safety of antiepileptic drugs towards the fetal health. All patients were followed up to December 31, 2017. Results We collected the clinical materials of 50 cases by the end of the follow-up, and the main age of their children was 4.5±4 years old(6 month to 13 years). A total of 26 patients took antiepileptic drugs during pregnancy. In the 27 infants born in 26 patients(one of them have a second child), one child whose mother taken valproate acid(VPA)and lamotrigine during pregnancy had developmental malformation of cerebral palsy, bifid spine, and syndactylia. Another patient taken carbamazepine suffered arrested fetal development and abortion at 10 weeks pregnancy. The rest of the infants and young children are healthy, and therewas no evident of different development than that of their peers. A total of 24 cases didn't take any anti-epileptic drugs during pregnancy. Among these patients, 4 cases suffered with complex partial seizure, 11 cases had secondary general tonic-clonic seizure, 3 cases had both the two seizure type, and 6 cases had no seizure attack. Except for one cerebral palsy child, the rest of the infants and young children are health. A total of 11 patients remained the antiepileptic drugs during lactation. All medication lactation infants were healthy. Conclusion The majority of cases who suffered from seizures during pregnancy did not affect fetal development, but we need to be aware of the influence of convulsion. Available data are insufficient to conclude that taking oxcarbazepine during pregnancy is safe. This has yet to be confirmed by more studies.
Objective To investigate the influence of seizure attack and safety of anti-epileptic drug during pregnancy. Method This study collected 50 cases of women with epilepsy at childbearing age in Chinese PLA General Hospital and Beijing Tiantan Hospital from March 5, 2003 to July 15, 2016. A survey was made about the patient preparation before pregnancy, seizure attack and medication prescription during pregnancy, postpartum lactation, infant health, and we assessed the seizure frequency and safety of antiepileptic drugs towards the fetal health. All patients were followed up to December 31, 2017. Results We collected the clinical materials of 50 cases by the end of the follow-up, and the main age of their children was 4.5±4 years old(6 month to 13 years). A total of 26 patients took antiepileptic drugs during pregnancy. In the 27 infants born in 26 patients(one of them have a second child), one child whose mother taken valproate acid(VPA)and lamotrigine during pregnancy had developmental malformation of cerebral palsy, bifid spine, and syndactylia. Another patient taken carbamazepine suffered arrested fetal development and abortion at 10 weeks pregnancy. The rest of the infants and young children are healthy, and therewas no evident of different development than that of their peers. A total of 24 cases didn't take any anti-epileptic drugs during pregnancy. Among these patients, 4 cases suffered with complex partial seizure, 11 cases had secondary general tonic-clonic seizure, 3 cases had both the two seizure type, and 6 cases had no seizure attack. Except for one cerebral palsy child, the rest of the infants and young children are health. A total of 11 patients remained the antiepileptic drugs during lactation. All medication lactation infants were healthy. Conclusion The majority of cases who suffered from seizures during pregnancy did not affect fetal development, but we need to be aware of the influence of convulsion. Available data are insufficient to conclude that taking oxcarbazepine during pregnancy is safe. This has yet to be confirmed by more studies.
引文
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[20]Cramer JA1,Gordon J,Schachter S,et al.Women with epilepsy:hormonal issues from menarche through menopause[J].Epilepsy Behav,2007,11(2):160-178.
[21]Herzog AG,MacEachern DB,Mandle HB,et al.Folic acid use by women with epilepsy:Findings of the Epilepsy Birth Control Registry[J].Epilepsy Behav,2017,72:156-160.
[22]Crettenand M,Rossetti AO,Buclin T,et al.Use of antiepileptic drugs during breastfeeding:What do we tell the mother?[J].Nervenarzt,2018,72:219-220.
[2]Shawahna R.Which information on women's issues in epilepsy does a community pharmacist need to know?A Delphi consensus study[J].Epilepsy Behav,2017,77:79-89.
[3]Cagnetti CS,Lattanzi N,Foschi L,et al.Seizure course during pregnancy in catamenial epilepsy[J].Neurology,2014,83(4):339-344.
[4]Battino DT,Tomson E,Bonizzoni J,et al.Seizure control and treatment changes in pregnancy:observations from the EURAPepilepsy pregnancy registry[J].Epilepsia,2013,54(9):1621-1627.
[5]La Neve A,Boero G,Francavilla T,et al.Prospective,case-control study on the effect of pregnancy on seizure frequency in women with epilepsy[J].Neurol Sci,2015,36(1):79-83.
[6]Edey S,Moran N,Nashef L,et al.SUDEP and epilepsy-related mortality in pregnancy[J].Epilepsia,2014,55(7):e72-74.
[7]MacDonald SC,Bateman BT,McElrath TF,et al.Hernandez-diaz,mortality and morbidity during delivery hospitalization among pregnant women with epilepsy in the united states[J].JAMANeurol,2015,72(9):981-988.
[8]Borthen I.Obstetrical complications in women with epilepsy[J].Seizure,2015,28:32-34.
[9]Viale L,Allotey J,Cheong-See F,et al.Thangaratinam,epilepsy in pregnancy and reproductive outcomes:a systematic review and metaanalysis[J].Lancet,2015,386(10006):1845-1852.
[10]Tomson T,Battino TD.Teratogenic effects of antiepileptic drugs[J].Lancet Neurol,2012,11(9):803-813.
[11]Pennell PB,Klein AM,Browning N,et al.Differential effects of antiepileptic drugs on neonatal outcomes[J].Epilepsy Behav,2012,24(4):449-456.
[12]Veiby G,Daltveit AK,Schj?lberg S,et al.Exposure to antiepileptic drugs in utero and child development:a prospective populationbased study[J].Epilepsia,2013,54(8):1462-1472.
[13]Borthen I,Eide MG,Daltveit AK,et al.Delivery outcome of women with epilepsy:a population-based cohort study[J].BJOG,117(12):1537-1543.
[14]Viale L,Allotey J,Cheong-See F,et al.Epilepsy in pregnancy and reproductive outcomes:a systematic review and meta-analysis[J].Lancet,2015,386(10006):1845-1852.
[15]Richards N,Reith D,Stitely M,et al.Antiepileptic drug exposure in pregnancy and pregnancy outcome from national drug usage data[J].BMC Pregnancy Childbirth,2018,18(1):84.
[16]成人癫痫患者癫痫长程管理共识专家协作组.关于成人癫痫患者长程管理的专家共识[J].中华神经科杂志,2013,46(7):496-499.
[17]Vajda FJ,O'Brien T,Lander C,et al.The efficacy of the newer antiepileptic drugs in controlling seizures in pregnancy[J].Epilepsia,2014,55(8):1229-1234.
[18]赵跃宏.妊娠合并癫痫32例临床分析[J].中国妇幼保健,2012,27(25):3903-3905.
[19]Harden CL,Pennell PB,Koppel BS,et al.Management issues for women with epilepsy--focus on pregnancy(an evidence-based review):III.Vitamin K,folic acid,blood levels,and breastfeeding:Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society[J].Epilepsia,2009,50(5):1247-1255.
[20]Cramer JA1,Gordon J,Schachter S,et al.Women with epilepsy:hormonal issues from menarche through menopause[J].Epilepsy Behav,2007,11(2):160-178.
[21]Herzog AG,MacEachern DB,Mandle HB,et al.Folic acid use by women with epilepsy:Findings of the Epilepsy Birth Control Registry[J].Epilepsy Behav,2017,72:156-160.
[22]Crettenand M,Rossetti AO,Buclin T,et al.Use of antiepileptic drugs during breastfeeding:What do we tell the mother?[J].Nervenarzt,2018,72:219-220.