Martínez Ferri Meritxell, Peña Mayor P, Pérez López-Fraile I, Castro Vilanova M D, Escartín Siquier A, Martín Moro M, Forcadas Berdusan M
Hospital Universitario Mútua de Terrasa, Barcelona.
Neurologia. 2009 Jul-Aug;24(6):360-5.
Pregnancy registries provide trustworthy information about the risks associated to antiepileptic drugs (AEDs). EURAP is a Prospective International Registry which include patients who takes AEDs at the time of conception. The data of the Spanish centers which are contributing to EURAP reflects the reality of our milieu.
To study the incidence of major congenital malformations (MCM) /and/or fetal-perinatal death (MFP) and determine his relationship to AEDs in the Spanish EURAP registry.
After informed consent, patients were included in the prospective Registry and evaluated: at the beginning, at the end of the second and third trimester, after delivery and one year after birth. A variety of variables were collected: demographic, type of epilepsy, frequency of seizures during pregnancy, AEDs and dose, potential toxics, folate use and dose, obstetric complications and information of the newborn. After 6 years of recruitment (June 2001-October 2007) we analyzed the results of this Registry in Spain with special attention on the incidence of major congenital malformations and foetal-perinatal death.
Of a whole of 540 cases included in the Registry, 490 were prospective (included before the 16th week), of these we had complete information in 368 cases. Major congenital maLformations were present in 5% (n=13) of the child exposed to monotherapy and 12% (n=6) of those exposed to polytherapy (p=0.08). All polytherapy combinations with MCM, contained valproate. Of the variables analyzed only low weight at birth and the AEDs used showed statistically significant association with MCM and MFP. The percentage of MCM was superior for valproate, particularly at doses equal or superior of 1000 mg/day (16%), although differences were not statistically significant. The majority of ours patients were on monotherapy (83%) with AEDs at low doses and were taking 5 mg of folate.
Patients on polytherapy, particularly those with valproate in combination present more risk of MCM. For monotherapy exposures only weight at birth and the AEDs used have association statistically significant with MC/MFP. Valproate in our series presents more risk than lamotrigine and does not show differences with regard to carbamazepine.
妊娠登记处提供了有关抗癫痫药物（AEDs）相关风险的可靠信息。EURAP是一个前瞻性国际登记处，纳入了在受孕时服用AEDs的患者。为EURAP提供数据的西班牙各中心的数据反映了我们环境的实际情况。
研究西班牙EURAP登记处中主要先天性畸形（MCM）和/或胎儿-围产期死亡（MFP）的发生率，并确定其与AEDs的关系。
在获得知情同意后，将患者纳入前瞻性登记处并进行评估：在开始时、妊娠中期和晚期结束时、分娩后以及出生后一年。收集了各种变量：人口统计学、癫痫类型、孕期发作频率、AEDs及其剂量、潜在毒物、叶酸使用情况及其剂量、产科并发症以及新生儿信息。在招募6年后（2001年6月至2007年10月），我们分析了西班牙该登记处的结果，特别关注主要先天性畸形和胎儿-围产期死亡的发生率。
在登记处纳入的540例病例中，490例为前瞻性病例（在第16周之前纳入），其中368例有完整信息。接受单药治疗的儿童中5%（n = 13）出现主要先天性畸形，接受联合治疗的儿童中12%（n = 6）出现主要先天性畸形（p = 0.08）。所有出现MCM的联合治疗方案中均含有丙戊酸盐。在分析的变量中，仅出生体重低和所使用的AEDs与MCM和MFP存在统计学显著关联。丙戊酸盐的MCM发生率更高，尤其是在剂量等于或高于1000毫克/天（16%）时，尽管差异无统计学意义。我们的大多数患者采用低剂量AEDs单药治疗（83%），并服用5毫克叶酸。
接受联合治疗的患者，尤其是联合使用丙戊酸盐的患者，出现MCM的风险更高。对于单药治疗，仅出生体重和所使用的AEDs与MC/MFP存在统计学显著关联。在我们的系列研究中，丙戊酸盐的风险高于拉莫三嗪，与卡马西平无差异。
