Multicenter Trial of Fetal Myelomeningocele Repair

自1997年以来，采用胎儿开放手术治疗180例胎儿脊髓脊膜膨出(MMC)宫内闭合症。初步 临床证据表明，该手术减少了分流依赖型脑积水的发生率，并恢复了 小脑和脑干的结构更加正常。然而，胎儿外科治疗MMC的临床结果是基于 与历史对照的比较和受试者只有疗效而不是安全性。 脊髓脊膜膨出修复术随机试验是一项涉及200名患者的多中心非随机临床试验 手术将在加州大学旧金山分校儿童医院的三个胎儿外科单元(FSU)进行 费城大学和范德比尔特大学医学中心，以及一个独立的数据和研究协调 乔治华盛顿大学生物统计中心。试验的主要目的是确定 妊娠18“至25”周的胎儿脊髓脊膜膨出的宫内修补术可以改善结局，以死亡率来衡量。 或者需要一年的生命和死亡的脑室减压分流术，或者贝利智力发育指数， 与标准的产后修复相比 符合资格标准的自愿患者将被集中随机分配到宫内或标准 MMC的产后修复。分配给胎儿手术组的病人将被送往附近的住处 手术后，除非不可行，否则他们将在怀孕32周时返回指定的FSU 妊娠3？0周剖宫产。被分配到产后手术组的患者将回家 37周后，返回指定的FSU进行剖腹产。磁共振成像将是 在登记、出院或足月妊娠以及一岁时进行，以确定宫内修复是否改善 Chiari II畸形的程度。新生儿发病率将被记录下来，手术次数也将被记录下来 情况与MMC、肌肉力量、行走状态和大小便控制有关。婴儿会让 在矫正年龄12个月和30个月时进行随访，以进行详细的神经运动功能分析、认知测试和 神经发育状况的评估。此外，长期的心理社会和生殖后果 母亲们将接受评估。 总之，拟议的试验将能够证明胎儿干预是否提供了改善结局的方法 脊柱裂儿童合理的生活质量。

Since 1997, 180 fetuses have had in utero closure of myelomeningocele (MMC) by open fetal surgery. Preliminary clinical evidence suggests that this procedure reduces the incidenceof shunt-dependent hydrocephalus and restores the cerebellum and brainstem to more normalconfiguration. However, clinical results of fetal surgery for MMC are based on comparisons with historical controlsand examineonly efficacy and not safety. The Myelomeningocele Repair RandomizedTrial is a multi-center unblindedrandomized clinical trial of 200 patients that will be conducted at three Fetal SurgeryUnits (FSU), the University of California-San Francisco, Children's Hospital of Philadelphia, and Vanderbilt University Medical Center, along with an independent Data and Study Coordinating Center, the George Washington UniversityBiostatisticsCenter. The primary objective of the trial is to determine if inrrauterine repair of fetal myelomeningocele at 18" to 25" weeks gestation improves outcome, as measured by 1)death or the need for ventricular decompressive shunting by one year of life and 2) death or Bayley Mental Development Index, as compared to standard postnatalrepair Consenting patients who satisfy eligibilitycriteria will be centrallyrandomizedto either intrauterineor standard postnatal repair of the MMC. Patientsassigned to the fetal surgery group will be discharged to nearby accommodation following surgery, unless infeasible, in which case they will return to their assigned FSU at 32^ weeks gestation for delivery at 3?0 weeks gestation by cesarean section. Patients assigned to the postnatal surgery group will return home and at 37^ weeks, return to their assigned FSU for deliveryby cesarean section. Magnetic Resonance Imaging will be conducted at enrollment,discharge or term gestation, and one year of age to determine if intrauterine repair improves the degree of the Chiari II malformation. Neonatal morbidity will be recorded as will the number of surgical procedures for conditions related to the MMC, musclestrength,ambulation status and urinary and fecal continence. Infants will make followup visits at twelve and thirty monthscorrected age for detailed neurbmotor function analysis, cognitive testing and evaluation of neurodevelopmental status. In addition, the long term psychosocial and reproductive consequences in mothers will be evaluated. In summary, the proposed trial will be able to demonstrate whether fetal intervention offers improved outcome with a reasonable quality of life for spina bifida children.