Multicenter Trial of Fetal Myelomeningocele Repair

自1997年以来，180例胎儿在子宫内通过开放式胎儿手术闭合脊髓脊膜膨出（MMC）。初步 临床证据表明，该手术降低了分流依赖性脑积水的发生率， 小脑和脑干恢复到更正常的形态。然而，MMC胎儿手术的临床结果是基于 与历史对照进行比较，仅检查有效性而非安全性。 脊髓脊膜膨出修复随机试验是一项200例患者的多中心非盲随机临床试验 这将在三个胎儿外科单位（FSU），加利福尼亚大学旧金山弗朗西斯科，儿童医院进行。 费城医院和范德比尔特大学医学中心，沿着进行了一项独立的数据和研究 协调中心，乔治华盛顿大学生物统计中心。试验的主要目的是 确定在妊娠18 - 256周时对胎儿脊髓脊膜膨出进行宫内修复是否能改善结局， 根据1）死亡或需要心室减压分流术，根据1年寿命和2）死亡或Bayley Mental 发育指数，与标准产后修复相比 符合资格标准的患者将被集中随机分配至宫内或标准 MMC的产后修复。分配到胎儿手术组的患者将出院到附近的住宿 手术后，除非不可行，在这种情况下，他们将在妊娠32周时返回指定的FSU， 在妊娠37周时通过剖腹产分娩。分配到产后手术组的患者将回家 在37周时，返回分配的FSU进行剖宫产分娩。磁共振成像将是 在入组、出院或足月妊娠时以及一岁时进行，以确定宫内修复术是否改善了 基亚里II畸形的程度。新生儿发病率将被记录， 与MMC、肌肉力量、截肢状态以及大小便失禁相关的状况。婴儿会使 在12个月和30个月矫正年龄时进行随访，进行详细的神经运动功能分析、认知测试和 评估神经发育状况。此外，长期的社会心理和生殖后果， 母亲将接受评估。 总之，拟议的试验将能够证明胎儿干预是否提供了改善的结果， 脊柱裂儿童的合理生活质量。

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 incidence of shunt-dependent hydrocephalus and restores the cerebellum and brainstem to more normal configuration. However, clinical results of fetal surgery for MMC are based on comparisons with historical controls and examine only efficacy and not safety. The Myelomeningocele Repair Randomized Trial is a multi-center unblinded randomized clinical trial of 200 patients that will be conducted at three Fetal Surgery Units (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 University Biostatistics Center. The primary objective of the trial is to determine if intrauterine repair of fetal myelomeningocele at 18¿to 256 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 postnatal repair Consenting patients who satisfy eligibility criteria will be centrally randomized to either intrauterine or standard postnatal repair of the MMC. Patients assigned to the fetal surgery group will be discharged to nearby accommodation following surgery, unless unfeasible, in which case they will return to their assigned FSU at 32¿ weeks gestation for delivery at 37¿ 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 delivery by 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, muscle strength, ambulation status and urinary and fecal continence. Infants will make followup visits at twelve and thirty months corrected age for detailed neuromotor 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.