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，这种手术减少了分流依赖型脑积水的发生率，并恢复了 小脑和脑干恢复到更正常的形态。然而，胎儿外科治疗MMC的临床结果是基于 与历史对照进行比较，只检查疗效而不检查安全性。 脊髓脊膜膨出修复术随机试验是一项有200名患者参加的多中心非盲法临床试验 这将在加州大学旧金山儿童医院的三个胎儿外科单元(FSU)进行 费城医院和范德比尔特大学医学中心，以及一项独立的数据和研究 乔治华盛顿大学生物统计中心协调中心。试验的主要目的是 确定妊娠18~256周胎儿脊髓脊膜膨出宫内修补术是否能改善结局 1)死亡或需要进行脑室减压术一年；2)死亡或贝利精神 与标准产后修复相比的发育指数 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。被分配到胎儿手术组的患者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37周时剖宫产.被分配到产后手术组的患者将回家 在37周时，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 病情与MMC、肌肉力量、行走状态以及大小便可控性有关。婴儿会让 在校正的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 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.