Minimally Invasive Fetal Neural Tube Defect Repair Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Feasibility
研究概览
简要总结
The purpose of the study is to evaluate the maternal and fetal outcomes of a new technique for the fetoscopic repair of fetal MMC at Texas Children's Hospital Pavilion for Women.
The investigators hypothesis is that this minimally invasive technique is feasible, and that this approach will have the same efficacy as open fetal surgery for MMC, but with significantly less maternal-fetal risk. Both mother and baby will benefit from the surgery. The fetus will have a repaired MMC defect, and the mother will not have a uterine incision (hysterotomy). A hysterotomy increases the risk of uterine rupture and requires that all subsequent deliveries are by cesarean section. There may also be a decreased risk of Pre-term Premature Rupture Of Membranes (PPROM) and prematurity when compared with the current open operation. Finally, a vaginal delivery is possible following the fetoscopic fetal surgery if the baby is shown to have a skin covered repair.
详细描述
Spina bifida can be a devastating neurological congenital anomaly . It results from incomplete closure of the neural tube between 22 and 28 embryological days. Its incidence is approximately 1-2 per 1,000 births. It is considered the most common congenital anomaly of the central nervous system that is compatible with life.
- The most frequent form is myelomeningocele (MMC), characterized by the extrusion of the spinal cord into a sac filled with cerebrospinal fluid (CSF), and is associated with lower limb paralysis and bowel and bladder dysfunction.
- The majority of MMCs can be diagnosed between 14 and 20 weeks of gestation. MMC is associated with Chiari II malformation, which includes a constellation of anomalies such as hindbrain herniation, brainstem abnormalities, low-lying venous sinuses and a small posterior fossa.The Chiari II malformation can have deleterious effects on motor, cranial nerve and cognitive functions. Postnatally most MMC patients develop hydrocephalus and require a ventriculoperitoneal shunt. Shunts require lifelong monitoring and have a high failure rate due to infection, obstruction, and fracture.
Experimental studies using animal models have shown that prenatal coverage of a spina bifida-like lesion can preserve neurological function and reduce or reverse hindbrain herniation.These studies suggest a "two-hit" hypothesis in which the ultimate neurologic deficit results from a combination of the failure of normal neural-tube closure (first hit) with secondary spinal cord injury resulting from prolonged exposure of sensitive neural elements to the amniotic fluid (second hit mechanism).
Based on this hypothesis, open fetal surgical repair of MMC was proposed, and the recent publication of the NICHD sponsored randomized controlled trial demonstrated clear neonatal benefit of open in-utero fetal surgical repair of MMC. The study showed a reduction in the incidence of hydrocephalus and in the radiographic severity of hindbrain herniation (relative risk: 0.67; 95% confidence interval: 0.56-0.81).
Open in-utero fetal surgery is not without risk and the NICHD study (MOMS Trial) showed an elevation in maternal-fetal morbidity/risk when compared to the postnatally treated group, including higher risk for chorioamniotic separation (26% vs. 0%, respectively), maternal pulmonary edema (6% vs. 0%), oligohydramnios (21% vs. 0%), placental abruption (6% vs. 0%), spontaneous membrane rupture (46%; RR: 6.15; 95% CI: 2.75-13.78), spontaneous labor (38%; RR: 2.80, 95%CI: 1.51-5.18), maternal blood transfusion (9%; RR: 7.18; 95%CI: 0.90-57.01), and preterm delivery before 34 weeks (46%; RR: 9.2; 95%CI: 3.81-22.19). The reason for the increased incidence of these complications is related to the nature of the open fetal procedure, which involves a multi-faceted invasive approach including maternal laparotomy, large hysterotomy with uterine edge stapling, and open fetal repair of the spina bifida defect that may involve manipulation and exposure of the fetus for a significant amount of time.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pregnant women - maternal age 18 years or older and capable of consenting for their own participation in this study,
- •Singleton pregnancy,
- •MMC with the upper boundary located between T1 and S1,
- •Evidence of hindbrain herniation (confirmed on MRI to have an Arnold-Chiari type II malformation),
- •Absence of chromosomal abnormalities and associated anomalies,
- •Gestational age at the time of the procedure will be between 19 0/7 weeks and 25 6/7 weeks,
- •Normal karyotype and/or normal chromosomal microarray (CMA) by invasive testing (amniocentesis or CVS). If there is a balanced translocation with normal MCA with no other anomalies the candidate can be included. Patients declining invasive testing will be excluded.
- •Family has considered and declined the option of termination of the pregnancy at less than 24 weeks,
- •Family meets psychosocial criteria (sufficient social support, ability to understand requirements of the study), and
- •Parental/guardian permission (informed consent) for follow up of child after birth.
排除标准
- •Fetal anomaly unrelated to MMC,
- •Severe kyphosis,
- •Increased risk for preterm labor including short cervical length (<1.5 cm), history of incompetent cervix with or without cerclage, and previous preterm birth,
- •Placental abnormalities (previa, abruption, accreta) known at time of enrollment,
- •A pre-pregnancy body-mass index ≥40,
- •Contraindications to surgery including previous hysterotomy (whether from a previous classical cesarean, uterine anomaly such as an arcuate or bicornuate uterus, major myomectomy resection, or previous fetal surgery) in active uterine segment,
- •Technical limitations precluding fetoscopic surgery, such as uterine fibroids, fetal membrane separation, and uterine anomalies,
- •Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune thrombocytopenia affecting the current pregnancy,
- •Maternal HIV, Hepatitis-B, Hepatitis-C status positive because of the increased risk of transmission to the fetus during maternal-fetal surgery. If the patient's HIV or Hepatitis status is unknown, the patient must be tested and found to have negative results before enrollment,
- •Maternal medical condition that is a contraindication to surgery or anesthesia,
- •Low amniotic fluid volume (Amniotic Fluid Index less than 6cm) if deemed to be due to fetal anomaly, poor placental perfusion or function, or membrane rupture. Low amniotic fluid volume that responds to maternal hydration is not an exclusion criterion,
- •Patient does not have a support person (e.g. Spouse, partner, mother) available to support the patient for the duration of the pregnancy,
- •Inability to comply with the travel and follow-up requirements of the trial,
- •Participation in another intervention study that influences maternal and fetal morbidity and mortality or participation in this trial in a previous pregnancy, and
- •Patient scores as severely depressed on the BDI-II questionnaire; a score of 29 or above.
- •Maternal hypersensitivity to collagen.
研究组 & 干预措施
fetoscopic surgical repair
Single arm study. All patients will receive the fetoscopic repair.
干预措施: fetoscopy (Device)
结局指标
主要结局
Feasibility
时间窗: Time of procedure
Whether the minimally invasive technique can be technically performed in human patients (success of primary skin closure) in a safe and effective manner.
次要结局
- Reversal of the Chiari II malformation with complete closure of the spinal defect.(at birth)
研究者
Michael A Belfort
Professor and Chairman, Department of Obstetrics and Gynecology
Baylor College of Medicine