Fetal Endoscopic Surgery for Spina Bifida (FESSB)

This study aims to assess the feasibility to perform a fetoscopic prenatal repair of an open neural tube defect, and secondly to assess the maternal, fetal and neonatal outcomes.

Study Overview

• Status: Recruiting
• Conditions: Neural Tube Defects; Chiari Malformation Type 2; Myelomeningocele; Surgery; Maternal, Uterus or Pelvic Organs, Affecting Fetus; Hydrocephalus; Congenital Abnormality; Fetal Disease; Spina Bifida, Open
• Intervention / Treatment: Procedure: Fetoscopic repair of spina bifida

Detailed Description

Introduction:

Spina bifida is a congenital malformation characterized by a failure in neural tube closure. Unprotected fetal neural tissue at the spine level undergoes not only progressive neurodegeneration in spinal cord, but also the impairment in brain development, hindbrain herniation or Chiari II malformation probably due to pressure disturbances resulting from a continuous leakage of cerebrospinal fluid through the defect. The neurological consequences at birth are irreversible and sometimes devastating, including paraplegia, sphincter urinary and fecal incontinence, hydrocephalus, cranial nerve disturbances, respiratory problems and death due to spinal cord injury and brain maldevelopment.

Intrauterine fetal open repair of the defect has proved to improve hindbrain herniation and decrease the need of cerebrospinal shunting.

Hypothesis:

The investigators hypothesize that minimally invasive surgery of spina bifida is feasible and may minimize surgical aggression and obstetrical complications, with similar neonatal and neurological results.

Intervention:

In this study the investigators propose a fetoscopic skin closure technique. After a maternal laparotomy the uterus is exteriorized, the amniotic cavity is accessed by fetoscopic approach. The placode is dissected from the surrounding tissue and dropped into the opened spinal canal, untethered. Part of the cystic tissue is resected. The edges are then closed to the midline.

Follow up:

After surgery patients are followed up at the Fetal Medicine Unit every one or two weeks.

The mode of delivery is decided according to obstetric criteria. Neonates will be examined at birth, and followed up regularly at least until 30 months. Patients are lifetime followed up by our Multidisciplinary myelomeningocele (MMC) Committee that comprises professionals from the Spina Bifida Unit, Neonatologists, Pediatric Surgeons, Pediatric Urologist, Pediatric Orthopedic Surgeons, Radiologists, Rehabilitation, Pathologists, Pediatric Neurosurgeons, Obstetricians and Fetal Therapists.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elena Carreras, PhD; Email: ecarreras@vhebron.net
• Study Contact Backup: Name: Nerea Maiz, PhD; Email: nmaiz@vhebron.net

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: Elena Carreras, PhD; Email: ecarreras@vhebron.net
    • Contact: Nerea Maiz, PhD; Email: nmaiz@vhebron.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Maternal age > 18 years old
• Singleton pregnancy
• Gestational age between 18 0/7 weeks and 26 6/7 weeks
• Isolated neural tube defect between T1 and S1
• Cerebellar herniation (Chiari type II)

Exclusion Criteria:

• Fetal anomalies non related to neural tube defect (NTD) including chromosomal abnormalities
• Body mass index > 35 kg/m2
• Maternal disorders contraindicating surgery
• Genetic anomalies with poor prognosis
• Sever kyphosis (>30º)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fetoscopic repair of spina bifida; This is a single arm study, all patients will receive a fetoscopic repair of the spina bifida	Procedure: Fetoscopic repair of spina bifida; Fetoscopic intrauterine repair of open spina bifida

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Capability to achieve successful closure of the neural tube defect by fetoscopic surgery (yes/no)	Binary variable (yes/no) describing if the neural tube defect has been successfully closed, (placode dissected and dropped into the open spinal canal, cystic tissue resected and edges closed to the midline), by fetoscopic surgery, and without conversion to open surgery	Time of procedure (day 0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Operating time (minutes)	Time between the skin opening and skin closure	Time of procedure (day 0)
Fetoscopy time (minutes)	Time between the introduction of the first cannula and the removal of the last cannula	Time of procedure (day 0)
Hospital stay (days)	Time between hospital admission and discharge	Between procedure and delivery, up to 21 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative hemoglobin (g/dL)	Hemoglobin level after the procedure	24 hours after procedure
Blood transfusion (yes/no)	Binary variable describing if a transfusion of blood derivates is carried out between the time of procedure and discharge	Between procedure and discharge, up to 21 weeks
Gestational age at delivery (weeks and days as x/7)	Gestational age at birth	At birth, up to 21 weeks after procedure
Surgery to delivery interval (days)	Interval between surgery and birth	At birth, up to 21 weeks after procedure
Premature rupture of membranes (PROM) (yes/no)	Binary variable describing amniotic fluid leakage before the onset of labor	Between the procedure and 37 weeks of pregnancy (18 weeks after procedure)
Chorioamnionitis (yes/no)	Binary variable describing the presence of a chorioamnionitis between the procedure and birth	Between the procedure and birth, up to 21 weeks after procedure
Oligohydramnios without PROM (yes/no)	Binary variable describing the presence of a oligohydramnios (deepest pool < 2 cm) without evidence of vaginal amniotic fluid leakage	Between the procedure and birth, up to 21 weeks after procedure
Placental abruption (yes/no)	Binary variable describing the presence of a placental abruption	Between the procedure and birth, up to 21 weeks after procedure
Mode of delivery (vaginal / cesarean)	Binary variable describing the mode of delivery, vaginal or cesarean section	At birth, up to 21 weeks after procedure
Uterine dehiscence (yes/no)	Binary variable describing the presence of a uterine dehiscence, regardless of whether it is symptomatic or it is diagnosed at the time of cesarean section	At birth, up to 21 weeks after procedure
Acute Pulmonary edema (yes/no)	Binary variable describing the presence of a maternal pulmonary edema, regardless of the severity, between the procedure and discharge.	Between the procedure and birth, up to 21 weeks after procedure
Closure of the spinal defect (yes/no)	Binary variable describing the watertight closure of the defect	Between birth and 1 month of life
Maintenance of the neurological level (Better / same / worse)	Categorical variable describing if the postnatally assessed neurological level is better / same or worse than the level assessed prenatally before the procedure. It will be assessed by physical examination	1 month of life
Reversal of Chiari malformation(completely reversed / mild improvement / no improvement) by MRI	Categorical variable comparing the postnatal and prenatal MRI assessment of the Chiari malformation	1 month of life
Ventriculoperitoneal shunting (yes/no)	Binary variable describing the need of a ventriculoperitoneal shunting	Between birth and 12 months

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute

Publications and helpful links

General Publications

• Belfort MA, Whitehead WE, Shamshirsaz AA, Bateni ZH, Olutoye OO, Olutoye OA, Mann DG, Espinoza J, Williams E, Lee TC, Keswani SG, Ayres N, Cassady CI, Mehollin-Ray AR, Sanz Cortes M, Carreras E, Peiro JL, Ruano R, Cass DL. Fetoscopic Open Neural Tube Defect Repair: Development and Refinement of a Two-Port, Carbon Dioxide Insufflation Technique. Obstet Gynecol. 2017 Apr;129(4):734-743. doi: 10.1097/AOG.0000000000001941.
• Maroto A, Illescas T, Melendez M, Arevalo S, Rodo C, Peiro JL, Belfort M, Cuxart A, Carreras E. Ultrasound functional evaluation of fetuses with myelomeningocele: study of the interpretation of results. J Matern Fetal Neonatal Med. 2017 Oct;30(19):2301-2305. doi: 10.1080/14767058.2016.1247262. Epub 2017 Jan 16.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: October 3, 2017
• First Submitted That Met QC Criteria: October 16, 2017
• First Posted (Actual): October 20, 2017

Study Record Updates

• Last Update Posted (Actual): October 20, 2017
• Last Update Submitted That Met QC Criteria: October 16, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pregnancy Complications; Nervous System Malformations; Congenital Abnormalities; Meningomyelocele; Spina Bifida Cystica; Neural Tube Defects; Hydrocephalus; Spinal Dysraphism; Arnold-Chiari Malformation; Fetal Diseases
• Other Study ID Numbers: PR(AMI)152/2015

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No