Neural Tube Defect Clinical Trial
Official title:
Open Fetal Myelomeningocele Repair With Maternal BMI Between 35.0 And 40.0
Spina bifida is a neurological abnormality characterized by an opening in the skin and
exposure of the spinal cord on the back of the baby at the time of birth. The complete
closure and separation of the spinal cord from the skin occurs in the first month of
pregnancy.
This form of spina bifida is associated with leg weakness, sensation loss, and bowel and
bladder incontinence. The majority of patients (>80%) also develop increased fluid in the
brain, called hydrocephalus, and require additional surgery to treat this problem. Standard
treatment of myelomeningocele (MMC) involves closing the opening in the back within the first
3 days of life. The surgery releases the spinal cord from the skin and brings the skin edges
together to prevent infection and injury to the exposed nerves. Of note, this type of surgery
does not improve function.
The investigators want to study the open in-utero fetal surgery technique in patients who are
candidates for the standard open fetal repair technique but have a pre-pregnancy BMI of
35.0-40.0. The latter is a reason for exclusion for open fetal repair in most centers in the
United States.
The research will be conducted at the following location(s):
Baylor College of Medicine and Texas Children's Hospital- Women's Pavilion.
About 15 subjects will be enrolled in this study. In order to be eligible for this study, the
participant must meet the established criteria for open fetal MMC surgery but also have a BMI
of 35.0-40.0.
PREOPERATIVE AND INTRAOPERATIVE CONCOMITANT MEDICATIONS:
The participant will receive two doses of 12 mg betamethasone, 24 hours apart, for fetal lung
maturation if the gestational age is greater than 23 weeks. The participant will also receive
the prophylactic tocolysis (medications to prevent preterm contractions) indomethacin 50 mg
prior to surgery, then 25-50 mg every six to eight hours for 24-48 hours following the
surgery, longer if clinically indicated. Magnesium sulfate may also be used intraoperatively
- 6 gram IV loading dose followed by a 2 gram/hour continuous infusion for 24 - 72 hours. In
addition, if medically indicated, nifedipine (10mg orally) or terbutaline (0.25mg
subcuticularly) may be substituted for the indomethacin or magnesium sulfate based on
condition and medical judgment. Prophylactic antibiotics will also be administered to the
participant prior to the procedure using cefazolin, azithromycin, and/or metronidazole, or if
medical history contraindicates the use of cefazolin, clindamycin,azithromycin, and
gentamicin will be administered. A solution of nafcillin and lactated ringers will be
injected into the amniotic cavity at the conclusion of the procedure. Additional medications,
including therapeutic antibiotics, may be used as part of standard of care by the medical
team.
MATERNAL-FETAL ANESTHESIA:
The participant will have a lumbar epidural catheter placed prior to surgery for
postoperative analgesia. The procedure will be performed under general anesthesia following a
rapid sequence intubation with propofol and succinylcholine. Anesthesia will be maintained
with 2-3 times MAC (Minimal anesthetic concentration) of volatile anesthetic agent. This high
concentration of anesthetic agent provides adequate uterine relaxation during surgery. After
the defect has been repaired and once closure of the skin incisions begins, local anesthetic
will be administered through the epidural catheter and the participant will be started on a
continuous epidural infusion of local anesthetic and opioid combination. The participant will
receive this medication via an epidural pump for approximately 3-4 days following surgery.
The epidural pump has the capability of the patient self-administering intermittent boluses
of medication on top of the continuous infusion rate if the participant becomes uncomfortable
in the post-operative period.
The fetus will receive an intramuscular injection of opioid (fentanyl 5-10 mcg/kg),
anticholinergic (atropine 20 mcg/kg), and muscle relaxant (vecuronium 0.3 mg/kg) into the
buttock or extremity using a 22G needle that is passed through the port in order to provide
muscle relaxation, sedation, and analgesia. The drug dosages are adjusted to the estimated
fetal weight. The fetus will receive the injection prior to starting the CO2 gas insufflation
into the uterus and will continue to receive the combo injection approximately every 45 - 60
minutes throughout the remainder of the procedure as deemed necessary by the medical team.
Subsequent combo injections will be administered by passing the 22G needle through one of the
uterine ports. General maternal anesthesia with anesthetic gases is known to provide fetal
anesthesia. The combination injection will provide muscle relaxation and additional analgesia
to the fetus. This combination of medications is routinely administered to fetuses during
open fetal surgery and has been found to adequately sedate the fetus during fetal
intervention procedures.
SURGICAL REPAIR:
The investigators will either make a lower transverse incision (also called the 'bikini cut')
or a midline vertical incision to gain access to the uterus. The incision will be about the
same size (about 8-10 inches) that is needed for a typical cesarean section procedure. Once
the uterus is exposed an ultrasound will be performed to determine the position of the fetus
for the surgery and cardiac function will be monitored. If necessary, the fetus will be
gently repositioned from outside the uterus so that the fetal back is facing upwards.
Ultrasound will be used to help the surgical team determine the position of the fetus at all
times.
The fetus will receive an anesthesia injection into the buttock or thigh prior to the start
of the repair. The anesthesia injection is a combination of medications that block pain and
help relax the muscles. In addition, maternal anesthesia is also known to provide anesthesia
to the fetus.
When the defect is clearly identified, the spinal cord will be released from its attachments
to the skin. The skin edges will be sewn together using an absorbable suture and repair
technique similar to the standard technique in women with BMI<35.0. Sometimes it might be
better to use one type or style of suture (surgical thread) during the surgery. While this
can be generally the same from one patient to the next, it may be in the participating
mother's or fetus's best interest to change the suture or suture technique to adapt to the
surgery being performed.
All pre- and post-operative care and all follow-up visits are the same as with any open
procedure and are considered standard of care; therefore, the participant will not be
responsible for any costs related to this research study other than the normal co-pays or
deductibles. Following the participant's discharge from the hospital, the participant will
need to stay within a 30-minute drive of Texas Children's Hospital Pavilion for Women to
allow for medical care after the operation. The participant will be responsible for any
accommodation costs in Houston.
POSTOPERATIVE FOLLOW-UP:
The investigators will collect clinical information from the participant's medical chart
during standard clinical care. In addition, the investigators will collect clinical
information about the participating child until he/she turns 5 years old. The following
information will be collected from clinical records of the participating mom and child : 1.
Demographics (age, parity, height, weight, BMI, use of drugs and alcohol, smoking, clinical
disease, medications, medical history); 2. Prenatal data (gestational age, ultrasound and MRI
findings, results of amniocentesis, vital signs) 3. Fetal intervention (surgery information,
gestational age, complications, post-procedure follow-up including ultrasound); 4.
Intra-partum data (ultrasound and MRI findings, gestational age at delivery, type of labor,
mode of delivery, indications and complications, status of port sites if cesarean delivery);
5. Immediate neonatal period data (birth weight, Apgar scores, physical exam findings,
hydrocephalus assessment, repair site condition, imaging, need for surgery or shunt
placement, imaging results); 6. Long-term follow-up every 3-4 months in the first year, Year
1, Year 2, Year 3, Year 4, and Year 5 (physical exam findings, imaging results, and
hydrocephalus assessment).
Like all children with spina bifida, the participating child will be taken care of by the
pediatric neurosurgery service after birth. Follow-up visits occur in the Spina Bifida Clinic
at Texas Children's Hospital. All follow up visits are considered standard of care and will
occur as follows:
After the baby is born, and before they leave the hospital, they will have a physical exam,
an assessment of hydrocephalus, urinary and orthopedic evaluations, and imaging of their
brain.
In the first year, the child will have a visit every 3-4 months where a physical exam and
urinary and orthopedic evaluations will be done. Year 1 and Year 2 visits will include: a
physical exam, developmental assessment, urinary and orthopedic evaluations, and an
assessment for hydrocephalus. The Year 1 visit will also include imaging of the child's brain
and spine (this may be repeated if needed at any point).
At Year 3 and Year 4, a physical exam and urinary and orthopedic evaluations will be done.
Year 5 is the end of participation in this study. This visit will include: a physical exam,
developmental assessment, assessment for hydrocephalus and imaging of the child's spine and
head.
After Year 5, there will be routine annual follow up visits. If the participant moves away
from Texas, the investigators will attempt to follow up with a review of the mom and child
medical records The participant will be asked to sign a medical record release, every year if
needed, to allow this to occur. The participant may be contacted by study staff regarding any
changes to the study and asked to sign a new informed consent form. The participant may be
contacted by phone by study staff about the medical release form or changes to the study.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT02230072 -
Fetoscopic Meningomyelocele Repair Study
|
Phase 1 |