Fetal Endotracheal Occlusion (FETO) in Severe and Extremely Severe Congenital Diaphragmatic Hernia
Fetal Endotracheal Occlusion (FETO) in Severe and Extremely Severe Congenital Diaphragmatic Hernia
Congenital diaphragmatic hernia (CDH) occurs when the diaphragm fails to fully fuse and
 leaves a portal through which abdominal structures can migrate into the thorax. In the more
 severe cases, the abdominal structures remain in the thoracic cavity and compromise the
 development of the lungs. Infants born with this defect have a decreased capacity for gas
 exchange; mortality rates after birth have been reported between 40-60%. Now that CDH can be
 accurately diagnosed by mid-gestation, a number of strategies have been developed to repair
 the hernia and promote lung tissue development.

 Fetal tracheal occlusion is one technique that temporarily closes the herniated area with the
 Goldvalve balloon to allow the lungs to develop and increase survival at birth. This is a
 pilot study of a cohort of fetuses affected by severe CDH that will undergo FETO to
 demonstrate the feasibility of performing the procedure, managing the pregnancy during the
 period of tracheal occlusion, and removal of the device prior to delivery at BCM/Texas
 Children's Hospital (TCH). It is anticipated that fetal tracheal occlusion plug-unplug
 procedure will improve mortality and morbidity outcomes as compared with current management,
 but this is not a primary endpoint of the feasibility study. We will perform 20 FETO
 procedures on fetuses diagnosed prenatally with severe and extremely severe CDH.
Enrollment

 Women carrying fetuses with severe or extremely severe CDH and a normal karyotype will
 undergo routine clinical evaluation. The fetuses will be 27+0/7 to 29+6/7 weeks of
 gestational age for severe CDH and can be as early as 22+0/7 weeks gestational age for those
 deemed as "extremely severe" cases of CDH. They will have ultrasound and/or MRI evaluation to
 rule out other anomalies, calculation of the LHR from ultrasound measurements,
 echocardiography, and detailed obstetric/perinatal consultation. Patients who meet the
 eligibility criteria will be extensively counseled, and those who wish to participate will
 provide written, informed consent for the study.

 Procedure

 The procedure will be performed under spinal anesthesia or local anesthesia with intravenous
 sedation. The technique of fetal endoscopic tracheal occlusion has been described. Using
 standard technique, a cannula loaded with a pyramidal trocar will be inserted into the
 amniotic cavity and a fetoscope or flexible operating endoscope will be passed through the
 cannula into the amniotic fluid. If, upon evaluation, the baby cannot be accessed through the
 way just described above, the uterus will be accessed through an incision in the belly
 (called a laparotomy). A laparotomy is a surgical technique that makes an incision in the
 abdomen. After the incision has been made, the uterus will be temporarily repositioned
 externally. The baby will then be accessed using the fetoscope and ultrasound, as described
 above. The laparotomy will only be done if the baby cannot be reached and repositioned to a
 more favorable one by doing external maneuvers (called external version) for the FETO
 procedure.

 The scope will be guided into the fetal larynx either through a nostril and then via the
 nasal passage or through the fetal mouth, and then through the fetal vocal cords with the aid
 of both direct vision through the scope and cross-sectional ultrasonographic visualization. A
 detachable latex balloon will be placed in the fetal trachea midway between the carina and
 the vocal cords. The balloon will be inflated with isosmotic contrast material so that it
 fills the fetal trachea.

 Postoperative

 The mothers will be discharged once stable. Serial measurements of sonographic lung volume
 and LHR will begin within 24-48 hours following surgery and continue weekly by targeted
 ultrasound evaluation. Amniotic fluid level and membrane status will also be monitored at
 weekly intervals. Comprehensive ultrasonography for fetal growth will be performed every four
 weeks (+/- 1 wk). All discharged patients will stay within 30 minutes of TCH to permit
 standardized postoperative management and emergent retrieval of the balloon in the event of
 preterm labor or premature rupture of membranes prior to the scheduled removal.

 After the FETO surgery, prior to leaving the hospital, the mother will be given a medical
 alert bracelet identifying her as a patient with a baby with blocked airways. She will be
 encouraged to wear the bracelet at all times so that in case of emergency, she and others
 will know who to contact. She will also be given a pamphlet with instructions for medical
 personnel describing how to remove the balloon in case of an emergency. She should carry it
 with her at all times.

 Balloon retrieval will be planned at between 32+0/7 and 34+6/7 weeks or no longer than 10 wks
 after placement, at the discretion of the FETO center. The patient will need to commit to
 remaining in 30 minutes of Texas Children's Hospital Pavilion for Women until the balloon is
 retrieved. In the event of a patient relocating after having the balloon placed, despite
 having committed to remain in the area during consent process, she will be asked to return
 for the removal. Every effort to make arrangements for her to be managed by the nearest
 center capable of an EXIT procedure or balloon retrieval (San Francisco or Philadelphia) will
 be made.

 After removal of the balloon, patients will have the choice of delivering at Texas Children's
 Hospital- Women's Pavilion with the CDH managed and repaired at TCH, or returning to their
 obstetrician for delivery with subsequent repair of the CDH by the pediatric surgeons at
 their referring facility. Given the severity of the CDH, the baby will need to be delivered
 in a facility that has the capability of immediate pediatric surgery services.

 We will need to monitor the baby at regular intervals (at 6 weeks, 3 months, 6 months, 1
 year, and 2 years) after delivery to see how well the baby is breathing and how well the baby
 is developing. These check- ups may be at Texas Children's Hospital- Women's Pavilion or can
 be coordinated with other doctors of the participant's choosing.

 If the child continues care at another institution, we will attempt to follow up with a
 review of the child's medical records.
INCLUSION CRITERIA:

 -  Patient is a pregnant woman between 18 and 45 years of age

 -  Singleton pregnancy

 -  Confirmed diagnosis of severe or extremely severe left, right or bilateral CDH of the
 fetus

 Severe CDH: -Fetal liver herniated into the hemithorax -Lung-head ratio (LHR) is less than
 or equal to 1.0 calculated between 27+0/7 and 29+6/7 weeks' gestation

 Extremely Severe CDH: -At least 1/3rd of the liver parenchyma herniated into the thoracic
 cavity -Lung-head ratio (LHR) is < 0.71 calculated between 22+0/7 and 29+6/7 weeks'
 gestation

 -  Normal fetal echocardiogram or echocardiogram with a minor anomaly (such a small VSD)
 that in the opinion of the pediatric cardiologist will not affect postnatal outcome

 -  Normal fetal karyotype

 -  The mother must be healthy enough to have surgery

 -  Patient provides signed informed consent that details the maternal and fetal risks
 involved with the procedure

 -  Patient willing to remain in Houston for the duration following the balloon placement
 until delivery

 -  Signed informed consent

 EXCLUSION CRITERIA:

 -  Contraindication to abdominal surgery, fetoscopic surgery, or general anesthesia

 -  Allergy to latex

 -  Allergy or previous adverse reaction to a study medication specified in this protocol

 -  Preterm labor, preeclampsia, or uterine anomaly (e.g., large fibroid tumor)

 -  Fetal aneuploidy, known structural genomic variants, other major fetal anomalies, or
 known syndromic mutation

 -  Suspicion of major recognized syndrome (e.g. Fryns syndrome) on ultrasound or MRI

 -  Maternal BMI >40

 -  High risk for fetal hemophilia