Fetal Endotracheal Occlusion (FETO) in the Resolution of Pulmonary Hypertension in Fetuses With Severe CDH
Fetal Endotracheal Occlusion (FETO) in the Resolution of Pulmonary Hypertension in Fetuses With Severe CDH
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 (FETO), using a fetoscopically delivered and removed balloon device,
 has been used to temporarily occlude the trachea and increase lung distension in CDH to allow
 the lungs to develop and has been shown to increase survival at birth. The role of FETO in
 the resolution of pulmonary hypertension in fetuses with severe left- and right- sided CDH
 remains unclear. Our recent observation that FETO is associated with a higher proportion of
 infants who resolve their pulmonary hypertension by the age of 1 year as compared with those
 who have not had FETO, is based on a retrospective cohort study, which, as with any such
 design, has some intrinsic limitations. Thus, a prospective cohort study that is
 appropriately powered to confirm or disprove this encouraging observation is needed. If our
 preliminary observation is confirmed, resolution of PH by the age of 1 year could be added to
 the benefits of the FETO procedure in severe left and right-sided CDH cases.

 The investigators will perform 40 FETO procedures on fetuses diagnosed prenatally with severe
 right- or left-sided CDH, and outcome data will be compared with that of a control group of
 severe right- or left-sided CDH who will not undergo the FETO procedure because of medical or
 social issues. Because the prevalence of left-sided CDH is higher than right-side CDH, the
 investigators will perform 25 FETO procedures in left sided CDH and 15 in right-sided CDH,
 and these outcomes will be compared to a cohort of 40 non FETO cases.
Enrollment

 Women carrying a fetus with severe CDH and a normal karyotype will undergo routine clinical
 evaluation. The fetus will be 28+0/7 to 31+6/7 weeks of gestational age and have severe CDH.
 These patients will have ultrasound and/or MRI evaluation to rule out other anomalies,
 calculation of the LHR from ultrasound measurements, calculation of observed/expected total
 lung volume and percentage of liver herniation from fetal MRI studies, 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 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 fetal trachea cannot be entered as described above, the uterus will be
 accessed through an incision in the belly (called a laparotomy). A laparotomy is a surgical
 technique tin which an incision is made 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 performed 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, 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 for no later than 36+6/7 weeks, 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 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.

 The investigators 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 - Pavilion
 for Women or can be coordinated with doctors from the hospital of the participant's choosing.

 If the child continues care at another institution, the investigators 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

 -  The fetuses will be 28+0/7 to 31+6/7 weeks of gestational age

 -  Confirmed diagnosis of severe left- or right-sided CDH of the fetus: Observed/expected
 total lung volume equal to or less than 0.32 with more than 21% of liver herniated
 into the hemithorax. (Ideally calculated between 28+0/7 and 31+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 or microarray

 -  The mother must be healthy enough to have surgery

 -  Patient and father of the baby provide signed informed consent that details the
 maternal and fetal risks involved with the procedure

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

 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) in the
 index pregnancy.

 -  Fetal aneuploidy, known structural genomic variants, other major fetal anomalies that
 may impact the fetal/neonatal survival 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