At Children’s Hospital of Philadelphia’s Center for Fetal Diagnosis and Treatment, we see a very large volume of patients with congenital diaphragmatic hernia (CDH), a serious birth defect in which there is a hole in a developing fetus’ diaphragm. We have provided a rare continuity of care for more than 1,350 CDH patients spanning the spectrum of severity.
Over time, our team has instituted a number of advances in the postnatal management of patients with CDH, which have resulted in improved survival rates. Among them:
- The creation of a Neonatal Surgical Team, which provides expert stabilization and, often, specialized ventilation techniques immediately after birth in our Special Delivery Unit (SDU), the first birth facility designed exclusively for healthy mothers carrying babies with known birth defects
- Performing postnatal surgical repair while a baby remains on a radiant warmer bed in our Newborn/Infant Intensive Care Unit (N/IICU) to reduce the risks of transport to the OR
- The creation of very detailed Optimal Care Guidelines for CDH care in the SDU and N/IICU
Despite these strides, there remain high rates of morbidity and mortality in cases of severe CDH. Experience has taught us that the essential problem in these cases is the resulting pulmonary hypoplasia, causing ventilatory insufficiency and pulmonary hypertension in the neonatal period and beyond.
Since the early ’90s, our team has been investigating tracheal occlusion — in which the airway is blocked in utero — as a viable alternative to the options of pregnancy termination and expectant management in these severe cases. Occlusion of the airway obstructs the normal egress of lung fluid during pulmonary development, leading to increased lung tissue stretch, increased cell proliferation and accelerated lung growth. Lungs that grow enough before birth will be more capable of sustaining life after birth.
Our colleagues in Europe — led by Jan Deprest, MD, professor of Obstetrics and Gynaecology at the University Hospitals Leuven in Belgium — have also been studying this approach and have significantly advanced the techniques and equipment for tracheal occlusion. Dr. Deprest leads the European “Tracheal Occlusion to Accelerate Lung Growth” (TOTAL) trial. Our team has spent the past five years consulting with Dr. Deprest and recently received FDA approval to pursue a feasibility study in the U.S. of fetoscopic endoluminal tracheal occlusion (FETO) for CDH cases in which we predict serious disease and death at birth based on ultrasound findings of an observed to expected lung-to-head circumference ratio (O/E LHR) < 30%.
FETO consists of two surgeries, the first of which occurs at 270 to 316 weeks gestation. A fetal bronchoscope is passed through a trocar and a balloon is inserted into the fetal airway under ultrasound guidance. The balloon is then inflated to dimensions of 7–8 mm wide and 22 mm long, slightly exceeding the tracheal dimensions to ensure occlusion as the trachea grows. Occlusion of the airway causes fluid to build up in the unborn baby’s lungs; pressure from the fluid, in turn, causes the lungs to grow.
The second surgery takes place at 340 to 346 weeks to remove the balloon from the fetal trachea. A needle is passed through the uterus to puncture and deflate the balloon. The built-up pressure in the lungs then pushes the deflated balloon out through the unborn baby’s mouth. If this technique for balloon removal doesn’t work, a fetal bronchoscope is passed through a trocar into the unborn baby’s airway and the balloon is then pulled out using a grasper. Children who undergo FETO will still need to undergo CDH repair after birth.
Up to 10 women will be enrolled in our feasibility study prior to joining the international TOTAL trial. Participants will be required to reside within 30 minutes of CHOP from the time of the first surgery through birth in our SDU, postnatal CDH repair and discharge from our N/IICU.
Our fetal medicine specialists have extensive experience in fetoscopy and the prenatal and postnatal care of a baby with CDH. We have standardized protocols that we have used for the past 19 years in cases of airway obstruction from other diagnoses, and have experience with more than 100 ex utero intrapartum treatment (EXIT) deliveries with personnel and protocols in place for emergently attending to the airway.
The expected hospital course after the first surgery is 24–48 hours. Serial measurements of sonographic lung volume and LHR will begin one to two days after surgery and continue weekly by targeted ultrasound evaluation. The patient will be discharged to a nearby accommodation and remain on modified bed rest for the first two weeks post discharge, but subsequently will graduate to moderate activity if the uterus is quiescent.
Long-term follow-up will mirror what non-FETO CDH patients undergo with checkups at 6 months, 12 months and 2 years. Those enrolled in our multidisciplinary Pulmonary Hypoplasia Program will also be evaluated patients at age 4–5, age 6 and every two years thereafter. These appointments include cardiology, pulmonary, medical, developmental/psychological, audiology, nutrition, surgery, and social work evaluations at designated intervals. Orthopedics, ophthalmology, speech, the feeding team, and gastroenterology also see children as needed.
Shown from left to right:
- While the baby is in the womb, a fetal bronchoscope is passed through a trocar into the unborn baby’s airway.
- A balloon is then inflated inside the unborn baby’s airway and left in place. This causes fluid to build up in the unborn baby’s lungs. Pressure from the fluid causes the lungs to grow.
- After several weeks a needle is passed through the uterus to puncture and deflate the balloon. The built up pressure in the lungs then pushes the deflated balloon out through the unborn baby’s mouth.
- In another approach, a fetal bronchoscope is passed through a trocar into the unborn baby’s airway and the balloon is then pulled out using a grasper.
Objectives and Enrollment Criteria
- Determine the feasibility and safety of performing FETO in fetuses with left CDH with O/E LHR < 30% as determined through ultrasound
- Demonstrate fetal lung growth due to successful FETO
- Determine survival rate and outcome measures of FETO patients at delivery, neonatal discharge, 6 months, 12 months and 2 years
Find detailed referral guidelines for when FETO may or may not be offered.
Eligible patients will be identified based on a
comprehensive evaluation that will include:
- Comprehensive obstetric ultrasound examination, including documentation of cervical length, gestational age, biometry, liver herniation, hepatic vasculature, sonographic lung volume, amniotic fluid level, membrane status and LHR calculation
- Detailed maternal history and physical
- Maternal MRI to confirm fetal liver herniation
- Fetal echocardiogram to rule out structural cardiac abnormalities
- Laboratory tests including karyotyping
- Psychosocial evaluation to identify family support and possible confounding social issues
- Patient education
While the balloon is in place, the fetal airway is blocked. Unexpected delivery could be life-threatening if the proper systems aren’t in place to manage the airway.
As a result, mothers enrolled in this study must remain near our fetal center, under close supervision, from the time of balloon placement through delivery in our Special Delivery Unit and discharge from our Newborn/Infant Intensive Care Unit.
Comprehensive evaluation of each pregnancy is essential to determine whether prenatal repair is appropriate. To refer a patient or discuss a case, please contact us at 1-800-IN UTERO (468-8376).
*Referral guidelines updated March 2017