Congenital Diaphragmatic Hernia
Conditions
Keywords
Hernias, Diaphragmatic, Congenital, Fetoscopic Endoluminal Tracheal Occlusion, Fetal Endoscopic Tracheal Occlusion, Hernia
Brief summary
The goal of this pilot trial is to learn more about the role of Fetal Endotracheal Occlusion (FETO) as an intervention in fetuses with severe congenital diaphragmatic hernia (CDH). The research team will investigate the feasibility and safety of the FETO procedure, as well as determine whether FETO can improve lung growth before birth, and survival after birth. This study will enroll 10 pregnant participants to undergo the FETO procedure at a gestational age of 27 weeks 0 days to 29 weeks 6 days. The participant will be monitored for a few weeks, and then the FETO removal procedure will be performed ideally at 34 weeks 0 days to 34 weeks 6 days, but may be indicated earlier as determined by the Maternal Fetal care team. The pregnant participant and their baby will continue to be monitored during delivery and up until the child reaches 2 years of age.
Detailed description
The goal of this study is to learn more about the role of Fetal Endotracheal Occlusion (FETO) as an intervention in fetuses with isolated severe congenital diaphragmatic hernia (CDH). CDH is a condition in which the diaphragm fails to completely close, leaving a gap through which abdominal organs can herniate and slide into and out of the chest. In severe cases, abdominal organs move into the chest and stay there, putting pressure on the heart and lungs and potentially causing the disruption or deformation of these structures. Impaired development of the lungs can often lead to a condition known as pulmonary hypertension, a form of high blood pressure that damages the heart. Pulmonary hypoplasia and pulmonary hypertension can be lethal. Congenital diaphragmatic hernia (CDH) affects 1 in 2,200 to 5,000 live births per year. FETO will be performed with the goal of promoting lung growth and improving neonatal outcomes. FETO is a minimally invasive procedure in which a balloon device is inserted into the trachea of the fetus. The devices involved are the Goldballoon Detachable Balloon (GOLDBAL2) along with the Delivery Microcatheter (BALTACCI-BDPE100). The balloon would be left in place for several weeks and allow the lungs to grow, after which it would be removed, enabling the lungs to mature before birth. Participants will continue to be monitored up until the child reaches 2 years of age in order to assess mental and physical development after FETO.
Interventions
DEVICEFetal Endotracheal Occlusion (FETO)
The FETO insertion procedure will be performed between gestational age 27 weeks 0 days and 29 weeks and 6 days. The Goldballoon Detachable Balloon (GOLDBAL2) will be inserted in the airway of the fetus using the Delivery Microcatheter (BALTACCI-BDPE100). The fetal tracheal balloon will be removed between 34 weeks 0 days and 34 weeks 6 days gestation or earlier as indicated.
Sponsors
Eyal Krispin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pregnant patient 18 and older who is able to consent * Singleton pregnancy * Ability to reside within 30 minutes of Boston Children's Hospital for the duration of the FETO intervention, from the time of balloon placement until balloon removal * Patient has a support person who is able to stay with them for the duration of the pregnancy Fetal: * Reassuring genetic analysis demonstrated by either normal Karyotype, normal fluorescence in situ hybridization (FISH) for chromosomes 13, 18, 21, X and Y, or chromosomal microarray (CMA) with non-pathologic variants * Diagnosis of isolated left CDH with liver up * Gestation at enrollment prior to 29 weeks 5 days * SEVERE pulmonary hypoplasia with ultrasound Observed/Expected Lung-to-Head Ratio (O/E LHR) \< 25%
Exclusion criteria
* Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy * Technical limitations precluding fetoscopic surgery, including uterine anomaly such as large or multiple fibroids, or Mullerian duct anomaly * Latex allergy * Preterm labor, shortened cervix (\<20mm at enrollment or within 24 hours of FETO balloon insertion procedure) or uterine anomaly strongly predisposing to preterm labor, placenta previa * Severe maternal obesity pre-pregnancy (BMI \> 40) * Psychosocial ineligibility, precluding consent, as determined by clinic social worker during review * Inability to remain at FETO site during time period of tracheal occlusion, delivery, and postnatal care * Right-sided or bilateral, left-sided CDH observed-to-expected lung to head ratio \> 25% on ultrasound * Additional fetal anomaly and chromosomal abnormalities by ultrasound, MRI, or echocardiogram that will significantly worsen prognosis * History of incompetent cervix with or without cerclage * Placental abnormalities (previa, abruption, accreta) known at time of enrollment * Maternal-fetal RH (rhesus) isoimmunization, Kell sensitization, or neonatal alloimmune thrombocytopenia affecting the current pregnancy * Maternal HIV, Hepatitis B, Hepatitis C status positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful Ballon Placement | Gestational age of 27 weeks 0 days to 29 weeks 6 days | Defined as direct visualization of balloon deployment above the carina at the time of FETO procedure |
| Successful Balloon Removal | Prior to delivery, ideally at 34 weeks | Removal of the balloon prior to delivery, ideally during 34 weeks gestation |
| Balloon placement operative time | Gestational age of 27 weeks 0 days to 29 weeks 6 days | Length of FETO procedure for successful balloon placement |
| Balloon removal operative time | Prior to delivery, ideally at 34 weeks | Length of FETO procedure for successful balloon removal |
| Type of FETO release | Prior to delivery, ideally at 34 weeks | Emergent or non-emergent FETO release |
| Maternal Complications | From balloon placement to delivery | Maternal complications include: preterm labor, premature rupture of membranes, oligohydramnios, polyhydramnios, chorioamnionitis |
| Gestational age at delivery | At delivery | Gestational age at delivery will be recorded |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fetal lung volume | Once per week from balloon placement to removal. This measure will be recorded at earliest gestational age of 27 weeks 0 days, and latest at 34+6/7 weeks' gestation. | Fetal lung volume will be monitored on ultrasound |
| Observed-to-Expected Lung to Head Ratio | Calculated at balloon removal, ideally at 34 weeks gestation | Prenatal ultrasound will measure the observed-to-expected lung to head ratio (o/e LHR) at weekly visits while the balloon is in place and after balloon removal. Fetal lung growth will be calculated as the difference between the o/e LHR pre-balloon placement and the o/e LHR after balloon removal. |
| Infant survival | At hospital discharge or 6 months of age, whichever comes first. Hospital discharge typically occurs at 2-3 months of age | Survival at discharge from the hospital, or at 6 months of age if still hospitalized |
| Oxygen dependency | At time of discharge, on average at 2-3 months of age | Infant dependency on oxygen as defined by Bancalari 2001 |
| Number of infants requiring ECMO (extracorporeal membrane oxygenation) | Birth to 6 months | Use of ECMO support will be documented |
| NICU (neonatal intensive care unit) stay | From birth until discharge, at an average of 2-3 months of age | Number of days spent in the neonatal intensive care unit |
| Ventilator support | Up to 2 years of age | Number of days on ventilator support |
| Presence of periventricular leukomalacia | From birth until 2 months of age | Incidence of periventricular leukomalacia at \<2 months postnatally |
| Presence of neonatal sepsis | From birth until 1 month of age | Incidence of neonatal sepsis |
| Presence of intraventricular hemorrhage | Up to 2 years of age | Incidence of intraventricular hemorrhage (grade 0-III) |
| Retinopathy of prematurity | From birth to 1 month of age | Incidence of retinopathy of prematurity (grade III or higher) |
| Presence of gastro-esophageal reflux | From birth until 2 years of age | Incidence of gastro-esophageal reflux |
| CDH repair type | Postnatal, at time of CDH repair, typically within 2 weeks of birth | CDH repair type will be documented as patch or muscle flap |
| Pulmonary function | At discharge around 2-3 months and at one year of age | Pulmonary function by spirometry |
| Infant Neurodevelopment | At 6 months, 12 months, and 24 months of age | Neurodevelopmental testing of the infant using the Bayley-4 |
| Route of delivery | At delivery | Delivery route will be recorded |
| Maternal hospitalization | From delivery until discharge, around 2-3 months of age | Total days of maternal hospital stay after delivery |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAlireza Shamshirsaz, MD
Director, Maternal Fetal Care Center
Outcome results
None listed