Fetal Endotracheal Occlusion (FETO) in Fetuses with Severe Congenital Diaphragmatic Hernia

N/ANot Yet RecruitingNCT06281717

Alireza Shamshirsaz10 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Successful Ballon Placement

Defined as direct visualization of balloon deployment above the carina at the time of FETO procedure

Time frame: Gestational age of 27 weeks 0 days to 29 weeks 6 days

Successful Balloon Removal

Removal of the balloon prior to delivery, ideally during 34 weeks gestation

Time frame: Prior to delivery, ideally at 34 weeks

Balloon placement operative time

Length of FETO procedure for successful balloon placement

Time frame: Gestational age of 27 weeks 0 days to 29 weeks 6 days

Balloon removal operative time

Length of FETO procedure for successful balloon removal

Time frame: Prior to delivery, ideally at 34 weeks

Type of FETO release

Emergent or non-emergent FETO release

Time frame: Prior to delivery, ideally at 34 weeks

Maternal Complications

Maternal complications include: preterm labor, premature rupture of membranes, oligohydramnios, polyhydramnios, chorioamnionitis

Time frame: From balloon placement to delivery

Gestational age at delivery

Gestational age at delivery will be recorded

Time frame: At delivery

Secondary Outcomes

Fetal lung volume

Fetal lung volume will be monitored on ultrasound

Time frame: 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.

Observed-to-Expected Lung to Head Ratio

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.

Time frame: Calculated at balloon removal, ideally at 34 weeks gestation

Infant survival

Survival at discharge from the hospital, or at 6 months of age if still hospitalized

Time frame: At hospital discharge or 6 months of age, whichever comes first. Hospital discharge typically occurs at 2-3 months of age

Oxygen dependency

Infant dependency on oxygen as defined by Bancalari 2001

Time frame: At time of discharge, on average at 2-3 months of age

Number of infants requiring ECMO (extracorporeal membrane oxygenation)

Use of ECMO support will be documented

Time frame: Birth to 6 months

NICU (neonatal intensive care unit) stay

Number of days spent in the neonatal intensive care unit

Time frame: From birth until discharge, at an average of 2-3 months of age

Ventilator support

Number of days on ventilator support

Time frame: Up to 2 years of age

Presence of periventricular leukomalacia

Incidence of periventricular leukomalacia at \<2 months postnatally

Time frame: From birth until 2 months of age

Presence of neonatal sepsis

Incidence of neonatal sepsis

Time frame: From birth until 1 month of age

Presence of intraventricular hemorrhage

Incidence of intraventricular hemorrhage (grade 0-III)

Time frame: Up to 2 years of age

Retinopathy of prematurity

Incidence of retinopathy of prematurity (grade III or higher)

Time frame: From birth to 1 month of age

Presence of gastro-esophageal reflux

Incidence of gastro-esophageal reflux

Time frame: From birth until 2 years of age

CDH repair type

CDH repair type will be documented as patch or muscle flap

Time frame: Postnatal, at time of CDH repair, typically within 2 weeks of birth

Pulmonary function

Pulmonary function by spirometry

Time frame: At discharge around 2-3 months and at one year of age

Infant Neurodevelopment

Neurodevelopmental testing of the infant using the Bayley-4

Time frame: At 6 months, 12 months, and 24 months of age

Route of delivery

Delivery route will be recorded

Time frame: At delivery

Maternal hospitalization

Total days of maternal hospital stay after delivery

Time frame: From delivery until discharge, around 2-3 months of age

Fetal Endotracheal Occlusion (FETO) in Fetuses with Severe Congenital Diaphragmatic Hernia

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts