Congenital Diaphragmatic Hernias
Conditions
Keywords
congenital diaphragmatic hernia, FETO, tracheal occlusion
Brief summary
The rationale for fetal therapy in severe congenital diaphragmatic hernia (CDH) is to restore adequate lung growth for neonatal survival.
Detailed description
Prenatal tracheal occlusion (TO) obstructs the normal egress of lung fluid during pulmonary development leading to increased lung tissue stretch, increased cell proliferation, and accelerated lung growth. European colleagues have developed foregut endoscopy and techniques to position and remove endoluminal tracheal balloons in utero. Recently, the Belgium group published summary results of FETO showing an improved survival in 175 patients with isolated left CDH from 24% to 49%. The goal of this pilot study is to study the feasibility of implementing FETO therapy in the most severe group of fetuses with left CDH Observed/expected lung-to-head ratio \< 25%(O/E LHR \< 25%).
Interventions
This study will position and remove an endoluminal tracheal balloon in utero (FETO) to study the feasibility of implementing FETO therapy in the most severe group of fetuses with left CDH and observed/expected length head ratio \<25% (O/E LHR).
Sponsors
Connecticut Children's Medical Center
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 women age 18 years and older, who are able to consent * Singleton pregnancy Fetal * Normal Karyotype * Fetal Diagnosis of Isolated Left CDH with liver up * Gestation at enrollment prior to 29 wks plus 6 days * SEVERE pulmonary hypoplasia with Ultra Sound O/E LHR \< 25%
Exclusion criteria
* Pregnant women \<18 years of age. * Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy * Technical limitations precluding fetoscopic surgery * Rubber latex allergy * Preterm labor, cervix shortened (\<15 mm at enrollment or within 24 hours of FETO balloon insertion procedure) or uterine anomaly strongly predisposing to preterm labor, placenta previa * Psychosocial ineligibility, precluding consent * Diaphragmatic hernia: right-sided or bilateral, major associated anomalies, isolated left-sided with the O/E LHR ≥ 25% * Inability to remain at FETO site during time period of tracheal occlusion, delivery and postnatal care
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of neonatal survivors at time of discharge | Discharge from the hospital, an expected average of 12 weeks. | Feasibility, safety, and survival rates of the FETO procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prenatal increase in lung volume | 2 weeks (prenatally) | Lung volume after FETO procedure |
| Number of days of Postnatal mechanical ventilator support | First 28 days of postnatal life | mechanical ventilator support will be monitored and recorded in days of use |
| Changes in RNA content of tracheal and amniotic fluid | At time of balloon placement and removal | Describe how tracheal occlusion affects the RNA content of amniotic and tracheal fluid in CDH fetuses, and to correlate this transcriptomic profile to the degree of lung hypoplasia and fetal and neonatal clinical outcomes. |
| Characterization of extracellular vesicles (EVs) and miRNAs in tracheal and amniotic fluid | At time of balloon placement and removal | To describe how extracellular vesicles (EVs) are derived from the amniotic and tracheal fluid of CDH patients before and after tracheal occlusion, and to determine whether the identified miRNAs of interest are intra- or extra-vesicular. |
Countries
United States
Contacts
CONTACTKatie E Boyle, MPH
PRINCIPAL_INVESTIGATORTimothy Crombleholme, MD
Connecticut Children's Medical Center
Outcome results
None listed