Prospective Registry for Long-term Outcomes Following FETO in Severe Left and Right CDH

Johns Hopkins University80 enrolled

Overview

This registry study aims to confirm that FETO increases neonatal survival to discharge and reduces long-term morbidity in fetuses with isolated left CDH and o/e LHR \< 30%, or isolated right CDH and o/e LHR ≤ 45%, compared to those receiving standard care. This prospective registry plans to enroll 80 pregnant women (40 treatment/40 control) with fetuses diagnosed with isolated CDH, and the children will be followed for up to 24 months.

The purpose of this study is to evaluate successful placement and removal of Fetoscopic Endoluminal Tracheal Occlusion (FETO) device in cases of intrathoracic liver herniation with isolated left congenital diaphragmatic hernia (LCDH) with Observed/Expected (O/E) Lung to Head Circumference Ratio (LHR) \< 30% or isolated right congenital diaphragmatic hernia (RCDH) with O/E LHR ≤ 45%,to compare survival to discharge from the neonatal intensive care units (NICU), between fetuses with intrathoracic liver herniation and isolated LCDH with O/E LHR \< 30% that receive FETO procedure performed at 27 weeks + 0 days to 29weeks + 6 days of gestation to those with intrathoracic liver herniation, isolated LCDH and o/e LRH \< 30% that undergo expectant management, to compare the neonatal survival rate to discharge from the neonatal intensive care units (NICU), between fetuses with intrathoracic liver herniation, isolated RCHD with o/e LHR ≤ 45% that undergo FETO procedure performed at 27 weeks + 0 days to 29 weeks + 6 days gestation to those with intrathoracic liver herniation, isolated RCHD and o/e LHR ≤ 45% that elect to proceed with expectant management, to evaluate the frequency of maternal and fetal complications associated with FETO procedure, to evaluate whether the FETO procedure is associated with reduced long-term mortality and morbidities in isolated LCDH survivors with o/e LHR \<30% when compared to isolated LCDH with o/e LRH \<30% that undergo expectant management where all fetuses were found to have intrathoracic liver herniation and to evaluate whether the FETO procedure is associated with reduced long-term mortality and morbidities in isolated RCDH survivors with o/e LHR ≤ 45% when compared to isolated RCHD with LHR ≤ 45% that undergo expectant management where all fetuses were found to have intrathoracic liver herniation.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Interventions

Fetal Treatment Arm (FETO Group)DEVICE

Participants will undergo FETO surgery between 27 weeks + 0 days to 29 weeks + 6 days gestation. The FETO intervention involves two procedures: (1) inserting a balloon into the fetal trachea, and (2) removing the balloon before delivery. After the first FETO procedure, participants will be monitored weekly by ultrasound. Removal of the balloon will be performed at 34 weeks + 0 days to 34 weeks + 6 days gestation. Planned delivery will occur after 37 weeks. The follow-up phase will be conducted from birth to 24 months of age.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Pregnant women age 18 years and older * Singleton pregnancy * Normal Karyotype, chromosomal microanalysis (CMA) with non-pathologic variants, whole exome sequencing (WES) or whole genome sequencing (WGS). Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is \> 26 weeks gestation. * Gestational age at enrollment is prior to 29 weeks + 6 days gestation. * Intrathoracic liver herniation: * Isolated left CDH with o/e LHR \< 30% at enrollment (18wks + 0 days to 29wks + 5 days gestation). * Isolated right CDH with o/e LHR ≤ 45% at enrollment (18wks + 0 days to 29wks + 5 days gestation). * Cervical length by transvaginal ultrasound ≥ 20 mm within 24 hours prior to FETO procedure. * Patient meets psychosocial criteria. * Informed consent understood. Exclusion Criteria: * Patient \< 18 years of age * Multi-fetal pregnancy * History of natural rubber latex allergy * Preterm labor, cervix shortened (\<20 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: 1. Inability to reside within 30 minutes of Johns Hopkins Hospital Center for Fetal Therapy. 2. The patient does not have a support person (e.g., spouse, partner, mother) available to stay with the patient for the duration of the pregnancy at Johns Hopkins Hospital Center for Fetal Therapy. * Bilateral CDH, isolated left sided CDH with O/E LHR ≥ 30% (18wks + 0 days to 29wks + 5 days gestation), isolated right sided CDH with O/E LHR \> 45% (18wks + 0 days to 29wks + 5 days gestation), as determined by ultrasound. * No liver herniation into thoracic cavity. * Additional fetal anomaly and chromosomal abnormalities by ultrasound, MRI, or echocardiogram at the fetal treatment center. Exclude chromosomal abnormalities, associated anomalies recognized to alter survival prognosis (i.e., CDH and congenital heart disease) or presence of an underlying genetic syndrome (i.e., Fryns). * Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy. * History of incompetent cervix with or without cerclage. * Placental abnormalities (previa, abruption, accreta) known at time of enrollment * Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune thrombocytopenia affecting the current pregnancy. * Maternal HIV, Hepatitis-B, Hepatitis-C status positive because of the increased risk of transmission to the fetus during maternal-fetal surgery. If the patient's HIV or Hepatitis status is unknown, the patient must be tested and found to have negative results before enrollment. * Uterine anomalies such as large or multiple fibroids or Mullerian duct abnormality. * There is no safe or technically feasible fetoscopic approach to balloon placement. * Participation in another intervention study that influences maternal and fetal morbidity and mortality. or participation in this trial in a previous pregnancy.

Outcomes

Primary Outcomes

Number of successful placement of FETO device

Time frame: 10-60 minutes after surgery begins

Number of successful removal of FETO device

Time frame: Immediately after the procedure (about 1 hour after start of surgery)

Number of FETO procedure complications

Complications include: Failure FETO insertion procedure, FETO device dislodgement potentially requiring a second FETO insertion, Fetal intraoperative injury, Procedural hemorrhage, Bleeding from insertion site or Abruptions, Post-procedural hemorrhage PPROM, Preterm delivery, Chorioamnion separation, Chorioamnionitis, Polyhydramnios, Oligohydramnios, Emergent removal due to obstetrical complication, Failed percutaneous or fetoscopic removal requiring cesarean section or exit procedure for removal, Neonatal death due to asphyxia if delivery before FETO removal, and Non-reassuring fetal heart rate monitoring.

Time frame: End of study (24 months)

Number of neonates that survived

Neonatal survival to discharge

Time frame: From delivery to hospital discharge

Secondary Outcomes

Number of infants that survived

Time frame: 6 months

Number of infants that survived

Time frame: 12 months

Number of infants that survived

Time frame: 18 months

Number of infants that survived

Time frame: 24 months

Number of infants that show presence of pulmonary hypertension

Time frame: 6 months

Number of infants that show presence of pulmonary hypertension

Time frame: 12 months

Number of infants that show presence of pulmonary hypertension

Time frame: 18 months

Number of infants that show presence of pulmonary hypertension

Time frame: 24 months

Number of infants that show need for supplemental oxygen

Time frame: 6 months

Number of infants that show need for supplemental oxygen

Time frame: 12 months

Number of infants that show need for supplemental oxygen

Time frame: 18 months

Number of infants that show need for supplemental oxygen

Time frame: 24 months

Number of infants that show periventricular leukomalacia

Time frame: At less than 2 months postnatally

Number of Infants that develop sepsis

Time frame: 6 months

Number of Infants that develop sepsis

Time frame: 12 months

Number of Infants that develop sepsis

Time frame: 18 months

Number of Infants that develop sepsis

Time frame: 24 months

Number of infants that develop Intraventricular hemorrhage (grade 0-III)

Time frame: 6 months

Number of infants that develop Intraventricular hemorrhage (grade 0-III)

Time frame: 12 months

Number of infants that develop Intraventricular hemorrhage (grade 0-III)

Time frame: 18 months

Number of infants that develop Intraventricular hemorrhage (grade 0-III)

Time frame: 24 months

Number of infants that develop retinopathy of prematurity (grade 3 or higher)

Time frame: 6 months

Number of infants that develop retinopathy of prematurity (grade 3 or higher)

Time frame: 12 months

Number of infants that develop retinopathy of prematurity (grade 3 or higher)

Time frame: 18 months

Number of infants that develop retinopathy of prematurity (grade 3 or higher)

Time frame: 24 months

Number of infants that develop gastro-esophageal reflux

Time frame: 6 months

Number of infants that develop gastro-esophageal reflux

Time frame: 12 months

Number of infants that develop gastro-esophageal reflux

Time frame: 18 months

Number of infants that develop gastro-esophageal reflux

Time frame: 24 months

Number of infant hospital readmissions

Time frame: End of study (24 months)

Cause of infant hospital readmissions

Time frame: End of study (24 months)

Number of infants that show childhood growth failure

Time frame: 6 months

Number of infants that show childhood growth failure

Time frame: 12 months

Number of infants that show childhood growth failure

Time frame: 18 months

Number of infants that show childhood growth failure

Time frame: 24 months

Number of infants that show recurrence of CDH repair

Time frame: 6 months

Number of infants that show recurrence of CDH repair

Time frame: 12 months

Number of infants that show recurrence of CDH repair

Time frame: 18 months

Number of infants that show recurrence of CDH repair

Time frame: 24 months

Number of infants that develop bowel obstruction

Time frame: 6 months

Number of infants that develop bowel obstruction

Time frame: 12 months

Number of infants that develop bowel obstruction

Time frame: 18 months

Number of infants that develop bowel obstruction

Time frame: 24 months

Number of infants that show neurodevelopmental delay as assessed by the Bayley Scales of Infant and Toddler Development-III(BSID)

Three domains will be measured as follows: Cognitive Scale, Language Scale (Receptive and Expressive) and Motor Scale (Fine and Gross Motor Skills). Scores are derived by converting raw scores from completed tasks into scale scores and composite scores. These scores are then utilized to assess the child's performance in relation to norms established based on typically developing children of the same age Mean score of 100 (SD=15) at the 50th percentile signifies mid-average functioning. Scores below 85 (1 SD below the mean), at the 16th percentile, indicate mild impairment of being 'at risk' of developmental delay. Score below 70 (2 SD below the mean), at the second percentile, indicate moderate to severe impairment. In general, scores falling in the lowest 10th percentile indicate developmental delay

Time frame: 24 months

Number of infants that develop bronchopulmonary dysplasia

Time frame: 6 months

Number of infants that develop bronchopulmonary dysplasia

Time frame: 12 months

Number of infants that develop bronchopulmonary dysplasia

Time frame: 18 months

Number of infants that develop bronchopulmonary dysplasia

Time frame: 24 months

Prospective Registry for Long-term Outcomes Following FETO in Severe Left and Right CDH

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts