Fetoscopic Endoluminal Tracheal Occlusion (FETO) for Severe Left Diaphragmatic Hernia (CDH)

  • STATUS
    Recruiting
  • End date
    Mar 14, 2023
  • participants needed
    35
  • sponsor
    Johns Hopkins University
Updated on 14 October 2021
MRI
nitric oxide
prenatal
diaphragmatic hernia
pulmonary hypoplasia
e 25
nitric oxide therapy
fetal therapy

Summary

Despite advances in prenatal diagnosis and postnatal therapies, including extracorporeal membrane oxygenation (ECMO), inhaled nitric oxide therapy, and ventilator strategies that minimize ventilator-induced lung injury, morbidity and mortality rates for babies with congenital diaphragmatic hernia (CDH) remain high. The survival relates to the degree of prenatal lung compression and the subsequent impairment of pulmonary function following delivery. Prenatal assessment by ultrasound or magnetic resonance imaging allows to estimate the severity by relating the circumference of the lung contralateral to the hernia to the fetal head circumference lung to head ratio (LHR) and by noting the degree of upward herniation of the liver. Based on the observed to expected lung to head ratio (O/E LHR), prenatally diagnosed congenital diaphragmatic hernia can be prognostically assessed. While overall survival of congenital diaphragmatic hernia is approximately 60%, an O/E LHR <25% is associated with survival between 11-24%.

The rationale for fetal therapy in severe congenital diaphragmatic hernia is to restore adequate lung growth for neonatal survival. Prenatal tracheal occlusion 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 intrauterine endoscopic techniques (fetoscopy) to position and remove endoluminal tracheal balloons in utero (fetoscopic endotracheal occlusion = FETO). Recently, the Belgium group published summary results of FETO showing an improved survival in 175 patients with isolated left CDH from 24% to 49%. We hypothesize that FETO can be performed and may increase survival and decrease morbidity when compared to standard prenatal care for the treatment of severe CDH in the most severe group of fetuses with left CDH (O/E LHR < 30%). FETO therapy will be considered in two subgroups: those with and O/E LHR <25% (severe group) and those with an O/E between 25 to <30% (less severe group).

Description

Comprehensive fetal evaluations will be completed at the Johns Hopkins Center for Fetal Therapy to confirm eligibility. This includes an ultrasound, magnetic resonance imaging, a fetal echocardiogram and fetal genetic studies to identify cases with isolated CDH. Participant must be willing to remain under supervision of the Center for Fetal Therapy at the Johns Hopkins Hospital while the fetal airway is occluded.

Participants will undergo FETO with standardized preoperative, intraoperative, post-operative care, and delivery. The FETO will be timed between 27+0 to 29+6 weeks gestation for fetuses with an O/E LHR <25% and between 30+0 to 31+6 weeks gestation for fetuses with an O/E LHR between 25% to <30%. Fetal analgesia and immobilization will consist of fentanyl, atropine and vecuronium. A 10 Fr cannula, 1.3 mm fetoscope within a 3.3 mm sheath (Karl Storz, Tuttlingen, Germany), and a detachable balloon occlusion (BALTACCI-BDPE, Balt, Montmorency, France) system will be used.

Serial ultrasound measurements of lung volume and LHR will begin within 24-48 hours following surgery and continue weekly. Amniotic fluid level and membrane status will also be monitored at weekly intervals. Ultrasonography for fetal growth will be performed every 4 weeks.

All discharged participants and their support person need to remain within 30 minutes of the surgery center until delivery to permit standardized postoperative management. The social worker at the Center for Fetal Therapy will serve as the participant advocate and assist families in identifying subsidized appropriate accommodation as required. Participants will be on modified bed rest for the first 2 weeks post discharge, but subsequently allowed to graduate to moderate activity if the uterus is quiescent.

At 34+0 weeks to 34 + 6 weeks, participants will undergo removal of the tracheal balloon. Balloon retrieval can be either by in utero puncture by ultrasound-guided percutaneous needling or fetoscopic retrieval. In the event there is a need for emergent balloon removal prior to 34 weeks due to the development of preterm labor, shortening of the cervix, preterm rupture of membranes, abnormally vigorous lung response, or development of fetal hydrops, delivery by EXIT or cesarean section will be performed. If percutaneous puncture of balloon is unsuccessful prior to delivery, immediate bronchoscopy and establishment of airway will be performed. Maternal corticosteroids (betamethasone 12 mg intramuscularly and repeated once at 24 hours) will be administered 48 hours prior to fetoscopic balloon removal (due to risks of preterm delivery associated with instrumentation) or for impending preterm delivery.

Timing for induction of labor at 37 weeks to 39 weeks will depend upon favorable status of the cervix. Cesarean section will be based upon standard obstetrical indications. In regards to postnatal care, a resuscitation team from neonatology and pediatric surgery will be present at delivery. A standardized protocol will be utilized for postnatal care, using lung protection strategy.

Continued follow-up of children until age 2 is planned as the current standard of care. These follow-ups may include bronchoscopy, brain imaging, audiology exam, pulmonary function testing, chest radiograph and developmental assessment.

The study duration per mother and child will be up to 877 days, with up to 82 days screening, up to 55 days in the intervention phase, and 744 days in delivery and follow-up.

Follow-up will be conducted from birth to 24 months of age at which time the study will conclude.

Details
Condition Growth Hormone Deficiencies/Abnormalities, Male Hormonal Deficiencies/Abnormalities, Birth Defects, CONGENITAL ANOMALY NOS, Female Hormonal Deficiencies/Abnormalities, Congenital Diaphragmatic Hernia
Treatment 11540KE and Balt Goldbal 2 balloon
Clinical Study IdentifierNCT02710968
SponsorJohns Hopkins University
Last Modified on14 October 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Pregnant women age 18 years and older, who are able to consent
Singleton pregnancy
Anatomically and chromosomally normal fetus
Left sided diaphragmatic hernia with liver up
Gestation at enrollment prior to 27+0 to 29+6 weeks in patients with O/E LHR of 25% or 30+0 to 31+6 weeks in patients with O/E 25 -<30%
SEVERE pulmonary hypoplasia with O/E LHR < 30%

Exclusion Criteria

Pregnant women < 18 years
Women with allergy to Latex
Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy
Technical limitations precluding fetoscopic surgery
History of natural rubber latex allergy
Preterm labor, cervix shortened <15 mm within 24 hours prior to the FETO balloon insertion or uterine anomaly strongly predisposing to preterm labor, placenta previa
Psychosocial ineligibility, precluding consent
Maternal depression as assessed by a Beck Depression Inventory score equal to or greater than 17
Diaphragmatic hernia: right-sided or bilateral, major associated anomalies, isolated left-sided with the O/E LHR 30%
Inability to remain close to the FETO site during time period of tracheal occlusion
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