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

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.

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.
• SEVERE pulmonary hypoplasia with O/E LHR < 30%.
• In patients with O/E LHR 25% to <30%, enrollment prior to gestational age 30 weeks+0 days to 31 weeks+6 days.
• In patients with O/E LHR <25%, enrollment prior to gestational age 27 weeks+0 days to 29 weeks+6 days.

Exclusion criteria

• Pregnant women < 18 years.
• Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy.
• Technical limitations precluding fetoscopic surgery.
• Women with 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.
• Diaphragmatic hernia: right-sided or bilateral, major associated anomalies, isolated left-sided with the O/E LHR ≥ 30%.