Fetoscopic Endoluminal Tracheal Occlusion (FETO) for Severe Left Diaphragmatic Hernia (CDH)
Study Details
Study Description
Brief 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).
| Condition or Disease | Intervention/Treatment | Phase |
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N/A |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 11540KE and Balt Goldbal 2 balloon Patients meeting inclusion criteria will receive fetoscopic tracheal occlusion using the fetoscopy sheath 11540 KE and the Balt Goldbal2 detachable balloon. Participants with an O/E LHR 25% (severe group) will have FETO completed at 27 weeks + 0 days to 29 weeks + 6 days gestation. Balloon removal is 4-5 weeks after that. Participants with an O/E LHR 25 - <30% (less severe group) will have FETO completed at 30 weeks + 0 days to 31 weeks + 6 days gestation. Balloon removal is 3 - 4 weeks after that. |
Device: 11540KE and Balt Goldbal 2 balloon
Fetoscopic tracheal occlusion will be performed using above devices and reversed after 4-5 weeks.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Successful balloon insertion and removal [4 to 7 weeks]
The feasibility of performing the procedure, managing the pregnancy during the period of tracheal occlusion, and removal of the device prior to delivery at Johns Hopkins Hospital.
Secondary Outcome Measures
- Survival [28 days after delivery]
The neonatal survival of participants receiving FETO expressed as a percentage of the total number of participants undergoing the procedure.
- Percentage of lung growth [4 to 7 weeks]
The percentage of size increase in the contralateral fetal lung as related to the pre-procedure lung size
Eligibility Criteria
Criteria
Inclusion Criteria:
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Pregnant women age 18 years and older, who are able to consent.
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Singleton pregnancy.
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Anatomically and chromosomally normal fetus.
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Left sided diaphragmatic hernia with liver up.
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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%.
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SEVERE pulmonary hypoplasia with O/E LHR < 30%.
Exclusion Criteria:
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Pregnant women < 18 years.
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Women with allergy to Latex.
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Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy.
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Technical limitations precluding fetoscopic surgery.
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History of natural rubber latex allergy.
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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.
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Psychosocial ineligibility, precluding consent.
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Maternal depression as assessed by a Beck Depression Inventory score equal to or greater than 17.
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Diaphragmatic hernia: right-sided or bilateral, major associated anomalies, isolated left-sided with the O/E LHR ≥ 30%.
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Inability to remain close to the FETO site during time period of tracheal occlusion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Johns Hopkins Center for Fetal Therapy | Baltimore | Maryland | United States | 21287 |
Sponsors and Collaborators
- Johns Hopkins University
Investigators
- Principal Investigator: Ahmet A Baschat, MD, Johns Hopkins University
Study Documents (Full-Text)
None provided.More Information
Publications
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- Bratu I, Flageole H, Laberge JM, Chen MF, Piedboeuf B. Pulmonary structural maturation and pulmonary artery remodeling after reversible fetal ovine tracheal occlusion in diaphragmatic hernia. J Pediatr Surg. 2001 May;36(5):739-44.
- Bratu I, Flageole H, Laberge JM, Possmayer F, Harbottle R, Kay S, Khalife S, Piedboeuf B. Surfactant levels after reversible tracheal occlusion and prenatal steroids in experimental diaphragmatic hernia. J Pediatr Surg. 2001 Jan;36(1):122-7.
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- Davey M, Shegu S, Danzer E, Ruchelli E, Adzick S, Flake A, Hedrick HL. Pulmonary arteriole muscularization in lambs with diaphragmatic hernia after combined tracheal occlusion/glucocorticoid therapy. Am J Obstet Gynecol. 2007 Oct;197(4):381.e1-7.
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- Harrison MR, Adzick NS, Flake AW, VanderWall KJ, Bealer JF, Howell LJ, Farrell JA, Filly RA, Rosen MA, Sola A, Goldberg JD. Correction of congenital diaphragmatic hernia in utero VIII: Response of the hypoplastic lung to tracheal occlusion. J Pediatr Surg. 1996 Oct;31(10):1339-48.
- Hedrick HL, Kaban JM, Pacheco BA, Losty PD, Doody DP, Ryan DP, Manganaro TF, Donahoe PK, Schnitzer JJ. Prenatal glucocorticoids improve pulmonary morphometrics in fetal sheep with congenital diaphragmatic hernia. J Pediatr Surg. 1997 Feb;32(2):217-21; discussion 221-2.
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- Kitano Y, Flake AW, Quinn TM, Kanai M, Davies P, Sablich TJ, Schneider C, Adzick NS, von Allmen D. Lung growth induced by tracheal occlusion in the sheep is augmented by airway pressurization. J Pediatr Surg. 2000 Feb;35(2):216-21; discussion 221-2.
- Luks FI, Deprest JA, Vandenberghe K, Laermans I, De Simpelaere L, Brosens IA, Lerut T. Fetoscopy-guided fetal endoscopy in a sheep model. J Am Coll Surg. 1994 Jun;178(6):609-12.
- Luks FI, Wild YK, Piasecki GJ, De Paepe ME. Short-term tracheal occlusion corrects pulmonary vascular anomalies in the fetal lamb with diaphragmatic hernia. Surgery. 2000 Aug;128(2):266-72.
- Papadakis K, De Paepe ME, Tackett LD, Piasecki GJ, Luks FI. Temporary tracheal occlusion causes catch-up lung maturation in a fetal model of diaphragmatic hernia. J Pediatr Surg. 1998 Jul;33(7):1030-7.
- Quinn TM, Sylvester KG, Kitano Y, Kitano Y, Liechty KW, Jarrett BP, Adzick NS, Flake AW. TGF-beta2 is increased after fetal tracheal occlusion. J Pediatr Surg. 1999 May;34(5):701-4; discussion 704-5.
- Schnitzer JJ, Hedrick HL, Pacheco BA, Losty PD, Ryan DP, Doody DP, Donahoe PK. Prenatal glucocorticoid therapy reverses pulmonary immaturity in congenital diaphragmatic hernia in fetal sheep. Ann Surg. 1996 Oct;224(4):430-7; discussion 437-9.
- Schnitzer JJ, Thompson JE, Hedrick HL. A new ventilator improves CO2 removal in newborn lambs with congenital diaphragmatic hernia. Crit Care Med. 1999 Jan;27(1):109-12.
- Sylvester KG, Rasanen J, Kitano Y, Flake AW, Crombleholme TM, Adzick NS. Tracheal occlusion reverses the high impedance to flow in the fetal pulmonary circulation and normalizes its physiological response to oxygen at full term. J Pediatr Surg. 1998 Jul;33(7):1071-4; discussion 1074-5.
- Wild YK, Piasecki GJ, De Paepe ME, Luks FI. Short-term tracheal occlusion in fetal lambs with diaphragmatic hernia improves lung function, even in the absence of lung growth. J Pediatr Surg. 2000 May;35(5):775-9.
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