Ex utero intrapartum treatment to extracorporeal membrane oxygenation: lifesaving management of a giant cervical teratoma.

BACKGROUND: Ex utero intrapartum treatment ('EXIT' procedure) is a well described method for maintaining maternal-fetal circulation in the setting of airway obstruction from compressive neck masses. When ex utero intrapartum treatment to airway is not feasible, ex utero intrapartum treatment to extracorporeal membrane oxygenation ('ECMO') has been described in fetal cardiopulmonary abnormalities. OBJECTIVE: This paper presents the case of a massively compressive midline neck teratoma managed with ex utero intrapartum treatment to extracorporeal membrane oxygenation, allowing for neonatal survival, with controlled airway management and subsequent resection. CASE REPORT: A 34-year-old-female presented with a fetal magnetic resonance imaging scan demonstrating a 15 cm compressive midline neck teratoma. Concern for failure of ex utero intrapartum treatment to airway was high. The addition of the ex utero intrapartum treatment to extracorporeal membrane oxygenation procedure provided time for the planned subsequent resection of the mass and tracheostomy. CONCLUSION: Ex utero intrapartum treatment procedures allow for securement of the difficult neonatal airway, while maintaining a supply of oxygenated blood to the newborn. Ex utero intrapartum treatment circulation lasts on average less than 30 minutes. The arrival of extracorporeal membrane oxygenation has enabled the survival of neonates with disease processes previously incompatible with life.

Prenatal MRI of neck masses with special focus on the evaluation of foetal airway.

BACKGROUND: Prenatal magnetic resonance imaging is the best tool to visualize foetal airway. OBJECTIVE: To evaluate the performance of MRI in the assessment of foetal airway status in the presence of a neck mass. MATERIALS AND METHODS: Two paediatric radiologists with 12- and 2-year experience in foetal imaging retrospectively analysed 23 foetal MRI examinations, performed between 2001 and 2016, after a second-level ultrasound suspicious for presence of a neck mass. Postnatal imaging, postoperative report, histology, autopsy, and clinical outcomes were the reference standard to calculate sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of prenatal MRI in detecting airway patency. We used the Cohen к statistics to estimate the interobserver agreement. We also assessed MRI performance in the diagnosis of the mass nature. RESULTS: We obtained data about postnatal airway status in 19 of 23 patients; prenatal MRI demonstrated a sensitivity of 9/9 [100%, 95% confidence interval (CI) 66-100%], specificity 8/10 (80%, 44-98%), accuracy 17/19 (89%, 67-99%), PPV 9/11 (82%, 48-98%), and NPV 8/8 (100%, 63-100%); the interobserver agreement was perfect. Prenatal MRI correctly identified 21 of 23 masses (к = 0.858); the interobserver agreement was almost perfect (к = 0.851). CONCLUSION: Prenatal MRI demonstrated high accuracy in assessing foetal airway status and diagnosing mass nature, allowing proper delivery planning.

Locating the Level and Extent of Congenital High Airway Obstruction: Fluid in the Airway Tract as Reference Points.

Described here are a series of four cases of congenital high airway obstruction in the fetus. All of the patients presented in the second trimester and all had hydrops fetalis. Three cases had bilateral hyperinflated lungs, midline shift of heart, flattening or inversion of the diaphragm, and fetal ascites. Autopsy was performed in one of these three and showed laryngeal atresia. In one fetus, there was only a unilateral huge enlargement of the lung with mediastinal shift. On autopsy, this fetus had atresia of right main bronchus. All parents had terminated the pregnancy following the prenatal diagnosis. Laryngeal atresia is an extremely rare fetal anomaly with dismal prognosis. It is important to differentiate the condition from other lesions with a more favorable prognosis, such as congenital adenomatoid malformation of the lung. Much research is needed in the future to explore the therapeutic options, including fetoscopic intervention or transplantation of stem cell-derived airways.

Effects of tracheal occlusion with retinoic acid administration on normal lung development.

INTRODUCTION: Tracheal occlusion (TO) is an investigational therapy for severe congenital diaphragmatic hernia that decreases pulmonary hypoplasia, but sustained TO also induces deficient surfactant synthesis. Intramuscular maternal administration of retinoic acid (RA) in a surgical rabbit model of congenital diaphragmatic hernia showed a beneficial effect on lung maturation. We evaluated the potential of RA delivery into the trachea and studied the combined effects of TO and RA on normal lung development. METHODS: Experiments were performed on normal rabbit fetuses. Liposomes and capric triglyceride (Miglyol® ), alone and with RA, were administered in the trachea just before TO (d26). Lung morphology and surfactant production were studied at term (d30). RESULTS: Tracheal occlusion increased lung weight and enhanced alveolar development but increased apoptotic activity and decreased surfactant expression. Tracheal injection of RA improved surfactant production to levels of normal controls. CONCLUSION: We established the potential of liposome and Miglyol as RA vehicle for delivering this bioactive molecule in the fetal airways. Tracheal RA injection seems to oppose the effects of TO in fetuses with normal lungs. © 2017 John Wiley & Sons, Ltd.

Fraser syndrome: features suggestive of prenatal diagnosis in a review of 38 cases.

OBJECTIVE: Fraser syndrome (FS) is a rare malformation recessive disorder. Major criteria are cryptophtalmos, syndactyly, respiratory, genital and urinary tract anomalies. Few prenatal presentations have been reported. METHOD: We analyzed the prenatal and postnatal fetal phenotype in 38 cases of FS, including 25 pregnancy termination cases, 8 intra-uterine death cases and 4 cases that died after birth. RESULTS: Including both prenatal and postnatal fetal phenotypic evaluation, all cases presented dysmorphic features with nose and ear dysplasia. Renal anomalies and syndactyly were present in 37/38 cases, cryptophtalmos in 36/38, airways anomalies in 30/37 and genital anomalies in 30/35 cases. Anomalies of the abdominal wall such as low set umbilicus and omphalocele were found in 31 cases. Among the 26 cases for which ultrasound data were available, detectable anomalies included oligohydramnios (22), ascites/hydrops (9), renal anomalies (20), evidence for high airways obstruction (11), ophthalmologic anomalies (4), ear dysplasia (2) and syndactyly (2). CONCLUSION: This study shows that the postnatal phenotype of FS is very specific, whereas oligohydramnios hampers the prenatal recognition of the cardinal FS diagnosis criteria. Association of oligohydramnios, kidney agenesis and CHAOS should lead to consider this diagnosis. © 2016 John Wiley & Sons, Ltd.

Treatment of a Fetal Tracheal Obstruction by Fetoscopy and Laser.

We report below a case of in utero tracheoscopy with laser collapse of a bronchogenic cyst obstructing the fetal trachea. The patient was referred for ultrasonography at 24 weeks of gestation because of fetal hydrops. Tracheoscopy was performed via fetoscopic approach using a single trocar under local anesthesia with lidocaine and ultrasound guidance. This revealed an image suggestive of a cyst obstructing the middle third at the anterior base of the trachea. Coagulation using a diode laser enabled us to collapse this fluid-filled cyst with three 10-watt bursts (3 times 3 s) and to visualize a completely unobstructed tracheobronchial tree with significant pulmonary fluid reflux on removal of the obstacle. The fetal condition improved markedly within 48 h after the procedure. To the best of our knowledge, this is the first described case of in utero treatment of a tracheal obstruction by tracheoscopy and laser. In severe cases of obstruction of the fetal airways, whether the obstacle is situated in a high or low position, fetal endoscopy is of diagnostic and potentially therapeutic utility.

Experimental fetal endoscopic tracheal occlusion in rhesus and cynomolgus monkeys: nonhuman primate models.

OBJECTIVE: The monkey model is the best model to investigate some physiological response to the fetal transitory tracheal occlusion but it has never been described in Macaca monkeys. The aim of this study was to evaluate the feasibility of fetal endoscopic tracheal occlusion (FETO) in a non-human primate model. METHODS: Pregnant rhesus monkeys and cynomolgus were tested as a potential experimental model for FETO in the third trimester of pregnancy, by performing fetal tracheoscopies with and without tracheal occlusion. RESULTS: A total of 22 pregnancies were followed in 16 monkeys and underwent fetal surgery. Percutaneous endoscopic access to the uterine cavity was possible in 20 cases (91%). Of these 20 pregnant monkeys, fetal tracheoscopy could be achieved in 15 cases (75%). In rhesus monkeys, the time between the onset of endoscopy and tracheal penetration decreases as operator experience increases. Neither maternal morbidity nor mortality was related to surgery. Two fetal losses were possibly due to the procedure. CONCLUSION: FETO is feasible in the non-human primate, which closely reflects procedures in humans. The non-human primate model for FETO, specially the rhesus monkeys, may be useful for future studies concerning the mechanisms related to the lung growth after transitory fetal tracheal occlusion.

Long-term outcomes after fetal therapy for congenital high airway obstructive syndrome.

BACKGROUND/PURPOSE: Congenital high airway obstructive syndrome (CHAOS) is a rare and devastating condition that is uniformly fatal without fetal intervention. We sought to describe fetal treatment and long-term outcomes of CHAOS at a single referral center. METHODS: The medical records of patients with fetal CHAOS evaluated at our center between 1993 and 2011 were reviewed. Maternal history, radiographic findings, antenatal management, and postnatal outcomes were compared. RESULTS: Twelve fetuses with CHAOS were identified. Eleven had concomitant hydrops at diagnosis. Six were electively terminated, and 2 had intra- or peripartum demise. Four patients underwent fetal intervention. Two underwent delivery via ex utero intrapartum treatment (EXIT) procedure with tracheostomy placement only, and 2 underwent fetal bronchoscopy with attempted wire tracheoplasty followed by EXIT with tracheostomy at delivery. All 4 patients who underwent EXIT were alive at last follow-up. One patient was ventilator and tracheostomy free and feeding by mouth. CONCLUSION: Long-term and tracheostomy-free survival is possible with appropriate fetal intervention even in the presence of hydrops. Fetal intervention earlier in pregnancy may improve long-term outcomes, but patient selection for intervention remains challenging. Magnetic resonance imaging may help select those patients for whom fetal intervention before EXIT delivery may be beneficial.

Ex utero intrapartum treatment in the management of giant cervical teratomas.

PURPOSE: The purpose of this study is to present the outcome and technical details of the Ex Utero Intrapartum Treatment (EXIT) procedure performed in the management of the fetus with a giant cervical teratoma. METHODS: A retrospective review of the medical records of patients undergoing the EXIT procedure between September 1995 and September 2010 was performed. RESULTS: Eighty-seven EXIT procedures were performed. In 20% of cases (17/87), the indication was giant cervical teratoma. There were 10 females and 7 males. Polyhydramnios was present in 82%. Median gestational age at EXIT was 35 weeks (range, 30-39 weeks). Median birth weight was 2.5 kg (range, 1.7-3.7 kg). Access to the airway under placental support was established in all cases via direct laryngoscopy/bronchoscopy in 8 patients (47%) and via surgical exploration (tracheostomy or retrograde intubation) in 9 patients (53%). The mortality rate under placental support was zero. Seven patients had the tumors resected immediately after the EXIT, 6 patients had the resection later, and 4 patients died before resection. The neonatal mortality rate was 23% (4/17 patients). Patients who died had severe pulmonary hypoplasia that resulted from the upward traction by the giant cervical mass on the airway and compression of the lungs against the thoracic apex. CONCLUSIONS: We conclude that the EXIT procedure continues to be the optimal delivery strategy for patients with prenatally diagnosed giant cervical teratomas and potential airway obstruction at birth. A thorough evaluation of the prenatal images and an experienced multidisciplinary team are key factors for an effective approach to the obstructed fetal airway.

CHAOS in the mirror: Ballantyne (mirror) syndrome related to congenital high upper airway obstruction syndrome.

In the mirror syndrome, maternal edema mirrors fetal edema. The pathogenesis is unknown. The most common etiologic associations are rhesus isoimmunization, twin-twin transfusion syndrome, and viral infections. Less than 10% of reported cases are associated with congenital anomalies. We report a case due to congenital laryngeal stenosis, which also caused congenital high airway obstruction syndrome (CHAOS), characterized by pulmonary hyperplasia and edema or anasarca, related to airway abnormality. The fetal manifestations of the mirror syndrome and CHAOS overlap, but occurrence of the two in the same patient does not seem to have been reported.

Fetal tracheolaryngeal airway obstruction: prenatal evaluation by sonography and MRI.

We reviewed the sonographic and MRI findings of tracheolaryngeal obstruction in the fetus. Conditions that can cause tracheolaryngeal obstruction include extrinsic causes such as lymphatic malformation, cervical teratoma and vascular rings and intrinsic causes such as congenital high airway obstruction syndrome (CHAOS). Accurate distinction of these conditions by sonography or MRI can help facilitate parental counseling and management, including the decision to utilize the ex utero intrapartum treatment (EXIT) procedure.

Congenital high airway obstruction syndrome due to complete tracheal agenesis: an accident of nature with clues for tracheal development and lessons in management.

Congenital high airway obstruction syndrome (CHAOS) is a life-threatening condition characterized by complete blockage of the fetal airways associated with hydrops. We present a case of CHAOS due to the rare cause of complete tracheal agenesis. The ex utero intrapartum therapy (EXIT) strategy was employed to allow for neck and mediastinal exploration. Thymectomy allowed dissection to the level of the carina demonstrating the confluence of dilated mainstem bronchi but no trachea and no connection to the esophagus. A 2.5 endotracheal tube was inserted into the right mainstem bronchus and secured to the left clavicle. At 3 months of age, the infant succumbed to sepsis from Enterobacter mediastinitis due to friction between the tracheostomy tube and the nasogastric tube resulting in erosion of the esophagus. Complete tracheal agenesis, as seen in this case, is consistent with the failure of normal tracheal elongation as suggested by newer theories of foregut development. This case illustrates the most severe form of tracheal atresia causing CHAOS ever salvaged by the EXIT procedure at birth. The subsequent postnatal course highlights the need for early tracheal replacement in this particularly challenging form of CHAOS.

[EXIT procedure in the management of severe foetal airway obstruction. the paediatric otolaryngologist's perspective]. / Procedimiento EXIT en el manejo de fetos con severo compromiso respiratorio. La perspectiva del otorrinolaringólogo pediátrico.

The ex-utero intrapartum treatment (EXIT) procedure is a technique designed to allow partial foetal delivery via caesarean section with establishment of a safe foetal airway by either intubation, bronchoscopy, or tracheostomy while foetal oxygenation is maintained through utero-placental circulation. The most common indication for the EXIT procedure is the presence of foetal airway obstruction, which is usually caused by a prenatal diagnosed neck mass. We report three cases of head and neck tumours with airway obstruction treated by means of EXIT and with different solutions in the management of the airway. With the involvement of Paediatric Otolaryngologists in EXIT, new indications and select variations from the standard EXIT protocol should be considered.

The transcription factor MEF2C is required for craniofacial development.

MEF2 transcription factors are well-established regulators of muscle development. We have discovered an unanticipated role for MEF2C in the neural crest, where tissue-specific inactivation results in neonatal lethality due to severe craniofacial defects. We show that MEF2C is required for expression of the Dlx5, Dlx6, and Hand2 transcription factor genes in the branchial arches, and we identify a branchial arch-specific enhancer in the Dlx5/6 locus, which is activated synergistically by MEF2C and Dlx5, demonstrating that these factors interact to induce transcription. Mef2c and Dlx5/6 also interact genetically. Mice heterozygous for either Dlx5/6 or Mef2c are normal at birth and survive to weaning. By contrast, heterozygosity for both Mef2c and Dlx5/6 results in defective palate development and neonatal lethality. Taken together, the studies presented here define a feed-forward transcriptional circuit between the MADS-box transcription factor MEF2C and the homeodomain transcription factors Dlx5 and Dlx6 in craniofacial development.

Fetal laryngeal stenosis/atresia and congenital high airway obstructive syndrome (CHAOS): a case report.

Congenital high airway obstructive syndrome (CHAOS) is a rare but fatal disease with predictably characteristic features including stenotic or atretic upper airway, hyperplastic lungs, elevated diaphragm, massive fetal ascites and fetal hydrops. Diagnosis of CHAOS by ultrasound scan is possible and clinically important since advanced intrauterine surgery to correct the defect is possible. We report a case of fetus of CHAOS with massive ascites, pulmonary hyperplasia and laryngeal stenosis/atresia. We feel that it is important to recognize the entity both by ultrasound scan and by the pathologist so that some cases can be corrected by intrauterine fetal surgery.