Fetal Therapy, EXIT Procedure and Neonatal Surgery for Congenital High Airway Obstruction Syndrome: A Successful Sequential Management of a Fetus with Congenital Laryngeal Atresia

Introduction Congenital laryngeal atresia (CLA) is one of the primary etiologies of congenital high airway obstruction syndrome (CHAOS), and it is a rare malformation with an extremely high neonatal mortality rate. The core cause of neonatal death lies in the failure of airway establishment after birth. Although some medical institutions can perform intrapartum tracheotomy to establish the airway, the obstruction of the upper airway will still lead to the retention of pulmonary fluids, which in turn causes overdistension of the fetal lungs and airways, and induces diaphragmatic reversal and even fetal hydrops. Eventually, it results in severe pulmonary hypoplasia and diaphragmatic dysfunction, thus keeping the neonatal mortality rate persistently high. The whole-process management including fetal therapy, the EXIT procedure and neonatal surgery remains challenging, but offers the possibility of fetal salvage and good long-term outcomes. Patient history A 30-year-old female (G2P0) underwent successful IVF-ET and underwent regular prenatal care. At 24 weeks of gestation, a routine systemic ultrasonography at a local hospital revealed a dilated trachea, increased bilateral lung volume, and a flattened diaphragm. Congenital High Airway Obstruction Syndrome (CHAOS) was highly suspected. Subsequent amniocentesis, including chromosome analysis and whole-exome sequencing, revealed no abnormal findings. At 28 weeks of gestation, fetal MRI, performed without contrast material owing to pregnancy, identified an obstruction in the laryngeal region, a flattened diaphragm, and a dilated trachea and main bronchus. The trachea measured 4.8 mm in diameter (Supplementary Fig. 1, https://links.lww.com/MFM/A116). At 30 weeks of gestation, re-evaluation using ultrasound showed that diaphragmatic flattening and tracheal dilation had worsened, and the diameter of the trachea had increased to 6.8 mm. Fetal ascites was also detected (Supplementary Fig. 2, https://links.lww.com/MFM/A116). This study was approved by the Medical Ethics Committee of Women and Children’s Hospital of Chongqing Medical University (2021YL018-01). Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Treatment Fetal therapy procedure After obtaining detailed informed consent from the family, fetoscopy was performed at 31 weeks and 2 days (31+2) of gestation. Maternal regional anesthesia and fetal intramuscular anesthesia (fentanyl 1 µg/kg and vecuronium 0.1 mg/kg) were administered. Under real-time ultrasound guidance, a fetoscopic sheath loaded with a sharp obturator (KARL STORZ 11540 KE) was inserted into the amniotic cavity in the placenta-free area. After the obturator was withdrawn, a fetoscope (STORZ 11540AA) was introduced and directed into the fetal oral cavity. Although the fetal epiglottis was identified, the glottic fissure and trachea could not be exposed, confirming laryngeal atresia. Fetoscopic laser ablation was successfully performed for fetal laryngeal surgical recanalization using a 30 W laser power setting (continuous mode, Dornier MediLas D60, diode 940 nm, fiber optic diameter 600 μm) (Supplementary Fig. 3, https://links.lww.com/MFM/A116). On postoperative ultrasound, a 0.2-cm-wide anechoic strip, which extended to the trachea, was visible in the fetal larynx, and the amniotic fluid depth had decreased from 8.2 to 5.6 cm. MRI re-examination on postoperative day three revealed that the main airways were no longer dilated, and the bilateral diaphragm was curved into the thorax (Supplementary Fig. 4, https://links.lww.com/MFM/A116). The fetal ascites resolved within two weeks post-surgery. EXIT procedure and tracheotomy Preterm membrane rupture occurred at 34+5 weeks of gestation, and EXIT was performed at 35 weeks of gestation under maternal general anesthesia (inhalation of sevoflurane 2.5%–3.5%; fentanyl 4 μg/kg, continuous infusion of remifentanil 4–5 ng/ml; vecuronium 0.15 mg/kg), which inhibited uterine contractions. During a lower-segment Cesarean section, only the head and shoulders of the fetus were initially delivered, and placed in a supine position. The status of the placenta, along with cord hemodynamic parameters, was monitored by real-time ultrasound. Intubation was attempted twice but failed because of tracheal stenosis. A pediatric otolaryngologist immediately performed a tracheotomy and tracheal intubation. Successful tracheotomy was completed eight minutes after head delivery (Supplementary Fig. 5, https://links.lww.com/MFM/A116). Following tracheal intubation, a male baby was delivered with a birthweight of 2150 g. The Apgar scores were 3, 6, and 7 points after delivery. The newborn was immediately transferred to the neonatal intensive care unit for further treatment. Neonatal surgery The newborn infant was initially provided ventilatory support using a combination of synchronized intermittent mandatory ventilation (SIMV), positive end-expiratory pressure (PEEP), and volume guarantee (VG) mode. The initial parameters were: FIO2 30%, PIP/PEEP:16–18/5 cm H2O, RR 40 bpm, and VG 5 ml/kg. Analgesia was maintained with fentanyl (1 µg/kg per hour). After one week of mechanical ventilation, the infant was weaned off support (FIO2 21%, PIP/PEEP 13–14/3–4 cm H2O, RR 15–20 bpm, VG 4 ml/kg), and spontaneous breathing was established with an artificial nose. A neck computed tomography assessment revealed no aerated development in the epiglottis, and laryngoscopy confirmed re-adhesion at the laryngeal region. The epiglottis injury was likely caused by the previous laser ablation (Supplementary Fig. 6, https://links.lww.com/MFM/A116). After 23 days of hospitalization in the neonatal intensive care unit, the baby demonstrated stable spontaneous breathing and adequate feeding. The baby subsequently received a laryngeal atresia incision, balloon dilation, and laryngeal stent implantation in the Department of Otolaryngology, Children’s Hospital of Chongqing Medical University. An appropriate silicone T-tube was inserted (Supplementary Fig. 7, https://links.lww.com/MFM/A116). At the age of one year, the T-tube was removed. Examination revealed a 5-mm ventilation hole in the glottic area, a small residual epiglottic root, and improved tracheomalacia. After closure of the stoma, the child had no dyspnea, could move normally, and had weak airflow speech. Follow-up Re-examination via laryngoscopy at the age of two years revealed that the child had vocal cord problems (Supplementary Fig. 8, https://links.lww.com/MFM/A116). Pulmonary function assessment at 19 months indicated a moderate obstructive lesion (TV 11.9 ml/kg, TPF/TE 19%, VPF/VE 23.6%). Voice evaluations conducted at four years of age using the GRBAS (grade, roughness, breathiness, asthenia, strain) score system showed a severe voice disorder (G3R3B3A3S2). The patient’s parents expressed deep gratitude and satisfaction with the overall outcome. Discussion CHAOS is an extremely rare developmental malformation, with an incidence of approximately 1 in 20,000 births. The main etiologies include laryngeal atresia, laryngeal web, and airway atresia. Due to the failure of airway establishment after birth, coupled with severe pulmonary hypoplasia and diaphragmatic dysfunction, the mortality rate among neonates is strikingly high.1 Prenatal ultrasound is the most economical and convenient method for CHAOS screening and diagnosis. This condition is often highly suspected based on characteristic ultrasound findings, such as increased bilateral lung volume, tracheal dilatation, and a decreased cardiothoracic ratio. Severe cases of CHAOS can present with fetal hydrops, manifesting as fetal pleural and ascitic fluids. MRI serves as a more important supplementary examination compared with ultrasound, as it provides an accurate assessment of the location of airway obstruction, the degree of tracheal dilatation, and the morphology of the diaphragm.2,3 Despite significant advancements in neonatal surgical techniques and neonatal intensive care unit treatment capabilities, the mortality rate associated with CHAOS remains persistently high. The EXIT procedure represents a crucial and life-saving method for airway establishment immediately after birth in cases of congenital high airway obstruction.4,5 However, the success of EXIT requires smooth multidisciplinary collaboration. This procedure is performed under maternal general anesthesia, with uterine relaxation maintained to prevent placental abruption due to uterine contractions.6 This measure preserves the placental blood supply and facilitates the ability of otolaryngologists to perform a tracheotomy for airway establishment. If placental perfusion is poorly maintained or the tracheotomy is prolonged, it can lead to neonatal asphyxia and hypoxia. In this case, the low Apgar scores of the neonate were considered to be a direct result of the extended time taken to establish the airway. This delay was due to the failed intubation attempts stemming from tracheal stenosis and epiglottic re-adhesion. Meanwhile, intraoperative ultrasound can only roughly assess indicators such as umbilical blood flow and fetal heart rate, and cannot accurately reflect the fetal perfusion status during the procedure. For fetuses with high airway obstruction complicated by fetal hydrops, although the EXIT procedure can establish the airway, the main causes of neonatal death are severe ventilatory and circulatory dysfunction after birth. These impairments result from lung overexpansion, diaphragmatic reversal, and cardiac compression. Fetal therapy, involving incision at the obstruction site to allow the outflow of pulmonary fluids, reduces the persistent high pressure in the fetal lungs, thereby lowering the risk of pulmonary hypoplasia. Fetoscopic laser ablation for recanalization is a therapeutic option for CHAOS complicated by fetal hydrops.7 However, any intrauterine fetal intervention remains extremely challenging. Subglottic stenosis (SGS) and vocal cord abnormality are common complications after airway reconstruction. Recently, the evolution of balloon dilatation of the airway has led to it being an invaluable adjunct for managing SGS, reducing the need for open airway reconstruction.8,9 In the present case, subglottic stenosis was observed after the initial resection of the laryngeal atresia. Balloon dilatation followed by placement of a T-tube stent was selected as the management strategy, yielding favorable postoperative results. Furthermore, as most CHAOS cases have vocal cord abnormalities, this baby received continued voice rehabilitation training. Conclusion The comprehensive management of CHAOS is still challenging. This case report indicated that a combination of fetal therapy, the EXIT procedure, and neonatal surgery may improve the prognosis of CHAOS. Successful sequential management of this condition requires the close, seamless collaboration of multiple disciplinary teams. Acknowledgements The authors would like to thank the child and her parents for their cooperation with this study. Funding The present study was supported by funding from the National Key Research and Development Program of China (grant no.2023YFC2705904). Author Contributions Xingbo Tian, Bingshan Xia, and Jia Liang designed the structure and drafted the paper. Qiaoli Yang and Xiaohang Zhang provided the accurate data, Xinye Tang revised the paper, and Gongli Chen was in charge of the final review and editing of the paper. All authors contributed to critical revision of the manuscript for important intellectual content and approved the final version before submission. Conflicts of Interest None. Data Availability All data generated or analyzed during this study are included in this published article.