Fetal Surgery for Congenital High Airway Obstruction

Congenital high airway obstruction syndrome (CHAOS) is defined by complete or near-complete obstruction of the fetal airway. The term was first used by Hedrick et al in a description of four fetuses with upper-airway obstruction and a constellation of ultrasonographic (US) findings considered incompatible with survival (eg, echogenic large lungs, flattened or inverted diaphragm, and dilated tracheobronchial tree). ^{[1, 2, 3]}  CHAOS remains a rare antenatal diagnosis but is no longer universally fatal; with better antenatal and perinatal management, outcomes have improved. Because many fetuses with CHAOS die in utero or are stillborn, the true incidence is unknown and probably underestimated. ^{[4, 5, 6, 7]}

As the name suggests, CHAOS results from obstruction of the upper airway and is thought to occur when the upper airway fails to recanalize around week 10 of gestation. ^{[1, 3]}  Fluid secreted by the fetal lung is typically cleared through the larynx, and obstruction of the upper airway prevents evacuation of this fluid; this represents the pathophysiology behind CHAOS. ^[8]  

Secretions accumulate in the bronchopulmonary tree and cause hyperinflation of the lungs and secondary proliferative lung growth. Excessive distention of the lungs, in turn, leads to an increase in the intrathoracic pressure, which results in flattening and, sometimes, eversion of the diaphragms with compromised venous return and cardiac output. This can lead to fetal cardiac failure with resultant ascites, placentomegaly, and, eventually, nonimmune fetal hydrops. It is noteworthy that hydrops is better tolerated by patients with CHAOS than by those with other congenital abnormalities associated with hydrops.

Upper-airway obstruction may occur at the level of the larynx (laryngeal atresia, rings, webs, or cysts) or along the trachea (tracheal agenesis, rings, webs, and stenosis or subglottic stenosis). Laryngeal atresia is the most common cause of CHAOS. Tracheal agenesis may be complete or partial, and a concurrent tracheoesophageal fistula (TEF) may be present ^[9] . If a TEF is present, lung fluid can pass into the esophagus and stomach, and lung pressure can remain normal. Oropharyngeal masses are another cause of CHAOS. ^[10]

The presence of other congenital anomalies suggests that CHAOS may occur as part of a syndrome or association—for example, Fraser syndrome, VACTERL association (Vertebral anomalies, Anal atresia, Cardiac anomalies, Tracheal anomalies, Esophageal atresia, Renal and Limb anomalies), or TACRD association (Tracheal Agenesis, Cardiac, Renal, and Duodenal malformations). Fraser syndrome is a congenital disorder characterized by ambiguous genitalia, urinary tract anomalies, cryptophthalmos, and syndactyly. ^[11]  The literature is scant, but a 2016 study by Tessier et al suggested that approximately 40% of neonates diagnosed with Fraser syndrome had evidence of CHAOS before birth. ^[12]

CHAOS is most commonly diagnosed in the second trimester by US, but it has been diagnosed as early as week 12 of gestation. ^[9]  It is suggested by large echogenic lungs, dilated airways, flattened or everted diaphragms, ascites, and, possibly, fetal hydrops. ^{[9, 3]}  Whereas antenatal US can identify the location of upper-airway obstruction, the cause of the obstruction is often unclear. ^[3]  Fetal magnetic resonance imaging (MRI) can be performed to further delineate the level of obstruction and to help exclude extrinsic causes of obstruction and has been noted to be superior to US. ^[13]  

Historically, intrauterine fetal demise (IUFD) was uniform in the presence of CHAOS, but with the advent of the ex-utero intrapartum treatment (EXIT) procedure, survival rates have drastically improved. ^{[14, 15, 16, 17, 3, 18, 19, 10, 20, 21, 22]}  The EXIT approach preserves fetal uteroplacental circulation so as to allow time for an airway to be established. After establishment of a secure airway and postnatal recovery, laryngeal or tracheal reconstruction is generally planned as an elective procedure at a later age. ^[3]

The natural history of CHAOS is grim, with only one patient in 48 reported cases surviving the disease in the pre-EXIT era. ^[1] . Reliable airway patency diagnosis is crucial for selection and planning of an EXIT delivery, ^[23]  and antenatal diagnosis is vital for any successful perinatal management. ^[24]  EXIT-to-airway delivery is therefore recommended for all viable fetuses with an antenatal diagnosis of CHAOS in the absence of contraindictations (see Contraindications). Rare instances of survival without an EXIT delivery have been described among patients with a concurrent TEF; the TEF provides a passage for evacuation of pulmonary secretions. ^[25]

In selected patients who present with life-threatening hydrops and short-segment lesions or webs, fetoscopy with wire tracheoplasty ^[26] or laser interventions ^{[2, 27, 28, 29, 30]} may be beneficial. Determining which patients are more likely to benefit from fetoscopic intervention poses a challenge, and this procedure is typically reserved for fetuses who present with hydrops early in pregnancy (ie, 17-30 weeks’ gestation).

Because patients with CHAOS seem to tolerate hydrops better than those with other disease processes, expectant management is generally preferred for those who present later in the third trimester until an EXIT-to-airway delivery can safely be performed. 

Given the complexity of in-utero management of CHAOS and the challenges of managing the difficult airway at birth, it is recommended that these cases be referred to and managed at a fetal care center. ^{[31, 32]}

Contraindications for fetal intervention may be either maternal or fetal in origin.

Maternal contraindications include the following:

• Frequent contractions
• Membrane rupture
• Short cervix
• Uncontrolled comorbidities that may predispose the patient to preeclampsia or HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome
• Maternal morbidity warranting cesarean section with immediate tracheostomy instead of an EXIT delivery

Fetal contraindications include the following:

• Multiple fetal anomalies
• Significant chromosomal abnormalities
• Complete or near-complete tracheal agenesis
• Anatomic restrictions that may prohibit safe access

Options for fetal intervention

An EXIT-to-airway delivery procedure is the most common fetal intervention for CHAOS. The authors' current practice is to offer an EXIT delivery for all viable fetuses with an antenatal diagnosis of CHAOS in the absence of contraindictations. The EXIT procedure can also be used in conjunction with fetoscopic intervention, as described below. Some research suggests the possibility that early fetoscopic interventions may allow avoidance of an EXIT delivery and its associated maternal morbidity; however, outcome data are limited.  

Fetal wire tracheoplasty is considered early in pregnancy, but it is a challenging procedure that requires considerable preoperative planning. The procedure is performed fetoscopically under US guidance to avoid placental injury. (See the image below.) A stiff guide wire is passed through the side port of the fetoscope, with subsequent puncture through a membrane or short segment of tracheal atresia. Fetal lie is a critical consideration because a direct path is required for introduction of the fetal bronchoscope and guide wire; if fetal head orientation is unfavorable, the procedure can be challenging, if not impossible. In reported cases, patients who underwent this procedure later underwent EXIT-to-airway delivery. ^[26]  

Fetoscopic laser interventions have also been described for management of CHAOS. ^{[2, 27, 28, 29, 30]} Fetoscopic laser laryngotomy has been used to create small openings in the laryngeal membrane to allow decompression of fetal lung fluid; long-term survival was reported in one third of cases in one small series. ^[2]

Fetoscopic laser perforation of a tracheal obstruction has also been described. In one case, an isolated tracheal web leading to complete airway occlusion was perforated by means of fetoscopic laser intervention, which resulted in rapid normalization of lung size, resolution of hydrops, and a term delivery of a well infant who did not require any respiratory support. ^[27] In another case of CHAOS, a fetus with hydrops underwent fetoscopic laser perforation of the tracheal obstruction followed by EXIT delivery with tracheostomy, which resulted in long-term survival. ^[28]

One case report described diagnosis of laryngeal stenosis via fetoscopic evaluation at 32 weeks, followed by balloon dilation and stent placement; an EXIT procedure was avoided, and maternal morbidity was thus decreased. ^[33] Preterm contractions developed on postoperative day 7 with persistent signs of CHAOS on US, prompting repeat fetoscopy confirming a patent fetal airway, followed by cesarean delivery under neuraxial anesthesia. Subsequent attempts to intubate through the tracheal stent were limited; the stent was removed, and a tracheostomy was immediately performed for long-term airway management. Laryngeal stenosis with a small TEF was confirmed by direct laryngoscopy and bronchoscopy. 

Another case report described fetoscopy-assisted percutaneous needle decompression of the distal trachea and lung in a 25-week fetus with CHAOS due to laryngeal atresia and associated hydrops. ^[34] Fetal laryngoscopy confirmed fusion of the vocal cords, and the atretic segment could not be intubated. The fetoscope was then used to stabilize the head and neck while percutaneous US-guided needle drainage of the cervical trachea through the anterior fetal neck was performed; 17 mL of viscous fluid was removed, resulting in immediate lung decompression. Hydrops subsequently resolved, and the patient was delivered via an EXIT procedure at 30 weeks' gestation. 

Yet another case report described successful management of CHAOS due to isolated laryngeal atresia by means of intact cord resuscitation. ^[35] In this patient, tracheostomy was performed successfully under local anesthesia within 5 minutes of spontaneous vaginal delivery at 38 weeks' gestation, while the umbilical cord remained attached to the placenta. This infant had supraglottic stenosis on computed tomography (CT). In contrast to the EXIT procedure, intact cord resuscitation does not preserve uteroplacental gas exchange, as uterine contraction and the start of placental separation are present. ^[36]

Procedural planning

The EXIT procedure requires careful planning with a multidisciplinary team, typically including two pediatric/fetal surgeons, one obstetrician specializing in maternal fetal medicine, one neonatologist, one pediatric cardiologist, one ultrasonographer, and one nurse scrub.

Complication prevention

Appropriate anesthesia and tocolytics are important for preventing uterine contractions and placental separation. Uterine atony can lead to diffuse bleeding, and a special uterine stapler (uterine stapler with absorbable staples [US Surgical Corporation, Norwalk, CT]) can reduce the risk of hemorrhage during the EXIT procedure.

Survival is contingent upon early antenatal diagnosis, close antenatal follow-up, and fetal or immediately postnatal intervention. Whereas a few fetuses with CHAOS have been saved by emergency tracheostomy immediately after delivery, it is the implementation of the EXIT procedure for this rare condition that has dramatically improved survival. ^{[3, 14, 15, 16, 18, 19, 10, 20, 21, 37]}  

Case series have supported the assertion that long-term survival and tracheostomy-free survival are possible. ^[26]  It must be kept in mind, however, that although EXIT-to-airway delivery has significantly improved survival, this strategy by itself serves only to stabilize those fetuses who survive to delivery. Consequently, there is a push to develop management strategies that address this diagnosis earlier in fetal development (eg,  the various fetoscopic interventions described earlier). 

CHAOS occupies a significant spectrum of severity, secondary to the sequence of events set in motion by fetal airway obstruction that can ultimately lead to fetal demise. Early presentation with hydrops or associated anomalies portends a poor prognosis despite performance of the EXIT procedure ^{[3, 2]} ; however, there have been reported cases of fetuses with CHAOS, associated hydrops, and additional congenital anomalies who underwent fetal intervention and had long-term survival. ^[26]  Nonetheless, outcomes in cases of isolated CHAOS without hydrops are more favorable and frequently require shorter periods of postnatal ventilator support. ^{[3, 2]}

Despite remarkable progress in CHAOS management, tracheostomy dependence and speech impairments are to be expected.