| Airway physiology |
The larynx connects the pharynx to the trachea and esophagus. This complex structure is composed of the supraglottis (which includes the arytenoid cartilages and epiglottis), the glottis (composed of the false and true vocal folds), and the subglottis (i.e., the opening to the trachea). Normally, the epiglottis rests vertically and the vocal cords are abducted, allowing free flow of air through the glottis.
During the swallowing phase, the pharynx rises, causing the epiglottis to close over the glottis while the vocal cords adduct, preventing particles from entering the trachea. During phonation, air moves through the larynx and vibrates the vocal cords in adduction.
The radius of the upper airway is one of the most important factors contributing to airway resistance and airflow. According to Poiseuille’s law, a decrease in airway radius causes an exponential increase in resistance, resulting in the need for a much greater pressure gradient to maintain sufficient airflow.
The body compensates by using accessory muscles, which clinically presents as increased work of breathing. Turbulent airflow due to obstruction (i.e., decreased airway lumen), increased work of breathing, or an otherwise abnormal upper airway may cause inspiratory, expiratory, or biphasic stridor.
Inspiratory stridor occurs due to extrathoracic airway obstruction when intratracheal pressure falls below atmospheric pressure during inspiration, causing the upper airway to collapse.
Expiratory stridor occurs due to obstruction in the intrathoracic region when increased pleural pressure during expiration causes compression of the lower airways. In fixed lesions, such as laryngeal membranes, vascular rings, or vocal cord paralysis, stridor may be present during both phases of breathing (biphasic stridor).
| Clinical presentation |
Respiratory distress caused by a laryngotracheal abnormality may occur immediately after birth or have a more insidious onset.
The infant may present with cyanosis, tachypnea, or mild to severe retractions.
Babies with tracheal or laryngeal agenesis will not make a sound, while those with partial vocal cord paralysis may be hoarse and those with complete vocal cord paralysis will often have noisy breathing and weak crying.
Other signs and symptoms of upper airway anomalies in the neonate include episodes of recurrent bradycardia and cyanosis, aspiration, radiographic evidence of persistent atelectasis or lobar hyperinflation, persistent cough, feeding difficulties or growth retardation, signs of other congenital anomalies or dysmorphisms and repeated failed extubation attempts.
A high index of suspicion is required as these signs and symptoms can be broad and overlap with lung pathology.
Occasionally, prenatal ultrasound findings may indicate a laryngotracheal deformity. For example, findings of large echoic lungs and everted diaphragms with polyhydramnios may indicate obstruction of the trachea or larynx, which prevents normal outflow of fluid (as seen in congenital upper airway obstruction syndrome [SCOVAR]). . There may also be polyhydramnios due to compression of the esophagus due to dilation of the airways and/or obstruction of swallowing.
Obstruction may be due to a congenital mass or agenesis/stenosis of the larynx or trachea. Relevant sonographic features are often not evident until after 16 weeks of gestation.
“Pinhole” lesions can allow fluid to leak, causing an obstructive waxing and waning appearance of the lungs in utero and severe respiratory distress after delivery.
In patients with a mild or moderate degree of obstruction in the fetal period, the diagnosis may not be detected until affected infants develop postnatal respiratory distress. If identified prenatally, SCOVAR is best managed with an ex utero intrapartum treatment procedure, in which the airway is secured endoscopically or by tracheostomy while the child remains on placental support.2
| Diagnostic evaluation |
> Endoscopy
In flexible laryngoscopy, a flexible fiberoptic nasopharyngoscope is passed through the nasal cavity of an awake patient to visualize the pharynx and larynx. This procedure provides information on upper airway obstruction, dynamic collapse, and vocal fold mobility.
The view of the subglottis is often limited, especially in newborns, and the trachea is not examined.
Tracheobronchoscopy is performed by passing the same flexible instrument through a tracheostomy tube. Bronchoscopy and microdirect laryngoscopy are operative or sedated procedures that use a rigid telescope (Hopkins bar) or bronchoscope to evaluate the airway. This is the gold standard for evaluating the airway as it provides a comprehensive examination of the larynx, trachea, and bilateral main bronchi.
When combined with flexible laryngoscopy, most airway abnormalities can be diagnosed by endoscopy.
> Images
Although endoscopy can be used to diagnose most laryngotracheal abnormalities, chest computed tomography (CT) with angiography is useful to help delineate vascular anatomy (which may be compressing the airway). Newer high-resolution CT provides lower doses of radiation, making it a safer option for newborns.
Magnetic resonance imaging (MRI) provides significantly less radiation exposure and is another imaging option in neonates.
MRI offers better soft tissue delineation than CT, but CT is better at imaging denser tissues (eg, cartilage), is faster (potentially allowing imaging without sedation), and is cheaper. As such, CT is the most commonly used modality for laryngotracheal imaging.
Tracheobronchography is a rarely used imaging technique that provides dynamic evaluation of the airway. In tracheobronchography, a small volume of water-soluble nonionic contrast is injected into the airway and the baby is evaluated during spontaneous breathing with CT to look for signs of malacia.3
There are significant limitations to this imaging technique, and it has been gradually replaced by endoscopic evaluation.
> Swallowing evaluation
Swallowing assessment tools in newborns include videofluoroscopic assessment and flexible endoscopic evaluation of swallowing (EEFD). In EEFD, swallowing is evaluated while a flexible fiberoptic nasopharyngoscope is placed in the pharynx overlooking the larynx. Coloring may be placed in food or saliva to control the possibility of aspiration.
The benefit of EEFD is that it can be used in infants to observe secretion management in those with minimal or no oral intake and evaluate laryngeal structure simultaneously. However, swallowing assessment is limited to the oropharyngeal phase and there is a “washout” period during swallowing.
Videofluoroscopic swallowing study, although associated with radiation exposure, allows a complete evaluation of swallowing (from the oral phase to the esophageal phase) and can also be used to evaluate the effects of different milk consistencies.
| Laryngotracheal deformities |
Laryngotracheal deformities that occur in the neonatal period are often congenital and secondary to defects in embryogenesis.
However, acquired deformities can also occur in patients after airway instrumentation. Various laryngotracheal anomalies are described below based on the level of the upper airway, with their diagnostic, medical and surgical approaches.
> Supraglottic anomaly: Laryngomalacia
The most common cause of stridor in babies is laryngomalacia, which is the result of supraglottic collapse during inspiration. This collapse may be due to neuromuscular hypotonia and/or structural abnormalities. Laryngomalacia typically develops in the first 2 weeks after birth and is characterized by acute inspiratory stridor that worsens with feeding, agitation, and supine position.
Endoscopically, laryngomalacia is defined by redundant arytenoid tissue, shortened aryepiglottic folds, and an omega-shaped epiglottis. On inspiration, redundant tissue and epiglottis collapse into the glottis, causing obstruction.
Spontaneous resolution is common and usually occurs by 18 months of age. In severe cases (up to one-third of cases), affected babies may experience apneas or cyanotic episodes, growth retardation, or dysphagia requiring surgical intervention, such as a supraglottoplasty.4
> Glottal anomalies
Paralysis of the vocal cords. Vocal cord paralysis (VCP) is the second most common cause of neonatal stridor. PCV is characterized by weak crying, aspiration, or dysphagia. The recurrent laryngeal nerve, which controls most of the intrinsic laryngeal musculature, courses toward the thorax before entering the larynx. The long course of the nerve and its proximity to vascular structures make the recurrent laryngeal nerve particularly susceptible to injury. As such, the majority of PCV cases in pediatrics are iatrogenic and related to cardiac procedures.
PCV can also be idiopathic due to birth trauma (neck traction), intubation injury (direct damage to the glottis), or other iatrogenic causes (neck or cardiac surgery).
Management of unilateral PCV usually involves observation versus medialization by injection with temporary filler substances. If paralysis persists for more than 12 months, a recurrent laryngeal nerve reinnervation procedure may be considered.
Neonates with bilateral PCV often have severe airway obstruction, which may require tracheostomy or laryngotracheoplasty. Approximately two-thirds of patients with non-iatrogenic (including bilateral) PCV regain mobility within 2 to 3 years without intervention.5
Laryngeal membrane. Laryngeal membranes represent 5% of congenital laryngeal lesions, and the majority occur at the level of the glottis.6 The membranes most frequently affect the anterior commissure. Laryngeal webs may be associated with velocardiofacial syndrome, prior intubation, or laryngeal surgery. Symptoms vary depending on the size of the membrane, but may include stridor or weak/hoarse crying. Surgical management of incomplete membranes typically requires endoscopic division. Laryngeal atresia with complete membrane can cause SCOVAR in utero, as described above.
Laryngeal cleft. Laryngeal clefts are abnormal communications between the airway and the esophagus that occur in 1 in every 10,000 to 20,000 live births.7 This anomaly results from failure to separate the common tracheoesophageal lumen. The severity of the anomaly is determined by how quickly the process is interrupted and is classified into 4 types.8 Type 1, the mildest, involves an interarytenoid defect that extends to the level of the vocal cords. Type 2 involves a portion of the cricoid cartilage while type 3 extends across the length of the cricoid and into the cervical trachea. Type 4 is the most severe and extends to the thoracic trachea.
Laryngeal clefts have been associated with multiple syndromes, such as CHARGE (coloboma, cardiac defects, nasal choanal atresia, growth restriction, genital and ear malformations), VACTERL (vertebral anomalies, anal imperforation/atresia, cardiac anomalies, tracheoesophageal fistula [ FTE], renal malformations, and agenesis of the extremities), Pallister Hall syndrome, Opitz-Frías syndrome and Di George syndrome. Up to two-thirds of children with laryngeal cleft may have concurrent gastrointestinal, urogenital, cardiac, or craniofacial malformations.9
Affected children may present with recurrent respiratory infections, chronic cough, feeding difficulties, aspiration, growth retardation, noisy breathing, dysphonia, or cyanosis.
Direct laryngoscopy is required to palpate and determine the depth of the cleft, which is not well visualized with flexible laryngoscopy. Type 1 and 2 clefts can be repaired endoscopically. Type 3 clefts can be repaired endoscopically or through an open procedure. Type 4 clefts require open repair and historically had a 90% mortality rate; however, this has improved significantly over time.7
Posterior glottic stenosis. Posterior glottic stenosis is a rare posterior-based narrowing of the glottis, most commonly due to long-term intubation. Prolonged intubation can cause mucosal ischemia, granulation tissue edema, ulceration, and scarring between the vocal cords. Due to the proximity of the posterior glottis to the endotracheal tube, this area is at particularly high risk for injury. In newborns, the cricoid is the narrowest portion of the airway, which can cause significant stenosis. Given such multilevel obstruction, laryngotracheoplasty and tracheostomy are common treatments. Unfortunately, due to the rarity and disparate nature of this condition, the literature does not provide a good measure of outcomes.10
> Subglottic anomalies
Subglottic stenosis. As noted above, in neonates the level of the cricoid cartilage is the narrowest portion of the airway. Subglottic stenosis (SGS) is defined as narrowing of the airway to less than 4 mm at the level of the cricoid, which is equivalent to a 3.0 endotracheal tube in a full-term baby. Most commonly, ESG is acquired (e.g., as a sequel to long-term intubation), but rare congenital causes exist. Although the incidence of ESG has decreased with advances in neonatal care, it remains a problem in the NICU due to improved survival of extremely preterm infants. ESG should be suspected in any child with a history of intubation who presents with stridor, increased work of breathing, retractions, regular weight gain, and persistent need for respiratory assistance.
Diagnosis of ESG requires rigid assessment of the airway with endotracheal tube sizing. The severity of the stenosis is determined using the Cotton-Myer grading scale (I-IV), which compares the expected size of the airway with the actual size.11
Serial endoscopic management with scar division, steroid injection, and balloon dilation are usually the first-line treatment. If this fails or in cases of high-grade stenosis (grade III-IV), children may require a tracheostomy before airway reconstruction. For stenosis refractory to endoscopic treatment, laryngotracheoplasty or cricotracheal resection may allow decannulation.
Subglottic hemangioma. Infantile hemangiomas are the most common head and neck tumors in the pediatric population, but they only represent less than 1% of congenital laryngeal anomalies.12 They are benign vascular lesions that exhibit rapid growth in the first months of life followed by involution. slow and spontaneous.
Infants with subglottic and cutaneous hemangiomas should be evaluated for PHACE syndrome (posterior fossa brain malformations, hemangioma, arterial lesions, cardiac anomalies, and ocular anomalies). Newborns with subglottic hemangiomas are usually asymptomatic. However, the proliferation phase begins around 1 to 2 months of age, which can lead to biphasic stridor, barking cough, respiratory distress, and feeding difficulties.
The diagnosis is made with direct laryngoscopy. Historically, patients with subglottic hemangiomas were treated using various modalities, including intralesional and systemic steroids, systemic interferon, endoscopic resection, tracheostomy, and open excision. Oral propranolol is now considered the first-line treatment, with surgical excision reserved for unresponsive or life-threatening lesions.13
> Tracheal anomalies
Tracheomalacia. Tracheomalacia (TM) is tracheal collapse due to increased compliance and sagging of the cartilaginous structure. TM may be due to intrinsic tracheal weakness or may be secondary to tracheal deformity due to trauma or external compression.
Bronchomalacia occurs in up to 30% of TM cases. Symptoms can range from mild to severe and may include barking cough, wheezing that does not respond to bronchodilators, and difficulty clearing secretions.
Most cases of TM will improve after a growth period of 6 to 12 months with typical resolution by 2 years of age. Patients with more severe conditions may have symptoms of reflex apnea that cause episodes of cyanosis, and may require tracheostomy and/or positive pressure ventilation.14
Vascular rings. Anomalies of the aortic arch or great vessels represent approximately 1% of congenital cardiovascular anomalies. These patients may be asymptomatic or present with difficulty feeding or respiratory symptoms such as wheezing, stridor, barking cough, recurrent respiratory infections, and dyspnea. They may also be associated with other congenital anomalies, such as heart disease, kidney anomalies, TEF, and diaphragmatic anomalies. Vascular rings (VAs) are subdivided into complete and incomplete types and are evaluated with CT angiography.
Complete AVs envelop both the trachea and esophagus, which can cause severe compression and TM. Double aortic arch is the most common type of symptomatic complete VA. Other complete VAs include the right aortic arch with aberrant left subclavian artery and the right aortic arch with mirror image branching. Incomplete VAs may be due to pulmonary artery sling or an aberrant innominate artery. VAs may require open repair by a cardiothoracic surgeon.15
Tracheoesophageal fistula. TEF and esophageal atresia (EA) are congenital anomalies that involve an abnormal communication between the trachea and esophagus. These are commonly diagnosed in utero through prenatal findings of polyhydramnios and absence of a stomach bubble. However, undiagnosed TEF/AE should be suspected in newborns with excessive salivation, choking/coughing with feeding, or respiratory distress.
50% of babies with FTE/AE have other congenital anomalies such as VACTERL association, CHARGE syndrome and trisomy 18. There are 5 types of FTE/AE according to the Gross Classification. Type C is the most common, occurring in 86% of TEF cases and is associated with AE and distal TEF. Surgical repair of the TEF/AE may be necessary to prevent worsening respiratory function and/or gastric perforation.16
Tracheal stenosis. Tracheal stenosis can be congenital or acquired. Acquired stenosis is usually due to trauma or intubation injury. Congenital stenosis is usually due to complete tracheal rings and makes up less than 1% of all laryngotracheal stenosis. Other causes include aplasia of the tracheal or bronchial ring, tracheal sheaths, and chondrodysplasia punctata causing tracheal calcification.
Extratracheal anomalies are present in most children with complete tracheal rings.
Symptoms include biphasic “washing machine” stridor, increased work of breathing, and episodes of cyanosis . Conservative management can be used when the patient is asymptomatic or mildly symptomatic, although most cases diagnosed in childhood will require surgical correction with sliding tracheoplasty. This procedure shortens the trachea, but doubles the luminal diameter.
Historically, infants with tracheal stenosis had a mortality rate of ~80%, but this has decreased with new surgical techniques and improved critical care.17
Tracheal agenesis. Tracheal agenesis is a very rare and almost universally fatal anomaly characterized by the absence of part or all of the trachea. This anomaly is classified into 3 subtypes. Type I is characterized by agenesis of the proximal trachea with a distal TEF. In type II, the most common form, there is no proximal or distal trachea, only a fistula in the carina that bifurcates the bronchi.
Type III, the most severe, is characterized by the total absence of the trachea and carina, with the bilateral bronchi arising directly and independently from the esophagus. Most children with tracheal agenesis have other congenital anomalies. There is usually prenatal polyhydramnios and FTE/AE.
With a fistula present, affected fetuses may not show signs of SCOVAR. At birth, affected infants have aphonia, immediate respiratory distress, cyanosis, and an inability to undergo intubation despite a normal-appearing glottis.
Short-term ventilation through a fistula may be possible with an endotracheal tube placed in the esophagus just above the fistula.
Creating a tracheostomy using the esophagus and ventilating through the FTE has allowed long-term survival in very few cases in the literature; However, this is the rare exception in a generally fatal congenital anomaly.18
| Medical management |
> Respiratory support
The main goal of treatment of neonates with laryngotracheal deformities is to support their respiratory function. These children may require varying degrees of invasive and non-invasive respiratory support.
Depending on the defect, intubation may be challenging and require the expertise of an otolaryngologist. However, intubation should be attempted when otolaryngologists are not available if the baby has significant respiratory distress. Smaller endotracheal tubes may be necessary and sedation with or without paralysis could be considered.
The use of sedation and paralysis has been shown to increase the success of first-pass intubation in newborns19; However, in cases of difficult airway without access to otorhinolaryngology, sedation and paralysis should be used with caution because this will result in the loss of the infant’s spontaneous respiratory drive.20
Other tools that are useful when the neonatal team cannot secure the airway with an endotracheal tube include the oral/nasal airway or laryngeal mask airway. It may be necessary to provide continuous positive pressure or bag-mask ventilation until a specialist can secure the airway.
> Medical support
Medications available for the treatment of laryngotracheal anomalies are limited. Glucocorticoids have commonly been used to decrease airway edema after prolonged intubation.21 However, when corticosteroids, such as dexamethasone, are used, it is important to consider the total dose administered.
The dose of dexamethasone for airway inflammation is 0.25 to 0.5 mg/kg every 8 hours for a total of 3 doses. The total dose administered may be up to 1.5 mg/kg; Depending on the context, those on dexamethasone for the treatment of bronchopulmonary dysplasia (BPD) according to the Dexamethasone Randomized Trial (DART) dosing schedule may receive a total of 0.91 mg/kg for 10 days. (22)
It is common to counsel families about the complications of neurodevelopmental delay in those receiving dexamethasone for BPD; However, the risk of neurodevelopmental impairment is not commonly discussed when dexamethasone is administered for respiratory indications. No research has been conducted to evaluate neurodevelopmental outcomes in these patients.
In general, bronchodilator therapies should be avoided in patients with laryngotracheal abnormalities, as bronchodilators may decrease airway tone, contributing to increased dynamic collapse. However, bronchodilators may be indicated in patients with severe BPD who have increased small airway resistance.
A trial of bronchodilators, such as albuterol or ipratropium bromide, may be indicated if the device is able to maintain central airway patency with sufficient positive pressure; however, the clinical efficacy of inhaled bronchodilators is mixed in this population.23,24
At high doses, ipratropium bromide acts primarily as an M3 receptor antagonist causing smooth muscle relaxation, and may benefit patients with severe TM.25 Additionally, the systemic cholinergic drug bethanechol has also been studied in patients with severe TM and It has been reported to be safe in the pediatric population, but there is no evidence to support its use in neonates.26 Likewise, there is evidence for the use of glucocorticoids, antihistamines, and leukotriene inhibitors for the treatment of airway inflammation,27 although There are no data in newborns.
> Enteral feeding support
Laryngotracheal anomalies often contribute to dysphagia and feeding difficulties in the neonatal population. Obstructive airway pathologies can complicate the coordination of breathing and swallowing,28 which can lead to growth retardation due to the increased metabolic demand associated with breathing against an obstructive airway.29
An abnormal sensorimotor integrative function has also been described in patients with laryngomalacia.30 Abnormalities that affect airway protection can cause aspiration due to lack of glottic competence during swallowing and/or communication between the esophagus and trachea. Secondary structural airway abnormalities are common in children with TEF/AE and are associated with long-term dysphagia in these patients.31
Approximately one-third of infants admitted to the NICU with tracheostomies have aspiration, and two-thirds or more are discharged with feeding tubes.32 Children ages 1 to 3 years who have tracheostomies demonstrate slower and more restrictive functioning in their pharyngeal phase. of swallowing.33,34,35,36 Unlike in adults, the presence of a one-way speaking valve (Passy-Muir valve) does not decrease laryngeal penetration or aspiration in children with tracheostomies.37
Common interventions to prevent aspiration and improve safe oral intake in patients with pharyngeal phase dysphagia are positional changes, modifications to the nipple or teat flow rate, and the addition of thickener.38,39 Gastrostomy tubes or long-term nasogastric tubes in patients who cannot safely tolerate oral feedings.
A speech therapist or occupational therapist with specialized training in pediatric feeding should continue to follow these patients in hospital and after discharge as part of a multidisciplinary team of specialists through an aerodigestive team. This team often includes gastroenterology, otolaryngology, pulmonology, speech-language pathology, occupational therapy, and nutrition.
An aerodigestive team is necessary to manage complex aerodigestive needs, optimizing safe oral intake, and minimizing the need for enteral tube feeding over time.40 Non-nutritive oral stimulation therapies should be initiated so that the child maintains interest in oral feeding.41 As patients progress in their oral sensory feeding skills, children’s transition from feeding tubes to oral feeding can be optimized by inducing short-term hunger under the guidance and supervision of an aerodigestive team. .42,43
| Surgical management |
There are several surgical options available for the management of airway problems in the neonatal period. After diagnostic procedures, interventions can be performed endoscopically or openly. The surgical approach is dictated by the anomaly and the child’s general clinical picture. A concise description of various surgical options is included in the clinically relevant sections above. The final option, tracheostomy, is detailed below.
> Tracheostomy
Tracheostomy placement is indicated in infants with upper airway abnormalities or laryngotracheal stenosis who are not amenable to other interventions. A tracheostomy can help ease the transition from hospital to home in selected patients. Complications after a tracheostomy are common and can affect up to 40% of patients.44
Complications of pediatric tracheostomy are often divided into early and late complications, with early complications being those that occur within 7 days of the procedure. The most worrying early complications are those related to accidental decannulation, mucosal plugging, and creation of a false passage when attempting to replace the tracheostomy.
Late complications of pediatric tracheostomy include infection, peristomal/suprastomal granulation, tracheal stenosis, tracheocutaneous fistula, TM, stoma rupture, and death. Complications are more common in children under 1 year of age, with low birth weight, with neurological or cardiac comorbidities, or receiving mechanical ventilation.44 In recent years, the need for long-term tracheostomy has increased, making long-term management are an important area of study.45
| Comment |
Neonatal laryngotracheal anomalies range from common benign lesions to rare and probably fatal pathologies. These anomalies can be syndromic, idiopathic or iatrogenic, some of which can be detected in utero and others in the immediate neonatal period.
Regardless of the etiology, diagnosis and follow-up by a multidisciplinary team is essential.
Treatment for most of these conditions is surgical, although in some cases watchful waiting and/or medical treatment may be chosen as the child grows.
The goal of treatment will be to provide affected infants with the ability to breathe and feed in the best possible way to support their development and growth.
