Case 3: An Uncommon Cause of Respiratory Distress in a Term Newborn

A term infant presents with cyanosis at birth after vaginal delivery with clear amniotic fluid. Maternal history includes group B Streptococcus carrier status and von Willebrand disease. During resuscitation, the infant is stridulous with oxygen saturation in the 80s in room air. Heart rate and respiratory rate are normal for a newborn transitioning from in utero, and there is no increase in work of breathing. Due to stridor and cyanosis, visualization of the vocal cords with a manual laryngoscope is performed, revealing normal anatomy. The infant’s stridor and pulse oximetry improve without further intervention, and he remains with his mother in the mother-baby unit without supplemental oxygen. On day 2, the infant has oxygen desaturation to 81% in room air with tachypnea and retractions. His lung sounds are clear bilaterally. He is transferred to the neonatal intensive care unit (NICU) for respiratory support and evaluation. A sepsis workup is done, including complete blood count, C-reactive protein, and blood culture; all results are normal. A chest radiograph shows prominence of the right heart, which is expected in a newborn, with no focal pulmonary consolidation. His work of breathing and oxygen saturation improve on nasal cannula. His respiratory support is weaned to room air that same day. While off oxygen, an echocardiogram is obtained and shows a structurally normal heart with a mildly dilated right ventricle and flattened interventricular septum, which can be normal findings in a newborn.1 Later that day during a feeding, he has tachypnea and retractions requiring reinitiation of nasal cannula support. A repeat chest radiograph again shows mild cardiomegaly and clear lung fields without pulmonary consolidation or edema.Over the next 2 days, he is intermittently tachypneic with retractions, most often with feeds. On day 4, his respiratory distress worsens with oxygen desaturation to the 70s despite nasal cannula support, requiring escalation to continuous positive airway pressure and additional oxygen. A chest radiograph shows right upper lobe consolidation, concerning for pneumonia in the setting of respiratory distress and hypoxemia (Figure 1). Hence, he is initiated on a 10-day course of ampicillin and gentamicin, and oral feeds are discontinued while working on weaning respiratory support. He is able to be weaned to room air by day of life 8 and a speech language pathologist (SLP) is consulted at the time of oral feed reinitiation. “Gurgling” noises are observed with milk let-down during breastfeeding, in addition to persistent oxygen desaturation requiring restarting nasal cannula support. Assessment of botte feeding while on 1 L per minute through the nasal cannula is notable for coughing and oxygen desaturation to the 80s that resolves with cessation of feeding. The infant breastfeeds exclusively and is able to wean off of respiratory support with paced breastfeeding. As a part of discharge planning, the patient fails the car seat tolerance testing within minutes due to desaturation to the 70s in room air that resolves with removal from the car seat. Due to recurrent intermittent stridor, desaturation events, and failed car seat tolerance testing, the otolaryngology service is consulted for airway assessment. Flexible laryngoscopy reveals laryngomalacia, and outpatient follow-up is initially recommended. However, because of recurrent desaturations and a failed repeat car seat test due to desaturation, the patient is transferred to a level IV NICU for evaluation and management.The differential diagnosis for respiratory distress in a newborn includes transient tachypnea of the newborn (TTN), sepsis, pneumonia, meconium aspiration syndrome, congenital heart defects, hyaline membrane disease, and persistent pulmonary hypertension. Less common causes include neuromuscular issues such as hypoxic ischemic encephalopathy, seizures, or intracranial hemorrhage.Respiratory distress in a newborn that is specifically associated with stridor and that worsens with feeding broadens the differential to include airway abnormalities, including vascular ring, tracheoesophageal fistula, laryngeal cleft, vocal cord paralysis, and esophageal stricture. Standard workup for respiratory distress in a newborn includes an evaluation of a blood gas, complete blood counts with differentials, chest radiography, and pulse oximetry.2 In this case, the clinical presentation and chest radiographs ruled out TTN, meconium aspiration syndrome, and hyaline membrane disease. The echocardiogram ruled out congenital heart disease. Flexible laryngoscopy ruled out vocal cord paralysis, esophageal stricture, and tracheoesophageal fistula.After arrival to the level IV NICU, the infant was taken to the operating room by the otolaryngologist for microlaryngoscopy. A type III laryngeal cleft was discovered.A laryngeal cleft is a congenital defect in which there is an opening between the posterior laryngotracheal wall and the esophagus due to disruption of the development of the tracheoesophageal septum.3 This disruption causes incomplete separation of the trachea from the esophagus that can lead to the creation of a laryngeal cleft or tracheoesophageal fistula. This opening can allow for aspiration of ingested materials, commonly meconium in utero or milk during feeding. Aspiration can lead to pneumonia, respiratory distress, dysphagia, and hypoxia.3 Laryngeal clefts are rare, with approximately 1 case per 10 000 to 20 000 births.4 Although the exact cause is unknown, an autosomal dominant inheritance pattern has been reported. Laryngeal clefts can occur in isolation or in association with anomalies in the gastrointestinal, genitourinary, and/or cardiovascular systems. Additionally, laryngeal clefts have been associated with Pallister-Hall and Opitz-Frias syndromes.3 The gold standard of diagnosis is microlaryngoscopy to examine the larynx, parted arytenoids, trachea, and bronchial tree; endoscopic palpation of the interarytenoid area is required so as not to miss a barely visible cleft (Figure 2).5According to the Benjamin-Inglis Classification system, there are 4 types of laryngeal clefts (Figure 3): Type I: Interarytenoid cleft with the cleft located superiorly to the vocal cords;Type II: Partial cleft of the cricoid cartilage located below the vocal cords;Type III: Complete cleft of the cricoid cartilage typically encroaching into the trachea; andType IV: Complete cleft with involvement of the trachea.6Due to the diagnostic invasiveness and rarity of a laryngeal cleft, it is a commonly missed or delayed diagnosis. In one series that looked at children with type I clefts, the average age at symptom onset (when able to be determined from medical record review) was 5 months and the average age at diagnosis was around 3 years. As a result, patients live with recurrent asthma-like symptoms, feeding difficulties, viral illnesses, infections, and chronic coughs for months before diagnosis.5 Although the aforementioned series reported onset of symptoms at around 5 months of age, symptom onset can begin at birth or shortly thereafter and manifest in multiple ways including intermittent stridor, hoarseness, difficulty feeding, coughing, choking, and/or significant respiratory distress. Studies have shown an overall mortality rate of 46% in patients with a laryngeal cleft and secondary comorbidities.3 Thus, a high index of suspicion is vital to an early, accurate diagnosis. Pediatricians should carefully evaluate histories in patients with recurrent feeding and/or respiratory issues.This case highlights that symptoms from a laryngeal cleft can present at birth. The newborn had cyanosis, stridor, and hypoxemia at delivery. As the infant progressed in oral intake, respiratory distress and hypoxia worsened, requiring increasing respiratory support. Further, during the patient’s hospital course, a diagnosis of pneumonia was made, likely a consequence of aspiration related to the laryngeal cleft. The recurrent nature of the infant’s clinical picture and worsening with feeding points to an anatomical abnormality. Pediatricians should consider referral for endoscopy in any patient with recurrent respiratory issues associated with feeding. Additionally, both pediatricians and pediatric otolaryngologists should maintain high levels of suspicion in looking for a cleft abnormality in any child presenting with chronic cough, feeding difficulties, stridor, recurrent respiratory tract infections, or frequent asthma-like symptoms.5Due to the complexity and varying severities of laryngeal clefts, treatment is patient specific, ranging from observation to complex open airway surgery requiring multidisciplinary care.7 Mild clefts (type I) can often be managed medically with optimization of aspiration and reflux using medications and thickened paced feeding. Significant clefts, as in this case, however, require a multidisciplinary approach with surgical correction by otolaryngologists and thoracic surgeons.7 As in this case, until complete repair is pursued, patients may need tube feeding.Due to the nature of the type III cleft in this report, the otolaryngologist recommended that the infant wait until age 6 months before surgical repair. During the interim, oral feeding was halted and a gastrostomy tube was placed for feeding to reduce the risk of aspiration. As part of his workup, the infant underwent a chest computed tomography that showed narrowing of the intrathoracic trachea, but no other abnormalities. At age 6 months, the patient underwent surgical correction of his type III laryngeal cleft with an excellent result. He followed up with the SLP and otolaryngologists. He was fed solely via gastrostomy tube. When developmentally ready to attempt solids by mouth, he had persistent dysphagia and cough, prompting further investigation. He required subsequent surgical correction of a residual type I laryngeal cleft at age 19 months. With outpatient follow-ups, he was able to tolerate thickened oral feeds, which led to intermittent use of his gastrostomy tube. However, the patient developed a chronic cough and right lobe pneumonia that required intensive care hospitalization. A swallow study revealed development of an H-type tracheoesophageal fistula as a complication of his multiple airway surgeries. This required surgical repair at approximately age 3. Just before age 5, the patient again presented with stridor and respiratory distress; he required open laryngeal cleft repair with muscle rotation flap. This case emphasizes the need for close multidisciplinary follow-up given the risk of postoperative complications.In children with recurrent respiratory difficulties with feeding, anatomic/congenital airway anomalies should be considered early in the differential diagnosis. Multidisciplinary evaluation with otolaryngology and gastroenterology can help make the diagnosis in such scenarios.A laryngeal cleft is a rare congenital abnormality and is often misdiagnosed. It is a result of the failure of the fusion of the tracheoesophageal septum.3Patients with laryngeal clefts can present with stridor, choking and aspiration of feeds, cyanosis, pneumonia, dysphagia, recurrent infections, or chronic cough.