Esophageal perforation is uncommon and often iatrogenic in the neonatal period.^[1] It has been described extensively in various case reports and series.^{[2], [3], [4], [5]} Premature and low birth weight infants (<1500 g) are particularly susceptible, and in this population, the most common causes are nasogastric tube insertion, endotracheal intubation, or nasotracheal suctioning.^[6] Spontaneous Esophageal injury in neonates usually occurs at the pharyngoesophageal junction and can be confused with esophageal atresia due to respiratory signs and excessive salivation.^{[7], [8], [9], [10], [11]} Diagnostic evaluation and treatment are still debated. We describe two neonatal cases of iatrogenic esophageal perforation, diagnosed after thoracotomy. The diagnostic difficulties and therapeutic modalities are discussed

Case 1:

A preterm newborn female was referred to our neonatal intensive care unit for prematurity and need of invasive ventilation. The baby was born at 33 weeks gestation by emergency cesarean section for premature rupture of membrane (PROM) in a 38 years-old gravida 2, a nulliparous mother. No evidence of polyhydramnios in the prenatal ultrasound scan was observed. Birth weight was 1990g and the one-minute Apgar score was 8. Physical examination was normal. In the second minute of life, due to acute respiratory distress with retractions and expiratory groans, the baby initially needed high-flow oxygenation (4L/min) and a continuous positive airway pressure (CPAP) with a positive end-expiratory pressure of 5 cmH2O and FiO2 30% and then required orotracheal intubation after 2 unsuccessful attempts of passing an orotracheal tube.

Additionally, the negative outcome of the nasogastric tube’s positioning was noted, pointing to potential esophageal atresia. No hypersalivation was noted. A babygram showed the presence of gastric and intestinal air, while the tube ended in the mid-thorax. (Fig. 1) Hyperlucency around the tube was suggestive of the upper esophageal pouch and no pneumothorax or pleural collection was noted. The patient was hemodynamically stable without any inotropic support. Oxygen saturation was 98% using low-flow oxygenation and FIO2 of 0.30.

Since a type C esophageal atresia was suspected a tracheoscopy was performed to locate the distal fistula and to rule out the presence of an upper pouch fistula. The procedure failed to demonstrate any tracheoesophageal fistulas.

Due to this unexpected finding, an esophagram was performed through the naso-esophageal tube; an irregular fusiform structure was demonstrated and no passage of contrast medium into the stomach was observed; additionally, an extraluminal mediastinal leak was evident. (Fig. 2) Considering the high risk for an esophageal endoscopy, a Computerized tomography scan was performed showing pneumomediastinum. (Fig. 3)

After a multidisciplinary discussion, a right postero-lateral muscle-sparing thoracotomy was performed; the mediastinum was accessed via the extra-pleural route. The tube was found at the right aspect of the thoracic esophagus. No atresia was found. Since the esophageal perforation was not accessible from the thoracotomy, the baby required right trans-cervical access which confirmed a large perforation (1.5 cm diameter) of the posterior wall of the cervical esophagus, with frayed edges. An interrupted repair was performed with an absorbable suture over a 6-Fr nasogastric tube. A cervical drain was positioned (Penrose type) and a 10-Fr chest tube was left in place and the thoracotomy wound was closed.

Case 2:

A full-term newborn was referred, after a planned cesarean section for podalic presentation in a 37 years-old gravida 9, para 7 mother. Birth weight was 2490g and the one-minute Apgar score was 7. Also in this case physical examination was normal and no hypersalivation was noted. Due to acute respiratory distress syndrome, the baby was supported with positive pressure ventilation. Repeated attempts to introduce an orogastric tube were unsuccessful and esophageal atresia was suspected. A Replogle aspiration tube was placed in the upper esophagus and a babygram showed the presence of air around the tube. (Fig. 4) A tracheoscopy was performed, and the procedure failed to demonstrate any tracheoesophageal fistula. Therefore, an intraoperative esophagram was performed, showing a fusiform cul-de-sac consistent with the upper esophageal pouch (Fig. 5).

As in the previous case, a right postero-lateral muscle-sparing thoracotomy was performed, but even this time no evidence of atresia was found. The baby required right trans-cervical esophageal repair and cervical drainage, and a 10-Fr chest tube was left in place.

A contrast study was performed on postoperative day 10 showing for both patients complete healing of the esophagus without stricture or leak (Fig. 6a-b), and discharged on full oral feeds. At 6 months of age, a repeat contrast study showed no stricture or gastroesophageal reflux.

At a two-year follow-up, they are growing well, and no evidence of any issue or late complication.

Esophageal perforation has an incidence of 0.4-0.5% in the neonatal intensive care unit, increasing to ten-fold in babies <750g.^[12] Some large population studies do not confirm these figures.^{[4], [13]} Premature and low birth weight infants, less than 1500 g, are also particularly susceptible to iatrogenic esophageal perforation. These infants are inevitably exposed to multiple procedures and interventions such as nasogastric tube insertion, endotracheal intubation, or nasotracheal suctioning, which predispose them to esophageal perforation.^[14] The literature describes spontaneous esophageal perforation in this population.^[15]

Early recognition and management are necessary, and untreated esophageal perforation can lead to mediastinitis, sepsis, and death.^{[16], [17]} Historically, neonatal esophageal perforation was treated similarly to adults, often involving operative drainage, repair, and /or esophageal or gastric diversion. Currently, the preferred treatment has shifted toward a non-operative approach, unless esophageal atresia is suspected.^{[18], [19]}

Preoperative differential diagnosis is necessary to plan the correct therapeutic approach. Neonates with esophageal perforation will demonstrate excessive mucous secretion, drooling of saliva, and respiratory distress.^{[7], [14]} Though the same symptoms may be present in esophageal atresia, early recognition of an iatrogenic perforation can avoid unnecessary explorations.^{[2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]}

Esophagram is not indicated and not even routinely performed before the correction of esophageal atresia. Other evidence as prematurity and low birth weight, forceful and unsuccessful endotracheal intubation, vigorous oropharyngeal suction, and bloody aspirate from the “pouch” is required to be analyzed to raise the surgeon’s suspicion of esophageal perforation.

Plain radiographs can show subcutaneous emphysema, pneumomediastinum, pneumothorax, pleural effusion, and/or lobe atelectasis; a feeding tube located too high or having variable or eccentric positions are unusual findings and very suggestive.^{[6], [7], [8], [9], [10], [11], [12], [13], [14], [15]}

The diagnosis can be recognized by esophageal contrast studies under fluoroscopic control, which can demonstrate a classical “double esophagus”.^{[13], [14]} If contrast-study findings are negative, some radiologic clues mentioned above have to be looked for.^{[15], [16], [17]}

Chest computed tomography is useful when perforations are difficult to locate or when contrast esophagography cannot be performed.^[20] In our cases, pre-operative diagnosis of isolated esophageal perforation was not achievable. The diagnosis could have been suggested by the anomalous position of the distal extremity of the Replogle/nasogastric tube (too high – too low), a very tiny upper esophageal pouch at the esophagram, and the presence of pneumo-mediastinum. While atresia requires surgical treatment, neonatal esophageal perforation can be treated medically with broader antibiotics, gastrostomy feedings, or intravenous nutrition, and in the eventuality that pneumothorax or pleural effusion is evident, with tube thoracostomy. In 2022, Kaczmarek et al. also described the management of esophageal perforation in infants with endoscopic vacuum therapy.^[21] Flexible upper GI endoscopy can directly facilitate the discovery of the perforation and is accurate for making a diagnosis and for conservative treatment ^[21], while a tracheobronchial fibroscopy likely will yield negative results.

Table 1 shows various case reports/series describing infants with iatrogenic esophageal perforation in the pediatric literature.^{[1], [2], [6], [7], [8], [9], [10], [11], [22]} Almost all were symptomatic and in the majority of cases, the diagnosis was made based on clinical manifestations and esophagram with water-soluble contrast. The gestational age at birth ranged between 26 and 40 weeks and the birth weight was between 900 and 3100 g. More than half received a thoracotomy. Postoperative complications include esophageal strictures and sepsis, with a large number of deaths. Mortality percentage in neonates with esophageal perforation remains high (21-30%), and is mainly due to comorbidities, like congenital heart diseases, brain hemorrhage, necrotizing enterocolitis, and sepsis.^{[23], [24]}

In 2021, Elgendy et al. published a large retrospective cohort study utilizing the US National Inpatient Sample dataset for the years 2000 to 2017.^[4] A total of 861 esophageal perforations were diagnosed in very low birth weights infants, the majority <1000 g and <28 weeks of gestation. In this population mortality was 25.8%, but there was no association between esophageal perforation and increased mortality in preterm infants (p = 0.991). These two cases report our experience with iatrogenic esophageal perforation in two infants who present respiratory distress but no suggestive pre-natal signs or post-natal symptoms of esophageal atresia. Differential diagnosis also includes esophageal web or congenital esophageal stenosis. The diagnosis was not achieved by contrast exam or CT scan, and the babies needed surgical intervention. After a control contrast study, full oral feeding was started and short-term and long-term follow-up didn’t show any complication.

To conclude, esophageal perforation in the neonate is often iatrogenic and may mimic esophageal atresia. Early diagnosis is necessary to reduce the risk of death. These two cases show the importance of the clinical clues (anamnesis and clinical findings) to suspect the diagnosis; an aware interpretation of the radiological finding is desirable to avoid unnecessary invasive maneuvers.