Epidemiology

The incidence of esophageal atresia (EA), with or without tracheoesophageal fistula (TEF), is approximately 1 in 3400.¹ There is a reported slight preponderance in males and children of diabetic or older mothers.² Chromosomal anomalies have been reported in 6 to 10 percent of cases.³ Although EA–TEF can be an isolated finding, epidemiologic studies suggest that up to 60 percent will have other anomalies.² Some will present with other anomalies that lead to a specific genetic diagnosis, whereas others will present with a nonrandom association of other defects. These other defects include coloboma, heart, atresia choanae, retarded development, genital hypoplasia, and ear abnormalities (CHARGE associations), as well as vertebral, anal, cardiac, tracheoesophageal fistula, renal, and limb defects (VACTERL).

Embryology

EA constitutes a spectrum of incomplete esophageal development, which arises from interruptions in endoderm–mesoderm interactions. Although the exact embryologic mechanism of EA–TEF is not well characterized, some of the mechanisms have been recently discovered. Most studies on EA–TEF have used intraperitoneal Adriamycin injections in pregnant rodents, which reproduces the VACTERL association that is identical to the defects found in humans.⁴ In this model, the esophagotracheal foregut tube fails to divide into ventral and dorsal parts, and a fistula develops. Several molecular pathways seem to play an important role. Some studies have shown that when genes for the retinoic acid receptors were deleted in mice, the foregut tube failed to separate.⁵ The hedgehog signaling pathway has also been implicated.⁶ Targeted deletion of the sonic hedgehog gene resulted in mice embryos with severe TEF malformations.⁶ The Hox genes are thought to play a role in endodermal patterning and are expressed in the endodermal and mesodermal germ layers. Mice that are null mutant for Hoxc4 develop a partially or completely blocked esophageal lumen.⁷ In another study, T-box transcription factor 4 misexpression resulted in failure of tracheoesophageal septum formation in chicks.^8,9 Despite these studies, the exact pathogenic mechanism behind EA–TEF remains elusive.

Classification, Clinical Presentation, and Diagnosis

EA is characterized using the Ladd¹⁰ or Gross¹¹ classification system. In general, the different variants include isolated EA, EA with distal TEF, EA with proximal TEF, EA with proximal and distal TEF, and N-type TEF. EA with distal TEF (gross class C or Ladd III/IV) is the most common EA anomaly, seen in approximately 87 percent (Table 13-1). Infants with N-type EA and those weighing less than 2000 g are more likely to present with associated anomalies.¹² The most common associated anomalies are cardiovascular malformations, seen in up to 30 percent infants with EA.¹³ These include atrial and ventricular septal defects, patent ductus arteriosus, tetralogy of Fallot, and anomalies of the aortic arch.

The diagnosis of EA–TEF is usually made in the first 24 hours of life, but can be made antenatally or delayed.^14,15 Prenatal ultrasound detects EA by the presence of polyhydramnios (amniotic fluid index >97.5 percentile) with a small or absent stomach.¹⁶ Polyhydramnios occurs because of the fetus’ inability to swallow amniotic fluid. If an EA is detected on ultrasound without polyhydramnios, a distal TEF allows the amniotic fluid to pass into the stomach.

In early postnatal life, infants with EA–TEF will accumulate excess saliva, drool, develop rhonchi with mild-to-moderate respiratory distress, and demonstrate inability to feed. Workup of EA–TEF is used to confirm diagnosis, plan for surgical intervention, and look for associated anomalies. On workup, infants with EA–TEF will fail to have a 10 F tube pass beyond 10 cm from the lips. On gentle insufflation of the esophageal tube, the size and shape of the esophageal pouch can be delineated on plain radiographs. Furthermore, dilute barium through the tube or air in the stomach may confirm TEF. The presence of a “gasless” abdomen suggests EA without TEF. Some centers favor endoscopy in an effort to identify a TEF and place a stent prior to surgical repair.

Diagnostic investigations for associated anomalies for patients diagnosed antenatally may include fetal echocardiogram and karyotyping. In the absence of dysmorphism and urinary difficulties, a chest plain film to evaluate vertebral anomalies and echocardiogram may be sufficient. Some centers include a renal ultrasound routinely.

If undiagnosed, infants suffer from aspiration and subsequent respiratory distress and cyanosis during feedings. In severe cases of aspiration, infants may become apneic and bradycardic with subsequent cardiopulmonary arrest. Infants with a distal TEF may develop more severe pulmonary infections and pneumonitis with subsequent severe respiratory distress since gastric secretions reflux into the tracheobronchial tree.

Delayed diagnosis of EA–TEF with survival beyond 25 days of life is rare but has been reported.¹⁷ Because the esophagus remains in continuity, delay in diagnosis is more common for N-type TEF. These infants will present with recurrent cough on feeding, recurrent pneumonias, cyanosis, increased flatulence, and intermittent abdominal distention.

Preoperative Management

Preoperative management of infants with EA–TEF includes suctioning with an esophageal tube, nil per os, and head of bed elevation to reduce regurgitation and aspiration risk. Intravenous access should be obtained, and maintenance intravenous fluids initiated. In the event of intubation, gastric distention can be reduced by positioning the tip of the endotracheal tube distal to any TEF. Although rare, gastric distention with subsequent perforation is a catastrophic complication, requiring emergency ligation of the distal TEF.

Surgical Management

Primary repair of EA–TEF is readily achieved through an extrapleural approach via a right posterolateral, muscle-sparing thoracotomy in the fourth intercostal space (Fig. 13-1). The TEF is identified and divided, and the tracheal cuff oversewn. The upper pouch and distal esophagus is identified and mobilized, and then repaired in a primary fashion using interrupted absorbable sutures. Advancement in minimally invasive techniques and technology has made thoracoscopic surgery a viable alternative to standard open repair for EA–TEF. Some series have shown equivalent results to open surgery, although long-term data are elusive.^18,19

The presence of 13 ribs or a short upper pouch suggests a “long gap.” Many strategies have been adopted to tackle the long gap and subsequent anastomotic tension. These approaches have had varying results and include circular or spiral myotomies, mobilization of the distal esophagus, and tubularization of an upper pouch flap.^20–23 Optimal repair for this group of patients is controversial, although a number of centers are now advocating retention of the native esophagus and the benefits of delayed primary repair.²⁴

Postoperative Complications

Anastomotic leak, which occurs in 15 to 20 percent cases, and subsequent sepsis remains a common and serious complication of EA–TEF repair in the early postoperative setting.²⁵ These infants may present with tension pneumothorax requiring thoracostomy tube placement and/or reoperation to oversew the leak. Smaller leaks are more common, and can be managed conservatively, but may lead to stricture or recurrent fistula in the long term.