AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Background

Although the recorded history of esophageal atresia (EA) and tracheoesophageal fistula (TEF) dates back to the 17th century, surgical treatment for these anomalies was not suggested until 1869. In 1939, Leven¹ and Ladd² independently completed the first successful treatments for EA; Haight performed the first successful primary repair 2 years later.³

For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article Bronchoscopy.

Related eMedicine topics:
Esophageal Atresia With or Without Tracheoesophageal Fistula
Tracheoesophageal Fistula
Gastroesophageal Reflux: Surgical Perspective

Related Medscape topics:
CME Management of Pediatric Reflux
Tracheoesophageal Fistula and Massive Pneumoperitoneum

Definitions and types of EA/TEF

EA is a condition in which the proximal and distal portions of the esophagus do not communicate. The upper segment of the esophagus is a dilated, blind-ending pouch with a hypertrophied muscular wall that typically extends to the level of the second to fourth thoracic vertebra. The distal esophageal portion is an atretic pouch with a small diameter and a thin muscular wall; it extends a variable distance above the diaphragm.^{4, 5, 6, 7}

TEF is an abnormal communication between the trachea and esophagus. When associated with EA, the fistula most commonly occurs between the distal esophageal segment and the trachea, just above the carina. An "H-type" TEF is a TEF without EA. Although they can occur at any level between the cricoid cartilage and the carina, TEFs usually course obliquely (with the tracheal end proximal) at or above the level of the second thoracic vertebra.^{5, 8, 9}

Five types of EA and TEF have been described. The most common abnormality is EA with a distal TEF (84%). Isolated atresia with no fistula is the next most common finding (8%), followed by H-type TEF (no atresia) (4%). EA with proximal and distal fistulas (3%) and EA with a proximal fistula (1%) are less common. The frequencies given for each type are calculated from a summary of 6 long-term studies.^{5, 7, 10, 11, 12, 13, 14, 15}

Etiologies and factors

The etiologies of EA and TEF are still largely unknown, but many theories concerning their origins have been proposed. The trachea and esophagus are foregut derivatives. During the fourth gestational week, lateral mesodermal ridges form in the proximal esophagus; the fusion of these grooves in the midline separates the esophagus from the trachea around the 26th day of gestation.

Notochord abnormalities, desynchronous esophageal mesenchymal and epithelial growth rates, neural crest cell involvement, and incomplete tracheoesophageal separation resulting from a lack of apoptosis are some of the conditions theorized for EA embryogenesis. Similarly, incomplete tracheoesophageal septation, lateral ridge fusion failure, and tracheal and esophageal proximity have been suggested as possible explanations for the origin of TEF. In addition, vascular insufficiencies; genetic factors; vitamin deficiencies; drug and alcohol exposures; and viral, chemical, and external physical events may contribute to the development of EA and/or TEF.

According to these theories, several factors appears to alter the rate and timing of cell growth and proliferation in the embryonic foregut. These events most likely occur before the 34th day of gestation. Other organs, such as the remainder of the intestinal tract, the heart, the kidneys, the ureters, and the skeletal system, are also developing around this time, and they are vulnerable to developmental irregularities as well.

Pathophysiology

Because of a discontinuous esophagus, infants with EA cannot clear their secretions. This defect leads to persistent drooling and aspiration or regurgitation of food after attempted feedings. TEF causes additional complications as a result of the communication between the trachea and the esophagus. When infants with TEF strain, cough, or cry, air enters the stomach through the fistula. As a result, the stomach and small intestine can become dilated, which elevates the diaphragm and makes respiration more difficult. Reflux of food and gastric secretions through the fistula into the tracheobronchial tree and up the esophagus may also occur; this reflux can contribute to pneumonia and atelectasis. Therefore, pneumonia and respiratory distress are common complications of TEF.

Abnormal esophageal motility has been observed in children with EA and/or TEF. Often, controversy exists as to whether the abnormality is inherently present in the child's esophagus or if EA and/or TEF develops as a result of the surgical treatment. Manometric studies have shown that the motility disorder is present before surgical treatment. Animal studies have also shown that esophageal transection followed by repair does not precipitate disturbances in motility. Discoordinated peristalsis has been reported from the level of the fistula to the stomach in patients with cases of isolated TEF.

Medscape Related topic:
CME  Management of Pediatric Reflux: Distinguishing Pathologic GERD From Physiologic GER

Frequency

United States

In the United States, the frequency is 1 case in 3000 live births.

International

The international occurrence varies throughout different regions of the world; estimates range from 0.4 to 3.6 cases per 10,000 live births.

Mortality/Morbidity

• The prognosis for children with EA and/or TEF has improved greatly over the past 60 years.^{16, 17}
• Despite an increased number of patients with severe anomalies, survival rates as high as 95% have been reported.
• In uncomplicated cases, survival rates approach 100%.

Race

• An increased propensity for EA and/or TEF development has not been associated with any specific race.
• Investigators in one study, however, noted a higher EA incidence in white populations (1.0 case per 10,000 births) compared with that in nonwhite populations (0.55 case per 10,000 births).

Sex

• Males have a slightly higher risk for EA and/or TEF than females.
• The male-to-female ratio for EA is 1.26, which is significantly higher than the male-to-female ratio of 1.06 in the general population.

Age

• EA and TEF are congenital malformations in neonates that are typically diagnosed within the first few hours of life. Some cases of isolated TEF, however, are not discovered until early childhood.
• A few studies have revealed correlations between EA risk and maternal age. One study revealed higher incidences of EA in children born to mothers younger than 19 years and older than 30 years, whereas a more recent study showed a trend of increasing EA risk with increasing maternal age.

Anatomy

An understanding of the esophageal blood supply is crucial to the successful repair of atresia and/or fistulas. The esophagus can be divided into several segments on the basis of its blood supply.^{18, 19, 20}

The cervical portion of the esophagus is well vascularized; interrupting a vessel to this segment during surgical manipulation is not catastrophic. The cervical esophageal portion is supplied by the inferior thyroid artery and accessory vessels derived from the common carotid, subclavian, vertebral, ascending pharyngeal, superficial cervical, and costocervical arteries. The thoracic portion of the esophagus has a segmental blood supply. The connections in this region are the most tenuous, and care should be taken to reduce the risk of ischemia during mobilization of this segment.

The region with the largest gap between arteries supplying the esophagus is at the level of the aortic arch. The bronchial arteries provide the main vascular supply at this level; 1 to 3 bronchial branches enter the esophagus at the level of the tracheal bifurcation. Variable branches originating directly from the aorta may also be present in this region. Three unpaired esophageal branches that arise directly from the aorta supply the lower thoracic esophagus. These branches may anastomose with branches from the intercostal and bronchial arteries. Branches from the internal mammary and carotid arteries may also be present here. The abdominal esophagus is vascularized by the ascending branch of the left gastric artery, as well as by branches from the left inferior phrenic artery.

Prior to surgical procedures, the position of the aortic arch should be confirmed, and the surgical approach should be performed on the side opposite the aortic arch. A right-sided aortic arch occurs in 5% of infants with EA.

The esophagus is innervated largely by the autonomic nervous system. Sympathetic innervation plays a minor role and arises from the pharyngeal plexus in the upper esophagus and the stellate ganglia in the lower cervical and upper thoracic portions. The aortic plexus, sympathetic chain, and splanchnic nerves supply the remainder of the thoracic esophagus. In the abdominal segment, fibers from the celiac ganglion pass around the left gastric and inferior phrenic arteries to innervate the esophagus. Parasympathetic innervation to the esophagus is provided by the vagus nerve.

Parasympathetic function includes stimulation of smooth muscle and secretory activity. The vagus nerve also aids the sphincteric function of the lower esophagus. The recurrent laryngeal nerves should be noted as they pass cranially in a groove between the esophagus and trachea, supplying the cervical and upper third of the thoracic esophagus. The vagus nerves descend caudally; they arborize to form the esophageal plexus and then subsequently coalesce into the left and right vagal trunks, which overlie the anterior and posterior lower esophagus, respectively.

Because of its course along the esophagus, the vagus nerve is another helpful landmark during surgical esophageal procedures. Disruption of the vagus during surgical manipulation has been proposed as a mechanism of dysmotility after esophageal repair, but manometric findings have confirmed the inaccuracy of this hypothesis. Injury of vagal fibers during esophageal mobilization may, however, further adversely affect motility.

Several other organs and structures should be noted during surgical esophageal repair. The thoracic duct is vulnerable near the cervical esophagus, and the locations of the trachea and aorta should be confirmed with palpation during a surgical procedure. Because the upper esophageal pouch may be virtually fused to the trachea, care should be taken not to enter the trachea when the upper pouch is mobilized. Contact of the esophageal wall and left atrium of the heart caudal to the carina is also noteworthy. In this region, the pericardium is the only structure that separates these 2 organs. Of special note in TEF repair, the left main bronchus crosses the ventral esophageal surface. Confirmation of bronchi locations is critical to fistula repair, especially in a trifurcation TEF.

Clinical Details

Clinical signs

The first clinical sign of an infant with EA is maternal polyhydramnios resulting from the infant's inability to swallow and absorb amniotic fluid through the gut. Polyhydramnios is seen in infants with many diagnoses, and only 1 in 12 infants with polyhydramnios has EA; however, polyhydramnios is seen in 95% of infants who have EA and no fistula and in 35% of patients who have EA with a distal fistula. Increased pressure caused by amniotic fluid accumulation results in a greater number of premature births and neonates with low birth weight. One third of infants with EA weigh less than 2250 g.

Most infants with EA become symptomatic within the first few hours of life; however, children with an isolated fistula have more subtle symptoms that may not be recognized initially. Excess salivation and fine, frothy bubbles in the mouth and, sometimes, the nose result from an inability to swallow. Any attempts at feeding can result in choking, coughing, cyanotic episodes, and food regurgitation. The presence of a fistula increases respiratory complications, which result from aspiration of food and secretions into the trachea and lungs. Pneumonitis and atelectasis develop quickly in the affected neonate, and rattles heard during respirations are common. Fistulas also allow air to enter the stomach and intestines, leading to abdominal distention. With atresia alone, the abdomen appears scaphoid.

Many anomalies are associated with EA; 50-70% of children with EA have some other defect. The acronym VACTERL (which stands for vertebral, anorectal, cardiac, tracheal, esophageal, renal, and limb) describes the most common combination of defects associated with EA.²¹ Cardiac abnormalities are the most common, especially ventricular septal defects and tetralogy of Fallot. Imperforate anus and skeletal malformations might also be found on examination. In the absence of such associated anomalies, the physical examination findings in infants with EA are fairly unremarkable.

Prognosis and complications

Traditionally, the prognosis for children with EA and/or TEF was centered on the Waterston risk classification, which is based on birth weight and the presence of pneumonia and associated congenital abnormalities. Because of advancements in neonatal care, however, this risk classification is no longer prognostic. Pneumonia may be successfully treated, except in some infants with severely low birth weight. Currently, cardiac and chromosomal abnormalities are the most significant causes of death. Regardless of the classification scheme, infants with a birth weight less than 1500 g, major congenital cardiac abnormalities, severe associated anomalies, preoperative ventilator dependence, and/or a long esophageal gap are at an increased risk.

Preoperatively, the greatest risk to a child with EA and/or TEF is aspiration. Gastric rupture has been reported in patients with TEF who are receiving ventilatory support as a result of air that is forced through the fistula into the distal esophagus and then into the stomach.

The severity of complications after EA repair is often dictated by the extent of the repair required. Primary anastomosis and fistula closure has fewer complications than esophageal replacement. The length of the gap between the esophageal segments is directly related to possible complications; patents with longer gaps experience a higher complication rate.^{22, 23, 24} The most common complications include anastomotic leak, recurrent fistula, stricture,²⁵ and gastroesophageal reflux (GER).

Anastomotic leakage into the mediastinum occurs in 14-21% of children that have undergone surgical EA repair. Leaks can result from the small, friable lower segment, ischemia of the esophageal ends, excess anastomotic tension, sepsis, technically poor suturing techniques, and inaccurate mucosal apposition. Most leaks are small, occur later (after the first 48 h after surgery), and require only conservative management with cessation of oral intake (total parenteral nutrition [TPN]) and antibiotics. Spontaneous healing occurs in 95% of leaks when a mediastinal drain is present. More significant leaks occur early (within the first few days) and should be explored immediately. Major anastomotic disruptions occur in only 3-5% of leaks, but large leaks can be fatal and require surgical repair. Mediastinal leaks can lead to TEF recurrence; therefore, they should be monitored carefully.

Fistula recurrence between the esophagus and trachea is observed in 3-14% of patients treated for EA with TEF, EA without TEF, or H-type TEF. Fistulas usually recur within a few months, but they may recur as late as 2 years after surgery. An anastomotic leak with local inflammation and erosion at the previous repair site, ischemia, and surgical dissection too near the trachea may cause a recurrent fistula. This condition should be suspected when choking episodes occur during feeding and/or recurrent pneumonia is observed. The best methods of diagnosis are bronchoscopy and esophagography under videofluoroscopic guidance with the patient in the prone position and with bolus injections of contrast agent into a nasoesophageal tube. Fistulas do not close spontaneously and require surgical division and ligation. About 10-20% of cases recur after the first TEF recurrence.

Esophageal strictures occur in 40% of children after surgical EA repair. Strictures result from natural healing and are caused by fibrosis, a difference in the sizes of the 2 anastomosed segments, tension, and GER. Leaks, as well as the use of a 2-layer anastomosis and/or silk sutures, enhance stricture formation. Strictures may be diagnosed with barium swallow examination or esophagoscopy. Although barium swallow studies aid in stricture reduction by dilating the anastomotic site, decreasing the size discrepancy between the 2 segments, and loosening the fibrosis of healing, it is not completely effective, and dilations are required for resolution. Dilation is 90% effective, but strictures that do not respond to dilation must be surgically resected.

GER is a common complication, occurring in 40-70% of patients after EA repair. Symptoms of GER include coughing, apnea, recurrent pneumonia, failure to thrive, and stricture formation. A barium swallow examination may demonstrate GER, which is caused by tension, dysmotility of the lower esophagus, and an altered angle of Hiss resulting from distal esophageal mobilization. GER may be medically treated by keeping the patient in a prone head-up position after feeding; by thickening the food; and by giving smaller, more frequent meals. If problems persist, acid-reduction agents such as histamine H₂-receptor blockers and prokinetic agents may be administered. If medical therapy is unsuccessful, fundoplication may be considered. Fundoplications are required in about half of the patients with GER. GER tends to diminish with time, but long-term GER leads to mucosal changes such as esophagitis and Barrett esophagus.

Additional complications in infants with EA/TEF include the following:

• Altered esophageal peristalsis (seen in all patients)
• Tracheomalacia (seen in all patients)
• Diverticula at the myotomy site
• Pulmonary complications (eg, hacking cough, bronchitis, frequent pneumonia)
• Swallowing difficulties
• Dyspepsia
• Anastomotic dehiscence, esophageal stenosis
• Failure to thrive
• Chest wall deformities, scoliosis

An esophageal substitution causes additional complications. Esophageal replacement has been associated with an increased surgical morbidity rate and a 68% complication rate. These conditions include the following:

• Colon
  • Early complications
  • • Cervical leaks (which heal well)
    • Pulmonary problems
    • Graft necrosis
  • Late complications
  • • Redundancy
    • GER
    • Anastomotic stenoses
    • Strictures
    • Deformity
  • Thin-walled, has poor function
  • Subject to pathology (polyps, villous adenomas)
  • Slow transit that leads to dilatation over the patient's lifetime (which leads to anemia, poor weight gain, recurrent pulmonary infections, and redundancy)
  • Intestinal obstruction in 20% of patients
  • Colon graft ulceration in 10% of cases (which leads to symptomatic GER in 30% of cases, especially in retrosternal placements; this may lead to Barrett epithelium in the lower esophagus if the lower segment is unused)
  • Limited mucosal acid resistance (the colon tends to dilate and form loops)
• Gastric tube
• • Has frequent leaks and strictures
  • Has high incidences of fistulas, stenoses, and peptic ulcerations
  • May lead to peptic esophagitis
  • Produces extensive GER in cervical esophagus, which may lead to peptic ulceration and Barrett epithelium
• Gastric transposition
• • Leakage in 6% of cases
  • Stricture at the anastomosis in 12% of cases
  • Microvasculature easily disturbed with handling
  • Late dilatation
  • Long-term effects of intrathoracic stomach ulceration (chronic GER, Barrett epithelium)²⁶
  • Aspiration
• Nutritional concerns
• • In 25% of children, height and weight after 1 year is less than 3rd percentile
  • Severe dumping is common
  • Decreased pulmonary function
  • Resultant depleted iron stores
• Jejunum
• • Infarction is common
  • High incidence of peptic ulceration
  • High free graft failure rate

Preferred Examination

Prenatally, ultrasonographic findings may suggest a diagnosis of isolated EA or EA and TEF; however, prenatal EA detection rates are low, and if suspected, the diagnosis must be confirmed postnatally. In neonates in whom EA and/or TEF is suspected, posteroanterior and lateral plain chest radiographs should be obtained first. The patient's inability to pass a rigid nasogastric tube from the mouth to the stomach is diagnostic of EA and/or TEF, but this finding should be confirmed with radiographic visualization of the tube coiled in the proximal pouch.

Contrast-enhanced studies are rarely indicated because of the risk of aspiration, but they may be necessary to identify or locate a fistula. Only an experienced radiologist should perform contrast-enhanced studies with fluoroscopic control.²⁷ Endoscopy and/or bronchoscopy may be performed to locate or rule out TEFs.

Limitations of Techniques

Sonographic evaluation will reveal the first findings suggestive of a congenital anomaly, but it is not conclusive. Many conditions involve polyhydramnios and a small or absent stomach bubble at ultrasonography.²⁸ Visualization of a dilated proximal pouch is suggestive of EA, but further tests are necessary to confirm the diagnosis. In addition, sonograms may not give any indication of EA  when it is present, and often, a fistula is not seen.

Plain radiographs provide much information, including findings for EA confirmation and depiction of the side of the aortic arch side, as well as the presence of any vertebral or other associated anomalies. Barium studies performed after the surgical placement of a gastrostomy tube may be used to evaluate the gap length and associated GI abnormalities, such as duodenal atresia or malrotation; however, radiographs may not always demonstrate the presence of a fistula.

DIFFERENTIALS

Section 3 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Other Problems to Be Considered

A tear of the oropharynx or esophagus should be considered, especially in patients who underwent vigorous attempts at feeding tube placement following delivery. The type of atresia and/or fistula should be considered as well. EA and TEF types include the following: isolated EA, EA with a proximal TEF, EA with a distal TEF, EA with proximal and distal TEFs, and isolated (H-type) TEF.

RADIOGRAPH

Section 4 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

The findings on posteroanterior and lateral chest images will confirm a diagnosis of EA by displaying a coiled nasogastric tube (placed for determination of EA) in the proximal esophageal pouch of a child with EA. The location of the aortic arch can also be discerned.^{29, 30, 31, 32, 33, 34, 35, 36}

Radiographic signs of a right-sided aortic arch include the following:

• A right ascending aorta, indicated by an opaque shadow on the right side of the mediastinum
• A right-sided tracheal indentation and/or deviation
• A dilated inlet of the aberrant left subclavian artery, which resembles a diverticulum and appears as a round shadow to the left of the trachea at the site of the normal aortic knot

Any vertebral anomalies may be visualized, and some cardiac anomalies may be suggested. Aspiration pneumonia (especially in the right upper lobe) and patchy atelectasis are frequently present. Barium studies performed by means of a surgically placed gastrostomy tube (gapogram) are useful for evaluating the gap length and visualizing additional GI anomalies. Esophageal motility disturbances are present in children with EA and can be visualized with videofluoroscopy. Peristaltic discontinuity often exists in a 6-15 cm segment extending above and below the anastomosis. Aside from these general findings, the radiographic observations in children with EA and/or TEF vary depending on the type of anomaly present.

These observations include the following:

• Isolated atresia
• • A dilated air-filled blind-ending proximal pouch, which often displaces the trachea anteriorly, may be present.
  • A gasless abdomen may be depicted. Air is normally present in the stomach 15 minutes after birth.³⁷
  • The lower pouch is visualized with barium or air refluxed through a gastrostomy.
• EA with a distal fistula
• • Gaseous distention of the stomach and small bowel (caused by air passing through the fistula) may be observed.
  • Images may show an airless abdomen if the fistula is occluded or obliterated.
  • Excessive air may be present in the esophagus; however, some air in the esophagus is normal in neonates and children.
• EA with a proximal fistula
• • On plain radiographs, this may have an appearance similar to that of isolated EA.
  • A gasless abdomen may be depicted.
  • A barium swallow examination may fail to demonstrate this anomaly.
  • Fistula visualization requires rapid-sequence or videofluoroscopic studies during cautious filling of the proximal pouch.
• Isolated TEF (H-type fistula)
• • Recurrent pneumonia may be present, with a widespread pneumonia pattern.
  • Fistula delineation can be difficult.
  • Excessive air may be present in the esophagus.
  • Contrast-swallow is the study of choice for diagnosis. An isotonic, nonionic iodinated contrast agent is the contrast of choice; dilute barium can be used as an alternative contrast agent. If the patient is intubated or the contrast swallow demonstrated tracheal contrast without visualization of a fistula, an esophagram with a feeding tube should be performed.³⁸ Using cross-table fluoroscopy with the patient lying prone on a waist-high footstep with the fluoroscopic table erect, serial injections of contrast are administered through a nasoesophageal catheter as the catheter is withdrawn proximally.³⁹ Tracheal filling is noted at the site of the fistula.
  • When the patient is intubated, care should be taken that the endotracheal tube tip is above the thoracic inlet, as the endotracheal tube may occlude the tracheal fistula opening.

After surgical repair of EA and/or TEF, plain radiographs show the condition of the repair and any developing complications. Mild narrowing at the anastomotic site is a common finding, but more severe obstructive strictures may also be observed. Esophagography can be used to demonstrate an asymptomatic leak. In addition, a dilated proximal esophageal segment (particularly if the repair included myotomy) and distal esophageal stenosis are noted postoperatively.

Degree of Confidence

The finding of a coiled nasogastric tube at radiographic examination confirms the presence of EA. Occasionally, the tube may coil because of extrinsic compression on the esophagus, and repeat placement should be attempted. If the tube passes to the stomach, the possibility of the tube passing through a TEF must be investigated. The infant's cry should be profoundly affected if the tube passes through the vocal cords on the way through a distal TEF and into the stomach.

On occasion, determination of the side of the aortic arch may be difficult on plain images. Echocardiography, magnification, high-kilovoltage techniques, computed tomography (CT), or ultrasonography may be used to detect its location. Fistula identification may be difficult in some cases; further testing with endoscopy, bronchoscopy, or tracheoscopy may be necessary. If tracheal filling is observed with the use of a contrast material, these methods can aid in determining whether this observation is the result of a fistula or of aspiration.

Appropriate follow-up examinations of any concomitant congenital anomalies may be required, depending on the type of abnormality present. Although videofluoroscopy demonstrates dysmotility, the dysfunction is quantified with manometry and scintigraphy. Fluoroscopy is the best method for the identification of anastomotic leaks.

CT SCAN

Section 5 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

CT is not typically used in the evaluation of EA and/or TEF; however, CT does allow 3-dimensional (3D) examination of the esophagus in relation to its adjacent structures. Its use in patients with EA and/or TEF has increased in recent years.^{19, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49}

Axial images can be difficult to interpret; a fistula may be only partially demonstrated or missed. Direct sagittal CT has been used in newborns to accurately diagnose EA and TEF. This method enables visualization of the entire length of the esophagus, complete with atresias, fistulas, and gap length. Three-dimensional CT with virtual endoscopy provides similar benefits, in addition to facilitating the understanding of complex anatomic relationships. Virtual endoscopy can be used to traverse stenoses, unlike traditional endoscopy. Cardiac and respiratory motion artifacts, however, are problems. Although this technique provides an image of the anatomic relationships that is easy to understand, it does not provide any additional information beyond that on axial images.

CT imaging may also be used to identify the location of the aortic arch, but other methods are typically used. After surgical correction of EA and/or TEF, helical ultrafast CT can be used to quantify tracheomalacia, a ubiquitous finding. In addition, abnormal tracheal shape and size, an abnormally broad posterior tracheal wall, and abundant air and fluid within the esophagus have been recorded with postoperative CT.

Degree of Confidence

Diagnosis of EA with 3D CT is highly reliable, with 100% sensitivity and specificity.^{41, 50} Findings with this technique have been shown to be well correlated with surgical and/or bronchoscopic findings. CT diagnosis of tracheomalacia is reliable, but suspicions should be confirmed with biopsy or endoscopy.

False Positives/Negatives

No false-positive or false-negative findings have been observed in the diagnosis of EA and TEF with 3D CT and virtual bronchoscopy. False-positive and false-negative findings with helical CT are unknown to the authors.

MRI

Section 6 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Postnatally, MRI has no role in the routine imaging of EA and TEF; however, MRI does offer the ability to image the entire length of the esophagus in both the sagittal and coronal planes, and its contrast resolution is superior to that of CT. MRI is rarely used to determine the location of the aortic arch, but it has been used prenatally to diagnose congenital malformations.^{19, 47, 51, 52}

Unlike ultrasonography, prenatal MRI allows visualization of the entire lesion and the anatomic relationships. Fetal MRI has proven accurate for establishing or ruling out a prenatal diagnosis of EA in high-risk infants based on ultrasonographic findings; however, fetal MRI may be difficult in cases of polyhydramnios because of poor image quality.

Degree of Confidence

Images obtained from MRI are highly accurate. Fetal MRI has 100% sensitivity in prenatally diagnosing EA  in high-risk infants.

False Positives/Negatives

No known variants mimic EA on fetal MRI examinations. The appearance of esophageal indentations, however, may mimic that of fistulas. If findings are questionable, postnatal imaging should be performed to confirm the presence or absence of a fistula.

ULTRASOUND

Section 7 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Although ultrasonography has no role in the routine postnatal evaluation of EA and/or TEF, prenatal sonography is a valuable screening tool for EA and/or TEF.^{22, 51, 53, 54} The ultrasonographic finding of an absent or small fetal stomach bubble in combination with maternal polyhydramnios is suggestive of EA and/or TEF.²⁸ The diagnostic accuracy is increased if an anechoic area is present in the middle of the fetal neck; this sign differentiates EA from diseases with possible swallowing impairments.

The presence of a dilated blind-ending esophageal pouch on a sonogram is suggestive of EA. This pouch sign has been confirmed with direct visualization after 26 weeks' gestation,^{55, 56, 57} but its onset has been suggested as early as the 22nd week. The possibility of an association between increased nuchal translucency observed in the first trimester and EA with fistula has been investigated.⁵⁸

Postnatally, endoscopic ultrasonography produces a 5-layered image of the esophageal wall that has been used in cancer staging; it may have a future use in fistular localization. In addition, the aortic arch may be located sonographically to plan for EA and/or TEF repair.

Degree of Confidence

The pouch sign is the most reliable sonographic sign indicative of EA,^{55, 56, 57} and it is noted in the presence of EA with or without TEF. The prenatal diagnosis rate of EA is low; it has been reported to be 9.2%. Unless the dilated blind-ending proximal pouch is directly visualized, suspicion requires postnatal confirmation. The positive predictive value of the finding of a small or absent fetal stomach bubble in association with maternal polyhydramnios is 56%, and the sensitivity of prenatal ultrasonography in the diagnosis of EA is 42%.

Polyhydramnios alone is a poor predictor of EA.²⁸ Only 1 in 12 patients with polyhydramnios has EA. Similarly, a small or absent fetal stomach bubble has multiple associations in addition to EA.²⁸ These findings, then, are not conclusive and require further testing with the passage of a postnatal nasogastric tube from the mouth to the stomach and with plain chest radiography to confirm diagnosis.²⁸

Prenatal ultrasonography can also cause many cases of fistula to be missed because fluid may pass through the fistula, contributing to the appearance of a normal fluid-filled stomach. Sonography can depict TEF in about one third of affected fetuses.

False Positives/Negatives

No normal variants mimic the prenatal sonographic findings of EA and/or TEF. Transient visualization of esophageal fluid and the absence of visualization of the stomach may be seen in healthy patients. Polyhydramnios, while not normal, is a nonspecific finding.

Polyhydramnios can be seen in the following conditions:

• Agnathia, microstomia, synotia
• DiGeorge velocardiofacial syndrome
• Placental insufficiency
• Maternal diabetes mellitus
• Chromosomal disorders, isoimmunologic disease, congenital abnormalities, multiple gestations, idiopathic conditions
• Epignathus
• Hydrolethalus
• Tetralogy of Fallot, Treacher Collins syndrome
• Myasthenia gravis, pseudohypoaldosteronism

NUCLEAR MEDICINE

Section 8 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Typically, nuclear medicine is not used in the evaluation of EA and TEF; however, it may be useful in the assessment of motility after repair.⁵⁹ Scintigraphy and radionuclide studies enable detection and quantification of esophageal transit, esophageal clearance, and GER.¹⁹

Degree of Confidence

Radionuclide esophageal transit studies are associated with a high degree of confidence, with 97.3% sensitivity and a 94.7% positive predictive value for the determination of motility dysfunctions and 92.3% sensitivity and 90.9% specificity for the evaluation of GER. Gastroesophageal scintiscans are also accurate for the diagnosis of GER, with sensitivity reported to be as high as 90%.

ANGIOGRAPHY

Section 9 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Angiography is not generally used for the evaluation of children with EA/TEF. These studies may be useful in planning for an esophageal replacement, if such a repair is chosen.

INTERVENTION

Section 10 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Dilation of anastomotic strictures or strictures caused by esophagitis may be performed with balloon angioplasty catheters.²⁵ A jejunal feeding tube may be placed in the perioperative period to maintain nutrition.^{27, 60, 61, 62}

Medical/Legal Pitfalls

• No special medical/legal pitfalls exist in the radiologic diagnosis and management of EA/TEF, other than the risks of contrast agents discussed in Special Concerns below.

Special Concerns

• The use of contrast agents for examining children with EA and/or TEF is of special concern because of the risk of aspiration. If an agent is used, the type of contrast material should be carefully considered.⁶³
• Barium possibly enables the best visualization; however, the use of extraluminal barium has a risk of a possible granulomatous and fibrotic reaction that can result in fibrous mediastinitis.
• Aqueous low-osmolality agents, such as Visipaque and Optiray, are preferred. These agents have no deleterious effects on the GI system, but they are more expensive than standard agents. Aqueous contrast agents are preferred in neonates, premature infants, and children with a suspected esophageal perforation. They remain in the GI tract for prolonged periods, and they are not absorbed because they are hypertonic and hyperosmolar.
• Unfortunately, aqueous contrast agents are quickly diluted and less fluoroscopically visible because of their decreased coating ability; therefore, as many as 15-25% of thoracic perforations and 50% of cervical perforations may not be detected.
• Hyperosmolar agents, such as Hypaque and Gastroview, should not be used because they cause marked irritation and pulmonary edema if they are aspirated.
• In addition, the use of hypertonic and hyperosmolar agents may result in hypovolemia resulting from the displacement of intravascular fluids into the GI tract, severe dehydration, and pneumonitis caused by significant irritation of the trachea and bronchi.
• Only experienced radiologists should perform contrast-enhanced examinations in children with EA and/or TEF.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Media file 1:  Esophageal atresia (EA) with distal tracheoesophageal fistula (TEF). Frontal view of the chest and abdomen of a neonate demonstrates a tube in the proximal pouch in this patient with EA. The presence of bowel gas implies the presence of a distal TEF, making this the most common type of EA/TEF.
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Media type:  X-RAY

Media file 2:  Isolated esophageal atresia (EA). Frontal view of the chest and abdomen demonstrates a catheter in the proximal pouch in this patient with EA. Note the absence of bowel gas in this patient with EA, but it is not associated with a tracheoesophageal fistula (TEF).
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Media type:  X-RAY

Media file 3:  H-type tracheoesophageal fistula (TEF). Oblique barium esophagogram demonstrates a fistula (arrow) arising from the anterior esophagus and extending anterosuperiorly to the trachea.
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Media type:  X-RAY

Media file 4:  Vertebral, anorectal, cardiac, tracheal, esophageal, renal, and limb (VACTERL) association. Frontal radiograph in a patient with esophageal atresia (EA) without a tracheoesophageal fistula (TEF). Note the catheter in the proximal pouch and the butterfly vertebra (asterisks) at the level of T8 in this patent with associated VACTERL.
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Media type:  X-RAY

Media file 5:  False-positive finding of esophageal atresia (EA). Image demonstrates a feeding tube coiled in the proximal esophagus (E). An umbilical arterial catheter (U) is noted at the level of T11. The catheter was repositioned and extended to the stomach, with no alteration of the infant's cry (see Image 6.)
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Media type:  X-RAY

Media file 6:  False-positive finding of esophageal atresia. Follow-up image in the patient in Image 5 demonstrates the tube (T) extending to the stomach. The endotracheal tube (ET) and umbilical arterial catheter (U) are also identified.
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Media type:  X-RAY

Media file 7:  Gapogram shows the location of the proximal pouch (P), which is suggested by the position of the catheter. The distal pouch location (D) is visualized with the reflux of contrast material through a previously placed gastrostomy tube (G). The distance between the proximal and distal pouches is measured on the adjacent radiopaque ruler.
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Media type:  Photo

Media file 8:  Barium esophagogram obtained in a patient 3 weeks after esophageal repair shows the relative narrowing at the anastomotic site (A). Reflux (arrow) is seen with an associated sliding hiatal hernia (R).
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Media type:  Photo

Media file 9:  Stricture with food bolus. Frontal view from a barium swallow examination in a patent with a repaired EA shows a stricture at the anastomotic site, with a bolus of food proximal to the stricture.
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Media type:  Photo

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

1. Leven NL. Congenital atresia of the esophagus with tracheo-esophageal fistula: report of fistulous communication and cervical esophagostomy. J Thoracic Surg. 1941;10:648–657.
2. Ladd WE. The surgical treatment of esophageal atresia and tracheoesophageal fistulas. New Eng J Med. 1944;230:625–637.
3. Haight C, Towsley H. Congenital atresia of the esophagus with tracheoesophageal fistula: extrapleural ligation of fistula and end-to-end anastomosis of esophageal segments. Surg Gynecol Obstet. 1943;76:672–688.
4. Brown AK, Roddam AW, Spitz L. Oesophageal atresia, related malformations, and medical problems: a family study. Am J Med Genet. Jul 2 1999;85(1):31-7. [Medline].
5. Holder TM. Esophageal atresia and tracheoesophageal fistula. In: Pediatric Esophageal Surgery. 1986: 29-52.
6. Orford J, Manglick P, Cass DT. Mechanisms for the development of esophageal atresia. J Pediatr Surg. Jul 2001;36(7):985-94. [Medline].
7. Sparey C, Jawaheer G, Barrett AM. Esophageal atresia in the Northern Region Congenital Anomaly Survey, 1985-1997: prenatal diagnosis and outcome. Am J Obstet Gynecol. Feb 2000;182(2):427-31. [Medline].
8. Konstantinidou AE, Agapitos E, Korkolopoulou P. Tracheoesophageal malformation: pathogenetic evidence provided by two cases. Teratology. Jan 2001;63(1):11-4. [Medline].
9. Nebot-Cegarra J, Fabregas PJ, Campillo M. Separation between the digestive and the respiratory lumina during the human embryonic period: morphometric study along the tracheo- oesophageal septum. J Anat. Jan 2001;198(Pt 1):117-24. [Medline].
10. Cumming WA. Neonatal radiology. Esophageal atresia and tracheoesophageal fistula. Radiol Clin North Am. Aug 1975;13(2):277-95. [Medline].
11. Dutta HK, Mathur M, Bhatnagar V. A histopathological study of esophageal atresia and tracheoesophageal fistula. J Pediatr Surg. Mar 2000;35(3):438-41. [Medline].
12. Foker JE, Boyle EM. Congenital anomalies: esophageal atresia and tracheoesophageal fistula. In: Esophageal Surgery. 1995: 151-83.
13. Harmon CM, Coran AG. Congenital anomalies of the esophagus. In: Pediatric Surgery. 1998: 941-67.
14. Hupscher DN. Congenital anomalies. In: Radiology of the Esophagus. 1988: 27-30.
15. Sharma AK, Shekhawat NS, Agrawal LD. Esophageal atresia and tracheoesophageal fistula: a review of 25 years'' experience. Pediatr Surg Int. 2000;16(7):478-82. [Medline].
16. Choudhury SR, Ashcraft KW, Sharp RJ. Survival of patients with esophageal atresia: influence of birth weight, cardiac anomaly, and late respiratory complications. J Pediatr Surg. Jan 1999;34(1):70-3; discussion 74. [Medline].
17. Engum SA, Grosfeld JL, West KW. Analysis of morbidity and mortality in 227 cases of esophageal atresia and/or tracheoesophageal fistula over two decades. Arch Surg. May 1995;130(5):502-8; discussion 508-9. [Medline].
18. Botet JF, Lightdale CJ. Normal anatomy and techniques of examination of the esophagus: endosonography. In: Margulis and Burhenne's Alimentary Tract Radiology. 1994: 186-91.
19. Ekberg O. Normal anatomy and techniques of examination of the esophagus: fluoroscopy, CT, MRI, and scintigraphy. In: Margulis and Burhenne's Alimentary Tract Radiology. 1994: 168-85.
20. Hupscher DN. Anatomy and physiology of the esophagus. In: Radiology of the Esophagus. 1988: 19-26.
21. Kim J, Kim P, Hui CC. The VACTERL association: lessons from the Sonic hedgehog pathway. Clin Genet. May 2001;59(5):306-15. [Medline].
22. Khan KM, Foker JE. Use of high-resolution endoscopic ultrasonography to examine the effect of tension on the esophagus during primary repair of long-gap esophageal atresia. Pediatr Radiol. Jan 2007;37(1):41-5. [Medline].
23. Lessin MS, Wesselhoeft CW, Luks FI. Primary repair of long-gap esophageal atresia by mobilization of the distal esophagus. Eur J Pediatr Surg. Dec 1999;9(6):369-72. [Medline].
24. Upadhyaya VD, Gangopadhyaya AN, Gupta DK, Sharma SP, Kumar V, Pandey A. Prognosis of congenital tracheoesophageal fistula with esophageal atresia on the basis of gap length. Pediatr Surg Int. Jun 20 2007;[Medline].
25. Laín A, Cerdá J, Cañizo A, Parente A, Fanjul M, Molina E, et al. [Analysis of esophageal strictures secondary to surgical correction of esophageal atresia]. Cir Pediatr. Oct 2007;20(4):203-8. [Medline].
26. Krug E, Bergmeijer JH, Dees J, de Krijger R, Mooi WJ, Hazebroek FW. Gastroesophageal reflux and Barrett's esophagus in adults born with esophageal atresia. Am J Gastroenterol. Oct 1999;94(10):2825-8. [Medline].
27. Hoffer FA, Sandler RH, Kaplan LC. Fluoroscopic placement of jejunal feeding tubes. Pediatr Radiol. 1992;22:287-289.
28. Houben CH, Curry JI. Current status of prenatal diagnosis, operative management and outcome of esophageal atresia/tracheo-esophageal fistula. Prenat Diagn. Feb 27 2008;[Medline].
29. Altman AR, Ball WS Jr, Kosloske AM. Radiographic evaluation of the postoperative neonatal chest. Curr Probl Diagn Radiol. Jan-Feb 1984;13(1):1-40. [Medline].
30. Berdon WE, Baker DH. Radiographic findings in esophageal atresia with proximal pouch fistula (type B). Pediatr Radiol. Mar 20 1975;3(2):70-4. [Medline].
31. Berdon WE, Baker DH, Schullinger JN. Plain film detection of right aortic arch in infants with esophageal atresia and tracheoesophageal fistula. J Pediatr Surg. Aug 1979;14(4):436-7. [Medline].
32. Ho CS. Imaging. In: Esophageal Surgery. 1995: 71-104.
33. Hupscher DN. Radiological examination techniques. In: Radiology of the Esophagus. 1988: 3-7.
34. Stewart ET, Dodds WJ. Radiology of the esophagus. In: Margulis and Burhenne's Alimentary Tract Radiology. 1994: 192-263.
35. Stringer DA, Babyn P. Pharynx and esophagus. Pediatric gastrointestinal imaging and intervention. 2000;2nd edition:161-236.
36. Sumner TE, Auringer ST, Cox TD. A complex communicating bronchopulmonary foregut malformation: diagnostic imaging and pathogenesis. Pediatr Radiol. Oct 1997;27(10):799-801. [Medline].
37. Swischuk LE. Alimentary tract. In: Imaging of the Newborn, Infant, and Young Child. 1997: 352-71.
38. Laffan EE, Daneman A, Ein SH, Kerrigan D, Manson DE. Tracheoesophageal fistula without esophageal atresia: are pull-back tube esophagograms needed for diagnosis?. Pediatr Radiol. Nov 2006;36(11):1141-7. [Medline].
39. Stringer DA, Ein SH. Recurrent tracheo-esophageal fistula: a protocol for investigation. Radiology. Jun 1984;151(3):637-41. [Medline].
40. Day DL. Aortic arch in neonates with esophageal atresia: preoperative assessment using CT. Radiology. Apr 1985;155(1):99-100. [Medline].
41. Fitoz S, Atasoy C, Yagmurlu A. Three-dimensional CT of congenital esophageal atresia and distal tracheoesophageal fistula in neonates: preliminary results. AJR Am J Roentgenol. Nov 2000;175(5):1403-7. [Medline].
42. Griscom NT, Martin TR. The trachea and esophagus after repair of esophageal atresia and distal fistula: computed tomographic observations. Pediatr Radiol. 1990;20(6):447-50. [Medline].
43. Halber MD, Daffner RH, Thompson WM. CT of the esophagus: I. Normal appearance. AJR Am J Roentgenol. Dec 1979;133(6):1047-50. [Medline].
44. Hupscher DN. Computed tomography of the esophagus. In: Radiology of the Esophagus. 1988: 53-58.
45. Inoue K, Yanagihara J, Ono S. Utility of helical CT for diagnosis and operative planning in tracheomalacia after repair of esophageal atresia. Eur J Pediatr Surg. Dec 1998;8(6):355-7. [Medline].
46. Kao SC, Smith WL, Sato Y. Ultrafast CT of laryngeal and tracheobronchial obstruction in symptomatic postoperative infants with esophageal atresia and tracheoesophageal fistula. AJR Am J Roentgenol. Feb 1990;154(2):345-50. [Medline].
47. Quint LE, Glazer GM, Orringer MB. Esophageal imaging by MR and CT: study of normal anatomy and neoplasms. Radiology. Sep 1985;156(3):727-31. [Medline].
48. Schmalfuss IM, Mancuso AA, Tart RP. Postcricoid region and cervical esophagus: normal appearance at CT and MR imaging. Radiology. Jan 2000;214(1):237-46. [Medline].
49. Tam PK, Chan FL, Saing H. Diagnosis and evaluation of esophageal atresia by direct sagittal CT. Pediatr Radiol. 1987;17(1):68-70. [Medline].
50. Lam WW, Tam PK, Chan FL. Esophageal atresia and tracheal stenosis: use of three-dimensional CT and virtual bronchoscopy in neonates, infants, and children. AJR Am J Roentgenol. Apr 2000;174(4):1009-12. [Medline].
51. Langer JC, Hussain H, Khan A. Prenatal diagnosis of esophageal atresia using sonography and magnetic resonance imaging. J Pediatr Surg. May 2001;36(5):804-7. [Medline].
52. Quinn TM, Hubbard AM, Adzick NS. Prenatal magnetic resonance imaging enhances fetal diagnosis. J Pediatr Surg. Apr 1998;33(4):553-8. [Medline].
53. Hayden CK Jr, Schwartz MZ, Davis M. Combined esophageal and duodenal atresia: sonographic findings. AJR Am J Roentgenol. Feb 1983;140(2):225-6. [Medline].
54. Tio TL. Endosonography of the esophagus. In: Margulis and Burhenne's Alimentary Tract Radiology. 1994: 264-71.
55. Kalache KD, Chaoui R, Mau H. The upper neck pouch sign: a prenatal sonographic marker for esophageal atresia. Ultrasound Obstet Gynecol. Feb 1998;11(2):138-40. [Medline].
56. Kalache KD, Wauer R, Mau H. Prognostic significance of the pouch sign in fetuses with prenatally diagnosed esophageal atresia. Am J Obstet Gynecol. Apr 2000;182(4):978-81. [Medline].
57. Rossi C, Domini M, Aquino A. A simple and safe method to visualize the inferior pouch in esophageal atresia without fistula. Pediatr Surg Int. Sep 1998;13(7):535-6. [Medline].
58. Brown RN, Nicolaides KH. Increased fetal nuchal translucency: possible association with esophageal atresia. Ultrasound Obstet Gynecol. Jun 2000;15(6):531-2. [Medline].
59. Taillefer R, Jadliwalla M, Pellerin E. Radionuclide esophageal transit study in detection of esophageal motor dysfunction: comparison with motility studies (manometry). J Nucl Med. Dec 1990;31(12):1921-6. [Medline].
60. Ko HK, Shin JH, Song HY, Kim YJ, Ko GY, Yoon HK. Balloon dilation of anastomotic strictures secondary to surgical repair of esophageal atresia in a pediatric population: long-term results. J Vasc Interv Radiol. Aug 2006;17(8):1327-33. [Medline].
61. Samuel M, Burge DM, Moore IE. Gastric tube graft interposition as an oesophageal substitute. Aust N Z J Surg. Jan 2001;71(1):56-61. [Medline].
62. Stringer DA, Pablot SM, Mancer K. Gruentzig angioplasty dilatation of an esophageal stricture in an infant. Pediatr Radiol. 1985;15:424-426.
63. Ginai AZ, ten Kate FJ, ten Berg RG. Experimental evaluation of various available contrast agents for use in the upper gastrointestinal tract in case of suspected leakage. Effects on lungs. Br J Radiol. Oct 1984;57(682):895-901. [Medline].
64. Altman DH, Mencia LF, Litt RE. Esophageal atresia. A simple radiological technic to facilitate surgical management. Radiology. Jun 1966;86(6):1112-4. [Medline].
65. Bax KN, Roskott AM, van der Zee DC. Esophageal atresia without distal tracheoesophageal fistula: high incidence of proximal fistula. J Pediatr Surg. Mar 2008;43(3):522-5. [Medline].
66. Beasley SW, Diez Pardo J, Qi BQ. The contribution of the adriamycin-induced rat model of the VATER association to our understanding of congenital abnormalities and their embryogenesis. Pediatr Surg Int. 2000;16(7):465-72. [Medline].
67. Bowie JD, Clair MR. Fetal swallowing and regurgitation: observation of normal and abnormal activity. Radiology. Sep 1982;144(4):877-8. [Medline].
68. Burhenne HJ, Margulis AR. Histo