Oesophageal Atresia

Oesophageal atresia (OA) is diagnosed when a blind-ending interruption of the oesophagus is identified, with or without a tracheoesophageal fistula (TEF), which is a persistent communication with the trachea.

Q39.0 Atresia of the oesophagus NOS

Population-based studies have reported a prevalence of OA of 1:2500-4500 pregnancies (1-8).

The pathogenesis of OA remains unclear (9). Embryologic studies have shown that the post-pharyngeal foregut splits into two parts and is separated by the tracheoesophageal septum. The anterior part, known as the respiratory diverticulum, develops into the respiratory tract organs, while the posterior part leads to the development of the oesophagus. Following division, the oesophagus starts growing longitudinally. Any abnormality occurring at this stage, including the persistence of an undivided foregut or a failure in the growth of the trachea or the proximal oesophagus likely cause this malformation (10-12).

The etiology of OA is multifactorial and remains unknown, however defects in the expression of the Sonic hedgehog (Shh) gene and mutations in GL13 have been described in genetic models of tracheo-oesophageal malformation (9).

The clinical presentation is dependent upon the co-existence of TEF. The interruption of the oesophagus causes an abnormal cycling of amniotic fluid. In the absence of TEF, persistent non-visualization of the stomach and polyhydramnios, which typically develops in the third trimester are pathognomonic.  When TEF is present, polyhydramnios and persistently small or non-visualized  stomach may be present, however, these cases are more difficult to find since the amniotic fluid volume and the size and shape of the stomach appear normal in most cases.

The most commonly used classification of OA delineates five sub-types of OA  based on the presence or absence of a TEF and the position of the TEF (13).

In over 50% of cases, OA is associated with one or more abnormalities affecting the cardiovascular, the gastrointestinal, the genitourinary or the central nervous systems (14, 15). Common genetic syndromes seen in cases of OA include VACTERL and CHARGE. Chromosomal abnormalities including trisomy 21 and 18 are seen in about 5-10% of all cases of OA (9).

The risk of recurrence risk of oesophageal atresia is about 1% (9) in isolated, non-syndromic chromosomally normal cases.

The antenatal suspicion of OA has mostly relied on the identification of direct or indirect ultrasound signs, which include:

1. Polyhydramios, which typically develops in the third trimester, and which can be quite severe;
2. Persistently small or non-visualized foetal stomach;
3. Proximal oesophageal pouch. This is best seen in sagittal views of the foetus.

Indirect signs are more common in the third trimester. In some cases, a TEF may close spontaneously in late gestation.

Recently, several groups have described the sonographic appearance of the foetal oesophagus on 2D and 3D US (16-18), however to date no formal prospective evaluation of these techniques has been performed.

The antenatal diagnosis of OA is challenging even for expert investigators. The combination of polyhydramnios and small stomach has proved to yield poor sensitivity (from 40 to 50%) particularly in the case of co-existent TEF, which allows the passage of amniotic fluid to the stomach. Over the last decade, the development of high-frequency transducers with improved tissue penetration and three-dimensional (3D) US techniques have offered a unique opportunity for the evaluation of the fetal anatomy. This has led to the development of different sonographic techniques which allow the direct visualization of the fetal oesophagus and opened the possibility of prenatal characterization of OA subtypes (16-18).

The differential diagnosis includes all of the conditions where the stomach is not visualized. They include a “physiologic” empty stomach, mechanical obstruction, neuromuscular dysfunction, oligohydramnios, hernia or congenital microgastria. Additionally, the differential diagnosis includes all the potential causes of polyhydramnios such as diabetes, infections and foetal anaemia.

A standard obstetric sonogram entails the evaluation of the amniotic fluid volume and a survey of the foetal anatomy including the stomach. The findings of polyhydramnios associated with a persistently small or non-visualized stomach should prompt referral for expert assessment. If OA is suspected, the foetus should be assessed for associated anomalies and the karyotyping with CGH-array should be offered.

MRI has also been suggested as a potentially useful tool to support the diagnosis of OA by allowing the antenatal demonstration of the “oesophageal pouch” (19, 20).

The co-existence of structural or chromosomal anomalies, low birthweight and preoperative pneumonia are independent risk factors for mortality and morbidity of neonates affected by OA (21).  Several classification systems for the prediction of mortality in foetuses affected by oesophageal atresia have been described. The most widely quoted classification of risk proposed by Spitz divides the patients into 3 sub-groups on the basis of the birthweight and of the presence of an associated major cardiac malformation. The survival rate is 97%, 59% and 22% for the first, the second and the third subgroups, respectively. Birthweight below 1500 grams and the coexistence of major cardiac anomalies represent poor prognostic indicators (22).

Outpatient monitoring is recommended in foetuses with a suspicion of or a diagnosis of OE. Polyhydramnios can become quite severe and may require amnioreduction for temporary maternal comfort. Preterm contractions and preterm labour may develop. Counselling by a geneticist, paediatric intensive care doctor and a paediatric surgeon is also recommended. Invasive testing for karyotyping with CGH-array should be offered. Delivery is recommended at a tertiary referral hospital with a neonatal intensive care and a paediatric surgery facilities.

Following delivery a suction catheter is placed in the upper oesophageal pouch in order to remove secretions and prevent aspiration. A careful physical exam to exclude associated anomalies is warranted. Vital signs monitoring, and vascular accesses should be performed as preventative measures (9). Neonates should be cared for in the Neonatal Intensive Care Unit (NICU) (23).

If respiratory distress occurs – particularly in preterm neonates –, intubation and mechanical ventilation may be required. In such cases, there is an increased risk of gastric over-distension and rupture of the stomach due to escape of gases from the respiratory tract through the fistula down into the stomach. This risk can be minimised by positioning the end of the endotracheal tube distal to the fistula and performing a low-pressure ventilation (9).

The placement of a nasogastric tube confirms diagnosis of OA. Chest X-ray and/or MRI may allow the anatomical classification of the anomaly and the measurement of the oesophageal gap (23). Additional imaging exams, such as neonatal echocardiogram, can be performed in order to exclude congenital heart disease (9).

The surgical treatment of OA can be performed either by thoracotomy or by thoracoscopy, includes the creation of an anastomosis between the proximal and the distal oesophageal pouch and the removal of the TEF, if present. The surgical treatment most commonly consists in early or delayed primary repair, which can be preceded by traction or elongation techniques, or in transposition techniques such as gastric transposition, colonic interposition, and jejunum interposition (23,24). The individualized approach usually depends on type of OA/TEF and its severity, by the extent of the oesophageal gap and by the expertise of the surgeon and operative team (24).

The comorbidities related to OA include postnatal growth retardation, recurrence of the TEF, gastroesophageal reflux, oesophageal dysmotility with feeding difficulties, tracheomalacia, and recurrent respiratory infections (9, 24, 25). Long-term follow-up is required and, in most instances, patients treated for OA have a good long term functional outcome (25).

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^{18. Dall'Asta A, Grisolia G, Nanni M, Volpe N, Schera GBL, Frusca T, Ghi T. Sonographic demonstration of fetal esophagus using three-dimensional ultrasound imaging. Ultrasound Obstet Gynecol. 2019 Dec;54(6):746-751.}

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^{23.Chiarenza SF, Conighi ML, Esposito C, et al. Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the esophageal atresia. Pediatr Med Chir. 2019;41(2):10.4081/pmc.2019.230. Published 2019 Dec 19. doi:10.4081/pmc.2019.230}

^{24. Van Lennep M, Singendonk MMJ, Dall'Oglio L, et al. Oesophageal atresia. Nat Rev Dis Primers. 2019;5(1):26. Published 2019 Apr 18. doi:10.1038/s41572-019-0077-0}

^{25. Little DC, Rescorla FJ, Grosfeld JL, West KW, Scherer LR, Engum SA. Long-term analysis of children with esophageal atresia and tracheoesophageal fistula. J Pediatr Surg. 2003;38(6):852-856. doi:10.1016/s0022-3468(03)00110-6}

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