G Model
YPRRV-1103; No. of Pages 6
Paediatric Respiratory Reviews xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Paediatric Respiratory Reviews
Mini-symposium: Esophageal Atresia and Tracheoesophageal Fistula
Motility, digestive and nutritional problems in Esophageal Atresia
Madeleine Gottrand, Laurent Michaud, Rony Sfeir, Fre´de´ric Gottrand *
CHU Lille, University Lille, National reference center for congenital malformation of the esophagus, Department of Pediatrics, F-59000 Lille, France
EDUCATIONAL AIMS
The reader will come to appreciate that:
Digestive and nutritional problems are frequent and interlinked in esophageal atresia.
A multidisciplinary approach is needed in esophageal atresia.
Esophageal atresia is not only a surgical neonatal problem but has lifelong consequences for digestive and nutritional
morbidity.
A R T I C L E I N F O S U M M A R Y
Keywords:
Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is a rare congenital
Anastomotic stricture
malformation. Digestive and nutritional problems remain frequent in children with EA both in early
Growth Retardation
infancy and at long-term follow-up. These patients are at major risk of presenting with gastroesophageal
Dysphagia
reflux and its complications, such as anastomotic strictures. Esophageal dysmotility is constant, and can
Gastro-Esophageal Reflux
Dysmotility have important consequences on feeding and nutritional status. Patients with EA need a systematic
Nutrition follow-up with a multidisciplinary team.
Children ß 2015 Elsevier Ltd. All rights reserved.
Esophageal atresia (EA) with or without tracheoesophageal Anastomotic stricture
fistula (TEF) is a rare congenital malformation [1,2]. The live-birth
prevalence of EA is 1.8 per 10 000 births in France [3]. The prognosis An astomotic stricture [AS] may arise because of important
of EA has benefited from advances in medical care, including anastomotic tension related to a long-gap between the two
neonatal and surgical procedures, and has therefore improved esophageal pouches, occurrence of a post-operative anastomotic
significantly over the past three decades. Its survival rate now leak and GER [18].
exceeds 95% and an increasing number of patients reach adulthood
[2,3]. However, digestive/nutritional problems remain frequent in
this population both in early infancy and at long-term follow-up [4]. Dysmotility
Dysmotility is not only a consequence of surgical repair as
WHY ARE DIGESTIVE, MOTILITY AND NUTRITIONAL PROBLEMS
abnormal innervation is present at birth. It involves the Auerbach
A CONCERN IN PATIENTS WITH EA?
plexus, ganglion cells, interstitial cells of Cajal (ICC), and both
excitatory and inhibitory intramural nerves mostly in the distal
Gastro-esophageal reflux (GER)
esophageal segment rather than in the proximal esophagus [19–
22]. Dysmotility is explained by an imbalance of neurotransmitter
Patients with EA are at major risk of having GER [5]. Several
excretion in nerve cells with decreased expression of neuronal
factors contribute to the physiopathology of GER in EA (Table 1).
markers, including vasoactive intestinal polypeptide (VIP) and
nitric oxide synthase (NOS) [19,20]. These congenital changes in
* Corresponding author. Tel.: +333 20 44 61 26; fax: +333 20 44 61 34. the innervation may lead to abnormal contraction and relaxation
E-mail addresses: [email protected] (M. Gottrand), and subsequent dysphagia, GER, and feeding difficulty in children
[email protected] (L. Michaud), [email protected] (R. Sfeir),
with EA [23]. [email protected] (F. Gottrand).
http://dx.doi.org/10.1016/j.prrv.2015.11.005
1526-0542/ß 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Gottrand M, et al. Motility, digestive and nutritional problems in Esophageal Atresia. Paediatr. Respir.
Rev. (2015), http://dx.doi.org/10.1016/j.prrv.2015.11.005
G Model
YPRRV-1103; No. of Pages 6
2 M. Gottrand et al. / Paediatric Respiratory Reviews xxx (2015) xxx–xxx
Table 1
Mechanisms of gastro esophageal reflux in esophageal atresia
Causes Mechanisms References
Excessive tension at the esophageal anastomosis - Decrease in lower sphincter tone [6,7] (Yanchar 2001, Montedonico 1999)
- Shortening of the intra-abdominal esophageal
segment
- Deformity of the cardioesophageal junction
Abnormal esophageal motility - Reduction of esophageal clearance [8–10] (Kawahara 2007, Van Wijk 2013,
- Longer acid and bolus clearing times Catalano 2011)
- Transient lower esophageal sphincter relaxation
Slow gastric emptying (controversial) - Congenital [5,11–13] (Jolley 1980, Lopes 2007,
- Surgically induced vagal nerve injury Romeo 2000, Montgomery 1998)
Abnormal gastric myoelectrical activity (minor role) - Disturbed neuromuscular function [12,14,15] (Yagi 1997, Bokay 2005,
- Antral hypomotility Romeo 2000)
Gastrostomy as an aggravating role (controversial) - Gastrostomy can worsen GER [16,17] (Black 1991, Shah 2015)
- Long-gap EA worsens GER and
- Long-gap EA often necessitate gastrostomy
(selection bias)
Nutritional problems prevalence of GER increased gradually from 16% at age 6 months to
51% at age of 5 years, while 44% of children still had GER at the age
Dysphagia is one of the main causes of nutritional problems. of 10 years [41]. Nonetheless, after 3 years of age, new cases of GER
Causes of dysphagia include esophagitis, GER, eosinophilic are rare and most of the patients presenting with GER are
esophagitis, dysmotility, anastomotic strictures, esophageal outlet symptomatic [41].
obstruction, aspiration and fear of feeding. Predictors of poor oral 24 hour esophageal pH-metry remains the gold standard for
intake are long gap atresia, CHARGE association, and neurologic the diagnosis of GER [46]. Koivusalo et al. suggested that early
abnormalities [24]. GER and esophagitis have been implicated as esophageal pH-metry (i.e before the age of 6 months) has a good
causes of feeding difficulties. However, motility abnormalities may specificity and positive predictive value for the outcome of EA
contribute to a much greater extent to dysphagia. Anastomotic associated GER but is not a good predictor of unfavorable GER or
strictures are another frequent cause of dysphagia and feeding need for anti-reflux surgery [38]. Specific normal values for
difficulties. esophageal pH-metry are not available in EA patients, but reflux
Fundoplication, which can create a functional esophageal outlet index, total number of reflux periods with pH<4 and numbers of
obstruction in the context of dysmotility, may also cause or periods of pH<4 lasting more than 5 minutes are very similar in EA
aggravate dysphagia and feeding difficulties. This is supported by a patients to those in normal infants of the same age [47,48]. A
study of children receiving a fundoplication, where 4.3% of the systematic esophageal pH-metry screening for GER by 9-12
cohort without EA presented with dysphagia, versus 17% in months of age is recommended.
children with EA [25]. Esophageal pH-impedance monitoring is a more recent
Aspiration is an under-recognized cause of feeding difficulty in technique that presents advantages compared to isolated esoph-
children with EA. Any respiratory symptom during feeding, ageal pH-metry. It allows the evaluation of retrograde bolus
including tachypnea, wheezing, and cough may compromise movements in the esophagus independent of the pH, identifying
feeding especially in infants [26–28]. non acidic reflux also in the postprandial period and in patients
Finally, EA patients may develop a fear of eating or texture receiving acid-suppressing therapy. It is a dynamic technique and,
aversions related to a history of food impaction [29]. therefore, can detect the direction of the flow, so that reflux can be
All these mechanisms are often associated and contribute to distinguished from swallowed oropharyngeal contents. Moreover,
reduced energy intake which leads to under-nutrition and growth it can accurately determine the height of the reflux and reflux-
failure. related symptoms. Combined with pH monitoring, it can distin-
guish between acidic and non-acidic reflux episodes [10]. However,
THE PREVALENCE AND HOW TO EXPLORE DIGESTIVE, MOTILITY the technique still has limitations: high cost, limited added value
AND NUTRITIONAL PROBLEMS IN PATIENTS WITH EA (TABLE 2) regarding therapeutic implications, and lack of evidence-based
parameters for the assessment of gastroesophageal reflux and
GER symptom association in children [49]. Experience of esophageal
pH-impedancemetry is increasing in EA patients [9,10,17,44,50,51]
GER is frequent in patients with EA, especially in isolated forms, and has demonstrated that reflux events are mainly non acidic
where it is reported in almost all the patients and often requires (62.7% of reflux episodes), and that mean acid clearing time and
fundoplication [30]. Depending on age, patient selection and mean bolus clearing time were significantly longer in EA patients
diagnostic methods, the prevalence of GER in patients with EA
varies from 20% to 63% [4,6,10,17,31–45]. GER can persist lifelong.
Complications such as late or recurrent anastomotic stenosis, Table 2
esophagitis and Barrett’s Esophagus (BE) can be observed during Frequency and age of complications of esophageal atresia
childhood, adolescence and adulthood (Table 3). There are few
Complications Frequency Age
longitudinal studies of the natural history of Gastro-esophageal
- GER - 20-63% - 1-10 years
Reflux in the EA population, and as a result the risk of recurrence of
- Peptic esophagitis - 9-53% - 3-5 years
GER has not been accurately assessed. GER appears to be
- Barrett esophagus - 1-2% - Adolescence,
particularly frequent during the first months of life, but especially adulthood
within the first 5 years in type C EA patients [the most common - Dysphagia - 61% - 5 years
- Anastomotic stricture - 18-60% - 1 year
type of TEF]. Koivusalo longitudinally assessed GER with esoph-
- Growth retardation, under-nutrition - 30% - 5 years
ageal pH-metry and histology in 61 children and showed that the
Please cite this article in press as: Gottrand M, et al. Motility, digestive and nutritional problems in Esophageal Atresia. Paediatr. Respir.
Rev. (2015), http://dx.doi.org/10.1016/j.prrv.2015.11.005
G Model
YPRRV-1103; No. of Pages 6
M. Gottrand et al. / Paediatric Respiratory Reviews xxx (2015) xxx–xxx 3
Table 3
screening for anastomotic stenosis has been advocated by some
Complications of gastro esophageal reflux over time
authors starting 1 month after surgery [59,62], while the majority
Time of occurrence Complication Frequency recommend to wait for clinical signs suggestive of esophageal
stenosis [54,56,57].
Short term Laryngomalacia aggravation
Anastomotic stenosis 18-60%
Peptic esophagitis 9-53% Dysmotility
Feeding difficulties 6-11%
Middle term Recurrent anastomotic stenosis 6%
Dysphagia is a common complaint occurring in 22-48% of older
Bronchial hyperreactivity
children and adults with EA [11,36,63]. Esophageal motility can be
Long term Barrett esophagus 5-36%
Esophageal adenocarcinoma (3 cases reported) assessed by a contrast study, esophageal manometry (water
perfused or more recently high resolution) or video manometry. All
studies suggested one can ascertain the degree of dysmotility;
rating it as mild, moderate or severe esophageal dysmotility
compared to controls, adding to the understanding of the [64]. With manometry, the patterns of esophageal dysmotility
pathophysiology of GER in this population [9,10,50]. On rare include 3 types: pressurization 15%, distal contraction 50% and
occasions, such as in infants presenting with dying/cyanotic spells aperistalsis 35%. Consistently, the pattern of esophageal dysmo-
or those found to have a direct time-related event with non-acidic tility is not predictive of the presence or severity of dysphagia [65]
reflux (using a score), pH-impedancemetry can be helpful when nor the outcome of fundoplication. There is currently no evidence
considering the indication for fundoplication. Thus, it is a for the benefit of using esophageal manometry to direct medical
convenient technique in research for the evaluation of new drugs management.
and for the study of swallowing abnormalities [9,10,51]. An upper gastro intestinal contrast study is predictive of
There are no studies assessing the benefit of routine upper delayed esophageal emptying and dysmotility. When performed,
gastrointestinal endoscopy in the follow-up of patients with EA. an upper gastrointestinal contrast series allows for early detection
Eighty percent of grade C or D EA patients present with either of dysmotility, and can differentiate degrees of severity [31].
moderate or severe esophagitis or gastric metaplasia at any time in
follow-up, but the risk of occurrence is maximal during the first Nutritional problems
3 to 5 years of life. The risk of having unfavorable histology after
6 years of repeated normal biopsies is very low [42,43]. Endoscopic The reported rates of feeding abnormalities varies from 6% to
esophageal mucosal abnormalities can be observed in patients 11% [24,29,66]. After solid food introduction in the diet, the
with EA despite the absence of symptoms. following food difficulties have been observed: slow to feed (52%),
When performed, upper gastrointestinal endoscopy should cough or choking with feeds (32%), vomiting with feeds (16%) [67],
carefully examine the upper part of the esophagus (inlet patch is food refusal (16%) or dysphagia (61%) [4]. Children with EA have a
more frequent in this population [52]), esogastric junction and significant reduction of height and weight (mean height z score -
anastomosis area. In addition, the endoscopist should look for 1.78Æ1.7) and mean weight for height (-1.1Æ0.9). Only 7% of patients
th
stenosis, a diverticulum or fistula, hiatal hernia, and peptic or with EA are less than the 5 percentile for height and weight and low
eosinophilic esophagitis. In any case, when an endoscopy is birth weight is predictor of a smaller size [37].
performed and even when it appears macroscopically normal, at Initial evaluation of dysphagia includes an endoscopy to
least 4 biopsies, in quadrants, one centimeter above the Z line and evaluate the anastomotic site and esophageal inflammation
one biopsy in the middle part of the esophagus are recommended contributing to symptoms. There is a poor correlation with the
for Barrett and eosinophilic esophagitis screening. The number of symptom of dysphagia and inflammation. It has been reported that
biopsies should be increased in the presence of macroscopic 38% of patients with normal esophageal biopsies have food
abnormalities. GER can remain asymptomatic, and several studies impactions and only 32% of patients with endoscopic inflammation
have shown the absence of correlation between clinical signs and have food impactions [42].
complications of GER (mainly esophagitis) in this population
[17,35,36,42,43]. TREATMENT AND FOLLOW-UP
In children who underwent a fundoplication, repeated system-
atic endoscopy is recommended, as recurrence of GER and peptic Gastro-esophageal Reflux
esophagitis or Barrett’s Esophagus are possible for these patients
[25,30,53]. GER is frequent during infancy and complications due to GER
are observed mostly during the first 2 years of life [42]. Most of the
Anastomotic stricture complications due to GER in EA are linked to acid reflux (ie
esophagitis, refusal to eat, anastomotic stenosis) rather than non-
AS is the most frequent post-operative complication occurring acidic reflux. Medical management of GER by whatever the agent
in 18% to 60% of patients with EA [18,54–57]. Clinical signs include used (mainly proton pump inhibitor (PPI) and H2 receptor
dysphagia, vomiting, cough, recurrent respiratory infections and antagonists) is successful by reducing gastro-intestinal symptoms,
poor weight gain [56,58]. A history of an esophageal foreign body respiratory symptoms or showing an improved weight gain
in a young child with EA [usually retained food such as chicken] is [68]. There are no efficient pro-kinetics currently available.
highly suggestive of an AS. There is no evidence to justify increasing systematically the
AS is diagnosed by a contrast X-ray or endoscopy. Although no dosage of PPI in EA: neither evidence of abnormal high acidic
consensus definition of AS exists, it is defined by a reduction of secretion in this condition, nor resistance to PPI reported.
esophageal diameter compared to an age-related normal esopha- Esophagitis seems more frequent in EA patients and is the
gus with associated symptoms. Stricture index (SI) can be leading cause of Barrett’s Esophagus, which is a premalignant
calculated with the formula SI= (D-d)/D, in which ‘‘D’’ is the lesion that can be prevented by PPI [69]. Long-term treatment with
largest diameter of the esophagus closed from the stricture and ‘‘d’’ PPI might expose the patient to adverse events although this has
is the stricture diameter. SI has been used to assess the degree of been poorly studied in children. Long term PPI treatment is not
the stricture at contrast X-Ray [59,60] or at endoscopy [61]. Routine generally recommended in the pediatric population. Therefore, the
Please cite this article in press as: Gottrand M, et al. Motility, digestive and nutritional problems in Esophageal Atresia. Paediatr. Respir.
Rev. (2015), http://dx.doi.org/10.1016/j.prrv.2015.11.005
G Model
YPRRV-1103; No. of Pages 6
4 M. Gottrand et al. / Paediatric Respiratory Reviews xxx (2015) xxx–xxx
benefit/risk of long term PPI treatment should be balanced in this semi-rigid dilators (as Savary-Giliard bougies) or balloons. There is
population and the need for prolonged treatment reassessed on a no consensus about the optimal diameter and frequency of the
regular basis. dilations [59,75]. Dilations sessions are usually repeated every 1 to
Indications for fundoplication vary widely from one center to 2 weeks until a stable diameter is obtained [59,75] or resolution of
another. Cumulative risk to have a fundoplication performed in EA the symptoms is achieved [54,61]. Anastomotic stricture (AS)
patients is up to 45%. In the literature, indications may include resection and re-anastomosis or partial or total esophageal
failure of maximum conservative therapy for GER and/or substitution is reserved for conservative management failures.
esophagitis, an apparent life-threatening event, recurrent anasto- Recurrent AS is defined as reappearance of symptoms, 3 or more
motic stenosis, fistula recanalization and failure to thrive times, more than 30 days after last dilation [75]. Experimental data
[37,68,70]. In long gap EA, GER seems particularly frequent and as well as clinical experience suggest that GER is the major cause of
is associated with a higher risk of anastomotic stenosis, suggesting recurrent anastomotic stenosis [76,77] and in these cases
that fundoplication should be proposed for a large proportion of fundoplication has to be considered [18]. Recurrent AS can also
those children. The timing of fundoplication varies from one center be treated by steroid stricture injection [78–81], topical applica-
to another but is often performed during early childhood, between tion of the anti-fibroblastic agent mitomycine C [82] (Figure 1) and
1 and 24 months after the atresia repair [70]. However, performing stents [83–86].
a fundoplication early in life exposes the child to a higher risk of
failure [71]. Dysmotility
In highly selected cases, when severe reflux persists despite
fundoplication, or after repair of a tracheoesophageal cleft, or in Intrinsic abnormal motility of the esophagus is a constant
severe microgastry, total gastric dissociation could be considered feature in EA where pro-kinetics are unlikely to be as efficient as in
[72]. However, long term complications including dumping a child with normal esophageal motility [87]. Therefore, due to
syndrome, nutritional deficiency and growth failure, long term their potential side effects and lack of efficiency, the use of pro-
dependency to enteral feeding, Barrett’s Esophagus and eso- kinetics is not recommended in EA patients. There is no current
phago-jejunal anastomosis stenosis have been recently reported specific drug option to treat dysmotility.
[73,74].
Due to the high frequency of GER in infancy and risk of Nutritional problems
complications, there is a general recommendation to systemati-
cally treat all EA patients with PPI during the first months of life. An Aggressive pulmonary toileting, early treatment of infections,
esophageal pH-metry after stopping PPI is recommended at that and use of inhaled medications are all critical to maintain lung
time. Long-term regular endoscopic follow-up of EA patients is also health and reduce the risk of feeding difficulties.
recommended. Careful nutritional follow-up is required and relies on growth
and height charts. Several measures can be combined to prevent
Anastomotic stricture or treat under-nutrition: individually adapted food consistency
and timing of introducing solid foods, oral rehabilitation with
Conservative treatment consists of intraluminal dilations, to help of a speech therapist and psychologist, nutritional comple-
obtain a stable esophageal diameter that allows normal eating and ments, even enteral nutrition via a gastrostomy or via a naso-
disappearance of symptoms. Dilations can be done either using gastric tube.
Figure 1. Left: Recurrent anastomotic stenosis in a 15 months old patient with esophageal atresia (arrow) Right: Upper GI series 3 years after one application of mitomycine C
showing the absence of stenosis.
Please cite this article in press as: Gottrand M, et al. Motility, digestive and nutritional problems in Esophageal Atresia. Paediatr. Respir.
Rev. (2015), http://dx.doi.org/10.1016/j.prrv.2015.11.005
G Model
YPRRV-1103; No. of Pages 6
M. Gottrand et al. / Paediatric Respiratory Reviews xxx (2015) xxx–xxx 5
complications associated with repair of esophageal atresia. J Pediatr Surg
SPECIAL FOCUS ON LONG GAP EA
2001;36:815–22.
[7] Montedonico S, Diez-Pardo JA, Posso¨gel AK, Tovar JA. Effects of esophageal
Long-gap (LG) EA is a high-risk group for digestive and shortening on the gastroesophageal barrier: an experimental study on the
causes of reflux in esophageal atresia. J Pediatr Surg 1999;34:300–3.
nutritional problems. LG represents 10% to 26% of the total
[8] Kawahara H, et al. Lack of distal esophageal contractions is a key determinant
esophageal atresia (EA) patients –according to its definition- mainly
of gastroesophageal reflux disease after repair of esophageal atresia. J Pediatr
observed in type A (pure EA >50%) but also in other forms (type B, C Surg 2007;42:2017–21.
[9] Van Wijk M, Knu¨ ppe F, Omari T, de Jong J, Benninga M. Evaluation of
and D). It is a major surgical challenge. Options for esophageal
gastroesophageal function and mechanisms underlying gastroesophageal re-
reconstruction include the use of native esophagus –which is the
flux in infants and adults born with esophageal atresia. J Pediatr Surg
preferred strategy- or esophageal replacement with stomach, colon, 2013;48:2496–505.
or small intestine. Besides surgical difficulties, digestive and [10] Catalano P, Di Pace MR, Caruso AM, Casuccio A, De Grazia E. Gastroesophageal
reflux in young children treated for esophageal atresia: evaluation with pH-
nutritional problems appear much more frequent than in other
multichannel intraluminal impedance. J Pediatr Gastroenterol Nutr 2011;52:686–90.
forms of EA and are responsible for a high morbidity. These
[11] Lopes MF, Botelho MF. Midterm follow-up of esophageal anastomosis for
problems result from the combination of several factors: EA per se esophageal atresia repair: long-gap versus non-long-gap. Dis Esophagus 2007;20:
428–35.
(gastric and esophageal dysmotility, GER), anatomical form
[12] Romeo C, et al. Gastric motility disorders in patients operated on for esoph-
(microgastria), and surgery (lack of oral feeding due to delayed
ageal atresia and tracheoesophageal fistula: long-term evaluation. J Pediatr
anastomosis, anastomotic tension, anastomotic stenosis, GER, Surg 2000;35:740–4.
[13] Montgomery M, Escobar-Billing R, Hellstro¨m PM, Karlsson KA, Frenckner B.
consequences of esophageal replacement).
Impaired gastric emptying in children with repaired esophageal atresia: a
Several factors contribute to the physiopathology of GER in long
controlled study. J Pediatr Surg 1998;33:476–80.
gap EA. Excessive tension at the esophageal anastomosis is [14] Yagi M, et al. Electrogastrography after operative repair of esophageal atresia.
Pediatr Surg Int 1997;12:340–3.
associated with a higher incidence of GER.
[15] Bo´ kay J, Kis E, Verebe´ly T. Myoelectrical activity of the stomach after surgical
Compared to non-long gap population, the need of repeated
correction of esophageal atresia. J Pediatr Surg 2005;40:1732–6.
dilations (up to 50%), fundoplication (20 to 44%, often performed [16] Black TL, et al. The effect of tube gastrostomy on gastroesophageal reflux in
patients with esophageal atresia. J Pediatr Surg 1991;26:168–70.
very early in life), as well as gastrostomy (almost 100%), and
[17] Shah R, Varjavandi V, Krishnan U. Predictive factors for complications in
malnutrition (33%) are much more frequent in long gap EA.
children with esophageal atresia and tracheoesophageal fistula. Dis Esophagus
Microgastria, when severe, often represents an additional 2015;28:216–23.
challenging problem for gastrostomy feeding (feeding intolerance, [18] Chittmittrapap S, Spitz L, Kiely EM, Brereton RJ. Anastomotic stricture follow-
ing repair of esophageal atresia. J Pediatr Surg 1990;25:508–11.
leakage around the stoma, dumping syndrome) and need for
[19] Zuccarello B, et al. Intramural ganglion structures in esophageal atresia: a
fundoplication.
morphologic and immunohistochemical study. Int J Pediatr 2009;2009:
Although there are no randomized studies comparing esophage- 695837.
[20] Boleken M, et al. Reduced neuronal innervation in the distal end of the
al end to end anastomosis to gastro/coloplasty, and the published
proximal esophageal atretic segment in cases of esophageal atresia with distal
series are small and retrospective, it has been suggested a higher risk
tracheoesophageal fistula. World J Surg 2007;31:1512–7.
of recurrent esophageal stenosis in end to end anastomosis, similar [21] Nakazato Y, Landing BH, Wells TR. Abnormal Auerbach plexus in the esopha-
gus and stomach of patients with esophageal atresia and tracheoesophageal
rate of GERD but more under-nutrition is observed in the long term
fistula. J Pediatr Surg 1986;21:831–7.
following gastro/coloplasty. The long gap population is a small but
[22] Midrio P, et al. Reduction of interstitial cells of Cajal in esophageal atresia.
high-risk group for prolonged digestive and nutritional problems. J Pediatr Gastroenterol Nutr 2010;51:610–7.
[23] Li Y, Litingtung Y, Ten Dijke P, Chiang C. Aberrant Bmp signaling and notochord
These patients require a prolonged multidisciplinary follow-up and
delamination in the pathogenesis of esophageal atresia. Dev Dyn 2007;236:
should be referred to reference centers. 746–54.
[24] Koivusalo AI, Pakarinen MP, Rintala RJ. Modern outcomes of oesophageal
atresia: single centre experience over the last twenty years. J Pediatr Surg
CONFLICTS OF INTEREST
2013;48:297–303.
[25] Holschneider P, Du¨ bbers M, Engelskirchen R, Trompelt J, Holschneider AM.
None Results of the operative treatment of gastroesophageal reflux in childhood
with particular focus on patients with esophageal atresia. Eur J Pediatr Surg
2007;17:163–75.
FUTURE DIRECTIONS FOR CLINICAL RESEARCH
[26] Smith IJ, Beck J. Mechanical feeding difficulties after primary repair of oeso-
phageal atresia. Acta Paediatr Scand 1985;74:237–9.
To assess natural history of gastro-esophageal reflux with pH- [27] Khoshoo V, Edell D. Previously healthy infants may have increased risk of
impedancemetry. aspiration during respiratory syncytial viral bronchiolitis. Pediatrics 1999;104:
1389–90.
To assess the incidence of Barrett esophagus and esophageal
[28] Khoshoo V, Ross G, Kelly B, Edell D, Brown S. Benefits of thickened feeds in
carcinoma in children and adults with esophageal atresia. previously healthy infants with respiratory syncytial viral bronchiolitis.
Pediatr Pulmonol 2001;31:301–2.
To assess the prognostic value of high definition manometry in
[29] Khan KM, et al. Achievement of feeding milestones after primary repair of
esophageal atresia.
long-gap esophageal atresia. Early Hum Dev 2009;85:387–92.
To test new prokinetics in the management of dysphagia. [30] Lindahl H, Rintala R. Long-term complications in cases of isolated esophageal
atresia treated with esophageal anastomosis. J Pediatr Surg 1995;30:1222–3.
[31] Montgomery M, Frenckner B. Esophageal Atresia: Mortality and Complications
Related to Gastroesophageal Reflux. Eur J Pediatr Surg 1993;3:335–8.
References [32] Engum, S.A., Grosfeld, J.L., West, K.W., Rescorla, F.J. & Scherer, L.R. Analysis of
morbidity and mortality in 227 cases of esophageal atresia and/or tracheoe-
sophageal fistula over two decades. Arch. Surg. 130, 502–8; discussion 508–9
[1] Shaw-Smith C. Genetic factors in esophageal atresia, tracheo-esophageal (1995).
fistula and the VACTERL association: roles for FOXF1 and the 16q24.1 FOX
[33] Chetcuti P, Myers NA, Phelan PD, Beasley SW. Adults who survived repair
transcription factor gene cluster, and review of the literature. Eur J Med Genet
of congenital oesophageal atresia and tracheo-oesophageal fistula. BMJ
2010;53:6–13. 1988;297:344–6.
[2] Spitz L. Oesophageal atresia. Orphanet J Rare Dis 2007;2:24.
[34] Somppi E, et al. Outcome of patients operated on for esophageal atresia:
[3] Sfeir R, Michaud L, Salleron J, Gottrand F. Epidemiology of esophageal atresia.
30 years’ experience. J Pediatr Surg 1998;33:1341–6.
Dis Esophagus 2013;26:354–5.
[35] Krug E, et al. Gastroesophageal reflux and Barrett’s esophagus in adults born
[4] Legrand C, et al. Long-term outcome of children with oesophageal atresia type
with esophageal atresia. Am J Gastroenterol 1999;94:2825–8.
III. Arch Dis Child 2012;97:808–11.
[36] Deurloo JA, et al. Gastroesophageal reflux: prevalence in adults older than
[5] Jolley SG, et al. Patterns of gastroesophageal reflux in children following repair
28 years after correction of esophageal atresia. Ann Surg 2003;238:686–9.
of esophageal atresia and distal tracheoesophageal fistula. J Pediatr Surg
[37] Deurloo JA, Ekkelkamp S, Schoorl M, Heij HA, Aronson DC. Esophageal atresia:
1980;15:857–62.
historical evolution of management and results in 371 patients. Ann Thorac
[6] Yanchar NL, Gordon R, Cooper M, Dunlap H, Soucy P. Significance of
Surg 2002;73:267–72.
the clinical course and early upper gastrointestinal studies in predicting
Please cite this article in press as: Gottrand M, et al. Motility, digestive and nutritional problems in Esophageal Atresia. Paediatr. Respir.
Rev. (2015), http://dx.doi.org/10.1016/j.prrv.2015.11.005
G Model
YPRRV-1103; No. of Pages 6
6 M. Gottrand et al. / Paediatric Respiratory Reviews xxx (2015) xxx–xxx
[38] Koivusalo A, Pakarinen M, Rintala RJ, Lindahl H. Does postoperative pH [62] Hagander L, Muszynska C, Arnbjornsson E, Sandgren K. Prophylactic treatment
monitoring predict complicated gastroesophageal reflux in patients with with proton pump inhibitors in children operated on for oesophageal atresia.
esophageal atresia? Pediatr Surg Int 2004;20:670–4. Eur J Pediatr Surg 2012;22:139–42.
[39] Konkin DE, O’hali WA, Webber EM, Blair GK. Outcomes in esophageal atresia [63] Little DC, et al. Long-term analysis of children with esophageal atresia and
and tracheoesophageal fistula. J Pediatr Surg 2003;38:1726–9. tracheoesophageal fistula. J Pediatr Surg 2003;38:852–6.
[40] Taylor ACF, et al. Gastroesophageal reflux and related pathology in adults who [64] Deurloo JA, Klinkenberg EC, Ekkelkamp S, Heij HA, Aronson DC. Adults with
were born with esophageal atresia: a long-term follow-up study. Clin Gastro- corrected oesophageal atresia: is oesophageal function associated with com-
enterol Hepatol 2007;5:702–6. plaints and/or quality of life? Pediatr Surg Int 2008;24:537–41.
[41] Koivusalo A, Pakarinen MP, Rintala RJ. The cumulative incidence of significant [65] Lemoine C, et al. Characterization of esophageal motility following esophageal
gastrooesophageal reflux in patients with oesophageal atresia with a distal atresia repair using high-resolution esophageal manometry. J Pediatr Gastro-
fistula–a systematic clinical, pH-metric, and endoscopic follow-up study. enterol Nutr 2013;56:609–14.
J Pediatr Surg 2007;42:370–4. [66] Baird R, Levesque D, Birnbaum R, Ramsay M. A pilot investigation of feeding
[42] Castilloux J, Bouron-Dal Soglio D, Faure C. Endoscopic assessment of children problems in children with esophageal atresia. Dis Esophagus 2015;28:224–8.
with esophageal atresia: Lack of relationship of esophagitis and esophageal [67] Puntis JW, Ritson DG, Holden CE, Buick RG. Growth and feeding problems after
metaplasia to symptomatology. Can J Gastroenterol 2010;24:312–6. repair of oesophageal atresia. Arch Dis Child 1990;65:84–8.
[43] Sistonen SJ, Pakarinen MP, Rintala RJ. Long-term results of esophageal [68] Shawyer AC, D’Souza J, Pemberton J, Flageole H. The management of postop-
atresia: Helsinki experience and review of literature. Pediatr Surg Int erative reflux in congenital esophageal atresia–tracheoesophageal fistula: a
2011;27:1141–9. systematic review. Pediatr Surg Int 2014;30:987–96.
[44] Pedersen RN, et al. Esophageal atresia: gastroesophageal functional follow-up [69] Schneider A, Michaud L, Gottrand F. Esophageal atresia: metaplasia. Barrett Dis
in 5-15 year old children. J Pediatr Surg 2013;48:2487–95. Esophagus 2013;26:425–7.
[45] Bouguermouh D, Salem A. Esophageal atresia: a critical review of management [70] Bergmeijer JH, Tibboel D, Hazebroek FW. Nissen fundoplication in the man-
at a single center in Algeria. Dis Esophagus 2015;28:205–10. agement of gastroesophageal reflux occurring after repair of esophageal
[46] Vandenplas Y, et al. Pediatric gastroesophageal reflux clinical practice guide- atresia. J Pediatr Surg 2000;35:573–6.
lines: joint recommendations of the North American Society for Pediatric [71] Lopez-Fernandez S, et al. Failed Nissen fundoplication in children: causes and
Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European management. Eur J Pediatr Surg 2014;24:79–82.
Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). [72] De Lagausie P, et al. Reflux in esophageal atresia, tracheoesophageal cleft, and
J Pediatr Gastroenterol Nutr 2009;49:498–547. esophagocoloplasty: Bianchi’s procedure as an alternative approach. J Pediatr
[47] Bergmeijer JH, Bouquet J, Hazebroek FW. Normal ranges of 24-hour pH-metry Surg 2005;40:666–9.
established in corrected esophageal atresia. J Pediatr Gastroenterol Nutr [73] Gottrand M, et al. Barrett esophagus and esophagojejunal anastomotic steno-
1999;28:162–3. sis as complications of esophagogastric disconnection in children with esoph-
[48] Vandenplas Y, Sacre´-Smits L. Continuous 24-hour esophageal pH monitoring ageal atresia. J Pediatr Gastroenterol Nutr 2013;57:93–5.
in 285 asymptomatic infants 0-15 months old. J Pediatr Gastroenterol Nutr [74] Madre C, et al. Prolonged enteral feeding is often required to avoid long-term
1987;6:220–4. nutritional and metabolic complications after esophagogastric dissociation.
[49] Wenzl TG, Benninga MA, Loots CM, Salvatore S, Vandenplas Y. Indications, J Pediatr Gastroenterol Nutr 2010;50:280–6.
methodology, and interpretation of combined esophageal impedance-pH [75] Antoniou D, Soutis M, Christopoulos-Geroulanos G. Anastomotic strictures
monitoring in children: ESPGHAN EURO-PIG standard protocol. J Pediatr following esophageal atresia repair: a 20-year experience with endoscopic
Gastroenterol Nutr 2012;55:230–4. balloon dilatation. J Pediatr Gastroenterol Nutr 2010;51:464–7.
[50] Di Pace MR, et al. Evaluation of esophageal motility and reflux in children [76] Banjar HH, Al-Nassar SI. Gastroesophageal reflux following repair of esoph-
treated for esophageal atresia with the use of combined multichannel intra- ageal atresia and tracheoesophageal fistula. Saudi Med J 2005;26:781–5.
luminal impedance and pH monitoring. J Pediatr Surg 2011;46:443–51. [77] McKinnon LJ, Kosloske AM. Prediction and prevention of anastomotic com-
[51] Fro¨hlich T, et al. Combined esophageal multichannel intraluminal impedance plications of esophageal atresia and tracheoesophageal fistula. J Pediatr Surg
and pH monitoring after repair of esophageal atresia. J Pediatr Gastroenterol 1990;25:778–81.
Nutr 2008;47:443–9. [78] Lilly JR, Bensard D. Intralesional steroid injection in the management of
[52] Georges A, et al. Inlet Patch: Clinical Presentation and Outcome in Children. esophageal stricture. J Pediatr Surg 1989;24:1312.
J Pediatr Gastroenterol Nutr 2011;52:419–23. [79] Gandhi, R.P., Cooper, A. & Barlow, B.A. Successful management of esophageal
[53] Lindahl H, Rintala R, Louhimo I. Failure of the Nissen fundoplication to control strictures without resection or replacement. J. Pediatr. Surg. 24, 745–9; dis-
gastroesophageal reflux in esophageal atresia patients. J Pediatr Surg 1989;24: cussion 749–50 (1989).
985–7. [80] Zein NN, Greseth JM, Perrault J. Endoscopic intralesional steroid injections in
[54] Michaud L, et al. [Anastomotic stenosis after surgical treatment of esophageal the management of refractory esophageal strictures. Gastrointest Endosc
atresia: frequency, risk factors and effectiveness of esophageal dilatations]. 1995;41:596–8.
Arch Pediatr 2001;8:268–74. [81] Hirdes MMC, et al. Endoscopic corticosteroid injections do not reduce dys-
[55] Kovesi T, Rubin S. Long-term complications of congenital esophageal atresia phagia after endoscopic dilation therapy in patients with benign esophago-
and/or tracheoesophageal fistula. Chest 2004;126:915–25. gastric anastomotic strictures. Clin Gastroenterol Hepatol 2013;11. 795–801.e1.
[56] Spitz L. Esophageal atresia. J Pediatr Surg 2006;41:1635–40. [82] Uhlen S, et al. Mitomycin C: an alternative conservative treatment for refrac-
[57] Serhal L, et al. Anastomotic stricture after surgical repair of esophageal atresia: tory esophageal stricture in children? Endoscopy 2006;38:404–7.
frequency, risk factors, and efficacy of esophageal bougie dilatations. J Pediatr [83] Kramer RE, Quiros JA. Esophageal stents for severe strictures in young chil-
Surg 2010;45:1459–62. dren: experience, benefits, and risk. Curr Gastroenterol Rep 2010;12:203–10.
[58] Gatzinsky V, Jo¨nsson L, Ekerljung L, Friberg L-G, Wennergren G. Long-term [84] Broto J, Asensio M, Vernet JMG. Results of a new technique in the treatment of
respiratory symptoms following oesophageal atresia. Acta Paediatr 2011;100: severe esophageal stenosis in children: poliflex stents. J Pediatr Gastroenterol
1222–1225. Nutr 2003;37:203–6.
[59] Said M, et al. Balloon dilatation of anastomotic strictures secondary to surgical [85] Manfredi MA, et al. Externally removable stents in the treatment of benign
repair of oesophageal atresia. Br J Radiol 2003;76:26–31. recalcitrant strictures and esophageal perforations in pediatric patients with
[60] Zhao R, Li K, Shen C, Zheng S. The outcome of conservative treatment for esophageal atresia. Gastrointest Endosc 2014;80:246–52.
anastomotic leakage after surgical repair of esophageal atresia. J Pediatr Surg [86] Caldaro T, et al. Dynamic esophageal stents. Dis Esophagus 2013;26:388–91.
2011;46:2274–8. [87] Tovar JA, et al. Ambulatory 24-hour manometric and pH metric evidence of
[61] Parolini F, et al. Anastomotic strictures and endoscopic dilatations following permanent impairment of clearance capacity in patients with esophageal
esophageal atresia repair. Pediatr Surg Int 2013;29:601–5. atresia. J Pediatr Surg 1995;30:1224–31.
Please cite this article in press as: Gottrand M, et al. Motility, digestive and nutritional problems in Esophageal Atresia. Paediatr. Respir.
Rev. (2015), http://dx.doi.org/10.1016/j.prrv.2015.11.005