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Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e318202a3e5
Original Articles: Gastroenterology

Gastroesophageal Reflux in Young Children Treated for Esophageal Atresia: Evaluation With pH-Multichannel Intraluminal Impedance

Catalano, Pieralba; Di Pace, Maria R; Caruso, Anna M; Casuccio, Alessandra; De Grazia, Enrico

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Author Information

Pediatric Surgical Unit, Department of Mother and Child Care, University of Palermo, Italy.

Received 10 September, 2009

Accepted 18 October, 2010

Address correspondence and reprint requests to Pieralba Catalano, Division of Pediatric Surgery, University of Palermo, Via Alfonso Giordano 3, Palermo, Italy (e-mail:

The authors report no conflicts of interests.

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Objectives: Gastroesophageal reflux (GER) and dismotility occur frequently after repair of esophageal atresia (EA). GER-associated complications can manifest either early or later; then precocious diagnosis and treatment are essential. The aim of the study was to evaluate characteristics of GER and esophageal clearance in children treated for EA with distal tracheoesophageal fistula, using pH-multichannel intraluminal impedance (pH-MII).

Patients and Methods: Twenty-two children (ages 3–40 months) treated for EA at birth, and 20 normal children of similar age with suspected GER disease were included in the study. Impedance parameters were analyzed according to age and symptoms.

Results: Reflux events were mainly nonacidic. About bolus exposure index, mean acid clearing time (MACT), and mean bolus clearing time (MBCT), a significant difference was found between 2 groups: the median MACT and MBCT were longer, with values of 281 and 39 seconds, respectively, in the EA group and 110 and 15 seconds in the control group (P < 0.0005).

Conclusions: Our data show that in young patients the majority of refluxes are not acid. This implies that the incidence of GER may be underestimated if pH-metry is used. The pH-MII is an ideal test in children because it studies both GER with its characteristics and motility pattern. The quality of reflux does not seem to influence the onset of symptoms that are related to an impaired esophageal clearance. Hence, this technique could be useful to study patients treated for EA, avoiding the onset of complications.

Esophageal atresia (EA) is a relatively common congenital malformation occurring in 1:2500 births (1). Pathological gastroesophageal reflux (GER) is a major cause of complications after repair of EA and can require long-term medical therapy or antireflux surgery in cases of failure of medical management (2). Reflux is reported to be more common in patients with anastomosis under tension, after gastrostomy, and after delayed primary repair; however, an impaired esophageal motility may have a role in increasing the incidence of reflux (3). GER disease (GERD) can manifest either early after the operation with anastomotic stricture, dysphagia, and bronchopulmonary complications, or later with respiratory problems and esophagitis (4); Barrett esophagus and adenocarcinoma or squamous cell carcinoma in adults have been described (5). Then, an early diagnosis with appropriate treatment is important. Recently, endoscopic and pH-metric evaluations have been used in the routine follow-up program of patients treated for EA; however, these techniques can underestimate GER and its complications, especially in young children with nonacid refluxes and without esophageal lesions even with severe symptoms.

Multichannel intraluminal impedance (MII) was recently introduced as an alternative diagnostic tool in the evaluation of GER, and a large number of studies have been published demonstrating that pH-MII is superior to pH-metry in infants and children (5–14). This impedance allows the evaluation of retrograde bolus movements in the esophagus independent of the pH, identifying nonacidic reflux also in the postprandial period and in patients receiving acid-suppressing therapy. It is also a dynamic technique and, therefore, can detect the direction of the flow, so that refluxate can be distinguished from swallowed oropharyngeal contents. Moreover, it can accurately determine the height of the reflux and reflux-related symptoms. Combined with pH monitoring, it can distinguish between acidic and nonacidic refluxes (15).

MII allows the evaluation of esophageal motility and assesses bolus transport throughout the entire esophagus in real time, without the use of radiation: for this reason, MII has been used in adults to evaluate the esophageal function directly. Manometry gives information about esophageal pressure pattern and sphincter function, but does not give information about the bolus transit. MII not only detects the presence of esophageal flow but it also evaluates the direction of bolus transit, the duration of bolus presence, and the time of acid and bolus clearance.

MII in combination with pH-metry not only detects all GER but it also enables us to more accurately reveal associations between GER and symptoms: a clear temporal association between GER episodes and symptoms seems to provide convincing evidence of one causing the other. With pH-MII the correlation between symptoms and impaired esophageal clearance is possible (16).

The aim of our study was to evaluate, in the first years of life, the characteristics of GER and esophageal clearance in patients treated for EA and distal tracheoesophageal fistula (EADF) at birth using combined pH-MII, comparing them with a group of children without EA.

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Twenty-two children who underwent primary repair for EADF between January 2004 and December 2008 were included in the study. All of the patients were operated on by 1 surgeon, with an extrapleural approach through a right-sided thoracotomy. No long gap between esophageal segments was reported and a tension-free anastomosis was performed in all of the patients. No postoperative complication was recorded. In all of the patients a contrast study was performed, with no evidence of stenosis. All of the patients underwent endoscopy 1 month before the pH-MII, and it was negative for esophagitis.

At a median age of 15 months (3–40 months), a 24-hour pH-MII study was performed in all of the patients with EA as screening for GER; informed consent was obtained. In patients who were being treated with antacid therapy, medications were discontinued at least 10 days before the investigation. Parents were asked to fill out a diary during the procedure to record the exact time of every meal, recumbent position, and symptoms as regurgitate, heartburn, dysphagia, agitation, and cough or other respiratory symptoms. Dysphagia was defined and reported in the diary by parents as difficulty in swallowing during the meal. All of the patients were allowed to eat and drink only during regular meals and not allowed to drink or eat acidic foods. The procedure was performed using hardware and software by Sandhill Technologies (Sandhill Scientific Inc, Highlands Ranch, CO). We used a ComforTec MII-pH single-use “infant type” endoesophageal probe, 2.1 mm in outer diameter, with 6 impedance amplifiers 1.5-cm apart, the first one just above the tip. The probe included a single esophageal pH recording channel 2 cm above the tip. The probe underwent nasoesophageal positioning without anesthesia; the tip of the probe was placed 2 vertebral bodies above the diaphragm with fluoroscopy assessment of its position. All of the examinations were included in the study, because they lasted more than 20 hours.

Analysis of the pH-MII tracings was performed with Sandhill Scientific software (BioView Analysis version 5.2.3). The tracings were revised visually and manually for bolus and symptom events by 1 investigator.

The following parameters were evaluated:

1. Number of acidic (pH < 4) and nonacidic (pH > 4) retrograde bolus movements: decreased in impedance in at least 2 consecutive recording channels with upward direction

2. Height of reflux: refluxes that reached at least the second most proximal channel in the upper esophagus were considered high refluxes

3. Symptom index: reflux-related symptom events/total symptom events. It was considered abnormal if >50%; a symptom was correlated with a reflux event if the reflux event occurred 2 minutes before or 2 minutes after a symptom occurred: we defined a symptom as being “induced” by reflux (“reflux-symptom”) if the symptom occurred within 2 minutes after the onset of the reflux episode, whereas we defined a symptom as “precipitating” reflux (“symptom-reflux”) if the reflux event occurred within 2 minutes immediately following a symptom (16). In our analysis we excluded refluxes precipitated by symptoms.

4. Reflux index (RIpH): percentage of time with esophageal pH < 4. We considered pathological RIpH when >4.2% for patients older than 12 months, whereas the cutoff was assumed to be 10% for patients younger than 12 months.

5. Bolus exposure index (BEI): percentage of time with retrograde movement of bolus in the esophagus (in adults it is considered pathological if >1.4%)

6. Mean acid-clearing time (MACT): mean time in seconds required for the pH to go back to >4 after an acidic reflux

7. Mean bolus-clearing time (MBCT): mean time in seconds required for the impedance to go back to the initial value after an episode of reflux

8. The results related to number, type and height of reflux, BEI, and pH reflux index (pHRI) were evaluated with regard to the age (older or younger than 1 year) and symptoms.

9. Because normal ranges of same parameters have not yet been established for pediatric patients, the data obtained in patients with EA were compared with a non-EA group of similar age, who underwent pH-MII evaluation for clinically suspected GERD.

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Statistical Analysis

Data were analyzed by the EpiInfo software (version 6.0, CDC, Atlanta, GA) and SPSS version 14.0 (SPSS Inc, Chicago, IL). For analysis, patients were divided according to age: 1 year and younger and older than 1 year. Frequency analysis was performed by Pearson chi square test and Fisher exact test, as appropriate. The Mann-Whitney U statistic test was used for nonparametric variables to evaluate the intergroup difference. All P values were 2-sided and P < 0.05 were considered to indicate statistical significance.

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In the EA group patients, a total number of 3884 reflux episodes were detected, 918 of which were acidic (23.6%) and 2966 nonacidic (76.4%). In patients younger than 1 year, the episodes of nonacidic retrograde bolus movement accounted for 89.2%, whereas in patients older than 1 year, acidic refluxes were significantly higher than in patients younger than 1 year (29.6% vs 10.8%, P < 0.001). High refluxes accounted for 72.9% of total refluxes, 27% of which were acidic and 73% nonacidic (Table 1).

Table 1
Table 1
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A total of 351 symptom occurrences were observed; in 8 of 22 patients (36%) no symptoms were recorded. Of all 351 symptom events, 305 (86%) were associated with retrograde bolus movements (RAS: reflux associated symptom). In children younger than 1 year, symptoms are associated mainly with nonacidic reflux (nonacidic RAS 50% vs acidic RAS 31%), whereas in children older than 1 year, the symptoms are associated with acid reflux (acidic RAS 64% vs nonacidic RAS 32%). Regurgitation, dysphagia, and agitation showed the highest association with retrograde bolus movement (98%, 92%, and 91%, respectively); regurgitation and agitation were more frequent in younger children, whereas dysphagia was more often recorded in older children. Other symptoms, namely cough and heartburn, were associated in >50% of cases with reflux events (Table 2).

Table 2
Table 2
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The median pHRI was 6.1%, ranging from 1.3% to 13.8%, and it was pathological in 10 patients (45.5%), all ages older than 1 year. In fact, the median pHRI was 2.6% in children younger than 1 year and 8.1% in those older than 1 year (P = 0.003) (Tables 3 and 4).

Table 3
Table 3
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Table 4
Table 4
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Because BEI, MACT, and MBCT normal values are not yet established in the pediatric population, we compared the EA group patients with a non-EA group of healthy children with similar age and clinically suspected GERD.

The median BEI was 7.2% (range 2.5%–13.7%). If the 1.4% cutoff, established for adults, is applied to our children, then all of our patients had a pathologic BEI without a significant difference between children younger than 1 year and those older than 1 year (6.1% vs 7.9%). However, the comparison between the EA group and the non-EA group patients showed a significantly higher median BEI value in the first group (7.2% vs 2.8%, ranging from 1.4% to 5.7%, P < 0.0005) (Table 3).

The median MACT and MBCT were significantly longer in patients with EA than in patients without EA, with values of 281 and 39 seconds, respectively (P < 0.0005), in the EA group and 110 and 15 seconds (P < 0.0005) in the non-EA group, without any difference with respect to age in both groups. Moreover, correlation between symptoms and clearance time in the EA group showed that the median MACT and MBCT were significantly shorter in patients without symptoms than in those with symptoms (129 vs 368.2 seconds, P < 0.0005, and 26.5 vs 46.5 seconds, P = 0.002, respectively) apart from age (Table 5).

Table 5
Table 5
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GER and disordered peristalsis of the esophagus may be considered late complications in patients operated on for EA. GERD is a common cause of morbidity in patients treated for EA, its incidence varying from 30% to 80% in different series depending on patients' age and the diagnostic criteria (symptoms, radiologic findings, pH-metry, or endoscopy) (17–19). Motility disorders are frequent in patients with EA, with a prevalence of 75% to 100% (2) and different mechanisms have been proposed to explain it, both congenital and acquired. The identification of motility disorders of the esophagus in neonates with EA before surgical intervention suggests a congenital origin of these disorders. Morphological studies confirmed this hypothesis, describing abnormalities of Auerbach plexus both in the esophagus and in the stomach of these patients (20,21). However, surgical procedure during EA repair can be responsible for disruption of its motor supply with vagal denervation, vascular interruption, or increased traction on the lower esophagus. It is likely that both components, congenital and acquired, can coexist with differing grades of severity, predisposing to motility disorders and GER.

The adverse effect of GER after EA repair is compounded by the dismotility, which reduces acid clearance and, therefore, peptic lesions could secondarily impair normal peristalsis (3,22). The esophageal contractility is abnormal in the majority of patients, despite the good results on clinical evaluation and this puts patients with EA at greater risk for complication. Conservative treatment of GER in these children is often unsuccessful and surgical correction is generally considered the best option for medically refractory reflux. Hence, a precocious diagnosis and treatment are important to improve the quality of life in patients treated for EA, avoiding the onset of complications.

A recent clinical pH-metric and endoscopic study reported that the number of children treated for EA with GERD progressively increases in the first years of life and more than doubles from 6 months to 1 year after primary repair (23). According to our experience, especially younger children treated for EA may be asymptomatic or show atypical symptoms.

Endoscopic and pH-metric monitoring have been used as the criterion standard in the routine follow-up of children with EA. However, in infancy, more than in older patients, these techniques can be responsible for false-negative cases because esophageal lesions are not as frequent as in older children or adults, even in cases of severe GERD, and the episodes of reflux are mainly nonacidic, probably due to milk feeding that buffers gastric acid for a long time (24). Moreover, patients with EA may be insensitive to symptoms of GER, and correlation between symptoms and criteria for GERD, such as histological esophagitis, is difficult to create. The actual incidence of GER after EA repair may be, therefore, underestimated, especially in children younger than 1 year.

Recently, MII monitoring was used for diagnosis of GER in children (8–14). To our knowledge, only 1 study has been published in patients with EA, using combined MII and pH measurement, but this study included a heterogeneous sample of patients between 4 months and 23 years, without any distinction with regard to age (25).

Manometry and videofluoroscopy have been used to study esophageal motility in patients with EA and showed an impaired bolus transit in the distal esophagus (26,27). This was demonstrated by Fröhlich et al (25), performing an impedance-swallowing test in 5 patients treated for EA, ages between 9 and 23 years. However, in younger children, especially younger than 6 years, it is difficult to perform controlled swallows of saline or viscous material.

We studied at a median age of 15 months (range 3–40 months) a homogeneous cohort of patients with EA who were operated on at birth by 1 surgeon, without esophageal anastomosis under tension and with an uneventful postoperative course. In our patients, reflux episodes were mainly nonacidic (76.4% of total refluxes), and this was particularly clear in children younger than 1 year (89.2%). Actually, we found a pathological pHRI in only 10 of 22 patients (45%), all older than 1 year, whereas a BEI above the values reported in healthy adults was found in all of the children, without a significant difference with regard to age (6.1% vs 7.9%). For this reason, the incidence of GER in children younger than 1 year would have been underestimated with conventional pH-metry. To exclude an overestimation of BEI, we compared the EA group with a control group of otherwise healthy children with similar age and suspected GERD, and we found a significant difference between the 2 groups (7.2%, range 2.5%–13.7% vs 2.8%, range 1.4%–5.7%; P < 0.0005).

A pathologic value of BEI with normal pHRI can be caused by nonacid GER as well as esophageal dismotility. This result is more evident in patients with EA with more prolonged values.

For this reason, in younger children an alternative way to study esophageal motility could be pH-MII monitoring through BEI, MACT, and MBCT evaluation, to establish a correlation between onset of symptoms, severity of reflux, and intrinsic esophageal dismotility. However, normal values have not been established yet. In children without EA and with GERD, a median MACT of 111 seconds and a median MBCT of 13 seconds have been reported (6), in line with our control group (110 and 15 seconds), without a significant difference according to age. In our study we compared values of MACT and MBCT in patients with EA (281 and 39 seconds, respectively) with control patients and there was a significantly longer (P < 0.0005) acid and bolus clearance time in the first group, confirming a pathologic esophageal bolus transit in children with EA. Moreover, the correlation between symptoms and clearance time showed that asymptomatic patients with EA had a median MACT and MBCT (129 and 26.5 seconds) that was significantly shorter (P < 0.0005 and P = 0.002, respectively) than symptomatic patients with EA (368.2 and 46.5 seconds) and similar to the values of patients with GERD but without EA.

Generally, symptomatic patients have an SI between 50% and 70%; in our analysis, the EA group reported a mean SI >80%. Probably an SI this high is correlated to esophageal dismotility that worsens the reflux and symptoms.

All of this evidence confirms the role of esophageal dismotility on GERD in children treated for EA. In contrast with other studies, the quality of reflux does not seem to influence the appearance of symptoms that are instead related to an impaired clearance.

In conclusion, our data clearly show that pH-MII monitoring detects more episodes of refluxes than pH-metry because it is able to evaluate retrograde bolus movements in the esophagus independent of pH. This is important in infancy, when nonacidic refluxes are prevalent and some patients can be asymptomatic. Even if asymptomatic and with tension-free anastomosis, patients with EA are at major risk for GER and its complications; hence, a follow-up program even in asymptomatic children is important, to avoid the onset of complications. Moreover, allowing an indirect evaluation of esophageal motility, this technique can be used to establish prognosis of esophageal disease and evaluate the patients before possible surgical treatment.

Finally, we emphasize the need for a larger multicentric study to establish normal ranges for MII parameters and allow the evaluation of esophageal clearance together with reflux events.

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esophageal atresia; esophageal dismotility; gastroesophageal reflux disease; multichannel intraluminal impedance; pH-metry

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