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Original Articles: Gastroenterology

Correlation Between Clinical Signs and High-resolution Manometry Data in Children

Juzaud, Marine; Lamblin, Marie-Dominique†,‡; Fabre, Alexandre∗,§; Alessandrini, Marine; Baumstarck, Karine; Bazin, Camille||; Esteve, Clothilde∗∗; Laborde, Nolwenn††,‡‡; Osei, Lindsay§§; Michaud, Laurent; Gottrand, Frederic; Vitton, Veronique||

Author Information
Journal of Pediatric Gastroenterology and Nutrition: May 2019 - Volume 68 - Issue 5 - p 642-647
doi: 10.1097/MPG.0000000000002232


What Is Known

  • High-resolution esophageal manometry has revolutionized the study of esophageal motility. However, the position of high-resolution manometry in the diagnostic strategy of children presenting with upper gastrointestinal symptoms remains unclear.

What Is New

  • This is the first study to show that weight loss is the only clinical sign predicting an abnormal high-resolution manometry result.
  • It is the largest cohort of children on high-resolution esophageal manometry showing ineffective esophageal motility as the most frequent abnormality.

High-resolution manometry (HRM) is the gold standard for the diagnosis of esophageal motility disorders (1,2). Since the 2000s, conventional manometry has been progressively replaced by HRM. This new technique allows a topographic analysis of pressures (2) and a more accurate study with spatiotemporal representation of esophageal pressure values. HRM is also easier to perform and is better tolerated by patients (3,4). A randomized multicenter study of adult patients showed that HRM was faster to perform and that it was possible to diagnose esophageal motility disorders earlier (5). For adult patients, HRM indications are well defined: dysphagia, noncardiac chest pain, preoperative evaluation of gastroesophageal reflux disease (GERD) (6,7), and scleroderma (8). Current indications for esophageal manometry in children are suspicion of achalasia, suspicion of chronic intestinal pseudo-obstruction syndrome, treatment-resistant GERD, and dysphagia with esophageal atresia or scleroderma (9). For some authors, noncardiac chest pain and determination of the location of the lower esophageal sphincter (LES) before pH monitoring are also indications in children (10). Clinical signs that may be associated with esophageal motility disorders in children include dysphagia, food blockage, vomiting, regurgitation, choking with food, pyrosis, chest pain, and some respiratory symptoms [such as pneumonia (11)], weight loss, eating difficulties, nausea, diarrhea, or constipation (12). However, in adult and pediatric patients, clinical signs associated with esophageal motility disorders are nonspecific (13), and it is difficult to correlate results of esophageal manometry with clinical presentation. Although few clinical signs are predictive of an esophageal motility disorder apart from dysphagia in adult patients (13), there are currently no available studies on this condition in children (14). No clinically suggestive signs of esophageal motility disorders are currently identified for children, and the use of esophageal manometry, which is an invasive examination, is currently not determined in children (9).

The primary objective of our study was to estimate the positive predictive values (PPV) and negative predictive values (NPV) for each of the patient's clinical sign as well as their sensitivity and specificity for the diagnosis of esophageal motility disorders, and the secondary objective was to describe the frequency of esophageal motility disorders in children, indications for this examination, and its feasibility in pediatric patients.



This was a bicentric retrospective cohort study based on HRM data from Lille and Marseille University Hospitals (France). All patients below age 20 who were referred for a first HRM study for any indication between May, 2012 and May, 2016 were eligible. We excluded patients who refused to participate in the study or with incomplete or unavailable data and follow-up HRMs.

This study was approved by the Ethics Institutional Review Board of Aix-Marseille University on November, 2017. Medical data collected were age, sex, medical history, clinical signs, and test results from upper gastrointestinal endoscopy (UGIE) or upper gastrointestinal series (UGIS).

Clinical Signs

A committee of 2 adult gastroenterologists, 1 pediatrician, and 3 pediatric gastroenterologists with a strong expertise in HRM, were in charge of the validation of the clinical signs assessed in this study. These clinical signs and their definitions were weight loss, feeding difficulties, swallowing disorders, dysphagia, food blockages, vomiting, GERD, belching, and respiratory symptoms (see Table, Supplemental Digital Content 1, Weight loss was defined as loss of at least 1 standard deviation (SD) over 6 months and/or denutrition (weight/height ratio <80th percentile) and/or body mass index less than third percentile (15). Dysphagia was defined by difficulty to swallow (difficulty to initiate swallowing and to propel food into the esophagus or discomfort during the progression of food) (16). GERD was defined as the passage of gastric contents into the esophagus with or without regurgitation and vomiting that leads to troublesome symptoms that affect daily functioning and/or complications (17) (eg, heartburn and epigastric pain) (18,19).

High-resolution Manometry Protocol

HRM is an examination performed after transnasal introduction of a high-resolution esophageal tube with its distal end in the stomach and its proximal end in the pharynx. This technique allows to collect pressure plots for analysis of the quality of peristalsis, esophageal body, position and length of the upper and lower sphincters of the esophagus (UES and LES, respectively), and data on sphincters’ tone and relaxation (9).

The HRM catheter contains 36 circumferential pressure sensors, regularly placed along the catheter, placed 1 cm apart (Manoscan; Sierra Scientific Instruments Inc., Los Angeles, CA). The catheter is placed transnasally and fixed in place once its correct position is verified (identification of 2 areas of high pressure: UES and esophagogastric junction [EGJ]). With the catheter in place, the patient consecutively swallows 5 ml of water 10 times for a complete study of esophageal peristalsis. The analysis of the 10 deglutitions was only made with liquid. The catheter is connected to a computer installed with ManoView analysis software (Sierra Scientific Instruments Inc), which gives a color-coded reading of the esophageal pressure. The manometric probe does not include an impedance analysis.

Data Analysis

All HRM data were reviewed by 2 experts according to the Chicago Classification (CC) criteria v3.0 (20). The CC was only validated for adult patients. For children, there is no scientific validation, but several studies showed its applicability with some adaptations depending on the age and size of the child (21,22).

Esophageal motility disorders were classified into 7 categories according to the following criteria:

Categories 1 to 5: According to CC criteria v3.0 (15): disorders with EGJ outflow obstruction (achalasia subtypes I–III and EGJ outflow obstruction), major peristalsis disorders (absent contractility, distal esophageal spasm, and hypercontractile esophagus), minor peristalsis disorders (ineffective esophageal motility [IEM] and fragmented peristalsis), and normal esophageal motility. The last 2 categories (4 and 5) correspond to UES and LES abnormalities without disorders of the esophageal body and are not in the CC.

Category 6: Isolated abnormalities of the LES: transient LES relaxations or hypotensive LES pressure. In fact, this anomaly only affects the LES with a normal esophageal motility function (23).

Category 7: UES disorders (not found in the CC). Indeed, these disorders of pharyngeal motility and UES can also be diagnosed by HRM (24).

Statistical Analysis

A descriptive analysis of the population was carried out: quantitative values were presented as means and standard deviations or median with interquartile intervals (or accompanied by extreme minimum and maximum values), and qualitative values as numbers and percentages. Comparative analyses of the groups (patients with normal manometry vs patients with abnormal manometry) were carried out using the chi-square or Fisher exact tests for qualitative data and Student t-test for quantitative data. The same comparative analyses were carried out for 2 other groups (patients who benefited from an UGIE or not).

Sensitivities, specificities, PPVs, and NPVs were calculated for each clinical sign and for each parameter of manometric status (normal or abnormal manometry). These parameters are presented as percentages with their 95% confidence interval. Statistical analysis was performed using PASW Statistics software version 17.0.2 (SPSS Inc., Chicago, IL). All tests were 2-sided, and statistical significance was defined as P ≤ 0.05.


Characteristics of the Cohort: Demographic and Epidemiological Data

We collected 300 HRM data (carried out between 2012 and 2016): 262 in Lille and 38 in Marseille. We excluded 26 HRM data because they were gathered during patient follow-up, without any new symptoms. Moreover, 3 patients were not included because of missing records. Overall, 271 patients were included: 50 infants (0–23 months), 146 children (2–10 years), and 75 teenagers (11–19 years); see Table 1). Patients were comparable in terms of sex (P = 0.971) or age (P = 0.591).

Patient characteristics in our study population

Clinical Signs and High-resolution Manometry Indication

Clinical signs leading to HRM are shown in Table 2.

Symptoms of patients in our study population

HRM was performed with the following indications: weight loss, feeding difficulties, swallowing disorders, dysphagia, food blockage, vomiting, refractory GERD or before fundoplication, belching, or respiratory symptoms. Details are given in Table 2.

The main indication of an HRM was symptomology of GERD in 111 patients (40.9%). HRM was performed for 2 indications associated with GERD: in case of refractory GERD or to evaluate esophageal function before Nissen fundoplication. The second indication was weight loss in 92 patients (33.9%). Dysphagia and blockage were present in 49 (18%) and 39 (14.4%) patients, respectively.

GERD alone was the only indication in 33 cases. In other cases, GERD was associated with weight loss (n = 30/111), feeding difficulty (n = 21/111), swallowing disorders (n = 16/111), dysphagia (n = 8/111), food blockages (n = 7/111), vomiting (n = 22/111), belching (n = 2/111), or respiratory symptoms (n = 23/111).

Weight loss alone was the only indication in 2 cases. In the other cases, weight loss was associated with feeding difficulty (n = 43/92), swallowing disorders (n = 20/92), dysphagia (n = 16/92), food blockages (n = 10/92), vomiting (n = 24/92), GERD (n = 31/92), or respiratory symptoms (n = 19/92). Weight loss was not reported in patients with belching (n = 0/92).

High-resolution Manometry Findings

Twenty-six HRMs obtained normal findings compared with 245 HRMs (90.4%) with abnormal findings.

The most frequent esophageal motility disorder was IEM, followed by disorders with EGJ outflow obstruction (35 patients, including 16 patients with achalasia) and major peristalsis abnormalities (19 patients, including esophageal spasms). Disorders with EGJ outflow obstruction include achalasia types I, II, and III (the most frequent were types I and II) and disorders that cannot be classified as types I, II, or III (including incomplete or mechanical obstruction [post-Nissen obstruction]). No patient had an HRM profile showing hypercontractile esophagus (jackhammer esophagus). Diagnoses derived from HRM are listed in Table 3.

Diagnoses based on the Chicago Classification

Predictive Values, Sensitivity, and Specificity of Clinical Sign on High-resolution Manometry Results

In univariate analysis, weight loss was significantly associated (P = 0.003) with an abnormal HRM finding with a 95.7% PPV. No other sign was significantly associated with an abnormal HRM finding. No neurological (peripheral or central), gastroenterological (esophageal atresia, Hirschsprung disease, esophagitis, and Barrett's esophagus), ENT, or metabolic history was significantly associated with an abnormal HRM finding.

The predictive values (PPV and NPV), sensitivity, and specificity of each clinical sign are shown in Table 4.

Positive and negative predictive value, sensitivity and specificity, of each clinical sign or history associated with abnormal high-resolution manometry; with their confidence intervals and P-values

Distribution of High-resolution Manometry Disorders in Patients Who Experienced Weight Loss

Among the 92 patients who presented weight loss, 40.2% had IEM, 13% had isolated LES hypotonia, 12% had achalasia, 8.7% had EGJ major disorders, and 7.6% had EGJ outflow obstruction. Moreover, 4.3% of these patients presented normal HRM results, and 19.6% of patients with UES disorders presented weight loss (see Table, Supplemental Digital Content 2,


HRM was well tolerated in our cohort (91%). Only 25 patients did not tolerate well the procedure (14 infants, 8 children, and 3 teenagers; cried or lack of cooperation). However, it was possible to interpret the results for all patients in the cohort.

Complementary Medical Examinations

Among the 271 patients, only 93 experienced UGIE before HRM (25 presented dysphagia) and 48 had UGIS. We observed no significant difference (P = 0.383) on weight loss between patients with or without an UGIE.


To our best knowledge, we present herein the largest HRM pediatric cohort so far. Our study showed that of the 9 studied clinical signs, weight loss is the only one to be significantly associated with an abnormal HRM result. This is also the first study assessing the predictive value of clinical signs in favor of esophageal motility disorders. Indeed, other publications in the field of pediatric HRM presented cohorts of 35–137 patients (12,14). Moreover, these studies focused on the technical aspects of the HRM procedure and the interpretation of findings (11,21,22) or on specific diseases, such as achalasia (25) and esophageal atresia (26).

Our cohort was heterogeneous, as patients were included regardless of HRM indication. The studied clinical signs were validated by a group of experts, which was similar to other previous studies in children (9,11,12).

We used the CC to interpret HRM data. As this classification system was developed with data acquired from a healthy adult population (12), it might not be directly applicable to children. However, there are studies proving its reliability in pediatric patients (27). Singendonk et al highlight the crucial role of the HRM expert: diagnosis with the HRM software is not sufficient. HRM data should be interpreted by an expert, which was the case in our study. We did not attempt to make any adjustments for age and esophagus length, as there are currently no validated data in children (28), but normal HRM data have been observed in infants (29). These data support the hypothesis that normal HRM results (according to adult standards) could exist in infants and children by extrapolation.

Herein, we report for the first time that weight loss was significantly associated with abnormal HRM metrics. An earlier adult study of Jain et al (13) reported similar findings: minor motility disorders was the most frequent symptom in their cohort (33% of 154 patients), followed by major motility disorders (31%) and then normal HRM result (30%). However, this study did not show any correlation between clinical signs and esophageal HRM results. An earlier study in children yielded similar results (30). Weight loss could be a reflection of severity or chronicity of another clinical sign. In fact, all symptoms that may suggest an esophageal mobility disorder may cause weight loss because of the decrease in food ration. Furthermore, weight loss is associated with another clinical sign in 98% in our study, and this can be a limit.

In our study, no associated conditions were significantly associated with an abnormal HRM result. Nevertheless, some diseases are known to be associated with motility disorders: esophageal atresia (26,31–33), surgically corrected diaphragmatic hernia (DH) (34), esophagitis (35), and central nervous system diseases (36). We cannot exclude the existence of these associations even if results are not significant in our study. These results could be explained by the small number of patients in each category (esophageal atresia n = 11; DH n = 5; esophagitis n = 5) leading to a low statistical power.

Although HRM was described as an invasive and painful procedure (9), it was well tolerated in 91% of the patients in our cohort, and interpretation was possible in 100% of cases. In line with our result, in 2010, Goldani et al (37) reported only 1 failed procedure in 31 patients (ages between 6 months and 15 years). Few studies evaluated this aspect, so it would be useful to assess the impact of HRM tolerance on the interpretation in pediatric population.

In this study, in most cases, HRM result was abnormal (90%). It was slightly higher than in literature (55%–80% of abnormal HRM result in smaller cohorts) (12,38). This difference has several explanations, such as different indications according to the centers and the fact that we have not made any adjustments to size and age. We did not attempt to make any adjustments for age and esophagus length because it is not realized in Marseille and Lille centers. There are currently no validated data in children that recommended performing this adjustment. On the contrary, our work included UES disorders, which is not generally included in most other studies, which increases the prevalence of esophageal motility disorders. In our cohort, 59 patients have UES disorders (see Table 3). Finally, other studies have smaller cohorts.

In our cohort, the most frequent esophageal motility disorder was IEM (with or without LES hypotonia) affecting more than one-third of the patients. This result is similar to that of a recent study including 137 children in the USA (12). Moreover, IEM is the most frequent esophageal motility disorder in adult patients (39). As defined for adult patients, this clinical entity could be an IEM of the esophageal corpus, IEM of the LES, or both (23). However, its clinical significance is not clearly known (13). Although there are few case reports of progression to major peristaltic abnormalities (40), these esophageal motility disorders are persistent even during long-term follow-up (41). To the best of our knowledge, esophageal IEM is not well described in pediatrics. As for adult patients, this manometric profile is frequent in GERD, systemic scleroderma, diabetes, and hypothyroidism (39). In systemic scleroderma, esophageal motility disorder leads to the increase risk of Barrett's esophagus and esophageal adenocarcinoma (42,43). Although it is difficult to extrapolate these data to pediatrics, we could also assume that clinical signs, HRM, and endoscopic monitoring could be appropriate in this context.

As seen in literature data (1,9,30), esophageal IEM was associated with GERD in 49.5% of the patients in our cohort (see Table, Supplemental Digital Content 2, Gyawali et al (44) (International GERD Consensus Working Group) defined motility disorders associated with GERD in adult patients as both EGJ dysfunction and motility disorder of the esophageal corpus. HRM clinical guidelines for the diagnosis and management of GERD in infants and children are described in recent publications of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. HRM is a very informative tool for the evaluation of extra-esophageal signs in order to exclude esophageal motility disorders whose presenting symptoms are often similar. However, there are no objective criteria in favor of HRM for GERD diagnosis (17).

This study has some limitations because of its retrospective approach and the lack of systematic UGIE. Among the 271 patients of the cohort, only 115 experienced complementary examination as well as UGIE or UGIS before HRM, whereas according to pediatric guidelines, UGIE and biopsy and in some cases pH monitoring and/or UGIS should be done first to assess upper digestive issues in children. Indeed, performing UGIE is required to rule out esophageal malformation or organic abnormality in case of upper digestive symptoms as dysphagia (45). The lack of systematic UGIE could also explain the absence of eosinophilic esophagitis, the most frequent etiology in pediatric population presenting persistent dysphagia (9,46). It would be interesting to perform a large-scale prospective study to find associations between clinical signs and HRM results in order to set up predictive scores that would help clinicians to better define the position of HRM in daily pediatric clinical practice.

In conclusion, this study showed 4 major points: weight loss is a predictive sign of an abnormal HRM result when esophageal motility disorder is suspected. This finding could be helpful for clinicians to appropriately select children requiring esophageal manometry procedures. HRM is feasible in infants and children when performed by a well-trained team of experts. As found in numerous studies in adult population, ineffective esophageal motility was the most commonly observed abnormality in our pediatric cohort. Finally, in case of suspicion of abnormalities of esophageal mobility especially with weight loss, HRM should be performed. Finally, in case of suspicion of abnormalities of esophageal motility, especially in case of weight loss in patients in whom an esophageal malformation or organic abnormality has been ruled out by performing UGIE, HRM must be realized.

Indeed, our results showed high rate of abnormal HRM and should encourage specialist to perform it and thoroughly analyze the results.


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esophageal motility disorders; children; Chicago Classification

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