Follow-up after pH-metry and pH impedance in pediatric gastroesophageal reflux disease.

OBJECTIVES: It is unclear how diagnostic tests for gastroesophageal reflux disease (GERD) in children relate to the course of symptoms during follow-up. METHODS: During 1 year, all children (ages 0-18 years), who underwent pH-metry and/or pH multichannel intraluminal impedance (MII), were included after written informed consent was obtained. pH-metry and pH-MII test characteristics, such as reflux index (RI, % time that esophageal pH < 4), were obtained from the measurements. A questionnaire containing subcategories (medical history, gastrointestinal [GI] symptoms, extraesophageal symptoms, symptom burden, and therapeutic agents) was used; subjects were asked to fill the questionnaire at the time of inclusion and 3, 6, and 12 months afterward. RESULTS: A total of 162 infants and 42 children were included. pH-MII was performed in 15.4% and 57.4% of infants and children, respectively. All of the other subjects underwent pH-metry. Median RI was 2.0% (interquartile range 3.4) in infants and 1.7% (interquartile range 2.3) in children. RI was considered positive in 6.8% and 12.8% of infants and children, respectively. In infants, RI at baseline was significantly associated with symptom burden at baseline and at 3 and 12 months of follow-up. RI at baseline and reported GI symptoms at 3 months were also significantly associated. In infants and children using medication, symptom burden was significantly higher compared with those not using medication. This difference was found at baseline, after 3 and 12 months. CONCLUSIONS: In infants, an initial high RI is associated with persistence of GI symptoms at 3 months and a higher burden of symptoms during the course of 1 year. In children there were no such findings.

Body positioning and medical therapy for infantile gastroesophageal reflux symptoms.

OBJECTIVE: Proton-pump inhibitors (PPIs) reduce acid gastroesophageal reflux (GER) and esophageal acid exposure in infants; however, they do not reduce total GER or symptoms attributed to GER. Reflux is reduced in the left lateral position (LLP). We hypothesize that the effect of LLP in combination with acid suppression is most effective in reducing GER symptoms in infants. METHODS: In this prospective sham-controlled trial, infants (0-6 months) with symptoms suggestive of gastroesophageal reflux disease were studied using 8-hour pH-impedance, cardiorespiratory and video monitoring, direct nurse observation, and a validated questionnaire. Infants demonstrating a positive GER symptom association were randomized to 1 of 4 groups; PPI + LLP, PPI + head of cot elevation (HE), antacid (AA) + LLP, or AA + HE. HE and AA were considered "sham" therapies. After 2 weeks the 8-hour studies were repeated on-therapy. RESULTS: Fifty-one patients were included (aged 13.6 [2-26] weeks). PPI + LLP was most effective in reducing GER episodes (69 [13] to 46 [10], P < 0.001) and esophageal acid exposure (median [interquartile range] 8.9% [3.1%-18.1%] to 1.1% [0%-4.4%], P = 0.02). No treatment group showed improvement in crying/irritability, although vomiting was reduced in AA + LLP (from 7 [2] to 2 [0] episodes P = 0.042). LLP compared with HE produced greater reduction in total GER (-21 [4] vs -10 [4], P = 0.056), regardless of acid-suppressive therapy. Acid exposure was reduced on PPI compared with AA (-6.8 [2.1] vs -0.9 [1.4]%, pH < 4, P = 0.043) regardless of positional intervention. A post-hoc analysis using automated analysis software revealed a significant reduction in crying symptoms in the PPI + LLP group (99 [65-103] to 62 [32-96] episodes, P = 0.018). CONCLUSIONS: "Symptomatic gastroesophageal reflux disease" implies disease causation for distressing infant symptoms. In infants with symptoms attributed to GER, LLP produced a significant reduction in total GER, but did not result in a significant improvement in symptoms other than vomiting; however, automated analysis appeared to identify infants with GER-associated crying symptoms who responded to positioning therapy. This is an important new insight for future research.

Gastroesophageal reflux, esophageal function, gastric emptying, and the relationship to dysphagia before and after antireflux surgery in children.

OBJECTIVES: To assess gastroesophageal reflux (GER), esophageal motility, and gastric emptying in children before and after laparoscopic fundoplication and to identify functional measures associated with postoperative dysphagia. STUDY DESIGN: Combined impedance-manometry, 24-hour pH-impedance, and gastric-emptying breath tests were performed before and after laparoscopic anterior partial fundoplication. Impedance-manometry studies were analyzed with the use of conventional analysis methods and a novel automated impedance manometry (AIM) analysis. RESULTS: Children with therapy resistent GER disease (n = 25) were assessed before fundoplication, of whom 10 (median age 6.4 years; range, 1.1-17.1 years; 7 male; 4 with neurologic impairment) underwent fundoplication. GER episodes reduced from 97 (69-172) to 66 (18-87)/24 hours (P = .012). Peristaltic contractions were unaltered. Complete lower esophageal sphincter relaxations decreased after fundoplication (92% [76%-100%] vs 65% [29%-91%], P = .038). Four (40%) patients developed postoperative dysphagia, which was transient in 2. In those patients, preoperative gastric emptying was delayed compared with patients without postoperative dysphagia, 96 minutes (71-104 minutes) versus 48 minutes (26-68 minutes), P = .032, and AIM analysis derived dysphagia risk index was greater (56 [15-105] vs 2 [2-6] P = .016). Two patients underwent a repeat fundoplication. DISCUSSION: Fundoplication in children reduced GER without altering esophageal motility. Four patients who developed dysphagia demonstrated slower gastric emptying and greater dysplasia risk index preoperatively. AIM analysis may allow detection of subtle esophageal abnormalities potentially leading to postoperative dysphagia.

Outcomes of endoscopy and novel pH-impedance parameters in children: is there a correlation?

OBJECTIVES: Discordance exists between outcomes of endoscopy, multichannel intraluminal impedance monitoring (pH-MII), MII baselines, and gastroesophageal reflux symptoms. The aim of the present study was to determine the association between endoscopy, pH-MII and MII baselines, in children with gastroesophageal reflux symptoms. METHODS: Endoscopies were graded for reflux esophagitis (RE). Biopsies of the distal esophagus were assessed for signs suggestive of esophagitis. Reflux index (RI), symptom association probability (SAP), number of reflux episodes, and mean baseline values were calculated. pH-MII was considered positive in children when RI was ≥ 3% and/or SAP was ≥ 95% and for infants when RI was ≥ 10% and/or SAP was ≥ 95%. Baselines were manually calculated and compared with an automated analysis. For MII baselines, patients were divided in 3 groups: normal endoscopy and negative overall pH-MII; normal endoscopy and an overall positive pH-MII; and RE. RESULTS: A total of 26 children and 14 infants were included, median age: 26.5 months (2 months-16.2 years). Thirteen (32.5%) had RE. A significant negative association was found for RI and MII baselines (P = 0.009) and between SAP and RE (P = 0.039, odds ratio 1.018). MII baseline values were predictive for neither conventional pH-MII parameters nor RE. Manual analysis and automated calculation of MII baselines showed a perfect correlation. Distal MII baselines were significantly lower in children with a positive overall pH-MII outcome compared with the proximal esophagus (P = 0.049). No significant changes were found in baselines among the different groups 1 to 3. CONCLUSIONS: Acid-related parameters are significantly related to MII baselines. A perfect correlation between manual- and automated analysis of MII baselines was found. Large prospective studies are needed to confirm the exact role of endoscopy and MII baselines.

Interobserver and intraobserver variability in pH-impedance analysis between 10 experts and automated analysis.

OBJECTIVE: To determine interobserver and intraobserver variability in pH-impedance interpretation between experts and accuracy of automated analysis (AA). STUDY DESIGN: Ten pediatric 24-hour pH-impedance tracings were analyzed by 10 observers from 7 world groups and with AA. Detection of gastroesophageal reflux (GER) episodes was compared between observers and AA. Intraobserver agreement was assessed in 3 observers after 3 to 5 months. RESULTS: Overall, 1242 liquid and mixed GER events were detected, 490 (42%) were scored by the majority of observers, yielding moderate agreement (Cohen's kappa [κ] = 0.46). Intraclass co-efficient for numbers of GER per study was 0.84 (P < .001). AA has 94% sensitivity rate and 74% specificity rate compared with majority consensus (≥6 observers). Agreement for gas GER was poor (κ = 0.11). Intraobserver agreement was κ = 0.49, κ = 0.71, and κ = 0.85 in 3 observers. CONCLUSION: Interobserver agreement in combined pH-multichannel intraluminal impedance analysis in experts is moderate; only 42% of GER episodes were detected by the majority of observers. Detection of total GER numbers is more consistent. Considering these poor outcomes, AA seems favorable compared with manual analysis because of its reproducibility. However, the lower specificity rate suggests the need for refinement of AA before widespread use can be advocated.

Indications, methodology, and interpretation of combined esophageal impedance-pH monitoring in children: ESPGHAN EURO-PIG standard protocol.

AIM: The aim of the study was to provide an updated position statement from the ESPGHAN European Pediatric Impedance Working Group on different technical aspects such as indications, methodology, and interpretation of multichannel intraluminal impedance-pH monitoring (MII-pH). METHODS: Evidence was used where available, but the article is based mainly on expert opinion and consensus. RESULTS: MII-pH provides more information than simple pH monitoring because reflux detection is not limited to acid reflux. Different companies provide commercialized MII-pH recording systems, making the method widely available and useable in daily clinical practice; however, the technique still has limitations: high cost, limited additional value regarding therapeutic implications, and lack of evidence-based parameters for the assessment of gastroesophageal reflux and symptom association in children. CONCLUSIONS: MII-pH recording is a promising procedure needing further validation and development to increase its additional benefit over conventional investigation techniques. The added value of the technique regards mainly clinical circumstances in which nonacid or weakly acid reflux may be relevant such as persisting symptoms during antireflux treatment with proton pump inhibitors and feeding-related reflux; and assessing specific discontinuous symptoms thought to be associated with gastroesophageal reflux; and research.

Esophageal acid exposure decreases intraluminal baseline impedance levels.

OBJECTIVES: Intraluminal baseline impedance levels are determined by the conductivity of the esophageal wall and can be decreased in gastroesophageal reflux disease (GERD) patients. The aim of this study was to investigate the baseline impedance in GERD patients, on and off proton pump inhibitor (PPI), and in healthy controls. METHODS: Ambulatory 24-h pH-impedance monitoring was performed in (i) 24 GERD patients with and 24 without pathological esophageal acid exposure as well as in 10 healthy controls and in (ii) 20 patients with refractory GERD symptoms despite PPI, once on PPI and once off PPI. Baseline impedance levels in the most distal and the most proximal impedance channels were assessed. RESULTS: Median (interquartile range) distal baseline impedance in patients with physiological (2,090 (1,537-2,547) Ω) and pathological (781 (612-1,137) Ω) acid exposure was lower than in controls (2,827 (2,127-3,270) Ω, P<0.05 and P<0.001). A negative correlation between 24-h acid exposure time and baseline impedance was observed (r=-0.7, P<0.001). In patients measured off and on PPI, median distal baseline impedance off PPI was significantly lower than on PPI (886 (716-1,354) vs. 1,372 (961-1,955) Ω, P<0.05) and distal baseline impedance in these groups was significantly lower than in healthy controls (P<0.05 and P<0.001). Proximal baseline impedance did not differ significantly between the patients off PPI and on PPI (1,793 (1,384-2,489) vs. 1,893 (1,610-2,561) Ω); however, baseline impedance values in both measurements were significantly lower than in healthy controls (3,648 (2,815-3,932) Ω, both P<0.001). CONCLUSIONS: These findings suggest that baseline impedance is related to esophageal acid exposure and could be a marker of reflux-induced changes to the esophageal mucosa.

Measurement of mucosal conductivity by MII is a potential marker of mucosal integrity restored in infants on acid-suppression therapy.

Esophageal multichannel intraluminal impedance (MII) allows measurement of the conductivity of adjacent contents. During esophageal rest, raw impedance levels may represent mucosal integrity. We assessed the influence of proton pump inhibitors (PPIs) on presumed mucosal integrity by reanalyzing raw MII levels of 21 pH-MII tracings from infants with gastroesophageal reflux (GER) disease before and after esomeprazole treatment. Median (interquartile range) esophageal MII increased during treatment, 938 (652-1304) versus 1885 (1360-2183) Ohm, P < 0.0001. Patients with lower MII levels demonstrated a larger increase on therapy: Spearman r2 = 0.28, P = 0.014. No correlation with standard GER parameters was observed. In conclusion, PPI therapy increases MII levels in infants with symptomatic GER disease.

Addition of pH-impedance monitoring to standard pH monitoring increases the yield of symptom association analysis in infants and children with gastroesophageal reflux.

OBJECTIVE: To assess the additional yield of combined multichannel intraluminal pH-impedance (pH-MII) monitoring compared with standard pH monitoring on gastroesophageal reflux (GER) symptom associations in infants and children. STUDY DESIGN: In 80 patients, 24-hour ambulatory pH-MII monitoring was performed. Tracings were analyzed with established pH-MII criteria. Symptoms of regurgitation and belching were excluded from analysis, because these were considered to be a direct consequence of GER. Standard GER-symptom correlation indices were calculated with: 1) standard pH monitoring; 2) MII detection of liquid and mixed bolus GER; 3) MII detection of all bolus GER (liquid, mixed, and gas); 4) pH-MII detection of all GER, including pH-only GER. RESULTS: Fifty patients (21 children) were included. MII detection of all bolus GER yielded a significantly greater number of patients who were symptom-positive, 36 (72%) compared with 25 (50%) with standard pH-monitoring (P = .04). A positive symptom association was observed in 8 of 10 (80%) patients with pathological esophageal acid exposure and 28 of 40 (70%) patients with negative pH-findings. CONCLUSIONS: A high proportion of patients with normal esophageal acid exposure had a positive symptom association on pH-MII monitoring. Including all MII-detected bolus GER and excluding pH-only GER for analysis optimizes the yield of GER-symptom associations in infants and children.