The sensitivity and specificity of pH monitoring for the diagnosis of GERD in children are not well established. pH monitoring appears to be a good predictor of esophagitis in children, with sensitivity ranging from 83 to 100 %; on the other hand, the severity of reflux as measured by pH monitoring correlates poorly with the severity of symptoms, especially in infants [3, 16]. For children with non-erosive reflux disease, the clinical utility of pH monitoring has not been well studied.

Reports on intrasubject reproducibility of esophageal pH results in children have had varied results. Vandenplas et al. studied infants and children over two consecutive 24-h periods; the correlation coefficients for the reflux index and number of reflux episodes between days 1 and 2 were 0.95 and 0.98, respectively [17]. In contrast, the correlation coefficient for the reflux index reported by Mahajan and colleagues was only 0.62 between days 1 and 2 [18]. In another study, 9 out of 30 children had discordant (normal versus abnormal) results between the two recording days, yielding an overall reproducibility of 70 % [19]. Overall, there appears to be some degree of day-to-day variability among patients; whether these differences are clinically significant is debatable. When the clinical picture is unclear, consideration should be given for repeat testing.

In addition to the quantification of reflux, 24-h esophageal pH monitoring also provides the opportunity to assess the temporal relationship between episodes of reflux and onset of symptoms. This may be especially helpful for patients with nonspecific or extraesophageal symptoms. Lam et al. found that using a 2-min time window was best for correlation of chest pain with reflux, although the optimal time window for symptom-reflux association may vary depending on the particular symptom of interest [20].

Several statistical methods have been developed to better quantify the association of symptoms and reflux episodes, but there is no conclusive data proving one index to be superior to the others. The symptom index (SI) is defined as the percentage of symptom episodes that are related to reflux, with a score of ≥50 % suggesting a positive relationship between symptom and reflux [21, 22]. A second approach is the symptom sensitivity index (SSI), which divides the number of reflux episodes associated with symptoms by the total number of reflux episodes [23]. An arbitrary cutoff of 10 % or higher is commonly used to indicate a significant association between symptoms and reflux episodes. Both the SI and SSI fail to integrate, however, all the factors determining symptom correlation. As a result, the SI may overestimate the relationship between reflux and symptoms when there are a high number of reflux episodes, and the SSI is more likely to be positive when the number of symptom episodes is high. More recently, the symptom association probability (SAP) was introduced. Using Fisher’s exact test, this method expresses the statistical likelihood that the patient’s symptoms are related to reflux [24]. By statistical convention, SAP ≥95 % indicates that the probability that the observed association between reflux and the symptom occurred by chance is <5 %.

Although patients with a positive relationship between symptoms and reflux have been shown to more likely to respond to medical and surgical therapy, further prospective validation studies are needed [25, 26]. Ultimately, these indices may be helpful in evaluating the relationship between symptoms and reflux, but a statistically significant result does not necessarily imply causality.

To overcome the limitation of patient discomfort seen with catheter-based pH monitoring, a wireless method is also available. The Bravo pH system (Medtronic, Shoreview, MN) consists of an antimony electrode contained within a small capsule which is securely pinned to the mucosal wall of the distal esophagus and transmits pH data wirelessly to a portable receiver using radio telemetry. In adults, the capsule is placed 6 cm above the squamocolumnar junction, with placement confirmation by endoscopy [27]. There are currently no specific guidelines for placement in children.

In published studies of children older than 4 years old, pH monitoring with the Bravo capsule was better tolerated than the trans-nasal catheter in terms of appetite, activity, and satisfaction, with no significant complications other than mild chest discomfort [28–30].

Another advantage of the Bravo system is the ability to perform prolonged monitoring over a 48-h period, which has the potential for maximizing time for symptom-reflux correlation and reducing the overall miss rate for days where pathologic acid reflux may be present. There are no outcome data however proving that a 48-h study is better than 24-h monitoring for predicting response to treatment in either adults or children. Furthermore, given the need for sedation for capsule placement on day 1, there has been concern about the reliability of day 1 data. Adult studies comparing days 1 and 2 of wireless pH have shown variable results, with some studies reporting no difference in reflux between days 1 and 2 [27], while others have reported increased reflux on day 1, and still others showing increased reflux on day 2 [31, 32]. Similarly conflicting data has been reported in children. Some studies have reported no significant difference in pH measurements between days 1 and 2 [33]. In Cabrera et al., there was also no significant difference between reflux index recorded on day 1 versus day 2 overall; however, for 9 % of patients, the reflux index was normal on day 1 and abnormal on day 2 [34]. In contrast, in our own series of 145 Bravo studies in children, there were significantly higher values on day 1 versus day 2 for the number of long reflux episodes, duration of longest episode, and fraction of time with pH < 4 in the upright position [28]. Day-to-day variability between the first and second 24-h periods may be due to the effect of anesthesia or to differences in lifestyle and dietary intake, but it is not yet clear if these differences are clinically significant. Currently, there is no consensus on how 48-h data should be interpreted in children, whether the average of 2 days or only the 24-h period with the greatest acid exposure (worst day analysis) should be used.

The Bravo wireless system appears to be a reasonable alternative to catheter-based pH monitoring for older children, given the potential advantages in terms of patient tolerance and less effect on daily routines, diet, and activity levels. In addition, there is the potential advantage of performing an extended 48-h study to help minimize the effects of day-to-day variability. Limitations include the cost of the capsule, the need for endoscopy and anesthesia for capsule placement, as well as the risks of chest discomfort, perforation, and early capsule detachment [35, 36].

Proximal esophageal pH monitoring is designed to assess the proximal extent of acid reflux and its relationship with oropharyngeal and respiratory symptoms. Studies employing dual-probe pH monitoring of both the distal and proximal esophagus have had mixed results however, in terms of sensitivity and specificity for extraesophageal manifestations of reflux, intrasubject reproducibility, and prediction of response to therapy [37–39]. The main limitations with proximal pH monitoring are related to the lack of consensus on the best location for probe placement and optimal pH threshold for defining a proximal reflux event. Conventionally, the same pH < 4 threshold for distal esophageal reflux has been applied to proximal measurements. There have been proposals to revise the pH criteria for proximal reflux however, based on data suggesting that nonacid reflux with pH 4–7 may also play a clinically significant role in aerodigestive disease [40, 41].

Other diagnostic modalities for the detection of proximal reflux, such as oropharyngeal pH monitoring [42–44], and the noninvasive measurement of exhaled breath condensates for the detection of proximal reflux [45, 46] have had mixed results. At the present time, the clinical advantage of proximal esophageal pH monitoring in children is not yet clearly proven, and more research is needed before these new methodologies can become part of the routine evaluation of children with extraesophageal manifestations of reflux.

To overcome the limitations of pH probe, multichannel intraluminal impedance has been developed. This catheter-based system uses sensors distributed throughout the esophagus to measure resistance to flow rather than pH changes alone. The advantages to MII-pH are the following: (1) the sensors are able to determine the directionality of flow so that reflux events can be distinguished from swallows, (2) multiple sensors throughout the esophagus allows for accurate determination of refluxate height, (3) the sensors, which do not rely on pH, are able to detect nonacid reflux which is common in the pediatric and the acid-suppressed patient and in the postprandial period [47–49], and (4) because liquid and gas have different impedances, the sensors can differentiate the composition of the refluxed material.

There are seven impedance sensors placed in series which generate six impedance waves, one for each pair of adjacent sensors (Fig. 12.1a, b). Sensors are distributed throughout the esophagus at different spacing depending on the size of the catheter that is used (2–4 cm spacing on adult catheter, 2 cm spacing on the pediatric catheter, and 1 cm spacing on infant catheter). Since the impedance sensors cannot differentiate between acid versus nonacid material, a distal pH sensor has been added to the catheter which allows the clinician to determine whether the flow across the catheter is acidic, weakly acidic, or nonacidic, depending on the pH value.

The MII-pH catheter is inserted through the nose in the same fashion as traditional esophageal pH monitoring, and the catheter is positioned so the distal pH sensor is at the third vertebral body above the diaphragmatic angle (Fig. 12.2) [5]. Studies are performed for 24 h, and as with pH studies, meals are conventionally excluded from analyses. Typically, with pH studies, acid suppression medications are stopped a minimum of 48 h prior to testing because the pH probe cannot detect nonacid reflux which is prevalent in the acid-suppressed patient [50]. Since the MII-pH catheter can detect acid and nonacid reflux, the studies can be performed off or on acid suppression therapy though adult studies suggest that symptom correlation may be improved if medications are stopped prior to MII-pH testing [51].