This is the first study to evaluate the current clinical practice in conducting ADM and CM studies in pediatric centers worldwide.

ADM and CM studies are time-consuming, and the effect of anesthesia on these studies is a major debate among providers. Same-day studies shorten inpatient stays, reduce the risk of catheter dislodgment, and increase study feasibility. While one previous study showed that anesthesia did not affect CM findings, a later larger cohort showed that it significantly increased the rate of abnormal studies, which were interpreted as normal when repeated on the following day.16,17 Our survey reflects this clinical dilemma as 38% of the centers perform next-day CM manometry studies and 46% perform next–day ADM manometry studies, while another 46% perform same-day CM studies and 38% perform same-day ADM studies. This variability in practice affects the reliability and interpretation of manometry studies, especially due to previously published doubts regarding the anesthesia effect. Furthermore, the validity of abnormal findings noted in a study that was conducted on the same day after anesthesia is questionable. The combined same-day to next-day strategy is implemented by 4 (10.8%) centers in ADM and CM studies; this protocol takes advantage of both strategies, with an option to conclude the study if normal findings are noted on day one. While this strategy has the potential to shorten overall hospital stay, it requires more specialized staffing to perform manometry recording in the evening and may add additional risks to the patients, including fluid overload if run overnight. In addition, centers conducting studies with this combined, conditional approach have valuable data that, by retrospective and prospective evaluation in a multi-center large cohort of patients, can provide a better understanding of the effect of anesthesia on ADM and CM. Such data will support a universal standardized approach that can be implemented in international consensus guidelines and adopted among pediatric centers worldwide. In addition, a cost analysis should be performed to assess the cost-effectiveness of that strategy.

Great variability of the recording of ADM studies was noted in our survey with significantly longer studies (almost double on average) being conducted outside of the USA. While some centers stick to the minimal required standards for performing 6-hour long studies, others conduct studies that last 24 hours. While prolonged studies were shown to identify specific motor abnormalities in adult patients, study duration not only affects healthcare costs and reduces feasibility (especially in small children and children with developmental delay or behavioral disorders), but it also increases potential side effects in centers conducting studies with water-perfused catheters.19 In addition, Prolonged perfusion was shown to be a risk for electrolyte disturbance and prompts close electrolyte monitoring.20 Further research is needed to determine the optimal length of manometry studies in pediatric patients, aiming to maximize diagnostic value while minimizing the risk of adverse events and optimizing healthcare cost.

The main finding that reflects intact neuromuscular integrity on ADM is the presence of motor migrating complex III (MMC III), which is noted during the fasting phase.9 Accordingly, longer recording in the fasting period increases the chance to capture a MMC III. While in some centers, the recording of fasting period during ADM study lasts 1 hour, others record for up to 8 hours. No studies have been conducted to assess the optimal length of recording of fasting period during ADM studies. Such variability was noted to a lesser extent in the length of recording of the postprandial period (range of 1 to 4 hours).

The presence of phase III MMC in either fasting phase or after provocation with a pharmacologic agent during the ADM study, is interpreted as normal. Pharmacological agents to stimulate MMC can potentially shorten or replace the fasting phase. Duodenal provocation was reported to be performed mainly with octreotide – a protocol implemented by >90% of the centers. Erythromycin was also used by one-third of pediatric centers worldwide, with one center reporting the use of amoxicillin-clavulanate. Amoxicillin-clavulanate was previously shown to induce phase III MMC in a small cohort of patients, but further studies are needed to confirm this effect.21 Using different agents with different half-life and potency, which has not been previously compared in head-to-head studies, limits the interpretation of ADM studies. It should be noted that pharmacological stimulation is not performed by more than 10% of centers due to reasons that were not assessed in our study.

For gastric stimulation, most centers use erythromycin or azithromycin, with a minority using octreotide. Erythromycin was previously shown as an agent that can provoke MMC, but the rate of erythromycin-induced MMC in pediatrics has not been reported.22 Octreotide was reported to induce gastric motor activity in 76% of pediatric patients.23 A stepwise approach, using octreotide as the first agent that has the potential to provoke both gastric and duodenal activity, may spare the need to use an additional pharmacologic agent for gastric stimulation in a large subset of patients.

Repeating pharmacological stimulation is not part of the current ADM guidelines, but it is implemented by 42% of the centers for both gastric and duodenal provocation. The effect of repeated stimulation in studies with lack of gastric or duodenal response, has not been previously described, and further studies will help in determining the need for repeated stimulation.

CM studies were reported to be shorter than ADM, with an average total length of 6.8 hours and without significant difference between the US and non-US centers. The range of length of recording of the fasting phase was reported from 1 to 8 hours with an average length of 2.2 hours. High amplitude propagated contractions (HAPC) are the hallmark sign of a normal CM study and can occur both during the fasting as well as the postprandial phases. Like for ADM studies, shortening the length or omitting the fasting phase during a CM study can be adopted with the use of pharmacologic stimulation if an HAPC is not noted in the postprandial phase24. Pharmacologic stimulation during a CM study is always performed in 89% of centers. An additional 8% reported using provocative agents only if no HAPC is noted during prior phases. This latter approach may reduce the total length of CM study and avoid the need for colonic stimulants, with potential side effects of abdominal cramping. It does, however, necessitate constant survey of the CM tracings to make the decision if a stimulant is needed.

Bisacodyl was reported to be the agent used for colonic stimulation by all centers, with an additional 5.5% percent of centers reporting the use of either bisacodyl or glycerin. Glycerin was shown to be inferior to bisacodyl in a recent pediatric prospective, single-center study using a cross-over design.25 One center in US reported using prucalopride and senna as the provocative agents, in addition to bisacodyl. The effect of prucalopride or senna on CM findings, has not been previously described.

Repeating stimulation with bisacodyl, which was previously shown to be beneficial for the exclusion of dysmotility during CM studies,26 was reported to be implemented by the majority of centers ( > 94%). The length of post-stimulation CM recording was reported over a wide range, from 30 minutes up to 3 hours.

When assessing the difference between the US and non-US centers, US centers more frequently utilize both solid-state and water-perfused catheters, whereas none of the non-US centers employ both systems within the same institution. Most non-US centers rely on the less expensive water-perfused systems, likely due to financial constraints.

Additionally, pharmacological stimulation during ADM studies is performed more commonly in US centers compared to non-US centers (30/31, 96.8%, vs. 3/6, 50%; p = 0.0018). The reasons for this difference are unclear but may involve cost considerations, limited access to pharmacological agents, or a preference for simpler protocols with fewer steps.

Interestingly, the total duration of ADM recordings was significantly longer in non-US centers, possibly as a compensatory approach for not conducting provocative tests. Overall, a noteworthy variability was noted among ADM and CM studies conducted in pediatric centers globally. This diversity was noted in the timing of study (same day vs. next day), study length, agents used for stimulation, and repeating stimulation. Currently published guidelines address the minimum standards for performing ADM and CM, allowing for a significant variability among different centers, which is reflected in our study. In adults, the Chicago classification establishes a standardized universal protocol for conducting esophageal manometry studies, and the London classification sets a standard procedure for anorectal manometry studies. However, there is currently a lack of similar standardization for ADM and CM studies both in adults and pediatrics.27,28

Our study is limited by its anonymous survey design, which lacks the ability to assess the reliability of the responses. Moreover, most centers are located in the US, with non-US centers being underrepresented. The predominance of US centers in our study may reflect more specialized pediatric NGM centers in the US relative to the rest of the world, larger US pediatric neurogastroenterology society, or a lower response rate among centers worldwide. There is no international global registry that comprehensively lists all pediatric centers performing ADM and CM, which could be utilized as a resource. This could lead to a selection bias in our manuscript. In addition, our survey did not cover all aspects of manometry procedures, such as placement techniques, the use of endoclips, sedation protocols, or performance with or without prokinetic medications. These aspects should be further investigated and addressed in the future development of a standardized universal protocol by an international experts working group.

ADM and CM are conducted in highly specialized centers by trained pediatric neurogastroenterologists. These studies have many indications, offering both diagnostic and therapeutic benefits. ADM findings have been shown to guide therapeutic approaches in pediatric patients with pseudo-obstruction, while CM has demonstrated value in decision-making prior to colonic resections or the reconnection of diverting ileostomies.9,12,14,29 Additionally, CM plays a crucial role in evaluating symptomatic patients with Hirschsprung disease.30 Standardizing procedures, reducing the duration of these studies, and expanding neurogastroenterology training will be pivotal in increasing their accessibility and widespread adoption.