Gastric motility abnormalities in pediatric gastroesophageal reflux disease: A comprehensive review of mechanisms and therapeutic implications

Abstract

Gastroesophageal reflux disease (GERD) is a common pediatric gastrointestinal disorder associated with significant morbidity, especially when persistent or severe. Although the primary underlying mechanism for GERD is lower esophageal sphincter dysfunction, there is accumulating evidence that disturbances in gastric motility significantly contribute. Described gastric motor abnormalities in GERD include delayed emptying, antral hypomotility, impaired gastric accommodation, abnormal intragastric meal distribution, disordered gastric myoelectrical activity, duodeno-gastro-esophageal reflux, and altered migrating motor complexes. These disturbances are hypothesized to contribute to GERD by increasing intragastric pressure, delaying gastric emptying, and facilitating retrograde flow of gastric contents into the esophagus, acting through complementary mechanisms. The relationship between gastric dysmotility and GERD symptoms remains unclear, leading to uncertainty regarding its clinical significance. Furthermore, there is uncertainty about the role of investigations such as gastric emptying scintigraphy, ¹³C-breath tests, and advanced motility techniques in routine practice. Therapeutic approaches for correcting motility disturbances, including prokinetic medications and neuromodulation, show promise but have limited evidence for their effectiveness in children. Future research should better delineate the role of gastric dysmotility in GERD, refine indications for gastric motility investigations, and evaluate the benefits of targeted motility-based therapies to optimize management strategies in pediatric GERD.

Key Words: Gastric emptying; Gastric motility; Gastroesophageal reflux disease; Pathophysiological mechanisms; Diagnosis; Management

Core Tip: Gastroesophageal reflux disease (GERD) is common in infants and children and significantly affects their well-being. While lower esophageal sphincter dysfunction is central to its pathophysiology, gastric dysmotility is increasingly recognized as a key contributor. This narrative review examines the relationship between gastric motor dysfunction and pediatric GERD, highlighting associated abnormalities, diagnostic challenges, and therapeutic strategies. Future research should focus on developing safe, non-invasive diagnostic tools and targeted treatments addressing gastric motility disturbances. A deeper understanding of gastric motor dysfunction will help clinicians tailor interventions, improving outcomes and quality of life of affected children.

INTRODUCTION

Gastroesophageal reflux (GER) is the involuntary movement of stomach contents into the esophagus, a common physiological process frequently observed after a meal. Increased GER often leads to troublesome symptoms, including regurgitation, heartburn, epigastric pain or discomfort, cough and other respiratory symptoms, frequent belching, and difficulty swallowing. GER can also occasionally lead to esophagitis, Barrett's esophagus, and esophageal strictures. GER causing symptoms and complications is diagnosed as GER disease (GERD)[1-3].

GERD pathophysiology

Commonly suggested pathophysiological mechanisms for GERD are transient lower esophageal sphincter relaxations (TLESR), decreased lower esophageal sphincter (LES) pressure, hiatal hernia, esophageal hypomotility leading to impaired acid clearance and delayed gastric emptying[4,5].

Prevalence of GERD in children

Although GERD is a common gastrointestinal disorder, its prevalence varies widely with age groups, geographic regions, diagnostic criteria, and data collection methods[6-8]. Some studies have shown varying prevalence across regions and ethnic groups within the same country[9,10].

Determining the exact GERD burden in the pediatric population is difficult due to the high prevalence of nonspecific symptoms, the lack of precise diagnostic criteria, and the scarcity of well-designed epidemiological studies. According to a 2019 systematic review[6], the pooled prevalence of daily GERD symptoms among infants was 26.9%. Prospective cohort studies in the review demonstrated that reflux symptoms decline steadily during infancy, decreasing from approximately 25.5% at 1 month to 1.1%-1.6% by 12 months. Among older children, the reported prevalence of GERD symptoms ranged from 0.5% to 3.2% in those younger than 10 years and from 0.2% to 18.8% in those aged 10 years or older, reflecting considerable heterogeneity across studies[6].

GERD symptoms

The characteristic symptoms of GERD are heartburn and regurgitation[7]. However, studies have reported other symptoms, such as bloating, respiratory symptoms, and belching[3]. Compared with adults, infants and children with GERD present with diverse nonspecific symptoms, and the clinical diagnosis of GERD is challenging. Common symptoms of GERD in children are listed in Figure 1[11,12].

Figure 1 Clinical features of pediatric gastroesophageal reflux disease and their overlap with gastroparesis.

Pediatric GERD symptoms are non-specific, and several gastric motility disorders can mimic GERD. Conditions such as gastroparesis, functional dyspepsia, rumination syndrome, and functional vomiting often present with overlapping symptoms, including nausea, vomiting, early satiety, postprandial discomfort, regurgitation, and chest pain[11]. The overlap of symptoms and positive gastric motility findings arising from other motility disorders can complicate GERD diagnosis, leading to misdiagnosis, inappropriate treatment, and an overestimation of the role of gastric dysmotility in GERD pathophysiology. Recognizing these mimics is crucial for achieving an accurate diagnosis and developing effective, targeted management strategies.

Diagnosis of pediatric GERD

There are currently no gold standard diagnostic tools for pediatric GERD. The standard diagnosis of GERD is based on the clinical profile of patients[13,14]. A systematic review defined symptomatic GERD in children as the presence of heartburn and/or regurgitation of any severity, or other compatible symptoms, as determined by a clinician or documented using a GERD symptom questionnaire or diary[6]. When infants and children present with nonspecific symptoms, diagnosis can be delayed. A further challenge to accurate clinical diagnosis is children presenting with disorders that mimic GERD, such as functional dyspepsia, esophageal motor disorders (e.g., achalasia), rumination and functional vomiting[11].

There are multiple confirmatory investigations for GERD, including upper gastrointestinal endoscopy and pH impedance monitoring[3,13-15], but they are generally not recommended for infants and children unless there are atypical symptoms, warning signs, diagnostic uncertainty, suspected complications, or symptoms that persist despite adequate therapy[16]. Interpretation of these test results for the diagnosis of pediatric GERD is more challenging than in adults because of the limited availability of normative pediatric data and the higher prevalence of non-acid reflux and non-erosive GERD in infants and children. As a result, the investigations may not reveal the true prevalence among infants and children[17,18].

Impact of GERD

Complications of GERD are rare in pediatric practice, but include esophagitis, feeding difficulty, weight loss/failure to thrive, anemia, aspiration, respiratory tract infections and otitis media[19-21]. Later complications, such as Barrett’s esophagus, strictures, and adenocarcinoma, are seen only in a minority of children with GERD[22]. The chronic and recurrent nature of this condition can also lead to poorer quality of life in both affected children and their parents, even after successful surgery (fundoplication)[23].

GASTRIC MOTILITY ABNORMALITIES IN GERD

Children with GERD commonly have symptoms of gastroparesis in addition to the typical symptoms of GERD. Figure 1 demonstrates the overlapping symptoms of GERD and gastroparesis in children. Additionally, both GERD and gastric dysmotility share several risk factors such as obesity, emotional stress, high-fat and spicy diets, and insufficient physical activity[24-29].

Gastric motility is essential for the movement of food through the digestive tract and for mechanical and chemical digestion. The main postprandial motor patterns of the stomach include accommodation or receptive relaxation of the proximal stomach, peristaltic contractions of the distal stomach and coordinated gastric emptying. During the fasting period, migrating motor complexes (MMC) originate in the distal stomach and propagate to the duodenum, keeping the stomach clean of residue. Gastric motility patterns vary with age. The gastric pacemakers, myoelectrical properties of gastrointestinal smooth muscles, inputs from enteric and autonomic nervous systems, and hormonal signals regulate gastric motility[30]. GERD-associated gastric motor abnormalities are depicted in Figure 2.

Figure 2 Gastric motor abnormalities recognized in children with gastroesophageal reflux disease. The background graphic of the stomach in this figure was transformed from the original hand-drawn schematic diagram into a high-resolution electronic image using the generative artificial intelligence tool Gemini (from Google).

Delayed gastric emptying

Delayed gastric emptying is associated with prolonged gastric retention, which increases intragastric volume and pressure. High intragastric pressure reduces the pressure gradient between the stomach and the LES, increasing the risk of reflux. In addition to gastric motor abnormalities, increased intragastric pressure generated by bending down and straining can also trigger GER[31]. Intragastric volume is another recognized determinant of GER. Previous studies have demonstrated backflow of gastric contents after fluid injection into the stomach, and reflux appears to occur at lower fluid volumes in symptomatic GERD patients than in asymptomatic patients, suggesting a higher gastric sensitivity to distension[31]. Some studies have suggested an association between the duration of gastric food retention and the number of postprandial TLESRs, slower emptying, a lower pH, and a more proximal extent of refluxate[32]. In addition, gastric distension causes progressive shortening of the LES's abdominal length and reduced pressure, increasing GER and esophageal mucosal exposure to acidic gastric contents[33].

Delayed gastric emptying is considered an important pathophysiological mechanism of GERD in both adults and children[34,35]. However, its exact pathophysiological role in GERD remains unclear[36-39].

Several studies in adults have demonstrated an association between delayed gastric emptying and GERD[40-42]. Delayed gastric emptying has been reported in 10%-33% of adults with GERD, supporting this association[32]. However, other studies have failed to demonstrate a significant association between the two conditions[43,44]. In the pediatric age group, the relationship between delayed gastric emptying and GERD remains uncertain. In 1997, Cucchiara et al[42] reported several gastric motor abnormalities, including delayed gastric emptying in children with GERD symptoms, including both non-ulcer dyspepsia and GERD. Another study in 67 children with GERD confirmed by upper gastrointestinal endoscopy or 24-hour pH monitoring found intestinal malrotation in most patients (54.5%), which was associated with delayed gastric emptying, suggesting that malrotation is an important factor contributing to the delay in pediatric GERD patients[45]. Several studies have also compared gastric emptying with GERD severity. Argon and colleagues evaluated the relationship between gastric emptying and GER in 108 infants and children and found no significant difference in gastric emptying (T½) between children with and without GER. However, when GER was categorized according to severity, those with more severe GER (≥ grade 2) had significantly delayed gastric emptying[46].

In contrast, other studies have not identified a relationship between GERD and delayed gastric emptying. One study compared gastric emptying using radionuclide scintigraphy in 51 children with GERD (confirmed by 24-hour pH monitoring) and 24 healthy controls. The mean T½ for gastric emptying of milk was not significantly different between the GERD and control groups[43]. Similarly, another study assessing gastric emptying in 36 infants using the ¹³C-octanoic breath test failed to demonstrate a significant difference in gastric emptying between infants with GERD and control infants[47].

Furthermore, many previous studies failed to demonstrate a strong relationship between delayed gastric emptying and GERD symptoms, including regurgitation and epigastric fullness, resting LES pressure, acid reflux severity, or esophagitis, thereby failing to establish its exact clinical significance[32,40,48,49].

Altered gastric accommodation

Compliance of both the stomach and esophagus is likely to play a key role in determining LES tone and upper esophageal sphincter relaxation[50,51]. An association between the duration of gastric food retention and the number of postprandial TLESRs has been reported[50]. A previous study showed more pronounced postprandial gastric relaxation in patients with GERD than in those with normal or dyspeptic conditions[52]. Similarly, another study has shown a larger sagittal area of the proximal stomach in patients with mild or moderate reflux esophagitis than in healthy subjects. In this cohort, the sagittal area of the proximal stomach correlated with postprandial fullness, suggesting a possible symptom association[53]. In addition, delayed recovery of proximal gastric tone after a meal and increased visceral sensitivity in patients with GERD have been reported. Increased visceral sensitivity may contribute to the higher prevalence of reflux during TLESR[54].

In contrast, a previous study found no significant differences in minimal distending pressure or proximal gastric compliance among patients with GERD, patients who had undergone Nissen fundoplication, or healthy controls[55]. Furthermore, scintigraphic studies have demonstrated diminished retention of a solid meal in the proximal stomach in patients with GERD and dyspeptic symptoms, a sign of impaired proximal gastric accommodation that correlates with increased postprandial acid reflux[56]. These findings suggest that impaired gastric accommodation may elevate intragastric pressure at lower gastric volumes, facilitating TLESRs and increasing the risk of GER.

These findings support the concept that proximal stomach dysfunction plays an important role in GERD pathogenesis by disrupting gastric accommodation and postprandial motor responses, thereby predisposing to TLESR and acid reflux.

Impaired postprandial antral motility

Reduced postprandial antral contractions delay gastric emptying, leading to increased gastric distension and potentially increasing the risk of reflux. Impaired antral motility is a well-recognized feature of functional dyspepsia in children[57]. Consistent with this, a previous study demonstrated reduced postprandial antral motility in children with GERD and functional dyspepsia[58]. Similarly, adults with reflex esophagitis exhibited lower antral contractility, reflected by fewer antral contractions and reduced cumulative antral activity. than healthy controls[43].

However, in a study of 10 infants with GER, including five with delayed gastric emptying and five with normal gastric emptying, Cannon and Stadalnik[59] found no significant differences in postprandial gastric motility between the two groups. Furthermore, metoclopramide treatment did not significantly affect postprandial gastric motility in either group.

Abnormal intragastric distribution of meals

Abnormal intragastric distribution of a meal has been proposed as a potential predisposing factor for GERD. Maldistribution of gastric contents may promote the formation of acid pockets in the proximal stomach, thereby facilitating acid reflux[34]. Several studies have reported increased proximal gastric retention in patients with GERD. In addition, among patients with both GERD and dyspepsia, proximal gastric retention was significantly and inversely correlated with the number of acid reflux episodes[56]. However, a subsequent study by the same research group, which evaluated the intragastric distribution of a liquid meal, failed to demonstrate abnormal food retention within the intra-junctional region of the stomach[60].

Abnormal myoelectrical activity

Gastric electrical dysrhythmias have been reported in patients with GERD. Recognized postprandial myoelectrical abnormalities in adults include a lower percentage of normogastria, a lower power ratio in electrogastrography (EGG), reduced dominant power and increased variability of the electrical dominant frequency[41,42]. Myoelectrical disturbances could possibly result in abnormalities in meal distribution, accommodation and gastric emptying, all of which may at least partially contribute to reflux. In contrast, some studies failed to demonstrate significant differences in the frequency of 3-cycle-per-minute waves or peak frequency in patients with GERD[44].

Pyloric dysfunction

Abnormal coordination and increased tone of the pyloric sphincter can impair gastric emptying, thus contributing to GERD. Patients with pylorospasm[61] and congenital hypertrophic pyloric stenosis[62] sometimes present with GERD or related symptoms.

Duodeno-gastro-esophageal reflux

Duodenogastric reflux is the retrograde flow of bile and pancreatic secretions from the duodenum into the stomach. When this alkaline fluid refluxes into the esophagus, it is termed duodeno-gastro-esophageal reflux (DGER). In DGER, bile refluxed from the small intestine distends the stomach, increasing acid secretion and exacerbating esophageal mucosal damage[63,64]. DGER in non-acidic environments (i.e., in partial gastrectomy patients) may cause symptoms but does not cause esophageal mucosal injury[63]. In a study of 67 patients with either treatment-resistant GERD or GERD with complications, 11% had isolated pathological acid exposure, 38% had pathological DGER exposure only, and 26% had pathological exposure to both acid and DGER, highlighting the high prevalence of DGER[65]. Although it may play a pathophysiological role in GERD, there are no pediatric studies that demonstrate the presence of DGER in children with reflux.

Abnormal MMC

Cucchiara et al[58] demonstrated several abnormalities in fasting motor patterns in children with GERD and functional dyspepsia. These include the absence of antral phase III of MMC, reduced antral and/or duodenojejunal motility during the fasting period, and diminished length of MMC phase III, which was sometimes irregularly propagated.

ASSESSMENT OF GASTRIC MOTILITY IN CHILDREN WITH GERD

Figure 3 lists the available investigation techniques for assessing gastric motility and the relevant motility parameters assessed by each test.

Figure 3 Diagnostic techniques for assessing gastric motility and their measured parameters. The background graphic of the stomach in this figure was transformed from the original hand-drawn schematic diagram into a high-resolution electronic image using the generative artificial intelligence tool Gemini (from Google). EGG: Electrogastrography.

Gastric emptying studies

Gastric motility studies are included in the diagnostic algorithms for pediatric GERD[66]. Techniques such as scintigraphy, ultrasonography, and ¹³C-octanoic breath tests are used to evaluate gastric emptying in children.

Scintigraphy is considered the “gold standard” for measuring gastric emptying. In this test, a radio-labeled meal is ingested and its transit is traced using a gamma camera, which is the most objective method for assessing gastric emptying[67]. The main disadvantage of scintigraphy is radiation exposure, which limits its use in pediatric practice and prevents repeated assessments. In addition, the patient must remain still for prolonged periods during scintigraphy, which is practically challenging in young children. Its exceptionally high cost also limits its use, especially in low or middle-income countries.

The ¹³C-octanoic acid breath test is a promising method for noninvasive, radiation-free evaluation of gastric emptying. The ¹³C isotope can be incorporated into a solid meal, which then gets emptied by the stomach, digested, absorbed in the proximal small intestine, metabolized by the liver and excreted by the lungs, resulting in increased ¹³CO₂ level in expired air, over baseline. This technique has been compared with scintigraphic methods and proven to be accurate. Its pitfalls include potential loss of accuracy in patients with other diseases affecting the intestinal mucosa and the respiratory system[68].

The real-time ultrasound technique is a safe, non-invasive method for assessing gastric emptying and can be used in both neonates and older children. It is based on measuring the width of the gastric antrum before and after a test meal. The gastric antrum is visible in almost all subjects, including those with obesity[69]. This method has been validated against both scintigraphy[70-73] and the ¹³C-octanoic acid breath test[74] and has demonstrated good interobserver agreement[75]. With three-dimensional ultrasonography, gastric volumes and the intragastric distribution of a meal can be assessed, and more accurate measurements of gastric emptying can be obtained[76]. However, ultrasound assessment of gastric emptying is time-consuming, highly operator-dependent, and requires dedicated, well-trained professionals.

Non-digestible wireless motility capsules can measure pH, intraluminal pressure, and temperature throughout the gastrointestinal tract. The abrupt change in pH from the acidic stomach to the almost alkaline duodenum is usually associated with phase III of the MMC. Therefore, the wireless motility capsule does not measure emptying of digestible food, but rather the emptying of indigestible materials, which are emptied with phase III of the MMC[77].

Other radiological methods have been used to assess gastric emptying, such as computed tomography and magnetic resonance imaging (MRI).

Postprandial antral motility

A group of Japanese researchers introduced a real-time ultrasound technique to assess postprandial antral motility. It is safe, non-invasive, and can be used in pediatric patients[69].

Gastric accommodation

The gastric barostat is considered the gold standard for assessing gastric accommodation. One of the main disadvantages is that the procedure is invasive because it involves the introduction of an intragastric catheter and bag. In addition, it is costly, invasive, not always well tolerated, and the barostat bag itself may influence motility, affecting the accuracy of results. This limits its use in pediatric practice[78].

The water load test (WLT) involves drinking a measured amount of water, either at a fixed rate or until the participant feels full. The WLT can be used to evaluate the extent of gastric expansion and the degree of gastric sensitivity to distension. It is a simple, non-invasive method for assessing gastric accommodation and visceral hypersensitivity, and it can be used in children[79]. WLT results are abnormal in patients with GERD, indicating gastric accommodation dysfunction[80].

Real-time ultrasonography is a noninvasive, safe technique for assessing gastric accommodation. Gastric accommodation can be assessed using both two-dimensional and three-dimensional ultrasonography. Three-dimensional approaches provide a more comprehensive visualization of the stomach and enable more precise measurements of gastric volumes. The main advantage of this technique is that other gastric motility parameters, such as gastric emptying, antral motility, and duodeno-gastric reflux, can be assessed simultaneously[81].

Other imaging techniques, such as scintigraphy, MRI, and single-photon emission computed tomography (SPECT), can be used to assess gastric accommodation. MRI and SPECT are gaining popularity because they are non-invasive, do not alter gastric motility like the barostat, and are therefore more accurate[78].

Gastric myoelectrical activity

EGG assesses the myoelectrical activity of gastric smooth muscle using cutaneous electrodes[82,83]. Even though there is evidence of gastric myoelectrical abnormalities in adults and children with GERD, the clinical value of EGG is limited in the diagnosis and management of this condition. EGG is rarely recommended as part of the standard diagnostic workup for pediatric GERD[35].

MMC

Antroduodenal manometry is considered the gold standard for assessing MMC. This technique measures intraluminal pressure changes associated with gastric antral contraction and relaxation. They are useful for detecting phase III of MMCs but cannot identify abnormalities in postprandial gastric contractions[84]. Due to its invasive nature, its usage is limited, especially in children.

DGER

Bilirubin monitoring tests (e.g., Bilitec) measure bilirubin levels in the esophagus, which is a marker for the presence of bile. DGER is common in treatment-resistant GERD. Combined pH-impedance and bilirubin monitoring helps confirm the diagnosis and support effective management[65].

Color doppler ultrasound is a safe, noninvasive method for assessing duodeno-gastric reflux[85]. However, the validity of this technique must be established before it is introduced into routine clinical practice.

GASTRIC MOTILITY-TARGETED THERAPIES FOR PEDIATRIC GERD

Three principal patterns of dysmotility identified in pediatric GERD, delayed gastric emptying, antral hypomotility, and impaired gastric accommodation, are the primary focus of motility targeting therapies used in pediatric GERD. Although previous studies have reported an inconsistent association between delayed gastric emptying and GERD and its contribution to symptoms, emerging data suggest that gastric dysmotility is one of the key predictors of persistent reflux symptoms and complications, including erosive esophagitis and treatment-resistant GERD, in specific high-risk pediatric populations, such as children with repaired esophageal atresia or a history of lung transplantation[86,87]. Children who respond poorly to standard medical therapy may have coexisting structural and functional abnormalities of the esophagus and stomach, contributing to more severe and treatment-resistant GERD.

These findings underscore the importance of evaluating motility and using motility-enhancing drugs as part of a comprehensive approach to GERD management, particularly in complex or high-risk cases.

Lifestyle and dietary modifications targeting gastric dysmotility

The key publication guiding the conventional management of GERD in children is the 2018 Consensus Management Guideline from the North American and European Societies of Pediatric Gastroenterology, Hepatology, and Nutrition[12]. This guideline recommends lifestyle and dietary modifications that impact gastric motility. The main practical points highlighted in this guideline are summarized in Table 1.

Table 1 Key medical management points of gastroesophageal reflux disease in children.

No.	Key medical management points
1	Use of thickened feeding for visible regurgitation/vomiting in infants with GERD
2	Modification of feeding volumes and frequency according to age and weight to minimize overfeeding
3	Use of a 2-4-week trial of extensively hydrolyzed protein-based (or amino-acid-based) formula in infants when optimal pharmacological management failed to improve symptoms
4	Use of head elevation and left lateral positioning in children, not in infants
5	Providing parental/patient educational material and support
6	Use of PPI as first-line treatment of reflux-related erosive esophagitis in infants and children with GERD for 8 weeks
7	Use of H2RAs in the treatment of reflux-related erosive esophagitis when PPIs are not available

GERD: Gastroesophageal reflux disease; H2RA: Histamine-2 receptor antagonists; PPI: Proton pump inhibitor.

Weight reduction has consistently been shown to alleviate GERD symptoms, with one key underlying mechanism being improved gastric emptying. Excess body weight, especially central adiposity, increases intra-abdominal pressure, impairs LES function and promotes reflux of gastric contents into the esophagus. A landmark prospective cohort study involving over 10000 women demonstrated that even modest weight loss was associated with significant reductions in GERD symptoms[88]. Furthermore, obesity has been linked to delayed gastric emptying, which can exacerbate reflux by increasing gastric volume and pressure[89]. Weight loss can reverse this delay[90].

Quitadamo et al[91] reported that obese children and adolescents exhibit delayed gastric emptying along with increased GER burden on pH-impedance monitoring and reduced quality of life. Malaty et al[92] found that children with endoscopically confirmed GERD have higher body mass index compared with age-adjusted population norms, suggesting an association between increased body weight and GERD. Patel et al[93] further reported that childhood overweight is associated with reflux esophagitis, supporting a potential link between excess body weight and reflux-related disease.

Therefore, weight reduction should be considered as part of the GERD management strategy in obese children, as it may help alleviate reflux symptoms while also addressing other obesity-related comorbidities.

Positioning is often used in infants and young children to reduce GERD symptoms. Studies have shown that positioning infants and children in the left lateral position reduces the number of reflux episodes and improves gastric emptying[94,95]. However, other studies have failed to demonstrate a significant reduction in vomiting in the left lateral position and have suggested that positioning reduces acid reflux by improving the clearance of refluxed acid from the esophagus rather than by improving gastric emptying[96]. However, concerns have been raised about keeping infants in any position other than supine, as that increases the risk of sudden infant death.

Large meals and high caloric intake can increase the reflux burden. Frequent small meals improve gastric emptying, reduce gastric pressure, and decrease reflux frequency[97]. Although physiologically possible, no studies have confirmed this hypothesis in children with GERD. Patients are often advised on frequent small feeds. However, the current European and North American guideline does not directly recommend this feeding method. Instead, it emphasizes the importance of avoiding overfeeding by adjusting feeding frequency and volume to age and weight while maintaining an appropriate total daily volume[12].

A low-fat diet is often recommended in GERD, as a high-fat diet is thought to reduce LES tone and gastric emptying. Therefore, a low-fat diet has been recommended to improve gastric emptying and, hence, symptoms in children with GERD. High-fat diet increases acid reflux frequency[98], but care must be taken to avoid nutritional deficiencies and food aversion behaviors when manipulating the diet of young children and infants, which may have long-term repercussions.

The gut microbiome plays a pivotal role in regulating gastrointestinal motility[99], as microbial metabolites such as short-chain fatty acids and bile acids interact with the enteric nervous system and smooth muscle to influence gastric emptying and intestinal transit[100]. Dysbiosis has been associated with motility disorders, including irritable bowel syndrome and chronic constipation, underscoring the microbiome’s role in normal gastrointestinal motor function[101].

Although probiotics have been investigated as an adjunct therapy for pediatric GERD, current evidence does not support their efficacy in improving gastric emptying. Systematic reviews report modest reductions in regurgitation episodes, but findings are inconsistent and limited by small sample sizes[102]. Based on this, the 2018 ESPGHAN/NASPGHAN guideline does not recommend probiotics for managing GERD in children[12].

Pharmacological interventions that increase gastric motility

The cornerstone of pharmacological management for GERD is the suppression of gastric acid production. This is crucial for reducing the acidity of refluxate and minimizing mucosal injury. Several classes of medications are used for this purpose, including histamine-2 receptor antagonists and proton pump inhibitors (PPIs). Each of these therapies helps reduce the overall acid burden, thereby alleviating symptoms[12]. In addition, it is evident that deranged gastric function plays a role in generating and exacerbating symptoms of pediatric GERD. Consequently, pharmacological interventions that enhance gastric motor function have gained attention as adjunct therapies. Prokinetics, drugs that improve gastric accommodation, and neuromodulators targeting TLESR represent promising approaches to reduce reflux episodes and improve the quality of life of affected children. Table 2 summarizes gastric prokinetic agents, their mechanism of action and clinical relevance in pediatric GERD.

Table 2 Gastroprokinetic agents, their mechanisms of action and clinical relevance in pediatric gastroesophageal reflux disease.

Drug	Mechanism of action	Effects on gastrointestinal motility	Use in pediatric GERD	Key limitations
Domperidone	D-2 receptor agonist	Increased GE, increased LES tone	Common	QT prolongation
Metoclopramide	D-2 and 5HT4 receptor agonist	Increased GE, increased LES tone	Limited	Neurological side effects
Erythromycin	Motilin receptor agonist	Increased MMC, increased GE	Off label	Tachyphylaxis
Buspirone	5HT1A receptor agonist	Increased gastric accommodation, increased esophageal motility	Emerging	Limited pediatric data
Acotiamide	A muscarinic receptor antagonist	Decreased postprandial symptoms, enhanced accommodation and antral motility	Emerging	Mostly adult data
Camicinal	Small molecular motilin receptor agonist	Increased gastrointestinal motility and GE	Emerging	No pediatric data
Relamorelin	Ghrelin receptor agonist	Increased GE	Emerging	No pediatric data

D-2: Dopamine-2; GE: Gastric emptying; GERD: Gastroesophageal reflux disease; LES: Lower esophageal sphincter; MMC: Migrating motor complexes.

In this section, we explore the traditional and novel agents that affect gastric function and are useful in treating children with GERD.

Domperidone: Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. The drug has high affinity for receptors in the upper gastrointestinal tract, hence; higher concentrations of domperidone are found in the esophagus, stomach, and small intestine[103]. Therefore, its prokinetic effects primarily manifest in the esophagus and stomach. Domperidone stimulates esophageal motility and increases LES pressure. In the stomach, it increases the duration of antral and duodenal contractions, accelerates gastric emptying of liquids and semisolids, and enlarges pyloric sphincter diameter[104-110]. These effects support its use in GERD.

Several pediatric studies have been conducted to assess the utility of domperidone in treating children with GERD[111-116]. Table 3 depicts details of the trials, the majority of which have included small numbers of children and infants with symptoms that are difficult to evaluate. Some studies, although randomized, were open-label. The age ranges widely vary in some studies, making it challenging to interpret for a particular age group in day-to-day clinical practice.

Table 3 Clinical trials assessing the efficacy of domperidone in the treatment of gastroesophageal reflux disease in children.

Ref.	Participants, n (age range)	Cases/controls	Design	Outcome	Comments on the study
De Loore et al[111], 1979	47 (3 weeks to 8 years)	Children with regurgitation/vomiting	Blinded RCT with placebo-controlled arm; domperidone vs metoclopramide vs placebo	Domperidone was superior to a placebo. Domperidone proved to be superior in reducing symptoms compared to metoclopramide	Assessment of symptoms of younger children, especially regurgitation, may have been problematic
Carroccio, et al[112], 1994	80 (1-18 months)	GERD with no erosion. All children were assessed with upper GI endoscopy and pH study	Blinded RCT: Group 1: Domperidone with magnesium hydroxide + aluminium hydroxide; Group 2: Domperidone with alginate; Group 3: Domperidone; Group 4: Placebo, duration 8 weeks	Group 1 showed significant improvement of symptoms and reflux index compared to Groups 2 and 3 (P < 0.018 and P < 0.034 respectively). The domperidone group reported fewer reflux episodes (59 vs 48.5, P < 0.009) and improvement in clinical score before and after treatment (P < 0.04)	A well-conducted study with real-life use of domperidone combined with antacids or alginates. The control group was also appropriate. Assessment was done with pH
Bines et al[113], 1992	17 (5 months to 12 years)	GERD is unresponsive to non-pharmacological treatments and confirmed with pH studies	Blinded RCT with domperidone and placebo arms for 8 weeks	No significant difference in symptom improvement. Only 25% reduction in postprandial reflux episodes in children on domperidone	A small number of patients; age range varies widely, and it could be difficult to assess symptoms in younger children; randomization was not clear; some patients had other diseases
Grill et al[114], 1985	15 (3-13 months)	Babies with symptoms of GERD, like vomiting, spitting, coughing, irritability, and choking, after 2 weeks of non-pharmacological interventions	Open-label study with domperidone for 6 weeks	Improvement of the mean symptom score at 3 weeks and 6 weeks. Reduction of post-prandial reflux time and peristaltic esophageal contractions	The study's open-label design makes it difficult to interpret the results
Hegar et al[115], 2009	20 (2-9 months)	Symptomatic GERD not responding to conservative interventions	Randomized, investigator-blind, open label trial domperidone vs cisapride for 4 weeks	Both drugs were equally effective in reducing the daily frequency of regurgitation, reducing the trends of reflux index, and the number of refluxes/24 hours. No statistical difference between drugs	The open-label nature of the prescription makes it difficult to interpret results. However, the authors have randomized the population, and the investigators are blinded
Cresi et al[116], 2008	26 term and preterm neonates	Symptomatic GERD not responding to non-pharmacological interventions	Open-label, randomized, placebo-controlled trial. Domperidone was given at 8 hours and 16 hours during a 24-hour pH recording with a meal	Increase in reflux frequency and reduction in reflux duration in the group receiving domperidone	The open-label nature of the study makes it difficult to interpret the results. Assessment of symptoms in preterm babies could have been misinterpreted

GERD: Gastroesophageal reflux disease; RCT: Randomized controlled trial; GI: Gastrointestinal.

De Loore et al[111] evaluated the clinical efficacy of domperidone in infants and children with GERD. Forty-seven patients were randomized into a 2-week, double-blind trial comparing domperidone, metoclopramide, and placebo. The investigators reported a significant improvement in symptoms, with a lower percentage of patients experiencing vomiting at the end of the treatment period in the domperidone group than in the placebo group.

In another study, 80 patients were randomized into four equal groups to receive domperidone alone, domperidone in combination with two different antacids (either aluminum hydroxide or magnesium hydroxide), domperidone with alginate or placebo. At the time of diagnosis and 8 weeks after treatment, children underwent 24-hour continuous esophageal pH monitoring. The results demonstrated that domperidone in combination with antacids significantly improved both clinical symptoms and pH-metry parameters compared with placebo[112].

A 2022 meta-analysis compared the efficacy of combining PPIs with domperidone vs PPI monotherapy in the management of GERD. The analysis showed that adding domperidone to PPI therapy resulted in a significant reduction in global GERD symptom scores compared with PPI therapy alone. Notably, the incidence of adverse effects was comparable between the combination therapy and PPI monotherapy groups, suggesting that adding domperidone did not increase the risk of treatment-related side effects[117].

However, there are growing concerns regarding the safety of domperidone. A recent systematic review found that domperidone is associated with an increased risk of sudden cardiac death and ventricular arrhythmias in doses over 30 mg per day in adults[118]. In a systematic review of five studies of domperidone-associated QT interval prolongation in children, three found no evidence of QT prolongation during the study period, while two studies reported significant QT prolongation, while none of the five studies reported cardiac deaths[119]. A Sri Lankan study that treated children with functional abdominal pain disorders with domperidone for 8 weeks found no notable QT prolongation or adverse reactions related to the intervention[120].

Despite the rationale for use of domperidone due to its ability to enhance gastric emptying and antral motility, the clinical evidence for its use in pediatric GERD remains weak and inconsistent. Trials have been hampered by small sample sizes, heterogeneous age groups, subjective symptom assessments in infants, and frequent reliance on open-label designs that introduce bias. Even well-conducted randomized studies show conflicting results, with some reporting symptomatic benefit and others demonstrating minimal or paradoxical effects. The lack of standardized diagnostic criteria, objective outcome measures, and rigorous methodology undermines the reliability of these findings. In addition, the potential deleterious adverse reaction of prolonged QT interval is also over-emphasized. The current evidence does not provide sufficient scientific rigor to justify domperidone as an established therapy for GERD in children. There is a pressing need for well-designed, adequately powered randomized controlled trials that employ objective endpoints, such as pH monitoring and validated symptom scores, and safety profiles to clarify the true therapeutic value of domperidone in the pediatric population.

Metoclopramide: Metoclopramide is used to augment gastric emptying and improve LES tone. In their systematic review on the usefulness of metoclopramide for GERD in infants, Hibbs and Lorch[121] reviewed 12 articles. Among them, five were well-conducted randomized trials, with 2 showing no significant improvement, and another 2 showing only a placebo effect. Several adverse effects, including irritability, drowsiness, dystonic reactions, and oculogyric crisis, have been reported[121]. Given its limited usefulness and significant side-effect profile, it is currently not recommended for the treatment of GERD in pediatric practice.

Erythromycin: Erythromycin functions as a motilin receptor agonist, enhancing phase III MMC activity and inducing potent antral contractions, thereby accelerating gastric emptying by promoting coordinated gastrointestinal motility. Several studies have reported its efficacy in treating motility disorders[122,123]. However, two clinical trials have failed to show any beneficial effects in reducing acid or non-acid reflux when measured using pH impedance studies[124,125]. Erythromycin is also known to predispose children to develop prolonged QT syndrome. It is evident that the field of GERD research is moving toward non-antibiotic motility agents, and it is very unlikely that erythromycin will be used in future clinical trials for GERD in children. In this context, erythromycin is not recommended as a therapeutic modality for children with GERD.

Current evidence suggests that, apart from domperidone, other prokinetic agents (metoclopramide and erythromycin) are unlikely to offer significant therapeutic benefit in the management of GERD in children. To overcome domperidone's predisposition to cardiac arrhythmias and prolonged QT syndrome, researchers should develop novel agents with gastrointestinal tract-specific effects and minimal cardiac effects.

5-HT agonists: Prucalopride is a next-generation, highly selective, high-affinity 5-HT4 receptor agonist. The 5-HT4 receptor is expressed in enteric neurons. When it is adequately stimulated, releases acetylcholine from cholinergic neurons, which can induce intestinal motility, propagatory contractions, and propulsion[51]. These 5-HT4 receptors are also distributed throughout the gastrointestinal tract, including smooth muscle cells and enterochromaffin-like cells.

It is primarily used to manage chronic constipation. Beyond its prokinetic effects on the colon, prucalopride can enhance upper gastrointestinal motility, including esophageal and gastric functions. Clinical trials in adults have demonstrated that prucalopride increases the amplitude of esophageal peristaltic waves, improves the number of swallows associated with complete peristalsis, and accelerates gastric emptying, thereby contributing to overall gastrointestinal motility enhancement[126-129]. Hirsch et al[130] studied 71 children with upper gastrointestinal symptoms (11% with reflux symptoms) and reported a significant improvement in reflux symptoms following prucalopride administration. The common treatment-associated adverse reactions include headache, vomiting, diarrhea, and abdominal pain. Considering its beneficial effects on foregut motility and favorable safety profile, prucalopride merits further evaluation as a potential therapeutic option for GERD in well-designed clinical trials.

Buspirone: Buspirone exerts its effects on gastrointestinal motility primarily by activating 5-HT1A receptors[131], and this activation can increase the amplitude of esophageal peristaltic contractions and augment LES pressure in healthy volunteers. The esophageal motor effects observed in earlier studies may reflect the local action of buspirone on 5-HT1 receptors, resulting in contraction of human esophageal smooth muscle[131,132]. Buspirone also improves gastric accommodation[133]. One trial compared the efficacy of omeprazole plus buccal buspirone vs omeprazole plus placebo in treating GERD. In this study, 34 adults with GERD were randomized to receive interventions. At the end of 4 weeks, 29 patients from each arm completed the study. Symptom severity was assessed using the Frequency Scale for the Symptoms of GERD (FSSG) at baseline and after 4 weeks. The trial showed a statistically significant improvement in FSSG in patients treated with buspirone compared with placebo (P < 0.0001). Similarly, at the end of the 4-week period, the buspirone group showed a significant improvement in health-related quality of life[132]. There are no pediatric trials for buspirone in GERD treatment. Given the fact that it has effects on esophageal motility and improves gastric accommodation, further research should be conducted to explore the possibility of its use in pediatric GERD.

Acotiamide: Acotiamide is a novel prokinetic agent that has a high affinity for M1 and M2 cholinergic receptors in the neuromuscular junction, particularly in the presynaptic region of the cholinergic nerve endings, increasing acetylcholine levels and resulting in enhanced gastric motility[134,135]. The efficacy of acotiamide in improving gastric accommodation and emptying has been demonstrated in adult patients with functional dyspepsia[136,137].

However, acotiamide did not reduce esophageal motor function or postprandial acid/nonacid reflux in healthy volunteers[138]. A Japanese double-blind randomized, placebo-controlled trial studied the utility of adding acotiamide to PPIs for 2 weeks in 70 adults with refractory non-erosive gastritis. The primary endpoint was the overall treatment effect recommended by the Rome guideline. A subsection of patients underwent high-resolution manometry and pH study. There was no significant difference in overall treatment effect between acotiamide and placebo groups (P = 0.145), although acotiamide reduced total acid reflux episodes, proximal reflux, and liquid reflux[139]. This study was conducted in patients with refractory symptoms, and the physiological studies were conducted only on a subset of patients. These two issues make it difficult to predict treatment effects in patients with simple reflux.

These controversial pharmacological features make it an interesting candidate for treating GERD in real-world clinical trials, as both delayed gastric emptying and impaired gastric accommodation are key gastric abnormalities in GERD.

Novel prokinetics: Camicinal (GSK-962040) is an investigational, small-molecule motilin receptor agonist developed for treating gastroparesis. It enhances gastrointestinal motility by stimulating cholinergic activity in the gastric antrum, thereby prolonging contractions and accelerating gastric emptying[140].

In a double-blind, crossover, placebo-controlled trial, Hobson et al[141] evaluated the efficacy of camicinal on gastroesophageal function. The study included 12 healthy volunteers, who, after randomization, received either a placebo or camicinal. GER was assessed using 24-hour ambulatory multichannel intraluminal impedance and pH monitoring, and the wireless motility capsule measured gastric and intestinal transit. The subjects were evaluated with an alternative intervention after 7 days. Compared with placebo, camicinal accelerated gastric emptying time and decreased the total number of acid reflux events. Therefore, it would be useful to conduct further clinical trials to evaluate the usefulness of camicinal as a therapeutic modality for GERD.

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor and plays a key role in regulating gastrointestinal motility through its prokinetic effects. Ghrelin receptor agonists such as relamorelin accelerate gastric emptying and alleviate gastroparesis symptoms[142], and may have therapeutic potential for GERD by improving gastric emptying.

Surgical interventions that improve gastric motility

Botulinum toxin injection: Botulinum toxin relaxes smooth muscles by blocking acetylcholine at the neuromuscular junction. Relaxation of smooth muscle at the gastric pylorus enhances gastric emptying, leading to improvement of GERD symptoms, especially when associated with gastroparesis. A preliminary study from Iran that included 11 patients reported improvement of refractory GERD symptoms following endoscopic intrapyloric injection of botulinum toxin[143]. It is difficult to draw firm conclusions from this study due to the non-randomized nature of the intervention and the small number of patients. In a prospective observational study, 45 children with chronic nausea and vomiting underwent intrapyloric injection of botulinum toxin. A subset of children (n = 23) underwent a subsequent pyloric EndoFLIP procedure. The authors noted that children with delayed gastric emptying tended to have lower pyloric distensibility. In addition, there was a significant improvement in symptoms and quality of life 1 month after the injection, which persisted for up to 6 months of follow-up[144]. Several other studies in children have proven the value of the botulinum toxin in children with gastroparesis[145,146]. The ages of children included in these studies range from 6 months to 15 years. Endoscopic intrapyloric botulinum toxin injection appears to have an excellent safety profile in children[145,146]. In a multicenter study by Mercier et al[145], there were no reports of procedure-related complications, while the largest pediatric series reported only one child with transient worsening of symptoms that resolved within a week, with no serious adverse events[146]. These findings suggest the potential benefits of intrapyloric botulinum injection in children with refractory GERD with poor gastric emptying. However, proper randomized controlled trials are necessary to assess the efficacy before its routine recommendation.

Pyloroplasty: In selected children with documented delayed gastric emptying associated with GERD, a pyloroplasty may be added to fundoplication to improve gastric drainage and enhance surgical outcomes. The rationale is to reduce stasis, which can otherwise perpetuate reflux or postoperative symptoms such as bloating and retching. However, a study involving neurologically impaired children with GERD found no additional benefits regarding recurrence of symptoms, readmissions and reoperations[147]. Therefore, its routine use remains controversial, as evidence is inconclusive and highlights possible short-term complications, including dumping syndrome, diarrhea, and prolonged post-operative recovery. The decision to include pyloroplasty, with or without fundoplication, should be individualized, guided by the severity of dysmotility, clinical context, and surgical expertise.

Other surgical interventions: Gastric peroral endoscopic pyloromyotomy (G-POEM), also referred to as peroral pyloromyotomy, is an advanced minimally invasive endoscopic intervention designed for the management of disorders characterized by impaired gastric emptying, most notably refractory gastroparesis. The technique is derived from the principles of peroral endoscopic myotomy, originally developed for the treatment of esophageal motility disorders, and has been adapted to target pyloric dysfunction. Adult studies have shown the benefits of G-POEM in gastroparesis, including improvements in quality of life and reductions in reflux scores[148]. It had been recommended for adults with gastroparesis refractory to medical interventions[149]. There is no evidence of its therapeutic value in children with GERD, and further high-quality evidence and refinement of technical aspects are required before the G-POEM can be recommended for children with refractory GERD with impaired gastric emptying. Emerging data provide a preliminary framework for careful, selective consideration of this procedure in certain pediatric patients[150].

Radiofrequency ablation of the cardia and esophagogastric junction can improve gastroparesis-associated GERD symptoms by enhancing gastric emptying and strengthening the antireflux barrier, thereby reducing reflux episodes and hypersensitivity. Clinical studies show normalization of gastric emptying in most patients and significant improvement in reflux-related quality of life[151,152]. There are no pediatric clinical trials evaluating the efficacy of radiofrequency ablation in children with refractory GERD[150], although it may benefit those with delayed gastric emptying.

Novel therapeutic modalities enhancing gastric motility

Neuromodulation: Neuromodulation therapies have emerged as promising, novel approaches for managing GERD, particularly in patients who are refractory to conventional medical or surgical treatments. These interventions aim to modulate the neural pathways regulating the esophageal motility, LES function and gastric emptying, thereby minimizing reflux.

Various neuromodulation techniques have been explored for GERD. Transcutaneous electrical acustimulation (TEA) involves non-invasive stimulation of specific acupoints to enhance gastric motility, gastric emptying and LES pressure. Recent systematic reviews have analyzed available clinical trials and concluded that LES electrical stimulation and TEA are supported by moderate-quality evidence as effective therapeutic options for GERD[153].

When TEA has been used therapeutically in children with selected motility disorders, such as functional abdominal pain and constipation, it has been proven to be effective and safe[154,155]. It is a potential therapeutic modality for children with GERD who have failed to respond to standard medical management.

FUTURE DIRECTIONS IN GASTRIC MOTILITY-TARGETED THERAPY FOR PEDIATRIC GERD

The pharmacological landscape for managing pediatric GERD through motility enhancement remains unsettled. Traditional agents such as domperidone, metoclopramide, and erythromycin have provided important insights but have failed to establish themselves as reliable long-term therapies due to inconsistent efficacy and significant safety concerns. Despite its ability to increase LES tone and accelerate gastric emptying, domperidone suffers from weak trial evidence and ongoing concerns about QT prolongation. Metoclopramide’s neurological side effects have largely excluded it from pediatric practice, while erythromycin’s tachyphylaxis and antibiotic resistance risks make it unsuitable for sustained use. These limitations underscore the urgent need for safer, more selective motility agents.

The future of motility-targeted therapy lies in novel pharmacological classes that act on specific pathways with improved safety profiles. These include 5-HT4 agonists such as prucalopride, which selectively stimulate enteric neurons to enhance gastric and esophageal motility without the cardiac toxicity associated with earlier agents such as cisapride. Early pediatric data suggest symptomatic benefit, but larger, rigorously designed trials are required to confirm efficacy and tolerability. Similarly, buspirone, a 5-HT1A agonist, has demonstrable improvements in gastric accommodation and esophageal peristalsis in adults, highlighting the potential of accommodation-targeted therapies in children with GERD. With its dual effects on gastric emptying and accommodation, acotiamide remains an intriguing candidate, though evidence for its use in pediatric practice is lacking. Novel motilin (e.g., camicinal) and ghrelin (e.g., relamorelin) receptor agonists are emerging as innovative approaches to accelerate gastric emptying without the drawbacks associated with erythromycin.

Future clinical trials must address the methodological weaknesses that have plagued earlier studies. Small sample sizes, heterogeneous age groups, reliance on subjective symptom reporting, and lack of standardized diagnostic criteria have limited the interpretability of past findings. Upcoming trials should be multicentered, adequately powered, and stratified by age and motility phenotype, recognizing that infants, school-aged children, and adolescents may respond differently to motility-targeted interventions. Objective endpoints such as pH impedance monitoring, validated symptom scores, and gastric emptying studies should be incorporated to provide robust measures of efficacy. Equally important is the systematic evaluation of safety, particularly cardiac monitoring for agents with arrhythmogenic potential and neurological surveillance for drugs acting on central pathways.

The future of managing children with GERD should move toward precision medicine approaches to identify subgroups of children most likely to benefit from motility-targeted therapy. For example, children with repaired esophageal atresia, lung transplantation, or severe gastroparesis may represent high-risk populations in whom motility enhancement could meaningfully reduce reflux burden. Integration of motility agents with standard acid suppression and lifestyle measures may yield synergistic benefits, particularly in refractory GERD. Finally, the development of non-invasive biomarkers and motility assessment tools will be critical for guiding therapy selection and monitoring treatment response in real-world pediatric practice.

Neuromodulation therapies, such as TEA and LES electrical stimulation, represent promising adjuncts for pediatric GERD, particularly in children who fail conventional medical management. By targeting neural pathways that regulate esophageal motility, LES tone, and gastric emptying, these approaches expand the therapeutic landscape beyond acid suppression and prokinetics. Early evidence suggests their safety and efficacy in pediatric motility disorders, underscoring the need for well-designed trials to establish their role in GERD.

In summary, while traditional prokinetics have reached the limits of their utility, the next generation of motility agents, selective serotonin agonists, accommodation enhancers, and novel motilin/ghrelin agonists, offer genuine promise. The future of pediatric GERD management will depend on rigorous, phenotype-driven trials that balance efficacy with safety, and on translating mechanistic insights into clinically meaningful outcomes. By shifting the focus from acid suppression to comprehensive modulation of motility, the field has the potential to redefine therapeutic strategies and improve the quality of life for children living with GERD.

CONCLUSION

Gastric motor abnormalities trigger pediatric GERD by increasing stomach volume and elevating intragastric pressure. This reduces the LES's physical length and baseline tone. Despite this strong functional association, pediatric studies have yielded inconsistent, often conflicting findings, with limited correlation between gastric dysmotility and symptom severity, and no consistent evidence of clear therapeutic benefit from interventions targeting gastric motor dysfunction. Because traditional prokinetic medications pose potential life-threatening cardiotoxic risks like QT prolongation, managing pediatric reflux remains dependent on acid-suppressing therapies. Overcoming these barriers requires further clinical validation of safer, targeted alternatives, including new 5-HT and motilin receptor agonists, DELL and TEA.