Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction

Abstract

Upper gastrointestinal Disorders of Gut-Brain Interaction (DGBI) present from infancy through adolescence. The Rome V criteria have expanded to include DGBI of the esophagus, disorders of air-transit and feeding disorders as well as rumination syndrome, cyclic vomiting, chronic nausea syndrome and functional dyspepsia. This expansion provides a diagnostic framework for patients presenting with chest and throat pain, feeding difficulties, belching, pain with eating, nausea and vomiting. Given the advances in impedance technology and high-resolution manometry, testing plays a greater role in these diagnostic criteria than they have in past Rome iterations. This harmony between symptoms and testing results in more precision in therapeutic approaches that are critically multidisciplinary. The ability to assign new, positive diagnoses across the upper gastrointestinal tract offers new opportunities for pediatric-focused therapeutic trials.

Introduction:

The Rome V pediatric upper gastrointestinal (GI) disorders mirror some adult diagnoses while developing several new pediatric diagnoses, particularly within the realm of esophageal and functional feeding disorders where more specific subtypes are added to provide more diagnostic clarity and targeted management.

G1.Esophageal Disorders

The use of pH-impedance technology has increased the awareness of esophageal DGBI. In the past, non-erosive reflux disease was the all-encompassing diagnosis for children without pathologic amounts of gastroesophageal reflux. The use of pH-impedance has allowed for additional phenotyping of patients with significant symptoms that are typically associated with gastroesophageal reflux disease (GERD) (Figure 1).

Figure 1.

Algorithm for esophageal pain disorders. GERD: Gastroesophageal reflux disease; RNEPD: Reflux-negative esophageal pain disorder; GER: Gastroesophageal reflux; EoE: Eosinophilic esophagitis.

G1a.Reflux Hypersensitivity (RH)

G1a.Diagnostic Criteria* for Reflux Hypersensitivity
Patients <8 years old	Patients >8 years old
Must include all of the following: 1. Intermittent symptoms that  a. Are thought to be gastro-esophageal reflux related;  b. Are suggestive of pain;  c. Are more severe than could be expected based on normal developmental age;  d. Impact on age-expected daily activities and/or quality of life;  e. Occur at least 3 days per week; 2. Normal macroscopic esophageal findings on endoscopy and absence of histologic evidence of eosinophilic esophagitis 3. Evidence of triggering of symptoms by acid and/or non-acid reflux events on pH- or pH-impedance monitoring despite normal acid exposure. 4. After appropriate evaluation, the symptoms cannot be fully explained by another medical condition. An eating disorder must be ruled out.	Must include all of the following:  1. Intermittent retrosternal pain, heartburn, throat pain or burning sensation in the throat that   a. Impact on age-expected daily activities and/or quality of life;   b. Occur at least 3 days per week;  2. Normal macroscopic esophageal findings on endoscopy and absence of histologic evidence for eosinophilic esophagitis  3. Evidence of triggering of symptoms by acid and/or non-acid reflux events on pH- or pH-impedance monitoring despite normal acid exposure.  4. After appropriate evaluation, the symptoms cannot be fully explained by another medical condition. An eating disorder must be ruled out.

^*Criteria fulfilled for at least 2 months prior to diagnosis

Definitions

Rome V defines RH similar to adult RH except the description of pain may include not only heartburn and chest pain, but other types of pain/discomfort. The definition in younger children (< 8yrs) is more complicated due to inability to describe the pain.^1,2 Therefore, the symptoms must be consistent with pain, and more severe than expected based on the developmental stage of the child.

Epidemiology

There is scarce data on its epidemiology in children due to the new pediatric classification.^{3, 4} In two studies of children ≥5 year old undergoing both endoscopy and pH-impedance testing, 20–29% of children met the adult Rome IV criteria for RH.^3,4

Pathophysiology

The mechanisms underlying RH are multifactorial, and include reflux episode type (pH, height, composition), impaired mucosal integrity, central and peripheral sensitization, neuronal positioning in the mucosa, genetic and psychological factors.^{5,6–8,9–14} Patient factors may also impact symptoms, including anxiety, hypervigilance and sleep disturbances.^{15– 18}

Clinical Evaluation

Both endoscopy and catheter/wireless reflux monitoring are needed to accurately diagnose RH. Diagnosis requires a grossly normal endoscopy without eosinophilic esophagitis (EoE) microscopically and pH-Impedance testing (or pH-metry or wireless pH testing) with normal acid exposure (i.e., pH< 4 for <12% of the time for infants <1 yr and <6% of the time for children > 1 yr) along with positive symptom association to acid or non-acid reflux (Figure 1).^{3, 4,19} A positive symptom association includes either: 1) a symptom index (i.e., the number of symptoms associated with reflux within a 2 minute time window divided by the total number of symptoms) ≥50% or 2) a symptom associated probability (i.e., a Fisher exact test to determine the probability that symptom-reflux relationship does not occur by chance) of >95%.

Treatment

Empiric Acid Suppression Trial

An empiric proton pump inhibitor (PPI) trial is often an initial step for typical symptoms such as heartburn or chest pain, particularly when testing is unavailable. However, while PPI response is often used diagnostically for GERD, PPI response does not reliably predict reflux phenotype^3,4; 0–67% of pediatric patients with acid RH had at least some symptomatic improvement with PPI use.^3,4 Empiric acid suppression trials should be time-limited up to 8 weeks and further diagnostic testing (i.e. endoscopy, pH-impedance and CYP2C19 gene testing if possible) should be pursued if there is no improvement.²⁰ Histamine-2 receptor antagonists (H2RAs) can also treat esophageal hypersensitivity and a first line therapy for patients awaiting endoscopy.

Prokinetics

Two pediatric studies found that 43–66% of RH patients improved when starting PPI and/or prokinetics but neither study addressed which patients improved with the use of prokinetics alone.^{21, 22}

Neuromodulators

Selective serotonin reuptake inhibitors (SSRIs) have been studied in adults with RH; 62% of adults receiving 20 mg of citalopram had complete symptom resolution compared to 33% of patients receiving placebo.²³ Similarly, tricyclic antidepressants (TCAs) (imipramine and nortriptyline) have been successfully used to treat typical symptoms in adults.^24,25 There are no equivalent pediatric studies of SSRIs or TCAs.

Cognitive Behavioral Therapy and other Psychological Interventions

While there are no pediatric studies, a randomized trial of adults with nonerosive reflux disease (NERD) and mood disorders found cognitive behavioral therapy (CBT) (alone or in combination with medications) superior to medications (omeprazole and domperidone) alone.²⁶ Esophageal-directed hypnotherapy, acupuncture, deep breathing and biofeedback may also be helpful.^27–30

G1b.Reflux-Negative Esophageal Pain Disorder(RNEPD)

Definition

G1b.Diagnostic Criteria* for Reflux Negative Esophageal Pain Disorder
Patients <8 years old	Patients >8 years old
Must include all of the following: 1. Intermittent symptoms* that  a. Are thought to be gastroesophageal reflux related;  b. Are suggestive of pain;  c. Are more severe than could be expected based on normal developmental physiology for age;  d. Impact on age-expected daily activities and/or quality of life;  e. Occur at least 3 days per week;  f. Cannot be fully explained by another medical condition after appropriate evaluation. 2. Normal macroscopic esophageal findings on endoscopy and absence of histologic evidence of eosinophilic esophagitis. 3. Normal esophageal acid exposure on pH- or pH-impedance monitoring. 4. No temporal correlation between symptoms and acid or non-acid reflux events on pH- or pH-impedance monitoring.	Must include all of the following: 1. Intermittent symptoms of: retrosternal pain, heartburn or throat pain or burning sensation in the throat that  a. Occur at least 3 days per week  b. Impacts on age-expected daily activities and/or quality of life;  c. Cannot be fully explained by another medical condition after appropriate evaluation. 2. Normal macroscopic esophageal findings on endoscopy and absence of histologic evidence of eosinophilic esophagitis. 3. Normal esophageal acid exposure on pH- or pH-impedance monitoring. 4. No temporal correlation between symptoms and acid or non-acid reflux events on pH- or pH-impedance monitoring.
• Criteria fulfilled for at least 2 months prior to diagnosis

Epidemiology

Patients with RNEPD have a visually normal upper endoscopy and no evidence of pathologic acid reflux with negative reflux-symptom correlation by pH-impedance (or pH-metry or wireless testing). This is equivalent to functional heartburn (FH) in adults. However, unlike adult FH, symptoms of RNEPD may include intermittent retrosternal pain, heartburn, throat pain or burning sensation in the throat, at least three times a week for two months.³¹ Younger children may present with crying or repeatedly pointing to areas of discomfort. Two studies found that 38–44% of pediatric patients with normal endoscopy undergoing pH-impedance testing met criteria for FH per adult Rome IV definition^4,3.

Pathophysiology

Visceral hypersensitivity likely plays a main pathogenetic role as these patients have intact mucosal integrity, normal mucosal nerve location, and normal esophageal refluxate clearance. The presence of microscopic esophagitis does not preclude a diagnosis of RNEPD as 20%–23% of children with RNEPD had microscopic esophagitis which did not correlate with symptom severity.^{3, 4}

There is also a role for gut-brain interplay in symptom perception. In adults, patients with FH often report other DGBI, have increased symptom hypervigilance and exhibit more psychological comorbidities compared to healthy volunteers.^{15, 32–37} Stress also increases pain perception to esophageal stimuli.^38–40

Clinical evaluation

Symptoms are non-specific in children, complicating a symptom-based RNEPD diagnosis. To separate it from GERD, NERD or RH, diagnostic testing (endoscopy and pH-impedance testing) is required for children with persistent symptoms that could be interpreted as GERD (Figure 1).

Treatment

The treatment of RNEPD patients is multimodal, involving medication and CBT. An empiric trial of acid suppression is often attempted prior to testing. In one pediatric study, 25–75% of patients showed partial or complete symptom resolution. ^{3 4} However, response to acid suppression may be a placebo response since RNEPD is not caused by acid reflux. For treatment refractory patients, it is critical to do further testing as antireflux surgery is not indicated.^{41, 42}

Since RNEPD falls on the spectrum of visceral hypersensitivity, neuromodulators should be the mainstay of therapy. While there are no pediatric trials, in an adult trial of PPI-refractory heartburn, fluoxetine led to more heartburn-free days than omeprazole or placebo.⁴³ In addition, there are some limited adult data suggesting that melatonin may be helpful in reducing symptoms in FH patients when compared to nortriptyline or placebo.⁴⁴

G1c.Disorders of esophageal air-transit (DEAT)

Understanding disorders of air-transit has become clearer using impedance and high-resolution manometry with impedance testing. With the ability to detect directionality of air movement, clinicians can differentiate different subtypes of belching as related to supragastric belching, aerophagia or GERD.

G1c.Diagnostic Criteria for Disorders of Esophageal Air Transit
Symptoms that  1. Are related to the passage of esophageal air  2. Impact on age-expected daily activities and/or quality of life  3. Occur at least 3 days per week  4. After appropriate evaluation, the symptoms cannot be fully explained by other medical condition Subgroups include   G1c.i Aerophagia syndrome   G1c.ii Supragastric belching syndrome
*Criteria fulfilled for at least 2 months prior to diagnosis
G1c.i.Diagnostic criteria for Aerophagia Syndrome
Must include both of the following:   1. Excessive air swallowing that results in bothersome signs or symptoms   2. Abdominal distension due to intraluminal air that increases during the day Supportive criteria  1. Increased flatus  2. Increased belching and/or gastric venting when a feeding tube is present  3. Intraluminal impedance measurement supporting the diagnosis. Note that absence of aerophagia during the measurement does not exclude the diagnosis  4. Abdominal X-ray showing that intraluminal air is the cause of the distension
G1c.ii.Diagnostic Criteria for Supragastric Belching Syndrome
Must include all of the following:  1. Bursts of repetitive belching originating from the esophagus  2. Does not fulfill criteria for functional dyspepsia, physiological reflux related esophageal pain disorder, reflux-negative esophageal pain disorder Supportive criteria   1. Does not occur during sleep   2. No air expulsion during distraction or speech   3. Impedance and/or impedance-manometry measurement can support the diagnosis but absence of supragastric belching during the measurement does not exclude the diagnosis

G1c.i. Aerophagia syndrome

Definition

Normally, most liquid and solid boluses that children swallow are preceded by small amounts of air.^{45, 46} However, a pattern of excessive air swallowing leading to a typical symptom pattern, with abdominal distension that increases over the day and/or excessive belching and flatulence is defined as aerophagia syndrome.

Epidemiology

Prevalence in healthy children ranges from 0.5–6.3% and varies in different regions of the world.^47,48,49 Prevalence is higher (7%) in children visiting a pediatric gastroenterology clinic.⁵⁰ There is substantial overlap between aerophagia and other DGBI.^51–53

Rationale for change in Criteria

Aerophagia, a normal physiologic phenomenon, should only be considered a syndrome if it impacts quality of life and causes symptoms. Previously, increased flatus was considered a major criterion but because flatus may go unnoticed, it is no longer a major criterion. Since the recognition of supragastric belching, excessive belching as a clinical symptom is a supportive criterion. Patients with abdominal bloating without evidence of intra-abdominal air do not fall into this category.

Pathophysiology

When air swallowing is excessive, gas can result in luminal distension throughout the gastrointestinal tract. In the stomach, vagal tension receptors are activated resulting in increases in transient lower esophageal sphincter relaxations and gastric belching. In the large intestine, luminal distension causes bloating, pain and flatulence.

Clinical Evaluation

Clinical history will typically include a pattern of gradually worsening abdominal distension associated with belching and flatulence during the day. Early satiety, abdominal pain, nausea and loss of appetite may occur and can worsen over the day. In addition, a more acute presentation can be seen in patients that have episodes of intense air swallowing, that can lead to gastric or intestinal volvulus and/or respiratory distress due to the increased abdominal pressure.⁵⁴ Repetitive behaviors that may increase air swallowing, like chewing gum or drinking carbonated beverages should be assessed.

If the clinical picture lacks alarm symptoms (e.g., weight loss, anemia), testing is not needed. If there is diagnostic uncertainty, pH-impedance testing or esophageal high resolution impedance manometry (HRIM) may be indicated.

An abdominal X-ray may show large volumes of intestinal air without air-fluid levels and can help to differentiate between intestinal air and other causes of distension (e.g. constipation, abdomino-phrenic dyssynergia, ileus).

Treatment

No therapeutic trials exist. However, in patients with severe distension, a nasogastric tube or an existing gastrostomy tube can be used to vent air from the stomach.⁵⁵ If colonic distension is present, rectal decompression may be appropriate. In patients with chronic stable symptoms, a conservative approach is sufficient. Speech therapy or CBT aimed at reducing the air swallowing may be tried. Benzodiazepines can be considered in severe cases. Circumstantial evidence suggests that infants swallow less air using different bottle/nipple systems.⁵⁶

G1c.ii.Supragastric belching syndrome (SGB)

Definition

SGBis defined as esophageal air ingestion immediately followed by active expulsion from the esophagus back into the pharynx.⁵⁷ It can occur in healthy children but is considered a disorder when it is excessive and impacts daily activities.

Epidemiology

In children with a suspicion of GERD, SGB was found during pH-impedance testing in 7/287 (2.4%) patients and, of these, 3/7 had more than 13 episodes per 24 hours, which is considered the abnormal cut-off in adults.^{46, 58} In patients with a suspicion of rumination, the effortless regurgitation of gastric contents, 3/16 (18.7%) showed a pattern of predominantly SGB on impedance-manometry rather than rumination.

Pathophysiology

SGB is a voluntary, yet subconscious behavior. Two mechanisms are described in adults.⁵⁹ First, patients create negative thoracic pressures, leading to the suction of air into the esophagus when the upper esophageal sphincter opens. Immediately after the air has entered the esophagus, it is expelled by straining. Second, patients may push air into the esophagus by tongue retraction, and expel the air with straining.⁵⁹ SGB can be an unintentional reaction to an unpleasant feeling such as pressure retrosternally or in the abdomen.⁶⁰

Clinical Evaluation

Most patients present with excessive belching as the primary symptom. However, the symptoms may sound like hiccups to patients/parents. Often no tests are needed as the story of multiple repeated belches is nearly pathognomonic for SGB. SGB typically occurs outside of meal periods and does not occur during sleep. pH-impedance or HRIM can be performed to confirm the diagnosis. However, absence of belching during testing does not exclude the diagnosis as events can be sporadic.

Treatment

In a single randomized trial of behavioral interventions in adults which included education about the disorder, warning signs for oncoming events and breathing exercises, patients who received the behavioral interventions had higher rates of symptom improvement lasting up to 6 months.⁶¹ Specific speech therapy interventions have been described and were successful in an open trial.⁶²

G2.Functional Pediatric Feeding Disorders (FPFD)

The prevalence of pediatric feeding disorders have been increasing. Currently the two terms to describe these disorders, avoidant/restrictive food intake disorder (ARFID) and pediatric feeding disorders, have been used to describe a range of different signs and symptoms in children, making it challenging to determine the most appropriate therapies for each patient. The goal of defining FPFD is to provide more clarity about which therapies are most appropriate for patients without a structural cause for symptoms.

Definitions

G.2.Diagnostic Criteria* for Functional Feeding Disorders
Altered feeding patterns that (a) interfere with functioning; (b) occur for at least three times per week; and (c) cannot be attributed to an underlying medical or skill-based diagnosis that has been effectively evaluated and managed. The diagnosis should have at least one of the following components:  1. Evidence of nutritional compromise (micronutrient deficiency, macronutrient deficiency)  2. Use of supplemental enteral or parenteral nutrition  3. Active or passive avoidance behavior(s)  4. Use of a restricted/selective diet or a diet that is not developmentally appropriate to treat symptoms  5. Lack of developmentally expected self-feeding  6. Excessive use of routine feeding strategies (e.g., chewing, liquid wash down, pacing) to complete a meal
*Criteria fulfilled for at least 1 month prior to diagnosis
G2a.Diagnostic Criteria for Hypersensitive Dysphagia A feeding disorder characterized by perception of liquids and/or solid foods passing abnormally through the oropharynx or esophagus that is associated with all of the following characteristics:  1. No evidence of pharyngeal or esophageal mucosal or structural abnormalities  2. Absence of major esophageal motor disorders  3. No evidence of bolus transit abnormalities
G2b.Diagnostic criteria for Anticipatory Restrictive Feeding A functional feeding disorder driven by the anticipation of aversive experiences while eating and is associated with one or more of the following:  1. Significant weight loss (or failure to achieve expected weight gain or faltering growth in children)  2. Significant nutritional deficiency  3. Dependence on enteral feeding or oral nutritional supplements  4. Marked interference with other psychosocial functioning
G2c.Diagnostic Criteria for Hunger Dysregulation Disorders A feeding disorder that is characterized by either: G2c.i Reduced hunger drive: The patient will not voluntarily eat or drink calorically appropriate foods after periods of age-appropriate fasting AND the patient requires prompting and/or scheduling of meals in order to insure adequate intake. G2c.iiExcessive hunger drive: The patient has excessive hunger manifested by inability to stop eating even after finishing a meal and excessive eating between meals even after completing a full meal.
G2d.Diagnostic Criteria for Medically-Triggered Functional Feeding Disorder A feeding disorder that:  1. Developed in the context of a medical condition but the feeding dysfunction persisted after the medical disorder has resolved or is adequately treated and cannot be attributed to the underlying medical condition  2. Manifests as a regression or lack of progression of feeding patterns or skills that previously achieved and cannot be attributed to the medical condition

Pediatric feeding disorders affect 5–20% of children and are associated with significant morbidity, decreased quality of life, and increased resource utilization.^{63, 64} Up until now, functional feeding disorders have only been addressed in the DSM-V and the definitions lacked the specificity needed to guide diagnostic testing and therapies. The Rome V Committee felt that their inclusion was critical because: 1) many patients present to gastroenterologists for evaluation, the placement of feeding tubes and/or parenteral nutrition and; 2) many of the patients presenting with DGBI also have concurrent functional feeding disorders that need to be addressed.

The definitions of ARFID in the DSM-V created confusion in the realm of pediatric feeding disorders stating⁶⁵:

ARFID is “an eating or feeding disturbance (e.g., apparent lack of interest in eating or food; avoidance based on the sensory characteristics of food; concern about aversive consequences of eating) as manifested by persistent failure to meet appropriate nutritional and/or energy needs.⁶⁵”

By merging examples of different feeding disorders under a single term, ARFID, the definition lacks needed granularity to refer patients for appropriate therapies. Therefore, we propose that the ARFID term should be eliminated and, instead, replaced by more precise terms (Figure 2).

Figure 2.

Algorithm for pediatric feeding disorders. Patients may have a medically grounded feeding disorder that develops into a functional feeding disorder or visa versa.

In the case of FPFD, impairments may include the inability to efficiently take adequate diverse nutrition, eating difficulties outside of preferred settings, and challenging mealtime behaviors. Symptoms should be present for at least 4 weeks to allow for symptom resolution if triggered by acute events (e.g., infection) and for appropriate targeted testing to exclude other diagnoses (e.g., EoE, which is present in up to 15% of patients).⁶⁶ As these are new diagnoses, the relative proportions of subgroups is not known. In one study of children with ARFID, 43–82% had a lack of interest in eating (the new hunger dysregulation diagnosis), 21–68% had sensory-driven food refusal, and 11–21% had swallowing difficulties (the new hypersensitive dysphagia diagnosis).⁶⁷

G2a.Hypersensitive dysphagia (HD)

Children with HD present with sensations of food feeling stuck despite normal esophageal anatomy, motor function and bolus clearance. This diagnosis is equivalent to the “functional dysphagia” diagnosis in adults with some key differences. First, HD includes both oropharyngeal and esophageal sensations since children cannot often differentiate locations or they will not put food in the mouth or will chew and spit food/drinks. Second, normal bolus transit (as measured by HRIM or esophagram if the former is not available) was added to the definition.

i G2b.Anticipatory Restrictive Feeding (ARF)

ARF is characterized by the fear of an aversive experience with eating (e.g., nausea, pain, bloating, gagging, choking or vomiting). Clinically, these patients may present with significant diet restrictions resulting in elimination of entire food groups, specific food textures, or food temperatures. Children may express experiences of anxiety, disgust, or fear when consuming new, symptom-triggering or nonpreferred foods. ARF differs from a medically triggered functional feeding disorder in that the latter is associated with the loss or halting of feeding milestones or skills with the development of a medical illness. ARF does not have a loss of skills or milestones but is associated with fear of eating. ARF is common in children with concurrent DGBI and the majority (>80%) of these patients have underlying gastrointestinal symptoms.^68,69

G2c.Hunger dysregulation feeding disorder

There are two subtypes, reduced and excessive hunger drive. With reduced hunger drive, patients are rarely if ever hungry or thirsty. In contrast, the excessive hunger drive patients manifest with excessive drive to eat. These feeding disorders typically manifest early in childhood including during toddlerhood and even infancy.

G2d.Medically triggered functional feeding disorder (MTFFD)

The key feature to this diagnosis is that (1) the underlying medical disorder needs to have been successfully treated and (2) there is a halting of oral progression or a regression of oral skills (i.e., skills needed for children to eat and drink safely and efficiently such as chewing, bolus propulsion, sensory processing of oral contents) coinciding with a clear medical event. Often, these patients present during late infancy or toddlerhood in the context of severe GERD or EoE where these patients continue only to drink a liquid diet despite complete mucosal healing and no evidence of bolus retention. In contrast, if a patient has EoE and develops a food impaction, is successfully treated for EoE, but then does not want to eat any solid food for fear that it will get stuck, that patient would have ARF because the fear of eating is at the root of the feeding disorder. Finally, if the patient has active EoE and does not eat solid food, this is a medically triggered pediatric feeding disorder (because there is persistent inflammation and potentially esophageal dysmotility) but not a medically triggered functional feeding disorder. The term functional is added when there is no structural reason to explain the inability to take solid or liquid food.

Epidemiology

Feeding problems occur with estimation ranging from 25% to 45% of children in the general population, 33% of children with developmental disabilities and in up to 80% of children with severe cognitive disabilities. ^70–72 Medical and oral problems occurred more often in patients age < 2 years, and behavioral or functional feeding problems occurred more in children < 2 years old;⁷³ In a large cohort of young children with feeding disorders, 86% of the patients had a medical disorder; 61% had an oropharyngeal dysfunction and 18% had a behavioral problem.⁷³

Pathophysiology

There are no studies for these new diagnoses. Ghrelin, oxytocin, CCK and PYY have all been studied in adults and/or children with ARFID with no clear signal emerging as a causative factor for symptoms.^{69, 74–76} One common cause for symptoms is the initial restriction of food in an effort to improve gastrointestinal symptoms. This could be driven by well-intentioned self or family observation, medical recommendations, or online social media.^{77, 78}

Clinical Evaluation

All structural and skill-based etiologies should be assessed or managed prior to starting any behavioral treatments. If diagnostic testing is not available, behavioral interventions can be trialed but, if these interventions are ineffective, then re-assessment of the medical condition and feeding skills is necessary.

Key questions providers should ask patients/families are shown in Table 1. History should be multimodal and is accomplished via clinical histories, school reports, video recordings of mealtimes, and neuropsychological testing. Cultural meal practices need to be considered. Since feeding disorders increase caregiver stress, diminish parental confidence, and result in negative parent-child interactions, assessment of whole family wellbeing is important.^{79, 80}

History, signs, symptoms and symptoms that may suggest a diagnosis other than a FPFD are shown in Supplemental Table 1 and Supplemental Figure 1. Mealtime or feeding assessment is critical to assess for feeding skills and to watch for avoidance behaviors, tantrums, or oral pocketing of food.⁸¹

Unlike many other DGBI, significant testing may be required before a FPFD can be made because of the medical masqueraders (Figure 2) that may mimic a FPFD.⁷³ Testing by feeding diagnosis is shown in Supplemental Table 2. Upper gastrointestinal endoscopy is almost always recommended for pediatric feeding disorders because EoE can present with symptoms mimicking a FPFD; 25–50% of patients with EoE have dysphagia and feeding issues and 15% of children with feeding issues have EoE.^82–84 Laboratory testing for celiac disease, thyroid disease, a complete blood count, and electrolytes are indicated and, potentially expanded labs for iron, Vitamin A, C, D, B12, carnitine, folate, liver function tests, thiamin and zinc depending on the history.^{83, 85}

Treatment

For the majority of patients, outpatient nutritional management is feasible and preferred. Nutritional management may include the addition of vitamins, addition of nutritionally complete formula or calorically dense additives, or strategic rotation of preferred foods. If there is significant weight loss, barium imaging for evaluation of superior mesenteric artery syndrome may be needed. Changes in vital signs (low heart rates, hypotension) may merit urgent inpatient nutritional rehabilitation. In addition, restrictive diets such as the low Fermentable Oligo-saccharides, Di-saccharides, Mono-saccharides, And Polyols (FODMAP) diet, gluten free diets, and dairy free diets are not usually recommended for symptom control as they may increase meal-related anxiety, thus worsening or triggering a FPFD.⁸⁶

While enteral tubes may play an important role for urgent nutritional rehabilitation, the majority of patients do not need enteral tube support. In the ARFID literature, 20–46% of patients were reliant on some form of enteral support though the approach to ARFID has recently moved away from enteral tube use towards multidisciplinary behavioral therapies.⁶⁷ Intravenous parenteral nutrition is not recommended for FPFD.

Medications are often trialed for FPFD subtypes. For patients lacking a hunger drive, cyproheptadine has been shown to increase appetite and improve gastric accommodation.^{87, 88} In retrospective review of intrapyloric botulinum toxin injections in 85 young children with feeding disorders, have shown some improvement with intrapyloric botulinum toxin injections.⁸⁹ While the mechanism is not known, improvements in gastric accommodation or sensory perception have been suggested. In small case series, neuromodulators such as TCAs, gabapentin and mirtazapine may be beneficial.^90–92 In addition to the medications above, it is important to treat any underlying mental health issues either through psychological interventions or, when needed, medications (e.g., fluoxetine, escitalopram, sertraline, olanzapine, and mirtazapine).^{93, 94} Finally, for patients with gastrointestinal symptoms triggering ARF, it is important to maximize symptom control to improve behavioral outcomes.

Behavior management techniques are designed to strengthen adaptive behaviors and reduce challenging behaviors. The goal in HD is to help the child overcome fears through a combination of exposure therapy, including discrimination training, along with cognitive restructuring methods.^{95 96} Children with ARF benefit from environmental control methods including repeated exposures to new and non-preferred foods, and interventions which focus on the schedule to promote appetite.^{97 98} Teenagers with ARF may benefit from CBT.⁹⁹ Patients with ARF are also encouraged to develop fear/avoidance hierarchies paired with graded exposure to the feared foods allowing for non-traumatic experiences. Behavioral management of dysregulated hunger typically involves a combination of medical management of hunger cues along with strict behavioral environmental controls. Patients with MTFFD often require interdisciplinary care with gastroenterologists, deglutologists, psychologists and other members of the care team.¹⁰⁰

G3.Gastroduodenal Disorders

Highlights of this Rome V iteration include updates in the prevalence literature for these disorders, and increased expansion of therapeutic options.

G3a.Rumination Syndrome (RS)

Definition

RS is an acquired behavioral disorder characterized by repetitive and volitional, although subconscious, episodes of regurgitation of gastric contents.

G3a.Diagnostic Criteria* for Rumination Syndrome

Must include all of the following symptoms for minimum 2 months, starting after 3 months of age: 1. Repeated, seemingly effortless regurgitation of gastric contents that is:   a. Re-swallowed and/or re-chewed and/or expelled during or immediately after a meal or ingestion of fluids   b. Does not occur during sleep 2. Does not respond to standard management for gastroesophageal reflux disease or infant regurgitation. After appropriate evaluation, the symptoms cannot be fully explained by another medical condition. An eating disorder must be ruled out. Supportive Criteria  1. The repeated regurgitation of gastric contents might occur during or after physical or psychological stress  2. High resolution esophageal impedance manometry (HRIM) may help confirm the diagnosis in cases of unusual symptomatology or family skepticism. HRIM allows for prompt identification of the rumination episodes, with the sensitivity maximized by an extended recording after a test meal

^*Criteria fulfilled for at least 2 months prior to diagnosis with onset of symptoms after 3 months of age:

Epidemiology

The reported prevalence ranges between 0% and 9.7%, with no differences in both gender and age.^101–102

Justification for changes in diagnostic criteria

Previous pediatric criteria on rumination distinguished among infants, children, and adolescents. Although RS differs by age in pathophysiology, diagnosis, and treatment, shared clinical features support unified criteria. “Seemingly effortless” regurgitation remains appropriate, as abdominal and diaphragmatic contractions often go unnoticed. Regurgitation after fluid intake was added due to its common occurrence. The exclusion of retching was removed, as some children may experience it before episodes. The revised criteria require lack of response to GERD treatment—or, in infants, troubling regurgitation—before diagnosing RS. Descriptions of repetitive muscle contractions in infants were removed, as they reflect pathophysiology rather than clinical criteria.

Pathophysiology

RS involves unconscious contraction of the abdominal wall, increasing intragastric pressure and triggering regurgitation.^{104, 105} This is facilitated by intercostal muscle contraction and relaxation of the upper esophageal sphincter(UES) and esophagogastric junction(EGJ), leading to retrograde flow. Relaxation of EGJ include diaphragmatic relaxation, transient LES relaxation, and LES displacement.¹⁰⁴ HRIM reveals pressure spikes (“R waves”) with retrograde bolus movement.¹⁰⁶

Triggers may include unpleasant postprandial sensations (e.g., nausea, burning, reflux), which act as premonitory urges and successful treatment often improves these sensations.^107,108 These may result from gastric sensory-motor dysfunction or neuroimmune changes.¹⁰⁹ Delayed gastric emptying is seen in up to 45% of pediatric RS cases.¹⁰⁷ Increased mast cells, eosinophils, and intraepithelial lymphocytes have also been observed.¹⁰⁹

Learned behaviors, body image concerns, and self-soothing tendencies (especially in infants or neurologically impaired children) may initiate or sustain rumination.¹⁰⁶ RS symptoms may follow physical (e.g., viral illness to 43%, non-viral illness 11%) or psychological (e.g., anxiety, trauma) triggers in 7%.¹¹⁰ Impaired caregiver interactions may also contribute.¹¹¹

Clinical Evaluation:

RS presents as effortless, repetitive regurgitation during or shortly after meals, sometimes triggered by fluids or activity. The regurgitated material reaches the mouth and is either spit out or reswallowed, depending on social circumstances. Episodes don’t occur during sleep and may be preceded by nausea or after a burst of coughing or hiccupping. RS can overlap with other DGBI ¹⁰⁶ Up to 40% of affected children experience weight loss; severe malnutrition or disorders like POTS are less common.^{104, 111} Clinical observation during or after meals is often sufficient for diagnosis.¹¹² Confirmatory tests, such as HRIM (R wave), 24-hour pH-impedance monitoring or upper endoscopy and contrast studies may be needed for atypical presentations or when there is diagnostic uncertainty.^{110, 113, 114}

Younger children with RS are more likely to have developmental delays, and less likely to have psychiatric comorbidities.¹¹² In older children, up to 70% of children have at least one psychiatric comorbidity.^{110, 111} Anxiety, depression, and eating disorders are most common, although attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and adjustment disorder have been reported.¹¹²

Treatment

The first step is to explain pathophysiology and offer reassurance to families that no further testing is needed and that effective therapies exist.¹¹⁵ In fact, 23% of children diagnosed with RS showed a self-resolution of symptomatology without treatment after only the initial counseling.¹¹⁶ In infants and young children, management focuses on supporting the caregiver-infant relationship and provide family support to maximize developmental progress and addressing potential triggers (neurologic, dietary, positional, or stress-related). The treatment in older children and adolescents focuses on implementing behavioral strategies, modulating food and liquid intake, managing mental health–related issues, and implementing diaphragmatic breathing around mealtimes.^{108, 117}

Diaphragmatic breathing (DB) is the first-line therapy and is effective both in-person and via telemedicine. Modifications using imagery or toys may help younger children.^{108, 117} CBT complements DB, targeting premonitory urges and maladaptive behaviors. Teaching children to re-swallow regurgitated material reinforces control and maintains nutrition.^{108, 117}

Patients with psychological comorbidities should be referred to a mental health professional as their presence is associated with both poor treatment outcomes and longer treatment durations.^117–119 In children and adolescents experiencing severe symptoms or medical complications, an intensive inpatient multidisciplinary program may be required.^117–119

Baclofen may be an adjunctive therapy, though data in children are limited. A recent retrospective study in children has shown that baclofen is safe and effective in almost 50% of children.¹²⁰ Other drugs and interventions (e.g., anti-reflux surgery, botulinum toxin) are not routinely recommended.

Complete remission rates vary (16–74%), but most patients show significant improvement, especially younger children.^{116, 118, 119} Long-term outcomes are generally positive with sustained behavioral strategies though symptom flares may occur with stress or illness.¹¹⁸

G3b.Cyclic Vomiting Syndrome (CVS)

Definition:

CVS is a disorder characterized by stereotypical episodes of repetitive nausea, vomiting, and/or retching dispersed with symptom-free periods.¹²¹

G3b.Diagnostic Criteria for Cyclic Vomiting Syndrome
1. Stereotypical episodes of acute onset, repetitive vomiting multiple times per hour  2. ≥4 discrete episodes in the prior 12 months, lasting 2 hours to 7 days  3. Episodes at least 1 week apart  4. Return to baseline health between episodes  5. After appropriate evaluation, the symptoms cannot be fully explained by other medical conditions   Supportive remarks:  1. History or family history of migraine headaches  2. Episodes associated with listlessness, diaphoresis, photophobia, unrelenting nausea, abdominal pain, and/or incessant retching after emptying stomach  3. Less acute or intermittent symptoms such as abdominal pain and nausea can be present between episodes  4. After appropriate evaluation, the symptoms cannot be fully explained by other medical conditions
G3b.i. Diagnostic Criteria for Cannabinoid Hyperemesis Syndrome
1. Stereotypical episodes of vomiting resembling cyclic vomiting syndrome (CVS) in terms of onset, duration and frequency  2. Presentation after prolonged (e.g. 1–2 years), excessive (e.g. near daily) cannabis use  3. Resolution of vomiting episodes by sustained (at least 6 months) cessation of cannabis use Supportive remarks:  1. May be associated with pathologic bathing behavior (prolonged hot baths or showers)  2. Diagnosis strengthened by positive urine Δ-9-tetrahydrocannabinol (THC) test

Rationale for change in diagnostic criteria:

The revised criteria provide terminology that would be accepted internationally by both clinicians and researchers. A subcategory on cannabinoid hyperemesis syndrome (CHS) is included based on a rising prevalence and recognition in children.¹²²

Epidemiology

CVS is a common condition but often underrecognized. Prevalence rates reach up to 2% in infants, toddlers and school aged children.¹²¹ Misdiagnoses, especially as viral gastroenteritis, often delay diagnosis by up to 10 years.¹²³ CVS leads to significant disability, including an average of 24 missed school days per year, and more quality of life impairment than other DGBI.¹²⁴

Pathophysiology

While the exact mechanisms are unclear, several overlapping pathways have been proposed. CVS is often considered a migraine-equivalent disorder due to similarities in symptoms, triggers, mitochondrial polymorphisms, and treatment response.¹²⁵ Mitochondrial dysfunction is supported by maternal inheritance patterns and metabolic abnormalities during attacks. Autonomic nervous system (ANS) imbalance is documented in pediatric CVS.¹²⁶ Symptoms like diaphoresis, palpitations, and listlessness are common and patients develop dysautonomia over time.¹²⁷ Stress-related activation of the hypothalamic-pituitary-adrenal axis and elevated morning CRF levels may delay gastric emptying which can contribute to episodes.^128–130 Dysfunctional signaling in the brainstem and hypothalamus may trigger emetic responses to stress, involving autonomic dysregulation and activation of the vomiting reflex.

Clinical Evaluation

CVS is diagnosed based on stereotypical, high-intensity vomiting or retching episodes that occur in cycles, often several times per hour, lasting from hours to a week, with return to baseline between episodes. Associated symptoms often include pallor, nausea, abdominal pain, diaphoresis, and other signs of sympathetic overactivity. The committee supports the clinical evaluation outlined in the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) guidelines for children aged 0 to 18 years which may include barium imaging, upper endoscopy and laboratory tests.¹²¹ Early symptom onset and fasting or high protein triggered episodes may indicate an underlying neurometabolic disorder, and metabolic testing should be performed during vomiting episodes—prior to IV fluid administration—for optimal diagnostic yield. In adolescents, consider CHS, characterized by recurrent severe vomiting, nausea, and abdominal pain linked to chronic cannabis use.¹²¹

Diagnosis is clinical but supported by tests to rule out mimics, especially if red flags (e.g., bilious vomiting, neurologic symptoms, hepatomegaly) are present or if no response to standard treatment occurs within 2 months.

Specific subtypes are important to help target therapy appropriately. These include migraine-associated, menstrual-triggered (“catamenial”), and the more severe Sato-variant CVS. While migraine-associated CVS often responds to typical abortive and/or prophylactic migraine interventions, calendar-timed and catamenial CVS may benefit from therapies initiated immediately before the anticipated cycle.¹²¹ Comorbid anxiety is very common (occurring in 59% of school-aged children), and a subset of children with a particularly low threshold for stress-triggered episodes may benefit from mindfulness and behavioral interventions.^{121,131, 132}

Treatment

The committee supports the treatment approach outlined in the NASPGHAN CVS guidelines.¹²¹ Effective treatment requires a stepwise, individualized approach based on episode severity, disability, and psychosocial impact. Management includes lifestyle changes/behavioral interventions/alternative therapies for all patients, abortive and/or prophylactic medications or emergency care based on severity. Lifestyle interventions focus on trigger avoidance and early recognition of prodromal symptoms. Abortive treatments (e.g., antimigraine, antiemetic, analgesic, and sedative agents) should be given early, using non-oral routes when possible. Emergency care involves IV medications to manage nausea, pain, and induce sleep—often the only effective relief during the emetic phase. Early ED treatment reduces hospital admissions. Prophylactic medications are considered for frequent or prolonged episodes that impair functioning. Complementary approaches like mitochondrial supplements, neuromodulation, and mindfulness interventions along with treatment of comorbidities are essential.

G3b.i. Cannabinoid Hyperemesis Subgroup

Epidemiology

CHS, a subtype of CVS, requires cannabis cessation counseling and medical management.^{133, 134} Though more common in adults, CHS also affects teens, who may underreport cannabis use, complicating diagnosis. Limited data suggest adolescent CHS may be more common in females and causes symptoms throughout the day, unlike the morning pattern seen in adults.¹³⁵

Pathophysiology

The pathophysiology remains poorly understood but is thought to affect genetically susceptible individuals.¹³⁴ Prolonged cannabinoid receptor-1 activation by THC (Delta-9-tetrahydrocannabinol) may disrupt the endocannabinoid system, leading to cannabinoid receptor-1 downregulation and altered stress and temperature regulation through the Transient Receptor Potential Vanilloid (TRPV) system and other neurotransmitters.^{133, 135}

Clinical Evaluation

The clinical evaluation of CHS is identical to that of CVS. CHS typically occurs after years of near-daily cannabis use and should only be diagnosed if symptoms improve with sustained cessation, helping avoid misdiagnosis in CVS patients with occasional THC use.^{121, 134} Hot bathing, while common in CHS, also occurs in CVS. A positive urine THC test can support diagnosis, with higher THC-COOH levels indicating chronic use.^{121, 134} Providers should account for false positives and prolonged detection of THC in urine.

Treatment

CHS treatment mirrors CVS and includes abortive and preventive therapies.^{121, 133, 134} Long-term management centers on cannabis cessation and TCAs like amitriptyline. As sudden cessation may cause withdrawal and relapse, gradual reduction and lower-THC products may improve success.

G3c.Chronic nausea syndrome (CNS)

Definition

Nausea, a common symptom, is an unpleasant feeling, usually in the epigastrium or throat, associated with a sense of needing to vomit.¹³⁶ CNS is now recognized as a disabling condition often linked to multiple comorbidities.

G3c.Chronic Nausea Syndrome*
Must include all of the following:  1. Bothersome nausea as the predominant symptom, occurring at least twice per week  2. Not associated with vomiting  3. After appropriate evaluation, the nausea cannot be fully explained by another medical condition

^*Criteria fulfilled for at least 2 months before diagnosis

Rationale for Change in Diagnostic Criteria

Since its inclusion in Rome IV, studies have confirmed the prevalence of functional nausea and its link to comorbidities like POTS and other autonomic disorders, suggesting it may be part of a broader syndrome. Rome V now uses the term “chronic nausea syndrome” to better reflect this. The diagnostic criteria remain similar to Rome IV. Vomiting is excluded from the definition, as children typically present with nausea alone.

Epidemiology

Chronic or intermittent nausea affects 15–23% of school-aged children, with higher rates in girls and private school students.^136–138 It often coexists with other DGBI, especially pain-related disorders and functional constipation.^{138, 139}

Nausea is linked to poor school and social functioning, high somatization, anxiety, depression, and reduced quality of life.^{138, 139} Children with nausea tend to have more upper GI symptoms and comorbidities like headaches, fatigue, sleep issues, and POTS.^{5, 139} Using strict Rome IV criteria, functional nausea is rare (0.7%). Nausea is also a fundamental symptom in episodic DGBI such as abdominal migraines and CVS, and many patients with chronic nausea fulfill criteria for POTS.^139–141

Pathophysiology

The cause remains unclear but likely involves complex interactions between the brain, gut, ANS, and psychological factors (anxiety, depression).^141–144 Symptoms may result from alterations in gastric electrical rhythm, abnormalities of gastric accommodation, and amplified or attenuated CNS signaling. Other symptoms may be triggered by environmental circumstances or psychiatric comorbidities. Nausea often co-occurs with physiologic changes such as diaphoresis, eye blinking, salivation, palpitations, and pallor.^141–144 Morning nausea may reflect ANS dysfunction or school-related stress.

Clinical Evaluation

Before diagnosing chronic nausea syndrome, other causes—like mucosal disease, obstruction, or motility disorders—should be considered. Nausea can be hard to describe, so child-friendly language or pictograms may help.¹⁴⁵ Routine labs may be done, but extensive testing rarely provides alternative diagnoses.¹³⁹ Diagnostic endoscopy is not recommended unless red flags are present.¹³⁹ Gastric emptying studies are also not routinely needed unless vomiting is severe, the diagnosis is unclear, or the nausea is intractable. When associated with vomiting, a more detailed central nervous system assessment with imaging or a motility evaluation may be considered. Like in other DGBI, diagnostic tests should only be performed in the presence of other alarm signs or features (e.g., weight loss, severe pain, bilious vomiting, etc.).¹³⁹

Treatment

CNS is difficult to treat and lacks standardized therapies.^{136, 139, 141, 146} Hypnotherapy may be more effective than standard medical care, especially short term.¹⁴⁷ Medications like ondansetron, domperidone, cyproheptadine, aprepitant and amitriptyline have shown some benefit, though evidence is mostly anecdotal.¹⁴⁷ Neuromodulators like mirtazapine may help but can cause side effects and are best reserved for refractory cases.¹⁴⁸

Interventions like intrapyloric botulinum toxin injection and gastric electrical stimulation have shown promise in select patients, though data are limited.^{149, 150} IPBI may help even without delayed gastric emptying, with effects lasting up to 3 months.¹⁵¹ Other emerging treatments include percutaneous nerve field stimulation.¹⁵²

Supportive care—including hydration, sleep, exercise, and salt intake—may help, especially in patients with POTS. A multidisciplinary approach involving education, reassurance, psychological support, and functional maintenance is key for optimal outcomes.

G3d.Functional Dyspepsia (FD)

C3d.i Postprandial Distress Syndrome (PDS)

C3d.ii Epigastric Pain Syndrome (EPS)

Definition

FD describes upper GI discomfort that may include a variable combination of features, including epigastric pain, postprandial upper abdominal fullness, early satiety, bloating, nausea, belching, and vomiting. Two main subtypes have been identified: PDS and EPS.^{153, 154,155}

G3d.Diagnostic Criteria* for Functional Dyspepsia
Must include 1 or more of the following bothersome symptoms  1. Postprandial fullness  2. Early satiation  3. Epigastric pain or burning After appropriate evaluation, the symptoms cannot be fully explained by another medical condition. *Criteria fulfilled for at least 2 months prior to diagnosis Two subtypes:   G3d.i. Postprandial distress syndrome   G3d.ii. Epigastric pain syndrome
G3d.i.Diagnostic criteria for Post Prandial Distress Syndrome
Must include one or more of the following bothersome symptoms at least 3 days per week 1. Bothersome postprandial **fullness that occurs with completion of a developmentally and culturally appropriate meal 2. Early satiation that prevents finishing a developmentally and culturally appropriate meal Supportive features include upper abdominal bloating, postprandial nausea, discomfort or excessive belching. ** Postprandial means that’s symptoms are triggered within 2 hours after meal intake
G3d.ii. Diagnostic criteria for Epigastric Pain Syndrome
Must include one or more of the following bothersome symptoms (interferes with function or quality of life) at least one day per week 1. Pain or burning localized to the epigastrium. 2. The pain is not present in any other abdominal or chest region 3. Symptoms can be induced or worsened post-prandially or can occur independently of meals but PDS criteria are not fulfilled 4. After appropriate evaluation, the symptoms cannot be fully explained by another medical condition including functional abdominal pain or IBS

Justification

The Rome V committee revised the pediatric criteria to align with adult standards; the required symptom frequency for PDS was increased from one to three times per week, reflecting typical meal patterns and preliminary pediatric data. A postprandial episode is now defined as occurring within 2 hours of a developmentally and culturally appropriate meal.

Epidemiology

In children, a meta-analysis reported a global FD pooled prevalence of 2.1%, though rates vary widely by region—from 2.8% in Japan to nearly 30% in Argentina.¹⁵⁶ In an Italian study of 100 children, 17% had EPS, 47% had PDS, and 36% had overlapping symptoms. Symptom overlap and transitions between subtypes were common over a 6-month follow-up.¹⁵³

Pathophysiology

FD is a heterogeneous disorder likely associated with different underlying pathophysiologic mechanisms. Common abnormalities include impaired gastric accommodation (40%), hypersensitivity to gastric distension (30%), and abnormal gastric emptying (25%). Other contributors include central sensitization, low-grade inflammation, genetic predisposition, and psychological factors (anxiety).^{157, 158} Fifty percent of pediatric patients with FD had an abnormal EGG, and 47% showed delayed gastric emptying.^159–161 In a study of 104 children with dyspeptic symptoms, gastric emptying was abnormal in 50% and only nausea correlated with the percentage of food retention at 4 hours.¹⁵⁷ In a study of 16 FD children undergoing barostat testing, there was a lower gastric accommodation and a lower discomfort threshold compared to non-FD patients and tere was no relationship between gastric emptying and barostat findings.^{162, 163}

Duodenal eosinophilia and mast cell activity, sometime with food triggers, may also contribute to FD by affecting gut nerve signaling.^{164, 165} H. pylori infection is not typically associated with pediatric FD and does not require routine testing.¹⁶⁶

Clinical Evaluation

Diagnosis requires clinical judgment, as symptoms overlap with other conditions. Unnecessary testing should be avoided whenever possible. Ultrasound or HIDA scan is reserved for specific cases with right upper quadrant pain. Upper endoscopy (EGD) is not routinely required in children unless alarm signs are present.¹⁶⁷ Risk factors for abnormal EGD include male sex, multiple alarm features, and black race. Expert consensus supports EGD in selected cases—older children, symptoms >6 months, family history of ulcers, or significant impact on daily life. Gastric emptying may be indicated in intractable patients with PDS.

Treatment

Clinicians should explain the biopsychosocial nature of FD, discuss symptom triggers and introduce the concept of the gut-brain axis.^{168, 169} Treatment remains primarily supportive.

Despite many patients reporting food-related symptoms, no specific diet is consistently effective in children.¹⁷⁰ Recommendations however may include (1) slow and regular eating, (2) avoidance of high-fat food items, (3) a reduction of coffee and alcohol consumption, (4) a Mediterranean diet, (5) an increase fresh food intake and (6) a decrease intake of ultra-processed foods.

A course of acid suppression may be used for EPS symptoms. In refractory cases, low dose TCAs and other neuromodulators are often considered despite limited evidence for benefit.^171–173

Occasionally, prokinetic agents such as prucalopride or domperidone may be beneficial where available, particularly in those with PDS and abnormal gastric emptying. A review of 57 children treated with mirtazapine for functional nausea or-PDS found an 82% response rate and, in the PDS group, 76% improved, with 45% reporting complete relief.¹⁴⁸ Common side effects included weight gain (16%) and dysphoria (9%). Cyproheptadine may also be an effective treatment for FD.¹⁷²

In a trial of 100 children with chronic nausea or FD, hypnotherapy showed a trend toward better outcomes at 3 and 6 months and was more effective in functional nausea but not in FD.¹⁷⁴ For treatment-resistant cases, peripheral auricular stimulation may be promising. In a pediatric study of FD, combined IPBI and pyloric dilation improved symptoms in 76% of patients versus 49% in controls, with better outcomes in those with delayed gastric emptying.¹⁷⁵

Conclusion

Rome V opens the field for new research into the prevalence and natural history of new disorders and the efficacy of psychological and medical interventions for new and old disorders alike.

Table 1.

Suggested questions to consider for functional feeding diagnoses

Disorder	Key Questions?
General	How long does a meal take to complete? Do you need your food cut up in small pieces? Do you chew your food more than others? How much liquid do you drink with each meal? Does feeding happen overnight? What happens if meals are off schedule? What are preferred foods? What are avoided foods? Has there been weight loss? Gain? Are meals stressful for you? For your family? Are there any allergies? Are there any cultural requirements for meals? How do you eat at home compared to school? Can you go out to eat as a family? Do you need to bring food with you when you leave the house and if so, why? Do you have issues wearing clothes with tags or walking on sand or grass barefoot? Are you bothered by loud noises?
Hypersensitive dysphagia	Do you feel that liquids, solids or both get stuck? Are there particular foods that get stuck? What makes the stuck feeling go away? How much liquid do you need to drink at a meal? How much chewing is required during a meal?
Anticipatory restrictive feeding	Do you experience worry about eating? What symptoms have been associated with a meal? After a meal? Are there foods that you typically worry about eating and what happens if you try to eat them? Are you able to go out to eat with friends?
Hunger dysregulation disorder	How long can you go without eating? What happens if you cannot eat due to a change in schedule, fasting for medical procedures? Do you need to lock up food between meals? Do you graze on food throughout the day?
Medically-triggered functional feeding disorder	Can you pinpoint when the feeding trouble started? Are you able to eat age-appropriate food consistencies (liquids, semisolids, solids) before the medical condition started? Have you had any infections? Do you take any medications? Have you received any new medical diagnoses? When was the last assessment of medical conditions? What testing have you recently had done?

Abbreviations:

ARF

Anticipatory Restrictive Feeding (ARF)

ARFID

Avoidant/Restrictive Food Intake Disorder

CHS

cannabinoid hyperemesis syndrome

CNS

Chronic Nausea Syndrome

CVS

Cyclic Vomiting Syndrome

DGBI

Disorders of Gut Brain Interaction

DEAT

Disorders of Esophageal Air Transit

FD

Functional Dyspepsia

FH

Functional Heartburn

FPFD

Functional Pediatric Feeding Disorders

PDS

Postprandial Distress Syndrome

EPS

epigastric pain syndrome

RNEPD

Reflux Negative Esophageal Pain Disorder

RH

Reflux Hypersensitivity

RS

Rumination Syndrome

SGB

Supragastric Belching