Gastroesophageal reflux disease in children: clinical guidelines

List of Abbreviations

AR — anti-reflux formula

GER — gastroesophageal reflux

GERD — gastroesophageal reflux disease

DGR — duodenogastric reflux

PPI - proton pump inhibitors

CT — computed tomography

MRI — magnetic resonance imaging

LES — lower esophageal sphincter

NERD — non-erosive reflux disease

BE — Barrett's esophagus

PS — polysaccharides

HH — hiatal hernia

Ultrasound — ultrasound examination

EGD — esophagogastroduodenoscopy

CGD — chronic gastroduodenitis

ECG - electrocardiography

ERD — erosive reflux disease

H₂RA - H₂-receptor antagonists

Terms and Definitions

Gastroesophageal reflux (GER) is the involuntary retrograde flow of gastric or gastrointestinal contents into the esophagus.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of gastric contents into the esophagus causes troublesome symptoms and/or leads to complications [1]. In older children (unlike infants, in whom GERD is primarily based on morphofunctional immaturity and the morphological changes of the esophageal mucosa described below are not characteristic), the definition of GERD can be somewhat broadened to mean a chronic relapsing disease caused by impaired motor and evacuation function of the upper gastrointestinal tract (GIT) and predominantly the gastroesophageal junction, characterized by regularly recurring reflux of gastric and, in some cases, gastrointestinal contents into the esophagus, leading to the onset of clinical esophageal and extraesophageal symptoms that impair patients' quality of life, damage to the mucosa of the distal esophagus with the development of dystrophic changes in the non-keratinized stratified squamous epithelium, non-erosive or erosive-ulcerative esophagitis (reflux esophagitis), and, in some patients, columnar cell metaplasia and other reflux-induced pathological conditions [2].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

GERD is a multifactorial disease whose direct cause is gastroesophageal reflux (GER)—the involuntary reflux of gastric or gastrointestinal contents into the esophagus, which, due to a pathologically high frequency and/or duration of episodes, can cause physicochemical damage to the esophageal mucosa. The pathogenesis of GERD is determined by the disruption of equilibrium (the "balance scale" model) between "aggressive" factors (hypersecretion of hydrochloric acid; aggressive effects of lysolecithin, bile acids, pancreatic juice in duodenogastric reflux; certain medications and certain foods) and "protective" factors (antireflux function of the cardia; mucosal resistance of the esophagus, effective clearance, timely evacuation of gastric contents). The predominance of aggressive factors with adequate defense, defense defects with unchanged levels of aggressive factors, or a combination of increased aggressiveness of the intraluminal environment with inadequate defense leads to the development of GERD.

1.3 Epidemiology of the Disease or Condition

According to a meta-analysis published in 2018, the global prevalence of GERD is 13.3% (95% CI: 12.0–14.6%) [3]. In Russia, the prevalence of GERD ranges from 11.3 to 23.6% [4]. In the pediatric population, according to available publications, the prevalence of GERD in adolescence is 12.4–18.8% [5, 6].

At the same time, GERD is a common condition in children with the following pathological conditions: neurological disorders (cerebral palsy, neuromuscular diseases, etc.), chronic lung diseases including cystic fibrosis, obesity, and following surgical treatment of esophageal malformations, being detected in more than 70% of cases [7].

1.4 Features of Coding the Disease or Condition

Gastroesophageal reflux (K21):

K21.0 - Gastroesophageal reflux with esophagitis

K21.9 - Gastroesophageal reflux without esophagitis

Note: Clinical manifestations of newborn esophageal reflux (ICD-10 code: P78.8 Other specified perinatal digestive disorders (Esophageal reflux of newborn)) are covered in the relevant clinical guidelines.

1.5 Classification of the disease or condition

1. There are two main forms of GERD [1]:

○ non-erosive reflux disease (NERD) - GERD without visible erosive lesions of the esophageal mucosa (including endoscopy-negative GERD), accounting for approximately 60% of all cases,

○ erosive (erosive esophagitis) - characterized by erosive changes in the esophageal mucosa, accounting for about 35%.

2. In the case of erosive GERD (based on endoscopic findings), the Los Angeles classification stages A-D are indicated.

3. Extraesophageal manifestations of GERD (if present):

○ Bronchopulmonary

○ Otorhinolaryngological

○ Cardiological

○ Dental

4. Complications of GERD (if present):

○ Esophageal ulcer

○ Hemorrhage

○ Perforation

○ Esophageal stricture/stenosis

○ Posthemorrhagic anemia

○ Barrett's esophagus

To assess the severity of erosive reflux esophagitis, the unified Los Angeles classification (1994) [8, 9, 10] is used (Table 1).

Table 1 The unified Los Angeles classification of the severity of erosive reflux esophagitis (1994) [8, 9, 10]

*A limitation of the LA classification is the lack of criteria for assessing non-erosive changes in the mucosa of the esophagus and the esophagogastric junction. Therefore, the endoscopist should separately describe signs of minimally expressed or non-erosive reflux esophagitis in the procedure report [11, 12].

1.6 Clinical presentation of the disease or condition

It is customary to distinguish between esophageal and extraesophageal symptoms.

Esophageal symptoms:

Heartburn, being the key complaint in adults and adolescent patients with GERD, may be absent in preschool and early school-aged children.

Regurgitation is the passive movement of gastric contents due to reflux into the lower pharynx, oral cavity, and/or beyond the oral cavity. It is aggravated in the supine position or when bending the torso (due to increased intra-abdominal pressure).

Belching (air, sour, bitter). Belching air after a heavy meal or carbonated beverages is considered a physiological phenomenon. Belching bitter is characteristic not so much of GER as of duodenal motility disorders with increased intraluminal pressure of the duodenum. Belching sour is often evaluated by patients as heartburn.

Periodic retrosternal pain, pain or discomfort when food passes through the esophagus (odynophagia). It develops due to irritation of esophageal pain receptors by the refluxate. This symptom is relatively rare in children, although in adult practice, according to some authors, pain syndrome ranks second after heartburn.

Dysphagia is the sensation of an obstacle to the normal passage of food from the mouth to the stomach during swallowing. This complaint is based on impaired esophageal motility. Esophageal motility disorders of functional origin can occur with various esophageal dyskinesias, as well as a result of neurogenic spasm of the pharyngeal circular muscles or the esophageal opening, for example, in hysterical personalities. Some children, to get rid of dysphagia, help themselves by making frequent swallowing motions, washing food down with water, squeezing the chest, assuming a forced posture while swallowing, and leaning forward slightly. Dysphagia that occurs after eating any food is more typical of esophagitis, while dysphagia after liquid food is more typical of functional disorders. The appearance of this symptom after eating solid food is often noted against the background of severe organic pathology (tumor, stricture, stenosis). Paradoxical dysphagia is possible, when solid food passes better than liquid, and larger volumes pass better than small ones (Lichtenstern's sign). The temperature of the consumed food is important for the occurrence of dysphagia (very cold or hot food passes worse). In addition, emotions, eating in a hurry, eating dry foods, consuming certain foods (e.g., persimmons), or fright can cause short-term dysphagia even in healthy individuals.

Lump in the throat (globus pharyngeus) is the sensation of a lump in the throat unrelated to swallowing. The sensation may occur due to referred pain from esophagitis, esophageal muscle discoordination, cricopharyngeal hypertension, or the direct irritant effect of the refluxate on the laryngeal mucosa.

Extraesophageal symptoms

Extraesophageal symptoms are mainly represented by complaints indicating involvement of the bronchopulmonary system, ENT organs, cardiovascular system, and teeth [13, 14, 15, 16, 17]:

○ Prolonged chronic cough; coughing fits and/or asphyxia at night, triggered by heavy meals;

○ Recurrent bronchitis/pneumonia;

○ Apnea (in infants);

○ Periodic sensation of tickling in the throat and hoarseness;

○ Adenoid hypertrophy [17] when chronic persistent viral infections and allergic rhinitis are ruled out [18, 19];

○ Recurrent otitis media;

○ Rhythm and conduction disturbances;

○ Dental enamel erosions.

At the same time, extraesophageal manifestations rarely occur in isolation, without the main complaints typical of GERD.

In some cases, any clinical signs of GERD may be absent, and the diagnosis is established as a result of special diagnostic methods (for example, esophagogastroduodenoscopy (EGD) performed for gastric and duodenal pathology).

Features of the course of GERD in infants and young children

In young children with GERD, recurrent vomiting and regurgitation are more frequently noted. They often present with "alarm symptoms": weight loss, projectile vomiting, vomiting mixed with blood or bile, as well as respiratory disorders up to apnea and sudden infant death syndrome.

The frequency of regurgitation in infants varies over a fairly wide range: from 50–66% in the first half of life to 5–10% by the end of the first year.

When assessing the severity of regurgitation, it is recommended to take into account the frequency and volume of regurgitation:

○ mild course (up to 3–5 regurgitations per day, volume of 2.5–5.0),

○ moderate course (regurgitation in half of feedings or more frequently, up to 1/2 of the volume of ingested food),

○ severe course — regurgitation in more than half of feedings, volume greater than 1/2 of a feeding and/or delayed physical development.

According to literature data, pathological GER in infants occurs with a frequency of 8–11% [16, 20].

Among the main causes for the development of this condition are: birth trauma of the cervical spine, cow's milk protein allergy, lactase deficiency, sliding hiatal hernia (HH), autonomic regulation disorders, and prematurity.

Numerous studies conducted in various countries have not found a correlation between the severity of clinical, histological, endoscopic, and pH-metric changes in infants and young children with GERD. In this age group, it is impossible to judge the presence and severity of esophagitis based solely on clinical manifestations [16, 20, 21].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for diagnosing GERD

The diagnosis of GERD is established based on:

○ Complaints, taking into account the severity of symptoms or signs that may be associated with GERD, keeping in mind that subjective symptoms are unreliable in young children and most suspected GERD symptoms are non-specific;

○ Anamnestic data — the presence of pathological conditions/diseases in which the frequency of GERD increases, or a previously established diagnosis of GERD;

○ Instrumental data — if necessary, barium swallow X-ray of the esophagus (ultrasound examination (ultrasound) of the upper gastrointestinal tract with a water-siphon test (ultrasound examination of the esophagus, radiological examination (fluoroscopy and radiography) of the esophagus with oral contrast), gastric endosonography, esophagogastroduodenoscopy, intraluminal pHmetry, pH-impedanceometry, esophageal manometry);

○ The diagnosis of GERD is established only in the presence of persistent clinical ("esophageal") symptoms or provided there is a clear link between symptoms and signs and episodes of reflux, while alternative diagnoses are excluded.

Criteria for medical therapy-refractory GERD:

- absence of convincing clinical and endoscopic remission within 4–8 weeks of therapy with a standard dose of PPIs.

2.1 Complaints and Anamnesis

Clinical manifestations of GERD are non-specific, numerous, and depend on the patient's age (Table 2):

Table 2. Symptoms of GERD depending on the age of children

• Due to the lack of specific symptoms characteristic of GERD, it is recommended to pay attention to the presence of alarm symptoms for differential diagnosis and identification of diseases with a clinical presentation similar to GERD [22].

  Alarm symptoms:

  ○ Vomiting mixed with bile, nighttime or intractable vomiting;

  ○ Persistent dysphagia;

  ○ Abdominal distention;

  ○ Hematemesis;

  ○ Fever;

  ○ Pathological findings on physical examination (gastrointestinal, respiratory, cardiovascular, or nervous system);

  ○ Weight loss / delayed physical development;

  ○ Psychomotor development delay;

  ○ Recurrent bronchitis/pneumonia.

2.2 Physical Examination

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: there are no pathognomonic physical signs for GERD. A standard complete physical examination of the child should be performed.

The physical examination is carried out within the framework of the initial appointment (examination, consultation) of a primary care pediatrician and/or primary care gastroenterologist and/or initial appointment (examination, consultation) of a pediatric surgeon.

2.3 Laboratory Diagnostics

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: anemia is of iron-deficiency type: hypochromic, micro- or normocytic, normoregenerative. Serum iron and ferritin levels are decreased, and total iron-binding capacity is increased.

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: acetonemic syndrome (cyclic vomiting syndrome) is a predominantly childhood disorder manifested by repeated episodes of vomiting due to elevated blood ketone levels and developing acidosis.

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comment: at this age, such complaints are often caused by cow's milk protein allergy. The test is preferably performed using an immunochemical method. Allergy testing is carried out in accordance with relevant clinical guidelines.

2.4 Instrumental Diagnostics

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: Visualization of the esophagus is usually possible for 1.5–2.5 cm of the abdominal segment. The normal esophageal diameter in children is considered to be 7–10 mm. With a diameter of more than 13 mm (15 mm or more during a swallow), the diagnosis of hiatal hernia in children becomes practically definitive.

The use of ultrasound for the diagnosis of GERD is currently not recommended by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), because while the method has a high sensitivity (about 95%), its specificity is only 11%. Furthermore, there is no correlation between esophageal wall thickness and signs of esophagitis [7].

• Children with suspected GERD are recommended to undergo esophagogastroduodenoscopy (EGD) for diagnostic purposes and differential diagnosis [2, 22].

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: the procedure evaluates the condition of the esophageal mucosa. It allows for:

○ diagnosing a number of congenital developmental anomalies of the upper GI tract (atresia, stenosis, "short esophagus", etc.), as well as acquired inflammatory and non-inflammatory diseases;

○ diagnosing erosive reflux esophagitis, which is determined by the presence of visible erosive lesions of the distal esophageal mucosa [8].

○ identifying complications of GERD – peptic stricture, esophageal ulcers, Barrett's esophagus;

○ excluding other conditions that may present with similar symptoms (eosinophilic esophagitis, infectious esophagitis, inflammatory bowel disease, congenital malformations, etc.);

○ diagnosing conditions predisposing to GERD (e.g., hiatal hernias). However, the anatomical features of children at various age periods must be taken into account to avoid overdiagnosis [25];

○ detecting and diagnosing neoplastic diseases of the esophagus and monitoring the condition of the esophagus after surgical interventions.

EGD is indicated in the presence of alarm symptoms (see section 2.1) [22].

Detection of erosive mucosal defects during EGD (without specifying size) in the presence of symptoms confirms the diagnosis of GERD in children [22].

Assessment of the severity of erosive reflux esophagitis should be performed using the unified Los Angeles classification (1994) [8, 9].

However, the universal application of the LA classification is limited by the lack of internationally approved additional criteria for assessing non-erosive changes in the mucosa of the esophagus and the esophagogastric junction [22, 26].

Despite the recognized unreliability of endoscopic criteria for reflux esophagitis such as hyperemia and edema of the esophageal mucosa, and blurriness or discontinuity of the Z-line, EGD in children with suspected GERD and symptoms should still focus on signs of minimally expressed or non-erosive reflux esophagitis, which must be recorded in the endoscopy report.

These include:

○ straightening, induration, small triangular protrusions, and segmental elevations of the Z-line (less than 10 mm);

○ hyperemia and tiny circular/triangular erosions in the area of the esophagogastric junction;

○ reactive hyperplasia of the cardia epithelium with or without the formation of hyperplastic polyps;

○ linear mucosal thickening along the crests of the folds in the lower third of the esophagus (whitish streaks).

It should be noted that to improve diagnostic quality, the endoscopic physician should, when technically feasible, use advanced imaging methods in addition to white-light endoscopy (e.g., narrow-band imaging) [27, 28, 29, 30].

A normal endoscopic finding does not exclude a diagnosis of GERD in children. PPI therapy prior to EGD may cause GERD to transition into the NERD phenotype, thereby reducing the sensitivity of endoscopy as a diagnostic method [22].

In children, EGD should be performed under anesthesia whenever possible (preferably under general anesthesia or deep sedation) with careful medical monitoring [Anesthetic management (including early postoperative care)] [25, 31].

LeveR – B, LoE – 3

Comments: performing an esophageal biopsy during EGD allows for the identification of microscopic signs of reflux esophagitis (eosinophilic infiltration, elongation of epithelial papillae, basal cell hyperplasia, widening of intercellular spaces), referred to as microscopic esophagitis.

It is important to note that even minor deviations in biopsy technique affect the reliability of pathomorphological examination as a diagnostic method for determining reflux esophagitis. For reliable diagnosis, it is necessary to take at least two biopsy specimens (preferably 4) at a distance of two centimeters or more above the Z-line.

However, microscopic changes neither reliably exclude nor confirm GERD in children; therefore, routine biopsy during EGD is not advisable for the diagnosis of GERD [22].

Diagnosis of Barrett's Esophagus.

Barrett's esophagus (BE) is an acquired pathological condition resulting from long-standing GERD complications, characterized by the replacement of the normal stratified squamous epithelium of the esophagus with metaplastic columnar epithelium. The prevalence of BE in children is low, and the age of disease onset remains unclear.

BE is diagnosed predominantly in children with severe congenital or comorbid conditions (diaphragmatic and hiatal hernias, esophageal atresia, neuromuscular disorders, chronic respiratory diseases, severe obesity), as well as in the presence of genetic predisposition. Special attention should be paid to the cohort of children with severe musculoskeletal disorders and intellectual disability (cerebral palsy), which is characterized by late diagnosis due to the absence of specific symptoms [22].

There are no uniform guidelines for the diagnosis and treatment of BE in children. It is recommended to rely on 2 criteria for diagnosis: endoscopic and histological [32].

When performing EGD, clear identification of anatomical landmarks is required: the esophageal hiatus of the diaphragm (EHD), the esophagogastric junction (EGJ), and the Z-line (the squamocolumnar junction).

The metaplastic segment is defined between the EGJ and the Z-line displaced proximally to it; its description requires the use of the Prague Criteria (The Barrett’s Prague C&M Criteria, 2004) – determination in cm of the proximal extent of the circumferential metaplastic segment (the "C" value), as well as the maximal extent of the tongues of metaplasia (the "M" value) [33].

When BE is suspected in children, the term "suspected columnar metaplasia of the esophagus" should be used, indicating the length of the segment, followed by multiple biopsies for histological examination.

A four-quadrant biopsy should be performed every 1 cm of the circumferential metaplastic segment, obtaining the maximum number of biopsy specimens closer to the proximal edge of the "flames", as specialized intestinal metaplasia is most frequently detected there in both adults and children.

Upon detection of columnar epithelium in biopsy specimens, the term BE should be applied regardless of the presence of intestinal metaplasia and the length of its segment [22].

Since 2022, this has been consistent with the definition of BE in adults, which, according to the latest Kyoto Consensus, is defined as a pathological condition in which columnar metaplastic epithelium (regardless of its type) prone to neoplasia replaces the normal squamous epithelium of the distal esophagus (regardless of the length of the metaplastic segment) [34].

• In children with refractory GERD (absence of convincing clinical and endoscopic remission within 4–8 weeks of therapy) and suspected hiatal hernia based on EGD findings, it is recommended to perform a barium swallow X-ray of the esophagus for differential diagnosis and to rule out/confirm anatomical anomalies [2, 22].

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: The applied X-ray detection technique for GERD is performed in accordance with the methodological recommendations of the USSR Ministry of Health of 1981 [35]. Indications for an X-ray examination include clinical data suggestive of GERD and extraesophageal manifestations of GERD. In infants during the first year of life (including the first months of life), an indication is recurrent vomiting lasting for more than 3 days, provided it is not accompanied by symptoms definitively pointing to mechanical or functional obstruction [36].

The procedure must be performed on an empty stomach, prior to the scheduled feeding. A preliminary fluoroscopy of the esophagus and abdominal cavity is performed. Next, the stomach must be filled. Filling of the stomach can be carried out either via a tube (following the standard insertion protocol) or independently, from a glass, cup, or sippy cup. The volume of the administered contrast agent (barium sulfate without suspending agents) must correspond to the volume of a single feeding. Thus, infants under 3 months are administered 40–80 ml, and older children 60 to 200 ml. Administering over 200 ml, regardless of age, is inexpedient. At this stage, upon positioning the patient, or as a result of rotation, GERD may be detected in some cases.

Following the complete filling of the stomach, the next step is performing the water-siphon test (contrast esophagoscopy). The water-siphon test involves drinking water in a horizontal position. The test is considered positive if barium sulfate** contained in the stomach refluxes into the esophagus. The height of the reflux, the volume of the refluxate, the rate of esophageal clearance from the refluxate, and the frequency of reflux recurrences are taken into account. At the same time, moderate pendulum-like pressure can be applied to the anterior abdominal wall to assess the competence of the lower esophageal sphincter [37]. During the water-siphon test, the presence of a sliding hiatal hernia can be identified.

Next, a multi-position examination of the stomach and duodenum is performed: their anatomy and topography, the rate of evacuation of barium sulfate** from the stomach and duodenum, the presence of obstruction to passage, dyskinesia, and pendulum-like movements of barium are assessed. The examination must be performed in the supine position, on the right and left sides, and vertically.

Palpation may be performed for diseases of the esophagus, stomach, and duodenum to accelerate passage and serve as a provocative factor. Provocative tests include patient rotation, moderate abdominal compression, and straining of the abdominal muscles (coughing, straining, the patient lifting their legs). In infants, the test is considered positive if abdominal compression for 30 seconds and immediately thereafter reveals at least two episodes of barium sulfate** reflux from the stomach into the esophagus.

In case of negative results from contrast esophagoscopy, the patient is examined in the Trendelenburg position. This maneuver allows for an increased detection rate of GERD and, particularly, hiatal hernias [38], specifically sliding hernias. Next, the table is tilted to a position parallel to the floor. To assess esophageal patency and motility, a stress test should be performed: swallowing a bolus of thick barium sulfate** contrast medium [36] in a volume of one swallow (if the patient is able to swallow consciously). The progression of the thick contrast bolus makes it possible to adequately evaluate the esophageal clearance capacity, motility, and the functioning of the esophageal sphincters.

• In suspected non-erosive reflux disease, refractory GERD, and prominent and/or persistent extraesophageal symptoms of GERD, children are recommended to undergo 24-hour esophageal pHmetry (which detects only acid reflux), if available [2, 39, 40, 41].

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: 24-hour esophageal pHmetry makes it possible to detect the reflux of acidic gastric contents into the esophagus with high accuracy. Using this method, it is not only possible to document the fact of esophageal acidification itself, but also to evaluate its duration.

During the study in children, standard 2-, 3-, or 5-channel pH catheters are used. One of the electrodes is positioned in the esophagus 5 cm above the cardia.

This method allows not only for the detection of reflux, but also for determining its severity, as well as clarifying the influence of various provoking factors on its occurrence and selecting adequate therapy.

When evaluating the obtained results, globally accepted normative values developed by T.R. DeMeester are used (Table 3) [42].

Table 3. Normal values of 24-hour pH monitoring (according to T.R. DeMeester).

The reflux index (RI) is also determined, which represents the ratio of the study time with pH < 4 to the total study time (in %). For acid reflux, normal RI values are 4.45%. Analysis of the obtained results is carried out using specialized computer software. One of the fundamental integrative indicators is considered to be the composite DeMeester score, which normally should not exceed specific threshold values.

These parameters can be used in children older than 12 years.

For young children, a separate normative scale has been developed (J. Boix-Ochoa et al.). According to the author, the parameters of 24-hour pH monitoring in infants under one year of age differ from those in adults (fluctuations of ± 10%). Normative values for children of this age group are given in Table 4.

Table 4. Normal values of 24-hour pH monitoring in children under 1 year of age (according to J. Boix-Ochoa et al.) [43].

The method is not universally available; if it needs to be performed, the child should be referred to a specialized hospital or specialized consultative and diagnostic center.

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: performing 24-hour pH-impedance monitoring makes it possible to overcome the limitations of standard 24-hour pHmetry and detect both acidic and non-acidic reflux (alkaline and weakly acidic). Additionally, the method allows for determining the height of the refluxate ascent into the esophagus and predicting the risk of refluxate aspiration. Combined 24-hour pH-impedance monitoring is promising as an objective diagnostic method for GERD; however, more normative data are needed before this method can be considered a "gold standard" test [22].

Alkaline and mixed types of reflux are detected in at least half of the cases in children [22].

Normative standards for alkaline GERD do not exist, since the very fact of duodenal contents entering the esophagus is a pathological sign.

The method is not universally available; if it needs to be performed, the child should be referred to a specialized hospital or specialized consultative and diagnostic center.

• In cases where standard therapy regimens are ineffective (lack of convincing clinical and endoscopic remission within an average of 4–8 weeks of therapy), when esophageal motility disorders are suspected, and prior to planned surgical antireflux treatment in children, esophageal manometry is recommended selectively [2, 22, 44, 45, 46].

Level of Evidence – C, Grade of Recommendation – 4

Comments: Esophageal manometry is one of the most accurate methods for studying LES function, through which the boundaries of the LES are established, and its competence and relaxation ability during swallowing are assessed. Numerous studies have shown that the lower limits of normal for the LES are a pressure of 6 mm Hg, a total sphincter length of 2 cm, and an intra-abdominal segment length of 1 cm. Currently, simultaneous esophageal pH monitoring and LES manometry is considered the most promising approach. Limitations of the method include its low availability and technical complexity in children under 15 years of age.

2.5 Other Procedures

Differential diagnosis

List of diseases and pathological conditions in which symptoms characteristic of GERD may be observed.

1. Esophageal diseases

1.1 Acute and chronic esophagitis

1.2 Esophageal ulcer

1.3 Esophageal stricture

1.4 Esophageal diverticula

1.5 Esophageal tumors

1.6 Scleroderma

1.7 Sideropenia

2. Diseases of the central, peripheral nervous, and muscular systems

2.1. Esophagospasm

2.2. Esophageal atonia

2.3. Achalasia cardia

3. Esophageal strictures caused by pathological changes in adjacent organs

3.1. Mediastinal tumors and cysts

3.2. Foreign bodies

3.3. Posterior mediastinitis

3.4. Pleuropulmonary fibrosis

3.5. Mitral valve disease

3.6. Aortic aneurysm

3.7. Right-sided aorta

3.8. Vascular anomalies

3.9. Thyroid enlargement

4. Drug-induced effects

5. Mental disorders

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Therapy for gastroesophageal reflux disease, given the multicomponent nature of this pathophysiological phenomenon, is comprehensive. It includes diet therapy, postural, pharmacological, and non-pharmacological therapy, and surgical correction ("step-down therapy"). The choice of treatment method or their combination depends on the causes of reflux, its severity, and the spectrum of complications. Treatment is based on three main principles:

1. A complex of non-pharmacological interventions, mainly normalization of lifestyle, daily routine, and diet.

2. Pharmacological therapy aimed at:

   ○ normalizing the peristaltic activity of the esophagus and stomach,

   ○ restoring and normalizing the acid-producing function of the stomach,

   ○ restoring the structure of the esophageal mucosa and managing inflammatory changes in the mucosa.

3. Surgical treatment.

In practice, the following tactics are usually applied in children with GERD:

1. Initial PPI treatment for approximately 8 weeks.

2. Monitoring the child after PPI discontinuation.

3. If symptoms return – performing an X-ray contrast study, and other instrumental studies if necessary (cl. 2.4).

4. Based on the evaluation of examination results and the confirmation of ineffectiveness – consider surgical treatment (usually the process of treatment, monitoring, and evaluation of therapy results takes, on average, about 1 year).

3.1 Conservative Treatment

3.1.1 Treatment of infants and young children

Level of Reliability of Evidence – C, Grade of Recommendation – 5

• If postural therapy is ineffective, it is recommended to adjust the diet using anti-regurgitation formula milk, the viscosity of which is increased by adding thickeners. The use of thickened formulas in infants with regurgitation and vomiting syndrome reduces the frequency of GER [47].

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: the use of specialized products enriched with complex carbohydrates to prevent the backflow of gastric contents and improve gastric emptying is a fundamental approach to the diet therapy of GER in infants. For infants with mild regurgitation and adequate or slightly delayed weight gain, this nutritional approach is highly effective. Its efficacy combined with postural therapy is 90–95%. The best effect is achieved by introducing anti-regurgitation formulas at the earliest stages of the disease.

When prescribing formulas that use indigestible polysaccharides (PS) (locust bean gum) as a thickener, it should be kept in mind that:

○ these formulas are therapeutic and must be prescribed by a physician;

○ they require precise selection of the volume in the child's daily diet (1/2, 1/3, or 1/4);

○ the duration of use is determined individually based on clinical symptoms (up to 2–3 months);

○ they are only one of the components of treatment programs.

Options for prescribing anti-reflux formulas

1. At the beginning of each feeding with an adapted formula, an anti-reflux (AR) formula is prescribed in an amount equal to 1/2 – 1/4 of the feeding volume.

2. The AR formula is prescribed 1–3 times a day in the feeding volume; an adapted formula is used for the remaining feeds.

3. The AR formula is prescribed in the full daily volume; the duration of use is determined individually.

4. The question of pharmacological treatment in infants with regurgitation syndrome is decided strictly individually, and the choice of program depends on the specific case and cannot be standardized.

If there is no effect from the administration of the AR formula and poor weight gain is observed, the use of an extensively hydrolyzed protein formula or an amino acid formula is recommended. The lack of improvement in clinical symptoms within 2 weeks indicates the ineffectiveness of the chosen diet therapy tactics and suggests a return to the previously used formula. In case of a positive effect, it is recommended to continue the formula for up to 12 months, but for at least 6 months [104, 105, 106, 107, 108, 109, 110, 111].

• Routine pharmacological therapy is not recommended for infants with uncomplicated GER because in most cases symptoms in infants disappear spontaneously after 6 months [22, 48, 49, 50].

Level of Evidence (LoE) – C, Grade of Recommendation (GoR) – 5

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: drug dosages according to the instructions.

3.1.2 Treatment of older children

Non-pharmacological treatment

• All children and adolescents with GERD should be advised to change their lifestyle (weight loss in case of overweight, avoiding situations that increase intra-abdominal pressure, etc.) (Table 5) for the purpose of non-pharmacological antireflux treatment [22].

Level of Evidence (LoE) – C, Grade of Recommendation (GoR) – 5

Table 5. Recommendations for lifestyle modifications in patients with GERD.

Comments: when drawing up a diet therapy program for children with GERD, it should be taken into account that in most cases this disease is combined with gastritis, gastroduodenitis, diseases of the biliary system, pancreas, and intestines. Therefore, the corresponding dietary tables (diets 1, 5, and 4) are recommended as a "basic" diet.

Postural therapy should be performed, especially at night. This simple measure prevents the reflux of gastric contents into the esophagus in a horizontal position. Trying to achieve this by increasing the number or size of pillows is a mistake. The optimal approach is to place blocks up to 15 cm high under the legs of the bed. Sleeping on the left side and with the head of the bed elevated reduces the frequency of GER.

Mineral water is another treatment method. Low-mineralization alkaline waters, such as Essentuki No. 4, Slavyanovskaya, Smirnovskaya, etc., should be used; they are prescribed in a warm, degassed form 30–40 minutes before meals for 4 weeks [52].

Drug therapy

• In children older than one year with esophageal manifestations of GERD, proton pump inhibitors (PPIs) (antisecretory drugs) omeprazole**, esomeprazole**, #rabeprazole are recommended as drugs of choice in a course averaging 4–8 weeks or longer if confirmed esophagitis is present [1, 2, 22, 53].

Level of Certainty of Evidence – C, Target Confidence Level of Evidence – 5

Comments: according to randomized comparative studies (including meta-analyses), PPIs have shown the highest efficacy in the treatment of this category of patients compared to other antisecretory drugs (H₂-histamine receptor blockers) [54, 55]. Omeprazole** is prescribed to children over two years old at a dose of 1–4 mg/kg/day (maximum up to 40 mg in two divided doses) once daily. Esomeprazole** is indicated for use in children over one year old at a dose of 0.5 mg/kg in 1–2 doses, maximum up to 40 mg 1–2 times a day. Rabeprazole can be used from the age of 12 up to 20 mg per day.

There is evidence indicating that long-term PPI use increases the risks of certain metabolic, infectious, and nutritional disorders as the duration of drug use increases. This must be taken into account when extending the duration of drug administration beyond 8 weeks [22, 56, 57, 58].

• In children over 6 years of age, to protect the esophageal mucosa from damage by the refluxate and restore its integrity, the administration of esophagoprotective therapy (an agent for creating a gastroesophageal barrier (code 267550) in the form of a combination of sodium hyaluronate and chondroitin sulfate on a bioadhesive poloxamer 407 carrier) is recommended in combination with PPIs. Combination therapy with PPIs and a gastroesophageal barrier-forming agent promotes a more pronounced elimination of esophageal and extraesophageal symptoms of GERD and is significantly more effective than PPI monotherapy for the epithelialization of esophageal erosions in patients with erosive GERD [59, 60].

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: the combination of sodium hyaluronate and sodium chondroitin sulfate provides protection for the gastric and esophageal mucosa. The presence of poloxamer 407, which has a high bioadhesion capacity, ensures reliable contact of the hyaluronic acid — chondroitin sulfate complex with the surface of the esophageal wall, helping to protect it from the aggressive action of gastric hydrochloric acid. Chondroitin sulfate also promotes the restoration of the esophageal and gastric mucosa. The bioadhesive formula based on hyaluronic acid and chondroitin sulfate for mucosal protection helps reduce inflammation and heal esophageal erosions, including when used in combination with PPIs. It should be taken as 1 sachet (10 ml) after meals and at bedtime. Clinical studies have proven its efficacy when used for 4–5 weeks. The use of esophagoprotective therapy in the form of a combination of sodium hyaluronate and chondroitin sulfate on a bioadhesive poloxamer 407 carrier in children was documented in a double-blind randomized study in patients with esophagitis [61] and a multicenter observational study in a combination of esophageal and extraesophageal symptoms of GERD [59]. Compared to placebo, the use of esophagoprotective therapy achieved a more pronounced relief of heartburn and epigastric pain, and also contributed to an improvement in the endoscopic picture in the form of reduced severity of inflammation [61]. With a combination of esophageal and extraesophageal symptoms of GERD at the end of the study, 70.5% (95% CI: 57.4–81.5) of patients who used the combination of sodium hyaluronate and chondroitin sulfate on a bioadhesive poloxamer 407 carrier showed complete disappearance of extraesophageal symptoms of GERD; in patients whose symptoms persisted by the end of the study, a significant regression of both esophageal and extraesophageal manifestations of GERD was noted. The proportion of patients taking antacid-containing drugs decreased significantly: from 34.4% (95% CI: 21.7–47.2) to 4.9% (95% CI: 0.0–11.2), while 24.6% of patients in the study did not take PPIs.

• If PPI use is not possible or there are contraindications, it is recommended to selectively use the H₂-histamine receptor blocker #Famotidine** 1 mg/kg/day for a course of 4-8 weeks in the treatment of erosive esophagitis associated with reflux in children over 3 years of age [22].

Level of Certainty of Evidence – C, Target Confidence Level of Evidence – 5

Comment: used with caution: H₂-histamine receptor blockers have lower efficacy, an unfavorable pharmacotherapeutic profile, and a high risk of tachyphylaxis.

• It is recommended to prescribe antacids and combination antacids, preferably in the form of a gel or suspension (aluminum phosphate, algeldrate + magnesium hydroxide (for children aged 10 years and older), sodium alginate + sodium bicarbonate + calcium carbonate (for children aged 12 years and older)) as part of complex therapy for the treatment of heartburn in order to rapidly relieve pain [22].

Level of Certainty of Evidence – C, Target Confidence Level of Evidence – 5

Comment: these drugs should not be used long-term for the treatment of GERD.

Level of Certainty of Evidence – C, Target Confidence Level of Evidence – 5

Comments: the use of these medications for GERD in children is limited. Prokinetics are most effective when GERD is combined with functional dyspepsia. The efficacy of prokinetics in the treatment of GERD is due to their ability to influence the pathogenesis of GERD: to increase lower esophageal sphincter tone and accelerate gastric emptying. Accelerated gastric emptying under the action of prokinetics leads to a reduction in the impact of pathological GER on the esophagus in patients with reflux esophagitis.

These drugs should be taken by patients according to indications in the presence of accompanying complaints of delayed evacuation of gastric contents and/or constipation [64].

Trimebutine doses depend on age:

3–5 years – 25 mg 3 times/day,

6–12 years – 50 mg 3 times/day,

12 years and older – 100–200 mg 3 times/day.

Itopride may be used from the age of 16.

3.1.3 Antirecurrent treatment

Level of Certainty of Evidence – C, Target Confidence Level of Evidence – 5

• As anti-relapse therapy for children with GERD, it is recommended to selectively carry out rehabilitation measures: balneotherapy, physiotherapy procedures (see clause 4) [52].

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: the level of evidence for interventions is low.

• Considering that GERD often occurs against the background of chronic gastroduodenitis and Helicobacter pylori colonization, it is recommended to include the main stages of examination and management of patients with gastric and duodenal pathology in the patient monitoring program [102, 103].

Level of Certainty of Evidence – C, Target Confidence Level of Evidence – 5

Comments: see relevant clinical guidelines.

• For patients with GERD in the stage of incomplete clinical and endoscopic remission, physical exercise in a preparatory group is recommended; in the stage of complete clinical and endoscopic remission, in the main group [52].

Level of Certainty of Evidence – C, Target Confidence Level of Evidence – 5

3.2 Surgical Treatment

• For patients with GERD refractory to medical therapy (lack of convincing clinical and endoscopic remission within 4–8 weeks of therapy with a standard dose of PPI, the need for continuous pharmacotherapy to control GERD symptoms, presence of stricture, Barrett's esophagus) or leading to life-threatening complications, including apnea episodes, recurrent aspiration, reactive airway disease, neurological disorders, physical growth retardation, esophageal stricture formation, in the presence of a severe underlying disease (neurological or, for example, cystic fibrosis) if there is a significant risk of complications associated with GERD, surgical treatment – laparoscopic fundoplication / Nissen fundoplication is recommended [22, 65, 66, 67].

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: Antireflux surgery is usually performed after other treatments have failed, or as a treatment option for GERD-associated complications [68]. Fundoplication reduces reflux by increasing baseline lower esophageal sphincter pressure, decreasing the number of transient lower esophageal sphincter relaxations and baseline pressure during swallow-induced relaxation, increasing the length of the intraabdominal esophagus, accentuating the angle of His, and reducing a hiatal hernia, if present.

Various antireflux surgical interventions exist. Laparoscopic Nissen fundoplication is considered the gold standard of surgical treatment for severe GERD, and it has largely replaced open Nissen fundoplication as the preferred antireflux procedure due to reduced invasiveness, shorter hospital stay, and fewer perioperative problems [69, 70, 71]. Robot-assisted Nissen fundoplication is a safe alternative to conventional laparoscopic surgery in children, but does not provide significant clinical advantages [72, 73].

Most of the literature on the surgical treatment of children with GERD consists of retrospective case series that lack documented confirmation of the GERD diagnosis and detailed information on prior medical therapy. This makes it difficult to assess indications for surgery and response to it. In addition, many surgical series have a high percentage of children with conditions predisposing to the most severe forms of GERD. In general, the outcomes of antireflux surgery have been evaluated more thoroughly in adults than in children. In adults, laparoscopic Nissen fundoplication is associated with approximately 95% patient satisfaction and improved quality of life in patients with chronic GERD. According to the guidelines of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), surgical treatment of GERD yields a positive outcome in 85–93% of cases [74, 75, 76, 77].

A systematic literature review in adults showed that antireflux surgery may be more effective in preventing esophageal adenocarcinoma compared with medical therapy in patients with Barrett's esophagus [78]. The failure rate of laparoscopic fundoplication in adults ranges from 3 to 16%, yet 37 to 62% of patients take PPIs several years after the procedure [71, 79, 80, 81].

Postoperative dysphagia, although often resolving over time, is the most frequent complication reported in the literature regarding adult patients and children [82, 83, 84, 85].

According to a systematic review of the pediatric literature, antireflux surgery in children demonstrates a good overall success rate (median 86%) in terms of complete relief of typical GERD symptoms [86].

Based on a prospective multicenter study of 25 children (aged 2–18 years) with therapy-refractory GERD, laparoscopic Nissen fundoplication reduced reflux symptoms, total acid exposure time, and the number of (weakly acidic) reflux episodes. However, 3/25 patients experienced persistent/recurrent reflux symptoms, and 3 patients developed dysphagia [87].

In a retrospective review of 823 children (< 18 years of age) who underwent laparoscopic Nissen fundoplication, the reoperation rate was 12.2%. This risk increased with the presence of hiatal hernia dissection, postoperative retching, and younger age at the time of the initial surgery [88]. In another series of 2,008 laparoscopic Nissen fundoplications in children (aged 5 to 19 years), the failure rate of fundoplication was 4.6% after the initial surgery and 6.8% after reoperation [71]. Anti-reflux surgery has the lowest success rate in treating extraesophageal symptoms, including aspiration pneumonia, in patients with neurological impairments [89]. At the same time, there is evidence of very good surgical outcomes (> 90% improvement) [90].

Anti-reflux surgery may be beneficial for children with confirmed GERD who cannot adhere to optimal medical therapy or have life-threatening complications of proven GERD. Before surgery, non-GERD causes of symptoms must be excluded, and it must be ensured that the diagnosis of chronic/recurrent GERD is firmly established. In all cases, the risks of surgery must be weighed against the potential benefits, and patient selection is critical; only patients with clearly proven GERD should be considered for surgery. Risks of laparoscopic Nissen fundoplication include gas bloat, early satiety, dysphagia, retching, dumping syndrome, increased risk of aspiration due to esophageal stasis and wrap failure, leading to the need for reoperation.

3.3 Other Treatment

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: usually performed without surgical treatment, combined with medical anti-reflux therapy (if indicated) (see section 3.1).

In the absence of efficacy, surgical treatment is performed as a second-line therapy (see section 3.2).

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comments: limitations of this intervention include: impairment of intestinal adaptation and worsening of absorptive capacity, which is already limited in patients with short bowel syndrome. In addition, the presence of a nasojejunal tube (nasoenteric tube) may increase the risk of intestinal contamination with alterations in the gut microbiome and subsequent small intestinal bacterial overgrowth. However, if nasojejunal tube feeding (nasoenteric tube) is the only method of delivering enteral nutrition, it should be used when feasible and in the absence of contraindications.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Non-pharmacological treatment for children with GERD includes lifestyle modification recommendations, physical exercise, and balneotherapy [96, 97].

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comment 1. Positioning training includes the following recommendations: avoiding the supine position after eating and sleeping on the left side, as lying on the right side increases the reflux of acidic gastric contents into the esophagus; patients should also be informed that an elevated head position minimizes reflux and reduces intra-abdominal pressure [96]. Children with GERD should avoid tight-fitting clothing and belts around the chest and waist, avoid exercising immediately after meals, eat small meals, elevate the head of the bed by approximately 15 cm, lose weight if overweight, and may chew sugar-free gum after meals to stimulate saliva production and neutralize acid.

Comment 2. Children with GERD should avoid foods and beverages that exacerbate symptoms: caffeine, carbonated beverages, chocolate, citrus fruits, tomatoes and tomato sauce, spicy or fatty foods, and high-fat dairy products [98].

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comment 1. Studies have shown that performing exercises developed by R. Shaker helps improve swallowing and reduce dysphagia [99].

The use of these exercises helps strengthen the muscles of the lower esophageal sphincter, thereby preventing the gastric contents from entering the esophagus.

R. Shaker's exercise protocol:

Starting position: lying on the back on a firm, flat surface without a pillow, arms extended along the torso. Breathing is slow and steady throughout the exercise.

Lift and hold the head (to look at the toes).

Shoulders must remain pressed against the surface; only the head is lifted.

Hold the position for 1 minute, then lower the head back to the starting position.

Repeat 2 more times, resting for 1 minute between each repetition.

Head lifts and lowerings: lift the head up to look at the chin, then return to the starting position. Repeat 30 times with relaxation periods.

Performed as indicated.

• Children with GERD are recommended to selectively undergo spa-and-resort therapy with the use of drinking mineral waters, terrain cures, and climatotherapy to reduce the severity of dysphagia and heartburn [100].

Level of Reliability of Evidence – C, Grade of Recommendation – 5

Comment 1. Sanatorium-and-resort treatment for patients with GERD includes climatotherapy, balneotherapy (internal use of natural mineral waters), as well as terrain-cure walking along designated routes in resort parks at low-mountain, lowland, and seaside resorts.

Therapeutic walking (terrain cure) during the resort stay is conducted daily during cool hours (in the morning, before lunch, or in the late afternoon) no earlier than 2 hours after a meal, adhering to a mandatory hydration regimen. Exercise intensity is individually dosed (by distance, uphill angle from 3 to 20°, walking pace, number and duration of stops) based on the submaximal heart rate (determined via a physical tolerance test) to achieve a training effect on the cardiovascular system, reduce cardiovascular disease risk factors, and improve carbohydrate and lipid metabolism parameters.

A randomized controlled trial (RCT) investigated the efficacy of internal administration of low-mineralized drinking mineral water (sulfate sodium-magnesium-calcium with a mineralization of 1.9 – 3.2 g/dm³) in children with GERD aged 9–17 years. Mineral water was prescribed to patients in the main group as part of combination therapy (antacids, prokinetics) in the second week of treatment at a dose of 5 ml/kg, taken three times a day, warm (t 28–30 °C) 1–1.5 hours before meals, for 3 weeks. The comparison group consisted of 40 children with grade I GERD who received antacids and prokinetics for 4 weeks. The esophageal and gastric pH levels were studied using parietal endoscopic pH-metry ("Gastroduodenal Motility Analysis System"). The levels of free sialic acids (FSAs), oligosaccharide-bound sialic acids (OBSAs), and protein-bound fucose (PBF) in gastric juice were measured. After the treatment course, the baseline acidity in the observation group approached normal values in the esophagus (before treatment 1.92 ± 0.14; after treatment 4.83 ± 0.3; p < 0.001), the gastric body (before treatment 1.92 ± 0.14; after treatment 2.45 ± 0.18; p < 0.05), and the antrum (before treatment 1.23 ± 0.1; after treatment 3.63 ± 0.23, p < 0.05). In the comparison group, a certain increase in pH in the esophagus and gastric fundus was also observed after therapy, but overall, the indicators indicated persistent hyperacidity. In the observation group, the concentration of OBSAs significantly decreased by 3.4-fold (p < 0.001), free FSAs by 1.6-fold (p < 0.05), and PBF by 1.4-fold (p < 0.05). The authors concluded that the use of low-mineralized mineral water in a balneological resort setting for treating GERD in children provides an antacid and anti-inflammatory effect [100]. Further research is needed regarding the catamnestic follow-up of patients who received mineral waters.

Comment 2. Physiotherapy modalities can be used, such as sinusoidal modulated current therapy (SMT therapy), electrosleep therapy (low-frequency pulsed electrotherapy according to the electrosleep method), microwave therapy (superhigh-frequency electromagnetic field), structural-resonance electromagnetotherapy (SRT), and local low-frequency magnetotherapy (low-frequency alternating magnetic field) [52].

Contraindications to physical factors:

○ Severe GERD complicated by strictures, ulcers, or esophageal variceal bleeding;

○ Presence of a hiatal hernia requiring surgical treatment;

○ Barrett's esophagus;

○ Presence of a benign or malignant tumor;

○ Presence of general contraindications to physical therapy methods [101].

5. Prevention and Dispensary Observation

5.1 Prevention

• Weight loss management;

• Limitation of foods that increase intra-abdominal pressure (carbonated beverages, beer, legumes);

• Exclusion of foods that enhance peristalsis and gastroesophageal reflux (coffee, chocolate, fatty and spicy foods, etc.);

• Limitation of foods with acid-stimulating effects: flour products, chocolate, citrus fruits, spices, fatty and fried dishes, radishes, daikon;

• Meals should be taken in small portions, chewing slowly, avoiding talking while eating;

• Limitation of heavy lifting (no more than 8-10 kg);

• Elevating the head of the bed by ten to fifteen centimeters;

• Limitation of medications that relax the esophageal sphincter;

• Avoiding the horizontal position for two to three hours after eating.

• Patients should be educated on the adverse effects of tobacco smoke and alcohol on the esophageal mucosa and the condition of the cardiac sphincter [22].

Vaccination

GERD is not a contraindication to vaccination with any type of vaccine [Order of the Russian Ministry of Health No. 1122n dated December 6, 2021, "On Approval of the National Schedule of Preventive Vaccinations and the Schedule of Preventive Vaccinations by Epidemiological Indications", Methodological Guidelines MU 3.3.1.1095–02. Medical contraindications to preventive vaccinations with preparations of the national vaccination schedule].

5.2 Dispensary monitoring

• The recommended frequency of specialist examinations (dispensary appointment (examination, consultation) by a pediatrician and/or gastroenterologist) is at least 2 times per year for 3 years from the date of the last visit [94], taking into account the severity of clinical symptoms and clinical-endoscopic findings.

Level of Certainty of Evidence – C, Target Confidence Level of Evidence – 5

Comments:

Performance of EGD: the frequency of EGD depends on clinical and anamnestic data, results of previous endoscopic examinations, and the duration of clinical remission:

A) in endoscopically negative GERD and grade I reflux esophagitis, EGD is indicated upon exacerbation of the disease,

B) in GERD and/or grade II-III reflux esophagitis, EGD is indicated once a year, as well as upon exacerbation of the disease,

C) in GERD with grade IV reflux esophagitis (esophageal ulcer, Barrett's esophagus), EGD is indicated every 6 months in the first year of follow-up and once a year (provided clinical remission of the disease is achieved) in subsequent years of follow-up.

6. Organization of Medical Care

Children with GERD may receive medical care of any form, setting, and type depending on the clinical situation.

○ Children with GERD are followed up by a pediatrician/general practitioner (family doctor) and a gastroenterologist; in the presence of comorbid pathology, jointly with relevant specialists, including a pediatric surgeon.

○ Patients with complicated GERD (esophageal strictures, bleeding, Barrett's esophagus) are followed up in cooperation with a pediatric surgeon; if malignancy is suspected, children with Barrett's esophagus should be referred to a pediatric oncologist.

○ Patients with symptoms requiring emergency intervention (dysphagia, weight loss, hematemesis, or recurrent vomiting) require an urgent consultation with a pediatric surgeon [94] (as a rule, children with GERD do not need inpatient care in a 24-hour hospital, except for complicated cases and indications for surgical intervention. Hospitalization in a day hospital is advisable to establish the diagnosis, adjust therapy if necessary, and carry out rehabilitation measures. Indications for emergency hospitalization include repeated episodes of apnea and profuse bleeding from esophageal erosions or ulcers).

○ The organization of dietary nutrition for patients during inpatient treatment in medical organizations is carried out in accordance with Appendix 3 of the Order of the Russian Ministry of Health No. 1008n dated September 23, 2020, "On Approval of the Procedure for Providing Patients with Therapeutic Nutrition".

7. Additional Information

7.1 Complications

A formidable complication of GERD is esophageal strictures, which occur upon scarring of ulcerative defects. In this case, against the background of chronic inflammation, the deep layers of the esophageal wall and perieploeic/periesophageal tissues become involved in the process, i.e., peri-esophagitis occurs. The predominance of fibrosis leads to scar formation, resulting in the development of peptic esophageal stricture.

One of the most serious complications of GERD is Barrett's esophagus (BE), a precancerous condition and background disease for the development of esophageal adenocarcinoma. Literature data indicate that the frequency of BE in children with esophagitis ranges from 6.2 to 13%. One study presents the results of endoscopic examinations in which BE was detected in 2.7% of children. The main diagnostic method that helps suspect BE is EGD. This method allows for a visual assessment of the esophagus and the esophagogastric junction, as well as obtaining biopsy material for histological and, if necessary, immunohistochemical examination.

Another serious complication of GERD is posthemorrhagic anemia, which can occur both in sliding hiatal hernia, the strangulation of which injures the mucosa of the diaphragmatic "sac", and as a result of erosive and ulcerative lesions of the esophageal mucosa.

7.2 Outcomes and Prognosis

The prognosis is favorable in the majority of children with GERD.

In children with Barrett's esophagus, one should keep in mind the likelihood of developing adenocarcinoma or squamous cell carcinoma, even despite ongoing treatment. Prognostically unfavorable signs include: an area of esophageal epithelial metaplasia with a diameter of 8 cm or more, as well as the presence of a hiatal hernia. Malignancy of BE in children is extremely rare, however, there is evidence that 33% of children with clinical GERD may develop a malignant neoplasm in the esophagus in the subsequent 50 years of life.

Criteria for Evaluating the Quality of Medical Care

Table 1 – Criteria for the quality of specialized medical care.

References

Appendix A1. Working Group Composition

Alekseeva A.A. — Candidate of Medical Sciences, Deputy Head of the Consultative and Diagnostic Center for Children, Pediatrician, Head of the Multidisciplinary Pediatric Day Hospital, Allergist-Immunologist, Leading Research Scientist at the Department of Clinical Immunology and Allergology, Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Member of the Union of Pediatricians of Russia.

Apkhanova T.V. — Doctor of Medical Sciences, Chief Research Scientist at the Department of Physiotherapy and Reflexology, National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health, Member of the National Association of Health Resort Treatment Experts.

Baranov A.A. — Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences; Honorary President of the Union of Pediatricians of Russia, Advisor to the Head of the Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Professor at the Department of Pediatrics and Pediatric Rheumatology, Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University), Chief freelance Pediatrician of the Russian Ministry of Health.

Bataev S.M. — Doctor of Medical Sciences, Professor at the Department of Pediatrics and Pediatric Surgery, Burnasyan Federal Medical Biophysical Center of the Federal Medical-Biological Agency (FMBA of Russia), Pediatric Surgeon at the Surgical Department of the Federal Scientific and Clinical Center for Children and Adolescents of the Federal Medical-Biological Agency.

Batysheva T.T. — Doctor of Medical Sciences, Professor, Chief freelance Pediatric Specialist in Medical Rehabilitation of the Russian Ministry of Health, Chief freelance Pediatric Specialist in Neurology of the Moscow Healthcare Department, Director of the Scientific and Practical Center for Child Psychoneurology of the Moscow Healthcare Department, Honored Physician of the Russian Federation, Head of the Department of Neurology, Physical Rehabilitation Medicine, and Child Psychology, Advanced Training Faculty for Medical Workers, Peoples' Friendship University of Russia (RUDN University), Moscow.

Belmer S.V. — Professor, Doctor of Medical Sciences, Professor at the Department of Hospital Pediatrics No. 2, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Co-Chair of the Society of Pediatric Gastroenterologists, Hepatologists, and Nutritionists, Member of the Union of Pediatricians of Russia.

Belyaeva I.A. — Doctor of Medical Sciences, Head of the Department of Preconceptional, Antenatal, and Neonatal Medicine, Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University), Member of the Union of Pediatricians of Russia, Honorary Professor of the Russian Association of Perinatal Medicine Specialists.

Budkina T.N. — Candidate of Medical Sciences, Endoscopist at the Endoscopic Research Department, Senior Research Scientist at the Laboratory of Endoscopic, Morphological, and Pathological Anatomy Research, National Medical Research Center for Children's Health of the Russian Ministry of Health.

Bykova O.V. — Doctor of Medical Sciences, Head of the Research Department, Scientific and Practical Center for Child Psychoneurology of the Moscow Healthcare Department, Professor at the Department of Neurology, Physical and Rehabilitation Medicine of Childhood, Advanced Training Faculty for Medical Workers, Peoples' Friendship University of Russia (RUDN University), Moscow.

Vishneva E.A. — Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Deputy Head of the Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health, Member of the Union of Pediatricians of Russia.

Volynets G.V. — Doctor of Medical Sciences, Professor at the Department of Innovative Pediatrics and Pediatric Surgery, Faculty of Postgraduate Medical Education, Associate Professor at the Department of Pediatrics with Infectious Diseases in Children, Faculty of Postgraduate Medical Education, Pirogov Russian National Research Medical University of the Russian Ministry of Health. Head of the Department of Gastroenterology, Veltischev Research Institute of Pediatrics. Member of the Society of Pediatric Gastroenterologists, Hepatologists, and Nutritionists, Member of the Union of Pediatricians of Russia.

Gavrilyuk V.P. — Doctor of Medical Sciences, Associate Professor, Head of the Department of Pediatric Surgery and Pediatrics, Institute of Continuing Education, Vice-Rector for Educational Activities and General Affairs, Kursk State Medical University of the Russian Ministry of Health, Member of the Russian Association of Pediatric Surgeons.

Gordeeva E.A. — Pediatrician, Filatov City Children's Clinical Hospital of the Moscow Healthcare Department.

Gundobina O.S. — Candidate of Medical Sciences, Gastroenterologist, Leading Research Scientist at the Department of Orphan Diseases and Prevention of Disabling Conditions, Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Member of the Union of Pediatricians of Russia.

Gurova M.M. — Doctor of Medical Sciences, Leading Research Scientist at the Laboratory of Medical and Social Problems in Pediatrics, Scientific Research Center of Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health, Professor at the Department of Propaedeutics of Children's Diseases with a Course in General Nursing, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health, Professor at the Department of Pediatrics, Medical Institute, Belgorod State National Research University, Member of the Union of Pediatricians of Russia, Member of the Society of Pediatric Gastroenterologists, Hepatologists, and Nutritionists, Deputy Chief Medical Officer, Saint Petersburg Consultative and Diagnostic Center for Children.

Zagorsky S.E. (Minsk) — Professor, Doctor of Medical Sciences.

Zokirov N.Z. — Doctor of Medical Sciences, Head of the Department, Academy of Postgraduate Education, Federal Scientific and Clinical Center of the Federal Medical-Biological Agency, Federal Scientific and Clinical Center for Children and Adolescents of the Federal Medical-Biological Agency, Member of the Union of Pediatricians of Russia.

Kaitukova E.V. — Candidate of Medical Sciences, Deputy Head for Medical Operations — Head of the Consultative and Diagnostic Center for Children, Gastroenterologist, Leading Research Scientist at the Department of Orphan Diseases and Prevention of Disabling Conditions, Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Associate Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University), Member of the Union of Pediatricians of Russia.

Karatseva M.S. — Junior Research Scientist, Pediatrician, Scientific and Practical Center for Child Psychoneurology of the Moscow Healthcare Department, Member of the Union of Pediatricians of Russia.

Klimov Yu.A. — Candidate of Medical Sciences, Deputy Director for Medical Work, Scientific and Practical Center for Child Psychoneurology of the Moscow Healthcare Department; Head of the Department of Neurology and Neurosurgery, Russian State Social University.

Komarova E.V. — Doctor of Medical Sciences, Deputy Head for Expertise of Innovative Treatment and Rehabilitation Methods, Gastroenterologist, Chief Research Scientist at the Department of Orphan Diseases and Prevention of Disabling Conditions, Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University), Member of the Union of Pediatricians of Russia.

Konchugova T.V. — Doctor of Medical Sciences, Professor, Chief Research Scientist at the Department of Physiotherapy and Reflexology, National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health, Member of the National Association of Health Resort Treatment Experts.

Kornienko E.A. – Doctor of Medical Sciences, Professor at the Department of Children's Diseases named after Professor I.M. Vorontsov, Faculty of Postgraduate and Additional Professional Education, St. Petersburg State Pediatric Medical University of the Russian Ministry of Health; Chief freelance pediatric gastroenterologist of the Health Committee of the Government of St. Petersburg; Member of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists; Member of the Union of Pediatricians of Russia.

Korolev G.A. – Candidate of Medical Sciences, endoscopist at the Endoscopic Research Department, National Medical Research Center for Children's Health of the Russian Ministry of Health.

Kulikova N.V. – Thoracic surgeon, N.F. Filatov Children's City Clinical Hospital of the Moscow Healthcare Department.

Lokhmatov M.M. – Doctor of Medical Sciences, endoscopist, Head of the Endoscopic Research Department, Chief Researcher at the Laboratory of Endoscopic, Morphological and Pathological Studies, National Medical Research Center for Children's Health of the Russian Ministry of Health; Professor at the Department of Pediatric Surgery and Urology-Andrology named after Professor L.P. Alexandrov, I.M. Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University).

Luppova N.E. – Candidate of Medical Sciences.

Mitupov Z.B. – Doctor of Medical Sciences, Professor at the Department of Pediatric Surgery named after Yu.F. Isakov, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University).

Naletov A.V. – Doctor of Medical Sciences, Professor, Head of the Department of Pediatrics No. 2, Donetsk State Medical University named after M. Gorky of the Ministry of Health of the Russian Federation; Chief freelance pediatric specialist gastroenterologist of the Ministry of Health of the Donetsk People's Republic.

Namazova-Baranova L.S. – Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, President of the Union of Pediatricians of Russia; Past President of EPA/UNEPSA; Head of the Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Center of Surgery; Head of the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University); Chief freelance pediatric specialist in preventive medicine of the Russian Ministry of Health.

Novikova V.P. – Doctor of Medical Sciences, Professor, Head of the Department of Propaedeutics of Children's Diseases with a Course in General Nursing, St. Petersburg State Pediatric Medical University of the Russian Ministry of Health; Head of the Laboratory of Medicosocial Problems of Pediatrics, Research Center of St. Petersburg State Pediatric Medical University of the Russian Ministry of Health; Member of the Union of Pediatricians of Russia; Member of the Russian Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists.

Oldakovsky V.I. – Endoscopist at the Endoscopic Research Department, Junior Researcher at the Laboratory of Endoscopic, Morphological and Pathological Studies, National Medical Research Center for Children's Health of the Russian Ministry of Health.

Pakhomovskaya N.L. – Candidate of Medical Sciences, Member of the Union of Pediatricians of Russia

Pechkurov D.V. – Doctor of Medical Sciences, Professor, Head of the Department of Children's Diseases, Samara State Medical University of the Russian Ministry of Health; Member of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists; Member of the Union of Pediatricians of Russia.

Platonova M.M. – Candidate of Medical Sciences, Researcher at the Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Center of Surgery; Pulmonologist.

Poddubny I.V. – Doctor of Medical Sciences, Professor, Head of the Department of Pediatric Surgery, N.A. Semashko Research Institute of Clinical Medicine, Russian University of Medicine of the Russian Ministry of Health; Head of the Thoracoabdominal Surgery Center, Federal Scientific and Clinical Center for Children and Adolescents of the Federal Medical-Biological Agency; Member of the Russian Association of Pediatric Surgeons.

Potapov A.S. – Doctor of Medical Sciences, Professor, Head of the Center for Inflammatory Bowel Diseases in Children, Head of the Gastroenterology Department, National Medical Research Center for Children's Health of the Russian Ministry of Health; Professor at the Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University (Sechenov University); Member of the Union of Pediatricians of Russia, Member of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN); National Representative for Russia in the European Crohn's and Colitis Organisation (ECCO).

Privorotsky V.F. – Professor, Doctor of Medical Sciences, Member of the Society of Pediatric Gastroenterologists and Hepatologists.

Razumovsky A.Yu. – Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Head of the Department of Pediatric Surgery named after Yu.F. Isakov, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University); President of the Russian Association of Pediatric Surgeons.

Revunenkov G.V. – Candidate of Medical Sciences, Leading Researcher, Head of the Department of Innovative Diagnostic Research Methods, Ultrasound Diagnostics Physician at the Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Center of Surgery; Member of the Union of Pediatricians of Russia.

Selimzyanova L.R. – Candidate of Medical Sciences, Head of the Department of Standardization and Study of Evidence-Based Medicine Foundations, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Center of Surgery; Associate Professor at the Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University); Associate Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University); Member of the Union of Pediatricians of Russia.

Surkov A.N. – Doctor of Medical Sciences, Head of the Pediatric Gastroenterology Department (Inpatient Unit for Children), Head of the Department of Scientific Foundations of Pediatric Gastroenterology, Hepatology and Metabolic Disorders, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Center of Surgery; Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University); Member of the Union of Pediatricians of Russia.

Sytkov V.V. – Candidate of Medical Sciences, Associate Professor at the Department of Pediatric Surgery, N.A. Semashko Research Institute of Clinical Medicine, Russian University of Medicine of the Russian Ministry of Health; Coloproctologist, pediatric surgeon at the Surgical Department, Federal Scientific and Clinical Center for Children and Adolescents of the Federal Medical-Biological Agency; Member of the Union of Pediatricians of Russia; Member of the Russian Association of Pediatric Surgeons, Russian Society of Colorectal Surgeons.

Tikhonov S.V. – Candidate of Biological Sciences, Scientific Secretary, Scientific and Practical Center for Child Psychoneurology of the Moscow Healthcare Department; Associate Professor at the Department of Neurology, Physical and Rehabilitation Medicine, Faculty of Continuous Medical Education, Medical Institute of RUDN University, Moscow.

Teplov V.O. – Candidate of Medical Sciences, endoscopist, N.F. Filatov Children's City Clinical Hospital of the Moscow Healthcare Department.

Tupylenko A.V. – Candidate of Medical Sciences, endoscopist at the Endoscopic Research Department, Senior Researcher at the Laboratory of Endoscopic, Morphological and Pathological Studies, Assistant at the Department of Pediatric Surgery with a Course in Anesthesiology and Intensive Care, Institute of Medical Personnel Training, National Medical Research Center for Children's Health of the Russian Ministry of Health.

Turti T.V. – Doctor of Medical Sciences, Chief Researcher at the Department of Preconceptional, Antenatal and Neonatal Medicine, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Center of Surgery; Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University); Member of the Union of Pediatricians of Russia.

Khavkin A.I. – Doctor of Medical Sciences, Professor, Head of the A.V. Mazurin Moscow Regional Center for Pediatric Gastroenterology and Hepatology, Research Clinical Institute of Childhood of the Ministry of Health of the Moscow Oblast; Professor at the Department of Pediatric Diseases, Medical Institute, Belgorod State National Research University; Chairman of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists of Russia; Member of the Union of Pediatricians of Russia.

Fedoseenko M.V. – Candidate of Medical Sciences, Head of the Department for the Development of Scientific Approaches to Immunization of Patients with Health Deviations and Chronic Diseases, Leading Researcher, Pediatrician at the Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Center of Surgery; Associate Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Russian Ministry of Health (Pirogov University); Member of the Union of Pediatricians of Russia.

Tsatsa M.V. – Pediatric surgeon at the Surgical Department, Federal Scientific and Clinical Center for Children and Adolescents of the Federal Medical-Biological Agency.

Shcherbak V.A. – Professor, Doctor of Medical Sciences, Member of the Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists.

Efendieva K.E. — PhD in Medicine, Deputy Head for International Relations and Educational Activities, Leading Researcher, Allergist-Immunologist at the Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Center of Surgery, Associate Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health, Member of the Union of Pediatricians of Russia.

Yablokova E.A. — PhD in Medicine, Associate Professor at the Department of Children's Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Russian Ministry of Health, Leading Researcher at the Department of Pediatrics, Research Institute of Pediatrics of the Ministry of Health of the Moscow Region, Chief Freelance Pediatric Gastroenterologist of the Ministry of Health of the Moscow Region, Member of the Union of Pediatricians of Russia, Member of the Society of Pediatric Gastroenterologists, Hepatologists, and Nutritionists.

The authors declare no financial support or conflicts of interest that need to be disclosed.

Appendix A2. Methodology for Developing Clinical Guidelines

The development adhered to the principles that guarantee high-quality and reliable clinical guidelines.

Methods used for collecting/selecting evidence

Search in electronic databases.

Description of methods used for collecting/selecting evidence

The evidence base includes publications included in the Cochrane Library, EMBASE, and MEDLINE databases. The search depth was 10 years.

Methods used for assessing the quality and strength of evidence

Expert consensus.

Table 1. Scale for assessing the levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing the levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for assessing the grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The update mechanism for clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more than once every 6 months.

Methods used for evidence analysis:

• Reviews of published meta-analyses;

• Systematic reviews with evidence tables.

Description of methods used for evidence analysis

To eliminate the influence of subjective factors and minimize potential errors, each study was evaluated independently by at least two independent members of the working group. Any discrepancies in evaluations were discussed by the full working group. If consensus could not be reached, an independent expert was involved.

Methods used to formulate the recommendations

Expert consensus.

Method for validation of recommendations

- External peer review

- Internal peer review

Description of the recommendation validation method

The draft version of these recommendations was reviewed by independent experts who determined that the evidence underlying these recommendations is comprehensible.

These recommendations were reviewed by pediatricians who noted the clarity of presentation and their importance as a working tool in daily practice.

All comments received from experts were carefully systematized and discussed by the chair and members of the working group, and amendments were made to the clinical guidelines where necessary.

Economic analysis

Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.

Consultation and peer review

The latest amendments to these guidelines were submitted for discussion in a preliminary version at the meeting of the working group, the Executive Committee of the Union of Pediatricians of Russia, and members of the specialized commission in February 2015.

The draft guidelines were also peer-reviewed by independent experts who were asked to comment on the clarity and accuracy of the interpretation of the evidence base underlying the guidelines.

Appendix A3. Reference Materials

Regulatory and legal documentation:

1. Order of the Ministry of Health and Social Development of the Russian Federation No. 366n of April 16, 2012, "On Approval of the Procedure for Providing Pediatric Care";

2. Order of the Russian Ministry of Health No. 1094n dated November 24, 2021, "On Approval of the Procedure for Prescribing Medicinal Products, Prescription Form Templates for Medicinal Products, the Procedure for Issuing These Forms, Their Accounting and Storage, Templates of Prescription Forms Containing Prescriptions for Narcotic Drugs or Psychotropic Substances, the Procedure for Their Manufacture, Distribution, Registration, Accounting and Storage, as well as the Rules for Issuing Prescription Forms, Including in the Form of Electronic Documents";

3. Order of the Government of the Russian Federation No. 3053-r dated December 31, 2018, "On approval of the lists of medical devices implanted into the human body when providing medical care within the framework of the state guarantee program for the free provision of medical care to citizens and dispensed on prescriptions for medical devices when providing a set of social services";

4. International Statistical Classification of Diseases and Related Health Problems (ICD-10);

5. Order of the Russian Ministry of Health No. 205n dated May 2, 2023 (as amended on December 4, 2023) "On approval of the Nomenclature of positions of medical workers and pharmaceutical workers" (Registered with the Ministry of Justice of Russia on June 1, 2023, No. 73664);

6. Order of the Ministry of Health of the Russian Federation No. 541n dated July 23, 2010. Unified Qualification Handbook of Positions of Managers, Specialists, and Employees, section Qualification Characteristics of Healthcare Sector Employee Positions;

7. Federal Law No. 489-FZ dated December 25, 2018, "On Amendments to Article 40 of the Federal Law 'On Compulsory Health Insurance in the Russian Federation' and the Federal Law 'On the Basics of Protecting the Health of Citizens in the Russian Federation' Regarding Clinical Guidelines";

8. Order of the Russian Ministry of Health No. 103n dated February 28, 2019, "On Approval of the Procedure and Timelines for the Development of Clinical Practice Guidelines, Their Revision, Standard Template of Clinical Practice Guidelines and Requirements for Their Structure, Composition and Scientific Validity of Information Included in Clinical Practice Guidelines";

9. Order of the Russian Ministry of Health No. 804n dated October 13, 2017, "On approval of the nomenclature of medical services";

10. Order of the Ministry of Health and Social Development of Ukraine/Russian Federation «On the procedure for the use of medicinal products in patients for vital indications» dated August 9, 2005, No. 494;

11. Information letter of the Russian Ministry of Health on the possibility of procuring a medicinal product by its trade name (https://www.rosminzdrav.ru/news/2019/12/18/13043-minzdrav-podgotovil-informatsionnoe-pismo-po-vozmozhnosti-zakupki-lekarstvennogo-preparata-po-torgovomu-naimenovaniyu);

12. Order of the Ministry of Health of the Russian Federation No. 1008n dated September 23, 2020, "On Approval of the Procedure for Providing Patients with Therapeutic Nutrition."

Appendix A3.1 Example of diagnosis formulation

Gastroesophageal reflux disease (reflux esophagitis grade II), erosive esophagitis, stage A

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

What causes reflux?

After swallowing, food travels down the esophagus. Upon entering the stomach, it stimulates cells that produce acid and pepsin (an enzyme), which are necessary for digestion. A bundle of muscle at the lower end of the esophagus, called the lower esophageal sphincter (LES), acts as a barrier to prevent the backward flow (reflux) of stomach contents into the esophagus. To allow a swallowed portion of food to pass into the stomach, the LES relaxes. When this barrier relaxes at the wrong time, when it is weak, or when it is insufficiently effective for other reasons, reflux can occur. Factors such as bloating, delayed gastric emptying, a significant hiatal hernia, or too much acid in the stomach can also trigger acid reflux.

Gastroesophageal reflux can be aggravated by certain foods. Most commonly causing concern are chocolate, onions, fried foods, fatty foods, mint, alcohol, caffeine, carbonated beverages, and acidic foods. Spicy foods and citrus products can increase heartburn. A large amount of fatty food, which slows down gastric emptying, eaten late in the evening can contribute to nighttime heartburn. Alcohol can relax the lower esophageal sphincter and thereby increase reflux.

Gastroesophageal reflux disease (GERD) is a relapsing and chronic condition for which long-term medical therapy is generally effective. It is important to recognize that chronic reflux does not resolve on its own. There is currently no cure for GERD. Therefore, GERD requires long-term and adequate therapy. Treatment may include lifestyle modifications, drug therapy, surgery, or a combination thereof.

Factors that may exacerbate symptoms should be avoided; therefore, it is necessary to: reduce fat intake (they delay gastric emptying and lower lower esophageal sphincter pressure), decrease the intake of caffeine, chocolate, onions, mint, and carbonated beverages (they decrease LES pressure), stop or reduce the intake of citrus fruits and tomatoes (acidic foods increase esophageal sensitivity to acid), and increase protein intake (it can accelerate gastric emptying). Alcohol and smoking also negatively affect LES pressure and acid secretion. Lying down within 3–4 hours after eating is discouraged (stomach distension stimulates LES relaxation).

Bending over or exercises that may increase intra-abdominal pressure must be avoided.

Elevating the head of the bed by about 15 cm can help clear acid refluxed during the night from the esophagus more quickly. Sleeping on one side (usually the left) can help reduce the amount of reflux. Try to ensure a sound night's sleep by engaging in calm activities before bedtime and going to bed at the same time.

You should inform your doctor about all medications you are taking. Some medications can worsen symptoms. Here are a few examples: nonsteroidal anti-inflammatory drugs (used to treat arthritis and general inflammatory processes) can cause direct damage to the esophagus; sedatives (a number of calming agents) and calcium channel blockers (used mainly to treat high blood pressure) relax the LES; sedatives slow down gastric emptying and provoke reflux.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Not applicable.