Gastroesophageal reflux (GER) refers to the backflow of gastric contents, including bile salts and pancreatic enzymes from the duodenum into the stomach, and further into the esophagus or even the oropharynx. It is categorized as either physiological or pathological. Under physiological conditions, infants may experience reflux—commonly referred to as "spit-up"—because of the immature development of the lower esophageal sphincter (LES) and poor neuromuscular coordination. Pathological reflux, however, is caused by LES dysfunction and/or structural abnormalities of related tissues, leading to reduced LES pressure. This type of reflux can occur during sleep, in the supine position, or when fasting, resulting in a series of clinical symptoms and complications, collectively termed gastroesophageal reflux disease (GERD). As children spend more time upright and transition to solid foods, symptoms resolve spontaneously in about 60% of cases by the age of 2 years, though some may persist beyond age 4. Children with developmental conditions such as cerebral palsy, Down syndrome, or developmental delays of other causes have a higher prevalence of GER.
Etiology and Pathogenesis
Decreased Anti-Reflux Barrier Function
Reduced LES pressure is the primary cause of GER. Normally, during swallowing, LES relaxes reflexively, its pressure decreases, and peristalsis propels food into the stomach. This is followed by a return to normal pressure, with a reactive increase in pressure to prevent reflux. When gastric or intra-abdominal pressure rises, LES actively contracts to exceed this pressure, serving as a barrier against reflux. Disruptions in these mechanisms, such as transient LES relaxation, can allow gastric contents to flow back into the esophagus.
Impaired function of surrounding tissues can also contribute. For example, the absence of an intra-abdominal esophageal segment may prevent LES from responding to increases in abdominal pressure. Additionally, large anatomical angles at the gastroesophageal junction (His angle, normally 30°–50°), reduced crural diaphragm function, structural or functional abnormalities in the diaphragm-esophageal ligament and lower esophageal mucosal folds, as well as increased gastric and intra-abdominal pressures, can all compromise anti-reflux defenses.
Decreased Esophageal Clearing Capacity
Effective esophageal clearing relies on coordinated peristalsis, saliva to wash away refluxate and neutralize acid, gravitational effects on the food bolus, and bicarbonate secretion by esophageal mucosa. A weakened or absent peristalsis, or abnormal motility, can impair clearing of the refluxate. This lengthens the contact time of harmful substances with esophageal mucosa, increasing the risk of damage.
Disrupted Esophageal Mucosal Barrier Function
The mucosal barrier is composed of the mucus layer, intracellular buffers, cell metabolism, and blood supply. Components of refluxate, such as gastric acid, pepsin, bile salts, and pancreatic enzymes from duodenal reflux, can impair this mucosal barrier, causing inflammation of the esophageal lining.
Gastrointestinal Dysfunctions
Delayed gastric emptying increases the volume and pressure of gastric contents. When gastric pressure exceeds LES pressure, reflux occurs. An over-expanded stomach from increased gastric volume can shorten the gastroesophageal segment, further weakening anti-reflux defenses. Dysfunction of the duodenum or incomplete pyloric sphincter closure facilitates duodenogastroesophageal reflux (DGER).
Clinical Manifestations
Symptoms vary in severity depending on the intensity and duration of reflux, presence of complications, and patient age.
Vomiting
Vomiting is the predominant symptom in neonates and young children. Most cases present within the first week of life, while others emerge within 6 weeks. Vomiting is often triggered by feeding, sometimes occurring at night or on an empty stomach, and may become forceful in severe cases. The vomit often consists of gastric contents, sometimes with traces of bile. Some infants exhibit spitting up, regurgitation, or producing frothy bubbles. Older children may present with regurgitation, acidic reflux, or belching.
Reflux Esophagitis
The following are commonly observed symptoms:
- Heartburn: Reported by older children capable of verbal expression, often felt in the lower sternum. Symptoms worsen with consumption of acidic beverages.
- Odynophagia: Infants may display feeding difficulties, irritability, or refusal to eat; older children may complain of pain while swallowing. Esophageal strictures can result in severe vomiting and persistent dysphagia.
- Hematemesis or Melena: Severe esophagitis can cause erosions or ulcers, resulting in vomiting blood or passing black, tarry stools. Advanced esophagitis can lead to iron-deficiency anemia.
Barrett's Esophagus
Chronic GER may cause squamous epithelium in the distal esophagus to transform into columnar epithelium, which is more resistant to acid but more prone to complications such as esophageal ulcers, strictures, or even adenocarcinoma. Severe ulcerations may also lead to tracheoesophageal fistula formation.
Extra-Esophageal Symptoms
Respiratory System Disorders Linked to GERD
Recurrent Respiratory Infections
Direct or indirect effects of gastric refluxate contribute to recurrent respiratory infections and aspiration pneumonia.
Asthma
Gastric reflux irritates esophageal sensory receptors, which trigger reflex bronchospasms. Asthma associated with early onset, poor response to asthma medications, and lack of familial allergy history may have GERD as an underlying cause.
Apnea and Suffocation
These are more frequent in premature or young infants, with laryngospasms induced by reflux causing airway obstruction. Symptoms include cyanosis, pallor, bradycardia, or even sudden infant death syndrome.
Nutritional Deficiencies
Feeding difficulties resulting from vomiting and esophagitis may lead to inadequate nutrient intake, causing poor weight gain, growth retardation, and anemia.
Other Complications
These include hoarseness, otitis media, sinusitis, recurrent oral ulcers, and dental caries. Some children may also develop psychological or neurological symptoms:
Sandifer Syndrome is seen in pathological GER, characterized by unusual posturing resembling torticollis in which infants adopt a "cock-robin" head position after feeding as a protective mechanism to maintain airway patency and reduce acid reflux-related pain. It may also be accompanied by digital clubbing, protein-losing enteropathy, or anemia.
Crying-Fussiness Syndrome in Infants manifests as irritability, night terrors, and crying during feeding.
Auxiliary Tests
Esophageal Barium Swallow
This procedure evaluates the morphology, motility, reflux of the barium contrast agent, and the structural connection between the esophagus and the stomach. Congenital abnormalities, such as hiatal hernias, can be identified, as well as complications in severe cases, such as esophageal ulcers or strictures.
Esophageal pH Monitoring
A microelectrode is inserted through the nostril and positioned above the lower esophageal sphincter (LES) to monitor esophageal pH over 24 hours. A drop in pH indicates the occurrence of acidic GER. Computer software analyzes reflux frequency, duration, and the retention of refluxate in the esophagus, as well as the relationship between reflux events, daily activities, and clinical symptoms. Scoring systems can distinguish between physiological and pathological reflux, making this approach the most reliable diagnostic method. It is particularly valuable in cases with atypical symptoms or to investigate symptoms such as coughing, choking, wheezing, or apnea. Concurrent pH monitoring of both the esophagus and stomach can help identify alkaline GER or duodenogastroesophageal reflux (DGER) when pH in the distal esophagus does not decline.
Esophageal Manometry
Measurement equipment such as low-compliance perfusion catheter systems or intraluminal micro-sensor catheter systems is used to evaluate esophageal motility and LES function. Continuous pressure monitoring and dynamic observation of esophageal motor function are necessary in patients with normal LES pressure.
Esophagoscopy and Mucosal Biopsy
Diagnostic criteria and grading for endoscopic examination are as follows:
- Grade 0: No abnormalities in esophageal mucosa.
- Grade I: Punctate or linear erythema and erosion without fusion.
- Grade II: Linear erythema and erosion with fusion (less than two-thirds of the mucosal circumference).
- Grade III: Extensive erythema and erosion with circumferential involvement or ulceration.
Histological findings from esophageal mucosal biopsy may include squamous epithelial basal cell hyperplasia and thickening, elongation of lamina propria papillae into the epithelium, infiltration of neutrophils, eosinophils, and lymphocytes in the epithelial layer, as well as mucosal erosion, ulceration, granulation tissue formation, and/or fibrosis. Barrett's esophagus is characterized by intestinal metaplasia of normal distal stratified squamous epithelium into columnar epithelium containing goblet cells.
Esophageal Bilirubin Monitoring
A portable 24-hour bilirubin monitoring probe is inserted through the nostril and placed above the LES. Data collected during supine and upright positions, meal times, and symptomatic episodes are processed using specialized software. This test provides evidence for bile reflux into the esophagus, indicative of duodenogastroesophageal reflux.
Gastroesophageal Radionuclide Scintigraphy
A liquid labeled with technetium-99m (99mTc) is administered orally or via a gastric tube. A gamma camera measures reflux volume, providing information on esophageal motility function.
Diagnosis
The clinical manifestations of GER are complex and lack specificity, making it challenging to differentiate GER from other conditions causing vomiting based on symptoms alone. Even when GER is identified, it is often difficult to distinguish between physiological and pathological reflux. GER should be considered in cases of recurrent vomiting, dysphagia, chronic or recurring respiratory tract infections, refractory asthma, growth retardation, malnutrition, unexplained irritability, anemia, repeated choking or apnea. Appropriate auxiliary tests should be selected based on the clinical context to establish a definitive diagnosis.
Differential Diagnosis
Achalasia of the Cardia
Also known as cardiospasm, this condition involves LES relaxation dysfunction, leading to esophageal functional obstruction. Symptoms in infants and young children include feeding difficulties and vomiting, with severe cases also presenting with malnutrition and growth retardation. Older children report chest pain, heartburn, and regurgitation. Diagnosis can be confirmed through barium swallow, endoscopy, and esophageal manometry.
Organic Gastrointestinal Disease
In neonates and young infants with vomiting as the primary symptom, organic gastrointestinal abnormalities should be excluded. These include obstructive disorders such as congenital hypertrophic pyloric stenosis, gastric volvulus, or malrotation of the intestines.
Injuries Due to Other Pathogenic Factors
For children with reflux esophagitis and complications, injuries caused by physical, chemical, or biological factors that present with similar symptoms must be excluded.
Treatment
A diagnosis of GER, particularly in cases involving complications or affecting growth and development, necessitates timely intervention.
Positional Therapy
The head of the bed is raised by 30 degrees. For infants, the optimal position is prone with the head tilted forward; however, to reduce the risk of sudden infant death syndrome (SIDS), a left lateral sleeping position is recommended during sleep. For children, an upright or seated position is ideal when awake, and a left lateral sleeping position with the upper body elevated is recommended during sleep to reduce the frequency of reflux and minimize the risk of aspiration of refluxate.
Dietary Therapy
A thickened dietary approach is adopted with frequent small meals. For infants, the frequency of milk feeding is increased, and formula-fed infants may benefit from the addition of starchy foods to the formula or consumption of cereal-based foods. Older children should similarly adhere to small, frequent meals, emphasizing a diet rich in protein and low in fat. Food intake is avoided within two hours before bedtime to maintain the stomach in a non-distended state. Foods that reduce LES pressure or increase gastric acid secretion, such as acidic beverages, high-fat diets, chocolate, and spicy foods, are avoided. Additionally, weight gain is regulated, and exposure to smoking and secondhand smoke is avoided.
Pharmacological Therapy
This strategy primarily aims to reduce the acidity of gastric contents and improve upper gastrointestinal motility. This includes prokinetic agents, antacids or acid-suppressing medications, and mucosal protectants. The appropriate age indications and potential side effects of medications are carefully considered during use.
Prokinetic Agents
A four-week treatment course is typically prescribed. These drugs increase LES tone, enhance esophageal and gastric motility, improve esophageal clearance, and promote gastric emptying. This combination decreases reflux and reduces the retention of refluxate in the esophagus. Examples include dopamine receptor antagonists, such as domperidone, with commonly recommended doses of 0.2–0.3 mg/kg per dose, administered three times a day orally, 30 minutes before meals and at bedtime (use is recommended for individuals over the age of 12 due to potential cardiac side effects).
Antacids and Acid-Suppressing Medications
An 8- to 12-week treatment course is typically prescribed. The primary goal is to inhibit acid secretion and neutralize gastric acid, thereby reducing mucosal damage caused by refluxate and increasing LES tone.
Acid-Suppressing Medications
H2-receptor blockers, such as cimetidine, ranitidine, famotidine, and nizatidine; or proton pump inhibitors (PPIs), including omeprazole, lansoprazole, and esomeprazole, can be selected based on the patient’s age.
Antacids
Aluminum hydroxide gel is an example of an antacid used to neutralize gastric acid, particularly in older children.
Mucosal Protectants
A 4- to 8-week treatment course is typically prescribed. Options include sucralfate, aluminum silicate salts, or aluminum phosphate. Detailed recommendations for the use of antacids, acid suppressants, and mucosal protectants can be found in Section V of this chapter.
Surgical Treatment
Most children experience significant improvement or complete resolution of symptoms with timely positional, dietary, and pharmacological treatments. Surgery may be considered under the following indications:
- Absence of improvement after 6–8 weeks of medical treatment, accompanied by severe complications, such as gastrointestinal bleeding, malnutrition, or growth retardation.
- Reflux caused by congenital esophageal hiatus hernia or severe esophagitis associated with bleeding, ulceration, or stricture.
- Presence of severe respiratory complications, such as airway obstruction, recurrent aspiration pneumonia, or asphyxia, potentially combined with bronchopulmonary dysplasia.
- Coexistence of severe neurological disorders.