Pediatric Gastroesophageal Reflux

Practice Essentials

In pediatric gastroesophageal reflux disease (GERD), immaturity of lower esophageal sphincter function is manifested by frequent transient lower esophageal relaxations, which result in retrograde flow of gastric contents into the esophagus.

Signs and symptoms

The symptoms of gastroesophageal reflux are most often directly related to the consequences of emesis (eg, poor weight gain) or result from exposure of the esophageal epithelium to the gastric contents. The typical adult symptoms (eg, heartburn, vomiting, regurgitation) cannot be readily assessed in infants and children.

Pediatric patients with gastroesophageal reflux disease typically cry and show sleep disturbance and decreased appetite. Other common signs and symptoms in infants and young children include the following:

• Typical or atypical crying and/or irritability
• Apnea and/or bradycardia
• Poor appetite; weight loss or poor growth (failure to thrive)
• Apparent life-threatening event
• Vomiting
• Wheezing, stridor
• Abdominal and/or chest pain
• Recurrent pneumonitis
• Sore throat, hoarseness and/or laryngitis
• Chronic cough
• Water brash
• Sandifer syndrome (ie, posturing with opisthotonus or torticollis)

Signs and symptoms in older children include all of the above plus heartburn and a history of vomiting, regurgitation, unhealthy teeth, and halitosis.

See Clinical Presentation for more detail.

Diagnosis

Most cases of pediatric gastroesophageal reflux are diagnosed based on the clinical presentation. Conservative measures can be started empirically. However, if the presentation is atypical or if therapeutic response is minimal, further evaluation via imaging is warranted.

There are no recognized classic physical signs of gastroesophageal reflux in the pediatric population. Some findings may include the following:

• Nonverbal infant: Crying and irritability, failure to thrive, hiccups, sleep disturbances, Sandifer syndrome (arching)
• Toddlers and older children: Significant dental problems from excessive regurgitation, causing acid effects on tooth enamel

Procedures

The following procedures are used to visually assess the esophagus and stomach:

• Esophageal manometry
• Esophagogastroduodenoscopy

Biopsies may also be performed during esophagogastroduodenoscopy for histopathologic evaluation.

Imaging studies

Radiologic studies used to evaluate pediatric gastroesophageal reflux include the following:

• Upper gastrointestinal imaging series
• Gastric scintiscan study
• Esophagography

Physiologic and electrophysiologic studies

The following studies are used to detect gastroesophageal reflux:

• Intraesophageal pH probe monitoring: Criterion standard for quantifying gastroesophageal reflux
• Intraluminal esophageal electrical impedance: For detecting acid and nonacid reflux by measuring retrograde flow in the esophagus; normal values have not been determined in the pediatric age group.

See Workup for more detail.

Management

The goals of medical therapy in gastroesophageal reflux are to decrease acid secretion and, in many cases, to reduce gastric emptying time.

Nonpharmacotherapy

Conservative measures in treating children with gastroesophageal reflux include the following^[1] :

• Providing small, frequent feeds thickened with cereal
• Upright positioning after feeding
• Elevating the head of the bed
• Prone positioning (infants >6 months)

Older children with gastroesophageal reflux may benefit from the following:

• Diet that avoids tomato and citrus products, fruit juices, peppermint, chocolate, and caffeine-containing beverages
• Smaller, more frequent feeds
• Relatively lower fat diet (lipids retards gastric emptying)
• Proper eating habits
• Weight loss
• Avoidance of alcohol and tobacco, when applicable

For patients who fail medical therapy, continuous intragastric administration of feeds alone (via nasogastric tube) may be used as an alternative to surgery.^[2]

Pharmacotherapy

The following medications are used in pediatric patients with gastroesophageal reflux disease:

• Antacids (eg, aluminum hydroxide, magnesium hydroxide)
• Histamine H2 antagonists (eg, nizatidine, cimetidine, ranitidine, famotidine)
• Proton pump inhibitors (eg, lansoprazole, omeprazole, esomeprazole,^[3] dexlansoprazole, rabeprazole sodium, pantoprazole)

No currently available prokinetic drug (eg, metoclopramide) has been demonstrated to exert a significant influence on the number or frequency of reflux episodes.

Surgical option

Surgical intervention such as gastrostomy or fundoplication (see the image below) is required in only a very small minority of patients with gastroesophageal reflux (eg, when rigorous medical step-up therapy has failed or when the complications of gastroesophageal reflux pose a short- or long-term survival risk). The goal of surgical antireflux procedures is to "tighten" the region of the lower esophageal junction and, if possible, to reduce hiatal herniation of the stomach (occasionally seen in patients with gastroesophageal reflux disease).

View Image

Illustration of the Nissen fundoplication. Note how the stomach is wrapped around the esophagus (360-degree wrap).

See Treatment and Medication for more detail.

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Background

Gastroesophageal reflux represents the most common gastroenterologic disorder that leads to referral to a pediatric gastroenterologist during infancy. In pediatric gastroesophageal reflux, immaturity of lower esophageal sphincter (LES) function is manifested by frequent transient lower esophageal relaxations (tLESRs), which result in retrograde flow of gastric contents into the esophagus. (See Etiology and Pathophysiology.)

Although minor degrees of gastroesophageal reflux are noted in children and adults, the degree and severity of reflux episodes are increased during infancy. Thus, gastroesophageal reflux represents a common physiologic phenomenon in the first year of life. As many as 60-70% of infants experience emesis during at least 1 feeding per 24-hour period by age 3-4 months. (See Epidemiology and Prognosis.)

The distinction between this "physiologic" gastroesophageal reflux and "pathologic" gastroesophageal reflux in infancy and childhood is determined not merely by the number and severity of reflux episodes (when assessed by intraesophageal pH monitoring), but also, and most importantly, by the presence of reflux-related complications, including failure to thrive, erosive esophagitis, esophageal stricture formation, and chronic respiratory disease. (See Prognosis, Presentation, and Workup.)

Other complications noted in adults with gastroesophageal reflux, including Barrett esophagus and esophageal mucosal dysplasia, are uncommon in childhood.

Gastroesophageal reflux is classified as follows (see Presentation, Workup, Treatment, and Medication):

• Physiologic (or functional) gastroesophageal reflux - These patients have no underlying predisposing factors or conditions; growth and development are normal, and pharmacologic treatment is typically not necessary
• Pathologic gastroesophageal reflux or gastroesophageal reflux disease (GERD) - Patients frequently experience the complications noted above, requiring careful evaluation and treatment^[4]
• Secondary gastroesophageal reflux - This refers to a case in which an underlying condition may predispose to gastroesophageal reflux; examples include asthma (a condition which may also be, in part, caused by or exacerbated by reflux) and gastric outlet obstruction

Patient education

For patient education information, see the Heartburn and GERD Center and the Children's Health Center, as well as Spitting Up in Infants, Gastroesophageal Reflux Disease (GERD) FAQs, Acid Reflux (GERD), Heartburn and GERD Medications, and Sudden Infant Death Syndrome (SIDS).

In addition, extremely useful patient information and provider-focused information can be accessed by visiting the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Web site.

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Etiology and Pathophysiology

Risk factors

Reflux after meals occurs in healthy persons; however, these episodes are generally transient and are accompanied by rapid esophageal clearance of refluxed acid. Some consider the small reservoir capacity of the infant's esophagus to be a predisposing factor to vomiting. The causes and risk factors for gastroesophageal reflux in children are frequently multifactorial.

Anatomic factors that predispose to gastroesophageal reflux include the following:

• The angle of His (made by the esophagus and the axis of the stomach) is obtuse in newborns but decreases as infants develop; this ensures a more effective barrier against gastroesophageal reflux
• The presence of a hiatal hernia may displace the lower esophageal sphincter (LES) into the thoracic cavity, where the lower intrathoracic pressure may facilitate gastroesophageal reflux; however, the presence of a hiatal hernia by itself does not predict gastroesophageal reflux, which means that many patients who have a hiatal hernia do not have gastroesophageal reflux
• Resistance to gastric outflow raises intragastric pressure and leads to reflux and vomiting; examples include gastroparesis, gastric outlet obstruction, and pyloric stenosis

Other factors that predispose individuals to gastroesophageal reflux include the following:

• Medications - Eg, diazepam, theophylline; methylxanthines exacerbate reflux secondary to decreased sphincter tone.
• Smoking
• Alcohol
• Poor dietary habits - Eg, overeating, eating late at night, assuming a supine position shortly after eating
• Food allergies
• Certain foods - Eg, greasy, highly acidic
• Motility disorders (postulated to potentially cause reflux) - These include antral dysmotility and delayed gastric emptying; such disorders are considered functional problems and frequently do not have an identifiable anatomic or organic cause
• Transient lower esophageal sphincter relaxation (tLESR) - This is currently believed to be the main mechanism of gastroesophageal reflux, accounting for 94% of reflux episodes in children and adults; poor basal LES tone was previously thought to be a cause
• Obesity -Obesity has been cited as a major risk factor for gastroesophageal reflux; in studies conducted with adult patients, weight loss has been demonstrated to be one of the lifestyle modifications that can decrease the severity and frequency of reflux
• Supine position
• Decreased gastric emptying and reduced acid clearance from the esophagus - These can cause abnormal reflux
• Neurodevelopmental disabilities - Children with neurodevelopmental disabilities, including cerebral palsy, Down syndrome, and other heritable syndromes associated with developmental delay, have an increased prevalence of gastroesophageal reflux

Chronic LES laxity

Reflux is facilitated when an increase in intraabdominal pressure occurs. In some cases, and particularly in children with neurodevelopmental disabilities, the presence of a chronically lax LES associated with decreased or even absent sphincter tone results in severe gastroesophageal reflux.

Transient lower esophageal relaxations

For many years, gastroesophageal reflux during infancy and childhood was thought to be a consequence of absent or diminished LES tone. However, studies have shown that baseline LES pressures are normal in pediatric patients, even in preterm infants.

The major mechanism in infants and children has now been demonstrated to involve increases in tLESRs. Factors that may promote gastroesophageal reflux during tLESRs include increased intragastric liquid volume and supine and "slumped" seated positioning.

Fluid diet

Likely because of reduced viscosity and increased gastric volumes, the fluid diet of the infant facilitates the process of regurgitation compared with solid meals ingested by older children and adults.

Esophageal clearance

Esophageal clearance is similar in infants and adults, although evidence of reduced peristaltic activity in preterm infants has been reported.

Differences between adults and infants

The volume ratio of meal-stomach-esophagus differs between adults and infants. Necessary amounts of infant caloric requirements easily overwhelm gastric capacity. Reflux occurs when esophageal capacity is exceeded by refluxate.

Decreased gastric compliance is believed to lead to LES relaxation at lower intragastric volumes in infants. This aspect, in conjunction with abdominal wall muscle contraction (if it occurs during periods of LES relaxation) propels refluxate into the esophagus, with subsequent regurgitation.

An association between gastroesophageal reflux and delayed gastric emptying is recognized. This is more common in premature infants.

Respiratory symptoms

Gastroesophageal reflux has been associated with significant respiratory symptoms in infants and children. The infant's proximal airway and esophagus are lined with receptors that are activated by water, acid, or distention. Activation of these receptors can increase airway resistance, leading to the development of reactive airway disease.^[5]

In 1892, Osler first postulated a relationship between asthma and gastroesophageal reflux, manifested by a bidirectional cause-and-effect presentation. Accordingly, although gastroesophageal reflux may be involved in the etiology and progression of reactive airway disease, the asthmatic condition (in addition to antiasthmatic medications) may play a role in exacerbation of gastroesophageal reflux.

One postulated mechanism for gastroesophageal reflux–mediated airway disease involves microaspiration of gastric contents that leads to inflammation and bronchospasm. However, experimental evidence also supports the involvement of esophageal acid–induced reflex bronchospasm, in the absence of frank aspiration. In such cases, gastroesophageal reflux therapy using either histamine 2 (H₂) blockers or proton pump inhibitors has been shown to benefit patients with steroid-dependent asthma, nocturnal cough, and reflux symptoms. Data from a systematic review of randomized controlled trials do not support the use of proton pump inhibitors to decrease infant crying and irritability.^{[6, 7]}

A study by Lang et al suggested that misattribution of gastroesophageal reflux symptoms to asthma may be a contributing mechanism to excess asthma symptoms in obese children. The study reported that obese children had seven times higher odds of reporting multiple GERD symptoms and that asthma symptoms were closely associated with gastroesophageal reflux symptom scores in obese patients but not in lean patients.^[8]  

Other associated conditions

Two major areas of controversy surround the relationship between gastroesophageal reflux and both apnea and otolaryngologic disease. Early studies appeared to demonstrate a link between gastroesophageal reflux and obstructive apnea (including an association with apparent life-threatening events [ALTEs]); however, recent investigations now suggest only a weak relationship between these disorders.^[9] Although the relationship between gastroesophageal reflux and ALTEs is controversial, where an association with apnea has been found, it is as likely to occur with nonacid as with acid reflux. Accordingly, a comprehensive evaluation of this phenomenon will likely require a bioelectrical impedance study (to identify nonacid reflux; see below) in conjunction with respiratory monitoring.

Laryngeal tissues are exquisitely sensitive to the noxious effect of acid, and studies support a significant relationship between laryngeal inflammatory disease (manifested by hoarseness, stridor, or both) and gastroesophageal reflux.

Conversely, no conclusive clinical evidence supports a link between gastroesophageal reflux and other supraesophageal problems, including otalgia, recurrent otitis media, and chronic sinusitis.

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Epidemiology

Gastroesophageal reflux is most commonly seen in infancy, with a peak at age 1-4 months. However, it can be seen in children of all ages, even healthy teenagers.

Occurrence in the United States

Approximately 85% of infants vomit during the first week of life, and 60-70% manifest clinical gastroesophageal reflux at age 3-4 months.

Symptoms abate without treatment in 60% of infants by age 6 months, when these infants begin to assume an upright position and eat solid foods. Resolution of symptoms occurs in approximately 90% of infants by age 8-10 months.

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Prognosis

During infancy, the prognosis for gastroesophageal reflux resolution is excellent (although developmental disabilities represent an important diagnostic exception); most patients respond to conservative, nonpharmacologic treatment.

Indeed, most cases of gastroesophageal reflux in infants and very young children are benign, and 80% resolve by age 18 months (55% resolve by age 10 mo), although some patients require a “step-up” to acid-reducing medications. Symptoms that persist after age 18 months suggest a higher likelihood of chronic gastroesophageal reflux; in such cases, the long-term risks of the condition are increased.^[10]

In refractory cases of gastroesophageal reflux or when complications related to reflux disease are identified (eg, stricture, aspiration, airway disease, Barrett esophagus), surgical treatment (fundoplication) is typically necessary. The prognosis with surgery is considered excellent. The surgical morbidity and mortality is higher in patients who have complex medical problems in addition to gastroesophageal reflux.

As previously mentioned, children with neurodevelopmental disabilities, including cerebral palsy, Down syndrome, and other heritable syndromes associated with developmental delay, have an increased prevalence of gastroesophageal reflux. When these disorders are associated with motor abnormalities (particularly spastic quadriplegia), medical gastroesophageal reflux management is often particularly difficult, and suck and/or swallow dysfunction is often present. Infants with neurologic dysfunction who manifest swallowing problems at age 4-6 months may have a very high likelihood of developing a long-term feeding disorder.

Despite the immense volume of data examining diagnosis, management and prognosis related to pediatric gastroesophageal reflux, a recent review of 46 articles (out of more than 2400 publications identified) demonstrated wide variations and inconsistencies in definitions, management approaches and in outcome measures.^[11]

Strictures

Gastroesophageal reflux strictures typically occur in the mid-esophagus to distal esophagus. Patients present with dysphagia to solid meals and vomiting of nondigested foods. As a rule, the presence of any esophageal stricture is an indication that the patient needs surgical consultation and treatment (usually surgical fundoplication). When patients present with dysphagia, barium esophagraphy is indicated to evaluate for possible stricture formation. In these cases, especially when associated with food impaction, eosinophilic esophagitis must be ruled out prior to attempting any mechanical dilatation of the narrowed esophageal region.

Barrett esophagus

Barrett esophagus, a complication of GERD, greatly increases the patient’s risk of adenocarcinoma. As with esophageal stricture, the presence of Barrett esophagus indicates the need for surgical consultation and treatment (usually surgical fundoplication).

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History

The symptoms of gastroesophageal reflux are most often directly related to the consequences of emesis (eg, poor weight gain) or result from exposure of the esophageal epithelium to the gastric contents.

One must remember that the typical symptoms (eg, heartburn, vomiting, regurgitation) in adults cannot be readily assessed in infants and children. Pediatric patients with gastroesophageal reflux typically cry and report sleep disturbance and decreased appetite. The following are some of the common signs and symptoms of gastroesophageal reflux in infants and young children:

• Typical or atypical crying and/or irritability
• Apnea and/or bradycardia
• Poor appetite
• Apparent life-threatening event (ALTE)
• Vomiting
• Wheezing
• Abdominal and/or chest pain
• Stridor
• Weight loss or poor growth (failure to thrive)
• Recurrent pneumonitis
• Sore throat
• Chronic cough
• Water brash
• Sandifer syndrome - Ie, posturing with opisthotonus or torticollis
• Hoarseness and/or laryngitis

Signs and symptoms in older children include all of the above plus heartburn and a history of vomiting, regurgitation, unhealthy teeth, and halitosis.

ALTEs

ALTEs that involve apnea associated with bradycardia, pallor, and/or cyanosis have been linked to gastroesophageal reflux, especially in premature infants. In these events, reflux into the hypopharynx is postulated to lead to laryngospasm and subsequent obstructive apnea. However, data suggest only a weak association between these phenomena. Any such relationship can be objectively determined only by esophageal pH monitoring or, preferably, by esophageal multichannel intraluminal impedance testing,  performed in conjunction with pneumography and either nasal thermistor or pulse oximetry recording.

Regurgitation

Regurgitation of food, one of the most common presenting symptoms in children, ranges from drooling to projectile vomiting. Most often, regurgitation is postprandial, although delays of 1-2 hours occur. One must also consider anatomic anomalies and protein allergy in a vomiting child, as well as inborn metabolic disorders (rare).

Bronchial and other symptoms

Some patients have atypical symptoms (eg, nocturnal cough, wheezing, or hoarseness as the only major complaint). Gastroesophageal reflux is a complicating factor in asthma. The mechanism may include microaspiration, which leads to reflex bronchoconstriction. The association of gastroesophageal reflux and airway or respiratory tract disease is common. Cough, stridor, and pharyngitis have all been linked to gastroesophageal reflux. In addition, an association with rumination is commonly observed in patients with developmental delay.

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Physical Examination

No classic physical signs of gastroesophageal reflux are recognized in the pediatric population (although an infant or toddler arriving in the office wearing a bib is often a sure tip off). One exception would be the relatively uncommon Sandifer syndrome, which is often misdiagnosed as spastic torticollis.

In toddlers and older children, excessive regurgitation may lead to significant dental problems caused by acid effects on tooth enamel. In the vast majority of cases, a diagnosis of gastroesophageal reflux is typically made once the primary care provider has obtained a clinical history that suggests this disorder.

Esophagitis may manifest as crying and irritability in the nonverbal infant. Failure to thrive can result from insufficient caloric intake secondary to repeated vomiting and nutrient losses from emesis. Hiccups, sleep disturbances, and Sandifer syndrome (arching) have also been shown to be associated with gastroesophageal reflux and esophagitis.

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Approach Considerations

In most cases of gastroesophageal reflux, the diagnosis can be made from the history and physical examination. Conservative measures can be started empirically. However, if the presentation is atypical or if the response to therapy is minimal, further evaluation via imaging is warranted.

Manometry

This is becoming a more accessible tool for use in infants and children. It is used to assess esophageal motility and lower esophageal sphincter (LES) function. Esophageal multichannel intraluminal impedance testing has the advantage of being able to assess these motility variable, but also to evaluate both acid and non-acid reflux.

Esophagogastroduodenoscopy

This modality is useful in patients who are unresponsive to medical therapy. It allows for visualization of the mucosa for diagnosis of peptic ulcer disease, Helicobacter pylori infection, strictures, and peptic esophagitis. It also provides access to obtain biopsies for histopathologic examination.

Histologic findings

Histologic signs of peptic esophagitis include basal cell hyperplasia, extended papillae, and mucosal eosinophils. The number of mucosal eosinophils may be important because finding more than 20 per high-powered field (hpf) has been associated with eosinophilic (allergic) esophagitis rather than with peptic esophagitis.

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Imaging Studies

Upper GI imaging series

Such studies are used to evaluate the anatomy of the upper gastrointestinal (GI) tract, but contrast imaging is neither sensitive nor specific for gastroesophageal reflux. However, imaging may be useful in the evaluation of gastric emptying time, which may be delayed in gastroesophageal reflux.

Gastric scintiscan

A gastric scintiscan study, using milk or formula that contains a small amount of technetium sulfur colloid, can assess gastric emptying and reveal reflux (although not the degree or severity of it). However, its major diagnostic role is in the assessment of pulmonary aspiration.

A major error in performing scintigraphy is not performing a delayed scan over the pulmonary bed. Gastroesophageal reflux–related aspiration may occur as an early or late postprandial phenomenon. Accordingly, in addition to the "acute" (ie, 1 h) scintiscan, patients should be rescanned after 24 hours, in order to assess delayed pulmonary soilage by refluxed gastric contents.

Esophagography

In cases of mild gastroesophageal reflux, diagnosis is made by clinical assessment and is confirmed by the response to therapy. Esophagography, conducted under fluoroscopic control, may reveal the integrity of esophageal peristalsis; however, it should not be used to assess the degree and severity of gastroesophageal reflux. Strictures can also be demonstrated by esophagography.

Chronic esophageal mucosal injury secondary to gastroesophageal reflux involves a mucosal/submucosal inflammatory cell infiltrate, as well as basal cell hyperplasia. In severe cases, this may appear as a ragged mucosal outline on radiography.

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Intraesophageal pH Probe Monitoring

Although pH monitoring has become a widely overused modality, it remains the criterion standard for quantifying gastroesophageal reflux.

A continuous esophageal pH probe in the distal esophagus documents the severity and frequency of reflux. Although this is a very sensitive monitoring modality, some controversy persists with respect to the precise criteria for differentiating physiologic from pathologic gastroesophageal reflux. More recently, dual pH probe monitoring has come into use to assess distal and proximal esophageal reflux in an attempt to correlate gastroesophageal reflux with laryngeal and pulmonary symptoms.

Advantages in using pH monitoring include the quantification of reflux and the ability to establish a temporal relationship with atypical symptoms (eg, obstructive apnea) and reflux events.

Esophageal pH monitoring is not indicated in cases of obvious gastroesophageal reflux but is useful in demonstrating an association between reflux and symptoms in atypical presentations and in grading the risk of esophagitis.

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Intraluminal Esophageal Electrical Impedance

Intraluminal esophageal electrical impedance (EEI) is useful for detecting both acid reflux and nonacid reflux by measuring retrograde flow in the esophagus. Gastroesophageal reflux episodes as brief as 15 seconds may be measured. (See the image below.)

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The image is a representation of concomitant intraesophageal pH and esophageal electrical impedance measurements. The vertical solid arrow indicates c....

In adult studies, impedance measurements have been used in conjunction with 24-hour intraesophageal pH monitoring in order to provide a more complete picture of bolus movement in the esophagus.

EEI has not been thoroughly validated, and normal values have not been determined in the pediatric age group.

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Approach Considerations

Conservative and pharmacologic therapy

Conservative measures in treating gastroesophageal reflux may include upright positioning after feeding, elevating the head of the bed, prone positioning (infants >6mo), and providing small, frequent feeds thickened with cereal.^[1] In more severe cases, in addition to dietary management, pharmacologic intervention directed at reducing gastric acid secretion can be employed.

Results of medical therapy are generally met with a better long-term response, leading to elimination of antisecretory medications (when prescribed) during infancy. This is primarily because normal development of GI motility includes resolution of physiologic gastroesophageal reflux by age 1 year (in most cases, by age 6 mo).

Older children benefit from a diet that avoids tomato and citrus products, fruit juices, peppermint, chocolate, and caffeine-containing beverages. Smaller, more frequent feeds are recommended, as is a relatively lower fat diet (because lipid retards gastric emptying). Proper eating habits are encouraged and weight loss and avoidance of alcohol and tobacco are recommended when applicable.

About two thirds of otherwise healthy infants spit up because of their physiology ("happy spitters"); these infants have simple gastroesophageal reflux (GER) rather than true gastroesophageal reflux disease (GERD), which is characterized by troublesome symptoms or complications (eg, irritability, weight loss, refusing to eat, coughing, or wheezing).^{[12, 13]} Many cases of the former are inappropriately treated with proton pump inhibitors (PPIs).

According to the guidelines of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, infants with uncomplicated physiologic GER should be treated not with medication but with modest lifestyle changes; medications should be reserved for infants with GERD.^[13] The most aggressive treatments, including surgery, should be reserved for children whe have intractable symptoms or are at risk for life-threatening complications. Older children and adolescents should be counseled to adopt recommended dietary changes.

Surgery

Surgery is required in only a very small minority of patients with gastroesophageal reflux. Indeed, as pharmacotherapy has improved, the need for surgical therapy (fundoplication) has markedly decreased. Nevertheless, antireflux surgery remains one of the most common surgical procedures performed during infancy and early childhood.

Intragastric feeding

For patients who fail medical therapy, continuous intragastric administration of feeds alone (via nasogastric tube) may be used as an alternative to surgery.^[2] This method is often used in preterm infants who have a significantly greater surgical risk. In these cases, adequate nutritional management, in conjunction with appropriate medical therapy, may permit the infant to "outgrow" reflux while optimizing weight gain.

Consultations

In addition to pediatric gastroenterologic referral, pulmonary consultation may be required so that respiratory complications can be comanaged. Surgical consultation may be required if medical treatment is not successful.

The diagram below presents a diagnostic and therapeutic algorithm to aid in the evaluation and management of gastroesophageal reflux.

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Algorithm for evaluation and "step-up" management of gastroesophageal reflux (GER).

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Positioning

Infants and children diagnosed with gastroesophageal reflux should avoid the seated or the supine position shortly after meals.

Prone positioning may be recommended for the patient, at least for the first postprandial hour. Sleeping in the prone position has been demonstrated to decrease the frequency of gastroesophageal reflux. However, the association of prone positioning with sudden infant death syndrome (SIDS) has brought its use into debate. Observations suggest that SIDS in the prone position is related to either suffocation or rebreathing of carbon dioxide and is associated with puffy bedding material.

Clearly, the use of the prone position during infancy must be based on a careful risk-to-benefit analysis. When it is advised, only very firm bedding material (no pillows) must be used. Bed elevations offer no added advantage to the prone position, and seated positions are not recommended.

Studies that monitored esophageal acid exposure after elevation of the head of the bed showed a decrease in reflux activity in adults. Placing blocks under the head of the bed or placing a foam wedge under the patient's mattress can accomplish this.

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Dietary Measures

Thickening an infant’s formula provides a therapeutic advantage against gastroesophageal reflux, particularly when excessive vomiting is associated with suboptimal weight gain. Even for infants with normal weight gain, thickened and reduced volume feedings may reduce the frequency and amount of vomiting episodes, ameliorating the concerns of an anxious caregiver.^[14] For formula-fed infants older than 3 months, thickening is typically achieved by the addition of 1 tablespoon of rice cereal per 2 oz of formula.

Younger formula-fed infants may benefit from a prethickened, proprietary formula (Enfamil-AR; Mead-Johnson Nutritionals Inc, Evansville, IN). For breast-fed infants, aside from increasing feeding frequency, expressed breast milk may be thickened as described. In addition, early introduction of rice cereal feedings (at age 3 mo) may be attempted. Research suggests that formula thickening is superior to positioning in promoting weight gain and reducing clinical symptoms in infants with gastroesophageal reflux.^[1]

In children, small, frequent meals are also recommended. Greasy and spicy foods, which encourage postprandial reflux by increasing gastric distention and slowing gastric emptying, should be avoided. Chocolate, peppermint, tomato products, citrus, and caffeine, which lowers LES pressure, should also be avoided.

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Step-Up and Step-Down Therapy

Guidelines from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) discuss the use of step-up and step-down therapies, which should be instituted under the guidance of a pediatric gastroenterologist.^{[15, 16]}

In the case of pharmacologic intervention, step-up therapy involves progression from diet and lifestyle changes to H₂ -receptor blockade medications (eg, ranitidine, nizatidine) to proton pump inhibitors (eg, omeprazole, lansoprazole).^[17] Both classes of acid antisecretory agents have proven safe and effective for infants and children in reducing gastric acid output.

The proton-pump inhibitor rabeprazole sodium is now approved by the US Food and Drug Administration (FDA) for the treatment of GERD in pediatric patients aged 1-11 years.^{[18, 19]} This agent was already indicated for (1) treatment of adults with GERD and duodenal ulcers, (2) eradication of Helicobacter pylori in adults, and (3) short-term treatment of symptomatic gastroesophageal reflux in adolescents (≥12 years).

In combination with diet and lifestyle changes, this management guideline should render surgery unnecessary in the vast majority of cases. One important exception, however, may be children with moderate to severe neurodevelopmental disabilities who typically manifest both dysphagia and GERD and are at high risk for aspiration. In these patients, conservative therapy alone may not be sufficient for preventing reflux-associated complications. However, careful monitoring under optimal nonsurgical therapy should be conducted before operative intervention is considered.

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Indications for Fundoplication and Gastrostomy

The goals of medical therapy in gastroesophageal reflux are to decrease acid secretion and, in many cases, to reduce gastric emptying time. The previously described step-up approach is directed at decreasing acid content of the refluxate.

However, other components of the refluxate (eg, bile, pepsin, trypsin) may also lead to esophageal mucosal injury. These gastric fluid components may exert damaging effects even under conditions of gastric alkalinization; thus, some patients under antisecretory treatment may have normal pH probe studies and yet continue to have the symptoms of gastroesophageal reflux.^{[20, 21]} In these cases, the development of EEI as a diagnostic tool may prove invaluable.

When rigorous step-up therapy has failed or when the complications of gastroesophageal reflux pose a short- or long-term survival risk, the goal of surgical antireflux procedures is to "tighten" the region of the LES and, if possible, to reduce hiatal herniation of the stomach (occasionally seen in patients with GERD).

To summarize, surgical treatment of gastroesophageal reflux should be considered for the following patients:

• Infants and children who have failed step-up therapy for gastroesophageal reflux (typically over 12 wk) and those who cannot be weaned off of acid-reducing medications should be considered for surgical treatment
• Those with an atypical presentation, especially respiratory, whose symptoms are clearly associated with gastroesophageal reflux (eg, obstructive apnea temporally associated with reflux during pH monitoring) should be considered for surgical treatment; however, a period of medical therapy (including acid blockade) under close monitoring conditions should be attempted in many cases prior to recommending a surgical approach
• Patients with complications of gastroesophageal reflux, such as aspiration, stricture of the esophagus, or Barrett esophagus, should be considered for surgical treatment
• Patients with neurologic impairment that requires feeding gastrostomy who are found to have pathologic reflux and who remain medication dependent should be considered for surgery
• Patients with chronic reflux and recurrence of anastomotic stricture after repair of esophageal atresia should be considered for surgical treatment

Observations related to the possible need for gastrostomy include the following:

• Small gastric volumes, decreased compliance in infants, and a slow gastric emptying rate following the fundoplication procedure may necessitate a gastrostomy procedure to accompany a fundoplication
• Patients who are neurologically impaired or who have an inability to tolerate feeds also need an accompanying gastrostomy

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Fundoplication

The goal of surgery for patients with GERD is to reestablish the antireflux barrier without creating obstruction to the food bolus. In general, the Nissen fundoplication (shown in the image below), which is a complete 360° wrap, best controls the symptoms of gastroesophageal reflux.^[22] However, this technique may lead to more episodes of dysphagia (swallowing difficulty and discomfort) and gas bloat than would a partial wrap.

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Illustration of the Nissen fundoplication. Note how the stomach is wrapped around the esophagus (360-degree wrap).

Before operative intervention, patients should be evaluated with a thorough history and physical examination and the results of medical treatment (nonoperative therapy) should be well documented. In infants and young children, performing an upper GI series (upper GI contrast study) prior to the performance of fundoplication is advisable in order to rule out other possible pathologies that may be causing emesis.

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Guidelines

Clinical practice guidelines on pediatric gastroesophageal reflux by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recommend the following^{[23, 24]} :

• Four to eight weeks of acid-suppression therapy is recommended to treat typical reflux symptoms. This should only occur after dietary modifications in infants are unsuccessful.
• Avoid acid suppression in infants and children with extraesophageal symptoms (eg, cough, wheezing, asthma).
• GERD complications should be assessed with esophagogastroduodenoscopy (EGD) with biopsies.
• pH/impedance studies are recommended to see the role of acid reflux in esophagitis and whether acid-suppression therapy was effective.
• Diagnosing GERD with salivary pepsin, extraesophageal biomarkers, and scintigraphy is not recommended.
• Only use manometry if there is suspicion of an underlying motility disorder.
• Positional therapy to treat reflux in infants is not recommend.
• Proton pump inhibitors can be used as treatment for erosive esophagitis.

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Medication Summary

A therapeutic response to treatment for gastroesophageal reflux may take up to 2 weeks. If treatment is successful, weight increases and vomiting episodes decrease. Recurrent aspiration pneumonia or apnea is cause for decreased length of medical therapy. Note that the so-called prokinetic agents have been omitted from the following drug list. No currently available prokinetic drug (eg, metoclopramide) has been demonstrated to exert a significant influence on the number or frequency of reflux episodes.

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Aluminum hydroxide (ALternaGEL)

• Dosing, Interactions, etc.

Clinical Context:  Aluminum hydroxide increases gastric pH (>4) and inhibits the proteolytic activity of pepsin, reducing acid indigestion. Antacids can initially be used in mild cases. Aluminum hydroxide has no effect on the frequency of reflux but decreases its acidity.

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Magnesium hydroxide (Phillips Milk of Magnesia)

• Dosing, Interactions, etc.

Clinical Context:  Magnesium hydroxide is used as an antacid to relieve indigestion. It also causes the osmotic retention of fluid, which distends the colon and increases peristaltic activity, providing a laxative effect. This agent forms magnesium chloride in vivo after reacting with stomach hydrochloric acid.

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Class Summary

These agents are used as diagnostic tools to provide symptomatic relief in infants. Associated benefits include symptomatic alleviation of constipation (aluminium antacids) or loose stools (magnesium antacids).

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Nizatidine (Axid)

• Dosing, Interactions, etc.

Clinical Context:  Nizatidine competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reductions in gastric acid secretion, gastric volume, and hydrogen concentrations.

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Cimetidine (Tagamet)

• Dosing, Interactions, etc.

Clinical Context:  Cimetidine inhibits histamine at the H2 receptors of gastric parietal cells, causing reductions in gastric acid secretion, gastric volume, and hydrogen ion concentrations.

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Ranitidine (Zantac)

• Dosing, Interactions, etc.

Clinical Context:  Ranitidine inhibits histamine stimulation of the H2 receptor in gastric parietal cells, reducing gastric acid secretion, gastric volume, and hydrogen ion concentrations.

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Famotidine (Pepcid)

• Dosing, Interactions, etc.

Clinical Context:  Famotidine competitively inhibits histamine at the H2 receptors of gastric parietal cells, reducing gastric acid secretion, gastric volume, and hydrogen ion concentrations.

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Class Summary

Like antacids, these agents do not reduce the frequency of reflux but do decrease the amount of acid in the refluxate by inhibiting acid production. All H₂ -receptor antagonists are equipotent when used in equivalent doses. They are most effective in patients with nonerosive esophagitis. H₂ -receptor antagonists are considered the drugs of choice for children because pediatric doses are well established and the medications are available in liquid form.

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Lansoprazole (Prevacid)

• Dosing, Interactions, etc.

Clinical Context:  Lansoprazole suppresses gastric acid secretion by specific inhibition of the H+/K+-adenosine triphosphatase (ATPase) enzyme system (ie, proton pump) at the secretory surface of the gastric parietal cell. The drug blocks the final step of acid production, inhibiting basal and stimulated gastric acid secretion and therefore increasing gastric pH. Lansoprazole's effect is dose related. The drug is easy to administer to children because it is available as a capsule or an oral disintegrating tablet or in granular form for use in an oral suspension.

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Omeprazole (Prilosec)

• Dosing, Interactions, etc.

Clinical Context:  Omeprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATPase pump. It is used for the short- and long-term treatment (4-8wk to 12mo) of GERD.

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Esomeprazole (Nexium)

• Dosing, Interactions, etc.

Clinical Context:  Esomeprazole is an (S)-isomer of omeprazole. It inhibits gastric acid secretion by inhibiting the H+/K+-ATPase enzyme system at the secretory surface of the gastric parietal cells. Esomeprazole is used in severe cases and in patients not responding to H2-antagonist therapy. The drug is administered for up to 4 weeks to treat and relieve the symptoms of active duodenal ulcers; it may be used for up to 8 weeks to treat all grades of erosive esophagitis.

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Dexlansoprazole (Dexilant)

• Dosing, Interactions, etc.

Clinical Context:  Dexlansoprazole suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.

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Rabeprazole sodium (AcipHex)

• Dosing, Interactions, etc.

Clinical Context:  Rabeprazole sodium suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.

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Pantoprazole (Protonix)

• Dosing, Interactions, etc.

Clinical Context:  Pantoprazole suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.

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Class Summary

These agents are indicated in patients who require complete acid suppression (eg, infants with chronic respiratory disease or neurologic disabilities). Administer proton pump inhibitors with the first meal of the day. Children with nasogastric or gastrostomy tubes may have granules mixed with an acidic juice or a suspension; tubes must then be flushed to prevent blockage.

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