Gastroesophageal reflux (GER) is a normal physiologic process. It is important to distinguish GER from GER disease (GERD) since GER does not require treatment. Although a diagnosis of GERD can largely be based on history and physical alone, endoscopy and pH impedance studies can help make the diagnosis when there in atypical presentation. In children and adolescents, lifestyle changes and acid suppression are first-line treatments for GERD. In infants, acid suppression is not effective, but a trial of hydrolyzed formula can be considered, as milk protein sensitivity can be difficult to differentiate from GER symptoms.
Key points
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Gastroesophageal reflux is a normal physiologic process that does not require treatment.
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In infants, reducing feeding volumes, offering smaller, more frequent meals, thickening feeds, and positioning can reduce reflux episodes; these infants should not be placed on acid suppression.
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Gastroesophageal reflux disease (GERD) occurs when reflux of gastric contents causes troublesome symptoms or complications. First-line treatment in children and adolescents includes lifestyle modification and acid suppression.
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GERD can have atypical presentations, such as recurrent pneumonia, upper airway symptoms, nocturnal or difficult to control asthma, dental erosions, and Sandifer syndrome.
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Diagnosis of GERD is largely based upon history and physical, but endoscopy and pH impedance can be used to help support the diagnosis in atypical presentations.
Introduction
Gastroesophageal reflux (GER) is a normal physiologic process. It is defined as the involuntary flow of stomach content back into the esophagus. Most episodes of reflux are into the distal esophagus, brief, and asymptomatic. GER disease (GERD) occurs when reflux causes troublesome symptoms or complications.
Introduction
Gastroesophageal reflux (GER) is a normal physiologic process. It is defined as the involuntary flow of stomach content back into the esophagus. Most episodes of reflux are into the distal esophagus, brief, and asymptomatic. GER disease (GERD) occurs when reflux causes troublesome symptoms or complications.
Physiology
Multiple mechanisms are in place to protect from reflux: the antireflux barrier, esophageal clearance, and esophageal mucosal resistance. The antireflux barrier is composed of the lower esophageal sphincter (LES), the angle of His, the crural diaphragm, and the phrenoesophageal ligament. The LES consists of tonically contracted circular smooth muscles, composed of the intrinsic muscles of the distal esophagus and the sling fibers of the proximal stomach. The crural diaphragm forms the esophageal hiatus and encircles the proximal LES. The phrenoesophageal ligament anchors the distal esophagus to the crural diaphragm. A small portion of the LES, up to 2 cm in adults, is intraabdominal. The LES resting pressure is higher than the intraabdominal pressure, and this prevents reflux of gastric contents into the distal esophagus. The angle of His is an acute angle between the great curvature of the stomach and the esophagus, and acts as an antireflux barrier by functioning like a valve. Esophageal clearance limits the duration of contact between luminal contents and esophageal epithelium. Gravity and esophageal peristalsis remove volume from the esophageal lumen, and salivary and esophageal secretions neutralize acid. Esophageal mucosal resistance comes into play when acid contact time is prolonged, and this is determined genetically.
Mechanisms of gastroesophageal reflux
Anything that interferes with these lines of defense can lead to GER. Inappropriate transient LES relaxation is among the most important causes of GERD in children. Increased intraabdominal pressure relative to LES resting pressure permits the reflux of gastric contents into the distal esophagus. Increased intraabdominal pressure can be caused by medications, the Valsalva maneuver, the Trendelenburg position, or lifting. Position and posture influence the angle of His, with esophageal acid exposure greater in the right side sleeping position than in the left position. Esophageal clearance is also delayed in the right position. Although little is known about the angle of His in infants, it is hypothesized that this angle is less acute in young infants and becomes acute after 1 year of age; this would predispose their stomach to a more vertical lie and therefore increased ease of reflux. In sliding hiatal hernias, there is a weakness of the phrenoesophageal ligament leading to an upward displacement of the LES into the lower mediastinum. As a result, the defense of the LES, angle of His, and the diaphragm are compromised. The LES and crural diaphragm no longer overlap, and the LES length and pressure are reduced. Another proposed mechanism by which hiatal hernia leads to GER is by creating a hernia sac between the LES proximally and the crural diaphragm distally. This sac has increased acid exposure and impaired clearance, and can reflux during subsequent swallow relaxations of the LES.
Distinguishing gastroesophageal reflux from gastroesophageal reflux disease
Whereas GER is a normal physiologic process, GERD occurs when reflux of gastric contents causes troublesome symptoms or complications. In infants, crying and fussiness are often attributed to GERD, but are nonspecific and difficult to distinguish from other causes. GERD can cause infants to associate feeding with pain, and as a result feeding aversion, anorexia, and failure to thrive can develop. Respiratory complications are less common, but recurrent pneumonia and interstitial lung disease secondary to reflux can occur owing to aspiration of gastric contents. Reflux worsening asthma symptoms has also been reported. Histologic changes can also help distinguish the two, with esophageal biopsies in GERD typically showing findings of basal zone hyperplasia, papillary lengthening, and neutrophil infiltration.
Epidemiology
There are few pediatric-specific data on GER and GERD epidemiology with incidence and prevalence based on questionnaires. The incidence of GERD in pediatrics was estimated to be 0.84 per 1000 person-years. After 1 year of age, the incidence of GERD decreases with until age 12, and then reaches a maximum at age 16 to 17. The prevalence varies by study and age. It is estimated that 10% of all children have GER and 1.8% to 8.2% have GERD. The estimated prevalence of GERD in infants 0 to 23 months, children 2 to 11 years old, and adolescents 12 to 17 years old is 2.2% to 12.6%, 0.6% to 4.1%, and 0.8% to 7.6%, respectively.
Presenting symptoms
Infancy
Daily regurgitation in healthy infants is physiologic and common, with the prevalence being highest in the first 3 to 4 months of life, at between 41% and 73%. A large proportion of these infants regurgitate more than 4 times a day. Prevalence decreases to 14% at 7 months of age, and to less than 5% after 12 months of age. GERD can be difficult to diagnose in infants because they present with nonspecific symptoms that can be difficult to distinguish from other conditions ( Box 1 ). These symptoms include choking, gagging, irritability, regurgitation, refusal to feed, and poor weight gain. Crying, irritability, and vomiting are often attributed to GERD, but can be indistinguishable from milk protein allergy and do not correlate well with reflux on pH impedance studies, or improve after trials of proton pump inhibitors (PPIs). A history and physical examination should be done to rule out warning signals that require further investigation ( Box 2 ), before attributing them to GERD.
Gastrointestinal obstruction
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Esophageal web
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Esophageal stricture
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Tracheoesophageal fistula
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Pyloric stenosis
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Duodenal atresia
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Malrotation with intermittent volvulus
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Intestinal duplication
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Antral/duodenal web
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Hirschsprung disease
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Foreign body/bezoar
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Incarcerated hernia
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Imperforate anus
Other gastrointestinal disorders
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Celiac disease
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Milk/soy protein allergy
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Achalasia
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Gastroparesis
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Peptic ulcer
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Eosinophilic esophagitis/gastroenteritis
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Inflammatory bowel disease
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Appendicitis
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Pancreatitis
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Cholecystitis/choledocholithiasis
Neurologic
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Intracranial mass
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Hydrocephalus
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Subdural hematoma
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Intracranial hemorrhage
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Infant migraine
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Chiari malformation
Infectious
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Meningitis
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Gastroenteritis
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Sinusitis
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Urinary tract infection
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Pneumonia
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Otitis media
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Hepatitis
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Sepsis
Metabolic/endocrine
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Galactosemia
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Hereditary fructosemia
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Urea cycle defects
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Amino and organic acidemias
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Fatty acid oxidation disorders
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Lysosomal storage disorders
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Congenital adrenal hyperplasia
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Diabetic ketoacidosis
Renal
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Obstructive uropathy
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Nephrolithiasis
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Renal tubular acidosis
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Renal insufficiency
Other
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Self-induced vomiting
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Cyclic vomiting syndrome
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Rumination
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Overfeeding
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Autonomic dysfunction
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Munchausen syndrome by proxy
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Medication/vitamin/drug toxicity
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Child abuse
Bilious emesis
Gastrointestinal bleeding: hematemesis, coffee ground emesis, hematochezia
Choking, gagging, coughing with feeds
Forceful emesis
Onset of emesis after 6 months of life
Failure to thrive
Diarrhea/constipation
Fever
Lethargy
Hepatosplenomegaly
Bulging fontanelle
Microcephaly or macrocephaly
Seizures
Abdominal tenderness or distention
Suspected genetic syndrome
Childhood
GERD is often diagnosed in adults based on a history of substernal, burning pain, with or without regurgitation. The diagnosis of GERD can similarly be made in adolescents. However, history is unreliable in children under the age of 12, and these children can also present with different symptoms. In addition to the aforementioned typical GERD symptoms, 21% of children reported nausea or vomiting. Abdominal pain and cough are also reported frequently. In children with erosive esophagitis, cough, anorexia, and feeding refusal were found to be more frequent and severe in children ages 1 to 5 years of age, as compared with older children, while heartburn was less severe. Symptoms have not been found to be predictive of mucosal damage.
Children with certain underlying disorders are at high risk for developing severe and chronic GERD ( Table 1 ).
| Condition | Contributing Factors |
|---|---|
| Neurologic impairment |
|
| Obesity | |
| Esophageal atresia | Esophagus is congenitally dysmotile After surgery, a hiatal hernia is often present |
| Unknown |
| Lung transplantation | Pneumonectomy contributes to esophageal and gastric motor dysfunction |
Atypical Presentations
An association between asthma and reflux measured by pH or impedance has been reported, although the etiology is not established. Proposed mechanisms of GERD contributing to asthma include aspiration of gastric acid resulting in airway inflammation and causing vagally mediated bronchial or laryngeal spasm. Alternatively, asthma may contribute to GERD. Pulmonary hyperinflation occurs as a result of chronic asthma. This hyperinflation causes the diaphragm to flatten, displacing the LES into the thoracic cavity, which has a negative atmosphere pressure, and thereby reduces the LES resting pressure and eliminates the angle of His. Studies have shown that the majority of children with asthma have an abnormal pH impedance study ; however, the use of a PPI in unselected patients with wheezing or asthma is of limited benefit. Patients who may benefit from GERD treatment include those with heartburn, nocturnal asthma symptoms, or steroid-dependent and difficult-to-control asthma.
Recurrent pneumonia and interstitial lung disease may be complications of GERD owing to aspiration of gastric contents. Although an abnormal esophageal pH study may increase the probability of GERD causing recurrent aspirations, there is no definitive test that can prove GERD’s causal role.
Upper airway symptoms attributed to GERD include hoarseness, chronic cough, or a sensation of a lump in the throat, although there are no strong data to support this claim. Laryngoscopic findings attributed to reflux include erythema, edema, cobblestoning, and nodularity, although with low sensitivity and specificity and poor correlation with pH probe studies.
Studies revealed a cause and effect relationship between GERD and dental erosions, with worse dental erosions when GERD symptoms are present. Other contributing factors to dental erosions include drinking juice, bulimia, racial and genetic factors affecting the characteristic of enamel and saliva, and children with neurologic impairment.
Sandifer syndrome, in which there is spasmodic torsional dystonia with arching of the back and rigid opisthotonic posturing of the neck and back, is an uncommon but specific presentation of GERD. It must be distinguished from seizures, dystonia, or infantile spasms. When related to GERD, it improves with antireflux treatment.
An apparent life-threatening event (ALTE) was first defined in 1986 as an episode that is frightening to the observer and that is characterized by some combination of apnea, color change, marked change in muscle tone, choking, or gagging. The term ALTE was recently replaced by the term “brief resolved unexplained event,” which is characterized by a sudden, brief, and resolved episode occurring in an infant under 1 year of age that consists of one of more of the following: cyanosis or pallor; absent, decreased, or irregular breathing; marked change in tone; and altered level of responsiveness. Because the change was recently made, published studies have evaluated GERD association with the ALTE definition. The results are conflicting. Although most series fail to demonstrate a temporal relationship between the two, multiple studies do show that there is an association. If other causes have been ruled out and GER is suspected, the diagnosis can be better evaluated by recording synchronous symptoms on multichannel intraluminal impedance (MII)/pH esophageal monitoring in combination with cardiorespiratory monitoring. When using esophageal manometry in conjunction with cardiorespiratory monitoring, infants with ALTE were found to have swallowing as the most frequent esophageal event associated with spontaneous respiratory events. This suggests a dysfunctional regulation of the swallow–respiratory interactions, and needs to be investigated further. When using polysomnography with esophageal pH and impedance monitoring, apnea was seldom associated with reflux. When it was, the predominant sequence of events was obstructive or mixed apnea followed by reflux, suggesting against reflux as a cause of apnea.
Apnea and sleep quality have similarly been evaluated by a combination of polysomnography with esophageal pH and impedance monitoring. The data, again, are conflicting. In some, GER was found unlikely to be related to apneic events and rarely seemed to cause sleep awakening. Instead, awakening and arousal was precipitating GER. Another group has shown that acid and non–acid reflux was associated with sleep interruption in infants, and acid reflux was associated with sleep interruption in obese children.
Diagnosis
The diagnosis of GERD can largely be based on history and physical examination alone. There are several tools, however, to help make the diagnosis when there is an atypical presentation and to assess the severity and consequence of GERD.
Endoscopy
On endoscopy, visualizing endoscopic breaks in the mucosa is the most reliable evidence of reflux esophagitis. The classic histologic findings of GERD are basal zone hyperplasia, papillary lengthening, and neutrophilic infiltration. Although the histologic findings are not specific to GERD alone and have not correlated well with symptom severity of GERD in children, they can help to support the diagnosis. The sensitivity of histology increases if multiple biopsies are taken, sampling in the mid and distal esophagus. If using this method, the sensitivity of histology was 96% in patients with erosive esophagitis and 76% with nonerosive reflux disease. The additional usefulness of pursuing endoscopy includes ruling out other disorders that can masquerade as GERD, such as eosinophilic esophagitis; identifying complications of reflux disease; and evaluating for empirical treatment failure.
pH and Impedance
Twenty-four–hour esophageal pH monitoring measures the frequency and duration of acid esophageal reflux. This test can be performed by either placing a nasal catheter, or by clipping a wireless sensor to the esophageal mucosa via endoscopy. A decrease in the intraesophageal pH to less than 4 is considered acidic exposure. For criteria to diagnose acid reflux, please refer to the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition–European Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus paper from 2009. The main indications for pH monitoring include evaluating endoscopy-negative patients for abnormal esophageal acid exposure if they are being considered for antireflux procedures and evaluating patients who are refractory to PPI therapy. There are limitations to standard pH monitoring. It is a poor detector of weakly acidic (pH of 4-7) reflux and can also overestimate acid exposure by picking up “pH-only” episodes, in which there is no reflux. In infants and children, weakly acidic GER is more prevalent than in adults, which can explain why abnormal esophageal pH monitoring does not correlate with symptom severity in infants. Abnormal esophageal pH is observed more frequently in adults and children with erosive esophagitis.
MII uses change in impedance to measure the anterograde and retrograde movement of fluid, solids, and air in the esophagus. Dual pH-MII is able to detect reflux regardless of pH value, detect anterograde versus retrograde flow thereby distinguishing between swallows and GER, determine the height of refluxate, and differentiate between liquid, gas, or mixed refluxate. Nonacid pH is defined as a pH of greater than 4 and the reflux index is defined as the percentage of time the pH drops to less than 4. Tables 2 and 3 provide the reflux parameter definitions and normal values for reflux per 24 hours in infant and children. Normal values for infants and children with nonacid and acid reflux were determined by Mousa and colleagues in a multicenter study evaluating multiple parameters of reflux via pH/MII in a very clean population. The infant and children selected had no evidence of acid reflux or symptoms associated with regurgitation. They were also off antireflux medications at the time of the procedure and did not have a fundoplication. Based on the study, in infants, more than 48 acid reflux episodes or more than 67 nonacid reflux episodes in 24 hours are considered pathologic. With children, more than 55 acid reflux episodes or more than 34 nonacid reflux episodes in 24 hours is considered pathologic.
| Definitions | |
| Liquid reflux | Drop in impedance of ≤50% of baseline value with subsequent recovery, in ≥2 of the distal-most channels |
| Acid GER | pH decreases and remains <4 for ≥5 s; if pH was already <4, it decreases by ≥1 pH unit for ≥5 s; with or without a decrease in impedance of ≤50% of baseline value |
| Nonacid GER | pH increases, remains unchanged, or decreases by ≥1 pH unit while remaining ≥4, with a retrograde decrease in impedance of ≤50% of baseline value in ≥2 of the distal-most channels |
| Gas reflux | Simultaneous and rapid increases in impedance in ≥2 channels (>3000 Ohms) of the distal-most channels |
| Extent of reflux migration | |
| Localized to distal esophagus | Height of reflux is confined to the 2 most distal impedance channels (channels 5 and 6) |
| Proximal | Height of refluxate reaches either or both of the most proximal channels (channels 1 and/or 2) |
| Parameters of symptom association | |
| Reflux index | Percent of time pH is <4 |
| Symptom index |
|
| Symptom sensitivity index |
|
| Symptoms associated probability |
|
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