George Gershman, MD
A 9-year-old boy reports frequent episodes of epigastric pain right after eating. The pain is associated with nausea and infrequent vomiting. The pain is described as dull and lasts less than 15 to 20 minutes. The patient also reports a burning sensation in his chest after eating and a cough at night. The patient lacks energy, and his voice is hoarse in the morning. There is no history of dysphagia, odynophagia, or weight loss. The physical examination is normal.
1. What are the characteristics of gastroesophageal reflux?
2. What is the difference between gastroesophageal reflux and gastroesophageal reflux disease?
3. What groups of children are at risk for gastroesophageal reflux disease?
4. What is the appropriate workup for an infant with suspected gastroesophageal reflux disease?
5. What is the appropriate management of infants and children with gastroesophageal reflux and gastroesophageal reflux disease?
6. What is the natural history of gastroesophageal reflux in children?
Gastroesophageal reflux (GER) is the passage of gastric contents into the esophagus. It is a normal physiological process that occurs in healthy children and adults. Most episodes of reflux in healthy individuals are brief and asymptomatic and are rarely accompanied by regurgitation, defined as passage of gastric fluid into the pharynx or mouth. In otherwise healthy, thriving infants, GER is often associated with effortless expulsion of refluxate from the mouth; the condition is colloquially known as spitting up. Those infants fall into the category of “happy spitters.”
In contrast with uncomplicated GER, symptomatic GER is defined as GER disease (GERD) and induces conditions such as esophagitis, failure to thrive, and aspiration pneumonia. While GER may require only anticipatory guidance and monitoring, GERD necessitates further evaluation and medical therapy. Thus, although GER could be a sign of GERD, it is important to distinguish these 2 entities for proper patient care.
Gastroesophageal reflux is very common in infants; at least one-half of healthy infants experience some degree of GER. Most infants with GER or GERD who are brought in for medical care became symptomatic before 6 months of age. Regurgitation occurs at least once daily in one-half of infants younger than 3 months and in nearly two-thirds of infants by 4 months. The frequency and volume of spit-up decrease after age 7 to 8 months, when infants are upright for more of the day. By 12 months of age, only 5% of infants will remain symptomatic. By 18 months of age, most infants become asymptomatic.
Little is known about the prevalence of GERD in children and adolescents. A cross-sectional observational study in more than 10,000 children and adolescents (mean age 3.8 ± 5.6 years) in France revealed the prevalence of GERD as 6%. One retrospective study in the United States showed that 5% to 8% of children and adolescents suffered from weekly symptoms of GERD.
Available data suggest that children who were diagnosed with GERD at 5 years or older have a high prevalence of GERD symptoms in adolescence and as young adults. A small retrospective study of adults who had been diagnosed with GERD in infancy or childhood showed increased symptoms of GERD in those who had a history of GERD in childhood but not in infancy.
Patients with neurological disorders have an increased prevalence of GERD. Management of these individuals requires a more aggressive approach. Individuals with neurological impairments are more likely to have esophagitis or aspiration. Infants who have undergone repair of esophageal atresia also have more severe disease, with at least one-half requiring anti-reflux surgery. Chronic respiratory disease, such as cystic fibrosis, is associated with GERD. Gastroesophageal reflux disease is described in two-thirds of patients with asthma, but this association is controversial. It is not clear whether the altered physiology of these diseases causes reflux or if reflux exacerbates the pulmonary dysfunction. Similar triggers for asthma and GERD are described, so it may be that they coexist and are unrelated. Studies with intraluminal impedance monitoring (see the Evaluation section) show that nonacid reflux occurs frequently in patients with asthma. This helps explain the lack of success of therapy aimed at acid suppression in this group of patients.
The most frequent presentation for infants with GER is recurrent non-forceful and small volume emeses (Box 121.1). Vomiting typically occurs after feeding and does not seem to disturb the patient. Some parents report a link between fussiness and crying with feeding, but this is not reproducible in trials comparing symptoms with pH studies. Additional symptoms, such as poor weight gain, anemia, or swallowing difficulties, could be linked to GERD. Sandifer syndrome is a rare presentation of GERD in infants, with characteristic paroxysmal movements involving spasmodic torticollis and dystonia. Nodding and rotation of the head, neck extension, gurgling, writhing movements of the limbs, and severe hypotonia can also be witnessed. Infants and children can develop extraesophageal manifestations of GERD such as nighttime cough, sleep apnea, wheezing, and recurrent pneumonia. Children older than 8 years and adolescents may have symptoms of adult-type GERD, such as frequent heartburn, chest and abdominal pain, and dysphagia.
Gastroesophageal reflux occurs when intra-abdominal pressure surpasses intrathoracic pressure. There are 3 main preventive barriers to GER: lower esophageal sphincter (LES), the crus of the diaphragm, and the intra-abdominal esophagus. A contracted LES generates a pressure gradient of 8 to 30 mm Hg between the esophagus and the stomach. The LES relaxes during swallowing, allowing a food bolus to enter the stomach. The skeletal muscle of the crus diaphragm contracts during inspiration or straining, augmenting the pressure of the LES. Contraction of the intra-abdominal esophagus in response to rising of intra-abdominal pressure adds to GER preventive forces.
Most episodes of GER occur during transient esophageal relaxation of LES that is not related to swallowing or straining. Transient esophageal relaxation of LES is considered to be a venting mechanism of the distended stomach and is manifested by belching in typical individuals. Transient esophageal relaxation of LES occurs up to 6 times per hour in typical adults, more frequently with gastric distension after meals, and rarely at night. In children, including preterm and term infants, transient esophageal relaxation of LES is responsible for most GER. Transient esophageal relaxation of LES is mediated by a brain stem reflex involving the vagal nerve and release of nitric oxide. Consumption of a large quantity of milk, poor compliance of the stomach, and a relatively short esophagus of a rapidly growing infant leads to frequent effortless regurgitation of gastric fluid into the esophagus. Posterior location of the gastroesophageal junction in the supine position and raised intra-abdominal pressure when the infant is resting in a car safety seat also facilitate regurgitation.
Box 121.1. Diagnosis of Gastroesophageal Reflux Disease in the Pediatric Patient
Presenting Signs and Symptoms
•Fussiness or sleep disturbance
•Poor weight gain
•Hematemesis or anemia
•Odynophagia or dysphagia
Transient esophageal relaxation of LES that is too frequent or prolonged exposes the esophageal mucosa to noxious material. Swallowed saliva and coordinated esophageal peristalsis neutralize gastric fluid within the esophagus and sweeps the fluid into the stomach. Inflammation of the esophagus may disrupt this process by decreasing peristaltic activity. Lack of mucus secretion by the esophageal mucosa and poor esophageal clearance increase the risk of esophagitis by exposing the esophageal mucosa to hydrochloric acid, pepsin, bile acids, and pancreatic enzymes. In contrast, frequent feedings with large volume of human milk or formula neutralize gastric acidity and decrease caustic damage of the esophagus in infants.
Before food leaves the esophagus, the stomach must be ready to accept it. The gastric fundus normally relaxes without an increase in pressure. Dysfunction of this fundic accommodation or delay in gastric emptying can increase pressure in the stomach and exacerbate GER.
A diverse group of symptoms, each with its own list of potential diagnoses, are associated with reflux disease. Regurgitation and vomiting are the most commonly reported symptoms. Many of the causes of vomiting in the newborn can be separated from reflux with a history and physical examination (Box 121.2). Forceful, bilious, or bloody emesis is not typical of reflux. Fussiness and crying are nonspecific symptoms with etiologies ranging from infantile colic to meningitis. Eosinophilic esophagitis (EoE) should be considered in toddlers and children with recurrent emesis and atopic dermatitis, food allergy, or asthma and older children and adolescents with dysphagia. Children with EoE may also experience recurrent food impaction in the esophagus. The primary therapy for EoE focuses on dietary manipulation and the elimination of identified foods to which the child is allergic.
Infants who fit into the definition of happy spitter (normal appearing, thriving, with recurrent emesis) do not require any diagnostic workup. It is important to reassure parents or guardians and encourage proper feeding technique. However, the presence of red flag symptoms, such as bilious vomiting, poor weight gain, food avoidance, chronic cough, unexplained anemia, or significant chest or abdominal pain, should prompt thorough diagnostic evaluation.
Targeted questions about the timing and volume of feedings and their relationship to regurgitation can help build the case for reflux. Specific attention should be paid to respiratory symptoms such as nighttime cough or previous episodes of pneumonia. Difficulties with feeding and swallowing should be outlined carefully. Gagging or dysphagia with different consistencies of food should be noted. Family history of reflux, especially as an infant, may be helpful. Clinical questionnaires, including the Infant Gastroesophageal Reflux Questionnaire, have been validated but do not predict prognosis or severity. They are more useful in the research setting.
Box 121.2. Common Non-reflux Causes of Vomiting
•Urinary tract infection
•Peptic ulcer disease
•Gall bladder disease
•Urea cycle defects
•Hydrocephalus and shunt malfunctions
•Dietary protein intolerance
•Congestive heart failure
Other (Seen in Adolescents)