Gastroesophageal Reflux

After completing this article, readers should be able to: Gastroesophageal reflux is a common disorder in the pediatric population. The spectrum of symptom presentation varies substantially, and the disease manifestations can differ, depending on the patient’s age and health status. For example, a healthy 3-month-old infant can present with regurgitation in the absence of other symptoms. On the other hand, a 14-year-old child who has cerebral palsy may present with anemia, food refusal, and recurrent aspiration pneumonia. The first case is an example of physiologic gastroesophageal reflux (GER), the second of gastroesophageal reflux disease (GERD). The challenges in managing reflux lay in determining what is physiologic and what is pathologic.GER is defined as the passage of gastric contents into the esophagus, which can be a normal physiologic process in many infants. GERD, on the other hand, is defined as symptoms or complications of GER. Regurgitation is defined as the passage of gastric contents into the oral pharynx. Vomiting is defined as expulsion of the refluxed gastric contents from the mouth. Rumination is a rare functional disorder characterized by voluntary, habitual regurgitation of stomach contents into the mouth for self-stimulation. The material can be rechewed and either reswallowed or brought out of the mouth. Rumination in infants may signify a psychiatric disorder or social deprivation.GER is common in infancy. A report on its prevalence in 948 infants in Chicago revealed that 50% of infants ages 0 to 3 months regurgitated at least once daily, 67% at age 4 months, and 5% by age 12 months. (1) Thus, the majority of infants who have GER eventually “outgrow” their reflux. In children 3 to 17 years of age, the prevalence of the different symptoms of reflux range between 1.4% and 8.2%. (2) In a survey of predominantly African-American high school students, the prevalence of esophageal symptoms of GERD (heartburn, regurgitation, and dysphagia) was 33%, and the association with smoking was significant. (3)Reflux occurs because of the transient relaxation of the lower esophageal sphincter. The short infant esophagus that has limited volume and the predominantly recumbent position of infants facilitate the regurgitation of gastric contents. In addition, delayed gastric emptying and increased abdominal pressure contribute to the development of GER. Some reports of increased familial concordance for GERD symptoms, hiatal hernia, erosive esophagitis, Barrett esophagus, and esophageal adenocarcinoma propose chromosome 13 locus (13q14) as being associated with severe pediatric GERD. (4) Chromosome 9 locus has been proposed as having an association with infantile esophagitis. (5)Common presenting signs and symptoms of reflux can differ by age (Table 1). The most common manifestation of GER in infants is vomiting. Fortunately, only a small number of infants develop GERD with complications such as failure to thrive, irritability, dysphagia, odynophagia, and arching of the back during feedings. Infants who have GERD may develop apparent life-threatening events (ALTEs), reactive airway disease, recurrent aspiration pneumonia, and chronic cough. Rarely, GERD results in stereotypic repetitive stretching and arching movements that may be mistaken for atypical seizures or dystonia, a condition known as Sandifer syndrome.In preschool-age children, GERD may present as intermittent vomiting, food refusal, or respiratory complications. Older children are more likely to have adult-type symptoms such as heartburn, regurgitation, dysphagia, or food impaction. More severe inflammation may cause chronic blood loss with anemia and hematemesis. Chronic inflammation rarely leads to the development of the premalignant condition known as Barrett esophagus.One of the challenges facing the practitioner caring for children is to distinguish vomiting due to GER or GERD from vomiting caused by other disorders. Diseases affecting a variety of systems can produce vomiting. A detailed history and physical examination can help eliminate many of these disorders. Table 2 summarizes some of the common causes of nonreflux-related emesis. Among the warning signs suggestive of nonreflux disease is bilious or forceful vomiting, which can be caused by bowel obstruction or pyloric stenosis. Other warning signals include hematemesis, hematochezia, diarrhea, abdominal tenderness or distention, onset of vomiting after 6 months of age, fever, lethargy, hepatosplenomegaly, seizures, macrocephaly, or microcephaly.A history and examination are the first and most important steps in evaluating a child who has reflux. It is important to address questions directly to a child who is able to communicate. Important elements of the history are listed in Table 3. These findings can help to delineate reflux disease or point to nonreflux conditions.For most infants and children who have GER, a history and physical examination are sufficient to diagnose nonpathologic GER reliably. Diagnostic testing should be saved for the child who has complications or when the diagnosis of GERD is in question. The decision to select a specific diagnostic test is based on the clinical question that needs to be answered. For example, a child suspected of having esophagitis needs esophageal biopsies, whereas a child who has pulmonary symptoms and no clinical GERD symptoms may benefit from a pH probe study.The upper gastrointestinal (UGI) series is a common modality for evaluating the UGI tract. A positive contrast agent, such as barium, is used to opacify the UGI tract, and fluoroscopic and radiographic images are obtained, yielding both functional and structural information. Examples of conditions that can be identified on UGI imaging are malrotation, esophageal or antral webs, pyloric stenosis, and a congenital band around the lower esophagus known as a Schatzki ring, which is associated with hiatal hernia (Figs. 1 and 2). In general, UGI contrast studies cannot discriminate between physiologic and nonphysiologic reflux. Esophageal pH monitoring measures the frequency and duration of acid reflux episodes into the esophagus through transnasal placement of microelectrodes that continuously sense the presence of acid. This is used widely as an index of esophageal acid exposure and can be useful in determining the presence of a temporal association between acid reflux and frequently occurring symptoms and for assessing the adequacy of dosage of histamine-2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) in children whose GERD symptoms are not improving. The reproducibility of the reflux index for this test ranges from 69% to 85%, and it cannot detect nonacidic reflux. If apnea is suspected, simultaneous correlation with respiratory efforts and chest wall movement is necessary. An alternative to the traditional esophageal pH monitoring employing a nasal catheter wireless system is being evaluated in older children. A small capsule containing a radio transmitter can be placed endoscopically in the distal esophagus. The capsule can monitor pH wirelessly for 48 hours. The capsule then detaches from the esophageal wall and passes through the GI tract.Upper endoscopy allows macroscopic and microscopic evaluation of the esophagus and the UGI tract (Fig. 3). The severity of esophagitis can be evaluated, as can the presence of complications such as esophageal strictures or Barrett esophagus. Endoscopy allows exclusion of other conditions that mimic GERD, such as eosinophilic esophagitis, pill esophagitis, or Crohn disease. White specks have been reported as a specific esophageal finding for eosinophilic esophagitis (Fig. 4). (6) The sensitivity of white specks in the esophageal mucosa was only 30%, but the specificity was 95%. The stomach and duodenum can be evaluated for disorders such as peptic ulcer and celiac disease. Visual inspection alone may not be adequate because macroscopic diagnosis does not correlate with histologic features 50% of the time. (7) Therefore, it is useful to obtain biopsies at the time of endoscopy to detect microscopic disease and differentiate between reflux and nonreflux inflammation.MII is a new technology that allows detection of reflux without measuring pH. It captures changes in the electrical impedance during the movement of a bolus between the measuring electrodes. MII allows detection of the direction of the moving bolus, thus distinguishing a swallow from a regurgitated bolus. A pH sensor is included as an additional channel. Some data are being published regarding normal impedance values for preterm infants, (8) but validated standards for different pediatric populations are still lacking. In its current state, the significance of this technology is the correlation of events, especially respiratory, with nonacid reflux.This technology is based on the consumption of a technetium-labeled feeding. A nuclear image scan is performed to detect technetium in the GI or respiratory tract. The scan allows the measurement of gastric emptying, detects acid and nonacid reflux, and may detect aspiration in 60-minute or delayed films. The sensitivity of this test is low, ranging from 15% to 59%, but the specificity is higher at 33% to 100%.Complications of GERD are numerous and manifest as both esophageal and extraesophageal disorders.Pulmonary complications of GERD include asthma, bronchitis, apnea, ALTE, chronic cough, and recurrent aspiration pneumonia. Ear, nose, and throat complications include hoarseness, laryngitis, sinusitis, dental erosions, and recurrent otitis media. There is an increased association of such disorders in children who have GERD compared with other children. For example, a study associating asthma with GERD showed a 13.2% prevalence with reflux versus a 6.8% prevalence in children who had no reflux (P<0.0001). (9) The same investigators found similar associations with pneumonia, sinusitis, and laryngitis. The nature of the relationship between respiratory disorders and GERD is controversial. Both GERD and asthma are common pediatric disorders that can coexist. However, studies show that GERD can be a contributing factor in patients who have asthma, especially in severe refractory cases. Other studies suggest that reflux occurs as a secondary phenomenon.Will medical treatment of GER disease improve symptoms of asthma? Studies suggest that approximately two thirds of children who have asthma improve with reflux therapy. (10)(11)(12) Such improvement can be quantified as a reduction of dosages of bronchodilator therapy or anti-inflammatory medications, including inhaled or systemic steroids. Therefore, in a subset of patients who have asthma and reflux, medical therapy for reflux is warranted.Chronic aspiration occurs when airway protective mechanisms fail and gastric or oral contents are seen inside the lungs. Consequently, severe pneumonia, interstitial lung disease, and pulmonary fibrosis can occur. Neurologically impaired children are at higher risk for developing reflux and aspiration.Chronic esophageal exposure to acid can result in inflammation and subsequent development of reflux esophagitis, esophageal strictures, Barrett esophagus, and adenocarcinoma. In severe chronic cases, UGI bleeding and anemia may develop. Children who are neurologically impaired are at greater risk for developing such complications. Barrett esophagus and esophageal adenocarcinoma rarely develop in the pediatric age group. In addition to neurologic impairment, other risk factors for long-term complications of GERD include lifestyle factors such as obesity, size and gestational age at birth, and repaired esophageal atresia. Adult studies correlate body mass index not only with severity of symptoms such as heartburn, erosive esophagitis, and hiatal hernia, but with severe complications such as Barrett esophagus and cancer.GERD occurs more frequently in neurologically impaired children, whose reflux often is resistant to standard medical therapy and frequently requires surgical correction through fundoplication. Moreover, such children are at higher risk for developing complications related to their surgery, with higher rates of additional operations. A report by Del Giudice and associates (13) showed a high prevalence of GERD-related disease in children who had cerebral palsy. Symptomatic GI disease was seen in as many as 92% of the children. Swallowing disorder and dysfunction of oral and pharyngeal phases was found in 93% of patients. Vomiting, regurgitation, and abdominal pain occurred in 33% of patients, and chronic pulmonary aspiration occurred in about 40%. Interestingly, 91% of those patients studied had reflux on pH probe study or biopsy-proven esophagitis, and almost 67% had a significant delay in emptying (by scintigraphic gastric emptying studies).GER in infants carries a favorable prognosis because most children tend to “outgrow” their reflux symptoms by 12 months of age. Children who have neurologic impairment, prematurity, obesity, esophageal atresia, or a strong family history of severe complicated GERD are at higher risk for developing complications and carry a poorer prognosis compared with infants who have physiologic reflux.The goal of treating children who have GERD is to eliminate symptoms, heal the esophagitis, and manage and prevent complications. In physiologic reflux, reassuring the family may be the only intervention necessary for this usually self-limited condition.The rationale for empiric therapy in adults who have GERD is widely accepted. Empiric treatment trials with omeprazole have been reported for treating cough, heartburn, noncardiac chest pain, and dyspepsia in adult patients. In pediatric patients, the decision to proceed to empiric therapy has not been validated for any symptom presentation. However, when presenting symptoms are typical, the diagnosis can be based on the history, and additional diagnostic investigation is unlikely to affect the prognosis or management. If pharmacotherapy is warranted, most patients respond to treatment with acid suppression. Therefore, a therapeutic trial may be cost-effective. Currently, PPIs help many patients who have severe GERD.A prompt diagnostic evaluation is indicated for patients presenting initially with unusual or serious complications, including emesis, failure to thrive, dysphagia, or severe respiratory complications. Diagnostic investigation is warranted when patients either do not respond to therapy or have an unusual course. No single test is appropriate for all patients suspected of having GERD. Which test to order depends on the clinical presentation and the questions the clinician would like to have answered.Lifestyle changes can be helpful for children who have mild disease. Pharmacologic therapy is advocated for the child who has significant reflux disease, especially in the presence of complications. Because neurologically impaired children develop GERD more frequently and are more likely to develop GERD-related complications, management of these children may need to be more aggressive.The natural history of physiologic reflux in most infants is resolution as lower esophageal sphincter function matures. Reassuring and educating the family about this disorder are keys for management. In an otherwise healthy infant, no testing or therapeutic intervention is necessary.Infants who have GERdo not benefit from changing formula protein. However, in a subset of infants who vomit due to milk protein intolerance, some authorities advocate a 2-week trial of hypoallergenic formula. Thickening the milk or formula with agents such as rice cereal does not improve GER index scores but can decrease the number of episodes of vomiting. Thickening the formula with thickening agents such as rice cereal increases the caloric density of the feedings, which may be beneficial in underweight infants who have reflux.A number of pH probe studies have demonstrated a decrease in GERD episodes for infants placed in the prone position. However, the American Academy of Pediatrics advocates the supine position for infants to reduce the risk for sudden infant death syndrome (SIDS). Therefore, prone positioning during sleep is considered only when the risk of death due to GERD outweighs the potential increased risk of SIDS.Mild symptoms of GERD in the absence of complications may be managed by lifestyle changes for older children and adolescents. Most of the evidence is extracted from adult studies. The recommendations include weight loss for obese patients and avoidance of tobacco and alcohol. Limited pediatric evidence suggests that avoiding caffeine, chocolate, and spicy foods that provoke symptoms is beneficial.Antacids, which buffer the acidic contents of the stomach, can be used for short-term therapy and relief of symptoms. Aluminum-containing antacids should be prescribed with caution in infants due to potential development of adverse effects such as neurotoxicity, anemia, and osteopenia.H2RAs inhibit histamine-2 receptors on the parietal cells. Cimetidine, famotidine, nizatidine, and ranitidine are examples of drugs in this family. A number of studies demonstrate efficacy of these drugs in treating esophagitis, but the healing rate of erosive esophagitis is 60% to 70%, which is less than the healing rate for PPIs. Table 4 provides doses and adverse effects of H2RAs.The primary underlying phenomenon contributing to GER is transient relaxation of the lower esophageal sphincter. Because prokinetic agents increase the tone of the sphincter, they could, theoretically, be effective drugs. However, studies have failed to demonstrate that prokinetic agents consistently reduce the frequency of reflux, suggesting that they do not affect the frequency of transient relaxations of the lower esophageal sphincter. Nevertheless, children can benefit from prokinetic therapy if gastric emptying is delayed, as evidenced by double-blind studies and randomized comparison studies for prokinetic agents such as cisapride, metoclopramide, and erythromycin.Sucralfate acts by adhering to peptic lesions, protecting the mucosal surface from the acidic or digestive enzyme effects. This agent has been shown to have similar efficacy as H2RAs in the treatment of esophagitis. Because sucralfate contains aluminum, the potential adverse effects of aluminum, especially in infants, need to be considered.Similarly, sodium alginate forms a surface gel that decreases the regurgitation of gastric contents into the esophagus and protects the esophageal mucosa. Efficacy studies have demonstrated conflicting results. The formulation used in most published studies is not available in the United States.PPIs deactivate the H+, K+ATPase pumps. Their efficacy is related to their ability to maintain higher gastric pH for a prolonged period of time and suppress the meal-induced acid secretion that did not occur with H2R blockade. The use of PPIs is indicated when GERD is refractory to therapy with H2RAs. The inhibition of acid secretion in the stomach is associated with lower gastric volumes, facilitating gastric emptying and decreasing the volume of refluxed material. Omeprazole and lansoprazole are the PPIs studied most frequently in children. The pharmacokinetic profiles of PPIs are similar to those in adults. However, because children have higher metabolic activities than adults, they need higher doses on a per-kilogram basis (Table 5). The effective dose of PPIs ranges from 0.5 to 3.3 mg/kg per day.Antireflux surgery is indicated for children who have significant complications of GERD and have failed to respond to adequate medical therapy. Surgical treatment can be an attractive option because it can be curative, avoiding the need for long-term medication use, but the failure rates to control symptoms are high, and morbidity and occasionally death are reported in the literature. related to surgery occur at higher in neurologically impaired children, those who have repaired esophageal atresia, and children with chronic lung disease compared with otherwise normal children. of recurrent GERD after surgery requires a high of and the use of more than contrast studies are useful for the or a However, pH probe monitoring and endoscopy are to the functional adequacy of the surgery in acid reflux and is a common disorder in Most infants develop the physiologic and need intervention because the condition as they Diagnostic testing should be to the clinical for medical therapy usually gastric acid surgical therapy is indicated for children who have significant reflux complications resistant to medical therapy. Children who are neurologically impaired are especially at risk for developing reflux and complications.