Version May 2024
INTRODUCTION — The passage of gastric contents into the esophagus (gastroesophageal reflux [GER]) is a normal physiologic process that occurs in healthy infants, children, and adults. Most episodes are brief and do not cause symptoms, esophageal injury, or other complications. In contrast, GER disease (GERD) occurs when the reflux episodes are associated with symptoms or complications. The type of symptoms and complications of GERD in children vary with the child's age.
Several treatment options are available for controlling symptoms and preventing complications in children with GERD. The choice among them depends on the patient's age, type and severity of symptoms, and response to treatment.
This topic review focuses on the management of GERD in children and adolescents. Other topic reviews relevant to GER and GERD in the pediatric age group are:
●(See "Gastroesophageal reflux in infants".)
●(See "Gastroesophageal reflux in premature infants".)
These discussions are generally consistent with the consensus guideline issued by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) [1], and the American Academy of Pediatrics (AAP) [2].
DEFINITIONS — The following definitions are used in this topic review, consistent with the guideline [1]:
●Gastroesophageal reflux (GER) – The passage of gastric contents into the esophagus, with or without regurgitation and vomiting
●Gastroesophageal reflux disease (GERD) – GER that leads to troublesome symptoms and/or complications
●Erosive esophagitis – Esophageal inflammation that leads to erosions that are visible at endoscopy
REFERRALS
●Gastroenterology – We suggest referral to a pediatric gastroenterologist in the following circumstances, consistent with the guideline [1]:
•Alarm signs or symptoms that suggest an underlying disease, including unexplained weight loss, persistent forceful vomiting, dysphagia or odynophagia or hematemesis.
•GERD symptoms that are refractory to treatment (ie, little or no symptomatic response to optimal treatment by eight weeks).
•Endoscopically confirmed GERD that requires chronic treatment with acid-suppressing medication, ie, the patient cannot be permanently weaned from acid-suppressing medications within 6 to 12 months, despite repeated attempts.
●Pulmonology or otolaryngology – Patients with unexplained chronic respiratory symptoms, chronic cough, or unexplained hoarseness usually should be evaluated first by a pulmonologist or otolaryngologist. The specialty evaluation typically includes a focused history, examination, chest radiograph, and spirometry. (See "Approach to chronic cough in children" and "Hoarseness in children: Evaluation".)
TREATMENT APPROACH BY PRESENTING SYMPTOMS — Definite indications for treatment of GERD are:
●Heartburn (distinct and recurrent symptoms) (see 'Heartburn' below)
●Esophagitis (documented on endoscopy) (see 'Esophagitis' below)
By contrast, extraesophageal disease (asthma or pneumonia) usually has causes other than GERD. Treatment for GERD is appropriate only for selected patients. (See 'Extraesophageal manifestations of GERD' below.)
The treatment approach for each of these presenting symptoms is outlined in the following sections, followed by a more detailed discussion of each type of intervention. (See 'Lifestyle changes' below and 'Pharmacotherapy' below and 'Surgery' below.)
Heartburn — Patients with both heartburn and alarm symptoms (dysphagia, weight loss, odynophagia, hematemesis, or recurrent forceful vomiting) should be referred to a gastroenterologist for further evaluation, which may include upper endoscopy.
For patients with typical esophageal symptoms (eg, heartburn, increased salivation, retrosternal or epigastric discomfort, and no alarm symptoms), we recommend a "step-up" approach, starting with conservative options and progressing to more intensive therapy if needed (algorithm 1).
●Mild – For children and adolescents with mild or infrequent heartburn (averaging once a week or less), we suggest a trial of lifestyle changes (weight management for overweight patients; cessation of smoking and vaping and avoidance of tobacco smoke; head of bed elevation; and avoidance of chocolate, caffeine, spicy foods, alcohol, and other foods that exacerbate symptoms). Occasional use of antacids or histamine type 2 receptor antagonists (H2RAs) is acceptable for short-term relief of symptoms, but frequent use of these drugs (more than once/week) calls for advancement of therapy [2]. (See 'Lifestyle changes' below.)
●Moderate or severe – If the heartburn symptoms are moderate or severe, or fail to respond to lifestyle changes, we recommend a trial of acid-suppression therapy. For this trial, we typically use a proton pump inhibitor (PPI). An H2RA is a reasonable alternative but may be limited by the possibility of tachyphylaxis that can occur during a typical trial duration of four to eight weeks [1,3]. If symptoms do not improve, or recur after stopping treatment, the patient should be evaluated by a pediatric gastroenterologist. If an H2RA is used initially and there is no improvement or partial improvement in two to four weeks, or if long-term treatment is required, therapy should be advanced to a PPI. (See 'Pharmacotherapy' below.)
For neurologically impaired children with symptoms consistent with GERD, empiric treatment with acid-suppressing medications, usually a PPI, is appropriate because GERD is common in this population [4]. However, if long-term pharmacotherapy is planned, endoscopy should be performed to evaluate for esophagitis. (See 'Pharmacotherapy' below and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents", section on 'Endoscopy and histology'.)
Children with autism spectrum disorder who are nonverbal often present with nonspecific, atypical signs and symptoms, including food refusal, chest tapping, pica, chewing on objects, and/or excessive salivation. (See "Autism spectrum disorder in children and adolescents: Clinical features".)
Esophagitis
●Treatment strategy – For patients with endoscopically documented esophagitis, we employ a "step down" approach, in which we treat with a PPI for 8 to 12 weeks, then withdraw treatment as tolerated, or extend treatment if necessary (algorithm 2). We suggest using a PPI because this class of medication is more effective than H2RAs for initial healing of esophagitis [1,2]. Dosing and adverse effects are outlined in the table (table 1). (See 'Proton pump inhibitors' below.)
●Follow up – Further evaluation and treatment of patients with esophagitis depends on the severity of the esophagitis at baseline and on the degree of symptom relief with treatment. The histologic findings and differential diagnosis of esophagitis, and grading of erosive esophagitis are reviewed separately. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Endoscopic findings' and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents", section on 'Endoscopy and histology'.)
•Patients with only mild esophagitis (eg, histologic findings consistent with GERD but no grossly visible findings) can be treated for four to eight weeks and reassessed based on the degree of symptom relief.
•Patients with peptic erosive esophagitis at baseline should undergo a repeat endoscopy after three to six months of treatment; the repeat endoscopy is important to demonstrate healing and also to identify the possibility of stricture.
Distinguishing peptic esophagitis (ie, esophagitis caused by acid reflux) from eosinophilic esophagitis (EoE) may be difficult because both disorders are characterized by esophageal eosinophilia, and they may have similar symptoms. However, in peptic esophagitis the inflammation is usually greatest in the distal esophagus, and in EoE the number of eosinophils often exceeds 15 per high-power field. Six to eight biopsies from different areas of the esophagus are recommended [5,6]. Esophagitis and symptoms that persist despite several months of effective acid suppression also should raise suspicion for EoE. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE)".)
When continuous therapy is necessary to control symptoms, we suggest treatment with a PPI; however, H2RAs are a reasonable choice for brief or intermittent treatment [1]. Long-term treatment with PPIs is sometimes necessary but should be undertaken for clear indications and with caution due to potential long-term side effects (see 'Safety' below). If the symptoms are well controlled, a trial of discontinuing treatment should be performed every three to six months, unless the patient has either a history of severe and recurrent esophagitis, or the endoscopy demonstrates Barrett esophagus (replacement of the normal squamous epithelium with metaplastic columnar epithelium). Long-term treatment with acid-suppressing medications is appropriate if symptoms or endoscopy indicate chronic or recurrent esophagitis, without evidence for EoE; such patients should be managed by a pediatric gastroenterologist, if possible. (See 'Discontinuing proton pump inhibitors' below and "Barrett's esophagus: Surveillance and management".)
Dysphagia or odynophagia — For patients with dysphagia (difficulty swallowing) or odynophagia (pain with swallowing), empiric treatment for reflux (lifestyle changes or pharmacotherapy) is not recommended unless other causes of the symptoms have been excluded. Instead, these patients should have a careful diagnostic evaluation including upper endoscopy.
Dysphagia may be caused by GERD but also may be due to other causes, such as EoE, pill-induced esophagitis (direct mucosal injury from swallowed medications, such as tetracycline that remain in the esophagus causing ulceration), esophageal dysmotility (eg, achalasia), or foreign body. Pill esophagitis is also an important cause of odynophagia; other causes include infectious esophagitis caused by cytomegalovirus, herpes, or Candida. (See "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents", section on 'Dysphagia or odynophagia'.)
Rumination — Children who do not respond to conventional treatment for GERD should be evaluated for rumination. A small study of children with refractory GERD reported that 44 percent met criteria for rumination, but interpretation of these findings is limited because the study used novel high-resolution impedance indices to diagnose rumination rather than the standard antroduodenal manometry. Reflux events in patients with rumination were more likely to occur in the proximal esophagus, were often nonacidic, occurred more often postprandially, and were highly associated with symptoms [7]. (See "Approach to the infant or child with nausea and vomiting", section on 'Rumination syndrome'.)
Extraesophageal manifestations of GERD
Asthma with gastroesophageal reflux
●With GERD symptoms – For patients with persistent moderate to severe asthma (particularly, nocturnal wheezing) and clear symptoms suggesting GERD, including frequent heartburn or regurgitation, we suggest a trial of effective acid suppression for four to eight weeks [1]. Management after the trial depends on the response. (See "Gastroesophageal reflux and asthma", section on 'Empiric therapy in patients with symptomatic GERD'.)
This empiric approach to treatment is appropriate because although gastroesophageal reflux (GER) is an established trigger for asthma in many patients, it is difficult to predict which patients will respond to treatment [8]. In approximately 60 percent of children with asthma and clinical or laboratory evidence of GER, asthma control will improve with effective treatment for reflux [9]. In adults with GERD symptoms and moderate to severe asthma (or nocturnal asthma), randomized controlled trials of PPIs demonstrated small but significant improvements in numbers of asthma exacerbations. (See "Gastroesophageal reflux and asthma", section on 'Evidence that GERD treatment improves asthma'.)
●Without GERD symptoms – A trial of acid-suppressing medication is generally not recommended for children or adults with asthma in the absence of GERD symptoms [1]. However, in some patients with asthma, GERD may be silent and diagnosed only with esophageal pH-impedance monitoring (pH-MII). Thus, pH-MII or an empiric trial of antireflux treatment is reasonable in selected patients with asthma who are difficult to control (steroid-dependent) and/or have nocturnal onset of asthma, even in the absence of apparent symptoms of GERD. Other causes of wheezing should be carefully excluded, including foreign body aspiration. (See "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents", section on 'Asthma' and "Evaluation of wheezing in infants and children".)
Antireflux surgery (fundoplication) is generally not recommended as a treatment for asthma that is thought to be related to GERD. Evidence to support the efficacy, patient selection, and role of antireflux surgery for patients with asthma and GERD is inadequate [10]. Moreover, outcomes following fundoplication in children with asthma have a low rate of success, and as many as 75 percent of children continue to need acid-suppressing medications following surgery [1].
Recurrent pneumonia — When aspiration and recurrent pneumonia are strongly suspected to be related to GERD, aggressive treatment is appropriate to prevent chronic progression of pulmonary disease [1,11]. If pulmonary disease is mild, medical treatment with acid suppression can be used; pulmonary function should be carefully monitored in follow-up.
There are no definitive tests to determine whether GERD is the cause of recurrent pneumonia in a given patient. Clinical decisions must be based on an individual patient's clinical risk and a combination of tests for GER, aspiration, and immune deficiency. The possibility of antegrade aspiration (aspiration during swallowing) should be fully investigated because this is a more common cause of recurrent pneumonia than retrograde aspiration (GERD). If the pneumonia is consistently in the same region of the lung, the patient should be evaluated for a rare H-type tracheoesophageal fistula. (See "Aspiration due to swallowing dysfunction in children" and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents", section on 'Recurrent pneumonia'.)
If pulmonary disease is severe or progressive, transpyloric feeding or surgical treatment with fundoplication should be considered, but the success rate of fundoplication for treating pulmonary disease is poor [1]. (See 'Surgery' below.)
Other extraesophageal symptoms — GERD is not a common cause of isolated chronic cough in children, except in those with neurologic abnormalities predisposing to aspiration; however, whether GERD causes cough remains unknown [12]. Stridor, hoarseness, sinusitis, and otitis media have been associated with GERD, mostly in case reports and case series in children. Neither the association with GER nor the benefits of antisecretory therapy have been established [1]. (See "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents", section on 'Chronic cough' and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents", section on 'Other conditions'.)
MEDICAL TREATMENT
Lifestyle changes — We suggest lifestyle changes as an initial approach to treatment for children and adolescents with mild or infrequent symptoms of gastroesophageal reflux (GER), such as occasional heartburn or painless regurgitation. Lifestyle changes also may be helpful as an adjunct to pharmacologic treatment in patients with moderate or severe symptoms suggestive of GERD, or with documented esophagitis.
The type of lifestyle changes that may be beneficial depend on the patient's age and symptom characteristics. An empiric approach is appropriate since there is little evidence that one of these approaches is more effective than others. Because few studies have examined the efficacy of lifestyle modifications in children and adolescents with GERD [1], recommendations are mostly extrapolated from studies in adults. Even in adults, there is limited evidence supporting efficacy for these interventions. (See "Medical management of gastroesophageal reflux disease in adults", section on 'Lifestyle and dietary modification'.)
The following approaches have some benefit in adult patients with reflux, but have not been rigorously evaluated in children [1,13]:
●Weight loss or weight management for individuals who are overweight [1].
●Head of bed elevation and left lateral positioning – This is important for individuals with nocturnal or laryngeal symptoms, but its value for other situations is unclear. A trial of positional therapy is reasonable for children with symptoms of GERD but is not recommended for sleeping infants [1].
The following lifestyle approaches also are used frequently. The efficacy of these measures for managing symptoms is inconsistent, but there is some evidence that they improve laboratory measures of reflux (such as lower esophageal sphincter pressure) [1,13]:
●Dietary modification – Sensitivity to dietary triggers varies among individuals. Therefore, dietary restriction should be limited to those foods that are associated with symptoms in a specific patient, as determined by trials of individual foods. Options include:
•Avoid foods that tend to induce reflux by reducing lower esophageal sphincter pressure, including chocolate, peppermint, and caffeinated beverages.
•Avoid acidic foods, including colas, orange juice, and tomato sauce. Although their contribution to gastric acidity is probably minimal, ingestion of these foods seems to exacerbate symptoms in some patients.
•Avoid high-fat foods in selected patients. This strategy is recommended in adults with GERD because fatty foods tend to slow gastric emptying and thereby promote reflux; however, the benefit of reducing fat intake in children is unproven. Decisions about whether to restrict dietary fat depend on the infant or child's overall nutritional status and the clinical response.
●Positioning – Avoid the supine position soon after eating.
●Salivation – Promote salivation by either chewing gum or using oral lozenges. Salivation neutralizes refluxed acid, thereby increasing the rate of esophageal acid clearance.
●Alcohol, tobacco, and vaping – Avoid alcohol and tobacco (including passive exposure to tobacco smoke). Substances that contain nicotine reduce lower esophageal sphincter pressure, and smoking also diminishes salivation [14].
Lifestyle modifications also are used to manage GER in infants, including changes in feeding, positioning, and avoidance of tobacco smoke and nicotine exposure. These approaches are discussed in detail in a separate topic review. (See "Gastroesophageal reflux in infants" and "Gastroesophageal reflux in premature infants".)
Pharmacotherapy — Drugs that are used for treatment of GERD can be grouped into the following categories (table 1):
●Proton pump inhibitors (PPIs)
●Histamine type 2 receptor antagonists (H2RAs)
●Antacids
●Surface agents
●Prokinetics
The experience with each of these categories of drugs in children and adolescents is detailed in the following sections. Pharmacotherapy for GER in adults is discussed in detail separately. (See "Medical management of gastroesophageal reflux disease in adults".)
Proton pump inhibitors — PPIs block acid secretion by irreversibly binding to and inhibiting the hydrogen-potassium ATPase pump that resides on the luminal surface of the parietal cell membrane. The drugs in this class include omeprazole, lansoprazole, rabeprazole, pantoprazole, esomeprazole, and dexlansoprazole. The differences in efficacy among drugs in this class appear to be small and of uncertain clinical significance; thus, it is reasonable to make treatment decisions based on cost and on which dosing formulation is easiest to administer to the child. Aspects of the pharmacology of PPIs and their efficacy in adults are discussed in detail separately. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Pharmacology'.)
Omeprazole, esomeprazole, lansoprazole and dexlansoprazole, and pantoprazole have been most extensively studied in children and are approved by the US Food and Drug Administration (FDA) for this age group [1]. Approval updates and labeling changes are available on the FDA website [15].
Indications and efficacy — The evidence for efficacy of PPIs depends on the patient population:
●Esophagitis or marked GERD symptoms – For treatment of endoscopy-proven peptic esophagitis and esophagitis-associated symptoms, we suggest use of a PPI rather than an H2RA. This suggestion is primarily based on randomized studies in adults, which demonstrated that PPIs are effective and superior to H2RAs [1,16]. Compared with H2RAs, PPIs produce a greater reduction in acid secretion, have a longer duration of action, and tolerance does not develop. (See "Medical management of gastroesophageal reflux disease in adults".)
Our suggestion that PPIs be selected in preference to other forms of acid suppression in patients with documented esophagitis is based on extrapolation from studies in adults, and a few clinical trials in children, as well as observations that tachyphylaxis (loss of response) tends to occur with H2RAs [17]. In addition, there may be better compliance with PPIs that can be given once daily as compared with multiple-dose regimens.
The efficacy of PPIs for treating esophagitis or heartburn in children and adolescents is based on limited evidence [18]. Several case series report that PPIs have healed severe esophagitis that had been unresponsive to H2RAs [11,19]. The only controlled trials compare PPIs with alternate forms of acid suppression. These demonstrated that PPIs were as effective as H2RAs for initial treatment of esophagitis [20], marked GERD symptoms [21], or maintenance of remission after initial treatment with PPIs [22]. The superiority of PPIs over H2RAs is largely based on indirect evidence that PPIs are more effective for reducing gastric acidity and that H2RAs become less effective over time (tachyphylaxis) [23].
●Asthma and other GERD manifestations – The benefit of PPIs on extraesophageal manifestations of GERD in children, such as asthma, has not been well studied, although they are used for this purpose in children based on data in adults. (See 'Asthma with gastroesophageal reflux' above and "Gastroesophageal reflux and asthma".)
●Infants – Several randomized trials and a systematic review concluded that PPIs are not beneficial in infants with irritability or regurgitation, because they do not improve symptoms as compared with placebo [23-26]. However, PPIs or other acid-suppressing regimens are appropriate for an infant with moderate or severe esophagitis on endoscopic biopsies, a rare occurrence in this age group. (See "Gastroesophageal reflux in infants", section on 'Pharmacotherapy'.)
Dosing — Dosing guidelines for PPIs vary considerably; typical doses are outlined in the table (table 1). Infants and younger children appear to metabolize PPIs more rapidly and may require higher per-kilogram dosing than older individuals [1,27,28]. In pediatric studies, effective doses of omeprazole ranged from 0.3 to 3.5 mg/kg/day (maximum 80 mg/day) and doses of lansoprazole ranged from 0.73 to 1.66 mg/kg/day (maximum 30 mg/day) [29]. However, there is little evidence to support doses of omeprazole over 40 mg daily for children, even for the treatment of endoscopically documented esophagitis. Some children may require twice-daily dosing to achieve optimal acid suppression; we suggest starting with once-daily dosing and advancing to twice-daily dosing if there is breakthrough of symptoms. Some providers alternate doses of a PPI with an H2RA, but there is no specific evidence supporting this practice.
For infants who require acid suppression (eg, due to documented esophagitis), higher doses might be needed to achieve adequate levels of acid suppression, due to differences in pharmacokinetics in infants compared with older children. (See "Gastroesophageal reflux in infants", section on 'Pharmacotherapy'.)
The duration of therapy is four to eight weeks for moderate to severe heartburn and up to 12 weeks for documented esophagitis. If the esophagitis is severe (erosive), PPI treatment may be prolonged for three to six months, followed by repeat endoscopy to assess for healing. (See 'Esophagitis' above and "Medical management of gastroesophageal reflux disease in adults", section on 'Proton pump inhibitors'.)
The form of drug is important when choosing a PPI for children, for whom swallowing a capsule can be difficult. Several of these drugs are formulated as capsules containing enteric-coated granules that can be sprinkled onto soft foods (eg, applesauce), dissolvable tablets that can be placed on the tongue or dissolved in water, or powder packets that can be dissolved or compounded and flavored in a suspension.
Safety — Although PPIs are generally well tolerated, long-term studies have raised concerns that long-term treatment with PPIs is associated with increased risk for some infectious, metabolic, and nutritional disorders. Most data on the long-term safety of PPIs are from studies in adults.
Potential safety concerns based on case-control studies in infants and children suggest an increased risk of necrotizing enterocolitis, pneumonia, upper respiratory tract infections, sepsis, urinary tract infections, Clostridioides difficile infections, and fractures [1,30,31]:
●Infectious complications – In 2012, the FDA issued a Safety Alert about the association of PPI treatment with C. difficile and encouraged providers to consider the possibility of C. difficile-associated diarrhea in PPI users with persistent diarrhea [32]. (See "Clostridioides difficile infection in children: Microbiology, pathogenesis, and epidemiology", section on 'Other risk factors'.)
Other possible infectious complications of PPIs include community-acquired pneumonia [33,34] and small intestine bacterial overgrowth [35] and others [31]. A possible explanation for the infectious complications is supplied by a study reporting that treatment with acid-suppressing medications was associated with gastric bacterial overgrowth [36]. Moreover, patients on acid-suppressing medications who experienced significant nonacid reflux also had higher bacterial concentrations in the lungs. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Gastrointestinal effects' and "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Pneumonia'.)
●Malabsorption and bone health – Other safety concerns include malabsorption of vitamin B12, iron, and magnesium [37,38]. Concerns about long-term effects on bone metabolism have been raised based on studies in adults. Several studies reported an association between PPI use during infancy and subsequent fractures during childhood [39-41]. Although the effect size is small, the finding is consistent with studies in adults showing an association between PPI use and osteoporotic fractures [42]. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Adverse effects' and "Drugs that affect bone metabolism", section on 'Proton pump inhibitors'.)
Other concerns about the safety of PPIs have been raised but are not well supported by available data. A theoretical concern for gastric carcinoid tumors or colon cancer was raised because of the observation that long-term use of PPIs may increase serum gastrin levels and induce mild enterochromaffin cell hyperplasia and/or atrophic gastritis. However, no increased risk for cancer has been shown in studies in adults treated with PPIs for up to 11 years [43] or children treated for a median 2.8 years [44]. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Hypergastrinemia'.)
Limited data in adults have raised the possibility of an association between PPI use and nephritis, chronic kidney disease or food allergy. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Kidney disease' and "Pathogenesis of food allergy", section on 'Acid blockade'.)
Discontinuing proton pump inhibitors — Because of the safety concerns described above, patients treated with PPIs should be reevaluated on a regular basis to determine if ongoing use is necessary. Patients who have ongoing symptoms after four to eight weeks of PPI therapy should be reevaluated for treatment adherence and to exclude other causes of the symptoms [1]. If long-term PPI therapy is undertaken, our practice is to attempt to wean patients from PPIs after six months of treatment and then periodically thereafter, depending on symptom control.
Stopping PPIs may be associated with acid rebound, in which discontinuation causes a temporary increase in gastric acid output to levels higher than at baseline, with a corresponding rebound of reflux-related symptoms during the first few weeks after discontinuation of the PPI [45]. The optimal management strategy to minimize problems with acid rebound has not been established. When attempting to discontinue PPIs in patients treated chronically, our practice is to gradually taper PPIs to minimize the potential problem of acid rebound (eg, stepwise reduction in dose over two to four weeks), although there is no clinical evidence that this approach improves the likelihood of successful weaning. In particular, a study of this type of tapering regimen in adults failed to establish a clinical benefit [46]. An alternate approach is to wean the patient initially to an H2RA. The evidence for acid rebound is from studies in adults and is described in detail in a separate topic review. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Discontinuing PPIs'.)
Histamine type 2 receptor antagonists — For patients with mild or intermittent symptoms of GERD that do not respond to lifestyle changes, we suggest a trial of H2RAs rather than PPIs or other drugs. Commonly used H2RAs and doses are outlined in the table (table 1). H2RAs have moderate effects on GER, as measured by relief of symptoms and mucosal healing, but because they have a relatively rapid onset of action, they are well suited for providing symptomatic relief. However, they are somewhat less effective than the PPI class, especially for chronic use [1].
The H2RAs inhibit acid secretion by blocking histamine H2 receptors on the parietal cell. The H2RAs are available in the United States, in both prescription strength and a lower strength for nonprescription (over-the-counter) sales are:
●Cimetidine (Tagamet)
●Famotidine (Pepcid)
●Nizatidine (Axid)
Multiple controlled trials in adults have evaluated the efficacy of H2RAs in adults [16]. These studies have shown that H2RAs are superior to placebo for healing esophagitis and improving symptoms, with little clinical difference among the formulations when dosed appropriately. However, their benefit is greatest for patients with mild esophagitis, and tolerance (tachyphylaxis) develops within days to a few weeks of beginning treatment, limiting efficacy for long-term management [1,17]. H2RAs reach peak onset of action approximately 2.5 hours after dosing, and the duration of action is 4 to 10 hours, so they are useful for on-demand treatment of occasional symptoms, or for short-term continuous use. (See "Medical management of gastroesophageal reflux disease in adults", section on 'Histamine 2 receptor antagonist'.)
Fewer studies have been performed in children, but the results are similar to the experience in adults [47,48]. One randomized trial included 32 children (21 to 29 months) with esophagitis who were randomly assigned to receive cimetidine (30 to 40 mg/kg per day) or placebo [47]. After 12 weeks, healing was observed significantly more often in the cimetidine-treated group. Improvement of esophagitis was seen in all patients with mild or moderate esophagitis compared with only 57 percent of patients with severe esophagitis. In another small trial, children with dyspepsia and abdominal pain who were randomized to famotidine experiences significant improvement in a subjective global pain assessment compared with placebo [49].
The use of H2RAs is associated with an increased risk of enteric infection, particularly C. difficile and community-acquired pneumonia [33] (see "Clostridioides difficile infection in children: Microbiology, pathogenesis, and epidemiology", section on 'Other risk factors'). Cimetidine is a moderate inhibitor of cytochrome P450 (CYP) metabolism and can increase levels of some co-administered medications, such as theophylline, selective serotonin reuptake inhibitors, warfarin, and cisapride (refer to the drug interactions program included with UpToDate). Famotidine and nizatidine do not inhibit CYP metabolism or alter levels of co-administered drugs metabolized by CYP. Of note, ranitidine was withdrawn from the market in the United States in April 2020 because of concerns about contamination with N-Nitrosodimethylamine (NDMA) [50]; low levels of NDMA contaminants have also been found in some nizatidine products [51].
Antacids — Antacids should not be used chronically for treatment of GERD but are appropriate for short-term relief of heartburn in older children, adolescents, or adults with infrequent symptoms (less than once a week) [1]. Antacids often begin to provide relief of heartburn within five minutes, but the duration of the effect is approximately 30 to 60 minutes. Chronic use of antacids is not recommended, due to safety concerns, especially in infants due to potential complications such as hypophosphatemic rickets or in children with renal disease [1,52].
Antacids work by neutralizing gastric pH and thereby decreasing the exposure of the esophageal mucosa to gastric acidity during episodes of reflux. Various preparations that are commercially available usually contain the combination of magnesium and aluminum hydroxide or calcium carbonate. At least two studies suggested that high-dose antacid therapy with magnesium/aluminum-containing acids was as effective as cimetidine for the short-term treatment of esophagitis in children [53,54].
Aluminum-containing antacids can cause aluminum toxicity in infants or in individuals with renal failure. Aluminum toxicity is associated with complications such as osteopenia, microcytic anemia, and neurotoxicity [55-58]. Magnesium-containing antacids can cause hypermagnesemia in patients with renal insufficiency. As a result, use of antacids generally is restricted to short-term relief of symptoms in older children and adolescents. The efficacy and safety of other types of antacids in children have not been well-studied. (See "Antiulcer medications: Mechanism of action, pharmacology, and side effects", section on 'Antacids'.)
Prokinetics — Prokinetic drugs are generally not recommended for management of GERD, because of significant safety concerns and limited efficacy [1,4]. Systematic reviews have not supported the use of metoclopramide [59], cisapride [60], or domperidone [18,61] for treatment of GERD [62]. These drugs should be considered for use only in carefully selected patients who have GERD along with delayed gastric emptying and in whom constipation has been ruled out as a confounding factor. Erythromycin also is used for patients with gastric dysmotility, such as postviral gastroparesis, but its use is limited by side effects and tachyphylaxis (tolerance). The use of these drugs for gastroparesis in adults is discussed in a separate topic review. (See "Treatment of gastroparesis".)
A trial of baclofen may be appropriate in selected patients with refractory GERD, as an alternative to antireflux surgery [1]. Baclofen is a gamma-amino-butyric acid B receptor agonist that inhibits the transient relaxations of the lower esophageal sphincter that are a predominant mechanism of GER. A limited body of evidence in adults and children suggests that baclofen reduces reflux symptoms after acute or chronic dosing, reduces the frequency of esophageal sphincter relaxation and esophageal acid exposure, and accelerates gastric emptying [63-66]. Potential side effects include dyspepsia, drowsiness, and lowered seizure threshold [1]. Because of side effects, baclofen is rarely used to treat GERD in children without underlying neurologic problems. Baclofen is occasionally used for children with cerebral palsy, primarily to improve spasticity. (See "Cerebral palsy: Treatment of spasticity, dystonia, and associated orthopedic issues", section on 'Oral antispasticity drugs'.)
Surface agents — Surface agents work by creating a barrier that impedes acid peptic injury to mucosal surfaces. Only two such substances have been evaluated in the treatment of GERD: sucralfate and sodium alginate. These agents are not recommended for chronic treatment of GERD in children, although they may be used for short-term management of symptoms in selected patients [1]. (See "Medical management of gastroesophageal reflux disease in adults", section on 'Surface agents and alginates'.)
Sucralfate (aluminum sucrose sulfate) adheres to the damaged mucosal surface, promoting healing and protecting the surface from further peptic injury by mechanisms that are incompletely understood. A study in adults with nonerosive esophagitis found that it decreased symptoms and promoted healing [67]. One controlled trial in children suggested that sucralfate was as effective as cimetidine for treatment of esophagitis [68]. However, because of short duration of action, concerns related to aluminum toxicity and limited efficacy as compared with PPIs, sucralfate has minimal, if any, role in the treatment of GERD in children or adults [1].
Sodium alginate, which is derived from seaweed, forms a surface gel that creates a physical barrier against regurgitation of gastric contents and protects the esophageal mucosa. Studies of its efficacy in improving symptoms and reducing esophageal acid exposure compared with other available treatments have produced conflicting results [69-72]. It is not recommended for chronic treatment of GERD in children, due to lack of evidence for efficacy in low-quality clinical studies [1]. A preparation available in the United States (Gaviscon) also contains an antacid and is used for the temporary relief of heartburn in adults [73].
Complementary and alternative medicine — A variety of herbal remedies are sometimes used for acid reflux or other gastrointestinal complaints, including chamomile, slippery elm, and ginger root [74]. Many anecdotal reports suggest that these herbs sometimes improve symptoms, but no randomized trials are available to guide their use. Since many families seek and use these remedies, it is important to inquire about their use in an open, nonjudgmental fashion, and to review the specific remedies used for potential toxicities. The National Institutes of Health's National Center for Complementary and Integrative Health provides reliable information on complementary and alternative medicine practices [75]. (See "Complementary and integrative health in pediatrics" and "Overview of herbal medicine and dietary supplements".)
SURGERY
Gastrostomy placement — Placement of a percutaneous endoscopic gastrostomy (PEG) is often considered in neurologically impaired children with feeding problems, poor weight gain, and GERD. The PEG usually should be performed without fundoplication, followed by medical antireflux therapy if clinically indicated [4,76]. This is because fundoplication increases the risk of complications and does not improve reflux-related outcomes [77,78]. This was shown in a retrospective multiinstitutional study of infants with neurologic impairment who underwent PEG placement with or without fundoplication, which showed that fundoplication did not reduce hospital admissions for reflux-related problems during one-year follow-up [77]. For the minority (5 to 29 percent) of patients who fail medical therapy, fundoplication can be performed as a second step [79].
Another alternative to antireflux surgery is transpyloric or jejunal feeding (via nasojejunal or gastrojejunal feeding tubes, or surgical placement of a jejunal feeding ostomy), which reduce reflux by bypassing the stomach [1]. The efficacy of this approach is variable, and its utility is limited by tube dislodgement and other practical considerations [4]. (See "Overview of enteral nutrition in infants and children", section on 'Poor gastric emptying or aspiration risk'.)
Fundoplication
Indications and presurgical evaluation — Antireflux surgery is sometimes indicated in patients with debilitating GERD that is refractory to medical management, after other causes of the symptoms have been excluded [1,80]. Many candidates for antireflux surgery have underlying neurologic impairment such as cerebral palsy. Surgery should be approached with caution because indications for surgery have not been definitively established, estimates of efficacy and failure rates vary widely, and complications are common, as discussed below. (See 'Efficacy' below and 'Complications' below.)
Candidates for surgery should be carefully evaluated to exclude other causes of the symptoms and signs. The diagnostic tests and surgical considerations depend on the patient's clinical presentation:
●Intractable esophagitis – Children with chronic esophagitis unresponsive to acid suppression might be considered for antireflux surgery. They should first undergo a full evaluation to exclude other causes of esophageal inflammation, especially eosinophilic esophagitis (EoE). At a minimum, the evaluation should include upper endoscopy with biopsies and esophageal pH monitoring while on proton pump inhibitor (PPI) therapy, to confirm whether gastric acid was adequately suppressed. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE)".)
●Pulmonary disease that is thought to be due to aspiration – In children with neurologic impairment and suspected aspiration, the possibility of anti-reflux surgery should be approached with caution. This is because it may be difficult to discriminate retrograde aspiration (due to GERD) from antegrade aspiration (due to swallowing dysfunction). Moreover, surgery has low success rates for preventing progression of pulmonary disease, as outlined below (see 'Efficacy' below). Although the fundoplication can reduce gastroesophageal reflux (GER), it can also impede esophageal clearance and increase the likelihood of aspiration. For this group of patients, alternative approaches to reducing aspiration should be considered, such as transpyloric feeding or gastrostomy. (See 'Gastrostomy placement' above.)
The evaluation of patients suspected to have pulmonary disease related to GERD often includes review of all radiographic studies, swallowing studies, esophageal pH and impedance monitoring, polysomnography, and bronchoalveolar lavage. The combined results of all these studies should be interpreted by clinicians with experience in swallowing dysfunction because no single test can determine the role that GERD is playing in pulmonary disease. (See "Aspiration due to swallowing dysfunction in children" and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents".)
Relative contraindications — Fundoplication is relatively contraindicated for individuals with:
●Gastrointestinal dysmotility, recurrent vomiting or retching (rather than regurgitation/effortless reflux) – These individuals are at high risk for feeding intolerance and intractable retching after fundoplication [81].
●Neurologic disability – These individuals tend to have poor outcomes after fundoplication, including retching, failure of the surgery (due to breakdown of the wrap), and other complications that may be life-threatening [82-86]. Because they have impaired central inhibition, gastrointestinal dysmotility (impaired gastric accommodation) and visceral hypersensitivity may occur after fundoplication, activating the emetic reflex and causing breakdown of the wrap [87,88]. Percutaneous gastrostomy feedings are an alternative approach to managing chronic GERD and poor feeding in these patients [79]. (See 'Gastrostomy placement' above.)
Although postoperative retching is particularly common in the above groups of patients, it can also occur in patients without these characteristics. (See 'Complications' below.)
Technique — The most commonly performed operation is a Nissen fundoplication. This procedure originally involved passage of the gastric fundus behind the esophagus to encircle up to 6 cm of the distal esophagus. However, many variations and modifications have been described, and a Nissen fundoplication may be performed differently by different surgeons (figure 1). Variables include approach (transthoracic or abdominal); portion of stomach wall used (anterior and posterior or anterior only); combination with other procedures (eg, vagotomy or gastroplasty); as well as the tightness, the length, and the completeness (270º to 360º) of the wrap.
The Nissen fundoplication is now performed laparoscopically at many centers. In experienced centers, short-term complication rates are similar for laparoscopic and the open techniques [89]. Some studies suggest that laparoscopic surgery has fewer complications, such as retching [90-93], while others report somewhat higher rates of reoperation and recurrence of GERD compared with open fundoplication [94-96].
Efficacy — Symptom improvement has been described in approximately 60 to 90 percent of children undergoing fundoplication [1], but "failure rates" (variously defined) vary widely among reports, ranging from 2 to 50 percent [94,97]. As an example, in one study, nearly two-thirds of children had ongoing reflux requiring treatment two months following fundoplication; a majority of the subjects had neurodevelopmental delay [98]. In studies that have reported longer-term outcomes, most demonstrate higher rates of failure within one to three years [77,82]. Several studies suggest higher failure rates in children with neurologic impairment, chronic respiratory conditions, repaired esophageal atresia, and in infants [1,94,99-101]. In particular, antireflux surgery has low success rates as an intervention for aspiration pneumonia [1,77,102-104]. Similar unsatisfactory outcomes were seen in a report of children with cystic fibrosis and GERD [105]. Nearly one-half of the children had ongoing symptoms of GERD after fundoplication, and overall there was little benefit to pulmonary function. Twelve percent of patients had complications that required a subsequent surgical procedure.
The wide variation in efficacy estimates is likely due to the use of different inclusion criteria, with short follow-up periods and reported variable endpoints; many of these studies focused on neurologically impaired children [93,98,99,106-110]. These limitations and the absence of controlled trials are critical impediments to defining the role of antireflux surgery in the long-term management of GERD in children.
Experience in adults has demonstrated that patients who do not respond to adequate doses of medical therapy (particularly those with typical features of GERD, such as heartburn) also may have a poor response to surgery, questioning the role of antireflux surgery in patients with symptoms refractory to medical therapy. Furthermore, long-term follow-up of patients who underwent standard antireflux surgery reveals that even after surgery, many continue to depend on medical therapy to control symptoms. (See "Surgical treatment of gastroesophageal reflux in adults".)
Complications — Complications of antireflux surgery range from 2 to 45 percent [1,111-113]. The most common complications included breakdown of the wrap (1 to 13 percent), small bowel obstruction (1 to 11 percent), gas bloat syndrome (2 to 8 percent), infection (1 to 9 percent), atelectasis or pneumonia (4 to 13 percent), perforation (2 to 4 percent), persistent esophageal stricture (1 to 9 percent), and esophageal obstruction (1 to 9 percent). Complications that occurred less frequently included an incisional hernia, gastroparesis, and dumping syndrome. Reoperation was required in 3 to 19 percent of patients, and operative mortality ranged from 0 to 5 percent. The presenting symptoms of dumping syndrome are often irritability after feeds, diaphoresis, or diarrhea; management is described separately. (See "Enteral feeding: Gastric versus post-pyloric", section on 'Feeding intolerance'.)
Retching (dry heaves) is common in children who have undergone fundoplication, particularly children who are neurologically impaired [94,114]. The presence of preoperative forceful vomiting (versus effortless regurgitation) is a significant predictor of the development of postoperative retching [115]. Treatment for this complication is difficult, and, if the retching is not controlled, it may disrupt the surgical repair. The optimal treatment varies among patients, so a trial-and-error approach is appropriate. Options include modification of feeding content and route (including jejunal feeding), use of antiemetics and motility agents (cyproheptadine, ondansetron, aprepitant, alimemazine), neuromodulation, and other novel therapies (eg, tricyclic antidepressants, gabapentinoids, cannabinoids, acupuncture or vagal nerve/gastric electrical stimulation) [81]. Most of these interventions are supported by only low-quality evidence (case series or expert opinion). Symptoms tend to improve after several months.
Patients with neurologic impairment, obesity, or those requiring a second antireflux operation appear to have a somewhat higher frequency of complications [82,83]. Some surgeons will not perform fundoplications on patients with a significantly elevated body mass index. However, children without underlying disorders also may have poor outcomes. (See 'Relative contraindications' above.)
Other surgical interventions — Other techniques such as endoscopic radiofrequency ablation of the lower esophageal sphincter, endoscopic full-thickness fundoplication, and total esophagogastric disconnection have been described, primarily in adults. None of these techniques is recommended at this time for primary therapy of GERD in children [1]. Total esophagogastric disconnection may be appropriate as a "rescue" procedure for selected children with neurologic impairment who have failed fundoplication [1,4,116].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gastroesophageal reflux in children".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Acid reflux and GERD in children and teens (The Basics)")
●Beyond the Basics topics (see "Patient education: Gastroesophageal reflux disease in children and adolescents (Beyond the Basics)" and "Patient education: Acid reflux (gastroesophageal reflux) in babies (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Definitions – Gastroesophageal reflux (GER) is a normal physiologic process that occurs in healthy infants, children, and adults. In contrast, GER disease (GERD) occurs when the reflux episodes are associated with symptoms or complications. (See 'Definitions' above.)
●Treatment approach – Our suggested approach depends on the patient's characteristics:
•Heartburn – For children or adolescents with mild or infrequent heartburn (averaging once a week or less), we suggest a trial of lifestyle changes (Grade 2C). Occasional use of antacids or histamine type 2 receptor antagonists (H2RAs) is acceptable for short-term relief of symptoms (algorithm 1). If the heartburn symptoms are moderate or severe, or fail to respond to lifestyle changes, we recommend a trial of acid-suppression therapy (Grade 1A). We generally prefer a proton pump inhibitor (PPI); an H2RA is a reasonable alternative but may lose efficacy over time. A typical trial duration is four to eight weeks. (See 'Heartburn' above.)
Patients with alarm symptoms (dysphagia, odynophagia, weight loss, hematemesis, or recurrent vomiting), or those with persistent or recurrent symptoms on a PPI, should be referred to a gastroenterologist for an upper endoscopy with biopsy.
•Esophagitis – For children with endoscopically documented peptic esophagitis, we recommend treatment with an acid-suppressing medication (algorithm 2) (Grade 1A). We also suggest a concurrent trial of lifestyle changes (Grade 2C). For initial treatment, we suggest a PPI rather than an H2RA (Grade 2B). Younger children appear to metabolize PPIs more rapidly and may require higher per-kilogram dosing than older individuals (table 1). Further evaluation and treatment depends on the initial severity of the esophagitis and on the response to treatment. (See 'Esophagitis' above.)
•Dysphagia – Dysphagia (difficulty swallowing) may be caused by GERD but also may have other causes, such as eosinophilic esophagitis (EoE), esophageal dysmotility, or foreign body. Children or adolescents with odynophagia (pain with swallowing) also should be evaluated for pill esophagitis and infectious esophagitis. Children with dysphagia should undergo an evaluation for other causes, including endoscopy, rather than empiric treatment for GER. (See 'Dysphagia or odynophagia' above and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents", section on 'Dysphagia or odynophagia'.)
•Asthma – For children with asthma and clinical or laboratory evidence of GER, asthma control may improve with acid-suppressing medication, but it is difficult to predict who will be responders. Therefore, we suggest a three-month trial of a PPI for patients with persistent moderate to severe asthma (particularly, nocturnal wheezing) and frequent heartburn or regurgitation suggesting GERD (Grade 2B). (See 'Asthma with gastroesophageal reflux' above.)
●Treatment options
•Lifestyle changes – Lifestyle changes that may reduce GER include weight management in overweight patients; cessation of smoking or vaping; elevation of the head of bed; and avoidance of chocolate, caffeine, spicy foods, alcohol, and other foods that exacerbate symptoms. Lifestyle changes may be used as an initial approach to treatment for children and adolescents with mild or infrequent symptoms of GER, or as an adjunct to pharmacologic treatment in patients with moderate or severe symptoms suggestive of GERD. (See 'Lifestyle changes' above.)
•Pharmacotherapy
-Acid-suppressing medications are reasonably safe and effective for the treatment of established acid-related GERD. PPI medications are the most effective for short- or long-term acid suppression but also are associated with acid rebound on discontinuation, as well as some adverse effects with chronic use. H2RAs appear to be somewhat less effective than PPIs but are a reasonable alternative for short-term use. (See 'Proton pump inhibitors' above and 'Histamine type 2 receptor antagonists' above.)
-We do not recommend using prokinetic agents for the routine treatment of children with GER or GERD (Grade 1B). Available prokinetic agents either have limited efficacy or significant safety concerns. (See 'Prokinetics' above.)
•Surgery – Antireflux surgery (fundoplication) is an option for children with chronic esophagitis that is refractory to PPI treatment but must be undertaken with caution because of substantial failure rates and complications including persistent retching. Surgery should be approached with particular caution in children with neurologic impairment and/or pulmonary disease thought to be related to aspiration. (See 'Surgery' above.)
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