Gastroesophageal Reflux Disease (GERD) in Children Management

Principles of Therapy

Conservative therapy is always the initial management scheme for pediatric patients with GERD. The 3 steps involved in the management of GERD include lifestyle modification, acid-suppressive medications, and administration of gastric protectants (prokinetic agents) to improve transit of stomach contents. Following PPI therapy, histological exam is recommended to be able to characterize Barrett’s esophagus and to rule out presence of dysplasia.  

The treatment goals are:

• Relief of symptoms
• Healing esophagitis
• Prevention of recurrence and complications

Pharmacological therapy

Empiric Therapy  

Empiric therapy is an appropriate initial management for uncomplicated GERD in older children and adolescents. It is not recommended for infants and young children with uncomplicated GER. It may be considered in infants whose GER is accompanied by complications and in cases where non-pharmacologic therapies have been deemed ineffective. A 4-week trial period is recommended.  

Histamine-2 Receptor Antagonists (H₂RAs)  

Example drugs: Cimetidine, Famotidine, Nizatidine, Ranitidine  

H₂RAs inhibit gastric acid secretion by blocking histamine 2 receptors in the parietal cells. They effectively reduce gastric pH up to 90% when given 3 times daily. They also possess therapeutic properties against erosive esophagitis. However, their use is limited due to tachyphylaxis or tolerance with chronic use.  

Proton Pump Inhibitors (PPIs)  

Example drugs: Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole  

PPIs demonstrate superior efficacy compared to other acid suppressants for older children and adolescents. They can maintain intragastric pH ≥4 longer and inhibit food-induced acid secretion. They are also able to reduce symptoms and possess therapeutic properties against erosive esophagitis.They inhibit gastric acid secretion by blocking the Sodium-Potassium ATPase enzyme activity in parietal cells. Lastly, their efficacy remains unchanged even with chronic use compared to H₂RAs.  

Maintenance Therapy  

The goal of maintenance therapy is to have a symptom-free patient without evidence of esophagitis. The lowest dose and the least potent medication that can obtain a complete and sustained symptomatic response is utilized. The need for maintenance therapy is determined by the impact of the residual symptoms on the patient’s quality of life. The recommended duration of therapy for moderate to severe heartburn is 2-4 weeks, 4-8 weeks for diagnosed esophagitis, and 3-6 months for severe erosive esophagitis (followed by repeat endoscopy).  

Options for Chronic Acid Suppression  

Step-up therapy involved starting treatment with less potent agents and escalating to more potent options based on the patient's treatment response. If the patient does not respond to an H₂RA within 2 weeks, switch to a PPI. If the patient does not respond to this regimen, but there is improvement seen, the dose of the PPI is recommended to be increased. Other therapeutic options may be considered in PPI-resistant GERD such as switching to a different PPI, changing the medication time, or adding a prokinetic agent or an H₂RA at night. If the patient is still unresponsive to the above regimens, the patients’ symptoms are likely not secondary to reflux and would warrant diagnostic testing and referral to a pediatric gastroenterologist.  

Step-down therapy makes use initially of a potent acid suppressant, then decreasing the dose or switching to less-potent agents. The PPI dose should be tapered for at least 4 weeks, after which H₂RAs may be considered to manage rebound symptoms. This is then followed by stepping down further to on-demand use of antacids if the patient was asymptomatic while taking an H₂RA.  

Adjunctive Pharmacotherapy  

Antacids  

Example drugs: Aluminum hydroxide, Bismuth salicylate, Calcium carbonate, Magnesium hydroxide, Sodium bicarbonate  

Antacids neutralize gastric secretions in the gastrointestinal tract. However, long-term antacid therapy is not recommended in pediatric patients.  

Prokinetic Agents  

Example drugs: Baclofen, Bethanecol, Cisapride, Domperidone, Eryhtromycin, Metoclopramide  

Prokinetic agents serve as alternative treatment and are not for routine use in patients with GERD. Cisapride increases gastric emptying time and helps improve esophageal and intestinal peristalsis. This drug significantly reduced RI but efficacy for symptom control is not established. It must be noted that the need for Cisapride therapy should be weighed against its adverse effects (eg QT-interval prolongation, ventricular tachycardia, ventricular fibrillation) before initiating therapy. Antidopaminergic agents (eg Domperidone, Metocloparmide) help facilitate gastric emptying and RI, reducing symptoms in infants with reflux. Bethanecol, a quarternary ammonium sympathomimetic, has been used as an alternative treatment for GERD but efficacy and safety are yet to be proven. Baclofen, a γ-amino-butyric acid (GABA) receptor agonist, possesses functions that reduce the time for gastric emptying. Studies have also shown that Baclofen may also decrease emesis frequency. Erythromycin is another treatment option that may be considered to reduce the time for gastric emptying. However, it must be remembered that further studies are needed to prove the efficacy of prokinetic agents for the treatment of GERD in children.  

Surface Protective Agents  

Example drugs: Alginate, Sucralfate  

Surface protective agents are treatment options against mucosal erosions. However, they are not recommended as monotherapy for GERD. Alginate may be used for formula-fed infants to help thicken liquid preparations during feeding. It is a potential treatment option for weakly acidic or non-acid infant reflux.

Management Based on Symptomatology  

There is no gold standard for the diagnosis of GERD. The duration of treatment with PPIs or H₂RAs depends on the patients’ symptoms.  

Regurgitation and Vomiting

A thorough history and physical examination may be sufficient to distinguish uncomplicated from complicated GER in infants and children with recurrent regurgitation. Infants with recurrent regurgitation but with poor weight gain should undergo thorough history and physical exam with laboratory examinations (eg CBC, serum electrolytes, BUN, serum creatinine) to rule out other possible etiologies of the symptoms.

Dietary modifications (extensively hydrolyzed formula, amino acid-based formula) to test for cow's milk allergy may also be considered. Infants in unexplained state of distress with constant crying bouts should be investigated for diseases other than GERD, as reflux is not a common cause for these symptoms.  

Heartburn

Conservative therapies (eg lifestyle changes, avoidance of trigger factors) are encouraged prior to initiation of drug treatments. PPIs may be given for 2-4 weeks to test for responsiveness to this treatment and for patients with moderate to severe heartburn. Gradual discontinuation of PPI and continuation of conservative therapies are recommended after positive results with PPIs. As needed use of PPIs, antacids, and H₂RAs may also be considered for symptomatic relief.

Reflux Esophagitis  

Three months of PPI therapy is recommended as initial therapy in patients with erosive esophagitis. The dose may be increased if the patient is unresponsive after 4 weeks. Endoscopic monitoring may be used to assess treatment response in patients with atypical signs and symptoms, persistent symptoms despite appropriate therapy, or those with esophageal stricture or moderate to severe esophagitis. Long-term PPI therapy or surgery may be considered for chronic or relapsing reflux esophagitis.  

Dysphagia Odynophagia, and Food Refusal  

Odynophagia and dysphagia have been associated with the presence of esophagitis. Feeding refusal may be related to GER/GERD but further studies are needed to establish this association. Some studies incorporated abnormal pH probe findings in infants and children with feeding difficulty, except in infants with excessive regurgitation. Upper GI barium contrast radiography is suggested in infants with feeding refusal and/or feeding difficulty and for older children with dysphagia. Pharmacological therapy may only be considered in patients with symptoms highly suggestive of GERD.  

Apnea

The presence of prolonged apnea has been associated with acid reflux in premature infants. Combined esophageal monitoring and MII may help establish a relationship between the presence of apnea and regurgitation in a patient. Infants with regurgitation complicated by apparent life-threatening events (ALTEs) may benefit from milk mixed with thickeners. Pharmacological therapies are not recommended as symptoms of apnea are most likely to resolve as the child ages.  

Reactive Airway Disease  

Studies have shown that GER may produce airway hyperresponsiveness and airflow obstruction leading to asthma exacerbation in asthmatic patients. Asthma, in turn, may be a factor in the development of GERD due to reduced resting LES pressure. Studies have shown that 60-80% of children with asthma have abnormal pH or MII findings. PPI therapy may be considered in asthmatic patients with persistent heartburn or regurgitation.  

Recurrent Pneumonia  

Reflux of gastric contents has been associated with recurrent pneumonia and interstitial lung disease. Pharmacologic therapy (eg PPI, H₂RAs, prokinetic agents) may be considered in patients with minimal lung disease associated with GERD and should be advised about the importance of prompt follow-up. Antireflux surgery should be considered in patients with severely impaired lung function to prevent further pulmonary damage.  

Upper Airway Symptoms  

Upper respiratory tract manifestations such as chronic cough, hoarseness, sinusitis, otitis media, and laryngoscopic features (eg edema, erythema, nodularity) have been linked to the presence of GERD. Other etiologies should be taken into consideration prior to starting therapy for GERD. Children may undergo laryngoscopy to rule out possible functional or anatomical abnormalities.  

Dental Erosions  

Several studies have found the association of GERD with dental erosions secondary to acidic pH exposure. Referral to a pediatric dentist is recommended.  

Sandifer Syndrome  

Sandifer syndrome is a rare disorder associated with GERD characterized by spasmodic torsional dystonia with arching of the neck, head, eyes, and trunk. Antireflux medications and specialist referral are recommended.  

Barrett’s Esophagus  

The diagnosis of Barrett’s esophagus should be established prior to therapy. Following PPI therapy, histological examination is recommended to be able to characterize Barrett’s esophagus and to rule out presence of dysplasia.

Nonpharmacological

Dietary Changes   

One may consider switching to milk formula that contains extensively hydrolyzed protein or amino acid-based formula instead of regular formulas. Maternal diet modification is also encouraged for mothers of breastfeeding infants. Avoidance of egg and milk intake may be considered. Thickeners (eg thickening agent, rice cereals, corn starch, carob bean gum, soybean polysaccharides) may be considered in healthy formula-fed infants but should be used with caution especially in preterm infants at increased risk of necrotizing enterocolitis. Carob bean gum (locust bean gum) thickened formulas may be used as alternative in reducing infant regurgitation and acid reflux-related symptoms, with studies demonstrating its constantly high viscosity in milk formula. While wheat, tapioca, corn, rice, or potato starch may be used but should be cooked carefully in water and added to infant formula to avoid recurrence of fermentative diarrhea. Thickeners are recommended treatments for symptomatic non-acid reflux in infants due to their strong efficacy and safety profile. Small, frequent feedings may be tried instead of one big meal while ensuring an appropriate total daily amount of nutrition. Eating before bedtime should also be avoided. Food that may trigger symptoms in adolescents (eg caffeine, carbonated drinks, chocolate, mint-containing food, spicy food) should be avoided.    

Patient, Parent, Guardian Education  

Positional Modifications  

Infants should be kept in an upright position during feeding. Infants and children should be fully awake when ingesting food. Avoiding meals within 2-4 hours of bedtime is suggested. Additionally, due to the risk of sudden infant death syndrome (SIDS), supine positioning during sleep is recommended for infants until 12 months of age. Placing a child in an infant carrier or car seat in a semisupine position especially after feeding should be avoided to reduce the risk of GER. For children and adolescents, prone or left-side sleeping position and/or elevating the head of the bed decreases GERD symptoms.  

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Surgery

Indications for Antireflux Surgery:

• Failed medical management
• Noncompliance with therapy
• Medication side effects
• Inadequate symptom control
• Refractory GERD: Persistence of GERD symptoms in compliant patients despite standard treatment or twice-daily dosing of PPI for at least 8 weeks
• Severe erosive GERD or severe GERD complications (eg peptic stricture, Barrett’s esophagus)
• Extraesophageal conditions (eg pulmonary aspiration, asthma, recurrent aspiration related to GERD)
• Other conditions have been ruled out
• Long-term management required
• Patient, parent, guardian preference
  • Despite success with medications, may opt for surgery due to cost of medications or life-long need to take acid-suppressive agents
  • Should be advised against surgery if symptoms are well controlled on medical therapy

Antireflux Surgery  

Antireflux surgery has evolved from open type to laparoscopic procedure and in recent years, to transoral incisionless fundoplication. Surgical success is highest in patients presenting with typical GERD symptoms and demonstrating good response to treatment with PPI. In considering antireflux surgery, the patients are informed regarding the risk of long-term PPI therapy after surgery. Esophageal manometry and ambulatory reflux studies should be done before surgery to rule out other disorders such as achalasia, nonreflux induced esophageal spasm, scleroderma.  

Fundoplication  

Fundoplication involves either a partial (Toupet or Thal) or a complete (Nissen, 360 degrees) wrap of the LES with a section of the stomach, thus increasing the LES pressure. Nissen fundoplication is more commonly performed in children while partial fundoplication is preferred in patients with more severe disease accompanied by motor abnormalities. It must be noted that there has been no statistically significant difference observed in normal children when studies compared Nissen, Toupet, and Thal fundoplication. However, recurrence rate was lower for children with neurological disorders who underwent Nissen fundoplication. Laparoscopic Nissen technique is preferred over open Nissen fundoplication due to lower morbidity rates, shorter hospital stay, and fewer perioperative complications. Complications of the procedure include inability to belch and vomit, persistent dysphagia, postprandial pain, epigastric fullness, bloating, temporary swallowing discomfort, and intense flatus.  

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