The following flags should alert the clinician to consider different etiologies. [Lightdale: 2013] For a more expansive list of differential diagnoses, refer to Table 3 in [Rosen: 2018].

Neither routine screening or procedural testing is currently advised for routine diagnosis of pediatric GERD in the primary care setting.

Questionnaires and screening instruments to help detect GERD include the Infant Gastrointestinal Symptom Questionnaire [Riley: 2015], Gastroesophageal Reflux Questionnaire (GERQ), and GERQ-Revised [Kleinman: 2006]. The GERD Symptom Questionnaire in Infants (GSQ-I) and Young Children (GSQ-YC) [Deal: 2005] are sometimes referenced; however, their usefulness in primary care has not been clearly demonstrated.

A multichannel impedance pH probe can detect and measure anterograde and retrograde movement of acid and non-acid fluids, and it detects solids and air moving through the esophagus. The impedance probe can correlate with reflux, cough, apnea, rumination, and risk for aspiration. [Lightdale: 2013]

It also can help differentiate between GERD, reflux hypersensitivity, rumination, and functional heartburn in patients with normal endoscopic findings. Limitations include confounding results in the presence of motility disorders or significant esophagitis and lack of evidence to: [Rosen: 2018]

• Determine if the patient should be tested on or off reflux medications
• Reliably define reference ranges
• Determine if the study influences outcomes

An esophagogastroduodenoscopy (EGD) may be used in moderately to severely symptomatic patients to identify erosions or collect biopsies of tissue changes to confirm a suspected diagnosis of GERD. Be aware that lack of visible erosions and normal histology can be found even when GERD is present. [Rosen: 2018] EGD can help in diagnosing other conditions of the upper GI tract that include abnormal esophageal anatomy, eosinophilic esophagitis, celiac disease, esophageal Crohn disease, webs, infections (including candida, herpes, or H. pylori), Barrett esophagus, or peptic ulcers. There is lack of current evidence to determine whether proton pump inhibitors should be discontinued prior to an EGD. [Rosen: 2018] Since the test is invasive and requires sedation, its value should be weighed against the severity of symptoms, response to treatment, and risks of sedation.

Transnasal endoscopy using a thin endoscope may be performed without sedation, thus lowering risks, cost, and duration of the procedure and increasing tolerability. It can be used to diagnose GERD and esophagitis, but its main current use is to evaluate patients with eosinophilic esophagitis (EoE).

Endolumenal functional lumenal imaging probe (EndoFLIP ®) is FDA approved to measure esophageal pressure and dimensions. The technology uses specialized impedence planimetry during volume-controlled distension to measure mechanical properties of the esophagus and opening dynamics of the gastroesophageal junction. The role of FLIP in GERD evaluation and management is still limited and undergoing study. [Hirano: 2017]

An upper gastrointestinal barium study (UGI) can be ordered to evaluate anatomy and to document the presence of reflux, but the study lacks sensitivity. Reflux may not occur during the study, and sensitivity to diagnose esophagitis is also low. However, the UGI can identify abnormalities, such as an esophageal stricture, duodenal web, malrotation, or delayed gastric emptying. The clinician can consider including delayed films (“small bowel follow-through”) to evaluate abnormalities in the small intestine.

A modified barium swallow study (MBSS) or videofluoroscopic swallow study (VFSS) evaluates aspiration risk and swallowing disorders. While evidence of reflux may be noted during the study, it lacks sensitivity or specificity to diagnose GERD.

Ultrasonography is useful for diagnosis of pyloric stenosis, hiatal hernia, and other abnormal structures, and it is possibly useful for diagnosing delayed gastric motility. It lacks specificity for GERD even when obtained as a post-prandial study. [Rosen: 2018]

Manometry/motility studies can be used to evaluate for esophageal dysmotility, which can mimic GERD, as well as the workings of the esophageal sphincter. [Rosen: 2018] Newer possible uses include providing information to aid in decision-making about whether a fundoplication is likely to be successful. [Rosen: 2018]

Scintigraphy involves using radioisotopes placed in the stomach and measurement of scintillations through the stomach and esophagus. Although there are protocols for use of scintigraphy to diagnose GERD, the methods currently lack standardization for pediatric use.

Extra-esophageal biomarkers are gaining attention by gastroenterologists in the study of pediatric GERD but are not currently recommended for diagnosing pediatric GERD: [Rosen: 2018]

• Salivary pepsin – lacks sensitivity and normative data
• Lipid-laden macrophage index – lacks evidence as a biomarker for reflux
• Bilirubin in the esophagus –fiber optics used in the study impair normal digestion

GER is often managed through lifestyle changes. Management of GERD involves lifestyle changes as well as judicious use of medications, and less commonly, surgical interventions. When recommending lifestyle changes, recognize the family's perceived burden and that there is limited evidence for many of the interventions.

Considerations for infants:

• Offer smaller, more frequent feeds.
• Thicken breastmilk or formula. Use of thickeners for infants with reflux lacks quality evidence. Expert opinion is that thickened feeds improve visible regurgitation but do not alter the acid reflux burden assessed by pH-MII. [Rosen: 2018] Keep in mind that thickening breastmilk and formula increases caloric density. Little is known about the long-term effects of using thickeners. See Thickened Liquids & Modified Foods
• For breastfed infants, remove dairy products, including casein and whey, from the maternal diet for 2-4 weeks to determine if a protein allergy may be causing reflux-like symptoms.[Rosen: 2018] Egg, soy, or wheat exclusion may also be considered if balanced with the mother's nutritional needs.
• In formula-fed infants, initiate a trial of extensively hydrolyzed formula for at least 2 weeks. An amino-acid-based formula could be trialed if an extensively hydrolyzed formula. Use of soy formula for this purpose is not advised due to the frequency of soy protein intolerance in infants with cow milk protein allergy. [Rosen: 2018] See Formulas for examples of brands.
• Consider head elevation or positioning the awake infant in the left-lateral lying position during and after feeds [Rosen: 2018], or prone while observed and awake. Supine and semi-supine positions, such as in a car seat, increase reflux. Positioning recommendations mostly are based on pH probe or pH/impedance studies. The AAP advises against using commercial positioners to elevate the infant’s head due to risk for SIDS (sudden Infant death syndrome). [Lightdale: 2013] [Eichenwald: 2018]
• Eliminate second- and third-hand smoke exposure (residue from tobacco products that is left behind after smoking). The chemicals increase the risk of gastrointestinal dysregulation. [Shenassa: 2004] This intervention has little evidence related to GERD, but it is a no-risk option.
• Prebiotics and probiotics, as well as herbal medicines and complementary therapies, do not have enough evidence for safe treatment of infant GERD. Probiotics (L. reuteri) used preventatively in one study reduced crying time and number of regurgitations; however, these symptoms are not specific to GERD. [Rosen: 2018]

Considerations for children and adolescents:

• Reduce excess body weight to reduce pressure on the esophageal sphincter. [Rosen: 2018]
• No smoking. Avoid second- and third-hand smoke exposure.
• Avoid alcohol use
• Avoid foods that may increase reflux (chocolate, peppermint, onions, garlic) and spicy, fatty, or acidic (citrus- or tomato-based) foods.
• Chew sugarless gum after meals to promote motility. [Lightdale: 2013]

Considerations for patients with pre-existing feeding tubes and reflux:

• Adjustments in feeding schedule (reducing bolus sizes, limiting feedings given in the recumbent position, and continuous nocturnal feedings) may be helpful.
• Switching to transpyloric (e.g., gastrostomy-jejunal) tube feeds is often done for intractable reflux symptoms. [Rosen: 2018] [Campwala: 2015]
• In children with neurologic impairment, transpyloric feeding reduces the reflux burden about the same as a fundoplication.[Stone: 2017] Experts suggest that transpyloric feedings may be considered as treatment options for patients refractory to medications. [Rosen: 2018]

Typically, treatment trials start with a short course (14 days) of an H2 blocker (histamine-2 receptor antagonists). If the H2 blocker is insufficient for treatment and the suspicion for GERD is still high, a step-up therapy with a proton pump inhibitors (PPIs) is considered.

• For infants, use of anti-reflux medications is usually considered as a last resort after attempting lifestyle changes. [Lightdale: 2013] Current expert opinion recommends consultation of a pediatric gastroenterologist, when available, prior to starting anti-reflux medications in infants. When using medications, the general advice is to proceed with caution and limit duration of therapy. For premature infants in the neonatal intensive care unit (NICU), avoid use of medications because clinical symptoms are unreliable indicators of true reflux, and using reflux medications in this population has limited benefits and increased risks, such as necrotizing enterocolitis. [Eichenwald: 2018]
• For medically complex children who may require long-term medication use for GERD, frequently review the benefits and risks with caregivers and attempt to wean medications, whenever possible, in coordination with the child’s specialists. Use of medications for treatment of GERD in children, particularly in children with neurodisability, has limited high-quality evidence. [Tighe: 2014]
• Over-the-counter formulations for acid suppression and prokinetic agents are available.

Acid Suppressants

H2 Receptor Antagonists (H2RA)

While many consider PPIs to be the most effective for treatment of GERD, H2Ras (aka H2 blockers) usually cost less and are covered more by insurers (who may require treatment failure with H2RAs before authorizing coverage for a PPI). When taken orally, H2RAs offer faster relief than PPIs and start working within an hour to neutralize acid and relieve reflux pain. The effect lasts 10-12 hours. Administration is typically 2 times daily (BID) at meals or bedtime, or 3 times daily in smaller doses for children whose symptoms recur quickly.

Experts recommend limited use of H2RAs (4-8 weeks) in children with typical symptoms of GERD, but not for extraesophageal symptoms (e.g., cough, wheezing, asthma) without typical GERD symptoms or suggestive diagnostic testing. Experts also advise against the use of H2RAs for otherwise healthy infants who have excessive crying or frequent regurgitation. [Rosen: 2018] Be aware that H2RAs may impair iron absorption.

Long-term use can induce tachyphylaxis or tolerance. [Vandenplas: 2009] Risks of longer-term use can include vitamin B12 deficiency and increased risk for developing gastroenteritis and pneumonia. Use caution in patients with renal or hepatic impairment. Consult a drug reference due to multiple interactions with other drugs. Frequent evaluation of children on long-term acid suppression is advised.

Ranitidine (Zantac)
The U.S. Food and Drug Administration requested that all prescription and over-the-counter ranitidine (Zantac) products be pulled from the market in 2020. An ongoing investigation uncovered levels of N-Nitrosodimethylamine (NDMA), a probable human carcinogen, which seems to increase over time, especially when stored at higher room temperatures. The agency urges patients and providers to consider taking alternative medications. See FDA Updates and Press Announcements about NDMA in Zantac (ranitidine) & Axid (nizatidine).

Famotidine (Pepcid) [Lightdale: 2013]

• Considerations: FDA indicated for ages 0 and older for treatment of GERD. Benzyl alcohol solution is associated with adverse events in neonates. Torsades de pointes has been associated with use of famotidine in patients with renal impairment.
• Formulations: Cherry-banana-mint solution (40 mg/5 mL) and tablets (10 mg, 20 mg, 40 mg), max 40 mg/day
• Dosing:
  • Infants <3 months: 0.5 mg/kg/dose given once daily due to prolonged elimination half-life in infants <3 months
  • For infants >=3 months and children: 0.5 mg/kg/day divided BID, may increase up to 1 mg/kg/day divided BID, max 40 mg/day

Nizatidine (Axid) [Lightdale: 2013]

• Considerations: FDA indicated for ages ≥12 years. A voluntary recall of nizatidine started in 2020 due to detection of an impurity known as N-nitrosodimethylamine (NDMA); check the FDA drug safety updates (FDA Updates and Press Announcements about NDMA in Zantac (ranitidine) & Axid (nizatidine)) prior to prescribing this medication.
• Formulations: Bubble-gum flavored solution (15 mg/1 mL), capsules (150 mg, 300 mg), and tablets (75 mg)

• Dosing: 5-10 mg/kg/day divided BID, max 300 mg/day, or:
  • ≥12 years old: 150 mg BID

Cimetidine (Tagamet) [Lightdale: 2013]

• Considerations: FDA indicated for ages ≥16 years
• Formulations: Solution (300 mg/5 mL) and tablets (200 mg, 300 mg, 400 mg, 800 mg)
• Dosing: 30–40 mg/kg/d, divided in 4 doses, max 800 mg/day, or:
  • Infants: 10-20 mg/kg/day divided every 6-12 hours
  • Children: 20-40 mg/kg/day in divided doses every 6 hours

Proton Pump Inhibitors (PPIs)

PPIs work in the stomach to prevent gastric acid production, thus alleviating pain associated with acid reflux. Moderate evidence supports short-term use (1-2 months) of PPIs in children with GERD [Tighe: 2014], but not for extraesophageal symptoms (e.g., cough, wheezing, asthma) without typical GERD symptoms or suggestive diagnostic testing. [Rosen: 2018]

PPIs are more highly recommended than H2RAs for GERD with erosive esophagitis. If costs, availability, or contraindications are a concern, then H2RAs are a reasonable alternative. No evidence demonstrates a clear benefit for PPI use in infants to help with crying, irritability, or visible regurgitation. [Chen: 2012] [Rosen: 2018]

Depending on the formulation, PPIs are given 30-60 minutes before breakfast. Since symptom relief is slower (1-5 hours) than H2RAs and antacids and the effect can last 3-5 days, PPIs are usually given daily to achieve a steady effect and not used for an as-needed/quick-relief effect. Insurers may require prescribers to demonstrate the patient’s lack of response to less costly H2RAs and receive prior authorization before covering PPIs.

PPIs historically have been considered safe; however, prescribers are growing increasingly concerned about risks with long-term use. Risks may include enteric infections, including Clostridium difficile, dysbiosis (an imbalance of microflora in the body), small intestinal bacterial overgrowth, acute interstitial nephritis, lower levels of vitamin B12, magnesium, and calcium, and possibly pneumonia in infants. [Scarpignato: 2016] Frequent reevaluation of children on long-term acid suppressants is advised.

Use additional caution when prescribing these medications for children with liver disease or children taking anticoagulants, seizure medications, antibiotics, chemo agents, and other medications. Since PPIs work in the stomach, children with feeding tubes that bypass the stomach may not benefit from use.

Lansoprazole (Prevacid, First-Lansoprazole) [Lightdale: 2013] [Rosen: 2018]

• Considerations: FDA indicated for 1 year and older
• Formulations: Capsules (15 mg, 30 mg) that can be swallowed whole, sprinkled on soft food, dissolved in certain juices, or used for a nasogastric tube, and strawberry-flavored orally disintegrating tablets (15 mg, 30 mg) that can be dissolved and delivered via syringe or a nasogastric tube
• Dosing: 3 months-13 years: 1.4 mg/kg/day (range 0.7–3 mg/kg/day) once daily. Younger infants requiring PPI use may be dosed at 0.5-1 mg/kg/day, or:
  • ≥3 months old - 7.5 mg BID or 15 mg once daily
  • 1-11 years old - ≤30 kg: 15 mg once daily; >30 kg: 30 mg once daily
  • ≥12 years old-adolescents - 15 mg once daily
  • Max 30 mg/day

Omeprazole (Prilosec, First-Omeprazole) [Lightdale: 2013]

• Considerations: FDA indicated for 1 year and older
• Formulations: Delayed-release capsules (10 mg, 20 mg, 40 mg) (can sprinkle into soft foods); delayed-release tablets (20 mg) (swallow whole); packets (2.5 mg, 10 mg) (reconstitute with water for each dose – recommended if using a nasogastric tube); and suspension (compounded to 2 mg/1 mL). FDA indicated for ages ≥2 years.
• Dosing: 1-4 mg/kg/day, or:
  • 5 kg - <10 kg - 5 mg once daily
  • 10 kg - ≤20 kg - 10 mg once daily
  • >20 kg: 20 mg - once daily, or 1 mg/kg/dose once or BID
  • Max 40 mg/day

Esomeprazole (Nexium) [Lightdale: 2013]

• Considerations: FDA indicated for ages ≥1 year
• Formulations: Delayed-release capsules (20 mg, 40 mg) (can open and sprinkle contents into soft foods or used for nasogastric tube; delayed release tablets (20 mg) (swallow whole); and packets (2.5 mg, 5 mg, 10 mg, 20 mg, 40 mg) (ok for nasogastric tube)
• Dosing: <20 kg – 10 mg once daily, >=20 kg – 20 mg once daily, or:
  • 1-11 years old - 10 mg
  • ≥12 years old - 20 mg
  • Max 40 mg/day

Rabeprazole (Aciphex) [Lightdale: 2013]

• Considerations: FDA indicated for ages ≥12 years
• Formulations: Capsules (5 mg, 10 mg) (sprinkle contents into soft food) and tablets (10 mg, 20 mg).
• Dosing:
  • 1-11 years - <15 kg: 5-10 mg once daily; ≥15 kg: 10 mg once daily
  • ≥12 years-adolescents - 20 mg once daily.

Pantoprazole (Protonix) [Rosen: 2018]

• Considerations: FDA indicated for pediatric GERD with history of erosive esophagitis
• Formulations - Tablets (20 mg, 40 mg) and delayed-release granules for oral suspension (40 mg in a unit dose packet) (mix with applesauce or apple juice, or used for nasogastric tube)
• Dosing -≥5 years - 1-2 mg/kg/day, or:
  • 15-39 kg: 20 mg orally once a day
  • ≥40 kg: 40 mg orally once a day
  • Max 40 mg/day

Antacids and Alginates
Over-the-counter medications used for occasional reflux symptoms include acid neutralizers (e.g., Tums) and other types of medications (alginates or sucralfate) that coat the surface of the stomach. Alginates have demonstrated slight improvement in visible regurgitation and vomiting in pediatric GERD; the side effects of long-term treatment are unknown. [Rosen: 2018] Expert opinion is that alginates could be trialed for as needed (PRN) or short-term use. Though other antacids are commonly used for symptomatic relief in adults and sometimes to help determine if the child’s symptoms improve with acid neutralization, these medications are not recommended for use in children and can result in toxicity from components such as calcium or aluminum. [Lightdale: 2013] [Rosen: 2018]

Prokinetics

Slow gut motility can prolong gastric emptying and contribute to retrograde flow of stomach contents into the esophagus, potentially causing irritation and inflammation. If impaired gut motility is suspected to be contributing to a child’s reflux symptoms (e.g., in those with neurological impairments like cerebral palsy), prokinetic agents may reduce reliance on acid suppressants or be used as adjuvant therapy; however, evidence is lacking about efficacy, potential side effects, and safety risks. Effectively managed constipation is an essential precursor to use of a prokinetic because stool clogging the intestines could block the passage of stomach contents. Details about management of constipation in children can be found in the Portal's Constipation.

Due to the risks associated with these medications, strongly consider consultation with a pediatric gastroenterologist prior to initiating therapy with a prokinetic agent. Dosing guidelines are provided here only for erythromycin ethylsuccinate, which is considered the safest option.

Erythromycin Ethylsuccinate (EES)
Initially developed as an antibiotic, researchers found that low-dose EES stimulates the hormone motilin, which results in increased contractions in the antrum of the stomach and faster gastric emptying. Low-dose EES may have better efficacy than metoclopramide with increasing gastric motility.

• Considerations: Common side effects include gastrointestinal upset and rashes. When used for chronic treatment, tachyphylaxis may develop, so 2-week breaks are frequently employed. [Waseem: 2009] EES increases the risk of cardiac toxicity, particularly when used with certain other medications, including antipsychotics, and when used at antibiotic doses. [Ericson: 2015] EES use in neonates in the first 2 weeks of life is associated with increased risk for pyloric stenosis. Consider electrocardiograph monitoring before treatment and periodically during treatment; avoid use in patients with prolonged QT interval.
• Formulations: Various fruit-flavored suspensions (200 mg/5 mL, 400 mg/5 mL); tablets (200 mg, 400 mg, 500 mg); and delayed release tablets (250 mg, 333 mg, 500 mg) [Lightdale: 2013]
• Dosing: 3 mg/kg/dose 4 times daily (may increase as needed to effect); maximum dose: 10 mg/kg or 250 mg [Lightdale: 2013] or 3-5 mg/kg/dose 3-4 times daily

Azithromycin
Azithromycin has been used by pediatric gastroenterologists as an alternative to EES in certain cases. Consultation with a pediatric gastroenterologist is recommended before starting azithromycin for motility.

Baclofen
After other medications have failed, baclofen may be considered prior to a surgical intervention for GERD. [Rosen: 2018] This GABA-B receptor antagonist is typically used to reduce muscle spasticity; it also can improve gastric motility and reduce relaxations of the lower esophageal sphincter, which prevent some refluxing episodes. Therefore, a seizure-free child with reflux (related to slow motility), cerebral palsy, and spasticity may be an ideal candidate for using baclofen and may receive dual benefit from using this medication.

Side effects include sedation and lowered seizure threshold. Consultation with a pediatric rehabilitation medicine specialist (physiatrist) is recommended when using baclofen to treat spasticity (Pediatric Physical Medicine & Rehabilitation (see NM providers [3])).

Metoclopramide (Reglan)
Experts generally advise against use of metoclopramide for treatment of pediatric GERD. [Rosen: 2018] Metoclopramide may mediate its impact through increased lower esophageal sphincter pressure, accelerated gastric emptying, and increased small bowel peristalsis. Metoclopramide also has centrally acting anti-emetic properties.

In a large percentage of children, metoclopramide can cause significant central nervous system side effects that include fatigue, restlessness, tremors, increased tone, extrapyramidal reactions (dystonic, oculogyric crisis), and tardive dyskinesia. Monitor for irritability, sedation, diarrhea, increased emesis/feeding intolerance, and neurological symptoms. There is a black box warning due to the risk of tardive dyskinesia.

Cisapride
Because severe cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation) have been reported in patients taking cisapride, this medication is only available through a limited access protocol or as part of a clinical trial. This medication may be considered by a pediatric gastroenterologist for use with certain patients.

Domperidone
Due to the risk of multiple severe side effects, this medication is not available in the United States. Experts generally advise against the use of domperidone for treatment of pediatric GERD. [Rosen: 2018]

Bethanechol
Mentioned in the pediatric GERD guideline [Rosen: 2018], this medication is not commonly used.

For intractable GERD or risk of severe complications associated with GERD, referral to pediatric gastroenterology is advised. In consultation with these specialists, surgical procedures such as a feeding tube or anti-reflux surgery (e.g., Nissen fundoplication) may be considered. The Nissen fundoplication is performed laparoscopically unless there is a contraindication. Expert opinion suggests consideration of fundoplication in medically refractory patients despite lack of good evidence. [Rosen: 2018]

Total esophageal disconnection (creating an anastomosis from the esophagus to the small intestine and using gastrostomy tube to feed into the stomach is not a first-line surgical procedure for medically refractory GERD patients but may be considered in some situations. [Rosen: 2018]

Other procedures, such as radiofrequency ablation of the lower esophageal sphincter and endoscopic full-thickness plication, are not currently advised for pediatric patients with medically refractory GERD.