CE/CME

Pediatric GERD

Clinician Reviews. 2013 May;23(5):40-47

References

1. Diaz DM, Winter HS, Colletti RB, et al. Knowledge, attitudes and practice styles of North American pediatricians regarding gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2007;45:56-64.

2. van der Pol RJ, Smits MJ, van Wijk MP, et al. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127:925-935.

3. Nelson SP, Kothari S, Wu EQ, et al. Pediatric gastroesophageal reflux disease and acid-related conditions: trends in incidence of diagnosis and acid suppression therapy. J Med Econ. 2009;12:348-355.

4. Tolia V, Gilger MA, Barker PN, Illueca M. Healing of erosive esophagitis and improvement of symptoms of gastroesophageal reflux disease after esomeprazole treatment in children 12 to 36 months old. J Pediatr Gastroenterol Nutr. 2010;51:593-598.

5. Vakil N. Disease definition, clinical manifestations, epidemiology and natural history of GERD. Best Pract Res Clin Gastroenterol. 2010;24:759-764.

6. Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009;49:498-547.

7. Michail S. Gastroesophageal reflux. Pediatr Rev. 2007;28:101-111.

8. Orenstein SR, McGowan JD. Efficacy of conservative therapy as taught in the primary care setting for symptoms suggesting infant gastroesophageal reflux. J Pediatr. 2008;152:310-314.

9. Vandenplas Y, Lifshitz JZ, Orenstein S, et al. Nutritional management of regurgitation in infants. J Am Coll Nutr. 1998;17:308-316.

10. Sherman PM, Hassall E, Fagundes-Neto U, et al. A global, evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric population. Am J Gastroenterol. 2009;104:1278-1295.

11. Digestive Diseases Information Clearinghouse. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. Heartburn, gastroesophageal reflux (GER), and gastroesophageal reflux disease (GERD)(2007). http://digestive.niddk.nih.gov/ddiseases/pubs/gerd. Accessed April 4, 2013.

12. Vakil N, van Zanten SV, Kahrilas P, et al; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900-1920.

13. Bharwani S. Gastroesophageal reflux disease in children: from infancy to adolescence. J Med Sci. 2011;4:25-39.

14. Patel NR, Ward MJ, Beneck D, et al. The association between childhood overweight and reflux esophagitis. J Obes. 2010;2010.

15. Quitadamo P, Buonavolontà R, Miele E, et al. Total and abdominal obesity are risk factors for gastroesophageal reflux symptoms in children. J Pediatr Gastroenterol Nutr. 2012;55:72-75.

16. Pashankar DS, Corbin Z, Shah SK, Caprio S. Increased prevalence of gastroesophageal reflux symptoms in obese children evaluated in an academic medical center. J Clin Gastroenterol. 2009;43:410-413.

17. Elitsur Y, Dementieva Y, Elitsur R, Rewalt M. Obesity is not a risk factor in children with reflux esophagitis: a retrospective analysis of 738 children. Metab Syndr Relat Disord. 2009;7:211-214.

18. Hill DJ, Heine RG, Cameron DJ, et al. Role of food protein intolerance in infants with persistent distress attributed to reflux esophagitis. J Pediatr. 2000;136:641-647.

19. Franciosi JP, Liacouras CA. Eosinophilic esophagitis. Immunol Allergy Clin N America. 2009;29:19-27.

20. Thakkar K, Boatright RO, Gilger MA, El-Serag HB. Gastroesophageal reflux and asthma in children: a systematic review. Pediatrics. 2010; 125:e925-e930.

21. Tolia V, Vandenplas Y. Systematic review: the extra-oesophageal symptoms of gastro-oesophageal reflux disease in children. Aliment Pharmacol Ther. 2009;29:258-272.

22. Cresi F, Locatelli E, Marinaccio C, et al. Prognostic values of multichannel intraluminal impedance and pH monitoring in newborns with symptoms of gastroesophageal reflux disease. J Pediatr. 2012 Nov 10. [Epub ahead of print]

23. Dalby K, Nielsen RG, Markoew S, et al. Reproducibility of 24-hour combined multiple intraluminal impedance (MII) and pH measurements in infants and children: evaluation of a diagnostic procedure for gastroesophageal reflux disease. Dig Dis Sci. 2007;52:2159-2165.

24. Tucker ME. FDA approves pediatric formulation of proton-pump inhibitor. www.medscape.com/viewarticle/781615. Accessed April 4, 2013.

25. Zannikos PN, Doose DR, Leitz GJ, et al. Pharmacokinetics and tolerability of rabeprazole in children 1 to 11 years old with gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2011;52:691-701.

26. Orenstein SR, Hassall E. Infants and proton pump inhibitors: tribulations, no trials. J Pediatr Gastroenterol Nutr. 2007;45:395-398.

27. Barron JJ, Tan H, Spalding J, et al. Proton pump inhibitor utilization patterns in infants. J Pediatr Gastroenterol Nutr. 2007;45:421-427.

28. Sopo SM, Radzik D, Calvani M. Does treatment with proton pump inhibitors for gastroesophageal reflux disease (GERD) improve asthma symptoms in children with asthma and GERD? A systematic review. J Investig Allergol Clin Immunol. 2009;19:1-5.

29. Anvari M, Allen C, Marshall J, et al. A randomized controlled trial of laparoscopic Nissen fundoplication versus proton pump inhibitors for the treatment of patients with chronic gastroesophageal reflux disease (GERD): 3-year outcomes. Surg Endosc. 2011;25:2547-2554

EVALUATION AND DIAGNOSIS
In 2009, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN and ESPGHAN)⁶ released international guidelines for the management of pediatric GERD, including evaluation, diagnosis, and treatment. Making a diagnosis of GERD in an infant or a toddler can be challenging, since no reliable pathognomonic symptoms are known. Older children and adolescents are better able to articulate their presenting symptoms (which resemble those of adults); thus, a detailed history and physical exam are ordinarily adequate to diagnose GERD and introduce treatment in these patients.⁶

The diagnostic tool that is considered the gold standard for pediatric patients, including infants, is 24-hour esophageal pH monitoring. This test directly measures the quantity of acid present in the esophagus by way of an internal probe that is passed through the mouth or nose and worn for 24 hours. Esophageal pH monitoring quantifies the amount of acid to which the esophagus is exposed over this time period, compared with standard pediatric values.^6,13

However, a newer combined multichannel intraluminal impedance and pH monitoring (MII/pH) tool offers advantages over esophageal pH monitoring, as it detects nonacidic or weakly acidic reflux events, in addition to more obvious episodes of acidic reflux.^6,13,22

Clinical benefits of the MII/pH are:

• Better efficiency than pH monitoring alone in the evaluation of respiratory symptoms and GERD

• Ability to correlate timing of reflux episodes with symptoms, including chronic cough, apnea, and other respiratory symptoms

• Improved accuracy in monitoring postprandial reflux episodes, which are typically less acidic.^13,23

Additionally, MII/pH provides a graphic readout from which the duration, height, and frequency of the reflux episodes can be analyzed. Currently, the chief disadvantage to its use is the absence of standardized pediatric values.¹³

Endoscopic biopsy should not be used to establish whether esophagitis is due to reflux. Endoscopically visible breaks in the distal esophageal mucosa are the most reliable indicators of reflux esophagitis. However, because other signs, such as mucosal erythema, pallor, and vascular patterns have normal variations, they cannot be considered evidence of reflux esophagitis.⁶ Endoscopic biopsy is mainly recommended for confirmation of suspected Barrett’s esophagus (which is rare in children) or for eosinophilic esophagitis, as it can confirm infiltrating mucosal eosinophils.^6,19

Nuclear scintigraphy uses imaging to time the passage of a radioisotope-labeled meal through the upper GI tract. It can provide information about gastric emptying, which may be delayed in children with GERD. It may also be useful in diagnosing aspiration in patients with chronic intractable respiratory symptoms.⁶ Because standardized techniques and age-specific norms are lacking, however, nuclear scintigraphy is not recommended for patients with other potentially reflux-related symptoms. The sensitivity of this test is low, and negative results may not exclude the possibility of reflux and aspiration.⁶

Barium contrast radiography (upper GI series) is not recommended due to its poor sensitivity and specificity. This test is useful for confirming anatomic anomalies, however.⁶

For infants and toddlers with symptoms suggestive of GERD, the NASPGHAN/ESPGHAN authors⁶ find no evidence to support an empiric trial of pharmacologic treatment to confirm the diagnosis. For older, verbal children and adolescents who present with heartburn and/or chest pain, a short-term trial (as long as 4 weeks) of acid suppressants may be used to identify acid reflux as the cause of these symptoms.

Based on the guidelines by Vandenplas et al,⁶ a clinician’s initial approach to evaluation for GERD and its diagnosis should begin with a thorough history and physical exam and the least invasive diagnostic process possible. The child’s specific symptoms and suspected involvement of other organ systems will dictate the use of progressively invasive diagnostic strategies.

MANAGEMENT OF GERD
Conservative Treatment
Nonpharmacologic, age-appropriate approaches focus on diet and lifestyle changes. An effective treatment option for infants uses dry rice cereal to thicken the formula, resulting in decreased visible reflux and regurgitation.^6,8 Recommended amounts of thickened formula are 4 oz/kg/d, divided into four to eight daily feedings, depending on the age of the patient; infants close to 1 year require only four feedings.⁸ For breastfed infants, expressed breast milk can be thickened with rice cereal and given at comparable volumes.⁸

Recommendations from the NASPGHAN/ESPGHAN clinical practice guidelines⁶ include a two- to four-week trial of an extensively hydrolyzed protein formula for formula-fed infants who vomit frequently. These formulas are considered hypoallergenic and contain shorter protein particles, allowing for easier digestion.⁸

Lifestyle changes recommended for adults with GERD can also be tailored for use in pediatric patients (see Table 3^8,11). They include avoidance of overfeeding by giving smaller portions at greater frequency (as described above), avoidance of foods known to cause GERD symptoms, avoidance of cigarette smoke, restriction of eating and drinking close to bedtime, elevation of the head of the bed or crib (use of a pillow is not recommended in children younger than 1 year), and a left-sided sleeping position for adolescents.^6,11

Holding infants upright for 30 minutes after feeding with ample burping may reduce reflux.¹¹ In infants, the prone position provides the greatest benefit for reducing acid reflux, according to findings from one study based on pH monitoring.¹³ Nonetheless, the association between prone positioning and sudden infant death syndrome (SIDS) has led to recommendations of supine position when infants sleep unobserved.⁶ Perhaps supervised “tummy time” several times per day (eg, after feeding) can help reduce GERD symptoms in infants.

Finally, breastfeeding mothers are advised to avoid consuming cow’s milk, eggs, and soy products, as their presence in breast milk may promote reflux in an infant with unrecognized food allergy.^6,8

Pharmacologic Treatment
Since esophagitis develops as a result of continuous acid exposure from the refluxate, the primary pharmacologic therapy for the treatment of GERD is aimed at acid reduction in the upper GI tract. Current pharmacologic options include histamine₂-receptor antagonists (H₂RAs) and proton pump inhibitors (PPIs).⁶ H₂RAs have been shown to alleviate symptoms and promote mucosal healing. To their disadvantage, long-term use of H₂RAs may lead to drug tolerance.

PPIs are superior to H₂RAs in symptom relief and esophageal healing without causing tolerance; however, although certain agents are FDA approved for treatment of children age 1 year or older with GERD (including esomeprazole, lansoprazole, and omeprazole), use of PPIs in infants younger than 1 year is controversial.^6,13 (See “New Solution for Pediatric GERD?”^24,25)

According to results from existing studies of PPI use in infants with GERD ages 34 weeks to 1 year, PPIs are no more effective at symptom reduction than placebo.^2,26 Further, data to demonstrate efficacy of long-term PPI use in infants and toddlers are scant.^6,27 Safety results from various trials are inconsistent, ranging from no reported adverse effects to rare but severe adverse events, including necrotizing enterocolitis in infants, and lower respiratory tract infections, community-acquired pneumonia, gastric polyps, and acute gastroenteritis in children.^2,26

The most common adverse effects of esomeprazole use in infants and children are nausea, vomiting, diarrhea, pyrexia, and headache.^4,6 Because of these potential risks, none of the PPIs is approved for use in infants younger than 1 year. However, a short-term PPI trial for as long as 4 weeks (along with lifestyle changes) for symptom reduction in older children is recommended by the NASPGHAN/ESPGHAN clinical practice guidelines.^2,6,13

Also based on the NASPGHAN/ESPGHAN guidelines,⁶ empiric PPI therapy is not recommended in pediatric patients presenting with wheezing or asthma. One research team has reported that asthma symptoms may be validly treated with a PPI in patients who do not respond to standard asthma treatment and who have a high reflux index.²⁸ However, an absence of studies to support this finding makes a firm recommendation impossible.

According to the NASPGHAN/ESPGHAN guidelines,⁶ there is insufficient evidence to justify the use of prokinetic agents (eg, metoclopramide, erythromycin, bethanechol, domperidone) for pediatric GERD, as their potential risks outweigh their potential benefits. Neither are alginates nor sucralfate recommended for long-term therapy, because PPIs and H2RAs are considered more effective.⁶

Surgical Treatment
As with adults, surgery should be a last resort for treatment. Antireflux surgery is deemed appropriate only in children who cannot tolerate long-term medical therapy due to life-threatening complications, who cannot comply with the treatment schedule, or in whom medications have been found ineffective.⁶

The gold standard for the surgical treatment of GERD is laparoscopic Nissen fundoplication, a procedure in which the shape of the stomach fundus is modified to provide strength and functional support to the lower esophageal sphincter.²⁹ Although children with heartburn, asthma, nocturnal asthma symptoms, or steroid-dependent asthma have been found to benefit clinically from long-term medical therapy or antireflux surgery, the comparable benefits of surgical versus medical treatment in these children is unknown.⁶

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