Gastro-esophageal reflux in children:Symptoms, diagnosis and treatment

Abstract

Gastroesophageal reflux (GER) is the passage of gastric contents into the esophagus and is a normal physiologic process occurring several times per day in healthy individuals. In infants and toddlers, no symptoms allow to diagnose GERD or to predict response to therapy. In older children and adolescents, history and physical examination may be sufficient to diagnose GERD. Endoscopically visible breaks in the distal esophageal mucosa are the most reliable evidence of reflux esophagitis. Esophageal pH monitoring quantitatively measures esophageal acid exposure. The severity of pathologic acid reflux does not predict symptom severity or treatment outcome. Combined multiple intraluminal impedance and pH monitoring (MII-pH) measures both acid, weakly acid, non-acid and gas reflux episodes. MII-pH is superior to pH monitoring alone for evaluation of the temporal relationship between symptoms and GER. Barium contrast radiography is not useful for the diagnosis of GERD, but is useful to detect anatomic abnormalities. Tests on ear, lung and esophageal fluids for lactose, pepsin or lipid laden macrophages have all been proposed without convincing evidence. An empiric trial of acid suppression as a diagnostic test can be used in older children (> 10 years). Parental education, guidance and support are always required and usually sufficient to manage healthy, thriving infants with symptoms likely due to physiologic GER. Use of a thickened feed, by preference commercially available anti-regurgitation formula, decrease visible regurgitation. Positional therapy brings additional benefit. Prone (beyond the age of sudden infant death syndrome) or left side sleeping position, and/or elevation of the head of the bed decrease GER. Chronic use of buffering agents or sodium alginate is not recommended for GERD since some have absorbable components that may have adverse effects with long-term use. Potential adverse effects of currently available prokinetic agents outweigh the potential benefits of these medications for treatment of GERD. Proton pump inhibitors (PPIs) are superior to histamine-2 receptor antagonists (H2RAs). Administration of long-term acid suppression without a diagnosis is not recommended. No PPI has been approved for use in infants < 1 year of age. The potential adverse effects of acid suppression, including increased risk of community-acquired pneumonias and gastrointestinal infections, need to be balanced against the benefits of therapy. Anti-reflux surgery is of benefit in selected children with chronic, relapsing GERD. Indications include failure of optimized medical therapy; dependence on long-term medical therapy; significant non-adherence with medical therapy; or pulmonary aspiration of refluxate.

Keywords

• Gastroesophageal reflux, children

References

1. Vandenplas Y. Gastroesophageal reflux. In: Paediatric Gastrointestinal and Liver Disease. Editors: R. Wyllie, J. Hyams. Elsevier (in press)
2. Hegar B, Dewanti NR, Kadim M, Alatas S, Firmansyah A, Vandenplas Y. Natural evolution of regurgitation in healthy infants. Acta Paediatr. 2009;98:1189-93
3. Nelson SP, Chen EH, Syniar GM, Christoffel KK. gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Grouup. Arch Pediatr Adolesc Med. 1997;151:569-72
4. Sherman PM, Hassall E, Fagundes-Neto U, Gold BD, Kato S, Koletzko S, Orenstein S, Rudolph C, Vakil N, Vandenplas Y. A Global, Evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric population. Am J Gastroenterol 2009;104:1278-95
5. Nelson SP, Chen EH, Syniar GM, Christoffel KK. One-year follow-up of symptoms of gastroesophageal Pediatric Practice Research Group. Pediatrics. 1998;102:E67 during infancy.
6. Nelson SP, Chen EH, Syniar GM, Christoffel KK. gastroesophageal reflux during childhood: a pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med. 2000;154:150-4. of
7. Tolaymat N, Chapman DM. Gastroesophageal reflux disease in children older than two years of age. W V Med J. 1998;94:22-5.
8. Johnston BT, Carré IJ, Thomas PS, Collins BJ. Twenty to 40 year follow up of infantile hiatal hernia. Gut. 1995;36:809-12.

9. Waring JP, Feiler MJ, Hunter JG, Smith CD, Gold BD. Childhood gastroesophageal reflux symptoms in adult patients. J Pediatr Gastroenterol Nutr. 2002;35:334-8.
10. Lee WS, Beattie RM, Meadows N,
11. Walker-Smith JA. Gastro-oesophageal reflux: clinical profiles and outcome. J Paediatr Child Health. 1999;35:568-71
12. Carre IJ, Johnston BT, Thomas PS, Morrisson PJ. Familial hiatal hernia in a large five generation family confirming true autosomal dominant inheritance. Gut 1999;45:649-652
13. Hassall E. Co-morbidities in childhood Barrett’s esophagus. J Pediatr Gastroenterol Nutr 1997;25:255-260
14. Trudgill NJ, Kapur KC, Riley SA. Familial clustering of reflux symptoms. Am J Gastroenterol 1999;94:1172-1178
15. Cameron AJ, Lagergren J, Henriksson C. Gastroesophageal monozygotic Gastroenterology 2002;122:55-59 in and dizygotic twins.
16. Hu FZ, Preston RA, Post JC. Mapping of a gene for severe pediatric gastroesophageal reflux 2000;284:325-34 13q14. JAMA
17. Orenstein SR, Shalaby TM, Barmada MM, Whitcomb DC. Genetics of gastroesophageal reflux Gastroenterol Nutr 2002;34:506-510 J Pediatr
18. Kang JY, Ho KY. Different prevalences of reflux oesophagitis and hiatus hernia among dyspeptic patients in England and Singapore. Eur J Gastroenterol Hepatol 1999;11:845-850
19. Sonnenberg A, El-Serag HB. Clinical epidemiology gastroesophageal reflux disease. Yale J Biol Med 1999;72:81-92 history of
20. Kim SL, Hunter JG, Wo JM, Davis LP, Waring JP. NSAIDs, aspirin, and esophageal strictures: are over-the-counter medications harmful Gastroenterol 1999;29:32-34 J Clin
21. Vandenplas Y, Rudolph CD, Di Lorenzo C, Hassall E, Liptak G, Mazur L, Sondheimer J, Staiano A, Thomson M, Veereman-Wauters G, Wenzl TG. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society Hepatology, and Nutrition (NASPGHAN) and the Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009;49:498-547
22. Gastroenterology, European Society for Pediatric
23. Salvatore S, Hauser B, Vandemaele K, Novario R, Vandenplas Y. Gastroesophageal reflux disease in infants: how much is predictable with questionnaires, pH-metry, endoscopy Gastroenterol Nutr 2005;40:210-5. J Pediatr
24. Salvatore S, Hauser B, Vandenplas Y. The natural course of gastro-oesophageal reflux. Acta Paediatr 2004;93:1063-9.
25. Salvatore S, Vandenplas Y. Gastroesophageal reflux and cow milk allergy: is there a link? Pediatrics 2002;110:972-84
26. Jordan B, Heine RG, Meehan M, Catto-Smith AG, Lubitz L. Effect of antireflux medication, placebo and infant mental health intervention on persistent crying: a randomized clinical trial. J Paediatr Child Health 2006;42:49-58.
27. Stanford EA, Chambers CT, Craig KD. The role of developmental factors in predicting young children's use of a self-report scale for pain. Pain 2006;120:16-23.
28. Orenstein SR, Shalaby TM, Cohn JF. Reflux symptoms in 100 normal infants: diagnostic validity of the infant gastroesophageal reflux questionnaire. Clin Pediatr (Phila)
29. Kleinman L, Rothman M, Strauss R, Orenstein SR, Nelson S, Vandenplas Y, Cucchiara S, Revicki DA. The infant gastroesophageal reflux questionnaire revised: development and validation as an evaluative instrument. 2006;4:588-96. Hepatol
30. Di Lorenzo C, Piepsz A, Ham H, Cadranel S. Gastric emptying with gastro-oesophageal reflux. Arch Dis Child 1987;62:449-53
31. Ravelli AM, Panarotto MB, Verdoni L, Consolati aspiration gastroesophageal reflux-related respiratory disease. Chest 2006;130:1520-6. Pulmonary by scintigraphy in 30. Gleeson K, Eggli DF, Maxwell SL. Quantitative aspiration during sleep in normal subjects. Chest 1997;111:1266-72
32. Jang HS, Lee JS, Lim GY, Choi BG, Choi GH, Park SH. Correlation of color Doppler sonographic findings with pH measurements in gastroesophageal reflux in children. J Clin Ultrasound 2001;29:212-7.
33. Mattioli G, Sacco O, Repetto P, Pini Prato A, Castagnetti M, Carlini C, Torre M, Leggio S, Gentilino V, Martino F, Fregonese B, Barabino A, Gandullia P, Rossi GA, Jasonni V. Necessity for surgery in children with gastrooesophageal supraoesophageal symptoms. Eur J Pediatr Surg 2004;14:7-13. reflux and disease: is there Scand J correlate?
34. Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis PA, Hassall E, Straumann A, Rothenberg ME. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007;133:1342-1363.
35. Spechler SJ, Genta RM, Souza RF. Thoughts on gastroesophageal eosinophilic esophagitis. Am J Gastroenterol 2007;102:1301-6 between reflux disease and
36. Hill DJ, Heine RG, Cameron DJ, Catto-Smith AG, Chow CW, Francis DE, Hosking CS. Role of food protein intolerance in infants with persistent distress attributed to reflux esophagitis. J Pediatr 2000;136:641-7.
37. Orenstein SR, Shalaby TM, Kelsey SF, Frankel E. Natural history of infant reflux esophagitis: symptoms and morphometric histology pharmacotherapy. 2006;101:628-40 year without Am J Gastroenterol
38. Tuttle SG, Grossman MI. Detection of gastro- esophageal measurement of intraluminal pressure and pH. Proc Soc Exp Biol Med 1958;98:225-7. 39. Vandenplas Y,
39. Franckx-Goossens A,
40. Pipeleers-Marichal M, Derde MP, Sacre-Smits
41. L. Area under pH 4: advantages of a new
42. parameter in the interpretation of esophageal
43. pH monitoring data in infants. J Pediatr
44. Gastroenterol Nutr 1989;9:34-9.
45. Vandenplas Y, Badriul H, Verghote M, Hauser B, Kaufman L. Oesophageal pH monitoring and reflux oesophagitis in irritable infants. Eur J Pediatr 2004;163:300-4.
46. Silny J. J. Silny, Intraluminal multiple electric impedance procedure for measurement of gastrointestinal motility. J Gastrointest Motil 1991;3:151-162.
47. Rosen R, Lord C, Nurko S. The sensitivity of multichannel intraluminal impedance and the pH gastroesophageal reflux in children. Clin Gastroenterol Hepatol 2006;4:167-72. of
48. Peter CS, Sprodowski N, Ahlborn V, Wiechers C, Schlaud M, Silny J, Poets CF. Inter- and intraobserver agreement for gastroesophageal reflux detection in infants using multiple intraluminal impedance. Biol Neonate 2004;85:11-4.
49. Dalby K, Nielsen RG, Markoew S, Kruse- Andersen S, Husby S. Reproducibility of 24- hour impedance (MII) and pH measurements in infants and children. Evaluation of a diagnostic procedure for gastroesophageal reflux disease. Dig Dis Sci 2007;52:2159-65.
50. Wenzl TG, Schenke S, Peschgens T, Silny J, Heimann G, Skopnik H. Association of apnea and nonacid gastroesophageal reflux in infants: Investigations with the intraluminal impedance 2001;31:144-9. Pediatr Pulmonol
51. Loots CM, Benninga MA, Davidson GP, Omari monitoring to standard pH monitoring increases the yield of symptom association analysis in infants and children with gastroesophageal of pH-impedance reflux. J Pediatr
52. Orel R, Brecelj J, Homan M, Heuschkel R. Treatment of oesophageal bile reflux in children: the results of a prospective study with omeprazole. J Pediatr Gastroenterol Nutr 2006;42:376-83.
53. Tack J. Review article: the role of bile and pepsin in the pathophysiology and treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2006;24 Suppl 2:10-6.
54. He Z, O'Reilly RC, Bolling L, Soundar S, Shah M, Cook S, Schmidt RJ, Bloedon E, Mehta DI. Detection of gastric pepsin in middle ear fluid of children with otitis media. Otolaryngol Head Neck Surg 2007;137:59-64.
55. Starosta V, Kitz R, Hartl D, Marcos V, Reinhardt D, Griese M. Bronchoalveolar pepsin, inflammation gastroesophageal 2007;132:1557-64. oxidation, children with Chest disease.
56. Numans ME, Lau J, de Wit NJ, Bonis PA. Short-term inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. 2004;140:518-27 with proton-pump Ann Intern Med
57. Vakil N. Review article: how valuable are proton-pump inhibitors in establishing a diagnosis disease? Aliment Pharmacol Ther 2005;22 Suppl 1:64-9 reflux J Pediatr Gastroenterol Nutr
58. Malcolm WF, Gantz M, Martin RJ, Goldstein RF, Goldberg RN, Cotton CM, National Institute of Child Health and Human Development Neonatal research Network. Use of medications for gastroesophageal reflux at discharge among extremely low birth weight infants. Pediatrics 2008;121:22-7
59. Sheikh S, Stephen T, Howell L, Eid N. Gastroesophageal reflux in infants with wheezing. Pediatr Pulmonol 1999;28:181-6.
60. Molle LD, Goldani HA, Fagondes SC, Vieira VG, Barros SG, Silva PS, Silveira TR. Nocturnal reflux in children and adolescents with persistent asthma and gastroesophageal reflux. J Asthma. 2009;46:347-50.
61. Ramaiah RN Stevenson M, McCallion WA.. Hypopharyngeal and distal esophageal pH monitoring in children with gastroesophageal reflux and respiratory symptoms. J Pediatr Surg. 2005;40:1557-61
62. Ayazi S, Lipham JC, Hagen JA, Tang AL, Zehetner J, Leers JM, Oezcelik A, Abate E, Banki F, DeMeester SR, DeMeester TR. A new technique for measurement of pharyngeal pH: normal values and discriminating pH threshold. J Gastrointest Surg. 2009;13:1422- 9.
63. Morigeri C, Bhattacharya A, Mukhopadhyay K, Narang A, Mittal BR. Radionuclide scintigraphy gastroesophageal reflux in symptomatic and asymptomatic pre-term infants. Eur J Nucl Med Mol Imaging. 2008;35:1659-65
64. Khoshoo V, Ross G, Brown S, Edell D. Smaller volume, thickened formulas in the management of gastroesophageal reflux in thriving infants. J Pediatr Gastroenterol Nutr
65. Chao HC, Vandenplas Y. Effect of cereal- thickened formula and upright positioning on regurgitation, gastric emptying and weight gain in infants with regurgitation. Nutrition 2007;23:23-8
66. Xinias I, Mouane N, Le Luyer B, Spiroglou K, Demertzidou V, Hauser B, Vandenplas Y. Cornstarch oesophageal acid exposure time in infants. Dig Liver Dis 2005;37:23-7 reduces
67. Hegar B, Rantos R, Firmansyah A, De Schepper J, Vandenplas Y. Natural evolution of infantile regurgitation versus the efficacy of thickened formula. J Pediatr Gastroenterol Nutr 2008;47:26-30
68. Levtchenko E, Hauser B, Vandenplas Y. Nutritional value of an "anti-regurgitation" formula. 1998;61:285-7 Belg
69. Ferry GD, Selby M, Pietro TJ. Clinical response to short-term nasogastric feeding in infants with gastroesophageal reflux and growth failure. J Pediatr Gastroenterol Nutr 1983;2:57-61.
70. Vandenplas Y, Hauser B. Gastro-oesophageal reflux, sleep pattern, apparent life threatening event and sudden infant death. The point of view of a gastro-enterologist. Eur J Pediatr 2000;159:726-9
71. Oyen N, Markestad T, Skaerven R, Irgens LM, Helweg-Larsen K, Alm B, Norvenius G, Wennergren G. Combined effects of sleeping position and prenatal risk factors in sudden infant Epidemiological SIDS Study. Pediatrics 1997;100:613-21. the Nordic
72. Adams EJ, Chavez GF, Steen D, Shah R, Iyasu S, Krous HF. Changes in the epidemiologic profile of sudden infant death syndrome as rates decline among California infants: 1990-1995. Pediatrics 1998;102:1445- 51.
73. Omari TI, Rommel N, Staunton E, Lontis R, Goodchild L, Haslam RR, Dent J, Davidson GP. Paradoxical impact of body positioning on gastroesophageal reflux and gastric emptying in the premature neonate. J Pediatr 2004;145:194-200.
74. van Wijk MP, Benninga MA, Dent J, Lontis R, Goodchild L, McCall LM, Haslam R, Davidson GP, Omari T. Effect of body position gastroesophageal reflux and gastric emptying in the healthy premature neonate. J Pediatr 2007;151:585-90, 590 e1-2. postprandial
75. Orenstein SR, Whitington PF, Orenstein DM. The gastroesophageal reflux. N Engl J Med 1983;309:760-3. as treatment for
76. Vandenplas Y, De Schepper J, Verheyden S, Devreker T, Franckx J, Peelman M, Denayer E, Hauser B. A preliminary report on the efficacy of the Multicare AR-Bed in 3-week- 3-month-old associated symptoms and acid reflux. Arch Dis Child. 2010;95:26-30 on regurgitation,
77. Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence- based 2006;166:965-71. Intern Med
78. Austin GL, Thiny MT, Westman EC, Yancy WS, Jr., Shaheen NJ. A very low- carbohydrate diet improves gastroesophageal reflux and its symptoms. Dig Dis Sci 2006;51:1307-12.
79. Piesman M, Hwang I, Maydonovitch C, Wong RK. Nocturnal reflux episodes following the administration of a standardized meal. Does timing 2007;102:2128-34. J Gastroenterol
80. Avidan B, Sonnenberg A, Schnell TG, Sontag SJ. Walking and chewing reduce postprandial acid 2001;15:151-5. Pharmacol Ther
81. Moazzez R, Bartlett D, Anggiansah A. The effect of chewing sugar-free gum on gastro- esophageal reflux. J Dent Res 2005;84:1062- 5.
82. Smoak BR, Koufman JA. Effects of gum chewing on pharyngeal and esophageal pH. Ann Otol Rhinol Laryngol 2001;110:1117-9.
83. Meining A, Classen M. The role of diet and lifestyle measures in the pathogenesis and treatment of gastroesophageal reflux disease. Am J Gastroenterol 2000;95:2692-7.