Skip to main content
Log in

Current Pharmacological Management of Gastro-Esophageal Reflux in Children

An Evidence-Based Systematic Review

  • Review Article
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

Gastro-esophageal reflux (GER) is a common phenomenon, characterized by the regurgitation of the gastric contents into the esophagus. Gastro-esophageal reflux disease (GERD) is the term applied when GER is associated with sequelae or faltering growth.

The main aims of treatment are to alleviate symptoms, promote normal growth, and prevent complications. Medical treatments for children include (i) altering the viscosity of the feeds with alginates; (ii) altering the gastric pH with antacids, histamine H2 receptor antagonists, and proton pump inhibitors; and (iii) altering the motility of the gut with prokinetics, such as metoclopramide and domperidone.

Our aim was to systematically review the evidence base for the medical treatment of gastro-oesophageal reflux in children. We searched PubMed, AdisOnline, MEDLINE, and EMBASE, and then manually searched reviews from the past 5 years using the key words ‘gastro-esophageal’ (or ‘gastroesophageal’), ‘reflux’, ‘esophagitis’, and ‘child$’ (or ‘infant’) and ‘drug$’ or ‘therapy’. Articles included were in English and had an abstract. We used the levels of evidence adopted by the Centre for Evidence-Based Medicine in Oxford to assess the studies for all reported outcomes that were meaningful to clinicians making decisions about treatment. This included the impact of clinical symptoms, pH study profile, and esophageal appearance at endoscopy.

Five hundred and eight articles were reviewed, of which 56 papers were original, relevant clinical trials. These were assessed further. Many of the studies considered had significant methodological flaws, although based on available evidence the following statements can be made. For infant GERD, ranitidine and omeprazole and probably lansoprazole are safe and effective medications, which promote symptomatic relief, and endoscopic and histological healing of esophagitis. Gaviscon® Infant sachets are safe and can improve symptoms of reflux. There is less evidence to support the use of domperidone or metoclopramide. More evidence is needed before other anti-reflux medications can be recommended. For older children, acid suppression is the mainstay of treatment. The largest evidence base supports the early use of H2 receptor antagonists or proton pump inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Table I
Table II
Table III
Table IV
Table V
Table VI
Table VII
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Tighe MP, Cullen M, Beattie RM. How to use: a pH study. Arch Dis Child Ed Pract Feb 2009; 94: 18–23

    Article  CAS  Google Scholar 

  2. North American Society of Pediatric Gastroenterology, Hepatology and Nutrition. Paediatric gastro-esophageal reflux clinical practice guidelines. J Pediatr Gastroenterol Nutr 2001; 32Suppl. 2: S1–31

    Google Scholar 

  3. Nelson SP, Chen EH, Syniar GM, et al. Prevalence of symptoms of gastrooesophageal reflux during infancy: a paediatric practice-based survey. Arch Pediatr Adolesc Med 1997; 151: 569–72

    Article  PubMed  CAS  Google Scholar 

  4. Martin AJ, Pratt N, Kennedy JD, et al. Natural history and familial relationships of infant spilling to 9 years of age. Pediatrics 2002; 109: 1061–7

    Article  PubMed  Google Scholar 

  5. Carre IJ. The natural history of partial thoracic stomach (hiatus hernia) in children. Arch Dis Child 1959; 34: 344–53

    Article  PubMed  CAS  Google Scholar 

  6. Shepherd RW, Wren J, Evans S, et al. Gastroesophageal reflux in children: clinical profile, course and outcome with active therapy in 126 cases. Clin Pediatr (Phila) 1987; 26: 55–60

    Article  CAS  Google Scholar 

  7. Hyams JS, Ricci Jr A, Leichtner AM. Clinical and laboratory correlates of esophagitis in young children. J Pediatr Gastroenterol Nutr 1988; 7: 52–6

    Article  PubMed  CAS  Google Scholar 

  8. Salvatore S, Hauser B, Salvatoni A, et al. Oral ranitidine and duration of gastric pH <4.0 in infants with persisting reflux symptoms. Acta Paediatr 2006; 95(2): 176–81

    Article  PubMed  Google Scholar 

  9. Aggett PJ, Agostoni C, Goulet O, et al. Antireflux or antiregurgitation milk products for infants and young children: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 2002 May; 34(5): 496–8

    Article  PubMed  Google Scholar 

  10. Thomson M, Fritscher-Ravens A, Hall S, et al. Endoluminal gastroplication in children with significant gastro-oesophageal reflux disease. Gut 2004 Dec; 53(12): 1745–50

    Article  PubMed  CAS  Google Scholar 

  11. Hassall E. Outcomes of fundoplication: causes for concern, newer options. Arch Dis Child 2005 Oct; 90(10): 1047–52

    Article  PubMed  CAS  Google Scholar 

  12. Phillips B, Ball C, Sackett D, et al. Levels of evidence: Oxford Centre for Evidence-Based Medicine [online]. Available from URL: http://www.cebm.net/index.aspx?o=1025 [Accessed 2001 May]

  13. Mandel KG, Daggy BP, Brodie DA. Review article alginate-raft formulations in the treatment of heartburn and acid reflux. Alimen Pharmacol Ther 2000; 14: 669–90

    Article  CAS  Google Scholar 

  14. Gaviscon product information. Hull: Reckitt Benckiser Healthcare (UK) Limited, 2009. (Data on file)

  15. Keady S. Update on drugs for gastro-oesophageal reflux disease. Arch Dis Childhood Educ Pract 2007; 92: ep114–8

    Article  Google Scholar 

  16. Joint publication of the British Medical Association, the Royal Pharmaceutical Society of Great Britain, the Royal College of Paediatrics and Child Health, and the Neonatal and Paediatric Pharmacists Group. British national formulary for children. Section 1.1.2. London: BMJ Group, 2007: 53

  17. Miller S. Comparison of the efficacy and safety of a new aluminum-free paediatric alginate preparation and placebo in infants with recurrent gastrooesophageal reflux. Curr Med Res Opin 1999; 15(3): 160–8

    Article  PubMed  CAS  Google Scholar 

  18. Carroccio A, Iacono G, Montalto F, et al. Domperidone plus magnesium hydroxide and aluminium hydroxide: a valid therapy in children with gastroesophageal reflux. Scand J Gastroenterol 1994; 29: 300–4

    Article  PubMed  CAS  Google Scholar 

  19. Del Buono R, Wenzl TG, Ball G, et al. Effect of Gaviscon Infant on gastro-oesophageal reflux in infants assessed by combined intraluminal impedance/pH. Arch Dis Child 2005 May; 90: 460–3

    Article  PubMed  Google Scholar 

  20. Buts JP, Barudi C, Otte JB. Double-blind controlled study on the efficacy of sodium alginate (Gaviscon) in reducing gastroesophageal reflux assessed by 24h continuous pH monitoring in infants and children. Eur J Pediatr 1987 Mar; 146(2): 156–8

    Article  PubMed  CAS  Google Scholar 

  21. Forbes D, Hodgson M, Hill R. The effects of Gaviscon and metoclopramide in gastroesophageal reflux in children. J Pediatr Gastroenterol Nutr 1986 Jul–Aug; 5(4): 556–9

    Article  PubMed  CAS  Google Scholar 

  22. Greally P, Hampton FJ, MacFadyen UM, et al. Gaviscon and carobel compared with cisapride in gastro-oesophageal reflux. Arch Dis Child 1992; 67: 618–21

    Article  PubMed  CAS  Google Scholar 

  23. Joint publication ofthe British Medical Association, the Royal Pharmaceutical Society of Great Britain, the Royal College of Paediatrics and Child Health, and the Neonatal and Paediatric Pharmacists Group. British national formulary for children. Section 1.1.1. London: BMJ Group, 2007: 51

  24. Cucchiara S, Staiano A, Romaniello G, et al. Antacids and cimetidine treatment for gastro-oesophageal reflux and peptic oesophagitis. Arch Dis Child 1984; 59: 842–7

    Article  PubMed  CAS  Google Scholar 

  25. Cucchiara S, Franco MT, Terrin G, et al. Role of drug therapy in the treatment of gastro-oesophageal reflux disorder in children. Paediatr Drugs 2000 Jul–Aug; 2(4): 263–72

    Article  PubMed  CAS  Google Scholar 

  26. Karjoo M, Kane R. Omeprazole treatment of children with peptic esophagitis refractory to ranitidine therapy. Arch Pediatr Adolescent Med 1995 Mar; 149: 267–71

    Article  CAS  Google Scholar 

  27. Cucchiara S, Minella R, Iervolino C, et al. Omeprazole and high dose ranitidine in the treatment of refractory reflux oesophagitis. Arch Dis Child 1993; 69: 655–9

    Article  PubMed  CAS  Google Scholar 

  28. Cucchiara S, Gobio-Casali L, Balli F, et al. Cimetidine treatment of reflux esophagitis in children: an Italian multicentre study. J Ped Gastroenterol Nutr 1989; 8: 150–6

    Article  CAS  Google Scholar 

  29. Lambert J, Mobassaleh M, Grand RJ. Efficacy of cimetidine for gastric acid suppression in pediatric patients. J Pediatr 1992; 120: 474–8

    Article  PubMed  CAS  Google Scholar 

  30. Argüelles-Martin F, Gonzalez-Fernandez F, Gentles MG. Sucralfate versus cimetidine in the treatment of reflux esophagitis in children. Am J Med 1989 Jun 9; 86(6A): 73–6

    Article  PubMed  Google Scholar 

  31. Orenstein SR, Shalaby TM, Devandry SN, et al. Famotidine for infant gastro-oesophageal reflux: a multi-centre, randomized, placebo-controlled, withdrawal trial. Aliment Pharmacol Ther 2003; 17: 1097–107

    Article  PubMed  CAS  Google Scholar 

  32. Champion G, Richter JE, Vaezi MF, et al. Duodenogastric reflux: relationship to pH and importance to Barrett’s oesophagus. Gastroenterology 1994; 107: 747–54

    Article  PubMed  CAS  Google Scholar 

  33. Israel DM, Hassall E. Omeprazole and other proton pump inhibitors: pharmacology, efficacy and safety with special reference to use in children. J Pediatr Gastroenterol Nutr 1998; 27: 566–79

    Article  Google Scholar 

  34. Peghini P, Katz P, Bedassy A, et al. Nocturnal acid breakthrough during twice daily (bid) administration of proton pump inhibitor (PPI) [abstract]. Gastroenterology 1997; 112: A255

    Google Scholar 

  35. Joint publication of the British Medical Association, the Royal Pharmaceutical Society of Great Britain, the Royal College of Paediatrics and Child Health, and the Neonatal and Paediatric Pharmacists Group. British national formulary for children. Section 1.3.5. London: BMJ Group, 2007: 63

  36. Messaouik D, Sautou-Miranda V, Bagel-Boithias S, et al. Comparative study and optimisation of the administration mode of three proton pump inhibitors by nasogastric tube. Int J Pharm 2005 Aug 11; 299(1–2): 65–72

    Article  PubMed  CAS  Google Scholar 

  37. Nelis GF. Ranitidine in the management of gastro-oesophageal reflux disease. Neth J Med 1985; 28(5): 197–200

    PubMed  CAS  Google Scholar 

  38. Joint publication of the British Medical Association, the Royal Pharmaceutical Society of Great Britain, the Royal College of Paediatrics and Child Health, and the Neonatal and Paediatric Pharmacists Group. British national formulary for children. Section 1.3.5. London: BMJ Group, 2007: 62

  39. El-Matary W, Dalzell M. Omeprazole-induced hepatitis. Pediatr Emerg Care 2005 Aug; 21(8): 529–30

    Article  PubMed  Google Scholar 

  40. Tran A, Rey E, Pons G, et al. Pharmacokinetic-pharmacodynamic study of oral lansoprazole in children. Clin Pharm Ther 2002 May; 71(5): 359–67

    Article  CAS  Google Scholar 

  41. Langtry HD, Wilde MI. Lansoprazole: an update of its pharmacological properties and clinical efficacy in the management of acid-related disorders. Drugs 1997; 54: 473–500

    Article  PubMed  CAS  Google Scholar 

  42. Clissold SP, Campoli-Richards DM. Omeprazole. Drugs 1986; 32: 15–47

    Article  PubMed  CAS  Google Scholar 

  43. Hassall E, Israel D, Shepherd R, et al. Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy safety, tolerability and dose requirements. J Pediatr 2000; 137(6): 800–7

    Article  PubMed  CAS  Google Scholar 

  44. Martin PB, Imong SM, Krischer J, et al. The use of omeprazole for resistant oesophagitis in children. Eur J Ped Surg 1996; 4: 195–7

    Article  Google Scholar 

  45. Gunasekaran TS, Hassall EG. Efficacy and safety of omeprazole for severe gastroesophageal reflux in children. J Pediatr 1994 Feb; 124(2): 332–4

    Google Scholar 

  46. Kato S, Ebina K, Fuji K, et al. Effect of omeprazole in the treatment of refractory acid-related diseases in childhood: endoscopic healing and 24 hour intragastric activity. J Pediatr 1996; 128(3): 415–21

    Article  PubMed  CAS  Google Scholar 

  47. Alliet P, Raes M, Bruneel E, et al. Omeprazole in infants with cimetidine-resistant peptic esophagitis. J Pediatr 1998; 132(2): 352–4

    Article  PubMed  CAS  Google Scholar 

  48. De Giacomo C, Bawa P, Franceschi M, et al. Omeprazole for severe reflux esophagitis in children. J Pediatr Gastroenterol Nutr 1997; 24(5): 528–32

    Article  PubMed  Google Scholar 

  49. Franco MT, Salvin G, Terrin G, et al. Lansoprazole in the treatment of gastro-oesophageal reflux disease in childhood. Dig Liver Dis 2000; 32: 600–6

    Article  Google Scholar 

  50. Fiedorek S, Tolia V, Gold B, et al. Efficacy and safety of lansoprazole in adolescents with symptomatic erosive and non-erosive gastro-oesophageal reflux disease. J Ped Gastroenterol Nutr 2005; 40(5): 319–27

    Article  CAS  Google Scholar 

  51. Tolia V, Bishop P, Tsou V, et al. Multicenter randomised double blind study comparing 10, 20 and mg pantoprazole in children 5–11years with symptomatic gastroesophageal reflux disease. J Ped Gastroenterol Nutr 2006; 42(4): 384–91

    Article  CAS  Google Scholar 

  52. Tsou VM, Baker R, Book L, et al. Multicenter, randomized, double-blind study comparing 20 and 40 mg of pantoprazole for symptom relief in adolescents (12 to 16 years of age) with gastroesophageal reflux disease (GERD). 326 Study Group. Clin Pediatr (Phila) 2006 Oct; 45(8): 741–9

    Article  Google Scholar 

  53. Gold BD, Gunasekaran T, Tolia V, et al. Safety and symptom improvement with esomeprazole in adolescents with gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr 2007 Nov; 45(5): 520–9

    Article  PubMed  CAS  Google Scholar 

  54. Terrin BN, McWilliams NB, Maurer HM. Side-effects of metoclopramide as an antiemetic in childhood cancer-chemotherapy. J Pediatr 1984; 104: 183–40

    Google Scholar 

  55. Hyams JS, Zamett LO, Walters JK. Effect of metoclopramide on prolonged intraesophageal pH testing in infants with gastroesophageal reflux. J Pediatr Gastroenterol Nutr 1986; 5: 716–20

    Article  PubMed  CAS  Google Scholar 

  56. Tolia V, Calhoun J, Kuhns L, et al. Randomized, prospective double-blind trial of metoclopramide and placebo for gastroesophageal reflux in infants. J Pediatr 1989; 115(1): 141–5

    Article  PubMed  CAS  Google Scholar 

  57. Pons G, Duhamel JF, Guillot M, et al. Dose-response study of metoclopramide in gastroesophageal reflux in infancy. Fundam Clin Pharmacol 1993; 7(3–4): 161–6

    Article  PubMed  CAS  Google Scholar 

  58. De Loore I, Van Ravenstein H. Ameryckx L. Domperidone drops in the symptomatic treatment of chronic paediatric vomiting and regurgitation: a comparison with metoclopramide. Postgrad Med J 1979; 55: 40–2

    PubMed  Google Scholar 

  59. Leung A, Lai P. Use ofmetoclopramide for the treatment of gastrooesophageal reflux in infants and children. Curr Ther Res 1984; 36(5): 911–5

    Google Scholar 

  60. Craig WR, Hanlon-Dearman A, Sinclair C, et al. Metoclopramide, thickened feeding and positioning for gastro-oesophageal reflux in children under 2 years. Cochrane Database Syst Rev 2004; (3): CD003502

    Google Scholar 

  61. Hibbs AM, Lorch SH. Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review. Pediatrics 2006; 118: 746–52

    Article  PubMed  Google Scholar 

  62. Shafrir Y, Levy Y, Ben-Amitai D, et al. Oculogyric crisis due to domperidone therapy [case report]. Helv Paediatr Acta 1985; 40(95): 85

    Google Scholar 

  63. Franckx J, Noel P. Acute extrapyramidal dysfunction after domperidone administration. Helv Paediatr Acta 1984; 39: 285–8

    PubMed  CAS  Google Scholar 

  64. Bines J, Quinlan JE, Treves S, et al. Efficacy of domperidone in infants and children with gastro-oesophageal reflux. J Pediatr Gastroenterol Nutr 1992; 14: 400–5

    Article  PubMed  CAS  Google Scholar 

  65. Clara R. Chronic regurgitation and vomiting treated with domperidone: a multicenter evaluation. Acta Paediatric Belg 1979; 32: 203–7

    Google Scholar 

  66. Grill BB, Hillemeier C, Semeraro LA, et al. Effects of domperidone therapy on symptoms and upper gastrointestinal motility in infants with gastro-oesophageal reflux. J Pediatr 1985; 106(2): 311–6

    Article  PubMed  CAS  Google Scholar 

  67. Pritchard DS, Baber N, Stephenson T. Should domperidone be used for the treatment of gastro-oesophageal reflux in children? Systematic review of randomized controlled trials in children aged 1 month to 11 years old. Br J Clin Pharmacol 2005; 59(6): 725–9

    Article  PubMed  CAS  Google Scholar 

  68. Vandenplas Y. A proposition for the diagnosis and treatment of gastro-oesophageal reflux in children: a report from ESPGHAN. Eur J Pediatr 1993; 152: 704–11

    Article  PubMed  CAS  Google Scholar 

  69. Committee on Safety of Medicines and Medicines Control Agency. Cisapride (Prepulsid) withdrawn. Curr Prob Pharmacovigil 2000; 26: 9–14

    Google Scholar 

  70. Vandenplas Y, Belli DC, Benatar A, et al. The role of cisapride in the treatment of pediatric gastroesophageal reflux. J Paediatr Gastroenterol Nutr 1999; 28: 518–28

    Article  CAS  Google Scholar 

  71. Vandenplas Y. Reflux esophagitis in infants and children: a report from the working group on gastro-oesophageal reflux disease of the European Society of Paediatric Gastroenterology Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 1994; 18: 413–22

    Article  PubMed  CAS  Google Scholar 

  72. Augood C, MacLennon S, Gilbert R, et al. Cisapride treatment for gastro-oesophageal reflux in children. Cochrane Database Syst Rev 2003; (4): CD002300

    PubMed  Google Scholar 

  73. Peeters TL. Erythromycin and other macrolides as prokinetic agents. Gastroenterology 1993; 105: 1886–99

    PubMed  CAS  Google Scholar 

  74. Chicella MF, Batres LA, Heesters MF, et al. Prokinetic drug therapy in children: a review of current options. Annals Pharmacother 2005; 39(4): 706–11

    Article  CAS  Google Scholar 

  75. Janssens J, Peters TL, Vantrappen G, et al. Improvement of gastric emptying in diabetic gastroparesis by erythromycin. N EngI J Med 1990; 322: 10218–31

    Article  Google Scholar 

  76. Honein MA, Paulozzi LJ, Himelright IM, et al. Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromycin: a case review and cohort study. Lancet 1999; 354: 2101–5

    Article  PubMed  CAS  Google Scholar 

  77. Orenstein SR, Lofton SW, Orenstein DM, et al. Bethanechol for pediatric gastroesophageal reflux: a prospective blind controlled study. J Pediatr Gastroenterol Nutr 1986; 5: 549–55

    Article  PubMed  CAS  Google Scholar 

  78. Levi P, Marmo F, Saluzzo C, et al. Bethanechol versus antiacids in the treatment of gastroesophageal reflux. Helv Paediatr Acta 1985 Dec; 40(5): 349–59

    PubMed  CAS  Google Scholar 

  79. Brodgen RN, Heel RC, Speight TM, et al. Sucralfate: a review of its pharmacodynamic properties and therapeutic use in peptic ulcer disease. Drugs 1984; 27: 194–209

    Article  Google Scholar 

  80. Herbst JJ. Gastro-oesophageal reflux and gastric emptying. J Pediatr Gastroenterol Nutr 1983; 2Suppl. 1: 335–8

    Article  Google Scholar 

  81. Khan M, Santana J, Donnellan C, et al. Medical treatments in the short term management of reflux oesophagitis. Cochrane Database Syst Rev 2007; (2): CD003244

    PubMed  Google Scholar 

  82. Gold BD, Freston JW. Gastroesophageal reflux in children: pathogenesis, prevalence, diagnosis, and role of proton pump inhibitors in treatment. Pediatr Drugs 2002; 4(10): 673–85

    Google Scholar 

  83. Gibbons TE, Gold BD. The use of proton pump inhibitors in children: a comprehensive review. Pediatr Drugs 2003; 5(1): 25–40

    Google Scholar 

  84. Vandenplas Y, Salvatore S, Hauser B. The diagnosis and management of gastro-oesophageal reflux in infants. Early Human Dev 2005; 81: 1011–24

    Article  Google Scholar 

  85. Cezard JP. Managing gastro-oesophageal reflux in children. Digestion 2004; 69Suppl. 1: 3–8

    Article  PubMed  CAS  Google Scholar 

  86. Croom KF, Scott LJ. Lansoprazole in the treatment of gastro-oesophageal reflux disease in children and adolescents. Drugs 2005; 65(15): 2129–35

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Mark Beattie.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tighe, M.P., Afzal, N.A., Bevan, A. et al. Current Pharmacological Management of Gastro-Esophageal Reflux in Children. Pediatr-Drugs 11, 185–202 (2009). https://doi.org/10.2165/00148581-200911030-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00148581-200911030-00004

Keywords

Navigation