Pediatric Drugs

, Volume 15, Issue 1, pp 19–27 | Cite as

Gastroesophageal Reflux Disease in Neonates and Infants

When and How to Treat
  • Steven J. Czinn
  • Samra BlanchardEmail author
Therapy in Practice


Gastroesophageal reflux (GER) is defined as the involuntary retrograde passage of gastric contents into the esophagus with or without regurgitation or vomiting. It is a frequently experienced physiologic condition occurring several times a day, mostly postprandial and causes no symptoms. These infants are also called ‘happy spitters’. GER disease (GERD) occurs when reflux of the gastric contents causes symptoms that affect the quality of life or pathologic complications, such as failure to thrive, feeding or sleeping problems, chronic respiratory disorders, esophagitis, hematemesis, apnea, and apparent life-threatening events.

About 70–85 % of infants have regurgitation within the first 2 months of life, and this resolves without intervention in 95 % of infants by 1 year of age. The predominant mechanism causing GERD is transient lower esophageal sphincter (LES) relaxation, which is defined as an abrupt decrease in LES pressure to the level of intragastric pressure, unrelated to swallowing and of relatively longer duration than the relaxation triggered by a swallow.

Regurgitation and vomiting are the most common symptoms of infant reflux. A thorough history and physical examination with attention to warning signals suggesting other causes is generally sufficient to establish a clinical diagnosis of uncomplicated infant GER. Choking, gagging, coughing with feedings or significant irritability can be warning signs for GERD or other diagnoses. If there is forceful vomiting, laboratory and radiographic investigation (upper gastrointestinal series) are warranted to exclude other causes of vomiting. Irritability coupled with back arching in infants is thought to be a non-verbal equivalent of heartburn in older children. Other causes of irritability, including cow’s milk protein allergy, neurologic disorders, constipation and infection, should be ruled out. The presentation of cow’s milk protein allergy overlaps with GERD, and both conditions may co-exist in 42–58 % of infants. In these infants, symptoms decrease significantly within 2–4 weeks after elimination of cow’s milk protein from the diet. For non-complicated reflux, no intervention is required for most infants.

Effective parental reassurance and education regarding regurgitation and lifestyle changes are usually sufficient to manage infant reflux. Sandifer syndrome, apnea and apparent life-threatening events are the extraesophageal manifestations of GERD in infants.

Pharmacotherapeutic agents used to treat GERD encompass antisecretory agents, antacids, surface barrier agents and prokinetics. Currently, North American Society for Pediatric Gasroenterology, Hepatology and Nutrition (NASPGHAN) and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) practice guidelines concluded that there is insufficient evidence to justify the routine use of prokinetic agents. Esomeprazole (Nexium) is now approved in the US for short-term treatment of GERD with erosive esophagitis in infants aged from 1 to 12 months. Although Nissen fundoplication is now well established as a treatment option in selected cases of GERD in children, its role in neonates and young infants is unclear and is only reserved for selective infants who did not respond to medical therapy and have life-threatening complications of GERD.


Esophagitis Baclofen Lower Esophageal Sphincter Esomeprazole Cisapride 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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


  1. 1.
    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;104:1278–95.PubMedCrossRefGoogle Scholar
  2. 2.
    Hegar B, Dewanti NR, Kadim M, et al. Natural evolution of regurgitation in healthy infants. Acta Paediatr. 2009;98:1189–93.PubMedCrossRefGoogle Scholar
  3. 3.
    Osatakul S, Sriplung H, Puetpaiboon A, et al. Prevalence and natural course of gastroesophageal reflux symptoms: a 1-year cohort study in Thai infants. J Pediatr Gastroenterol Nutr. 2002;34(1):63–7.PubMedCrossRefGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Vandeplas Y, Goyvaerts H, Helven R, et al. Gastroesophageal reflux, as measured by 24-hour pH monitoring, in 509 healthy infants screened for risk of sudden infant death syndrome. Pediatrics. 1991;88:834–40.Google Scholar
  6. 6.
    Coletti RB, DiLorenzo C. Overview of pediatric gastroesophageal reflux disease and proton pump inhibitor therapy. J Pediatr Gastroenterol Nutr. 2003;37:S7–11.CrossRefGoogle Scholar
  7. 7.
    Omari TI, Barnett CP, Benninga MA, et al. Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux disease. Gut. 2002;51(4):475–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Davidson G. The role of lower esophageal sphincter function and dysmotility in gastroesophageal reflux in premature infants and in the first year of life. J Pediatr Gastroenterol Nutr. 2003;37:S17–22.PubMedCrossRefGoogle Scholar
  9. 9.
    Omari TI, Miki K, Fraser R, et al. Esophageal body and lower esophageal sphincter function in healthy premature infants. Gastroenterology. 1995;109:1757–64.PubMedCrossRefGoogle Scholar
  10. 10.
    Di Lorenzo C, Mertz H, Alvarez S, et al. Gastric receptive relaxation is absent in newborn infants [abstract]. Gastroenterology. 1993;104:A498.Google Scholar
  11. 11.
    Ravelli AM, Tobanelli P, Volpi S, et al. Vomiting and gastric motility in infants with cow’s milk allergy. J Pediatr Gastroenterol Nutr. 2001;32:59–64.PubMedCrossRefGoogle Scholar
  12. 12.
    Jadcherla SR, Duong HQ, Hoffmann RG, et al. Esophageal body and upper esophageal sphincter motor responses to esophageal provocation during maturation in preterm newborns. J Pediatr. 2003;143:31–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Kelly EJ, Newell SJ, Brownlee KG, et al. Gastric acid secretion in preterm infants. Early Hum Dev. 1993;35:215–20.PubMedCrossRefGoogle Scholar
  14. 14.
    Weisselberg B, Yahav J, Reichman B, et al. Basal and meal-stimulated pepsinogen secretion in preterm infants: a longitudinal study. J Pediatr Gastroenterol Nutr. 1992;15:58–62.PubMedCrossRefGoogle Scholar
  15. 15.
    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. J Pediatr Gastroenterol Nutr. 2009;49(4):498–547.PubMedCrossRefGoogle Scholar
  16. 16.
    Khan S, Orenstein SR. Gastroesophageal reflux disease in infants and children. In: Granderath FA, Kamolz T, Pointner R, editors. Gastroesophageal reflux disease. New York: Springer; 2006. p. 45–64.CrossRefGoogle Scholar
  17. 17.
    Feranchak AP, Orenstein SR, Cohn JF. Behaviors associated with onset of gastroesophageal reflux episodes in infants: prospective study using split-screen video and pH probe. Clin Pediatr. 1994;33:654–62.CrossRefGoogle Scholar
  18. 18.
    Vandenplas Y, Badriul H, Verghote M, et al. Oesophageal pH monitoring and reflux oesophagitis in irritable infants. Eur J Pediatr. 2004;163:300–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Salvatore S, Vandenplas Y. Gastroesophageal reflux and cow milk allergy: is there a link? Pediatrics. 2002;110:972–84.PubMedCrossRefGoogle Scholar
  20. 20.
    Nielsen RG, Bindslev-Jensen C, Kruse-Andersen S, et al. Severe gastroesophageal reflux disease and cow milk hypersensitivity in infants and children: disease association and evaluation of a new challenge procedure. J Pediatr Gastroenterol Nutr. 2004;39:383–91.PubMedCrossRefGoogle Scholar
  21. 21.
    Poets CF. Apnea of prematurity: what can observational studies tell us about pathophysiology. Sleep Med. 2010;11:701–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Kimball AL, Carlton DP. Gastroesophageal reflux medications in the treatment of apnea in premature infants. J Pediatr. 2001;138:355–60.PubMedCrossRefGoogle Scholar
  23. 23.
    Orenstein SR, Shalaby TM, Cohn JF. Reflux symptoms in 100 normal infants: diagnostic validity of the infant gastroesophageal reflux questionnaire. Clin Pediatr. 1996;35:607–14.CrossRefGoogle Scholar
  24. 24.
    Kleinman L, Rothman M, Strauss R, et al. The infant gastroesophageal reflux questionnaire revised: development and validation as an evaluative instrument. Clin Gastroenterol Hepatol. 2006;4:588–96.PubMedCrossRefGoogle Scholar
  25. 25.
    Aggarwal S, Mittal SK, Kalra KK, et al. Infant gastroesophageal reflux disease score: reproducibility and validity in a developing country. Trop Gastroenterol. 2004;25:96–8.PubMedGoogle Scholar
  26. 26.
    Abell TL, Camilleri M, Donohoe K, et al. Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine. Am J Gastroenterol. 2008;103(3):753–63.PubMedCrossRefGoogle Scholar
  27. 27.
    Mousa HM, Rosen R, Woodley WW, et al. Esophageal impedance monitoring for gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 2011;52:129–39.PubMedCrossRefGoogle Scholar
  28. 28.
    Vandenplas Y. Oesophageal pH monitoring for gastroesophageal reflux in infants and children. New York: Wiley; 1992. p. 235–44.Google Scholar
  29. 29.
    Dahms BB. Reflux esophagitis: sequelae and differential diagnosis in infants and children including eosinophilic esophagitis. Pediatr Dev Pathol. 2004;7:5–16.PubMedCrossRefGoogle Scholar
  30. 30.
    Heine RG, Cameron DJ, Chow CW, et al. Esophagitis in distressed infants: poor diagnostic agreement between esophageal pH monitoring and histopathologic findings. J Pediatr. 2002;140(1):14–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Wenzl TG. Role of diagnostic tests in GERD. J Pediatr Gastroenterol Nutr. 2011;53:S4–6.PubMedGoogle Scholar
  32. 32.
    Lopez-Alonso M, Moya MJ, Cabo JA, et al. Twenty-four hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acid, and weakly alkaline gastroesophageal reflux. Pediatrics. 2006;118:299–308.CrossRefGoogle Scholar
  33. 33.
    Shalaby TM, Orenstein SR. Efficacy of telephone teaching of conservative therapy for infants with symptomatic gastroesophageal reflux referred by pediatricians to pediatric gastroenterologist. J Pediatr. 2003;142:57–61.PubMedCrossRefGoogle Scholar
  34. 34.
    Horvath A, Dziechciarz P, Szajewska H. The effect of thickened-feed interventions on gastroesophageal reflux in infants: systematic review and meta-analysis of randomized, controlled trials. Pediatrics. 2008;122:e1268–77.PubMedCrossRefGoogle Scholar
  35. 35.
    Iacono G, Carroccio A, Cavataio F, et al. Gastroesophageal reflux and cow’s milk allergy in infants: a prospective study. J Allergy Clin Immunol. 1996;97(3):822–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Meyers WF, Herbst JJ. Effectiveness of positioning therapy for gastroesophageal reflux. Pediatrics. 1982;62:768–72.Google Scholar
  37. 37.
    American Academy of Pediatrics Task Force on Infant Sleep Position and Sudden Infant Death Syndrome. Changing concepts of sudden infant death syndrome: Implications for Infant sleep environment and sleep position. Pediatrics. 2000;105:650–6.CrossRefGoogle Scholar
  38. 38.
    American Academy of Pediatrics Task Force on Sudden Infant Death Syndrome. The changing concept of sudden death syndrome: diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk. Pediatrics. 2005;116:1245–55.CrossRefGoogle Scholar
  39. 39.
    Omari TI, Rommel N, Staunton E, et al. Paradoxical impact of body position on gastroesophageal reflux and gastric emptying in the premature neonate. J Pediatr. 2004;145:194–200.PubMedCrossRefGoogle Scholar
  40. 40.
    Van Wijk MP, Benniga MA, et al. Effect of body position changes on post prandial gastroesophageal reflux and gastric emptying in the healthy premature neonate. J Pediatr. 2007;151:591–6.CrossRefGoogle Scholar
  41. 41.
    Del Buono R, Wenzl TG, Ball G, et al. Effect of Gaviscon Infant on gastroesophageal reflux in infants assessed by combined intraluminal impedance /pH. Arch Dis Child. 2005;90:460–3.PubMedCrossRefGoogle Scholar
  42. 42.
    Levi P, Marmo F, Saluzzo C, et al. Bethanechol versus antiacids in treatment of gastroesophageal reflux. Helv Paediatr Acta. 1985;40(5):349–59.PubMedGoogle Scholar
  43. 43.
    Tighe MP, Afazal NA, Bevan A, et al. Current pharmacological management of gastro-esophageal reflux in children: an evidence-based systematic review. Pediatr Drugs. 2009;11(3):185–202.CrossRefGoogle Scholar
  44. 44.
    Carroccio A, Iacono G, Montalto F, et al. Domperidone plus magnesium hydroide and aluminium hydroxide: a valid therapy in children with gastroesophageal reflux. Scand J Gastroenterol. 1994;29:300–4.PubMedCrossRefGoogle Scholar
  45. 45.
    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;106:311–6.PubMedCrossRefGoogle Scholar
  46. 46.
    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;59:725–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Vandenplas Y, ESPGHAN Cisapride Panel, European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Current pediatric indications for cisapride. J Pediatr Gastroenterol Nutr. 2000;31(5):480–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Maclennan S, Augood C, Cash-Gibson L, et al. Cisapride treatment for gastro-oesophageal reflux in children. Cochrane Database Syst Rev. 2010;(4):CD002300.Google Scholar
  49. 49.
    Khoshoo V, Edell D, Clarke R. Effect of cisapride on the QT interval in infants with gastroesophageal reflux. Pediatrics. 2000;105:e24.PubMedCrossRefGoogle Scholar
  50. 50.
    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;115:141–5.PubMedCrossRefGoogle Scholar
  51. 51.
    De Loore I, Van Ravensteyn H, Ameryckx L. Domperidone drops in the symptomatic treatment of chronic paediatric vomiting and regurgitation: a comparison with metoclopramide. Postgrad Med J. 1979;55(Suppl. 1):40–2.PubMedGoogle Scholar
  52. 52.
    Jadcherla SR, Berseth CL. Effect of erythromycin on gastroduodenal contractile activity in developing neonates. J Pediatr Gastroenterol Nutr. 2002;34:16–22.PubMedCrossRefGoogle Scholar
  53. 53.
    Cooper WO, Griffin MR, Arbogast P, et al. Very early exposure to erythromycin and infantile hypertrophic pyloric stenosis. Arch Pediatr Adolesc Med. 2002;156:647–50.PubMedGoogle Scholar
  54. 54.
    Ng E, Shah VS. Erythromycin for the prevention and treatment of feeding intolerance in preterm infants. Cochrane Database Syst Rev. 2008;(3):CD001815.Google Scholar
  55. 55.
    Omari T, Benninga M, Sansom L, et al. Effect of baclofen on esophagogastric motility and gastroesophageal reflux in children with gastroesophageal reflux disease: a randomized controlled trial. J Pediatr. 2006;149(4):468–74.PubMedCrossRefGoogle Scholar
  56. 56.
    Moran LR, Cincotta T, Krishnamoorthy K, et al. The use of baclofen in full-term neonates with hypertonia. J Perinatol. 2005;25:66–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Cucchiara S, Gobio-Casali L, Balli F, et al. Cimetidine treatment of reflux esophagitis in children: an Italian multicentric study. J Pediatr Gastroenterol Nutr. 1989;8:150–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Oderda G, Dell’olio D, Forni M, et al. Treatment of childhood peptic oesophagitis with famotidine and alginate-antacid. Ital J Gastroenterol. 1990;22:346–9.PubMedGoogle Scholar
  59. 59.
    Simeone D, Caria MC, Miele E, et al. Treatment of childhood esophagitis: a double-blind placebo-controlled trial of nizatidine. J Pediatr Gastroenterol Nutr. 1997;25:51–5.PubMedCrossRefGoogle Scholar
  60. 60.
    Mallet E, Mouterde O, Dubois F, et al. Use of ranitidine in young infants with gastro-oesophageal reflux. Eur J Clin Pharmacol. 1989;36:641–2.PubMedCrossRefGoogle Scholar
  61. 61.
    Kuusela A. Long-term gastric pH monitoring for determining optimal dose of ranitidine for critically ill preterm and term neonates. Arch Dis Child Fetal Neonatal Ed. 1998;78:F151–3.PubMedCrossRefGoogle Scholar
  62. 62.
    Ribeiro JM, Lucas M, Baptista A, et al. Fatal hepatitis associated with ranitidine. Am J Gastroenterol. 2000;95:559–60.PubMedGoogle Scholar
  63. 63.
    Garcia Rodriguez LA, Wallander MA, Stricker BH. The risk of acute liver injury associated with cimetidine and other acid-suppressing anti-ulcer drugs. Br J Clin Pharmacol. 1997;43:183–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Garcia Rodriguez LA, Jick H. Risk of gynecomastia associated with cimetidine, omeprazole and other antiulcer drugs. BMJ. 1994;308:503–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Stedman CAM, Barclay ML. Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors. Aliment Pharmacol Ther. 2000;14:963–78.PubMedCrossRefGoogle Scholar
  66. 66.
    Barron JJ, Tan H, Spalding J, et al. Proton pump inhibitor utilization patterns in infants. J Pediatr Gastroenterol Nutr. 2007;45:421–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Moore DJ, Tao BS, Lines DR, et al. Double-blind placebo controlled trial of omeprazole in irritable infants with gastroesophageal reflux. J Pediatr. 2003;143:219–23.PubMedCrossRefGoogle Scholar
  68. 68.
    Orenstein SR, Hassall E, Furmaga-Jablonska W, et al. Multicenter, double-blind, randomized, placebo controlled trial assessing efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease. J Pediatr. 2009;154:514–20.PubMedCrossRefGoogle Scholar
  69. 69.
    Tsou VM, Young RM, Hart MH, et al. Elevated plasma aluminum levels in normal infants receiving antacids containing aluminum. Pediatrics. 1991;87(2):148–51.PubMedGoogle Scholar
  70. 70.
    Omari TI, Haslam RR, Lundborg P, et al. Effect of omeprazole on acid gastroesophageal reflux and gastric acidity in preterm infants with pathological reflux. J Pediatr Gastroenterol Nutr. 2007;44:41–4.PubMedCrossRefGoogle Scholar
  71. 71.
    Sorbie AL, Symon DN, Stockdale EJ. Gaviscon bezoars. Arch Dis Child. 1984;59(9):905–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Portuguez-Malavasi A, Aranda JV. Antacid bezoar in a newborn. Pediatrics. 1979;63:679–80.PubMedGoogle Scholar
  73. 73.
    Hassall E. Talk is cheap, often effective: symptoms in infants often respond to non-pharmacologic measures. J Pediatr. 2008;152:301–3.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of GastroenterologyUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Pediatric Gastroenterology and NutritionUniversity of Maryland Medical CenterBaltimoreUSA

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