Skip to main content
SpringerLink
Log in

Optimizing the Use of Medications and Other Therapies in Infant Gastroesophageal Reflux

  • Therapy in Practice
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

Gastroesophageal reflux (GER) is the retrograde movement of gastric (and sometimes duodenal) contents into the esophagus. While the majority of GER is physiologic, for patients, it can be associated with symptoms. While some symptoms are merely bothersome (crying), others can be life threatening (cough, gagging, choking). The main driver of GER in infants is the frequent feedings that produce increased intra-abdominal pressure, which is known to trigger transient relaxations of the lower esophageal sphincter. The recent 2018 clinical practice guidelines reported by the North American and European Societies for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN/ESPGHAN) have recommended non-pharmacologic management initially with subsequent consideration of brief trials with acid suppressants. The main target for these acid suppressants is the gastric parietal cells. Our review of the literature has revealed a paucity of data regarding the use of histamine-2 receptor antagonists and proton pump inhibitors in infants. Despite the absence of well-controlled clinical studies, the prescription rate of these medications has increased internationally. Risks to patients of all ages have become increasingly recognized, with new associations being reported all too often. Here we report our review of all pharmacologic modalities as well as some non-surgical options.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Hegar B, Dewanti NR, Kadim M, et al. Natural evolution of regurgitation in healthy infants. Acta Paediatr. 2009;98:1189–93.

    PubMed  Google Scholar 

  2. Rosen R, Vandenplas Y, Singendonk M, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2018;66:516–54.

    PubMed  Google Scholar 

  3. Corvaglia L, Martini S, Faldella G. Gastro-esophageal reflux: pathogenesis, symptoms, diagnostic and therapeutic management. Early Hum Dev. 2013;8954:S18–9.

    Google Scholar 

  4. Modlin IM, Sachs G. Developmental anatomy and physiology of the stomach, p 262–268 in Wyllie and Hyams 4th ed. Acid related disease: biology and treatment (book). Schnetztor-Verlag GmbH Koonstanz. 2011. p. 92–110.

  5. Boyle JT. Acid secretion from birth to adulthood. J Pediatr Gastroenterol Nutr. 2003;37:S12–6.

    PubMed  Google Scholar 

  6. Ward RM, Kearns GL. Proton pump inhibitors in pediatrics: mechanism of action, pharmacokinetics, pharmacogenetics, and pharmacodynamics. Paediatr Drugs. 2013;15:119–31.

    PubMed  PubMed Central  Google Scholar 

  7. 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):4–9.

    Google Scholar 

  8. Vandenplas Y, Badriul H, Verghote M, et al. Oesophageal pH monitoring and reflux oesophagitis in irritable infants. Eur J Pediatr. 2004;163:300–4.

    PubMed  Google Scholar 

  9. Holloway RH. The anti-reflux barrier and mechanisms of gastroesophageal reflux. Baillieres Clin Gastroenterol. 2000;14:681–99.

    CAS  Google Scholar 

  10. Chang K-C, Wu J-F, Hsu W-C, et al. Impacts of endoscopic gastroesophageal flap valve grading on pediatric gastroesophageal reflux disease. PLoS One. 2014;9:e107954.

    PubMed  PubMed Central  Google Scholar 

  11. Omari TI, Barnett CP, Benninga MA, et al. Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux disease. Gut. 2002;51:475–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Dodds W, Dent J, Hogan W, et al. Effects of atropine on esophageal motor functions in humans. Am J Physiol. 1981;240:G290–6.

    CAS  PubMed  Google Scholar 

  13. Biancani P, Sohn US, Rich HG, et al. Signal transduction pathways in esophageal and lower esophageal sphincter circular muscle. Am J Med. 1997;103:23S–8S.

    CAS  PubMed  Google Scholar 

  14. Castell DO, Murray JA, Tutuian R, et al. Review article: the pathophysiology of gastro-oesophageal reflux disease—oesophageal manifestations. Aliment Pharmacol Ther. 2004;20:14–25.

    PubMed  Google Scholar 

  15. Dennish GW, Castell DO. Inhibitory effect of smoking on the lower esophageal sphincter. N Eng J Med. 1971;284:1136–7.

    CAS  Google Scholar 

  16. Kadakia SC, De La Baume HR, Shaffer RT. Effects of transdermal nicotine on lower esophageal sphincter and esophageal motility. Dig Dis Sci. 1996;41:2130–4.

    CAS  PubMed  Google Scholar 

  17. Salvatore S, Hauser B, Vandemaele K, et al. Gastroesophageal reflux disease in infants: how much is predictable with questionnaires, pH-metry, endoscopy and histology? J Pediatr Gastroenterol Hepatol Nutr. 2005;40:210–5.

    Google Scholar 

  18. Czinn SJ, Blanchard S. Gastroesophageal reflux disease in neonates and infants. Pediatr Drugs. 2013;15:19–27.

    Google Scholar 

  19. Vandenplas Y, Goyvaerts H, Helven R, et al. Gastroesophageal reflux, as measured by 24-h pH monitoring, in 509 healthy infants, screened for risk of sudden infant death syndrome. Pediatrics. 1991;88:834–40.

    CAS  PubMed  Google Scholar 

  20. Richter J, Pandolfino J, Vela M, et al. Utilization of wireless pH monitoring technologies: a summary of the proceedings from the Esophageal Diagnostic Working Group. Dis Esophagus. 2013;26:755–65.

    CAS  PubMed  Google Scholar 

  21. Woodley FW, Hayes J, Mousa H. Acid gastroesophageal reflux in symptomatic infants is primarily a function of classic 2-phase and pH-only acid reflux types. J Pediatr Gastroenterol Nutr. 2009;48:550–8.

    CAS  PubMed  Google Scholar 

  22. Woodley FW, Mousa H. pH-only acid reflux events in infants during later phases of the feeding cycle are less acidic and cleared more efficiently than classic 2-phase acid reflux events. J Pediatr Gastroenterol Nutr. 2009;48:41–7.

    PubMed  Google Scholar 

  23. Mousa H, Rosen R, Woodley FW, et al. Esophageal impedance monitoring for gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 2011;52:129–39.

    PubMed  PubMed Central  Google Scholar 

  24. Woodley FW, Machado R, Di Lorenzo C, Mousa H. Chemical clearance in infants and children with acid reflux in the physiologic range. J Pediatr Gastroenterol Nutr. 2015;60:783–6.

    CAS  PubMed  Google Scholar 

  25. Shin MS. Esophageal pH and combined impedance-pH monitoring in children. Pediatr Gastroenterol Hepatol Nutr. 2014;17:13–22.

    PubMed  PubMed Central  Google Scholar 

  26. Wiener GJ, Richter JE, Copper JB, et al. The symptom index: a clinically important parameter of ambulatory 24-h esophageal pH monitoring. Am J Gastroenterol. 1988;83:358–61.

    CAS  PubMed  Google Scholar 

  27. Breumelhof R, Smout AJPM. The symptom sensitivity index: a valuable additional parameter in 24-h esophageal pH recording. Am J Gastroenterol. 1991;86:160–4.

    CAS  PubMed  Google Scholar 

  28. Taghavi SA, Ghasedi M, Saberi-Firoozi M, et al. Symptom association probability and symptom sensitivity index: preferable but still suboptimal predictors of a response to high dose omeprazole. Gut. 2005;54:1067–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Orr WC. The physiology and philosophy of cause and effect. Gastroenterology. 1994;107:1897–901.

    Google Scholar 

  30. Numans ME, Lau J, de Wit NJ, et al. Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Ann Intern Med. 2004;140:518–27.

    CAS  PubMed  Google Scholar 

  31. Kushnir VM, Sathyamurthy A, Drapekin J, et al. Assessment of concordance of symptom reflux association tests in ambulatory pH monitoring. Aliment Pharmacol Ther. 2012;35:1080–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Rosen R. Symptom association: an imperfect pairing. J Pediatr Gastroenterol Nutr. 2016;62:517–8.

    PubMed  PubMed Central  Google Scholar 

  33. Funderburk A, Nawab U, Abraham A, et al. Temporal association between reflux-like behaviors and gastroesophageal reflux in preterm and term infants. J Pediatr Gastroenterol Nutr. 2016;62:556–61.

    PubMed  PubMed Central  Google Scholar 

  34. Farre R, Blobeau K, Clement D, et al. Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique. Gut. 2011;60:885–92.

    PubMed  Google Scholar 

  35. Zhong C, Duan L, Wang K, et al. Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease. J Gastroenterol. 2013;48:601–10.

    CAS  PubMed  Google Scholar 

  36. Loots CM, von Wijk MP, Smits MJ, et al. Measurement of mucosal conductivity by MII is a potential marker of mucosal integrity restored in infants on acid-suppression therapy. J Pediatr Gastroenterol Nutr. 2011;53:120–3.

    PubMed  Google Scholar 

  37. Palmer WL. Bertram Welty sippy (1866–1924). Gastroenterology. 1979;77:152–5.

    CAS  PubMed  Google Scholar 

  38. Modulin IM, Sachs G. Acid related diseases: biology and treatment. 2nd ed. New York: Lippinscott Williams & Wilkins; 2004.

    Google Scholar 

  39. Winkelstein A. Studies in gastric secretion during the night, with a preliminary note on a new therapy for peptic ulcer. Am J Surg. 1932;15:523–4.

    Google Scholar 

  40. Winkelstein A. A new therapy of peptic ulcer: continuous alkalinized milk drip into stomach. Am J Med Sci. 1933;185:695–703.

    Google Scholar 

  41. Doll R, Price AV, Pygott F, et al. Continuous intragastric milk drip in treatment of uncomplicated gastric ulcer. Lancet. 1956;267:70–3.

    Google Scholar 

  42. Winkelstein A, Cornell A, Hollander F. Intragastric drip therapy for peptic ulcer. JAMA. 1942;120:743–745.

    Google Scholar 

  43. Miller S. Comparison of the efficacy and safety of a new aluminium-free paediatric alginate preparation and placebo in infants with recurrent gastro-oesophageal reflux. Curr Med Res Opin. 1999;15:160–8.

    CAS  PubMed  Google Scholar 

  44. 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;90:460–3.

    PubMed  PubMed Central  Google Scholar 

  45. Corvaglia L, Spizzichino M, Zama D, et al. Sodium alginate (Gaviscon®) does not reduce apnoeas related to gastro oesophageal reflux in preterm infants. Early Hum Dev. 2011;87:775–8.

    CAS  PubMed  Google Scholar 

  46. Corvaglia L, Aceti A, Mariani E, et al. The efficacy of sodium alginate (Gaviscon) for the treatment of gastro-oesophageal reflux in preterm infants. Aliment Pharmacol Ther. 2011;33:466–70.

    CAS  PubMed  Google Scholar 

  47. Ummarino D, Miele E, Martinelli M, et al. Effect of magnesium alginate plus simethicone on gastroesophageal reflux in infants. J Pediatr Gastroenterol Nutr. 2015;60:230–5.

    CAS  PubMed  Google Scholar 

  48. Atasay B, Erdeve O, Arsan S, et al. Effect of sodium alginate on acid gastroesophageal reflux disease in preterm infants: a pilot study. J Clin Pharmacol. 2010;50:1267–72.

    CAS  PubMed  Google Scholar 

  49. Salvatore S, Ripepi A, Huysentruyt K, et al. The effect of alginate in gastroesophageal reflux in infants. Pediatr Drugs. 2018. https://doi.org/10.1007/s40272-018-0309-x

    Article  Google Scholar 

  50. 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;55:40–2.

    PubMed  Google Scholar 

  51. Carroccio A, Iacono G, Montalto G, et al. Domperidone plus magnesium hydroxide and aluminum hydroxide: a valid therapy in children with gastroesophageal reflux. A double-blind randomized study versus placebo. Scand J Gastroenterol. 1994;29:300–4.

    CAS  PubMed  Google Scholar 

  52. 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.

    CAS  PubMed  Google Scholar 

  53. Nuntnarumit P, Kiatchoosakun P, Tantiprapa W, et al. Efficacy of oral erythromycin for treatment of feeding intolerance in preterm infants. J Pediatr. 2006;148:600–5.

    CAS  PubMed  Google Scholar 

  54. Ng PC, So KW, Fung KS, et al. Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2001;84:F177–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Ng PC, Fok TF, Lee CH, Wong W, Cheung KL. Erythromycin treatment for gastrointestinal dysmotility in preterm infants. J Paediatr Child Health. 1997;33:148–50.

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  57. Vadlamudi NB, Hitch MC, Dimmitt RA, et al. Baclofen for the treatment of pediatric GERD. J Pediatr Gastroenterol Nutr. 2013;57:808–12.

    CAS  PubMed  Google Scholar 

  58. Orenstein SR, Hassall E, Furmaga-Jablonska W, et al. Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease. J Pediatr. 2009;154:514–20.

    CAS  PubMed  Google Scholar 

  59. Kuusela AL, Ruuska T, Karikoski R, et al. A randomized, controlled study of prophylactic ranitidine in preventing stress-induced gastric mucosal lesions in neonatal intensive care unit patients. Crit Care Med. 1997;25:346–51.

    CAS  PubMed  Google Scholar 

  60. Bilali A, Galanis P, Bartsocas C, et al. H2RA-blocker therapy and incidence of necrotizing enterocolitis in preterm infants: a case-control study. Pediatr Neonatol. 2013;54:141–2.

    PubMed  Google Scholar 

  61. Guillet R, Stoll BJ, Cotten CM, et al. National Institute of Child Health and Human Development Neonatal Research Network. Association of H2RA-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2006;117:e137–42.

    PubMed  Google Scholar 

  62. Terrin G, Passariello A, De Curtis M, et al. Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics. 2012;129:e40–5.

    PubMed  Google Scholar 

  63. Santana RNS, Santos VS, Ribeiro-Júnior RF, et al. Use of ranitidine is associated with infections in newborns hospitalized in a neonatal intensive care unit: a cohort study. BMC Infect Dis. 2017;17:375.

    PubMed  PubMed Central  Google Scholar 

  64. Carrion V, Egan EA. Prevention of neonatal necrotizing enterocolitis. J Pediatr Gastroenterol Nutr. 1990;11:317–23.

    CAS  PubMed  Google Scholar 

  65. Chhattriwalla Y, Colon AR, Scanlon JW. The use of cimetidine in the newborn. Pediatrics. 1980;65:301–2.

    CAS  PubMed  Google Scholar 

  66. Agarwal AK, Saili A, Pandey KK, et al. Role of cimetidine in prevention and treatment of stress induced gastric bleeding in neonates. Indian Pediatr. 1990;27:465–9.

    CAS  PubMed  Google Scholar 

  67. Orenstein SR, Gremse DA, Pantaleon CD, et al. Nizatidine for the treatment of pediatric gastroesophageal reflux symptoms: an open-label, multiple-dose, randomized, multicenter clinical trial in 210 children. Clin Ther. 2005;27:472–83.

    CAS  PubMed  Google Scholar 

  68. James LP, Marotti T, Stowe CD, et al. Pharmacokinetics and pharmacodynamics of famotidine in infants. J Clin Pharmacol. 1998;38(1089):1095 (Erratum. In: J Clin Pharmacol 2000;40:1298).

    Google Scholar 

  69. Wenning LA, Murphy MG, James LP, et al. Pharmacokinetics of famotidine in infants. Clin Pharmacokinet. 2005;44:395–406.

    CAS  PubMed  Google Scholar 

  70. Wu YY. Efficacy and safety of famotidine for the treatment of stress ulcers in neonates. Zhongguo Dang Dai Er Ke Za Zhi. 2008;10:593–5.

    CAS  PubMed  Google Scholar 

  71. 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.

    CAS  PubMed  Google Scholar 

  72. Moore DJ, Tao BS, Lines DR, Hirte C, Heddle ML, Davidson GP. Double-blind placebo-controlled trial of omeprazole in irritable infants with gastroesophageal reflux. J Pediatr. 2003;143:219–23.

    CAS  PubMed  Google Scholar 

  73. Omari TI, Haslam RR, Lundborg P, Davidson GP. Effect of omeprazole on acid gastroesophageal reflux and gastric acidity in preterm infants with pathological acid reflux. J Pediatr Gastroenterol Nutr. 2007;44:41–4.

    CAS  PubMed  Google Scholar 

  74. Orsi M, Donato G, Busoni V, Naisberg G, Caruso N. Gastric acid suppression of a new oral powder omeprazole suspension for infants with gastroesophageal reflux disease. A pilot study. Acta Gastroenterol Latinoam. 2011;41:111–8.

    PubMed  Google Scholar 

  75. Kaguelidou F, Alberti C, Biran V, et al. Dose-finding study of omeprazole on gastric pH in neonates with gastro-esophageal acid reflux using a Bayesian sequential approach. PLoS One. 2016;11:e0166207.

    PubMed  PubMed Central  Google Scholar 

  76. Khoshoo V, Dhume P. Clinical response to 2 dosing regimens of lansoprazole in infants with gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 2008;46:352–4.

    CAS  PubMed  Google Scholar 

  77. Illueca M, Alemayehu B, Shoetan N, et al. Proton pump inhibitor prescribing patterns in newborns and infants. J Pediatr Pharmacol Ther. 2014;19:283–7.

    PubMed  PubMed Central  Google Scholar 

  78. Davidson G, Wenzl TG, Thomson M, et al. Efficacy and safety of once-daily esomeprazole for the treatment of gastroesophageal reflux disease in neonatal patients. J Pediatr. 2013;163:692–8.

    CAS  PubMed  Google Scholar 

  79. Winter H, Gunasekaran T, Tolia V, et al. Esomeprazole for the treatment of GERD in infants ages 1–11 months. J Pediatr Gastroenterol Nutr. 2012;55:14–20.

    CAS  PubMed  Google Scholar 

  80. Omari T, Davidson G, Bondarov P, et al. Pharmacokinetics and acid-suppressive effects of esomeprazole in infants 1–24 months old with symptoms of gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2015;60(Suppl 1):S2–8.

    PubMed  Google Scholar 

  81. Omari T, Davidson G, Bondarov P, et al. Pharmacokinetics and acid-suppressive effects of esomeprazole in infants 1–24 months old with symptoms of gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2007;45(5):530–7.

    CAS  PubMed  Google Scholar 

  82. Hussain S, Kierkus J, Hu P, et al. Safety and efficacy of delayed release rabeprazole in 1- to 11-month-old infants with symptomatic GERD. J Pediatr Gastroenterol Nutr. 2014;58:226–36.

    PubMed  Google Scholar 

  83. Kierkus J, Furmaga-Jablonska W, Sullivan JE, et al. Pharmacodynamics and safety of pantoprazole in neonates, preterm infants, and infants aged 1 through 11 months with a clinical diagnosis of gastroesophageal reflux disease. Dig Dis Sci. 2011;56:425–34.

    CAS  PubMed  Google Scholar 

  84. Winter H, Kum-Nji P, Mahomedy SH, et al. Efficacy and safety of pantoprazole delayed-release granules for oral suspension in a placebo-controlled treatment-withdrawal study in infants 1–11 months old with symptomatic GERD. J Pediatr Gastroenterol Nutr. 2010;50:609–18.

    CAS  PubMed  Google Scholar 

  85. Nelson SP, Chen EH, Syniar GM, et al. One-year follow-up of symptoms of gastroesophageal reflux during infancy. Pediatric Practice Research Group. Pediatrics. 1998;102:E67.

    CAS  PubMed  Google Scholar 

  86. Kwok TC, Ojha S, Dorling J. Feed thickener for infants up to 6 months of age with gastro-oesophageal reflux. Cochrane Database Syst Rev. 2017;12:CD003211.

    PubMed  Google Scholar 

  87. Karagas MR, Punshon T, Sayarath V, et al. Association of rice and rice-product consumption with arsenic exposure early in life. JAMA Pediatr. 2016;170:609–16.

    PubMed  PubMed Central  Google Scholar 

  88. Beal J, Silverman B, Bellant J, et al. Late onset necrotizing enterocolitis in infants following use of a xanthan gum-containing thickening agent. J Pediatr. 2012;161:354–6.

    PubMed  Google Scholar 

  89. Vandenplas Y, Koletzko S, Isolauri E, et al. Guidelines for the diagnosis and management of cow’s milk protein allergy in infants. Arch Dis Child. 2007;92:902–8 (Review. Erratum in: Arch Dis Child. 2008; 93: 93. Arch Dis Child. 2007; 92:following 908).

    PubMed  PubMed Central  Google Scholar 

  90. Indrio F, Di Mauro A, Riezzo G, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr. 2014;168:228–33.

    PubMed  Google Scholar 

  91. Tobin JM, McCloud P, Cameron DJ. Posture and gastro-oesophageal reflux: a case for left lateral positioning. Arch Dis Child. 1997;76:254–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Ewer AK, James ME, Tobin JM. Prone and left lateral positioning reduce gastro-oesophageal reflux in pre-term infants. Arch Dis Child Fetal Neonatal Ed. 1999;81:F201–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Omari T, Rommel N, Staunton E, et al. Paradoxical impact of body positioning on gastroesophageal reflux and gastric emptying in the premature neonate. J Pediatr. 2004;145:194–200.

    PubMed  Google Scholar 

  94. van Wijk MP, Benninga MA, Dent J, et al. Effect of body position changes on triggering of postprandial gastroesophageal reflux and gastric emptying in the premature neonate. J Pediatr. 2007;151:585–90.

    PubMed  Google Scholar 

  95. Corvaglia L, Rotatori R, Ferlini M, et al. The effect of body positioning on gastroesophageal reflux in premature infants: evaluation by combined impedance and pH monitoring. J Pediatr. 2007;151:591–6.

    PubMed  Google Scholar 

  96. Omari T. Gastroesophageal reflux in infants: can a simple left side positioning strategy help this diagnostic and therapeutic conundrum? Minerva Pediatr. 2008;60:193–200.

    CAS  PubMed  Google Scholar 

  97. Loots C, Kritas S, van Wijk M, et al. Body positioning and medical therapy for infantile gastroesophageal reflux symptoms. J Pediatr Gastroenterol Nutr. 2014;59:237–43.

    PubMed  Google Scholar 

  98. Task Force on Sudden Infant Death Syndrome. SIDS and other sleep-related infant deaths: updated 2016 recommendations for a safe infant sleeping environment. Pediatrics. 2016;138:e20162938.

    Google Scholar 

  99. Koebnick C, Getahun D, Ning Smith, et al. Extreme childhood obesity is associated with increased risk for gastroesophageal reflux disease in a large population-based study. Int J Pediatr Obes. 2011;6:e257–63.

    PubMed  Google Scholar 

  100. Cohen S, Bueno de Mesquita M, Mimouni FB. Adverse effects reported in the use of gastroesophageal reflux disease treatments in children: a 10 years literature review. Br J Clin Pharmacol. 2015;80:200–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Tolia V, Boyer K. Long-term proton pump inhibitor use in children: a retrospective review of safety. Dig Dis Sci. 2008;53:385–93.

    CAS  PubMed  Google Scholar 

  102. Treem W, Hu P, Sloan S. Normal and proton pump inhibitor-mediated gastrin levels in infants 1–11 months old. J Pediatr Gastroenterol Nutr. 2013;57:520–6.

    CAS  PubMed  Google Scholar 

  103. Turco R, Martinelli M, Miele E, et al. Proton pump inhibitors as a risk factor for paediatric Clostridium difficile infection. Aliment Pharmacol Ther. 2010;31:754–9.

    CAS  PubMed  Google Scholar 

  104. Adams DJ, Eberly MD, Rajnik M, et al. Risk factors for community-associated Clostridium difficile infection in children. J Pediatr. 2017;186:105–9.

    PubMed  Google Scholar 

  105. Freedberg DE, Lamousé-Smith ES, Lightdale JR, et al. Use of acid suppression medication is associated with risk for C. difficile infection in infants and children: a population-based study. Clin Infect Dis. 2015;61:912–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Jimenez J, Drees M, Loveridge-Lenza B, et al. Exposure to gastric acid-suppression therapy is associated with health care- and community-associated Clostridium difficile infection in children. J Pediatr Gastroenterol Nutr. 2015;61:208–11.

    CAS  PubMed  Google Scholar 

  107. FDA. https://www.fda.gov/Drugs/DrugSafety/ucm290510.htm. Accessed 29 Mar 2018.

  108. Hassing RJ, Verbon A, de Visser H, et al. Proton pump inhibitors and gastroenteritis. Eur J Epidemiol. 2016;31:1057–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Fujimori S. What are the effects of proton pump inhibitors on the small intestine? World J Gastroenterol. 2015;21:6817–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Lebwohl B, Spechler SJ, Wang TC, et al. Use of proton pump inhibitors and subsequent risk of celiac disease. Dig Liver Dis. 2014;46:36–40.

    CAS  PubMed  Google Scholar 

  111. Toh JW, Ong E, Wilson R. Hypomagnesaemia associated with long-term use of proton pump inhibitors. Gastroenterol Rep (Oxf). 2015;3:243–53.

    PubMed  Google Scholar 

  112. Masclee GM, Coloma PM, Kuipers EJ, et al. Increased risk of microscopic colitis with use of proton pump inhibitors and non-steroidal anti-inflammatory drugs. Am J Gastroenterol. 2015;110:749–59.

    CAS  PubMed  Google Scholar 

  113. Yang YX. Chronic proton pump inhibitor therapy and calcium metabolism. Curr Gastroenterol Rep. 2012;14:473–9.

    PubMed  PubMed Central  Google Scholar 

  114. Toth-Manikowski S, Grams ME. Proton pump inhibitors and kidney disease—GI upset for the nephrologist? Kidney Int Rep. 2017;2:297–301.

    PubMed  PubMed Central  Google Scholar 

  115. Li XQ, Andersson TB, Ahlström M, et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004;32:821–7.

    CAS  PubMed  Google Scholar 

  116. Zvyaga T, Chang SY, Chen C, et al. Evaluation of six proton pump inhibitors as inhibitors of various human cytochromes P450: focus on cytochrome P450 2C19. Drug Metab Dispos. 2012;40:1698–711.

    CAS  PubMed  Google Scholar 

  117. Meyer UA. Interaction of proton pump inhibitors with cytochromes P450: consequences for drug interactions. Yale J Biol Med. 1996;69:203–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Barron JJ, Tan H, Spalding J, et al. Proton pump inhibitor utilization patterns in infants. J Pediatr Gastroenterol Nutr. 2007;45:421–7.

    CAS  PubMed  Google Scholar 

  119. Slaughter JL, Stenger MR, Reagan PB, et al. Neonatal histamine-2 receptor antagonist and proton pump inhibitor treatment at United States children’s hospitals. J Pediatr. 2016;174(63–70):e3.

    Google Scholar 

  120. D’Agostino JA, Passarella M, Martin AE, et al. Use of gastroesophageal reflux medications in premature infants after NICU discharge. Pediatrics. 2016;138:e20161977.

    PubMed  PubMed Central  Google Scholar 

  121. Blank ML, Parkin L. National study of off-label proton pump inhibitor use among New Zealand infants in the first year of life (2005–2012). J Pediatr Gastroenterol Nutr. 2017;65:179–84.

    PubMed  Google Scholar 

  122. Erenoglu C, Miller A, Schirmer B. Laproscopic troupet versus nissen fundoplication for treatment of gastroesophageal reflux disease. Int Surg. 2003;88:219–25.

    PubMed  Google Scholar 

  123. Yoo BG, Yang HK, Lee YJ, et al. Fundoplication in neonates and infants with primary gastroesophageal reflux. Pediatr Gastroenterol Hepatol Nutr. 2014;17:93–7.

    PubMed  PubMed Central  Google Scholar 

  124. Justo RN, Gray PH. Fundoplication in preterm infants with gastro-oesophageal reflux. J Pediatr Child Health. 1991;27:250–4.

    CAS  Google Scholar 

  125. Kazerooni NL, VanCamp J, Hirschi RB, et al. Fundoplication in 160 children under 2 years of age. J Pediatr Surg. 1991;29:677–81.

    Google Scholar 

  126. Kubiak R, Spitz L, Kiely EM, et al. Effectiveness of fundoplication in early infancy. J Pediatr Surg. 1999;34:295–9.

    CAS  PubMed  Google Scholar 

  127. Srivastava R, Berry JG, Hall M, et al. Reflux-related hospital admissions after fundoplication in children with neurological impairment: retrospective cohort study. BMJ. 2009;339:b4411.

    PubMed  PubMed Central  Google Scholar 

  128. Jackson HT, Kane TD. Surgical management of pediatric gastroesophageal reflux disease. Gastroenterol Res Pract. 2013;2013:1–8.

    Google Scholar 

  129. Wales PW, Diamond IR, Dutta S, et al. Fundoplication and gastrostomy versus image-guided gastrojejunal tube for enteral feeding in neurologically impaired children with gastroesophageal reflux. J Pediatr Surg. 2002;37(4):07–412.

    Google Scholar 

  130. Boubnova J, Hery G, Ughetto F, et al. Laparoscopic total esophagastric dissociation. J Pediatr Surg. 2009;44:e1–3.

    PubMed  Google Scholar 

  131. Woodley FW. A positive reflux-symptom association is not marked when the onset of the reflux episode does not occur within the pre-symptom time window. J Neurogastroenterol Motil. 2018;24:324–5.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Hepatology and Nutrition, Center for Functional Motility Disorders, Nationwide Children’s Hospital, Columbus, OH, 43205, USA

    Steven L. Ciciora & Frederick W. Woodley

  2. Department of Pediatrics, The Ohio State University College of Medicine, 700 Children’s Drive, Columbus, OH, 43205, USA

    Steven L. Ciciora & Frederick W. Woodley

Authors
  1. Steven L. Ciciora
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frederick W. Woodley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frederick W. Woodley.

Ethics declarations

Funding

No external funding was used in the writing of this manuscript.

Conflict of interest

Drs. Ciciora and Woodley have no conflicts of interest to report related to this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ciciora, S.L., Woodley, F.W. Optimizing the Use of Medications and Other Therapies in Infant Gastroesophageal Reflux. Pediatr Drugs 20, 523–537 (2018). https://doi.org/10.1007/s40272-018-0311-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40272-018-0311-3

Search

Navigation