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Gastroesophageal Reflux

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Textbook of Pediatric Gastroenterology, Hepatology and Nutrition

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Abstract

The guidelines of the North American and European Societies for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN/ESPGHAN) define gastroesophageal reflux (GER) as the physiologic passage of gastric contents into the esophagus and GER disease (GERD) as reflux associated with troublesome symptoms or complications. Although there is overlap between GER and GERD, their recognition is important to implement best management practice across all pediatric age groups. Clinical manifestations of GER and GERD in term infants, children, and adolescents allow to identify patients who can be managed with conservative treatment or who need referral for a diagnostic workup. History and physical examination including elimination of alarm symptoms remain the cornerstones and are important to rule out differential diagnoses. Endoscopy and histology are the standard diagnostic tool for esophagitis, enabling the diagnosis of eosinophilic esophagitis. Esophageal impedance measures acid and nonacid reflux episodes and allows to better evaluate a time association between symptoms and GER. The diagnosis of nonacid GERD avoids the unneeded administration of acid-blocking medication. Similar to the adult population, there is an increasing but inappropriate prescription rate of proton-pump inhibitors in pediatrics, but especially in infants when presenting with inconsolable crying. Adverse effects on proton-pump inhibitors such as dysbiosis, small bowel bacterial overgrowth, increased respiratory and gastrointestinal tract infections, nutritional consequences, hypomagnesemia, etc. have been highlighted. The management of nonacid GER(D) remains a challenge as long as there is no effective drug. Conservative recommendations such as reassurance, dietary, and positional treatment are indicated in patients with uncomplicated troublesome regurgitation and GERD. In infants, GER(D) may be difficult to distinguish from cow’s milk protein allergy as the presenting symptoms may be very similar. Children with acid GERD may benefit from acid-blocking medication. Laparoscopic surgery is indicated to manage more severe cases, such as children with intractable symptoms or who are at risk for severe complications of GERD.

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Abbreviations

AAF:

Amino acid formula

AR:

Antireflux

BAL:

Broncho-alveolar liquid

CM:

Cow’s milk

CMPA:

Cow’s milk protein allergy

eHF:

Extensively hydrolyzed formula

ENT:

Ear-nose-throat

GER(D):

Gastroesophageal reflux (disease)

H2 RA:

H2 receptor antagonist

LES:

Lower esophageal sphincter

LLM:

Lipid-laden macrophages

NERD:

Nonerosive reflux disease

PPI:

Proton-pump inhibitor

TLESR:

Transient lower esophageal sphincter relaxation

References

  1. 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 of Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2009;49:498–547.

    Google Scholar 

  2. Rosen R, Vandenplas Y, Singendonk M, Cabana M, DiLorenzo C, Gottrand F, Gupta S, Langendam M, Staiano A, Thapar N, Tipnis N, Tabbers M. 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.

    Google Scholar 

  3. Nelson SP, Kothari S, Wu EQ, Beaulieu N, McHale JM, Dabbous OH. Pediatric gastroesophageal reflux disease and acid-related conditions: trends in incidence of diagnosis and acid suppression therapy. J Med Econ. 2009;12:348–55.

    CAS  Google Scholar 

  4. Scherer LD, Zikmund-Fisher BJ, Fagerlin A, Tarini BA. Influence of “GERD” label on parents’ decision to medicate infants. Pediatrics. 2013;131:839–45.

    Google Scholar 

  5. 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 on the definition of gastroesophageal reflux disease in the pediatric population. Am J Gastroenterol. 2009;104:1278–95.

    Google Scholar 

  6. Bredenoord AJ, Pandolfino JE, Smout AJPM. Gastro-oesophageal reflux disease. Lancet. 2013;381:933–42.

    Google Scholar 

  7. von Baeyer CL, Spagrud LJ. Systematic review of observational (behavioral) measures of pain for children and adolescents aged 3 to 18 years. Pain. 2007;127:140–50.

    Google Scholar 

  8. 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.

    Google Scholar 

  9. Galmiche JP, Clouse RE, Balint A. Functional esophageal disorders. Gastroenterology. 2006;130:1459–65.

    Google Scholar 

  10. Heine RG, Jordan B, Lubitz L, Meehan M, Catto-Smith AG. Clinical predictors of pathological gastro-oesophageal reflux in infants with persistent distress. J Paediatr Child Health. 2006;42:134–9.

    Google Scholar 

  11. Benninga MA, Faure C, Hyman PE, St James Roberts I, Schechter NL, Nurko S. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology. 2016;150:1443–55.e2.

    Google Scholar 

  12. Kim SL, Hunter JG, Wo JM, Davis LP, Waring JP. NSAIDs, aspirin, and esophageal strictures: are over-the-counter medications harmful to the esophagus? J Clin Gastroenterol. 1999;29:32–4.

    CAS  Google Scholar 

  13. Kang JY, Ho KY. Different prevalences of reflux oesophagitis and hiatus hernia among dyspeptic patients in England and Singapore. Eur J Gastroenterol Hepatol. 1999;11:845–50.

    CAS  Google Scholar 

  14. Nwokediuko SC, Adekanle O, Akere A, Olokoba A, Anyanechi C, Umar SM, Maiyaki A, Ijoma U, Obienu O, Uhunmwangho A, Ndububa D. Gastroesophageal reflux disease in a typical African population: a symptom-based multicenter study. BMC Gastroenterol. 2020;20:107. https://doi.org/10.1186/s12876-020-01261-8.

    Article  Google Scholar 

  15. El-Serag H, Hill C, JonesR. Systematic review: the epidemiology of gastro-esophageal reflux disease in primary care, using the UK General Practice Data Base? Aliment Pharmacol Ther. 2009;29:470–80.

    CAS  Google Scholar 

  16. Dent J, El-Serag H, Wallander MA, Johansson S. Epidemiology of gastro-oesophageal reflux disease : a systematic review. Gut. 2005;54:710–7.

    CAS  Google Scholar 

  17. Eusebi LH, Ratnakumaran R, Yuan Y, Solaymani-Dodaran M, Bazzoli F, Ford A. Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis. Gut. 2018;67:430–40. https://doi.org/10.1136/gutjnl-2016-313589. Epub 2017 Feb 23.

    Article  Google Scholar 

  18. Ruigómez A, Wallander MA, Lundborg P, Johansson S, Rodriguez LA. Gastroesophageal reflux disease in children and adolescents in primary care. Scand J Gastroenterol. 2010;45:139–46.

    Google Scholar 

  19. Martigne L, Delaage PH, Thomas-Delecourt F, Bonnelye G, Barthélémy P, Gottrand F. Prevalence and management of gastroesophageal reflux disease in children and adolescents: a nationwide cross-sectional observational study. Eur J Pediatr. 2012;171:1767–73.

    Google Scholar 

  20. Rey E, Moreno-Elola-Olaso C, Rodriguez-Artalejo F, Diaz-Rubio M. Medical consultation for gastro-oesophageal reflux symptoms: reasons and associated factors. Digestion. 2004;70:173–7.

    Google Scholar 

  21. Flameling RD, Numans ME, ter Linde J, de Wit NJ, Siersema PD. Different characteristics of patients with gastro-oesophageal reflux disease on their path through healthcare: a population follow-up study. Eur J Gastroenterol Hepatol. 2010;22:578–82. https://doi.org/10.1097/MEG.0b013e328335638c.

    Article  Google Scholar 

  22. Quitadamo P, Buonavolontà R, Miele E, Masi P, Coccorullo P, Staiano A. Total and abdominal obesity are risk factors for gastroesophageal reflux symptoms in children. J Pediatr Gastroenterol Nutr. 2012;55:72–5.

    Google Scholar 

  23. de Vries DR, ter Linde JJ, van Herwaarden MA, Smout AJ, Samsom M. Gastroesophageal reflux disease is associated with the C825T polymorphism in the G-protein beta3 subunit gene (GNB3). Am J Gastroenterol. 2009;104:281–5.

    Google Scholar 

  24. Cameron AJ, Lagergren J, Henriksson C. Gastroesophageal reflux disease in monozygotic and dizygotic twins. Gastroenterology. 2002;122:55–9.

    Google Scholar 

  25. Argyrou A, Legaki E, Koutserimpas C, Gazouli M, Papaconstantinou I, Gkiokas G, Karamanolis G. Risk factors for gastroesophageal reflux disease and analysis of genetic contributors. World J Clin Cases. 2018;6:176–82.

    Google Scholar 

  26. Hu FZ, Preston RA, Post JC. Mapping of a gene for severe pediatric gastroesophageal reflux to chromosome 13q14. JAMA. 2000;284:325–34.

    CAS  Google Scholar 

  27. Orenstein SR, Shalaby TM, Barmada MM, Whitcomb DC. Genetics of gastroesophageal reflux disease: a review. J Pediatr Gastroenterol Nutr. 2002;34:506–10.

    Google Scholar 

  28. An J, Gharahkhani P, Law MH, Ong JS, Han X, Olsen CM, Neale RE, Lai J, Vaughan TL, Gockel I, Thieme R, Böhmer AC, Jankowski J, Fitzgerald RC, Schumacher J, Palles C, BEACON; 23andMe Research Team, Whiteman DC, MacGregor S. Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases. Nat Commun. 2019;10:4219.

    Google Scholar 

  29. Vandenplas Y, Hassall E. Mechanisms of gastroesophageal reflux and gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2002;35:119–36.

    Google Scholar 

  30. van Hoeij FB, Weijenborg PW, van den Bergh Weerman MA, van den Wijngaard RM, Verheij J, Smout AJ, Bredenoord AJ. Mucosal integrity and sensitivity to acid in the proximal esophagus in patients with gastroesophageal reflux disease. Am J Physiol Gastrointest Liver Physiol. 2016;311:G117–22. https://doi.org/10.1152/ajpgi.00134.2016. Epub 2016 May 19.

    Article  Google Scholar 

  31. Kindt S, Vos R, Blondeau K, Tack J. Inflluence of intra-oesophageal capsaicin instillation on heartburn induction and oesophageal sensitivity in man. Neurogastroenterol Motil. 2009;21:1032–e82.

    CAS  Google Scholar 

  32. Woodland P, Shen Ooi JL, Grassi F, Nikaki K, Lee C, Evans JA, Koukias N, Triantos C, McDonald SA, Peiris M, Aktar R, Blackshaw LA, Sifrim D. Superficial esophageal mucosal afferent nerves may contribute to reflux hypersensitivity in nonerosive reflux disease. Gastroenterology. 2017;153:1230–9.

    Google Scholar 

  33. Salvatore S, Pagliarin F, Huysentruyt K, Van De Maele K, Agosti M, Vandenplas Y. Distress in infants: don’t blame acid reflux. J Pediatr Gastroenterol Nutr. 2020;71:465–9.

    CAS  Google Scholar 

  34. Borrelli O, Mancini V, Thapar N, Giorgio V, Elawad M, Hill S, Shah N, Lindley KJ. Cow’s milk challenge increases weakly acidic reflux in children with cow’s milk allergy and gastroesophageal reflux disease. J Pediatr. 2012;161:476–81.

    Google Scholar 

  35. Mancini V, Ribolsi M, Gentile M, de’Angelis G, Bizzarri B, Lindley KJ, Cucchiara S, Cicala M, Borrelli O. Oesophageal mucosal intercellular space diameter and reflux pattern in childhood erosive and non-erosive reflux disease. Dig Liver Dis. 2012;44:981–7.

    Google Scholar 

  36. Iijima K, Shimosegawa T. Involvement of luminal nitric oxide in the pathogenesis of the gastroesophageal reflux disease spectrum. J Gastroenterol Hepatol. 2014;29:898–905.

    CAS  Google Scholar 

  37. Sifrim D, Holloway R, Silny J, Zhang X, Tack J, Lerut A, Janssens J. Acid, non-acid and gas reflux in patients with gastroesophageal reflux disease during 24hr ambulatory pH-impedance recordings. Gastroenterology. 2001;120:1588–98.

    CAS  Google Scholar 

  38. Kuiken S, Van Den Elzen B, Tytgat G, Bennink R, Boeckxstaens G. Evidence for pooling of gastric secretions in the proximal stomach in humans using single photon computed tomography. Gastroenterology. 2002;123:2157–8.

    Google Scholar 

  39. Shay SS, Johnson LF, Richter JE. Acid rereflux: a review, emphasizing detection by impedance, manometry, and scintigraphy, and the impact on acid clearing pathophysiology as well as interpreting the pH record. Dig Dis Sci. 2003;48(1):1–9.

    Google Scholar 

  40. Sifrim D, Holloway R. Transient lower esophageal sphincter relaxations: how many or how harmful? Am J Gastroenterol. 2001;96:2529–32.

    CAS  Google Scholar 

  41. Levine A, Milo T, Broide E, Wine E, Dalal I, Boaz M, Avni Y, Shirin H. Influence of Helicobacter pylori eradication on gastroesophageal reflux symptoms and epigastric pain in children and adolescents. Pediatrics. 2004;113:54–8.

    Google Scholar 

  42. Lupu VV, Ignat A, Ciubotariu G, Ciubară A, Moscalu M, Burlea M. Helicobacter pylori infection and gastroesophageal reflux in children. Dis Esophagus. 2016;29:1007–12.

    CAS  Google Scholar 

  43. Babaei A, Venu M, Naini SR, Gonzaga J, Lang IM, Massey BT, Jadcherla S, Shaker R. Impaired upper esophageal sphincter reflexes in patients with supraesophageal reflux disease. Gastroenterology. 2015;149:1381–91.

    Google Scholar 

  44. Cleveland RH, Kushner DC, Schwartz AN. Gastroesophageal reflux in children: results of a standardized fluoroscopic approach. Am J Roentgenol. 1983;141:53–6.

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  46. Pilic D, Fröhlich T, Nöh F, Pappas A, Schmidt-Choudhury A, Köhler H, Skopnik H, Wenzl TG. Detection of gastroesophageal reflux in children using combined multichannel intraluminal impedance and pH measurement: data from the German Pediatric Impedance Group. J Pediatr. 2011;158:650–4.e1.

    Google Scholar 

  47. Di Pace MR, Caruso AM, Catalano P, Casuccio A, De Grazia E. Evaluation of esophageal motility using multichannel intraluminal impedance in healthy children and children with gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 2011;52:26–30.

    Google Scholar 

  48. Bellaiche M, Oozeer R, Gerardi-Temporel G, Faure C, Vandenplas Y. Multiple functional gastrointestinal disorders are frequent in formula-fed infants and decrease their quality of life. Acta Paediatr. 2018;107:1276–82.

    Google Scholar 

  49. Nelson SP, Chen EH, Syniar GM, Christoffel KK. Prevalence of symptoms of gastroesophageal reflux during childhood. Arch Pediatr Adolesc Med. 2000;154:150–4.

    CAS  Google Scholar 

  50. Martin AJ, Pratt N, Kennedy JD, Ryan P, Ruffin RE, Miles H, Marley J. Natural history and familial relationships of infant spilling to 9 years of age. Pediatrics. 2002;109:1061–7.

    Google Scholar 

  51. Vandenplas Y, Koletzko S, Isolauri E, Hill D, Oranje AP, Brueton M, Staiano A, Dupont C. Guidelines for the diagnosis and management of cow’s milk protein allergy in infants. Arch Dis Child. 2007;92:902–8.

    Google Scholar 

  52. Heine RG, Jaquiery A, Lubitz L, Cameron DJ, Catto-Smith AG. Role of gastro-oesophageal reflux in infant irritability. Arch Dis Child. 1995;73:121–5.

    CAS  Google Scholar 

  53. Koletzko S, Niggemann B, Arato A, Dias JA, Heuschkel R, Husby S, Mearin ML, Papadopoulou A, Ruemmele FM, Staiano A, Schäppi MG, Vandenplas Y, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Diagnostic approach and management of cow’s-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines. J Pediatr Gastroenterol Nutr. 2012;55:221–9.

    CAS  Google Scholar 

  54. Nielsen RG, Bindslev-Jensen C, Kruse-Andersen S, Husby S. 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.

    CAS  Google Scholar 

  55. Garzi A, Messina M, Frati F, Carfagna L, Zagordo L, Belcastro M, Parmiani S, Sensi L, Marcucci F. An extensively hydrolysed cow’s milk formula improves clinical symptoms of gastroesophageal reflux and reduces the gastric emptying time in infants. Allergol Immunopathol (Madr). 2002;30:36–41.

    CAS  Google Scholar 

  56. Vandenplas Y, Gottrand F, Veereman-Wauters G, De Greef E, Devreker T, Hauser B, Benninga M, Heymans HS. Gastrointestinal manifestations of cow’s milk protein allergy and gastrointestinal motility. Acta Paediatr. 2012;101:1105–9.

    CAS  Google Scholar 

  57. El-Serag HB, Bailey NR, Gilger M, Rabeneck L. Endoscopic manifestations of gastroesophageal reflux disease in patients between 18 months and 25 years without neurological deficits. Am J Gastroenterol. 2002;97:1635–9.

    Google Scholar 

  58. Moayyedi P, Axon AT. Review article: gastro-oesophageal reflux disease--the extent of the problem. Aliment Pharmacol Ther. 2005;22(Suppl 1):11–9.

    Google Scholar 

  59. Venables TL, Newland RD, Patel AC, Hole J, Wilcock C, Turbitt ML. Omeprazole 10 milligrams once daily, omeprazole 20 milligrams once daily, or ranitidine 150 milligrams twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal reflux disease in general practice. Scand J Gastroenterol. 1997;32(10):965–73.

    CAS  Google Scholar 

  60. Talley NJ. Review article: gastro-oesophageal reflux disease -- how wide is its span? Aliment Pharmacol Ther. 2004;20(Suppl 5):27–37; discussion 38-9.

    Google Scholar 

  61. Herrera Elizondo JL, Monreal Robles R, García Compean D, González Moreno EI, Borjas Almaguer OD, Maldonado Garza HJ, González González JA. Prevalence of Barrett’s esophagus: an observational study from a gastroenterology clinic. Rev Gastroenterol Mex. 2017;82(4):296–300. https://doi.org/10.1016/j.rgmx.2017.01.006.

    Article  CAS  Google Scholar 

  62. Veldhuyzen van Zanten SJ, Thomson AB, Barkun AN, Armstrong D, Chiba N, White RJ, Escobedo S, Sinclair P. The prevalence of Barrett’s oesophagus in a cohort of 1040 Canadian primary care patients with uninvestigated dyspepsia undergoing prompt endoscopy. Aliment Pharmacol Ther. 2006;23(5):595–9.

    CAS  Google Scholar 

  63. Keyashian K, Hua V, Narsinh K, Kline M, Chandrasoma PT, Kim JJ. Barrett’s esophagus in Latinos undergoing endoscopy for gastroesophageal reflux disease symptoms. Dis Esophagus. 2013;26(1):44–9. https://doi.org/10.1111/j.1442-2050.2011.01316.x.

    Article  CAS  Google Scholar 

  64. Gilger MA, El-Serag HB, Gold BD, Dietrich CL, Tsou V, McDuffie A, Shub MD. Prevalence of endoscopic findings of erosive esophagitis in children: a population-based study. J Pediatr Gastroenterol Nutr. 2008;47:141–6.

    Google Scholar 

  65. Malcolm WF, Gantz M, Martin RJ, Goldstein RF, Goldberg RN, Cotten 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.

    Google Scholar 

  66. Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis P, Hassall E, Straumann A, Rothenberg ME, First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133:1342–63.

    CAS  Google Scholar 

  67. Papadopoulou A, Koletzko S, Heuschkel R, Dias JA, Allen KJ, Murch S, Chong S, Gottrand F, Husby S, Lionetti P, Mearin ML, Ruemmele FM, Schäppi MG, Staiano A, Wilschanski M, Vandenplas Y. Management guidelines of eosinophilic esophagitis in childhood: a position paper of the Eosinophilic Esophagitis Working Group and the Gastroenterology Committee of ESPGHAN. J Pediatr Gastroenterol Nutr. 2014;58:107–18.

    CAS  Google Scholar 

  68. Tourlamain G, Garcia-Puig R, Gutiérrez-Junquera C, Papadopoulou A, Roma E, Kalach N, Oudshoorn J, Sokollik C, Karolewska-Bochenek K, Oliva S, Strisciuglio C, Bauraind O, Auth MK, Thomson M, Otte S, Rok O, Dias JA, Tzivinikos C, Urbonas V, Kostovski A, Zevit N, Vande Velde S, ESPGHAN EGID Working group. Differences in management of eosinophilic esophagitis in Europe: an assessment of current practice. J Pediatr Gastroenterol Nutr. 2020;71(1):83–90.

    Google Scholar 

  69. Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA, American College of Gastroenterology. ACG clinical guideline: Evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013;108:679–92.

    Google Scholar 

  70. Gutiérrez-Junquera C, Zevit N. Dietary treatment of eosinophilic gastrointestinal disorders in children. Curr Opin Clin Nutr Metab Care. 2020;23:210–6.

    Google Scholar 

  71. Wang R, Hirano I, Doerfler B, Zalewski A, Gonsalves N, Taft T. Assessing adherence and barriers to long-term elimination diet therapy in adults with eosinophilic esophagitis. Dig Dis Sci. 2018;63(7):1756–62. https://doi.org/10.1007/s10620-018-5045-0.

    Article  Google Scholar 

  72. Nebel OT, Fornes MF, Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am J Dig Dis. 1976;21(11):953–6.

    CAS  Google Scholar 

  73. Mold JW, Reed LE, Davis AB, Allen ML, Decktor DL, Robinson M. Prevalence of gastroesophageal reflux in elderly patients in a primary care setting. Am J Gastroenterol. 1991;86(8):965–70.

    CAS  Google Scholar 

  74. Chai G, Governale L, McMahon AW, Trinidad JP, Staffa J, Murphy D. Trends of outpatient prescription drug utilization in US children, 2002-2010. Pediatrics. 2012;130:23–31.

    Google Scholar 

  75. Levy EI, Hoang DM, Vandenplas Y. The effects of proton pump inhibitors on the microbiome in young children. Acta Paediatr. 2020;109(8):1531–8. https://doi.org/10.1111/apa.15213.

    Article  CAS  Google Scholar 

  76. Shaker R, Castell DO, Schoenfeld PS, Spechler SJ. Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association. Am J Gastroenterol. 2003;98(7):1487–93.

    Google Scholar 

  77. Kindt S, Imschoot J, Tack J. Prevalence of and impact of pantoprazole on nocturnal heartburn and associated sleep complaints in patients with erosive esophagitis. Dis Esophagus. 2011;24(8):531–7. https://doi.org/10.1111/j.1442-2050.2011.01189.x.

    Article  CAS  Google Scholar 

  78. Nandurkar S, Talley NJ. Epidemiology and natural history of reflux disease. Bailliere’s Clin Gastroenterol. 2000;14:743–57.

    CAS  Google Scholar 

  79. Haycox A, Einarson T, Eggleston A. The health economic impact of upper gastrointestinal symptoms in the general population: results from the Domestic/International Gastroenterology Surveillance Study (DIGEST). Scand J Gastroenterol Suppl. 1999;231:38–47. https://doi.org/10.1080/003655299750025255.

  80. Nelson SP, Chen EH, Syniar GM. One year follow-up of symptoms of gastroesophageal reflux during infancy. Pediatrics. 1998;102:e67.

    CAS  Google Scholar 

  81. Orenstein SR, Hassall E, Furmaga-Jablonska W, Atkinson S, Raanan M. 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  Google Scholar 

  82. Duncan DR, Larson K, Rosen RL. Clinical aspects of thickeners for pediatric gastroesophageal reflux and oropharyngeal dysphagia. Curr Gastroenterol Rep. 2019;21:30.

    Google Scholar 

  83. Starosta V, Kitz R, Hartl D, Marcos V, Reinhardt D, Griese M. Bronchoalveolar pepsin, bile acids, oxidation, and inflammation in children with gastroesophageal reflux disease. Chest. 2007;132:1557–64.

    CAS  Google Scholar 

  84. Zenzeri L, Quitadamo P, Tambucci R, Ummarino D, Poziello A, Miele E, Staiano A. Role of non-acid gastro-esophageal reflux in children with respiratory symptoms. Pediatr Pulmonol. 2017;52:669–74.

    Google Scholar 

  85. Kim SY, Kim HJ, Lim H, Kong IG, Kim M, Choi HG. Bidirectional association between gastroesophageal reflux disease and depression: two different nested case-control studies using a national sample cohort. Sci Rep. 2018;8:11748.

    Google Scholar 

  86. Engelkes M, Baan EJ, de Ridder MAJ, Svensson E, Prieto-Alhambra D, Lapi F, Giaquinto C, Picelli G, Boudiaf N, Albers F, Evitt LA, Cockle S, Bradford E, Van Dyke MK, Suruki R, Rijnbeek P, Sturkenboom MCJM, Janssens HM, Verhamme KMC. Incidence, risk factors and re-exacerbation rate of severe asthma exacerbations in a multinational, multidatabase pediatric cohort study. Pediatr Allergy Immunol. 2020;31(5):496–505.

    Google Scholar 

  87. Sheikh S, Stephen T, Howell L, Eid N. Gastroesophageal reflux in infants with wheezing. Pediatr Pulmonol. 1999;28:181–6.

    CAS  Google Scholar 

  88. 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.

    Google Scholar 

  89. Khoshoo V, Le T, Haydel RM Jr, Landry L, Nelson C. Role of gastro-esophageal reflux in older children with persistent asthma. Chest. 2003;123:1008–13.

    Google Scholar 

  90. Stordal K, Johannesdottir GB, Bentsen BS, Knudsen PK, Carlsen KC, Closs O, Handeland M, Holm HK, Sandvik L. Acid suppression does not change respiratory symptoms in children with asthma and gastro-oesophageal reflux disease. Arch Dis Child. 2005;90:956–60.

    CAS  Google Scholar 

  91. Kilic M, Ozturk F, Kirmemis O, Atmaca S, Guner SN, Caltepe G, Sancak R, Kalayci AG. Impact of laryngopharyngeal reflux and gastro-esophageal reflux on asthma control in children. Int J Pediatr Otorhinolaryngol. 2013;77:341–5.

    Google Scholar 

  92. Blake K, Teague WG. Gastroesophageal reflux disease and childhood asthma. Curr Opin Pulm Med. 2013;19:24–9.

    Google Scholar 

  93. 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.

    CAS  Google Scholar 

  94. Ummarino D, Vandermeulen L, Roosens B, Urbain D, Hauser B, Vandenplas Y. Gastroesophageal reflux evaluation in patients affected by chronic cough: restech versus multichannel intraluminal impedance/pH metry. Laryngoscope. 2013;123:980–4.

    Google Scholar 

  95. Ravelli AM, Panarotto MB, Verdoni L, Consolati V, Bolognini S. Pulmonary aspiration shown by scintigraphy in gastroesophageal reflux-related respiratory disease. Chest. 2006;130:1520–6.

    Google Scholar 

  96. Morigeri C, Bhattacharya A, Mukhopadhyay K, Narang A, Mittal BR. Radionuclide scintigraphy in the evaluation of gastroesophageal reflux in symptomatic and asymptomatic pre-term infants. Eur J Nucl Med Mol Imaging. 2008;35:1659–65.

    CAS  Google Scholar 

  97. Sacco O, Silvestri M, Ghezzi M, Capizzi A, Rossi GA. Airway inflammation and injury in children with prevalent weakly acidic gastroesophageal refluxes. Respir Med. 2018;143:42–7.

    Google Scholar 

  98. Blondeau K, Pauwels A, Dupont L, Mertens V, Proesmans M, Orel R, Brecelj J, López-Alonso M, Moya M, Malfroot A, De Wachter E, Vandenplas Y, Hauser B, Sifrim D. Characteristics of gastroesophageal reflux and potential risk of gastric content aspiration in children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2010;50:161–6.

    CAS  Google Scholar 

  99. Dziekiewicz MA, Banaszkiewicz A, Urzykowska A, Lisowska A, Rachel M, Sands D, Walkowiak J, Radzikowski A, Albrecht P. Gastroesophageal reflux disease in children with cystic fibrosis. Adv Exp Med Biol. 2015;873:1–7.

    Google Scholar 

  100. Hauser B, De Schepper J, Malfroot A, De Wachter E, De Schutter I, Keymolen K, Vandenplas Y. Gastric emptying and gastro-oesophageal reflux in children with cystic fibrosis. J Cyst Fibros. 2016;15(4):540–7. https://doi.org/10.1016/j.jcf.2015.12.015.

    Article  Google Scholar 

  101. Pauwels A, Decraene A, Blondeau K, Mertens V, Farre R, Proesmans M, Van Bleyenbergh P, Sifrim D, Dupont LJ. Bile acids in sputum and increased airway inflammation in patients with cystic fibrosis. Chest. 2012;141:1568–74.

    Google Scholar 

  102. Young LR, Hadjiliadis D, Davis RD, Palmer SM. Lung transplantation exacerbates gastroesophageal reflux disease. Chest. 2003;124(5):1689–93.

    Google Scholar 

  103. Jamie Dy F, Freiberger D, Liu E, Boyer D, Visner G, Rosen R. Impact of gastroesophageal reflux and delayed gastric emptying on pediatric lung transplant outcomes. J Heart Lung Transplant. 2017;36(8):854–61. https://doi.org/10.1016/j.healun.2017.01.005.

    Article  Google Scholar 

  104. Hathorn KE, Chan WW. Lo WK Role of gastroesophageal reflux disease in lung transplantation. World J Transplant. 2017;7(2):103–16. https://doi.org/10.5500/wjt.v7.i2.103.

    Article  Google Scholar 

  105. Blondeau K, Mertens V, Dupont L, Pauwels A, Farré R, Malfroot A, De Wachter E, De Schutter I, Hauser B, Vandenplas Y, Sifrim D. The relationship between gastroesophageal reflux and cough in children with chronic unexplained cough using combined impedance-pH-manometry recordings. Pediatr Pulmonol. 2011;46:286–94.

    CAS  Google Scholar 

  106. Chang AB, Oppenheimer JJ, Kahrilas PJ, Kantar A, Rubin BK, Weinberger M, Irwin RS, CHEST Expert Cough Panel. Chronic cough and gastroesophageal reflux in children: CHEST guideline and expert panel report. Chest. 2019;156(1):131–40. https://doi.org/10.1016/j.chest.2019.03.035.

    Article  Google Scholar 

  107. Abdel-aziz MM, El-Fattah AM, Abdalla AF. Clinical evaluation of pepsin for laryngopharyngeal reflux in children with otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2013;77:1765–70.

    Google Scholar 

  108. Klimara MJ, Samuels TL, Johnston N, Chun RH, McCormick ME. Detection of pepsin in oral secretions of infants with and without laryngomalacia. Ann Otol Rhinol Laryngol. 2020;129(3):224–9. https://doi.org/10.1177/0003489419884332.

    Article  Google Scholar 

  109. Woodland P, Singendonk MMJ, Ooi J, Nikaki K, Wong T, Lee C, Glasinovic E, Koning R, Lutter R, Benninga MA, van Wijk MP, Sifrim D. Measurement of salivary pepsin to detect gstroesophageal reflux disease is not ready for clinical application. Clin Gastroenterol Hepatol. 2019;17(3):563–5. https://doi.org/10.1016/j.cgh.2018.05.016.

    Article  CAS  Google Scholar 

  110. Farahmand F, Sabbaghian M, Ghodousi S, Seddighoraee N, Abbasi M. Gastroesophageal reflux disease and tooth erosion: a cross-sectional observational study. Gut Liver. 2013;7:278–81.

    Google Scholar 

  111. Marsicano JA, de Moura-Grec PG, Bonato RC, Sales-Peres Mde C, Sales-Peres A, Sales-Peres SH. Gastroesophageal reflux, dental erosion, and halitosis in epidemiological surveys: a systematic review. Eur J Gastroenterol Hepatol. 2013;25:135–41.

    Google Scholar 

  112. Ganesh M, Hertzberg A, Nurko S, Needleman H, Rosen R. Acid rather than nonacid reflux burden is a predictor of tooth erosion. J Pediatr Gastroenterol Nutr. 2016;62:309–13.

    Google Scholar 

  113. De Oliveira PA, Paiva SM, De Abreu MH, Auad SM. Dental erosion in children with gastroesophageal reflux disease. Pediatr Dent. 2016;38:246–50.

    Google Scholar 

  114. Mindlina I. Diagnosis and management of Sandifer syndrome in children with intractable neurological symptoms. Eur J Pediatr. 2020;179:243–50.

    CAS  Google Scholar 

  115. Romano C, Van Wynckel M, Hulst J, Broekaert I, Bronsky J, Dall’Oglio L, Mis NF, Hojsak I, Orel R, Papadopoulou A, Schaeppi M, Thapar N, Wilschanski M, Sullivan P, Gottrand F. European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for the evaluation and treatment of gastrointestinal and nutritional complications in children with neurological impairment. J Pediatr Gastroenterol Nutr. 2017;65:242–64.

    Google Scholar 

  116. Capito C, Leclair MD, Piloquet H, Plattner V, Heloury Y, Podevin G. Long-term outcome of laparoscopic Nissen-Rossetti fundoplication for neurologically impaired and normal children. Surg Endosc. 2008;22(4):875–80. https://doi.org/10.1007/s00464-007-9603-3.

    Article  CAS  Google Scholar 

  117. Mathei J, Coosemans W, Nafteux P, Decker G, De Leyn P, Van Raemdonck D, Hoffman I, Deboeck C, Proesmans M, Lerut T. Laparoscopic Nissen fundoplication in infants and children: analysis of 106 consecutive patients with special emphasis in neurologically impaired vs. neurologically normal patients. Surg Endosc. 2008;22(4):1054–9. https://doi.org/10.1007/s00464-007-9578-0.

    Article  Google Scholar 

  118. Steyaert H, Al Mohaidly M, Lembo MA, Carfagna L, Tursini S, Valla JS. Long-term outcome of laparoscopic Nissen and Toupet fundoplication in normal and neurologically impaired children. Surg Endosc. 2003;17(4):543–6. https://doi.org/10.1007/s00464-002-9058-5.

    Article  CAS  Google Scholar 

  119. Kim E, Lee YJ, Park JS, Cho YJ, Yoon HI, Lee JH, Lee CT, Kim SJ. Associations between obstructive sleep apnea severity and endoscopically proven gastroesophageal reflux disease. Sleep Breath. 2018;22:85–90.

    Google Scholar 

  120. Takada K, Matsumoto S, Kojima E, Iwata S, Okachi S, Ninomiya K, Morioka H, Tanaka K, Enomoto Y. Prospective evaluation of the relationship between acute exacerbations of COPD and gastroesophageal reflux disease diagnosed by questionnaire. Respir Med. 2011;105(10):1531–6. https://doi.org/10.1016/j.rmed.2011.03.009.

    Article  Google Scholar 

  121. Shepherd K, Ockelford J, Ganasan V, Holloway R, Hillman D, Eastwood P. Temporal relationship between night-time gastroesophageal reflux events and arousals from sleep. Am J Gastroenterol. 2020;115(5):697–705. https://doi.org/10.14309/ajg.0000000000000627.

    Article  Google Scholar 

  122. Zimbric G, Bonkowsky JL, Jackson WD, Maloney CG, Srivastava R. Adverse outcomes associated with gastroesophageal reflux disease are rare following an apparent life-threatening event. J Hosp Med. 2012;7:476–81.

    Google Scholar 

  123. 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 technique. Pediatr Pulmonol. 2001;31:144–9.

    CAS  Google Scholar 

  124. Cresi F, Martinelli D, Maggiora E, Locatelli E, Liguori SA, Baldassarre ME, Cocchi E, Bertino E, Coscia A. Cardiorespiratory events in infants with gastroesophageal reflux symptoms: is there any association? Neurogastroenterol Motil. 2018;30:e13278.

    CAS  Google Scholar 

  125. Machado R, Woodley FW, Skaggs B, Di Lorenzo C, Splaingard M, Mousa H. Gastroesophageal reflux causing sleep interruptions in infants. J Pediatr Gastroenterol Nutr. 2013;56:431–5.

    Google Scholar 

  126. Cresi F, Castagno E, Storm H, Silvestro L, Miniero R, Savino F. Combined esophageal intraluminal impedance, pH and skin conductance monitoring to detect discomfort in GERD infants. PLoS One. 2012;7:e43476.

    CAS  Google Scholar 

  127. Al-Adnani M, Cohen MC, Scheimberg I. Gastroesophageal reflux disease and sudden infant death: mechanisms behind an under-recognized association. Pediatr Dev Pathol. 2011;14:53–6.

    Google Scholar 

  128. Tovar JA, Fragoso AC. Gastroesophageal reflux after repair of esophageal atresia. Eur J Pediatr Surg. 2013;23:175.

    CAS  Google Scholar 

  129. Raicevic M, Saxena AK. Barrett’s esophagus in children: what is the evidence? World J Pediatr. 2018;14:330–4.

    CAS  Google Scholar 

  130. Schneider A, Gottrand F, Bellaiche M, Becmeur F, Lachaux A, Bridoux-Henno L, Michel JL, Faure C, Philippe P, Vandenplas Y, Dupont C, Breton A, Gaudin J, Lamireau T, Muyshont L, Podevin G, Viola S, Bertrand V, Caldari D, Colinet S, Wanty C, Sauleau E, Leteurtre E, Michaud L. Prevalence of Barrett esophagus in adolescents and young adults with esophageal atresia. Ann Surg. 2016;264:1004–8.

    Google Scholar 

  131. Carre I. The natural history of the partial thoracic stomach (“hiatal hernia”) in children. Arch Dis Child. 1959;34:344–53.

    CAS  Google Scholar 

  132. Krug E, Bergmeijer JH, Dees J. Gastroesophageal reflux and Barrett’s esophagus in adults born with esophageal atresia. Am J Gastroenterol. 1999;94:2825–8.

    CAS  Google Scholar 

  133. Hassall E. Barrett’s esophagus: new definitions and approaches in children. J Pediatr Gastroenterol Nutr. 1993;16:345–64.

    CAS  Google Scholar 

  134. Oberg S, Peters JH, DeMeester TR, Lord RV, Johansson J, DeMeester SR, Hagen JA. Determinants of intestinal metaplasia within the columnar-lined esophagus. Arch Surg. 2000;135:651–6.

    CAS  Google Scholar 

  135. Dubecz A, Solymosi N, Stadlhuber RJ, Schweigert M, Stein HJ, Peters JH. Does the incidence of adenocarcinoma of the esophagus and gastric cardia continue to rise in the twenty-first century?-a SEER database analysis. J Gastrointest Surg. 2013; https://doi.org/10.1007/s11605-013-2345-8. [Epub ahead of print].

  136. Lagergren J, Bergstrom R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999;340:825–31.

    CAS  Google Scholar 

  137. Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout AJPM, Vaezi M, Sifrim D, Fox MR, Vela MF, Tutuian R, Tack J, Bredenoord AJ, Pandolfino J, Roman S, Gyawali CP, et al. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018;67(7):1351–62. https://doi.org/10.1136/gutjnl-2017-314722.

    Article  Google Scholar 

  138. Ghisa M, Barberio B, Savarino V, Marabotto E, Ribolsi M, Bodini G, Zingone F, Frazzoni M, Savarino E, Ghisa M, et al. The Lyon Consensus: does it differ from the previous ones? J Neurogastroenterol Motil. 2020;26(3):311–21. https://doi.org/10.5056/jnm20046.

    Article  Google Scholar 

  139. Ribolsi M, Giordano A, Guarino MPL, Tullio A, Cicala M. New classifications of gastroesophageal reflux disease: an improvement for patient management? Expert Rev Gastroenterol Hepatol. 2019;13(8):761–9. https://doi.org/10.1080/17474124.2019.1645596.

    Article  CAS  Google Scholar 

  140. Orenstein SR, Cohn JF, Shalaby T. Reliability and validity of an infant gastroesophageal questionnaire. Clin Pediatr. 1993;32:472–84.

    CAS  Google Scholar 

  141. 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. Clin Gastroenterol Hepatol. 2006;4:588–96.

    Google Scholar 

  142. Aggarwal S, Mittal SK, Kalra KK, Rajeshwari K, Gondal R. Infant gastroesophageal reflux disease score: reproducibility and validity in a developing country. Trop Gastroenterol. 2004;25:96–8.

    Google Scholar 

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

    Google Scholar 

  144. Deal L, Gold BD, Gremse DA, Winter HS, Peters SB, Fraga PD, Mack ME, Gaylord SM, Tolia V, Fitzgerald JF. Age-specific questionnaires distinguish GERD symptom frequency and severity in infants and young children: development and initial validation. J Pediatr Gastroenterol Nutr. 2005;41:178–85.

    Google Scholar 

  145. Hauser B, Roelants M, De Schepper J, Veereman G, Caveliers V, Devreker T, De Greef E, Vandenplas Y. Gastric emptying of solids in children: reference values for the (13) C-octanoic acid breath test. Neurogastroenterol Motil. 2016;28:1480–7.

    CAS  Google Scholar 

  146. Hauser B, Roelants M, De Schepper J, Veereman G, Caveliers V, Devreker T, De Greef E, Vandenplas Y. Gastric emptying of liquids in children. J Pediatr Gastroenterol Nutr. 2016;62:403–8.

    Google Scholar 

  147. Behar J, Ramsby G. Gastric emptying and antral motility in reflux esophagitis. Effect of oral metoclopramide. Gastroenterology. 1978;74(2 Pt 1):253–6.

    CAS  Google Scholar 

  148. Savino A, Cecamore C, Matronola MF, Verrotti A, Mohn A, Chiarelli F, Pelliccia P. US in the diagnosis of gastroesophageal reflux in children. Pediatr Radiol. 2012;42:515–24.

    Google Scholar 

  149. Lundell LR, Dent J, Bennett JR, Blum AL, Armstrong D, Galmiche JP, Johnson F, Hongo M, Richter JE, Spechler SJ, Tytgat GN, Wallin L. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999;45(2):172–80. https://doi.org/10.1136/gut.45.2.172.

    Article  CAS  Google Scholar 

  150. Kahrilas PJ, Sifrim D. High-resolution manometry and impedance-pH/manometry: valuable tools in clinical and investigational esophagology. Gastroenterol Clin N Am. 2008;135(3):756–69. https://doi.org/10.1053/j.gastro.2008.05.048.

    Article  Google Scholar 

  151. Michael Mello M, Gyawali CP. Esophageal manometry in gastroesophageal reflux disease. Gastroenterology. 2014;43(1):69–87. https://doi.org/10.1016/j.gtc.2013.11.005.

    Article  Google Scholar 

  152. Vandenplas Y, Lepoudre R. Helven R Dependability of esophageal pH-monitoring data in infants on cutoff limits: the oscillatory index. J Pediatr Gastroenterol Nutr. 1990;11:304–9.

    CAS  Google Scholar 

  153. Vandenplas Y, Franckx-Goossens A, Pipeleers-Marichal M, Derde MP, Sacré-Smits L. Area under pH 4: advantages of a new parameter in the interpretation of esophageal pH monitoring data in infants. J Pediatr Gastroenterol Nutr. 1989;9:34–9.

    CAS  Google Scholar 

  154. Salvatore S, Salvatoni A, Van Steen K, Ummarino D, Hauser B, Vandenplas Y. Behind the (impedance) baseline in children. Dis Esophagus. 2014;27:726–31.

    CAS  Google Scholar 

  155. Rosen R, Lord C, Nurko S. The sensitivity of multichannel intraluminal impedance and the pH probe in the evaluation of gastroesophageal reflux in children. Clin Gastroenterol Hepatol. 2006;4:167–72.

    CAS  Google Scholar 

  156. Loots CM, van Wijk MP, Blondeau K, Dalby K, Peeters L, Rosen R, Salvatore S, Wenzl TG, Vandenplas Y, Benninga MA, Omari TI. Interobserver and intraobserver variability in pH-impedance analysis between 10 experts and automated analysis. J Pediatr. 2012;160:441–6.e1.

    Google Scholar 

  157. 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.

    CAS  Google Scholar 

  158. Klokkenburg JJ, Hoeve HL, Francke J, Wieringa MH, Borgstein J, Feenstra L. Bile acids identified in middle ear effusions of children with otitis media with effusion. Laryngoscope. 2009;119:396–400.

    CAS  Google Scholar 

  159. Orenstein SR, Shalaby TM, Kelsey SF, Frankel E. Natural history of infant reflux esophagitis: symptoms and morphometric histology during one year without pharmacotherapy. Am J Gastroenterol. 2006;101:628–40.

    Google Scholar 

  160. Vandenplas Y, Gutierrez-Castrellon P, Velasco-Benitez C, Palacios J, Jaen D, Ribeiro H, Shek PC, Lee BW, Alarcon P. Practical algorithms for managing common gastrointestinal symptoms in infants. Nutrition. 2013;29:184–94.

    Google Scholar 

  161. Vandenplas Y, Leluyer B, Cazaubiel M, Housez B, Bocquet A. Double-blind comparative trial with two anti-regurgitation formulae. J Pediatr Gastroenterol Nutr. 2013;57:389–93.

    CAS  Google Scholar 

  162. 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.

    Google Scholar 

  163. Vandenplas Y. Thickened infant formula does what it has to do: decrease regurgitation. Pediatrics. 2009;123:e549–50.

    Google Scholar 

  164. Bosscher D, Van Caillie-Bertrand M, Deelstra H. Do thickening properties of locust bean gum affect the amount of calcium, iron and zinc available for absorption from infant formula? In vitro studies. Int J Food Sci Nutr. 2003;54:261–8.

    CAS  Google Scholar 

  165. Bosscher D, van Caillie-Bertrand M, van Dyck K. Thickening of infant formula with digestible and indigestible carbohydrate availability of calcium, iron and zinc in vitro. J Pediatr Gastroenterol Nutr. 2000;30:373–8.

    CAS  Google Scholar 

  166. Levtchenko E, Hauser B, Vandenplas Y. Nutritional value of an “anti-regurgitation” formula. Acta Gastroenterol Belg. 1998;61:285–7.

    CAS  Google Scholar 

  167. Salvatore S, Savino F, Singendonk M, Tabbers M, Benninga MA, Staiano A, Vandenplas Y. Thickened infant formula: What to know. Nutrition. 2018;49:51–6.

    CAS  Google Scholar 

  168. Shergill-Bonner R. Infantile colic: practicalities of management, including dietary aspects. J Fam Health Care. 2010;20:206–9.

    Google Scholar 

  169. Vandenplas Y, De Greef E, Xinias I, Vrani O, Mavroudi A, Hammoud M, Al Refai F, Khalife MC, Sayad A, Noun P, Farah A, Makhoul G, Orel R, Sokhn M, L’Homme A, Mohring MP, Merhi BA, Boulos J, El Masri H, Halut C, Allar Study Group. Safety of a thickened extensive casein hydrolysate formula. Nutrition. 2016;32:206–12.

    CAS  Google Scholar 

  170. Indrio F, Di Mauro A, Riezzo G, Civardi E, Intini C, Corvaglia L, Ballardini E, Bisceglia M, Cinquetti M, Brazzoduro E, Del Vecchio A, Tafuri S, Francavilla R. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr. 2014;168:228–33.

    Google Scholar 

  171. Indrio F, Riezzo G, Giordano P, Ficarella M, Miolla MP, Martini S, Corvaglia L, Francavilla R. Effect of a partially hydrolysed whey infant formula supplemented with starch and Lactobacillus reuteri DSM 17938 on regurgitation and gastric motility. Nutrients. 2017;9:1181.

    Google Scholar 

  172. Garofoli F, Civardi E, Indrio F, Mazzucchelli I, Angelini M, Tinelli C, Stronati M. The early administration of Lactobacillus reuteri DSM 17938 controls regurgitation episodes in full-term breastfed infants. Int J Food Sci Nutr. 2014;65:646–8.

    Google Scholar 

  173. Vandenplas Y, De Schepper J, Verheyden S, Franckx J, Devreker T, Peelman M, Denayer E, Hauser B. A preliminary report on the efficacy of the “Multicare AR-Bed(R)” in 3 weeks - 3 month old infants on regurgitation, associated symptoms and acid reflux. Arch Dis Child. 2010;95:26–30.

    CAS  Google Scholar 

  174. van Wijk MP, Benninga MA, Dent J, Lontis R, Goodchild L, McCall LM, Haslam R, Davidson GP, Omari T. Effect of body position changes on postprandial gastroesophageal reflux and gastric emptying in the healthy premature neonate. J Pediatr. 2007;151:585–90.

    Google Scholar 

  175. Mitchell EA, Tuohy PG, Brunt JM, Thompson JM, Clements MS, Stewart AW, Ford RP, Taylor BJ. Risk factors for sudden infant death syndrome following the prevention campaign in New Zealand: a prospective study. Pediatrics. 1997;100:835–40.

    CAS  Google Scholar 

  176. Scragg RK, Mitchell EA. Side sleeping position and bed sharing in the sudden infant death syndrome. Ann Med. 1998;30:345–9.

    CAS  Google Scholar 

  177. Czinn SJ, Blanchard S. Gastroesophageal reflux disease in neonates and infants: when and how to treat. Paediatr Drugs. 2013;15:19–27.

    Google Scholar 

  178. Maclennan S, Augood C, Cash-Gibson L, Logan S, Gilbert RE. Cisapride treatment for gastro-oesophageal reflux in children. Cochrane Database Syst Rev. 2010;4:CD002300.

    Google Scholar 

  179. Craig WR, Hanlon-Dearman A, Sinclair C, Taback S, Moffatt M. Metoclopramide, thickened feedings, and positioning for gastro-oesophageal reflux in children under two years. Cochrane Database Syst Rev. 2004;(4):CD003502.

    Google Scholar 

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

    Google Scholar 

  181. Lau Moon Lin M, Robinson PD, Flank J, Sung L, Dupuis LL. The safety of metoclopramide in children: a systematic review and meta-analysis. Drug Saf. 2016;39(7):675–87. https://doi.org/10.1007/s40264-016-0418-9.

    Article  CAS  Google Scholar 

  182. 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.

    CAS  Google Scholar 

  183. Ryan PM, Mondal T. Does domperidone prolong QTc in a clinically relevant manner in infants with GORD? Arch Dis Child. 2020;105:202–5.

    Google Scholar 

  184. Morris AD, Chen J, Lau E, Poh J. Domperidone-associated QT interval prolongation in non-oncologic pediatric patients: a review of the literature. Can J Hosp Pharm. 2016;69:224–30.

    Google Scholar 

  185. Hegar B, Alatas S, Advani N, Firmansyah A, Vandenplas Y. Domperidone versus cisapride in the treatment of infant regurgitation and increased acid gastro-oesophageal reflux: a pilot study. Acta Paediatr. 2009;98:750–5.

    CAS  Google Scholar 

  186. Vieira MC, Miyague NI, Van Steen K, Salvatore S, Vandenplas Y. Effects of domperidone on QTc interval in infants. Acta Paediatr. 2012;101:494–6.

    CAS  Google Scholar 

  187. Michaud V, Turgeon J. Domperidone and sudden cardiac death: how much longer should we wait? J Cardiovasc Pharmacol. 2013;61:215–7.

    CAS  Google Scholar 

  188. Scott B. Question 2. How effective is domperidone at reducing symptoms of gastro-oesophageal reflux in infants? Arch Dis Child. 2012;97:752–5.

    Google Scholar 

  189. Taghvaei T, Kazemi A, Hosseini V, Hamidian M, Fakheri HT, Hashemi SA, Maleki I. Evaluation of the additive effect of domperidone on patients with refractory gastroesophageal reflux disease; a randomized double blind clinical trial. Middle East J Dig Dis. 2019;11(1):24–31. https://doi.org/10.15171/mejdd.2018.124.

    Article  Google Scholar 

  190. Kim YS, Kim TH, Choi CS, Shon YW, Kim SW, Seo GS, Nah YH, Choi MG, Choi SC. Effect of itopride, a new prokinetic, in patients with mild GERD: a pilot study. World J Gastroenterol. 2005;11(27):4210–4. https://doi.org/10.3748/wjg.v11.i27.4210.

    Article  CAS  Google Scholar 

  191. Yamashita H, Okada A, Naora K, Hongoh M, Kinoshita Y. Adding acotiamide to gastric acid inhibitors is effective for treating refractory symptoms in patients with non-erosive reflux disease. Dig Dis Sci. 2019;64(3):823–31. https://doi.org/10.1007/s10620-018-5377-9.

    Article  CAS  Google Scholar 

  192. Sirinawasatien A, Kantathavorn N. Efficacy of the four weeks treatment of omeprazole plus mosapride combination therapy compared with that of omeprazole monotherapy in patients with proton pump inhibitor-refractory gastroesophageal reflux disease: a randomized controlled trial. Clin Exp Gastroenterol. 2019;12:337–47. https://doi.org/10.2147/CEG.S214677.

    Article  CAS  Google Scholar 

  193. Yamaji Y, Isomura Y, Yoshida S, Yamada A, Hirata Y, Koike K, Yamaji Y, et al. Randomized controlled trial comparing the efficacy of mosapride plus omeprazole combination therapy to omeprazole monotherapy in gastroesophageal reflux disease. J Dig Dis. 2014;15(9):469–76.

    CAS  Google Scholar 

  194. Liu Q, Feng CC, Wang EM, Yan XJ, Chen SL. Efficacy of mosapride plus proton pump inhibitors for treatment of gastroesophageal reflux disease: a systematic review. World J Gastroenterol. 2013;19(47):9111–8. https://doi.org/10.3748/wjg.v19.i47.9111.

    Article  CAS  Google Scholar 

  195. Omari TI, Benninga MA, Sansom L, Butler RN, Dent J, Davidson GP. Effect of baclofen on esophagogastric motility and gastroesophageal reflux in children with gastroesophageal reflux disease: a randomized controlled trial. J Pediatr. 2006;149:468–74.

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  197. van Herwaarden MA, Samsom M, Rydholm H, Smout AJPM. The effect of baclofen on gastro-oesophageal reflux, lower oesophageal sphincter function and reflux symptoms in patients with reflux disease. Aliment Pharmacol Ther. 2002;16(9):1655–62. https://doi.org/10.1046/j.1365-2036.2002.01325.x.

    Article  Google Scholar 

  198. Ciccaglione AF, Marzio L. Effect of acute and chronic administration of the GABA B agonist baclofen on 24 hour pH metry and symptoms in control subjects and in patients with gastro-oesophageal reflux disease. Gut. 2003;52(4):464–70. https://doi.org/10.1136/gut.52.4.464.

    Article  CAS  Google Scholar 

  199. Beaumont H, Boeckxstaens GEE. Does the presence of a hiatal hernia affect the efficacy of the reflux inhibitor baclofen during add-on therapy? Am J Gastroenterol. 2009;104(7):1764–71. https://doi.org/10.1038/ajg.2009.247.

    Article  CAS  Google Scholar 

  200. Ericson JE, Arnold C, Cheeseman J, Cho J, Kaneko S, Wilson E, Clark RH, Benjamin DK Jr, Chu V, Smith PB, Hornik CP, Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee. Use and safety of erythromycin and metoclopramide in hospitalized infants. J Pediatr Gastroenterol Nutr. 2015;61:334–9.

    CAS  Google Scholar 

  201. Ballengee CR, Davalian F, Conaway MR, Sauer CG, Kaufman DA. Erythromycin and reflux events in premature neonates: a randomized clinical trial. J Pediatr Gastroenterol Nutr. 2018;67:720–5.

    CAS  Google Scholar 

  202. Rohof WO, Bennink RJ, de Ruigh AA, Hirsch DP, Zwinderman AH, Boeckxstaens GE. Effect of azithromycin on acid reflux, hiatus hernia and proximal acid pocket in the postprandial period. Gut. 2012;61:1670–7.

    CAS  Google Scholar 

  203. Mertens V, Blondeau K, Pauwels A, Farre R, Vanaudenaerde B, Vos R, Verleden G, Van Raemdonck DE, Dupont LJ, Sifrim D. Azithromycin reduces gastroesophageal reflux and aspiration in lung transplant recipients. Dig Dis Sci. 2009;54:972–9.

    CAS  Google Scholar 

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

    Google Scholar 

  205. Tighe M, Afzal NA, Bevan A, Hayen A, Munro A, Beattie RM. Pharmacological treatment of children with gastro-oesophageal reflux. Cochrane Database Syst Rev. 2014;11:CD008550.

    Google Scholar 

  206. National Institute for Health and Care Excellence (NICE). Gastro-oesophageal reflux disease: recognition, diagnosis and management in children and young people. (Clinical Guideline 193) 2015. http://www.nice.org.uk/guidance/NG1.

  207. Salvatore S, Ripepi A, Huysentruyt K, van de Maele K, Nosetti L, Agosti M, Salvatoni A, Vandenplas Y. The effect of alginate in gastroesophageal reflux in infants. Paediatr Drugs. 2018;20:575–83.

    Google Scholar 

  208. Palmieri B, Merighi A, Corbascio D, Rottigni V, Fistetto G, Esposito A. Fixed combination of hyaluronic acid and chondroitin-sulphate oral formulation in a randomized double blind, placebo controlled study for the treatment of symptoms in patients with non-erosive gastroesophageal reflux. Eur Rev Med Pharmacol Sci. 2013;17(24):3272–8.

    CAS  Google Scholar 

  209. Savarino V, Pace F, Scarpignato C, Esoxx Study Group. Randomised clinical trial: mucosal protection combined with acid suppression in the treatment of non-erosive reflux disease - efficacy of Esoxx, a hyaluronic acid-chondroitin sulphate based bioadhesive formulation. Aliment Pharmacol Ther. 2017;45(5):631–42. https://doi.org/10.1111/apt.13914.

    Article  CAS  Google Scholar 

  210. Sigterman KE, van Pinxteren B, Bonis PA, Lau J, Numans ME. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2013;5:CD002095.

    Google Scholar 

  211. Salvatore S, Hauser B, Salvatoni A, Vandenplas Y. Oral ranitidine and duration of gastric pH >4.0 in infants with persisting reflux symptoms. Acta Paediatr. 2006;95:176–81.

    Google Scholar 

  212. Hemmink GJ, Bredenoord AJ, Weusten BL, Monkelbaan JF, Timmer R, Smout AJ. Esophageal pH-impedance monitoring in patients with therapy-resistant reflux symptoms: ‘on’ or ‘off’ proton pump inhibitor? Am J Gastroenterol. 2008;103:2446–53.

    Google Scholar 

  213. Turk H, Hauser B, Brecelj J, Vandenplas Y, Orel R. Effect of proton pump inhibition on acid, weakly acid and weakly alkaline gastro-esophageal reflux in children. World J Pediatr. 2013;9:36–41.

    CAS  Google Scholar 

  214. Wagner JA, Colombo JM. Medicine and media: the ranitidine debate. Clin Transl Sci. 2020;13(4):649–51.

    Google Scholar 

  215. Levy EI, Hoang DM, Vandenplas Y. The effects of proton pump inhibitors on the microbiome in young children. Acta Paediatr. 2020;109(8):1531–8. https://doi.org/10.1111/apa.15213.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  217. Ward RM, Kearns GL, Tammara B, Bishop P, O’Gorman MA, James LP, Katz MH, Maguire MK, Rath N, Meng X, Comer GM. A multicenter, randomized, open-label, pharmacokinetics and safety study of pantoprazole tablets in children and adolescents aged 6 through 16 years with gastroesophageal reflux disease. J Clin Pharmacol. 2011;51:876–87.

    CAS  Google Scholar 

  218. Ponrouch MP, Sautou-Miranda V, Boyer A, Bourdeaux D, Montagner A, Chopineau J. Proton pump inhibitor administration via nasogastric tube in pediatric practice: comparative analysis with protocol optimization. Int J Pharm. 2010;390:160–4.

    CAS  Google Scholar 

  219. Chen IL, Gao WY, Johnson AP, Niak A, Troiani J, Korvick J, Snow N, Estes K, Taylor A, Griebel D. Proton pump inhibitor use in infants: FDA reviewer experience. J Pediatr Gastroenterol Nutr. 2012;54:8–14.

    CAS  Google Scholar 

  220. Hudson B, Alderton A, Doocey C, Nicholson D, Toop L, Day AS. Crying and spilling--time to stop the overmedicalisation of normal infant behaviour. N Z Med J. 2012;125:119–26.

    Google Scholar 

  221. Kindt S, Imschoot J, Tack J. Prevalence of and impact of pantoprazole on nocturnal heartburn and associated sleep complaints in patients with erosive esophagitis. Dis Esophagus. 2011;24(8):531–7. https://doi.org/10.1111/j.1442-2050.2011.01189.x.

    Article  CAS  Google Scholar 

  222. Malcolm WF, Cotten CM. Metoclopramide, H2 blockers, and proton pump inhibitors: pharmacotherapy for gastroesophageal reflux in neonates. Clin Perinatol. 2012;39:99–109.

    Google Scholar 

  223. Golski CA, Rome ES, Martin RJ, Frank SH, Worley S, Sun Z, Hibbs AM. Pediatric specialists’ beliefs about gastroesophageal reflux disease in premature infants. Pediatrics. 2010;125:96–104.

    Google Scholar 

  224. Williams C, McColl KE. Review article: proton pump inhibitors and bacterial overgrowth. Aliment Pharmacol Ther. 2006;23:3–10.

    CAS  Google Scholar 

  225. Moledina DG, Perazella MA. PPIs and kidney disease: from AIN to CKD. J Nephrol. 2016;29(5):611–6. https://doi.org/10.1007/s40620-016-0309-2. Epub 2016 Apr 12.

    Article  CAS  Google Scholar 

  226. Trikha A, Baillargeon JG, Kuo YF, Tan A, Pierson K, Sharma G, Wilkinson G, Bonds RSD. Development of food allergies in patients with gastro-esophageal reflux disease treated with gastric acid suppressive medications. Pediatr Allergy Immunol. 2013;24:582–8.

    Google Scholar 

  227. Haenisch B, von Holt K, Wiese B, Prokein J, Lange C, Ernst A, Brettschneider C, König HH, Werle J, Weyerer S, Luppa M, Riedel-Heller SG, Fuchs A, Pentzek M, Weeg D, Bickel H, Broich K, Jessen F, Maier W, Scherer M. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):419–28. https://doi.org/10.1007/s00406-014-0554-0.

    Article  Google Scholar 

  228. Welu J, Metzger J, Bebensee S, Ahrendt A, Vasek M. Proton pump inhibitor use and risk of dementia in the veteran population. Fed Pract. 2019;36(Suppl 4):S27–31.

    Google Scholar 

  229. Shinozaki S, Osawa H, Kobayashi Y, Sakamoto H, Hayashi Y, Miura Y, Kawarai Lefor A, Yamamoto H. Long-term outcomes of patients with symptomatic gastroesophageal reflux disease treated with vonoprazan. Scand J Gastroenterol. 2018;53(8):897–904. https://doi.org/10.1080/00365521.2018.1486883.

    Article  CAS  Google Scholar 

  230. Cheng Y, Liu J, Tan X, Dai Y, Xie C, Li X, Lu Q, Kou F, Jiang H, Li J. Direct comparison of the efficacy and safety of vonoprazan versus proton-pump inhibitors for gastroesophageal reflux disease: a systematic review and meta-analysis. Dig Dis Sci. 2021;66(1):19–28. https://doi.org/10.1007/s10620-020-06141-5. Online ahead of print.

    Article  CAS  Google Scholar 

  231. Miyazaki H, Igarashi A, Takeuchi T, et al. Vonoprazan versus proton-pump inhibitors for healing gastroesophageal reflux disease: a systematic review. J Gastroenterol Hepatol. 2019;34(8):1316–28. https://doi.org/10.1111/jgh.14664.

    Article  CAS  Google Scholar 

  232. Helgadottir H, Bjornsson ES. Problems associated with deprescribing of proton pump inhibitors. Int J Mol Sci. 2019;20(21):5469. Published 2019 Nov 2. https://doi.org/10.3390/ijms20215469.

    Article  CAS  Google Scholar 

  233. Boghossian TA, Rashid FJ, Thompson W, et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017;3(3):CD011969. Published 2017 Mar 16. https://doi.org/10.1002/14651858.CD011969.pub2.

    Article  Google Scholar 

  234. Farrell B, Pottie K, Thompson W, et al. Deprescribing proton pump inhibitors: evidence-based clinical practice guideline. Can Fam Physician. 2017;63(5):354–64.

    Google Scholar 

  235. Bytzer P. Deprescribing proton pump inhibitors: why, when and how. Med J Aust. 2018;209:436–8.

    Google Scholar 

  236. McAteer J, Larison C, Lariviere C, Garrison MM, Goldin AB. Antireflux procedures for gastroesophageal reflux disease in children: influence of patient age on surgical management. JAMA Surg. 2014;149:56–62.

    Google Scholar 

  237. Smits MJ, Loots CM, Benninga MA, Omari TI, van Wijk MP. New insights in gastroesophageal reflux, esophageal function and gastric emptying in relation to dysphagia before and after anti-reflux surgery in children. Curr Gastroenterol Rep. 2013;15:351.

    CAS  Google Scholar 

  238. Patti MG. An evidence-based approach to the treatment of gastroesophageal reflux disease. JAMA Surg. 2016;151(1):73–8. https://doi.org/10.1001/jamasurg.2015.4233.

    Article  Google Scholar 

  239. Yadlapati R, Vaezi MF, Vela MF, Spechler SJ, Shaheen NJ, Richter J, Lacy BE, Katzka D, Katz PO, Kahrilas PJ, Gyawali PC, Gerson L, Fass R, Castell DO, Craft J, Hillman L, Pandolfino JE. Management options for patients with GERD and persistent symptoms on proton pump inhibitors: recommendations from an expert panel. Am J Gastroenterol. 2018;113(7):980–6. https://doi.org/10.1038/s41395-018-0045-4.

    Article  Google Scholar 

  240. Loots CM, van Herwaarden MY, Benninga MA, VanderZee DC, van Wijk MP, Omari TI. Gastroesophageal reflux, esophageal function, gastric emptying, and the relationship to dysphagia before and after antireflux surgery in children. J Pediatr. 2013;162:566–73.

    Google Scholar 

  241. Koivusalo AI, Pakarinen MP. Outcome of surgery for pediatric gastroesophageal reflux: clinical and endoscopic follow-up after 300 fundoplications in 279 consecutive patients. Scand J Surg. 2018;107(1):68–75.

    CAS  Google Scholar 

  242. Galmiche JP, Hatlebakk J, Attwood S, El C, Fiocca R, Eklund S, Långström G, Lind T, Lundell L, LOTUS Trial Collaborators. Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial. JAMA. 2011;305(19):1969–77. https://doi.org/10.1001/jama.2011.626.

    Article  CAS  Google Scholar 

  243. Spechler SJ, Lee E, Ahnen D, Goyal RK, Hirano I, Ramirez F, Raufman JP, Sampliner R, Schnell T, Sontag S, Vlahcevic ZR, Young R, Williford W. Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial. JAMA. 2001;285:2331–8.

    CAS  Google Scholar 

  244. Wijnhoven BP, Lally CJ, Kelly JJ, Myers JC, Watson DI. Use of antireflux medication after antireflux surgery. J Gastrointest Surg. 2008;12:510–7.

    Google Scholar 

  245. Esposito C, De Luca C, Alicchio F, Giurin I, Miele E, Staiano AM, Settimi A. Long-term outcome of laparoscopic Nissen procedure in pediatric patients with gastroesophageal reflux disease measured using the modified QPSG Roma III European Society for Pediatric Gastroenterology Hepatology and Nutrition’s questionnaire. J Laparoendosc Adv Surg Tech A. 2012;22:937–40.

    Google Scholar 

  246. Granero Cendón R, Ruiz Hierro C, Garrido Pérez JI, Vargas Cruz V, Lasso Betancor CE, Paredes Esteban RM. Evaluation of quality of life in patients operated on for gastroesophageal reflux in the pediatric age. Cir Pediatr. 2012;25:82–6.

    Google Scholar 

  247. Mauritz FA, van Herwaarden-Lindeboom MY, Stomp W, Zwaveling S, Fischer K, Houwen RH, Siersema PD, van der Zee DC. The effects and efficacy of antireflux surgery in children with gastroesophageal reflux disease: a systematic review. J Gastrointest Surg. 2011;15:1872–8.

    Google Scholar 

  248. Marret JB, Dupont-Lucas C, Petit T, Menahem B, Godet C, Ravasse P, Rod J. Safety of laparoscopic fundoplication in children under 5 kg: a comparative study. Surg Endosc. 2018;32(10):4191–9. https://doi.org/10.1007/s00464-018-6164-6. Epub 2018 Mar 30.

    Article  Google Scholar 

  249. Lopez-Fernandez S, Hernandez F, Hernandez-Martin S, Dominguez E, Ortiz R, Torre CD, Martinez L, Tovar JA. Failed Nissen fundoplication in children: causes and management. Eur J Pediatr Surg. 2014;24:79–82.

    Google Scholar 

  250. Hambraeus M, Arnbjörnsson E, Anderberg M. A literature review of the outcomes after robot-assisted laparoscopic and conventional laparoscopic Nissen fundoplication for gastro-esophageal reflux disease in children. Int J Med Robot. 2013;9(4):428.

    Google Scholar 

  251. Hill SJ, Wulkan ML. Cardiaplication as a novel antireflux procedure for infants: a proof of concept in an infant porcine model. J Laparoendosc Adv Surg Tech A. 2013;23:74–7.

    Google Scholar 

  252. Thomson M, Antao B, Hall S, Afzal N, Hurlstone P, Swain CP, Fritscher-Ravens A. Medium-term outcome of endoluminal gastroplication with the EndoCinch device in children. J Pediatr Gastroenterol Nutr. 2008;46:172–7.

    Google Scholar 

  253. Prakash Gyawali C, Fass R. Management of gastroesophageal reflux disease. Gastroenterology. 2018;154(2):302–18. https://doi.org/10.1053/j.gastro.2017.07.049.

    Article  Google Scholar 

  254. Chen S, Jarboe MD, Teitelbaum DH. Effectiveness of a transluminal endoscopic fundoplication for the treatment of pediatric gastroesophageal reflux disease. Pediatr Surg Int. 2012;28:229–34.

    Google Scholar 

  255. Islam S, Geiger JD, Coran AG, Teitelbaum DH. Use of radiofrequency ablation of the lower esophageal sphincter to treat recurrent gastroesophageal reflux disease. J Pediatr Surg. 2004;39(3):282–6; discussion 282-6. https://doi.org/10.1016/j.jpedsurg.2003.11.031.

    Article  Google Scholar 

  256. Gold BD, Gunasekaran T, Tolia V, Wetzler G, Conter H, Traxler B, Illueca M. Safety and symptom improvement with esomeprazole in adolescents with gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2007;45(5):520–9. https://doi.org/10.1097/MPG.0b013e318148c17c.

    Article  CAS  Google Scholar 

  257. Gilger MA, Tolia V, Vandenplas Y, Youssef NN, Traxler B, Illueca M. Safety and tolerability of esomeprazole in children with gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2008;46(5):524–33. https://doi.org/10.1097/MPG.0b013e318176b2cb.

    Article  CAS  Google Scholar 

  258. Baker R, Tsou VM, Tung T, Baker SS, Li H, Wang W, Rath N, Maguire MK, Comer GM. Clinical results from a randomized, double-blind, dose-ranging study of pantoprazole in children aged 1 through 5 years with symptomatic histologic or erosive esophagitis. Clin Pediatr (Phila). 2010;49(9):852–65. https://doi.org/10.1177/0009922810369253.

    Article  Google Scholar 

  259. Higginbotham TW. Effectiveness and safety of proton pump inhibitors in infantile gastroesophageal reflux disease. Ann Pharmacother. 2010;44(3):572–6. https://doi.org/10.1345/aph.1M519.

    Article  CAS  Google Scholar 

  260. 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(5):593–8. https://doi.org/10.1097/MPG.0b013e3181ddcf11.

    Article  CAS  Google Scholar 

  261. Winter H, Kum-Nji P, Mahomedy SH, Kierkus J, Hinz M, Li H, Maguire MK, Comer GM. 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(6):609–18. https://doi.org/10.1097/MPG.0b013e3181c2bf41.

    Article  CAS  Google Scholar 

  262. van der Pol RJ, Smits MJ, van Wijk MP, Omari TI, Tabbers MM, Benninga MA. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127(5):925–35. https://doi.org/10.1542/peds.2010-2719.

    Article  Google Scholar 

  263. Lee JH, Kim MJ, Lee JS, Choe YH. The effects of three alternative treatment strategies after 8 weeks of proton pump inhibitor therapy for GERD in children. Arch Dis Child. 2011;96(1):9–13. https://doi.org/10.1136/adc.2010.188565.

    Article  Google Scholar 

  264. Winter H, Gunasekaran T, Tolia V, Gottrand F, Barker PN, Illueca M. Esomeprazole for the treatment of GERD in infants ages 1-11 months. J Pediatr Gastroenterol Nutr. 2012;55(1):14–20. https://doi.org/10.1097/MPG.0b013e3182496b35.

    Article  CAS  Google Scholar 

  265. Ummarino D, Miele E, Masi P, Tramontano A, Staiano A, Vandenplas Y. Impact of antisecretory treatment on respiratory symptoms of gastroesophageal reflux disease in children. Dis Esophagus. 2012;25(8):671–7. https://doi.org/10.1111/j.1442-2050.2011.01301.x.

    Article  CAS  Google Scholar 

  266. Davidson G, Wenzl TG, Thomson M, Omari TI, Barker P, Lundborg P, Illueca M. Efficacy and safety of once-daily esomeprazole for the treatment of gastroesophageal reflux disease in neonatal patients. J Pediatr. 2013;163(3):692–8.e1-2. https://doi.org/10.1016/j.jpeds.2013.05.007.

    Article  CAS  Google Scholar 

  267. Tjon JA, Pe M, Soscia J, Mahant S. Efficacy and safety of proton pump inhibitors in the management of pediatric gastroesophageal reflux disease. Pharmacotherapy. 2013;33(9):956–71. https://doi.org/10.1002/phar.1299.

    Article  CAS  Google Scholar 

  268. Shashidhar H, Tolia V. Esophagitis in children: an update on current pharmacotherapy. Expert Opin Pharmacother. 2013;14(18):2475–87. https://doi.org/10.1517/14656566.2013.847921.

    Article  CAS  Google Scholar 

  269. Gold BD, Pilmer B, Kierkuś J, Hunt B, Perez MC, Gremse D, Gold BD, et al. Dexlansoprazole for heartburn relief in adolescents with symptomatic, nonerosive gastro-esophageal reflux disease. Dig Dis Sci. 2017;62(11):3059–68. https://doi.org/10.1007/s10620-017-4743-3.

    Article  CAS  Google Scholar 

  270. Gremse D, GOLD BD, Pilmer B, Hunt B, Korczowski B, Perez MC. Dual delayed-release dexlansoprazole for healing and maintenance of healed erosive esophagitis: a safety study in adolescents. Dig Dis Sci. 2019;64(2):493–502. https://doi.org/10.1007/s10620-018-5325-8.

    Article  CAS  Google Scholar 

  271. Shimizu T, Nakayama Y, Ishii E, Ida S, Satou T, Tokuhara D, Arai K, Nii M, Rydholm H, Yajima T, J-NEPECS (Japan Nexium Pediatrics Study) Group. Oral esomeprazole in Japanese pediatric patients with gastric acid-related disease: Safety, efficacy, and pharmacokinetics. Pediatr Int. 2019;61(1):87–95. https://doi.org/10.1111/ped.13733.

    Article  CAS  Google Scholar 

  272. Salvatore S, Vandenplas Y. Gastroesophageal reflux and cow milk allergy: is there a link? Pediatrics. 2002;110:972–84.

    Google Scholar 

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Authors and Affiliations

  1. Vrije Unversiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium

    Yvan Vandenplas

  2. Department of Gastroenterology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

    Sébastien Kindt

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  1. Section of Pediatric Gastroenterology Hepatology and Nutrition, University of Chicago, Chicago, IL, USA

    Stefano Guandalini

  2. Pediatric Liver, GI and Nutrition Center, Child Health, King’s College Hospital, London, UK

    Anil Dhawan

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Vandenplas, Y., Kindt, S. (2022). Gastroesophageal Reflux. In: Guandalini, S., Dhawan, A. (eds) Textbook of Pediatric Gastroenterology, Hepatology and Nutrition. Springer, Cham. https://doi.org/10.1007/978-3-030-80068-0_10

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