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Reflux in Pediatrics

  • Nina Gluchowski
  • Rachel Rosen
Chapter

Abstract

Gastroesophageal reflux (GER) is the passage of gastric contents into the esophagus with or without regurgitation or vomiting. This process occurs multiple times a day in healthy infants and children and most episodes cause few or no symptoms. When the refluxate reaches the mouth, the reflux is caused regurgitation. GER becomes gastroesophageal reflux disease (GERD) when the passage of gastric contents into the esophagus is associated with troublesome symptoms and/or complications. However, deciding what symptoms are troublesome is often difficult in children who are non-verbal or who are unable to accurately convey symptoms [1, 2].

Abbreviations

AHR

Airway hyper-responsiveness

AR

Anti regurgitation

BAL

Broncho-alveolar lavage

COPD

Chronic obstructive pulmonary disease

GER

Gastroesophageal reflux

GERD

Gastroesophageal reflux disease

H2

Histamine2

LARS

Laparoscopic anti-reflux surgery

LES

Lower esophageal sphincter

LPR

Laryngo-pharyngeal reflux

MII

Multiple intraluminal impedance

NASPGHAN

North American Society of Gastroenterology, Hepatology and Nutrition

OSA

Obstructive sleep apnea

pH-MII

Multiple intraluminal impedance with pH

PPI

Proton pump inhibitor

SIDS

Sudden infant death syndrome

TLESR

Transient lower esophageal sphincter relaxation

tLESRs

Transient lower esophageal sphincter relaxations

VCD

Vocal cord dysfunction

References

  1. 1.
    Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009;49(4):498–547.  https://doi.org/10.1097/MPG.0b013e3181b7f563.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Sherman PM, Hassall E, Fagundes-Neto U, et al. A global, evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric population. Am J Gastroenterol. 2009;104:1278–95; quiz1296.  https://doi.org/10.1038/ajg.2009.129.CrossRefPubMedGoogle Scholar
  3. 3.
    Nelson SP, Chen EH, Syniar GM, Christoffel KK. Prevalence of symptoms of gastroesophageal reflux during infancy: a pediatric practice-based survey. Arch Pediatr Adolesc Med. 1997;151(6):569–72.  https://doi.org/10.1001/archpedi.1997.02170430035007.CrossRefPubMedGoogle Scholar
  4. 4.
    Campanozzi A, Boccia G, Pensabene L, et al. Prevalence and natural history of gastroesophageal reflux: pediatric prospective survey. Pediatrics. 2009;123(3):779–83.  https://doi.org/10.1542/peds.2007-3569.CrossRefPubMedGoogle Scholar
  5. 5.
    Miyazawa R, Tomomasa T, Kaneko H, Tachibana A, Ogawa T, Morikawa A. Prevalence of gastro-esophageal reflux-related symptoms in Japanese infants. Pediatr Int. 2002;44(5):513–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Osatakul S, Sriplung H, Puetpaiboon A, Junjana C-O, Chamnongpakdi S. Prevalence and natural course of gastroesophageal reflux symptoms: a 1-year cohort study in Thai infants. J Pediatr Gastroenterol Nutr. 2002;34(1):63–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Hegar B, Boediarso A, Firmansyah A, Vandenplas Y. Investigation of regurgitation and other symptoms of gastroesophageal reflux in Indonesian infants. World J Gastroenterol. 2004;10(12):1795–7.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Martin AJ, Pratt N, Kennedy JD, et al. Natural history and familial relationships of infant spilling to 9 years of age. Pediatrics. 2002;109(6):1061–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Chen J-H, Wang H-Y, Lin HH, Wang C-C, Wang L-Y. Prevalence and determinants of gastroesophageal reflux symptoms in adolescents. J Gastroenterol Hepatol. 2014;29(2):269–75.  https://doi.org/10.1111/jgh.12330.CrossRefPubMedGoogle Scholar
  10. 10.
    Koebnick C, Getahun D, Smith N, Porter AH, Der-Sarkissian JK, Jacobsen SJ. Extreme childhood obesity is associated with increased risk for gastroesophageal reflux disease in a large population-based study. Int J Pediatr Obes. 2011;6(2-2):e257–63.  https://doi.org/10.3109/17477166.2010.491118.CrossRefPubMedGoogle Scholar
  11. 11.
    Debley JS, Carter ER, Redding GJ. Prevalence and impact of gastroesophageal reflux in adolescents with asthma: a population-based study. Pediatr Pulmonol. 2006;41(5):475–81.  https://doi.org/10.1002/ppul.20399.CrossRefPubMedGoogle Scholar
  12. 12.
    Gunasekaran TS, Dahlberg M, Ramesh P, Namachivayam G. Prevalence and associated features of gastroesophageal reflux symptoms in a Caucasian-predominant adolescent school population. Dig Dis Sci. 2008;53(9):2373–9.  https://doi.org/10.1007/s10620-007-0150-5.CrossRefPubMedGoogle Scholar
  13. 13.
    Woodley FW, Machado RS, Hayes D, et al. Children with cystic fibrosis have prolonged chemical clearance of acid reflux compared to symptomatic children without cystic fibrosis. Dig Dis Sci. 2014;59(3):623–30.  https://doi.org/10.1007/s10620-013-2950-0.CrossRefPubMedGoogle Scholar
  14. 14.
    Werlin SL, Dodds WJ, Hogan WJ, Arndorfer RC. Mechanisms of gastroesophageal reflux in children. J Pediatr. 1980;97(2):244–9.  https://doi.org/10.1111/j.1572-0241.2001.03865.x.CrossRefPubMedGoogle Scholar
  15. 15.
    Dent J, Holloway RH, Toouli J, Dodds WJ. Mechanisms of lower oesophageal sphincter incompetence in patients with symptomatic gastrooesophageal reflux. Gut. 1988;29(8):1020–8.  https://doi.org/10.1136/gut.29.8.1020.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Cucchiara S, Bortolotti M, Minella R, Auricchio S. Fasting and postprandial mechanisms of gastroesophageal reflux in children with gastroesophageal reflux disease. Dig Dis Sci. 1993;38(1):86–92.CrossRefPubMedGoogle Scholar
  17. 17.
    Omari TI, Barnett CP, Benninga MA, et al. Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux disease. Gut. 2002;51(4):475–9.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Omari TI, Barnett C, Snel A, et al. Mechanisms of gastroesophageal reflux in healthy premature infants. J Pediatr. 1998;133(5):650–4.  https://doi.org/10.1016/s0022-3476(98)70106-4.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    van Wijk M, Knüppe F, Omari T, de Jong J, Benninga M. Evaluation of gastroesophageal function and mechanisms underlying gastroesophageal reflux in infants and adults born with esophageal atresia. J Pediatr Surg. 2013;48(12):2496–505.  https://doi.org/10.1016/j.jpedsurg.2013.07.024.CrossRefPubMedGoogle Scholar
  20. 20.
    Jadcherla SR, Chan CY, Moore R, Malkar M, Timan CJ, Valentine CJ. Impact of feeding strategies on the frequency and clearance of acid and nonacid gastroesophageal reflux events in dysphagic neonates. J Parenter Enter Nutr. 2012;36(4):449–55.  https://doi.org/10.1177/0148607111415980.CrossRefGoogle Scholar
  21. 21.
    Knatten CK, Åvitsland TL, Medhus AW, et al. Gastric emptying in children with gastroesophageal reflux and in healthy children. J Pediatr Surg. 2013;48(9):1856–61.  https://doi.org/10.1016/j.jpedsurg.2013.03.076.CrossRefPubMedGoogle Scholar
  22. 22.
    Orenstein SR, Cohn JF, Shalaby TM, Kartan R. Reliability and validity of an infant gastroesophageal reflux questionnaire. Clin Pediatr. 1993;32(8):472–84.  https://doi.org/10.1177/000992289303200806.CrossRefGoogle Scholar
  23. 23.
    Orenstein SR, Shalaby TM, Cohn JF. Reflux symptoms in 100 normal infants: diagnostic validity of the infant gastroesophageal reflux questionnaire. Clin Pediatr. 1996;35(12):607–14.  https://doi.org/10.1177/000992289603501201.CrossRefGoogle Scholar
  24. 24.
    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(2):96–8.PubMedGoogle Scholar
  25. 25.
    Gupta SK, Hassall E, Chiu Y-L, Amer F, Heyman MB. Presenting symptoms of nonerosive and erosive esophagitis in pediatric patients. Dig Dis Sci. 2006;51(5):858–63.  https://doi.org/10.1007/s10620-006-9095-3.CrossRefPubMedGoogle Scholar
  26. 26.
    Chiu J-Y, Wu J-F, Ni Y-H. Correlation between gastroesophageal reflux disease questionnaire and erosive esophagitis in school-aged children receiving endoscopy. Pediatr Neonatol. 2014;55(6):439–43.  https://doi.org/10.1016/j.pedneo.2014.01.004.CrossRefPubMedGoogle Scholar
  27. 27.
    Hochman JA, Favaloro-Sabatier J. Tolerance and reliability of wireless pH monitoring in children. J Pediatr Gastroenterol Nutr. 2005;41(4):411–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Croffie JM, Fitzgerald JF, Molleston JP, et al. Accuracy and tolerability of the Bravo catheter-free pH capsule in patients between the ages of 4 and 18 years. J Pediatr Gastroenterol Nutr. 2007;45(5):559–63.  https://doi.org/10.1097/MPG.0b013e3180dc9349.CrossRefPubMedGoogle Scholar
  29. 29.
    Wenner J, Johansson J, Johnsson F, Öberg S. Optimal thresholds and discriminatory power of 48-h wireless esophageal pH monitoring in the diagnosisof GERD. Am J Gastroenterol. 2007;102(9):1862–9.  https://doi.org/10.1111/j.1572-0241.2007.01269.x.CrossRefPubMedGoogle Scholar
  30. 30.
    Mahajan L, Wyllie R, Oliva L, Balsells F, Steffen R, Kay M. Reproducibility of 24-hour intraesophageal pH monitoring in pediatric patients. Pediatrics. 1998;101(2):260–3.  https://doi.org/10.1542/peds.101.2.260.CrossRefPubMedGoogle Scholar
  31. 31.
    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(2):167–72.  https://doi.org/10.1053/S1542-3565(05)00854-2.CrossRefPubMedGoogle Scholar
  32. 32.
    Rosen R, Hart K, Warlaumont M. Incidence of gastroesophageal reflux during transpyloric feeds. J Pediatr Gastroenterol Nutr. 2011;52(5):532–5.  https://doi.org/10.1097/MPG.0b013e31820596f8.CrossRefPubMedGoogle Scholar
  33. 33.
    Holbrook JT, Wise RA, Gold BD, Blake K. Randomized clinical trial of lansoprazole for poorly controlled asthma in children: the American Lung Association Asthma Clinical Research Centers. JAMA. 2012;307:373.  https://doi.org/10.1001/jama.2011.2035.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Peter CS, Wiechers C, Bohnhorst B, Silny J, Poets CF. Detection of small bolus volumes using multiple intraluminal impedance in preterm infants. J Pediatr Gastroenterol Nutr. 2003;36(3):381–4.CrossRefPubMedGoogle Scholar
  35. 35.
    Dalby K, Nielsen RG, Markoew S, Kruse-Andersen S, Husby S. Reproducibility of 24-hour combined multiple intraluminal impedance (MII) and pH measurements in infants and children. Evaluation of a diagnostic procedure for gastroesophageal reflux disease. Dig Dis Sci. 2007;52(9):2159–65.  https://doi.org/10.1007/s10620-006-9731-y.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Wenzl TG. Investigating esophageal reflux with the intraluminal impedance technique. J Pediatr Gastroenterol Nutr. 2002;34(3):261–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Wenzl TG, Moroder C, Trachterna M, et al. Esophageal pH monitoring and impedance measurement: a comparison of two diagnostic tests for gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 2002;34(5):519–23.CrossRefPubMedGoogle Scholar
  38. 38.
    Rosen R, Amirault J, Giligan E, Khatwa U, Nurko S. Intraesophageal pressure recording improves the detection of cough during multichannel intraluminal impedance testing in children. J Pediatr Gastroenterol Nutr. 2014;58(1):22–6.  https://doi.org/10.1097/MPG.0b013e3182a80059.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Rosen R, Amirault J, Heinz N, Litman H, Khatwa U. The sensitivity of acoustic cough recording relative to intraesophageal pressure recording and patient report during reflux testing. Neurogastroenterol Motil. 2014;26(11):1635–41.  https://doi.org/10.1111/nmo.12445.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Arbizu RA, Rodriguez L. Use of Clostridium botulinum toxin in gastrointestinal motility disorders in children. World J Gastrointest Endosc. 2015;7(5):433–7.  https://doi.org/10.4253/wjge.v7.i5.433.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Rosen R, Amirault J, Johnston N, et al. The utility of endoscopy and multichannel intraluminal impedance testing in children with cough and wheezing. Pediatr Pulmonol. 2014;49(11):1090–6.  https://doi.org/10.1002/ppul.22949.CrossRefPubMedGoogle Scholar
  42. 42.
    Ravelli AM, Panarotto MB, Verdoni L, Consolati V, Bolognini S. Pulmonary aspiration shown by scintigraphy in gastroesophageal reflux-related respiratory disease. Chest. 2006;130(5):1520–6.  https://doi.org/10.1378/chest.130.5.1520.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    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(5):1557–64.  https://doi.org/10.1378/chest.07-0316.CrossRefPubMedGoogle Scholar
  44. 44.
    Grabowski M, Kasran A, Seys S, et al. Pepsin and bile acids in induced sputum of chronic cough patients. Respir Med. 2011;105(8):1257–61.  https://doi.org/10.1016/j.rmed.2011.04.015.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Hayat JO, Gabieta-Somnez S, Yazaki E, et al. Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease. Gut. 2015;64(3):373–80.  https://doi.org/10.1136/gutjnl-2014-307049.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Rosen R, Johnston N, Hart K, Khatwa U, Nurko S. The presence of pepsin in the lung and its relationship to pathologic gastro-esophageal reflux. Neurogastroenterol Motil. 2012;24(2):129–33, e84-5.  https://doi.org/10.1111/j.1365-2982.2011.01826.x.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Orenstein SR, Whitington PF, Orenstein DM. The infant seat as treatment for gastroesophageal reflux. N Engl J Med. 1983;309(13):760–3.  https://doi.org/10.1056/NEJM198309293091304.CrossRefPubMedGoogle Scholar
  48. 48.
    Vandenplas Y, Sacre-Smits L. Seventeen-hour continuous esophageal pH monitoring in the newborn. J Pediatr Gastroenterol Nutr. 1985;4(3):356–61.  https://doi.org/10.1097/00005176-198506000-00006.CrossRefPubMedGoogle Scholar
  49. 49.
    Ewer AK, James ME, Tobin JM. Prone and left lateral positioning reduce gastro-oesophageal reflux in preterm infants. Arch Dis Child Fetal Neonatal Ed. 1999;81(3):F201–5.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    van Wijk MP, Benninga MA, Dent J, et al. Effect of body position changes on postprandial gastroesophageal reflux and gastric emptying in the healthy premature neonate. J Pediatr. 2007;151(6):585–90, 590.e1-2.  https://doi.org/10.1016/j.jpeds.2007.06.015.CrossRefPubMedGoogle Scholar
  51. 51.
    Corvaglia L, Rotatori R, Ferlini M, Aceti A, Ancora G, Faldella G. The effect of body positioning on gastroesophageal reflux in premature infants: evaluation by combined impedance and pH monitoring. J Pediatr. 2007;151(6):591–6, 596.e1.  https://doi.org/10.1016/j.jpeds.2007.06.014.CrossRefPubMedGoogle Scholar
  52. 52.
    American Academy of Pediatrics Task Force on Sudden Infant Death Syndrome. The changing concept of sudden infant death syndrome: diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk. Pediatrics. 2005;116(5):1245–55.  https://doi.org/10.1542/peds.2005-1499.CrossRefGoogle Scholar
  53. 53.
    Chao HC, Vandenplas Y. Comparison of the effect of a cornstarch thickened formula and strengthened regular formula on regurgitation, gastric emptying and weight gain in infantile regurgitation. Dis Esophagus. 2007;20(2):155–60.  https://doi.org/10.1111/j.1442-2050.2007.00662.x.CrossRefPubMedGoogle Scholar
  54. 54.
    Khoshoo V, Ross G, Brown S, Edell D. Smaller volume, thickened formulas in the management of gastroesophageal reflux in thriving infants. J Pediatr Gastroenterol Nutr. 2000;31(5):554–6.CrossRefPubMedGoogle Scholar
  55. 55.
    Corvaglia L, Ferlini M, Rotatori R, et al. Starch thickening of human milk is ineffective in reducing the gastroesophageal reflux in preterm infants: a crossover study using intraluminal impedance. J Pediatr. 2006;148(2):265–8.  https://doi.org/10.1016/j.jpeds.2005.09.034.CrossRefPubMedGoogle Scholar
  56. 56.
    Bailey DJ, Andres JM, Danek GD, Pineiro-Carrero VM. Lack of efficacy of thickened feeding as treatment for gastroesophageal reflux. J Pediatr. 1987;110(2):187–9.  https://doi.org/10.1016/S0022-3476(87)80151-8.CrossRefPubMedGoogle Scholar
  57. 57.
    Wenzl TG, Schneider S, Scheele F, Silny J, Heimann G, Skopnik H. Effects of thickened feeding on gastroesophageal reflux in infants: a placebo-controlled crossover study using intraluminal impedance. Pediatrics. 2003;111(4):e355–9.  https://doi.org/10.1542/peds.111.4.e355.CrossRefPubMedGoogle Scholar
  58. 58.
    Xinias I, Mouane N, Le Luyer B, et al. Cornstarch thickened formula reduces oesophageal acid exposure time in infants. Dig Liver Dis. 2005;37(1):23–7.  https://doi.org/10.1016/j.dld.2004.07.015.CrossRefPubMedGoogle Scholar
  59. 59.
    Orenstein SR, Magill HL, Brooks P. Thickening of infant feedings for therapy of gastroesophageal reflux. J Pediatr. 1987;110(2):181–6.  https://doi.org/10.1016/s0022-3476(87)80150-6.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Chao H-C, Vandenplas Y. Effect of cereal-thickened formula and upright positioning on regurgitation, gastric emptying, and weight gain in infants with regurgitation. Nutrition. 2007;23(1):23–8.  https://doi.org/10.1016/j.nut.2006.10.003.CrossRefPubMedGoogle Scholar
  61. 61.
    Hill DJ, Hudson IL, Sheffield LJ, Shelton MJ, Menahem S, Hosking CS. A low allergen diet is a significant intervention in infantile colic: results of a community-based study. J Allergy Clin Immunol. 1995;96(6 Pt 1):886–92.CrossRefPubMedGoogle Scholar
  62. 62.
    Jakobsson I, Lothe L, Ley D, Borschel MW. Effectiveness of casein hydrolysate feedings in infants with colic. Acta Paediatr. 2000;89(1):18–21.CrossRefPubMedGoogle Scholar
  63. 63.
    Lucassen PLBJ, Assendelft WJJ, Gubbels JW, van Eijk JT, Douwes AC. Infantile colic: crying time reduction with a whey hydrolysate: a double-blind, randomized, placebo-controlled trial. Pediatrics. 2000;106(6):1349–54.  https://doi.org/10.1542/peds.106.6.1349.CrossRefPubMedGoogle Scholar
  64. 64.
    Heine RG. Gastroesophageal reflux disease, colic and constipation in infants with food allergy. Curr Opin Allergy Clin Immunol. 2006;6(3):220–5.  https://doi.org/10.1097/01.all.0000225164.06016.5d.CrossRefPubMedGoogle Scholar
  65. 65.
    Borrelli O, Mancini V, Thapar N, et al. Cow’s milk challenge increases weakly acidic reflux in children with cow’s milk allergy and gastroesophageal reflux disease. J Pediatr. 2012;161(3):476–481.e1.  https://doi.org/10.1016/j.jpeds.2012.03.002.CrossRefPubMedGoogle Scholar
  66. 66.
    Scott DR, Simon RA. Supraesophageal reflux: correlation of position and occurrence of acid reflux; effect of head-of-bed elevation on supine reflux. J Allergy Clin Immunol Pract. 2015.  https://doi.org/10.1016/j.jaip.2014.11.019.
  67. 67.
    Piesman M, Hwang I, Maydonovitch C, Wong RKH. Nocturnal reflux episodes following the administration of a standardized meal. Does timing matter? Am J Gastroenterol. 2007;102(10):2128–34.  https://doi.org/10.1111/j.1572-0241.2007.01348.x.CrossRefPubMedGoogle Scholar
  68. 68.
    Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach. Arch Intern Med. 2006;166(9):965–71.  https://doi.org/10.1001/archinte.166.9.965.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Tolia V, Youssef NN, Gilger MA, Traxler B, Illueca M. Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study. BMC Pediatr. 2010;10(1):41.  https://doi.org/10.1186/1471-2431-10-41.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Faure C, Michaud L, Shaghaghi EK, et al. Lansoprazole in children: pharmacokinetics and efficacy in reflux oesophagitis. Aliment Pharmacol Ther. 2001;15(9):1397–402.  https://doi.org/10.1046/j.1365-2036.2001.01076.x.CrossRefPubMedGoogle Scholar
  71. 71.
    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(1):41–4.  https://doi.org/10.1097/01.mpg.0000252190.97545.07.CrossRefPubMedGoogle Scholar
  72. 72.
    Omari T, Davidson G, Bondarov P, Nauclér E, Nilsson C, Lundborg P. 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.  https://doi.org/10.1097/MPG.0b013e31812e012f.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Moore DJ, Tao B, Lines DR, Hirte C, Heddle ML. Double-blind placebo-controlled trial of omeprazole in irritable infants with gastroesophageal reflux. J Pediatr. 2003.  https://doi.org/10.1067/S0022-3476(03)00207-5.
  74. 74.
    Orenstein SR, Blumer JL, Faessel HM, et al. Ranitidine, 75 mg, over-the-counter dose: pharmacokinetic and pharmacodynamic effects in children with symptoms of gastro-oesophageal reflux. Aliment Pharmacol Ther. 2002;16(5):899–907.  https://doi.org/10.1046/j.1365-2036.2002.01243.x.CrossRefPubMedGoogle Scholar
  75. 75.
    Sutphen JL, Dillard VL. Effect of ranitidine on twenty-four-hour gastric acidity in infants. J Pediatr. 1989;114(3):472–4.  https://doi.org/10.1016/s0022-3476(89)80576-1.CrossRefPubMedGoogle Scholar
  76. 76.
    Hyman PE, Garvey TQ, Abrams CE. Tolerance to intravenous ranitidine. J Pediatr. 1987;110(5):794–6.CrossRefPubMedGoogle Scholar
  77. 77.
    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(9):1097–107.  https://doi.org/10.1046/j.1365-2036.2003.01559.x.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Jordan B, Heine RG, Meehan M, Catto-Smith AG, Lubitz L. Effect of antireflux medication, placebo and infant mental health intervention on persistent crying: a randomized clinical trial. J Paediatr Child Health. 2006;42(1-2):49–58.  https://doi.org/10.1111/j.1440-1754.2006.00786.x.CrossRefPubMedGoogle Scholar
  79. 79.
    Rosen R, Amirault J, Liu H, et al. Changes in gastric and lung microflora with acid suppression. JAMA Pediatr. 2014;168(10):932–7.  https://doi.org/10.1001/jamapediatrics.2014.696.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    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(4):514–520.e514.  https://doi.org/10.1016/j.jpeds.2008.09.054.CrossRefPubMedGoogle Scholar
  81. 81.
    Canani RB, Cirillo P, Roggero P, et al. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics. 2006;117(5):e817–20.  https://doi.org/10.1542/peds.2005-1655.CrossRefPubMedGoogle Scholar
  82. 82.
    Dial S, Delaney JAC, Barkun AN, Suissa S. Use of gastric acid–suppressive agents and the risk of community-acquired Clostridium difficile–associated disease. JAMA. 2005;294(23):2989–95.  https://doi.org/10.1001/jama.294.23.2989.CrossRefPubMedGoogle Scholar
  83. 83.
    Trikha A, Baillargeon JG, Kuo Y-F, et al. Development of food allergies in patients with gastroesophageal reflux disease treated with gastric acid suppressive medications. Pediatr Allergy Immunol. 2013;24(6):582–8.  https://doi.org/10.1111/pai.12103.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Wagner T, Burns JL. Anti-inflammatory properties of macrolides. Pediatr Infect Dis J. 2007.  https://doi.org/10.1097/01.inf.0000253037.90204.9f.
  85. 85.
    Di Lorenzo C, Orenstein S. Fundoplication: friend or foe? J Pediatr Gastroenterol Nutr. 2002;34(2):117–24.CrossRefPubMedGoogle Scholar
  86. 86.
    Berquist WE, Fonkalsrud EW, Ament ME. Effectiveness of Nissen fundoplication for gastroesophageal reflux in children as measured by 24-hour intraesophageal pH monitoring. J Pediatr Surg. 1981;16(6):872–5.CrossRefPubMedGoogle Scholar
  87. 87.
    Fung KP, Seagram G, Pasieka J, Trevenen C, Machida H, Scott B. Investigation and outcome of 121 infants and children requiring Nissen fundoplication for the management of gastroesophageal reflux. Clin Invest Med. 1990;13(5):237–46.PubMedGoogle Scholar
  88. 88.
    Lundell L, Attwood S, Ell C, et al. Comparing laparoscopic antireflux surgery with esomeprazole in the management of patients with chronic gastro-oesophageal reflux disease: a 3-year interim analysis of the LOTUS trial. Gut. 2008;57(9):1207–13.  https://doi.org/10.1136/gut.2008.148833.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Lee SL, Shabatian H, Hsu J-W, Applebaum H, Haigh PI. Hospital admissions for respiratory symptoms and failure to thrive before and after Nissen fundoplication. J Pediatr Surg. 2008;43(1):59–63; discussion 63-5.  https://doi.org/10.1016/j.jpedsurg.2007.09.020.CrossRefPubMedGoogle Scholar
  90. 90.
    Barnhart DC, Hall M, Mahant S, et al. Effectiveness of fundoplication at the time of gastrostomy in infants with neurological impairment. JAMA Pediatr. 2013;167(10):911–8.  https://doi.org/10.1001/jamapediatrics.2013.334.CrossRefPubMedGoogle Scholar
  91. 91.
    Goldin AB, Sawin R, Seidel KD, Flum DR. Do antireflux operations decrease the rate of reflux-related hospitalizations in children? Pediatrics. 2006;118(6):2326–33.  https://doi.org/10.1542/peds.2006-2212.CrossRefPubMedGoogle Scholar
  92. 92.
    Boesch RP, Acton JD. Outcomes of fundoplication in children with cystic fibrosis. J Pediatr Surg. 2007;42(8):1341–4.  https://doi.org/10.1016/j.jpedsurg.2007.03.030.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Pegna V, Mickevičius A, Tsang C. How useful is antireflux surgery in lung transplant patients with gastroesophageal reflux? Medicina (Kaunas). 2014;50(6):318–22.  https://doi.org/10.1016/j.medici.2014.11.006.CrossRefGoogle Scholar
  94. 94.
    Vakil N. Review article: the role of surgery in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2007;25(12):1365–72.  https://doi.org/10.1111/j.1365-2036.2007.03333.x.CrossRefPubMedGoogle Scholar
  95. 95.
    Rosen R. Gastroesophageal reflux in infants. JAMA Pediatr. 2014;168(1):83–9.  https://doi.org/10.1001/jamapediatrics.2013.2911.CrossRefPubMedGoogle Scholar
  96. 96.
    Heyland DK, Drover JW, MacDonald S, Novak F, Lam M. Effect of postpyloric feeding on gastroesophageal regurgitation and pulmonary microaspiration: results of a randomized controlled trial. Crit Care Med. 2001;29(8):1495–501.CrossRefPubMedGoogle Scholar
  97. 97.
    Srivastava R, Downey EC, O’Gorman M, et al. Impact of fundoplication versus gastrojejunal feeding tubes on mortality and in preventing aspiration pneumonia in young children with neurologic impairment who have gastroesophageal reflux disease. Pediatrics. 2009;123(1):338–45.  https://doi.org/10.1542/peds.2007-1740.CrossRefPubMedGoogle Scholar
  98. 98.
    Lien HC, Chang CS, Yeh HZ. The effect of jejunal meal feeding on gastroesophageal reflux. Scand J Gastroenterol. 2001;36(4):343–6.  https://doi.org/10.1080/00365520121289.CrossRefPubMedGoogle Scholar
  99. 99.
    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(3):407–12.  https://doi.org/10.1053/jpsu.2002.30849.CrossRefPubMedGoogle Scholar
  100. 100.
    Misra S, Macwan K, Albert V. Transpyloric feeding in gastroesophageal-reflux-associated apnea in premature infants. Acta Paediatr. 2007;96(10):1426–9.  https://doi.org/10.1111/j.1651-2227.2007.00442.x.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Gastroenterology, Hepatology and Nutrition, Aerodigestive CenterBoston Children’s HospitalBostonUSA

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