Gastroesophageal Reflux (GER) in the Preterm Baby

  • Christophe DupontEmail author


Gastroesophageal reflux (GER) is very common among preterm infants, but its real frequency is not well established. GER may be obvious, manifesting with regurgitations or emesis or more difficult to detect when associated with general symptoms such as apnea, bradycardia, pallor, oxygen desaturation, severe malaise, feeding difficulties with weight loss or poor growth (failure to thrive), crying, hematemesis, and melena. The origin probably resides in motor problems in some and in cow’s milk allergy in others. Diagnosis is difficult to make, in the absence of reference values. Impedancemetry coupled to a pH probe is interesting since reflux is frequently nonacid. The treatment should always be conservative and stepwise. None of the drugs used are licensed in this age range and some have severe adverse effect.


Preterm Gastroesophageal reflux Apnea pH meter Cow’s milk allergy Thickener Proton pump inhibitor Extensively hydrolyzed formulas Necrotizing enterocolitis 


  1. 1.
    Dhillon AS, Ewer AK. Diagnosis and management of gastrooesophageal reflux in preterm infants in neonatal intensive care units. Acta Paediatr. 2004;93:88–93.CrossRefPubMedGoogle Scholar
  2. 2.
    McGuire W, Henderson G, Fowlie PW. Feeding the preterm infant. BMJ. 2004;329(7476):1227–30.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Morgan J, Bombell S, McGuire W. Early trophic feeding versus enteral fasting for very preterm or very low birth weight infants. Cochrane Database Syst Rev. 2013;3:CD000504. doi: 10.1002/14651858.CD000504.CrossRefGoogle Scholar
  4. 4.
    Morgan J, Young L, McGuire W. Slow advancement of enteral feed volumes to prevent necrotizing enterocolitis in very low birth weight infants (VLBW). Cochrane Database Syst Rev. 2013;3:CD001241. doi: 10.1002/14651858.CD001241.CrossRefGoogle Scholar
  5. 5.
    Morgan J, Young L, McGuire W. Delayed introduction of progressive enteral feeds to prevent necrotizing enterocolitis in very low birth weight infants. Cochrane Database Syst Rev. 2013;5:CD001970.Google Scholar
  6. 6.
    SIFT Investigators group, Abbot J, Berrington JE, Boyle E, Dorling JS, Embleton NE, et al. Early enteral feeding strategies for very preterm infants: current evidence from Cochrane reviews. Arch Dis Child Fetal Neonatal Ed. 2013;98:F470–2.CrossRefGoogle Scholar
  7. 7.
    Basuki F, Hadiati DR, Turner T, McDonald S, Hakimi M. Dilute versus full strength formula in exclusively formula-fed preterm or low birth weight infants. Cochrane Database Syst Rev. 2013;11:CD007263. doi: 10.1002/14651858.CD007263.CrossRefGoogle Scholar
  8. 8.
    Shulman RJ, CN O, Smith EO. Evaluation of potential factors predicting attainment of full gavage feedings in preterm infants. Neonatology. 2011;99:38–44.CrossRefPubMedGoogle Scholar
  9. 9.
    Sankar MJ, Agarwal R, Mishra S, Deorari AK, Paul VK. Feeding of low birth weight infants. Indian J Pediatr. 2008;75:459–69.CrossRefPubMedGoogle Scholar
  10. 10.
    Omari TI, Barnett CP, Benninga A, et al. Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux disease. Gut. 2002;51:475–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Peter CS, Wiechers C, Bohnhorst B, Silny J, Poets CF. Influence of nasogastric tubes on gastroesophageal reflux in preterm infants: a multiple intraluminal impedance study. J Pediatr. 2002;141:277–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Ewer AK. Can pH monitoring reliably detect gastro-oesophageal reflux in preterm infants?. (Commentary to article by Grant L, Cochran D). Arch Dis Child Fetal Neonatal Ed. 2001;85:F157–8.Google Scholar
  13. 13.
    Salvatore S, Vandenplas Y. Gastroesophageal reflux and cow milk allergy: is there a link? Pediatrics. 2002;110:972–84.CrossRefPubMedGoogle Scholar
  14. 14.
    D’Netto MA, Herson VC, Hussain N, et al. Allergic gastroenteropathy in preterm infants. J Pediatr. 2000;137:480–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Coviello C, Rodriquez DC, Cecchi S, Tataranno ML, Farmeschi L, Mori A, et al. Different clinical manifestation of cow’s milk allergy in two preterm twins newborns. J Matern Fetal Neonatal Med. 2012;25(Suppl 1):132–3.CrossRefPubMedGoogle Scholar
  16. 16.
    Abdelhamid AE, Chuang SL, Hayes P, Fell JM. Evolution of in vitro cow’s milk protein-specific inflammatory and regulatory cytokine responses in preterm infants with necrotising enterocolitis. J Pediatr Gastroenterol Nutr. 2013;56(1):5–11.CrossRefPubMedGoogle Scholar
  17. 17.
    Baldassarre ME, Cappiello A, Laforgia N, Vanderhoof J. Allergic colitis in monozygotic preterm twins. Immunopharmacol Immunotoxicol. 2013;35(1):198–201.CrossRefPubMedGoogle Scholar
  18. 18.
    Manuyakorn W, Benjaponpitak S, Siripool K, Prempunpong C, Singvijarn P, Kamchaisatian W, et al. Cow milk protein allergy presenting as feeding intolerance and eosinophilia: case reports of three preterm neonates. Paediatr Int Child Health. 2015;35(4):337–41.CrossRefPubMedGoogle Scholar
  19. 19.
    Zachariassen G. Nutrition, growth, and allergic diseases among very preterm infants after hospital discharge. Dan Med J. 2013;60(2):B4588. ReviewPubMedGoogle Scholar
  20. 20.
    Corvaglia L, Mariani E, Aceti A, Galletti S, Faldella G. Extensively hydrolyzed protein formula reduces acid gastro-esophageal reflux in symptomatic preterm infants. Early Hum Dev. 2013;89(7):453–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Cordova J, Sriram S, Patton T, Jericho H, Gokhale R, Weinstein D, et al. Manifestations of cow’s-milk protein intolerance in preterm infants. J Pediatr Gastroenterol Nutr. 2016;62(1):140–4.CrossRefPubMedGoogle Scholar
  22. 22.
    Dupont C, Soulaines P, Lapillonne A, Donne N, Kalach N, Benhamou P. Atopy patch test for early diagnosis of cow's milk allergy in preterm infants. J Pediatr Gastroenterol Nutr. 2010;50(4):463–4.PubMedGoogle Scholar
  23. 23.
    Lucchini R, Bizzarri B, Giampietro S, DeCurtis M. Feeding intolerance in preterm infants: how to understand the warning signs. J Matern Fetal Neonatal Med. 2011;24(Suppl 1):72–4.CrossRefPubMedGoogle Scholar
  24. 24.
    Poets CF. Myth: gastroesophageal reflux is a pathological entity in the preterm infant. Semin Fetal Neonatal Med. 2011;16:259–63.CrossRefPubMedGoogle Scholar
  25. 25.
    Di Fiore J, Arko M, Herynk B, Martin R, Hibbs AM. Characterization of cardiorespiratory events following gastroesophageal reflux in preterm infants. J Perinatol. 2010;30:683–7.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Jadcherla SR, Gupta A, Fernandez S, Nelin LD, Castile R, Gest AL, et al. Spatiotemporal characteristics of acid refluxate and relationship to symptoms in premature and term infants with chronic lung disease. Am J Gastroenterol. 2008;103(3):720–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Dupont C, Kalach N, de Boissieu D, Barbet JP, Benhamou PH. Digestive endoscopy in neonates. J Pediatr Gastroenterol Nutr. 2005;40:406–20.CrossRefPubMedGoogle Scholar
  28. 28.
    Bredenoord AJ, Weusten BL, Timmer R, et al. Addition of esophageal impedance monitoring to pH monitoring increases the yield of symptom association analysis in patients off PPI therapy. Am J Gastroenterol. 2006;101:453–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Zerbib F, Roman S, Ropert A, et al. Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy. Am J Gastroenterol. 2006;101(9):1956–63.CrossRefPubMedGoogle Scholar
  30. 30.
    López-Alonso M, Moya MJ, Cabo JA, Ribas J, del Carmen Macías M, Silny J, et al. Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux. Pediatrics. 2006;118(2):e299–308.CrossRefPubMedGoogle Scholar
  31. 31.
    Zhang J, Li Z, Ge Y, Wang K, Xu Z, Xia Z, et al. Role of the twenty-four-hour esophageal multichannel intraluminal impedance-pH monitoring in preterm infants. Zhonghua Er Ke Za Zhi. 2014;52(4):298–302.PubMedGoogle Scholar
  32. 32.
    Indrio F, Magistà AM, Cavallo L, Francavilla R. Gastroesophageal reflux in preterm infants: how acid should it be?. Omari TI, Haslam RR, Lundborg P. Author’s response to letter. J Pediatr Gastroenterol Nutr. 2008;46(1):96.CrossRefPubMedGoogle Scholar
  33. 33.
    Rudolph CD, Mazur LJ, Liptak GS, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr. 2001;32(Suppl 2):S1–31.CrossRefPubMedGoogle Scholar
  34. 34.
    Vandenplas Y, Colin DR, Di Lorenzo C, Hassall E, Liptak G, Mazur L, et al. 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.CrossRefPubMedGoogle Scholar
  35. 35.
    Corvaglia L, Martini S, Aceti A, Arcuri S, Rossini R, Faldella G. Nonpharmacological management of gastroesophageal reflux in preterm infants. Biomed Res Int. 2013;2013:141967. doi: 10.1155/2013/141967. ReviewCrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Corvaglia L, Monari C, Martini S, Aceti A, Faldella G. Pharmacological therapy of gastroesophageal reflux in preterm infants. Gastroenterol Res Pract. 2013;2013:714564. doi: 10.1155/2013/714564. ReviewCrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Blumenthal I, Lealman GT. Effect of posture on gastrooesophageal reflux in the newborn. Arch Dis Child. 1982;57:555–6.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Omari TI, Rommel N, Staunton E, et al. Paradoxical impact of body positioning on gastroesophageal reflux and gastric emptying in the premature neonate. J Pediatr. 2004;145:194–200.CrossRefPubMedGoogle Scholar
  39. 39.
    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;151:585–90.CrossRefPubMedGoogle Scholar
  40. 40.
    Bhat RY, Rafferty GF, Hannam S, Greenough A. Acid gastroesophageal reflux in convalescent preterm infants: effect of posture and relationship to apnea. Pediatr Res. 2007;62(5):620–3.CrossRefPubMedGoogle Scholar
  41. 41.
    Birch JL, Newell SJ. Gastrooesophageal reflux disease in preterm infants: current management and diagnostic dilemmas. Arch Dis Child Fetal Neonatal Ed. 2009;94(5):F379–83.CrossRefPubMedGoogle Scholar
  42. 42.
    Poets CF. Gastroesophageal reflux: a critical review of its role in preterm infants. Pediatrics. 2004;113(2):e128–32. ReviewCrossRefPubMedGoogle Scholar
  43. 43.
    Corvaglia L, Ferlini M, Rotatori R, Paoletti V, Alessandroni R, Cocchi G, 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.CrossRefPubMedGoogle Scholar
  44. 44.
    Corvaglia L, Aceti A, Mariani E, Legnani E, Ferlini M, Raffaeli G, et al. Lack of efficacy of a starch-thickened preterm formula on gastro-oesophageal reflux in preterm infants: a pilot study. J Matern Fetal Neonatal Med. 2012;25(12):2735–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Clarke P, Robinson MJ. Thickening milk feeds may cause necrotising enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2004;89(3):F280.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Beal J, Silverman B, Bellant J, Young TE, Klontz K. Late onset necrotizing enterocolitis in infants following use of a xanthan gum-containing thickening agent. J Pediatr. 2012;161(2):354–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Kuschel CA, Harding JE. Multicomponent fortified human milk for promoting growth in preterm infants. Cochrane Database Syst Rev. 2004;(1):CD000343. Review Update in: Cochrane Database Syst Rev. 2016;(5):CD000343.Google Scholar
  48. 48.
    Aceti A, Corvaglia L, Paoletti V, Mariani E, Ancora G, Galletti S, et al. Protein content and fortification of human milk influence gastroesophageal reflux in preterm infants. J Pediatr Gastroenterol Nutr. 2009;49(5):613–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Corvaglia L, Aceti A, Mariani E, De Giorgi M, Capretti MG, Faldella G. The efficacy of sodium alginate (Gaviscon) for the treatment of gastro-oesophageal reflux in preterm infants. Aliment Pharmacol Ther. 2011;33(4):466–70.CrossRefPubMedGoogle Scholar
  50. 50.
    Wheatley E, Kennedy KA. Cross-over trial of treatment for bradycardia attributed to gastroesophageal reflux in preterm infants. J Pediatr. 2009;155(4):516–21.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Ng PC, Lee CH, Wong SP, Lam HS, Liu FY, So KW, et al. High-dose oral erythromycin decreased the incidence of parenteral nutrition-associated cholestasis in preterm infants. Gastroenterology. 2007;132(5):1726–39.CrossRefPubMedGoogle Scholar
  52. 52.
    Ng YY, PH S, Chen JY, Quek YW, JM H, Lee IC, et al. Efficacy of intermediate-dose oral erythromycin on very low birth weight infants with feeding intolerance. Pediatr Neonatol. 2012;53(1):34–40.CrossRefPubMedGoogle Scholar
  53. 53.
    Ng SC, Gomez JM, Rajadurai VS, Saw SM, Quak SH. Establishing enteral feeding in preterm infants with feeding intolerance: a randomized controlled study of low-dose erythromycin. J Pediatr Gastroenterol Nutr. 2003;37(5):554–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Jadcherla SR, Berseth CL. Effect of erythromycin on gastroduodenal contractile activity in developing neonates. J Pediatr Gastroenterol Nutr. 2003;37(5):554–8.Google Scholar
  55. 55.
    Bilali A, Galanis P, Bartsocas C, Sparos L, Velonakis E. H2-blocker therapy and incidence of necrotizing enterocolitis in preterm infants: a case-control study. Pediatr Neonatol. 2013;54(2):141–2.CrossRefPubMedGoogle Scholar
  56. 56.
    Omari TI, Haslam RR, Lundborg P, et al. Effect of omeprazole on acid gastroesophageal reflux and gastric acidity in preterm infants with pathological acid reflux. J Pediatr Gastroenterol Nutr. 2007;44:41–4.Google Scholar
  57. 57.
    Magistà AM, Indrio F, Baldassarre M, Bucci N, Menolascina A, Mautone A, et al. Multichannel intraluminal impedance to detect relationship between gastroesophageal reflux and apnoea of prematurity. Dig Liver Dis. 2007;39(3):216–21.CrossRefPubMedGoogle Scholar
  58. 58.
    Omari T, Lundborg P, Sandström M, Bondarov P, Fjellman M, Haslam R, et al. Pharmacodynamics and systemic exposure of esomeprazole in preterm infants and term neonates with gastroesophageal reflux disease. J Pediatr. 2009;155(2):222–8.CrossRefPubMedGoogle Scholar
  59. 59.
    Davidson G, Wenzl TG, Thomson M, Omari T, Barker P, Lundborg P, et al. Efficacy and safety of once-daily esomeprazole for the treatment of gastroesophageal reflux disease in neonatal patients. J Pediatr. 2013;163(3):692–8.CrossRefPubMedGoogle Scholar
  60. 60.
    Terrin G, Passariello A, Ruggieri A, et al. Increased risk of infections in gastric acidity inhibitors treated newborn. Dig Liver Dis. 2006;38:A94.Google Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Necker HospitalParisFrance

Personalised recommendations