Skip to main content
SpringerLink
Log in

Characteristics of esophageal refluxate and symptoms in infants compared between pre-treatment and on treatment with proton pump inhibitors

  • Article
  • Published:
Journal of Perinatology Submit manuscript

Abstract

Objective

To examine longitudinal pH-impedance characteristics from those infants who remained on proton pump inhibitors therapy for gastroesophageal reflux disease (GERD) as parents/providers refused to discontinue therapy after 4 weeks.

Study design

Eighteen infants with acid reflux index >3% underwent treatment, and pH-impedance data were compared prior to and on proton pump inhibitors at 42 ± 1 and 46 ± 1 weeks’ postmenstrual age, respectively. Esophageal acid and bolus exposure, symptoms and swallowing characteristics were examined.

Results

Proton pump inhibitors reduces the acid-mediated effects of reflux but modifies impedance and clearance mechanisms (P < 0.05). Prolonged therapy did not reduce symptoms (P > 0.05). Infants evaluated while on proton pump inhibitors were 1.8 times more likely to have swallows before and after reflux.

Conclusions

Prescription of proton pump inhibitors for objectively determined GERD should have time limits, as prolonged treatment can result in prolonged esophageal bolus clearance time without relieving symptoms.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1: Association of swallows with gastroesophageal reflux events in pH-impedance study.
Fig. 2: pH-impedance patterns and characteristics of gastroesophageal reflux events pre-vs. on proton pump inhibitors treatment.
Fig. 3: Association of swallows and symptoms with gastroesophageal reflux events: pre-proton pump inhibitors vs. after 4 weeks on proton pump inhibitors treatment.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available upon reasonable request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions.

References

  1. Vandenplas Y, Rudolph CD, Di Lorenzo C, Hassall E, Liptak G, Mazur L, 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;49:498–547.

    Article  PubMed  Google Scholar 

  2. Rosen R, Vandenplas Y, Singendonk M, Cabana M, DiLorenzo C, Gottrand F, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for pediatric gastroenterology, hepatology, and nutrition and the european society for pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr. 2018;66:516–54.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Orenstein SR, McGowan JD. Efficacy of conservative therapy as taught in the primary care setting for symptoms suggesting infant gastroesophageal reflux. J Pediatr. 2008;152:310–4.

    Article  PubMed  Google Scholar 

  4. Sultana Z, Hasenstab KA, Moore RK, Osborn EK, Yildiz VO, Wei L, et al. Symptom scores and pH-Impedance: secondary analysis of a randomized controlled trial in infants treated for gastroesophageal reflux. Gastro Hep Adv. 2022;1:869–81.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Levy EI, Salvatore S, Vandenplas Y, de Winter JP. Prescription of acid inhibitors in infants: an addiction hard to break. Eur J Pediatr. 2020;179:1957–61.

    Article  PubMed  Google Scholar 

  6. Jadcherla SR, Sultana Z, Hasenstab-Kenney KA, Prabhakar V, Gulati IK, Di Lorenzo C. Differentiating esophageal sensitivity phenotypes using pH-impedance in intensive care unit infants referred for gastroesophageal reflux symptoms. Pediatr Res. 2021;89:636–44.

    Article  CAS  PubMed  Google Scholar 

  7. Jadcherla SR, Slaughter JL, Stenger MR, Klebanoff M, Kelleher K, Gardner W. practice variance, prevalence, and economic burden of premature infants diagnosed with GERD. Hosp Pediatr. 2013;3:335–41.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Corsonello A, Lattanzio F, Bustacchini S, Garasto S, Cozza A, Schepisi R, et al. Adverse events of proton pump inhibitors: potential mechanisms. Curr Drug Metab. 2018;19:142–54.

    Article  CAS  PubMed  Google Scholar 

  9. Slaughter JL, Stenger MR, Reagan PB, Jadcherla SR. Neonatal Histamine-2 receptor antagonist and proton pump inhibitor treatment at United States Children’s Hospitals. J Pediatr. 2016;174:63–70.e3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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;163:692–8.e1-2.

    Article  CAS  PubMed  Google Scholar 

  11. Loots CM, Benninga MA, Davidson GP, Omari TI. Addition of pH-impedance monitoring to standard pH monitoring increases the yield of symptom association analysis in infants and children with gastroesophageal reflux. J Pediatr. 2009;154:248–52.

    Article  PubMed  Google Scholar 

  12. Woodley FW, Moore-Clingenpeel M, Machado RS, Nemastil CJ, Jadcherla SR, Hayes D Jr, et al. Not all children with cystic fibrosis have abnormal esophageal neutralization during chemical clearance of acid reflux. Pediatr Gastroenterol Hepatol Nutr. 2017;20:153–9.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout A, et al. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018;67:1351–62.

    Article  PubMed  Google Scholar 

  14. Sivalingam M, Sitaram S, Hasenstab KA, Wei L, Woodley FW, Jadcherla SR. Effects of esophageal acidification on troublesome symptoms: an approach to characterize true acid GERD in dysphagic neonates. Dysphagia. 2017;32:509–19.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jadcherla SR, Hanandeh N, Hasenstab KA, Nawaz S. Differentiation of esophageal pH-impedance characteristics classified by the mucosal integrity marker in human neonates. Pediatr Res. 2019;85:355–60.

    Article  CAS  PubMed  Google Scholar 

  16. Jadcherla SR, Peng J, Chan CY, Moore R, Wei L, Fernandez S, et al. Significance of gastroesophageal refluxate in relation to physical, chemical, and spatiotemporal characteristics in symptomatic intensive care unit neonates. Pediatr Res. 2011;70:192–8.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Weusten BL, Roelofs JM, Akkermans LM, Van Berge-Henegouwen GP, Smout AJ. The symptom-association probability: an improved method for symptom analysis of 24-hour esophageal pH data. Gastroenterology. 1994;107:1741–5.

    Article  CAS  PubMed  Google Scholar 

  18. Frazzoni M, Savarino E, de Bortoli N, Martinucci I, Furnari M, Frazzoni L, et al. Analyses of the post-reflux swallow-induced peristaltic wave index and nocturnal baseline impedance parameters increase the diagnostic yield of impedance-pH monitoring of patients with reflux disease. Clin Gastroenterol Hepatol. 2016;14:40–6.

    Article  PubMed  Google Scholar 

  19. Frazzoni M, de Bortoli N, Frazzoni L, Tolone S, Furnari M, Martinucci I, et al. The added diagnostic value of postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance in refractory reflux disease studied with on-therapy impedance-pH monitoring. Neurogastroenterol Motil. 2017;29:e12947.

  20. Castellani C, Huber-Zeyringer A, Bachmaier G, Saxena AK, Hollwarth ME. Proton pump inhibitors for reflux therapy in infants: effectiveness determined by impedance pH monitoring. Pediatr Surg Int. 2014;30:381–5.

    Article  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. Gibbons TE, Gold BD. The use of proton pump inhibitors in children: a comprehensive review. Paediatr Drugs. 2003;5:25–40.

    Article  PubMed  Google Scholar 

  24. Welsh C, Kasirer MY, Pan J, Shifrin Y, Belik J. Pantoprazole decreases gastroesophageal muscle tone in newborn rats via rho-kinase inhibition. Am J Physiol Gastrointest Liver Physiol. 2014;307:G390–6.

    Article  CAS  PubMed  Google Scholar 

  25. Mitchell DJ, McClure BG, Tubman TR. Simultaneous monitoring of gastric and oesophageal pH reveals limitations of conventional oesophageal pH monitoring in milk fed infants. Arch Dis Child. 2001;84:273–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Borrelli O, Salvatore S, Mancini V, Ribolsi M, Gentile M, Bizzarri B, et al. Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non-erosive reflux disease. Neurogastroenterol Motil. 2012;24:828–e394.

    Article  CAS  PubMed  Google Scholar 

  27. Jadcherla SR, Helmick R, Hasenstab KA, Njeh M, Alshaikh E. Impact of esophageal mucosal permeability markers on provocation-induced esophageal reflexes in high-risk infants. Physiol Rep. 2022;10:e15366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cohen Sabban J, Bertoldi GD, Ussher F, Christiansen S, Lifschitz C, Orsi M. Low-impedance baseline values predict severe esophagitis. J Pediatr Gastroenterol Nutr. 2017;65:278–80.

    Article  PubMed  Google Scholar 

  29. Xu H, Ye B, Ding Y, Wang M, Lin L, Jiang L. Factors of reflux episodes with post-reflux swallow-induced peristaltic wave in gastroesophageal reflux disease. J Neurogastroenterol Motil. 2020;26:378–83.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Frazzoni M, Manta R, Mirante VG, Conigliaro R, Frazzoni L, Melotti G. Esophageal chemical clearance is impaired in gastro-esophageal reflux disease-a 24-h impedance-pH monitoring assessment. Neurogastroenterol Motil. 2013;25:399–406.e295.

    Article  CAS  PubMed  Google Scholar 

  31. Gupta A, Gulati P, Kim W, Fernandez S, Shaker R, Jadcherla SR. Effect of postnatal maturation on the mechanisms of esophageal propulsion in preterm human neonates: primary and secondary peristalsis. Am J Gastroenterol. 2009;104:411–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Jadcherla SR, Duong HQ, Hoffmann RG, Shaker R. Esophageal body and upper esophageal sphincter motor responses to esophageal provocation during maturation in preterm newborns. J Pediatr. 2003;143:31–8.

    Article  PubMed  Google Scholar 

  33. Collins CR, Hasenstab KA, Nawaz S, Jadcherla SR. Mechanisms of aerodigestive symptoms in infants with varying acid reflux index determined by esophageal manometry. J Pediatr. 2019;206:240–7.

    Article  PubMed  Google Scholar 

  34. Zerbib F, Duriez A, Roman S, Capdepont M, Mion F. Determinants of gastro-oesophageal reflux perception in patients with persistent symptoms despite proton pump inhibitors. Gut. 2008;57:156–60.

    Article  CAS  PubMed  Google Scholar 

  35. Herregods TV, Bredenoord AJ, Smout AJ. Pathophysiology of gastroesophageal reflux disease: new understanding in a new era. Neurogastroenterol Motil. 2015;27:1202–13.

    Article  CAS  PubMed  Google Scholar 

  36. Zoizner-Agar G, Rotsides JM, Shao Q, Rickert S, Ward R, Greifer M, et al. Proton pump inhibitor administration in neonates and infants. Lack of consensus - An ASPO survey. Int J Pediatr Otorhinolaryngol. 2020;137:110200.

    Article  PubMed  Google Scholar 

  37. Safe M, Chan WH, Leach ST, Sutton L, Lui K, Krishnan U. Widespread use of gastric acid inhibitors in infants: Are they needed? Are they safe? World J Gastrointest Pharm Ther. 2016;7:531–9.

    Article  Google Scholar 

  38. Eichenwald EC, Committee On F, Newborn. Diagnosis and Management of Gastroesophageal Reflux in Preterm Infants. Pediatrics. 2018;142:e20181061.

  39. Jadcherla SR, Hasenstab KA, Gulati IK, Helmick R, Ipek H, Yildiz V, et al. Impact of feeding strategies with acid suppression on esophageal reflexes in human neonates with gastroesophageal reflux disease: a single-blinded randomized clinical trial. Clin Transl Gastroenterol. 2020;11:e00249.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Levy EI, Hoang DM, Vandenplas Y. The effects of proton pump inhibitors on the microbiome in young children. Acta Paediatr. 2020;109:1531–8.

    Article  CAS  PubMed  Google Scholar 

  41. Jadcherla SR, Hasenstab KA, Wei L, Osborn EK, Viswanathan S, Gulati IK, et al. Role of feeding strategy bundle with acid-suppressive therapy in infants with esophageal acid reflux exposure: a randomized controlled trial. Pediatr Res. 2021;89:645–52.

Download references

Funding

Supported by the National Institutes of Health (RO1 DK 068158 [to SRJ]) and the National Center for Advancing Translational Sciences (UL1TR002733 [to The Ohio State University Center for Clinical and Translational Science for REDCap support]).

Author information

Authors and Affiliations

  1. Innovative Feeding Disorders Research Program, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH, USA

    Zakia Sultana, Vedat O. Yildiz & Sudarshan R. Jadcherla

  2. Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, USA

    Vedat O. Yildiz

  3. Division of Neonatology and Center for Perinatal Research, Nationwide Children’s Hospital, Columbus, OH, USA

    Sudarshan R. Jadcherla

  4. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA

    Sudarshan R. Jadcherla

Authors
  1. Zakia Sultana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vedat O. Yildiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sudarshan R. Jadcherla
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ZS and SRJ performed studies. ZS, and VOY analyzed data. ZS and SRJ drafted the initial manuscript. SRJ conceptualized study, obtained funding, and IRB approvals. ZS, VOY, and SRJ validated and interpreted data, critically reviewed, and revised the manuscript, approved the final version, and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Sudarshan R. Jadcherla.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sultana, Z., O. Yildiz, V. & Jadcherla, S.R. Characteristics of esophageal refluxate and symptoms in infants compared between pre-treatment and on treatment with proton pump inhibitors. J Perinatol 44, 87–93 (2024). https://doi.org/10.1038/s41372-023-01825-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-023-01825-y

  • Springer Nature America, Inc.

Search

Navigation