Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Short-term effect of domperidone on gastroesophageal reflux in newborns assessed by combined intraluminal impedance and pH monitoring

Abstract

Objective:

Neonatal gastroesophageal reflux (GER) is primarily due to a transient motility disorder and characterized by a prevalence of weakly acid refluxes. Drug management, where necessary, must set out to reduce the number of refluxes besides correct their acidity. Prokinetics could be of assistance in this respect, though the evidence in favor of their efficacy and safety is still far from sufficient. In this randomized controlled study, the action of domperidone, a prokinetic antidopaminergic drug with little effect on the central nervous system, was evaluated in newborns with symptomatic GER.

Study Design:

Combined multichannel intraluminal impedance and pH measuring for 24 h was carried out in 13 newborns receiving 0.3 mg per kg domperidone per os at the eighth and the sixteenth hour, and 13 controls. Each newborn was compared to the control nearest in postconceptional age.

Result:

GER episodes per hour increased significantly compared to the baseline in the domperidone group (4.06±1.16 vs 2.8±1.42; P=0.001) and were shorter (16.68±4.49 vs 20.18±7.83 s; P=0.043), whereas there were no differences in the maximu proximal extent reached by the refluxes (3.37±0.45 vs 3.34±0.94 channels; P=0.894) and their pH (4.72±0.69 vs 4.60±1.17; P=0.634).

Conclusion:

This paradoxical increase in the number of GER episodes could be the expression of a domperidone-induced amplification of the motor incoordination of the neonatal gastroesophageal tract. Doubt is thus cast on the efficacy of prokinetics in this age bracket, especially in view of their adverse effects as described in the literature.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Tolia V, Wuerth A, Thomas R . Gastroesophageal reflux disease: review of presenting symptoms, evaluation, management, and outcome in infants. Dig Dis Sci 2003; 48: 1723–1729.

    Article  Google Scholar 

  2. Nelson SP, Chen EH, Syniar GM, Christoffel KK . Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med 1997; 151: 569–572.

    Article  CAS  Google Scholar 

  3. Milla P, Cucchiara S, DiLorenzo C, Rivera NM, Rudolph C, Tomomasa T . Motility disorders in childhood: Working Group Report of the first world congress of pediatric gastroenterology, hepatology and nutrition. J Pediatr Gastroenterol Nutr 2002; 35 (Suppl 2): S187–S195.

    Article  Google Scholar 

  4. Omari TI, Barnett CP, Benninga MA, Lontis R, Goodchild L, Haslam RR et al. Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux disease. Gut 2002; 51: 475–479.

    Article  CAS  Google Scholar 

  5. Davidson G . The role of lower esophageal sphincter function and dysmotility in gastroesophageal reflux in premature infants and in first year of life. J Pediatr Gastroenterol Nutr 2003; 37 (Suppl 1): S17–S22.

    Article  Google Scholar 

  6. 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: 265–268.

    Article  Google Scholar 

  7. Wenzl TG . Evaluation of gastroesophageal reflux events in children using multichannel intraluminal electrical impedance. Am J Med 2003; 115 (Suppl 3A): S161–S165.

    Article  Google Scholar 

  8. Condino AA, Sondheimer J, Pan Z, Gralla J, Perry D, O’Connor JA . Evaluation of infantile acid and non-acid gastroesophageal reflux using combined ph monitoring and impedance measurement. J Pediatr Gastroenterol Nutr 2006; 42: 16–21.

    Article  Google Scholar 

  9. Ramirez B, Richter JE . Review article: promotility drugs in the treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1993; 7: 5–20.

    Article  CAS  Google Scholar 

  10. Vandenplas Y, Belli D, Benhamou P, Cadranel S, Cesard JP, Cucchiara S et al. A critical appraisal of current management practices for infant regurgitation recommendations of a working party. Eur J Pediatr 1997; 156: 343–357.

    Article  CAS  Google Scholar 

  11. Rampe D, Roy ML, Dennis A, Brown AM . A mechanism for the proarrhythmic effects of cisapride (Propulsid): high affinity blockade of the human cardiac potassium channel HERG. FEBS Lett 1997; 417: 28–32.

    Article  CAS  Google Scholar 

  12. Craig WR, Hanlon-Dearman A, Sinclair C, Taback S, Moffatt M . Metoclopramide, thickened feedings, and positioning for gastro-esophageal reflux in children under two years. The Cochran library 2008; 2: 1–34.

    Google Scholar 

  13. Ganzini L, Casey DE, Hoffman WF, McCall AL . The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders. Arch Intern Med 1993; 153: 1469–1475.

    Article  CAS  Google Scholar 

  14. Ahmad N, Keith-Ferris J, Gooden E, Abell T . Making a case for domperidone in the treatment of gastrointestinal motility disorders. Curr Opin Phamacol 2006; 6: 571–576.

    Article  CAS  Google Scholar 

  15. Pritchard DS, Baber N, Stephenson T . Should domperidone be used for the treatment of gastro-esophageal reflux in children? Systematic review of randomized controlled trials in children aged 1 month to 11 years old. Br J Clin Pharmacol 2005; 59: 725–729.

    Article  CAS  Google Scholar 

  16. Niemegeers CJ, Schellekens KH, Janssen PA . The antiemetic effects of domperidone, a novel potent gastrokinetic. Arch Int Pharmacodyn Ther 1980; 244: 130–140.

    CAS  PubMed  Google Scholar 

  17. Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS . Domperidone. A review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dispepsia and as an antiemetic. Drugs 1982; 24: 360–400.

    Article  CAS  Google Scholar 

  18. Heykants J, Hendriks R, Meuldermans W, Michiels M, Scheygrond H, Reyntjens H . On the pharmacokinetics of domperidone in animals and man. The pharmacokinetics of intravenous domperidone and its bioavailability in man following intramuscular, oral and rectal administration. Eur J Drug Metab Pharmacokinet 1981; 6: 61–70.

    Article  CAS  Google Scholar 

  19. Clara R, Van Hollebeke J, Heck E . A multicentre pilot study of parenteral and rectal administration of domperidone in the treatment of severe vomiting in children. Postgrad Med J 1979; 55: 43–44.

    PubMed  Google Scholar 

  20. Barone JA . Domperidone: a peripherally acting dopamine2-receptor antagonist. Ann Pharmacother 1999; 33: 429–440.

    Article  CAS  Google Scholar 

  21. Biasini A, Alberti A . Extrapyramidal dysfunction after domperidone. Helv Pediatr Acta 1985; 40: 93–94.

    CAS  Google Scholar 

  22. Shafrir Y, Levy Y, Ben-Amitai D, Nitzan M, Steinherz R . Oculogyric crisis due to domperidone therapy. Helv Parediatric Acta 1985; 40: 95.

    CAS  Google Scholar 

  23. Rocha CM, Barbosa MM . QT interval prolongation associated with the oral use of domperidone in an infant. Pediatr Cardiol 2005; 26: 720–723.

    Article  CAS  Google Scholar 

  24. Drolet B, Rousseau G, Daleau P, Cardinal R, Turgeon J . Domperidone should not be considered a no-risk alternative to cisapride in the treatment of gastrointestinal motility disorders. Circulation 2000; 102: 1883–1885.

    Article  CAS  Google Scholar 

  25. Strobel CT, Byrne WJ, Ament ME, Euler AR . Correlation of esophageal lengths in children with height: application to the Tuttle test without prior esophageal manometry. J Pediatr 1979; 94: 81–84.

    Article  CAS  Google Scholar 

  26. Tutuian R, Castell DO . Use of multichannel intraluminal impedance to document proximal esophageal and pharyngeal nonacidic reflux episodes. Am J Med 2003; 115 (Suppl 3A): S119–S123.

    Article  Google Scholar 

  27. Wenzl TG . Investigating oesophageal reflux with the intraluminal impedance technique. J Pediatr Gastroenterol Nutr 2002; 34: 261–268.

    Article  Google Scholar 

  28. Sifrim D, Castell D, Dent J, Kahrilas PJ . Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut 2004; 53: 1024–1031.

    Article  CAS  Google Scholar 

  29. 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: 381–384.

    Article  Google Scholar 

  30. Peter CS, Sprodowski N, Ahlborn V, Wiechers C, Schlaud M, Silny J et al. Inter- and intraobserver agreement for gastroesophageal reflux detection in infants using multiple intraluminal impedance. Biol Neonate 2004; 85: 11–14.

    Article  Google Scholar 

  31. Clark RH, Bloom BT, Spitzer AR, Gerstmann DR . Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics 2006; 117: 1979–1987.

    Article  Google Scholar 

  32. Dhillon AS, Ewer AK . Diagnosis and management of gastro-oesophageal reflux in preterm infants in neonatal intensive care units. Acta Paediatr 2004; 93: 88–93.

    Article  CAS  Google Scholar 

  33. Carroccio A, Iacono G, Montalto G, Cavataio F, Soresi M, Notarbartolo A . Domperidone plus magnesium hydroxide and aluminum hydroxide: a valid therapy in children with gastroesophageal reflux. A double-blind randomised study versus placebo. Scand J Gastroenterol 1994; 29: 300–304.

    Article  CAS  Google Scholar 

  34. Bines JE, Quinlan JE, Treves S, Kleinman RE, Winter HS . Efficacy of domperidone in infants and children with gastroesophageal reflux. J Pediatr Gastroenterol Nutr 1992; 14: 400–405.

    Article  CAS  Google Scholar 

  35. De Loore I, Van Ravensteyn H, Ameryckx L . Domperidone drops in the symptomatic treatment of chronic paediatric vomiting and regurgitation. A comparison with metoclopramide. Postgrad Med J 1979; 55: 40–42.

    PubMed  Google Scholar 

  36. Cresi F, de Sanctis L, Savino F, Bretto R, Testa A, Silvestro L . Relationship between gastro-oesophageal reflux and gastric activity in newborns assessed by combined intraluminal impedance, pH metry and epigastric impedance. Neurogastroenterol Motil 2006; 18: 361–368.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are particularly grateful to the nursing staff for their most valuable assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F Cresi.

Additional information

Disclosure/Conflicts of Interest

The authors declare that there is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cresi, F., Marinaccio, C., Russo, M. et al. Short-term effect of domperidone on gastroesophageal reflux in newborns assessed by combined intraluminal impedance and pH monitoring. J Perinatol 28, 766–770 (2008). https://doi.org/10.1038/jp.2008.81

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2008.81

Keywords

Search

Quick links