Extensively hydrolyzed protein formula reduces acid gastro-esophageal reflux in symptomatic preterm infants

Early Hum Dev. 2013 Jul;89(7):453-5. doi: 10.1016/j.earlhumdev.2013.04.003. Epub 2013 May 1.


Background: Gastro-esophageal reflux (GER) is diagnosed frequently in preterm infants. Pharmacological treatment of GER has some potential side effects. Conservative treatment of GER should be the first-line approach and should include body positioning and diet modifications. Formula-fed preterm infants experience frequently symptoms of feeding intolerance. Hydrolyzed protein formula (HPF) is often used in these infants due to their effects on gastrointestinal motility.

Aims: To investigate the role of an extensively HPF (eHPF) on GER indexes in formula-fed preterm infants with symptoms of both GER and feeding intolerance.

Study design: Randomized crossover trial.

Subjects: Preterm infants (gestational age ≤33 weeks) with symptoms of feeding intolerance (large gastric residuals, abdominal distension and constipation) and GER (frequent regurgitations and/or postprandial desaturations).

Outcome measures: GER indexes detected by 24-h combined multichannel intraluminal impedance and pH monitoring. GER indexes detected after 4 feeds of an eHPF were compared to those detected after 4 feeds of a standard preterm formula (SPF) by Wilcoxon signed ranks test. A p<0.05 was considered statistically significant.

Results: eHPF significantly reduced the number of GERs detected by pH monitoring (p=0.036) and also the reflux index (p=0.044) compared to SPF. No differences in impedance bolus exposure indexes nor in GER height were detected.

Conclusions: The use of an eHPF should be evaluated for reducing esophageal acid exposure in preterm infants with feeding intolerance and symptoms of GER. Future research should focus on the evaluation of an eHPF adequate for preterm infants in improving clinical symptoms of GER.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Cross-Over Studies
  • Female
  • Gastroesophageal Reflux / diagnosis
  • Gastroesophageal Reflux / diet therapy*
  • Humans
  • Infant Formula / chemistry*
  • Infant Formula / pharmacology
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / diagnosis
  • Infant, Premature, Diseases / diet therapy*
  • Male
  • Protein Hydrolysates / administration & dosage*


  • Protein Hydrolysates