Effect of Tube Feeding on Gastroesophageal Reflux in Preterm Infants (FT-GER-SO)

August 10, 2023 updated by: Luigi Corvaglia, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Effect of Different Modalities of Enteral Tube Feeding (ETF) on Gastroesophageal Reflux (GER) in Symptomatic Preterm Infants

Due to several promoting factors, gastro-esophageal reflux (GER) is very frequent in preterm infants. To limit the potentially harmful widespread of pharmacological treatment, a step-wise approach, which firstly undertakes conservative strategies, is currently considered the best choice to manage GER in the preterm population. Among the most common conservative strategies, postural measures seem to effectively reduce GER features in symptomatic preterm babies, whereas feed thickening is almost ineffective.

Due to their prematurity, preterm infants <34 weeks gestation are often unable to coordinate sucking, swallowing and breathing, thus requiring a feeding tube to ensure adequate enteral intakes. Continuous feeding and boluses are the most common techniques of enteral tube feeding in Neonatal Intensive Care Units; at present, however, the effects of these techniques on GER features have not been clearly established.

This observational, prospective and explorative study primarily aims to evaluate the effect of different techniques of enteral tube feeding on GER frequency and features in symptomatic preterm infants (gestational age ≤33 weeks) undergoing a diagnostic combined pH and multiple intraluminal impedance (pH-MII) for GER evaluation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Due to several promoting factors related to the physiological immaturity of the gastro-intestinal tract, gastro-esophageal reflux (GER) is a frequent condition among preterm infants.

GER clinical presentation may vary within a wide range of symptoms, being vomiting, regurgitations and cardiorespiratory events the most common in the preterm population.

Combined pH and multiple intraluminal impedance (pH-MII) is currently considered the best choice for GER diagnosis in preterm infants. While pH monitoring is limited to the detection of acid reflux, combined pH-MII effectively identifies both acid and non-acid GER, which is predominant in preterm infants. Moreover, it allows to evaluate the height reached by the refluxate within the esophageal lumen and to distinguish retrograde fluid bolus movements (reflux) from the anterograde ones (swallows).

In the last decade, GER pharmacological treatment has increasingly widespread in Neonatal Intensive Care Units (NICUs). The provision of anti-histamine2 blockers and proton pump inhibitors in the preterm population, however, might lead to such adverse effects as an increased incidence of necrotizing enterocolitis and infections. Hence, to avoid a useless and potentially harmful pharmacological overtreatment, a step-wise approach, firstly promoting conservative strategies, is currently considered the most advisable choice for GER management in symptomatic preterm infants.

Postural and dietary interventions are the most common conservative strategies and their efficacy in improving GER symptoms and features has been largely investigated.

As previously assessed by pH-MII, both prone and left-side positions were more effective than the right-side or supine ones to significantly improve both acid and non-acid GER features.

Feed thickening is widely employed to reduce vomiting and regurgitations in symptomatic term infants; with regard to the preterm population, however, little data is currently available. The efficacy of thickened fortified human milk on preterm infants with GER symptoms has been previously investigated, observing no benefits. Furthermore, standard human milk fortification itself has been shown to increase GER frequency in preterm infants.

With regard to anti-regurgitation (AR) formulas, the effectiveness of a specific AR formula, thickened with amylopectin and specifically tailored for preterm infants' nutritional needs, has been recently evaluated; the tested thickened formula effectively reduced the number of acid GERs, but no difference was observed in the frequency of non-acid GERs and in the mean esophageal acid exposure, which is known to be the main determinant for the development of gastro-esophageal reflux disease (GERD). Thus, according to these data, feed thickening seem to be almost ineffective in improving GER symptoms and features in preterm infants.

Due to their prematurity, preterm infants <34 weeks gestation are unable to coordinate sucking, swallowing and breathing; thus, to ensure adequate enteral intakes, they are usually fed via an intragastric tube. Continuous and bolus feeding are the most common techniques of enteral tube feeding in NICU settings.

The latter is shown to stimulate cyclical surges of gastrointestinal hormones, thus being considered more physiological. It entails the administration of the meal by gravity or through an infusion pump for a total duration of about 10 minutes, after which the feeding tube could be removed. However, the short time elapsing between the tube insertion for bolus administration and its subsequent removal might provoke a vagal response, characterized by bradycardia and temporary reduction of cardiac output. Moreover, the rapid gastric distension following bolus administration could increase the pressure of lower esophageal sphincter (LES), thus contributing to the refluxate of gastric contents into the esophageal lumen.

On the other hand, continuous feeding allows administering enteral feeds over a longer period (e.g. 2 or 3 hours), at a slower flow rate. It has been associated with better absorption of nutrients and faster gastric emptying, thus it may be preferable in case of delayed gastric motility, gastric residuals and abdominal distension. Moreover, its slow rate of infusion prevents a rapid gastric distension; however, this feeding method requires the permanence of the feeding tube through the LES for the whole feeding period, and this could predispose to the occurrence of gastro-esophageal reflux.

The effect of bolus and continuous feeding on cardio-respiratory events, which could represent clinical atypical manifestations of GER, has been recently evaluated, observing a slight but significant increase of apneic episodes during continuous feeding.

A recent systematic review has aimed to evaluate which of these tube-feeding methods could be more suitable in low birth weight infants with GER symptoms; however, current data are scarce and controversial and do not allow to draw any definitive conclusion.

The aim of this study is to evaluate the effect of different enteral tube feeding modalities, such as bolus and continuous feeding, on pH-MII GER features in tube-fed preterm infants ≤33 weeks gestation, undergoing a diagnostic pH-MII evaluation.

Overall, thirty preterm infants ≤33 weeks gestation will be enrolled if suffering from moderate/severe GER symptoms and if a diagnostic 24-hour pH-MII monitoring has been scheduled to evaluate GER features, according to our clinical practice.

During the 24-h pH-MII monitoring, each infant will receive his meals (usually 8) according to the following sequence:

  • 1st meal: optional modality (not considered for statistical analysis);
  • 2nd meal: continuous feeding over 3 hours;
  • 3rd meal: bolus feeding; the feeding tube remains in place for the whole post-prandial period;
  • 4th meal: bolus feeding; the feeding tube is removed after feed administration;
  • 5th: continuous feeding over 3 hours;
  • 6th : bolus feeding; the feeding tube remains in place for the whole post-prandial period;
  • 7th: bolus feeding; the feeding tube is removed after feed administration;
  • 8th: optional modality (not considered for statistical analysis). Healthcare assistants will inspect the correct application of this sequence.

The pH-MII device in use for this study (Comfortec pH-MII Sandhill Scientific®) is a nasogastric probe with seven rings, composed by six dipolar impedance channels and one antimony electrode responsible for pH detection and placed in the middle of the distal impedance dipole. Due to these characteristics, pH-MII is able to measure the esophageal height reached by refluxate and to identify the direction of esophageal bolus movements, thereby distinguish between a retrograde flow (reflux) and an anti-retrograde flow (swallow).

The distance between the infant's nose and LES will be determined with Strobel's formula: [baby length (cm) x 0.252 + 5)] - 13%. After placement, the probe's position will be radiographically confirmed.

Data from the pH-MII recording will be automatically acquired on a portable Sleuth Sandhill Scientific system and then stored in a personal computer containing a specific software (BioVIEW Analysis Sandhill Scientific, version 5.0.9). Data analysis will be performed by the aforementioned software and confirmed by direct visual evaluation.

Statistical analysis will be performed by SPSS 20 (Statistical Package for the Social Sciences, SPSS Inc., Chicago, IL, USA) for Windows. Differences between the different modalities in terms of GER frequency and features will be tested by Friedman test (level of significance: p <0.05).

Study Type

Observational

Enrollment (Actual)

31

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bologna, Italy, 40138
        • Neonatal Intensive Care Unit of the S.Orsola-Malpighi Hospital
      • Milano, Italy
        • SC Neonatologia e Terapia Intensiva Neonatale, Ospedale dei Bambini "V. Buzzi"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 week to 4 months (Child)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Due to the exploratory nature of this study, at least 30 preterm infants fulfilling the inclusion criteria will be enrolled.

Description

Inclusion Criteria:

  • Preterm newborns (≤ 33 weeks gestation), able to tolerate at least 100 ml kg-1 day-1 of fortified human milk or standard preterm formula, affected by severe/moderate GER symptoms (recurrent regurgitations, feeding difficulties, failure to thrive and/or post-prandial desaturations), whose usual treatment includes a 24-h pH-MII diagnostic evaluation.
  • Need for tube feeding at the time of pH-MII
  • Weight ≥ 1100 g at the time of enrollment
  • Obtained written parental consent.

Exclusion Criteria:

  • Newborns with serious chronic pathology.
  • Ongoing pharmacological treatment that could interfere with gastro-enteral motion functions (pro-kinetics) and/or with gastric acidity (H2 antagonists; proton pump inhibitors; sodium alginate).
  • Major congenital malformations (e.g. congenital heart diseases, gastrointestinal abnormalities, malformation syndromes).
  • Neonatal necrotizing enterocolitis.
  • Ongoing infections.
  • Patients with severe clinical conditions that can hinder their participation in this trial (e.g. patent ductus arteriosus, intra-ventricular hemorrhage, hemodynamic instability).
  • Administration of experimental medication treatments during the previous two weeks.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increase/reduction in the frequency of pH-MII GERs
Time Frame: 24 hours
changes in the number of acid, non-acid, liquid and gaseous refluxes
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increase/reduction in the duration of pH-MII GERs
Time Frame: 24 hours
Changes in the duration of GERs recorded
24 hours
Increase/reduction in the esophageal height reached by MII GERs
Time Frame: 24 hours
Changes in the height reached by MII GERs
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Collaborators

Ospedale dei Bambini "V. Buzzi", Milano

Investigators

  • Principal Investigator: Luigi T Corvaglia, Prof., Neonatal Intensive Care Unit, S.Orsola-Malpighi University Hospital, Bologna (Italy)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2016

Primary Completion (Actual)

February 28, 2023

Study Completion (Actual)

February 28, 2023

Study Registration Dates

First Submitted

February 7, 2016

First Submitted That Met QC Criteria

July 18, 2016

First Posted (Estimated)

July 19, 2016

Study Record Updates

Last Update Posted (Actual)

August 14, 2023

Last Update Submitted That Met QC Criteria

August 10, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SO-2016-TF

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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