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Continuous versus bolus intragastric tube feeding for preterm and low birth weight infants with gastro-oesophageal reflux disease

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Authors

Robyn Richards1, Jann P Foster2,3, Kim Psaila4

Background - Methods - Results - Characteristics of Included Studies - References - Data Tables and Graphs


1Newborn Care, Liverpool Hospital, Liverpool, Australia [top]
2School of Nursing & Midwifery, University of Western Sydney, Sydney, Australia [top]
3Central Clinical School, Discipline of Obstetrics, Gynaecology and Neonatology, Sydney Medical School/Sydney Nursing School, University of Sydney, Sydney, Australia [top]
4CHoRUS Project, Family and Community Health Research Group, School of Nursing and Midwifery, University of Western Sydney, College of Health and Science, Penrith South DC, Australia [top]

Citation example: Richards R, Foster JP, Psaila K. Continuous versus bolus intragastric tube feeding for preterm and low birth weight infants with gastro-oesophageal reflux disease. Cochrane Database of Systematic Reviews 2014, Issue 7. Art. No.: CD009719. DOI: 10.1002/14651858.CD009719.pub2.

Contact person

Robyn Richards

Newborn Care
Liverpool Hospital
Locked Bag 7103
South Western Sydney Area Health Service
Liverpool
NSW
1871
Australia

E-mail: Robyn.Richards@sswahs.nsw.gov.au

Dates

Assessed as Up-to-date: 28 October 2012
Date of Search: 27 September 2013
Next Stage Expected: 10 October 2014
Protocol First Published: Issue 3, 2012
Review First Published: Issue 7, 2014
Last Citation Issue: Issue 7, 2014

Abstract

Background

Gastro-oesophageal reflux disease is a particularly common condition in preterm and low birth weight infants. These infants are also more likely to have excessive regurgitation, as they do not have a fully developed antireflux mechanism. Preterm and low birth weight infants who are unable to suck oral feeds are required to be fed via an intragastric tube for varying lengths of time. Intragastric tube feeding can be delivered by the intermittent bolus or continuous feeding method. Use of continuous or intermittent bolus intragastric feeding may have a positive or negative effect on the incidence or severity of gastro-oesophageal reflux disease.

Objectives

To determine whether continuous or intermittent bolus intragastric tube feeding reduces the number of episodes and the duration of gastro-oesophageal reflux disease (GORD) in preterm and low birth weight infants.

We intended to perform subgroup analyses for gestational age; birth weight; age in days from birth at full enteral feeding via intragastric tube (breast vs bottle); frequency of intermittent bolus feed; and type of medication for treatment of GORD (only if medication prescribed and given similarly to both intervention groups).

Search methods

We used the standard search strategy of the Cochrane Neonatal Group as described in The Cochrane Library External Web Site Policy to search for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), MEDLINE (1966 to September 2013), EMBASE (1980 to September 2013) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to September 2013). We also searched previous reviews, including cross-references, abstracts and conference and symposia proceedings of the Perinatal Society of Australia and New Zealand and the Pediatric Academic Societies (American Pediatric Society/Society for Pediatric Research and European Society for Paediatric Research) from 1990 to 2012.

Selection criteria

Published and unpublished RCTs and quasi-RCTs were eligible for inclusion in this review, as were cluster-randomised and cross-over randomised trials that compared the effects of continuous versus intermittent bolus intragastric tube feeding on gastro-oesophageal reflux disease in preterm and low birth weight infants.

Data collection and analysis

Two review authors independently assessed study eligibility and quality.

Results

We found no trials that met the inclusion criteria for this review.

Authors' conclusions

We did not identify any randomised trials that evaluated the effects of continuous versus intermittent bolus intragastric tube feeding on gastro-oesophageal reflux disease in preterm and low birth weight infants. Well-designed and adequately powered trials are needed.

Plain language summary

Continuous versus intermittent bolus feeding for gastro-oesophageal reflux disease

Preterm and low birth weight infants are often unable to be fed orally because they cannot suck and swallow effectively. Therefore, they need to be fed via a tube placed into the stomach (intragastric). Tube feeding can be given by the intermittent bolus method, whereby milk is given over a short time (15 to 30 minutes), or by the continuous feeding method, by which milk is given over several hours. It is unclear which method is better for reducing reflux of milk into the oesophagus. We found no randomised controlled trials and therefore recommend that well-designed randomised trials be conducted to conclusively prove which method is more appropriate.

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Background

Description of the condition

Gastro-oesophageal reflux (GOR) is the term used to describe the reflux of stomach contents into the oesophagus. In its mildest form, GOR is classified as a physiologically normal process (Vanderplas 1998).

Whether GOR becomes clinically relevant in infants depends on the acidity and the quantity of the refluxate (Poets 2004; Van Wijk 2007). When retrograde movement of gastrointestinal contents results in sequelae such as injury to the oesophagus or supra-oesophageal structures, it is considered pathological, and the infant is said to have gastro-oesophageal reflux disease (GORD) (Vanderplas 1998; Tipnis 2009). Other complications resulting from GORD include vomiting, posseting (regurgitation of small quantities of milk after feeding), choking, gagging, oesophagitis, feed refusal, constant or sudden crying, irritability, poor sleep patterns, apnoea, oxygen desaturation, stridor, bradycardia (Hawdon 2000Khalaf 2001; Henry 2004), laryngospasm and bronchial asthma (Serra 2007), as well as insufficient growth and weight gain (Frakaloss 1998). Gastric acid reflux can enter the adenoids and cause oedema of the tubal orifices, later possibly leading to relapsing disease of the middle ear in children (Serra 2007). Another important aspect of GORD is the increased parental anxiety that is caused by an irritable, crying infant (Vanderplas 1998; Moore 2003).

GORD is particularly common among preterm and low birth weight infants. These babies are also more likely to have excessive regurgitation; episodes can occur three to five times per hour (Poets 2004). Premature babies do not have a fully developed antireflux mechanism (Premji 2005). GORD in preterm infants can lead to obstructive or central apnoea (Marino 1995). In healthy preterm infants as young as twenty-six weeks' gestation, GORD has been associated with transient lower oesophageal sphincter relaxation (Omari 2002; Van Wijk 2007). Bronchopulmonary dysplasia or chronic lung disease of infancy (CLDI) is a chronic condition that usually evolves after premature delivery and respiratory distress syndrome. Small, fragile infants with CLDI are prone to GORD, which may complicate enteral feeding and worsen an already compromised respiratory system by causing asymptomatic aspiration or by triggering bronchospasm (Radford 1995).

Diagnosis of GORD can be made by oesophageal pH monitoring, with 24-hour pH measurement the presumed gold standard of diagnostic tools. However, with this method, only acid (pH < 4) and alkaline (pH > 7) GORD can be detected. GORD with an oesophageal pH in the physiological range (pH 5 to 6.8) may represent many cases of suspected GORD that are unrecognised by pH metry, as 90% of reflux episodes in preterm infants are non-acidic (Wenzi 1999). Another relatively new method of detection of gastro-oesophageal reflux involves the use of multiple intraluminal impedance (Peter 2002). This technique allows detection of reflux via changes in impedance caused by a liquid bolus inside the oesophagus, and is independent of pH (Peter 2003).

Description of the intervention

Oral feeding is the preferred method of feeding infants; however, many infants cannot be fed this way because they are unable to suck and swallow effectively, possibly as the result of prematurity, central nervous system disturbances, disease or congenital conditions (Macagno 1994). Preterm babies who are unable to suck oral feeds are required to be fed via an intragastric tube for varying lengths of time (Lau 2003).

Intragastric tube feeding can be delivered by the intermittent bolus or continuous feeding method. Intragastric feeding tubes can be placed into the stomach for each feed and removed afterwards (Toce 1987), or they can be left in situ between feeds (Premji 2011). Intermittent bolus feeds are given over a short time, usually over a 15- to 30-minute period at a preselected number of times per day (e.g. two-hourly, three- to four-hourly). No universally accepted definition for bolus feeding is known. Intermittent bolus feeds can be given by allowing the volume of milk to be administered via a syringe slowly by gravity, or by delivering the feed volume by compressing the syringe while using pressure until the feed is delivered (Dawson 2005). On the other hand, continuous intragastric feeds are given by an infusion pump, usually over a 24-hour period (Jawaheer 2001).

It has been argued that different endocrine effects can occur in infants, depending on whether they are fed continuously or intermittently (Aynsley-Green 1982). For example, when compared with continuous feeding, intermittent bolus feeding has been shown to induce cyclical bursts of gut hormones and is associated with high serum concentrations of gastrin, insulin and gastric inhibitory polypeptide, as seen in healthy term infants (Aynsley-Green 1982; Aynsley-Green 1990). Therefore, continuous enteral feeding is not recommended by some commentators (Macagno 1994). Continuous enteral feeding in infants has also been shown to have a role in inducing gallbladder stasis, leading to an enlarged, non-contractile gallbladder (Jawaheer 2001).

How the intervention might work

Use of continuous or intermittent bolus intragastric feeding may have a positive or negative effect on the incidence or severity of GORD. Delayed gastric emptying and transient lower oesophageal sphincter relaxation (Omari 2002) have been found to be pathogenetic factors in GORD (Argon 2006). Continuous intragastric feeding is generally regarded as causing less gastric distension and pressure on the lower oesophageal sphincter (Coben 1994) and leads to better nutrient absorption (Parker 1981) and significantly faster gastric emptying (De Ville 1998) when compared with intermittent bolus feeding.

In relation to intermittent bolus feeding, it has been proposed that greater gastric distension secondary to quickly instilled large volumes of feed weakens the lower oesophageal sphincter, resulting in GORD (Bowling 2008). One randomised controlled trial (RCT) in an adult population (Bowling 2008) compared the effects of bolus and continuous nasogastric feeding on GOR (as opposed to GORD), gastric emptying and pulmonary aspiration among healthy volunteers who did not have a previous history of any gastrointestinal motility disorders. This study concluded that, contrary to popular belief, bolus feeding did not result in pulmonary aspiration or in an increased incidence of GOR or gastric emptying.

Why it is important to do this review

Concern has been expressed about the effects of time and temperature on composition and bacterial growth in milk (Hamosh 1996). For example, Greer 1984 recommended not using continuous feeding because this study found that the slower the infusion rate with continuous intragastric feeding, the greater the decrease in fat concentration caused by separation and layering out of fat in human milk along the infusion system. In addition, a large fat load was delivered if the line was flushed in the last hour of the infusion. Hamosh 1996 warns that because of increasing bacterial counts over time, human milk should be changed every four hours when delivery is provided through continuous infusion. Continuous intragastric feeding is more expensive than intermittent bolus feeding because it requires the use of syringe pumps and infusion tubing (Macagno 1994). However, preterm infants fed by intermittent bolus intragastric feeding have to maintain metabolic homeostasis during alternating periods of feeding and fasting (Aynsley-Green 1982).

Disparate views have been noted on whether continuous or intermittent bolus intragastric feeding is the more effective way to feed infants with GORD. Generally, gastric intermittent bolus feeding is the most commonly used method (Macagno 1994; Dawson 2005; Bowling 2008). However, anecdotal evidence indicates that some clinicians change over to continuous feeding from intermittent bolus feeding if GORD is suspected or confirmed. It is important to determine the effectiveness and clinical benefits and risks of each method, so that clinicians can make informed decisions regarding the most appropriate intragastric feeding method for an individual infant with GORD. Therefore, we performed a systematic review of trials comparing the two methods of intragastric milk feeding in preterm infants with GORD.

Objectives

To determine whether continuous or intermittent bolus intragastric tube feeding reduces the number of episodes and the duration of gastro-oesophageal reflux disease (GORD) in preterm and low birth weight infants.

We intended to perform subgroup analyses for gestational age; birth weight; age in days from birth at full enteral feeding via intragastric tube (breast vs bottle); frequency of intermittent bolus feed; and type of medication for treatment of GORD (only if medication prescribed and given similarly to both intervention groups).

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Methods

Criteria for considering studies for this review

Types of studies

We considered all published and unpublished RCTs and quasi-RCTs eligible for inclusion in this review. Studies reported only by abstracts were eligible for inclusion. We intended to include cluster-randomised and cross-over randomised trials.

Types of participants

Preterm (< 37 weeks' gestation) and low birth weight (< 2500 grams) infants, three months of age and younger (corrected), with a diagnosis of gastro-oesophageal reflux disease or suspected gastro-oesophageal reflux disease based on clinical symptoms and receiving enteral feeding through nasogastric or orogastric tube feeding.

We excluded infants who had a gastrostomy tube in situ and those who had undergone abdominal surgery.

Types of interventions

Continuous (intervention group) versus intermittent bolus (control group) intragastric tube feeding in preterm infants with gastro-oesophageal reflux disease. Both treatment groups must have compared the same amount of enteral feeding (mL/kg/d) prescribed over a 24-hour period.

Types of outcome measures

Primary outcomes
  • Gastro-oesophageal reflux disease, as diagnosed by pH metry, multiple intraluminal impedance or endoscopy within two hours postprandial (after eating a meal).
Secondary outcomes
  • Gastro-oesophageal reflux disease: number of episodes over a 24-hour period using pH metry or multiple intraluminal impedance.
  • Gastro-oesophageal reflux disease: duration (i.e. number of minutes) until clearance of any GORD episode over a 24-hour period using pH metry or multiple intraluminal impedance.
  • Gastro-oesophageal reflux disease: duration of longest GORD episode in minutes (within two hours postprandial over a 24-hour period) using pH metry or multiple intraluminal impedance.
  • Days to full enteral feeding via an intragastric tube.
  • Discontinuation of intervention.
  • Weight gain (grams/d).
  • Apnoea (number of episodes over a 24-hour period): defined as any cessation of breathing > 20 seconds or a shorter pause associated with bradycardia or cyanosis within two hours postprandial.
  • Apnoea requiring respiratory support.
  • Oxygen desaturation (number of episodes over a 24-hour period): defined as any spontaneous fall in oxygen saturation (SpO2) less than/or equal to 85% within two hours postprandial.
  • Vomiting (total number of events over a 24-hour period). 
  • Behavioural disturbances (e.g. irritability, disruption in sleep pattern) documented on hospital record within two hours postprandial.
  • Pain (as measured on validated measurement tool, e.g. Neonatal Infant Pain Scale (NIPS), Preterm Infant Pain Profile (PIPP), Children's Hospital of Eastern Ontario Pain Scale (CRIES), completed within two hours postprandial).
  • Duration of hospital stay (total number of days from birth to discharge).
  • Number of hospital readmissions within first year of life.
  • Need for surgery (related to GORD) (yes/no).
  • Parent stress and/or satisfaction (as measured on validated measurement tool, e.g. Parental Stressor Scale, Neonatal Intensive Care Unit).
  • Death (before hospital discharge; within first year of life).
  • Aspiration pneumonia/pneumonitis (clinical and/or radiological evidence of lower respiratory tract compromise that has been attributed to covert or evident aspiration of gastric contents).
  • Need for medications to treat GORD.

Search methods for identification of studies

We attempted to identify all relevant studies, regardless of language or publication status (published, unpublished, in press and in progress).

Electronic searches

We used the standard search strategy of the Cochrane Neonatal Group as described in The Cochrane Library External Web Site Policy, to search for RCTs in the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), MEDLINE (1966 to September 2013), EMBASE (1980 to September 2013) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to September 2013), using the following subject headings (MeSH) and text words: [infant -newborn / OR infan* , or Neonat*, OR prematur* OR preterm OR low birth weight] AND [GORD, GERD, gastro-oesophageal reflux, gastroesophageal reflux, infantile reflux, gastric regurgitation, gastric emptying, enteral feeding, enteral nutrition, feeding behaviour AND infant feeding, gavage feeding, intermittent feeding, bolus feeding, continuous feeding, tube feeding, gastric feeding].

We imposed no restriction by language. Two review authors (RR and JF) independently performed the electronic database searches.

Searching other resources

We planned to communicate with expert informants and to search bibliographies of reviews and trials to look for references to other trials. We searched previous reviews, including cross-references, abstracts and conference and symposia proceedings of the Perinatal Society of Australia and New Zealand and the Pediatric Academic Societies (American Pediatric Society/Society for Pediatric Research and European Society for Paediatric Research) from 1990 to October 2012. If we identified any unpublished trial, we planned to contact the corresponding investigator to request information. We planned to consider unpublished studies and studies reported only as abstracts as eligible for review if methods and data could be confirmed by the study author and to contact the corresponding authors of identified RCTs to ask for additional information about their studies if further data were required. We searched clinical trials registries for ongoing and recently completed trials (ClinicalTrials.gov, Controlled-Trials.com External Web Site Policy and WHO International Clinical Trials Registry Platform (ICTRP) External Web Site Policy.

Data collection and analysis

We used the standard systematic review methods of The Cochrane Collaboration, as documented in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Selection of studies

Two review authors (RR and JF) independently assessed for inclusion all of the potential studies identified as a result of the search strategy.

Data extraction and management

We intended to use the agreed upon form to extract data from eligible studies. However, no eligible studies were identified. The methods to be used in subsequent updates of this review, as data become available, are outlined in Appendix 1.

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Results

Description of studies

See Characteristics of excluded studies.

Results of the search

Electronic and non-electronic searches identified 23 citations. The titles and abstracts were read by two review authors (RR and JF) to determine whether they met criteria for inclusion in this review. It was clear from the title or abstract that 22 of these failed to meet the inclusion criteria and therefore should be excluded. We gave further consideration to one trial report (Bowling 2008).

Included studies

We did not include any studies.

Excluded studies

We excluded from the review one study (Bowling 2008) that examined the effects of continuous versus intermittent bolus intragastric feeding for GOR (as opposed to GORD) in the adult population.

Risk of bias in included studies

No trials met the inclusion criteria for this review.

Effects of interventions

No trials met the inclusion criteria for this review.

Discussion

Use of continuous or intermittent bolus intragastric feeding may have a positive or negative effect on the incidence or severity of GORD. However, we were unable to determine whether continuous or intermittent bolus intragastric tube feeding reduces GORD in preterm and low birth weight infants.

A number of outcomes have been examined when the two feeding methods were compared, and they remain pertinent factors when use of the two feeding methods is considered. Premji 2011 (a Cochrane review) compared the clinical benefits and risks of continuous versus intermittent bolus nasogastric tube milk feeding for infants < 1500 grams. This review revealed that it took infants significantly longer to reach full enteral feeds when fed by the continuous tube feeding method. However, a more recent study by Dsilna 2005 reported that continuously fed infants weighing < 1299 grams reached full enteral feeds faster than those fed intermittently. Meta-analysis could not be performed in the Premji 2011 review for the outcome of feeding intolerance (as opposed to GORD) because the measures of feeding intolerance were not comparable. However, each of the three studies found no difference in feed intolerance between continuous and intermittent bolus feeding methods (Premji 2011). The Cochrane review also compared bolus intermittent and continuous intragastric feeding for number of episodes of apnoea per infant per day. Again, meta-analysis could not be performed, but the studies reported conflicting results. Two studies reported fewer episodes of apnoea for the intermittent bolus feeding group, and two others reported fewer events of apnoea in the continuous feeding group. No difference was noted between continuous and intermittent bolus feeding in the risk of necrotising enterocolitis (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.49 to 1.90) (Premji 2011).

Well-designed large randomised controlled trials are needed to evaluate which method of intragastric feeding is more effective for reducing gastro-oesophageal reflux in preterm and low birth weight infants.

Summary of main results

No trials met the inclusion criteria for this review.

Overall completeness and applicability of evidence

No trials met the inclusion criteria for this review.

Quality of the evidence

No trials met the inclusion criteria for this review.

Potential biases in the review process

No trials met the inclusion criteria for this review.

Agreements and disagreements with other studies or reviews

We did not identify any other trials or reviews.

Authors' conclusions

Implications for practice

In view of the lack of evidence, further evidence is required before evidence-based recommendations for practice can be made.

Implications for research

Well-designed and adequately powered randomised trials are needed.

Acknowledgements

  • None noted.

Contributions of authors

Robyn Richards and Jann P Foster wrote the protocol and the first draft of the review and revised subsequent drafts; they also assessed study eligibility.

Kim Psaila commented on drafts of the protocol and of the review.

Declarations of interest

  • None noted.

Differences between protocol and review

  • None noted.

Published notes

  • None noted.

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Characteristics of studies

Characteristics of included studies

  • None noted.

Characteristics of excluded studies

Bowling 2008

Reason for exclusion Randomised controlled trial that examined the effects of continuous versus intermittent bolus intragastric feeding on gastro-oesophageal reflux (GOR) (as opposed to gastro-oesophageal reflux disease (GORD)) in the adult population

Characteristics of studies awaiting classification

  • None noted.

Characteristics of ongoing studies

  • None noted.

Additional tables

  • None noted.

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References to studies

Included studies

  • None noted.

Excluded studies

  • None noted.

Bowling 2008

Bowling TE, Cliff B, Wright JW, Blackshaw PE, Perkins AC, Lobo DN. The effects of bolus and continuous nasogastric feeding on gastro-oesophageal reflux and gastric emptying in healthy volunteers: a randomised three-way crossover pilot study. Clinical Nutrition 2008;27(4):608-13.

Studies awaiting classification

  • None noted.

Ongoing studies

  • None noted.

Other references

Additional references

Argon 2006

Argon M, Duygun U, Daglioz G, Omur O, Demir E, Aydogdu S. Relationship between gastric emptying and gastroesophageal reflux in infants and children. Clinical Nuclear Medicine 2006;31(5):262-5.

Aynsley-Green 1982

Aynsley-Green A, Adrian TE, Bloom SR. Feeding and the development of enteroinsular hormone secretion in the preterm infant: effects of continuous gastric infusions of human milk compared with intermittent boluses. Acta Paediatrica Scandinavica 1982;71(3):379-83.

Aynsley-Green 1990

Aynsley-Green A, Lucas A, Lawson GR, Bloom SR. Gut hormones and regulatory peptides in relation to enteral feeding, gastroenteritis, and necrotizing enterocolitis in infancy. Journal of Pediatrics 1990;117(1 Pt 2):24-32.

Coben 1994

Coben RM, Weintraub A, DiMarino AJ, Cohen S. Gatroesophageal reflux during gastrostomy feeding. Gastroenterology 1994;106(1):8-13.

Dawson 2005

Dawson J, Summan R, Badawi N. Push versus gravity for intermittent bolus gavage tube feeding of premature and low birth weight infants [Protocol]. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD005249. DOI: 10.1002/14651858.CD005249.

De Ville 1998

De Ville K, Knapp E, Al -Taawil Y. Slow infusion feeding enhances duodenal motor responses and gastric emptying in preterm infants. American Journal of Clinical Nutrition 1998;68(1):103-8.

Dsilna 2005

Dsilna A, Christensson K, Alfredsson L. Continuous feeding promotes gastrointestinal tolerance and growth in very low birth weight infants. Journal of Paediatrics 2005;147(1):43-9.

Frakaloss 1998

Frakaloss G, Burke G, Sanders MR. Impact of gastroesophageal reflux on growth and hospital stay in premature infants. Journal of Pediatric Gastroenterology and Nutrition 1998;26:146-50.

Greer 1984

Greer FR, McCormick A, Loker J. Changes in fat concentration of human milk during delivery by intermittent bolus and continuous mechanical pump infusion. The Journal of Pediatrics 1984;105(5):745-9.

Hamosh 1996

Hamosh, M. Breastfeeding and the working mother: effect of time and temperature of short-term storage on proteolysis, lipolysis, and bacterial growth in milk. Pediatrics 1996;97(4):492.

Hawdon 2000

Hawdon JM, Beauregard N, Slattery J, Kennedy G. Identification of neonates at risk of developing feeding problems in infancy. Developmental Medicine and Child Neurology 2000;42(4):235-9.

Henry 2004

Henry SM. Discerning differences: gastroeosophageal reflux and gastroesophageal reflux disease in Infants. Advances in Neonatal Care 2004;4(4):235-47.

Higgins 2011

Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. www.cochrane-handbook.org.

Jawaheer 2001

Jawaheer G, Shaw NJ, Pierro A. Continuous enteral feeding impairs gallbladder emptying in infants. Journal of Pediatrics 2001;138(6):822-5.

Khalaf 2001

Khalef MN, Porate R, Brodsky NL, Bhandari V. Clinical correlations in infants in the neonatal intensive care unit with varying severity of gastroesophageal reflux. Journal of Paediatric Gastroenterology and Nutrition 2001;32(1):45-9.

Lau 2003

Lau C, Smith EO, Schandler RJ. Coordination of suck-swallow and swallow respiration in preterm infants. Acta Paediatrica 2003;92(6):721-7.

Macagno 1994

Macagno F, Demarini S. Techniques of enteral feeding in the newborn. Acta Paediatrica 1994;Suppl 402:11-3.

Marino 1995

Marino A, Assing E, Carbone M. The incidence of gastroesophageal reflux in preterm infants. Journal of Perinatology 1995;15(5):369-71.

Moore 2003

Moore DJ, Tao BS, Lines DR, Hirte C, Heddle ML, Davidson GP. Double-blind placebo-controlled trial of omeprazole in irritable infants with gastroesophageal reflux. Journal of Paediatrics 2003;143(2):219-23.

Omari 2002

Omari TI, Barnett CP, Benninga MA, Longis R, Goodchild L, Haslam RR, et al. Mechanisms of gastroesophageal reflux in preterm and term infants with reflux disease. Gut 2002;51(4):475-9.

Parker 1981

Parker P, Stroop S, Greene H. A controlled comparison of continuous versus intermittent feeding in the treatment of infants with intestinal disease. Journal of Pediatrics 1981;99(3):360-4.

Peter 2002

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. Pediatrics 2002;141(2):277-9.

Peter 2003

Peter CS, Wiechers C, Bohnhorst B, Silny J, Poets CF. Detection of small bolus volumes using multiple intraluminal impedance in preterm infants. Journal of Pediatric Gastroenterology and Nutrition 2003;36(3):381-4.

Poets 2004

Poets CF. Gastroesophageal reflux: a critical review of its role in preterm infants. Pediatrics 2004;113(2):e128-32.

Premji 2005

Premji S. Enteral feeding for high-risk neonates. A digest for nurses into putative risk and benefits to ensure safe and comfortable care. Journal of Perinatal neonatal Nursing 2005;19(1):59-71.

Premji 2011

Premji S, Chessell L. Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature infants less than 1500 grams. Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No.: CD001819. DOI: 10.1002/14651858.CD001819.pub2. [Other: ]

Radford 1995

Radford PJ, Stillwell PC, Blue B, Hertel G. Aspiration complicating bronchopulmonary dysplasia. Chest 1995;107(1):185-8.

RevMan 2011

Review Manager (RevMan) [Computer program]. RevMan. Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.

Serra 2007

Serra A, Cocuzza S, Poli G, La Mantia I, Messina A, Pavone P. Otologic findings in children with gastroesophageal reflux. International Journal of Pediatric Otorhinolaryngology 2007;71(11):1693-7.

Tipnis 2009

Tipnis NA, Tipnis SM. Controversies in the treatment of gastroesophageal reflux disease in preterm infants. Clinics in Perinatology 2009;36(1):153-64.

Toce 1987

Toce SS, Keenan WJ, Homan SM. Enteral feeding in very-low-birth-weight infants. American Journal of Diseases in Childhood 1987;141(4):439-44.

Van Wijk 2007

Van Wijk MP, Benninga MA, Dent J, Lontis R, Goodchild L, McCall LM, et al. Effect of body position changes on postprandial gastroesophageal reflux and gastric emptying in the healthy premature neonate. The Journal of Pediatrics 2007;151(6):585-90.

Vanderplas 1998

Vanderplas Y, Lifshitz JZ, Orenstein S, Lifschitz CH, Shepherd RW, Casaubón PR, et al. Nutritional management of regurgitation in infants. Journal of the American College of Nutrition 1998;17(4):308-16.

Wenzi 1999

Wenzi T, Silny J, Schenke S, Peschgens T, Heimann G, Skopnik H. Gastroesophageal reflux and respiratory phenomena in infants: status of the intraluminal impedance technique. Journal of Pediatric Gastroenterology Nutrition 1999;28(4):423-8.

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Data and analyses

  • None noted.

Sources of support

Internal sources

  • No sources of support provided

External sources

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA
  • Editorial support of the Cochrane Neonatal Review Group has been funded with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA, under Contract No. HHSN275201100016C

Appendices

1 Methods to be used in subsequent updates of this review

Data extraction and management

We will design a form onto which data can be extracted. For eligible studies, review authors will extract data using the agreed upon form. We will resolve discrepancies through discussion; if required, we will consult a review arbiter. We will enter data into Review Manager software (RevMan 2011) and will check them for accuracy.

When information regarding any of the above is unclear, we will attempt to contact authors of the original reports to obtain further details.

Assessment of risk of bias in included studies

Review authors will independently assess risk of bias for each study, using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will resolve disagreements by discussion or with involvement of a review arbiter. We will assess the following criteria.

  • Random sequence generation (checking for possible selection bias).
    We will describe for each included study the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups. We will assess the risk of bias methods as:
    • low risk (any truly random process, e.g. random number table; computer random number generator);
    • high risk (any non-random process, e.g. odd or even date of birth; hospital or clinic record number); or
    • unclear risk.
  • Allocation concealment (checking for possible selection bias).
    We will describe in sufficient detail for each included study the method used to conceal the allocation sequence and will determine whether intervention allocation could have been foreseen in advance of, or during, recruitment, or changed after assignment. We will assess the risk of bias methods as:
    • low risk (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);
    • high risk (open random allocation; unsealed or non-opaque envelopes; alternation; date of birth); or
    • unclear risk.
  • Blinding (checking for possible performance bias).
    We will describe for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We will judge studies to be at low risk of bias if they were blinded, or if we judge that lack of blinding could not have affected the results. We will assess blinding separately for different outcomes or classes of outcomes. We will assess the risk of bias methods as:
    • adequate, inadequate or unclear for participants;
    • adequate, inadequate or unclear for personnel; or
    • adequate, inadequate or unclear for outcome assessors.
  • Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts and protocol deviations).
    We will describe for each included study, and for each outcome or class of outcomes, the completeness of data, including attrition and exclusions from the analysis. We will state whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total number of randomly assigned participants), reasons for attrition or exclusion when reported and whether missing data were balanced across groups or were related to outcomes. When sufficient information is reported, or can be supplied by the trial authors, we will re-include missing data in the analyses that we undertake. We will assess the risk of bias methods as:
    • adequate (less than 20% missing data);
    • inadequate; or
    • unclear.
  • Selective reporting bias.
    We will describe for each included study how we investigated the possibility of selective outcome reporting bias and what we found. We will assess the risk of bias methods as:
    • low risk (when it is clear that all of the study’s prespecified outcomes and all expected outcomes of interest to the review have been reported);
    • high risk (when not all of the study’s prespecified outcomes have been reported; one or more reported primary outcomes were not prespecified; outcomes of interest were reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported); or
    • unclear risk.
  • Other sources of bias.
    We will describe for each included study any important concerns we have about other possible sources of bias (e.g. early termination of trial due to data-dependent process, extreme baseline imbalance). We will assess whether each study was free of other problems that could put it at risk of bias. We will assess other sources of bias as:
    • low risk;
    • high risk; or
    • unclear.
  • Overall risk of bias.
    We will make explicit judgements about whether studies are at high risk of bias, according to the criteria given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). With reference to the above, we will assess the likely magnitude and direction of the bias and whether we consider it likely to impact the findings. We will explore the impact of the level of bias by undertaking sensitivity analyses (see Sensitivity analysis).

This review is published as a Cochrane review in The Cochrane Library, Issue 7, 2014 (see http://www.thecochranelibrary.com External Web Site Policy for information).  Cochrane reviews are regularly updated as new evidence emerges and in response to feedback.  The Cochrane Library should be consulted for the most recent version of the review.