Intervention Review

You have free access to this content

Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature infants less than 1500 grams

  1. Shahirose S Premji1,*,
  2. Lorraine Chessell2

Editorial Group: Cochrane Neonatal Group

Published Online: 9 NOV 2011

DOI: 10.1002/14651858.CD001819.pub2


How to Cite

Premji SS, 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.

Author Information

  1. 1

    University of Calgary, Faculty of Nursing, Calgary, Alberta, Canada

  2. 2

    McMaster University, Neonatal Unit, Hamilton, Ontario, Canada

*Shahirose S Premji, University of Calgary, Faculty of Nursing, 2500 University Drive NW, Calgary, Alberta, T2N 1N4, Canada. premjis@ucalgary.ca.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 9 NOV 2011

SEARCH

 
Characteristics of included studies [ordered by study ID]

MethodsRandomised - Yes.

Blindness of randomisation - Yes.
Blindness of intervention - No. Complete follow-up - No.
Blinding of outcome measurement - Can't tell.


Participants89 infants randomised. 9 post-randomisation exclusions.
80 infants analysed.

Inclusion: Infants 700-1250g, haemodynamically stable and ready to start enteral feeds.

Exclusion: Apgar score < 3 at 5 minutes, to receive breast milk, documented sepsis, NEC or unable to start feeding before day 10 of life.


InterventionsFeeding did not begin until umbilical arterial catheter removed.

Continuous feeding by infusion pump. Intermittent feeding given every 3 hours for 15-30 minutes by gravity via indwelling feeding tube.

Feeding protocol for each 50-100 g weight category.

Protocol to manage feeding intolerance (feeds held > 12 hours).

Energy and protein intake kept identical between groups.

Feeds: undiluted preterm formula (20 Kcal/oz).

Timing of Feeds:
Protocol was < 10 postnatal days. Actual for Continuous group was 5.7 +/- 2.1 days and for
Intermittent group was 5.6 +/- 2.2 days.


OutcomesPrimary: Days to full feeds (100 Kcal/kg/d).

Secondary: Feeding intolerance, days to regain birth weight, days to discharge weight of 2040 g, NEC, and apnoea (>15 seconds).


NotesSample size calculation based on 35% decrease in number of days to full feeds in continuous group.

Did not exclude SGA infants.

Uncertain when feeds changed from continuous to bolus feeding.

Numbers unbalanced.

Exclusions: 4 Continuous (none due to protocol violation) and 5 Bolus (3 due to protocol violation).

Larger proportion of infants whose feeds were held in the continuous group had residuals, whereas in the bolus group infants had apnea/bradycardia. Guidelines for residuals may allow larger volumes than some other studies.


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskStratified according to birth weight into one of two groups (700-1000g and 1001-1250g).

Randomly assigned within each weight group by using sequentially numbered opaque sealed envelopes using a table of random numbers.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskCaregivers not blinded as would not be feasible.


MethodsRandomised - Yes

Blindness of randomisation - Yes.
Blindness of intervention - No.
Complete follow-up - No.
Blinding of outcome measurement - No.


Participants28 infants randomised.
5 post-randomisation exclusions.
23 infants analysed.

Inclusion: AGA, < 48 hours postnatal age, no major congenital malformations, and informed consent.


InterventionsContinuous feeding by syringe pump.
Intermittent feeding by gravity every 2 hours in 501 - 750g group; every 3 hours in other infants.

Feeding protocol for each weight group.

Protocol to manage feeding intolerance (gastric residual > 20% of the volume fed over the previous 4 hr).

Feeds: undiluted human milk, preterm formula, (initially diluted), or both.

Timing of Feeds:
Protocol was day 2-5.
Actual was not stated.


OutcomesDays to full feeds (160 mL/kg/day). Days to regain birth weight.
Delay between expected time to full feeds vs actual time to full feeds.


NotesPilot study.

Additional data re: intervention, sample size and methodologic criteria provided by investigator as study initially available as abstract (now published).

No sample size calculation. 5 post-randomisation exclusions.

Regression analysis suggested mode of feeding as the only variable affecting feeding tolerance.

Awaiting subgroup data.


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskStratified by birth weight (501 - 750g; 751 - 1000g; 1001 - 1250g).

Assigned randomly (using random numbers). The randomisation assignment was performed using sealed opaque envelopes that were grouped in an even blocked design, by the stratification variable (birthweight).

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskInvestigators were not blinded to the study group assignment, but caregivers responsible for the infants' care and for feeding protocol performance were not part of the investigation.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskOutcome assessors were not blinded.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskExcluded nine infants from analysis. Of four patients excluded from the continuous group, one had been switched to breastfeeding, but none were excluded for feeding intolerance. Of five infants excluded from the intermittent group, three infants were excluded for protocol violation (feeding intolerance not specified) and one had been switched to breastfeeding.


MethodsBlindness of randomisation - Yes.
Blindness of intervention - No.
Complete follow-up - No.
Blinding of outcome measurements - for outcome of necrotizing enterocolitis only.


Participants70 infants randomised.
2 post-randomisation exclusion. 68 infants analysed.

Inclusion: gestational age 24 to 29 weeks and birth weight < 1200 grams, stable respiratory status (i.e., arterial-alveolar oxygen tension ratio >= 0.18), no major congenital malformations, maternal ability to read in Swedish, and residing within geographical catchment area of 3 independent neonatal units at Karolinska University Hospital.


InterventionsFeeding initiated before 30 hours postnatal age. Actual not stated.

Feeds: mother's own milk or frozen pasturized human milk from the local milk bank.

Continuous feedings by electric infusion pump and intermittent orogastric or nasogastric feedings given every third hour over a period of 15 to 40 minutes. Duration of feeding based on volume given and feeding difficulties experienced by infant. Protocol, based on infant's birth weight, followed for increasing feedings. At postmenstrual age of 32 weeks continuous nasogastric feedings weaned to intermittent feeding.

Feeding intolerance managed by "clinical routine" which included reducing volume of feeding or temporarily withholding feeding.

Fortification of human milk was initiated for all infants when total parenteral nutrition was discontinued.


OutcomesPrimary: Days to achieve full enteral feedings.

Secondary: Time to regain birth weight, anthropometric measurements, enteral intolerance, necrotizing enterocolitis, and septicaemia.


NotesInfants in the continuous feeding method group compared with infants from the 2 control groups (intermittent orogastric group and intermittent nasogastric group) combined as the two control groups did not "differ in primary outcome, demographic and birth-related factors, and duration of feedings" (p. 45).
No significant difference in protein and energy intakes.

Sample size calculation based on 40% difference in time to achieving full enteral feedings.

Did not exclude SGA infants.

Exclusions - 2 post-randomisation because of diagnosed malformations.

Switched intermittent orogastric feeding to continuous nasogastric feeding for 14 days (N=1). Switched intermittent orogastric feeding to intermittent nasogastric feeding for 13 days (N=1). Switched intermittent nasogastric feeding to intermittent orogastric feeding for 6 days (N=1). (Not clear if intention-to-treat).

Mortality - one infant in each feeding group (total 3) died in the early intervention phase due to respiratory and circulatory collapse (not accounted for in sample of the study). Two infants died after postmenstrual ages of 33 and 47 weeks due to septicaemia combined with sever respiratory and circulatory distress and chronic lung disease. Both infants were in the continuous nasogastric feeding group (accounted for in the sample of the study).


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskRandomised - do not indicate what method was used (e.g., random number table; however, used sealed opaque envelopes.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskCaregivers not blinded as would not be feasible.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskOnly radiographic assessors for the outcome of NEC were blinded to patient group assignment.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskExcluded two infants post randomisation because of diagnosed malformations. One infant in the control group was switched to the continuous feeding method group because of severe apnoea and bradycardia secondary to gastroesophageal reflux. Data for this infant was included as randomised. In the early intervention phase, three infants died (one infant in each feeding group) due to respiratory and circulatory collapse. Two infants in the continuous feeding method group died at postmenstrual ages of 33 and 47 weeks secondary to septicaemia and severe respiratory and circulatory distress and chronic lung disease.


MethodsRandomised.

No Stratification.

Blindness of randomisation - Yes.

Blindness of intervention - No.

Complete follow-up - No.

Blinding of outcome measurement - Can't tell.


Participants43 infants randomised. 9 post-randomisation exclusions. 34 infants analysed.

Inclusion: Infants < 1400 g.

Exclusion: Infants who received expressed breast milk, major congenital malformations, developed hydrocephalus, and if there was intrauterine viral infections.


InterventionsMilk feeding started on day 2 of life with 1 mL/hr of SMA low birthweight formula (Wyeth). Increased 0.5 to 1.0 mL/hr until tolerating 150 mL/kg/day (supplemented with total parenteral nutrition). Unclear frequency of bolus feeding, frequency of increase in feeds, equipment for delivery of continuous feeds.

Selected method used until infant attained weight of 1600 g.

No energy supplements during study period.


OutcomesGrowth rate including weight gain (grams/week), length gain (mm/week), and occipitofrontal circumference (mm/week), and triceps and quadriceps skinfold thickness, oral energy input, days to full feedings, and chosen biochemical indices (e.g., alkaline phosphatase, urea, albumin, prealbumin, and transferrin).

Complications: extra abdominal radiographs, proved aspiration, NEC (proved and probable - ?used Bell's staging), septicaemia, gastric bleeding.


NotesNo sample size calculation.

Did not exclude SGA infants.

Feeding intervention not described in detail.

5 exclusions in transpyloric group, 1 in continuous group and 3 in bolus group.

Report pooled standard deviations for days to full feedings (awaiting mean and standard deviation).

Extra abdominal radiographs (n=31) were performed for transpyloric tube placements. Aspiration (1 in continuous group) occurred when babies were over 1600 grams, hence were being fed by bolus nasogastric route. Gastric bleeding ( 1 in bolus group) occurred before milk feedings were started. Staphylococcus epidermidis - 1 case in each group - unclear if this was during study period or during length of stay in NICU.
Sample size for each group obtained from author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskOn day 2 the feeding route was determined for each baby by opening a sealed envelope.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskCaregivers not blinded as would not be feasible.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskEnrolled 13 babies in the continuous feeding method group but only 12 completed the study as one infant was transferred to another hospital at age two weeks of life. Three of the 15 infants enrolled in the bolus feeding method group died within the first week of life, before milk feedings were established and were therefore excluded from the analysis.


MethodsRandomised - Yes

Blindness of randomisation - yes.
Blindess of intervention - no.
Complete follow-up - yes.
Blinding of outcome measurements - can't tell.


Participants171 infants randomised.

Inclusion: 26 to 30 weeks gestation, AGA, postnatal age < or = 96 hours, no congenital anomalies, fraction of inspired oxygen < 0.6 by 72 hours, and written informed consent.

Removed infants from treatment protocol if unable to adhere to feeding protocol for > 1 week.


InterventionsGI priming vs no enteral intake day 4 to 14 and continuous vs bolus nasogastric tube feedings. 4 Groups: NPO continuous, NPO bolus, GI priming continuous, and GI prime bolus. Bolus feeding given every 3 hours over 20 minutes. Continuous feeding method not described. Feeding protocol for infants. Protocol to manage feeding intolerance based on excess gastric residual volume. Nutrient intakes similar between groups. Feeds: undiluted human milk or initially diluted preterm infant formula. Timing of Feeds:
Protocol was 4 - 14 days.
Actual was 6 - 16 days.


OutcomesPrimary: time to full oral feeding (8 breast/bottle feeding per day).

Secondary: days to full enteral feeding (150cc/kg/d), weight gain, head circumference gain, length gain, skinfold thickness (5 sites), feeding intolerance, NEC, apnoea (>20 seconds), nutritional balance studies, bone mineral content and serum indices of protein and mineral status.


NotesData comparing continuous vs intermittent groups obtained from investigator.
Intent-to-treat analysis.

Sample size calculation based on a 2 week difference in the time to full oral feeds.

Infants randomised to early vs late enteral feeds (day 4 vs 14).
11 infants switched protocol (10 continuous and 1 bolus). Observed greater incidence of residuals with continuous feeds, and more infants unable to adhere to feeding protocols.

Infants in the intermittent bolus feeding group - tube placement predominantly (> 90%) orogastric (personal communication).

Small sample size given the number of effects being examined (NPO, early feeding, and stratification of gestation age and feed type).

Have established criteria for transition to oral feeds, however, not well described, some criteria subjective (e.g. favourable oral motor assessment, increased apnoea, or oxygen needs).

Methods section states "The assigned orogastric/nasogastric tube-feeding method (continuous vs bolus) was maintained throughout the three phases". There is no further mention of tube placement, and no way to know how the babies were in the intermittent group were fed.

Awaiting subgroup data.


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskStratified by gestational age (26-27 vs 28-30 weeks) and by diet (human milk vs preterm formula) and assigned randomly among four treatment combinations in a balanced two-way design where the two treatments were the use of GI priming versus "non per os", or no enteral intake (NPO) from day 4 through 14 after birth and the method of tube-feeding, continuous infusion versus bolus. Randomisation was performed using sealed opaque envelopes that were grouped, in an uneven blocked design, by stratification variables (gestational age, intent to feed human milk).

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskCaregivers not blinded as would not be feasible.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskTo ensure the objective assessment of the major outcome variable, the time required by the infant to attain full oral feeding (8 breast and/or bottle feedings per day), oral-motor function was assessed serially, using a method designed specially for this study.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComplete follow-up. Infants were removed from the treatment protocol if they were not able to adhere to the feeding protocol for more than one week. Ten infants in the continuous group and one in the intermittent group were removed from their assigned feeding protocols because of feeding intolerance. However, data from these infants were included in the analysis.


MethodsRandomised.

Stratified:
750-999g,
1000-1249g, and 1250-1499g.
Blindness of randomisation - Yes. Blindness of intervention - No. Complete follow-up - Partial (only for stratified group). Blinding of outcome measurement - Yes.


Participants93 infants randomised. 11 post randomisation exclusions. 82 infants analysed (all 93 infants included in analysis of stratified groups).

Inclusion: Infants AGA with birth weight 750-1500 grams, born between 27-34 weeks gestation, had no major congenital malformations and stable to start feeds on day 2 or 3 of life.


InterventionsContinuous feeds administered over 3 hours, every 3 hours. Intermittent bolus feeds every 3 hours over 15-30 minutes. Feeding protocol for infants. Criteria to define feeding intolerance predetermined (gastric residual volume >= 2 hr feed for continuous or >= 2mL bolus feeds). Feeds: water, initially diluted preterm infant formula.
Timing of Feeds:
Protocol was day 2-3. Actual was not stated.


OutcomesPrimary: rate of weight gain. (*growth data was converted to grams/week).

Secondary: days to full feeds, days to regain birth weight, days to discharge, length gain, and head circumference gain.


NotesClarification of data for head circumference requested (data printed in the article appears to be significant but was reported as insignificant - ? typographical error in data).

Data on complete study sample not "intent-to-treat". Intent-to-treat analysis by weight groups.

Sample size calculation based on >/= 10% increase rate of weight gain in continuous group.

Full feeds not defined.

11 exclusions:
3 in Continuous group (1 protocol violation), 8 in Bolus group
(3 feeding intolerance, 2 protocol violations). Unbalanced numbers between groups.

?criteria for discharge.

Initial feed of water given for different duration (2 hours in continuous group vs 6 hours in bolus group).

Nipple feeding 34 wks or 1500 grams.


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)Low riskInfants were randomly assigned to either continuous or intermittent feedings.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskIn this study, investigators were not unaware of the feeding group assignment.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors were blinded.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskReported complete follow-up only for stratified groups. In this study, 11 infants were removed from treatment protocols and excluded from overall analyses. Of three infants excluded from the continuous group, none were excluded for feeding intolerance, although one was excluded for protocol violation. Of eight infants excluded from the intermittent group, three were excluded for feeding intolerance and another two for protocol violation. Follow-up was incomplete in the remaining three studies.


MethodsQuasi-experimental. Alternate assignment within 16 groups.
Stratified:
<1250g,
1250-1500g,
sex,
IUGR, and prior need for ventilation.

Blindness of randomisation - Can't tell.
Blindness of intervention - No.
Complete follow-up - No.
Blinding of outcome measurement - Can't tell.


Participants83 infants
(obtained consent). 30 excluded (completed less than 7 days). 53 analysed.

Inclusion:
Preterm infants <= 1500grams, no major congenital anomalies, no longer ventilated, and ready for enteral nutrition.


InterventionsContinuous feeds delivered by infusion pump. Intermittent feeds every 3 hours by gravity. Feeding protocol for infants. Predetermined criteria to manage feeding intolerance (feeds held > 16 hours). Energy intake constant between groups. Feeds: sterile water, initially diluted formula.
Timing of Feeds:
Protocol was not stated.
Actual for Continuous group was 9.7 +/- 7.1 days and for Intermittent group was 7.3 +/- 4.8 days.


OutcomesSomatic growth (weight, length, head circumference, and skinfold thickness gains), feeding related complications, changes in total protein, bilirubin, and albumin.


NotesSubjective eligibility criteria, no sample size calculation, and not intent-to-treat.

Definition of feeding intolerance not described.

Significant differences in demographic factors between groups: low one-minute Apgar scores in the Continous group, and increase frequency of human milk feeding in the Intermittent bolus gavage feeding method.

Awaiting subgroup data.


Risk of bias

BiasAuthors' judgementSupport for judgement

Allocation concealment (selection bias)High riskQuasi-experimental. Alternate assignment within 16 groups.
Stratified: <1250g, 1250-1500g, sex, IUGR, and prior need for ventilation.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskCaregivers not blinded as would not be feasible.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskPost-randomisation exclusion of infants from the analysis resulted in loss to follow-up.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Baker 1997Outcomes not clinically relevant to this review - duodenal motor responses.

Berseth 1992Population unknown (i.e. weight). Outcomes not clinically relevant to this review - intestinal motor activity.

Dsilna 2008Outcomes reported are not clinically relevant to this review.

 
Comparison 1. Continuous versus intermittent bolus (nasogastric and orogastric tube) milk feeding - all infants

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Feeding performance6Mean Difference (IV, Fixed, 95% CI)Subtotals only

   1.1 Days to full feeds
5424Mean Difference (IV, Fixed, 95% CI)1.82 [-0.29, 3.93]

   1.2 Days to full oral feeds
1171Mean Difference (IV, Fixed, 95% CI)1.0 [-4.85, 6.85]

   1.3 Days feeds interrupted for feeding intolerance
1171Mean Difference (IV, Fixed, 95% CI)-3.0 [-9.50, 3.50]

   1.4 Hours NPO per day
153Mean Difference (IV, Fixed, 95% CI)0.90 [-0.67, 2.47]

   1.5 Days on parenteral nutrition
2239Mean Difference (IV, Fixed, 95% CI)-4.77 [-9.52, -0.03]

 2 Growth6Mean Difference (IV, Fixed, 95% CI)Subtotals only

   2.1 Days to regain birthweight
4401Mean Difference (IV, Fixed, 95% CI)-0.46 [-1.48, 0.55]

   2.2 Weight gain (g/kg/day)
2224Mean Difference (IV, Fixed, 95% CI)-1.13 [-2.28, 0.03]

   2.3 Weight gain (g/week)
2106Mean Difference (IV, Fixed, 95% CI)6.27 [-1.28, 13.81]

   2.4 Length gain (cm/week)
4330Mean Difference (IV, Fixed, 95% CI)0.08 [-0.01, 0.17]

   2.5 Head circumference gain (cm/week)
3248Mean Difference (IV, Fixed, 95% CI)-0.03 [-0.09, 0.04]

   2.6 Change in triceps skinfold thickness (mm/week)
2135Mean Difference (IV, Fixed, 95% CI)0.0 [-0.06, 0.06]

 3 Utilization of resources3Mean Difference (IV, Fixed, 95% CI)Subtotals only

   3.1 Days to discharge
2253Mean Difference (IV, Fixed, 95% CI)-1.94 [-8.26, 4.38]

   3.2 Days to discharge weight of 2040g
180Mean Difference (IV, Fixed, 95% CI)-2.0 [-7.92, 3.92]

   3.3 Days on mechanical ventilation
180Mean Difference (IV, Fixed, 95% CI)-0.5 [-5.05, 4.05]

 4 Complications (categorical)5Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

   4.1 Proven NEC (Bell's stage II or greater)
5465Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.58, 2.07]

   4.2 Probable NEC
2133Risk Ratio (M-H, Fixed, 95% CI)1.53 [0.40, 5.89]

   4.3 Failure to complete protocol because of feeding intolerance
2264Risk Ratio (M-H, Fixed, 95% CI)2.48 [0.83, 7.40]

 5 Complications (continuous)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

   5.1 Apnoea (episodes per day)
153Mean Difference (IV, Fixed, 95% CI)-0.60 [-1.99, 0.79]

   5.2 Apnoea (episodes during study)
1171Mean Difference (IV, Fixed, 95% CI)14.0 [-0.20, 28.20]

 
Comparison 2. Continuous versus intermittent bolus (nasogastric tube) milk feeding - all infants

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Feeding performance5Mean Difference (IV, Fixed, 95% CI)Subtotals only

   1.1 Days to full feeds
4229Mean Difference (IV, Fixed, 95% CI)1.82 [-0.44, 4.08]

   1.2 Days to full oral feeds
00Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

   1.3 Days feeds interrupted for feeding intolerance
00Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

   1.4 Hours NPO per day
153Mean Difference (IV, Fixed, 95% CI)0.90 [-0.67, 2.47]

   1.5 Days on parenteral nutrition
00Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Growth5Mean Difference (IV, Fixed, 95% CI)Subtotals only

   2.1 Days to regain birthweight
3206Mean Difference (IV, Fixed, 95% CI)-0.31 [-1.65, 1.03]

   2.2 Weight gain (g/kg/day)
153Mean Difference (IV, Fixed, 95% CI)1.20 [-1.01, 3.41]

   2.3 Weight gain (g/week)
2106Mean Difference (IV, Fixed, 95% CI)6.27 [-1.28, 13.81]

   2.4 Length gain (cm/week)
3159Mean Difference (IV, Fixed, 95% CI)0.07 [-0.04, 0.18]

   2.5 Head circumference gain (cm/week)
277Mean Difference (IV, Fixed, 95% CI)0.01 [-0.12, 0.13]

   2.6 Change in triceps skinfold thickness (mm/week)
2135Mean Difference (IV, Fixed, 95% CI)0.0 [-0.06, 0.06]

 3 Utilization of resources2Mean Difference (IV, Fixed, 95% CI)Subtotals only

   3.1 Days to discharge
182Mean Difference (IV, Fixed, 95% CI)-1.0 [-8.62, 6.62]

   3.2 Days to discharge weight of 2040g
180Mean Difference (IV, Fixed, 95% CI)-2.0 [-7.92, 3.92]

   3.3 Days on mechanical ventilation
180Mean Difference (IV, Fixed, 95% CI)-0.5 [-5.05, 4.05]

 4 Complications (categorical)4Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

   4.1 Proven NEC (Bell's stage II or greater)
4270Risk Ratio (M-H, Fixed, 95% CI)2.23 [0.58, 8.57]

   4.2 Probable NEC
2133Risk Ratio (M-H, Fixed, 95% CI)1.53 [0.40, 5.89]

   4.3 Failure to complete protocol because of feeding intolerance
193Risk Ratio (M-H, Fixed, 95% CI)0.15 [0.01, 2.87]

 5 Complications (continuous)1Mean Difference (IV, Fixed, 95% CI)Subtotals only

   5.1 Apnoea (episodes per day)
153Mean Difference (IV, Fixed, 95% CI)-0.60 [-1.99, 0.79]

   5.2 Apnoea (episodes during study)
00Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 3. Continuous versus intermittent bolus (nasogastric and orogastric tube) milk feeding in infants < 1000g

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Feeding performance3Mean Difference (IV, Fixed, 95% CI)Subtotals only

   1.1 Days to full feeds
3120Mean Difference (IV, Fixed, 95% CI)-1.37 [-4.59, 1.84]

   1.2 Days on parenteral nutrition
155Mean Difference (IV, Fixed, 95% CI)-10.5 [-17.16, -3.84]

 2 Growth3Mean Difference (IV, Fixed, 95% CI)Subtotals only

   2.1 Days to regain birthweight
3120Mean Difference (IV, Fixed, 95% CI)-0.13 [-2.11, 1.84]

   2.2 Weight gain (g/day)
130Mean Difference (IV, Fixed, 95% CI)2.0 [0.54, 3.46]

   2.3 Length gain (cm/week)
130Mean Difference (IV, Fixed, 95% CI)0.07 [-0.08, 0.22]

   2.4 Head circumference gain (cm/week)
130Mean Difference (IV, Fixed, 95% CI)0.07 [-0.03, 0.17]

 3 Utilization of resources270Mean Difference (IV, Fixed, 95% CI)-2.48 [-7.63, 2.66]

   3.1 Days to discharge
130Mean Difference (IV, Fixed, 95% CI)-11.0 [-21.83, -0.17]

   3.2 Days to discharge weight of 2040 grams
140Mean Difference (IV, Fixed, 95% CI)0.0 [-5.85, 5.85]

 4 Complications (categorical)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

   4.1 Proven NEC (Bell's stage II or greater)
144Risk Ratio (M-H, Fixed, 95% CI)5.0 [0.25, 98.52]

   4.2 Probable NEC
00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 4. Continuous versus intermittent bolus (nasogastric tube) milk feeding in infants < 1000g

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Feeding performance2Mean Difference (IV, Fixed, 95% CI)Subtotals only

   1.1 Days to full feeds
270Mean Difference (IV, Fixed, 95% CI)0.77 [-2.78, 4.31]

 2 Growth2Mean Difference (IV, Fixed, 95% CI)Subtotals only

   2.1 Days to regain birthweight
270Mean Difference (IV, Fixed, 95% CI)-0.46 [-3.51, 2.60]

   2.2 Weight gain (g/day)
130Mean Difference (IV, Fixed, 95% CI)2.0 [0.54, 3.46]

   2.3 Length gain (cm/week)
130Mean Difference (IV, Fixed, 95% CI)0.07 [-0.08, 0.22]

   2.4 Head circumference gain (cm/week)
130Mean Difference (IV, Fixed, 95% CI)0.07 [-0.03, 0.17]

 3 Utilization of resources270Mean Difference (IV, Fixed, 95% CI)-2.48 [-7.63, 2.66]

   3.1 Days to discharge
130Mean Difference (IV, Fixed, 95% CI)-11.0 [-21.83, -0.17]

   3.2 Days to discharge weight of 2040 grams
140Mean Difference (IV, Fixed, 95% CI)0.0 [-5.85, 5.85]

 
Comparison 5. Continuous versus intermittent bolus (nasogastric tube) milk feeding in infants > 1000g and < 1249g

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Feeding performance2Mean Difference (IV, Fixed, 95% CI)Subtotals only

   1.1 Days to full feeds
271Mean Difference (IV, Fixed, 95% CI)-0.17 [-2.54, 2.21]

 2 Growth2Mean Difference (IV, Fixed, 95% CI)Subtotals only

   2.1 Days to regain birthweight
271Mean Difference (IV, Fixed, 95% CI)-0.40 [-2.45, 1.66]

   2.2 Weight gain (g/day)
131Mean Difference (IV, Fixed, 95% CI)2.0 [0.16, 3.84]

   2.3 Length gain (cm/week)
131Mean Difference (IV, Fixed, 95% CI)0.0 [-0.15, 0.15]

   2.4 Head circumference gain (cm/week)
131Mean Difference (IV, Fixed, 95% CI)0.0 [-0.52, 0.52]

 3 Utilization of resources2Mean Difference (IV, Fixed, 95% CI)Subtotals only

   3.1 Days to discharge
131Mean Difference (IV, Fixed, 95% CI)-2.0 [-9.18, 5.18]

   3.2 Days to discharge weight of 2040 grams
140Mean Difference (IV, Fixed, 95% CI)1.0 [-3.01, 5.01]

 
Comparison 6. Continuous versus intermittent bolus (nasogastric tube) milk feeding in infants > 1250g and < 1499g

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Feeding performance1Mean Difference (IV, Fixed, 95% CI)Subtotals only

   1.1 Days to full feeds
132Mean Difference (IV, Fixed, 95% CI)5.0 [-0.48, 10.48]

 2 Growth1Mean Difference (IV, Fixed, 95% CI)Subtotals only

   2.1 Days to regain birthweight
132Mean Difference (IV, Fixed, 95% CI)0.0 [-3.53, 3.53]

   2.2 Weight gain (g/day)
132Mean Difference (IV, Fixed, 95% CI)0.0 [-1.77, 1.77]

   2.3 Length gain (cm/week)
132Mean Difference (IV, Fixed, 95% CI)0.14 [-0.08, 0.36]

   2.4 Head circumference gain (cm/week)
132Mean Difference (IV, Fixed, 95% CI)0.0 [-0.10, 0.10]

 3 Utilization of resources1Mean Difference (IV, Fixed, 95% CI)Subtotals only

   3.1 Days to discharge
132Mean Difference (IV, Fixed, 95% CI)1.0 [-3.85, 5.85]