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Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants

  1. Jessie Morgan,
  2. Lauren Young,
  3. William McGuire*

Editorial Group: Cochrane Neonatal Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 28 DEC 2012

DOI: 10.1002/14651858.CD001241.pub4

How to Cite

Morgan J, Young L, McGuire W. Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD001241. DOI: 10.1002/14651858.CD001241.pub4.

Author Information

  1. Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, UK

*William McGuire, Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, Y010 5DD, UK. William.McGuire@hyms.ac.uk.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 28 MAR 2013

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Characteristics of included studies [ordered by study ID]
Caple 2004

MethodsRandomised controlled trial


ParticipantsPreterm infants of birth weight 1000-2000 grams (appropriate birth weight for gestational age and of gestational age <35 weeks at birth), who were starting formula feeds

Setting: Neonatal Unit, Department of Pediatrics, University of Texas Medical School, Houston, Texas, USA


InterventionsFeeds advancement at 20 ml/kg/day (N = 74) versus 30 ml/kg/day (N = 84)


OutcomesNEC (Bell stage II/III)
Time to regain birth weight, time to achieve full enteral feeds, and time to hospital discharge


NotesFeeds were ceased if the residual gastric aspirate was more than one-third of the previous feed volume, or if there was frequent vomiting, abdominal distention, or bloody stools (including occult blood)

We have not been able to obtain data on all-cause mortality from the principal investigators


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number sequence

Allocation concealment (selection bias)Low riskBlinded draw from envelope by caregivers not involved in study

Blinding (performance bias and detection bias)
Clinical assessments
High riskCare givers and clinical investigators were not blinded once allocation to intervention groups had occurred

Blinding (performance bias and detection bias)
Radiological assessments
Low riskRadiologists interpreting x-rays were blinded to the intervention group

Incomplete outcome data (attrition bias)
All outcomes
Low riskThree infants excluded after enrolment because of protocol violations have been included in this review and meta-analysis. Two infants (one in each group) were excluded because they were determined not to be eligible for enrolment (because of an in utero gastrointestinal perforation and fetal alcohol syndrome); these infants were not included in the meta-analysis

Karagol 2012

MethodsRandomised controlled trial


ParticipantsPreterm infants < 32 weeks gestation with birth weights of 750-1250 grams. 32% of participants weighed <1000 grams Exclusion criteria included major congenital malformations, severe respiratory distress, presence of umbilical vessel catheters, contraindications to enteral feeding, perinatal asphyxia or cardiovascular compromise

Setting: Dr Sami Ulus Maternity Childrens' Education and Research Hospital, Division of Neonatology, Ankara, Turkey


InterventionsSlow advancement at 20 ml/kg/day (N=46) versus rapid advancement at 30 ml/kg/day (N=46)


OutcomesNEC (stage II/III), all-cause mortality, time to regain birth weight, time to reach full enteral feeds, feed intolerance, duration of hospital stay, rates of invasive infection

Subgroup analysis for ELBW infants


NotesFeeds were ceased if any of the following occurred: gastric residuals > 5 ml/kg or >50% of feed volume, vomiting >3 times in 24 hours, increase in abdominal girth >2 cm between feeds, abdominal tenderness or erythema, reduced bowel sounds, blood in the stools or recurrent apnoea


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer generated sequence

Allocation concealment (selection bias)Low riskOpaque sealed envelopes

Blinding (performance bias and detection bias)
Clinical assessments
High riskCaregivers and study investigators were not blinded

Blinding (performance bias and detection bias)
Radiological assessments
Unclear riskNo reference to whether staff interpreting radiological images were blinded to the study groups

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo participants lost to follow up

Krishnamurthy 2010

MethodsRandomised controlled trial


ParticipantsPreterm infants (birth weight 1000-1499 grams) and gestational age <34 weeks at birth. Exclusion criteria included respiratory distress, mechanical ventilation, inotrope support, and umbilical arterial or venous catheterisation

Setting: Department of Paediatrics, University College of Medical Sciences, Dehli, India


InterventionsFeeds advancement at 20 ml/kg/day (N = 50) versus 30 ml/kg/day (N = 50)


OutcomesNEC (stage II/III)

Incidence of nosocomial infection, in-hospital mortality, time to regain birth weight, time to achieve full enteral feeds, and time to hospital discharge


NotesAll feeds were delivered by gavage via nasogastric tubes at 2 hourly intervals

Feeds were ceased if the residual gastric contents were more than 50% of the previous feed volume (delayed if volume was 25-50%), or if there were more than 3 episodes of apnoea in the preceding hour, or abdominal distention or tenderness, or bloody stools (including occult blood)

Parenteral nutrition was not available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer generated sequence

Allocation concealment (selection bias)Low riskOpaque sealed envelopes

Blinding (performance bias and detection bias)
Clinical assessments
High riskCare givers and investigators were not blinded to the interventions

Blinding (performance bias and detection bias)
Radiological assessments
Low riskX-rays were interpreted by a radiologist blind to the intervention group

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo loss to follow up

Rayyis 1999

MethodsRandomised controlled trial


ParticipantsVery low birth weight infants of gestational age less than 34 weeks' at birth

Setting: Neonatal Unit, Department of Pediatrics, University of Alabama, Birmingham, Alabama, USA


InterventionsFeeds advancement at 15 ml/kg/day (N = 98) versus 35 ml/kg/day (N = 87)


OutcomesNEC (stage II/III).
Time to regain birth weight, time to achieve full enteral feeds, and time to hospital discharge


NotesInfants for whom full or partial feeding with expressed breast milk was planned were not eligible to participate. Feeding was commenced using standard 'term' artificial formula, then switched to nutrient-enriched 'preterm' formula when full enteral feeding had been achieved
Feeds were ceased if the residual gastric contents were more than 30% of the previous feed volume, or if there was abdominal distention or tenderness, or bloody stools (including occult blood)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot stated

Allocation concealment (selection bias)Low riskOpaque sealed envelopes

Blinding (performance bias and detection bias)
Clinical assessments
High riskCare givers and investigators not blinded to the intervention groups

Blinding (performance bias and detection bias)
Radiological assessments
Low riskRadiologist interpreting the x-rays was blinded to the study group

Incomplete outcome data (attrition bias)
All outcomes
Low risk7 protocol violations occurred after enrolment but all infants were included the final data analysis

Salhotra 2004

MethodsRandomised controlled trial


ParticipantsPreterm infants of birth weight <1250 grams. More than 95% of the participants were 'small for gestational age'. Exclusion criteria included recurrent apnoea, respiratory distress requiring supplemental oxygen, and receipt of inotrope support

Setting: Neonatal Unit , Maulana Azad Medical College (tertiary level teaching hospital), New Delhi, India


InterventionsFeeds advancement at 15 ml/kg/day (N = 26) versus 30 ml/kg/day (N = 27)


OutcomesNEC (stage II/III)

Neonatal mortality, time to regain birth weight, time to achieve full enteral feeds, and time to hospital discharge


NotesFeeds were ceased if the residual gastric content was more than 30% of the previous feed volume, or if there was abdominal distention

Mortality data courtesy of Dr Namasivayam Ambalavanan


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer generated sequence

Allocation concealment (selection bias)Low riskOpaque sealed envelopes

Blinding (performance bias and detection bias)
Clinical assessments
High riskInvestigators blinded at allocation stage but unclear if remained blinded thereafter. Caregivers not blinded to intervention group

Blinding (performance bias and detection bias)
Radiological assessments
Unclear riskNo statement about blinding of radiological assessors to intervention group

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo losses to follow up

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Berseth 2003Infants were allocated randomly to either a stable (not progressively increased) trophic feeding volume or to feed volume advancement at 20 ml/kg/day

Book 1976Enteral feeding volumes were advanced at 10 ml/kg/day versus 20 ml/kg/day, that is, both groups received 'slow' advancement of feed volumes

 
Comparison 1. Slow versus faster rates of feed advancement

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

 1 Incidence of necrotising enterocolitis5Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 All trials
5588Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.54, 1.74]

    1.2 Trials in which most infants were small for gestational age or growth restricted
153Risk Ratio (M-H, Fixed, 95% CI)0.21 [0.01, 4.12]

 2 Mortality4Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 All trials
4430Risk Ratio (M-H, Fixed, 95% CI)1.41 [0.81, 2.47]

    2.2 Trials in which most infants were small for gestational age or growth restricted
153Risk Ratio (M-H, Fixed, 95% CI)1.78 [0.83, 3.81]

 3 Feeds intolerance (causing interruption of enteral feeding)3245Risk Ratio (M-H, Fixed, 95% CI)1.29 [0.90, 1.85]

 4 Incidence of invasive infection2192Risk Ratio (M-H, Fixed, 95% CI)1.5 [0.71, 3.16]