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

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Referencias

References to studies included in this review

Caple 2004 {published data only}

Caple J, Armentrout D, Huseby V, Halbardier B, Garcia J, Sparks JW, et al. Randomized, controlled trial of slow versus rapid feeding volume advancement in preterm infants. Pediatrics 2004;114(6):1597‐600. [PUBMED: 15574620]

Karagol 2012 {published data only}

Karagol BS, Zenciroglu A, Okumus N, Polin RA. Randomized controlled trial of slow versus rapid enteral feeding advancements on the clinical outcomes of preterm infants with 750‐1250g. Journal of Parenteral and Enteral Nutrition 2013;37(2):223‐8. [PUBMED: 22664861]

Krishnamurthy 2010 {published data only}

Krishnamurthy S, Gupta P, Debnath S, Gomber S. Slow versus rapid enteral feeding advancement in preterm newborn infants 1000‐1499 g: a randomized controlled trial. Acta Paediatrica 2010;99(1):42‐6. [PUBMED: 20002013]

Mukhopadhyay 2014 {published data only}

Mukhopadhyay K, Jain S. Feed intolerance and necrotising enterocolitis in rapid vs slow feeding in preterm neonates with absent end diastolic flow: a randomised controlled trial. Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting. Vancouver, Canada: Pediatric Academic Societies, 2014.

Rayyis 1999 {published data only}

Rayyis SF, Ambalavanan N, Wright L, Carlo WA. Randomized trial of "slow" versus "fast" feed advancements on the incidence of necrotizing enterocolitis in very low birth weight infants. Journal of Pediatrics 1999;134(3):293‐7. [PUBMED: 10064664]

Salhotra 2004 {published data only}

Salhotra A, Ramji S. Slow versus fast enteral feed advancement in very low birth weight infants: a randomized control trial. Indian Pediatrics 2004;41(5):435‐41. [PUBMED: 15181294]

References to studies excluded from this review

Berseth 2003 {published data only}

Berseth CL, Bisquera JA, Paje VU. Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2003;111(3):529‐34. [PUBMED: 12612232]

Book 1976 {published data only}

Book LS, Herbst JJ, Jung AL. Comparison of fast‐ and slow‐feeding rate schedules to the development of necrotizing enterocolitis. Journal of Pediatrics 1976;89(3):462‐6. [PUBMED: 989057]

Beeby 1992

Beeby PJ, Jeffery H. Risk factors for necrotising enterocolitis: the influence of gestational age. Archives of Disease in Childhood 1992;67(4 Spec No):423‐5. [PUBMED: 1586186]

Bernstein 2000

Bernstein IM, Horbar JD, Badger GJ, Ohlsson A, Golan A. Morbidity and mortality among very‐low‐birth‐weight neonates with intrauterine growth restriction. The Vermont Oxford Network. American Journal of Obstetrics and Gynecology 2000;182(1 Pt 1):198‐206. [PUBMED: 10649179]

Bertino 2009

Bertino E, Giuliani F, Prandi G, Coscia A, Martano C, Fabris C. Necrotizing enterocolitis: risk factor analysis and role of gastric residuals in very low birth weight infants. Journal of Pediatric Gastroenterology and Nutrition 2009;48(4):437‐42. [PUBMED: 19330932]

Bisquera 2002

Bisquera JA, Cooper TR, Berseth CL. Impact of necrotizing enterocolitis on length of stay and hospital charges in very low birth weight infants. Pediatrics 2002;109(3):423‐8. [PUBMED: 11875136]

Bombell 2009

Bombell S, McGuire W. Early trophic feeding for very low birth weight infants. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD000504.pub3; PUBMED: 19588318]

Brown 1978

Brown EG, Sweet AY. Preventing necrotizing enterocolitis in neonates. JAMA 1978;240(22):2452‐4.

Chauhan 2008

Chauhan M, Henderson G, McGuire W. Enteral feeding for very low birth weight infants: reducing the risk of necrotising enterocolitis. Archives of Disease in Childhood. Fetal and Neonatal Edition 2008;93(2):F162‐6. [PUBMED: 18006565]

Cobb 2004

Cobb BA, Carlo WA, Ambalavanan N. Gastric residuals and their relationship to necrotizing enterocolitis in very low birth weight infants. Pediatrics 2004;113(1 Pt 1):50‐3. [PUBMED: 14702446]

Dorling 2005

Dorling J, Kempley S, Leaf A. Feeding growth restricted preterm infants with abnormal antenatal Doppler results. Archives of Disease in Childhood. Fetal and Neonatal Edition 2005;90(5):F359‐63. [PUBMED: 16113150]

Flidel‐Rimon 2004

Flidel‐Rimon O, Friedman S, Lev E, Juster‐Reicher A, Amitay M, Shinwell ES. Early enteral feeding and nosocomial sepsis in very low birthweight infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2004;89(4):F289‐92. [PUBMED: 15210657]

Flidel‐Rimon 2006

Flidel‐Rimon O, Branski D, Shinwell ES. The fear of necrotizing enterocolitis versus achieving optimal growth in preterm infants‐‐an opinion. Acta Paediatrica 2006;95(11):1341‐4. [PUBMED: 17062457]

Garite 2004

Garite TJ, Clark R, Thorp JA. Intrauterine growth restriction increases morbidity and mortality among premature neonates. American Journal of Obstetrics and Gynecology 2004;191(2):481‐7. [PUBMED: 15343225]

Guthrie 2003

Guthrie SO, Gordon PV, Thomas V, Thorp JA, Peabody J, Clark RH. Necrotizing enterocolitis among neonates in the United States. Journal of Perinatology 2003;23(4):278‐85. [PUBMED: 12774133]

Henderson 2009

Henderson G, Craig S, Brocklehurst P, McGuire W. Enteral feeding regimens and necrotising enterocolitis in preterm infants: a multicentre case‐control study. Archives of Disease in Childhood. Fetal and Neonatal Edition 2009;94(2):F120‐3. [PUBMED: 17768154]

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. Available from www.cochrane‐handbook.org.

Holman 1997

Holman RC, Stoll BJ, Clarke MJ, Glass RI. The epidemiology of necrotizing enterocolitis infant mortality in the United States. American Journal of Public Health 1997;87(12):2026‐31. [PUBMED: 9431297]

Härtel 2009

Härtel C, Haase B, Browning‐Carmo K, Gebauer C, Kattner E, Kribs A, et al. Does the enteral feeding advancement affect short‐term outcomes in very low birth weight infants?. Journal of Pediatric Gastroenterology and Nutrition 2009;48(4):464‐70. [PUBMED: 19322056]

Luig 2005

Luig M, Lui K, NSW & ACT NICUS Group. Epidemiology of necrotizing enterocolitis‐‐Part II: Risks and susceptibility of premature infants during the surfactant era: a regional study. Journal of Paediatrics and Child Health 2005;41(4):174‐9. [PUBMED: 15813870]

McKeown 1992

McKeown RE, Marsh TD, Amarnath U, Garrison CZ, Addy CL, Thompson SJ, et al. Role of delayed feeding and of feeding increments in necrotizing enterocolitis. Journal of Pediatrics 1992;121(5 Pt 1):764‐70. [PUBMED: 1432431]

Mihatsch 2002

Mihatsch WA, von Schoenaich P, Fahnenstich H, Dehne N,  Ebbecke H,  Plath C,  et al. The significance of gastric residuals in the early enteral feeding advancement of extremely low birth weight infants. Pediatrics 2002;109(3):457‐9. [PUBMED: 11875141]

Montori 2005

Montori VM,  Devereaux PJ,  Adhikari NK,  Burns KE,  Eggert CH,  Briel M, et al. Randomized trials stopped early for benefit: a systematic review. JAMA 2005;294(17):2203‐9. [PUBMED: 16264162]

Morgan 2011

Morgan J, Young L, McGuire W. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database of Systematic Reviews 2011, Issue 3. [DOI: 10.1002/14651858.CD001970.pub3; PUBMED: 21412877]

Patole 2005

Patole SK, de Klerk N. Impact of standardised feeding regimens on incidence of neonatal necrotising enterocolitis: a systematic review and meta‐analysis of observational studies. Archives of Disease in Childhood. Fetal and Neonatal Edition 2005;90(2):F147‐51. [PUBMED: 15724039]

Pike 2012

Pike K, Brocklehurst P, Jones D, Kenyon S, Salt A, Taylor D, et al. Outcomes at 7 years for babies who developed neonatal necrotising enterocolitis: the ORACLE Children Study. Archives of Disease in Childhood. Fetal and Neonatal Edition 2012;97(5):F318‐22. [PUBMED: 22933088]

Premji 2011

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. [DOI: 10.1002/14651858.CD001819.pub2; PUBMED: 22071802]

Quigley 2014

Quigley MA, McGuire W. Formula versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database of Systematic Reviews 2014, Issue 4. [DOI: 10.1002/14651858.CD002971.pub2; PUBMED: 24752468]

Rees 2007

Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Archives of Disease in Childhood. Fetal and Neonatal Edition 2007;92(3):F193‐8. [PUBMED: 16984980]

RevMan 2011 [Computer program]

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

Soraisham 2006

Soraisham AS, Amin HJ, Al‐Hindi MY, Singhal N, Sauve RS. Does necrotising enterocolitis impact the neurodevelopmental and growth outcomes in preterm infants with birthweight < or =1250 g?. Journal of Paediatrics and Child Health 2006;42(9):499‐504. [PUBMED: 16925534]

Stoll 2004

Stoll BJ, Hansen NI, Adams‐Chapman I, Fanaroff AA, Hintz SR, Vohr B, et al. Neurodevelopmental and growth impairment among extremely low‐birth‐weight infants with neonatal infection. JAMA 2004;292(19):2357‐65. [PUBMED: 15547163]

Tyson 2007

Tyson JE, Kennedy KA, Lucke JF, Pedroza C. Dilemmas initiating enteral feedings in high risk infants: how can they be resolved?. Seminars in Perinatology 2007;31(2):61‐73. [PUBMED: 17462490]

Uauy 1991

Uauy RD, Fanaroff AA, Korones SB, Phillips EA, Phillips JB, Wright LL. Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates. National Institute of Child Health and Human Development Neonatal Research Network. Journal of Pediatrics 1991;119(4):630‐8. [PUBMED: 1919897]

Walsh 1986

Walsh MC, Kliegman RM. Necrotizing enterocolitis: treatment based on staging criteria. Pediatric Clinics of North America 1986;33(1):179‐201. [PUBMED: 3081865]

References to other published versions of this review

Kennedy 2005

Kennedy KA, Tyson JE, Chamnanvanakij S. Rapid versus slow rate of advancement of feedings for promoting growth and preventing necrotizing enterocolitis in parenterally fed low‐birth‐weight infants. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD001241.pub2]

McGuire 2008

McGuire W, Bombell S. Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database of Systematic Reviews 2008, Issue 2. [DOI: 10.1002/14651858.CD001241.pub2; PUBMED: 18425870]

Morgan 2011a

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 2011, Issue 3. [DOI: 10.1002/14651858.CD001241.pub3; PUBMED: 21412870]

Morgan 2013

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. [DOI: 10.1002/14651858.CD001241.pub4; PUBMED: 23543511]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Caple 2004

Methods

Randomised controlled trial

Participants

Preterm infants of birth weight 1000 g to 2000 g (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

Interventions

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

Outcomes

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

Notes

Feeds 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

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number sequence

Allocation concealment (selection bias)

Low risk

Blinded draw from envelope by caregivers not involved in study

Blinding (performance bias and detection bias)
Clinical assessments

High risk

Caregivers and clinical investigators were not blinded once allocation to intervention groups had occurred.

Blinding (performance bias and detection bias)
Radiological assessments

Low risk

Radiologists interpreting X‐rays were blinded to the intervention group.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Three 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 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

Methods

Randomised controlled trial

Participants

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

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

Interventions

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

Outcomes

NEC (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

Notes

Feeds 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

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated sequence

Allocation concealment (selection bias)

Low risk

Opaque, sealed envelopes

Blinding (performance bias and detection bias)
Clinical assessments

High risk

Caregivers and study investigators were not blinded.

Blinding (performance bias and detection bias)
Radiological assessments

Unclear risk

No reference to whether staff interpreting radiological images were blinded to the study groups

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No participants lost to follow‐up

Krishnamurthy 2010

Methods

Randomised controlled trial

Participants

Preterm infants (birth weight 1000 g to 1499 g) 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

Interventions

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

Outcomes

NEC (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

Notes

All feeds were delivered by gavage via nasogastric tubes at 2‐hour intervals.

Feeds were ceased if any of the following occurred: residual gastric contents more than 50% of the previous feed volume (delayed if volume was 25% to 50%); more than 3 episodes of apnoea in the preceding hour; abdominal distention or tenderness; or bloody stools (including occult blood).

Parenteral nutrition was not available.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated sequence

Allocation concealment (selection bias)

Low risk

Opaque, sealed envelopes

Blinding (performance bias and detection bias)
Clinical assessments

High risk

Caregivers and investigators were not blinded to the interventions.

Blinding (performance bias and detection bias)
Radiological assessments

Low risk

Radiologist interpreting X‐rays was blinded to the intervention group.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up

Mukhopadhyay 2014

Methods

Randomised controlled trial

Participants

Preterm infants (birth weight 1000 g to 1249 g) and gestational age > 30 weeks at birth who have antenatal evidence of absent end diastolic flow velocities (presumed in umbilical artery)

Setting: Department of Paediatrics, Postgraduate Institute of Medical Education & Research, Chandigarh, India

Interventions

Feeds advancement at 20 ml/kg/day (N = 15) versus 30 ml/kg/day (N = 15)

Outcomes

NEC (all stages)

Late‐onset bloodstream (culture‐positive) infection, in‐hospital mortality, time to achieve full enteral feeds

Notes

Pre‐specified subgroup of larger trial that enrolled infants with birth weight > 1250 g and compared feed advancement at 30 ml/kg/day versus 40 ml/kg/day

Published as conference abstract; further data courtesy of Dr Mukhopadhyay (September 2014)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated

Allocation concealment (selection bias)

Low risk

Sealed, opaque envelopes

Blinding (performance bias and detection bias)
Clinical assessments

High risk

Caregivers and investigators were not blinded to the interventions.

Blinding (performance bias and detection bias)
Radiological assessments

Unclear risk

Not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up for primary outcomes

Rayyis 1999

Methods

Randomised controlled trial

Participants

Very low birth weight infants of gestational age < 34 weeks at birth

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

Interventions

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

Outcomes

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

Notes

Infants 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 any of the following occurred: residual gastric contents more than 30% of the previous feed volume, abdominal distention or tenderness, or bloody stools (including occult blood).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated

Allocation concealment (selection bias)

Low risk

Opaque, sealed envelopes

Blinding (performance bias and detection bias)
Clinical assessments

High risk

Caregivers and investigators not blinded to the intervention groups.

Blinding (performance bias and detection bias)
Radiological assessments

Low risk

Radiologist interpreting the X‐rays was blinded to the study group.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

7 protocol violations occurred after enrolment, but all infants were included the final data analysis.

Salhotra 2004

Methods

Randomised controlled trial

Participants

Preterm infants of birth weight < 1250 g. 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

Interventions

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

Outcomes

NEC (stage II/III)

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

Notes

Feeds 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

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated sequence

Allocation concealment (selection bias)

Low risk

Opaque, sealed envelopes

Blinding (performance bias and detection bias)
Clinical assessments

High risk

Investigators were blinded at allocation stage, but it is unclear if they remained blinded thereafter. Caregivers were not blinded to intervention group.

Blinding (performance bias and detection bias)
Radiological assessments

Unclear risk

No statement about blinding of radiological assessors to intervention group

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Berseth 2003

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

Book 1976

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

Data and analyses

Open in table viewer
Comparison 1. Slow versus faster rates of feed advancement

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Incidence of necrotising enterocolitis Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.1

Comparison 1 Slow versus faster rates of feed advancement, Outcome 1 Incidence of necrotising enterocolitis.

Comparison 1 Slow versus faster rates of feed advancement, Outcome 1 Incidence of necrotising enterocolitis.

1.1 All trials

6

618

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.55, 1.70]

1.2 Trials in which most infants were small for gestational age or growth restricted

2

83

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.06, 2.04]

2 Mortality Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.2

Comparison 1 Slow versus faster rates of feed advancement, Outcome 2 Mortality.

Comparison 1 Slow versus faster rates of feed advancement, Outcome 2 Mortality.

2.1 All trials

5

460

Risk Ratio (M‐H, Fixed, 95% CI)

1.57 [0.92, 2.70]

2.2 Trials in which most infants were small for gestational age or growth restricted

2

83

Risk Ratio (M‐H, Fixed, 95% CI)

2.13 [1.02, 4.47]

3 Feeds intolerance (causing interruption of enteral feeding) Show forest plot

4

275

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.87, 1.73]

Analysis 1.3

Comparison 1 Slow versus faster rates of feed advancement, Outcome 3 Feeds intolerance (causing interruption of enteral feeding).

Comparison 1 Slow versus faster rates of feed advancement, Outcome 3 Feeds intolerance (causing interruption of enteral feeding).

4 Incidence of invasive infection Show forest plot

3

222

Risk Ratio (M‐H, Fixed, 95% CI)

1.58 [0.81, 3.09]

Analysis 1.4

Comparison 1 Slow versus faster rates of feed advancement, Outcome 4 Incidence of invasive infection.

Comparison 1 Slow versus faster rates of feed advancement, Outcome 4 Incidence of invasive infection.

Forest plot of comparison: 1 Slow versus faster rates of feed advancement, outcome: 1.1 Incidence of necrotising enterocolitis.
Figuras y tablas -
Figure 1

Forest plot of comparison: 1 Slow versus faster rates of feed advancement, outcome: 1.1 Incidence of necrotising enterocolitis.

Forest plot of comparison: 1 Slow versus faster rates of feed advancement, outcome: 1.2 Mortality.
Figuras y tablas -
Figure 2

Forest plot of comparison: 1 Slow versus faster rates of feed advancement, outcome: 1.2 Mortality.

Forest plot of comparison: 1 Slow versus faster rates of feed advancement, outcome: 1.3 Feeds intolerance (causing interruption of enteral feeding).
Figuras y tablas -
Figure 3

Forest plot of comparison: 1 Slow versus faster rates of feed advancement, outcome: 1.3 Feeds intolerance (causing interruption of enteral feeding).

Forest plot of comparison: 1 Slow versus faster rates of feed advancement, outcome: 1.4 Incidence of invasive infection.
Figuras y tablas -
Figure 4

Forest plot of comparison: 1 Slow versus faster rates of feed advancement, outcome: 1.4 Incidence of invasive infection.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 5

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Comparison 1 Slow versus faster rates of feed advancement, Outcome 1 Incidence of necrotising enterocolitis.
Figuras y tablas -
Analysis 1.1

Comparison 1 Slow versus faster rates of feed advancement, Outcome 1 Incidence of necrotising enterocolitis.

Comparison 1 Slow versus faster rates of feed advancement, Outcome 2 Mortality.
Figuras y tablas -
Analysis 1.2

Comparison 1 Slow versus faster rates of feed advancement, Outcome 2 Mortality.

Comparison 1 Slow versus faster rates of feed advancement, Outcome 3 Feeds intolerance (causing interruption of enteral feeding).
Figuras y tablas -
Analysis 1.3

Comparison 1 Slow versus faster rates of feed advancement, Outcome 3 Feeds intolerance (causing interruption of enteral feeding).

Comparison 1 Slow versus faster rates of feed advancement, Outcome 4 Incidence of invasive infection.
Figuras y tablas -
Analysis 1.4

Comparison 1 Slow versus faster rates of feed advancement, Outcome 4 Incidence of invasive infection.

Comparison 1. Slow versus faster rates of feed advancement

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Incidence of necrotising enterocolitis Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 All trials

6

618

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.55, 1.70]

1.2 Trials in which most infants were small for gestational age or growth restricted

2

83

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.06, 2.04]

2 Mortality Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 All trials

5

460

Risk Ratio (M‐H, Fixed, 95% CI)

1.57 [0.92, 2.70]

2.2 Trials in which most infants were small for gestational age or growth restricted

2

83

Risk Ratio (M‐H, Fixed, 95% CI)

2.13 [1.02, 4.47]

3 Feeds intolerance (causing interruption of enteral feeding) Show forest plot

4

275

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.87, 1.73]

4 Incidence of invasive infection Show forest plot

3

222

Risk Ratio (M‐H, Fixed, 95% CI)

1.58 [0.81, 3.09]

Figuras y tablas -
Comparison 1. Slow versus faster rates of feed advancement