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Meta-Analysis
. 2021 Mar 9;3(3):CD012413.
doi: 10.1002/14651858.CD012413.pub3.

High versus standard volume enteral feeds to promote growth in preterm or low birth weight infants

Thangaraj Abiramalatha  1 , Niranjan Thomas  2 , Sivam Thanigainathan  3
Affiliations
Meta-Analysis

High versus standard volume enteral feeds to promote growth in preterm or low birth weight infants

Thangaraj Abiramalatha et al. Cochrane Database Syst Rev. .

Abstract

Background: Human milk is the best enteral nutrition for preterm infants. However, human milk, given at standard recommended volumes, is not adequate to meet the protein, energy, and other nutrient requirements of preterm or low birth weight infants. One strategy that may be used to address the potential nutrient deficits is to give a higher volume of enteral feeds. High volume feeds may improve nutrient accretion and growth, and in turn may improve neurodevelopmental outcomes. However, there are concerns that high volume feeds may cause feed intolerance, necrotising enterocolitis, or complications related to fluid overload such as patent ductus arteriosus and chronic lung disease. This is an update of a review published in 2017.

Objectives: To assess the effect on growth and safety of high versus standard volume enteral feeds in preterm or low birth weight infants. In infants who were fed fortified human milk or preterm formula, high and standard volume feeds were defined as > 180 mL/kg/day and ≤ 180 mL/kg/day, respectively. In infants who were fed unfortified human milk or term formula, high and standard volume feeds were defined as > 200 mL/kg/day and ≤ 200 mL/kg/day, respectively.

Search methods: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020 Issue 6) in the Cochrane Library; Ovid MEDLINE (1946 to June 2020); Embase (1974 to June 2020); and CINAHL (inception to June 2020); Maternity & Infant Care Database (MIDIRS) (1971 to April 2020); as well as previous reviews, and trial registries.

Selection criteria: We included randomised controlled trials (RCTs) that compared high versus standard volume enteral feeds for preterm or low birth weight infants.

Data collection and analysis: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) and risk difference for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. The primary outcomes were weight gain, linear and head growth during hospital stay, and extrauterine growth restriction at discharge.

Main results: We included two new RCTs (283 infants) in this update. In total, we included three trials (347 infants) in this updated review. High versus standard volume feeds with fortified human milk or preterm formula Two trials (283 infants) met the inclusion criteria for this comparison. Both were of good methodological quality, except for lack of masking. Both trials were performed in infants born at < 32 weeks' gestation. Meta-analysis of data from both trials showed high volume feeds probably improves weight gain during hospital stay (MD 2.58 g/kg/day, 95% CI 1.41 to 3.76; participants = 271; moderate-certainty evidence). High volume feeds may have little or no effect on linear growth (MD 0.05 cm/week, 95% CI -0.02 to 0.13; participants = 271; low-certainty evidence), head growth (MD 0.02 cm/week, 95% CI -0.04 to 0.09; participants = 271; low-certainty evidence), and extrauterine growth restriction at discharge (RR 0.71, 95% CI 0.50 to 1.02; participants = 271; low-certainty evidence). We are uncertain of the effect of high volume feeds with fortified human milk or preterm formula on the risk of necrotising enterocolitis (RR 0.74, 95% CI 0.12 to 4.51; participants = 283; very-low certainty evidence). High versus standard volume feeds with unfortified human milk or term formula One trial with 64 very low birth weight infants met the inclusion criteria for this comparison. This trial was unmasked but otherwise of good methodological quality. High volume feeds probably improves weight gain during hospital stay (MD 6.2 g/kg/day, 95% CI 2.71 to 9.69; participants = 61; moderate-certainty evidence). The trial did not provide data on linear and head growth, and extrauterine growth restriction at discharge. We are uncertain as to the effect of high volume feeds with unfortified human milk or term formula on the risk of necrotising enterocolitis (RR 1.03, 95% CI 0.07 to 15.78; participants = 61; very low-certainty evidence).

Authors' conclusions: High volume feeds (≥ 180 mL/kg/day of fortified human milk or preterm formula, or ≥ 200 mL/kg/day of unfortified human milk or term formula) probably improves weight gain during hospital stay. The available data is inadequate to draw conclusions on the effect of high volume feeds on other growth and clinical outcomes. A large RCT is needed to provide data of sufficient quality and precision to inform policy and practice.

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Conflict of interest statement

TA has no interest to declare.

NT was the principal investigator in one study included in this review (Thomas 2012). However, TA performed the 'Risk of bias' assessment and data extraction for the trial. NT received no funding for Thomas 2012.

ST has no interest to declare.

Core editorial and administrative support for this review has been provided by a grant from The Gerber Foundation. The Gerber Foundation is a separately endowed, private foundation, independent from the Gerber Products Company. The grantor has no input on the content of the review or the editorial process (see Sources of support).

Figures

1
1
Updated study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for the included study.
3
3
Forest plot of comparison: 1 High versus standard volume of fortified human milk or preterm formula, outcome: 1.1 Weight gain during hospital stay (g/kg/day).
4
4
Forest plot of comparison: 1 High versus standard volume of fortified human milk or preterm formula, outcome: 1.5 Necrotising enterocolitis.
5
5
Forest plot of comparison: 1 High versus standard volume of fortified human milk or preterm formula, outcome: 1.8 Weight at a specified postmenstrual age (g).
6
6
Forest plot of comparison: 1 High versus standard volume of fortified human milk or preterm formula, outcome: 1.10 Head circumference at a specified postmenstrual age (cm).
7
7
Forest plot of comparison: 2 High versus standard volume of unfortified human milk or term formula, outcome: 2.1 Weight gain during hospital stay (g/kg/day).
1.1
1.1. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 1: Weight gain during hospital stay (g/kg/day)
1.2
1.2. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 2: Linear growth during hospital stay (cm/week)
1.3
1.3. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 3: Head growth during hospital stay (cm/week)
1.4
1.4. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 4: Extrauterine growth restriction at discharge
1.5
1.5. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 5: Necrotising enterocolitis
1.6
1.6. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 6: Feed interruption episodes
1.7
1.7. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 7: Time to regain birth weight (days)
1.8
1.8. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 8: Weight at a specified postmenstrual age (g)
1.9
1.9. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 9: Length at a specified postmenstrual age (cm)
1.10
1.10. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 10: Head circumference at a specified postmenstrual age (cm)
1.11
1.11. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 11: PDA requiring treatment
1.12
1.12. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 12: Chronic lung disease
1.13
1.13. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 13: All‐cause mortality before discharge
1.14
1.14. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 14: Duration of hospital stay (days)
1.15
1.15. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 15: Weight < 10th percentile at 12 months' corrected age
1.16
1.16. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 16: Length < 10th percentile at 12 months' corrected age
1.17
1.17. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 17: Head circumference < 10th percentile at 12 months' corrected age
1.18
1.18. Analysis
Comparison 1: High versus standard volume of fortified human milk or preterm formula, Outcome 18: Neurodevelopmental impairment at 12 months' corrected age
2.1
2.1. Analysis
Comparison 2: High versus standard volume of unfortified human milk or term formula, Outcome 1: Weight gain during hospital stay (g/kg/day)
2.2
2.2. Analysis
Comparison 2: High versus standard volume of unfortified human milk or term formula, Outcome 2: Necrotising enterocolitis
2.3
2.3. Analysis
Comparison 2: High versus standard volume of unfortified human milk or term formula, Outcome 3: Time to regain birth weight (days)
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References

References to studies included in this review

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References to other published versions of this review

Abiramalatha 2016
    1. Abiramalatha T, Thomas N, Gupta V, Viswanathan A, McGuire W. High versus standard volumes of enteral feeds for preterm or low birth weight infants. Cochrane Database of Systematic Reviews 2016, Issue 10. Art. No: CD012413. [DOI: 10.1002/14651858.CD012413] - DOI - PMC - PubMed
Abiramalatha 2017
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