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. 2020 Sep 23;2020(9):CD000433. doi: 10.1002/14651858.CD000433.pub3

Summary of findings 1. Protein supplementation compared to control for promoting growth in preterm infants.

Protein supplementation compared to no supplementation for promoting growth in preterm infants
Patient or population: preterm infants
Setting: hospital
Intervention: protein supplementation
Comparison: no protein supplementation
Outcomes Anticipated absolute effects* (95% CI) Relative effect
(95% CI) № of participants
(studies) Quality of the evidence
(GRADE) Comments
Risk with control Risk with Protein supplementation
Growth: weight (weight gain g/kg/day) The meand
weight gain
in the unsupplemented
human milk group was
13.3 g/kg/day Mean weight gain 3.82 g/kg/day higher
(2.94 higher to 4.7 higher). 101
(5 RCTs) ⊕⊕⊝⊝
Low a b mean difference (MD) 3.82, 95% CI 2.94 to 4.70
Growth: length (cm/week) The meand
length gain
in the unsupplemented
human milk group was
0.41 cm/week Mean length gain 0.12 cm/week higher
(0.07 higher to 0.17 higher) 68
(4 RCTs) ⊕⊕⊝⊝
Low a b MD 0.12, 95% CI 0.07 to 0.17
Growth: head circumference (cm/week) The meand
head circumference gain
in the unsupplemented
human milk group was
0.68 cm/week Mean head growth 0.06 cm/week higher
(0.01 higher to 0.12 higher) 68
(4 RCTs) ⊕⊕⊝⊝
Low a b MD 0.06, 95% CI 0.01 to 0,12
Neurodevelopmental outcomes see comments see comments see comments see comments see comments None of the included studies reported on neurodevelopmental outcomes.
Duration of hospital stay (days) The mean duration of hospital stay in the unsupplemented human milk group was 48.7 days Mean difference 18.5 days higher
(4.39 higher to 32.61 higher) 20
(1 RCT) ⊕⊝⊝⊝
Very lowa c MD 18.5, 95% CI 4.39 to 32.61
Feeding intolerance 0 per 1000e 0 per 1000
(0 to 0) RR 2.70
(0.13 to 58.24) 17
(1 RCT) ⊕⊝⊝⊝
Very low a c No events reported in the control group (0/8). One event reported in the fortified group (1/9).
Necrotising enterocolitis 25 per 1000e 28 per 1000
(2 to 322) RR 1.11
(0.07 to 18.49) 76
(1 RCT) ⊕⊝⊝⊝
Very low a c One event reported in the control group (1/40). One event reported in the fortified group (1/36).
 
GRADE Working Group grades of evidenceHigh certainty: we are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

a Downgraded one level due to risk of bias; most studies rated as unclear due to lack of methodological details

bDowngraded one level due to moderate‐to‐high heterogeneity among the included studies estimating the population mean difference

cDowngraded two levels for imprecision ‐ few events, very wide confidence intervals

dThe base means were calculated as weighted mean, that is, the sum of (the mean from each study multiplied by the weight) divided by a summation of the weights for each study.

eThe assumed base risks were calculated as the total number of events in the control group divided by the total number of participants in the control group.