Summary of findings 2. Moderate compared to low protein concentration of human milk fortifier for promoting growth and neurological development in preterm infants.
| Moderate compared to low protein concentration of human milk fortifier for promoting growth and neurological development in preterm infants | ||||||
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Patient or population: preterm infants Setting: neonatal intensive care units in Canada, India, USA Intervention: addition of human milk fortifier Comparison: moderate (≥ 1 g to < 1.4 g protein/100 mL EBM) versus low (< 1 g protein/100 mL EBM) protein concentration of human milk fortifier | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with low protein concentration of human milk fortifier | Risk with moderate protein concentration of human milk fortifier | |||||
| Weight gain (g/kg/day) until the end of the intervention | Mean weight gain was 12.86 g/kg/day | MD 2.08 g/kg/day higher (0.38 higher to 3.77 higher) | — | 176 (2 RCTs) | ⊕⊝⊝⊝ Very lowa,b,c,d | — |
| Length gain (cm/week) until the end of the intervention | Mean length gain was 0.77 cm/week | MD 0.09 cm/week higher (0.05 higher to 0.14 higher) | — | 217 (3 RCTs) | ⊕⊕⊝⊝ Lowd,e | — |
| Head circumference gain (cm/week) until the end of the intervention | Mean head circumference gain was 0.71 cm/week | MD 0.13 cm/week higher (0 to 0.26 higher) | — | 217 (3 RCTs) | ⊕⊝⊝⊝ Very lowb,d,e,f | — |
| Cerebral palsy at ≥ 18 months | — | — | — | (0 studies) | — | None of the included studies reported cerebral palsy. |
| Developmental delay at ≥ 18 months | — | — | — | (0 studies) | — | None of the included studies reported developmental delay. |
| Mortality during the intervention period | Preterm infants | RR 0.48 (0.05 to 5.17) | 112 (1 study) | — | — | |
| 36 per 1000 | 17 per 1000 (2 to 188) | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; EBM: expressed breast milk; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence High 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. | ||||||
aRisk of bias: one study was rated low risk of bias overall and the other study provided insufficient details of methodology for assessment; therefore, the overall evidence was downgraded one level. bInconsistency: the evidence was downgraded two levels due to substantial heterogeneity (≥ 75%). cImprecision: the evidence was downgraded one level due to wide confidence intervals (10 times difference between lower and upper confidence interval), which includes a wide range of possible beneficial effects. dImprecision: the evidence was downgraded one level as the total sample size across RCTs was fewer than 400. eRisk of bias: one study was rated low risk of bias overall and the other two studies provided insufficient details of methodology for assessment; therefore, the overall evidence was downgraded one level. fImprecision: the evidence was downgraded two levels due to wide confidence intervals that crosses 0, which includes a possibility of no beneficial effect of the treatment.