Summary of findings 1. Probiotics compared to control in very preterm or very low birth weight infants.
| Probiotics compared to control in very preterm or very low birth weight infants | ||||||
| Patient or population: very preterm or very low birth weight infants Setting: neonatal care centres globally Intervention: probiotics Comparison: control | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Sensitivity analysis of trials at low risk of bias | |
| Risk with control | Risk with Probiotics | |||||
| Necrotising enterocolitis (before hospital discharge) | Study population | RR 0.54 (0.45 to 0.65) | 10,604 (54 studies) | ⊕⊕⊝⊝ Lowa,b | Sensitivity meta‐analysis of 16 trials (4597 infants) at low risk of bias showed a reduced risk of NEC: RR 0.70, 95% CI 0.55, 0.89 (I² = 25%) | |
| 61 per 1000 | 33 per 1000 (27 to 40) | |||||
| Mortality (all‐cause before hospital discharge) | Study population | RR 0.76 (0.65 to 0.89) | 10,170 (51 studies) | ⊕⊕⊕⊝ Moderatea | Sensitivity meta‐analysis of 16 trials (4597 infants) at low risk of bias did not show an effect: RR 0.86, 95% CI 0.69, 1.07 (I² = 0%) | |
| 65 per 1000 | 49 per 1000 (42 to 58) | |||||
| Invasive infection (before hospital discharge) | Study population | RR 0.89 (0.82 to 0.97) | 9762 (47 studies) | ⊕⊕⊕⊝ Moderatea | Sensitivity meta‐analysis of 16 trials (4597 infants) at low risk of bias did not show an effect: RR 0.90, 95% CI 0.79, 1.02 (I² = 8%) | |
| 173 per 1000 | 154 per 1000 (142 to 168) | |||||
| Severe neurodevelopmental impairment (18 months to 3 years) | Study population | RR 1.03 (0.84 to 1.26) | 1518 (5 studies) | ⊕⊕⊝⊝ Lowa,c | Sensitivity meta‐analysis of two trials (913 infants) at low risk of bias did not show an effect: RR 0.99, 95% CI 0.76, 1.27 (I² = 0%) | |
| 194 per 1000 | 200 per 1000 (163 to 245) | |||||
| *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; 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. | ||||||
aDowngraded one level for serious study limitations (high risk of bias due to uncertainty about methods used to generate random sequence, conceal allocation, and mask outcome assessment) in 12 trials
bDowngraded one level for serious publication bias (funnel plot asymmetry and statistical evidence consistent with trial size; trials favouring controls missing)
cDowngraded one level for serious imprecision of effect estimate (95% CI around estimate consistent with substantial harm or benefit)