. 2021 Mar 5;17(1):e1141. doi: 10.1002/cl2.1141

Table 3.

Probiotics supplementation during neonatal period

Probiotics supplementation compared to control during neonatal period
Patient or population: neonates (Mmost of the included studies had preterm and low birth weight neonates)
Setting: low and middle income countries
Intervention: probiotics/synbiotics
Comparison: control
Outcomes	No. of participants (studies) Follow up	Certainty of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects* (95% CI)
Outcomes	No. of participants (studies) Follow up	Certainty of the evidence (GRADE)	Relative effect (95% CI)	Risk with control	Risk difference with probiotics (intervention)
All‐cause mortality	10904 (25 RCTs)	⊕⊕⊕⊕ HIGH^a, ^b, ^c, ^d	RR, 0.80 (0.66–0.96)	Study population
All‐cause mortality	10904 (25 RCTs)	⊕⊕⊕⊕ HIGH^a, ^b, ^c, ^d	RR, 0.80 (0.66–0.96)	47 per 1000	9 fewer per 1000 (15 fewer to 1 fewer)
Neonatal sepsis	8918 (21 RCTs)	⊕⊕⊕⊕ HIGH^a, ^d, ^e	RR, 0.78 (0.70–0.86)	Study population
Neonatal sepsis	8918 (21 RCTs)	⊕⊕⊕⊕ HIGH^a, ^d, ^e	RR, 0.78 (0.70–0.86)	205 per 1000	45 fewer per 1000 (62 fewer to 29 fewer)
Necrotizing enterocolitis	55574 (29 RCTs)	⊕⊕⊕⊕ HIGH^a, ^d, ^f	RR, 0.46 (0.35–0.61)	Study population
Necrotizing enterocolitis	55574 (29 RCTs)	⊕⊕⊕⊕ HIGH^a, ^d, ^f	RR, 0.46 (0.35–0.61)	101 per 1000	55 fewer per 1000 (66 fewer to 41 fewer)
*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; OR: Odds 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

^{^a}

Even though three (Dongol Singh et al., 2017; Fernández‐Carrocera et al., 2013; Kaban et al., 2019) of the included studies in the analysis had high ROB related to randomizations, the exclusion of these studies did not have much effect on the magnitude of the summary estimate or its statistical significance.

^{^b}

I ² was 0%.

^{^c}

All‐cause mortality is an objective outcome and there were no concerns about the indirect measurement of the outcome.

^{^d}

The confidence interval of the summary estimate did not include 1.

^{^e}

I ² was 23% and the p. value for heterogeneity was 0.16.

^{^f}

The I ² was 24%.