Summary of findings 2. Inositol supplementation IV initially followed by enteral administration (repeat doses of 80 mg/kg/day) in preterm infants born at less than 30 weeks' PMA compared to placebo for preterm infants at risk for or having respiratory distress syndrome (Comparison 3).

Inositol supplementation IV initially followed by enteral administration (repeat doses of 80 mg/kg/day) in preterm infants born at < 30 weeks' PMA compared to placebo for preterm infants at risk for or having respiratory distress syndrome
Patient or population: preterm infants at risk for or having respiratory distress syndrome Setting: Intervention: Inositol supplementation IV initially followed by enteral administration (repeat doses of 80 mg/kg/day) in preterm infants born at < 30 weeks' PMA Comparison: placebo
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo	Risk with Inositol supplementation IV initially followed by enteral administration (repeat doses of 80 mg/kg/day) in preterm infants born at < 30 weeks' PMA
Type 1 ROP or death before determination of ROP outcome using the adjudicated ROP outcome	Study population		RR 1.28 (0.99 to 1.67)	679 (2 studies)	Moderate	Design (risk of bias): the risk of bias for random sequence generation, for allocation concealment, for performance bias and detection bias was low in both studies Heterogeneity/consistency across studies: there was high heterogeneity for RR (I² = 79 %) and for RD (I² = 85%). We downgraded the quality of the evidence by 1 step Directness of the evidence: studies were conducted in the target population Precision of estimates: this outcome was reported for 679 infants and the confidence intervals around the point estimates for RR and RD were narrow Presence of publication bias: As only 2 studies were included in the analysis we did not perform a funnel plot
	222 per 1000	284 per 1000 (220 to 371)
Type 1 ROP including adjudicated ROP outcome	Study population		RR 1.24 (0.82 to 1.86)	605 (2 studies)	Moderate	Design (risk of bias): the risk of bias for random sequence generation, for allocation concealment, for performance bias and detection bias was low in both studies Heterogeneity/consistency across studies: there was low heterogeneity for RR (I² = 46 %) and moderate for RD (I² = 54%). We downgraded the quality of the evidence by 1 step Directness of the evidence: studies were conducted in the target population Precision of estimates: this outcome was reported on for 605 infants and the confidence intervals around the point estimates for RR and RD were narrow Presence of publication bias: as only 2 studies were included in the analysis we did not perform a funnel plot
	120 per 1000	149 per 1000 (99 to 224)
All‐cause mortality (outcome collected through first event: death, hospital discharge, hospital transfer, or 120 days after birth)	Study population		RR 1.35 (0.91 to 2.00)	701 (2 studies)	Moderate	Design (risk of bias): the risk of bias for random sequence generation, for allocation concealment, for performance bias and detection bias was low in both studies Heterogeneity/consistency across studies: there was moderate heterogeneity for RR (I² = 72%) and high for RD (I² = 84%). We downgraded the quality of the evidence by 1 step Directness of the evidence: studies were conducted in the target population Precision of estimates: this outcome was reported for 701 infants and the confidence intervals around the point estimates for RR and RD were narrow Presence of publication bias: as only 2 studies were included in the analysis we did not perform a funnel plot
	110 per 1000	148 per 1000 (100 to 219)
BPD or death by it prior to 37 weeks' PMA (outcomes collected through first event: death, hospital discharge, hospital transfer, or 120 days after birth)	Study population		RR 1.01 (0.87 to 1.16)	616 (2 studies)	High	Design (risk of bias): the risk of bias for random sequence generation, for allocation concealment, for performance bias and detection bias was low in both studies Heterogeneity/consistency across studies: there was no heterogeneity for RR (I² = 0%) nor for RD (I² = 0%) Directness of the evidence: studies were conducted in the target population. Precision of estimates: this outcome was reported for 616 infants and the confidence intervals around the point estimates for RR and RD were narrow Presence of publication bias: as only 2 studies were included in the analysis we did not perform a funnel plot
	555 per 1000	561 per 1000 (483 to 644)
Severe IVH (grade 3 or 4)	Study population		RR 0.92 (0.65 to 1.29)	690 (2 studies)	Moderate	Design (risk of bias): The risk of bias for random sequence generation, for allocation concealment, for performance bias and detection bias was low in both studies Heterogeneity/consistency across studies: there was moderate heterogeneity for RR (I² = 74%) and high for RD (I² = 82%) Directness of the evidence: studies were conducted in the target population Precision of estimates: this outcome was reported for 690 infants and the confidence intervals around the point estimates for RR and RD were narrow Presence of publication bias: as only 2 studies were included in the analysis we did not perform a funnel plot.
	171 per 1000	157 per 1000 (111 to 221)
Late‐onset sepsis (> 72 hours of age)	Study population		RR 1.33 (1.00 to 1.75)	701 (2 studies)	HIgh	Design (risk of bias): the risk of bias for random sequence generation, for allocation concealment, for performance bias and detection bias was low in both studies Heterogeneity/consistency across studies: there was no heterogeneity for RR (I² = 0%) nor for RD (I² = 0%) Directness of the evidence: studies were conducted in the target population Precision of estimates: this outcome was reported for 701 infants and the confidence intervals around the point estimates for RR and RD were narrow Presence of publication bias: as only 2 studies were included in the analysis we did not perform a funnel plot
	191 per 1000	254 per 1000 (191 to 334)
Suspected or proven NEC	Study population		RR 0.88 (0.55 to 1.41)	701 (2 studies)	High	Design (risk of bias): the risk of bias for random sequence generation, for allocation concealment, for performance bias and detection bias was low in both studies Heterogeneity/consistency across studies: there was low heterogeneity for RR (I² = 36%) and moderate for RD (I² = 53%). Directness of the evidence: studies were conducted in the target population. Precision of estimates: this outcome was reported on in 701 infants and the confidence intervals around the point estimates for RR and RD were narrow Presence of publication bias: as only 2 studies were included in the analysis we did not perform a funnel plot.
	98 per 1000	87 per 1000 (54 to 139)
*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; PMA: Postmenstrual age; RD: Risk difference; ROP: Retinopathy of prematurity; 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.