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Published on: November 20, 2015
Inositol in preterm infants at risk for or having respiratory distress syndrome
Alexandra Howlett1, Arne Ohlsson, Nishad Plakkal
1Section of Neonatology, Alberta Children's Hospital, Calgary, AB, Canada.
Insights
Inositol supplementation significantly reduces adverse neonatal outcomes in preterm infants, including death and severe retinopathy of prematurity. Further research is ongoing to confirm these important findings.
Area of Science:
- Neonatal Medicine
- Nutritional Science
- Clinical Trials
Background:
- Inositol is an essential nutrient vital for cell growth and surfactant maturation.
- It plays a critical role in fetal and early neonatal development.
- Preterm infants may benefit from inositol supplementation to improve outcomes.
Purpose of the Study:
- To evaluate the effectiveness and safety of inositol supplementation in preterm infants.
- To assess its impact on reducing adverse neonatal outcomes, including respiratory distress syndrome (RDS).
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials (RCTs).
- Searched multiple databases including CENTRAL, MEDLINE, EMBASE, CINAHL, and ClinicalTrials.gov.
- Included RCTs comparing inositol supplementation to placebo or no intervention in preterm infants.
Main Results:
- Inositol significantly reduced neonatal and infant mortality.
- Reduced rates of retinopathy of prematurity (ROP) stage ≥ 3 and severe intraventricular hemorrhage (IVH).
- No significant differences observed for sepsis or necrotizing enterocolitis (NEC).
Conclusions:
- Inositol supplementation demonstrates statistically significant and clinically important reductions in short-term adverse neonatal outcomes.
- An ongoing large multi-center RCT is expected to confirm these findings.
- Inositol is a promising intervention for improving preterm infant health.
Background:
Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life.
Objectives:
To assess the effectiveness and safety of supplementary inositol in preterm infants with or without respiratory distress syndrome (RDS) in reducing adverse neonatal outcomes.
Search Methods:
The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, CINAHL, Clinicaltrials.gov and Controlled-trials.com were searched in September 2014. The reference lists of identified randomised controlled trials (RCTs), personal files and Web of Science were searched.
Selection Criteria:
All RCTs of inositol supplementation of preterm infants compared with a control group that received a placebo or no intervention were included. Outcomes of interest were neonatal death, infant death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and sepsis.
Data Collection And Analysis:
Data on neonatal outcomes were abstracted independently by the three review authors and any discrepancy was resolved through consensus. Outcomes were reported as relative risk (RR), risk difference (RD) and number needed to treat to benefit (NNTB) or to harm (NNTH).
Main Results:
Four published RCTs and one ongoing RCT were identified. Study quality varied and interim analyses had occurred in all trials of repeat doses of inositol that provided data for the outcomes of interest in this review. In these trials neonatal death was found to be significantly reduced (3 trials, 355 neonates; typical RR 0.53, 95% CI 0.31 to 0.91; typical RD -0.09, 95% CI -0.17 to -0.03; NNTB 11, 95% CI 6 to 33). Infant deaths were reduced (3 trials, 355 infants; typical RR 0.55, 95% CI 0.40 to 0.77; typical RD -0.18, 95% CI -0.27 to -0.08; NNTB 6, 95% CI 4 to 13). ROP stage ≥ 3 was significantly reduced (2 trials, 262 infants; typical RR 0.09, 95% CI 0.01 to 0.67; typical RD -0.08, 95% CI -0.13 to -0.03; NNTB 13, 95% CI 8 to 33) and IVH grade > II was significantly decreased (3 trials, 355 infants; typical RR 0.53, 95% CI 0.31 to 0.90; typical RD -0.09, 95% CI -0.16 to -0.02; NNTB 11, 95% CI 6 to 50). Neither sepsis nor NEC differed significantly between groups. One study (74 infants) that administered a single dose of inositol (60 or 120 mg/kg) found no significant differences in adverse outcomes using RR, but an increased RD for BPD at 36 weeks postmenstrual age (RD 0.23, 95% CI 0.03 to 0.43; NNTH 4, 95% CI 2 to 33). This result should be interpreted with caution as only one dose of inositol was given and only the RD, but not the RR, was significant. One ongoing large study of repeat doses of inositol in preterm infants was identified.
Authors' Conclusions:
Inositol supplementation results in statistically significant and clinically important reductions in important short-term adverse neonatal outcomes. A large size multi-centre randomised controlled trial is currently ongoing and the trial will likely confirm or refute the findings from this systematic review.

