Inositol in preterm infants at risk for or having respiratory distress syndrome.
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.


OBJECTIVE
To assess the effectiveness and safety of supplementary inositol in preterm infants with or without respiratory distress syndrome (RDS) in reducing adverse neonatal outcomes.


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.


METHODS
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.


METHODS
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).


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.


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.
Section of Neonatology, Alberta Children's Hospital, Calgary, AB, Canada.
Alexandra
A
Howlett
Arne
A
Ohlsson
Nishad
N
Plakkal
D019587:Dietary Supplements; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007294:Inositol / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000401:mortality; D014803:Vitamin B Complex / Q000627:therapeutic use*
D014803:Vitamin B Complex; D007294:Inositol