Inositol for respiratory distress syndrome in preterm infants

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.

To assess the effectiveness/safety of supplementary inositol in preterm infants with RDS in reducing adverse neonatal outcomes.

MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched in July, 2003 using key words: inositol and infant-newborn and random allocation or controlled trial or randomized trial (RCT). The reference lists of identified RCTs, personal files and Science Citation Index were searched. Unpublished additional information was obtained from the authors of one RCT published in abstract form.

All randomized controlled trials of inositol supplementation to preterm infants with a control group that received a placebo or no intervention were included. Outcomes of interest were bronchopulmonary dysplasia (BPD), death, BPD or death, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and sepsis.

Data on neonatal outcomes were abstracted independently by the two researchers and any discrepancy was resolved through consensus. Revman was used for analysis of the data.

Five reports of three RCTs were identified. One report was a duplicate publication. One new report included both randomized and non-randomized patients and data could not be extracted for the randomized neonates only and the study was excluded. An interim report of this study previously published as an abstract was included in the previous version of this review. The outcome of death or bronchopulmonary dysplasia was reported in two trials, and was found to be significantly reduced (RR 0.56, 95% CI 0.42, 0.77; RD -0.215, 95% CI -0.323, -0.107). The outcome of death was reported in two trials and was found to be significantly reduced (RR 0.48, 95% CI 0.28, 0.80; RD -0.131, 95% CI -0.218, -0.043). Retinopathy of prematurity, stage 4 or needing therapy, was reported in two trials, and was found to be significantly reduced (RR 0.09, 95% CI 0.01, 0.67; RD -0.078, 95% CI -0.128, -0.027). Intraventricular hemorrhage, grade III-IV, was significantly decreased (RR 0.55, 95% CI 0.32, 0.95; RD -0.090, 95% CI -0.170, -0.010). Neither sepsis nor necrotizing enterocolitis outcomes were increased. When a secondary analysis was done excluding a study published in abstract form, the results differed only in that there was a significant reduction in retinopathy of prematurity, any stage (RR 0.53, 95% CI 0.29, 0.97; RD -0.082, 95% CI -0.159,-0.005).

Inositol supplementation results in statistically significant and clinically important reductions in important short-term adverse neonatal outcomes. A multi-center RCT of appropriate size is justified to confirm these findings.