The Efficacy and Safety of Inositol Supplementation in Preterm Infants to Prevent Retinopathy of Prematurity: A Systematic Review and Meta-analysis

Background: Inositol supplementation has been linked to beneficial effects on reducing the incidence of retinopathy of prematurity (ROP); however, it’s controversial. The meta-analysis aimed to check out the efficacy and safety of inositol supplementation in preterm infants for preventing ROP.

Methods: We conducted searches through PubMed, EMBASE, Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, ClinicalTrials.gov website and conference proceedings. Randomized controlled trials comparing inositol supplementation with placebo were included. Two independent reviewers performed screening, review, and extraction. Statistical analysis was performed using R Project.

Results: Six studies (1194 infants) were proved eligible. In comparison with placebo, inositol supplementation revealed no effect on the incidence of severe ROP (relative risk [RR]=0.49, 95% confidence interval [CI], 0.18-1.32; heterogeneity, P =.02; I²=66%; low quality of evidence [QOE]), mortality (RR=1.25, 95% CI, 0.82-1.90; heterogeneity, P =.07; I²=51%; low QOE), all stages of ROP (RR=0.98, 95% CI, 0.87-1.11; heterogeneity, P =.41; I²=0%; moderate QOE) and other adverse events. Sensitivity analysis showed an increased mortality in the inositol group (RR=1.55, 95% CI, 1.14-2.11; heterogeneity, P =.30; I²=18%) after removing the study Hallman 1986, and meta-regression showed a significant association between publication year and efficacy of inositol compared with placebo (β=0.1241; 95% CI, 0.0417–0.0026; z = 2.9527; p =.0032).

Conclusions: Based on current evidence, inositol supplementation showed no significant effect on preventing severe ROP, and exploratory sensitivity analysis showed a trend toward an increase on mortality.

Protocol Registration: PROSPERO CRD42018115368.