The efficacy and safety of inositol supplementation in preterm infants to prevent retinopathy of prematurity: a systematic review and meta-analysis

Abstract

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; I 2 = 66%; low quality of evidence [QOE]), mortality (RR = 1.25, 95% CI, 0.82–1.90; heterogeneity, P = .07; I 2 = 51%; low QOE), all stages of ROP (RR = 0.98, 95% CI, 0.87–1.11; heterogeneity, P = .41; I 2 = 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; I 2 = 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. Electronic supplementary material The online version of this article (10.1186/s12886-019-1140-z) contains supplementary material, which is available to authorized users.

Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies and Supplementation

“…Despite many clinical trials evaluating the efficacy of INS in different settings, poor quality evidence is available on the safety of INS. A meta-analysis evaluating the safety and efficacy of inositol supplementation in preterm infants for the prevention of the prematurity retinopathy showed no effect on the study outcomes but an increase in mortality in babies younger than 32 weeks [64]. Furthermore, studies evaluating safety reported short-term outcomes; thus, long-term follow-up studies should be considered to obtain a better safety evaluation.…”

Concurrent Physiological and Pathological Angiogenesis in Retinopathy of Prematurity and Emerging Therapies

“…Over the past 70 years, numerous clinical trials have failed to identify effective and safe therapeutic strategies for ROP [ 55 , 84 ]. Such trials have included applications of recombinant human IGF-1 (rhIGF-1) in combination with rhIGFBP-3 [ 85 ], anti-oxidant vitamin E [ 86 , 87 ], inositol [ 88 ] and ω-3 PUFAs [ 89 ].…”

A safety review of drugs used for the treatment of retinopathy of prematurity

“…A recently published large multicenter randomized clinical trial did not confirm these data, but it reported that inositol administration resulted in a high incidence of serious adverse events, including necrotizing enterocolitis, hypotension, intraventricular hemorrhage, systemic infection, and respiratory distress [91]. An additional metaanalysis confirmed no benefits of inositol supplementation, while, on the other hand, it reported a trend toward an increase in mortality [92].…”