• Dale L Phelps, Kristi L Watterberg, Tracy L Nolen, Carol A Cole, C Michael Cotten, William Oh, Brenda B Poindexter, Kristin M Zaterka-Baxter, Abhik Das, Conra Backstrom Lacy, Ann Marie Scorsone, Michele C Walsh, Edward F Bell, Kathleen A Kennedy, Kurt Schibler, Gregory M Sokol, Matthew M Laughon, Satyanarayana Lakshminrusimha, William E Truog, Meena Garg, Waldemar A Carlo, Abbot R Laptook, Krisa P Van Meurs, David P Carlton, Amanda Graf, Sara B DeMauro, Luc P Brion, Seetha Shankaran, Faruk H Orge, Richard J Olson, Helen Mintz-Hittner, Michael B Yang, Kathryn M Haider, David K Wallace, Mina Chung, Denise Hug, Irena Tsui, Martin S Cogen, John P Donahue, Michael Gaynon, Amy K Hutchinson, Don L Bremer, Graham Quinn, Yu-Guang He, William R Lucas, Timothy W Winter, Stephen D Kicklighter, Kartik Kumar, Patricia R Chess, Tarah T Colaizy, Anna Marie Hibbs, Namasivayam Ambalavanan, Heidi M Harmon, Elisabeth C McGowan, Rosemary D Higgins, and Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.
• School of Medicine and Dentistry, University of Rochester, Rochester, New York.
• JAMA. 2018 Oct 23; 320 (16): 1649-1658.

ImportancePrevious studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety.ObjectiveTo test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age.Design, Setting, And ParticipantsRandomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group.InterventionsA 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks.Main Outcomes And MeasuresType 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP.ResultsAmong 638 infants (mean, 26 weeks' gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks' postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%).Conclusions And RelevanceAmong premature infants younger than 28 weeks' gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

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