Journal article
Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial
JAMA : the journal of the American Medical Association, Vol.320(16), pp.1649-1658
10/23/2018
DOI: 10.1001/jama.2018.14996
PMCID: PMC6233812
PMID: 30357297
Abstract
Previous 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.
To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age.
Randomized 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.
A 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.
Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP.
Among 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%).
Among 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.
Details
- Title: Subtitle
- Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial
- Creators
- Dale L Phelps - School of Medicine and Dentistry, University of Rochester, Rochester, New YorkEdward F Bell - Department of Pediatrics, University of Iowa, Iowa CityKristi L Watterberg - Health Sciences Center, University of New Mexico, AlbuquerqueRichard J Olson - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa CityTracy L Nolen - Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, North CarolinaTarah T Colaizy - Department of Pediatrics, University of Iowa, Iowa CityCarol A Cole - School of Medicine and Dentistry, University of Rochester, Rochester, New YorkHeidi M Harmon - Department of Pediatrics, School of Medicine, Indiana University, IndianapolisC Michael Cotten - Department of Pediatrics, Duke University, Durham, North CarolinaWilliam Oh - Department of Pediatrics, Women & Infants' Hospital, Brown University, Providence, Rhode IslandBrenda B Poindexter - Department of Pediatrics, School of Medicine, Indiana University, IndianapolisKristin M Zaterka-Baxter - Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, North CarolinaAbhik Das - Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, MarylandConra Backstrom Lacy - Health Sciences Center, University of New Mexico, AlbuquerqueAnn Marie Scorsone - School of Medicine and Dentistry, University of Rochester, Rochester, New YorkMichele C Walsh - Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OhioKathleen A Kennedy - Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center, HoustonKurt Schibler - Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OhioSatyanarayana Lakshminrusimha - Department of Pediatrics, State University of New York, BuffaloGregory M Sokol - Department of Pediatrics, School of Medicine, Indiana University, IndianapolisWilliam E Truog - Department of Pediatrics, Children's Mercy Hospital and University of Missouri School of Medicine, Kansas CityMatthew M Laughon - Division of Neonatal/Perinatal Medicine, Department of Pediatrics, University of North Carolina, Chapel HillMeena Garg - Department of Pediatrics, University of California, Los AngelesWaldemar A Carlo - Division of Neonatology, University of Alabama at BirminghamAbbot R Laptook - Department of Pediatrics, Women & Infants' Hospital, Brown University, Providence, Rhode IslandKrisa P Van Meurs - Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CaliforniaDavid P Carlton - Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GeorgiaAmanda Graf - Department of Pediatrics, Nationwide Children's Hospital, Columbus, OhioSara B DeMauro - Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, PhiladelphiaLuc P Brion - Department of Pediatrics, University of Texas Southwestern Medical Center, DallasSeetha Shankaran - Department of Pediatrics, Wayne State University, Detroit, MichiganFaruk H Orge - Department of Ophthalmology, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OhioHelen Mintz-Hittner - Department of Ophthalmology and Visual Science, McGovern Medical School, University of Texas Health Science Center, HoustonMichael B Yang - Department of Ophthalmology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OhioKathryn M Haider - Department of Ophthalmology, School of Medicine, Indiana University, IndianapolisDavid K Wallace - Department of Pediatrics, Duke University, Durham, North CarolinaMina Chung - University of Rochester Medical CenterDenise Hug - Department of Ophthalmology, Children's Mercy Hospital and University of Missouri School of Medicine, Kansas CityIrena Tsui - Department of Ophthalmology, University of California, Los AngelesMartin S Cogen - Department of Ophthalmology, University of Alabama at BirminghamJohn P Donahue - Alpert Medical School, Women & Infants' Hospital, Brown University, Providence, Rhode IslandMichael Gaynon - Department of Ophthalmology, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CaliforniaAmy K Hutchinson - Emory UniversityDon L Bremer - Department of Ophthalmology, Nationwide Children's Hospital, Columbus, OhioGraham Quinn - Department of Ophthalmology, Children's Hospital of Philadelphia and University of Pennsylvania, PhiladelphiaYu-Guang He - Department of Ophthalmology, University of Texas Southwestern Medical Center, DallasWilliam R Lucas Jr - Department of Ophthalmology, Wayne State University, Detroit, MichiganTimothy W Winter - Division of Ophthalmology, Department of Surgery, Health Sciences Center, University of New Mexico, AlbuquerqueStephen D Kicklighter - Department of Pediatrics, Division of Neonatology, WakeMed Health and Hospitals, Raleigh, North CarolinaKartik Kumar - Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center, HoustonPatricia R Chess - School of Medicine and Dentistry, University of Rochester, Rochester, New YorkAnna Marie Hibbs - Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OhioNamasivayam Ambalavanan - Division of Neonatology, University of Alabama at BirminghamElisabeth C McGowan - Department of Pediatrics, Women & Infants' Hospital, Brown University, Providence, Rhode IslandRosemary D Higgins - Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MarylandEunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
- Resource Type
- Journal article
- Publication Details
- JAMA : the journal of the American Medical Association, Vol.320(16), pp.1649-1658
- DOI
- 10.1001/jama.2018.14996
- PMID
- 30357297
- PMCID
- PMC6233812
- NLM abbreviation
- JAMA
- ISSN
- 0098-7484
- eISSN
- 1538-3598
- Grant note
- UG1 HD068244 / NICHD NIH HHS UG1 HD021385 / NICHD NIH HHS UG1 HD040492 / NICHD NIH HHS UG1 HD027851 / NICHD NIH HHS UG1 HD053089 / NICHD NIH HHS UG1 HD027904 / NICHD NIH HHS UG1 HD068284 / NICHD NIH HHS UG1 HD087229 / NICHD NIH HHS UG1 HD068270 / NICHD NIH HHS UG1 HD027880 / NICHD NIH HHS UG1 HD053109 / NICHD NIH HHS U10 HD036790 / NICHD NIH HHS UG1 HD034216 / NICHD NIH HHS UG1 HD027856 / NICHD NIH HHS UG1 HD021364 / NICHD NIH HHS UG1 HD027853 / NICHD NIH HHS UG1 HD068278 / NICHD NIH HHS UG1 HD068263 / NICHD NIH HHS
- Language
- English
- Date published
- 10/23/2018
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984093356802771
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