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JAMA. 2018 Oct 23;320(16):1649-1658. doi: 10.1001/jama.2018.14996.

Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial.

Author information

1
School of Medicine and Dentistry, University of Rochester, Rochester, New York.
2
Health Sciences Center, University of New Mexico, Albuquerque.
3
Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina.
4
Department of Pediatrics, Duke University, Durham, North Carolina.
5
Department of Pediatrics, Women & Infants' Hospital, Brown University, Providence, Rhode Island.
6
Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
7
Department of Pediatrics, School of Medicine, Indiana University, Indianapolis.
8
Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, Maryland.
9
Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio.
10
Department of Pediatrics, University of Iowa, Iowa City.
11
Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center, Houston.
12
Division of Neonatal/Perinatal Medicine, Department of Pediatrics, University of North Carolina, Chapel Hill.
13
Department of Pediatrics, State University of New York, Buffalo.
14
Department of Pediatrics, Children's Mercy Hospital and University of Missouri School of Medicine, Kansas City.
15
Department of Pediatrics, University of California, Los Angeles.
16
Division of Neonatology, University of Alabama at Birmingham.
17
Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California.
18
Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
19
Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio.
20
Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia.
21
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas.
22
Department of Pediatrics, Wayne State University, Detroit, Michigan.
23
Department of Ophthalmology, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio.
24
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City.
25
Department of Ophthalmology and Visual Science, McGovern Medical School, University of Texas Health Science Center, Houston.
26
Department of Ophthalmology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
27
Department of Ophthalmology, School of Medicine, Indiana University, Indianapolis.
28
Department of Ophthalmology, School of Medicine and Dentistry, University of Rochester, Rochester, New York.
29
Department of Ophthalmology, Children's Mercy Hospital and University of Missouri School of Medicine, Kansas City.
30
Department of Ophthalmology, University of California, Los Angeles.
31
Department of Ophthalmology, University of Alabama at Birmingham.
32
Alpert Medical School, Women & Infants' Hospital, Brown University, Providence, Rhode Island.
33
Department of Ophthalmology, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California.
34
Department of Ophthalmology, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
35
Department of Ophthalmology, Nationwide Children's Hospital, Columbus, Ohio.
36
Department of Ophthalmology, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia.
37
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas.
38
Department of Ophthalmology, Wayne State University, Detroit, Michigan.
39
Division of Ophthalmology, Department of Surgery, Health Sciences Center, University of New Mexico, Albuquerque.
40
Department of Pediatrics, Division of Neonatology, WakeMed Health and Hospitals, Raleigh, North Carolina.
41
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Abstract

Importance:

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.

Objective:

To 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 Participants:

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.

Interventions:

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.

Main Outcomes and Measures:

Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP.

Results:

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%).

Conclusions and Relevance:

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.

PMID:
30357297
PMCID:
PMC6233812
[Available on 2019-04-23]
DOI:
10.1001/jama.2018.14996
[Indexed for MEDLINE]

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