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Severe retinopathy of prematurity predicts delayed white matter maturation and poorer neurodevelopment
  1. Torin J A Glass1,2,
  2. Vann Chau1,2,3,
  3. Jane Gardiner3,4,
  4. Justin Foong2,
  5. Jillian Vinall5,
  6. Jill G Zwicker3,6,7,8,
  7. Ruth E Grunau3,9,
  8. Anne Synnes3,9,
  9. Kenneth J Poskitt3,10,
  10. Steven P Miller1,2,3
  1. 1Department of Pediatrics (Neurology), University of Toronto and the Hospital for Sick Children, Toronto, Canada
  2. 2Neurosciences & Mental Health, SickKids Research Institute, Toronto, Canada
  3. 3BC Children’s Hospital Research Institute, Vancouver, Canada
  4. 4Department of Ophthalmology and Vision Science, University of British Columbia and BC Children’s Hospital, Vancouver, Canada
  5. 5Department of Anesthesiology, University of Calgary, Calgary, Canada
  6. 6Department of Pediatrics (Developmental Pediatrics), University of British Columbia and BC Children’s and Women’s Hospitals, Vancouver, Canada
  7. 7Department of Occupational Science and Occupational Therapy, Vancouver, Canada
  8. 8Sunny Hill Health Centre for Children, Vancouver, Canada
  9. 9Department of Pediatrics (Neonatology), University of British Columbia and BC Children’s and Women’s Hospitals, Vancouver, Canada
  10. 10Department of Radiology, University of British Columbia and BC Children’s Hospital, Vancouver, Canada
  1. Correspondence to Steven P Miller, Department of Pediatrics (Neurology), University of Toronto and the Hospital for Sick Children, Toronto (Ontario) M5G 1X8, Canada; steven.miller{at}


Objective To determine whether severe retinopathy of prematurity (ROP) is associated with (1) abnormal white matter maturation and (2) neurodevelopmental outcomes at 18 months’ corrected age (CA) compared with neonates without severe ROP.

Design We conducted a prospective longitudinal cohort of extremely preterm neonates born 24–28 weeks’ gestational age recruited between 2006 and 2013 with brain MRIs obtained both early in life and at term-equivalent age. Severe ROP was defined as ROP treated with retinal laser photocoagulation. Using diffusion tensor imaging and tract-based spatial statistics (TBSS), white matter maturation was assessed by mean fractional anisotropy (FA) in seven predefined regions of interest. Neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development-III (Bayley-III) composite scores at 18 months’ CA. Subjects were compared using Fisher’s exact, Kruskal-Wallis and generalised estimating equations.

Setting Families were recruited from the neonatal intensive care unit at BC Women’s Hospital.

Patients Of 98 extremely preterm neonates (median: 26.0 weeks) assessed locally for ROP, 19 (19%) had severe ROP and 83 (85%) were assessed at 18 months’ CA.

Results Severe ROP was associated with lower FA in the posterior white matter, and with decreased measures of brain maturation in the optic radiations, posterior limb of the internal capsule (PLIC) and external capsule on TBSS. Bayley-III cognitive and motor scores were lower in infants with severe ROP.

Conclusions Severe ROP is associated with maturational delay in the optic radiations, PLIC, external capsule and posterior white matter, housing the primary visual and motor pathways, and is associated with poorer cognitive and motor outcomes at 18 months’ CA.

  • retinopathy of prematurity
  • diffusion tensor imaging
  • microstructure
  • preterm infant
  • preterm neonate
  • white matter development

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  • Contributors TJAG and VC had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study design and conduct of the study: TJAG, VC, JG, SPM. Collection, management, analysis and interpretation of the data: TJAG, VC, JG, AS, JGZ, JV, REG, JF, KJP, SPM. Drafting of the manuscript: TJAG. Critical revision of the manuscript for important intellectual content: VC, JG, AS, JGZ, JV, REG, SPM. Statistical analysis: TJAG, VC, SPM. Administrative, technical or material support: TJAG, VC, JG, AS, JGZ, REG, SPM.

  • Funding Canadian Institutes for Health Research (CIHR) operating grant MOP-79262 (SPM) and MOP-86489 (REG). SPM is supported by the Bloorview Children’s Hospital Chair in Pediatric Neuroscience. REG holds a Senior Scientist Salary Award from the BC Children’s Hospital Research Institute. JGZ is funded by the Michael Smith Foundation, Canadian Child Health Clinician Scientist Program and CIHR. JV is supported by the Louise and Allan Edward Foundation. TJAG’s research funding is provided by the UBC Clinician Investigator Program and is currently an MSc student of the University of Toronto.

  • Competing interests None declared.

  • Patient consent Consent obtained from guardian.

  • Ethics approval University of British Columbia/ Women’s and Children’s Research Ethics Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Unpublished data from this study are not currently available to researchers outside of the study team approved by our research ethics committees.