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September 24, 2019; 93 (13) Article

Predicting developmental outcomes in preterm infants

A simple white matter injury imaging rule

View ORCID ProfileDalit Cayam-Rand, Ting Guo, Ruth E. Grunau, View ORCID ProfileIsabel Benavente-Fernández, Anne Synnes, Vann Chau, Helen Branson, Beatrice Latal, Patrick McQuillen, Steven P. Miller
First published August 29, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008172
Dalit Cayam-Rand
From the Departments of Paediatrics (Neurology) (D.C.-R., T.G., I.B.-F., V.C., S.P.M.) and Radiology (H.B.), The Hospital for Sick Children and the University of Toronto; BC Children's Hospital Research Institute (R.E.G., A.S.); Department of Pediatrics (Neonatology) (R.E.G., A.S.), University of British Columbia and BC Women's Hospital and Health Centre, Vancouver, Canada; Department of Pediatrics (Neonatology) (I.B.-F.), University Hospital Puerta del Mar, Cadiz, Spain; Department of Pediatrics (Child Development Center) (B.L.), University Children's Hospital Zurich, Switzerland; and Department of Pediatrics (P.M.), University of California, San Francisco.
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Ting Guo
From the Departments of Paediatrics (Neurology) (D.C.-R., T.G., I.B.-F., V.C., S.P.M.) and Radiology (H.B.), The Hospital for Sick Children and the University of Toronto; BC Children's Hospital Research Institute (R.E.G., A.S.); Department of Pediatrics (Neonatology) (R.E.G., A.S.), University of British Columbia and BC Women's Hospital and Health Centre, Vancouver, Canada; Department of Pediatrics (Neonatology) (I.B.-F.), University Hospital Puerta del Mar, Cadiz, Spain; Department of Pediatrics (Child Development Center) (B.L.), University Children's Hospital Zurich, Switzerland; and Department of Pediatrics (P.M.), University of California, San Francisco.
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Ruth E. Grunau
From the Departments of Paediatrics (Neurology) (D.C.-R., T.G., I.B.-F., V.C., S.P.M.) and Radiology (H.B.), The Hospital for Sick Children and the University of Toronto; BC Children's Hospital Research Institute (R.E.G., A.S.); Department of Pediatrics (Neonatology) (R.E.G., A.S.), University of British Columbia and BC Women's Hospital and Health Centre, Vancouver, Canada; Department of Pediatrics (Neonatology) (I.B.-F.), University Hospital Puerta del Mar, Cadiz, Spain; Department of Pediatrics (Child Development Center) (B.L.), University Children's Hospital Zurich, Switzerland; and Department of Pediatrics (P.M.), University of California, San Francisco.
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Isabel Benavente-Fernández
From the Departments of Paediatrics (Neurology) (D.C.-R., T.G., I.B.-F., V.C., S.P.M.) and Radiology (H.B.), The Hospital for Sick Children and the University of Toronto; BC Children's Hospital Research Institute (R.E.G., A.S.); Department of Pediatrics (Neonatology) (R.E.G., A.S.), University of British Columbia and BC Women's Hospital and Health Centre, Vancouver, Canada; Department of Pediatrics (Neonatology) (I.B.-F.), University Hospital Puerta del Mar, Cadiz, Spain; Department of Pediatrics (Child Development Center) (B.L.), University Children's Hospital Zurich, Switzerland; and Department of Pediatrics (P.M.), University of California, San Francisco.
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Anne Synnes
From the Departments of Paediatrics (Neurology) (D.C.-R., T.G., I.B.-F., V.C., S.P.M.) and Radiology (H.B.), The Hospital for Sick Children and the University of Toronto; BC Children's Hospital Research Institute (R.E.G., A.S.); Department of Pediatrics (Neonatology) (R.E.G., A.S.), University of British Columbia and BC Women's Hospital and Health Centre, Vancouver, Canada; Department of Pediatrics (Neonatology) (I.B.-F.), University Hospital Puerta del Mar, Cadiz, Spain; Department of Pediatrics (Child Development Center) (B.L.), University Children's Hospital Zurich, Switzerland; and Department of Pediatrics (P.M.), University of California, San Francisco.
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Vann Chau
From the Departments of Paediatrics (Neurology) (D.C.-R., T.G., I.B.-F., V.C., S.P.M.) and Radiology (H.B.), The Hospital for Sick Children and the University of Toronto; BC Children's Hospital Research Institute (R.E.G., A.S.); Department of Pediatrics (Neonatology) (R.E.G., A.S.), University of British Columbia and BC Women's Hospital and Health Centre, Vancouver, Canada; Department of Pediatrics (Neonatology) (I.B.-F.), University Hospital Puerta del Mar, Cadiz, Spain; Department of Pediatrics (Child Development Center) (B.L.), University Children's Hospital Zurich, Switzerland; and Department of Pediatrics (P.M.), University of California, San Francisco.
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Helen Branson
From the Departments of Paediatrics (Neurology) (D.C.-R., T.G., I.B.-F., V.C., S.P.M.) and Radiology (H.B.), The Hospital for Sick Children and the University of Toronto; BC Children's Hospital Research Institute (R.E.G., A.S.); Department of Pediatrics (Neonatology) (R.E.G., A.S.), University of British Columbia and BC Women's Hospital and Health Centre, Vancouver, Canada; Department of Pediatrics (Neonatology) (I.B.-F.), University Hospital Puerta del Mar, Cadiz, Spain; Department of Pediatrics (Child Development Center) (B.L.), University Children's Hospital Zurich, Switzerland; and Department of Pediatrics (P.M.), University of California, San Francisco.
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Beatrice Latal
From the Departments of Paediatrics (Neurology) (D.C.-R., T.G., I.B.-F., V.C., S.P.M.) and Radiology (H.B.), The Hospital for Sick Children and the University of Toronto; BC Children's Hospital Research Institute (R.E.G., A.S.); Department of Pediatrics (Neonatology) (R.E.G., A.S.), University of British Columbia and BC Women's Hospital and Health Centre, Vancouver, Canada; Department of Pediatrics (Neonatology) (I.B.-F.), University Hospital Puerta del Mar, Cadiz, Spain; Department of Pediatrics (Child Development Center) (B.L.), University Children's Hospital Zurich, Switzerland; and Department of Pediatrics (P.M.), University of California, San Francisco.
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Patrick McQuillen
From the Departments of Paediatrics (Neurology) (D.C.-R., T.G., I.B.-F., V.C., S.P.M.) and Radiology (H.B.), The Hospital for Sick Children and the University of Toronto; BC Children's Hospital Research Institute (R.E.G., A.S.); Department of Pediatrics (Neonatology) (R.E.G., A.S.), University of British Columbia and BC Women's Hospital and Health Centre, Vancouver, Canada; Department of Pediatrics (Neonatology) (I.B.-F.), University Hospital Puerta del Mar, Cadiz, Spain; Department of Pediatrics (Child Development Center) (B.L.), University Children's Hospital Zurich, Switzerland; and Department of Pediatrics (P.M.), University of California, San Francisco.
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Steven P. Miller
From the Departments of Paediatrics (Neurology) (D.C.-R., T.G., I.B.-F., V.C., S.P.M.) and Radiology (H.B.), The Hospital for Sick Children and the University of Toronto; BC Children's Hospital Research Institute (R.E.G., A.S.); Department of Pediatrics (Neonatology) (R.E.G., A.S.), University of British Columbia and BC Women's Hospital and Health Centre, Vancouver, Canada; Department of Pediatrics (Neonatology) (I.B.-F.), University Hospital Puerta del Mar, Cadiz, Spain; Department of Pediatrics (Child Development Center) (B.L.), University Children's Hospital Zurich, Switzerland; and Department of Pediatrics (P.M.), University of California, San Francisco.
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Citation
Predicting developmental outcomes in preterm infants
A simple white matter injury imaging rule
Dalit Cayam-Rand, Ting Guo, Ruth E. Grunau, Isabel Benavente-Fernández, Anne Synnes, Vann Chau, Helen Branson, Beatrice Latal, Patrick McQuillen, Steven P. Miller
Neurology Sep 2019, 93 (13) e1231-e1240; DOI: 10.1212/WNL.0000000000008172

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Abstract

Objective To develop a simple imaging rule to predict neurodevelopmental outcomes at 4.5 years in a cohort of preterm neonates with white matter injury (WMI) based on lesion location and examine whether clinical variables enhance prediction.

Methods Sixty-eight preterm neonates born 24–32 weeks' gestation (median 27.7 weeks) were diagnosed with WMI on early brain MRI scans (median 32.3 weeks). 3D T1-weighted images of 60 neonates with 4.5-year outcomes were reformatted and aligned to the posterior commissure–eye plane and WMI was classified by location: anterior or posterior-only to the midventricle line on the reformatted axial plane. Adverse outcomes at 4.5 years were defined as Wechsler Preschool and Primary Scale of Intelligence full-scale IQ <85, cerebral palsy, or Movement Assessment Battery for Children, second edition percentile <5. The prediction of adverse outcome by WMI location, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP) was assessed using multivariable logistic regression.

Results Six children had adverse cognitive outcomes and 17 had adverse motor outcomes. WMI location predicted cognitive outcomes in 90% (area under receiver operating characteristic curve [AUC] 0.80) and motor outcomes in 85% (AUC 0.75). Adding IVH, BPD, and ROP to the model enhances the predictive strength for cognitive and motor outcomes (AUC 0.83 and 0.88, respectively). Rule performance was confirmed in an independent cohort of children with WMI.

Conclusions WMI on early MRI can be classified by location to predict preschool age outcomes in children born preterm. The predictive value of this WMI classification is enhanced by considering clinical factors apparent by term-equivalent age.

Glossary

AUC=
area under receiver operating characteristic curve;
BPD=
bronchopulmonary dysplasia;
CHD=
congenital heart disease;
CI=
confidence interval;
CP=
cerebral palsy;
FSIQ=
full-scale IQ;
IQR=
interquartile range;
IVH=
intraventricular hemorrhage;
MABC-2=
Movement Assessment Battery for Children, second edition;
NICU=
neonatal intensive care unit;
OR=
odds ratio;
PABAK=
prevalence-adjusted and bias-adjusted kappa;
PC=
posterior commissure;
ROP=
retinopathy of prematurity;
WMI=
white matter injury;
WPPSI-IV=
Wechsler Primary and Preschool Scale of Intelligence, fourth edition

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 569

  • Received January 14, 2019.
  • Accepted in final form May 3, 2019.
  • © 2019 American Academy of Neurology
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