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March 01, 2022; 98 (9) Research Article

Brain White Matter Development Over the First 13 Years in Very Preterm and Typically Developing Children Based on the T1-w/T2-w Ratio

Deanne K. Thompson, View ORCID ProfileJoseph Y. M. Yang, View ORCID ProfileJian Chen, Claire E. Kelly, Christopher L. Adamson, Bonnie Alexander, Courtney Gilchrist, Lillian G. Matthews, Katherine J. Lee, Rodney W. Hunt, View ORCID ProfileJeanie L. Y. Cheong, View ORCID ProfileMegan Spencer-Smith, Jeffrey J. Neil, Marc L. Seal, Terrie E. Inder, View ORCID ProfileLex W. Doyle, Peter J. Anderson
First published December 22, 2021, DOI: https://doi.org/10.1212/WNL.0000000000013250
Deanne K. Thompson
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Joseph Y. M. Yang
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Jian Chen
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Claire E. Kelly
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Christopher L. Adamson
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Bonnie Alexander
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Courtney Gilchrist
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Lillian G. Matthews
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Katherine J. Lee
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Rodney W. Hunt
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Jeanie L. Y. Cheong
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Megan Spencer-Smith
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Jeffrey J. Neil
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Marc L. Seal
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Terrie E. Inder
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Lex W. Doyle
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Peter J. Anderson
From the Victorian Infant Brain Study (VIBeS) (D.T., C.K.), Developmental Imaging (J. Chen, C.L.A., M.S.), and Clinical Epidemiology and Biostatistics Unit (K.J.L.), Murdoch Children's Research Institute; Department of Neurosurgery (J.Y.-M.Y., B.A.) and Neonatal Medicine (R.H.), The Royal Children's Hospital, Parkville; Neurodevelopment in Health and Disease Program (C.G.), School of Health and Biomedical Sciences, RMIT University, Bundoora; Turner Institute for Brain and Mental Health (L.M., M.S.-S., P.A.), Monash University, Clayton; Neonatal Services (J. Cheong), The Royal Women's Hospital, Parkville, Melbourne, Australia; Department of Pediatric Neurology (J.N.), Washington University School of Medicine, St. Louis, MO; Department of Pediatric Newborn Medicine (T.I.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Obstetrics and Gynaecology (L.D.), The University of Melbourne, Parkville, Australia.
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Brain White Matter Development Over the First 13 Years in Very Preterm and Typically Developing Children Based on the T1-w/T2-w Ratio
Deanne K. Thompson, Joseph Y. M. Yang, Jian Chen, Claire E. Kelly, Christopher L. Adamson, Bonnie Alexander, Courtney Gilchrist, Lillian G. Matthews, Katherine J. Lee, Rodney W. Hunt, Jeanie L. Y. Cheong, Megan Spencer-Smith, Jeffrey J. Neil, Marc L. Seal, Terrie E. Inder, Lex W. Doyle, Peter J. Anderson
Neurology Mar 2022, 98 (9) e924-e937; DOI: 10.1212/WNL.0000000000013250

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Abstract

Background and Objectives To investigate brain regional white matter development in full-term (FT) and very preterm (VP) children at term equivalent and 7 and 13 years of age based on the ratio of T1- and T2-weighted MRI (T1-w/T2-w), including (1) whether longitudinal changes differ between birth groups or sexes, (2) associations with perinatal risk factors in VP children, and (3) relationships with neurodevelopmental outcomes at 13 years.

Methods Prospective longitudinal cohort study of VP (born <30 weeks' gestation or <1,250 g) and FT infants born between 2001 and 2004 and followed up at term equivalent and 7 and 13 years of age, including MRI studies and neurodevelopmental assessments. T1-w/T2-w images were parcellated into 48 white matter regions of interest.

Results Of 224 VP participants and 76 FT participants, 197 VP and 55 FT participants had useable T1-w/T2-w data from at least one timepoint. T1-w/T2-w values increased between term equivalent and 13 years of age, with little evidence that longitudinal changes varied between birth groups or sexes. VP birth, neonatal brain abnormalities, being small for gestational age, and postnatal infection were associated with reduced regional T1-w/T2-w values in childhood and adolescence. Increased T1-w/T2-w values across the white matter at 13 years were associated with better motor and working memory function for all children. Within the FT group only, larger increases in T1-w/T2-w values from term equivalent to 7 years were associated with poorer attention and executive function, and higher T1-w/T2-w values at 7 years were associated with poorer mathematics performance.

Discussion VP birth and multiple known perinatal risk factors are associated with long-term reductions in the T1-w/T2-w ratio in white matter regions in childhood and adolescence, which may relate to alterations in microstructure and myelin content. Increased T1-w/T2-w ratio at 13 years appeared to be associated with better motor and working memory function and there appeared to be developmental differences between VP and FT children in the associations for attention, executive functioning, and mathematics performance.

Glossary

FDR=
false discovery rate;
FLIRT=
FMRIB linear image registration tool;
FT=
full term;
JHU=
Johns Hopkins University;
M-CRIB-WM=
Melbourne Children's Regional Infant Brain White Matter;
VP=
very preterm

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.

  • Received May 17, 2021.
  • Accepted in final form December 13, 2021.
  • © 2021 American Academy of Neurology
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Neurology | Print ISSN:0028-3878
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