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Altered white matter development in children born very preterm

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Abstract

Children born very preterm (VPT) at less than 32 weeks’ gestational age (GA) are prone to disrupted white matter maturation and impaired cognitive development. The aims of the present study were to identify differences in white matter microstructure and connectivity of children born VPT compared to term-born children, as well as relations between white matter measures with cognitive outcomes and early brain injury. Diffusion images and T1-weighted anatomical MR images were acquired along with developmental assessments in 31 VPT children (mean GA: 28.76 weeks) and 28 term-born children at 4 years of age. FSL’s tract-based spatial statistics was used to create a cohort-specific template and mean fractional anisotropy (FA) skeleton that was applied to each child’s DTI data. Whole brain deterministic tractography was performed and graph theoretical measures of connectivity were calculated based on the number of streamlines between cortical and subcortical nodes derived from the Desikan-Killiany atlas. Between-group analyses included FSL Randomise for voxel-wise statistics and permutation testing for connectivity analyses. Within-group analyses between FA values and graph measures with IQ, language and visual-motor scores as well as history of white matter injury (WMI) and germinal matrix/intraventricular haemorrhage (GMH/IVH) were performed. In the children born VPT, FA values within major white matter tracts were reduced compared to term-born children. Reduced measures of local strength, clustering coefficient, local and global efficiency were present in the children born VPT within nodes in the lateral frontal, middle and superior temporal, cingulate, precuneus and lateral occipital regions. Within-group analyses revealed associations in term-born children between FA, Verbal IQ, Performance IQ and Full scale IQ within regions of the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, forceps minor and forceps major. No associations with outcome were found in the VPT group. Global efficiency was reduced in the children born VPT with a history of WMI and GMH/IVH. These findings are evidence for under-developed and less connected white matter in children born VPT, contributing to our understanding of white matter development within this population.

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Acknowledgements

We thank all of the families who participated in the study. We also thank Tammy Rayner, Ruth Weiss, Dr. Steven Miller, Dr. Manohar Shroff, Dr. Charles Raybaud, Dr. Aideen Moore, Dr. Hilary Whyte, Dr. Bratislav Misic, Tamara Powell and Wayne Lee for their valuable support and contributions.

Funding

Canadian Institutes of Health Research (MOP-84399 and MOP-137115).

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Authors and Affiliations

  1. Diagnostic Imaging, Hospital for Sick Children, Toronto, ON, Canada

    Julia M. Young, Marlee M. Vandewouw, Benjamin R. Morgan & Margot J. Taylor

  2. Department of Psychology, Hospital for Sick Children, Toronto, ON, Canada

    Mary Lou Smith

  3. Neurosciences and Mental Health, SickKids Research Institute, Toronto, ON, Canada

    Julia M. Young, Marlee M. Vandewouw, Benjamin R. Morgan, Mary Lou Smith & Margot J. Taylor

  4. Translational Medicine, SickKids Research Institute, Toronto, ON, Canada

    John G. Sled

  5. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    John G. Sled

  6. Department of Medical Imaging, University of Toronto, Toronto, ON, Canada

    Margot J. Taylor

  7. Department of Psychology, University of Toronto, Toronto, ON, Canada

    Julia M. Young, Mary Lou Smith & Margot J. Taylor

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  1. Julia M. Young
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Young, J.M., Vandewouw, M.M., Morgan, B.R. et al. Altered white matter development in children born very preterm. Brain Struct Funct 223, 2129–2141 (2018). https://doi.org/10.1007/s00429-018-1614-4

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