Abstract

The preterm brain has been analysed after birth by a large body of neuroimaging studies; however, few studies have focused on white matter alterations in preterm subjects beyond infancy, especially in individuals born at extremely low gestation age - before 28 completed weeks. Neuroimaging data of extremely preterm young adults are now available to investigate the long-term structural alterations of disrupted neurodevelopment. We examined white matter hierarchical organisation and microstructure in extremely preterm young adults. Specifically, we first identified the putative hubs and peripheral regions in 85 extremely preterm young adults and compared them with 53 socio-economically matched and full-term born peers. Moreover, we analysed Fractional Anisotropy (FA), Mean Diffusivity (MD), Neurite Density Index (NDI), and Orientation Dispersion Index (ODI) of white matter in hubs, peripheral regions, and over the whole brain. Our results suggest that the hierarchical organisation of the extremely preterm adult brain remains intact. However, there is evidence of significant alteration of white matter connectivity at both the macro- and microstructural level, with overall diminished connectivity, reduced FA and NDI, increased MD, and comparable ODI; suggesting that, although the spatial configuration of WM fibres is comparable, there are less WM fibres per voxel. These alterations are found throughout the brain and are more prevalent along the pathways between deep grey matter regions, frontal regions and cerebellum. This work provides evidence that white matter abnormalities associated with the premature exposure to the extrauterine environment not only are present at term equivalent age but persist into early adulthood.

Highlights

  • Preterm babies are born at fewer than 37 completed weeks of gestation

  • We address the lack of long-term studies and investigate the impact of extremely preterm birth on the development of whole-brain White Matter (WM)

  • We investigate the microstructural parameters (FA, Mean Diffusivity (MD), Orientation Dispersion Index (ODI), Neurite Density Index (NDI)) along these tracts and test the hypothesis that extreme prematurity is associated with altered microstructural outcome

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Summary

Introduction

Preterm babies are born at fewer than 37 completed weeks of gestation. In 2010, the World Health Organization estimates that more than one in ten babies are born preterm worldwide, and this number is rising Organization (2012). Effects are not limited only to infancy but extend in the long term Saigal and Doyle (2008) This is of great concern since the absolute number of subjects with a broad spectrum of neurologic and cognitive disability is increasing, with associated costs for society, health care systems, and education Frey and Klebanoff (2016). Evaluating the extent of any impairment, and identifying which brain areas or neurological networks are most compromised enables prediction of the long-term effect of prematurity on the brain. This is crucial to inform personalised treatments and targeted therapies at an early stage

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