Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

Dimitrova, R.; Pietsch, M.; Ciarrusta, J.; Fitzgibbon, S. P.; Williams, L. Z.; Christiaens, D.; Cordero-Grande, L.; Batalle, D.; Makropoulos, A.; Schuh, A.; Price, A. N.; Hutter, J.; Teixeira, R. P.; Hughes, E.; Chew, A.; Falconer, S.; Carney, O.; Egloff, A.; Tournier, J.-D.; McAlonan, G.; Rutherford, M.; Counsell, S. J.; Robinson, E. C.; Hajnal, J. V.; Rueckert, D.; Edwards, D.; O'Muircheartaigh, J.

doi:10.1101/2021.06.03.446550

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bioRxiv · 10.1101/2021.06.03.446550

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

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Abstract

IntroductionThe dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors. MethodsWe sought to first map typical cortical micro and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth (n=270). Then we offer a comprehensive characterisation of the cortical consequences of preterm birth in 78 preterm infants scanned at term-equivalent age (37-44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months. ResultsIn the term-born neonatal brain, we observed regionally specific age-associated changes in cortical morphology and microstructure, including rapid surface expansion, cortical thickness increase, reduction in cortical anisotropy and increase in neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months. ConclusionWe showed that preterm birth alters cortical micro and macrostructural maturation near the time of fullterm birth. Deviations from normative development were highly variable between individual preterm infants.

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Dimitrova, R., Pietsch, M., Ciarrusta, J., Fitzgibbon, S. P., Williams, L. Z., Christiaens, D., Cordero-Grande, L., Batalle, D., Makropoulos, A., Schuh, A., Price, A. N., Hutter, J., Teixeira, R. P., Hughes, E., Chew, A., Falconer, S., Carney, O., Egloff, A., Tournier, J.-D., McAlonan, G., Rutherford, M., Counsell, S. J., Robinson, E. C., Hajnal, J. V., Rueckert, D., Edwards, D., O'Muircheartaigh, J.. 2021-06-03. Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age. https://doi.org/10.1101/2021.06.03.446550

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