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

Ralica Dimitrova, Maximilian Pietsch, Judit Ciarrusta, Sean P. Fitzgibbon, Logan Z.J. Williams, Daan Christiaens, Lucilio Cordero-Grande, Dafnis Batalle, Antonios Makropoulos, Andreas Schuh, Anthony N. Price, Jana Hutter, Rui PAG Teixeira, Emer Hughes, Andrew Chew, Shona Falconer, Olivia Carney, Alexia Egloff, J. Donald Tournier, Grainne McAlonanMary A. Rutherford, Serena J. Counsell, Emma C. Robinson, Joseph V. Hajnal, Daniel Rueckert, A. David Edwards, Jonathan O'Muircheartaigh

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Introduction: The 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. Methods: We 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 = 259). Then we offer a comprehensive characterization of the cortical consequences of preterm birth in 76 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. Results: In the term-born neonatal brain, we observed heterogeneous and regionally specific associations between age at scan and measures of cortical morphology and microstructure, including rapid surface expansion, greater cortical thickness, lower cortical anisotropy and higher 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. Conclusion: We showed that preterm birth alters cortical micro- and macrostructural maturation near the time of full-term birth. Deviations from normative development were highly variable between individual preterm infants.

Original languageEnglish
Article number118488
StatePublished - Nov 2021
Externally publishedYes


  • Cortical development
  • Heterogeneity
  • Neonatal neuroimaging
  • Preterm birth


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