Heterogeneous, temporally consistent, and plastic brain development after preterm birth

Melissa Thalhammer (), Jakob Seidlitz, Antonia Neubauer, Aurore Menegaux, Benita Schmitz-Koep, Maria A. Di Biase, Julia Schulz, Lena Dorfschmidt, Richard A. I. Bethlehem, Aaron Alexander-Bloch, Chris Adamson, Gareth Ball, Joana Sa de Almeida, Richard Beare, Claus Zimmer, Marcel Daamen, Henning Boecker, Peter Bartmann, Dieter Wolke, Dennis M. Hedderich and Christian Sorg
Additional contact information
Melissa Thalhammer: TUM Klinikum Rechts der Isar
Jakob Seidlitz: The Children’s Hospital of Philadelphia
Antonia Neubauer: TUM Klinikum Rechts der Isar
Aurore Menegaux: TUM Klinikum Rechts der Isar
Benita Schmitz-Koep: TUM Klinikum Rechts der Isar
Maria A. Di Biase: The University of Melbourne
Julia Schulz: TUM Klinikum Rechts der Isar
Lena Dorfschmidt: The Children’s Hospital of Philadelphia
Richard A. I. Bethlehem: University of Cambridge
Aaron Alexander-Bloch: The Children’s Hospital of Philadelphia
Chris Adamson: Murdoch Children’s Research Institute
Gareth Ball: Murdoch Children’s Research Institute
Joana Sa de Almeida: Murdoch Children’s Research Institute
Richard Beare: Murdoch Children’s Research Institute
Claus Zimmer: TUM Klinikum Rechts der Isar
Marcel Daamen: University Hospital Bonn
Henning Boecker: University Hospital Bonn
Peter Bartmann: University Hospital Bonn
Dieter Wolke: University of Warwick
Dennis M. Hedderich: TUM Klinikum Rechts der Isar
Christian Sorg: TUM Klinikum Rechts der Isar

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract The current view of neurodevelopment after preterm birth presents a strong paradox: diverse neurocognitive outcomes suggest heterogeneous neurodevelopment, yet numerous brain imaging studies focusing on average dysmaturation imply largely uniform aberrations across individuals. Here we show both, spatially heterogeneous individual brain abnormality patterns but with consistent underlying biological mechanisms of injury and plasticity. Using cross-sectional structural magnetic resonance imaging data from preterm neonates and longitudinal data from preterm children and adults in a normative reference framework, we demonstrate that brain development after preterm birth is highly heterogeneous in both severity and patterns of deviations. Individual brain abnormality patterns are also consistent for their extent and location along the life course, associated with glial cell underpinnings, and plastic for influences of the early social environment. Our findings extend conventional views of preterm neurodevelopment, revealing a nuanced landscape of individual variation, with consistent commonalities between subjects. This integrated perspective implies more targeted theranostic intervention strategies, specifically integrating brain charts and imaging at birth, as well as social interventions during early development.

Date: 2025
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DOI: 10.1038/s41467-025-63967-1

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