IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-63967-1.html
   My bibliography  Save this article

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

Author

Listed:
  • Melissa Thalhammer

    (TUM Klinikum Rechts der Isar
    TUM Klinikum Rechts der Isar)

  • Jakob Seidlitz

    (The Children’s Hospital of Philadelphia
    The Children’s Hospital of Philadelphia and Penn Medicine
    University of Pennsylvania
    University of Pennsylvania)

  • Antonia Neubauer

    (TUM Klinikum Rechts der Isar
    TUM Klinikum Rechts der Isar
    Ludwig-Maximilians-Universität Munich)

  • Aurore Menegaux

    (TUM Klinikum Rechts der Isar
    TUM Klinikum Rechts der Isar)

  • Benita Schmitz-Koep

    (TUM Klinikum Rechts der Isar
    TUM Klinikum Rechts der Isar)

  • Maria A. Di Biase

    (The University of Melbourne
    Harvard Medical School)

  • Julia Schulz

    (TUM Klinikum Rechts der Isar
    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
    University of Melbourne)

  • Joana Sa de Almeida

    (Murdoch Children’s Research Institute
    University Hospitals of Geneva)

  • Richard Beare

    (Murdoch Children’s Research Institute)

  • Claus Zimmer

    (TUM Klinikum Rechts der Isar
    TUM Klinikum Rechts der Isar)

  • Marcel Daamen

    (University Hospital Bonn
    Clinical Functional Imaging Group
    University Hospital Bonn)

  • Henning Boecker

    (University Hospital Bonn
    Clinical Functional Imaging Group)

  • Peter Bartmann

    (University Hospital Bonn)

  • Dieter Wolke

    (University of Warwick
    University of Warwick)

  • Dennis M. Hedderich

    (TUM Klinikum Rechts der Isar
    TUM Klinikum Rechts der Isar)

  • Christian Sorg

    (TUM Klinikum Rechts der Isar
    TUM Klinikum Rechts der Isar
    School of Medicine and Health, Department of Psychiatry)

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.

Suggested Citation

  • 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 &, 2025. "Heterogeneous, temporally consistent, and plastic brain development after preterm birth," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63967-1
    DOI: 10.1038/s41467-025-63967-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-63967-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-025-63967-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Michael J. Hawrylycz & Ed S. Lein & Angela L. Guillozet-Bongaarts & Elaine H. Shen & Lydia Ng & Jeremy A. Miller & Louie N. van de Lagemaat & Kimberly A. Smith & Amanda Ebbert & Zackery L. Riley & Chr, 2012. "An anatomically comprehensive atlas of the adult human brain transcriptome," Nature, Nature, vol. 489(7416), pages 391-399, September.
    2. Anna Baranowska-Rataj & Kieron Barclay & Joan Costa-Font & Mikko Myrskylä & Berkay Özcan, 2023. "Preterm birth and educational disadvantage: Heterogeneous effects," Population Studies, Taylor & Francis Journals, vol. 77(3), pages 459-474, September.
    3. Jakob Seidlitz & Ajay Nadig & Siyuan Liu & Richard A. I. Bethlehem & Petra E. Vértes & Sarah E. Morgan & František Váša & Rafael Romero-Garcia & François M. Lalonde & Liv S. Clasen & Jonathan D. Blume, 2020. "Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    4. Suijuan Zhong & Shu Zhang & Xiaoying Fan & Qian Wu & Liying Yan & Ji Dong & Haofeng Zhang & Long Li & Le Sun & Na Pan & Xiaohui Xu & Fuchou Tang & Jun Zhang & Jie Qiao & Xiaoqun Wang, 2018. "A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex," Nature, Nature, vol. 555(7697), pages 524-528, March.
    5. Leon D. Lotter & Amin Saberi & Justine Y. Hansen & Bratislav Misic & Casey Paquola & Gareth J. Barker & Arun L. W. Bokde & Sylvane Desrivières & Herta Flor & Antoine Grigis & Hugh Garavan & Penny Gowl, 2024. "Regional patterns of human cortex development correlate with underlying neurobiology," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    6. Hyo Jung Kang & Yuka Imamura Kawasawa & Feng Cheng & Ying Zhu & Xuming Xu & Mingfeng Li & André M. M. Sousa & Mihovil Pletikos & Kyle A. Meyer & Goran Sedmak & Tobias Guennel & Yurae Shin & Matthew B., 2011. "Spatio-temporal transcriptome of the human brain," Nature, Nature, vol. 478(7370), pages 483-489, October.
    7. Jakob Seidlitz & Ajay Nadig & Siyuan Liu & Richard A. I. Bethlehem & Petra E. Vértes & Sarah E. Morgan & František Váša & Rafael Romero-Garcia & François M. Lalonde & Liv S. Clasen & Jonathan D. Blume, 2020. "Author Correction: Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders," Nature Communications, Nature, vol. 11(1), pages 1-6, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. G. Ball & S. Oldham & V. Kyriakopoulou & L. Z. J. Williams & V. Karolis & A. Price & J. Hutter & M. L. Seal & A. Alexander-Bloch & J. V. Hajnal & A. D. Edwards & E. C. Robinson & J. Seidlitz, 2024. "Molecular signatures of cortical expansion in the human foetal brain," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Tingting Bo & Jie Li & Ganlu Hu & Ge Zhang & Wei Wang & Qian Lv & Shaoling Zhao & Junjie Ma & Meng Qin & Xiaohui Yao & Meiyun Wang & Guang-Zhong Wang & Zheng Wang, 2023. "Brain-wide and cell-specific transcriptomic insights into MRI-derived cortical morphology in macaque monkeys," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Vincent Bazinet & Justine Y. Hansen & Reinder Vos de Wael & Boris C. Bernhardt & Martijn P. Heuvel & Bratislav Misic, 2023. "Assortative mixing in micro-architecturally annotated brain connectomes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Lin Jiang & Sarah Genon & Jiayu Ye & Yan Zhu & Guangying Wang & Runyang He & Pedro A. Valdes-Sosa & Feng Wan & Dezhong Yao & Simon B. Eickhoff & Debo Dong & Fali Li & Peng Xu, 2025. "Gene transcription, neurotransmitter, and neurocognition signatures of brain structural-functional coupling variability," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    5. Golia Shafiei & Ben D. Fulcher & Bradley Voytek & Theodore D. Satterthwaite & Sylvain Baillet & Bratislav Misic, 2023. "Neurophysiological signatures of cortical micro-architecture," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Aleksandr Talishinsky & Jonathan Downar & Petra E. Vértes & Jakob Seidlitz & Katharine Dunlop & Charles J. Lynch & Heather Whalley & Andrew McIntosh & Fidel Vila-Rodriguez & Zafiris J. Daskalakis & Da, 2022. "Regional gene expression signatures are associated with sex-specific functional connectivity changes in depression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    7. Justine Y. Hansen & Golia Shafiei & Jacob W. Vogel & Kelly Smart & Carrie E. Bearden & Martine Hoogman & Barbara Franke & Daan Rooij & Jan Buitelaar & Carrie R. McDonald & Sanjay M. Sisodiya & Lianne , 2022. "Local molecular and global connectomic contributions to cross-disorder cortical abnormalities," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Stuart Oldham & Gareth Ball, 2023. "A phylogenetically-conserved axis of thalamocortical connectivity in the human brain," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Zongchang Du & Congying Chu & Weiyang Shi & Na Luo & Yuheng Lu & Haiyan Wang & Bokai Zhao & Hui Xiong & Zhengyi Yang & Tianzi Jiang, 2025. "Connectome-constrained ligand-receptor interaction analysis for understanding brain network communication," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    10. Jiao Li & Chao Zhang & Yao Meng & Siqi Yang & Jie Xia & Huafu Chen & Wei Liao, 2024. "Morphometric brain organization across the human lifespan reveals increased dispersion linked to cognitive performance," PLOS Biology, Public Library of Science, vol. 22(6), pages 1-24, June.
    11. Christine Ecker & Charlotte M. Pretzsch & Johanna Leyhausen & Lisa M. Berg & Caroline Gurr & Hanna Seelemeyer & Grainne McAlonan & Nicolaas A. Puts & Eva Loth & Flavio Dell’Aqua & Luke Mason & Tony Ch, 2025. "Transcriptomic decoding of surface-based imaging phenotypes and its application to pharmacotranscriptomics," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    12. Sheng Wang & Belinda Wang & Vanessa Drury & Sam Drake & Nawei Sun & Hasan Alkhairo & Juan Arbelaez & Clif Duhn & Vanessa H. Bal & Kate Langley & Joanna Martin & Pieter J. Hoekstra & Andrea Dietrich & , 2023. "Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    13. Elaine T. Lim & Yingleong Chan & Pepper Dawes & Xiaoge Guo & Serkan Erdin & Derek J. C. Tai & Songlei Liu & Julia M. Reichert & Mannix J. Burns & Ying Kai Chan & Jessica J. Chiang & Katharina Meyer & , 2022. "Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    14. Xinyuan Liang & Lianglong Sun & Xuhong Liao & Tianyuan Lei & Mingrui Xia & Dingna Duan & Zilong Zeng & Qiongling Li & Zhilei Xu & Weiwei Men & Yanpei Wang & Shuping Tan & Jia-Hong Gao & Shaozheng Qin , 2024. "Structural connectome architecture shapes the maturation of cortical morphology from childhood to adolescence," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    15. Jun Ding & Jian Ji & Zachary Rabow & Tong Shen & Jacob Folz & Christopher R. Brydges & Sili Fan & Xinchen Lu & Sajjan Mehta & Megan R. Showalter & Ying Zhang & Renee Araiza & Lynette R. Bower & K. C. , 2021. "A metabolome atlas of the aging mouse brain," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    16. Natalia García-San-Martín & Richard AI Bethlehem & Patricia Segura & Agoston Mihalik & Jakob Seidlitz & Isaac Sebenius & Claudio Alemán-Morillo & Lena Dorfschmidt & Golia Shafiei & Sarah E. Morgan & M, 2025. "Reduced brain structural similarity is associated with maturation, neurobiological features, and clinical status in schizophrenia," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    17. Junjiao Feng & Liang Zhang & Chunhui Chen & Jintao Sheng & Zhifang Ye & Kanyin Feng & Jing Liu & Ying Cai & Bi Zhu & Zhaoxia Yu & Chuansheng Chen & Qi Dong & Gui Xue, 2022. "A cognitive neurogenetic approach to uncovering the structure of executive functions," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    18. Leon D. Lotter & Amin Saberi & Justine Y. Hansen & Bratislav Misic & Casey Paquola & Gareth J. Barker & Arun L. W. Bokde & Sylvane Desrivières & Herta Flor & Antoine Grigis & Hugh Garavan & Penny Gowl, 2024. "Regional patterns of human cortex development correlate with underlying neurobiology," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    19. Samuel S. Kim & Buu Truong & Karthik Jagadeesh & Kushal K. Dey & Amber Z. Shen & Soumya Raychaudhuri & Manolis Kellis & Alkes L. Price, 2024. "Leveraging single-cell ATAC-seq and RNA-seq to identify disease-critical fetal and adult brain cell types," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    20. Xuelong Yao & Zongyang Lu & Zhanying Feng & Lei Gao & Xin Zhou & Min Li & Suijuan Zhong & Qian Wu & Zhenbo Liu & Haofeng Zhang & Zeyuan Liu & Lizhi Yi & Tao Zhou & Xudong Zhao & Jun Zhang & Yong Wang , 2022. "Comparison of chromatin accessibility landscapes during early development of prefrontal cortex between rhesus macaque and human," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63967-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.