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Normative growth trajectories of fetal brain regions validated by satisfactory maturation of neurodevelopmental domains at 2 years of age.

February 23, 2026pubmed logopapers

Authors

Wyburd MK,Kennedy SH,Fernandes M,Dinsdale NK,Hesse LS,Gunier RB,Cheikh Ismail L,Ohuma EO,Gravett MG,Purwar M,Qingqing W,Winsey A,Bertino E,Jaffer Y,Carvalho M,Barros FC,Stein A,Noble AJ,Molnár Z,Jenkinson M,Nichols TE,Smith S,Bhutta ZA,Papageorghiou AT,Villar J,Namburete AIL

Affiliations (28)

  • Oxford Machine Learning in Neuroimaging Laboratory, Department of Computer Science, University of Oxford, Oxford, United Kingdom. [email protected].
  • Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom.
  • Department of Paediatrics, Institute of Developmental and Regenerative Medicine, University of Oxford, Oxford, United Kingdom.
  • Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom.
  • Oxford Machine Learning in Neuroimaging Laboratory, Department of Computer Science, University of Oxford, Oxford, United Kingdom.
  • School of Public Health, University of California, Berkeley, CA, United States of America.
  • Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.
  • Departments of Obstetrics and Gynecology and of Global Health, University of Washington, Seattle, WA, United States of America.
  • Nagpur INTERGROWTH-21st Research Centre, Ketkar Hospital, Nagpur, India.
  • School of Public Health, Peking University, Beijing, China.
  • Dipartimento di Scienze Pediatriche e dell'Adolescenza, SCDU Neonatologia, Universita di Torino, Turin, Italy.
  • Department of Family and Community Health, Ministry of Health, Muscat, Sultanate of Oman.
  • Department of Obstetrics and Gynaecology, Faculty of Health Sciences, Aga Khan University Hospital, Nairobi, Kenya.
  • Post-graduate Course in Health in the Life Cycle, Universidade Católica de Pelotas, Pelotas, Brazil.
  • Blavatnik School of Government, University of Oxford, Oxford, United Kingdom.
  • African Health Research Institute, KwaZulu-Natal, South Africa.
  • MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Department of Engineering Science, University of Oxford, Oxford, United Kingdom.
  • Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
  • Oxford Centre for Integrative Neuroimaging (OxCIN), FMRIB Centre, Nuffield Department of Clinical Neurosciences (NDCN), University of Oxford, JR Hospital, Oxford, United Kingdom.
  • Australian Institute for Machine Learning (AIML), School of Mathematical and Computer Sciences, The University of Adelaide, Adelaide, Australia.
  • South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
  • Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
  • Center for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Institute for Global Health and Development at Aga Khan University, South-Central Asia & East Africa, Karachi, Pakistan.
  • Oxford Machine Learning in Neuroimaging Laboratory, Department of Computer Science, University of Oxford, Oxford, United Kingdom. [email protected].
  • Oxford Centre for Integrative Neuroimaging (OxCIN), FMRIB Centre, Nuffield Department of Clinical Neurosciences (NDCN), University of Oxford, JR Hospital, Oxford, United Kingdom. [email protected].

Abstract

We previously constructed a qualitative, 3D ultrasound derived atlas of the normative spatiotemporal dynamics of fetal brain maturation. Here, using the same healthy multi-national cohort, we applied deep learning methods to 4205 fetal brain scans from 18-27 weeks' gestation, to produce an extensive, quantitative description of the growth of 16 fetal brain structures associated with satisfactory domain-specific neurodevelopmental scores at 2 years of age. The methodology, which is publicly available, takes less than 10 seconds per scan. We define 28 region-specific, functionally relevant, normative growth trajectories, a ratio between the relative volumes of the insular (rILV) and parietal (rPLV) lobes reflecting asynchronous maturation of fetal brain regions, and introduce a fetal brain maturation index that quantifies biological age and deviations from chronological age. Finally, the very low percentage of variance explained by between site differences (0.6% to 5.8% of the total variance) reinforces a fundamental biological principle: fetal growth and development across populations with diverse ancestries is similar provided that environmental constraints on growth are minimal.

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