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Effects of gestational age at birth on perinatal structural brain development in healthy term-born babies

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
JournalHuman Brain Mapping
Accepted/In press2021
Published13 Dec 2021

Bibliographical note

Funding Information: This work was supported by the European Research Council under the European Union's Seventh Framework Programme (FP7/20072013)/ERC grant agreement No. 319456 (dHCP project). The authors acknowledge infrastructure support from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre (BRC) at South London, Maudsley NHS Foundation Trust, King's College London, and the NIHR‐BRC at Guys and St Thomas' Hospitals NHS Foundation Trust (GSTFT). The authors also acknowledge support in part from the Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering at Kings College London (WT 203148/Z/16/Z), MRC Strategic grant (MR/K006355/1), Medical Research Council Centre grant (MR/N026063/1), the Department of Health through an NIHR Comprehensive Biomedical Research Centre Award (to Guy's and St Thomas' National Health Service [NHS] Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust), the Sackler Institute for Translational Neurodevelopment at King's College London and the European Autism Interventions (EU‐AIMS) trial and the EU AIMS‐2‐TRIALS, a European Innovative Medicines Initiative Joint Undertaking under grant agreement Nos. 115300 and 777394, the resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (grant FP7/2007–2013). O. G. G. is supported by a grant from the UK Medical Research Council (MR/P502108/1). D. C. is supported by a post‐doctoral fellowship of the Flemish Research Foundation (FWO) (12ZV420N). J. O. M. and D. E. received support from the Medical Research Council Centre for Neurodevelopmental Disorders, King's College London (MR/N026063/1). L. C. G. is supported by a Beatriz Galindo Fellowship jointly funded by the Ministerio de Educación, Cultura y Deporte and the Universidad Politécnica de Madrid (BEAGAL18/00158). J. O. M. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (206675/Z/17/Z). T. A. is supported by a MRC Clinician Scientist Fellowship (MR/P008712/1) and Transition Support Award (MR/V036874/1). D. B. received support from a Wellcome Trust Seed Award in Science (217316/Z/19/Z). The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding information Publisher Copyright: © 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

King's Authors


Infants born in early term (37–38 weeks gestation) experience slower neurodevelopment than those born at full term (40–41 weeks gestation). While this could be due to higher perinatal morbidity, gestational age at birth may also have a direct effect on the brain. Here we characterise brain volume and white matter correlates of gestational age at birth in healthy term-born neonates and their relationship to later neurodevelopmental outcome using T2 and diffusion weighted MRI acquired in the neonatal period from a cohort (n = 454) of healthy babies born at term age (>37 weeks gestation) and scanned between 1 and 41 days after birth. Images were analysed using tensor-based morphometry and tract-based spatial statistics. Neurodevelopment was assessed at age 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Infants born earlier had higher relative ventricular volume and lower relative brain volume in the deep grey matter, cerebellum and brainstem. Earlier birth was also associated with lower fractional anisotropy, higher mean, axial, and radial diffusivity in major white matter tracts. Gestational age at birth was positively associated with all Bayley-III subscales at age 18 months. Regression models predicting outcome from gestational age at birth were significantly improved after adding neuroimaging features associated with gestational age at birth. This work adds to the body of evidence of the impact of early term birth and highlights the importance of considering the effect of gestational age at birth in future neuroimaging studies including term-born babies.

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