Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome

Abi Gartner; Ana Baburamani; Ralica Dimitrova; Prachi Patkee; Olatz Ojinaga-Alfageme; Alexandra Bonthrone; Daniel Cromb; Alena Uus; Serena Counsell; Jo Hajnal; Jonathan O'Muircheartaigh; Mary Rutherford

doi:https://doi.org/10.1093/cercor/bhad171

Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome

Abi Gartner^*, Ana Baburamani, Ralica Dimitrova, Prachi Patkee, Olatz Ojinaga-Alfageme, Alexandra Bonthrone, Daniel Cromb, Alena Uus, Serena Counsell, Jo Hajnal, Jonathan O'Muircheartaigh, Mary Rutherford^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide range of neurodevelopmental outcomes. To date, there have been very few in vivo neuroimaging studies of the neonatal brain in DS. In this study we used a cross-sectional sample of 493 preterm- to term-born control neonates from the developing Human Connectome Project to perform normative modeling of regional brain tissue volumes from 32 to 46 weeks postmenstrual age, accounting for sex and age variables. Deviation from the normative mean was quantified in 25 neonates with DS with postnatally confirmed karyotypes from the Early Brain Imaging in DS study. Here, we provide the first comprehensive volumetric phenotyping of the neonatal brain in DS, which is characterized by significantly reduced whole brain, cerebral white matter, and cerebellar volumes; reduced relative frontal and occipital lobar volumes, in contrast with enlarged relative temporal and parietal lobar volumes; enlarged relative deep gray matter volume (particularly the lentiform nuclei); and enlargement of the lateral ventricles, amongst other features. In future, the ability to assess phenotypic severity at the neonatal stage may help guide early interventions and, ultimately, help improve neurodevelopmental outcomes in children with DS.

Original language	English
Pages (from-to)	8921-8941
Number of pages	21
Journal	Cerebral Cortex
Volume	33
Issue number	14
Early online date	30 Apr 2023
DOIs	https://doi.org/10.1093/cercor/bhad171
Publication status	Published - 15 Jul 2023

Keywords

Down syndrome
magnetic resonance imaging
neonate
normative modelling
volumetric

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https://doi.org/10.1093/cercor/bhad171Licence: CC BY

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title = "Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome",

abstract = "Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide range of neurodevelopmental outcomes. To date, there have been very few in vivo neuroimaging studies of the neonatal brain in DS. In this study we used a cross-sectional sample of 493 preterm- to term-born control neonates from the developing Human Connectome Project to perform normative modeling of regional brain tissue volumes from 32 to 46 weeks postmenstrual age, accounting for sex and age variables. Deviation from the normative mean was quantified in 25 neonates with DS with postnatally confirmed karyotypes from the Early Brain Imaging in DS study. Here, we provide the first comprehensive volumetric phenotyping of the neonatal brain in DS, which is characterized by significantly reduced whole brain, cerebral white matter, and cerebellar volumes; reduced relative frontal and occipital lobar volumes, in contrast with enlarged relative temporal and parietal lobar volumes; enlarged relative deep gray matter volume (particularly the lentiform nuclei); and enlargement of the lateral ventricles, amongst other features. In future, the ability to assess phenotypic severity at the neonatal stage may help guide early interventions and, ultimately, help improve neurodevelopmental outcomes in children with DS.",

keywords = "Down syndrome, magnetic resonance imaging, neonate, normative modelling, volumetric",

author = "Abi Gartner and Ana Baburamani and Ralica Dimitrova and Prachi Patkee and Olatz Ojinaga-Alfageme and Alexandra Bonthrone and Daniel Cromb and Alena Uus and Serena Counsell and Jo Hajnal and Jonathan O'Muircheartaigh and Mary Rutherford",

note = "Funding Information: This work was supported by the Medical Research Council (MRC) (MR/K006355/1 and MR/LO11530/1), Rosetrees Trust (A1563), Fondation J{\'e}r{\^o}me Lejeune (2017b–1707), and Sparks and Great Ormond Street Hospital Children{\textquoteright}s Charity (V5318). The control sample was collected as part of the developing Human Connectome Project (dHCP), funded by the ERC grant agreement no. 319456. A.F.-G.{\textquoteright}.s PhD work is supported by the MRC Centre for Neurodevelopmental Disorders (CNDD) at King{\textquoteright}s College London. This research was supported by core funding from the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z), the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust & King{\textquoteright}s College London, and the NIHR Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Oxford University Press.",

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AU - Gartner, Abi

AU - Baburamani, Ana

AU - Dimitrova, Ralica

AU - Patkee, Prachi

AU - Ojinaga-Alfageme, Olatz

AU - Bonthrone, Alexandra

AU - Cromb, Daniel

AU - Uus, Alena

AU - Counsell, Serena

AU - Hajnal, Jo

AU - O'Muircheartaigh, Jonathan

AU - Rutherford, Mary

N1 - Funding Information: This work was supported by the Medical Research Council (MRC) (MR/K006355/1 and MR/LO11530/1), Rosetrees Trust (A1563), Fondation Jérôme Lejeune (2017b–1707), and Sparks and Great Ormond Street Hospital Children’s Charity (V5318). The control sample was collected as part of the developing Human Connectome Project (dHCP), funded by the ERC grant agreement no. 319456. A.F.-G.’.s PhD work is supported by the MRC Centre for Neurodevelopmental Disorders (CNDD) at King’s College London. This research was supported by core funding from the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z), the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust & King’s College London, and the NIHR Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press.

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N2 - Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide range of neurodevelopmental outcomes. To date, there have been very few in vivo neuroimaging studies of the neonatal brain in DS. In this study we used a cross-sectional sample of 493 preterm- to term-born control neonates from the developing Human Connectome Project to perform normative modeling of regional brain tissue volumes from 32 to 46 weeks postmenstrual age, accounting for sex and age variables. Deviation from the normative mean was quantified in 25 neonates with DS with postnatally confirmed karyotypes from the Early Brain Imaging in DS study. Here, we provide the first comprehensive volumetric phenotyping of the neonatal brain in DS, which is characterized by significantly reduced whole brain, cerebral white matter, and cerebellar volumes; reduced relative frontal and occipital lobar volumes, in contrast with enlarged relative temporal and parietal lobar volumes; enlarged relative deep gray matter volume (particularly the lentiform nuclei); and enlargement of the lateral ventricles, amongst other features. In future, the ability to assess phenotypic severity at the neonatal stage may help guide early interventions and, ultimately, help improve neurodevelopmental outcomes in children with DS.

AB - Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide range of neurodevelopmental outcomes. To date, there have been very few in vivo neuroimaging studies of the neonatal brain in DS. In this study we used a cross-sectional sample of 493 preterm- to term-born control neonates from the developing Human Connectome Project to perform normative modeling of regional brain tissue volumes from 32 to 46 weeks postmenstrual age, accounting for sex and age variables. Deviation from the normative mean was quantified in 25 neonates with DS with postnatally confirmed karyotypes from the Early Brain Imaging in DS study. Here, we provide the first comprehensive volumetric phenotyping of the neonatal brain in DS, which is characterized by significantly reduced whole brain, cerebral white matter, and cerebellar volumes; reduced relative frontal and occipital lobar volumes, in contrast with enlarged relative temporal and parietal lobar volumes; enlarged relative deep gray matter volume (particularly the lentiform nuclei); and enlargement of the lateral ventricles, amongst other features. In future, the ability to assess phenotypic severity at the neonatal stage may help guide early interventions and, ultimately, help improve neurodevelopmental outcomes in children with DS.

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DO - https://doi.org/10.1093/cercor/bhad171

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SP - 8921

EP - 8941

JO - Cerebral Cortex

JF - Cerebral Cortex

IS - 14

ER -

Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome

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