Prediction of childhood brain outcomes in infants born preterm using neonatal MRI and concurrent clinical biomarkers (PREBO-6): study protocol for a prospective cohort study

George, Joanne M.; Pagnozzi, Alex M.; Bora, Samudragupta; Boyd, Roslyn N.; Colditz, Paul B.; Rose, Stephen; Ware, Robert S.; Pannek, Kerstin; Bursle, J.; Fripp, Jürgen; Barlow, Karen M.; Iyer, Kartik K.; Leishman, Shaneen; Jendra, Rebecca L

doi:10.1136/bmjopen-2019-036480

Cited by 15 publications

(13 citation statements)

References 51 publications

(46 reference statements)

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“…This example shows that transient fetal structure, which is important for proliferation, migration, and synaptogenesis, disappears at term age and does not play a significant role in pathogenetic events during later development. However, all structural and functional indicators of neurogenetic and gliogenetic processes should be longitudinally studied in every child ( 15 , 17 , 25 , 83 , 126 , 127 ). For some processes that extend from fetal to childhood, such as synaptogenesis, dendritogenesis, myelination, and transmitter maturation, there is a prolonged period of vulnerability (called prolonged vulnerability) throughout childhood and adolescence.…”

Section: Correlation Of Developmental Connectivity Lesion With Neurodevelopmental Outcomementioning

confidence: 99%

Fundamentals of the Development of Connectivity in the Human Fetal Brain in Late Gestation: From 24 Weeks Gestational Age to Term

Kostović

Radoš

Kostović-Srzentić

et al. 2021

Journal of Neuropathology &Amp; Experimental Neurology

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During the second half of gestation, the human cerebrum undergoes pivotal histogenetic events that underlie functional connectivity. These include the growth, guidance, selection of axonal pathways, and their first engagement in neuronal networks. Here, we characterize the spatiotemporal patterns of cerebral connectivity in extremely preterm (EPT), very preterm (VPT), preterm and term babies, focusing on magnetic resonance imaging (MRI) and histological data. In the EPT and VPT babies, thalamocortical axons enter into the cortical plate creating the electrical synapses. Additionally, the subplate zone gradually resolves in the preterm and term brain in conjunction with the growth of associative pathways leading to the activation of large-scale neural networks. We demonstrate that specific classes of axonal pathways within cerebral compartments are selectively vulnerable to temporally nested pathogenic factors. In particular, the radial distribution of axonal lesions, that is, radial vulnerability, is a robust predictor of clinical outcome. Furthermore, the subplate tangential nexus that we can visualize using MRI could be an additional marker as pivotal in the development of cortical connectivity. We suggest to direct future research toward the identification of sensitive markers of earlier lesions, the elucidation of genetic mechanisms underlying pathogenesis, and better long-term follow-up using structural and functional MRI.

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Section: Correlation Of Developmental Connectivity Lesion With Neurodevelopmental Outcomementioning

confidence: 99%

Fundamentals of the Development of Connectivity in the Human Fetal Brain in Late Gestation: From 24 Weeks Gestational Age to Term

Kostović

Radoš

Kostović-Srzentić

et al. 2021

Journal of Neuropathology &Amp; Experimental Neurology

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“…An important step for future research is to investigate whether these early brain deviations persist in later life and are predictive of childhood and later neurodevelopment ( Boardman et al. 2020 ; George et al. 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Phenotyping the Preterm Brain: Characterizing Individual Deviations From Normative Volumetric Development in Two Large Infant Cohorts

et al. 2021

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The diverse cerebral consequences of preterm birth create significant challenges for understanding pathogenesis or predicting later outcome. Instead of focusing on describing effects common to the group, comparing individual infants against robust normative data offers a powerful alternative to study brain maturation. Here we used Gaussian process regression to create normative curves characterizing brain volumetric development in 274 term-born infants, modeling for age at scan and sex. We then compared 89 preterm infants scanned at term-equivalent age with these normative charts, relating individual deviations from typical volumetric development to perinatal risk factors and later neurocognitive scores. To test generalizability, we used a second independent dataset comprising of 253 preterm infants scanned using different acquisition parameters and scanner. We describe rapid, nonuniform brain growth during the neonatal period. In both preterm cohorts, cerebral atypicalities were widespread, often multiple, and varied highly between individuals. Deviations from normative development were associated with respiratory support, nutrition, birth weight, and later neurocognition, demonstrating their clinical relevance. Group-level understanding of the preterm brain disguises a large degree of individual differences. We provide a method and normative dataset that offer a more precise characterization of the cerebral consequences of preterm birth by profiling the individual neonatal brain.

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“…We reported an association between deviations from normative brain development at TEA and behaviour at 18-20 months. An important step for future research is to investigate whether these early brain deviations persist in later life and are predictive of childhood and later neurodevelopment (Boardman et al 2020; George et al 2020).…”

Section: Discussionmentioning

confidence: 99%

Phenotyping the preterm brain: characterising individual deviations from normative volumetric development in two large infant cohorts

Dimitrova

Arulkumaran

Carney

et al. 2020

Preprint

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ObjectivePreterm birth carries a significant risk for atypical development. While studies comparing group means have identified a number of early brain correlates of prematurity, they may ‘average out’ effects significant in a single individual. To understand better the cerebral consequences of prematurity, we created normative ‘growth curves’ characterizing neonatal brain development and explored the effect of preterm birth and related clinical risks in individual infants.MethodsWe used Gaussian process regression to map typical volumetric development in 275 healthy term-born infants, modelling for age at scan and sex. We compared magnetic resonance images of 89 preterm infants (born 28.7–34 weeks gestational age) scanned at term-equivalent age to these normative charts and related deviations from typical volumetric development to both perinatal clinical variables and neurocognitive scores at 18 months. We then tested if this approach can be generalized to an independent dataset of 253 preterm infants (born 28–31.6 weeks gestational age) also scanned at term-equivalent age but using different acquisition parameters and scanner, who were followed-up at 20 months.ResultsIn both preterm cohorts, cerebral atypicalities were widespread and often multiple, but varied highly between individual infants. Deviations from normative brain volumetric development were associated with perinatal factors including respiratory support, nutrition and postnatal growth, as well as with later neurocognitive outcome.ConclusionGroup-level understanding of the preterm brain might disguise a large degree of individual differences. We provide a method and a normative dataset for clinicians and researchers to profile the individual brain. This will allow a more precise characterization of the cerebral consequences of prematurity and improve the predictive power of neuroimaging.

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Prediction of childhood brain outcomes in infants born preterm using neonatal MRI and concurrent clinical biomarkers (PREBO-6): study protocol for a prospective cohort study

Cited by 15 publications

References 51 publications

Fundamentals of the Development of Connectivity in the Human Fetal Brain in Late Gestation: From 24 Weeks Gestational Age to Term

Fundamentals of the Development of Connectivity in the Human Fetal Brain in Late Gestation: From 24 Weeks Gestational Age to Term

Phenotyping the Preterm Brain: Characterizing Individual Deviations From Normative Volumetric Development in Two Large Infant Cohorts

Phenotyping the preterm brain: characterising individual deviations from normative volumetric development in two large infant cohorts

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