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

Dimitrova, Ralica; Arulkumaran, S; Carney, Olivia; Chew, Andrew; Falconer, Shona; Ciarrusta, Judit; Wolfers, Thomas; Batalle, Dafnis; Cordero‐Grande, Lucilio; Price, Anthony N.; Rpag, Teixeira; Hughes, Emer; Egloff, Alexia; Hutter, Jana; Makropoulos, Antonios; Schuh, Andreas; Vecchiato, Katy; Steinweg, Johannes K.; Macleod, Russell; Marquand, André F.; McAlonan, Gráinne; Rutherford, Mary; Counsell, Serena J.; Smith, Stephen M.; Rueckert, Daniel; Hajnal, Joseph V.; O’Muircheartaigh, Jonathan; Edwards, A. David

doi:10.1093/cercor/bhab039

Cited by 23 publications

(20 citation statements)

References 58 publications

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“…Very few cortical parcels had more than 8% of the preterm group with extreme deviations in a given metric. These findings are consistent with our previous work describing heterogeneous volumetric and whole-brain microstructure development at TEA following preterm birth ( Dimitrova et al., 2020 , 2021 ). This highlights that group level understanding of the preterm brain disguises a large degree of individual variability, that may be important to single infants.…”

Section: Discussionsupporting

confidence: 93%

“…The timing of the abrupt exposure to extrauterine environment might explain why cortical thickness appears more affected than SA but also why we did not observe group differences in SA between term-born and preterm infants. Given that SA is a better determinant of brain/cortical volume and size compared to cortical thickness ( Pakkenberg and Gundersen 1997 ; Im et al., 2008 ), the lack of atypical surface expansion here is consistent with a previous study of this cohort, showing that the development of total tissue /cortical volume in this preterm sample was largely normative ( Dimitrova et al., 2021 ).…”

Section: Discussionsupporting

confidence: 89%

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Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

et al. 2021

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Introduction The dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors. Methods We sought to first map typical cortical micro- and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth ( n = 259). Then we offer a comprehensive characterization of the cortical consequences of preterm birth in 76 preterm infants scanned at term-equivalent age (37–44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months. Results In the term-born neonatal brain, we observed heterogeneous and regionally specific associations between age at scan and measures of cortical morphology and microstructure, including rapid surface expansion, greater cortical thickness, lower cortical anisotropy and higher neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months. Conclusion We showed that preterm birth alters cortical micro- and macrostructural maturation near the time of full-term birth. Deviations from normative development were highly variable between individual preterm infants.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

et al. 2021

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“…Very few cortical parcels had more than 8% of the preterm group with extreme deviations in a given metric. These findings are consistent with our previous work describing heterogeneous volumetric and wholebrain microstructure development at TEA following preterm birth (Dimitrova et al 2020(Dimitrova et al , 2021. This highlights that group level understanding of the preterm brain disguises a large degree of individual variability, that may be important to single infants.…”

Section: Group-average Atypicality and Individual Variability In The Preterm Cortex At Term-equivalent Agesupporting

confidence: 92%

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

Dimitrova

Pietsch

Ciarrusta

et al. 2021

Preprint

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Introduction: The dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors. Methods: We sought to first map typical cortical micro and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth (n=270). Then we offer a comprehensive characterisation of the cortical consequences of preterm birth in 78 preterm infants scanned at term-equivalent age (37-44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months. Results: In the term-born neonatal brain, we observed regionally specific age-associated changes in cortical morphology and microstructure, including rapid surface expansion, cortical thickness increase, reduction in cortical anisotropy and increase in neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months. Conclusion: We showed that preterm birth alters cortical micro and macrostructural maturation near the time of full-term birth. Deviations from normative development were highly variable between individual preterm infants.

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“…Note that due to the inclusion of a range of gestational ages in the weekly templates (Schuh et al, 2018), more term-born infants are used to construct templates at older scan ages. It is therefore expected that our sample of preterm-born infants would show greater negative deviations from the respective templates as term-equivalent age approaches, given that preterm infants are known to show widespread reductions in regional brain volume (Alexander et al, 2019; Dimitrova et al, 2021; Peterson et al, 2003). This becomes particularly relevant when interpreting the second finding.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal neonatal brain development and socio-demographic correlates of infant outcomes following preterm birth

Vanes

Fenn-Moltu

Hadaya

et al. 2022

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Preterm birth results in premature exposure of the brain to the extrauterine environment during a critical period of neurodevelopment. Consequently, infants born preterm are at a heightened risk of adverse behavioural outcomes in later life. We characterise longitudinal development of neonatal regional brain volume and functional connectivity in the first weeks following preterm birth, sociodemographic factors, and their respective relationships to psychomotor outcomes and psychopathology in toddlerhood. We study 121 preterm infants preterm who underwent magnetic resonance imaging shortly after birth, at term-equivalent age, or both. Longitudinal regional brain volume and functional connectivity were modelled as a function of psychopathology and psychomotor outcomes at 18 months. Better psychomotor functioning in toddlerhood was associated with greater relative right cerebellar volume and a more rapid decrease over time of sensorimotor degree centrality in the neonatal period. In contrast, increased 18-month psychopathology was associated with a more rapid decrease in relative regional subcortical volume. Furthermore, while socio-economic deprivation was related to both psychopathology and psychomotor outcomes, cognitively stimulating parenting predicted psychopathology only. Our study highlights the importance of longitudinal imaging to better predict toddler outcomes following preterm birth, as well as disparate environmental influences on separable facets of behavioural development in this population.

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

Cited by 23 publications

References 58 publications

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

Longitudinal neonatal brain development and socio-demographic correlates of infant outcomes following preterm birth

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