Individualized brain development and cognitive outcome in infants with congenital heart disease

Alexandra F. Bonthrone; Ralica Dimitrova; Andrew Chew; Christopher J. Kelly; Lucilio Cordero-Grande; Olivia Carney; Alexia Egloff; Emer Hughes; Katy Vecchiato; John Simpson; Joseph V. Hajnal; Kuberan Pushparajah; Suresh Victor; Chiara Nosarti; Mary A. Rutherford; A. David Edwards; Jonathan O'Muircheartaigh; Serena J. Counsell

doi:10.1093/braincomms/fcab046

Individualized brain development and cognitive outcome in infants with congenital heart disease

Alexandra F. Bonthrone, Ralica Dimitrova, Andrew Chew, Christopher J. Kelly, Lucilio Cordero-Grande, Olivia Carney, Alexia Egloff, Emer Hughes, Katy Vecchiato, John Simpson, Joseph V. Hajnal, Kuberan Pushparajah, Suresh Victor, Chiara Nosarti, Mary A. Rutherford, A. David Edwards, Jonathan O'Muircheartaigh, Serena J. Counsell^*

^*Corresponding author for this work

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

22 Citations (Scopus)

Abstract

Infants with congenital heart disease are at risk of neurodevelopmental impairments, the origins of which are currently unclear. This study aimed to characterize the relationship between neonatal brain development, cerebral oxygen delivery and neurodevelopmental outcome in infants with congenital heart disease. A cohort of infants with serious or critical congenital heart disease (N = 66; N = 62 born ≥37 weeks) underwent brain MRI before surgery on a 3T scanner situated on the neonatal unit. T2-weighted images were segmented into brain regions using a neonatal-specific algorithm. We generated normative curves of typical volumetric brain development using a data-driven technique applied to 219 healthy infants from the Developing Human Connectome Project (dHCP). Atypicality indices, representing the degree of positive or negative deviation of a regional volume from the normative mean for a given gestational age, sex and postnatal age, were calculated for each infant with congenital heart disease. Phase contrast angiography was acquired in 53 infants with congenital heart disease and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 46) using the Bayley scales of Infant and Toddler Development-Third Edition. We assessed the relationship between atypicality indices, cerebral oxygen delivery and cognitive and motor outcome. Additionally, we examined whether cerebral oxygen delivery was associated with neurodevelopmental outcome through the mediating effect of brain volume. Negative atypicality indices in deep grey matter were associated with both reduced neonatal cerebral oxygen delivery and poorer cognitive abilities at 22 months across the whole sample. In infants with congenital heart disease born ≥37 weeks, negative cortical grey matter and total tissue volume atypicality indices, in addition to deep grey matter structures, were associated with poorer cognition. There was a significant indirect relationship between cerebral oxygen delivery and cognition through the mediating effect of negative deep grey matter atypicality indices across the whole sample. In infants born ≥37 weeks, cortical grey matter and total tissue volume atypicality indices were also mediators of this relationship. In summary, lower cognitive abilities in toddlers with congenital heart disease were associated with smaller grey matter volumes before cardiac surgery. The aetiology of poor cognition may encompass poor cerebral oxygen delivery leading to impaired grey matter growth. Interventions to improve cerebral oxygen delivery may promote early brain growth and improve cognitive outcomes in infants with congenital heart disease.

Original language	English
Article number	fcab046
Journal	Brain Communications
Volume	3
Issue number	2
DOIs	https://doi.org/10.1093/braincomms/fcab046
Publication status	Published - 2021

Keywords

brain
cognition
congenital heart disease
dHCP
MRI

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/braincomms/fcab046

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Bonthrone, A. F., Dimitrova, R., Chew, A., Kelly, C. J., Cordero-Grande, L., Carney, O., Egloff, A., Hughes, E., Vecchiato, K., Simpson, J., Hajnal, J. V., Pushparajah, K., Victor, S., Nosarti, C., Rutherford, M. A., Edwards, A. D., O'Muircheartaigh, J., & Counsell, S. J. (2021). Individualized brain development and cognitive outcome in infants with congenital heart disease. Brain Communications, 3(2), Article fcab046. https://doi.org/10.1093/braincomms/fcab046

@article{4ccae6ab0f0e4ea2bdfb609cfcf9a308,

title = "Individualized brain development and cognitive outcome in infants with congenital heart disease",

abstract = "Infants with congenital heart disease are at risk of neurodevelopmental impairments, the origins of which are currently unclear. This study aimed to characterize the relationship between neonatal brain development, cerebral oxygen delivery and neurodevelopmental outcome in infants with congenital heart disease. A cohort of infants with serious or critical congenital heart disease (N = 66; N = 62 born ≥37 weeks) underwent brain MRI before surgery on a 3T scanner situated on the neonatal unit. T2-weighted images were segmented into brain regions using a neonatal-specific algorithm. We generated normative curves of typical volumetric brain development using a data-driven technique applied to 219 healthy infants from the Developing Human Connectome Project (dHCP). Atypicality indices, representing the degree of positive or negative deviation of a regional volume from the normative mean for a given gestational age, sex and postnatal age, were calculated for each infant with congenital heart disease. Phase contrast angiography was acquired in 53 infants with congenital heart disease and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 46) using the Bayley scales of Infant and Toddler Development-Third Edition. We assessed the relationship between atypicality indices, cerebral oxygen delivery and cognitive and motor outcome. Additionally, we examined whether cerebral oxygen delivery was associated with neurodevelopmental outcome through the mediating effect of brain volume. Negative atypicality indices in deep grey matter were associated with both reduced neonatal cerebral oxygen delivery and poorer cognitive abilities at 22 months across the whole sample. In infants with congenital heart disease born ≥37 weeks, negative cortical grey matter and total tissue volume atypicality indices, in addition to deep grey matter structures, were associated with poorer cognition. There was a significant indirect relationship between cerebral oxygen delivery and cognition through the mediating effect of negative deep grey matter atypicality indices across the whole sample. In infants born ≥37 weeks, cortical grey matter and total tissue volume atypicality indices were also mediators of this relationship. In summary, lower cognitive abilities in toddlers with congenital heart disease were associated with smaller grey matter volumes before cardiac surgery. The aetiology of poor cognition may encompass poor cerebral oxygen delivery leading to impaired grey matter growth. Interventions to improve cerebral oxygen delivery may promote early brain growth and improve cognitive outcomes in infants with congenital heart disease. ",

keywords = "brain, cognition, congenital heart disease, dHCP, MRI",

author = "Bonthrone, {Alexandra F.} and Ralica Dimitrova and Andrew Chew and Kelly, {Christopher J.} and Lucilio Cordero-Grande and Olivia Carney and Alexia Egloff and Emer Hughes and Katy Vecchiato and John Simpson and Hajnal, {Joseph V.} and Kuberan Pushparajah and Suresh Victor and Chiara Nosarti and Rutherford, {Mary A.} and Edwards, {A. David} and Jonathan O'Muircheartaigh and Counsell, {Serena J.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.",

year = "2021",

doi = "10.1093/braincomms/fcab046",

language = "English",

volume = "3",

journal = "Brain Communications",

issn = "2632-1297",

publisher = "Oxford University Press",

number = "2",

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Bonthrone, AF , Dimitrova, R , Chew, A , Kelly, CJ , Cordero-Grande, L , Carney, O , Egloff, A, Hughes, E, Vecchiato, K , Simpson, J , Hajnal, JV, Pushparajah, K, Victor, S , Nosarti, C , Rutherford, MA , Edwards, AD , O'Muircheartaigh, J & Counsell, SJ 2021, 'Individualized brain development and cognitive outcome in infants with congenital heart disease', Brain Communications, vol. 3, no. 2, fcab046. https://doi.org/10.1093/braincomms/fcab046

TY - JOUR

T1 - Individualized brain development and cognitive outcome in infants with congenital heart disease

AU - Bonthrone, Alexandra F.

AU - Dimitrova, Ralica

AU - Chew, Andrew

AU - Kelly, Christopher J.

AU - Cordero-Grande, Lucilio

AU - Carney, Olivia

AU - Egloff, Alexia

AU - Hughes, Emer

AU - Vecchiato, Katy

AU - Simpson, John

AU - Hajnal, Joseph V.

AU - Pushparajah, Kuberan

AU - Victor, Suresh

AU - Nosarti, Chiara

AU - Rutherford, Mary A.

AU - Edwards, A. David

AU - O'Muircheartaigh, Jonathan

AU - Counsell, Serena J.

PY - 2021

Y1 - 2021

N2 - Infants with congenital heart disease are at risk of neurodevelopmental impairments, the origins of which are currently unclear. This study aimed to characterize the relationship between neonatal brain development, cerebral oxygen delivery and neurodevelopmental outcome in infants with congenital heart disease. A cohort of infants with serious or critical congenital heart disease (N = 66; N = 62 born ≥37 weeks) underwent brain MRI before surgery on a 3T scanner situated on the neonatal unit. T2-weighted images were segmented into brain regions using a neonatal-specific algorithm. We generated normative curves of typical volumetric brain development using a data-driven technique applied to 219 healthy infants from the Developing Human Connectome Project (dHCP). Atypicality indices, representing the degree of positive or negative deviation of a regional volume from the normative mean for a given gestational age, sex and postnatal age, were calculated for each infant with congenital heart disease. Phase contrast angiography was acquired in 53 infants with congenital heart disease and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 46) using the Bayley scales of Infant and Toddler Development-Third Edition. We assessed the relationship between atypicality indices, cerebral oxygen delivery and cognitive and motor outcome. Additionally, we examined whether cerebral oxygen delivery was associated with neurodevelopmental outcome through the mediating effect of brain volume. Negative atypicality indices in deep grey matter were associated with both reduced neonatal cerebral oxygen delivery and poorer cognitive abilities at 22 months across the whole sample. In infants with congenital heart disease born ≥37 weeks, negative cortical grey matter and total tissue volume atypicality indices, in addition to deep grey matter structures, were associated with poorer cognition. There was a significant indirect relationship between cerebral oxygen delivery and cognition through the mediating effect of negative deep grey matter atypicality indices across the whole sample. In infants born ≥37 weeks, cortical grey matter and total tissue volume atypicality indices were also mediators of this relationship. In summary, lower cognitive abilities in toddlers with congenital heart disease were associated with smaller grey matter volumes before cardiac surgery. The aetiology of poor cognition may encompass poor cerebral oxygen delivery leading to impaired grey matter growth. Interventions to improve cerebral oxygen delivery may promote early brain growth and improve cognitive outcomes in infants with congenital heart disease.

AB - Infants with congenital heart disease are at risk of neurodevelopmental impairments, the origins of which are currently unclear. This study aimed to characterize the relationship between neonatal brain development, cerebral oxygen delivery and neurodevelopmental outcome in infants with congenital heart disease. A cohort of infants with serious or critical congenital heart disease (N = 66; N = 62 born ≥37 weeks) underwent brain MRI before surgery on a 3T scanner situated on the neonatal unit. T2-weighted images were segmented into brain regions using a neonatal-specific algorithm. We generated normative curves of typical volumetric brain development using a data-driven technique applied to 219 healthy infants from the Developing Human Connectome Project (dHCP). Atypicality indices, representing the degree of positive or negative deviation of a regional volume from the normative mean for a given gestational age, sex and postnatal age, were calculated for each infant with congenital heart disease. Phase contrast angiography was acquired in 53 infants with congenital heart disease and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 46) using the Bayley scales of Infant and Toddler Development-Third Edition. We assessed the relationship between atypicality indices, cerebral oxygen delivery and cognitive and motor outcome. Additionally, we examined whether cerebral oxygen delivery was associated with neurodevelopmental outcome through the mediating effect of brain volume. Negative atypicality indices in deep grey matter were associated with both reduced neonatal cerebral oxygen delivery and poorer cognitive abilities at 22 months across the whole sample. In infants with congenital heart disease born ≥37 weeks, negative cortical grey matter and total tissue volume atypicality indices, in addition to deep grey matter structures, were associated with poorer cognition. There was a significant indirect relationship between cerebral oxygen delivery and cognition through the mediating effect of negative deep grey matter atypicality indices across the whole sample. In infants born ≥37 weeks, cortical grey matter and total tissue volume atypicality indices were also mediators of this relationship. In summary, lower cognitive abilities in toddlers with congenital heart disease were associated with smaller grey matter volumes before cardiac surgery. The aetiology of poor cognition may encompass poor cerebral oxygen delivery leading to impaired grey matter growth. Interventions to improve cerebral oxygen delivery may promote early brain growth and improve cognitive outcomes in infants with congenital heart disease.

KW - brain

KW - cognition

KW - congenital heart disease

KW - dHCP

KW - MRI

UR - http://www.scopus.com/inward/record.url?scp=85121370277&partnerID=8YFLogxK

U2 - 10.1093/braincomms/fcab046

DO - 10.1093/braincomms/fcab046

M3 - Article

AN - SCOPUS:85121370277

SN - 2632-1297

VL - 3

JO - Brain Communications

JF - Brain Communications

IS - 2

M1 - fcab046

ER -

Individualized brain development and cognitive outcome in infants with congenital heart disease

Abstract

Keywords

UN SDGs

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