Individual assessment of perioperative brain growth trajectories in infants with congenital heart disease: correlation with clinical and surgical risk factors

TY - JOUR

T1 - Individual assessment of perioperative brain growth trajectories in infants with congenital heart disease: correlation with clinical and surgical risk factors

AU - Cromb, Dan

AU - Bonthrone, Alexandra

AU - Maggioni, Alessandra

AU - Cawley, Paul

AU - Dimitrova, Ralica

AU - Kelly, Christopher

AU - Cordero-Grande, Lucilio

AU - Carney, Olivia

AU - Egloff Collado, Alexia

AU - Hughes, Emer

AU - Hajnal, Jo

AU - Simpson, John

AU - Pushparajah, Kuberan

AU - Rutherford, Mary

AU - Edwards, David

AU - O'Muircheartaigh, Jonathan

AU - Counsell, Serena

N1 - Funding Information: We thank the families who participated in this study. We also thank our research radiologists, our research radiographers, and our neonatal scanning team. In addition, we thank the staff from the St Thomas’ Hospital Neonatal Intensive Care Unit; the Evelina London Children’s Hospital Fetal and Paediatric Cardiology Departments; the Evelina London Paediatric Intensive Care Unit; and the Centre for the Developing Brain at King’s College London.This research was funded by the Medical Research Council UK (MR/ L011530/1; MR/V002465/1), the British Heart Foundation (FS/15/ 55/31649) and Action Medical Research (GN2630). The normative sample was collected as part of the Developing Human Connectome Project, funded by the European Research Council under the European Union’s Seventh Framework Program (FP7/20072013)/European Research Council grant agreement no. 319456. This research was supported by the Wellcome Engineering and Physical Sciences Research Council Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z), Medical Research Council UK strategic grant (MR/K006355/1), Medical Research Council UK Centre grant (MR/N026063/1) and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. LCG is supported by the Comunidad de Madrid-Spain (Support for R&D Projects; BGP18/ 00178). Funding Information: This research was funded by the Medical Research Council UK (MR/ L011530/1; MR/V002465/1), the British Heart Foundation (FS/15/ 55/31649) and Action Medical Research (GN2630). The normative sample was collected as part of the Developing Human Connectome Project, funded by the European Research Council under the European Union’s Seventh Framework Program (FP7/20072013)/European Research Council grant agreement no. 319456. This research was supported by the Wellcome Engineering and Physical Sciences Research Council Centre for Medical Engineering Funding Information: at King’s College London (WT 203148/Z/16/Z), Medical Research Council UK strategic grant (MR/K006355/1), Medical Research Council UK Centre grant (MR/N026063/1) and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. LCG is supported by the Comunidad de Madrid-Spain (Support for R&D Projects; BGP18/ 00178). Publisher Copyright: © 2023 The Authors.

PY - 2023/7/8

Y1 - 2023/7/8

N2 - BACKGROUND: Infants with congenital heart disease (CHD) are at risk of neurodevelopmental impairments, which may be associated with impaired brain growth. We characterized how perioperative brain growth in infants with CHD deviates from typical trajectories and assessed the relationship between individualized perioperative brain growth and clinical risk factors. METHODS AND RESULTS: A total of 36 infants with CHD underwent preoperative and postoperative brain magnetic resonance imaging. Regional brain volumes were extracted. Normative volumetric development curves were generated using data from 219 healthy infants. Z-scores, representing the degree of positive or negative deviation from the normative mean for age and sex, were calculated for regional brain volumes from each infant with CHD before and after surgery. The degree of Z-score change was correlated with clinical risk factors. Perioperative growth was impaired across the brain, and it was associated with longer postoperative intensive care stay (false discovery rate P<0.05). Higher preoperative creatinine levels were associated with impaired brainstem, caudate nuclei, and right thalamus growth (all false discovery rate P=0.033). Older postnatal age at surgery was associated with impaired brainstem and right lentiform growth (both false discovery rate P=0.042). Longer cardiopulmonary bypass duration was associated with impaired brainstem and right caudate growth (false discovery rate P<0.027). CONCLUSIONS: Infants with CHD can have impaired brain growth in the immediate postoperative period, the degree of which associates with postoperative intensive care duration. Brainstem growth appears particularly vulnerable to perioperative clinical course, whereas impaired deep gray matter growth was associated with multiple clinical risk factors, possibly reflecting vulnerability of these regions to short-and long-term hypoxic injury.

AB - BACKGROUND: Infants with congenital heart disease (CHD) are at risk of neurodevelopmental impairments, which may be associated with impaired brain growth. We characterized how perioperative brain growth in infants with CHD deviates from typical trajectories and assessed the relationship between individualized perioperative brain growth and clinical risk factors. METHODS AND RESULTS: A total of 36 infants with CHD underwent preoperative and postoperative brain magnetic resonance imaging. Regional brain volumes were extracted. Normative volumetric development curves were generated using data from 219 healthy infants. Z-scores, representing the degree of positive or negative deviation from the normative mean for age and sex, were calculated for regional brain volumes from each infant with CHD before and after surgery. The degree of Z-score change was correlated with clinical risk factors. Perioperative growth was impaired across the brain, and it was associated with longer postoperative intensive care stay (false discovery rate P<0.05). Higher preoperative creatinine levels were associated with impaired brainstem, caudate nuclei, and right thalamus growth (all false discovery rate P=0.033). Older postnatal age at surgery was associated with impaired brainstem and right lentiform growth (both false discovery rate P=0.042). Longer cardiopulmonary bypass duration was associated with impaired brainstem and right caudate growth (false discovery rate P<0.027). CONCLUSIONS: Infants with CHD can have impaired brain growth in the immediate postoperative period, the degree of which associates with postoperative intensive care duration. Brainstem growth appears particularly vulnerable to perioperative clinical course, whereas impaired deep gray matter growth was associated with multiple clinical risk factors, possibly reflecting vulnerability of these regions to short-and long-term hypoxic injury.

UR - http://www.scopus.com/inward/record.url?scp=85165220094&partnerID=8YFLogxK

U2 - 10.1161/JAHA.122.028565

DO - 10.1161/JAHA.122.028565

M3 - Article

SN - 2047-9980

VL - 12

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 14

M1 - e8599

ER -