Background Brain development is altered in neonates with congenital heart disease (CHD). However, development in the perioperative period remains incompletely understood.

Purpose This study used Structural Covariance Component (SCC) analysis to identify brain regions showing spatial patterns of coordinated expansion and contraction that differ between neonates with CHD after cardiac intervention and healthy controls, as well as pre-to postoperative changes and effects of perioperative risk factors.

Population The cohort included 41 neonates with CHD who underwent cardiac surgery or catheterization and 359 healthy neonates.

Field strength and sequence 3 Tesla T2-weighted turbo-spin-echo sequence.

Assessment Brain MRI were motion-corrected and reconstructed using an established neonatal algorithm. Jacobian determinants calculated from non-linear registration of MRI to a neonatal template were input into an Independent Component Analysis to identify SCCs (N=40). SCC weightings were extracted, reflecting the degree to which the pattern of covariance is expressed in each neonate.

Statistical tests Postoperative SCC weightings were compared to healthy neonates using a general linear model or robust regression. Pre- and postoperative SCC weightings were compared using a linear mixed effect model. Pre- to postoperative differences were calculated and associations with age at surgery, cardiopulmonary bypass duration, and postoperative paediatric intensive care unit stay were assessed using partial spearman’s rank correlation. Analyses were adjusted for covariates and corrected for multiple comparisons using False Discovery Rate.

Results 16/40 SCCs showed significant differences between neonates with CHD after surgery and controls, including white matter, cortical- and deep grey matter, brainstem, and CSF regions, with seven also showing significant perioperative change. A further nine SCCs only showed significant perioperative change. Perioperative risk factors were not associated with perioperative change.

Data conclusion This data-driven approach highlights region-specific postoperative alterations and perioperative changes in brain morphology of neonates with CHD. Evidence level. 1.

Technical Efficacy Stage 3.

The authors have declared no competing interest.

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 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.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The West London committee of the National Research Ethics Service (NRES) gave ethical approval for this work (dHCP: 14/LO/1169; CHiP: 07/H0707/105 and 21/WA/0075).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The data from the dHCP 3rd neonatal release is publicly available (https://nda.nih.gov/edit_collection.html?id=3955). Anonymized derived data from 25 infants with CHD acquired under ethics 21/WA/0075 and infants from dHCP (n = 359), as well as analysis scripts, are available from the corresponding author. We do not have ethical permission for sharing data for 16 infants with CHD acquired under ethics 07/H0707/105.

https://nda.nih.gov/edit_collection.html?id=3955