The aim of this study was to characterise the cortical structure in toddlers with congenital heart disease (CHD) of varying severities and to investigate its associations with preoperative laboratory values and neurodevelopmental outcomes. A cohort of 109 toddlers with CHD and 56 healthy controls (HCs) underwent magnetic resonance imaging between August 2021 and December 2023. All toddlers with CHD were assessed using the Gesell Developmental Schedules and stratified into mild, moderate, and severe groups. Generalised linear models were used to compare cortical structural (grey matter volume (GMV) and thickness) differences across CHD severity groups and HCs and to examine their relationships with preoperative laboratory values and neurodevelopmental outcomes. Compared with HCs, toddlers with mild and moderate-to-severe CHD exhibited reduced total brain volume and total GMV. Significant reductions in cortical GMV and thickness were observed in specific brain regions (p < 0.001, family-wise error corrected). Altered cortical structures demonstrated overlapping spatial distributions between the mild and moderate-to-severe CHD groups. In the mild and moderate-to-severe CHD groups, regional alterations were correlated with scores across multiple neurodevelopmental domains (adaptive, gross motor, and fine motor skills), and haemoglobin levels were associated with cortical thickness in the right superior frontal area (β = 0.422; pfwe = 0.021; 95% CI, 0.002–0.007).Conclusion: Toddlers with CHD exhibit GMV and cortical thickness variations across all CHD severity levels in this study. Notably, toddlers with mild CHD may demonstrate alterations comparable to those in the moderate-to-severe group at this developmental stage. These cortical alterations may merit early consideration during neurodevelopmental trajectories, irrespective of CHD severity.<Table Float="No" ID="Taba"> <tgroup cols="1"> <colspec align="left" colname="c1" colnum="1" /> <tbody> <row> <entry align="left" colname="c1"> What is Known: • While neurodevelopmental risks and behavioural abnormalities in children with complex CHD are well-established, less is known about the neuroanatomical alterations and neurodevelopmental outcomes of those with mild CHD. </entry> </row> <row> <entry align="left" colname="c1"> What is New: • Toddlers with CHD exhibit similar cortical structural alterations across all severity groups in this study. • Cortical structure was associated with haemoglobin levels and neurodevelopmental outcomes, suggesting it may lie on a pathway linking preoperative laboratory values to neurodevelopment. This positions it as a potential neuroimaging correlate of NDD and a candidate target for interventions aimed at improving outcomes. </entry> </row> </tbody> </tgroup> </Table>

Cortical structure alterations in toddlers with different severities of congenital heart disease: a cross-sectional study

期刊论文
发表日期：

2026年6月29日

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Fan Lu,
Yuting Liu,
Sizhe Lu,
Siyu Ma,
Meijiao Zhu,
Feng Yang,
Wei Yu,
Huijun Li,
Mingcui Fu,
Jia An,
Xuyun Wen,
Pengcheng Xue,
Xuming Mo,
Ming Yang

摘要

The aim of this study was to characterise the cortical structure in toddlers with congenital heart disease (CHD) of varying severities and to investigate its associations with preoperative laboratory values and neurodevelopmental outcomes. A cohort of 109 toddlers with CHD and 56 healthy controls (HCs) underwent magnetic resonance imaging between August 2021 and December 2023. All toddlers with CHD were assessed using the Gesell Developmental Schedules and stratified into mild, moderate, and severe groups. Generalised linear models were used to compare cortical structural (grey matter volume (GMV) and thickness) differences across CHD severity groups and HCs and to examine their relationships with preoperative laboratory values and neurodevelopmental outcomes. Compared with HCs, toddlers with mild and moderate-to-severe CHD exhibited reduced total brain volume and total GMV. Significant reductions in cortical GMV and thickness were observed in specific brain regions (p < 0.001, family-wise error corrected). Altered cortical structures demonstrated overlapping spatial distributions between the mild and moderate-to-severe CHD groups. In the mild and moderate-to-severe CHD groups, regional alterations were correlated with scores across multiple neurodevelopmental domains (adaptive, gross motor, and fine motor skills), and haemoglobin levels were associated with cortical thickness in the right superior frontal area (β = 0.422; p_fwe = 0.021; 95% CI, 0.002–0.007).

Conclusion: Toddlers with CHD exhibit GMV and cortical thickness variations across all CHD severity levels in this study. Notably, toddlers with mild CHD may demonstrate alterations comparable to those in the moderate-to-severe group at this developmental stage. These cortical alterations may merit early consideration during neurodevelopmental trajectories, irrespective of CHD severity.

What is Known:

• While neurodevelopmental risks and behavioural abnormalities in children with complex CHD are well-established, less is known about the neuroanatomical alterations and neurodevelopmental outcomes of those with mild CHD.

What is New:

• Toddlers with CHD exhibit similar cortical structural alterations across all severity groups in this study.

• Cortical structure was associated with haemoglobin levels and neurodevelopmental outcomes, suggesting it may lie on a pathway linking preoperative laboratory values to neurodevelopment. This positions it as a potential neuroimaging correlate of NDD and a candidate target for interventions aimed at improving outcomes.