165 - Disrupted Preoperative White Matter Brain Microstructure in Newborns with Complex Congenital Heart Disease

Publication Number: 165.4315

Josepheen De Asis-Cruz, Children's National Health System, Washington DC, DC, United States; Maria G.. Mora Alvarez, Children's National Hospital, Washington, DC, United States; Kushal Kapse, Children's National Health System, Washington, DC, United States; Caitlin McDermott, Children's National Health System, Washington, DC, United States; Gilbert Vezina, George Washington University School of Medicine and Health Sciences, Washington, DC, United States; Mary T. Donofrio, Children's National Health System, Washington, DC, United States; Catherine Limperopoulos, Children's National Health System, Washington DC, DC, United States

Background: Up to 50% of congenital heart disease (CHD) survivors experience neurodevelopmental disabilities. Executive dysfunction in school age children with CHD is found to be linked to aortic obstruction (AO). Studies suggest disrupted microstructural development plays a role, but the associations between AO and axonal integrity have not been established.

Objective: Neonates with complex CHD will have decreased, pre-operative FA values in susceptible WM regions of interest (ROIs; Fig. 1A) compared to healthy newborns. Further, CHD newborns with AO will have reduced FA values and lower arterial oxygenation levels compared to newborns without obstruction (no-AO).

Design/Methods: We prospectively enrolled 333 healthy and CHD newborns into a longitudinal observational study and performed diffusion tensor imaging (DTI) to elucidate brain microstructural integrity preoperatively. Images were preprocessed using our previously validated pipeline. WM ROIs defined using the Edinburgh Neonatal Atlas were warped onto subjects’ FA maps, eroded, and quality checked. Then, average regional FA values were compared in healthy controls, no-AO, and AO groups using linear models (covariates: biologic sex, postmenstrual age (PMA) at MRI, and APGAR score at 5 minutes). In the CHD cohort, similar models will be used to assess associations between FA and pre-operative PaO2 and O2.

Results: We compared 150 neonatal cases of CHD and 183 controls (PMA in weeks, CHD=39.9±2.4 vs controls=41.7±1.8; p< 0.01). Newborns with CHD had significantly reduced FA in all ROIs except the right posterior limb of the internal capsule (R.PLIC; p< 0.05; Fig. 1B). The AO group had significantly reduced FA in the R.PLIC and left pons (Fig. 1C) and reduced PaO2 and O2 saturation (p < 0.05) compared to no-AO. No significant pH or PaCO2 differences were observed between CHD groups. PaO2 and O2 saturation were not linked to FA in any ROI.

Conclusion(s): We compared 150 neonatal cases of CHD and 183 controls (PMA in weeks, CHD=39.9±2.4 vs controls=41.7±1.8; p< 0.01). Newborns with CHD had significantly reduced FA in all ROIs except the right posterior limb of the internal capsule (R.PLIC; p< 0.05; Fig. 1B). The AO group had significantly reduced FA in the R.PLIC and left pons (Fig. 1C) and reduced PaO2 and O2 saturation (p < 0.05) compared to no-AO. No significant pH or PaCO2 differences were observed between CHD groups. PaO2 and O2 saturation were not linked to FA in any ROI.

Figure 1. Fractional anisotropy (FA) in healthy neonates and neonates with congenital heart disease (CHD) requiring surgery.
PAS_2025_fig.pdfFigure 1A. Regions of interest (ROIs) labeled on FA map, Figure 1B: ROIs categorized by significance of FA values between CHD cases and controls, Figure 1C: FA values in healthy newborns versus neonates with complex CHD, with or without aortic obstruction