Brain injury and development in newborns with critical congenital heart disease

Objective: To determine the relationship between radiologically identifiable brain injuries and delayed brain development as reflected by brain metabolic and microstructural integrity. Methods: Term newborns with congenital heart disease (CHD) (120 preoperatively and 104 postoperatively) were studied with MRI to determine brain injury severity (BIS), microstructure reflected by fractional anisotropy (FA) and average diffusivity (D-av), and metabolism reflected by N-acetylaspartate (NAA)/choline (Cho) and lactate/Cho. Brain development is characterized by increasing NAA/Cho and white matter FA, and by decreasing D-av and lactate/Cho. Results: Newly acquired brain injury was common (41% preoperative, 30% postoperative). Lower white matter FA (p = 0.005) and lower NAA/Cho (p = 0.01) were associated with increasing preoperative BIS. Higher neonatal illness severity scores (p = 0.03), lower preoperative oxygen saturation (p = 0.002), hypotension (p < 0.001), and septostomy (p = 0.002) were also predictive of higher preoperative BIS. Preoperative FA, D-av, and NAA/Cho did not predict new postoperative BIS. Increasing preoperative BIS predicted higher postoperative D-av (p = 0.002) and lactate/Cho (p = 0.008). Within the postoperative scan, new brain injuries were associated with lower white matter FA (p = 0.04). Postoperative BIS (new lesions) was associated with lower postoperative systolic (p = 0.03) and mean (p = 0.05) blood pressures. Conclusions: Brain injuries in newborns with CHD are strongly related to abnormalities of brain microstructural and metabolic brain development, especially preoperatively. Both newly acquired preoperative and postoperative brain injuries are related to potentially modifiable clinical risk factors.