Background: Despite the high rate of neurological morbidity in patients with CHD, the CNS abnormalities involved have not been well-characterized. Aim: Analyze the incidence and nature of neuropathology in neonates with CHD. Subjects: Post-mortem CNS study of 126 patients: Group 1: 53 patients with isolated CHD,Group 2: 20 patients with CHD and a recognizable patterns of malformation, Group 3: 53 patients without CHD. Results: Developmental neuropathology: CHD was significantly related with poor opercularization (G1:21%, G2:35%, G3: 6%) and isolated mature neurons in white matter (G1:36%, G2:50%, G3:11%). Acquired neuropathology:CHD was accompanied by selective neuronal necrosis (63%) (widespread 62%, focal 38%), parenchymal necrosis (22%), brain edema (14%), intracranial hemorrhage(intraventricular 14%, subarachnoid 12%, intraparenchymal 4%).Conclusions: In patients with CHD, 1) minor CNS developmental defects were common, independently of recognizable patters of malformation, and 2) acquired neuropathology, particularly neuronal necrosis, was an important cause of morbidity. Patient management should focus on reducing risk factors.