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Congenital heart disease (CHD) is a leading birth defect in the United States, affecting about 40 000 neonates each year. Despite efforts to prevent developmental delays, many children with CHD have neurological deficits that last into adulthood, influencing employability, self-care, and quality of life.To determine if neonates with CHD have impaired cerebral autoregulation and poorer neurodevelopmental outcomes compared with healthy controls.A total of 44 full-term neonates, 28 with CHD and 16 without, were enrolled in the study. Inclusion criteria included confirmed diagnosis of CHD, stable hemodynamic status, and being no more than 12 days old. Exclusion criteria included intraventricular hemorrhage and intubation. Cerebral autoregulation was determined by measuring regional cerebral oxygenation during a postural change. The Einstein Neonatal Neurobehavioral Assessment Scale was used to measure overall neurodevelopmental outcomes (motor, visual, and auditory functions).Of the 28 neonates with CHD, 8 had single-ventricle physiology. A χ2 analysis indicated no significant difference in impaired cerebral autoregulation between neonates with CHD and controls (P = .38). Neonates with CHD had lower regional cerebral oxygenation than did neonates without CHD (P < .001). Regression analyses with adjustments for cerebral autoregulation indicated that neonates with CHD had poorer total neurodevelopmental outcomes scores (β = 9.3; P = .02) and motor scores (β = 7.6; P = .04).Preoperative neonates with CHD have poorer developmental outcomes and more hypoxemia than do controls.