Brain injury is a major complication in infants with complex congenital heart disease (CHD). There is growing evidence that impaired brain development has its origins in the fetal period. We prospectively characterized in vivo fetal brain metabolic profiles in 307 fetuses (210 health fetuses and 97 with CHD). Findings from measurements of metabolite concentrations of NAA, Cr, and Cho increased with advancing GA in healthy and CHD fetuses. In CHD fetuses, tNAA/tCh ratios were significantly lower while lactate concentrations were significantly higher compared to healthy fetuses, suggesting early-life disturbances in fetal brain biochemistry.