The objective was to determine in infants with perinatal depression whether the relative concentrations of N-acetylaspartate and lactate in the neonatal period are associated with (1) neurodevelopmental outcome at 30 mo of age or (2) deterioration in outcome from age 12 to 30 mo; and to determine whether socioeconomic factors are associated with deterioration in outcome. Thirty-seven term neonates were prospectively studied with single-voxel proton magnetic resonance spectroscopy of the basal nuclei and intervascular boundary zones. Thirty-month outcomes were classified as normal [if Mental Development Index of the Bayley Scales of Infant Development (MDI) >85 and neuromotor scores (NMS) <3; n = 15], abnormal [if MDI <or=85 and/or NMS >or=3 at 12 and 30 mo; n = 11], or deteriorated [if normal at 12 mo and abnormal at 30 mo (MDI <or=85 or NMS >or=3); n = 11]. Thirty percent (11/37) of our cohort deteriorated between 12 and 30 mo. N-acetylaspartate/choline decreased across the groups ordered as normal, deteriorated, and abnormal [in basal nuclei (p <or= 0.001) and intervascular boundary zones (p = 0.04)], but was not different between the normal and deteriorated groups (p = 0.08). Lactate/choline similarly increased across the groups [in basal nuclei (p = 0.01) and intervascular boundary zones (p = 0.05)]. The odds of deterioration, if normal at 12 mo, increased by a factor of 5.1 (95% confidence interval: 1.3-19.8) with each decrease in one of four household income strata. Infants with perinatal depression are at high risk of developmental deterioration between 12 and 30 mo of age, particularly if in a lower income home or with intermediate values of cerebral metabolites on neonatal proton magnetic resonance spectroscopy.