Altered brain metabolite concentration and delayed neurodevelopment in preterm neonates

BACKGROUND: A very-low-birth-weight (VLBW) preterm infants is associated with an increased risk of impaired neurodevelopmental outcomes. In this study, we investigated how neonatal brain metabolite concentrations changed with postmenstrual age and examined the relationship between changes in concentration (slopes) and neurodevelopmental level at 3–4 years. METHODS: We retrospectively examined 108 VLBW preterm infants who had brain single-voxel magnetic resonance spectroscopy at 34–42 weeks’ postmenstrual age. Neurodevelopment was assessed using a developmental test, and subjects were classified into four groups: developmental quotient <70, 70–84, 85–100, and >100. One-way analyses of covariance and multiple-comparison post hoc tests were used to compare slopes. RESULTS: We observed correlations between postmenstrual age and the concentrations of N-acetylaspartate and N-acetylaspartylglutamate (tNAA) (p < 0.001); creatine and phosphocreatine (p < 0.001); glutamate and glutamine (p < 0.001); and myo-inositol (p = 0.049) in the deep gray matter; and tNAA (p < 0.001) in the centrum semiovale. A significant interaction was noted among the tNAA slopes of the four groups in the deep gray matter (p = 0.022), and we found a significant difference between the <70 and 85–100 groups (post hoc, p = 0.024). CONCLUSIONS: In VLBW preterm infants, the slopes of tNAA concentrations (adjusted for postmenstrual age) were associated with lower developmental quotients at 3–4 years. IMPACT: In very-low-birth-weight preterm-born infants, a slower increase in tNAA brain concentration at term-equivalent age was associated with poorer developmental outcomes at 3–4 years. The increase in tNAA concentration in very-low-birth-weight infants was slower in poorer developmental outcomes, and changes in tNAA concentration appeared to be more critical than changes in tCho for predicting developmental delays. While tNAA/tCho ratios were previously used to examine the correlation with neurodevelopment at 1–2 years, we used brain metabolite concentrations.