Abstract
BackgroundA 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.MethodsWe 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.ResultsWe 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).ConclusionsIn VLBW preterm infants, the slopes of tNAA concentrations (adjusted for postmenstrual age) were associated with lower developmental quotients at 3–4 years.ImpactIn 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.
Highlights
A very low birth weight (VLBW) in preterm infants is associated with an increased risk of impaired neurodevelopmental outcomes, and early identification and intervention may effectively improve developmental outcomes.[1,2,3,4,5,6] The incidence of major brain injuries has decreased with advances in neonatal care for preterm infants
1234567890();,: INTRODUCTION A very low birth weight (VLBW) in preterm infants is associated with an increased risk of impaired neurodevelopmental outcomes, and early identification and intervention may effectively improve developmental outcomes.[1,2,3,4,5,6]
The MR spectral signal-to-noise ratio was 12 (9–13) [median], and the metabolite Cramér–Rao lower bounds, which are displayed as the percent SD in the LCModel fits, were as follows [median]: the concentrations of N-acetylaspartate and Nacetylaspartylglutamate (tNAA), 7% (6–8%); tCr, 4% (4–5%); tCho, 4% (4–4%); Glx, 15% (13–17%); and mIns, 5% (5–6%)
Summary
A very low birth weight (VLBW) in preterm infants is associated with an increased risk of impaired neurodevelopmental outcomes, and early identification and intervention may effectively improve developmental outcomes.[1,2,3,4,5,6] The incidence of major brain injuries has decreased with advances in neonatal care for preterm infants. In predicting neurodevelopmental outcomes for LBW preterm infants, MRS has been used to measure the ratios of brain metabolites.[10,11,12,13,14,15,16,17] studies have reported a number of different patterns, with some reporting correlations between the ratios of Nacetylaspartate and N-acetylaspartylglutamate (total N-acetylaspartate (tNAA)) to glycerophosphocholine (including cholinecontaining compounds) and phosphocholine (tCho), i.e., tNAA/ tCho, and subsequent neurodevelopment.[11,13,15,16] Since these ratios are affected by alterations in the levels of any of the abovementioned metabolites, it is difficult to determine which metabolic disturbances cause neurological impairments, and slight pathological changes at the metabolite level may be overlooked To address this in the present study, we retrospectively investigated neonatal brain metabolite concentrations in Received: 12 October 2020 Revised: 3 January 2021 Accepted: 25 January 2021 infants aged 23–25 gestational weeks,
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