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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\u20134 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively examined 108 VLBW preterm infants who had brain single-voxel magnetic resonance spectroscopy at 34\u201342 weeks\u2019 postmenstrual age. Neurodevelopment was assessed using a developmental test, and subjects were classified into four groups: developmental quotient &lt;70, 70\u201384, 85\u2013100, and &gt;100. One-way analyses of covariance and multiple-comparison post hoc tests were used to compare slopes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observed correlations between postmenstrual age and the concentrations of\n                      <jats:italic>N<\/jats:italic>\n                      -acetylaspartate and\n                      <jats:italic>N<\/jats:italic>\n                      -acetylaspartylglutamate (tNAA) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001); creatine and phosphocreatine (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001); glutamate and glutamine (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001); and myo-inositol (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.049) in the deep gray matter; and tNAA (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) in the centrum semiovale. A significant interaction was noted among the tNAA slopes of the four groups in the deep gray matter (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.022), and we found a significant difference between the &lt;70 and 85\u2013100 groups (post hoc,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.024).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In VLBW preterm infants, the slopes of tNAA concentrations (adjusted for postmenstrual age) were associated with lower developmental quotients at 3\u20134 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>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\u20134 years.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>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.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>While tNAA\/tCho ratios were previously used to examine the correlation with neurodevelopment at 1\u20132 years, we used brain metabolite concentrations.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-021-01398-6","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T12:03:18Z","timestamp":1614945798000},"page":"197-203","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Altered brain metabolite concentration and delayed neurodevelopment in preterm neonates"],"prefix":"10.1038","volume":"91","author":[{"given":"Moyoko","family":"Tomiyasu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shibasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikako","family":"Enokizono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuaki","family":"Toyoshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Obata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Aida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"1398_CR1","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/S0140-6736(08)60380-3","volume":"371","author":"B Larroque","year":"2008","unstructured":"Larroque, B. et al. 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