Temporal brain metabolite changes in preterm infants with normal development
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Updated: Mar 12, 2026

Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants
Published on: March 14, 2013
Sachiko Tanifuji1, Manami Akasaka1, Atsushi Kamei1
1Department of Pediatrics, School of Medicine, Iwate Medical University, Japan.
Insights
Brain metabolite levels, including gamma-aminobutyric acid (GABA), change over time in preterm infants. This study tracked these changes, providing normative data for brain development in this vulnerable population.
Area of Science:
- Neuroscience
- Developmental Biology
- Medical Imaging
Background:
- Preterm infants face risks for neurodevelopmental disorders like epilepsy and autism spectrum disorders.
- Gamma-aminobutyric acid (GABA) dysfunction is implicated in these conditions, but its temporal changes in preterm infants remain unstudied.
- Understanding brain metabolite dynamics is crucial for assessing neurodevelopmental trajectories.
Purpose of the Study:
- To investigate temporal changes in brain metabolites, including GABA, in normally developing preterm infants.
- To establish normative reference values for key brain metabolites during early development.
- To utilize advanced magnetic resonance spectroscopy techniques for precise metabolite quantification.
Main Methods:
- Single-voxel 3-Tesla (3T) proton magnetic resonance spectroscopy (¹H-MRS) was employed.
- Measurements were taken at two time points: 37-46 postmenstrual weeks (PMWs) and 64-73 PMWs.
- GABA was quantified using the MEGA-PRESS method, while other metabolites (NAA, Glx, Cr, Cho, Ins) were measured using the PRESS method, with LCModel for analysis.
Main Results:
- The GABA/Creatine (Cr) ratio significantly decreased between the two measurement periods (p=0.03).
- Ratios of N-acetyl aspartate (NAA)/Cr and Glutamate-Glutamine (Glx)/Cr increased significantly (p<0.01), while Choline (Cho)/Cr and myo-inositol (Ins)/Cr ratios decreased significantly (p<0.01).
- Absolute concentrations of NAA, Glx, and Cr increased significantly, while Ins decreased significantly (p<0.01).
Conclusions:
- This study provides novel insights into the normative development of brain metabolites in preterm infants.
- The observed temporal changes in GABA and other metabolites offer a baseline for future research.
- These findings contribute to a better understanding of brain maturation in the context of preterm birth.
Objective:
Preterm infants are at high risk for developmental delay, epilepsy, and autism spectrum disorders. Some reports have described associations between these conditions and gamma-aminobutyric acid (GABA) dysfunction; however, no study has evaluated temporal changes in GABA in preterm infants. Therefore, we assessed temporal changes in brain metabolites including GABA using single-voxel 3-Tesla (T) proton magnetic resonance spectroscopy (1H-MRS) in preterm infants with normal development.
Methods:
We performed 3T 1H-MRS at 37-46 postmenstrual weeks (PMWs, period A) and 64-73PMWs (period B). GABA was assessed with the MEGA-PRESS method. N-acetyl aspartate (NAA), glutamate-glutamine complex (Glx), creatine (Cr), choline (Cho), and myo-inositol (Ins) were assessed with the PRESS method. Metabolite concentrations were automatically calculated using LCModel.
Results:
Data were collected from 20 preterm infants for periods A and B (medians [ranges], 30 [24-34] gestational weeks, 1281 [486-2030]g birth weight). GABA/Cr ratio decreased significantly in period B (p=0.03), but there was no significant difference in GABA/Cho ratios (p=0.58) between the two periods. In period B, NAA/Cr, Glx/Cr, NAA/Cho, and Glx/Cho ratios were significantly increased (p<0.01), whereas Cho/Cr, Ins/Cr, and Ins/Cho ratios were significantly decreased (p<0.01). There was no significant difference for GABA or Cho concentrations (p=0.52, p=0.22, respectively). NAA, Glx, and Cr concentrations were significantly increased (p<0.01), whereas Ins was significantly decreased (p<0.01).
Conclusions:
Our results provide new information on normative values of brain metabolites in preterm infants.

