Temporal brain metabolite changes in preterm infants with normal development

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.

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.

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).

Our results provide new information on normative values of brain metabolites in preterm infants.