Elsevier

Brain and Development

Volume 39, Issue 3, March 2017, Pages 196-202
Brain and Development

Original article
Temporal brain metabolite changes in preterm infants with normal development

https://doi.org/10.1016/j.braindev.2016.10.006Get rights and content

Abstract

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 64–73 PMWs (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.

Introduction

Recent clinical advances in perinatal care have increased the survival rate of preterm infants. However, preterm infants still have higher risks of cerebral palsy, cognitive deficiency, behavioral or psychological problems, blindness, hearing loss, epilepsy, and autism spectrum disorders [1], [2]. Diagnoses of intraventricular hemorrhage or periventricular leukomalacia made using cranial ultrasonography (US) or conventional magnetic resonance imaging (MRI) show sufficient sensitivity to detect delayed complications such as spastic diplegia or quadriparesis and are usually the first imaging modalities used in preterm infants [3]. However, they cannot completely exclude later adverse neurologic outcomes: for example, preterm infants can appear normal on neonatal US and exhibit no white matter lesions on MRI but later develop cerebral palsy and suffer cognitive delays.

Proton magnetic resonance spectroscopy (1H-MRS) can noninvasively measure various brain metabolites that are known to be altered during rapid brain development in the first year of life [4]. MRS may provide additional diagnostic value to cranial US and MRI in infants. The use of 3 Tesla (T) MRS offers better quality spectra in shorter acquisition times than 1.5T MRS, and 3T MRS can also discriminate gamma-aminobutyric acid (GABA) spectrum. An immunohistochemical study showed GABAergic neuron loss following perinatal brain injury and revealed that white matter lesions affect cortical development and GABA receptor expression in cortical layers; the authors suggested that this may contribute to the pathogenesis of neurologic deficits [5]. GABA abnormalities have also been reported in the settings of childhood autism spectrum disorders and epilepsy [6], [7].

The purpose of this study was to assess temporal changes in brain metabolites including GABA with single-voxel 3T 1H-MRS in preterm infants with normal development until 64–73 postmenstrual weeks (PMWs, the gestational weeks plus the weeks after birth).

Section snippets

Patients

From April 2014 to March 2015, we prospectively recruited 79 preterm infants (gestational age  34 weeks) who were admitted to our neonatal intensive care unit. Cranial US, conventional MRI, and 1H-MRS were performed at 37–46 PMWs (period A). Follow-up MRI and 1H-MRS scans were performed at 64–73 PMWs (period B). The analysis included infants with data for both periods who were determined to have normal development at period B. Of 79 preterm infants, we excluded 59 due to early death (n = 2), major

Results

Table 1 shows the clinical characteristics of the study population. Data are expressed as numbers (%) or medians (ranges) unless otherwise indicated. They were born at 30 (24–34) gestational weeks of age with a birth weight of 1281 (486–2030) g, 7 (35%) of which were extremely low birth weight infants (<1000 g). Sixteen (80%) were appropriate for dates (AFD) infants and 4 (20%) were asymmetric small for dates (SFD) infants. SFD was defined as both birth weight and height less than the 10th

Discussion

Our results show brain metabolite alterations measured with 3T 1H-MRS during early infancy in preterm infants with normal psychomotor development. In a comparison of measurements taken during periods A and B, the GABA/Cr ratio was significantly decreased, but there were no significant differences in the GABA/Cho ratios and GABA concentrations. The changes in NAA/Cr, NAA/Cho, Cho/Cr, Ins/Cr, and Ins/Cho ratios are consistent with findings from our previous study using 1.5T 1H-MRS [10] and those

Acknowledgements

This work was supported by a grant-in-aid for Strategic Medical Science Research (S1491001, 2014-2018) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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