Abstract

Gamma-aminobutyric acid (GABA) and glutamate are principal neurotransmitters essential for late gestational brain development and may play an important role in prematurity-related brain injury. In vivo investigation of GABA in the preterm infant with standard proton magnetic resonance spectroscopy (1H-MRS) has been limited due to its low concentrations in the developing brain, and overlap in the spectrum by other dominant metabolites. We describe early postnatal profiles of in vivo GABA and glutamate concentrations in the developing preterm brain measured by using the J-difference editing technique, Mescher-Garwood point resolved spectroscopy. We prospectively enrolled very preterm infants born ≤32 weeks gestational age and non-sedated 1H-MRS (echo time 68 ms, relaxation time 2000 ms, 256 signal averages) was acquired on a 3 Tesla magnetic resonance imaging scanner from a right frontal lobe voxel. Concentrations of GABA + (with macromolecules) was measured from the J-difference spectra; whereas glutamate and composite glutamate + glutamine (Glx) were measured from the unedited (OFF) spectra and reported in institutional units. We acquired 42 reliable spectra from 38 preterm infants without structural brain injury [median gestational age at birth of 28.0 (IQR 26.0, 28.9) weeks; 19 males (50%)] at a median postmenstrual age of 38.4 (range 33.4 to 46.4) weeks. With advancing post-menstrual age, the concentrations of glutamate OFF increased significantly, adjusted for co-variates (generalized estimating equation β = 0.22, p = 0.02). Advancing postnatal weeks of life at the time of imaging positively correlated with GABA + (β = 0.06, p = 0.02), glutamate OFF (β = 0.11, p = 0.02) and Glx OFF (β = 0.12, p = 0.04). Male infants had higher GABA + (1.66 ± 0.07 vs. 1.33 ± 0.11, p = 0.01) concentrations compared with female infants. For the first time, we report the early ex-utero developmental profile of in vivo GABA and glutamate stratified by age and sex in the developing brain of very preterm infants. This data may provide novel insights into the pathophysiology of neurodevelopmental disabilities reported in preterm infants even in the absence of structural brain injury.

Details

Title
Age and Sex Influences Gamma-aminobutyric Acid Concentrations in the Developing Brain of Very Premature Infants
Author
Basu, Sudeepta K 1 ; Pradhan Subechhya 2 ; Jacobs, Marni B 3 ; Said, Mariam 4 ; Kapse Kushal 5 ; Murnick, Jonathan 6 ; Whitehead, Matthew T 6 ; Chang Taeun 7   VIAFID ORCID Logo  ; du Plessis Adre J 8 ; Limperopoulos, Catherine 9 

1  Neonatology, Children’s National Hospital, Washington, US; Center for the Developing Brain, Children’s National Hospital, Washington, US; The George Washington University School of Medicine, Washington, US (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
2  Center for the Developing Brain, Children’s National Hospital, Washington, US (GRID:grid.253615.6); The George Washington University School of Medicine, Washington, US (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
3  Division of Biostatistics and Study Methodology, Children’s National Hospital, Washington, US (GRID:grid.253615.6); The George Washington University School of Medicine, Washington, US (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
4  Neonatology, Children’s National Hospital, Washington, US (GRID:grid.253615.6); Center for the Developing Brain, Children’s National Hospital, Washington, US (GRID:grid.253615.6); The George Washington University School of Medicine, Washington, US (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
5  Center for the Developing Brain, Children’s National Hospital, Washington, US (GRID:grid.253615.6) 
6  Division of Diagnostic Imaging and Radiology, Children’s National Hospital, Washington, US (GRID:grid.253615.6); The George Washington University School of Medicine, Washington, US (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
7  Division of Neurology, Children’s National Hospital, Washington, US (GRID:grid.253615.6); The George Washington University School of Medicine, Washington, US (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
8  Fetal Medicine institute, Children’s National Hospital, Washington, US (GRID:grid.253615.6); The George Washington University School of Medicine, Washington, US (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
9  Center for the Developing Brain, Children’s National Hospital, Washington, US (GRID:grid.253615.6); Division of Diagnostic Imaging and Radiology, Children’s National Hospital, Washington, US (GRID:grid.253615.6); The George Washington University School of Medicine, Washington, US (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-020-67188-y
ProQuest document ID
2418452524
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.