Impact of bronchopulmonary dysplasia on brain GABA concentrations in preterm infants: Prospective cohort study

Authors

Sudeepta K. Basu, Neonatology, Children's National Hospital, Washington, D.C., USA; Developing Brain Institute, Children's National Hospital, Washington, D.C., USA; The George Washington University School of Medicine, Washington, D.C., USA.
Kushal J. Kapse, Developing Brain Institute, Children's National Hospital, Washington, D.C., USA.
Jonathan Murnick, The George Washington University School of Medicine, Washington, D.C., USA; Division of Diagnostic Imaging and Radiology, Children's National Hospital, Washington, D.C., USA.
Subechhya Pradhan, Developing Brain Institute, Children's National Hospital, Washington, D.C., USA; The George Washington University School of Medicine, Washington, D.C., USA.
Emma Spoehr, Developing Brain Institute, Children's National Hospital, Washington, D.C., USA.
Anqing Zhang, The George Washington University School of Medicine, Washington, D.C., USA; Division of Biostatistics and Epidemiology, Children's National Hospital, Washington, D.C., USA.
Nickie Andescavage, Neonatology, Children's National Hospital, Washington, D.C., USA; Developing Brain Institute, Children's National Hospital, Washington, D.C., USA; The George Washington University School of Medicine, Washington, D.C., USA; Division of Neurology, Children's National Hospital, Washington, D.C., USA.
Gustavo Nino, The George Washington University School of Medicine, Washington, D.C., USA; Division of Pulmonary and Sleep Medicine, Children's National Hospital, Washington, D.C., USA.
Adre J. du Plessis, The George Washington University School of Medicine, Washington, D.C., USA; Division of Neurology, Children's National Hospital, Washington, D.C., USA; Perinatal Pediatrics institute, Children's National Hospital, Washington, D.C., USA.
Catherine Limperopoulos, Developing Brain Institute, Children's National Hospital, Washington, D.C., USA; The George Washington University School of Medicine, Washington, D.C., USA; Division of Diagnostic Imaging and Radiology, Children's National Hospital, Washington, D.C., USA; Division of Neurology, Children's National Hospital, Washington, D.C., USA. Electronic address: climpero@childrensnational.org.

Document Type

Journal Article

Publication Date

9-21-2023

Journal

Early human development

Volume

186

DOI

10.1016/j.earlhumdev.2023.105860

Keywords

Bronchopulmonary dysplasia; GABA; Glutamate; MEGA-PRESS; MR spectroscopy; Premature brain

Abstract

BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with cognitive-behavioral deficits in very preterm (VPT) infants, often in the absence of structural brain injury. Advanced GABA-editing techniques like Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) can quantify in-vivo gamma-aminobutyric acid (GABA+, with macromolecules) and glutamate (Glx, with glutamine) concentrations to investigate for neurophysiologic perturbations in the developing brain of VPT infants. OBJECTIVE: To investigate the relationship between the severity of BPD and basal-ganglia GABA+ and Glx concentrations in VPT infants. METHODS: MRI studies were performed on a 3 T scanner in a cohort of VPT infants [born ≤32 weeks gestational age (GA)] without major structural brain injury and healthy-term infants (>37 weeks GA) at term-equivalent age. MEGA-PRESS (TE68ms, TR2000ms, 256averages) sequence was acquired from the right basal-ganglia voxel (∼3cm) and metabolite concentrations were quantified in institutional units (i.u.). We stratified VPT infants into no/mild (grade 0/1) and moderate-severe (grade 2/3) BPD. RESULTS: Reliable MEGA-PRESS data was available from 63 subjects: 29 healthy-term and 34 VPT infants without major structural brain injury. VPT infants with moderate-severe BPD (n = 20) had the lowest right basal-ganglia GABA+ (median 1.88 vs. 2.28 vs. 2.12 i.u., p = 0.025) and GABA+/choline (0.73 vs. 0.99 vs. 0.88, p = 0.004) in comparison to infants with no/mild BPD and healthy-term infants. The GABA+/Glx ratio was lower (0.34 vs. 0.44, p = 0.034) in VPT infants with moderate-severe BPD than in infants with no/mild BPD. CONCLUSIONS: Reduced GABA+ and GABA+/Glx in VPT infants with moderate-severe BPD indicate neurophysiologic perturbations which could serve as early biomarkers of future cognitive deficits.

APA Citation

Basu, Sudeepta K.; Kapse, Kushal J.; Murnick, Jonathan; Pradhan, Subechhya; Spoehr, Emma; Zhang, Anqing; Andescavage, Nickie; Nino, Gustavo; du Plessis, Adre J.; and Limperopoulos, Catherine, "Impact of bronchopulmonary dysplasia on brain GABA concentrations in preterm infants: Prospective cohort study" (2023). GW Authored Works. Paper 3364.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3364

Department

Pediatrics