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

Sudeepta K Basu; Kushal J Kapse; Jonathan Murnick; Subechhya Pradhan; Emma Spoehr; Anqing Zhang; Nickie Andescavage; Gustavo Nino; Adre J du Plessis; Catherine Limperopoulos

doi:10.1016/j.earlhumdev.2023.105860

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

Early Hum Dev. 2023 Nov:186:105860. doi: 10.1016/j.earlhumdev.2023.105860. Epub 2023 Sep 21.

Authors

Affiliations

¹ 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.
² Developing Brain Institute, Children's National Hospital, Washington, D.C., USA.
³ 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.
⁴ Developing Brain Institute, Children's National Hospital, Washington, D.C., USA; The George Washington University School of Medicine, Washington, D.C., USA.
⁵ The George Washington University School of Medicine, Washington, D.C., USA; Division of Biostatistics and Epidemiology, Children's National Hospital, Washington, D.C., USA.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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.

PMID: 37757548
PMCID: PMC10843009 (available on 2024-11-01)
DOI: 10.1016/j.earlhumdev.2023.105860

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 (∼3cm³) 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.

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

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Brain / diagnostic imaging
Brain / metabolism
Brain Injuries*
Bronchopulmonary Dysplasia*
Female
Fetal Growth Retardation
Gestational Age
Humans
Infant
Infant, Newborn
Infant, Premature
Prospective Studies
gamma-Aminobutyric Acid / metabolism

Substances

gamma-Aminobutyric Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding