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Age-related differences in neurometabolite concentrations during early infancy: A cross-sectional analysis of the HBCD Release 1.0

Murali-Manohar S, Zöllner HJ, Davies-Jenkins CW, Gudmundson AT, Hui SCN, Song Y, Simegn GL, Shams Z et al.

2026

201 participants

Abstract

Background: Developmental trajectories of low-concentration neurometabolites such as the neurotransmitter γ-aminobutyric acid (GABA), and the antioxidants glutathione (GSH) and ascorbate (Asc) across early infancy remain unexplored. Advances in spectral editing enabled the measurement of these key molecules together with high-concentration metabolites like N-acetylaspartate (NAA) and glutamate (Glu) in the HEALthy Brain and Child Development (HBCD) study, the largest longitudinal study of early brain development in the United States.

Purpose: To determine the age-associated trajectories of 14 key neurometabolites during early infancy from a cross-sectional 1 H-MRS dataset.

Materials and Methods: HBCD utilizes ISTHMUS, an integrated MRS sequence that includes both an unedited short-echo-time PRESS acquisition and an advanced 4-step Hadamard-encoded sequence, HERCULES to enable measurement of both high- and low-concentration metabolites. Metabolite quantification was carried out by the HBCD Data Coordinating Center (HDCC) using an automated Osprey pipeline, with data from 201 infants ages 0 – 10 weeks adjusted age included in the tabular imaging results in HBCD data release 1.0. After excluding preterm born infants and data with poor linewidth or model quality metric, we tested for linear associations with adjusted age for each metabolite.

Results: Concentration estimates of total NAA (tNAA), total creatine (tCr) and glutamate (Glu) as well as the combined sum of glutamate and…

How strong is the evidence?

Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 201 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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