Glymphatic System in Preterm Neonates: Developmental Insights Following Birth Asphyxia.

Background: Birth asphyxia (BA) and germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are common clinical events in preterm neonates. However, their effects on the glymphatic system (GS) development in preterm neonates remain arcane.

Purpose: To evaluate the developmental trajectory of the GS, and to investigate the effects of BA and GMH-IVH on GS function in preterm neonates.

Study type: Prospective.

Population: Two independent datasets, prospectively acquired internal dataset (including 99 preterm neonates, 40 female, mean [standard deviation] gestational age (GA) at birth, 29.95 [2.63] weeks) and the developing Human Connectome Project (dHCP) dataset (including 81 preterm neonates, 29 female, median [interquartile range] GA at birth, 32.71 [4.28] weeks).

Field strength/sequence: 3.0 T MRI and diffusion-weighted spin-echo planar imaging sequence.

Assessment: The diffusion-weighted images were preprocessed in volumetric space using the FMRIB Software Library and diffusion along the perivascular space (DTI-ALPS) index was accessed to evaluate GS function.

Statistical tests: Two sample t tests, one-way analysis of variance followed by least-significant difference (LSD) post hoc analysis, chi-squared tests, and Pearson's correlation analysis. Significance level: P < 0.05.

Results: In prospectively acquired internal dataset, preterm neonates with BA exhibited a significant lower DTI-ALPS index than those without BA (0.98 ± 0.08 vs. 1.08 ± 0.07, T = -5.89); however, GMH-IVH did not exert significant influences on the DTI-ALPS index (P = 0.83 and 0.27). The DTI-ALPS index increased significantly at postmenstrual age ranging from 25 to 34 weeks (r = 0.38) and then plateaued after 34 weeks (P = 0.35), which we also observed in the dHCP dataset.

Data conclusion: BA rather than GMH-IVH serves as the major influencing factor in the development of GS in preterm neonates. Moreover, as GS development follows a nonlinear trajectory, we recommend close monitoring of GS development in preterm neonates with a GA less than 34 weeks.

Level of evidence: 2 TECHNICAL EFFICACY: Stage 2.