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