Uncovering Urinary Proteome Differences in Very Preterm Infants with and without Preterm Brain Injury

Premature infants are at high risk for brain injuries such as intraventricular hemorrhage and periventricular white matter injury. This study applies omics technology to analyze urinary protein expression, aiming to clarify preterm brain injury mechanisms and identify therapeutic targets. Urine samples were collected from 29 very preterm infants (VPI) without brain injury and 11 with moderate/severe injury at eight time points: Days 1, 2, 3, 4, 6, 8, 28, and term-equivalent age (TEA). Brain damage was assessed using the Kidokoro scale and MRI at TEA. SWATH-MS and bioinformatics were used to identify differentially expressed urinary proteins and affected pathways. Fifty-six proteins showed significant expression differences. Notably, extracellular proteoglycans (NCAN, ACAN, BCAN), associated with neuroprotection, were markedly reduced in infants with brain injury. Conversely, fatty acid-binding proteins (FABP1, FABP3, FABP4, FABP7) decreased over time in uninjured infants but increased in those with brain injury, suggesting a role in exacerbating damage. In summary, the urinary proteome of VPI with moderate/severe brain injury differs significantly from those without injury. Reduced neuroprotective proteoglycans and elevated FABPs highlight potential molecular markers and targets for intervention in preterm brain injury.