Assessment of hPod measured by fNIRS as an indicator of brain development in preterm infants

The brain undergoes dramatic development during early life, particularly throughout the third trimester of pregnancy. Preterm infants experience this critical period in the extrauterine environment, which may alter brain development and has recently gained attention for its potential impact on subsequent neurodevelopmental challenges. Brain maturation involves not only neuronal growth but also the development of vascular and neurovascular coupling systems. Hemoglobin phase of oxygenation and deoxygenation (hPod) is a promising biomarker of neurovascular and metabolic functional development. In this study, we investigated differences in hPod values between active sleep (AS) and quiet sleep (QS), as well as regional variation throughout the brain. In all, 240 simultaneous electroencephalography and near-infrared spectroscopy recordings were obtained from 75 preterm infants and 54 term-born infants. The hPod values were calculated as the time-averaged phase difference between oxy- and deoxyhemoglobin signals during AS and QS, respectively. The hPod values exhibited significant positive correlations that were highly consistent within each subject, between AS and QS, and between the bilateral homologous channels. Notably, they exhibited a gradual shift from an in-phase to an anti-phase pattern with an increase in postnatal age prior to term-equivalent age in preterm infants; this pattern emerged earlier in the posterior-temporal regions and was most delayed in the frontal regions. These results suggest that hPod values may have potential as a biomarker of early brain maturation in vulnerable infants, although further validation, particularly in association with neurodevelopmental outcomes including high-risk infants, is required before clinical application.