The Longitudinal Physiological Reference Values of Middle Cerebral Artery Blood Flow Velocity in Extremely Preterm Infants: A Study Utilizing Multimodal Cerebral Hemodynamic Monitors.

BACKGROUND: Cerebral blood flow (CBF) is essential for maintaining cerebral metabolism in extremely preterm infants; however, no universally accepted reference standard exists for CBF velocity (CBFV). This study aimed to establish physiological reference patterns of middle cerebral artery CBFV under strictly defined physiological stability using multimodal monitoring. METHODS: This post-hoc analysis included extremely preterm infants (gestational age ≤ 28+6 weeks or birthweight 500-1000 g) from a prospective cohort study. Serial Doppler ultrasonography of the middle cerebral artery was performed along with near-infrared spectroscopy and electrical cardiometry. Normal CBFV datasets were defined based on systemic stability, adequate cardiac output (>150 mL/kg/min), normal regional cerebral oxygen saturation (65-85%), and the absence of major comorbidities. Associations between Doppler parameters and postmenstrual age (PMA) and concurrent weight were analyzed using generalized estimating equations. RESULTS: Forty infants contributed 194 normal CBFV datasets. Physiological reference ranges for peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV), resistance index (RI), and pulsatility index (PI) were established across PMA and concurrent weight strata. Both PSV and MV were associated with PMA and concurrent weight (p < 0.01), whereas EDV, RI, and PI were not. Mean blood pressure was not significantly associated with CBFV parameters. CONCLUSIONS: PSV and MV were maturation-dependent cerebral perfusion markers. Multimodally defined physiological stability provides a robust framework for establishing clinically relevant reference values for middle cerebral artery CBFV in extremely preterm infants.