Early soluble LOX-1, cerebral perfusion, and intrauterine inflammation in very and extremely preterm infants

Hypoxic-ischemic brain injury is a major cause of adverse neurodevelopment in preterm infants; however, bedside tools to quantify early cerebral perfusion remain limited. We investigated the relationship between soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and cerebral blood volume (CBV) and explored the clinical factors associated with sLOX-1 levels in the early neonatal period.

In this prospective observational study, we enrolled neonates born at <32 weeks of gestation or weighing <1500 g and admitted to a tertiary neonatal intensive care unit between August 2022 and July 2023. Within 24 h of birth, the CBV was calculated using time-resolved near-infrared spectroscopy, and the plasma sLOX-1 level was measured. Spearman's correlation and multivariable linear regression analyses identified factors independently associated with the sLOX-1 level.

Twenty-nine infants (median gestational age, 30.3 weeks; birth weight, 1246 g) were analyzed. The sLOX-1 levels correlated inversely with the CBV (r = -0.40; p = 0.037). In multivariable analysis, a lower CBV (β = -253 pg mL⁻¹/(mL 100 g⁻¹); p = 0.020) and histological chorioamnionitis (β = +240 pg mL⁻¹; p < 0.001) remained independent predictors of higher sLOX-1 levels (adjusted R² = 0.436).

Elevated sLOX-1 levels reflected reduced cerebral perfusion and intrauterine inflammation in very and extremely preterm infants, supporting its utility as a biomarker of early ischemic brain injury.

Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) is associated with cerebral hypoperfusion in very and extremely preterm infants and shows an inverse relationship with cerebral blood volume and an association with intrauterine inflammation. This is the first study to report an inverse association between circulating sLOX-1 levels and cerebral blood volume in very and extremely preterm infants, extending its known relevance beyond term hypoxic-ischemic encephalopathy. sLOX-1 may serve as a blood-based biomarker to complement bedside neuromonitoring tools and guide personalized hemodynamic management, enabling the earlier detection of cerebral ischemia in the neonatal intensive care unit.