Postnatal Changes in Fetal Hemoglobin and Tissue Oxygenation in Preterm and Term Neonates - A Prospective Observational Study

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Introduction Physiological postnatal changes in fetal hemoglobin fraction (FHbF) may affect neonatal tissue oxygenation through shifts in the oxyhemoglobin dissociation curve. We examined cross-sectional associations between FHbF and near-infrared spectroscopy (NIRS)-derived tissue oxygenation, and longitudinal associations between within-infant changes in FHbF and cerebral tissue oxygenation (cStO₂) and oxygen extraction (cFTOE) during the first 3 postnatal weeks in neonates without red blood cell transfusions. Methods This prospective observational study included 25 preterm (median [IQR] gestational age 33.6 [1.6] weeks) and 25 term (39.9 [1.4] weeks) neonates in a tertiary-center neonatal unit. Measurements were performed at T1 (days 2-3), T2 (days 5-10), and T3 (days 12-18). cStO₂ was assessed by time-resolved NIRS, peripheral tissue oxygenation by spatially resolved NIRS and peripheral fractional oxygen extraction by venous occlusion. cFTOE was calculated. Total hemoglobin (Hb) and FHbF were measured by co-oximetry. Cross-sectional associations were assessed using Spearman's rho correlations. Longitudinal trajectories and gestational-age-adjusted within-infant change-on-change associations were analyzed using linear mixed-effects models. Results No significant cross-sectional correlations were identified between FHbF and cerebral or peripheral NIRS-derived variables at any time point. Over time, Hb and cStO₂ declined, cFTOE increased, while peripheral oxygenation and extraction remained stable. Within-infant Hb changes were not associated with concurrent cerebral NIRS changes. In contrast, FHbF change was associated with change in cStO₂ (T2-T1: β per 1% FHbF, -0.19; 95% CI -0.33 to -0.05) and cFTOE (β 0.22; 95% CI 0.06 to 0.38). Conclusion Within-infant FHbF decline was associated with increased cStO₂ and decreased cFTOE, independent of total Hb.