A novel diagnostic approach to differentiate iron overload from inflammation in children using transferrin saturation (TSAT) and ferritin-based indices: A cross-sectional study

Objective To evaluate the TSAT*SF and SF/TSAT indices in children living at different altitudes, with and without inflammation, and to examine their correlations with markers of iron homeostasis. Methods A cross-sectional, multicenter study included 238 children aged 6 to 72 months. We assessed TSAT*SF and SF/TSAT indices in relation to serum hepcidin, total body iron (TBI), hematological and nutritional parameters, and inflammatory markers. Results Children with elevated inflammatory markers resided at high altitude (HA) and exhibited increased hemoglobin (Hb), hematocrit, and a higher prevalence of erythrocytosis, alongside lower rates of anemia. Log-transformed values of SF, TBI, hepcidin, SF/TSAT ratio, and log(SF/TSAT) were significantly elevated in the inflammation group. In contrast, TSAT*SF values were unaffected by inflammation, showing no significant differences between groups. Among children with normal C-reactive protein (CRP ≤10 mg/L), TSAT*SF > 900 was associated with higher Hb, serum iron, hepcidin, TBI, and TSAT, as well as reduced height-for-age and weight-for-age Z-scores. Across the full sample, CRP positively correlated with ferritin, hepcidin, TBI, neutrophils, and unadjusted Hb, and negatively with serum iron and lymphocytes. CRP showed no correlation with TSAT*SF but was positively associated with the SF/TSAT ratio. Multivariate analysis revealed that the TSAT*SF index correlated with iron status but not inflammation, whereas the SF/TSAT index correlated with both iron status and inflammation. The SF*TSAT ratio demonstrated differential performance, showing a higher area under the ROC curve for the diagnosis of iron deficiency compared to inflammation (0.75 vs 0.98, p < 0.05), whereas the log-transformed SF/TSAT ratio did not exhibit this distinction. Conclusion The TSAT*SF index effectively identifies tissue iron overload independently of inflammation. Its use may improve iron status assessment in pediatric populations exposed to HA and systemic inflammation. Elevated TSAT*SF was linked to erythrocytosis and impaired growth, underscoring its diagnostic and public health significance.