Differential Serum Phosphate Levels in Pediatric Febrile Syndromes and Their Clinical Significance

Background: The potential of hypophosphatemia (HP) to differentiate between febrile syndromes and its clinical significance in children without sepsis were not previously described. Methods: Data were retrospectively collected of febrile children 3 months to 18 years of age, hospitalized at general pediatric wards during 2010–2019. Phosphate levels were compared between bacterial infection (BI), viral infection (VI), and Kawasaki disease (KD). Regression analyses were used to evaluate the relationship between HP and outcome. Results: Of 3963 febrile children, 559 had BI, 3271 had VI, and 133 had KD. In BI compared to VI and KD, HP was more prevalent (49.2%, 19.7%, and 31.6%, respectively; P<0.001) and more severe [median (interquartile range) phosphate standard deviation score: −1.85 (2.08), −0.56 (2.08), and −1.20 (2.28), respectively; P<0.001]. In the BI group, Pi-SDS level was lower among patients with than without bacteremia (−2.33 ± 1.8 vs. –0.79 ± 1.68; P<0.001). Phosphate levels displayed discriminatory potential between bacterial and viral etiologies, with an area under the curve of 0.719 (95% CI, 0.697–0.742). Minimal phosphate standard deviation score values had a negative weak correlation with the maximal C-reactive protein levels and white blood cell count. Univariate and multivariate analyses showed an association of HP with a more severe disease course, manifested by longer hospital stay [+2.10 (95% CI, 0.75–3.46) days; P=0.003] and a higher rate of intensive care unit admission [odds ratio, 2.63 (95% CI, 1.94–3.56); P<0.001). Conclusions: Hypophosphatemia rates were highest in bacterial etiology, intermediate in KD, and lowest in viral etiology and were associated with poorer outcomes. Phosphate level may serve as a marker for ruling out a bacterial etiology.