Hypophosphatemia in Febrile Illnesses and its Clinical Significance

Background: Phosphorus is a key element in cell function and energy storage and its levels may be regulated by inflammatory signals. The extent of hypophosphatemia in different clinical syndromes and its clinical significance have not yet been elucidated.

Methods: Data were retrospectively collected for febrile children aged 3 months-18 years hospitalized at the pediatric wards at a tertiary care hospital, during 2010-2019, using an automated search in computerized medical records. A comparison of phosphorus level between bacterial infection (BI) and viral infection (VI) and inflammatory disease was carried-out. Univariate and multivariate analyses for factors associated with severe disease course were performed.

Results: The cohort included 3963 febrile children, of whom 559 had a BI, 3271 a VI and 133 had Kawasaki disease (KD). Patients with a BI had higher rates of hypophosphatemia (49.2% versus 19.7% in VI and 31.6% in KD, P<0.001) and hypophosphatemia was more severe (phosphate standard deviation score [P-SD]: -1.77 versus -0.67 and -1.15, in BI, VI and KD, respectively, p<0.001). A P-SD of -3.0 had 92.9% sensitivity and 75.5% specificity for the diagnosis of a BI. Univariate and multivariate analyses showed that hypophosphatemia was associated with a more severe disease course, manifested by longer hospital stay (+2.10 days, 95%CI: 0.75-3.46, p=0.003), higher rate of ICU admission (OR 2.63, 95%CI: 1.94-3.56, p<0.001), and a trend towards higher rate of death (0.3%versus 0.03%, p=0.07).

Conclusion: Hypophosphatemia is more common among hospitalized children with a BI compared to VI and KD and is associated with a more severe disease course.