Among infants, a very short fever means less effective blood biomarkers
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Key takeaways:
- Blood biomarkers perform worse when infants have very short fevers.
- The reduced performance makes clinical decisions more difficult.
Except for procalcitonin, blood biomarkers perform worse when young infants have very short fevers, decreasing the accuracy of common clinical decision rules, including those endorsed by the AAP, researchers reported in Pediatrics.
Roberto Velasco Zúñiga MD, PhD, assistant physician in pediatrics at Parc Taulí University Hospital in Sabadell, Spain, and colleagues said the results of their study indicate that physicians should be more cautious when managing the care of febrile young infants with very short fevers who may be at risk for an invasive bacterial infection.
“In recent years, we have observed that in our environment, families are increasingly coming to the emergency room earlier and earlier for their children's health problems,” Zúñiga told Healio. “We have also observed this in febrile infants.”
He added that although median time of evolution of fever in these patients has been measured at 6 hours in the past, in more recent studies, this time has decreased to 2 hours.
“Taking into account the kinetics of the biomarkers that we usually use, we were concerned that the performance of these would be lower,” Zúñiga said.
Zúñiga and colleagues conducted a secondary analysis of a prospective single-center registry at Cruces University Hospital that included all febrile infants aged younger than 90 days who were card for in the pediatric ED between 2008 and 2021.
They categorized patients according to the hours elapsed since their families measured a temperature equal to or higher than 38°C (around 100°F) and assessed common biomarkers for their ability to identify infants at risk for an invasive bacterial infection.
“We analyzed the performance of the usual biomarkers [such as] absolute neutrophil count, C-reactive protein and procalcitonin, and of the most commonly used clinical decision rules in these patients,” Zúñiga said.
Among 2,411 infants included in the study, 3% were diagnosed with an invasive bacterial infection. Participants had a median duration of fever of 4 hours, with 26.3% having a fever lasting 2 hours or less.
According to the researchers, the area under the curve was significantly lower among patients with a fever lasting less than 2 hours compared with 2 to 12 hours or 12-plus hours for absolute neutrophil count (0.562 vs. 0.609 and 0.728) and C-reactive protein (0.568 vs. 0.76 and 0.812), but not for procalcitonin (0.749 vs. 0.78 and 0.773).
Among infants aged older than 21 days who had a negative urine dipstick with less than 2 hours of fever, procalcitonin showed an improved sensitivity (100%; specificity of 53.8%), than a combination of the biomarkers indicated by the Step-by-Step guidelines (50% and 82.2%), and of the AAP and Pediatric Emergency Care Applied Research Network (83.3% and 58.3%) guidance.
Zúñiga said the findings “did cause us some concern.”
“Unfortunately, we have found that, in effect, one in 10 patients with less than 2 hours of fever may have an invasive infection despite having normal biomarkers, but we have not been able to offer an alternative management,” Zúñiga said. “Regardless of which clinical decision rule is used, the patient with a few hours of evolution is a patient who should be managed in a more cautious manner.”
Zúñiga said he and his colleagues are interested in possibly developing a large, multicenter study recruiting “a sufficient number of febrile infants with a short evolution time in which to find the appropriate management.”
“Our impression is that possibly the use of procalcitonin, with cut-off points different from the usual ones, could be the ideal option,” Zúñiga said.
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