Researchers show the noninvasive tests can reliably identify infants with fevers 28 days and younger who are at very low risk for invasive bacterial infections.


A combination of blood and urine tests may allow many febrile infants to safely avoid lumbar punctures, according to findings from an international study published in JAMA. The results show that these noninvasive tests can reliably identify infants with fevers 28 days and younger who are at very low risk for invasive bacterial infections.

The study evaluated the performance of an updated febrile infant prediction rule from the Pediatric Emergency Care Applied Research Network (PECARN). The PECARN rule classifies a febrile infant as low risk if three criteria are met: the urinalysis is negative, the serum procalcitonin level is at or below 0.5 ng/mL, and the absolute neutrophil count is at or below 4,000 per mm³. The rule relies only on blood and urine tests routinely used in emergency departments worldwide and does not require a spinal tap to determine risk.

“For more than 40 years, pediatric researchers have been trying to determine how to safely do less testing for febrile infants in the first month of life without missing uncommon, but dangerous infections,” says Brett Burstein, MDCM, PhD, MPH, lead author of the study and pediatric emergency physician at the Montreal Children’s Hospital, in a release.

Strong Diagnostic Performance Across International Cohorts

Among 2,531 infants from four international cohorts and two US-based cohorts from which the PECARN rule was originally derived, the rule demonstrated a sensitivity of 94.8% and a negative predictive value of 99.6% for ruling out all invasive bacterial infections. Most importantly, none of the 22 cases of bacterial meningitis were missed among infants classified as low risk.

“Our analysis included more than 2,500 febrile infants across multiple countries and, using three widely available laboratory tests without spinal taps, performed with excellent diagnostic accuracy for ruling out invasive bacterial infections. Importantly, achieving zero missed cases of bacterial meningitis in such a large number of febrile infants in the first month of life is a critical benchmark in this area of research,” says Burstein, also a scientist in the Child Health and Human Development Program at the Research Institute of the McGill University Health Centre, in a release.

Febrile infants younger than 28 days old are routinely evaluated for invasive bacterial infections such as bacterial meningitis because their early symptoms can be subtle. Most hospitals automatically perform a full infection workup, including spinal taps, then administer intravenous antibiotics, even when a febrile infant appears well.

Evidence-Based Approach for Clinical Decision-Making

“Fever in the first month of life is one of the highest stakes situations we face in pediatric care,” says Nathan Kuppermann, MD, MPH, senior author of the study, chief academic officer at Children’s National, a pediatric emergency physician and director of the Children’s National Research Institute, in a release. “Studying these uncommon infections really required international collaboration. Our findings show we can now use a validated, evidence-based rule to identify many of these young febrile infants who are extremely unlikely to have bacterial meningitis, which can support more personalized decisions for families.”

The updated PECARN rule offers an evidence-based way to identify young febrile infants for whom a less invasive approach may be appropriate. Clinical decisions for infants 28 days and younger remain individualized and should be guided by pediatric experts.

“These results provide the level of evidence clinicians need to feel confident to strongly consider this approach,” says Burstein in a release.

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