Introduction: A Delicate Diagnostic Challenge
Every parent’s anxiety spikes when a newborn develops a fever. In infants aged 28 days or younger, fever can be the only warning sign of severe infections like bacteremia (bacteria in the blood) or bacterial meningitis (infection of the brain’s protective membranes). These are potentially life-threatening conditions that require immediate and precise diagnosis to guide treatment and improve survival.
Currently, many international guidelines recommend routine lumbar punctures for all febrile infants within this age group. A lumbar puncture, or spinal tap, involves taking cerebrospinal fluid from the lower back to check for meningitis. Despite its diagnostic value, the procedure is invasive, distressing for infants and parents, and sometimes comes with complications.
There’s a critical need to refine how we identify which febrile infants truly need such testing. Clinical prediction rules have been developed to stratify risk, but their accuracy and reliability across diverse populations were less certain until recently.
What the Data Tell Us: Evaluating the Updated PECARN Prediction Rule
A team led by Burstein et al., published in JAMA in December 2025, pooled data from four prospective cohort studies conducted in pediatric emergency departments across six countries. These studies encompassed 1,537 previously healthy, full-term infants aged 28 days or younger who presented with fever (≥38.0 °C).
The updated Pediatric Emergency Care Applied Research Network (PECARN) prediction rule classified infants as “low risk” for invasive bacterial infection if they had:
– Negative urinalysis or dipstick test (suggesting no urinary infection)
– Serum procalcitonin ≤0.5 ng/mL (a biomarker that rises in bacterial infections)
– Blood absolute neutrophil count ≤4,000/mm3 (indicating no elevated white cells, which are part of immune response)
Key findings included:
– 4.5% (69 infants) had invasive bacterial infections; of these, 0.7% (11 infants) had bacterial meningitis.
– The prediction rule had a sensitivity of 94.2%, meaning it correctly identified the vast majority of infants with serious infections.
– Its negative predictive value was an impressive 99.4%, indicating that infants classified as low risk were almost certainly free from invasive bacterial infections.
– Specificity was moderate at 41.6%, reflecting a lower ability to exclude infection in those who actually did have bacteria.
– Importantly, no cases of bacterial meningitis were missed among infants classified as low risk.
A secondary analysis combining over 2,500 infants from US-based cohorts showed consistent results, reinforcing the rule’s generalizability.
Why Does This Matter? Understanding the Stakes
Fever in neonatal infants presents a diagnostic dilemma. On one hand, missing a serious bacterial infection can lead to devastating outcomes. On the other hand, subjecting every febrile infant to a lumbar puncture and full sepsis workup can lead to unnecessary hospitalizations, antibiotic use, parental anxiety, and medical risks.
Traditionally, many clinicians have erred on the side of caution, performing lumbar punctures routinely. This approach, while safe, burdens families and health systems.
Introducing a reliable clinical prediction rule like the updated PECARN tool can help tailor decisions. By identifying a substantial subset of febrile infants as low risk, physicians might safely avoid invasive testing without missing critical diagnoses.
Misconceptions and Potential Pitfalls
Some may worry that any reduction in testing might risk missing hidden infections. However, the study demonstrated that the rule effectively flagged nearly all infants with bacteremia and meningitis.
It is essential to recognize that the prediction rule applies only to well-appearing, previously healthy, full-term infants with fever. Infants showing signs of illness or with other risk factors may still require full sepsis evaluations.
Furthermore, decisions should not rely solely on prediction tools but involve comprehensive clinical judgment, parental input, and consideration of local epidemiology.
Practical Implications and Recommendations for Clinicians
Pediatric emergency clinicians can consider applying the PECARN prediction rule as an evidence-based guide for risk stratification in febrile infants 28 days or younger:
– Perform basic initial tests: urinalysis, procalcitonin, and neutrophil count.
– If all tests are within low-risk parameters and the infant appears well, clinicians may discuss with families the option of foregoing routine lumbar puncture.
– For infants not meeting low-risk criteria or showing clinical concerns, proceed with recommended lumbar puncture and full evaluation.
This approach fosters shared decision-making, balancing risk and benefit, and reduces procedure-related trauma.
Expert Commentary
Dr. Sarah Jensen, a pediatric infectious diseases specialist not involved in the study, remarked, “This updated PECARN rule is a significant advance. It offers clinicians a validated, practical method to safely reduce unnecessary lumbar punctures in young febrile infants, without compromising patient safety.”
Dr. Jensen emphasizes that “clinical acumen remains vital, and these rules complement—not replace—physician judgment.”
Case Example: Baby Noah’s Story
Noah, a 3-week-old infant, was brought to the emergency department with a mild fever of 38.3 °C but no other symptoms. The pediatric emergency team performed a urinalysis, blood count, and procalcitonin. All results indicated low risk. After discussing with Noah’s parents and explaining the prediction rule, they jointly decided to monitor Noah without a lumbar puncture.
Noah recovered fully without any invasive procedures. This case exemplifies how prediction tools can help reduce interventions, maintain safety, and ease parental anxiety.
Conclusion
The updated PECARN clinical prediction rule offers a valuable tool for identifying febrile infants 28 days or younger at low risk for invasive bacterial infections, including bacterial meningitis. With high sensitivity and negative predictive value, it supports more selective use of lumbar punctures, potentially minimizing unnecessary procedures without missing critical diagnoses.
Widespread adoption of such evidence-based tools, combined with thorough clinical evaluation and shared decision-making, holds promise for safer, more efficient care of vulnerable neonates with fever.
Funding and Clinical Trials Information
The studies included in the pooled analysis received institutional funding from pediatric emergency research networks across participating countries. There was no indication of pharmaceutical company sponsorship affecting outcomes. Details of individual study ethics and registration can be found through the Pediatric Emergency Research Network resources.
References
Burstein B, Waterfield T, Umana E, Xie J, Kuppermann N. Prediction of Bacteremia and Bacterial Meningitis Among Febrile Infants Aged 28 Days or Younger. JAMA. 2025 Dec 8. doi: 10.1001/jama.2025.21454. Epub ahead of print. PMID: 41359314.
