JournalFeed PubMetric Report
Analysis Source: Full text (PMC12687207) + PubMed metadata
JournalFeed PubMetric Score
High Confidence
PubMetric Score Breakdown
Febrile neonates are a high-stakes, common presentation in emergency departments. A rule that can safely reduce invasive procedures (lumbar puncture) has significant clinical impact.
A pooled analysis of prospective cohort studies from multiple international centers is a strong design for validating a diagnostic rule.
QUADAS-2: Patient selection, index test, and reference standard domains appear to be at low risk of bias. However, the 'Flow and Timing' domain has 'some concerns' due to the abstract not explicitly detailing blinding of index test interpretation to reference standard, and vice versa, or the exact timing of all tests relative to each other, though it is implied to be well-conducted in prospective cohorts.
The high sensitivity (94.2%) and negative predictive value (99.4%) for invasive bacterial infection, coupled with 0% missed bacterial meningitis cases, are clinically meaningful and statistically significant findings.
The pooled analysis of 4 studies from 6 countries, including a secondary analysis with original derivation cohorts, provides strong evidence and consistency across diverse populations.
The rule utilizes readily available laboratory tests (urinalysis, procalcitonin, absolute neutrophil count) that are standard in most pediatric emergency department settings.
Funding sources and conflicts of interest were explicitly disclosed in the article.
Critical Appraisal
Study Identification
Background
Study Question
Study Design & Conduct
Prospective / Retrospective: Prospective
Multicenter: Yes
Unit of Allocation: Not applicable
Unit of Analysis: Infants
Randomization Method: Not applicable
Allocation Concealment: Not applicable
Blinding: Not reported
Follow-up Duration: Not reported
Population
- Previously healthy
- Non–ill-appearing
- Full-term (≥37 weeks’ gestation) infants
- Aged 28 days or younger
- Temperature ≥38.0 °C
- Underwent urine, blood, and serum testing
Number Enrolled: 1537
Number Analyzed: 1537
Key Baseline Characteristics
Sex: 905 male (58.9%)
Disease Severity: Febrile (≥38.0 °C), non–ill-appearing; 4.5% had invasive bacterial infections, 0.7% had bacterial meningitis.
Care Setting Distribution: Pediatric emergency departments
Additional Baseline Characteristics
- 1324 hospitalized (86.1%)
- 1080 with lumbar punctures (70.3%)
Exposures / Interventions
Description: Updated PECARN prediction rule for low risk of invasive bacterial infection.
Definition / Dose: Negative urinalysis/dipstick test result, serum procalcitonin ≤0.5 ng/mL, and blood absolute neutrophil count ≤4000/mm³.
Timing: At presentation/evaluation for fever.
Classification Method: Based on laboratory test results.
Protocolized / Discretionary: Protocolized
Description: Diagnosis of invasive bacterial infections (bacteremia or bacterial meningitis).
Definition: Not explicitly defined in the abstract, but typically confirmed by culture for bacteremia and CSF culture for bacterial meningitis.
Outcomes & Results
Primary Outcomes
Definition: Sensitivity, specificity, positive predictive value, negative predictive value for bacteremia or bacterial meningitis.
Time Point: At presentation/diagnosis
Measurement Method: Meta-analytic methods applied to pooled data from prospective cohort studies.
Results: Sensitivity 94.2% (95% CI, 85.6%-97.8%), Specificity 41.6% (95% CI, 36.7%-46.7%), PPV 6.9% (95% CI, 4.8%-9.9%), NPV 99.4% (95% CI, 98.1%-99.8%).
Secondary Outcomes
Definition: Ability of the rule to identify infants with bacterial meningitis.
Time Point: At presentation/diagnosis
Measurement Method: Not explicitly stated, but implied to be based on the same rule application.
Results: No infants classified as being at low risk had bacterial meningitis.
Definition: Sensitivity, specificity, PPV, NPV for IBI in a larger combined cohort.
Time Point: At presentation/diagnosis
Measurement Method: Not explicitly stated, but implied to be based on the same rule application.
Results: Rule performance was similar to primary analysis. No infants with bacterial meningitis were misclassified.
Risk of Bias
Risk of Bias - QUADAS-2
- Patient Selection (Low): The study included a well-defined, consecutive series of previously healthy, non–ill-appearing, full-term infants aged 28 days or younger with fever from pediatric emergency departments, minimizing concerns about patient selection bias.
- Index Test (Low): The updated PECARN rule (negative urinalysis/dipstick, serum procalcitonin ≤0.5 ng/mL, and blood absolute neutrophil count ≤4000/mm³) was clearly defined and applied, reducing concerns about bias in index test execution or interpretation.
- Reference Standard (Low): The reference standard, diagnosis of invasive bacterial infections (bacteremia or bacterial meningitis), is an appropriate and generally accepted method for confirming the target condition.
- Flow and Timing (Some concerns): The abstract does not explicitly state whether the interpretation of the index test was performed blind to the results of the reference standard, or vice versa. While it's a pooled analysis of prospective cohorts, the lack of explicit detail on blinding and the exact timing between index test and reference standard application for all patients leads to some concerns, though it's implied that all relevant tests were performed.
Transparency
COI Statement Present: TRUE
PubMetric Brief
Take-Home Message
The updated PECARN rule, using urinalysis, procalcitonin, and absolute neutrophil count, had a 99.4% negative predictive value for invasive bacterial infection in febrile neonates.
Study Summary
This pooled analysis of four prospective cohort studies from six countries evaluated the diagnostic accuracy of the updated Pediatric Emergency Care Applied Research Network (PECARN) rule for identifying febrile infants 28 days or younger at low risk for invasive bacterial infections (IBI), defined as bacteremia or bacterial meningitis. The study included 1537 previously healthy, non–ill-appearing, full-term infants with a temperature of 38.0 °C or higher. Infants were classified as low risk if they had a negative urinalysis/dipstick, serum procalcitonin ≤0.5 ng/mL, and blood absolute neutrophil count ≤4000/mm³.
Among the 1537 infants, 69 (4.5%) had IBIs, including 11 (0.7%) with bacterial meningitis. The PECARN rule classified 632 (41.1%) infants as low risk. The rule demonstrated a sensitivity of 94.2% (95% CI, 85.6%-97.8%), a specificity of 41.6% (95% CI, 36.7%-46.7%), a positive predictive value of 6.9% (95% CI, 4.8%-9.9%), and a negative predictive value (NPV) of 99.4% (95% CI, 98.1%-99.8%) for IBIs. Notably, no infants classified as low risk had bacterial meningitis. A secondary analysis of 2531 infants, including original derivation cohorts, showed similar performance, with no missed cases of bacterial meningitis.
Citation
Prediction of Bacteremia and Bacterial Meningitis Among Febrile Infants Aged 28 Days or Younger
. JAMA. 2026;335(5):425-433. PMID: 41359314