How should a febrile newborn (≤28 days old) be evaluated and managed?

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Fever in Newborns: Temperature Definition and Management

All newborns ≤28 days old with a rectal temperature ≥100.4°F (38.0°C) require immediate hospitalization, complete sepsis workup including lumbar puncture, and empirical intravenous antibiotics before culture results return. 1

Temperature Threshold

  • Fever is defined as rectal temperature ≥100.4°F (38.0°C or 38°C) in newborns 1, 2
  • Rectal temperature measurement is the gold standard for documenting fever in this age group 3

Why Newborns Are Different

Newborns ≤28 days represent the highest-risk group for invasive bacterial infections due to:

  • Decreased immune function (reduced opsonin activity, macrophage function, and neutrophil activity) 4
  • Higher rates of serious bacterial infections: 25% in the first 2 weeks of life, 13% in weeks 3-4 5
  • Increased risk of bacteremia (4.8% in first 2 weeks) and bacterial meningitis 5
  • Delayed diagnosis is associated with increased morbidity and mortality 1

Mandatory Evaluation for All Febrile Newborns ≤28 Days

Complete sepsis workup must include: 1

  • Blood culture
  • Urinalysis and urine culture (via catheterization or suprapubic aspiration—never bag specimen)
  • Lumbar puncture for CSF analysis and culture (non-negotiable in this age group)
  • Complete blood count with differential
  • Inflammatory markers (CRP and/or procalcitonin)

Empirical Antibiotic Therapy

Start ampicillin PLUS gentamicin immediately after obtaining cultures 1

  • This combination covers the most common neonatal pathogens: E. coli, Group B Streptococcus, and Listeria monocytogenes 1
  • Do not wait for culture results to initiate antibiotics 1
  • Add acyclovir if HSV infection is suspected (maternal history, vesicular lesions, CSF pleocytosis) 2

Hospitalization Requirements

All febrile newborns ≤28 days must be hospitalized 1, 2

  • Facility must have nurses and staff experienced in neonatal care 1
  • Continuous monitoring capability required 1
  • Immediate access to pediatric specialists 1

Duration of Treatment and Discharge

If all cultures remain negative at 24-36 hours: 1

  • Discontinue antibiotics if infant is clinically well or improving
  • No other infection requiring treatment is present
  • Discharge with close follow-up

If cultures are positive: 1

  • Switch to targeted antimicrobial therapy
  • Treat for 7-10 days for bacteremia
  • Treat for 14-21 days for meningitis

Common Pitfalls to Avoid

  • Never discharge a febrile newborn ≤28 days without full evaluation and hospitalization, even if appearing well 1, 2
  • Do not skip lumbar puncture—meningitis cannot be ruled out by blood work alone 1
  • Do not use urine bag collection (high contamination rate); only catheterization or suprapubic aspiration 1
  • Do not rely on response to antipyretics to determine severity—this does not predict serious bacterial infection 4
  • Observation scales fail in infants ≤2 months old 4

Age-Specific Variation in Practice

While some variation exists for infants 29-60 days old who may be risk-stratified 4, 6, there is no safe outpatient management strategy for newborns ≤28 days with documented fever 1, 2. Studies show 24% of febrile infants <28 days were not fully evaluated, but this represents deviation from standard of care, not acceptable practice 7.

References

Guideline

Management of Fever in Neonates

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Evaluation and Management of Febrile Infants with Cyanosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pediatric Fever.

Emergency medicine clinics of North America, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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