Do all neonates (≤28 days old) with fever ≥38 °C require a full sepsis work‑up?

Do All Neonates Need Complete Workup for Fever?

Yes, all neonates ≤28 days old with fever ≥38°C require a full sepsis workup including lumbar puncture, blood culture, urinalysis with urine culture, and hospitalization with empiric antibiotics pending culture results. 1

Age-Specific Risk Profile

The neonatal period (≤28 days) represents the highest-risk window for serious bacterial infection (SBI):

• Bacteremia or bacterial meningitis occurs in 3.2-4.4% of febrile neonates, with overall SBI rates of 12-16.4% 2, 3
• Neonates have reduced opsonin activity, impaired macrophage function, and diminished neutrophil activity, making them uniquely vulnerable to invasive bacterial infections 4
• Only 58% of neonates with bacteremia or bacterial meningitis appear clinically ill, meaning clinical appearance alone cannot exclude life-threatening infection 1, 4

Mandatory Components of Full Sepsis Workup

Lumbar puncture with cerebrospinal fluid analysis is mandatory for all febrile neonates <28 days old because bacterial meningitis occurs in 0.7-1.3% of this population and cannot be reliably excluded by clinical examination or other laboratory tests alone 1, 2, 3, 5

The complete workup must include:

• Catheterized urine specimen for urinalysis and culture (never bag collection, which has 26% contamination rates) 1, 4
• Blood culture obtained before any antibiotics are administered 1, 4
• Complete blood count with differential and inflammatory markers 1, 4
• Lumbar puncture with cerebrospinal fluid cell count, glucose, protein, Gram stain, and culture 1, 5

Why Low-Risk Criteria Are Insufficient for Neonates

Although low-risk criteria (Boston and Philadelphia protocols) exist for older infants 1-2 months of age, applying these protocols to neonates ≤28 days would miss 3-3.5% of serious bacterial infections 3. This failure rate is unacceptable given:

• The 0.7-1.3% incidence of bacterial meningitis in this age group 2, 3, 5
• The devastating morbidity and mortality associated with delayed treatment of neonatal meningitis 1
• The fact that no infant with bacterial meningitis was misclassified when full workup was performed 5

Even when neonates meet laboratory low-risk criteria, 44.3% require reclassification within 2-3 days due to continued fever, poor activity, or evolving laboratory abnormalities 2

Management Algorithm

For all neonates ≤28 days with rectal temperature ≥38.0°C:

1. Document rectal temperature in the clinical setting (home thermometer readings are unreliable) 1, 4
2. Perform complete sepsis workup including lumbar puncture, blood culture, and catheterized urine culture 1, 5
3. Hospitalize and initiate empiric intravenous antibiotics immediately after cultures are obtained 1, 3
4. Maintain low threshold for treatment because delays in managing bacterial meningitis or sepsis markedly increase morbidity and mortality 1

Critical Pitfalls to Avoid

• Never defer lumbar puncture based on normal appearance, normal laboratory values, or positive viral testing—bacterial and viral infections frequently coexist 1, 4
• Never use bag-collected urine specimens due to high false-positive rates (26% vs 12% for catheterization) 1
• Never rely on antipyretic response to exclude serious infection—fever reduction does not correlate with infection likelihood 4
• Never discharge home without completing the full workup, even if the neonate appears well, because clinical appearance is unreliable in this age group 1, 2, 3

Special Consideration: Afebrile Neonates with History of Home Fever

Even neonates who are afebrile on presentation but had documented fever ≥38°C at home require full sepsis workup, as 37% of such infants have clinically significant infections including meningitis 6