Sepsis in Newborns - Neonatal Sepsis

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Fever in newborn; change in clinical status

Laboratory Testing

  • Initial testing – routine evaluation for sepsis, including CBC, blood culture, cerebrospinal fluid analysis from lumbar puncture, urinalysis
  • Good evidence supports use of C-reactive protein to rule out sepsis in full term infants
    • Recent studies suggest similar efficacy in preterm infants
    • Use in conjunction with white blood cell count and differential
    • Single measure may not be helpful
    • Obtain serial quantitative levels 24 hours after onset of symptoms of possible infection and obtain second measurement 24 hours later
    • Levels ≤10 mg/L indicate low probability of infection
  • Procalcitonin – proposed marker
    • May be used <24 hours after onset of critical illness as a marker of neonatal sepsis
    • Reliability too low to use as single marker in diagnosis of sepsis

Differential Diagnosis

Systemic infections are responsible for a significant number of hospitalizations during the neonatal period. Nonspecific symptoms make differentiating between bacterial and viral illnesses difficult. Markers such as C-reactive protein are a useful aid in differentiation.

Epidemiology

  • Incidence – 2/1,000 live births in the U.S.

Pathophysiology

  • C-reactive protein (CRP)
    • CRP is an acute phase reactant that binds to the following
      • Polysaccharides present in many bacteria, fungi, and protozoal parasites
      • Phosphocholine
      • Phosphatidylcholines such as lecithins
      • Polyanions such as nucleic acids
    • Once complexed, CRP becomes an activator of the classical complement pathway by the following processes
      • Recognizing potentially toxic autogenous substances released from damaged tissues
      • Binding these toxic substances
      • Detoxifying or clearing the toxic substances from the blood
    • CRP peaks and begins to decrease within 48 hours of acute insult (eg, infection) if no other inflammatory event occurs
  • Procalcitonin
    • Acute phase reactant produced by monocytes and hepatocytes
    • Rises 4 hours after exposure to bacterial endotoxin
    • Peaks at 6-8 hours
    • Remains elevated at least 24 hours, then rapidly decreases

Clinical Presentation

  • Nonspecific signs and symptoms
    • Fever
    • Lethargy
    • Irritability, poor feeding
    • Apnea
    • Abdominal distention
  • Rapid progression of sepsis with accompanying shock without initiation of early treatment
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Blood Culture 0060102
Method: Continuous Monitoring Blood Culture/Identification

Limitations 

Testing is limited to the University of Utah Health Sciences Center only

Electrolyte Panel 0020410
Method: Quantitative Ion-Selective Electrode/Enzymatic

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Cerebrospinal Fluid (CSF) Culture and Gram Stain 0060106
Method: Stain/Culture/Identification

Cell Count, CSF 0095018
Method: Cell Count/Differential

Glucose, CSF 0020515
Method: Enzymatic

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Protein, Total, CSF 0020514
Method: Reflectance Spectrophotometry

C-Reactive Protein, Neonatal 0050181
Method: Immunoassay

Limitations 

Recent medical events resulting in tissue injury, infections, or inflammation may cause elevated CRP levels

Procalcitonin 0020763
Method: Immunofluorescence

Limitations 

As various noninfectious conditions are known to induce procalcitonin as well, procalcitonin levels between 0.50 ng/mL and 2.00 ng/mL should be reviewed carefully to take into account the specific clinical background and condition(s) of the individual patient

Procalcitonin levels below 0.50 ng/mL do not exclude an infection because localized infections (without systemic signs) may also be associated with such low levels

Guidelines

Committee on Infectious Diseases, Committee on Fetus and Newborn, Baker CJ, Byington CL, Polin RA. Policy statement—Recommendations for the prevention of perinatal group B streptococcal (GBS) disease. Pediatrics. 2011; 128(3): 611-6. PubMed

General References

Arnon S, Litmanovitz I. Diagnostic tests in neonatal sepsis. Curr Opin Infect Dis. 2008; 21(3): 223-7. PubMed

Baraff LJ. Management of infants and young children with fever without source. Pediatr Ann. 2008; 37(10): 673-9. PubMed

Behjati S, Prentice P, Rennie J. Management of Group B streptococcal sepsis risk in well, term newborns. Acta Paediatr. 2012; 101(2): 128-31. PubMed

Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am. 2013; 60(2): 367-89. PubMed

Lam HS, Ng PC. Biochemical markers of neonatal sepsis. Pathology. 2008; 40(2): 141-8. PubMed

Pacifico L, Osborn JF, Natale F, Ferraro F, De Curtis M, Chiesa C. Procalcitonin in pediatrics. Adv Clin Chem. 2013; 59: 203-63. PubMed

Pammi M, Flores A, Leeflang M, Versalovic J. Molecular assays in the diagnosis of neonatal sepsis: a systematic review and meta-analysis. Pediatrics. 2011; 128(4): e973-85. PubMed

van de Laar R, van der Ham DP, Oei G, Willekes C, Weiner CP, Mol BW. Accuracy of C-reactive protein determination in predicting chorioamnionitis and neonatal infection in pregnant women with premature rupture of membranes: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2009; 147(2): 124-9. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Christensen RD, Yaish HM, Wiedmeier SE, Reading S, Pysher TJ, Palmer CA, Prchal JT. Neonatal death suspected to be from sepsis was found to be kernicterus with G6PD deficiency. Pediatrics. 2013; 132(6): e1694-8. PubMed

De BK, Smith LG, Owen WE, Roberts WL. Performance characteristics of an automated high-sensitivity C-reactive protein assay on the Dimension RXL analyzer. Clin Chim Acta. 2002; 323(1-2): 151-5. PubMed

She RC, Simmon KE, Bender JM, Ampofo K, Petti CA. Mollicute infections in neonates. Pediatr Infect Dis J. 2009; 28(3): 248-50. PubMed

Medical Reviewers

Last Update: September 2016