Sepsis in Newborns - Neonatal Sepsis

Neonatal sepsis is a major cause of hospitalization and infant death and can be caused by meningitis, pneumonia, gastroenteritis, or other infections. Early-onset sepsis, within 72 hours of birth, is usually caused by maternal pathogens such as group B streptococcus. Early detection and treatment can reduce morbidity and mortality. Nonspecific symptoms make differentiating between bacterial and viral infections difficult. Markers such as C-reactive protein (CRP) and procalcitonin can help differentiate pathogens.

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

Indications for Testing

  • Fever
  • Lethargy
  • Irritability
  • Poor feeding
  • Apnea
  • Abdominal distention

Laboratory Testing

  • Initial testing – routine evaluation for infection, including
    • CBC
    • Blood cultures
    • Cerebrospinal fluid analysis
    • Urinalysis
  • C-reactive protein (CRP) (Simonsen, 2014)
    • Good evidence supports use of CRP, in conjunction with white blood cell count and differential, to evaluate neonatal sepsis
    • Cutoff of 10 mg/L most commonly used; levels ≤10 mg/L indicate low probability of infection
    • Serial measures over time are useful
      • Obtain serial quantitative levels within 24 hours after onset of symptoms and obtain second measurement 24 hours later
      • 2 normal readings shown to be very strong negative predictor
  • Procalcitonin – proposed marker (Simonsen, 2014)
    • More sensitive than CRP for early detection of sepsis
    • More likely to be elevated in bacterial infection than viral infection
    • Levels decline rapidly in response to treatment
    • Levels may rise with noninfectious conditions and during first 24 hours of life (physiologic increase) – can complicate interpretation
  • Other biomarkers – have been studied as markers for neonatal sepsis; none in routine use (Simonsen, 2014)
    • Interleukin 6
    • Interleukin 8
    • Gamma interferon
    • Tumor necrosis factor alpha
    • Soluble intercellular adhesion molecule
    • CD64
  • Molecular testing – experimental
    • Polymerase chain reaction (PCR) – being evaluated for early detection of infection; not cost effective
    • Next generation sequencing – potential uses being explored in research trials
      • Eg, Explify respiratory pathogens test to detect respiratory pathogens (viral, bacterial, fungal) in patients with pneumonia

Differential Diagnosis

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
      • 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
      • 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

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

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

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

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

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

Explify Respiratory Pathogens by Next Generation Sequencing 2013694
Method: Massively Parallel Sequencing

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

Prevention of Perinatal Group B Streptococcal Disease. Revised Guidelines from CDC, 2010. November 19, 2010, Vol. 59, No. RR-10. Centers for Disease Control and Prevention. Atlanta, GA [Published: Nov 2010; Accessed: Sep 2017]

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

Simonsen KA, Anderson-Berry AL, Delair SF, Davies D. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014; 27(1): 21-47. 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

Couturier BA, Weight T, Elmer H, Schlaberg R. Antepartum screening for group B Streptococcus by three FDA-cleared molecular tests and effect of shortened enrichment culture on molecular detection rates. J Clin Microbiol. 2014; 52(9): 3429-32. 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

Content Reviewed: 
October 2017

Last Update: December 2017