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NICU guideline identifier

C-Reactive Protein (CRP)

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Indications

  • C - reactive protein should NOT be checked as a routine part of a sepsis screen, especially if a decision has already been made to start the antibiotics based on the clinical picture. 
  • It may be helpful in excluding infection, in some cases of suspected sepsis, if normal levels are obtained 24-48 hours after the onset of symptoms. Therefore CRP should be considered in cases in which diagnosis of sepsis is unclear, and where negative cultures may not give sufficient reassurance to discontinue antibiotics. Common examples include when maternal intrapartum IV antibiotics were given, and in late onset sepsis where lumbar puncture specimens were unobtainable or blood-stained. 
  • A level of greater than 10 mg/L is abnormal. CRP < 10 mg/L is normal and makes sepsis much less likely (see Background and Applications below). 
  • Judicious use of CRP to enable earlier discontinuation of antibiotics in some instances may be cost-effective, decrease the possibility of resistance and in some cases may decrease duration of hospital stay. 

Sample

The laboratory requires 0.10-0.15 ml of SERUM, therefore 0.3-0.5ml (depending on haematocrit) of whole blood will be required, in a lithium heparin (green top) tube.

Background

  • CRP is an acute phase protein synthesized in the liver in response to inflammatory cytokines. Its levels may increase up to a thousand-fold during an acute phase response. Its short half-life (19 hours) means levels should fall rapidly after elimination of the (often microbial) source.1 Any elevation of CRP in a newborn baby represents endogenous synthesis as CRP crosses the placenta in very low amounts.4 
  • It takes 6 to 12 hours, even up to 24 hours for CRP to rise following onset of infection. Sensitivity of the test at presentation is only 40% - that is, 60% of subsequently proven sepsis episodes will have a normal initial CRP (compared to 80% sensitivity of immature to total neutrophil ratio).2 
  • Thus CRP level should not be checked at birth or at initial presentation with symptoms suggestive of sepsis. 

Applications

  • The value of CRP is in its reliability in the 24-48 hours after birth/onset of infection. 
  • In early onset sepsis (before 72 hours old), a single CRP 24 hours into illness has a 93% sensitivity for "probable" sepsis.3 Two measures 24 hours apart are even better. 
  • In late onset sepsis the reliability of the test is similarly high. A single CRP at 24-48 hours after the onset of infection has a sensitivity of 85%.3 
  • The positive predictive value for a raised CRP is poor so a positive test is poorly predictive of sepsis. However, the negative predictive value is 93%; therefore it can aid the decision to stop treatment.5 
  • The current literature suggests that CRP may be elevated in some noninfectious conditions (prolonged rupture of membranes, maternal fever during labour, fetal distress, perinatal asphyxia, shock, intraventricular haemorrhage, pneumothorax, and meconium aspiration pneumonitis).6 
  • A level of 10 mg/L has consistently been shown to be the most reliable cut-off to indicate sepsis. There is a link between the level of elevation of the CRP and the risk of sepsis, with positive predictive value steadily increasing up to CRP >100 mg/L. 
  • A lower CRP response to infection was reported in preterm compared to term newborns with a consequent lower sensitivity.6 
  • The magnitude of the CRP response to sepsis was reported to depend on underlying pathogen. Low rise of CRP observed in coagulase negative staphylococci compared to Staphylococcus aureus, group B streptococci, and E.coli.6 
  • Serial CRP levels that fail to decrease, or that continue to rise after 48 hours of antibiotic therapy suggest treatment failure.4 

References

  1. Ehl, S., et al. C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection. Pediatrics, 1997; 99:216-21. 
  2. Franz, A.R., et al. Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections. Pediatrics 1999. 104:447-53. 
  3. Benitz, W.E., et al., Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics 1998;102:E41. 
  4. Lacaze-Masmonteil T, Rosychuk RJ, Robinson JL. Value of a single C-reactive protein measurement at 18 h of age. Arch Dis Child Fetal Neonatal Ed. 2014 Jan;99(1):F76-9 
  5. Hofer, N, et al. An Update on the Use of C-Reactive Protein in Early-Onset Neonatal Sepsis:Current Insights and New Tasks. Neonatology 2012;102:25-36

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Document Control

  • Date last published: 03 September 2013
  • Document type: Clinical Guideline
  • Services responsible: Neonatology
  • Owner: Newborn Services Clinical Practice Committee
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years