C-reactive protein test falls flat in newborns with suspected sepsis

By Emily Hayes, LabPulse.com editor in chief

February 12, 2020 -- Testing for C-reactive protein (CRP) is sometimes used as a diagnostic aid for suspected sepsis -- a common, life-threatening complication -- in newborn babies, but its value is low, according to a new analysis.

The systematic review and meta-analysis evaluated the accuracy of CRP for determining the risk of late-onset infection in hospitalized neonatal patients, most of whom were preterm and had low birthweight. In the studies included in the analysis, CRP was compared with microbiological blood culture results as a reference standard.

The prevalence of late-onset infection ranged from 20% to 82%, with a median of 40%. The median specificity based on reports of true positives was 0.74 and the calculated pooled sensitivity was 0.62, researchers reported in JAMA Pediatrics (February 3, 2020).

The results suggest that CRP is not accurate enough to be useful for diagnosing late-onset infection in newborns and for helping to avoid the unnecessary use of antibiotics, concluded Dr. William McGuire, a professor of child health at the Centre for Reviews and Dissemination, University of York, in the U.K., and colleagues. Further work on biomarkers and testing methods is needed based on the study results.

"Newer methods using molecular markers to identify pathogenic microorganisms (such as real-time polymerase chain reaction or microarray techniques) are worthy of further research," McGuire and colleagues wrote. "Those new techniques can provide results more quickly than standard microbiological culture (6-8 hours [versus] 24-36 hours), and evidence of their diagnostic accuracy is accumulating."

Current role of CRP 'varies greatly'

Funded by a Cochrane grant from the U.K. National Institute for Health Research (NIHR), the study was carried out to evaluate CRP as a diagnostic aid for late-onset infection. The researchers noted that late-onset infection is a common and serious complication that occurs 72 hours or more after birth. Newborns with infection are more likely to need intensive care and longer hospital stays and to sustain damage that leads to serious cognitive developmental problems.

"Currently, in the absence of robust evidence to inform guideline or protocol development, the role of serum CRP in diagnostic algorithms for late-onset infection varies greatly," McGuire et al wrote.

Rapid diagnosis of late-onset infection is crucial due to the risk for damage. Patients may be managed with broad-spectrum antibiotics prior to the availability of blood culture results.

"Such widespread use, particularly of broad-spectrum antibiotics, is associated with accelerated selective pressure and the emergence of drug resistance through mechanisms such as extended-spectrum β-lactamase production," the authors noted. "In addition, the exposure to antibiotics in early life carries a risk of adversely altering the developing microbiome, which could be detrimental, especially to unwell or preterm infants in whom concerns regarding gut health already exist."

The meta-analysis included 22 studies with a total of 2,225 infants. Most of the studies were single-center trials, and a threshold for elevated CRP was commonly applied.

Lab tests with 'questionable value'

In an editorial accompanying the study, authors from the University of Texas at San Antonio noted that CRP is one of many lab tests suggested to offer potential as a biomarker for neonatal sepsis, along with the following:

  • Complete blood counts with differential
  • Procalcitonin
  • Interleukins
  • Presepsin

However, these tests have questionable value in clinical management, wrote neonatal specialists Dr. Joseph Cantey and Dr. Charlene Bultmann in the editorial, which was also published on February 3 in JAMA Pediatrics.

Regarding CRP, its performance in the meta-analysis "renders the test essentially useless," they added.

"The sensitivity of the CRP test may be lowest among infants with lower gestational age and birthweight, meaning that CRP performs the worst among infants with the highest risk for sepsis," they wrote.

Poor specificity means it is not useful when culture results are negative because of the risk for false positives, and the positive predictive value becomes "truly abysmal" as the prevalence rate declines, the authors continued.

"Unfortunately, treatment of 'culture-negative' sepsis is both common and often driven by falsely positive ancillary laboratory testing, such as CRP," Cantey and Bultmann wrote.

"The systematic use of CRP in the diagnosis of late-onset sepsis is not only hazardous, it is wasteful," they concluded.


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