The Role of C-Reactive Protein in the Evaluation and Management of Infants With Suspected Sepsis

Joan M. Hengst, RNC, MSN, ARNP


Adv Neonatal Care. 2003;3(1) 

In This Article

Controversies Surrounding the Use of CRP in Infants

There is not an established standard of practice for the use of CRP in infants, and a variety of approaches are described in the literature. Some authors advocate the use of serial CRP levels as an early diagnostic tool for confirming the presence of sepsis,[20,25,26] whereas others view it as a screening tool to rule out the presence of sepsis.[11,15,22,23,49] Further, some authors advocate the use of CRP to monitor therapy and determine the length of antibiotic treatment[20,21,22,26,49]; others do not use it at all.

Ideally, a clinical laboratory test that is considered reliable and diagnostic must have a high level of sensitivity and specificity in identifying what it is measuring.[4] In other words, a test used to diagnose sepsis in the infant must always indicate abnormal results in those infants who have sepsis (sensitivity) and indicate normal results in infants who are not infected (specificity).[4] Because neonatal sepsis has a reported mortality rate between 5% and 50%,[4,5] it is critical that practitioners identify all infants with sepsis (high sensitivity), even if the trade-off is overdiagnosis and treatment of infants who are not infected (low specificity).[29]

Initial criteria for normal and abnormal CRP levels were developed in adult populations. Recent studies of healthy asymptomatic adults have documented CRP levels ranging from 0.08 to 6.1 mg/L.[48,50,51] Generally, CRP levels <10 mg/L are considered normal in adults and children.[12,29,35,37,50] Emerging evidence that serum CRP levels as low as 2 mg/L may suggest a chronic or low-grade systemic inflammatory response and may be a useful risk predictor of cardiovascular and peripheral vascular disease in adults is beginning to challenge this norm.[51,52,53,54]

CRP levels in healthy full-term and preterm infants may range from 2 to 5 mg/L during the first few days of life.[26,37,39,55] During the neonatal period, an established upper normal CRP level of 10 mg/L has been identified in many studies.[11,12,15,20,21,22,23,26,38,39,49,55] Other research teams have used upper normal reference levels ranging from 6 to 20 mg/L as cutoff levels to indicate the presence of sepsis or infection.[15,25,41] Conflicting values have added to the confusion and uncertainty in using CRP in clinical practice.

Benitz et al evaluated CRP levels in 1,186 term and preterm infants and constructed receiver-operator characteristic curves for serial serum CRP levels.[11] These data provide strong statistical evidence to establish 10 mg/L as the appropriate threshold level, that is, the level at which the test has the maximum ability to identify infants with proven or probable sepsis. The study also confirms that serial CRP levels drawn 12 to 24 hours after the onset of signs and symptoms of infection are superior to a single level.[11]


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