SERIAL SERUM C-REACTIVE PROTEIN-LEVELS IN THE DIAGNOSIS OF NEONATAL INFECTION

Objective. To evaluate serial serum Creactive protein (CRP) levels for diagnosis of neonatal infection. Setting. A regional intensive care n ursery and two community intensive care nurseries. Methods. All neonat es treated for suspected bacterial infection were prospectively evalua ted using a standardized clinical pathway. Infants were categorized as having proven sepsis (bacteria isolated from blood, cerebrospinal flu id, or urine culture), probable sepsis (clinical and laboratory findin gs consistent with bacterial infection without a positive culture), or no sepsis (findings not consistent with sepsis), without consideratio n of CRP levels. Infants whose blood cultures yielded skin flora but w ho demonstrated no other signs of bacterial infection were not conside red to have sepsis. CRP levels were determined at the initial evaluati on and on each of the next two mornings. Sensitivity, specificity, pre dictive values, and likelihood ratios were calculated for the first (C RP #1), second (CRP #2), higher of the second and third (CRP #2 and #3 ), or highest of all three CRP levels (CRP x 3). Results. Sepsis was s uspected within the first 3 days after birth in 1002 infants (early-on set) and on 184 occasions in 134 older infants (late-onset). There wer e 20 early-onset and 53 late-onset episodes of proven sepsis, and 74 e arly-onset and 12 late-onset episodes of probable sepsis. CRP #1 had s ensitivities of 39.4% and 64.6% for proven or probable sepsis and 35.0 % and 61.5% for proven sepsis in early-onset and late-onset episodes, respectively. CRP levels on the morning after the initial evaluation ( CRP #2) had higher sensitivities (92.4% and 85.0% for proven or probab le sepsis and 78.9% and 84.4% for proven sepsis in early-onset and lat e-onset episodes, respectively), and normal results were associated wi th lower likelihoods of infection (likelihood ratios for normal result s of 0.10 and 0.19 for proven or probable sepsis and 0.27 and 0.21 for proven sepsis, in early-onset and late-onset episodes, respectively). Three serial serum CRP levels had sensitivities of 97.8%;ind 98.1% fo r proven or probable sepsis and 88.9% and 97.5% for proven sepsis in e arly-onset and late-onset episodes, respectively. The negative predict ive values for CRP x 3 were 99.7% and 98.7% for both proven or probabl e sepsis and for proven sepsis in early-onset and late-onset episodes, respectively. A CRP level obtained at the time of the initial evaluat ion can be omitted without significant loss of sensitivity or negative predictive value: the sensitivities of CRP #2 and #3 were 97.6% and 9 4.4% for proven or probable sepsis and 88.9% and 96.4% for proven seps is in early-onset and late-onset episodes, respectively; negative pred ictive values were 99.7% both for proven and for proven or probable ea rly-onset sepsis, 97.6% for proven or probable late-onset infection, a nd 98.8% for proven late-onset infection. Serial normal CRP :Levels we re associated with a markedly reduced likelihood of infection as compa red with that in the entire population before testing, with likelihood ratios ranging from 0.03 to 0.16 for the various subgroups. Maximum C RP levels >3 mg/dL had positive predictive values >20% for proven or p robable early-onset infections and for proven or probable and proven l ate-onset infections, but only those >6 mg/dL had such a high positive predictive value for proven early-onset sepsis. Conclusions. Serial C RP levels are useful in the diagnostic evaluation of neonates with sus pected infection. Two CRP levels <1 mg/dL obtained 24 hours apart, 8 t o 48 hours after presentation, indicate that bacterial infection is un likely. The sensitivity of a normal CRP at the initial evaluation is n ot sufficient to justify withholding antibiotic therapy. The positive predictive value of elevated CRP levels is low, especially for culture -proven carl:ii-onset infections. p://www.pediatrics.org/cgi/content/f ull/102/4/e41;