The Role of Serial Serum C-Reactive Protein Level in the Diagnosis of Neonatal Infection

Background: Infection is one of the major problems in neonates. The diagnosis of neonatal septicemia is difficult to establish based on the clinical criteria alone. However, empirical therapy should not be delayed because of high mortality. Laboratory tests used to support the diagnosis have shown variable values. C-reactive protein (CRP), an acute phase protein, increases in inflammatory disorders and tissue injury. Serial CRP has been shown to be more useful than a single measured CRP in the diagnostic evaluation of neonates with suspected infection. This study was performed to determine prospectively whether, in the presence of proved or presumed bacterial infection, the sensitivity of serum C-reactive protein response could be enhanced by serial rather than single determinations.
Materials and Methods: All infants, aged<60 days treated for suspected bacterial infection were prospectively evaluated using a standardized clinical pathway, from march 2005 to march 2006. Infants were categorized as having proved sepsis (bacteria isolated from blood, cerebrospinal fluid, or urine culture) or probable sepsis (clinical and laboratory findings consistent with bacterial infection without a positive culture). CRP level was determined at initial evaluation and 24 hours later. Sensitivity, specificity, and predictive values were calculated for the first (CRP#1), second (CRP#2) and two serial serum CRP levels. CRP was measured qualitatively (a positive test result indicates a CRP level more than 6 mg/L). Infants who had received antibiotics prior to sepsis work-up were excluded. Positive blood culture was considered as the "Gold Standard" against which the performance of CRP was compared.
Results: One hundred infants underwent sepsis work-up during the study period of 1 to 6 days. Of 100 infants, 52 were females (52%) and 48 were males (48%). There were 9 cases (9%) of proven sepsis (positive blood culture) and 91 cases (91%) of probable sepsis as defined in method section. The most common causative organisms were Staphylococcus aureus (5), Coagulase negative staphylococcus (3) and Escherichia coli(1). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CRP#1 were 55.5%, 82.5%, 24% and 95% respectively. Sensitivity, specificity, PPV and NPV of serial CRP were 67%, 80%, 24% and 96% respectively.
Conclusion: Serial CRP levels are useful in diagnostic evaluation of neonates with suspected infection. CRP levels<6 mg/L, obtained 24 hours apart from the initial CRP after presentation, indicate that bacterial infection is unlikely.