C-reactive protein for late-onset sepsis diagnosis in very low birth weight infants

Abstract

Background: Late-onset sepsis in very low birth weight (VLBW) infants is a diagnostic challenge. We aimed to evaluate the diagnostic utility of the C-Reactive protein (CRP) and the complete blood count (CBC) for late-onset sepsis in VLBW infants.

Methods: In a 5-year retrospective cohort of 416 VLBW infants born at less than 1500 g, there were 590 separate late-onset sepsis evaluations. CRP and CBC were drawn at time of initial blood culture (T0), at 16-24 h (T24) and 40-48 h (T48) after. The positive cut-off values for abnormal values were the following: CRP ≥10 mg/L and CBC with at least one anomaly, including white blood cell count < 5000/mm³, immature neutrophil/total neutrophil ratio > 0.10, or platelet count < 100,000/uL. Sensitivity and specificity for predicting late-onset sepsis were calculated for each laboratory test and their combinations. Receiver operating characteristics curves were obtained for each test and for the absolute change from T0 to T24 in the laboratory value of CRP, white blood cell count and immature neutrophil/total neutrophil.

Results: At T0, combining the CBC and the CRP had the highest sensitivity of 66% (95% confidence interval [CI], 58-73) compared to both individual tests for predicting late onset sepsis. At T24, CRP's sensitivity was 84% (95% CI, 78-89) and was statistically higher than the CBC's 59% (95% CI, 51-67). The combination of CBC at T0 and CRP at T24 offered the greatest sensitivity of 88% (95% CI, 82-92) and negative predictive value 93% (95% CI, 89-96), with fewer samples, compared to any other combination of tests. The area under the curve for the change in the white blood cell count from T0 to T24 was 0.82.

Conclusion: At initial sepsis evaluation (T0), both CBC and CRP should be performed to increase sensitivity. A highly negative predictive value is reachable with only two tests: a CBC at T0 and a CRP a T24.

Keywords: C-reactive protein; Late-onset sepsis; Neonatology; Very low birth weight.

Fig. 1

Receiver operative characteristic (ROC) curves of different tests. a. CRP at T24. AUC = 0.82 (95% CI, 0.78–0.86). b. Absolute difference in the CRP values obtained at T0 and T24. AUC, 0.84 (95% CI, 0.79–0.88). c. Absolute difference in the white blood cell count at T0 and T24. AUC 0.82 (95% CI, 0.77–0.87). d. Absolute difference in the I/T ratio at T0 and T24. AUC 0.77 (95% CI, 0.70–0.82)