Is CRP in neonatal sepsis a helpful marker?

In this review, we examine the diagnostic value of CRP in conjunction with routine laboratory tests for the evaluation of the neonate with or at risk for early-onset sepsis.

A perilous condition

Group B streptococcus (GBS) emerged as the leading pathogen of EOS in the 1970s, with fatality rates as high as 55%.² The 1992 publication of national guidelines recommending the use of intrapartum antibiotic prophylaxis to prevent neonatal GBS infection³ brought a significant decrease in GBS EOS, especially among infants ≥34 weeks gestation.⁴ However, with this reduction came an increase in the number of infants exposed to antibiotics prior to delivery.⁵

The subsequent judicious use of antibiotics in this population has decreased overall GBS rates, but a recent study indicates it has also increased the incidence of Escherichia coli as an etiological organism for EOS,¹ and led to more infants being born with antibiotic exposure that may impede bacterial growth from blood cultures.

Regardless of the presumed organism, the challenges for clinicians are 1) to identify those infants at risk for sepsis and 2) to develop a treatment strategy that not only prevents serious infection, but also limits antibiotic therapy to those most likely infected.

Avenues toward identification

WHITE BLOOD CELL (WBC) INDICES such as the immature to total neutrophil ratio (I/T ratio) are frequently used to assist in identifying at-risk infants. However, its use has limitations. For example, interpretations of the I/T ratio can be subjective if manual differential counts are determined by varying laboratory personnel. In addition, non-infected infants can exhibit "abnormal" results (ie, I/T>0.2)⁶ due to the ratio's poor specificity (Table 1 in the print and digital editions). As a result, the I/T ratio may have limited diagnostic value when used alone.⁷BLOOD CULTURE, "the gold standard for sepsis," is limited by the time required for bacterial growth as well as other factors including inadequate sample volume,⁸ and differentiation of true infection versus potential contamination.⁹ Intrapartum antibiotic prophylaxis may also influence blood culture results, potentially masking true positive cultures in the early newborn period.¹⁰

PROCALCITONIN (PCT) has garnered attention as an adjunctive lab test for identifying neonates with infection. PCT levels, however, can be elevated with other conditions such as respiratory distress syndrome, pneumothorax, intracranial hemorrhage, and hemodynamic instability.¹¹ PCT also displays a physiologic surge within the first 48 hours of life.¹² Therefore, normal values for age would be necessary, which have not yet been validated.

INFLAMMATORY CYTOKINES AND LYMPHOCYTE SURFACE MARKERS such as interleukin (IL)-6, IL-8, CD11b, and CD64, while valuable biomarkers, are only available in specialized research labs, limiting their ability to assist clinicians in a timely manner.¹³

C-REACTIVE PROTEIN (CRP) is widely available and can be used in conjunction with classic lab tests (complete blood count, blood culture) to improve identification of at-risk infants, and guide the length of antibiotic treatment. As with any laboratory test, careful scrutiny of CRP concentrations to diagnose sepsis is necessary to ascertain its limits and benefits.