Refined C-Reactive Protein Cutoffs Help Assess Sepsis Risk in Preterm Babies

Early-onset sepsis (EOS) is a dangerous bloodstream infection that appears in the first three days of life, yet its early symptoms resemble many benign newborn conditions. To support urgent treatment decisions, clinicians often turn to C-reactive protein (CRP). While CRP is widely used and has a strong negative predictive value, its optimal cutoffs during the first 72 hours of life have been unclear. A multicenter retrospective study now offers a clearer solution by defining time- and gestation-specific CRP thresholds that help identify which newborns—particularly preterm infants—are most likely to have EOS.

In the study conducted at The Chinese University of Hong Kong (Hong Kong SAR), researchers reviewed electronic health records across all public hospitals to evaluate CRP’s diagnostic performance in more than 100,000 newborns over 11 years. The investigators found that CRP rises naturally after birth in healthy babies, peaking around 24 to 32 hours, and this rise is markedly higher in term infants.

Image: The pediatric investigation study examined the diagnostic utility of C-reactive protein for newborn early-onset sepsis (Photo courtesy of Shutterstock)

Because of this physiological spike, elevated CRP values early in life may not signal infection in term newborns and can lead to unnecessary antibiotic exposure. In contrast, CRP proved far more reliable in preterm infants. A cutoff above 8.0 mg/L after four hours of life identified infection with strong diagnostic performance among babies born before 34 weeks. For early-onset meningitis, a CRP level greater than 12.0 mg/L showed high specificity and strong negative predictive value, helping rule out disease.

The findings emphasize that CRP should not be interpreted using a universal cutoff for all newborns. Instead, clinicians must account for gestational age, timing of sampling, and the expected physiological rise after birth. Used selectively—especially in preterm infants—CRP can provide meaningful support in EOS screening and help guide when to pursue further testing for meningitis.

“Ours is the first population-based study to evaluate how well CRP testing can identify EOS in newborns, highlighting the fluctuations of CRP levels in a real-world setting,” said Prof. Hugh Simon Lam, who led the research team. “Although CRP isn’t a perfect biomarker for EOS detection, it can still help assess infection risk in preterm babies and guide clinicians on whether further testing for meningitis is needed.”

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The Chinese University of Hong Kong