Inflammatory biomarkers and physiomarkers of late-onset sepsis and necrotizing enterocolitis in premature infants.

Background: Early diagnosis of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in very low birth weight (VLBW, <1,500 g) infants is challenging due to non-specific clinical signs. Inflammatory biomarkers increase in response to infection, but non-infectious conditions also cause inflammation. Cardiorespiratory data contain physiological biomarkers, or physiomarkers, of sepsis that may be useful in combination with inflammatory hematologic biomarkers for sepsis diagnosis. Objectives: To determine whether inflammatory biomarkers measured at the time of LOS or NEC diagnosis differ from times without infection and whether biomarkers correlate with cardiorespiratory sepsis physiomarkers in VLBW infants. Methods: Remnant plasma sample collection from VLBW infants occurred with blood draws for routine laboratory testing and suspected sepsis. We analyzed 11 inflammatory biomarkers and a pulse oximetry sepsis warning score (POWS). We compared biomarker levels obtained at the time of gram-negative (GN) bacteremia or NEC, gram-positive (GP) bacteremia, negative blood cultures, and no suspected infection. Results: We analyzed 188 samples in 54 VLBW infants. Several biomarkers were increased at the time of GN LOS or NEC diagnosis compared with all other samples. POWS was higher in patients with LOS and correlated with five biomarkers. IL-6 had 78% specificity at 100% sensitivity to detect GN LOS or NEC and added information to POWS. Conclusions: Inflammatory plasma biomarkers discriminate sepsis due to GN bacteremia or NEC and correlate with cardiorespiratory physiomarkers.

Inflammatory Biomarkers and Physiomarkers of Late-Onset Sepsis and Necrotizing Enterocolitis in Premature Infants.

Background: Early diagnosis of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in VLBW (<1500g) infants is challenging due to non-specific clinical signs. Inflammatory biomarkers increase in response to infection, but non-infectious conditions also cause inflammation in premature infants. Physiomarkers of sepsis exist in cardiorespiratory data and may be useful in combination with biomarkers for early diagnosis. Objectives: To determine whether inflammatory biomarkers at LOS or NEC diagnosis differ from times without infection, and whether biomarkers correlate with a cardiorespiratory physiomarker score. Methods: We collected remnant plasma samples and clinical data from VLBW infants. Sample collection occurred with blood draws for routine laboratory testing and blood draws for suspected sepsis. We analyzed 11 inflammatory biomarkers and a continuous cardiorespiratory monitoring (POWS) score. We compared biomarkers at gram-negative (GN) bacteremia or NEC, gram-positive (GP) bacteremia, negative blood cultures, and routine samples. Results: We analyzed 188 samples in 54 VLBW infants. Biomarker levels varied widely, even at routine laboratory testing. Several biomarkers were increased at the time of GN LOS or NEC diagnosis compared with all other samples. POWS was higher in patients with LOS and correlated with five biomarkers. IL-6 had 78% specificity at 100% sensitivity to detect GN LOS or NEC and added information to POWS (AUC POWS = 0.610, POWS + IL-6 = 0.680). Conclusions: Inflammatory biomarkers discriminate sepsis due to GN bacteremia or NEC and correlate with cardiorespiratory physiomarkers. Baseline biomarkers did not differ from times of GP bacteremia diagnosis or negative blood cultures.