Serial Neutrophil Values Facilitate Predicting the Absence of Neonatal Early-Onset Sepsis

Objective To validate established neonatal neutrophil reference ranges (RRs) and determine the utility of serial measurements of neutrophil values in the first 24 hours to predict the absence of neonatal early-onset sepsis (EOS). Study design Retrospective study of 2073 admissions to the neonatal intensive care unit (2009-2011). Neonates were classified as blood culture-positive, proven EOS (n = 9), blood culture-negative but clinically suspect EOS (n = 292), and not infected (n = 1292). Neutrophil values from 745 not-infected neonates without perinatal complications were selected to validate RR distributions. Positive and negative predictive values were calculated; area under receiver operating characteristic curves (AUCs) were constructed to predict the presence or absence of EOS. Neutrophil value scores were established to determine whether serial neutrophil values predict the absence of EOS. Results Seventy-seven percent of admissions to the neonatal intensive care unit were evaluated for EOS: 9 (0.56%) had proven EOS with positive blood culture <= 37 hours; 18% had clinically suspect EOS. Neutropenia occurred in preterm neonates, and nonspecific neutrophilia was common in uninfected neonates. The distribution of neutrophil values differed significantly between study groups. The specificity for absolute total immature neutrophils and immature to total neutrophil proportions was 91% and 94%, respectively, with negative predictive value of 99% for proven and 78% for proven plus suspect EOS. Absolute total immature neutrophils and immature to total neutrophil proportions had the best predictability for EOS >6 hours postnatal with an AUC similar to 0.8. Neutrophil value scores predicted the absence of EOS with AUC of 0.9 and 0.81 for proven and proven plus suspect EOS, respectively. Conclusion Age-dependent neutrophil RRs remain valid. Serial neutrophil values at 0, 12, and 24 hours plus blood culture and clinical evaluation can be used to discontinue antimicrobial therapy at 36-48 hours.