nSeP: immune and metabolic biomarkers for early detection of neonatal sepsis-protocol for a prospective multicohort study.

INTRODUCTION: Diagnosing neonatal sepsis is heavily dependent on clinical phenotyping as culture-positive body fluid has poor sensitivity, and existing blood biomarkers have poor specificity.A combination of machine learning, statistical and deep pathway biology analyses led to the identification of a tripartite panel of biologically connected immune and metabolic markers that showed greater than 99% accuracy for detecting bacterial infection with 100% sensitivity. The cohort study described here is designed as a large-scale clinical validation of this previous work. METHODS AND ANALYSIS: This multicentre observational study will prospectively recruit a total of 1445 newborn infants (all gestations)-1084 with suspected early-or late-onset sepsis, and 361 controls-over 4 years. A small volume of whole blood will be collected from infants with suspected sepsis at the time of presentation. This sample will be used for integrated transcriptomic, lipidomic and targeted proteomics profiling. In addition, a subset of samples will be subjected to cellular phenotype and proteomic analyses. A second sample from the same patient will be collected at 24 hours, with an opportunistic sampling for stool culture. For control infants, only one set of blood and stool sample will be collected to coincide with clinical blood sampling. Along with detailed clinical information, blood and stool samples will be analysed and the information will be used to identify and validate the efficacy of immune-metabolic networks in the diagnosis of bacterial neonatal sepsis and to identify new host biomarkers for viral sepsis. ETHICS AND DISSEMINATION: The study has received research ethics committee approval from the Wales Research Ethics Committee 2 (reference 19/WA/0008) and operational approval from Health and Care Research Wales. Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites. TRIAL REGISTRATION NUMBER: NCT03777670.

Screening for early onset neonatal sepsis: NICE guidance-based practice versus projected application of the Kaiser Permanente sepsis risk calculator in the UK population.

OBJECTIVE: To compare management recommendations of the National Institute for Health and Care Excellence (NICE) guidelines with the Kaiser Permanente sepsis risk calculator (SRC) for risk of early onset neonatal sepsis (EONS). DESIGN: Multicentre prospective observational projection study. SETTING: Eight maternity hospitals in Wales, UK. PATIENTS: All live births ≥34 weeks gestation over a 3-month period (February-April 2018). METHODS: Demographics, maternal and infant risk factors, infant's clinical status, antibiotic usage and blood culture results from first 72 hours of birth were collected. Infants were managed using NICE recommendations and decisions compared with that projected by SRC. MAIN OUTCOME MEASURE: Proportion of infants recommended for antibiotics on either tool. RESULTS: Of 4992 eligible infants, complete data were available for 3593 (71.9%). Of these, 576 (16%) were started on antibiotics as per NICE recommendations compared with 156 (4.3%) projected by the SRC, a relative reduction of 74%. Of the 426 infants avoiding antibiotics, SRC assigned 314 (54.6%) to normal care only. There were seven positive blood cultures-three infants were recommended antibiotics by both, three were not identified in the asymptomatic stage by either; one was a contaminant. No EONS-related readmission was reported. CONCLUSION: The judicious adoption of SRC in UK clinical practice for screening and management of EONS could potentially reduce interventions and antibiotic usage in three out of four term or near-term infants and promote earlier discharge from hospital in >50%. We did not identify any EONS case missed by SRC when compared with NICE. These results have significant implications for healthcare resources.