Characterisation of the blood cell response in neonatal sepsis

Thesis

Neonatal sepsis remains a major cause of mortality and morbidity, particularly in neonates admitted to Neonatal Intensive Care Units (NICUs). The current gold standard for diagnosis is a positive blood culture, which is limited by its low sensitivity and slow turnaround time. There remains a need for a rapid diagnostic tool capable of early detection of neonates at risk of developing neonatal sepsis. This thesis investigates the diagnostic utility of the complete blood count (CBC) for neonatal sepsis, with a focus on late-onset sepsis. The main hypothesis was that specific CBC parameters, alone or in combination, could identify neonates with sepsis, and that multivariable diagnostic models would achieve sufficient accuracy to support clinical decision-making. A systematic review and meta-analysis assessing the current evidence found that, while some parameters demonstrated moderate potential, the evidence base was limited and yielded inconsistent results, highlighting the need for further investigation. To explore this, CBC results from neonates admitted to the John Radcliffe Hospital NICU were analysed, classified based on clinical and laboratory signs of sepsis. Comparisons between septic and control neonates revealed that several parameters had strong diagnostic potential, including novel immune activation markers. Building upon these findings, I developed multivariable models that performed well across training, internal testing, and external validation cohorts. In longitudinal case studies, these models detected infections earlier than C-reactive protein and remained elevated throughout infection. In conclusion, this work demonstrates that the neonatal CBC offers clinically valuable information for sepsis diagnosis. Individual parameters showed strong diagnostic potential, while multivariable models were highly accurate and generalisable. Although additional validation in larger, multicentre cohorts is necessary before clinical implementation, these findings suggest that the CBC, a widely available and inexpensive test, is a reliable diagnostic tool for neonatal sepsis.

Authors: Hyde, E

• DOI: 10.5287/ora-z6oqdvyjb
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: late-onset neonatal sepsis; neonatology; diagnostic models; haematology; neonatal sepsis
• Subjects: Neonatal hematology; Septicemia