Investigation of molecular and physiological early warning signals: towards the precision diagnosis of maternal sepsis

Sharma, Simran 2024. Investigation of molecular and physiological early warning signals: towards the precision diagnosis of maternal sepsis. MD Thesis, Cardiff University. Item availability restricted.

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Abstract

Background Immunometabolic changes that transpire during pregnancy in some way parallel the body’s response to infection. For example neutrophils go up in pregnancy and infection. This similarity complicates the diagnosis of maternal sepsis, a severe syndrome defined as a maladapted response to infection. Currently, maternal sepsis is poorly managed, with underand over-diagnosis being common. However, our understanding of immunology means there are likely to be specific immunometabolic signatures in the bloodstream that can be used as biomarkers to augment the early detection and clinical management of maternal sepsis. A more timely and accurate diagnosis will lead to better clinical management and outcomes for patients. Results Initially a PRISMA approach was used to write a systemic review of the literature on immunology in pregnancy – which was rewritten into a review (1), which encompassed the similarities between sepsis and infection – postulating that pregnancy provides an immunometabolic stepping-stone to sepsis. This work enabled myself and colleagues to establish an observational cohort study (2) to identify new biomarkers for maternal sepsis and development of a virtual reality training tool for students and staff (3). A key clinical biomarker identified was a sustained temperature >37.5C (ROC Area under the curve = 0.802). Through whole blood RNA-sequencing a few genes were identified to show a differentiation between labour and sepsis (chorioamnionitis) eg atosa. Through this work it was also established that sepsis recognition amongst clinicians is poor and therefore a virtual reality simulation training tool was created and tested. This was shown to increase confidence in recognition of sepsis amongst medical students. Discussion Overall this thesis demonstrated that improving maternal sepsis diagnosis and treatment requires better knowledge of maternal immune system and use of precise biomarkers. Maternal immune system acts as a stepping-stone to sepsis and some novel genes and proteins may lead the way in better diagnosis.

Item Type:	Thesis (MD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Medicine
Date of First Compliant Deposit:	10 October 2025
Last Modified:	10 Oct 2025 10:05
URI:	https://orca.cardiff.ac.uk/id/eprint/181495

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