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Pregnancy-specific reference intervals for infection markers : unblurring the limits of normality
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Dockree, Samuel (2022) Pregnancy-specific reference intervals for infection markers : unblurring the limits of normality. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3883984
Abstract
Background Maternal sepsis is a major global cause of maternal death, and bacterial infections in pregnancy are responsible for a huge proportion of maternal and neonatal adverse outcomes. A lot of time and resources are dedicated to investigating suspected infection in pregnancy and around the time of delivery, and blood tests are ubiquitously used in UK obstetric practice to objectively investigate the likelihood and severity of disease. However, it is poorly understood how infection/inflammatory markers behave in preg- nancy, and how (or whether) they should be interpreted to inform clinical decisions.
Methods Over the course of three years, I have authored a series of peer-reviewed articles, letters and conference abstracts, as part of an active working group. We have defined 95% reference intervals (RIs) for the major infection markers used in current clinical practice: C-reactive protein (CRP), white blood cells (WBC) and its subtypes, procalcitonin (PCT) and lac- tate. In several cases we have evaluated these new reference limits in other cohorts to investigate their added value for improving diagnostic accuracy in pregnancy.
Results The 95% RI for CRP is substantially and consistently elevated from the first trimester of pregnancy, and using this upper reference limit (19 mg/L) rather than that which is currently recommended (7 mg/L) confers a sig- nificant improvement in the overall diagnostic accuracy for chorioamnionitis. WBC are also elevated from early in pregnancy (5.7-15.0 x109/L), with subtype-specific changes in the differential counts. Both CRP and WBC are so dramatically and unpredictably elevated in labour and the postnatal period that they cannot reliably be interpreted to investigate in- fection and, while lactate in pregnancy is similar to non-pregnant women (<2 mmol/L), a much higher limit should be used to investigate the sever- ity of sepsis in labour (4 mmol/L). In contrast, levels of PCT are stable throughout pregnancy, and the existing upper limit (0.25 ng/mL) is valid throughout labour and the puerperium.
Discussion These publications constitute a substantial body of novel evidence in the field of obstetrics. Some of this may be applied directly to influence policy and clinical practice, while other findings may form the basis of important future research. By drawing reference to these publications and associated works, I present this thesis as an investigation of how we must re-evaluate our clinical practices to improve diagnostic accuracy and prevent morbid- ity and mortality from infections in pregnancy.
Item Type: | Thesis (PhD) | ||||
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Subjects: | R Medicine > RB Pathology R Medicine > RC Internal medicine R Medicine > RG Gynecology and obstetrics |
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Library of Congress Subject Headings (LCSH): | Pregnancy -- Complications, Infection -- Diagnosis, Septic abortion, Biochemical markers | ||||
Official Date: | September 2022 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Randeva, Harpal S. | ||||
Format of File: | |||||
Extent: | 41 pages | ||||
Language: | eng |
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