| Summary: | Pre-eclampsia is a pregnancy-specific, multi-system disorder of placental origin. Affecting between 2-8% of women, it is one of the leading causes of both maternal and fetal morbidity and mortality in the United Kingdom. Although the disorder presents after 20 weeks gestation with the classic symptoms of hypertension and proteinuria, the pathological process(es) leading to this syndrome initiate early in the first trimester. In current clinical practice, prediction of those who will get the disease and those who will have a poor outcome once it develops is poor. This thesis focuses on novel ways to enhance the prediction of the development of pre-eclampsia and poor outcome once the syndrome manifests. Firstly, the current risk factors for pre-eclampsia were challenged. Racial variation in these risk factors has demonstrated the importance of considering maternal ethnicity when assessing the likelihood of developing the disease. Obese Black women were more likely to develop pre-eclampsia than obese white women (aOR 2.06 (95%CI 1.34-3.23) p=0.002). In the normal BMI group Black women were less likely to develop pre-eclampsia than White women (aOR 0.421 (95%CI 0.24-0.73) p<0.001). Younger (<20 years of age) Black women were less likely to develop pre-eclampsia than younger white women (aOR 0.628 (95%CI 0.49-0.83) p<0.001). Conversely, older (>35 years of age) Black women were more likely to develop pre-eclampsia than older White women (aOR 1.67 (95%CI 1.39-1.99) p<0.001). Secondly, first trimester maternal plasma studies have identified a cohort of potential disease (and pathophysiological) markers that may allow for the development of an early screening test for pre-eclampsia. The ratio of angiotensinogen to Kallikrein is raised in the first trimester of pregnancies that later develop pre-eclampsia (p<0.001). The receiver operator curve (ROC) for the ratio of angiotensinogen to kallikrein had an area under the curve (AUC) of 0.81 (SE=0.05). A cut-off value of >0.27 has a sensitivity of 0.9 (95% CI = 0.74 – 0.97), a specificity of 0.5 (95% CI = 0.24-0.65), positive predictive value (PPV) 0.63 (95%CI = 0.47-0.75) and negative predictive value (NPV) of 0.87 (95% CI = 0.53-0.96) in predicting the onset of preeclampsia. Common haematological and biochemical tests are presented as markers for both the development of the disease and poor outcome when it occurs. The ratio of Neutrophil to Lymphocyte (NLR) is raised in the first trimester of pregnancies that develop pre-eclampsia (p<0.001). The ROC of the ratio to Neutrophil to Lymphocyte has an AUC of 0.84 (95% CI = 0.85-0.95). A cut off value of 2.53 has a sensitivity of 0.92 (95%CI = 0.85-0.95), specificity of 0.6 (95%CI = 0.51-0.67), PPV 0.68 (95%CI = 0.6-0.74) NPV 0.87 (95%CI = 0.8-0.93) for predicting the onset of pre-eclampsia. At the time of diagnosis of pre-eclampsia, a raised NLR predicts poor maternal outcome and the need for a caesarean section due to fetal distress (p<0.05). In addition, a reduced level of bilirubin predicts both poor fetal and maternal outcome and the need for a caesarean section (p<0.05).
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