Ledwozyw, A; (2016) Maternal cardiovascular and immune regulatory factors before the onset of pre-eclampsia. Doctoral thesis , UCL (University College London).

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Abstract

Pre-eclampsia is a pregnancy syndrome characterised by maternal hypertension and proteinuria and often associated with multi-organ dysfunction and fetal growth restriction. The aetiology of pre-eclampsia remains elusive, so a clearer understanding of the pathophysiology leading to the clinical syndrome would improve our ability to predict, prevent and treat this condition. Pre-eclampsia is known to be associated with impaired utero-placental blood flow, maternal endothelial dysfunction and an exaggerated systemic inflammatory response. Women at risk of pre-eclampsia have classical cardiovascular risk factors, including obesity and chronic hypertension. Surprisingly, smoking during pregnancy has a protective effect against pre-eclampsia. The reason behind this paradox is unknown. This thesis prospectively examines the sequence of changes in blood pressure, angiogenic and regulatory immune factors in a cohort of pregnant women recruited early in pregnancy and followed until childbirth. Pregnant women were assigned to three groups: low risk of pre-eclampsia, high risk of pre-eclampsia, or women who continued to smoke through pregnancy. Differences in prospectively determined immune-regulatory and angiogenic factors between groups were correlated with maternal blood pressure before the onset of pre-eclampsia, fetal growth restriction and pregnancy induced hypertension. Smokers were included to determine how they might be protected from developing pre-eclampsia, but vulnerable to fetal growth restriction. Results provide further insight into the pathogenesis of pre-eclampsia and a novel algorithm to identify women at risk of pre-eclampsia. Attempts to identify a putative angiotensin II receptor stimulating autoantibody are also described. Taken together, this thesis aims to enhance the understanding of the multiple pathological pathways leading to pre-eclampsia, in order to find novel pathways to improve the clinical outcome for mother and baby.

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