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Title: A prospective longitudinal study of maternal cardiovascular function from pre-conception to post-partum : the CONCEIVE Study
Author: Foo, Fung Lin
ISNI:       0000 0004 8499 5796
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Pre-eclampsia (PE) and fetal growth restriction (FGR) confer higher risk of later life maternal cardiovascular disease. It is unclear whether pre-existing inert cardiovascular dysfunction manifests as PE/FGR during pregnancy, or whether PE/FGR attribute an independent risk that augments cardiovascular disease with age. To clarify, subjects should be studied pre-conception, providing cardiovascular observations that are independent of pregnancy- or disease induced physiological changes. A pilot study (IMPOST) demonstrated the feasibility of investigating pre-conception cardiovascular function. CONCEIVE, on which this thesis is based, follows a similar protocol, but is powered to detect differences in cardiac output, reportedly abnormal in PE/FGR pregnancies102-104, 110. Protocol additions of ovulation/implantation tracking provided an opportunity to observe peri-conceptional events with spontaneous conceptions. Further, pre-pregnancy exercise stress-testing, hypothesised to mimic the physiological stress of pregnancy, was performed. The primary objective was to assess associations between pre-pregnancy cardiovascular function and PE/FGR in subsequent pregnancy. Secondary objectives were to investigate longitudinal trajectories of cardiovascular function and exercise testing in relation to PE/FGR, and peri-conceptional hormonal changes in relation to pregnancy viability. 387 healthy participants were recruited into the study. Cardiovascular assessments were performed pre-conception, through pregnancy (6, 10, 22 and 34 gestational weeks) and post-partum. Early pregnancy hormonal changes were tracked with a digital fertility monitor. Outcomes of unaffected pregnancy, PE/FGR and pregnancy loss were recorded and correlated to study parameters. There were significant differences in pre-pregnancy haemodynamics, with a low-output/high-resistance state associated with PE/FGR in next pregnancy. Subjects who developed PE/FGR had significantly different responses to pre-pregnancy exercise testing. An optimal ovulation-implantation window is associated with first trimester viability, and early differences in hCG rise can distinguish between pregnancy viability outcomes. The study concludes that cardiovascular dysfunction prior to pregnancy is associated with risks of developing PE/FGR in a subsequent pregnancy. Larger prospective studies of this nature may facilitate identifying women at risk, and providing intervention to alter maternal haemodynamics to improve pregnancy outcomes, at a pre-clinical stage.
Supervisor: Lees, Christoph ; Bennett, Phillip Sponsor: Imperial College London ; Action Medical Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral