Preconception and early pregnancy maternal haemodynamic changes in healthy women in relation to pregnancy viability.
Are there differences in preconception cardiovascular function between women who have a viable pregnancy and those who have a first trimester miscarriage?



Preconception cardiovascular function of central haemodynamics and arterial function are similar between women who have a viable pregnancy and those who have a first trimester miscarriage.



Miscarriages have been associated with increased long-term cardiovascular disease risk, and arterial and cardiovascular dysfunction has been hypothesised as the common link. It is not known if these risks are present prior to pregnancy or are a reflection of poor arterial and haemodynamic adaptation to pregnancy.



This prospective longitudinal preconception cohort study was conducted over 18 months. In total, 367 participants were recruited pre-pregnancy, from which 197 pregnancies were recorded; 39 of these pregnancies ended in first trimester miscarriage. Complete longitudinal data were available for 172 pregnancies (140 viable pregnancies, 32 first trimester miscarriages) from pre-pregnancy to 6 weeks gestation.



This was a single site study based at a maternity hospital in London. Healthy women were recruited prior to natural conception and followed up once they became pregnant. All underwent haemodynamic [cardiac output (CO), peripheral vascular resistance (PVR)] and arterial function [aortic augmentation index (AIx) and pulse wave velocity (PWV)] testing prior to pregnancy and at 6 weeks gestation, using non-invasive devices (gas re-breathing method, Innocor® and an occilometric device, Vicorder®). Cross-sectional measurements at pre-pregnancy and 6 weeks gestation and a longitudinal analysis of changes were compared between women who had a subsequent viable pregnancy, and those who had a subsequent first trimester miscarriage.



There were no differences between women destined to have a healthy ongoing pregnancy compared to those who miscarried, in terms of baseline cardiovascular function, assessed by CO, PVR, PWV or AIx. Similarly, between the groups, there were no differences in pregnancy adaptation with similar trends in cardiovascular function changes from pre-pregnancy to 6 weeks gestation.



Whilst this is the first study to investigate preconception and early pregnancy haemodynamic and arterial function in relation to viability, the relatively modest number of miscarriages may not be sufficient to show subtle differences in haemodynamic changes if these were present.



This study suggests that pre-pregnancy haemodynamic and arterial function is unlikely to be the causal link between miscarriages and future cardiovascular disease. Our findings suggests that factors other than the presence of a viable embryo drive cardiovascular changes in early pregnancy. This study raises new questions about miscarriages as an independent risk event which predisposes women to increased cardiovascular risk later in life.



The investigators are funded by NIHR Imperial BRC, NIHR Cambridge BRC, Action Medical Research, Imperial College Healthcare Charity and Tommy's Charity. We acknowledge the loan of ultrasound equipment from Samsung Medison (South Korea)/MIS Ltd and provision of fertility monitors from SPD Development Company Ltd (Bedford, UK). There are no competing interests. C.C.L. is supported by the UK National Institute for Health Research Biomedical Research Centre based at Imperial College Healthcare National Health Service Trust and Imperial College London.



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Institute for Reproductive and Developmental Biology, Imperial College London, Du Cane Road, London W12 0NN, UK.|Queen Charlotte's & Chelsea Hospital, Imperial Healthcare NHS Trust, Du Cane Road, London W12 0HS, UK.
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Foo
Queen Charlotte's & Chelsea Hospital, Imperial Healthcare NHS Trust, Du Cane Road, London W12 0HS, UK.
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Collins
Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK.
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McEniery
Institute for Reproductive and Developmental Biology, Imperial College London, Du Cane Road, London W12 0NN, UK.|Queen Charlotte's & Chelsea Hospital, Imperial Healthcare NHS Trust, Du Cane Road, London W12 0HS, UK.
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Bennett
Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK.
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Wilkinson
Institute for Reproductive and Developmental Biology, Imperial College London, Du Cane Road, London W12 0NN, UK.|Queen Charlotte's & Chelsea Hospital, Imperial Healthcare NHS Trust, Du Cane Road, London W12 0HS, UK.|Department of Development and Regeneration, KU Leuven, Belgium.
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Lees
D000022:Abortion, Spontaneous / Q000503:physiopathology*; D000328:Adult; D001794:Blood Pressure / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D012307:Risk Factors; D016387:Women's Health
cardiovascular; first trimester loss; maternal; miscarriage; preconception