 Hi, good evening. My name is Amy Humphries and I'm a medical student working up with the Departments of Anatomy and Medical Imaging and Obstetrics and Gynecology. And it's an absolute pleasure for me to present my work on the effect of physician on maternal hemodynamics, which is basically a fancy way of saying how blood flows around the body in late pregnancy. And I'd just like to start off by thanking my supervisors, Professor Peter Stone and Dr. Arlie Merjolele, for being fantastic supervisors. So I'm looking at this in relation to late stillbirth, which is defined as intrauterine death after 28 weeks gestation, which as you can imagine, for expecting parents only months away from welcoming their little baby girl or little baby boy into the world, this is a hugely devastating outcome. And it still occurs in around two to five per thousand births, even in high income countries, making it a significant obstetrics problem. Now the Auckland stillbirth study in 2011 was the first of its kind to show that maternal sleep position had a significant role in increasing the risk of late stillbirth. And this was later backed up by the Sydney stillbirth study in 2015, and a large study coming out of the UK this year. And what all of these studies have shown is that women who sleep in a supine position, that is lying on their back in late pregnancy, have a significantly increased risk for late stillbirth. And this is thought to come into play as part of a triple risk model, where you may have a mother at increased risk of stillbirth already, a fetus in an already compromised situation, and throw into the mix an acute fetal stressor, in this case maternal sleep position, and this may act as the tipping point resulting in stillbirth. And one of the proposed mechanisms behind this association is thought to be that when a woman in her third trimester lies on her back, the graved uterus acutely obstructs her inferior vena cava, which is the large vein returning blood back to the heart. This acute obstruction is thought to be compensated for by an adequate collateral venous system, providing an alternative route for blood to return back to the heart. And this therefore enables them to maintain their blood pressure at a normal level. However, we speculate that women with inadequate collateral venous drainage, potentially due to anatomical variations in this system, may have a reduced ability to compensate for this, and therefore may drop their blood pressure in the supine position. And this is seen clinically as supine hypotensive syndrome, which is where a woman feels faint or dizzy or may even lose consciousness when lying on her back, and occurs in around 8-10% of women in their third trimester. And we speculate whether women in this category may be at a further increased risk of late stillbirth due to this acting as that fetal stressor. Now these are a couple of MRI images taken in an axial plane, so if you imagine it's been cut right through the middle, of a woman in her third trimester. We have the graved uterus here with the fetus in sight, as you can see the abdomen here with the legs. And we've got the inferior vena cava and the aorta sitting just on top of the vertebral column here. Now in the left lateral position the RBC is completely patent. However when the woman turns supine, it becomes quite dramatically compressed. And in this scenario it's thought that a system of veins called the azogus system provides a collateral pathway from the pelvis back to the thorax. And I know this picture looks a little scary, but this is the inferior vena cava coming here, and it splits into the common iliac veins further down in the pelvis. This gives off the ascending lumbar vein, which travels up beside the vertebral column to join with the subcostal vein at the level of the diaphragm. This forms the hemiazogus vein on the left hand side and the azogus vein on the right hand side. And this hemiazogus along with its accessory hemiazogus eventually drained back into this main azogus vein, which drains back to the supere vena cava and therefore the heart, creating a nice collateral pathway from the pelvis back to the thorax. Now the following image I'm going to show is of a cadaver or a person who's donated their body to science, in which I've dissected out the system. So just to orientate you, the head is up this direction, the legs are down this direction, and we're looking at the vertebral column from a slightly left hand view. To make it easier the RBC has been reflected off to the right here and splits into the common iliac veins in the pelvis. The ascending lumbar vein travels up beside the vertebral column to join with the subcostal vein at the level of the diaphragm. Because we're looking at the left hand side, this forms the hemiazogus vein, which drains back into that main azogus vein, which then will drain back to the heart. So as you can appreciate, a nice alternative pathway from the pelvis back to the thorax. However, this system of veins has never been studied before in pregnancy. So the aim of our study was to investigate the effect of the supine and left lateral positions on maternal blood flow in late pregnancy using MRI. We obtained ethics approval to recruit healthy pregnant women and we used a 3T MRI scanner to scan them in the supine and left lateral positions. We took axial phase contrast images at the level of the aortic root and images of the azogus vein at a similar level just before it joined to that superior vena cava. We also took images of the abdominal aorta and the IVC just above the level of the renal veins and just above the aortic bifurcation. And we analyzed these images using a software called SINGOVIA, which allowed us to calculate net forward volume through a specified region of interest, in this case the ascending aorta as it comes off the ventricle. And we combined this with heart rate to calculate cardiac output, which is a measure of how much blood is pumped around the body per minute and blood flow through the azogus aorta and IVC. So we recruited 12 pregnant women without supine hypertensive syndrome and these women had a gestational age between 34 and 38 weeks, so in that third trimester. All of these women had a normal pre-pregnancy BMI with an average of 23.3 and went on to have normal pregnancy outcomes. So what we found was that blood flow reduced significantly in the supine position through the IVC by 43.5% at the level of the renal veins and 86.5% at the level of the IVC origin. So in keeping with that IVC compression that we've talked about. However, we also found that cardiac output reduced by 15.5% in the supine position and I'm going to talk about the significance of these results in just a moment. We found that blood flow through the azogus vein increased by 164.5%, and maternal heart rate increased by 11.7%. However, the most surprising results came when we measured the blood flow through the aorta, which reduced by 17% at the level of the renal veins and 36.6% at the level of the aortic bifurcation. Now to put all of these numbers into a bit of context, what we're seeing is that in the supine position, there is a reduction venous flow due to that IVC compression that we've talked about and that this is of the magnitude of 86.5%. This will reduce the blood flow back to the heart, therefore reducing cardiac output, which we've showed to decrease by 15.5%. Now cardiac output is directly related to the pressure within the arterial system, which will therefore also decrease. This will stimulate the maternal sympathetic nervous system to increase maternal heart rate in order to try and compensate for that drop in cardiac output, which we've showed to increase by 11.7%. Now the level of IVC obstruction and below, there will be an increase in venous pressure due to blood pooling in the extremities and unable to return back to the heart. This will force blood into the collateral venous circulation, which we've showed to increase by 164.5%, and that will serve to try and increase venous return back to the heart. However, this increase in venous pressure and a decrease in mean arterial pressure is likely to reduce driving pressure across the lower capillary beds and therefore explain the reduction in arterial blood flow that we're seeing. And this is of the magnitude of 36.6%, which is not insignificant, especially when you consider that the uterine artery, which supplies blood flow to the placenta, comes off below this point. So unless there are significant vascular resistance changes occurring across the placenta, there is likely to be a significant reduction in blood flow. This will reduce oxygen delivery to the fetus and therefore act as a significant fetal stressor. And this is important to remember that this is occurring in women who can lie on their back without experiencing any symptoms whatsoever. And if you think back to that triple risk model, while a healthy fetus may be able to tolerate these changes, an unhealthy one, this could be the tipping point. So our study is currently limited to normal pregnant women, but we have significant questions about how these results will change with women who do experience supine hypertensive syndrome. And we question whether this is potentially due to anatomical variations in that collateral venous system that I've talked about. So we're currently in the process of recruiting and scanning women with this syndrome. We also question whether these results will be different between lying on the left and the right-hand side due to normal anatomical differences between the two, with the RBC being more on the right-hand side. So again, we're currently in the process of doing this study as well. So in conclusion, the supine position causes important maternal hemodynamic changes during late pregnancy. And the azúcar system of veins has been shown for the first time to be utilised as a collateral venous pathway in order to try and compensate for this. However, despite this, we're still seeing significant reductions in maternal arterial blood flow, which has the potential to reduce placental blood flow and act as a fetal stressor. And this work, in combination with a lot of work that's being done by the Maternal Sleeping Pregnancy Research Group, is leading on to a future public health campaign to recommend women to not sleep on their back during late pregnancy. And I'd just like to quickly thank all the participants of the study for their invaluable contributions, the Maternal Sleeping Pregnancy Research Group that I've already mentioned, and the staff and technicians at the Centre for Advanced MRI and Keoghs for funding the project. Thank you very much.