Current Research in Fetal Doppler Ultrasound

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Terry DuBose, M.S., RDMS, FAIUM, FSDMS: “I’m with Kevin Harrington, and he’s going to tell us a little bit about new research in Doppler in the fetus.”

Kevin Harrington: “Good morning, I’m Kevin Harrington from the Academic Department of St. Bartholomew’s in the Royal London School of Medicine and Dentistry based at the Homerton Hospital in London, UK. There are two topics I’d like to talk about this morning, one is the use of uterine artery Doppler for the prediction of women at increased risk of placental problems like preeclampsia, intrauterine growth problems, growth restriction, growth retarded babies, and early delivery from these complications. The second part relates to the use of Doppler ultrasound and the fetal circulation to get a much closer view of what’s actually happening to the compromised fetus in utero and really looking at the future potential for that technology. 

The uterine artery story goes back about fifteen years when the realization that women with preeclampsia had reduced flow, actually uterine circulation. Doppler ultrasound could identify these pregnancies by showing the high resistance to flow and actual low flow in the uterine circulation in women with preeclampsia. That initial work led to some screening studies in the eighties. There were problems with those studies in that people used different timings during the pregnancy to investigate the circulation, they used different areas of the circulation, and they looked for different things such as looking for hypertension rather than just preeclampsia. By the late eighties they tested four hundred and some disrepute because people couldn’t reproduce the initial encouraging results. Two things changed in the nineties, one – we began to re-evaluate what our definition of an abnormal waveform was, and we began to appreciate the importance of the waveform shape, in particular, the presence of a dicrotic or early diastolic notch. 

The second big advance was color Doppler ultrasounds. With color Doppler ultrasound, we could identify the uterine artery more accurately and that led to improved reproducibility. When we combine that, we’re looking at the notch in the waveform, we began to get reproducible and encouraging results. By the mid-nineties, we began to realize that the real advantage was looking at women where the uterine circulation failed to modify in either uterine artery. Just going back to a simple bit of anatomy, you have a uterine artery that comes in through the right side and you have a uterine artery that comes in from the left side. If either of those uterine arteries develops a normal high flow, low resistance circulation during the pregnancy and, therefore, if the process of the pregnancy, the hormones, and the classification leads you to at least one vessel that modifies appropriately, then you’re low risk for developing the kind of serious placental-type complications you can get in the second half of pregnancy such as preeclampsia and IUGR. 

If you have both your uterine arteries remain high resistance into the second half of your pregnancy - the group that we call bilateral notches - where there is a high resistance waveform in the right uterine artery and in the left uterine artery, we’ve now discovered that that group of women is probably our highest risk group of women for developing perinatal complications. Over half of these women will go on to develop a perinatal complication, and depending on the prevalence of preeclampsia in the community, anything from 15%-35% will go on to develop preeclampsia. Most importantly is that women with bilateral notches pose the highest risk of ending up developing these complications before term, and that is where most of the risks of the fetus lies. The dilemma for the obstetrician is when these complications develop early because you want to prolong the pregnancy as long as possible in the interest of the baby but you don’t wish to compromise the mother unnecessarily. To buy a little time, you gamble to an extent. At term, if you get these complications, the decision is a lot easier - you deliver the baby. In terms of improving the outcome for this group of pregnancies, the first step is to find the highest risk group, and that is those women that will develop these complications early. The second step is to try to identify ways of improving the outcome through better surveillance and, hopefully, finding effective prophylactic therapies. We’ve reached the first step along that road which is we’ve identified a means of selecting these high-risk women. 

Hopefully, now that we have this tool, the next step will be to make sure that we can improve the outcome. The first step had to be to identify them because with any potential therapy you have to feel justified in applying it, therefore, you have to have a relatively good predictive value and you have to have a relatively high percentage of women who are actually going to get the complication. That forms the new developed Doppler ultrasound in terms of how we use the uterine circulation for the purpose of screening. Again, one of the great advantages of using Doppler ultrasound is that it allows us to gain a window or an insight into what happens to fetal hemodynamics during pregnancy. We know that the fetus and its circulation act in very similar ways to the adult or the child’s circulation. Prior to the introduction of Doppler ultrasound, what we didn’t have was a means of actually observing what happened to the fetus and how it coped with, say, anemia or hypoxia - lack of oxygen - or when it became asphyxiated with acidemia. How does a baby cope? Prior to the introduction of Doppler ultrasound, we had the fetal heart rate trace. The fetal heart rate trace is useful for telling you at any stage test that the baby’s about to die, that its heart and its brain are on their last legs, and really there’s not much time left - this baby’s going to die. Prior to the introduction of Doppler ultrasound, we didn’t have a lot more. We may have been able to look at the amniotic fluid but really the decision to deliver was often taken on the basis of knowing that the baby was not going to live if we didn’t deliver immediately. Doppler ultrasound, especially since the introduction of color Doppler, again, allows us accurate placement and accurate identification of the various fetal vessels, and it has allowed us to build up a picture of what the fetus does and how it copes in these circumstances. 

I think it’s important that when we talk about fetal Doppler here we’re not talking about umbilical artery Doppler. Umbilical artery Doppler primarily tells you about how the placenta is functioning, it doesn’t tell you precisely how the fetus is coping. Clearly when there’s elevated resistance in the umbilical arterial circulation, it’s not unsurprising that you often find a fetus that has had to make adaptation but the adaptation isn’t always directly correlated with changes in the umbilical artery. So really for us to be fetal physicians, we need to be able to look into the fetus and see how the fetus is coping because at the end of the day that’s what we want to deliver in good condition, not the placenta. The fetal circulation has allowed us to identify and confirm that the fetus undergoes the brain spurring effect just in the way that animal studies suggested it might. Essentially what happens to a fetus that’s deprived of oxygen and nutrients is that it reduces its growth velocity. So the first sign of a baby that’s getting into trouble or a fetus that’s getting into trouble is that it reduces its growth velocity. That reduction in growth velocity may not immediately lead it to being terribly small but if you’re watching with serial ultrasound scans; you can see a fall off in growth. The next step that happens if there’s insufficient oxygen coming from the placenta to supply the entire fetus, it would simply open up its circulation and ensure the brain remains well oxygenated, and it would start to sacrifice the good oxygenation of the rest of the body. If that fails to be adequate, the next step will be to actually shut down the peripheral circulation. By shutting down the peripheral circulation, it will try to encourage every ounce of fresh blood coming back from the placenta to go the fetal brain, the fetal heart, and the fetal adrenal glands. Eventually, if that strain continues, we will start to see changes in the venous site of the circulation, which is really a reflection of the heart beginning to fail. It’s at that point that we start to see the kind of fetal heart rate changes that we typically associate with a need to deliver.

By combining our understanding of changes in growth, fetal heart rate patterns, and Doppler ultrasound of the fetal circulation, we have now built a picture over time of how a fetus will cope and the steps it will take to adapt to cope and remain alive in utero despite the fact that there’s adverse conditions present. Now that we’ve achieved that, the next step is to try and identify using this technology when the best time to deliver the fetus will be. That’s likely to be dependent on a number of factors, especially the gestational age of the fetus and the size of the fetus. It is unlikely that we will be able to have a perfect test for every gestational age and for every size of fetus because, again, how you manage a pregnancy at thirty-six weeks is very different to how you manage a pregnancy at twenty-six weeks. But what this new technology and this new understanding does is it holds out the hope of being able in the future to be much more accurate about the condition of the fetus. With the relevant information from randomized studies, we’ll be able to confirm that this is the best time to deliver this baby because this baby will no longer benefit and we have the evidence. Again, the first step along this path was to identify what actually happened - the sequence of changes over time. The next step is to try and apply this as part of randomized management studies so that we can actually determine what is the best way to deliver, and what is the best time to deliver a baby at different gestational ages and different sizes. Prior to the introduction of this technology, we were left - and many places in the world still are - with simply waiting for the baby to be on its last legs and then to rush in and deliver. The future holds the prospect of us being able to be far more accurate and far more efficient in the way we manage these compromised babies.”

Terry DuBose, M.S., RDMS, FAIUM, FSDMS: “It’s really great research and exciting. I can see all kinds of benefits from it. Do you have a gut feeling as far as the uterine arteries whether this is a failure of dilatation due to hormones available or is it a counteracting effect of some other process?”

Kevin Harrington: “When I started doing uterine artery Doppler, we didn’t really know what or how it happened, whether you actually got these high resistance waveforms with the disease or whether they were always there. One of the projects we undertook was to actually look at pregnancies right from the beginning, from non-pregnancy all the way through. What became clear was that this is primarily a failure of the process of pregnancy to make the adaptive changes that you would expect. So you’re left with a waveform, and you’re left with flow that is more typical of the non-pregnant than the pregnant state. In other words, the uterine artery, the maternal circulation, and the placental bed don’t change in the way that you would expect. So the bilateral notching represents a failure of the system of the process of pregnancy to make the adaptive changes. It is that failure to make the adaptive changes that signals the high-risk nature of the case.”

Terry DuBose, M.S., RDMS, FAIUM, FSDMS: “Great, really good, Kevin. I appreciate it. This is Terry DuBose and we’ve been talking to Kevin Harrington at the Edinburgh 8th World Congress of the International Society of Ultrasound and Obstetrics in Gynecology. Thank you very much.”

Kevin Harrington: “Thank you.”