Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

Will I? Not? Good afternoon, ladies and gentlemen, my name is Doctor Dube. I'm going to be making this presentation from Zimbabwe. I'm an obstetrician and gynecologist based in Wa Zimbabwe. So this is like our second largest capital city. So today, I'm going to be taking you on uh strategies for any screening and prevention of uh of preeclampsia. II chose this topic because it's someone who works in a, in a low and middle-income country, Zimbabwe, we are actually faced with quite a burden of, of this disease and it's quite causing quite a lot of morbidity and mortality amongst our, our population. So in Zimbabwe, this is our commonest cause of morbidity and mortality in our, in our country. And I'm sure that it is more or less similar to some of our countries that we find also in Sub Saharan Africa. So informal disclosures I don't have that I need to make at the, at the moment. So the first light there is something that I picked up from from Figo, which is sort of a summary of the things that I'm going to be talking about. So this light is sort of a summary of of, of, of the challenge that this disease actually poses amongst our, our women, especially now in an African setting. So, as you would know, that is a condition that affects about 2 to 5% of our pregnant women. But the important figures are that globally, 76,000 women die each year from preeclampsia alone. And we are losing about 500,000 babies each year from, from the disease. And so certainly predicting and trying to prevent this disease. It's going to go a long way in mitigating against the morbidity and and the mortality. And I'm sure that most of you will be aware that it is associated with some major risk factors and some minor risk factors. So what are some of those, the major risk factors are someone who had the disease previously? Someone has had chronic hypertension in the past, someone with endocrine disorder such as diabetes, mellitus sine, uh acute and chronic kidney disease and the like and then the other minor risk factors that we need to be aware of as well. These include advanced maternal age parity is being your first pregnancy, a short and long interpregnancy interval and some of our women who have a family history of preeclampsia. So this is, this is how the disease is thought to be preexisting in some of our, in some of our patients. So you, you remember that is from 20 fi O actually came out with a, with a with an initiative where they presented a paper on a pragmatic guide for first trimester screening and, and prevention. In that guide. They said all countries have an obligation to implement the best preeclampsia testing and management practice that they can. And that all countries need to put greater efforts in raising awareness of the benefits of early pregnancy visits, target age age women, particularly in low resource countries. So you find out that in our, in the low resource countries, like the one I come from, we actually have quite a problem of of of antenatal visits where most of our women don't even come in the first trimester, they start to come in the second trimester, going to the third trimester when they start to have um uh fetal movements. So, but however, this pragmatic initiative I think is for all countries to be able to keep, try and reimplant to some to some extent, some may be asking why is it important to screen for preeclampsia or even to predict which woman is going to have it? I'm sure you also know that the risk of adverse outcomes for the mother and fetus is much higher with pre temporary eclampsia than with temporo eclampsia. So it is better that we need to predict the risk of a woman developing pre eclampsia more than we probably need for temporary eclampsia. Because in any case, if a woman is now term, you're probably going to deliver the woman and the baby is likely going to do better than when that baby is delivered pre premature. So identifying a woman who has got that risk factor has got that risk of developing, it becomes important and doing it so early is even more, more important. We also know that there are interventions that one can do in order to to prevent a woman from developing preeclampsia or even if she develops the disease, it is not the severest of the forms. We are going to talk about what interventions one can use. We also know that those interventions that we may we may use are likely to improve placentation and thus prevent at least or reduce the frequency of placental insufficiency. We also know that if we are to to screen and predict the disease early, we are going to ensure that there is early prenatal surveillance. So as such that we are able to recognize the onset of the clinical syndrome and manage it promptly. So it is very important that we do screen for for this disease. Uh This is just the background of the basics. I know you you are aware of how cursa is thought is thought to OK. In that it is thought for now that there are several theories and I know that currently literature, if you read the literature, there are some that are actually not consistent with this theory, but this is the the mostly recognized theory how preeclampsia is thought thought to exist. So it is thought that it is actually at the level of the placenta where there is impaired a spiral art remodeling at the level of the placenta interface between mother and the and the fetal blood vessels. Such that there is a decrease in blood flow leading to hypoxia. And is that hypoxia sets in. Now, there's a release of a lot of other other factors. Some are which are androgenic, some which are antiangiogenic. And it is thought that it is the balance between these two opposing factors that is thought to lead to to preeclampsia. So in short, you know that there will be a first stage that there'll be a second stage. And we know that the first stage is usually subclinical where there is thought to be abnormal placentation with reduced blood flow. But what I want you to to to think about really are these two most important um factors that are thought to be to be released that is spla growth factor and vascular endothelial growth factor. These are thought to be the to be the major factors that are are released at the level of the placenta interface. And when these now go back into the maternal circulation, they cause a lot of effects on the maternal circulation, including amongst other things, endothelial cell damage. This will then result in multi organ manifestation and depending on which organ is mostly affected. Some patients may present with kidney problems, some present with coagulation problems, some may present even in cerebral issues. So, preeclampsia screening really does not, it's not something that I'm talking about now, but it's something that has existed as far back as the early two thousands. But what has happened over time is that there have been a modification of, of how one screens for it. When does one start to screen and how one actually actually does it. So you see there that in 1009 with a combined first trimester prediction model by logistic recreation. And then in 2014, from America came out this, this us preventative task force that also came out with its own guidelines all the way up to 2019 where we have the Fetal Medicine Foundation triple test. That is something that was endorsed by FICO in 2019. And as far as I know right now, it is one of the best preeclampsia uh prediction models that are in existence. And these have actually been abducted by quite a number of other organizations including the EO including the nice and, and so many others. So you would see that a number of organizations or a number of colleges have actually come out with their own screening guidelines. Wh O has got its own guidelines. Rog is nice. Even the FI Medicine Foundation, the E OC, they have adopted some of their screening guidelines. So these are some of them that we are going to go through in a moment. Maybe before I do that. I think it would be very important to say what is the timing of this preeclampsia prediction and prevention. So there are two stages or there are 22 sort of 22 pathways that one can follow depending on when the woman comes for the first antenatal clinic or the visit. But ideally, it should be done in the first trimester. And most of the guidelines would say screening should be between 11 and 13 weeks so that you're able to identify women who are at higher risk where you can be able to administer prophylactic drugs that can substantially reduce the instance of preterm preeclampsia. But however, like I alluded before that sometimes in our setting low in, in, in low and middle income countries really, we have most of our population coming in the first trimester. So we missed quite a number of those, but they will come at some point during the 2nd and 3rd trimester. Should you screen? Yes, you should be able to screen. But the screening that you do now is not really for you to be able to put prophylactic drugs. But for you to identify those women who may need intensive monitoring, those women who may actually have developed preeclampsia and then you are able to, to do some form of risk reduction, either through treatment or even through, through delivery so that you, you are able to improve the perinatal outcomes and the maternal outcomes as well. I put up this slide because I think most of us may be aware of the binary scoring system. The binary scoring system has been in existence for a while now where you are basically dividing a women into high risk and into those with moderate risk. And for many, many years ago, people have always been been using this. But the problem now with this is that it misses quite a number of women and the detection rate is about 40% and it does not give you a personal, a personalized risk for the same woman. So if a woman has got previous preeclampsia and a woman with diabetes mellitus, both of them are going to be in the high risk category. But these are very, very different women with different conditions that are existence in them. But however, this scoring system is going to put them in the same category. So that's the problem that we have or that was found to be to be with this, that it is simple, but however, it missed quite a number of women. How do we use it? So you say if a woman has a high risk factor, she's already high risk in the high risk category. And you need to start preeclampsia prevention, inter interventions. However, if she has more than a risk, you need two of those for you to be able to, to start them on, on surveillance and also on, on aspirin, for example. So this system is the one I think that most of us may be familiar with. But the challenge is that it is, it is it is a very low detection detection rate. So what do we need? So we need a model that is able to increase that detection rate to something around eighties or nineties. And so the F medicine Foundation like I've alluded to before actually came up with, with a model that in my, in my view, I still feel or that I use or I still feel that it's probably the best for for us to implement in the current in the current in the current scenario. So what does it use? It doesn't use only maternal risk factors, it says over and above the maternal risk factors, you must be able to use biophysical markers and also bio biochemical markers so that you get an adjusted risk. And that, that risk is one that you are now going to to use to classify the patient. So this this model is thought really to have a higher detection rate than the binary by the binary method. So I'll come back to explain some of these later on in my talk. So it it uses a Multivariate logistic regression analysis. But in actual fact, or in a sense, it just combines the maternal risk factors. It also combined the mean arterial pressure to also combine skin findings of the uterine artery. It also has got where you are able to collaborate or to use some se markers such as PAP, a placental growth factor at 11 to 13 weeks gestation. And it is thought that it will yield a detection rate of 93% for prediction of early preeclampsia. So you see for to use this model, we're going to move our detection rate from 40% for the binary scoring system to around 93%. That is for earlier eclamp preeclampsia and then for late onset preeclampsia, it is about 36%. So it has got a superior detection rate to the traditional checklist based approach which relies on Matina factors factors only. And over the years, it has really evolved to become maybe the best model available. So these are some of the the the things that I was highlighting if you look at the the extreme left there. So when you're using maternal factors, your detection rate really will be about 53%. But look at the extreme, right? When you are using the, the the triple test where you are combining the maternal risk factors, the meter pressure, the ultrasound scan and also results of your serum markers, your detection rate goes up to to 90%. So you are probably going to miss about 10% of patients who are going to develop preterm preeclampsia. So I really think that this is a motto that we need to be implementing all of us. But the issues of how feasible this is, I'm going to discuss about them later. So this model I wanted to put up this slide to show you that it has been validated prospectively in Italy, Australian populations and in many other other different populations. So it can be applied right across the world. And almost all these validation studies have actually reported comparable predictive performances corresponding to the to the original original studies. So there are many other countries who are actually using them regardless of the population that is under consideration. So, Mina pressure, I put up this slide so that you know that in pregnancies that develop preeclampsia, the mire pressure is going to be to be increased and really that irenal pressure is more useful than just measuring the systolic and the diastolic BP. Remember we said the other component that you need is the uterine artery fertility index that we are supposed to incorporate into the module so that you increase your detection rate. I'm not going to bother you about how you're going to to do this or how this is done. But it's the ultrasound scan that you do of uterine arteries at um between 11 and and 13 weeks. This could be done transabdominally but more preferably transvaginal following a similar technique. So if you are going to use this alone for early onset, the preeclampsia addiction rate will be around 48% and 26% for late onset preeclampsia for a false positive rate of about about 8%. One of the important factors that I spoke about was the placenta growth factor. It is thought to be synthesized by the placenta and secreted by the trophoblastic cells. It is a potent angiogenic, it has potent angiogenic functions and we know that in pregnancy that develop preeclampsia, P GF is lower than in normal pregnancies. And if you had to use it alone, it has got its own detection rate of about 55% for early onset preeclampsia and about 33% for late onset uh preeclampsia. Then we have this um this molecule with a very long name, serum solo FMS, lactis in one. So this is thought to be to be the opposite or to play an opposite role to the placental growth to placental growth factor. And that it is an and it is thought that it really plays a central role in the pathogenesis of preeclampsia. And in those pregnancies where who, which have established preeclampsia, its value will be will be increased. And what is important about this is that the increase actually precedes the development of the disease by about five weeks and then appears to correlate with the disease severity. So this will speak about when time when to use it or how to use it or how to even interpret it in terms of the preeclampsia disease progression. But there are a few things that I want to say about this, that it is not routinely used for the first trimester screening but is more useful in the second and the third trimester. Why is it? So because if going to measure it, it really does not seem to improve your prediction rate that you achieve even by maternal factors only. But however, for those who who routinely do the 22 week screen, you find that it is more useful in the prison of clampsia then than in the in the first trimester. OK. There's another protein, the plasma pro associated plasma protein A, I'm sure those who work in uh in, in, in um in upper upper income countries actually use this in the first trimester for screening for unemployed D and the like. But however, it is thought that it does not really improve as well, the progress of combined screening with maternal factors. So it is really not to be incorporated into any more. At least for now, that can be able to improve the ejection rate that we already know from the FMF um model. So it is unlikely that it is going to change anything, even if you incorporate it into the into the model that is currently in existence, right? Having done all these, having determined your maternal risk factor, having done your scan and having done your serum markers, then how do you then get the risk for for a specific patient? So there are many calculators that are out there that one can use, but I just picked up one that one can use. So there are a lot of Softwares and a lot of licensed applications that that one can use. You can always buy the one from Medicine Foundation and be licensed to use it. So in not affect what you do, you, you incorporate these into, into a model where you enter the patient's previous history, you enter your scan findings into the model or into the application of software, you also have to incorporate um the serum marker findings. And then at the day, what the model is going to, it's going to generate a personal, a personalized risk for that particular patient. So if you say if your patient is diabetic, your paat index is this much, your s markers are, these are the values, these are the multiples of median, it will then be able to convert all that information into a personalized risk. That is, it will be able to tell you that the risk of developing pretemporal cancer in this patient is maybe one in 100 or one in 1000. It's also able to segregate it whether by maternal risk factors or by ultrasound scan or by a combination of both or by a combination of, of all the, all the factors into the, into the motel. So it is going to be able then to, to be able to tell you to tell you that. So then the question is, then how would you use that risk? What if it tells me that the risk of pre temp preeclampsia in this patient is one in 1000. So we know that the risk of pre temporary eclampsia at less than 37 weeks, if the model says it's less than, it's greater than one in 100. So let's say it's one in 45. That means that that patient is actually at higher risk of developing preeclampsia and that that patient needs to be started on prophylax prophylaxis, either with aspirin or calcium or whatever one is comfortable with or chooses in a particular setting. However, if he tells you that this patient is, is low risk, that patient can be reassured that the longer of pretemporal eclampsia at less than 37 weeks is unlikely. But however, these patients, they require reassessment of their risk again at 22 weeks of of gestation. So it's not like once it says low risk that patient, the risk is completely eliminated. Remember, this is a screen, a screen can only show you the the risk, but it's not going to give you the absolute whether someone is going to have the disease or not to have to have the disease. Why am I? Why am II am emphasizing this? Because I've seen it sometimes in my setting that once it says low risk people even even don't continue to offer the antila surveillance that they need to offer. They think that the patient is no longer going to develop the disease and yet patient comes at 35 weeks with full-blown symptoms of, of, of the disease. Does it mean that the, the motor did not work? Certainly not. It only means that the detection rate, you remember from detection rate, we said it's about 93%. So you're still going to miss other women. But however, you can really assure them that their development of pre of preeclampsia is not as high as those who will be greater than one in 100 right? So this is the Fetal Medicine Foundation, a sort of screening protocol. I'm not going to bother you about this. You can always get it online so that you are able to. But what it basically tells you here is that you, you should also be able to, to assess this patient in the second and also in the third trimester so that we are able to pick up those who develop term preeclampsia early or those who are going to, to develop the disease early. And then you are able to offer increased surveillance or even to, to offer some form of some some interventions. So for me really that this is proposed screening and management during pregnancy in the first trimester, you're going to use a triple test. You risk assess your patient with maternal factors, arterial pressure, uh uterine artery findings, placental growth factor. And then if it's high risk. You're going to start this patient on aspirin. If you are not low risk, there will be no aspirin. And then in the second trimester, there's something called the quadruple test. Remember I spoke about the use of SFL T one in the second, in, in the second trimester. That's where it becomes very, very useful. But for the purpose of this presentation, I'm going to to to confine myself to the first trimester. So first trimester, high risk aspirin, low risk, no aspirin increased surveillance, right? I think someone is asking me, what is the dose I can see there on the chart, what dose of aspirin would you give? It's the other question that I'm also asking the house to say, what is the dose that people are using? So you find that in literature, there's a lot of of doses of aspirin, a lot of studies, the data is just heterogeneous in terms of what aspirin dose to use. Some use. 75 other studies would use 100 and 50 others 100 so forth. But we know that aspirin is going to be good because of its ability to inhibit platelet aggregation and also to promote vasodilatation and ultimately improving the blood flow to the blood center. So the dosage in some of these guidelines ranges between 75 and 1 50 mg per day and the most recommended time to start the therapy is before the 10th, 20th week of gestation. So if you look at the nice guidelines, they recommend starting the usage of aspirin in the 12th gestational week with 75 to 1 50 mg. Wh O recommends 75 mg before the 20th week of gestation. The vitamins and foundation uses 1 50 mg nocte. So for our setting and for I awake, we are actually using 1 50 mg nocte. So we have actually adopted the FAM medicine and foundation guidelines of using 100 and 50 mg at um at night. What you would see is that the lower the dose that you're going to use, the more patient you are going to be the more patient you are going to be thinking that they did not respond. So the more patient you are going to so the higher the dose the better. But however, thea could find 75 to 150. And so I think each and every person is able to look at the guideline, be able to see what they can use in their own setting. But however, for our purposes and intentions at where I wake, we use 1 50 mg at night. So these ASIR trials, a trial that I put up there to show you how effective aspirin is going to be in actually reducing the risk of developing preeclampsia. And so you see there on the extreme right there, what I've put up there, there's an 89% decrease in the study that they did there was an 89% decrease in developing preeclampsia at less than 3032 weeks. But remember that these are, these were ideal conditions, patients who um who were in studies. It may be different when now it's in a, it's in a, it's in a treatment setup, it's in a hospital or it's in a population with its own cultural issues, adherence issues and other things. But it can be as high as 89% in terms of your, your risk reduction. If you're going to use prep, um if you're going to use um aspirin. So really for us, we tend to start it before 16 weeks because if you look at the theory of developing preeclampsia, there's this talk of a second wave of prolastic invasion that is thought to be suboptimal in those patients who develop preeclampsia. So you ideally want to want to give it before that time. So that by the time that second wave of tla invasion develops, you're already having the patient on, on aspirin. So we tend to give these patients by 16 weeks, we need to have started them. So this is a meta analysis really from 2017 that included the the aspirator results and other and other studies. So it actually confirmed that aspirin less than 100 mg per day starting at any station has no benefit. So it has no benefit in starting the aspirin at 25 weeks or 28 weeks. Why? Because the placenta issues have already started. The like the factors that I spoke about are already in, in in circulation and over plastic invasion is already OK. So it is not just about starting aspirin at any time. But we know again from that meta analysis that aspirin started greater than 100 mg a day started again after 16 weeks has no benefit. So if you are going to start the right dose, but in the wrong gestational age, you might not achieve any benefit. But what is thought to to be useful is that you start the aspirin above 100 mg a day before 16 weeks has major benefit. This is what that meta analysis actually concluded, right? So there are some people who have tried to study the potential benefits of low molecular weight her to say instead of aspirin, is are there any other interventions that one can, can use? And we know that there is 2016 meta analysis from Rob that really said that if you were to add low weight heparin to aspirin therapy, you could theoretically further reduce the odds of preeclampsia in women with a history of of pre of preeclampsia. But that benefit really is is is really not when you compare the risk and these are the benefits, those benefits sometimes are outweighed by the risk that we potentially expose the, expose the patients the patients to. You also know that again from from long et A they reported again recently in 2023 that if you add the low molecular weight heparin prophylaxis, you could potentially delay the onset of severe preeclampsia. But again, this has not been widely incorporated into most of these major, major guidelines. So it most of this remains really theoretical. Most of this really remains uh something that is experimental. But I think one can understand why use of low molecular heparin could potentially be thought to, to, to, to assist. Uh I'm I'm I'm quickly remembering maybe patients who come, who come in with antihost syndrome who are likely to develop preeclampsia. It could potentially prevent some of the preeclampsia risks or development of pre of preeclampsia. Slight calcium. I think calcium also in the vascular tone and to maintain a healthy BP and also in placenta development and function. So it plays a major role in maintaining a healthy BP and also in placenta function. So we have recent meta analysis that concluded that calcium supplementation is effective for preeclampsia prevention in women with low calcium intake. But however, there's been no consensus on the dosage and the timing. Unfortunately, and in populations with low dietary calcium intake, wh O the World Health Organization actually recommends that you need to supplement about 1.5 to 2 g or of elemental calcium for to for pregnant women to reduce the risk of of preeclampsia. So the case with calcium now is that it needs to be in those populations where there is a low calcium calcium intake. But if you look at many places, including our own, we fortify our food, our mealie meal and lots of other new um uh foods with uh with calcium. So it is highly likely that we are a calcium deficient. But however, I'm speaking from a point of, of no evidence for this. So even in our country right now, it's not something that we routinely use to offer calcium. But I think it may work in those patients who are coming above this gestational age where you are able to give them um aspirin to give them aspirin. So because wh O will say that you can give, potentially give this up to about 20 weeks of gestational age. So it may be something that one can consider maybe for those patients who are coming late in, in gestation. But however, in those patients in those populations where there's low calcium intake, definitely the World Health Organization actually recommends that you should be able to, to, to, to give, to give that. But however, in my view and those papers that I've seen aspirin remains superior to, to, to calcium. So if you are too, if you are probably maybe to, to decide on the two, you will probably, I will probably pick up aspirin based on the evidence that I've seen in some of the, some of the literature that it seems to be more superior than, than calcium. So there are other interventions in other and other things that are coming up now that people have tried to consider to see that over and above the calcium and the aspirin, whether we could give other things in terms of prophylaxis. So, statins, these have been getting promising results in the treatment and prevention of preeclampsia or how to are they thought to do so by raising the levels of placenta growth factor. And then also doing, they've been seen to also reduce the levels of of the antiangiogenic factor. SFL T one. But again, there is no universal consensus on the dosage and timing and use for preeclampsia prevention. And most of this really remains um remains experimental and um and really not incorporated into most of the of the major guidelines, right. So recently, there are some markers in preeclampsia that others have started to speak about where we have recent advancements in preeclampsia research, which is actually coming up with an identi identification of other markers that are thought to be really helpful in in detecting the disease earlier. And these will include a range of biological molecules, some specific proteins, the micro RNAs and some metabolites. This includes quite a number of those that I've listed at the bottom there, including allopurinol uric acid and and, and the like, but these really have not come out into the, into the mainstay or into the guidelines per se vit vitamins and natural supplements. Yes, we know that Vitamin D supplementation will enhance an angiogenic factors. In preeclampsia. They will raise the levels of vascular and the the growth factor and placenta growth factor. We know also that Vitamin C and E are actually antioxidants. So they are going to reduce the oxidative stress and also increase the the levels of nitric oxide levels in, in, in, in the patients. I know a lot maybe using omega three fatty acids. There's been a lot of research on a Mediterranean style diet that has also been been been proposed. But however, you find out supplementation for these for preeclampsia, prophylaxis is highly questionable in in many of these studies. And therefore for now, these are not routinely used for preeclampsia, prophylaxis, but they are good in other conditions and in other prophylactic um methods or interventions. But for preeclampsia prophylaxis, these really have not found widespread acceptance or or use, right. So having said all this, there are challenges that some of us are facing where we work in the low and middle-income countries being the fact that the the ultrasound scans that one needs to do to incorporate into the mole are not readily available. Neither is the measurement of of placental growth factor in most of our primary health settings. So this becomes one of the major the costs of doing all these and what is also the practicality of measuring the BP and calculating the mean arterial pressure? Do you have the software. Do you have the necessary funds to be able to, to get the licenses for this kind of software? So you find out that most of these answers would be the negative. We are struggling with a lot of um staff shortages, resource shortages. And so really, we found out that most of us are really lagging behind in implementing these, these models that seem to, to work. And you find out that in most of the low and middle-income countries like our Sub Saharan Africa, we are, most of us are still stuck really on the on using the maternal factors only or if we are to improve this, we probably just there about adding maybe the mean pressure to whatever form of screening that, that we are doing and to get to a patient who's going to come early enough for you to be able to to to do the scan, to be able to measure the serum markers becomes quite um a big challenge. But I know that in other countries in high-income countries, it's not even a major problem. So there have been a lot of debate to say, what kind of screening strategy should mid low and middle income countries be adopting? How many can really do the standard triple test where they do everything. Can we at least do a two-stage screening strategy? I will explain what this is. Can we just concentrate on maternal factors? I mean pressure for now given the problems that we have others will say, why don't you treat those who are high risk for maternal factors and only screen those who are at low risk. There are others. Now, we are quite, quite uh we are really talking about this to say, why are you going to go through this laborious process when the actual intervention that you are only going to give is either or aspirin, why don't you just give aspirin to all patients? Because whether the patient screens higher risk, the only thing you are going to do is to give him aspirin and calcium, you are already doing it with iron. For those who may not know we are giving iron tablets or iron prophylaxis to all our patients. There are patients, there are those other countries who have a high burden of malaria where they are giving malaria prophylaxis as well. So the same argument is now starting to come to to our setting to say, why do you even waste time doing the screening? Why don't we just give aspirin to all? So the two strategy, the two-stage strategy actually says um where resources are limited, you could be able to do a first a screening process, we are going to use the risk factors plus miter pressure. And then if the patient screens positive virus based on those two, then you are going to give them a second stage screening where you are now going to add them the scan and also the placental growth factor measurement. But however, if they screen negative on those two, they are already negative and there's no need for an intervention. So this will sort of seem to sort of reduce the number and the burden of those patients who are going to undergo to going to undergo screening, looking at the limitation of of the resources. So this speaks about a variation of the first trimester combined test that normal income countries may consider this where the resistors are limited. And that really the baseline or the baseline should really just be maternal factors with mini pressure. But I know that in some of our healthcare settings, even now, we have been struggling with measuring the BP. But at the baseline mire pressure and maternal factors should really be the first line of of screening. Then if that patient screen is positive, you can then add other things. But if they screen negative, then there's no need to continue to further interrogate those kind of patients. Then there are issues to do with investor prophylaxis to say why should you go through this process as evaluated for if the most effective intervention is aspirin or calcium for the high risk group. But there are studies that have come up to say really that the issue of compliance in this in this reduction of preeclampsia is something that one cannot under underestimate. And then there are issues of C of aspirin in large populations. What is the implication of giving everyone aspirin in a population? Every pregnant human population? Are you not going to start having increasing the risk of hemorrhagic disease in these, in these women? What about the the side effects of the of the disease at a population level and not at a high risk patient level? So those are some of the things that will then come up that 1 may need to balance, especially for those proponents of the universal prophylaxis. So now there's talk of universal prophylaxis versus universal screening. But I really think that we need to go the way of screening then of adopting individual screening. There is no middle income countries. Why? Because if a patient is told that your risk is so much, the compliance is going to be is going to be better and they're likely going to to take the tablet or they're likely going to get to take the intervention. Then if you just give everyone including the low risk patients exposing them to a lot of unwanted uh side effects of of of the drug. So how can one make a difference in terms of preventing preeclampsia? II got this slide from from the F website. So it will say we need to be pushing for comprehensive Universal health Systems approach where we need to to prioritize provide education, consistence, adherence to clinical guidelines, improvement in our in our referral pathways. And that in those low middle income countries like mine where they will, people are struggling or where they strive, there's everything they will likely be workforce shortages, even the availability of drugs becomes, become an issue. And then we have to look at issues and close gaps in governance and also in and also in financing. I believe that this is like Riko is saying it's probably the best way going forward. So in summary, let me just say that every country really needs to be adopting some form of preeclampsia, screening and prevention with aspirin or with calcium, preferably less than 16 weeks with the use at baseline of the maternal risk factors and the mean arterial pressure. And if resources are permitting to be able to increase that detection rate by the addition of the uterine artery po fertility index markers, I believe that if I adopt this this way universally, we may be able to win against the ke and against the the effects of preeclampsia and the mortality morbidity that it is causing in our, in our settings. Thank you very much. That will do all that I had prepared. Hello, sorry. Um We've got a few questions. I'm sure if you actually answered them in your presentation. Yes, I am seeing to him uh or three. Um So, is it correct to say that preeclampsia is more of a relative indication than an absolute indication for Cesarean section as long as you can control the BP, preeclampsia on its own is not an upsetting indication for, for a Cesarean section or for operating a patient for D or for an operative delivery. So patients with preeclampsia can be delivered vaginally either through induction of labor or otherwise. So it is not really uh an indication for a Cesarean section, be it relative or be it absolute. But however, it depends on the other upsetting indication that may be in the in the patient. I know for example, in our setting, sometimes patient who are eclamptic where we need delivery earlier than than later, we sometimes resort to a Cesarean section. But preeclampsia on its own is not an indication for Cesarean section unless there are additional factors that are pushing one to do. So, then I see another question there that says, what dose of aspirin would you give? Yes, he said there are many doses but in our setting, we are using 1 50 mg at night dose. I see another question it says um is missus gravidarum any risk to preeclampsia? Not necessarily. So, but what we have seen is that patients who have I PMSs tend to develop preeclampsia or tend to be at higher risk of developing a preeclampsia. So if I'm to put it as a risk, it will be in the moderate class or in the moderate grade. But certainly I've seen quite a number of patients with I PSS who go on to develop preeclampsia. So are there other questions? Yeah, I think that's, that's all. Yeah, I think, I think that's all questions. OK. What is the first drug choice form for eclampsia? II think for eclampsia, eclampsia is, is I think it's a multipronged approach. When you have a patient with eclampsia, there are a lot of things that you really want to do when a patient comes fitting, which is to stop fits, to prevent further fees to lower the BP. So there are a lot of drugs that one would use. So for example, one of the drugs is magnesium sulfate. It's quite, it's quite good, quite effective. Some of the drugs that one has to have where they are delivering women was it will prevent, to stop the fees to also prevent further fees. And it also has got some mild antihypertensive effect. It also has got some mild neuroprotective effect for for those patients who are having eclampsia, pretemporal eclampsia. It may sort of be able to, to assist. Certainly, in terms of reducing the BP, one would obviously need to have Nifedipine, labetalol and um hydrALAZINE. So those are the three that's very, very critical for one to to to for one to use. What triggers a patient to develop eclampsia from preeclampsia? Yes, like I said that it is a multiorgan system disorder. So depending on which organ is preferentially, uh sort of um affected by the preeclampsia, eclampsia. Remember these are these women who are going to be to be fitting. So those uh uh uncontrolled hypertension, the high BPS, those are the things and also the placenta remodeling that's going to happen, predispose a woman either to, to, to trigger to preeclampsia to sorry to eclampsia from, from preeclampsia. So really the trigger is in a patient who's not on prophylaxis and the patient whose disease when it develops is not managed accordingly or is not managed at all. I can't see any questions at the moment. Please do put questions in the chat if you have any. Um, don't forget to fill in the feedback form as well. Um, we really appreciate your feedback and also don't forget to follow me education, um, because you'll get notified of more education events such as this one. Um, we'll just wait for a few more minutes to see if there are any questions. Ok? I think there's no more questions. So we'll end it there. Thank you so much everyone for coming and we'll see you at the next talk.