This important talk from Annalisa Post, MD, a perinatologist with the UCSF Fetal Treatment Center, clarifies the definition of preeclampsia, lays out risk factors, and elucidates the tricky business of recognizing worsening hypertension in pregnancy. She covers which labs to order and when (and how to interpret borderline results) and presents new guidelines on care for pregnant patients with chronic high blood pressure. Bonus: Hear pros and cons of low-lose aspirin for every pregnancy.
So, first, just uh discussing the fetal treatment center, Oakland. So we have The fetal treatment center within UCSF refers to both of our sites. We have our, our site at Mission Bay in, in San Francisco, and then we have our site here in Oakland, which is within the Children's Hospital, and it's located right here, like I said, within the, the outpatient building of the Children's Hospital, and it's actually been around in some form for more than 10 years. It used to be just pediatric specialties, and neonatologists creating postnatal plans for, for patients who are pregnant. And over the last few years has really grown into a full-service fetal treatment center similar to the one that we have in, in San Francisco. So, We do ultrasounds for diagnosis. We do MFM consultation with myself and a couple of other MFMs that work here as well. And then over the last year, we've added a lot more services, so we also have our genetic counselor, Rebecca Freeman, who's here. We have a social work. We have our fetal coordinators, um, so we really do a lot of kind of whole care for women that we're co-managing with fetal anomalies. And these are the, the top two, Dr. Lee and Dr. Norton are, are directors of the Fetal Treatment Center in general on the medical side. Doctor Anderson here is the neonatologist who's the co-director of this Oakland site along with me, and then Erin, obviously, you guys have already met in this talk. He's our, our director of both sites. And these are many of our other clinic staff here in Oakland. I'm gonna skip past that and just briefly list the pediatric specialties that we hook patients up with for prenatal consultation, what, whatever they need for their fetus, and then making postnatal plans. So, you can see all this list. I'm sure you guys are very familiar with having patients who have some sort of fetal condition and kind of what our goal is, is to diagnose that, explain that. And then have them see the specialists before birth so that they understand the condition and what the plan is going to be and have that direct pipeline into that postnatal treatment plan. So that's exactly what we do. We, we get referred patients, we evaluate them, we have a plan, and then we hook them up with the appropriate pediatric specialties and make that postnatal plan. And of course, also have the genetic counseling, which is a really important part of, of what we do. And just to clarify, since I know it's very confusing with all the different MFM services and groups, especially in the East Bay. So, here, yes, I'm an MFM and we do MFM, but it's all surrounded around fetal anomalies. So we do fetal MFM consults and care and care of the fetus and postnatal planning for that infant. If maternal MFM care is needed, we don't have those services within this clinic. We can't, we can't even take a blood pressure on someone. It's just not, it's not designed for maternal care here. So if maternal MFM care is needed, then obviously other MFM sites have to be looped in, which I know you guys have workflows for that as well. And then how does that work for deliveries? So, most of the time, you know, I know your group delivers at Alta Bates or at Highland, and most of the anomalies that we care for can deliver at Alta Bates or Highland. It's very rare to have to transfer to, to Mission Bay in San Francisco and at Alta Bates or at Highland, if needed after birth, it's sometimes it's planned, sometimes it's unexpected, the infants can be transferred here to Children's Hospital to the intensive care nursery for all of the services that we discussed. So briefly, the referral pathway. If you were to have an ultrasound that diagnosed or suspects a fetal anomaly, the next step could be referral directly here. And what we do is we do ultrasounds, we confirm or clarify that diagnosis, and then, as you can see on the top, in most cases, we can then co-manage along with the referring group, even if it's a general OBGYN group, um, and just co-manage doing some of the, the Fetal care along with mom's regular prenatal care and make an appropriate plan for delivery and how that baby will be cared for after birth. And as you know, sometimes moms need their own MFM maternal fetal medicine care, so in that case, they might need to be transferred or have consults at another MFM site. And like I said, very rarely do we have to actually recommend delivery elsewhere, so delivery at Mission Bay. So, fortunately, almost all uh conditions we're able to just keep here and deliver it all to Bates or at Highland. These numbers your group already has, so we're, uh, they've already been sent. Um, we don't need to give you time to write them down because I think that we provided this earlier in the week, but we're always happy to answer any questions about that. Any questions about that? Pathway or what we do here in Oakland before I completely switch gears into preeclampsia. Would alta-based MSN refer to you like if they, the patient has got the ultrasound there and we're following up with genetic counseling or whatever and they found something or would. Like, are there other pathway, yeah, no, great question. So there's a lot of different referral pathways, and many of them do end up here. So there are a couple different MFM groups in the East Bay, as you know. Um, there's the group that used to be the East Bay Perinatal that's now UBCP, and if they make a diagnosis of an anomaly, then yes, they refer here, and we will co-manage along with their group and deliver it all to Bates in that case. There's also the Summit Perinatal Group, which is under the Sutter banner, and they will manage some of theirs on their own and for their postnatal planning, do some Stanford referrals, but there are some that they do send to us as well. It kind of depends on the diagnosis and what, cause there are some pediatric specialists that are not available in the Stanford and Sutter system that, that we do have at Children's. So yes, we do receive a lot of referrals directly from MFM. There's also MFM at Highland as well that will send patients here as well for diagnosis of anomalies. So yeah, we do directly get referrals from a lot of MFM groups. Yeah. Right. All right, I'm gonna dive into preeclampsia then. I wasn't, I wasn't sure exactly what direction to try and take this and how long it would be, so there's a lot of information here, so please feel free to just call out with questions midway through and I'll just kind of let us be guided by whatever seems best for what the interest is. Um, let me share this one. So we're gonna talk about preeclampsia. So not a fetal, not a fetal condition, totally changing directions. So, very briefly, I'm gonna cover definition of preeclampsia, what we do and don't understand about why it happens and where it comes from. Some outlines about management, both inpatient and outpatient, and then a little bit about like what we do have for prevention options and what we do and mostly don't know about prediction of preeclampsia. So Very briefly to define preeclampsia. This is a new diagnosis of hypertension in pregnancy in the second half of pregnancy after 20 weeks, plus proteinuria. Or and or severe features, and we're gonna go over about what those severe features are. So, it is a disorder that's actually a systemic disorder, which is why we can have features in multiple different parts of the body and it can cause end organ damage because of these changes. The prevalence really varies in different ethnicities, different countries. It's just a huge variations, but it's about 5% of pregnancies, and there's a lot of different factors that we think underlie the development of preeclampsia. It seems that Asian and Pacific Islander women have a lower risk of preeclampsia than both white women and black women. Black women have by far the highest risk of preeclampsia. Asian and Pacific Islander women seem to have about a 19% lower risk, and some of that seems to be related to the lower risk of hypertension in general, which is a major risk factor. But interestingly, some more recent studies have demonstrated that it seems that Asian and Pacific Islander women, while they're at lower risk of getting preeclampsia, have higher risks of having cardiovascular and endothelial or just general vascular complications when they do get preeclampsia. So it is a really important kind of diagnosis and a really important thing to understand and obvious we'll learn throughout this talk, we really still have a lot of gaps in our knowledge and our ability to treat and prevent. Lots of maternal and fetal morbidity. So in the CDC mortality reporting system, the most recent report in 2019 found that 6.3% of maternal deaths in the US are from preeclampsia or hypertensive disorders of pregnancy. And of course, there's morbidity that can occur both during pregnancy, after pregnancy, and of course, the fetus burden. So, the biggest part of that being early medically indicated delivery leading to prematurity. So why does it happen? So it seems that it's related to the way the placenta develops or does not develop early on. So abnormalities in the way that that placenta vasculature develops can then lead to poor placental perfusion later on, and the changes in the placenta that we'll see on pathology, for example, in someone with preeclampsia. That results in factors being released in that area to try and overcome this underperfusion, which has systemic effects throughout all of mom's body because those factors do not just stay in the placenta, and it alters the way mom's body is functioning throughout, which leads to the downstream effects. So we have hypertension, of course, from the vascular tone, and then other manifestations that we know are all related to that endothelial function within vessels. So it's endothelial dysfunction within. The kidneys that leads to kidney damage and to proteinuria, and then, of course, we know that there's all of the other things that we see, liver dysfunction and edema in the brain and cardiac uh complications. And just to go way, way back to when we were learning about this, so we've got the, on the left side here is the fetal side, on the right side here is the maternal blood vessel, and this spiral artery is that vessel within the muscle of the uterus, and in pregnancy, it is supposed to remodel into this very low resistance state where blood can just easily flow through it. And so it becomes large and forms this like spiraling around the fetal placental tissue. And when that doesn't happen properly, this bottom picture is meant to represent that where the spiral artery has not reformed into that nice wide blood vessel with easy flow. But why does that happen in the first place? This is what we don't know. There's a lot of factors. We know that there's genetic. Portions of this risk. We know that there's immunologic portions. We all have heard about how it seems that sometimes it's a new partner and that increases the risk. It sometimes is, it's more likely in the first pregnancies versus later and that's Seems to be something about the immune exposures to paternal antigens. Of course, we know it's higher risk in women who have lots of different autoimmune or inflammatory conditions. So there's just tons and tons, and this part, we really don't know, like, why do those result in these changes in the placental vasculature. And to define it, again, new hypertension in pregnancy greater than 20 weeks plus proteinuria and severe features, but there's obviously a lot more categorization below that. So, Just pre-eclampsia without severe features is blood pressure that's new, over 140/90, plus proteinuria, greater than 300 either on that protein to creatinine spot ratio or ideally a 24 hour urine collection. And of course, we have preeclampsia with severe features, we used to just say severe preeclampsia, but now we have to say two more words every time we say it and say preeclampsia with severe features. So, this is new high blood pressure that is in the severe range. And or other severe features. So you could still have mild blood pressures, but any of the other severe features would still make this preeclampsia with severe features. So those other severe features are, of course, the lab abnormalities, so the liver dysfunction that we see with elevated AST and ALT, anything above the lab's upper limit of normal. Elevated creatinine, ideally if we have someone's baseline, we usually say twice their baseline. If we don't have a baseline, certainly anything over one is abnormal in pregnancy and even getting near one tends to make us pretty nervous. Low platelets under 100. And then a headache, of course, not a headache that comes and then goes away completely, but a headache that doesn't go away. Same with the right upper quadrant pain. Vision changes can be a little subtle and hard, but vision changes, these spots and flashes in the vision again that are not going away. And then there's other things like pulmonary edema and um coagulopathy and getting into kind of HELP syndrome, which is a little more detailed than I, than I got into for this, but there's more features. These are the most basic severe features. Then we have the whole category of superimposed preeclampsia, and here's where it gets really tricky. So you've got a woman who already has chronic hypertension, and then there's new development of severe features after 20 weeks. Here's where it's really important and why it's recommended for these patients to have baseline labs in the first half of their pregnancy. So, ideally with their first trimester labs, in addition to all of your rubella and your regular, all of those labs. We should also be getting a urine protein to creatinine ratio or 24 hour urine if you want. We don't usually do that, um, unless someone has proteinuria, um, getting the AST and ALT, serum creatinine, and the platelet count, which of course we'll get on the CBC because then we can compare those if later there's changes, so it's very helpful to have those in the first half of pregnancy. So, if you develop lab abnormalities that are new, that's easy, but what about blood pressure? What if they're normally in the 140s over 90s and now all of a sudden in at 32 weeks, they're 162/109. Is that worsening hypertension? Is that new superimposed preeclampsia by the severe feature of severe blood pressures only? It can get really hard. I think this is where like the art of preeclampsia management most tricky, um, and it, this usually honestly just requires inpatient evaluation. You need to see, observe how is it getting worse if we up titrate their meds, are they still bumping through that with worse hypertension? OK, that's probably preeclampsia. So this is usually, it just, it needs inpatient evaluation and, and MFMs to just assist in trying to figure that out cause this is, I think, the trickiest part of preeclampsia often. So I added that to the bottom, existing chronic hypertension plus new proteinuria. Would make it superimposed preeclampsia, and then if you have severe features, it becomes superimposed preeclampsia with severe features. And finally, I've left a line at the top, and that's where I wanna put gestational hypertension, which of course doesn't have the name preeclampsia, but it all seems to be on a spectrum. It seems to be the same ideology. And we manage gestational hypertension with those mild range blood pressures, the same as we do for preeclampsia without severe features, which we'll talk about in a moment. So it really belongs in this group, kind of grouped together with preeclampsia without severe features. Any questions on that before I go into management? So management, obviously very different non-severe versus severe disease. So, Non-severe disease that includes your gestational hypertension, as long as the blood pressures are still in the mild range. Your preeclampsia without severe features, and this tricky diagnosis of superimposed preeclampsia without severe features, which essentially just applies to women who have chronic hypertension and now have new proteinuria, but nothing else severe, that would be managed under this non-severe disease group. So management for this non-severe disease is typically outpatient management, though it's never wrong for inpatient evaluation if you're not sure, if it may be changing. We do not at this time, start antihypertensives for this group of patients, and the easiest explanation for that is that Essentially, starting antihypertensives could mask development of severe disease, and it's very, it's very important that we know is it severe or non-severe because we manage them so differently. So if we have someone who's in the 150s over 99 and we bring their blood pressures down with a bunch of antihypertensives, And then it goes up a little and we bring it down some more, well, if we hadn't done that, they might now be in the 160s over 110s, and we need to change our management plan, so. I will just put a little asterisk here that I know there's proposals in the MFMU, our big network that does national studies about management of gestational hypertension and mild preeclampsia with antihypertensives, so that may change in the next few years if those, if those trials are done, but as of now, we don't treat non-severe disease with antihypertensives. Ideally, monitoring blood pressure at home if possible every day, if not weekly in the clinic, um, ideally twice weekly since these patients should also be getting twice weekly non-stress tests or other antenatal testing. And then weekly labs so that we can keep track and make sure that severe disease is not developing cause there's a really high risk for this non-severe disease becoming severe. And then delivery at 37 weeks for this group, or of course, if it's diagnosed after 37 weeks, immediate delivery. And then for severe disease, this is gonna include your preeclampsia with severe features, superimposed preeclampsia with severe features, and of course the more complex groups, so your HELP syndrome and eclampsia, of course, with actual seizures. In general, the management is just inpatient care. There's really no role for outpatient care of any severe disease that is never recommended because the need for really close surveillance is so high and the potential for rapid maternal or fetal decline is also so high. We do, now that we have the severe diagnosis and their blood pressures are in the severe range potentially, now it's really important to treat. So there's a lot of uh protocols out there and most hospitals have protocols for immediate IV medications for severe blood pressure. So within 15 minutes of a severe blood pressure, we should be treating with IV labetalol, IV hydralazine, or pionifedipine to bring it down and following an, an administration protocol for that. And then considering starting a new regimen of oral medications for ongoing control if this is someone that we're trying to prolong their pregnancy. Of course, magnesium is really important. Always during this initial evaluation, when you're figuring out, is this someone who's going to need delivery? Can we wait a while? And then always the highest risk time for complications and seizures related to preeclampsia is during the delivery and the first day postpartum, which is why we restart it when we're moving towards delivery and for that 1st 24 hours. And of course, we, if this is diagnosed before 34 weeks, our goal is expectant management, trying to prolong their pregnancy in the hospital until 34 weeks. If that patient meets criteria for expectant management, there's lots of, um, lots of criteria that bump you out of expectant management, so persistent neurologic symptoms, a headache that won't go away. We are, that's concerning for Edema in the brain, and that's not a candidate for. Um, expectant management, worsening liver function tests, coagulopathy, so there's a lot of things that can move towards delivery or of course, if you're already past 34 weeks and we make this diagnosis, then we're moving straight towards delivery. Any questions about management before I move into what we tools we do and don't have for prevention? I just want to backtrack a little bit about the diagnosis with the proteinuria. You said 300 is 300 the 24 hour protein, or if we do it a spot check, it's like, you know, protein to creatinine ratio that we're using. Yeah, it, it is somewhat lab dependent about how it reports it. At many labs, the protein to creatinine ratio is interpreted in a way that will give you an equivalent to a 24 hour urine, and it'll either report it as 300 or 0.3. And it's lab dependent on how that will be reported. So, if it's a, if it's a spot protein, then it would be uh at UCSF, the lab reports it still has 300, they kind of make it look the same as a 24 hour urine. Other labs I've worked at report it, I can't remember the units, but it ends up being 0.3 or 0.15 or, or whatever it is. Um, if it's borderline, I will, that's often an opportunity to do a 24 hour urine because obviously they're more accurate and sometimes you'll find it be a little over on the spot and a little under on 24 hour urine or vice versa. Does that answer your question? Yeah, I think we ought the spot urines that we tend to do are the microalbumin to creatinine ratio ratio. There is I've not ever ordered a protein to creatinine, I guess I've done it in the pregnant first. Alright, so I don't know how it's reported. Uh, yeah, I'm not sure if it, I would think it would be the same. It would look like a 0.3 0.3 on the ratio. It'll be, it'll look like a 0.3, yeah, and of course it'll flag, at least our, our labs and any lab I've ever been a part of will flag anything that's greater than 0.15 because outside of pregnancy that's considered abnormal, but we use the 0.3 is the equivalency for the 24 hour urine. Thank you, yeah, um, and I just want to clarify, so you talked about like gestational hypertension like on the spectrum, and so for those folks also, would we then also monitor and not start any type of anti-hypertensive treatment and yeah, yeah, and I, I see, I see this done differently a lot, honestly. So if you go by the book, the like 87 page document that ACOG put out, you know. Oh gosh, now, I don't know, 8 years ago, Sebagh is a big document about management of hypertension in pregnancy. Um, we are still not treating for gestation. So, unless the patient has some other reason why we really don't want them to be hypertensive. So I do have several patients right now that I'm personally treating for gestational hypertension because they also have atrial fibrillation or a brain aneurysm, and so like we don't want them to be even in the 140s over 90s and we need to be really cautious, but Outside of those rare conditions, gestational hypertension, we don't treat because again, we're waiting to see if it becomes severe and More recently, there's been some publications and some recommendations that if it does become severe, even without proteinuria, just new severe blood pressures, that we treat that as severe, severe gestational hypertension and it's the same as, as severe preeclampsia. So that's the rationale for why we are not treating it because it's important to know if it has become severe or not. Then once it becomes severe, we shift over to the severe pathway of management. Um, what about patients with preexisting hypertension? Yeah, in terms of our treatment goals. So, yes, I have a slide on that that comes a little bit later. Uh, here we go. So, we have some new management guidelines for that and so there's a large MFMU trial called the CHAPP trial, chronic hypertension and pregnancy, that was just published last year and Up until this point, we really did not know what to do, like, what should our goals be? Everyone was different. Do we treat just to keep it under 160/110? Do we treat to keep it normal range, somewhere in the middle? So, finally, we have some clarity from this really big multi-center trial that was done. So, the trial was looking at tighter versus less tight control for chronic hypertensives, whether that is titrating the meds they're already on or starting new meds to keep it under 140/90. And it did find that tighter blood pressure control reduced pregnancy adverse outcomes. So if you take a composite outcome of preeclampsia with severe features, medically indicated preterm birth, less than 35 weeks, abruption and fetal and neonatal death, it reduced the composite outcomes, I think it was 37 to 30%. So, not huge, but significant enough to change our clinical practice and recommendations and practice patterns are now changing. So this is now what we recommend as the treatment goals for patients who already have chronic hypertension. So we do, those patients should be treated, it's better, it reduces their pregnancy outcomes, of a pregnancy outcomes, and actually now we're trying to keep most blood pressures under 140/90, not necessarily all of them, but most blood pressures in the normal range. It seems to be better. And for a lot of people, this does mean maybe starting meds that they weren't on before cause, you know, so many people. Out in the world have 145/90s and their primary care doc does not feel the need to start blood pressure meds, but in pregnancy, it seems that much like diabetes, our goals should be a little bit tighter than outside of pregnancy. And then, of course, we do get into, like I mentioned before, that challenges about like, well, what if it starts getting worse at the end of pregnancy, as is so common with hypertension? Is it new preeclampsia or do we just keep going up on the meds and that's, that's where it's tricky and can't really easily say what to do in a slideshow because it's just very individual. Annalisa, can you, um, talk a little bit about postpartum preeclampsia? How far out do we worry about preeclampsia? When do we pull the trigger to get lab work done, um, and or start treatment? Great question. I actually didn't put that in here, and that's a great important portion, so I'm glad that you asked that question. So, Yeah, we, we know, like I said, the postpartum day one is a really high risk time, and so that's a very frequent time for diagnosis of preeclampsia. Day 2, also possible. Day 3, we know certainly for the next 2 weeks, preeclampsia can absolutely be diagnosed, so someone could go home and come back in with new severe range blood pressures and liver function abnormalities or whatever the, the case may be. The how how far out it is preeclampsia is debatable, and different experts have different opinions about how far out. A lot of people say 2 weeks, some people say longer, up to 1 month. That's, it's quite rare to diagnose preeclampsia beyond 2 weeks or to be considering that diagnosis, but In general, the treatment pattern is the same except we're not now worrying about a fetus and delivery planning, but it includes hospitalization, magnesium sulfate for 24 hours, and starting blood pressure medications to bring blood pressures into a safe range and then carefully watching for several days after discharge, um, keeping a close eye to see how the blood pressure trend goes, and most people can then taper off of those blood pressure medications over 2 to 4 weeks typically. So just to follow up on that question, so I had a patient who I'm seeing postpartum, and she's been having kind of, um, you know, mild range, um, high blood pressures, and we're following up with her and she's a month out now. She could just start, uh, blood pressure medications, um, and she's out of the range, it sounds like of preeclampsia. Likely, yeah, that's so interesting and The short answer is, yeah, if you feel like it's you're, you're weeks out now. Even if you weren't weeks out, it's very reasonable to start blood pressure medications postpartum. It's, the situation is a little less complex in terms of needing to make that critical diagnosis, you know, the one thing that would be the difference between severe and non-severe would be. Magnesium, but it does seem pretty common to have patients who have this hypertension postpartum, and treatment, if it's persistent and significant enough, is reasonable, and at UCSF we, we do do that. So, this is the exception to what I said before about not treating mild gestational hypertension or mild preeclampsia is postpartum, if you do a careful evaluation for severe features. Our thought is that it's not likely to get worse. They're not still pregnant and so it's very reasonable to treat with blood pressure medications and do that for as long as you need to, whether that's again just a couple of weeks or you're handing care off to primary, to their uh non-OB provider in a couple of weeks for further care. OK. Did you have one question in the chat? Are you able to see it? Oh yeah, I, I can. Let me open it up. We did have a patient with gestational hypertension or chronic hypertension, and their blood pressures do increase the severe range we treat. How frequently do you recommend checking labs? Um, yes. So, definitely if someone has severe range blood pressures, that's an indication to do a full lab panel to assess. Um, if those labs are normal and how frequently do you repeat them? So If you have someone with chronic hypertension, and it seems to be increasing. This is where we get into kind of the art of this. I'd say what I often do is repeat weekly just because we're trying to again see, is this something that's changing and the, the labs can help us feel more comfortable that things are stable rather than, you know, something that's evolving over time. The one little caveat to that that I'd say about gestation, if you have a patient, as you said in the chat with gestational hypertension and their blood pressures are now severe range, well, that's, that's technically now a severe disease. So again, I mentioned we do have this ability to say gestational hypertension with severe blood pressures, even if there's no proteinuria. is technically severe disease and should probably be treated as such with inpatient admission. So, yes, we sometimes get someone who has that like one time, they come in for an NST and it's high and then it's fine in triage and fine when they come back. OK, fine. But if they're like in the severe range now and it's a change and it's not a chronic hypertension diagnosis, they should be in the hospital cause that's likely severe disease. And I think it's never wrong to do weekly outpatient labs, at least when you're trying to figure something out. It can, it can be helpful. This is such a great question. All right. I'll do a little dive into aspirin and some other things and I'll skip through some of the more molecular stuff that I had in here just to, you know. Cause it's interesting, but it's, it's less clinically relevant, so. Obviously, we use a lot of aspirin now. We all know about aspirin, but just a little bit of background on aspirin. So, it's an NSAID. This terrible prostaglandin pathway that like I just, I can't keep in my brain and have to look at every time if I need to understand it, so. Arachidonic acid via these COX-2 enzymes turns into these prostaglandins, which then create thromboxane, and NSAIDs inhibit this process, so you can see the little aspirin molecule there, it blocks these COX molecules, COX1 and COX 2, and then downstream because that then blocks prostaglandins, is going to result in less prostacyclin on the right and thromboxane and This, they act in different ways, so the thromboxane is a platelet aggregator and vasoconstrictor, so it clots things up and squeezes blood vessels. When we use the lower dose of aspirin, we know that it seems to affect the platelet function versus these thromboxane molecules and the prostacyclin prostaglandins a little bit differently. This is relevant for later, but it does seem that some of aspirin's effects happen at any dose, include our lower dose of 81, but that the more complete platelet blocking is only when you get to higher doses of above 100. And that's, you know, one of the purposes of doing full dose aspirin for people who are using it in the setting of some sort of blood clotting disorder, you know, not what we're doing in pregnancy, but they would not do a baby aspirin because it's not fully effective on those platelets, but we are having an effect on the prostaglandins and thromboxane production. So, how well does it work and when should we do it and how much should we do? Lots and lots of studies. The largest clinical studies match up with this meta-analysis which showed that, yes, low-dose aspirin reduces the risk of specifically preterm preeclampsia, best of all, and the relative risk is anywhere from 0.62 all the way down to 0.33 in the subgroup in which we do. Earlier initiation and a dose of 100, and the reason the dose is 100 is that There's a lot of studies, and worldwide, the dose of aspirin, baby aspirin is not usually 81, that's a US thing. So in other countries, it tends to be 100, sometimes 150, so, 81 versus 100, 100 does seem to maybe be a little bit more effective, which is interesting and not, of course, what we have available here. So what should we do? So, the who, I'm gonna talk about a little bit more in a moment, but in general, we are treating women with risk factors according to the US Preventive Task Force guidelines. When should we do it? We usually start it at 12 weeks, but we should start it by 16 weeks to be the most effective. If someone hasn't started it yet, it seems that it may still be effective up to maybe 24 weeks, and then beyond that, it may not be beneficial to start. And it seems that dosing at night is actually more effective on that platelet function changes, and I should know why, but I, I don't know why. I think we do actually have some understanding of that, but. I cannot recall it. It's, it's really interesting though. So if someone can tolerate it at night, then that's what we recommend. So how much should we give? Of course, 81 mg is standard. That's what ACOG says and the US Preventive Task Force Services say and what most people do. But at some institutions, including ECSF, we actually consider and often use a double dose, so 162 mg in women that we deem higher risk, you know, kind of hand wavy, like who, who gives you that bad feeling, like, They've had preeclampsia twice before. They have chronic hypertension and lupus, like patients that are really high risk, not just that it's their first pregnancy and their BMI is 31, you know, the, the women that's really that we deem using our, you know, non-evidence based feelings, feelings, but that are, are higher risk, and the reason we're doing that is we're trying to get closer to the studies that have shown that being over 100 is probably a little better. It would be great if we had 100, you know, to use or 150. It seems that 160 is safe, but it is a little bit more than the trial doses, so, you know, that's something to consider and something that we do pretty routinely at UCSF. And of course, just as a View here, these are the US Preventive Task Force guidelines. There's other guidelines. The older ACOG guidelines were less aggressive, so less people would get aspirin if you use the older ACOG guidelines. More recently, they've said we should just use these. It seems that using more liberal guidelines is better and will, is, is now recommended. So, there's the high uh risk factors at the top, and so this is any one of these, aspirin. And the moderate where it's 2 of those, and then low risk is, you know, no risk factors essentially. So if you treat People who have high risk based on that, the number needed to treat is about 50. If you treat a low-risk group, the number needed to treat is, of course, a lot higher because their chance of getting out of preeclampsia is so much lower. So These risk factors are helpful. They can, if you use them, it helps you apply aspirin just to the people who need it because of the difference in this number needed to treat. But if you look at the positive predictive value of these risk factors, it's not great. You know, many people have these risk factors, and they don't get preeclampsia. We know that, and it's just a risk factor. So it's anywhere from 8 to 33% depending on how many you have and how bad they are. So, the risk factors on their own, because they can miss people and because they can overpredict. There is another thought, which is, should we just be doing aspirin for everyone, because we don't have other tools, clinical risk factors is low positive predictive value, using uterine artery Dopplers, which I have some slides on, but I probably won't get into his low positive predictive value, biomarkers, and it also seems aspirin may have benefits beyond preeclampsia prevention. There's been several studies in the last 2-3 years about universal aspirin use in other countries, reducing the rate of preterm birth. So, It's, it's interesting. It, it may have benefits beyond preeclampsia prevention. So should we just be giving aspirin to everyone? So what are the risks? It actually seems really, really low. We've done this so long for so many people, and unless someone has a contraindication, there's no demonstrated harm that we have found. Specifically in the first trimester also seems low, so you can't even consider starting before 12 weeks. If you're using it for everyone, well, maybe some people are not gonna use it cause it just becomes like, uh, prenatal vitamins, not like, oh, my doctor said I need this cause I am at high risk, so that's something people have proposed that it will seem less important if we just do it for everyone. That's not evidence-based yet, but that's a possibility. What about the cost? Well, yes, it's a cost for sure. It's one of the cheapest medications that we use, but there is still a cost, and if you use it for all the millions of pregnant people, that's, that's not a, a small thing. But the benefits are that it makes it so much easier on us as providers, you know, we don't have to go through the screening form, make sure that no one missed it, and like, we all have missed people, and it just reduce, it takes the human out of the factor and out of the equation, and with all the things that we now have to do in these first visits, which are just getting bigger and bigger, and now we have to talk about carrier screening or cell-free DNA screening, and like all of this stuff, it's, it's trying to take one thing out of that. And even though there's cost, if we reduce more cases of preeclampsia, it may actually be cost effective, and there's actually some studies on analyzing the potential cost effectiveness that actually seem to suggest it would be cost effective because of the additional cases of preeclampsia that you might prevent even in low risk women. Not yet recommended, but interesting. OK. As a reminder, there are some contraindications, some platelet disorders, some severe liver dysfunction, ulcers, obviously aspirin allergy, and nasal polyps, interestingly, because of this association with this asthma-induced, aspirin-induced asthma. But pretty rare. Most people can get it. I stuck this in here as a, cause I consider this a prevention for preeclampsia, so that tighter blood pressure control will also reduce preeclampsia but we already talked about this. Uh, this is just interesting. There is a study going on in Utah with using Cimzia that some people are on for autoimmune conditions like Crohn's disease, which may have benefits in certain high-risk women for preeclampsia prevention. So it's just an interesting study, um, that we don't need to talk about. Any aspirin, let me, there's something in the chat, let me check. Oh, it's 121. OK, thank you for that time check. I'm just going to kind of look through any questions? Uh, how long do you continue aspirin postpartum, or do you continue? They don't continue it postpartum, which is such a great question, like what, when should we stop it? When has it had its benefit and why on earth do people get preeclampsia postpartum when the placenta is gone? It's, it's just leftover endothelial factors that were already kind of stirring things up. I, we don't understand, so. There are two general schools of thought with, with aspirin. Stop it at 36 weeks as you're approaching delivery, or continue it up until you have your baby and then stop it. At this time, there's no rule or protocols for continuing it postpartum. Maybe someday there will be, maybe someday we'll find a benefit, but it seems that we stop it once the placenta is out. Most of us, myself included, will just tell people continue it up until birth. We just don't know if there's an additional benefit for those last few weeks of pregnancy. But the largest benefit is probably aspirin during that second trimester when the placenta is forming, so probably the, the greatest benefit is gone, and if someone is sick of taking pills, I always tell them it's fine, you know, you're 36, 37 weeks, if you just don't want to take it anymore, it's completely fine. So I stop it anywhere between 36 weeks and delivery, and at least at, I know at Alta Bates and at at UCSF are. Delivering providers and anesthesiologists don't mind the use of aspirin. If it's the low dose aspirin, it's not a risk for excess bleeding at delivery. Um, I have a question, and it's come up in our group a lot just in terms of like who we start aspirin on for prevention, and I guess your discussion about universal aspirin, I think helps a little bit in your perspective, but like, so we're at a community health clinic, basically almost all of our patients are low income, which is already like one moderate risk factor. So if they're like no liri, which you know we have many first time moms, essentially that basically means that everyone and it has a feeling of, yeah, then we are all we can almost basically find reasons to start on everyone and yeah, I guess. Yeah, and it often feels weird to do that and just like, what, why are we using these risk factors if everyone is just high risk? So, yeah, sorry, there's a trauma call overhead. Um, yeah, I mean, I, I still follow that and I think yes, often it in my group of patients as well, like pretty much everyone has aspirin and everybody, cause they all have some medical condition and Yeah, it, it does encompass a lot of people if you apply the USPF task force guidelines. It, it's, it's a lot. And I, I personally think that's OK. I feel very comfortable with the use of aspirin and I always have, if you have the time, which of course I have a lot more time as an MFM like we get a lot of time to talk, that's what we do. Like I have that conversation with patients as much as I can to try and bring them in and explain why and some people choose not to, but obviously most of the time we don't have the luxury of that time and I think it's OK to, to use it liberally. Right. I'm gonna skip the prediction because it's all kind of theoretical stuff. We know there's, there's a lot of Risk factors that we know increase people's risk, obviously with conditions, um, Uterine artery Dopplers is something that we've tried because if the spiral arteries haven't relaxed, you should have higher flow or different flow in those uterine arteries, and we, yes, we actually can see that it actually, there is a a decent positive predictive value of those uterine arteries compared to not using them, um, but we don't do it universally because The numbers are still not great. We, a lot of sonographers and MFMs don't know how to do that, and we don't have anything to do with it. So you find someone's at high risk for preeclampsia, well, Most of the time that we will already be on aspirin and we, we just don't have anything else to do. So, biomarkers not yet helpful. Lots of things have been studied. So, yeah, the summaries that preeclampsia can be tricky to diagnose in some situations. We don't fully understand why it happens. Management is sometimes straightforward and sometimes gets really complex, and we do a lot of like hand wringing and, and trying to figure out each individual patient. With prevention, we have aspirin, which many, many of our patients will end up being candidates for better hypertension control in people who already have hypertension, maybe some studies coming down the, the line. That's about it. Just barely got through.
