Aspirin in Pregnancy

Dr. Alicia Power and Dr. Michelle Morais, Assistant Professor in the Department of Obstetrics and Gynecology, and Maternal-Fetal Medicine specialist at McMaster University Medical Centre, discuss aspiring in pregnancy - how it affects the placenta, who we should be considering recommending it to, how to estimate risk and have conversations with patients around it, specific ways of taking aspirin, and any concerns around delivery for the delivering person or baby who may be still on aspirin.

Resources:

• The Fetal Medicine Foundation Assessment of Risk for Preeclampsia (PE): This application uses Bayes theorem to combine the prior risk from maternal factors and medical history with the results of various biophysical and biochemical measurements to estimate the posterior risk for PE. 

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Transcript

 [00:00:50] Dr. Alicia Power: Welcome to the Pregnancy for Professionals Podcast. Dr. Michelle Morais is joining me today from Hamilton, Ontario, where she works, and we are going to do a podcast [00:01:00] today on aspirin and pregnancy, how it works on our placenta, who we should be considering recommending it to. So Michelle, why don't you get started on telling us a little bit about yourself, and what you like to do outside of medicine as well?

[00:01:14] Dr. Michelle Morais: Oh, first of all, thank you so much for inviting me to be here today. I'm really excited to try and share some information that hopefully has a bit of evidence behind it that will help everybody in their day-to-day work. So I work as a high risk obstetrician. I live in Burlington and work out of McMaster Hospital, which is in Hamilton. We deliver about 4,500 patients a year at the high risk Obstetrics Center that I work in. But we have a catchment area of obviously a much larger area that we help to care for. My other roles include being a Program Director for The Obstetrics and Gynecology Residency Program. So I'm really invested kind of in the education of trainees and a lot of interdisciplinary work that we do through that training program. Outside of work I am a wife and a mother of two children. [00:02:00] So I have a nine-year-old and a six-year-old and we also have a 12 year old golden retriever. And I think one of the things that I enjoy doing outside of work would be spending time with family. We have a cottage about an hour away, so we love getting away there because we just unplug and really enjoy you know, the lake and the trails and things like that are around. So just getting outdoors.

[00:02:23] Dr. Alicia Power: Amazing. Thank you for introducing yourself. So why don't we get into it? So we're going to talk about aspirin and pregnancy, and this is a big topic with lots of interesting evidence emerging over the past few years, I'd say. So we would want to chat about aspirin and pregnancy. Why would we use it? Who would we recommend it to? Any risks associated with it and any kind of specific information that we should be giving patients. So the dosing, timing, all that type of stuff. So why don't we start with kind of, why are we talking and hearing so much about aspirin in pregnancy?

[00:02:56] Dr. Michelle Morais: Yeah, I think, over time, we're understanding more and more [00:03:00] about the physiology behind some different complications in pregnancy. Preeclampsia is the most well-known complication. So that would be blood pressure issues that develop in pregnancy, along with other manifestations that could include symptoms that a patient has or could include changes in blood work or changes in some of the fetal surveillance that's happening. And given up to 8% of the worldwide population develops preeclampsia, it's super common. So understanding if there are ways that we can help reduce that risk is a huge driver behind the information related to aspirin getting out. Now aspirin probably doesn't only have applications for the prevention or preeclampsia, but that's probably the area that there's the most robust evidence behind. I think some other reasons why there's more and more information about aspirin is it's not very expensive compared to a lot of other treatments that are available. And it's also widely available. Known to people because we've been using aspirin for years and years for so many other applications. So it's [00:04:00] also a natural thing to gravitate towards because it is something that's so accessible to most people, I think.

[00:04:05] Dr. Alicia Power: Yeah, we're doing some work in our community around hypertensive disorders in pregnancy. So pregnancy as a stress test and then how do we, as family doctors care for people, long-term when they've been identified as a bit higher risk of cardiovascular disease ongoing. And so that's hypertensive disorders in pregnancy, EGR unexplained, stillbirth unexplained, preterm birth, gestational diabetes. I feel like I'm missing something, but that group would be the hypertensive disorders in pregnancy group.

[00:04:31] Dr. Michelle Morais: Yeah, absolutely. So much of it is mediated by the placenta and it's not just high blood pressure. It's also like you mentioned growth restriction, you know, placental abruption, stillbirth, miscarriages, like the, the ripples of how the placenta works in pregnancy have so many different impacts for sure.

[00:04:47] Dr. Alicia Power: Yeah. And so aspirin, how is the, how is it actually affecting the placenta? So how has the, what's the pathophysiology of actually recommending aspirin and pregnancy?

[00:04:57] Dr. Michelle Morais: Yeah. So that's a great question. We know [00:05:00] from studies about the physiology of aspirin. That it can have an impact on a number of different pathways. At the lower doses that we typically use in pregnancy, the way that aspirin works is it helps to reduce the amount of something called thromboxane A2. So it's a cycle oxygenase inhibitor. And thromboxane A2, when it's unopposed helps to promote vasoconstriction and platelet aggregation. So basically aspirin helps to limit the impact that can have by promoting less basal constriction or less, sort of, constriction of the blood vessels and less clumping of platelets. And we know that both of those things are parts of what can lead to preeclampsia or other placental complications in pregnancy.

[00:05:44] Dr. Alicia Power: So it allows blood flow through to the placenta more effectively.

[00:05:49] Dr. Michelle Morais: That's right.

[00:05:49] Dr. Alicia Power: That's right or decreases the lack of flow. If

[00:05:53] Dr. Michelle Morais: Yeah, Absolutely.

[00:05:55] Dr. Alicia Power: Awesome. Thank you. So who, we've talked a bit about why we're hearing so [00:06:00] much about aspirin and how it can work to effect that placenta in pregnancy. So who should we be talking to about using aspirin and pregnancy? What are the kind of the risk factors? Either in previous pregnancy or from a, just a, person history type point of view that we should be chatting with people around starting aspirin in pregnancy or recommending it.

[00:06:19] Dr. Michelle Morais: Yeah that's actually a big question to unpack because the different societies across the globe, don't all agree exactly how we should approach that question. I think as a general starting point there are different ways that you can look at patients so you can look at what we know about them before they enter pregnancy, what we know about them during their pregnancy, from previous pregnancies, I should say, and what we know about them during their current pregnancy. So you can use a variety of clinical risk factors. You can use a variety of biochemical markers and then other physiologic markers in pregnancy. So when we talk about like past medical history issues, that could include [00:07:00] people who have longstanding high blood pressure or chronic hypertension. It can include people who have underlying, other chronic medical conditions, such as anti.

[00:07:10] Dr. Alicia Power: Antiphospholipid antibody syndrome.

[00:07:13] Dr. Michelle Morais: Yes.

[00:07:13] Dr. Alicia Power: Did I take the words out of your mouth?

[00:07:15] Dr. Michelle Morais: You did. That's, that's a big one. Things like pre-existing diabetes in pregnancy, so either type one or type two. People with conditions like lupus or other inflammatory conditions. Those are all part of a group of patients who just based on those pre-existing medical conditions will be predisposed to having high blood pressure complications. Potentially other placental immediated complications in pregnancy, when we look at previous pregnancy history some of the things that stand out would include previous history of a baby who was growth restricted, previous pregnancy impacted by either hypertensive complications, including just gestational hypertension or preeclampsia as a diagnosis, especially if it resulted in an early delivery. So preterm [00:08:00] delivery would be anything prior to 37 weeks. Those are going to be the group of people that are at the highest risk of developing recurrence issues in a future pregnancy.

[00:08:09] Dr. Alicia Power: Now can I ask a clarifying question around, yeah, people might ask: what if they were induced before they preterm or what if they had a C-section preterm because of that IUGR? That probably means that their IUGR was quite significant, therefore, yes, that would count even if it was a idiopathic or we caught no is idiopathic what we "cause" preterm birth, as opposed to them naturally going into preterm birth. That's what we're talking about. Right. Even higher risk.

[00:08:34] Dr. Michelle Morais: Yeah. Exactly. And I asked her genic things like where we intervene. It would definitely put people at further risk because it means that the severity is that much more, that we would be concerned about the risks of prolonging pregnancy in those cases. So in terms of some other previous pregnancy factors. I think that's probably the bulk of them as you know, any placental immediated complications that have happened before, so growth restrictions, stillbirth, placental abruption. And also the [00:09:00] risk of hypertensive complications. And then in terms of the things we can see in a current pregnancy, what does their blood pressure look like at the start of the pregnancy? Have they done any screening in their pregnancy for down syndrome that may also give us information about their risks for placental problems in this pregnancy. So all the provinces have their own screening strategies. I'm in Ontario, so in general, first trimester screening would be the most common strategy for screening. And as part of that, we include markers, one of which is called placental growth factor. Of all of the markers that you can look for, that's probably the biochemical marker that has the strongest weight behind it in terms of identifying pregnancies at risk. It's not good in isolation, but when you combine it with some of those other factors like what we've chatted about at this point. It can be a very helpful marker to include.

[00:09:49] Dr. Alicia Power: It can trigger you to keep a closer eye on things in the pregnancy as well, right?

[00:09:53] Dr. Michelle Morais: Yeah, of course. And then also including whether you've looked at any parameters on ultrasound that can be helpful. [00:10:00] Sometimes centers will look at uterine artery blood flows. So basically the blood flow to the uterus and the placenta. You can look at it at the same time that you would do a nuchal translucency ultrasound. So in that 11 to 14 week range, and you can also look at it later as well. The idea behind looking at it early is that we think that there's sort of a two-stage hypothesis to how a lot of placental complications happen. One is that people have underlying risk factors that predispose them to placenta that just doesn't develop those sort of normal, deep connections to the urine vasculature. And in those people, if there's further stresses that lead to oxidative stress and release of inflammatory markers, then they get the clinical manifestation of those placental issues. So if we can do something that limits transitioning from stage one to stage two, then you can hopefully reduce the likelihood of having some of those downstream impacts. And we think that aspirin helps intervene at that earlier stage, when it's given at that earlier stage [00:11:00] and doing screening at that earlier stage really helps to identify the people at highest risk. So if you look at your uterine artery Dopplers in that 11 to 14 week range, and you're identifying high resistance or notching, that can be indicators of risks for future, then those are people that you can flag as being potentially who will benefit from interventions or added surveillance. There's a group called the Fetal Medicine Foundation, which actually has a really great website that kind of lists out all of these clinical risk factors and some of the biochemical and physical like physiologic parameters that you can assess. And you just input all of the information and then it gives you a number and it tells you your patient's risk of having preeclampsia is 1 in 100, 1 in 1000, whatever that number may be to help you to stratify the person who is going to be most likely to benefit from using aspirin as a preventative strategy.

[00:11:55] Dr. Alicia Power: And what kind of risk would you say recommend. K, it's probably a good idea for you [00:12:00] to start aspirin and pregnancy using that calculator.

[00:12:03] Dr. Michelle Morais: Yeah. So if your risk is over one in a hundred, you're in the group that would probably benefit from starting aspirin to prevent preeclampsia, in particular like preterm preeclampsia.

[00:12:13] Dr. Alicia Power: Great. So we'll post that in the show notes. That's a great, I've never heard of that resource. So thank you for telling me that I'm going to start using it, try it out. What about, so there's some other kind of, if you look at I don't know that ACOG guidelines, they have minor and major risk factors. So obesity, nulliparity, age over 35, can we talk a little bit about those kind of factors? And associated with kind of starting and stop and not starting?

[00:12:40] Dr. Michelle Morais: Yeah. There's a group out of Toronto that actually looked at a lot of those individual risk factors. Joel Ray tried to identify like which of those risk factors are the most attributable to preeclampsia and other placental issues. And really to try and drill down on what's the biggest things that you would see on a history, or see a, with your [00:13:00] patient that would make you really want to make sure that you target. So some of those risk factors like elevated BMI over 35, first pregnancy, multiple gestation are definitely in the mix, but in and of themselves as a standalone might not be enough to put somebody over that kind of one in 100 risk factor. If you have preexisting diabetes, if you have longstanding high blood pressure, underlying kidney disease, other auto-immune conditions, you're probably in the group of people that would benefit from taking aspirin even without any other risk factors. But people who have maybe some of those other, what we would call minor criteria, we have a couple of them together. So maybe you have a low PRGF and it's your first pregnancy and you're 40 at the time of your pregnancy, those things would probably in combination be enough to benefit being on aspirin. The fetal medicine foundation, it gives you that calculator as a way if you're not sure if it adds up to enough, then that can be a useful tool to assist. [00:14:00]

[00:14:00] Dr. Alicia Power: Perfect. Thank you. Another question I have. What about a previous history of gestational diabetes? Does that count or no?

[00:14:06] Dr. Michelle Morais: That is unclear to be honest. One of the things that can help you is to make sure that at an early part of pregnancy, you screen to rule out the fact that they've actually have underlying type two diabetes. So in an ideal world, they've had their screening, you know, at least six weeks after birth, but we know that sometimes that doesn't happen for a number of reasons. So if you look at somebody's A1C in an either random or fasting blood sugar at the start of pregnancy, that could help you to stratify somebody that would be higher risk versus lower risk. I think gestational diabetes in and of itself that's not underlying type two diabetes without other risk factors, maybe not enough to start aspirin all on its own, but I think it's an area that's much debated for sure.

[00:14:46] Dr. Alicia Power: Any other factors that we have, we've talked a lot about a lot of factors. Any other factors that we have not chatted about that you think is important to mention?

[00:14:54] Dr. Michelle Morais: I think we have covered the ones that I can think of.

[00:14:59] Dr. Alicia Power: I think so too. [00:15:00] So we've chatted a little bit about aspirin and pregnancy. Why would we choose it? And the pathophysiology about how it affects the placenta. Do you mind if we get into the nitty gritty of when to start, when to stop, what dosage, what time of day we should be recommending all of those pieces of the puzzle?

[00:15:17] Dr. Michelle Morais: Yeah, for so there's been lot of literature on basically parsing out all of those details. To our best understanding, it seems that starting between 12 and 16 weeks is probably your highest yield time to be most effective to prevent a preterm preeclampsia and hypertensive disorders of pregnancy. The dose that seems to be the most effective is probably using 162 milligrams of aspirin, or basically two tablets of baby aspirin. There's definitely a dose response relationship when you look at how effective it is, and so using 81 milligrams of aspirin may have some benefits, but it seems that using 162 has more benefit. In terms of the [00:16:00] timing of when to take it, it seems that for reasons that are not totally clear, that taking it at night before bed seems to have the most impact at preventing complications. When I chat with patients about that, I do always kind of preface that by saying if that's going to be a really challenging time for you to remember to take medications, I would rather you take it at a different time of day when you're going to be consistent at it rather than worrying about trying to remember to take it at night. Most patients say that they'll put the bottle by their, like their toothbrush, or you know, something else that they do as part of their routine, as they're getting ready for bed to help trigger them to remember. And in studies that look at sort of adherence to taking, usually people are like, 90% or greater, with taking it on a regular basis as scheduled. If you, if you're looking at the optimal time to take it, it seems at night seems to be, for reasons that are not well understood, that has the most benefit.

[00:16:54] Dr. Alicia Power: And does it matter if it's enteric coated or not?

[00:16:56] Dr. Michelle Morais: We usually just recommend taking the, like the regular [00:17:00] baby aspirin.

[00:17:02] Dr. Alicia Power: Perfect. Thank you. And in terms of decreasing the risk. What kind of risk reduction are we looking at? So say we're doing it for hypertensive disorders of pregnancy or preterm delivery, atherogenic preterm delivery due to hypertension in their first pregnancy. And then we have them taking it in the second. What kind of risk reduction are we actually looking at?

[00:17:21] Dr. Michelle Morais: Yeah. So the numbers that are quoted in the literature vary, but in terms of reducing risks of preterm preeclampsia in particular it seems that the numbers can be 30 to 50% or sometimes greater in some populations. So when you consider things that we do for other reasons it, it can have a huge impact for sure.

[00:17:39] Dr. Alicia Power: That is very significant. Great. Anything else that you think we need to know about aspirin and pregnancy?

[00:17:46] Dr. Michelle Morais: We usually suggest stopping at around 36 weeks. We know that aspirin lingers in your system for probably about five days or so after you've stopped taking it. There are some theoretical concerns about the impact it may have on [00:18:00] bleeding at the time of delivery. There've been some observational studies that raise concerns that you know, could it have an impact on the baby at the time of birth? Is there any increase on like intercranial bleeding or other concerns? So a conservative approach to try and limit the likelihoods that aspirin is still in your system at the time of delivery is to look at stopping at around 36 weeks. So that way we try and limit that impact as much as we can. But even for people who are on aspirin, right up until the time of their birth, from the best information that we have, it, it may be linked to an higher estimate of blood loss at the time of birth, but when you actually look at objective measures like transfusion rates and hemoglobin numbers, they're not statistically different between people who are and aren't on aspirin. So there may be some bias and estimating blood loss when we know people are on aspirin. And also to the best of our knowledge, it does not seem to have clear adverse impacts for a baby who is born when they're exposed to aspirin right up until the time of birth. So if [00:19:00] for some reason, somebody delivers you know, within that window when aspirin is still in the system, people don't need to be worried that it's going to cause major issues.

[00:19:09] Dr. Alicia Power: Great. And what about epidural or spinal concerns from our anesthesiology colleagues?

[00:19:15] Dr. Michelle Morais: Yeah. So when I've chatted with our anesthesia colleagues about that, they in an ideal world would prefer patients not to be on aspirin, leading up to the time of delivery, and we'd have them off it for that timeframe. But again, it's not a contraindication to being able to have a spinal or epidural at the time of delivery, if they have happened to have exposure to aspirin within the week or so prior to birth.

[00:19:38] Dr. Alicia Power: Perfect. Thank you. We covered a lot today. We chat a little bit about aspirin and pregnancy, how it works on our placenta, who we should be considering recommending it to, and a great website that we will put up in the show notes, the Fetal Medicine Foundation website that has a calculator that we can all use to kind of estimate risk and have conversations with patients around. We've also [00:20:00] chatted about the specific ways of taking aspirin, and any concerns around delivery for the delivering person or baby who may be still on aspirin, just from a timing point of view. So thank you, Michelle. That was really great.

[00:20:15] Dr. Michelle Morais: It was my pleasure.

[00:20:16] Dr. Alicia Power: We appreciate your time.