Does Modern Medicine Underestimate the Power of the Placenta? Conversation with Dr. Mana Parast, Part II

This week's episode is a continuation of my conversation about developing our skills to best use the placenta as a diary of intrauterine life. 

Dr. Parast shares more of her work about the promise of placental pathology to better understand both the pregnancy that has been completed and potentially to better predict what a future pregnancy could hold. 

We also talk about: 
* how to prepare your body for pregnancy
* what biomarkers in conjunction with new screening methods can do to help with prediction during a pregnancy
and
* how studying the placenta could yield insights on aging more generally 

Transcript

This week's episode is a continuation of my conversation about developing our skills to best use the placenta as a diary of intrauterine life. Dr. Parast shares more of her work about the promise of placental pathology to better understand both the pregnancy that has been completed and potentially to better predict what a future pregnancy could hold. We also talk about how to prepare your body for pregnancy, what biomarkers in conjunction with new screening methods can do to help with prediction during a pregnancy and how studying the placenta could yield insights on aging more generally. 

Welcome to making sense of pregnancy. 

This show is a new pregnancy reference. I'm finding and talking with experts doing cutting-edge work to better understand what we do and don't know about pregnancy. And what you can do to better understand your own [00:01:00] experience each week, I'll be talking to scientists, doctors, and researchers who are trying to uncover the many mysteries that still exist in reproduction, giving you the most current evidence-based way to approach this enormous transition in your life. 

I hope it will become your go-to source for how to make your pregnancy better. Please enjoy the rest of my conversation with Dr. Mana Parast.

Paulette: So I'm having a baby and I go in and have a delivery and it seems fine. Can I ask for a placental pathology?

Is it something that a patient can ask for? It has to be ordered by the doctor and it's not easy to get. 

Dr. Parast: That's a good question. , the College of American pathologists,, has designated a list of criteria for when a placenta should be examined. Those are simply recommendations, though they were, , I think they initially came about in the late nineties, and they have most recently been updated over the last year or two, and they generally these indications for placental examination fall into two categories.

 Three categories basically, , some sort of maternal disease, some [00:02:00] sort of, adverse, pregnancy outcome that's kind of lumped into, mom and then, , adverse neonatal outcome. So if the baby goes to the NICU, if the baby's growth restricted. And even, those indications include if the placenta itself looks abnormal, if the cord appears to be, abnormally inserted or there is something, macroscopically wrong looking about the placenta, , those are kind of like the three categories.

In the absence of that, , I'm sure a patient can ask for it. It's not from my understanding. Part and parcel of your,, coverage of your delivery. There is not an additional charge, above and beyond that. So I would say that, yeah, especially if you think, there is always, fetal growth restriction cases, the question of, was my baby really small, or, you know, I was a small baby, so if I have a small baby, maybe the baby was just constitutionally small, and that doesn't matter, but, you never know, and if there is the opportunity to have the placenta examined, I would say it's good to do so. 

So if I [00:03:00] had to do it over again, I might talk to my OB before I gave birth to say, I would love to have the placenta examined if there's any possible reason to do it, because it has all this super useful information , for The trajectory I'm on and my new baby, whatever happens to the new baby.

So that might be something for people to consider. So we talked a bit about the placenta. Pathologists get it after the fact, but, a fair amount of your work is on looking at placental development, because it sounds like a lot of conditions that we could encounter in pregnancy.

are conditions that arise because of something that happened at the very beginning of placental development, when it attaches to the uterus, when it invades the uterus, all these,, points that are really important. And I'm wondering, one thing I saw in your basic research, , publications is your focus on the early, I'm gonna put this in quotes, environment of the placenta, , The article I read that you wrote talked about.

 Basically the, [00:04:00] those cells access to oxygen, in the uterus and other proteins that they have access to. And anybody who's following the longevity conversations will have heard of sirtuin, which is a protein that affects, mitochondria. Is that right? 

Yes. 

So if those things are among 

other things, 

I'm sure, I'm sure.

Right. , and I have seen a lot of people write about the importance of mitochondria for the oocyte and that early embryo., so I'm wondering if things that we do now to try to take care of mitochondria like improve NAD supplementation or something like that.

Can you imagine a time in the future when we would do that for moms, early in the pregnancy? Cause right now the protocol is you're on your own until like eight weeks and then you're followed by a doctor, but a lot is happening in those eight weeks. 

Absolutely. I would say that, perhaps, , especially patients that have undergone IVF might, might already know this, that, , the, [00:05:00] their reproductive endocrinologist, their IVF, , doctor will tell them, , it's best to sort of prepare.

Right. So we're learning, for example, that maternal obesity really affects pregnancy from the very beginning. So if there is, , ways to tackle, obesity associated effects on pregnancy, if it's possible, having, , treating that. prior to mom even getting pregnant is very important.

And, yeah, so IVF patients are , advised, in that manner, especially because they want to really increase their chances of, their cycles, going well from the very beginning. But yeah, it's very early right now. SIR2N1 And, , other, , changes that happen. , these are changes that are happening in specific cell types in the placenta. And as you mentioned, particularly , what are called the invasive, extra villus trophoblasts in the placenta. These are the. Placental epithelial cells that really behave [00:06:00] like cancer cells and invade , into mom's uterus and access maternal blood and provide, , that blood and therefore oxygen and nutrients to the placenta and therefore to the baby.

And when those cells don't function well, when they don't invade properly, you're setting up that pregnancy for preeclampsia and fetal growth restriction, but yeah, it is way too early for us to be able to say what can we do in order to optimize that, , uterine bed for receiving the placenta.

But that's my hope for the future is that, knowing, , especially metabolically, how do we metabolically prepare the sites, for these cells to invade the way they're supposed to. There's also a lot of, you mentioned, the immune system, there are a lot of, these trophoblasts crosstalk with maternal immune cells in the uterus.

So, we're learning more and more that, yeah, that specific crosstalk is really important for, again, how that, implantation site or the placental bed is prepared, to receive the placenta. 

Yeah, [00:07:00] I interviewed someone who looks at recurrent miscarriage, and he was saying there is some conversation going on between the endothelium and the, Embryo to figure out where to implant and 

His theory was we might be seeing recurrent miscarriage in.. women for whom the conversation is off between the endothelium and the embryo. Somehow the endothelium is doing some kind of screening work with each embryo at CS. 

So every embryo gets to implant whether it's going to be successful or not, but it does suggest that there's a lot going on Absolutely, at all those early stages and it would be interesting to see OB care Weighted a little more towards the beginning of the pregnancy once we understand better what's going on and can Potentially interject in that.

So to that end A couple questions here. One is I know things like the [00:08:00] NIPT the non invasive Prenatal testing is using the cell free DNA from the placenta right now to predict trisomies Basically, have you guys found if there's any other use for that? That blood data.

So, , not my group in particular, but definitely other groups at our Center for perinatal discovery and also around the country and around the world are looking at that for sure. And, not just, with cell free fetal DNA, but also circulating RNA. So what's called X RNA or extracellular or, RNA that's circulating in, vesicles, around the body.

So there are , many groups that are trying to, , use that as, , biomarkers for, , preeclampsia for, , preterm birth, , the difficulty, , with the RNA work right now is standardizing it across, RNA it's not a very , [00:09:00] Stable, , compound. And so, , how the different groups isolate that RNA.

And, what are the cutoffs that used? I think that's a big conversation , that's being had right now, but there's definitely a lot of work happening in that area. Also, , now with the growth of proteomics, so identifying, various proteins that are. derived from the placenta that are either increased or decreased or what's called metabolomics.

So metabolites, again, that are potentially derived from the placenta that are altered in, , various settings. And I think even a combination of all of these things potentially in the future could, set the stage for identifying, , what's going on in an ongoing pregnancy.

 So another, , way in which your lab is looking at the early phase of pregnancy as opposed to the placenta once it's done is to grow these organoids. Like little baby placentas, , in addition, you can watch them develop to see what the development looks like. I'm wondering if there's [00:10:00] any way to intervene with a placenta during pregnancy right now, , or even monitor it in a way that's more effective than MRI or 3d ultrasound, or do you think those things are sufficient?

So, , those are very good questions. So with regard to imaging, I know there are multiple groups, , that are, basically pushing the field forward in terms of using specific types of, ultrasound and MRI maternal vessels were the first foray into this field, but now looking inside the placenta at the fetal vessels in the placenta and what's going on.

I think we're making a lot of inroads in that. I don't think that is going to be sufficient by itself. We do need the biomarker. Side as well. This is again, if you think about cancer, it's the same kind of thing , you don't ask, should we image this patient or should we, draw blood you do both, right?

Yeah, and you say this is where the tumor is and this is where it's growing but you draw biomarkers Oh my god, PSA is elevated. So you worry about [00:11:00] prostate cancer, etc. So , same exact thing with the placenta. I think the biomarker, development side really needs to be pushed forward and as much as I think, what you're talking about in terms of being able to look really early on in pregnancy and affect , that is the ultimate goal, but right now, , where the field is going in terms of Being able to, for example, if you can identify fetal growth restriction in utero, right?

So baby's not growing well, this is usually detected, , in the late second or early third trimester, and, there are multiple groups that are looking at,, how do we target the placenta And, , potentially, , fix the fetal growth restriction, particularly if, this is happening really early on, and we're not sure if the baby is gonna, make it to the, , viable stage, how do we tweak the placenta, in order, , to improve its function, and, fix the fetal growth restriction in utero?

Well, it's really [00:12:00] important. Before going in and targeting the placenta. This is where I would say that biomarkers are really important. You don't want to just assume, for example, that the placenta has a vascular problem or assume that there's an inflammatory problem. You need to know what's going on.

going on so that you can target the placenta correctly with the correct, growth factor or other means of fixing the problem. So having biomarkers that tell you, what is the process that's, , happening in the placenta. Essentially, what we need is a placental function test, right?

So right now we have like liver function tests if you have GI symptoms and you go in, they draw blood and some labs come back abnormal and your doctor will tell you, hmm, there's something funny with your liver function. your liver. How do they know that? Because there are specific liver function tests that tell you that.

So essentially what we need is those kinds of tests for the placenta. , is there an inflammatory lesion? Is there a vascular lesion? Is there a combined inflammatory and vascular lesion? Before we can then see [00:13:00] placenta in this manner, in the latter half of pregnancy and then sure.

Yeah, I think long term, the idea would be, can we figure out really early on in pregnancy, if there is something, some sort of bad thing brewing and, fix it that early on such that, there's nothing to, , deal with later on in pregnancy, that would be the dream.

 And it's a beautiful dream. But it sounds like what you're saying is you can't interrupt a negative placental process at this point, even if you can use the cell free RNA to predict that the probability of preeclampsia is relatively high because we have these fragments in your blood that suggest that.

All we can do is manage that circumstance. We can't reverse it. 

Exactly. , I think that's probably the worst thing to have to tell someone, , who is pregnant, who is, facing an adverse outcome and if you read, anything about how do you, cure preeclampsia, you deliver the placenta.

, that's ridiculous. We [00:14:00] definitely need to make progress. I have also heard conversely what do we need predictive biomarkers for? What are we going to do for that patient anyway? Maybe it's better that they don't know. I think patients would disagree with that as well.

So, , we need to push both fronts. We need to push the biomarker field forward. be able to identify these patients, earlier, maybe even before they develop a symptoms and then, later on, figure out how do we use that in order to target the placenta with the correct therapy, be it again, vascular or some sort of anti inflammatory, et cetera, in order to correct course. 

So currently we don't know what causes preeclampsia. But it's believed that it has to do with abnormal placentation 

when the placenta attaches itself or invades the uterus in an abnormal way, which is why it's sometimes suggested that delivery of the placenta ends the problem. 

But even when the placenta is removed, The inflammatory cascade that the abnormal attachment initiated in the mother's body. [00:15:00] Can continue to affect blood vessels throughout the body and affect a host of different organs. The condition usually resolves within six weeks after birth, suggesting that changes caused by preeclampsia. 

Take time to normalize even after the placenta is delivered. And it's also the case that some women experienced preeclampsia in the postpartum, suggesting that factors beyond the presence of the placenta contribute to the conditions impact on the body.

Yeah, as someone who had an undiscovered autoimmune problem that tried to tank my pregnancy halfway through, I would love to plant a flag , in the ground that says more information is better. Hiding the ball from the pregnant person is a terrible idea better to know and have a plan to deal with 

a fear of uncertainty for the fetal development or whatever it is.

The shock of having something, go awry with a pregnancy , is hard enough. So I, I totally agree with that. One other thing I heard you talk about [00:16:00] was, umbilical cord donations. Yes. 

umbilical cord blood donations. Is it 

blood or is it, are you saving the cord in your work? 

Oh, well, in our work for stem cells, we actually, derive cells directly from the cord.

Yeah. So we have, we have an ongoing study at the center for perinatal discovery where patients can donate their placentas. And what we do is we, bank,, not just the tissue from the disc itself. But we also bank, cells from the umbilical cord. And those are the cells that can be reprogrammed, and made into the stem cells that can then, give rise to, organoids.

And we can discover, , again, what went wrong with that particular pregnancy early on. 

And are you looking for donations or you have all that you need? 

 Our IRB right now is confined to UCSD, we've definitely gotten a lot of interest from even patients delivering in and around San Diego, but unfortunately our IRB doesn't cover that.

 And [00:17:00] honestly, we need more funding than cells at this point because reprogramming of the cells is not, very easy. And, , so more funding would be, , welcome, , before. More donations 

based on your work with those things. Do you think it's useful for me as a pregnant person to bank my own umbilical cord or save my placenta or do something with it?

Or what would your advice be? 

Yeah, so I know patients bank, cord blood. , I don't know about banking cord cells at this time because, , the clinical utility of that, , is, many, many years down the line, the clinical utility even of, The cord blood that's banked, I think, , has sort of come under question.

 So I would say, I think more than anything else, knowing what your placental pathology, was, in a particular pregnancy and , if, if it wasn't read, by, perinatal or placental pathologist, , getting a second opinion, particularly if you had an adverse outcome, I think that's more warranted than getting any cells [00:18:00] banked right now.

Okay, well, even that is good advice because I remember having regret at not having banked any of those things, although my kids are 20, so I'm not sure it was that big a thing when I had kids. But, but it sounds like if you're going to put effort towards, , a keepsake from your pregnancy, it should be a pathology report rather than cord blood.

Absolutely. Absolutely. 

 And I'm going to ask you this last question, , with some sense of what you will say to this based on what you've already shared with us , but if you had a magic wand and could change the way pregnancy is handled today, what are your top three picks? 

Oh, wow. I would say let's.

 I feel like a lot of things need to happen before I can, say what I wish. So that's 

why I've given you the wand. 

I would wish, I would wish that, , we will have finished large multi center prospective trials that include placental [00:19:00] pathology. This is both on the obstetric side and on the neonatal side.

Such that we would then be able to, have a patient that's admitted for X, Y and Z, , be able to draw blood from mom and say, this is what's going on in their placenta again, have a placental function test that's, telling us what we can do that can get confirmed on placental pathology.

And then we would be ready. If not, while the patient is still pregnant, as soon as the baby's born, we would be ready with some sort of, , way to counteract what, , that, insufficient placenta provided to the baby or did to mom that could, , at least partially reverse, , the damage to mom's vessels, for example, or that can correct, some of the epigenetic programming that happened with the baby.

 If you gave me a wand, , that could do anything, that's what I would want. 

Okay., that's a good call. Let me ask one question though. , placentas are, you want to examine them if something has gone wrong in the [00:20:00] pregnancy, which implies to me that when a placenta works perfectly, we know exactly what's going on.

Yeah. That's also an interesting question because, again, the current recommendations right now from the college of American pathologist doesn't include looking at the placenta when everything is otherwise Well, , having said that, again, to the extent that, if there was An infinite amount of, funding available and a prospective study was being done , for example, like it was done with new mom to be study, following all nulliparous patients, I would say let's do placental pathology on all the patients, regardless of outcome.

 In the studies that we've done at our center, The chance of finding something abnormal in an otherwise normal pregnancy is significantly smaller, but we definitely have seen, for example, chronic volitis of unknown etiology in an otherwise normal pregnancy.

 Normal [00:21:00] placenta, normal pregnancy. And so who's to say that again, if we were to do these prospective studies, we know this lesion has a 10 to 15 percent chance of recurrence. So what if, in a subsequent, it didn't do anything to this first pregnancy, everything was fine, but what if the subsequent pregnancies were affected and the knowledge of, knowing that this patient had this lesion and therefore maybe following her just that much more closely in a subsequent pregnancy might help her in the second one.

That's definitely, I think in an ideal world, that's what we should do. 

Well, even beyond that, , Placentas are our only organs, correct me if I'm wrong, that age so quickly, right? They only last for nine months at best. So wouldn't that give us potentially information about longevity and aging and how organs weather and things like that?

Definitely. The question of whether, the placenta could, give insight into, [00:22:00] additional. information, for example, into maternal health or even, for neonatal, outcomes, , the chances of disease development in that particular, , baby's life later into adulthood.

Yeah, again, , The possibilities are endless and we should definitely explore them all. 

Okay. Well, I'm going to encourage everyone to talk to their OB about placental pathology and, , and to look at your work cause it's just amazing and, I'm so grateful that you're doing it. 

Thank you so much.

Thanks for your interest. 

Thanks for talking today. 

Thanks again to Dr purest. For sharing some of her basic research and clinical work with us today. Reading some of her work. And speaking with her, it's clear that the placenta has a lot of currently untapped potential. Scientists are starting to understand the long lived physical effects of pregnancy on a body. And having a more developed sense of whether diabetes or hypertension is in your future, or if your baby is at [00:23:00] risk in the future to develop certain health issues. Kids dramatically shaped your lifestyle choices in a way that can change your health trajectory. 

Andrew Childs. I appreciate some of dr. . specific advice. Rather than banking cord blood request to placental pathology. If anything is awry in the pregnancy. And make sure the placenta has been examined by someone with the appropriate training who can read the information encoded in it. Thanks for listening. 

If you like this show. Rate and review it and please share it with friends. We'll be back next week with more amazing research, pushing our understanding of pregnancy forward.