This Podcast Will Kill YouContent Warning: This episode includes mentions of miscarriage, pregnancy loss, pregnancy complications, traumatic birth experiences, and other potentially disturbing topics related to childbirth, pregnancy, and the postpartum period.
The second episode in our pregnancy series kicks off with a tribute to one of the most amazing organs: the placenta. We trace the evolutionary origins of the human placenta and examine how this organ allows for such an intimate and delicately balanced relationship between mother and fetus, as well as what can happen if that balance is disrupted. We then turn towards the pregnant person, exploring the broad physiological changes that happen body system by body system throughout pregnancy. Why do you pee so much? Feel nauseous? Have high blood pressure? We get into it all.
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We want to start with a disclaimer that throughout this series we feature explanations and stories that include some heavy material, including early pregnancy, loss, stillbirth, and other traumatic experiences of pregnancy, childbirth, and the postpartum period.
I'm Siena. I'm twenty eight years old and twenty eight weeks pregnant with my first child. It seems like a cliche, but my most daunting pregnancy symptom has been mourning sickness. I was aware that it was a misnomer and that it would not be restricted to the morning, but my biggest surprise was how frequent, long, and intense morning sickness is. I didn't expect to lose weight during the first time master or be woken up at one am because of the sudden urge to vomit. I'm not a stranger to vomiting. I've thrown up before with the flu, food poisoning, intense migraines, anxiety episodes, and of course after a night of having a little bit too much fun, as they say, But morning sickness is different. It feels similar to motion sickness, like you're on a boat all the time when there's nothing in your stomach. The urge to throw up is so intense, and you end up throwing up this thick, bright yellow fluid that looks like, honestly like lemon gatorade. I had my eyewatch give me sound warnings from my own vomiting, saying just ten minutes at this level can cause temporary hearing loss, and in my experience, the heaving has been so intense that even if I just went to the bathroom, I still end up peeing myself. It's just so aggressive. I actually have to wear diapers now just in the off chance that I happen to throw up, and that's just something I've accepted as part of my life now. With my pregnancy journey, it has been a challenge, especially with working full time and having to commute two and a half hours every day. You never know when morning sickness is going to strike, so I even have little bags in my car. My morning sickness started at week five and was pretty much all day every day until week twenty two. I got a little bit of a break, and then it started up again around week twenty six.
Although it's no longer all day.
It is truly just in the morning usually, and I've tried all the remedies that they tell you, ginger B six, unise pressure point bands, the list goes on. Zil friend has worked the best for me, but it's still very hit or miss on whether or will work on any given day.
When I went in from my first ultrasound at seven weeks, the doctor was able to see a gestational sack and a yolk sack, but no fetal pull. My doctor tried to assure me that it was possible I wasn't as far along as I'd thought, but I had been tracking my ovulation and I knew this wasn't a good sign, since this was a deeply wanted pregnancy. My doctor suggested we win week and do another ultrasound at eight weeks. The ultrasound showed some growth, a fetal pull, and a heartbeat. At first, I felt so relieved, certain that progress from the week before meant that maybe things would actually be okay. But then my doctor explained that the embryo was measuring less than six weeks and the heartbeat was only eighty four. When I got home, I turned to Google and found a study that said first trimester heart rates under ninety had a quote dismal prognosis The following week, when I was nine weeks into my pregnancy, I went in for my final ultrasound, which showed an embryo measuring only six weeks one day and no heart beat. My doctor was able to schedule me for a DNC the next day. My whole pregnancy, I had no indication that anything was wrong. I had strong dark lines on my home pregnancy test, and early blood tests showed my hCG doubling at an appropriate rate. I felt lucky that I was experiencing only mild nausea, but I did have all the usual pregnancy symptoms, and I had no bleeding or spotting at all, no cramping, absolutely nothing that led me to think my pregnancy wasn't progressing exactly as it should. I knew miscarriage was common, especially for women in their late thirties like me, but I always assumed that there would be some kind of outward sign. Going through a missed miscarriage led to feelings of profound betrayal. My pregnancy wasn't viable and my body had no idea. I feel as though I am no longer able to trust the signals that my body is sending.
New Thank you all so much for sharing your story with us, and really a huge thank you to everyone who has written in with their experiences. We read each and every single one of the hundreds of first hand accounts that people submitted, and we're so grateful and truly honored that you felt like you could share those with us, and we tried to include as many of your stories as possible and you'll hear more first hand accounts throughout the rest of this episode and the other episodes in this series.
Yeah, thank you again. It really was a huge privilege to be able to read all of your stories listen to all of the stories that you guys sent in. I genuinely like cried through, oh my most of whether it was happy or sad tears. So really, thank you again so much from the bottom of our hearts for sharing all of your stories with.
Us, truly.
Yeah. Hi, I'm erin Welsh and I'm erin Allman Updy.
And this is this podcast will kill You.
Today is episode two of our four part series, four parts on pregnancy. Yep, yeah, yet again coming to you from the exactly right studios.
I know, I feel like I'm getting more used to it now.
Yeah, it's good. It's going to be like this is this is the new normal.
This is the new normal. But before we get into this episode, we want to share a few words about what these four episodes will cover. And if you listen to our first episode, this will sound familiar to you, but in case this is your first time tuning in, welco just want to go everything over again. Yes, welcome, but we also want to get into the language that we'll be using and our goals with creating this series. So we decided early on to dedicate four episodes to cover pregnancy, one for E to trimester.
Not enough, we realized early on, but alas.
Very very much not enough. And yeah, and so we we did realize this, and you know, we're not going to be able to cover everything, and throughout the series we started to jot down like different ideas for future episodes, and so do keep in mind that, you know, if you're listening in and you're like, oh, I want to know more about that, Hey, send us your idea. Yeah, you know, maybe we will cover it in the future episod' sure we will, I'm sure that we will.
So knowing that this entire series will likely not answer all of your questions about pregnancy or cover every experience that a person can have during pregnancy. Pregnancy is an incredibly individual experience, as highlighted by all of our first hand accounts.
But what we aim to.
Do with this whole series is take you through the broad changes that we see in the human body and that you might experience during pregnancy, childbirth, and the postpartum period, and then also explore the historical and today especially the evolutionary aspects of pregnancy and childbirth. So each episode very roughly corresponds to each trimester. So last week we covered the first trimester, how you even know whether or not you're pregnant, and what was happening in very early development yep.
Then today and our second episode, we're going to talk about the amazing organ that is the placenta and some of the physiological changes which are really I'm so excited to learn more about what is happening. Okay, I can't tell you how I have two more episodes to like briefly go through, but we're gonna talk today about the placenta and these physiological changes that someone will experience as they go through pregnancy, including some of the complications that might arise.
And then next week in our third episode, we'll talk about childbirth itself, will cover labor, all of the different modes of delivery, and then the history of cesarean sections Yep, it's gonna be good.
It's gonna be good. And then finally, our fourth episode, which happens to be our season finale, will be about this concept of the fourth trimester, exploring the changes that happen after pregnancy, and we're also going to be talking big picture history about overall medicalization of pregnancy and childbirth and how the transition from home to hospital happened and some of the consequences of that.
We intend for all of these episodes to be inclusive of all families, and we recognize that not everyone who experiences pregnancy identifies as a woman, so we try wherever we can to use general neutral language such as pregnant person, while at the same time, we recognize that a lot of what we're going to discuss when it comes to medical bias during pregnancy and childbirth, both historically and today, really is the result of gender discrimination as well as racism, and so in those contexts we will also be using the term women and women, and throughout these episodes will be using terms like mother or maternal and paternal as these are terms that are very often used in the scientific and medical literature.
And we also want to acknowledge that there is no such thing as a normal pregnancy. Yeah right, there is no textbook pregnancy. There's plenty of textbooks about pregnancy, yes, but when it comes to pregnancy, there's no textbook example. Yeah, but we do want to also provide a baseline of the expected physiologic and anatomic changes that occurred during pregnancy, because that can help us to understand where these complications are coming from and what we actually mean by complication exactly.
Yeah.
And so now today we enter the second trimester. We shall but first first quarantine any time.
And we are drinking again.
Great expectations, great expectations. Yeah, I do have great expectations for this episode. I have great expectations for this whole series too. Yeah, remind us, Aaron, what is in great expectations?
Of course, it is blackberries and muddled with mint, some ginger ale and lemon. It's a plus.
Plusy Berita for a pregnancy series for obvious reasons. It's great And if you haven't already, please do check out YouTube where you can find the exactly right network channel that now includes our content, including a very special quarantine recipe by Georgia Hartstark made just for this series.
We're thrilled and we'll also be posting the recipes for this quarantining plus suber rita set on our social media and as well as our website. This podcast will kill you dot com?
Have you been there yet?
I get to shut it again to you?
On our website, This podcast will kill you dot Com, you can find so many incredible things. For example, you can find transcripts from each and every one of our episodes. You can find a good Reads list from uh where Aaron Welsh like story books mostly.
There's also a bookshop dot org affiliate.
Again, I was going to say that this time, I forgot it last time. We've also got merch, some pretty incredible merch that we're wrapping today. If you're seeing this on video. What else do we have? We have sources from every single one of our episodes. We have links to Bloodmobile who provide it's the music for all of our episodes. We've got a contact us form, a first hand account form. Have you been to our website yet?
No one is gonna want to go. They're like, I've seen it all. I've heard you talk about it all.
What else?
What else do I need?
Nothing new?
Nothing new?
Okay, shall we think? We shall?
I don't have any other business for today. Same so me Aaron all about the placenta.
I really can't wait. Good, Let's take a break out and then and then I'll get started.
Okay.
Hi.
My name is Tracy and I was thirty years old and went off the birth control pill. I had been on it since I was sixteen. Hoping for the best, my husband and I went for it. Three months into being off the pill, I was late having my period. It was a Friday night and I would normally be having a nice gen and tonic to greet the weekend, so I went to the store and bought a pregnancy test and immediately took it. It was negative. Okay, I guess I will be having a J ANDT and went into the kitchen to mix up my favorite cocktail. Five days later, on April first, I had a regular checkup at my o BA. She and I talked about what my plan was and that I was officially off the pill. I did the normal things at the appointment, you're in sample, etc. She was gone for a bit and when she came back into the room, she said, well, this is no April Fool's joke, but you're pregnant. WHOA Okay. I went home to tell my husband and thought I'd have a little fun with the fact that it was April Fool's Day. So, aside from being totally shocked, we were excited and a bit terrified. The next week, I went into the doctor's office to have my hCG levels measured. My doctor said they weren't great, but perhaps that is why I got a negative reading when I had taken the test. I would need to come back into the office a few days later to see if they had increased. But they had not increased. They should be doubling. At this point I figured this pregnancy might not make it. But the good news was as I had become pregnant and I could try again. A few days later, I went back in. Nope, not have any luck with the numbers. I went back several times over a couple of weeks, and it just didn't seem like this is going to happen. Then a couple of weeks into the process, I went in for yet another test, and my doctor came into the exam room and said, your numbers are all great. Everything had rebounded and I was exactly where I should be, So I thought I could get a little excited now from then on out, Aside from feeling very dizzy and sick for four months, she came bounding out a week early, a healthy baby girl, and now she is about to start her third year of medical school. You never really know how things are going to play out. And yes, she is the one who got me hooked on tp WK.
Why Hi. My name is Sarah and I live in Oxydghire, England, with my husband Mike and our younger son Ethan. Like many people, I didn't actually know my blood group until I became pregnant. Thankfully, being Reese's negative made very little difference to either of my first two pregnancies. I had the routine anti D injections and both boys were born full term and healthy. Sadly, my third pregnancy ended in early miscarriage. No reason was found and I was reassured that it wasn't connected to Reese's disease. However, when I became pregnant with Ethan the following year, signs of a Reese's reaction appeared very early. A blood test showed the presence of antibodies that were found to be resistant to anti D. Thankfully, the antibody levels remained low and regular skins reassured us that he was growing as expected. Each week that passed felt like a victory. Unfortunately, at about five months, the antibody levels rose sharply. Regular checkups continued as we monitored him for any sign of distress. The plan was supposedpone any intervention for as long as we could. We made it to seven months before the scans showed that he was developing fetal anemia. He needed a blood transfusion to limit the effects of the anemia and to give him more time before delivery became necessary. Despite signing all of the waivers who really weren't prepared for the transfusion to fail and for an emergency CEA section to be performed to save his life. I vividly remember the shock of seeing him for the first time, so small in his incubator, covered in wires, with a machine breathing for him. It just didn't feel real. I was dischonged a few days after Ethan was born, and going home without him was one of the hardest moments in my life. My husband's paternity leave was soon over, and I then faced continuing to recover from surgery while caring for our older boys and trying to visit the hospital as often as possible. Slowly, Ethan became stronger and he worked his way through the nurseries in a nicu and scaboo. Finally, after eight long weeks, we got to bring him home just a few days before his due date and without the need for any additional oxygen support. Our four pound Premium is now a happy, very tall, thirteen year old with a brilliant sense of humor. His difficult start in life has had no effect on his health, and most people can't believe that he was premature. We can never do enough to thank the NHS and everyone at the John Radcliffe Hospital in Oxford. Our lives are ritual with Ethan in them.
Around the world and over centuries, the placenta has held and continues to hold deep meaning. Some cultures revere it, honoring it with a special burial. Mummified placentas have been found in ancient Egyptian two ms. You know I would get back to ancient Egypt again and others consume it and recognition of its power. It's been used in beauty products preserved in a jar to ensure good health. It is varyingly seen as an older sibling, a twin part of the baby itself, a friend, the finest jacket. This reverence is not unwarranted. The placenta, at its core, represents the fundamental vital connection between a mother and developing fetus, a physical, metabolic, and immunologic bond. It's the first organ you make and the first you say goodbye to.
That feels so profound.
Because it is.
Am I going to cry about it?
I just teared up a little bit myself. I've read this over this a million times.
Yeah, but wow, aronkay.
It's the only organ ever connected to another individual. It filters waste, it transfers vital nutrients, and acts as an important immunological barrier between mother and fetus. It's remarkable.
I also, I have shared before how much I love the uterus. Yeah, and I still feel that way. Like I feel so. I have my earrings on today. I love thank you their gift from you.
Congrats to myself for the good gift.
I especially doing this research, and I haven't even learned what you're going to teach me yet. But I love the placenta, I know so much.
Yeah, you know, and I think it had always been just a secondary character what in your life story or in my life story, in the story that I imagine, you know. And I don't even know if I had a good idea of what a placenta looks like. Yeah, so Aaron, would you mind?
Do you want to see I would like to see I have today with us here today bottle of a plas not a placenta. Thank you to UCSC Family Medicine Department for letting me borrow this.
Shout out.
Yeah, I mean that's that's basically it.
It is round, it's discoyed. It's discoyed.
It has vessels on one side that is connected to the baby by a numbilical cord, and then on the other side where it was connected to the uterus. It usually is more rough and bumpy. That's why this one is like that.
Yeah, I think it's it's bigger than than I think. A lot of people think it's better that bigger than I thought.
Yeah it would be, and some of them are hefty.
Oh yeah, I was looking at pictures and I was just.
I don't know if I should leave this blown away or that's up to you. Keep it here there for the vibes.
But yeah it is good. Yeah we can. We can honor the placenta here. Yeah, but yeah it is. It is a remarkable organ it really is. And I really want, if nothing else, just for us to think more about the placenta, like going forward. Anyone who's listening, okay, because the placenta deserves this recognition. At the same time, the placenta is also at the root of some of the most common disorders of pregnancy, such as preclamsia. It can invade into the uterine wall too deeply, not deeply enough, or in a problematic spot. It can separate too early or not separate when it should, and the placenta acting in these unexpected ways can lead to potentially harmful or even deadly consequences for both fetus and pregnant person. As I'm always saying on this podcast, life is full of trade offs, and the placenta is no exception. The intimacy formed by this connection is necessary for fetal growth and development, but it can also leave both mother and fetus vulnerable when things go wrong. Despite this potentially high cost, the placenta is a widespread feature of mammals, and it has evolved in many other classes of animals. The how and why of that evolutionary story is what I'm going to talk about today. So exciting from the human placenta's ancient origins, to the diversity we see in the placentas of present day mammals, from the role viruses may have played in its development, to some of the trade offs that we humans face when it comes to our invasive placentas, and also what I mean by invasive. I'll get into it. My overall goal is to get us to think about why the placenta as opposed to other reproductive strategies like egg laying, and why the human placenta as opposed to other mammalian placentas, like why why these things? How did we get here? Before I dig in, I want to mention a couple of things upfront. The first is that I'll be talking about the placenta in terms of what it is expected to do throughout a pregnancy, which does not capture the incredible variation that can occur between individuals, or even within one individual. Pregnancy. Yeah, nor will I be exploring the multitude of things that can happen when the placenta acts Outside of that. We could do an entire episode on each placental disorder. We really really could. The other thing is that this is not a comprehensive review of the placenta in all of its dimensions, like the cultural importance, the history of its study, its physiology, and so on. It's just a quick tour through one of the coolest organs. But fortunately there are many sources where you can get that more detailed info, and we'll be posting those on our website. Okay, okay, you know that I love to start deep.
How deep are we going to go?
It's pretty deep. Before the dinosaurs life on Earth began in the water.
I love it when you do this, I really doh my gosh.
Ok And there it remained for hundreds of millions of years. We're going pretty deep.
I love it.
Around three hundred and fifty to four hundred million years ago, a group of four legged animals made their way onto land. This group is the ancestor of all vertebrates except for fish, so it includes humans right not fish. These first the land dwelling animals couldn't quite shake their aquatic roots, and so they continued to keep laying their unfertilized eggs in water, where a male would later come by and fertilize them. This water aspect of these eggs, it's not a preference, it was a necessity. Without it, the eggs would dry out. But this reliance on water was limiting, so some of these animals evolved another strategy, eggs covered with a more protective coating, which meant that they could last outside of water, which then enabled these animals to further explore land and go out deeper and deeper into land. But this coating made the eggs less permeable, which meant that fertilization had to happen internally, acquired a whole new set of things before the egg and the yulk had fully formed. Okay, yep, yeah, And then that was in contrast to externally, like the way that frogs will lay.
Eggs in or like a lot of fish, a lot of fish, right exactly.
And so then after fertilization internally and after the yolk and egg had formed, the female would then lay her eggs and wait for them to hatch like a crocodile, right, right.
Not the first egg laying animal that I think of, by the way, but I love that that for example.
What is the first one? A bird?
Yeah?
But like, yeah, I mean it's true, I think of crocodiles. I love that were turtles.
I don't often think about crocodile reproduction. I think that's what it is.
You.
Oh, but you think often about bird reproduction.
Well, I eat eggs, so, oh egg like that's mine.
Yeah, I guess I don't eat crocodile eggs.
But I just.
Also, that's so funny because when you said bird, I pictured like robins, not chickens, which is the most Oh my god, I love it.
Okay, so crocodiles, crocodiles la eggs and so.
But the time window between internal fertilization and egg laying, so like when those eggs were fertilized and formed and then when they were actually like deposited, right, was variable. If you kept your eggs inside longer, it meant that you could more closely control the temperature and humidity that these eggs were exposed to, which could increase the chances that your offspring survived. Okay, Eggs can be quite vulnerable to environmental threats, predators, weather extremes, fungal pathogens, and so some animals took this one step further, keeping the eggs inside until they were ready to hatch. Okay, one major transition remained though, How did the embryo get its nutrients? How did that embryo inside the eggs? So egg layers provided nutrients through the yolk encased in that less permeable barrier. But the thing is you were limited. So like when that egg was formed, that yolk it was usually going to deplete until that's all you have. It's all you have.
The embryo has to be able to survive and develop enough with just whatever is in that yolk.
Yeah, it's like meal prepping essentially.
Yeah, it's exactly.
That's exactly like prepping.
I love it.
Okay, Okay, there you go. See. But then what if you didn't want a meal prep and you're like this is not enough food. I'm yeah. Later in the week and you're like I'm starving. Yeah yeah, So what if instead you could provide nutrients to the embryo directly and continuously.
Continuous throughout pregnant. You could make your meals on the go right, Yeah.
You could always have like a resource. Oh well, just there's a little snack drawer.
Snack drawer.
Yeah, I don't know, these metaphors might not work. I really like we can. We can reel it back in. And so a subset of these egg laying animals evolved the ability to pass nutrients directly to the developing embryo, not via a yolk, but through an organ that connected mother to embryo, an organ that we know as the placenta. So we went from laying unfertilized eggs and water, to laying fertilized eggs on land, to retaining those fertilized eggs for longer periods of time, to then getting rid of this eggshell that didn't let nutrients in or out to directly connect with the fetus and remain in contact for the duration of pregnancy.
Okay, that's how we got boom boom boom to the placenta, straightforward, honestly, right.
Okay, it's an oversimplification, of course, it's like covering hundreds of billions of years. And I also don't want to with this, you know, with this explanation give off the impression that the placenta or live birth is like the end all, be all reproductive strategy, or that it's one unique to mammals. Like I said earlier, it evolved independently in many classes of animals. And the fact that we see so many different reproductive strategies today, like laying unfertilized eggs, laying fertilized eggs, retaining eggs until they're ready to hatch, life birth, and so on, the variation is endless. Yeah, what was the one that I like texted you about gastric brooding frogs?
Yeah, and then I came back with the sea horses.
Yes, yeah, I know. There are so many different ways, so many reproductive strategy It's incredible. And this shows us that there are pros and cons for each and that what works for one species might not work for another. So sure, laying eggs might make them more susceptible to external threats, but it frees you up out running or out flying a predator is more challenging when you're carrying around a load of offspring in your uterus literally. On the other hand, investment in offspring is generally higher than placental mammals, which can translate into higher survival for those offspring. I mean, we could spend hours discussing and you know, arguing the trade offs of different reproductive strategies, but we're not going to do it today.
No.
So I mentioned that the placenta evolved independently multiple times across the animal kingdom. Yeah, what in mammals though it happened just once?
Ok.
I gotta talk about the mammals.
Okay, Now I really want to know about the other ones. Interesting.
You know, I can send you some sources. Can go to our website, this podcast with you dot com, go to the sources tet. But this means that the incredible placental diversity that we see in mammals today comes from just one origin. Wow, around two hundred and fifty million years go. We still have to go far back. A group of animals called the thrapsids split off from the rest. And these were reptile like creatures, and they differed from the rest in three key ways. First, they could generate their own body heat and maintain temperature crucial. Second, they had body hair, which helped provide insulation for heat maintenance. And third they developed the ability to produce milk. Oh.
Interesting, I know, I didn't know it went that far back either.
Yeah, Okay.
Over the next one hundred million years or so, this group continued to diversify, splitting off into the three main groups that today make up modern mammals. We've got the monitories, the egg laying mammals like the platypus and the Echidna love them. We've got the marsupials, the one who use a pouch and birth teeny tiny young like the Tasmanian devil, kangaroo, Koala, etct some of my faves. And then the Eutherians or the placental mammals, which includes all other mammals today, including humans. I have to throw in this way actually because it just it bothered me as I read this, and it's probably old news to people who know more about the placenta. But marsupials also possess structures resembling a placenta. They just play a slightly different role and are very different than our placentas. And so one key difference between marsupials and Eutherians is when nutrient transfer takes place. So in marsupials it mostly takes place during lactation, while in Eutherians most nutrient transfer happens during gestation.
Got it right, I think I understand.
Yeah, so they have something that's like a placenta, but its main role is not.
Provided, not threading the nutrients. Yeah, yeah, makes sense. But it's like, but we still call the Eutherian mammals the placentals, okay, And I'm just like, well, actually, yeah, I know it's my I can't resist. But what I wanted to say about lactation was that in monotremes they don't have nipples. They have like little pores. Yes, I knew that, and they like the little the little babies lap up. I know, it's so so amazing.
I know I want to ask more about I won't though.
You get to ask me, and I'll just say I don't know.
Well, I don't know how to form my question.
Okay, problem because it's like going back to like those early early early apps, the thrapcids, like you know, dimetrodon Yeah was that a thrapsid or was that something? See it's only because I'm thinking of like our all of the dinosaur toys that we have at home, and I always go, well, this one's not right.
Which ones are therapids? In which ones or something like that.
Yeah.
See, and this is where.
My anyways, Yeah, I might did evo bio off topic, off topic.
Well, well we'll bring it back to the placenta.
That's please.
Okay. So, so these earliest Eutherian placenta having mammals probably emerged around one hundred and ten to one hundred and twenty five million years ago. Okay, Yeah, and from there nature did its thing. Evolution did its thing. The asteroid that caused a massed extinction event sixty six million years ago did its thing. Cleared the way for the age of mammals. Check out our blast of Mycosest episode for more, so much more, and the placenta diversified. When it comes to Eutherian placentas, there's a whole lot of variation from size to shape to invasiveness. You know, we held up the human placenta, which is like a discoid shape. They come in all different shapes. It's amazing. One book I read suggested that it is probably the most variable of all mammalian organs.
Really yeah, that's interesting.
I mean I wonder if every organ researcher says the same thing about their.
Organ, like my organ is actually the cold.
Blood is the most divert.
Sure it's not that one.
We'll do an episode on okay, but for today, I'm only going to get into one dimension of this variation in mammalian placentas, and that is in the invasiveness right of the placenta. So you can look at invasiveness in two ways. One is in the number of cell layers separating fetal and maternal bloodstreams, and the second is in how physically deeply fetal tissue invades and restructures maternal tissue. So one is like how many layers are in between, and the other is.
Like, how how deep do those villa I go?
Exactly? Yeah. Researchers generally group the invasiveness of the placenta into three categories. Sometimes there's a fourth one added depending on the number of cellular layers. So on the less invasive side of things, we've got like pigs, sheep, dolphin, hippo. In the medium invasive, we've got dogs, sloths, elephants, ardvarks, raccoons. And on the maximally invasive, Yeah.
That was like a really wide range.
Well that's okay, yeah, yeah, okay, in a second, kap. On the maximally invasive, as in the placental tissue is often referred to as being bathed in maternal blood. Right, We've got humans and other great apes, mice, rabbits, guinea pigs, nine banded armadillos, hyenas, and others.
Okay, that's also more than I realized. Yeah, that are like that considered that invasive.
Yeah, on the invasive side of yeah, like in terms of the cell layers. Yeah, And so unless I specify otherwise, when I'm talking about invasiveness, I'm usually referring to this classification based on cell layers between fetal and maternal blood. Why is there such variation? Is there a benefit to one type of placenta over another?
I mean, yes, well, yes, or trade offs? Yeah, yeah, I.
Mean, and it's it's a great we don't fully know the answer class classic, and it doesn't seem to be driven solely by like how related like different animal groups and like, oh well all of the you know, there are some broad trends, but for the most part, it doesn't really seem that way.
So it's like a bunch of examples of convergent evolution essentially.
Friend of like what is driving in different species? We don't fully understand.
I think the drivers for interesting for that.
Yeah, but one thing that we do know is that our invasive placenta, like the human invasive placenta, is the type that probably evolved first, and then it evolved to become less invasive.
Interesting.
Interesting. Indeed, Okay, it's possible that, like so we're talking about trade offs, it's possible that certain molecules like iron have a slightly more difficult time getting to the fetus in mammals with less invasive placentas. But that's not entirely clear. And another hypothesis is that the more invasive the placenta, the better the signaling in all directions like mom to fetus, fetus to mom, placenta to mom, et cetera. I also read that placental transfer of certain antibodies IgG if you're curious, which is the most abundant in our blood, has only been observed in invasive placentas, possibly demonstrating active transport of this antibody to the fetus, which could have then like protective roles.
Right, because then your fetus is basically your baby's being born with all of the antibodies that mom has had. Yeah, so like protection from all protections at least passively, at least for those first few months.
Right, which question mark? Okay is not fully clear?
Yeah, okay?
Why still, why do we have this invasive placenta? One popular but now largely discarded hypothesis is that our invasive placentas were necessary to get enough nutrients to the developing human fetal brain. For one, our big brains came after this invasive.
Clearly, if this was the first type first time, well it wasn't always known that that was the case.
Right, that makes sense.
But two, not all animals with invasive placentas have big brains, and not all animals with big brains have invasive placentas, like dolphins, which have among the least invasive type of placenta. And four, there is no evidence that transfer of nutrients is somehow greater or more efficient and more invasive placentas compared to less invasive books.
Okay, all right.
The idea that invasive placentas were necessary for our big brains was based on this arrogant assumption that whatever placenta we humans have must be the most advanced and the least primitive. It's the best, it's the best. But since that's not the case, we may have to consider instead two related questions, what are the potential downsides to an invasive placenta and how have those of us with invasive placentas adapted to deal with those downsides. So let's start with one of the major potential drawbacks, the fact that during pregnancy there is an alien thing growing inside you. Yes, yes, it's fifty percent you, but only fifty percent, but only fifty percent. That other fifty percent is not you, not you over the past five hundred million years, which is when the first natural killer cells are thought to have evolved.
Oh my god, wow, Okay, I know, wow.
I know.
That shows how fundamental this idea is.
And like just immunology of needing to be able to find non self.
That is the whole point of the immune system is distinguishing self and non self. Like that is pretty much the point of any I mean, and it's that's an oversimplification, sure, but pretty much at its core, y versus self. Yeah, And so sometimes our immune system works a little better than we want it to, like when we reject a transplanted organ. Sometimes it's a little overzealous and it blurs the line between self and non self. Is in the case of autoimmune diseases, and sometimes it might need a little help, but overall, this ability is so crucial to our survival that it's a universal feature in all multicellular life on this planet and has been for quite some time. And so pregnancy then should offer a pretty huge immunological challenge. Right, there's this non self thing inside that has.
To stay there for however many months, depending on what species you are, right, two hundred and sixty six days at least, there are yeah, yeah.
Yep, yeah yeah, And so from an immunological standpoint, our bodies should flag the newly implanted blasticist and mount a defense against it. Sometimes this is what happens. And one potential downside of our invasive placentas is that the deep for the invasion, the higher the risk for triggering an immune response from the mother. Right, Many species that have similarly invasive placentas like ours tend to have much shorter gestations, in part potentially to minimize this risk, but we seem to manage overall.
Right, This is though, why we see things like recist disease, right, where you have at least some fetal cells that are able to cross over this barrier and come onto the other side of our cells, and then we do see those and mount a defense against them in a future pregnancy.
Potentially with and with potentially really.
Really disastrous consequences. Exactly exactly, yeah.
Yeah, yeah.
And so there is like this immune relationship that is really complex.
It's a very tight rope that we are walking.
Yep, yeah, yeah. So what like how like why what allows for tolerance over rejection?
Yeah?
One thing that helps is that a fetus is not the same as an organ transplant. A transplanted organ is connected to the recipient's blood supply, whereas during pregnancy, the fetal and maternal blood are kept separate, right, and they are kept separate by the outer layer of the placenta. And this outer layer consists of a bunch of cells that are fused together to make a tissue. So it's not like individual cells anymore. The membranes have been fused together to create like one giant cell with like multinucleated cell.
That's why they call it a sensicio trophoblasts. If you remember our RSV episode, that stands for respiratories and social virus.
I'm going nerdy, I'm so sorry, but sensisium. Yeah, multinucleated cell.
Multinucleated cells, so it's just like one cell, but it's a long, giant cell.
It goes the whole entire outside of that lastosis.
Yep. And this tissue is pretty impenetrable because these cells are fused together. There are no more membranes between the cells, which means there aren't any gaps to let in let's say, for example, mom's antibodies, which might flag the fetus as non self. So it just creates this like there are no gaps, right, you can't you can't even get no foot in the door.
No maternal stuff can get in to the placenta at that point.
Yeah.
Yeah, And this is a pretty crucial tissue and its role is not limited to barrier right. It's also a hugely important regulator in the expression of hormones like upregulate that hormone, down regulate that hormone, proteins and other molecules that are used in communication between placenta and mom. And we owe it all to an ancient virus stop it oh yeah what?
Oh yeah.
At some point one of our ancestors was infected with a retrovirus which inserted its genetic material into one of their sperm or egg cells.
Okay, okay.
When those cells replicated, like when they formed an embryo and someone so did, the viral DNA carried it with it, okay, which was then also passed down to subsequent generations because it would have been an all all of the germ cells down the line. Over time, we lost bits of that viral DNA, but some crucial parts remained, genes that maybe we were like, huh, this seems like it could be worth keeping around. We call these viral remnants in general endogenous retroviruses, and our genome is chock full of them. I think I've talked about this before on the podcast being really excited. About five to eight percent of the human genome is a viral origin. Five to eight percent. That's a huge proportions. Not us virus, I mean, it is us the genes since it in one and since it in two, which help us to fuse these cells together to make that like one layer, and also help us escape detection from mom. They come from a couple of these ancient viruses. That's what allows for that that formation of tissue, that barrier.
Yeah.
Really, really, these genes these viral genes. Essentially, these genes that are viral in origin.
Yeah, wow it and one since it in two. Without these ancient viral infections, we would not be able to form the super important tissue. We wouldn't be here.
Wow.
Yeah. And what's amazing about these indogenous retroviruses, these since sittant genes, is that they appear across eutherean mammals, but not from just one infection event. Mammals have been infected over and over again with different viruses that have found their way into our genomes and have been co opted into helping us build this tissue layer.
Wow.
Wow.
I know I'm being mind blown right now.
I say I'm read being mind blown, and I've.
Wrote that, I wrote this, and it's still blowing my mind.
But the immunological relationship between mother and fetus isn't just one of avoiding detection or building barriers, right. The activation of the maternal immune system is actually a necessary part of pregnancy, and instead of that activation leading to a destructive response, it leads to a regulatory or protective one, one in which acceptance of the embryo is initiated. The portrayal of pregnancy as immunosuppressive isn't accurate. In fact, the mother is very aware. The mother's immune system is very aware of this new non self thing growing. And it's more that the maternal immunological self is modified a change in immune tolerance. As a side note, this shift in self might help to explain why some people with autoimmune diseases experienced symptoms lessening pregnancy. Yeah, but there may be a cost to this tolerance. Recent research has investigated whether our invasive placenta us, which require more immune tolerance than less invasive ones, may have made us more vulnerable to cancer as a species.
Really really, I did not know this connection.
Yeah, okay, it's been like I think, in the past ten ish years or so, there's been a lot more interest in this aspect of the immunological side of placentas interest and placentation.
Yeah okay.
In fact, many researchers have noted the similarities between cancer and placentation. The formation of the placenta very interesting. There is immune evasion, proliferation, invasion into other tissue and blood vessel remodeling.
Wow.
Yeah, I know, and it's like self, but not because it's abnormal cell division.
Ooh.
Interesting yep, And studies that have compared cancer rates across mammals have found that cancer tends to be higher in species that have more invasive placentas, like humans, compared to ones that don't, like cows. And I'm sure like that other things play a role, you know, lifespan, body, seze. It's never one thing. Yeah, yeah, but the pattern isn't cut and dry. Where is it clear how cancer and invasive placentation might be related mechanistically. It's a fascinating area for future study though, especially what it might be able to tell us about our individual responses to invasive placentation. Yeah, because wow, there is a range of responses. So, like we talked about, the placenta is more than just a gateway for communication between mother and fetus. It's also the place where we see maternal, fetal and paternal needs expressed. From the fetus's perspective, more is better, more resources, more nutrients, more everything to help you grow.
Sometimes and we'll get there, not always.
Not always. But also from mom's point of view, you also want fetus to grow, but you can't give away all of your resources since that would impact your ability to care for the fetus later in pregnancy after birth, in future pregnancies, and also for existing offspring. And so these needs might be in immediate conflict, but there seems to me to be an ultimate shared goal for the two, right, a healthy newborn while also not draining mom to the point where postpartum care is impossible.
Right, A little balance, a little balance.
It's like, I think a lot of people refer to it as maternal fetal conflict, which is a whole separate thing, and there are a lot of dimensions to that, and there's like also the social sociology and political side and legal side of that. But I have been thinking of it as like a maternal fetal conversation.
Right.
Yeah, it's a balance, a balance, it's a dance, a balance, and that balance is not always struck. Sometimes, for instance, the placenta invades too deeply into the uterine wall, past the dissidua, which can cause hemorrhage or perforation of the uterus. Or sometimes it doesn't invade deeply enough, and maybe this is because our immune system prevents it. This incomplete invasion is thought to be at the root of pre eclampsia. We don't know the precise mechanism or if preeclamsia has one root cause or multiple, is it a syndrome or is it well one? Yeah.
Well, also I'll talk more about like the different types of preeclampsia, whether it's early term, whether it's term, whether it's postpartum preeclamsia.
Are they different, are they the same.
It's the same pathway that's getting us to these things, or multiple pathways? Yeah, yeah. But one idea for preeclamsia is that the placenta doesn't invade deeply enough, which can limit the blood supply to the placenta and fetus. Initially, in earlier in pregnancy, that's not a problem since the fetus actually needs a low oxygen environment to develop. But as pregnancy progresses, oxygen demands increase, and if that initial invasion wasn't deep enough, if those arteries weren't remodeled enough, that can mean that the fetus is getting low or intermittently low oxygen. And so then mom senses this or through the placenta is told this, and then her blood pressure will spike to compensate, But that doesn't always solve the problem, and so then things can kind of get increasingly out of balance, and then there can be a lot of danger, right that happens. Yeah, Aaron, I know that You'll get into more of the details later on. But one of the things that I find fascinating about preeclampsia relates back to this idea that invasive placentas might be related to higher rates of cancer. If pre eclampsia has an immunological component, and if mother's immune system is preventing deep invasion of the placenta, might cancer rates be lower in people who have had pre eclampsia. Huh, I don't like so first of all that now I'm like, not, we're wondering.
You are wondering.
Yeah, I'm not saying like, and here's there's been reviews about this and meta analyzes. I did look up a few large studies and a meta analysis that did suggest that people who have had preeclamsia are overall less likely to develop breast cancer. Interesting, but there's like, there's so much more to that story or so many factors. How protective might pre acclamcia be. What's the mechanism of protection if there is one? Is this a causal connection or just you know, a correlation. And the same can be said for the placenta. Like, there's so so much more to the story. This was really just a brief or at least as brief as.
I could make it could keep going and keep listening to you.
Just a brief tour through the evolutionary history of one of the most fascinating mammalian organs out there. And I hope that even if you don't remember any one thing from this story, you at least find yourself thinking more about the placenta.
The placenta that we all used to have, we all use.
I think that's the thing that's interesting that no one ever thinks about, Like, yeah, we all because I think a lot about the uterus and how we all came from a uterus, whether you have one or not, right, you came from.
One, which is so interesting.
But then like we all, I never thought about the fact that, like, we all had at a.
Placenta and we all no longer do.
Yeah, unless unless you kept yours.
Yeah, but then that's not yours. That was your fetuses. That was your baby's placenta.
But if you, if someone, if you, if you kind of kept your.
Oh that's interesting thought about that. Yeah, Okay, so some people have their I.
Mean yeah, it's no longer attached to us. Yeah, it's no longer it doesn't serve using.
The function that after birth, it stops serving its function. I mean, it's just so interesting and it's huge.
Yeah, it's like that takes a lot of resources.
Oh my gosh.
Yes, yeah, it's hefty. It's a hefty organ and you can tell when they're not hefty. Oh interesting, Yeah, like I I mean, you see a whole variety of placentas when you've been delivering babies. I haven't done a lot of but seen a lot of fairy number and there they range for sure.
Which is amazing and interesting.
I know, I know.
Okay, we I mean we could we could keep talking about yeah. Yeah, but yeah no, that's I mean that and that basically is the placenta story. You know, let's think about viruses, Let's think about what the placenta allows us to do from what a journey we mede a logical standpoint, it's incredible. Yeah, so yeah, let's keep going with the journey. Aaron, tell me what's going on with your body and pregnancy?
Okay, I literally can't wait to take We'll take a quick break and then we'll get into it.
During both of my pregnancies, I experienced intrahabatic colostasis of pregnancy. This is a rare complication where your liver cannot process aile salts and acids, so those begin to accumulate in your blood. This causes itchy, which is mainly focused on the palms of your hands and soles of your feet. It was the worst age I have ever experienced. It was not a dangerous complication for me as a pregnant person, but it was extremely dangerous for the fetus. Mortality rate in utero is very high. That is why I have to be monitored very closely up until thirty seven weeks when I was used both times. During both of my pregnancies, I had to go to the hospital every few days to have a CTG taken. They did numerous ultrasounds and I was even hospitalized the first time around. They also prescribed urso, the oxygalic acid, which helped a lot with lowering bile salts and acids. Itchiness also went away after that. The last ten weeks of my pregnancies were very stressful, and looking back, I am amazed that I would call I managed to stay. Both of my kids were born healthy at thirty seven weeks after induction. Chances of getting intracapathic colostasis of pregnancy with every subsequent pregnancy are higher if you have had it before. Two was enough for me that feeling of unbearable itchiness will always stay with me.
My name is Sarah, she heard thirty six year old female mother to an awesome daughter. I had a positive home pregnancy tests on Christmas Day twenty twenty two. I was thirty four years old at the time. We were very lucky to conceive on our very first try. We had our confirmation ultrasound in eight weeks, and as I progressed towards the second dry master, I felt my mental health spiraling. In addition to all of the other common pregnancy side effects like morning sickness and fatigue, my anxiety started to worsen to the point of panic attacks. My body was changing in a million ways, and I had no control over any of it, let alone any peace of mind to assure me the baby was okay, or how to judge what was normal. I started to feel like maybe my medical background was not an advantage in this situation, because I knew too much when I brought my fears up to my OB. I felt dismissed. Each visit was short about five minutes. They checked the fetal heartbeat and sent me on my way. Even though this was my first pregnancy, I took it upon myself to research pregnancy mental health and found mostly postpartum articles. I eventually talked to my PCP, who started me on lexipro and busbar. I was referred to a mental health provider, and over the remaining six months of my pregnancy, I had weekly video calls with an LCSW. She helped me develop coping strategies for my anxiety and guided me in conversations with my OB and my husband. I made affirmation journals, mantras to recite, and fell asleep listening to guided hypno birthing podcasts, all of which eventually helped me to overcome my anxieties about giving birth. I had to learn how to be the patient, not to provide her, and to have faith in my husband, family, and healthcare team to take care of me. By all accounts, I had a very normal pregnancy and easy birth. At the pediatrician visits with my daughter, I filled out mood questionnaires at every visit to screen for postpartum depression, which thankfully I didn't develop, but it did make me wonder why aren't these types of questionnaires available throughout the entire pregnancy.
So I left off the biology last week kind of at the start of the second trimester. But in that episode I mostly was talking about the embryo and the invasion and the thing and etc. But in this episode, I'm going to focus on the pregnancy and the pregnant person and not the fetus. Okay, because as incredible and awesome as the process of fetal development is, like, it only happens inside of a uterus, and so like the changes that are required in our bodies in order for a pregnancy to actually continue to term, Like, that's where.
I'm that's where the money is for me, right now. Okay, someday we'll do fiddel development because it's really cool too.
Yeah.
Okay, So we're going to actually take steps backwards to the beginning of the pregnancy, okay, kind of, We're going to go back to fertilization, Okay. Yeah, So that we will recall from last week, is about two weeks after your last menstrual cycle, right, is when you ovulate and then you get fertilized, okay, and then about six days after that is when we have implantation that starts. So we're about day.
Twenty one ish of our menstrual cycle.
Okay.
By about this time, and then like the next week after, when you may have missed a period and may have had that positive pregnancy test, all ready your own physiology has changed dramatically because of the way that embryo has embedded itself into the wall of your uterus, Like you just walked us through and started secreting hormones that are going to cause our body to change in ways that it really only changes in the context of pregnancy. I get really excited, And what I'm going to do for this episode is go through these changes, not week by week like you might see on all of the websites, like your body is doing this this week.
No.
No, We're going to go body system by body system and explain why we see maybe some of the like weird or uncomfortable symptoms that you might experience, and why we are susceptible to some of the complications that then arise because of these changes in our physiology. Okay, I'm going a rapid fire through it, but stop me at anytime. Okay, We're going to start with our cardiovascular system because it's one of the most important and one of my favorites. One of the first changes that we see is in our blood vessels. So because of the increased levels of progesterone and other hormones like estrogen and prostaglandins, we see a dilation or a widening of our blood vessels. And what this does is decrease the resistance to flow of fluid because of physics. Yeah, and so right away you can start to see weird symptoms because this vasodilation can cause edema or swelling as these blood vessels, as they get wider, become a little bit more leaky. So then you get fluid that can go out through the blood vessels and into places like our ankles.
And this is like a body anywhere, your whole body.
It could have yeah, not like extreme, but a little bit.
I mean, like the blood vessel widening, yes, everywhere.
Everywhere in your whole body, which also means you might get things like nasal congestion or nose bleeds.
Oh my god.
Now, this vasodilation will also cause a decrease in your blood pressure, usually early in pregnancy, which is very interesting to then contrast with what we'll see in preeclampsia, which is when we have higher blood pressures. Now, on top of this change of the width of our blood vessels, we also have an increase in our blood volume by how much you might ask, I would by forty to fifty percent. What uh huh, okay, tell me more about what that means. It means that if you have I actually meant to look up, like what your normal blood volume is. However many leaders I don't remember, but it is now fifty percent higher.
Within a number of weeks.
Okay.
Uh.
And it's you literally just make.
More blood volume. It means your plasma Okay, we're gonna get a more into it. Yeah, because it's your plasma volume that's primarily increasing.
Okay.
And this means a few things. Number one, it means your heart has to be able to keep up with this increased amount of flow, and so to do that, we actually see structural changes to your heart to allow for an increase in cardiac output.
What kind of structural changes we see?
Thickening of the like wall of the left ventricle.
Do you bring over the heart? Oh my god?
If you have a diagram of a heart. Your left ventricle is over here, right, and that's the aorda is going to come out here, and this is what this is where your blood goes to the rest of your body from. So yeah, the left ventricle of your heart is going to get a little bit thicker, Your overall heart is going to get a little bit bigger. And then, as we'll talk about later, because of the changes in your diaphragm and the size of your thoracic cavity, it also gets shifted.
Up into the left.
Interesting, I know now.
Also I think you.
Give that back to you.
Now.
Also, we will see a compensatory increase as well in our heart rate because your overall cardiac output is a function of both the volume and also the rate. So we see an increase in heart rate, which I remember seeing on my smart watch where.
It was like you have a new normal. Oh interesting, and you're like, when I.
Was pregnant, how soon does that happen?
So that is that a lot of these changes are kind of gradual where they start really early, but then it just like continues to change all the way till the third trimester until term. Okay, for the most part. Okay, and it's sort of an up. It's just sort of this it's a linear well not yet not linear, I mean, but yes, it's a kind of contained directional, you know, for the most part. Okay, Yeah, there's probably nuance there that I'm skipping now. I said, your blood volume increases my fifty percent. However, your red blood cell volume, and remember red blood cells are the ones that actually carry oxygen to our tissues, so they're like kind of pretty important. They also increase, but only by about twenty to thirty percent.
What does this then, difference in rate increase? How does that manifest in other parts?
Like?
What is that?
What are the implications of that?
Okay, let me tell you.
Why aren't your red blood cells also increasing?
They are increasing, just not to the same not to the same degree. So what does this? What does it mean?
What are the implications? Means that you have during pregnancy a physiologic anemia and your blood is it has less viscosity, so it can less right because you have less part of Yeah, it can flow a little bit more easily. It also though, means that of course you can carry a little bit less oxygen relatively speaking, like on the whole you're carrying more because everything is increased, but you have this physiologic anemia. You also then have this fetus that is going to be relying on the oxygen that you are giving to them. So that means that you have to become very efficient with your oxygen transport, which is the thing I could go really too deep on, but I won't. But what we then see during pregnancy is an increase in this production of this compound on our red blood cells called two three DPG. It basically means that when you are pregnant, your body is better at giving away that oxygen, So your red blood cells are more efficient at offloading oxygen so that the fetus can get access to that oxygen. Okay, it's just like easier, it's easier to drop off exactly, Okay, exactly. Yeah, it's so interesting. There's also like fetal hemoglobin, things that are hemoglobin. I know, I know, it's cool, Okay, So but it also means you set another implication. Another implication is that in order for our bodies to keep up with this demand, iron requirements are significantly higher in pregnancy compared to outside of pregnancy. And that's for two reasons, one to support the growth of the fetus who needs iron to grow, but also to keep up with this increased red blood cell production, and so iron deficiency anemia can develop on top of this physiologic anemia. And so during pregnancy people are at pretty high risk of like anemia in general because you already have this physiologic anemia and now you have this increased iron requirement. So if you're not getting enough iron in your diet, then you're not able to make enough red blood cells.
Okay, makes sense, and so right.
And so then what if anemia di or if this one two punch happens, then what are some of the downstream.
I mean, it can affect It can be really problematic when we get then into delivery because in delivery you are going to lose some degree of blood most likely, and so that can put people at higher risk of complications from hemorrhage or just from blood loss in general.
Okay, yeah, okay, that's.
Mein I mean, it can cause problems for the fetuses all too if you were like severely deficient.
And so physiologic like are there I'm sure there's a range of physiologic anemia, like outside of iron deficient in the area, and so is there a point at which, just like physiologic anemia, is where it needs problematic.
Yeah, exactly, I don't think so.
Okay, yeah, because it's it is what is expected during pregnancy, right right, you expect that to happen. Okay, So if we move on from our blood vessels in our cardiovascular system, we'll move to another vessel that's being affected kind of is not really vessel, it's your kidneys.
They're connected by tubes. Okay, it's like a vessel.
You have all this extra blood, right, your kidneys are responsible for filtering all of your blood. That's what they do, and so your kidneys have to work a heck of a lot harder. And during pregnancy, your kidney's enlarge and increase their filtration rate by fifty percent, which is so impressive and means that you're making a crap ton of urine and you have to pee all the time, even before there is a fetus literally crushing your bladder.
That's that's something I had never I know, thought about it.
And that's why even early in pregnancy people be like, I'm peeing all the time, and it's not because of the fetus because that thing is like a couple cells big. It's because you're making so much more blood, and so your kidneys are filtering all that blood, and so you're peeing all the time, Okay, and then eventually, of course, this fetus is going to grow large enough to crush your bladder. And when they do, you also can get compression of some of the tubes that lead from your kidneys to your bladder. And then that along with the fact that progesterone, which I talked about already, that causes that vasodilation, progesterone also causes like a slow down of everything. Everything's just like moving more slowly, and so your bladder has a little bit more stasis. It's not like squeezing out as much.
Uh huh.
So you can be more prone to UTIs or urine aritract infections during pregnancy. Interesting because you, yeah, even though you're making so much p and ping all the time, it also just can kind of sit there a little bit longer. And and then because of all of these things that are happening with like compression and blah blah blah, you have a higher risk of those UTIs getting up into your kidneys and causing a kidney infection.
Okay, does that is that risk consistent throughout pregnancy?
I don't have an answer to that question. Okay, it's a good question.
And it's not like it's major, like that's not like, oh my god. It's just like you're a little bit higher some of the things that some of the things that can happen.
So that was a lot.
Someone take a big breath, just kidding. You can't take a deep breath during pregnancy.
Did you have that written now?
I did.
It was a joke, I wrote.
I love when your jokes are written out.
Thank you.
Still felt natural.
Thank you.
It was my segue into the respiratory system.
It's a good seg thank you.
So the changes that happen in your respiratory system, they actually start really early in pregnancy. I think we think about the changes later in pregnancy when you have a large volume that's compressing things, and we'll get there. But the hormonal changes actually cause an increase in ventilation called hyperventilation of pregnancy, and that starts really early. So your respiratory rate actually increases hormonally.
Okay, hormonally what hormone progesterone mostly progesterone. How does that work?
We're not going to go deep into mechanism here, Aaron, because I got too many other bodies make talk about it. I don't know why not have any answer to that in what I wrote so far, but I got plenty of papers that you can read about.
Because it does it.
Yeah, I'm just yeah, amazing, It's so cool.
And then, as I have alluded too many times now, as pregnancy progresses and this uterus increases in size significantly, it displaces every single other organ in your abdomen. It moves from being a pelvic organ to an abdominal organ, and in doing so, it elevates your diaphragm, which is that muscle between your chest and your belly, and your diaphragm is what allows for your lungs to expand. It has to move down for you to take a deep breath in. During pregnancy, this gets shoved about four centimeters upward, so your lungs cannot expand as fully as they could previously. That's what also causes that displacement of the heart, which gets pushed up and a little bit to the left. And now some of this is compensated for this displacement is compensated for by the same hormones like progesterone and also other ones like relaxing in things that cause ligamentous laxity.
There's a hormone called relaxing, relax and just relaxing. I want to know who named that.
I have no idea.
That's a main question. Relaxin.
Yeah, so it's what allows all of your ligaments to expand and relax so that you can like.
Fit a baby through your pelvist.
And then also so that the bottom part of your rib cage can flail out and actually expand in diameter this way, like front to back, about five to seven centimeters.
You get change here.
Wow, just the bottom part of your ribs all thanks to relaxing, well, relax in, progesterone, all of these hormones.
Not to throw a spotlight weight relaxes.
Spotlight it, I know, give it some cred. But with all of these changes combined, by the end of pregnancy, your total lung capacity decreases by about five percent, which isn't huge. However, because of increased demand, both because the fetus has increased demand, right you have to share with the fetus, and because your own basal metabolic rate during pregnancy increases by about fifteen percent. Your total oxygen consumption and need goes up by twenty to thirty percent.
Okay, so you've got first of all, you're breathing more because progesterone is telling me to breathe more.
Yep, that's how it goes.
We're somehow dig deeper into that. You've got less room for your lungs to expand, and you.
Need to breathe more, need more oxygen.
And so you're you're like just like panting.
You feel a little bit shorter breath, short breath. Yes, yeah, you're not panting, but you feel.
Okay, And then and then there's like is that and then also the metal ball. Yeah, okay, there's a lot of a lot of things.
There's a lot of reasons to feel a little bit shorter breath, especially towards the end of pregnancy. Now you also have, because of everything going on in your abdomen, right, you also have just a lot of pressure inside of your abdomen. And what this can do, especially if somebody ends up lying down flat on their back, is it can put pressure on the blood vessel that sends blood back to your heart. Called the inferior vena cava, and that because it's a vein, it has floppy walls, so it can actually become compressed later in pregnancy by the weight of the fetus and the uterus and everything else in there, and that can potentially be problematic, mostly for the fetus, because it can kind of reduce the blood flow back to the heart, thus reducing your cardiac output. And then you can have this drop in blood pressure that affects the profusion to the fetus. Okay, so that's why a lot of times late in pregnancy people are told like, don't lay flat on your back. Yeah, that's the reason why. Okay, yeah, we have so many more body systems. Okay, ready, blood in general, going back a little bit, I guess blood clotting factors completely changed during pregnancy. Nearly all of our clotting factors increase except for our platelet count. And we think this is helpful in terms of preventing postpartum hemorrhage. Oh, but it also means that people are at higher risk of a thrombotic event of a blood clot forming when it shouldn't.
But I thought that our blood was less viscous.
Oh my gosh, it is, but our clotting factors are higher.
Okay, so we're just sort of compensating for that in different viscosity and then it's like the clotting factors, I mean, really, we're getting to the same end result. Yeah, yeah, yeah, more clots, potential.
Potential for more clots. And the mechanism there, don't ask me exactly, is probably related to estrogen because some reason, if you're on estrogen birth control, you're at higher risk, which but not as high risk as when you're pregnant.
How have we not talked about that?
Okay we did, I thought during our birth control upsote. Oh yeah we did, Yeah, we did.
Okay, But all of this I've talked about so far, which was a lot and I've already skipped over what is a lot of people's first indication symptom wise that they might be pregnant, and that is the changes to our GI track.
Yeah.
So from the very beginning of pregnancy, hormones again like progesterone and others are causing smooth muscle relaxation. That's how we get dilation of our blood vessels. That's why we get the stasis in our bladder. All these things, and this results in a decrease in tone of our esophageal sphincter, which goes from our esophagus into our stomach, and that can mean that you get an increase of things like acid reflux. And we think that it's also related to nausea. Right, you have just like slow down of your GI tract and opening of your esophagus and going in so it just makes you feel more nauseous.
Why does why does the slow down happen.
Because of progesterone?
Yeah?
But why?
Yeah?
Is it just a consequence of the fact that like progesterone is causing this overall relaxation probably, like it.
Does it have a purpose? I don't know, Okay?
And then why does that lead to nausea? Like what is nausea?
Oh?
My, sorry, I.
Can't believe the questions you're asking me right now. Well, I'm sorry, it's like what is itch?
Oh my gosh, I still want to know what it is? It's yeah, I mean, I mean I know what nausea.
Is, right, you know what it feels like?
Right?
Like why does having I mean you can think about it too, as like your food is not able to move through as quickly so it's going to be sitting there for longer. You have things that are in you're supposed to be staying in your stomach coming up into your esophagus more readily.
OK.
Like, I don't I don't know a better answer than that, And there's probably a better answer out there, like a GI doc is like rolling right now. Sorry, No, I'm sorry, No, don't be sorry. But but yes, so this this happens. And what's interesting is that mild nausea and vomiting early in pregnancy is actually associated with a lower risk of miscarriage or early pregnancy loss in the first trimester.
Yes, I have heard that.
Yes, and so we think that it's that is a big part of the reason that we think it's very progesterone mediated, right, is that when you have adequate levels of progesterone, then your pregnancy is able to continue. And so if you have lesser then you might have less nausea. But then it also might mean.
You know what I'm saying, Yeah, I do know what you're saying, but it's not it's not cut and dry.
It's just like a slight association. Okay, But as you can also hear in several of our first hand accounts. Sometimes this nausea and vomiting can become very severe, and that's called hyperremesis gravidarum. We do not fully understand the cause of hyperemesis. We think that it's probably in part these changes to the gastrointestinal tract and the mobility of our gaster intestinal tract, but also like some contribution of is it maybe other hormones, like independent of their effect on the GI tract, there's probably some degree of genetic susceptibility.
We don't know.
In short, Okay, yeah, we don't fully understand that one at all. Yeah, but this slowdown of the GI tract can also, especially later in pregnancy, end up affecting the liver and the gall bladder, and that is what can result in intrahepatic colistasis of pregnancy or colas stasis.
Yes, I want to know more about this. This is I had only heard.
Yeah, yeah, yeah, so this is it's more rare than some of the other complications like maybe anemia or something like that. It's estimated at zero point two to two percent of pregnancies, depending on which studies you're looking at. But colostasis is when we see a build up of bile acids because bio acids are supposed to be they're made in the liver and then they have to be transported through a duct into the gall bladder. They're stored, and then from the gall bladder they have to be squeezed out and then squirted into our small intestine. Okay, And so we see a build up of these bile acid because they're not being squirted out and excreted by the gall bladder.
They're stuck in the gall blader. Their stup latter is the source of so much issue.
Like right, and so they're also then just they're not they're building up in general. So it's like the liver, the gallbladder, the whole situation. They're not going down the track like they're supposed to.
Okay, and so the salts are stuck in the liver, stuck in the gall it's just sort of like a again the slow down, slow down. It's a slow down, yeah, traffic jam in the gall blade.
Traffic jam.
And so then this bile acid accumulation will then be essentially like transported out of just the liver gall bladder situation and can potentially end up in our bloodstream. So then we see an increase in bio salts in our bloodstream. The symptoms of that end up being really really severe itching, and it's usually like whole body itching. Don't ask me why it causes itching?
What is itch? How does it get in the bloodstream.
Because it's not able to be transported out, so then there's just too much of it, and it's just like, ah, okay, okay, because your liver like has so much blood supply, and so if it's just backed up into your liver.
Then it's gonna be it's gonna go okay.
And so yeah, and the that does not pose a problem to the pregnant person, but those bile salts can pass through the placenta and be toxic to the fetus because these are cytotoxic compounds, right, That's why they're usually stored in our gall bladder where they're not causing problems. Usually, Okay, I've gone through a lot of physiologic changes so far.
Try to think of other don't ask me more questions. I'm gonna keep going.
I don't think of other body parts, like or what other body system. They're not the ones you would think of necessarily. Yeah, brain is interesting your brain definitely changes during pregnancy, and there are like fetal cells that make it all the way into your brain.
Yeah, but we don't I don't have data on like what are the changes.
We have no idea but the feel cell.
Okay, But here's what I'm going to do is now focus more on the two other major complications that we see and the body systems that they're involved in. So diabetes, h Okay, this is our endocrine system. And we already know that our endocrine system, which is our hormone system. You defined it last episode. I could be at some point.
Oh yeah, it was last episode. Because we've talked about hCG.
So our entire hormonal milieu is changed during pregnancy, and people end up susceptible to diabetes during pregnancy in large part because of a hormone that the placenta is secreting that's called human placental lactogen. There's other stuff that it's involved as well. But this is what I'm going to focus on, because what this does is it makes our pregnant bodies less sensitive to insulin. We have an increased insulin resistance. Okay, why do we need an increased insulence resistance? If we remember back to our diabetes episode, insulince job. What it does in our body is when we have high glucose and are like we eat something, right, and we have high glucose in our bloodstream, Insulin is secreted and it tells the glucose like, get away from here, pack yourself away so that we can store you and use you later. Okay, So insulin puts glucose into our cells. But a fetus needs glucose and they get it from our blood stream.
Got it.
So by making our insulin less effective, you can have more glucose to be available for the developing fetus. But if this process goes too far, like if are pancreas, because we're going to have this insulin resistance, right, so our cells are going to recognize, hey, glucose is too high, we need to make more insulin. If you're pincreas can't keep up with that increased demand, then you end up with gestational diabetes where we see too much glucose in our bloodstream. Levels get too high, and that has a couple of big consequences. One is it can cause increased growth of the fetus. Right, because the fed is just like getting a glucose pipeline. Yeah, yeah, okay, and that is called macrostomia. So it ends up being large. Babies are large for gestational age babies, and that can make delivery very risky.
Yes, okay.
But the second complication that I don't think people talk about as much is that while our glucose that's in our bloodstream passes through the placenta and into the fetus, our insulin does not. So if our glucose levels get really really high, fetus inside of us has to make more and more insulin because their body is also like, whoa, this is a lot of glucose. So they're having an increase amount of fetal insulin that they're making. And then after they're born, that sugar syrup bloodstream pipeline is cut off, and now they can get severely hypoglycemic because of how much insulin they've made in their bodies.
And so then what does that look like?
That can end up with seizures or coma or death. And that is like to imediately immediately following birth right or when yeah, exactly in the neonate in the new moral they can have really severe hypogacemia. And so that's why Babies that are born when the mom has had just national diabetes have to be monitored really closely, especially in the first like twenty four to forty eight hours.
Okay, so interesting. Can I ask some questions or you can try yeah, okay, okay, okay, okay. When typically do we see uh, gestational diabetes appear?
Okay, we usually test for it around weeks twenty four to twenty eight Okay. Doesn't mean it can't happen before that or after that, but that's usually in most places, that's the timeline that we test for it.
Okay. My second question is then what do you do about it?
Yeah?
Great question. Okay, do you have more that you want to keep going?
Yeah?
No, no, but you answer that okay, yeah.
Uh.
There's a few different things a lot of times that can be managed with just dietary changes alone, and so figuring out like what do you what are you eating that's maybe causing really big glucose spikes and can you just modify your diet to be able to have not have that and then you're good. Otherwise it's usually insulin, so we manage it with it.
My third question, and you may maybe I should just let you finish talking about the other complication. What are the differences between first pregnancies and subsequent pregnancies and the path this big, big picture question, you know, because I would I would imagine that like, Okay, first pregnancies, your body is like responding and doing all these things that it's doing for the first has never done it right, and the second time, it's like are those pathways carved out? How different are the hormone levels? How likely are same complications to occur between one pregnancy and subsequent pregnancies.
That's interesting. So we'll talk definitely more about that with preclamcya, which is what I'm going to do next. But I don't know when it comes to just stational diabetes. Certainly, if you've had just stational diabetes in one pregnancy, you are at higher risk for having it in another pregnancy. Just stational diabetes is also associated with an increased risk of type two diabetes later in life. So it's thought to be kind of like a marker. There's a lot of things that happen in pregnancy that are thought to kind of be markers, and we I don't know are they like causal or are they just like a kind of a snapshot in time where we're like, oh, maybe you are at higher risk for these complications later in life, but it's not like because you had it during pregnancy.
Does that make sense?
Yes?
But yeah, I don't. I don't know data on like what are the rates first pregnancy, second third. It also is going to vary with age as well too, so yeah, I don't know. That's an interesting question though. When it comes to diabetes.
Yeah, I don't know.
Overall though, the rate the estimates of like how many pregnancies are complicated by diabetes are like all over the map.
From like one to thirty percent depending on your studies.
So it's like what's food, what's the threshold? Like how do you? How do you?
How do you diagnose?
How do you diagnosed?
I really wanted to bring in a glue coola for you, but I couldn't get my hands on ones.
I'm sorry.
And it does differ different countries and different guidelines are a little bit different in terms of what how you how exactly you diagnose it. But most of the time it's by doing a glucose tolerance test, and so you give somebody a fixed volume of glucose seventy five grams whatever, and then you test their blood at intervals either one hour, two hours, three hours, or multiple times, and then see what their numbers are. Got it, what their glucose level is Okay, And there's different cutoffs, and that part's pouring. So let's move on, shall we.
Yeah, I want to pre aclampsia. Ye, big one, So that is it is the biggest.
It is a doozy and it can be for sure probably the most severe complication of pregnancy.
That might not be true, but it's a big one.
It's a big one.
So this is really truly not just it doesn't fit as neatly in a single organ system, because it is, like you mentioned Aaron, the result of a kind of dysfunctional relationship really between the placenta and our own cardiovascular system, and it can result in a whole spectrum of disorders that we call hypertensive disorders of pregnancy. So it's not just preaclamsia. It also includes gestational hypertension. So just high blood pressure, okay, preeclampsia and aclampsia, and then also help which is hemolysis, elevated liver enzymes, and low platelets. But often we think about and focus on preeclampsia, because that is a kind of point at which if this kicks in, if it's officially preeclampsia, then that's when the risks to both fetus and mom become pretty significant. Okay, preeclampsia overall is estimated to complicate between four and five percent of all pregnancies worldwide.
That's such a high rate.
It's pretty high, and it's estimated and estimason This really did vary in several papers that I read, but most reliably the papers that I read said it's estimated to result in seventy thousand maternal deaths every year. Seventy thousand maternal deaths every year, and five hundred thousand steel births or neonatal deaths, oh my gosh, which is just like heartbreakingly massive numbers. On top of that, for every maternal death that's really to preeclampsia, it's estimated that fifty to one hundred women are having significant morbidity as a result of it. So it's like affecting a huge number of people. Yeah, and I'm sorry that that started off like so heavy, but preclamsy can.
Get really scary.
Yeah, absolutely so, in terms of like what is when I say preclamcy, what does that mean? It's defined as hypertension, so elevated blood pressures and at least one of a few other features symptoms that we see. One big one is protein in the urine, because that's a sign that your kidney is being affected, okay, or sometimes other signs, other lab values that we see that tell us that your kidney is having kidney dysfunction, and that's like it's not filtering exactly exactly, or liver dysfunction, all right, and all of those we do like laboratory values to see what those numbers are. Or sometimes it's diagnosed by neurologic complications, which can be severe persistent headaches, visual changes, stroke or abnormal reflexes. Or sometimes it's hematologic complications, especially platelet abnormalities.
Okay, So there are a multitude of ways to dultitude.
Of criteria that you kind of like check the boxes, and if you're meeting these then it's called preeclampsia rather than just hypertension.
Interesting, Yeah, So that it would have to be like these neurological changes in addition to high blood pressure exactly, and you would also have to have protein in the urine or exact other liver enzyme elevation, okay.
And what it can cause is a number of different things. From the fetal perspective, it can cause fetal growth restriction because of abnormal blood flow into the placenta. But when preeclampsia, especially if it goes untreated or unchecked, it can result in a number of really severe complications, including a clampsia, which is preeclampsia but with seizures. So that's the line at which it becomes a clampsy Yeah, right, than preeclampsia down to down to nabby, I know, I think of that too. And then it also can sometimes cause stroke, especially a hemorrhagic stroke, which would be a very severe complication of preeclampsia. Sometimes it's not the nervous system, but it's a different organ that gets mainly affected. So it can cause severe liver damage and that often results in that HELP syndrome. Okay, because it's causing damage to the liver.
Yeah, So help is A is A is A. It's on the spectrum what so Okay, So what is that spectrum? I know there's there's high hypertension.
Gestational hypertension, preeclampsia, eclampsia, help, okay, Yeah, that's like the main spectrum, okay, But then within preeclampsia, we can also see these other companies and they're not discrete events necessarily, like it's not like help or this sure, right, okay, yeah, And pre eclampsia also, it doesn't discriminate. It can cause severe complications to your kidneys and end up causing renal failure. It can cause flash pulmonary edema, meaning fluid onto the lungs, largely from just such high blood pressures, because that's something we see with severely elevated blood pressures outside of pregnancy as well. And then, like I said, for the fetus, it can cause placental abruption as well, which is where the placenta detaches spontaneously before the baby has been delivered, and that can be potentially catastrophic and then also premature delivery or still birth. And we don't fully understand the mechanisms of preoclampsia, but you talked a lot Aarin about what we know about the placenta and this relationship between abnormal or whether it's inadequate, like not deep enough or too deep placentation and what we think is that that process results in these anti angiogenic factors that float around in our maternal bloodstream and end up causing damage to our blood vessels, and that causes us to have this increase in blood pressure and that is what ultimately leads to preeclampsia. So it's like inflammation and these like anti angiogenics like not making enough blood vessels, not getting enough remodeling in the uterus, and this whole like kind of perfect storm.
Almost signaling like, hey, there's not enough going on here, Send more, send more.
Exactly exactly.
And there are there is of course, a lot of interest in understanding like are there biomarkers. Are there things that we can identify, like in your blood to say either you definitely have preoclampsia or you are at higher risk of developing preeclampsia. And in several countries they actually do use a few different blood tests that test for a few different specific things. And I think I forgot to write down their names, but they're like PIF blah blah blah, some biomarkers exactly biomarkers. So far, as of twenty twenty four, we don't use those yet in the United States. So what we mostly look at in terms of trying to identify who is at risk for developing preeclampsia is what we know from the epidemiological data, and we know a lot about what the risk factors are that make someone higher risk for developing preeclampsia. We know that one of the biggest ones is having a previous pregnancy with preoclamsia.
Right.
The other huge one is having a first pregnancy. So you asked about the difference between like first pregnancies and subsequent pregnancies. First pregnancies are generally higher risk for preeclampsia compared to second, third, fourth pregnancies unless you had preoclamsia in your first one, right, And then you're at higher risk during the other ones as well too, And we don't fully understand that, but we think that it's related again to this immune tolerance thing, where your body has never seen these cells from this fetus floating around and you develop this immune response to it. Whereas if you've had a pregnancy before and your immune system tolerated it, you are at lower risk of having an abnormal reaction to them that in the future pregnancies. Yeah, if they're with the same paternal DNA that so.
That I find fascinating and I didn't get into this, but there is a lot about paternal DNA and like pre like exposure to paternal DNA before ye pregnancy.
Yeah, so like IVF pregnancies, especially those with donor sperm, are also a little bit higher risk than non IVF pregnancies or IVF without donor sperm. So it's really that's part of what lends support to this idea that there's like an immune tolerance spectrum kind of a thing.
Well, and it also makes sense then where why subsequent pregnancies where the first pregnancy there's preeclampsy, I would have pre eclamsy because it's almost sensitized exactly. Well, I've seen this before, right.
And I know what to do, Yeah, right, exactly. There's a lot of other risk factors though, having chronic hypertension prior to pregnancy, maternal age, so increasing age increases our risk why we do not know. And then a lot of other like complications that might affect the functioning of your organs prior to pregnancy, like kidney disease, things like lupus, which can affect blood clotting factors and things like that, having a family history of preeclampsia. And then this part's really important, especially in the United States, race is a risk factor for preeclampsia. Specifically, Black people who are pregnant are at significantly higher risk of pre eclamsia compared to white people who are pregnant. But that is not a biologic difference, and that this is specified in the ACOG guidelines. This is due to systemic racism. Because we also see that low income, regardless of race, which causes increase in life stressors, is also associated with an increased risk of preeclampsia. And so these are the kinds of differences that are really important to understand because by recognizing who is at risk, we can can we hopefully prevent preeclampsia.
How would prevent preeclampsia?
So glad that you asked, Darren right now, The only thing that we have to help prevent preeclampsia is low dose aspirin, of all things. Okay, So taking aspirin, which we did a whole episode on and you might remember, is an anti inflammatory agent that also irreversibly inhibits platelets from aggregating, so it stops your platelets from forming clots. And we think that these, like microthrombotic events are involved in the pathogenesis of preeclampsia and so by irreversibly inhibiting this platelet aggregation, we've shown through a lot of epidemiological studies that's what we think the mechanism is. But we know that starting low dose aspirin early in pregnancy, usually first or early second trimester, and continuing it until term can significantly reduce someone's risk of developing pre eclampsia, not make it zero. And the risks are different for whether it's term preeclamsia, pre term preclamsia, or postpartum preeclamsia.
So what are those I don't have like they sound.
Like they are.
They sound like it's like when in whin in pregnancy, does it develop? Yeah, most of the time, this is something that does not develop, or at least we don't see it. Can't recognize it clinically until after twenty weeks of pregnancy, okay, but it can potentially develop any time. We might just not like you might just not see the signs it might be. That's part of why people are looking for biomarkers. Can we find it. Can we find evidence of this super early on? Yeah, but usually it's after twenty weeks, the earlier that you start to see pre aclamsia. Usually the worst the outcomes are, which makes sense, yeah, because you're just going to have a bigger effect on the fetus and you're gonna have a longer time that you're having potentially complications to the mother as well, and postpartum and postpartum we really do not understand. But you can develop preclamsia for the first time postpartum, even if you did not have high blood pressure during pregnancy. We have no idea, no, And it is thought that like term, because some people also don't develop preclamsy until like right at the end, right they're after term, you're after thirty seven weeks, and you now all of a sudden have high blood pressure and then potentially preeclamsia. And we think that maybe those two entities are slightly different and less related to inadequate placentation early on, but maybe some other mechanism, but we don't know what that mechanism is yet, Like.
Is that the same, Is it related to any bits of the placenta remaining or like getting stuck.
To Sometimes, yes, it can be from the placenta not fully detaching or something like that, but not always. So it's not as like clear cut as that.
Right, Okay, there's still something that's sending that the signal of there's not enough foxygen exactly.
Okay, yeah, but we don't know exactly how it works. How is it different or is it not different?
And that kind of a thing.
In terms of other ways that we have to reduce the risk of preaclamsia, there's some evidence that maybe calcium supplementation might help, but it's not as clear cut as aspirin. And then in terms of if someone has preclamsia, how can we prevent it from getting severe or how do we cure it? Magnesium sulfate is given to prevent seizures, so specifically to prevent eclampsia. We don't know the mechanism or why it works, but it does. But the only cure for preclamsia is delivery of the fetus and the placenta. But that is not only something that you have to balance getting to a gestational age where the fetus can survive and hopefully thrive and also ensuring the health of the pregnant person. And of course that's not always the case because postpart in preclamsia does still exist. So it's a little bit complicated and we don't fully understand it.
Do you have a breakdown for the percentages of you.
And I really tried to find that, but I don't. I don't have a I don't have a good breakdown of that. Yeah, so that's preclamsia. And really, like the overall physiology of pregnancy, what about breasts. I wasn't gonna talk about breast until two episodes. They do start to change early on in pregnancy. Yeah, you actually start to make colostrum in like the second trimester, which is the first like stuff that you secrete. Right after that, the newborn usually eats for the first couple of days before your actual milk comes in.
Food aversions, food cravings.
I don't know.
Okay, there's a lot of talk about like the evolutionary significance of nausea and vomiting and food cravings.
And is it so that we speaks at the time that the fetus is most vulnerable to toxins crossing the placental Yeah, but I don't know. I mean, there seems to be some basis to that, like Darwinian medicine or whatever, but.
I don't know more about it than that.
But what I think is so interesting and part of the reason that I am so astounded by and fascinated by the physiology of pregnancy is that despite all of these changes to literally every organ system in our body, and despite all of the possible complications, some of which might be minor and not result in severe harm, and some of which can be very severe, despite all of that, the majority of pregnancies progress all the way to term and delivery without major complication, which is just astounding.
It is.
It is mind blowing that our bodies can change so dramatically. I have a question about that, Okay, permanent changes, What are there? And then how like what you can tell whether someone has been pregnant before anatom like looking at a lot.
Of times, I mean not all the time, h not all the time?
Yeah, what what are those things that give that that like signal that We'll.
Talk probably more about that in the fourth episode when we talk about postpartum stuff. Okay, So yeah, I don't have like an easy answer to that question. Okay, but yeah, I mean things change, like in terms of cervix changes and things like that that you can like maybe see on physical exam. There are there is evidence that like fetal cells remain in our tissues for like potentially the rest of our lives, which is crazy to think about it.
I mean again, it kind of is that relationship with cancer where it's like yeah, yeah, yeah, interesting, it's really really interesting.
But yeah, that's pregnancy erin.
In a short short and a half years that I've took to explain all of that, we went from a deep time. We've really crossed hundreds of millions of years.
Deep time all the way until delivery, which is deep time delivery.
Yeah.
So so if you'd like to learn more sources, boy, howdy, boy howdy, Okay, I have some sources here. Oh I bet.
There are two books that I read. One is called The Evolution of the Human Placenta, which is what it sounds like by Michael Power and Jay Schulkin. And then there's Life's Vital Link The Astonishing Role of the Placenta by Young Look. Then, uh, those are the books. I think they were pretty good overviews of what's going on. It is an overwhelming amount of information. If you want to learn more about retroviruses, there are a few papers that I have posted. One is by Chung from twenty thirteen called Retroviruses facilitate the rapid evolution of the mammalian placenta.
Love it.
There are some other ones too about retroviruses that are good. Then there's shits at All from twenty nineteen, Evolution of placental invasion and cancer metastasis are causally linked.
Ooh yeah, interesting, interesting, bold statement.
Bold statement. Then from twenty thirteen by Crosley Placental invasion, preeclampsia risk, and adaptive molecular evolution at the origin of the Great apes evidence from genome wide analyzes because humans are not the only species to get preeclampsia, which we thought for the longest time that we were.
But no.
I think there was a gorilla at the Houston Zoo last year the year before something that had preeclampsia or baby I know, she.
Okay, I think, so, okay good.
I have a number of sources for this, some of which focus more on just the basic physiology of pregnancy. One that I liked that was easy to read was called Physiology of Pregnancy from Anesthesion Intensive Care Medicine from twenty nineteen. I had a few others that were more focused on the cardiovascular physiology of pregnancy too that were great. A review paper on just stational diabetes called Justational Diabetes melodis really creative title from Nature Reviews Disease Primers twenty nineteen, and another from Nature Reviews Disease Primers on pre acclamsia called preaclamsia not really creative titling. I mean, I feel like it's pretty easy to understand what the is, what the papers are that know what you're getting.
It's real puns puns.
In this and then there was a bunch more so listen check out our website this podcast will Kill You dot com under the episode's tab, where you can find the list of all of the sources that we used from this episode in every single one of our episodes.
Single one. A huge thank you again to everyone who sent in their first hand account and shared them with us. We really can't thank you enough. Thank you, thank you, thank you, thank you.
We'll try though.
Thank you again to everybody here at Exactly Right Studios for having us. We're super excited about it. Thank you Tom, thank you Leana, thank you Jessica, thank you Brent, thank you, Craig everyone.
Thank you everyone. There's so many other people's do so much fun it has.
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