Speaker 1: We want to start with a disclaimer that throughout this
Speaker 1: series we feature explanations and stories that include some heavy material,
Speaker 1: including early pregnancy, loss, stillbirth, and other traumatic experiences of pregnancy, childbirth,
Speaker 1: and the postpartum period.
Speaker 2: I'm Siena. I'm twenty eight years old and twenty eight
Speaker 2: weeks pregnant with my first child. It seems like a cliche,
Speaker 2: but my most daunting pregnancy symptom has been mourning sickness.
Speaker 2: I was aware that it was a misnomer and that
Speaker 2: it would not be restricted to the morning, but my
Speaker 2: biggest surprise was how frequent, long, and intense morning sickness is.
Speaker 2: I didn't expect to lose weight during the first time
Speaker 2: master or be woken up at one am because of
Speaker 2: the sudden urge to vomit. I'm not a stranger to vomiting.
Speaker 2: I've thrown up before with the flu, food poisoning, intense migraines,
Speaker 2: anxiety episodes, and of course after a night of having
Speaker 2: a little bit too much fun, as they say, But
Speaker 2: morning sickness is different. It feels similar to motion sickness,
Speaker 2: like you're on a boat all the time when there's
Speaker 2: nothing in your stomach. The urge to throw up is
Speaker 2: so intense, and you end up throwing up this thick,
Speaker 2: bright yellow fluid that looks like, honestly like lemon gatorade.
Speaker 2: I had my eyewatch give me sound warnings from my
Speaker 2: own vomiting, saying just ten minutes at this level can
Speaker 2: cause temporary hearing loss, and in my experience, the heaving
Speaker 2: has been so intense that even if I just went
Speaker 2: to the bathroom, I still end up peeing myself. It's
Speaker 2: just so aggressive. I actually have to wear diapers now
Speaker 2: just in the off chance that I happen to throw up,
Speaker 2: and that's just something I've accepted as part of my
Speaker 2: life now. With my pregnancy journey, it has been a challenge,
Speaker 2: especially with working full time and having to commute two
Speaker 2: and a half hours every day. You never know when
Speaker 2: morning sickness is going to strike, so I even have
Speaker 2: little bags in my car. My morning sickness started at
Speaker 2: week five and was pretty much all day every day
Speaker 2: until week twenty two. I got a little bit of
Speaker 2: a break, and then it started up again around week
Speaker 2: twenty six.
Speaker 1: Although it's no longer all day.
Speaker 2: It is truly just in the morning usually, and I've
Speaker 2: tried all the remedies that they tell you, ginger B six,
Speaker 2: unise pressure point bands, the list goes on. Zil friend
Speaker 2: has worked the best for me, but it's still very
Speaker 2: hit or miss on whether or will work on any
Speaker 2: given day.
Speaker 3: When I went in from my first ultrasound at seven weeks,
Speaker 3: the doctor was able to see a gestational sack and
Speaker 3: a yolk sack, but no fetal pull. My doctor tried
Speaker 3: to assure me that it was possible I wasn't as
Speaker 3: far along as I'd thought, but I had been tracking
Speaker 3: my ovulation and I knew this wasn't a good sign,
Speaker 3: since this was a deeply wanted pregnancy. My doctor suggested
Speaker 3: we win week and do another ultrasound at eight weeks.
Speaker 3: The ultrasound showed some growth, a fetal pull, and a heartbeat.
Speaker 3: At first, I felt so relieved, certain that progress from
Speaker 3: the week before meant that maybe things would actually be okay.
Speaker 3: But then my doctor explained that the embryo was measuring
Speaker 3: less than six weeks and the heartbeat was only eighty four.
Speaker 3: When I got home, I turned to Google and found
Speaker 3: a study that said first trimester heart rates under ninety
Speaker 3: had a quote dismal prognosis The following week, when I
Speaker 3: was nine weeks into my pregnancy, I went in for
Speaker 3: my final ultrasound, which showed an embryo measuring only six
Speaker 3: weeks one day and no heart beat. My doctor was
Speaker 3: able to schedule me for a DNC the next day.
Speaker 3: My whole pregnancy, I had no indication that anything was wrong.
Speaker 3: I had strong dark lines on my home pregnancy test,
Speaker 3: and early blood tests showed my hCG doubling at an
Speaker 3: appropriate rate. I felt lucky that I was experiencing only
Speaker 3: mild nausea, but I did have all the usual pregnancy symptoms,
Speaker 3: and I had no bleeding or spotting at all, no cramping,
Speaker 3: absolutely nothing that led me to think my pregnancy wasn't
Speaker 3: progressing exactly as it should. I knew miscarriage was common,
Speaker 3: especially for women in their late thirties like me, but
Speaker 3: I always assumed that there would be some kind of
Speaker 3: outward sign. Going through a missed miscarriage led to feelings
Speaker 3: of profound betrayal. My pregnancy wasn't viable and my body
Speaker 3: had no idea. I feel as though I am no
Speaker 3: longer able to trust the signals that my body is sending.
Speaker 1: New Thank you all so much for sharing your story
Speaker 1: with us, and really a huge thank you to everyone
Speaker 1: who has written in with their experiences. We read each
Speaker 1: and every single one of the hundreds of first hand
Speaker 1: accounts that people submitted, and we're so grateful and truly
Speaker 1: honored that you felt like you could share those with us,
Speaker 1: and we tried to include as many of your stories
Speaker 1: as possible and you'll hear more first hand accounts throughout
Speaker 1: the rest of this episode and the other episodes in
Speaker 1: this series.
Speaker 4: Yeah, thank you again. It really was a huge privilege
Speaker 4: to be able to read all of your stories listen
Speaker 4: to all of the stories that you guys sent in.
Speaker 4: I genuinely like cried through, oh my most of whether
Speaker 4: it was happy or sad tears. So really, thank you
Speaker 4: again so much from the bottom of our hearts for
Speaker 4: sharing all of your stories with.
Speaker 1: Us, truly.
Speaker 5: Yeah. Hi, I'm erin Welsh and I'm erin Allman Updy.
Speaker 1: And this is this podcast will kill You.
Speaker 4: Today is episode two of our four part series, four
Speaker 4: parts on pregnancy. Yep, yeah, yet again coming to you
Speaker 4: from the exactly right studios.
Speaker 1: I know, I feel like I'm getting more used to
Speaker 1: it now.
Speaker 5: Yeah, it's good. It's going to be like this is
Speaker 5: this is the new normal.
Speaker 1: This is the new normal. But before we get into
Speaker 1: this episode, we want to share a few words about
Speaker 1: what these four episodes will cover. And if you listen
Speaker 1: to our first episode, this will sound familiar to you,
Speaker 1: but in case this is your first time tuning in,
Speaker 1: welco just want to go everything over again. Yes, welcome,
Speaker 1: but we also want to get into the language that
Speaker 1: we'll be using and our goals with creating this series.
Speaker 1: So we decided early on to dedicate four episodes to
Speaker 1: cover pregnancy, one for E to trimester.
Speaker 5: Not enough, we realized early on, but alas.
Speaker 1: Very very much not enough. And yeah, and so we
Speaker 1: we did realize this, and you know, we're not going
Speaker 1: to be able to cover everything, and throughout the series
Speaker 1: we started to jot down like different ideas for future episodes,
Speaker 1: and so do keep in mind that, you know, if
Speaker 1: you're listening in and you're like, oh, I want to
Speaker 1: know more about that, Hey, send us your idea. Yeah,
Speaker 1: you know, maybe we will cover it in the future episod'
Speaker 1: sure we will, I'm sure that we will.
Speaker 4: So knowing that this entire series will likely not answer
Speaker 4: all of your questions about pregnancy or cover every experience
Speaker 4: that a person can have during pregnancy. Pregnancy is an
Speaker 4: incredibly individual experience, as highlighted by all of our first
Speaker 4: hand accounts.
Speaker 5: But what we aim to.
Speaker 4: Do with this whole series is take you through the
Speaker 4: broad changes that we see in the human body and
Speaker 4: that you might experience during pregnancy, childbirth, and the postpartum period,
Speaker 4: and then also explore the historical and today especially the
Speaker 4: evolutionary aspects of pregnancy and childbirth. So each episode very
Speaker 4: roughly corresponds to each trimester. So last week we covered
Speaker 4: the first trimester, how you even know whether or not
Speaker 4: you're pregnant, and what was happening in very early development yep.
Speaker 1: Then today and our second episode, we're going to talk
Speaker 1: about the amazing organ that is the placenta and some
Speaker 1: of the physiological changes which are really I'm so excited
Speaker 1: to learn more about what is happening. Okay, I can't
Speaker 1: tell you how I have two more episodes to like
Speaker 1: briefly go through, but we're gonna talk today about the
Speaker 1: placenta and these physiological changes that someone will experience as
Speaker 1: they go through pregnancy, including some of the complications that
Speaker 1: might arise.
Speaker 4: And then next week in our third episode, we'll talk
Speaker 4: about childbirth itself, will cover labor, all of the different
Speaker 4: modes of delivery, and then the history of cesarean sections Yep,
Speaker 4: it's gonna be good.
Speaker 1: It's gonna be good. And then finally, our fourth episode,
Speaker 1: which happens to be our season finale, will be about
Speaker 1: this concept of the fourth trimester, exploring the changes that
Speaker 1: happen after pregnancy, and we're also going to be talking
Speaker 1: big picture history about overall medicalization of pregnancy and childbirth
Speaker 1: and how the transition from home to hospital happened and
Speaker 1: some of the consequences of that.
Speaker 4: We intend for all of these episodes to be inclusive
Speaker 4: of all families, and we recognize that not everyone who
Speaker 4: experiences pregnancy identifies as a woman, so we try wherever
Speaker 4: we can to use general neutral language such as pregnant person,
Speaker 4: while at the same time, we recognize that a lot
Speaker 4: of what we're going to discuss when it comes to
Speaker 4: medical bias during pregnancy and childbirth, both historically and today,
Speaker 4: really is the result of gender discrimination as well as racism,
Speaker 4: and so in those contexts we will also be using
Speaker 4: the term women and women, and throughout these episodes will
Speaker 4: be using terms like mother or maternal and paternal as
Speaker 4: these are terms that are very often used in the
Speaker 4: scientific and medical literature.
Speaker 1: And we also want to acknowledge that there is no
Speaker 1: such thing as a normal pregnancy. Yeah right, there is
Speaker 1: no textbook pregnancy. There's plenty of textbooks about pregnancy, yes,
Speaker 1: but when it comes to pregnancy, there's no textbook example. Yeah,
Speaker 1: but we do want to also provide a baseline of
Speaker 1: the expected physiologic and anatomic changes that occurred during pregnancy,
Speaker 1: because that can help us to understand where these complications
Speaker 1: are coming from and what we actually mean by complication exactly.
Speaker 5: Yeah.
Speaker 4: And so now today we enter the second trimester. We
Speaker 4: shall but first first quarantine any time.
Speaker 1: And we are drinking again.
Speaker 4: Great expectations, great expectations. Yeah, I do have great expectations
Speaker 4: for this episode. I have great expectations for this whole
Speaker 4: series too. Yeah, remind us, Aaron, what is in great expectations?
Speaker 1: Of course, it is blackberries and muddled with mint, some
Speaker 1: ginger ale and lemon. It's a plus.
Speaker 4: Plusy Berita for a pregnancy series for obvious reasons. It's
Speaker 4: great And if you haven't already, please do check out
Speaker 4: YouTube where you can find the exactly right network channel
Speaker 4: that now includes our content, including a very special quarantine
Speaker 4: recipe by Georgia Hartstark made just for this series.
Speaker 1: We're thrilled and we'll also be posting the recipes for
Speaker 1: this quarantining plus suber rita set on our social media
Speaker 1: and as well as our website. This podcast will kill
Speaker 1: you dot com?
Speaker 5: Have you been there yet?
Speaker 1: I get to shut it again to you?
Speaker 4: On our website, This podcast will kill you dot Com,
Speaker 4: you can find so many incredible things. For example, you
Speaker 4: can find transcripts from each and every one of our episodes.
Speaker 4: You can find a good Reads list from uh where
Speaker 4: Aaron Welsh like story books mostly.
Speaker 1: There's also a bookshop dot org affiliate.
Speaker 4: Again, I was going to say that this time, I
Speaker 4: forgot it last time. We've also got merch, some pretty
Speaker 4: incredible merch that we're wrapping today. If you're seeing this
Speaker 4: on video. What else do we have? We have sources
Speaker 4: from every single one of our episodes. We have links
Speaker 4: to Bloodmobile who provide it's the music for all of
Speaker 4: our episodes. We've got a contact us form, a first
Speaker 4: hand account form. Have you been to our website yet?
Speaker 1: No one is gonna want to go. They're like, I've
Speaker 1: seen it all. I've heard you talk about it all.
Speaker 5: What else?
Speaker 1: What else do I need?
Speaker 5: Nothing new?
Speaker 1: Nothing new?
Speaker 5: Okay, shall we think? We shall?
Speaker 4: I don't have any other business for today. Same so
Speaker 4: me Aaron all about the placenta.
Speaker 1: I really can't wait. Good, Let's take a break out
Speaker 1: and then and then I'll get started.
Speaker 6: Okay.
Speaker 3: Hi.
Speaker 7: My name is Tracy and I was thirty years old
Speaker 7: and went off the birth control pill. I had been
Speaker 7: on it since I was sixteen. Hoping for the best,
Speaker 7: my husband and I went for it. Three months into
Speaker 7: being off the pill, I was late having my period.
Speaker 7: It was a Friday night and I would normally be
Speaker 7: having a nice gen and tonic to greet the weekend,
Speaker 7: so I went to the store and bought a pregnancy
Speaker 7: test and immediately took it. It was negative. Okay, I
Speaker 7: guess I will be having a J ANDT and went
Speaker 7: into the kitchen to mix up my favorite cocktail. Five
Speaker 7: days later, on April first, I had a regular checkup
Speaker 7: at my o BA. She and I talked about what
Speaker 7: my plan was and that I was officially off the pill.
Speaker 7: I did the normal things at the appointment, you're in sample, etc.
Speaker 7: She was gone for a bit and when she came
Speaker 7: back into the room, she said, well, this is no
Speaker 7: April Fool's joke, but you're pregnant. WHOA Okay. I went
Speaker 7: home to tell my husband and thought I'd have a
Speaker 7: little fun with the fact that it was April Fool's Day. So,
Speaker 7: aside from being totally shocked, we were excited and a
Speaker 7: bit terrified. The next week, I went into the doctor's
Speaker 7: office to have my hCG levels measured. My doctor said
Speaker 7: they weren't great, but perhaps that is why I got
Speaker 7: a negative reading when I had taken the test. I
Speaker 7: would need to come back into the office a few
Speaker 7: days later to see if they had increased. But they
Speaker 7: had not increased. They should be doubling. At this point
Speaker 7: I figured this pregnancy might not make it. But the
Speaker 7: good news was as I had become pregnant and I
Speaker 7: could try again. A few days later, I went back in. Nope,
Speaker 7: not have any luck with the numbers. I went back
Speaker 7: several times over a couple of weeks, and it just
Speaker 7: didn't seem like this is going to happen. Then a
Speaker 7: couple of weeks into the process, I went in for
Speaker 7: yet another test, and my doctor came into the exam
Speaker 7: room and said, your numbers are all great. Everything had
Speaker 7: rebounded and I was exactly where I should be, So
Speaker 7: I thought I could get a little excited now from
Speaker 7: then on out, Aside from feeling very dizzy and sick
Speaker 7: for four months, she came bounding out a week early,
Speaker 7: a healthy baby girl, and now she is about to
Speaker 7: start her third year of medical school. You never really
Speaker 7: know how things are going to play out. And yes,
Speaker 7: she is the one who got me hooked on tp WK.
Speaker 8: Why Hi. My name is Sarah and I live in Oxydghire, England,
Speaker 8: with my husband Mike and our younger son Ethan. Like
Speaker 8: many people, I didn't actually know my blood group until
Speaker 8: I became pregnant. Thankfully, being Reese's negative made very little
Speaker 8: difference to either of my first two pregnancies. I had
Speaker 8: the routine anti D injections and both boys were born
Speaker 8: full term and healthy. Sadly, my third pregnancy ended in
Speaker 8: early miscarriage. No reason was found and I was reassured
Speaker 8: that it wasn't connected to Reese's disease. However, when I
Speaker 8: became pregnant with Ethan the following year, signs of a
Speaker 8: Reese's reaction appeared very early. A blood test showed the
Speaker 8: presence of antibodies that were found to be resistant to
Speaker 8: anti D. Thankfully, the antibody levels remained low and regular
Speaker 8: skins reassured us that he was growing as expected. Each
Speaker 8: week that passed felt like a victory. Unfortunately, at about
Speaker 8: five months, the antibody levels rose sharply. Regular checkups continued
Speaker 8: as we monitored him for any sign of distress. The
Speaker 8: plan was supposedpone any intervention for as long as we could.
Speaker 8: We made it to seven months before the scans showed
Speaker 8: that he was developing fetal anemia. He needed a blood
Speaker 8: transfusion to limit the effects of the anemia and to
Speaker 8: give him more time before delivery became necessary. Despite signing
Speaker 8: all of the waivers who really weren't prepared for the
Speaker 8: transfusion to fail and for an emergency CEA section to
Speaker 8: be performed to save his life. I vividly remember the
Speaker 8: shock of seeing him for the first time, so small
Speaker 8: in his incubator, covered in wires, with a machine breathing
Speaker 8: for him. It just didn't feel real. I was dischonged
Speaker 8: a few days after Ethan was born, and going home
Speaker 8: without him was one of the hardest moments in my life.
Speaker 8: My husband's paternity leave was soon over, and I then
Speaker 8: faced continuing to recover from surgery while caring for our
Speaker 8: older boys and trying to visit the hospital as often
Speaker 8: as possible. Slowly, Ethan became stronger and he worked his
Speaker 8: way through the nurseries in a nicu and scaboo. Finally,
Speaker 8: after eight long weeks, we got to bring him home
Speaker 8: just a few days before his due date and without
Speaker 8: the need for any additional oxygen support. Our four pound
Speaker 8: Premium is now a happy, very tall, thirteen year old
Speaker 8: with a brilliant sense of humor. His difficult start in
Speaker 8: life has had no effect on his health, and most
Speaker 8: people can't believe that he was premature. We can never
Speaker 8: do enough to thank the NHS and everyone at the
Speaker 8: John Radcliffe Hospital in Oxford. Our lives are ritual with
Speaker 8: Ethan in them.
Speaker 1: Around the world and over centuries, the placenta has held
Speaker 1: and continues to hold deep meaning. Some cultures revere it,
Speaker 1: honoring it with a special burial. Mummified placentas have been
Speaker 1: found in ancient Egyptian two ms. You know I would
Speaker 1: get back to ancient Egypt again and others consume it
Speaker 1: and recognition of its power. It's been used in beauty
Speaker 1: products preserved in a jar to ensure good health. It
Speaker 1: is varyingly seen as an older sibling, a twin part
Speaker 1: of the baby itself, a friend, the finest jacket. This
Speaker 1: reverence is not unwarranted. The placenta, at its core, represents
Speaker 1: the fundamental vital connection between a mother and developing fetus,
Speaker 1: a physical, metabolic, and immunologic bond. It's the first organ
Speaker 1: you make and the first you say goodbye to.
Speaker 5: That feels so profound.
Speaker 1: Because it is.
Speaker 5: Am I going to cry about it?
Speaker 1: I just teared up a little bit myself. I've read
Speaker 1: this over this a million times.
Speaker 5: Yeah, but wow, aronkay.
Speaker 1: It's the only organ ever connected to another individual. It
Speaker 1: filters waste, it transfers vital nutrients, and acts as an
Speaker 1: important immunological barrier between mother and fetus. It's remarkable.
Speaker 4: I also, I have shared before how much I love
Speaker 4: the uterus. Yeah, and I still feel that way. Like
Speaker 4: I feel so. I have my earrings on today. I
Speaker 4: love thank you their gift from you.
Speaker 1: Congrats to myself for the good gift.
Speaker 4: I especially doing this research, and I haven't even learned
Speaker 4: what you're going to teach me yet. But I love
Speaker 4: the placenta, I know so much.
Speaker 1: Yeah, you know, and I think it had always been
Speaker 1: just a secondary character what in your life story or
Speaker 1: in my life story, in the story that I imagine, you know.
Speaker 1: And I don't even know if I had a good
Speaker 1: idea of what a placenta looks like. Yeah, so Aaron,
Speaker 1: would you mind?
Speaker 4: Do you want to see I would like to see
Speaker 4: I have today with us here today bottle of a
Speaker 4: plas not a placenta. Thank you to UCSC Family Medicine
Speaker 4: Department for letting me borrow this.
Speaker 5: Shout out.
Speaker 1: Yeah, I mean that's that's basically it.
Speaker 5: It is round, it's discoyed. It's discoyed.
Speaker 4: It has vessels on one side that is connected to
Speaker 4: the baby by a numbilical cord, and then on the
Speaker 4: other side where it was connected to the uterus. It
Speaker 4: usually is more rough and bumpy. That's why this one
Speaker 4: is like that.
Speaker 1: Yeah, I think it's it's bigger than than I think.
Speaker 1: A lot of people think it's better that bigger than
Speaker 1: I thought.
Speaker 5: Yeah it would be, and some of them are hefty.
Speaker 1: Oh yeah, I was looking at pictures and I was just.
Speaker 5: I don't know if I should leave this blown away
Speaker 5: or that's up to you. Keep it here there for
Speaker 5: the vibes.
Speaker 1: But yeah it is good. Yeah we can. We can
Speaker 1: honor the placenta here. Yeah, but yeah it is. It
Speaker 1: is a remarkable organ it really is. And I really want,
Speaker 1: if nothing else, just for us to think more about
Speaker 1: the placenta, like going forward. Anyone who's listening, okay, because
Speaker 1: the placenta deserves this recognition. At the same time, the
Speaker 1: placenta is also at the root of some of the
Speaker 1: most common disorders of pregnancy, such as preclamsia. It can
Speaker 1: invade into the uterine wall too deeply, not deeply enough,
Speaker 1: or in a problematic spot. It can separate too early
Speaker 1: or not separate when it should, and the placenta acting
Speaker 1: in these unexpected ways can lead to potentially harmful or
Speaker 1: even deadly consequences for both fetus and pregnant person. As
Speaker 1: I'm always saying on this podcast, life is full of
Speaker 1: trade offs, and the placenta is no exception. The intimacy
Speaker 1: formed by this connection is necessary for fetal growth and development,
Speaker 1: but it can also leave both mother and fetus vulnerable
Speaker 1: when things go wrong. Despite this potentially high cost, the
Speaker 1: placenta is a widespread feature of mammals, and it has
Speaker 1: evolved in many other classes of animals. The how and
Speaker 1: why of that evolutionary story is what I'm going to
Speaker 1: talk about today. So exciting from the human placenta's ancient origins,
Speaker 1: to the diversity we see in the placentas of present
Speaker 1: day mammals, from the role viruses may have played in
Speaker 1: its development, to some of the trade offs that we
Speaker 1: humans face when it comes to our invasive placentas, and
Speaker 1: also what I mean by invasive. I'll get into it.
Speaker 1: My overall goal is to get us to think about
Speaker 1: why the placenta as opposed to other reproductive strategies like
Speaker 1: egg laying, and why the human placenta as opposed to
Speaker 1: other mammalian placentas, like why why these things? How did
Speaker 1: we get here? Before I dig in, I want to
Speaker 1: mention a couple of things upfront. The first is that
Speaker 1: I'll be talking about the placenta in terms of what
Speaker 1: it is expected to do throughout a pregnancy, which does
Speaker 1: not capture the incredible variation that can occur between individuals,
Speaker 1: or even within one individual. Pregnancy. Yeah, nor will I
Speaker 1: be exploring the multitude of things that can happen when
Speaker 1: the placenta acts Outside of that. We could do an
Speaker 1: entire episode on each placental disorder. We really really could.
Speaker 1: The other thing is that this is not a comprehensive
Speaker 1: review of the placenta in all of its dimensions, like
Speaker 1: the cultural importance, the history of its study, its physiology,
Speaker 1: and so on. It's just a quick tour through one
Speaker 1: of the coolest organs. But fortunately there are many sources
Speaker 1: where you can get that more detailed info, and we'll
Speaker 1: be posting those on our website. Okay, okay, you know
Speaker 1: that I love to start deep.
Speaker 5: How deep are we going to go?
Speaker 1: It's pretty deep. Before the dinosaurs life on Earth began
Speaker 1: in the water.
Speaker 5: I love it when you do this, I really doh
Speaker 5: my gosh.
Speaker 1: Ok And there it remained for hundreds of millions of years.
Speaker 1: We're going pretty deep.
Speaker 5: I love it.
Speaker 1: Around three hundred and fifty to four hundred million years ago,
Speaker 1: a group of four legged animals made their way onto land.
Speaker 1: This group is the ancestor of all vertebrates except for fish,
Speaker 1: so it includes humans right not fish. These first the
Speaker 1: land dwelling animals couldn't quite shake their aquatic roots, and
Speaker 1: so they continued to keep laying their unfertilized eggs in water,
Speaker 1: where a male would later come by and fertilize them.
Speaker 1: This water aspect of these eggs, it's not a preference,
Speaker 1: it was a necessity. Without it, the eggs would dry out.
Speaker 1: But this reliance on water was limiting, so some of
Speaker 1: these animals evolved another strategy, eggs covered with a more
Speaker 1: protective coating, which meant that they could last outside of water,
Speaker 1: which then enabled these animals to further explore land and
Speaker 1: go out deeper and deeper into land. But this coating
Speaker 1: made the eggs less permeable, which meant that fertilization had
Speaker 1: to happen internally, acquired a whole new set of things
Speaker 1: before the egg and the yulk had fully formed. Okay, yep, yeah,
Speaker 1: And then that was in contrast to externally, like the
Speaker 1: way that frogs will lay.
Speaker 4: Eggs in or like a lot of fish, a lot
Speaker 4: of fish, right exactly.
Speaker 1: And so then after fertilization internally and after the yolk
Speaker 1: and egg had formed, the female would then lay her
Speaker 1: eggs and wait for them to hatch like a crocodile, right, right.
Speaker 4: Not the first egg laying animal that I think of,
Speaker 4: by the way, but I love that that for example.
Speaker 1: What is the first one? A bird?
Speaker 3: Yeah?
Speaker 1: But like, yeah, I mean it's true, I think of crocodiles.
Speaker 1: I love that were turtles.
Speaker 5: I don't often think about crocodile reproduction. I think that's
Speaker 5: what it is.
Speaker 6: You.
Speaker 1: Oh, but you think often about bird reproduction.
Speaker 4: Well, I eat eggs, so, oh egg like that's mine.
Speaker 1: Yeah, I guess I don't eat crocodile eggs.
Speaker 5: But I just.
Speaker 1: Also, that's so funny because when you said bird, I
Speaker 1: pictured like robins, not chickens, which is the most Oh
Speaker 1: my god, I love it.
Speaker 4: Okay, so crocodiles, crocodiles la eggs and so.
Speaker 1: But the time window between internal fertilization and egg laying,
Speaker 1: so like when those eggs were fertilized and formed and
Speaker 1: then when they were actually like deposited, right, was variable.
Speaker 1: If you kept your eggs inside longer, it meant that
Speaker 1: you could more closely control the temperature and humidity that
Speaker 1: these eggs were exposed to, which could increase the chances
Speaker 1: that your offspring survived. Okay, Eggs can be quite vulnerable
Speaker 1: to environmental threats, predators, weather extremes, fungal pathogens, and so
Speaker 1: some animals took this one step further, keeping the eggs
Speaker 1: inside until they were ready to hatch. Okay, one major
Speaker 1: transition remained though, How did the embryo get its nutrients?
Speaker 1: How did that embryo inside the eggs? So egg layers
Speaker 1: provided nutrients through the yolk encased in that less permeable barrier.
Speaker 1: But the thing is you were limited. So like when
Speaker 1: that egg was formed, that yolk it was usually going
Speaker 1: to deplete until that's all you have. It's all you have.
Speaker 4: The embryo has to be able to survive and develop
Speaker 4: enough with just whatever is in that yolk.
Speaker 1: Yeah, it's like meal prepping essentially.
Speaker 5: Yeah, it's exactly.
Speaker 1: That's exactly like prepping.
Speaker 5: I love it.
Speaker 1: Okay, Okay, there you go. See. But then what if
Speaker 1: you didn't want a meal prep and you're like this
Speaker 1: is not enough food. I'm yeah. Later in the week
Speaker 1: and you're like I'm starving. Yeah yeah, So what if
Speaker 1: instead you could provide nutrients to the embryo directly and continuously.
Speaker 4: Continuous throughout pregnant. You could make your meals on the
Speaker 4: go right, Yeah.
Speaker 1: You could always have like a resource. Oh well, just
Speaker 1: there's a little snack drawer.
Speaker 5: Snack drawer.
Speaker 1: Yeah, I don't know, these metaphors might not work. I
Speaker 1: really like we can. We can reel it back in.
Speaker 1: And so a subset of these egg laying animals evolved
Speaker 1: the ability to pass nutrients directly to the developing embryo,
Speaker 1: not via a yolk, but through an organ that connected
Speaker 1: mother to embryo, an organ that we know as the placenta.
Speaker 1: So we went from laying unfertilized eggs and water, to
Speaker 1: laying fertilized eggs on land, to retaining those fertilized eggs
Speaker 1: for longer periods of time, to then getting rid of
Speaker 1: this eggshell that didn't let nutrients in or out to
Speaker 1: directly connect with the fetus and remain in contact for
Speaker 1: the duration of pregnancy.
Speaker 5: Okay, that's how we got boom boom boom to the placenta, straightforward, honestly, right.
Speaker 1: Okay, it's an oversimplification, of course, it's like covering hundreds
Speaker 1: of billions of years. And I also don't want to
Speaker 1: with this, you know, with this explanation give off the
Speaker 1: impression that the placenta or live birth is like the
Speaker 1: end all, be all reproductive strategy, or that it's one
Speaker 1: unique to mammals. Like I said earlier, it evolved independently
Speaker 1: in many classes of animals. And the fact that we
Speaker 1: see so many different reproductive strategies today, like laying unfertilized eggs,
Speaker 1: laying fertilized eggs, retaining eggs until they're ready to hatch,
Speaker 1: life birth, and so on, the variation is endless. Yeah,
Speaker 1: what was the one that I like texted you about
Speaker 1: gastric brooding frogs?
Speaker 4: Yeah, and then I came back with the sea horses.
Speaker 1: Yes, yeah, I know. There are so many different ways,
Speaker 1: so many reproductive strategy It's incredible. And this shows us
Speaker 1: that there are pros and cons for each and that
Speaker 1: what works for one species might not work for another.
Speaker 1: So sure, laying eggs might make them more susceptible to
Speaker 1: external threats, but it frees you up out running or
Speaker 1: out flying a predator is more challenging when you're carrying
Speaker 1: around a load of offspring in your uterus literally. On
Speaker 1: the other hand, investment in offspring is generally higher than
Speaker 1: placental mammals, which can translate into higher survival for those offspring.
Speaker 1: I mean, we could spend hours discussing and you know,
Speaker 1: arguing the trade offs of different reproductive strategies, but we're
Speaker 1: not going to do it today.
Speaker 3: No.
Speaker 1: So I mentioned that the placenta evolved independently multiple times
Speaker 1: across the animal kingdom. Yeah, what in mammals though it
Speaker 1: happened just once?
Speaker 9: Ok.
Speaker 1: I gotta talk about the mammals.
Speaker 5: Okay, Now I really want to know about the other ones. Interesting.
Speaker 1: You know, I can send you some sources. Can go
Speaker 1: to our website, this podcast with you dot com, go
Speaker 1: to the sources tet. But this means that the incredible
Speaker 1: placental diversity that we see in mammals today comes from
Speaker 1: just one origin. Wow, around two hundred and fifty million
Speaker 1: years go. We still have to go far back. A
Speaker 1: group of animals called the thrapsids split off from the rest.
Speaker 1: And these were reptile like creatures, and they differed from
Speaker 1: the rest in three key ways. First, they could generate
Speaker 1: their own body heat and maintain temperature crucial. Second, they
Speaker 1: had body hair, which helped provide insulation for heat maintenance.
Speaker 1: And third they developed the ability to produce milk. Oh.
Speaker 5: Interesting, I know, I didn't know it went that far
Speaker 5: back either.
Speaker 8: Yeah, Okay.
Speaker 1: Over the next one hundred million years or so, this
Speaker 1: group continued to diversify, splitting off into the three main
Speaker 1: groups that today make up modern mammals. We've got the monitories,
Speaker 1: the egg laying mammals like the platypus and the Echidna
Speaker 1: love them. We've got the marsupials, the one who use
Speaker 1: a pouch and birth teeny tiny young like the Tasmanian devil, kangaroo, Koala,
Speaker 1: etct some of my faves. And then the Eutherians or
Speaker 1: the placental mammals, which includes all other mammals today, including humans.
Speaker 1: I have to throw in this way actually because it
Speaker 1: just it bothered me as I read this, and it's
Speaker 1: probably old news to people who know more about the placenta.
Speaker 1: But marsupials also possess structures resembling a placenta. They just
Speaker 1: play a slightly different role and are very different than
Speaker 1: our placentas. And so one key difference between marsupials and
Speaker 1: Eutherians is when nutrient transfer takes place. So in marsupials
Speaker 1: it mostly takes place during lactation, while in Eutherians most
Speaker 1: nutrient transfer happens during gestation.
Speaker 5: Got it right, I think I understand.
Speaker 4: Yeah, so they have something that's like a placenta, but
Speaker 4: its main role is not.
Speaker 1: Provided, not threading the nutrients. Yeah, yeah, makes sense. But
Speaker 1: it's like, but we still call the Eutherian mammals the placentals, okay,
Speaker 1: And I'm just like, well, actually, yeah, I know it's
Speaker 1: my I can't resist. But what I wanted to say
Speaker 1: about lactation was that in monotremes they don't have nipples.
Speaker 1: They have like little pores. Yes, I knew that, and
Speaker 1: they like the little the little babies lap up. I know,
Speaker 1: it's so so amazing.
Speaker 5: I know I want to ask more about I won't though.
Speaker 1: You get to ask me, and I'll just say I
Speaker 1: don't know.
Speaker 5: Well, I don't know how to form my question.
Speaker 4: Okay, problem because it's like going back to like those
Speaker 4: early early early apps, the thrapcids, like you know, dimetrodon
Speaker 4: Yeah was that a thrapsid or was that something? See
Speaker 4: it's only because I'm thinking of like our all of
Speaker 4: the dinosaur toys that we have at home, and I
Speaker 4: always go, well, this one's not right.
Speaker 1: Which ones are therapids? In which ones or something like that.
Speaker 6: Yeah.
Speaker 1: See, and this is where.
Speaker 4: My anyways, Yeah, I might did evo bio off topic,
Speaker 4: off topic.
Speaker 1: Well, well we'll bring it back to the placenta.
Speaker 5: That's please.
Speaker 1: Okay. So, so these earliest Eutherian placenta having mammals probably
Speaker 1: emerged around one hundred and ten to one hundred and
Speaker 1: twenty five million years ago. Okay, Yeah, and from there
Speaker 1: nature did its thing. Evolution did its thing. The asteroid
Speaker 1: that caused a massed extinction event sixty six million years
Speaker 1: ago did its thing. Cleared the way for the age
Speaker 1: of mammals. Check out our blast of Mycosest episode for more,
Speaker 1: so much more, and the placenta diversified. When it comes
Speaker 1: to Eutherian placentas, there's a whole lot of variation from
Speaker 1: size to shape to invasiveness. You know, we held up
Speaker 1: the human placenta, which is like a discoid shape. They
Speaker 1: come in all different shapes. It's amazing. One book I
Speaker 1: read suggested that it is probably the most variable of
Speaker 1: all mammalian organs.
Speaker 5: Really yeah, that's interesting.
Speaker 1: I mean I wonder if every organ researcher says the
Speaker 1: same thing about their.
Speaker 5: Organ, like my organ is actually the cold.
Speaker 1: Blood is the most divert.
Speaker 5: Sure it's not that one.
Speaker 1: We'll do an episode on okay, but for today, I'm
Speaker 1: only going to get into one dimension of this variation
Speaker 1: in mammalian placentas, and that is in the invasiveness right
Speaker 1: of the placenta. So you can look at invasiveness in
Speaker 1: two ways. One is in the number of cell layers
Speaker 1: separating fetal and maternal bloodstreams, and the second is in
Speaker 1: how physically deeply fetal tissue invades and restructures maternal tissue.
Speaker 1: So one is like how many layers are in between,
Speaker 1: and the other is.
Speaker 5: Like, how how deep do those villa I go?
Speaker 1: Exactly? Yeah. Researchers generally group the invasiveness of the placenta
Speaker 1: into three categories. Sometimes there's a fourth one added depending
Speaker 1: on the number of cellular layers. So on the less
Speaker 1: invasive side of things, we've got like pigs, sheep, dolphin, hippo.
Speaker 1: In the medium invasive, we've got dogs, sloths, elephants, ardvarks, raccoons.
Speaker 1: And on the maximally invasive, Yeah.
Speaker 5: That was like a really wide range.
Speaker 1: Well that's okay, yeah, yeah, okay, in a second, kap.
Speaker 1: On the maximally invasive, as in the placental tissue is
Speaker 1: often referred to as being bathed in maternal blood. Right,
Speaker 1: We've got humans and other great apes, mice, rabbits, guinea pigs,
Speaker 1: nine banded armadillos, hyenas, and others.
Speaker 4: Okay, that's also more than I realized. Yeah, that are
Speaker 4: like that considered that invasive.
Speaker 1: Yeah, on the invasive side of yeah, like in terms
Speaker 1: of the cell layers. Yeah, And so unless I specify otherwise,
Speaker 1: when I'm talking about invasiveness, I'm usually referring to this
Speaker 1: classification based on cell layers between fetal and maternal blood.
Speaker 1: Why is there such variation? Is there a benefit to
Speaker 1: one type of placenta over another?
Speaker 5: I mean, yes, well, yes, or trade offs? Yeah, yeah, I.
Speaker 1: Mean, and it's it's a great we don't fully know
Speaker 1: the answer class classic, and it doesn't seem to be
Speaker 1: driven solely by like how related like different animal groups
Speaker 1: and like, oh well all of the you know, there
Speaker 1: are some broad trends, but for the most part, it
Speaker 1: doesn't really seem that way.
Speaker 4: So it's like a bunch of examples of convergent evolution essentially.
Speaker 1: Friend of like what is driving in different species? We
Speaker 1: don't fully understand.
Speaker 5: I think the drivers for interesting for that.
Speaker 1: Yeah, but one thing that we do know is that
Speaker 1: our invasive placenta, like the human invasive placenta, is the
Speaker 1: type that probably evolved first, and then it evolved to
Speaker 1: become less invasive.
Speaker 5: Interesting.
Speaker 1: Interesting. Indeed, Okay, it's possible that, like so we're talking
Speaker 1: about trade offs, it's possible that certain molecules like iron
Speaker 1: have a slightly more difficult time getting to the fetus
Speaker 1: in mammals with less invasive placentas. But that's not entirely clear.
Speaker 1: And another hypothesis is that the more invasive the placenta,
Speaker 1: the better the signaling in all directions like mom to fetus,
Speaker 1: fetus to mom, placenta to mom, et cetera. I also
Speaker 1: read that placental transfer of certain antibodies IgG if you're curious,
Speaker 1: which is the most abundant in our blood, has only
Speaker 1: been observed in invasive placentas, possibly demonstrating active transport of
Speaker 1: this antibody to the fetus, which could have then like
Speaker 1: protective roles.
Speaker 4: Right, because then your fetus is basically your baby's being
Speaker 4: born with all of the antibodies that mom has had. Yeah,
Speaker 4: so like protection from all protections at least passively, at
Speaker 4: least for those first few months.
Speaker 1: Right, which question mark? Okay is not fully clear?
Speaker 5: Yeah, okay?
Speaker 1: Why still, why do we have this invasive placenta? One
Speaker 1: popular but now largely discarded hypothesis is that our invasive
Speaker 1: placentas were necessary to get enough nutrients to the developing
Speaker 1: human fetal brain. For one, our big brains came after
Speaker 1: this invasive.
Speaker 4: Clearly, if this was the first type first time, well
Speaker 4: it wasn't always known that that was the case.
Speaker 5: Right, that makes sense.
Speaker 1: But two, not all animals with invasive placentas have big brains,
Speaker 1: and not all animals with big brains have invasive placentas,
Speaker 1: like dolphins, which have among the least invasive type of placenta.
Speaker 1: And four, there is no evidence that transfer of nutrients
Speaker 1: is somehow greater or more efficient and more invasive placentas
Speaker 1: compared to less invasive books.
Speaker 5: Okay, all right.
Speaker 1: The idea that invasive placentas were necessary for our big
Speaker 1: brains was based on this arrogant assumption that whatever placenta
Speaker 1: we humans have must be the most advanced and the
Speaker 1: least primitive. It's the best, it's the best. But since
Speaker 1: that's not the case, we may have to consider instead
Speaker 1: two related questions, what are the potential downsides to an
Speaker 1: invasive placenta and how have those of us with invasive
Speaker 1: placentas adapted to deal with those downsides. So let's start
Speaker 1: with one of the major potential drawbacks, the fact that
Speaker 1: during pregnancy there is an alien thing growing inside you. Yes, yes,
Speaker 1: it's fifty percent you, but only fifty percent, but only
Speaker 1: fifty percent. That other fifty percent is not you, not
Speaker 1: you over the past five hundred million years, which is
Speaker 1: when the first natural killer cells are thought to have evolved.
Speaker 5: Oh my god, wow, Okay, I know, wow.
Speaker 9: I know.
Speaker 1: That shows how fundamental this idea is.
Speaker 4: And like just immunology of needing to be able to
Speaker 4: find non self.
Speaker 1: That is the whole point of the immune system is
Speaker 1: distinguishing self and non self. Like that is pretty much
Speaker 1: the point of any I mean, and it's that's an oversimplification, sure,
Speaker 1: but pretty much at its core, y versus self. Yeah,
Speaker 1: And so sometimes our immune system works a little better
Speaker 1: than we want it to, like when we reject a
Speaker 1: transplanted organ. Sometimes it's a little overzealous and it blurs
Speaker 1: the line between self and non self. Is in the
Speaker 1: case of autoimmune diseases, and sometimes it might need a
Speaker 1: little help, but overall, this ability is so crucial to
Speaker 1: our survival that it's a universal feature in all multicellular
Speaker 1: life on this planet and has been for quite some time.
Speaker 1: And so pregnancy then should offer a pretty huge immunological challenge. Right,
Speaker 1: there's this non self thing inside that has.
Speaker 4: To stay there for however many months, depending on what
Speaker 4: species you are, right, two hundred and sixty six days
Speaker 4: at least, there are yeah, yeah.
Speaker 1: Yep, yeah yeah, And so from an immunological standpoint, our
Speaker 1: bodies should flag the newly implanted blasticist and mount a
Speaker 1: defense against it. Sometimes this is what happens. And one
Speaker 1: potential downside of our invasive placentas is that the deep
Speaker 1: for the invasion, the higher the risk for triggering an
Speaker 1: immune response from the mother. Right, Many species that have
Speaker 1: similarly invasive placentas like ours tend to have much shorter gestations,
Speaker 1: in part potentially to minimize this risk, but we seem
Speaker 1: to manage overall.
Speaker 4: Right, This is though, why we see things like recist disease, right,
Speaker 4: where you have at least some fetal cells that are
Speaker 4: able to cross over this barrier and come onto the
Speaker 4: other side of our cells, and then we do see
Speaker 4: those and mount a defense against them in a future pregnancy.
Speaker 1: Potentially with and with potentially really.
Speaker 4: Really disastrous consequences. Exactly exactly, yeah.
Speaker 5: Yeah, yeah.
Speaker 1: And so there is like this immune relationship that is
Speaker 1: really complex.
Speaker 5: It's a very tight rope that we are walking.
Speaker 1: Yep, yeah, yeah. So what like how like why what
Speaker 1: allows for tolerance over rejection?
Speaker 6: Yeah?
Speaker 1: One thing that helps is that a fetus is not
Speaker 1: the same as an organ transplant. A transplanted organ is
Speaker 1: connected to the recipient's blood supply, whereas during pregnancy, the
Speaker 1: fetal and maternal blood are kept separate, right, and they
Speaker 1: are kept separate by the outer layer of the placenta.
Speaker 1: And this outer layer consists of a bunch of cells
Speaker 1: that are fused together to make a tissue. So it's
Speaker 1: not like individual cells anymore. The membranes have been fused
Speaker 1: together to create like one giant cell with like multinucleated cell.
Speaker 4: That's why they call it a sensicio trophoblasts. If you
Speaker 4: remember our RSV episode, that stands for respiratories and social virus.
Speaker 5: I'm going nerdy, I'm so sorry, but sensisium. Yeah, multinucleated cell.
Speaker 1: Multinucleated cells, so it's just like one cell, but it's
Speaker 1: a long, giant cell.
Speaker 4: It goes the whole entire outside of that lastosis.
Speaker 1: Yep. And this tissue is pretty impenetrable because these cells
Speaker 1: are fused together. There are no more membranes between the cells,
Speaker 1: which means there aren't any gaps to let in let's say,
Speaker 1: for example, mom's antibodies, which might flag the fetus as
Speaker 1: non self. So it just creates this like there are
Speaker 1: no gaps, right, you can't you can't even get no
Speaker 1: foot in the door.
Speaker 4: No maternal stuff can get in to the placenta at
Speaker 4: that point.
Speaker 6: Yeah.
Speaker 1: Yeah, And this is a pretty crucial tissue and its
Speaker 1: role is not limited to barrier right. It's also a
Speaker 1: hugely important regulator in the expression of hormones like upregulate
Speaker 1: that hormone, down regulate that hormone, proteins and other molecules
Speaker 1: that are used in communication between placenta and mom. And
Speaker 1: we owe it all to an ancient virus stop it
Speaker 1: oh yeah what?
Speaker 5: Oh yeah.
Speaker 1: At some point one of our ancestors was infected with
Speaker 1: a retrovirus which inserted its genetic material into one of
Speaker 1: their sperm or egg cells.
Speaker 5: Okay, okay.
Speaker 1: When those cells replicated, like when they formed an embryo
Speaker 1: and someone so did, the viral DNA carried it with it, okay,
Speaker 1: which was then also passed down to subsequent generations because
Speaker 1: it would have been an all all of the germ
Speaker 1: cells down the line. Over time, we lost bits of
Speaker 1: that viral DNA, but some crucial parts remained, genes that
Speaker 1: maybe we were like, huh, this seems like it could
Speaker 1: be worth keeping around. We call these viral remnants in
Speaker 1: general endogenous retroviruses, and our genome is chock full of them.
Speaker 1: I think I've talked about this before on the podcast
Speaker 1: being really excited. About five to eight percent of the
Speaker 1: human genome is a viral origin. Five to eight percent.
Speaker 1: That's a huge proportions. Not us virus, I mean, it
Speaker 1: is us the genes since it in one and since
Speaker 1: it in two, which help us to fuse these cells
Speaker 1: together to make that like one layer, and also help
Speaker 1: us escape detection from mom. They come from a couple
Speaker 1: of these ancient viruses. That's what allows for that that
Speaker 1: formation of tissue, that barrier.
Speaker 8: Yeah.
Speaker 4: Really, really, these genes these viral genes. Essentially, these genes
Speaker 4: that are viral in origin.
Speaker 1: Yeah, wow it and one since it in two. Without
Speaker 1: these ancient viral infections, we would not be able to
Speaker 1: form the super important tissue. We wouldn't be here.
Speaker 5: Wow.
Speaker 1: Yeah. And what's amazing about these indogenous retroviruses, these since
Speaker 1: sittant genes, is that they appear across eutherean mammals, but
Speaker 1: not from just one infection event. Mammals have been infected
Speaker 1: over and over again with different viruses that have found
Speaker 1: their way into our genomes and have been co opted
Speaker 1: into helping us build this tissue layer.
Speaker 8: Wow.
Speaker 9: Wow.
Speaker 5: I know I'm being mind blown right now.
Speaker 1: I say I'm read being mind blown, and I've.
Speaker 5: Wrote that, I wrote this, and it's still blowing my mind.
Speaker 1: But the immunological relationship between mother and fetus isn't just
Speaker 1: one of avoiding detection or building barriers, right. The activation
Speaker 1: of the maternal immune system is actually a necessary part
Speaker 1: of pregnancy, and instead of that activation leading to a
Speaker 1: destructive response, it leads to a regulatory or protective one,
Speaker 1: one in which acceptance of the embryo is initiated. The
Speaker 1: portrayal of pregnancy as immunosuppressive isn't accurate. In fact, the
Speaker 1: mother is very aware. The mother's immune system is very
Speaker 1: aware of this new non self thing growing. And it's
Speaker 1: more that the maternal immunological self is modified a change
Speaker 1: in immune tolerance. As a side note, this shift in
Speaker 1: self might help to explain why some people with autoimmune
Speaker 1: diseases experienced symptoms lessening pregnancy. Yeah, but there may be
Speaker 1: a cost to this tolerance. Recent research has investigated whether
Speaker 1: our invasive placenta us, which require more immune tolerance than
Speaker 1: less invasive ones, may have made us more vulnerable to
Speaker 1: cancer as a species.
Speaker 5: Really really, I did not know this connection.
Speaker 1: Yeah, okay, it's been like I think, in the past
Speaker 1: ten ish years or so, there's been a lot more
Speaker 1: interest in this aspect of the immunological side of placentas
Speaker 1: interest and placentation.
Speaker 5: Yeah okay.
Speaker 1: In fact, many researchers have noted the similarities between cancer
Speaker 1: and placentation. The formation of the placenta very interesting. There
Speaker 1: is immune evasion, proliferation, invasion into other tissue and blood
Speaker 1: vessel remodeling.
Speaker 6: Wow.
Speaker 4: Yeah, I know, and it's like self, but not because
Speaker 4: it's abnormal cell division.
Speaker 6: Ooh.
Speaker 1: Interesting yep, And studies that have compared cancer rates across
Speaker 1: mammals have found that cancer tends to be higher in
Speaker 1: species that have more invasive placentas, like humans, compared to
Speaker 1: ones that don't, like cows. And I'm sure like that
Speaker 1: other things play a role, you know, lifespan, body, seze.
Speaker 1: It's never one thing. Yeah, yeah, but the pattern isn't
Speaker 1: cut and dry. Where is it clear how cancer and
Speaker 1: invasive placentation might be related mechanistically. It's a fascinating area
Speaker 1: for future study though, especially what it might be able
Speaker 1: to tell us about our individual responses to invasive placentation. Yeah,
Speaker 1: because wow, there is a range of responses. So, like
Speaker 1: we talked about, the placenta is more than just a
Speaker 1: gateway for communication between mother and fetus. It's also the
Speaker 1: place where we see maternal, fetal and paternal needs expressed.
Speaker 1: From the fetus's perspective, more is better, more resources, more nutrients,
Speaker 1: more everything to help you grow.
Speaker 5: Sometimes and we'll get there, not always.
Speaker 1: Not always. But also from mom's point of view, you
Speaker 1: also want fetus to grow, but you can't give away
Speaker 1: all of your resources since that would impact your ability
Speaker 1: to care for the fetus later in pregnancy after birth,
Speaker 1: in future pregnancies, and also for existing offspring. And so
Speaker 1: these needs might be in immediate conflict, but there seems
Speaker 1: to me to be an ultimate shared goal for the two, right,
Speaker 1: a healthy newborn while also not draining mom to the
Speaker 1: point where postpartum care is impossible.
Speaker 5: Right, A little balance, a little balance.
Speaker 1: It's like, I think a lot of people refer to
Speaker 1: it as maternal fetal conflict, which is a whole separate thing,
Speaker 1: and there are a lot of dimensions to that, and
Speaker 1: there's like also the social sociology and political side and
Speaker 1: legal side of that. But I have been thinking of
Speaker 1: it as like a maternal fetal conversation.
Speaker 8: Right.
Speaker 1: Yeah, it's a balance, a balance, it's a dance, a balance,
Speaker 1: and that balance is not always struck. Sometimes, for instance,
Speaker 1: the placenta invades too deeply into the uterine wall, past
Speaker 1: the dissidua, which can cause hemorrhage or perforation of the uterus.
Speaker 1: Or sometimes it doesn't invade deeply enough, and maybe this
Speaker 1: is because our immune system prevents it. This incomplete invasion
Speaker 1: is thought to be at the root of pre eclampsia.
Speaker 1: We don't know the precise mechanism or if preeclamsia has
Speaker 1: one root cause or multiple, is it a syndrome or
Speaker 1: is it well one? Yeah.
Speaker 4: Well, also I'll talk more about like the different types
Speaker 4: of preeclampsia, whether it's early term, whether it's term, whether
Speaker 4: it's postpartum preeclamsia.
Speaker 5: Are they different, are they the same.
Speaker 1: It's the same pathway that's getting us to these things,
Speaker 1: or multiple pathways? Yeah, yeah. But one idea for preeclamsia
Speaker 1: is that the placenta doesn't invade deeply enough, which can
Speaker 1: limit the blood supply to the placenta and fetus. Initially,
Speaker 1: in earlier in pregnancy, that's not a problem since the
Speaker 1: fetus actually needs a low oxygen environment to develop. But
Speaker 1: as pregnancy progresses, oxygen demands increase, and if that initial
Speaker 1: invasion wasn't deep enough, if those arteries weren't remodeled enough,
Speaker 1: that can mean that the fetus is getting low or
Speaker 1: intermittently low oxygen. And so then mom senses this or
Speaker 1: through the placenta is told this, and then her blood
Speaker 1: pressure will spike to compensate, But that doesn't always solve
Speaker 1: the problem, and so then things can kind of get
Speaker 1: increasingly out of balance, and then there can be a
Speaker 1: lot of danger, right that happens. Yeah, Aaron, I know
Speaker 1: that You'll get into more of the details later on.
Speaker 1: But one of the things that I find fascinating about
Speaker 1: preeclampsia relates back to this idea that invasive placentas might
Speaker 1: be related to higher rates of cancer. If pre eclampsia
Speaker 1: has an immunological component, and if mother's immune system is
Speaker 1: preventing deep invasion of the placenta, might cancer rates be
Speaker 1: lower in people who have had pre eclampsia. Huh, I
Speaker 1: don't like so first of all that now I'm like, not,
Speaker 1: we're wondering.
Speaker 5: You are wondering.
Speaker 1: Yeah, I'm not saying like, and here's there's been reviews
Speaker 1: about this and meta analyzes. I did look up a
Speaker 1: few large studies and a meta analysis that did suggest
Speaker 1: that people who have had preeclamsia are overall less likely
Speaker 1: to develop breast cancer. Interesting, but there's like, there's so
Speaker 1: much more to that story or so many factors. How
Speaker 1: protective might pre acclamcia be. What's the mechanism of protection
Speaker 1: if there is one? Is this a causal connection or
Speaker 1: just you know, a correlation. And the same can be
Speaker 1: said for the placenta. Like, there's so so much more
Speaker 1: to the story. This was really just a brief or
Speaker 1: at least as brief as.
Speaker 5: I could make it could keep going and keep listening
Speaker 5: to you.
Speaker 1: Just a brief tour through the evolutionary history of one
Speaker 1: of the most fascinating mammalian organs out there. And I
Speaker 1: hope that even if you don't remember any one thing
Speaker 1: from this story, you at least find yourself thinking more
Speaker 1: about the placenta.
Speaker 5: The placenta that we all used to have, we all use.
Speaker 4: I think that's the thing that's interesting that no one
Speaker 4: ever thinks about, Like, yeah, we all because I think
Speaker 4: a lot about the uterus and how we all came
Speaker 4: from a uterus, whether you have one or not, right,
Speaker 4: you came from.
Speaker 5: One, which is so interesting.
Speaker 4: But then like we all, I never thought about the
Speaker 4: fact that, like, we all had at a.
Speaker 5: Placenta and we all no longer do.
Speaker 1: Yeah, unless unless you kept yours.
Speaker 4: Yeah, but then that's not yours. That was your fetuses.
Speaker 4: That was your baby's placenta.
Speaker 1: But if you, if someone, if you, if you kind
Speaker 1: of kept your.
Speaker 4: Oh that's interesting thought about that. Yeah, Okay, so some
Speaker 4: people have their I.
Speaker 1: Mean yeah, it's no longer attached to us. Yeah, it's
Speaker 1: no longer it doesn't serve using.
Speaker 4: The function that after birth, it stops serving its function.
Speaker 4: I mean, it's just so interesting and it's huge.
Speaker 1: Yeah, it's like that takes a lot of resources.
Speaker 5: Oh my gosh.
Speaker 4: Yes, yeah, it's hefty. It's a hefty organ and you
Speaker 4: can tell when they're not hefty. Oh interesting, Yeah, like
Speaker 4: I I mean, you see a whole variety of placentas
Speaker 4: when you've been delivering babies. I haven't done a lot
Speaker 4: of but seen a lot of fairy number and there
Speaker 4: they range for sure.
Speaker 1: Which is amazing and interesting.
Speaker 8: I know, I know.
Speaker 1: Okay, we I mean we could we could keep talking
Speaker 1: about yeah. Yeah, but yeah no, that's I mean that
Speaker 1: and that basically is the placenta story. You know, let's
Speaker 1: think about viruses, Let's think about what the placenta allows
Speaker 1: us to do from what a journey we mede a
Speaker 1: logical standpoint, it's incredible. Yeah, so yeah, let's keep going
Speaker 1: with the journey. Aaron, tell me what's going on with
Speaker 1: your body and pregnancy?
Speaker 4: Okay, I literally can't wait to take We'll take a
Speaker 4: quick break and then we'll get into it.
Speaker 10: During both of my pregnancies, I experienced intrahabatic colostasis of pregnancy.
Speaker 10: This is a rare complication where your liver cannot process
Speaker 10: aile salts and acids, so those begin to accumulate in
Speaker 10: your blood. This causes itchy, which is mainly focused on
Speaker 10: the palms of your hands and soles of your feet.
Speaker 10: It was the worst age I have ever experienced. It
Speaker 10: was not a dangerous complication for me as a pregnant person,
Speaker 10: but it was extremely dangerous for the fetus. Mortality rate
Speaker 10: in utero is very high. That is why I have
Speaker 10: to be monitored very closely up until thirty seven weeks
Speaker 10: when I was used both times. During both of my pregnancies,
Speaker 10: I had to go to the hospital every few days
Speaker 10: to have a CTG taken. They did numerous ultrasounds and
Speaker 10: I was even hospitalized the first time around. They also
Speaker 10: prescribed urso, the oxygalic acid, which helped a lot with
Speaker 10: lowering bile salts and acids. Itchiness also went away after that.
Speaker 10: The last ten weeks of my pregnancies were very stressful,
Speaker 10: and looking back, I am amazed that I would call
Speaker 10: I managed to stay. Both of my kids were born
Speaker 10: healthy at thirty seven weeks after induction. Chances of getting
Speaker 10: intracapathic colostasis of pregnancy with every subsequent pregnancy are higher
Speaker 10: if you have had it before. Two was enough for
Speaker 10: me that feeling of unbearable itchiness will always stay with me.
Speaker 9: My name is Sarah, she heard thirty six year old
Speaker 9: female mother to an awesome daughter. I had a positive
Speaker 9: home pregnancy tests on Christmas Day twenty twenty two. I
Speaker 9: was thirty four years old at the time. We were
Speaker 9: very lucky to conceive on our very first try. We
Speaker 9: had our confirmation ultrasound in eight weeks, and as I
Speaker 9: progressed towards the second dry master, I felt my mental
Speaker 9: health spiraling. In addition to all of the other common
Speaker 9: pregnancy side effects like morning sickness and fatigue, my anxiety
Speaker 9: started to worsen to the point of panic attacks. My
Speaker 9: body was changing in a million ways, and I had
Speaker 9: no control over any of it, let alone any peace
Speaker 9: of mind to assure me the baby was okay, or
Speaker 9: how to judge what was normal. I started to feel
Speaker 9: like maybe my medical background was not an advantage in
Speaker 9: this situation, because I knew too much when I brought
Speaker 9: my fears up to my OB. I felt dismissed. Each
Speaker 9: visit was short about five minutes. They checked the fetal
Speaker 9: heartbeat and sent me on my way. Even though this
Speaker 9: was my first pregnancy, I took it upon myself to
Speaker 9: research pregnancy mental health and found mostly postpartum articles. I
Speaker 9: eventually talked to my PCP, who started me on lexipro
Speaker 9: and busbar. I was referred to a mental health provider,
Speaker 9: and over the remaining six months of my pregnancy, I
Speaker 9: had weekly video calls with an LCSW. She helped me
Speaker 9: develop coping strategies for my anxiety and guided me in
Speaker 9: conversations with my OB and my husband. I made affirmation journals,
Speaker 9: mantras to recite, and fell asleep listening to guided hypno
Speaker 9: birthing podcasts, all of which eventually helped me to overcome
Speaker 9: my anxieties about giving birth. I had to learn how
Speaker 9: to be the patient, not to provide her, and to
Speaker 9: have faith in my husband, family, and healthcare team to
Speaker 9: take care of me. By all accounts, I had a
Speaker 9: very normal pregnancy and easy birth. At the pediatrician visits
Speaker 9: with my daughter, I filled out mood questionnaires at every
Speaker 9: visit to screen for postpartum depression, which thankfully I didn't develop,
Speaker 9: but it did make me wonder why aren't these types
Speaker 9: of questionnaires available throughout the entire pregnancy.
Speaker 4: So I left off the biology last week kind of
Speaker 4: at the start of the second trimester. But in that
Speaker 4: episode I mostly was talking about the embryo and the
Speaker 4: invasion and the thing and etc. But in this episode,
Speaker 4: I'm going to focus on the pregnancy and the pregnant
Speaker 4: person and not the fetus. Okay, because as incredible and
Speaker 4: awesome as the process of fetal development is, like, it
Speaker 4: only happens inside of a uterus, and so like the
Speaker 4: changes that are required in our bodies in order for
Speaker 4: a pregnancy to actually continue to term, Like, that's where.
Speaker 5: I'm that's where the money is for me, right now. Okay,
Speaker 5: someday we'll do fiddel development because it's really cool too.
Speaker 8: Yeah.
Speaker 4: Okay, So we're going to actually take steps backwards to
Speaker 4: the beginning of the pregnancy, okay, kind of, We're going
Speaker 4: to go back to fertilization, Okay. Yeah, So that we
Speaker 4: will recall from last week, is about two weeks after
Speaker 4: your last menstrual cycle, right, is when you ovulate and
Speaker 4: then you get fertilized, okay, and then about six days
Speaker 4: after that is when we have implantation that starts. So
Speaker 4: we're about day.
Speaker 5: Twenty one ish of our menstrual cycle.
Speaker 1: Okay.
Speaker 4: By about this time, and then like the next week after,
Speaker 4: when you may have missed a period and may have
Speaker 4: had that positive pregnancy test, all ready your own physiology
Speaker 4: has changed dramatically because of the way that embryo has
Speaker 4: embedded itself into the wall of your uterus, Like you
Speaker 4: just walked us through and started secreting hormones that are
Speaker 4: going to cause our body to change in ways that
Speaker 4: it really only changes in the context of pregnancy. I
Speaker 4: get really excited, And what I'm going to do for
Speaker 4: this episode is go through these changes, not week by
Speaker 4: week like you might see on all of the websites,
Speaker 4: like your body is doing this this week.
Speaker 7: No.
Speaker 4: No, We're going to go body system by body system
Speaker 4: and explain why we see maybe some of the like
Speaker 4: weird or uncomfortable symptoms that you might experience, and why
Speaker 4: we are susceptible to some of the complications that then
Speaker 4: arise because of these changes in our physiology. Okay, I'm
Speaker 4: going a rapid fire through it, but stop me at anytime. Okay,
Speaker 4: We're going to start with our cardiovascular system because it's
Speaker 4: one of the most important and one of my favorites.
Speaker 4: One of the first changes that we see is in
Speaker 4: our blood vessels. So because of the increased levels of
Speaker 4: progesterone and other hormones like estrogen and prostaglandins, we see
Speaker 4: a dilation or a widening of our blood vessels. And
Speaker 4: what this does is decrease the resistance to flow of
Speaker 4: fluid because of physics. Yeah, and so right away you
Speaker 4: can start to see weird symptoms because this vasodilation can
Speaker 4: cause edema or swelling as these blood vessels, as they
Speaker 4: get wider, become a little bit more leaky. So then
Speaker 4: you get fluid that can go out through the blood
Speaker 4: vessels and into places like our ankles.
Speaker 1: And this is like a body anywhere, your whole body.
Speaker 5: It could have yeah, not like extreme, but a little bit.
Speaker 1: I mean, like the blood vessel widening, yes, everywhere.
Speaker 4: Everywhere in your whole body, which also means you might
Speaker 4: get things like nasal congestion or nose bleeds.
Speaker 5: Oh my god.
Speaker 4: Now, this vasodilation will also cause a decrease in your
Speaker 4: blood pressure, usually early in pregnancy, which is very interesting
Speaker 4: to then contrast with what we'll see in preeclampsia, which
Speaker 4: is when we have higher blood pressures. Now, on top
Speaker 4: of this change of the width of our blood vessels,
Speaker 4: we also have an increase in our blood volume by
Speaker 4: how much you might ask, I would by forty to
Speaker 4: fifty percent. What uh huh, okay, tell me more about
Speaker 4: what that means. It means that if you have I
Speaker 4: actually meant to look up, like what your normal blood
Speaker 4: volume is. However many leaders I don't remember, but it
Speaker 4: is now fifty percent higher.
Speaker 5: Within a number of weeks.
Speaker 1: Okay.
Speaker 9: Uh.
Speaker 5: And it's you literally just make.
Speaker 4: More blood volume. It means your plasma Okay, we're gonna
Speaker 4: get a more into it. Yeah, because it's your plasma
Speaker 4: volume that's primarily increasing.
Speaker 1: Okay.
Speaker 4: And this means a few things. Number one, it means
Speaker 4: your heart has to be able to keep up with
Speaker 4: this increased amount of flow, and so to do that,
Speaker 4: we actually see structural changes to your heart to allow
Speaker 4: for an increase in cardiac output.
Speaker 1: What kind of structural changes we see?
Speaker 4: Thickening of the like wall of the left ventricle.
Speaker 5: Do you bring over the heart? Oh my god?
Speaker 4: If you have a diagram of a heart. Your left
Speaker 4: ventricle is over here, right, and that's the aorda is
Speaker 4: going to come out here, and this is what this
Speaker 4: is where your blood goes to the rest of your
Speaker 4: body from. So yeah, the left ventricle of your heart
Speaker 4: is going to get a little bit thicker, Your overall
Speaker 4: heart is going to get a little bit bigger. And then,
Speaker 4: as we'll talk about later, because of the changes in
Speaker 4: your diaphragm and the size of your thoracic cavity, it
Speaker 4: also gets shifted.
Speaker 5: Up into the left.
Speaker 1: Interesting, I know now.
Speaker 5: Also I think you.
Speaker 1: Give that back to you.
Speaker 8: Now.
Speaker 4: Also, we will see a compensatory increase as well in
Speaker 4: our heart rate because your overall cardiac output is a
Speaker 4: function of both the volume and also the rate. So
Speaker 4: we see an increase in heart rate, which I remember
Speaker 4: seeing on my smart watch where.
Speaker 5: It was like you have a new normal. Oh interesting,
Speaker 5: and you're like, when I.
Speaker 1: Was pregnant, how soon does that happen?
Speaker 4: So that is that a lot of these changes are
Speaker 4: kind of gradual where they start really early, but then
Speaker 4: it just like continues to change all the way till
Speaker 4: the third trimester until term. Okay, for the most part. Okay,
Speaker 4: and it's sort of an up. It's just sort of
Speaker 4: this it's a linear well not yet not linear, I mean,
Speaker 4: but yes, it's a kind of contained directional, you know,
Speaker 4: for the most part. Okay, Yeah, there's probably nuance there
Speaker 4: that I'm skipping now. I said, your blood volume increases
Speaker 4: my fifty percent. However, your red blood cell volume, and
Speaker 4: remember red blood cells are the ones that actually carry
Speaker 4: oxygen to our tissues, so they're like kind of pretty important.
Speaker 4: They also increase, but only by about twenty to thirty percent.
Speaker 1: What does this then, difference in rate increase? How does
Speaker 1: that manifest in other parts?
Speaker 6: Like?
Speaker 8: What is that?
Speaker 1: What are the implications of that?
Speaker 5: Okay, let me tell you.
Speaker 1: Why aren't your red blood cells also increasing?
Speaker 5: They are increasing, just not to the same not to
Speaker 5: the same degree. So what does this? What does it mean?
Speaker 4: What are the implications? Means that you have during pregnancy
Speaker 4: a physiologic anemia and your blood is it has less viscosity,
Speaker 4: so it can less right because you have less part
Speaker 4: of Yeah, it can flow a little bit more easily.
Speaker 4: It also though, means that of course you can carry
Speaker 4: a little bit less oxygen relatively speaking, like on the
Speaker 4: whole you're carrying more because everything is increased, but you
Speaker 4: have this physiologic anemia. You also then have this fetus
Speaker 4: that is going to be relying on the oxygen that
Speaker 4: you are giving to them. So that means that you
Speaker 4: have to become very efficient with your oxygen transport, which
Speaker 4: is the thing I could go really too deep on,
Speaker 4: but I won't. But what we then see during pregnancy
Speaker 4: is an increase in this production of this compound on
Speaker 4: our red blood cells called two three DPG. It basically
Speaker 4: means that when you are pregnant, your body is better
Speaker 4: at giving away that oxygen, So your red blood cells
Speaker 4: are more efficient at offloading oxygen so that the fetus
Speaker 4: can get access to that oxygen. Okay, it's just like easier,
Speaker 4: it's easier to drop off exactly, Okay, exactly. Yeah, it's
Speaker 4: so interesting. There's also like fetal hemoglobin, things that are hemoglobin.
Speaker 4: I know, I know, it's cool, Okay, So but it
Speaker 4: also means you set another implication. Another implication is that
Speaker 4: in order for our bodies to keep up with this demand,
Speaker 4: iron requirements are significantly higher in pregnancy compared to outside
Speaker 4: of pregnancy. And that's for two reasons, one to support
Speaker 4: the growth of the fetus who needs iron to grow,
Speaker 4: but also to keep up with this increased red blood
Speaker 4: cell production, and so iron deficiency anemia can develop on
Speaker 4: top of this physiologic anemia. And so during pregnancy people
Speaker 4: are at pretty high risk of like anemia in general
Speaker 4: because you already have this physiologic anemia and now you
Speaker 4: have this increased iron requirement. So if you're not getting
Speaker 4: enough iron in your diet, then you're not able to
Speaker 4: make enough red blood cells.
Speaker 5: Okay, makes sense, and so right.
Speaker 1: And so then what if anemia di or if this
Speaker 1: one two punch happens, then what are some of the downstream.
Speaker 4: I mean, it can affect It can be really problematic
Speaker 4: when we get then into delivery because in delivery you
Speaker 4: are going to lose some degree of blood most likely,
Speaker 4: and so that can put people at higher risk of
Speaker 4: complications from hemorrhage or just from blood loss in general.
Speaker 5: Okay, yeah, okay, that's.
Speaker 4: Mein I mean, it can cause problems for the fetuses
Speaker 4: all too if you were like severely deficient.
Speaker 1: And so physiologic like are there I'm sure there's a
Speaker 1: range of physiologic anemia, like outside of iron deficient in
Speaker 1: the area, and so is there a point at which,
Speaker 1: just like physiologic anemia, is where it needs problematic.
Speaker 5: Yeah, exactly, I don't think so.
Speaker 4: Okay, yeah, because it's it is what is expected during pregnancy,
Speaker 4: right right, you expect that to happen. Okay, So if
Speaker 4: we move on from our blood vessels in our cardiovascular system,
Speaker 4: we'll move to another vessel that's being affected kind of
Speaker 4: is not really vessel, it's your kidneys.
Speaker 5: They're connected by tubes. Okay, it's like a vessel.
Speaker 4: You have all this extra blood, right, your kidneys are
Speaker 4: responsible for filtering all of your blood. That's what they do,
Speaker 4: and so your kidneys have to work a heck of
Speaker 4: a lot harder. And during pregnancy, your kidney's enlarge and
Speaker 4: increase their filtration rate by fifty percent, which is so
Speaker 4: impressive and means that you're making a crap ton of
Speaker 4: urine and you have to pee all the time, even
Speaker 4: before there is a fetus literally crushing your bladder.
Speaker 1: That's that's something I had never I know, thought about it.
Speaker 4: And that's why even early in pregnancy people be like,
Speaker 4: I'm peeing all the time, and it's not because of
Speaker 4: the fetus because that thing is like a couple cells big.
Speaker 4: It's because you're making so much more blood, and so
Speaker 4: your kidneys are filtering all that blood, and so you're
Speaker 4: peeing all the time, Okay, and then eventually, of course,
Speaker 4: this fetus is going to grow large enough to crush
Speaker 4: your bladder. And when they do, you also can get
Speaker 4: compression of some of the tubes that lead from your
Speaker 4: kidneys to your bladder. And then that along with the
Speaker 4: fact that progesterone, which I talked about already, that causes
Speaker 4: that vasodilation, progesterone also causes like a slow down of everything.
Speaker 4: Everything's just like moving more slowly, and so your bladder
Speaker 4: has a little bit more stasis. It's not like squeezing
Speaker 4: out as much.
Speaker 1: Uh huh.
Speaker 4: So you can be more prone to UTIs or urine
Speaker 4: aritract infections during pregnancy. Interesting because you, yeah, even though
Speaker 4: you're making so much p and ping all the time,
Speaker 4: it also just can kind of sit there a little
Speaker 4: bit longer. And and then because of all of these
Speaker 4: things that are happening with like compression and blah blah blah,
Speaker 4: you have a higher risk of those UTIs getting up
Speaker 4: into your kidneys and causing a kidney infection.
Speaker 1: Okay, does that is that risk consistent throughout pregnancy?
Speaker 5: I don't have an answer to that question. Okay, it's
Speaker 5: a good question.
Speaker 4: And it's not like it's major, like that's not like,
Speaker 4: oh my god. It's just like you're a little bit
Speaker 4: higher some of the things that some of the things
Speaker 4: that can happen.
Speaker 5: So that was a lot.
Speaker 4: Someone take a big breath, just kidding. You can't take
Speaker 4: a deep breath during pregnancy.
Speaker 1: Did you have that written now?
Speaker 6: I did.
Speaker 5: It was a joke, I wrote.
Speaker 1: I love when your jokes are written out.
Speaker 6: Thank you.
Speaker 1: Still felt natural.
Speaker 5: Thank you.
Speaker 4: It was my segue into the respiratory system.
Speaker 1: It's a good seg thank you.
Speaker 4: So the changes that happen in your respiratory system, they
Speaker 4: actually start really early in pregnancy. I think we think
Speaker 4: about the changes later in pregnancy when you have a
Speaker 4: large volume that's compressing things, and we'll get there. But
Speaker 4: the hormonal changes actually cause an increase in ventilation called
Speaker 4: hyperventilation of pregnancy, and that starts really early. So your
Speaker 4: respiratory rate actually increases hormonally.
Speaker 1: Okay, hormonally what hormone progesterone mostly progesterone. How does that work?
Speaker 4: We're not going to go deep into mechanism here, Aaron,
Speaker 4: because I got too many other bodies make talk about it.
Speaker 4: I don't know why not have any answer to that
Speaker 4: in what I wrote so far, but I got plenty
Speaker 4: of papers that you can read about.
Speaker 5: Because it does it.
Speaker 1: Yeah, I'm just yeah, amazing, It's so cool.
Speaker 4: And then, as I have alluded too many times now,
Speaker 4: as pregnancy progresses and this uterus increases in size significantly,
Speaker 4: it displaces every single other organ in your abdomen. It
Speaker 4: moves from being a pelvic organ to an abdominal organ,
Speaker 4: and in doing so, it elevates your diaphragm, which is
Speaker 4: that muscle between your chest and your belly, and your
Speaker 4: diaphragm is what allows for your lungs to expand. It
Speaker 4: has to move down for you to take a deep
Speaker 4: breath in. During pregnancy, this gets shoved about four centimeters upward,
Speaker 4: so your lungs cannot expand as fully as they could previously.
Speaker 4: That's what also causes that displacement of the heart, which
Speaker 4: gets pushed up and a little bit to the left.
Speaker 4: And now some of this is compensated for this displacement
Speaker 4: is compensated for by the same hormones like progesterone and
Speaker 4: also other ones like relaxing in things that cause ligamentous laxity.
Speaker 1: There's a hormone called relaxing, relax and just relaxing. I
Speaker 1: want to know who named that.
Speaker 5: I have no idea.
Speaker 1: That's a main question. Relaxin.
Speaker 4: Yeah, so it's what allows all of your ligaments to
Speaker 4: expand and relax so that you can like.
Speaker 5: Fit a baby through your pelvist.
Speaker 4: And then also so that the bottom part of your
Speaker 4: rib cage can flail out and actually expand in diameter
Speaker 4: this way, like front to back, about five to seven centimeters.
Speaker 5: You get change here.
Speaker 4: Wow, just the bottom part of your ribs all thanks
Speaker 4: to relaxing, well, relax in, progesterone, all of these hormones.
Speaker 1: Not to throw a spotlight weight relaxes.
Speaker 4: Spotlight it, I know, give it some cred. But with
Speaker 4: all of these changes combined, by the end of pregnancy,
Speaker 4: your total lung capacity decreases by about five percent, which
Speaker 4: isn't huge. However, because of increased demand, both because the
Speaker 4: fetus has increased demand, right you have to share with
Speaker 4: the fetus, and because your own basal metabolic rate during
Speaker 4: pregnancy increases by about fifteen percent. Your total oxygen consumption
Speaker 4: and need goes up by twenty to thirty percent.
Speaker 1: Okay, so you've got first of all, you're breathing more
Speaker 1: because progesterone is telling me to breathe more.
Speaker 5: Yep, that's how it goes.
Speaker 1: We're somehow dig deeper into that. You've got less room
Speaker 1: for your lungs to expand, and you.
Speaker 5: Need to breathe more, need more oxygen.
Speaker 1: And so you're you're like just like panting.
Speaker 5: You feel a little bit shorter breath, short breath. Yes, yeah,
Speaker 5: you're not panting, but you feel.
Speaker 1: Okay, And then and then there's like is that and
Speaker 1: then also the metal ball. Yeah, okay, there's a lot
Speaker 1: of a lot of things.
Speaker 4: There's a lot of reasons to feel a little bit
Speaker 4: shorter breath, especially towards the end of pregnancy. Now you
Speaker 4: also have, because of everything going on in your abdomen, right,
Speaker 4: you also have just a lot of pressure inside of
Speaker 4: your abdomen. And what this can do, especially if somebody
Speaker 4: ends up lying down flat on their back, is it
Speaker 4: can put pressure on the blood vessel that sends blood
Speaker 4: back to your heart. Called the inferior vena cava, and
Speaker 4: that because it's a vein, it has floppy walls, so
Speaker 4: it can actually become compressed later in pregnancy by the
Speaker 4: weight of the fetus and the uterus and everything else
Speaker 4: in there, and that can potentially be problematic, mostly for
Speaker 4: the fetus, because it can kind of reduce the blood
Speaker 4: flow back to the heart, thus reducing your cardiac output.
Speaker 4: And then you can have this drop in blood pressure
Speaker 4: that affects the profusion to the fetus. Okay, so that's
Speaker 4: why a lot of times late in pregnancy people are
Speaker 4: told like, don't lay flat on your back. Yeah, that's
Speaker 4: the reason why. Okay, yeah, we have so many more
Speaker 4: body systems. Okay, ready, blood in general, going back a
Speaker 4: little bit, I guess blood clotting factors completely changed during pregnancy.
Speaker 4: Nearly all of our clotting factors increase except for our
Speaker 4: platelet count. And we think this is helpful in terms
Speaker 4: of preventing postpartum hemorrhage. Oh, but it also means that
Speaker 4: people are at higher risk of a thrombotic event of
Speaker 4: a blood clot forming when it shouldn't.
Speaker 1: But I thought that our blood was less viscous.
Speaker 5: Oh my gosh, it is, but our clotting factors are higher.
Speaker 1: Okay, so we're just sort of compensating for that in
Speaker 1: different viscosity and then it's like the clotting factors, I mean, really,
Speaker 1: we're getting to the same end result. Yeah, yeah, yeah,
Speaker 1: more clots, potential.
Speaker 4: Potential for more clots. And the mechanism there, don't ask
Speaker 4: me exactly, is probably related to estrogen because some reason,
Speaker 4: if you're on estrogen birth control, you're at higher risk,
Speaker 4: which but not as high risk as when you're pregnant.
Speaker 1: How have we not talked about that?
Speaker 5: Okay we did, I thought during our birth control upsote.
Speaker 5: Oh yeah we did, Yeah, we did.
Speaker 4: Okay, But all of this I've talked about so far,
Speaker 4: which was a lot and I've already skipped over what
Speaker 4: is a lot of people's first indication symptom wise that
Speaker 4: they might be pregnant, and that is the changes to
Speaker 4: our GI track.
Speaker 5: Yeah.
Speaker 4: So from the very beginning of pregnancy, hormones again like
Speaker 4: progesterone and others are causing smooth muscle relaxation. That's how
Speaker 4: we get dilation of our blood vessels. That's why we
Speaker 4: get the stasis in our bladder. All these things, and
Speaker 4: this results in a decrease in tone of our esophageal sphincter,
Speaker 4: which goes from our esophagus into our stomach, and that
Speaker 4: can mean that you get an increase of things like
Speaker 4: acid reflux. And we think that it's also related to nausea. Right,
Speaker 4: you have just like slow down of your GI tract
Speaker 4: and opening of your esophagus and going in so it
Speaker 4: just makes you feel more nauseous.
Speaker 1: Why does why does the slow down happen.
Speaker 5: Because of progesterone?
Speaker 8: Yeah?
Speaker 5: But why?
Speaker 1: Yeah?
Speaker 4: Is it just a consequence of the fact that like
Speaker 4: progesterone is causing this overall relaxation probably, like it.
Speaker 5: Does it have a purpose? I don't know, Okay?
Speaker 1: And then why does that lead to nausea? Like what
Speaker 1: is nausea?
Speaker 6: Oh?
Speaker 1: My, sorry, I.
Speaker 5: Can't believe the questions you're asking me right now. Well,
Speaker 5: I'm sorry, it's like what is itch?
Speaker 1: Oh my gosh, I still want to know what it is?
Speaker 1: It's yeah, I mean, I mean I know what nausea.
Speaker 5: Is, right, you know what it feels like?
Speaker 9: Right?
Speaker 4: Like why does having I mean you can think about
Speaker 4: it too, as like your food is not able to
Speaker 4: move through as quickly so it's going to be sitting
Speaker 4: there for longer. You have things that are in you're
Speaker 4: supposed to be staying in your stomach coming up into
Speaker 4: your esophagus more readily.
Speaker 8: OK.
Speaker 4: Like, I don't I don't know a better answer than that,
Speaker 4: And there's probably a better answer out there, like a
Speaker 4: GI doc is like rolling right now. Sorry, No, I'm sorry, No,
Speaker 4: don't be sorry. But but yes, so this this happens.
Speaker 4: And what's interesting is that mild nausea and vomiting early
Speaker 4: in pregnancy is actually associated with a lower risk of
Speaker 4: miscarriage or early pregnancy loss in the first trimester.
Speaker 1: Yes, I have heard that.
Speaker 4: Yes, and so we think that it's that is a
Speaker 4: big part of the reason that we think it's very
Speaker 4: progesterone mediated, right, is that when you have adequate levels
Speaker 4: of progesterone, then your pregnancy is able to continue. And
Speaker 4: so if you have lesser then you might have less nausea.
Speaker 4: But then it also might mean.
Speaker 5: You know what I'm saying, Yeah, I do know what
Speaker 5: you're saying, but it's not it's not cut and dry.
Speaker 4: It's just like a slight association. Okay, But as you
Speaker 4: can also hear in several of our first hand accounts.
Speaker 4: Sometimes this nausea and vomiting can become very severe, and
Speaker 4: that's called hyperremesis gravidarum. We do not fully understand the
Speaker 4: cause of hyperemesis. We think that it's probably in part
Speaker 4: these changes to the gastrointestinal tract and the mobility of
Speaker 4: our gaster intestinal tract, but also like some contribution of
Speaker 4: is it maybe other hormones, like independent of their effect
Speaker 4: on the GI tract, there's probably some degree of genetic susceptibility.
Speaker 5: We don't know.
Speaker 4: In short, Okay, yeah, we don't fully understand that one
Speaker 4: at all. Yeah, but this slowdown of the GI tract
Speaker 4: can also, especially later in pregnancy, end up affecting the
Speaker 4: liver and the gall bladder, and that is what can
Speaker 4: result in intrahepatic colistasis of pregnancy or colas stasis.
Speaker 1: Yes, I want to know more about this. This is
Speaker 1: I had only heard.
Speaker 4: Yeah, yeah, yeah, so this is it's more rare than
Speaker 4: some of the other complications like maybe anemia or something
Speaker 4: like that. It's estimated at zero point two to two
Speaker 4: percent of pregnancies, depending on which studies you're looking at.
Speaker 4: But colostasis is when we see a build up of
Speaker 4: bile acids because bio acids are supposed to be they're
Speaker 4: made in the liver and then they have to be
Speaker 4: transported through a duct into the gall bladder. They're stored,
Speaker 4: and then from the gall bladder they have to be
Speaker 4: squeezed out and then squirted into our small intestine. Okay,
Speaker 4: And so we see a build up of these bile
Speaker 4: acid because they're not being squirted out and excreted by
Speaker 4: the gall bladder.
Speaker 1: They're stuck in the gall blader. Their stup latter is
Speaker 1: the source of so much issue.
Speaker 4: Like right, and so they're also then just they're not
Speaker 4: they're building up in general. So it's like the liver,
Speaker 4: the gallbladder, the whole situation. They're not going down the
Speaker 4: track like they're supposed to.
Speaker 1: Okay, and so the salts are stuck in the liver,
Speaker 1: stuck in the gall it's just sort of like a
Speaker 1: again the slow down, slow down. It's a slow down, yeah,
Speaker 1: traffic jam in the gall blade.
Speaker 5: Traffic jam.
Speaker 4: And so then this bile acid accumulation will then be
Speaker 4: essentially like transported out of just the liver gall bladder
Speaker 4: situation and can potentially end up in our bloodstream. So
Speaker 4: then we see an increase in bio salts in our bloodstream.
Speaker 4: The symptoms of that end up being really really severe itching,
Speaker 4: and it's usually like whole body itching. Don't ask me
Speaker 4: why it causes itching?
Speaker 1: What is itch? How does it get in the bloodstream.
Speaker 4: Because it's not able to be transported out, so then
Speaker 4: there's just too much of it, and it's just like, ah, okay, okay,
Speaker 4: because your liver like has so much blood supply, and
Speaker 4: so if it's just backed up into your liver.
Speaker 1: Then it's gonna be it's gonna go okay.
Speaker 4: And so yeah, and the that does not pose a
Speaker 4: problem to the pregnant person, but those bile salts can
Speaker 4: pass through the placenta and be toxic to the fetus
Speaker 4: because these are cytotoxic compounds, right, That's why they're usually
Speaker 4: stored in our gall bladder where they're not causing problems. Usually, Okay,
Speaker 4: I've gone through a lot of physiologic changes so far.
Speaker 5: Try to think of other don't ask me more questions.
Speaker 5: I'm gonna keep going.
Speaker 4: I don't think of other body parts, like or what
Speaker 4: other body system. They're not the ones you would think
Speaker 4: of necessarily. Yeah, brain is interesting your brain definitely changes
Speaker 4: during pregnancy, and there are like fetal cells that make
Speaker 4: it all the way into your brain.
Speaker 5: Yeah, but we don't I don't have data on like
Speaker 5: what are the changes.
Speaker 1: We have no idea but the feel cell.
Speaker 4: Okay, But here's what I'm going to do is now
Speaker 4: focus more on the two other major complications that we
Speaker 4: see and the body systems that they're involved in. So diabetes,
Speaker 4: h Okay, this is our endocrine system. And we already
Speaker 4: know that our endocrine system, which is our hormone system.
Speaker 4: You defined it last episode. I could be at some point.
Speaker 1: Oh yeah, it was last episode. Because we've talked about hCG.
Speaker 4: So our entire hormonal milieu is changed during pregnancy, and
Speaker 4: people end up susceptible to diabetes during pregnancy in large
Speaker 4: part because of a hormone that the placenta is secreting
Speaker 4: that's called human placental lactogen. There's other stuff that it's
Speaker 4: involved as well. But this is what I'm going to
Speaker 4: focus on, because what this does is it makes our
Speaker 4: pregnant bodies less sensitive to insulin. We have an increased
Speaker 4: insulin resistance. Okay, why do we need an increased insulence resistance?
Speaker 4: If we remember back to our diabetes episode, insulince job.
Speaker 4: What it does in our body is when we have
Speaker 4: high glucose and are like we eat something, right, and
Speaker 4: we have high glucose in our bloodstream, Insulin is secreted
Speaker 4: and it tells the glucose like, get away from here,
Speaker 4: pack yourself away so that we can store you and
Speaker 4: use you later. Okay, So insulin puts glucose into our cells.
Speaker 4: But a fetus needs glucose and they get it from
Speaker 4: our blood stream.
Speaker 8: Got it.
Speaker 4: So by making our insulin less effective, you can have
Speaker 4: more glucose to be available for the developing fetus. But
Speaker 4: if this process goes too far, like if are pancreas,
Speaker 4: because we're going to have this insulin resistance, right, so
Speaker 4: our cells are going to recognize, hey, glucose is too high,
Speaker 4: we need to make more insulin. If you're pincreas can't
Speaker 4: keep up with that increased demand, then you end up
Speaker 4: with gestational diabetes where we see too much glucose in
Speaker 4: our bloodstream. Levels get too high, and that has a
Speaker 4: couple of big consequences. One is it can cause increased
Speaker 4: growth of the fetus. Right, because the fed is just
Speaker 4: like getting a glucose pipeline. Yeah, yeah, okay, and that
Speaker 4: is called macrostomia. So it ends up being large. Babies
Speaker 4: are large for gestational age babies, and that can make
Speaker 4: delivery very risky.
Speaker 5: Yes, okay.
Speaker 4: But the second complication that I don't think people talk
Speaker 4: about as much is that while our glucose that's in
Speaker 4: our bloodstream passes through the placenta and into the fetus,
Speaker 4: our insulin does not. So if our glucose levels get
Speaker 4: really really high, fetus inside of us has to make
Speaker 4: more and more insulin because their body is also like, whoa,
Speaker 4: this is a lot of glucose. So they're having an
Speaker 4: increase amount of fetal insulin that they're making. And then
Speaker 4: after they're born, that sugar syrup bloodstream pipeline is cut off,
Speaker 4: and now they can get severely hypoglycemic because of how
Speaker 4: much insulin they've made in their bodies.
Speaker 1: And so then what does that look like?
Speaker 4: That can end up with seizures or coma or death.
Speaker 4: And that is like to imediately immediately following birth right
Speaker 4: or when yeah, exactly in the neonate in the new
Speaker 4: moral they can have really severe hypogacemia. And so that's
Speaker 4: why Babies that are born when the mom has had
Speaker 4: just national diabetes have to be monitored really closely, especially
Speaker 4: in the first like twenty four to forty eight hours.
Speaker 1: Okay, so interesting. Can I ask some questions or you
Speaker 1: can try yeah, okay, okay, okay, okay. When typically do
Speaker 1: we see uh, gestational diabetes appear?
Speaker 4: Okay, we usually test for it around weeks twenty four
Speaker 4: to twenty eight Okay. Doesn't mean it can't happen before
Speaker 4: that or after that, but that's usually in most places,
Speaker 4: that's the timeline that we test for it.
Speaker 1: Okay. My second question is then what do you do
Speaker 1: about it?
Speaker 3: Yeah?
Speaker 4: Great question. Okay, do you have more that you want
Speaker 4: to keep going?
Speaker 8: Yeah?
Speaker 1: No, no, but you answer that okay, yeah.
Speaker 3: Uh.
Speaker 4: There's a few different things a lot of times that
Speaker 4: can be managed with just dietary changes alone, and so
Speaker 4: figuring out like what do you what are you eating
Speaker 4: that's maybe causing really big glucose spikes and can you
Speaker 4: just modify your diet to be able to have not
Speaker 4: have that and then you're good. Otherwise it's usually insulin,
Speaker 4: so we manage it with it.
Speaker 1: My third question, and you may maybe I should just
Speaker 1: let you finish talking about the other complication. What are
Speaker 1: the differences between first pregnancies and subsequent pregnancies and the
Speaker 1: path this big, big picture question, you know, because I
Speaker 1: would I would imagine that like, Okay, first pregnancies, your
Speaker 1: body is like responding and doing all these things that
Speaker 1: it's doing for the first has never done it right,
Speaker 1: and the second time, it's like are those pathways carved out?
Speaker 1: How different are the hormone levels? How likely are same
Speaker 1: complications to occur between one pregnancy and subsequent pregnancies.
Speaker 4: That's interesting. So we'll talk definitely more about that with preclamcya,
Speaker 4: which is what I'm going to do next. But I
Speaker 4: don't know when it comes to just stational diabetes. Certainly,
Speaker 4: if you've had just stational diabetes in one pregnancy, you
Speaker 4: are at higher risk for having it in another pregnancy.
Speaker 4: Just stational diabetes is also associated with an increased risk
Speaker 4: of type two diabetes later in life. So it's thought
Speaker 4: to be kind of like a marker. There's a lot
Speaker 4: of things that happen in pregnancy that are thought to
Speaker 4: kind of be markers, and we I don't know are
Speaker 4: they like causal or are they just like a kind
Speaker 4: of a snapshot in time where we're like, oh, maybe
Speaker 4: you are at higher risk for these complications later in life,
Speaker 4: but it's not like because you had it during pregnancy.
Speaker 5: Does that make sense?
Speaker 8: Yes?
Speaker 4: But yeah, I don't. I don't know data on like
Speaker 4: what are the rates first pregnancy, second third. It also
Speaker 4: is going to vary with age as well too, so yeah,
Speaker 4: I don't know. That's an interesting question though. When it
Speaker 4: comes to diabetes.
Speaker 5: Yeah, I don't know.
Speaker 4: Overall though, the rate the estimates of like how many
Speaker 4: pregnancies are complicated by diabetes are like all over the map.
Speaker 5: From like one to thirty percent depending on your studies.
Speaker 1: So it's like what's food, what's the threshold? Like how
Speaker 1: do you? How do you?
Speaker 5: How do you diagnose?
Speaker 1: How do you diagnosed?
Speaker 4: I really wanted to bring in a glue coola for you,
Speaker 4: but I couldn't get my hands on ones.
Speaker 5: I'm sorry.
Speaker 4: And it does differ different countries and different guidelines are
Speaker 4: a little bit different in terms of what how you
Speaker 4: how exactly you diagnose it. But most of the time
Speaker 4: it's by doing a glucose tolerance test, and so you
Speaker 4: give somebody a fixed volume of glucose seventy five grams whatever,
Speaker 4: and then you test their blood at intervals either one hour,
Speaker 4: two hours, three hours, or multiple times, and then see
Speaker 4: what their numbers are. Got it, what their glucose level
Speaker 4: is Okay, And there's different cutoffs, and that part's pouring.
Speaker 4: So let's move on, shall we.
Speaker 1: Yeah, I want to pre aclampsia. Ye, big one, So
Speaker 1: that is it is the biggest.
Speaker 4: It is a doozy and it can be for sure
Speaker 4: probably the most severe complication of pregnancy.
Speaker 5: That might not be true, but it's a big one.
Speaker 1: It's a big one.
Speaker 4: So this is really truly not just it doesn't fit
Speaker 4: as neatly in a single organ system, because it is,
Speaker 4: like you mentioned Aaron, the result of a kind of
Speaker 4: dysfunctional relationship really between the placenta and our own cardiovascular system,
Speaker 4: and it can result in a whole spectrum of disorders
Speaker 4: that we call hypertensive disorders of pregnancy. So it's not
Speaker 4: just preaclamsia. It also includes gestational hypertension. So just high
Speaker 4: blood pressure, okay, preeclampsia and aclampsia, and then also help
Speaker 4: which is hemolysis, elevated liver enzymes, and low platelets. But
Speaker 4: often we think about and focus on preeclampsia, because that
Speaker 4: is a kind of point at which if this kicks in,
Speaker 4: if it's officially preeclampsia, then that's when the risks to
Speaker 4: both fetus and mom become pretty significant. Okay, preeclampsia overall
Speaker 4: is estimated to complicate between four and five percent of
Speaker 4: all pregnancies worldwide.
Speaker 1: That's such a high rate.
Speaker 4: It's pretty high, and it's estimated and estimason This really
Speaker 4: did vary in several papers that I read, but most
Speaker 4: reliably the papers that I read said it's estimated to
Speaker 4: result in seventy thousand maternal deaths every year. Seventy thousand
Speaker 4: maternal deaths every year, and five hundred thousand steel births
Speaker 4: or neonatal deaths, oh my gosh, which is just like
Speaker 4: heartbreakingly massive numbers. On top of that, for every maternal
Speaker 4: death that's really to preeclampsia, it's estimated that fifty to
Speaker 4: one hundred women are having significant morbidity as a result
Speaker 4: of it. So it's like affecting a huge number of people. Yeah,
Speaker 4: and I'm sorry that that started off like so heavy,
Speaker 4: but preclamsy can.
Speaker 5: Get really scary.
Speaker 4: Yeah, absolutely so, in terms of like what is when
Speaker 4: I say preclamcy, what does that mean? It's defined as hypertension,
Speaker 4: so elevated blood pressures and at least one of a
Speaker 4: few other features symptoms that we see. One big one
Speaker 4: is protein in the urine, because that's a sign that
Speaker 4: your kidney is being affected, okay, or sometimes other signs,
Speaker 4: other lab values that we see that tell us that
Speaker 4: your kidney is having kidney dysfunction, and that's like it's
Speaker 4: not filtering exactly exactly, or liver dysfunction, all right, and
Speaker 4: all of those we do like laboratory values to see
Speaker 4: what those numbers are. Or sometimes it's diagnosed by neurologic complications,
Speaker 4: which can be severe persistent headaches, visual changes, stroke or
Speaker 4: abnormal reflexes. Or sometimes it's hematologic complications, especially platelet abnormalities.
Speaker 1: Okay, So there are a multitude of ways to dultitude.
Speaker 4: Of criteria that you kind of like check the boxes,
Speaker 4: and if you're meeting these then it's called preeclampsia rather
Speaker 4: than just hypertension.
Speaker 1: Interesting, Yeah, So that it would have to be like
Speaker 1: these neurological changes in addition to high blood pressure exactly,
Speaker 1: and you would also have to have protein in the
Speaker 1: urine or exact other liver enzyme elevation, okay.
Speaker 4: And what it can cause is a number of different things.
Speaker 4: From the fetal perspective, it can cause fetal growth restriction
Speaker 4: because of abnormal blood flow into the placenta. But when preeclampsia,
Speaker 4: especially if it goes untreated or unchecked, it can result
Speaker 4: in a number of really severe complications, including a clampsia,
Speaker 4: which is preeclampsia but with seizures. So that's the line
Speaker 4: at which it becomes a clampsy Yeah, right, than preeclampsia
Speaker 4: down to down to nabby, I know, I think of
Speaker 4: that too. And then it also can sometimes cause stroke,
Speaker 4: especially a hemorrhagic stroke, which would be a very severe
Speaker 4: complication of preeclampsia. Sometimes it's not the nervous system, but
Speaker 4: it's a different organ that gets mainly affected. So it
Speaker 4: can cause severe liver damage and that often results in
Speaker 4: that HELP syndrome. Okay, because it's causing damage to the liver.
Speaker 1: Yeah, So help is A is A is A. It's
Speaker 1: on the spectrum what so Okay, So what is that spectrum?
Speaker 1: I know there's there's high hypertension.
Speaker 4: Gestational hypertension, preeclampsia, eclampsia, help, okay, Yeah, that's like the
Speaker 4: main spectrum, okay, But then within preeclampsia, we can also
Speaker 4: see these other companies and they're not discrete events necessarily,
Speaker 4: like it's not like help or this sure, right, okay, yeah,
Speaker 4: And pre eclampsia also, it doesn't discriminate. It can cause
Speaker 4: severe complications to your kidneys and end up causing renal failure.
Speaker 4: It can cause flash pulmonary edema, meaning fluid onto the lungs,
Speaker 4: largely from just such high blood pressures, because that's something
Speaker 4: we see with severely elevated blood pressures outside of pregnancy
Speaker 4: as well. And then, like I said, for the fetus,
Speaker 4: it can cause placental abruption as well, which is where
Speaker 4: the placenta detaches spontaneously before the baby has been delivered,
Speaker 4: and that can be potentially catastrophic and then also premature
Speaker 4: delivery or still birth. And we don't fully understand the
Speaker 4: mechanisms of preoclampsia, but you talked a lot Aarin about
Speaker 4: what we know about the placenta and this relationship between
Speaker 4: abnormal or whether it's inadequate, like not deep enough or
Speaker 4: too deep placentation and what we think is that that
Speaker 4: process results in these anti angiogenic factors that float around
Speaker 4: in our maternal bloodstream and end up causing damage to
Speaker 4: our blood vessels, and that causes us to have this
Speaker 4: increase in blood pressure and that is what ultimately leads
Speaker 4: to preeclampsia. So it's like inflammation and these like anti
Speaker 4: angiogenics like not making enough blood vessels, not getting enough
Speaker 4: remodeling in the uterus, and this whole like kind of
Speaker 4: perfect storm.
Speaker 1: Almost signaling like, hey, there's not enough going on here,
Speaker 1: Send more, send more.
Speaker 5: Exactly exactly.
Speaker 4: And there are there is of course, a lot of
Speaker 4: interest in understanding like are there biomarkers. Are there things
Speaker 4: that we can identify, like in your blood to say
Speaker 4: either you definitely have preoclampsia or you are at higher
Speaker 4: risk of developing preeclampsia. And in several countries they actually
Speaker 4: do use a few different blood tests that test for
Speaker 4: a few different specific things. And I think I forgot
Speaker 4: to write down their names, but they're like PIF blah
Speaker 4: blah blah, some biomarkers exactly biomarkers. So far, as of
Speaker 4: twenty twenty four, we don't use those yet in the
Speaker 4: United States. So what we mostly look at in terms
Speaker 4: of trying to identify who is at risk for developing
Speaker 4: preeclampsia is what we know from the epidemiological data, and
Speaker 4: we know a lot about what the risk factors are
Speaker 4: that make someone higher risk for developing preeclampsia. We know
Speaker 4: that one of the biggest ones is having a previous
Speaker 4: pregnancy with preoclamsia.
Speaker 7: Right.
Speaker 4: The other huge one is having a first pregnancy. So
Speaker 4: you asked about the difference between like first pregnancies and
Speaker 4: subsequent pregnancies. First pregnancies are generally higher risk for preeclampsia
Speaker 4: compared to second, third, fourth pregnancies unless you had preoclamsia
Speaker 4: in your first one, right, And then you're at higher
Speaker 4: risk during the other ones as well too, And we
Speaker 4: don't fully understand that, but we think that it's related
Speaker 4: again to this immune tolerance thing, where your body has
Speaker 4: never seen these cells from this fetus floating around and
Speaker 4: you develop this immune response to it. Whereas if you've
Speaker 4: had a pregnancy before and your immune system tolerated it,
Speaker 4: you are at lower risk of having an abnormal reaction
Speaker 4: to them that in the future pregnancies. Yeah, if they're
Speaker 4: with the same paternal DNA that so.
Speaker 1: That I find fascinating and I didn't get into this,
Speaker 1: but there is a lot about paternal DNA and like
Speaker 1: pre like exposure to paternal DNA before ye pregnancy.
Speaker 4: Yeah, so like IVF pregnancies, especially those with donor sperm,
Speaker 4: are also a little bit higher risk than non IVF
Speaker 4: pregnancies or IVF without donor sperm. So it's really that's
Speaker 4: part of what lends support to this idea that there's
Speaker 4: like an immune tolerance spectrum kind of a thing.
Speaker 1: Well, and it also makes sense then where why subsequent
Speaker 1: pregnancies where the first pregnancy there's preeclampsy, I would have
Speaker 1: pre eclamsy because it's almost sensitized exactly. Well, I've seen
Speaker 1: this before, right.
Speaker 4: And I know what to do, Yeah, right, exactly. There's
Speaker 4: a lot of other risk factors though, having chronic hypertension
Speaker 4: prior to pregnancy, maternal age, so increasing age increases our
Speaker 4: risk why we do not know. And then a lot
Speaker 4: of other like complications that might affect the functioning of
Speaker 4: your organs prior to pregnancy, like kidney disease, things like lupus,
Speaker 4: which can affect blood clotting factors and things like that,
Speaker 4: having a family history of preeclampsia. And then this part's
Speaker 4: really important, especially in the United States, race is a
Speaker 4: risk factor for preeclampsia. Specifically, Black people who are pregnant
Speaker 4: are at significantly higher risk of pre eclamsia compared to
Speaker 4: white people who are pregnant. But that is not a
Speaker 4: biologic difference, and that this is specified in the ACOG guidelines.
Speaker 4: This is due to systemic racism. Because we also see
Speaker 4: that low income, regardless of race, which causes increase in
Speaker 4: life stressors, is also associated with an increased risk of preeclampsia.
Speaker 4: And so these are the kinds of differences that are
Speaker 4: really important to understand because by recognizing who is at risk,
Speaker 4: we can can we hopefully prevent preeclampsia.
Speaker 1: How would prevent preeclampsia?
Speaker 4: So glad that you asked, Darren right now, The only
Speaker 4: thing that we have to help prevent preeclampsia is low
Speaker 4: dose aspirin, of all things. Okay, So taking aspirin, which
Speaker 4: we did a whole episode on and you might remember,
Speaker 4: is an anti inflammatory agent that also irreversibly inhibits platelets
Speaker 4: from aggregating, so it stops your platelets from forming clots.
Speaker 4: And we think that these, like microthrombotic events are involved
Speaker 4: in the pathogenesis of preeclampsia and so by irreversibly inhibiting
Speaker 4: this platelet aggregation, we've shown through a lot of epidemiological
Speaker 4: studies that's what we think the mechanism is. But we
Speaker 4: know that starting low dose aspirin early in pregnancy, usually
Speaker 4: first or early second trimester, and continuing it until term
Speaker 4: can significantly reduce someone's risk of developing pre eclampsia, not
Speaker 4: make it zero. And the risks are different for whether
Speaker 4: it's term preeclamsia, pre term preclamsia, or postpartum preeclamsia.
Speaker 1: So what are those I don't have like they sound.
Speaker 5: Like they are.
Speaker 4: They sound like it's like when in whin in pregnancy,
Speaker 4: does it develop? Yeah, most of the time, this is
Speaker 4: something that does not develop, or at least we don't
Speaker 4: see it. Can't recognize it clinically until after twenty weeks
Speaker 4: of pregnancy, okay, but it can potentially develop any time.
Speaker 4: We might just not like you might just not see
Speaker 4: the signs it might be. That's part of why people
Speaker 4: are looking for biomarkers. Can we find it. Can we
Speaker 4: find evidence of this super early on? Yeah, but usually
Speaker 4: it's after twenty weeks, the earlier that you start to
Speaker 4: see pre aclamsia. Usually the worst the outcomes are, which
Speaker 4: makes sense, yeah, because you're just going to have a
Speaker 4: bigger effect on the fetus and you're gonna have a
Speaker 4: longer time that you're having potentially complications to the mother
Speaker 4: as well, and postpartum and postpartum we really do not understand.
Speaker 4: But you can develop preclamsia for the first time postpartum,
Speaker 4: even if you did not have high blood pressure during pregnancy.
Speaker 4: We have no idea, no, And it is thought that
Speaker 4: like term, because some people also don't develop preclamsy until
Speaker 4: like right at the end, right they're after term, you're
Speaker 4: after thirty seven weeks, and you now all of a
Speaker 4: sudden have high blood pressure and then potentially preeclamsia. And
Speaker 4: we think that maybe those two entities are slightly different
Speaker 4: and less related to inadequate placentation early on, but maybe
Speaker 4: some other mechanism, but we don't know what that mechanism
Speaker 4: is yet, Like.
Speaker 1: Is that the same, Is it related to any bits
Speaker 1: of the placenta remaining or like getting stuck.
Speaker 4: To Sometimes, yes, it can be from the placenta not
Speaker 4: fully detaching or something like that, but not always. So
Speaker 4: it's not as like clear cut as that.
Speaker 1: Right, Okay, there's still something that's sending that the signal
Speaker 1: of there's not enough foxygen exactly.
Speaker 4: Okay, yeah, but we don't know exactly how it works.
Speaker 4: How is it different or is it not different?
Speaker 5: And that kind of a thing.
Speaker 4: In terms of other ways that we have to reduce
Speaker 4: the risk of preaclamsia, there's some evidence that maybe calcium
Speaker 4: supplementation might help, but it's not as clear cut as aspirin.
Speaker 4: And then in terms of if someone has preclamsia, how
Speaker 4: can we prevent it from getting severe or how do
Speaker 4: we cure it? Magnesium sulfate is given to prevent seizures,
Speaker 4: so specifically to prevent eclampsia. We don't know the mechanism
Speaker 4: or why it works, but it does. But the only
Speaker 4: cure for preclamsia is delivery of the fetus and the placenta.
Speaker 4: But that is not only something that you have to
Speaker 4: balance getting to a gestational age where the fetus can
Speaker 4: survive and hopefully thrive and also ensuring the health of
Speaker 4: the pregnant person. And of course that's not always the
Speaker 4: case because postpart in preclamsia does still exist. So it's
Speaker 4: a little bit complicated and we don't fully understand it.
Speaker 1: Do you have a breakdown for the percentages of you.
Speaker 4: And I really tried to find that, but I don't.
Speaker 4: I don't have a I don't have a good breakdown
Speaker 4: of that. Yeah, so that's preclamsia. And really, like the
Speaker 4: overall physiology of pregnancy, what about breasts. I wasn't gonna
Speaker 4: talk about breast until two episodes. They do start to
Speaker 4: change early on in pregnancy. Yeah, you actually start to
Speaker 4: make colostrum in like the second trimester, which is the
Speaker 4: first like stuff that you secrete. Right after that, the
Speaker 4: newborn usually eats for the first couple of days before
Speaker 4: your actual milk comes in.
Speaker 1: Food aversions, food cravings.
Speaker 5: I don't know.
Speaker 4: Okay, there's a lot of talk about like the evolutionary
Speaker 4: significance of nausea and vomiting and food cravings.
Speaker 1: And is it so that we speaks at the time
Speaker 1: that the fetus is most vulnerable to toxins crossing the
Speaker 1: placental Yeah, but I don't know. I mean, there seems
Speaker 1: to be some basis to that, like Darwinian medicine or whatever, but.
Speaker 5: I don't know more about it than that.
Speaker 4: But what I think is so interesting and part of
Speaker 4: the reason that I am so astounded by and fascinated
Speaker 4: by the physiology of pregnancy is that despite all of
Speaker 4: these changes to literally every organ system in our body,
Speaker 4: and despite all of the possible complications, some of which
Speaker 4: might be minor and not result in severe harm, and
Speaker 4: some of which can be very severe, despite all of that,
Speaker 4: the majority of pregnancies progress all the way to term
Speaker 4: and delivery without major complication, which is just astounding.
Speaker 7: It is.
Speaker 1: It is mind blowing that our bodies can change so dramatically.
Speaker 1: I have a question about that, Okay, permanent changes, What
Speaker 1: are there? And then how like what you can tell
Speaker 1: whether someone has been pregnant before anatom like looking at
Speaker 1: a lot.
Speaker 5: Of times, I mean not all the time, h not
Speaker 5: all the time?
Speaker 1: Yeah, what what are those things that give that that
Speaker 1: like signal that We'll.
Speaker 4: Talk probably more about that in the fourth episode when
Speaker 4: we talk about postpartum stuff. Okay, So yeah, I don't
Speaker 4: have like an easy answer to that question. Okay, but yeah,
Speaker 4: I mean things change, like in terms of cervix changes
Speaker 4: and things like that that you can like maybe see
Speaker 4: on physical exam. There are there is evidence that like
Speaker 4: fetal cells remain in our tissues for like potentially the
Speaker 4: rest of our lives, which is crazy to think about it.
Speaker 1: I mean again, it kind of is that relationship with
Speaker 1: cancer where it's like yeah, yeah, yeah, interesting, it's really
Speaker 1: really interesting.
Speaker 5: But yeah, that's pregnancy erin.
Speaker 1: In a short short and a half years that I've
Speaker 1: took to explain all of that, we went from a
Speaker 1: deep time. We've really crossed hundreds of millions of years.
Speaker 5: Deep time all the way until delivery, which is deep
Speaker 5: time delivery.
Speaker 1: Yeah.
Speaker 5: So so if you'd like to learn more sources, boy, howdy,
Speaker 5: boy howdy, Okay, I have some sources here. Oh I bet.
Speaker 1: There are two books that I read. One is called
Speaker 1: The Evolution of the Human Placenta, which is what it
Speaker 1: sounds like by Michael Power and Jay Schulkin. And then
Speaker 1: there's Life's Vital Link The Astonishing Role of the Placenta
Speaker 1: by Young Look. Then, uh, those are the books. I
Speaker 1: think they were pretty good overviews of what's going on.
Speaker 1: It is an overwhelming amount of information. If you want
Speaker 1: to learn more about retroviruses, there are a few papers
Speaker 1: that I have posted. One is by Chung from twenty
Speaker 1: thirteen called Retroviruses facilitate the rapid evolution of the mammalian placenta.
Speaker 9: Love it.
Speaker 1: There are some other ones too about retroviruses that are good.
Speaker 1: Then there's shits at All from twenty nineteen, Evolution of
Speaker 1: placental invasion and cancer metastasis are causally linked.
Speaker 5: Ooh yeah, interesting, interesting, bold statement.
Speaker 1: Bold statement. Then from twenty thirteen by Crosley Placental invasion,
Speaker 1: preeclampsia risk, and adaptive molecular evolution at the origin of
Speaker 1: the Great apes evidence from genome wide analyzes because humans
Speaker 1: are not the only species to get preeclampsia, which we
Speaker 1: thought for the longest time that we were.
Speaker 9: But no.
Speaker 1: I think there was a gorilla at the Houston Zoo
Speaker 1: last year the year before something that had preeclampsia or
Speaker 1: baby I know, she.
Speaker 5: Okay, I think, so, okay good.
Speaker 4: I have a number of sources for this, some of
Speaker 4: which focus more on just the basic physiology of pregnancy.
Speaker 4: One that I liked that was easy to read was
Speaker 4: called Physiology of Pregnancy from Anesthesion Intensive Care Medicine from
Speaker 4: twenty nineteen. I had a few others that were more
Speaker 4: focused on the cardiovascular physiology of pregnancy too that were great.
Speaker 4: A review paper on just stational diabetes called Justational Diabetes
Speaker 4: melodis really creative title from Nature Reviews Disease Primers twenty nineteen,
Speaker 4: and another from Nature Reviews Disease Primers on pre acclamsia
Speaker 4: called preaclamsia not really creative titling. I mean, I feel
Speaker 4: like it's pretty easy to understand what the is, what
Speaker 4: the papers are that know what you're getting.
Speaker 1: It's real puns puns.
Speaker 4: In this and then there was a bunch more so
Speaker 4: listen check out our website this podcast will Kill You
Speaker 4: dot com under the episode's tab, where you can find
Speaker 4: the list of all of the sources that we used
Speaker 4: from this episode in every single one of our episodes.
Speaker 1: Single one. A huge thank you again to everyone who
Speaker 1: sent in their first hand account and shared them with us.
Speaker 1: We really can't thank you enough. Thank you, thank you,
Speaker 1: thank you, thank you.
Speaker 5: We'll try though.
Speaker 4: Thank you again to everybody here at Exactly Right Studios
Speaker 4: for having us. We're super excited about it. Thank you Tom,
Speaker 4: thank you Leana, thank you Jessica, thank you Brent, thank you,
Speaker 4: Craig everyone.
Speaker 1: Thank you everyone. There's so many other people's do so
Speaker 1: much fun it has.
Speaker 9: Yeah.
Speaker 1: Thank you to Bloodmobile for providing the music for this
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Speaker 4: And thank you to all of you for listening and watching.
Speaker 4: And we hope that you enjoyed this episode and that
Speaker 4: you're ready for two more to more.
Speaker 1: I know we still have so much to cover its
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Speaker 5: Yeah, thank you.
Speaker 8: Yeah.
Speaker 5: Well, until next time, wash your handsalthy animals, U.