410 ‒ The biology of pregnancy: physiologic adaptation, childbirth, and long-term maternal health

1. 0:00 – 0:11

   Intro

   1. PAPeter Attia0:00

      [upbeat music] Hey, everyone. Welcome to the Drive Podcast. I'm your host, Peter Attia. [upbeat music]

2. 0:11 – 3:43

   What drew Katie to obstetrics and gynecology, and fundamental questions in the field that remain unanswered

   1. PAPeter Attia0:11

      Katie, thank you so much for coming out. It's awesome to meet you, and I'm super excited about what we're here to talk about.

   2. KGDr. Kathryn Gray0:16

      Yeah, me too.

   3. PAPeter Attia0:17

      Um, give folks just a little bit of a background in your, um, maybe what you're doing today, but also kind of the trajectory that got you here. You're a physician-scientist, uh, an MD-PhD. Uh, what, what led you to this field?

   4. KGDr. Kathryn Gray0:30

      I guess that's a good question [laughs] . But, um, I think, um, I've always been interested in, in science, and I, um, was an undergrad, and, um, I really liked all my classes and all, all the science classes. And I was thinking of just going to medical school, and then I, I had this one advisory meeting with our-- that was required at the University of Wisconsin where, um, this, in this one meeting, this professor sat down and said, "Well, my daughter went to medical school, and she really enjoyed it, but I, I thought she would've been so much happier if she also did a PhD. Have you ever heard of that?" And I was like, "No, I, I've never heard of that." But because of that one conversation, I investigated that further, and I, um, thought that that was fascinating and super interesting, and that was the beginning of me pursuing all the rest of the steps that happened after that. [laughs]

   5. PAPeter Attia1:23

      And so what, just briefly, what did you focus on during your PhD?

   6. KGDr. Kathryn Gray1:27

      Yeah. So I, um, I technically have a PhD in immunology, but what we really did was take, um, this benzodiazepine that was found from a, um, drug screen, uh, to-- and it, it had been shown by a previous student in the lab to help treat autoimmune lupus, uh, d-disease in mice, so lupus. Um, and, um, but they didn't know how it was working. So my PhD was focused on understanding the molecular mechanism of this novel benzodiazepine, um, and where it bound and how it actually induced apoptosis in cells. And so, um, basically, I took a lot of cow hearts and isolated mitochondria and did a lot of biochemical assays to show that it acted on the mitochondrial ATPase. So that is what I spent my time doing. [laughs]

   7. PAPeter Attia2:16

      Did that end up having human clinical benefit?

   8. KGDr. Kathryn Gray2:19

      Actually, that, um, uh, the drug itself is not very soluble, so it was hard to make into, like, a readily absorbed, um, drug. However, um, a derivative of that has actually become a treatment for in, that's in trials for, um, inflammatory bowel disease because it can act just in, in the gut.

   9. PAPeter Attia2:39

      And I assume you did your PhD in the sort of normal MSTP fashion, where you did the two years of pre-clinical, you went off to the lab, and then you came back for your rotations. So you come, you come out of your PhD. You've got a couple years left of medical school. What drew you to obstetrics and gynecology?

   10. KGDr. Kathryn Gray2:55

       Yeah. I, I had always been really interested in women's health. Um, I did all the clinical rotations as a third-year medical student. I really liked everything. I liked medicine, I liked surgery, um, but I really liked pregnant patients, um, and, uh, and deliveries, and I thought, um, it was such a unique patient population to take care of because I found people were uniquely motivated about their health during that time in a way that you didn't find in other parts of medicine. And thinking with the research half of, of my interest, I also was fascinated that we didn't understand anything. Like, why do people go into labor? Why do people have preterm labor? Why do people have preeclampsia? The answer is we don't, we don't know. And so I, um, I, I thought it was a great area of medicine to go into.

   11. PAPeter Attia3:42

       Well, let's

3. 3:43 – 14:07

   Pregnancy as a cardiovascular and metabolic stress test; the first symptoms and early changes

   1. PAPeter Attia3:43

      just jump into it then. Um, really, the first place I kind of wanted to start was understanding the sort of physiologic stress test that is pregnancy. Um, obviously, I have no personal experience, uh, but certainly watched my wife go through it three times. Actually more, unfortunately. Um, but, but three successful pregnancies. Um, and I shared with you some personal stuff that I probably won't disclose on the podcast about I've, I've, I've seen the most extreme sides of it. Um, I have to be honest with you. There's a part of me that thinks, how did our species propagate? Like, I don't understand how all the women and children didn't just die. So it's-- I know we talk about how infant and maternal mortality was such a huge driver of short life expectancy prior to the modernity of medicine. I'm still surprised it was as successful as it was. So, um, in whatever way you want to address it, just maybe talk us through the unbelievable demands that are placed on the women in this species [laughs] as they have to deal with this, uh, essential challenge of our, uh, reproduction.

   2. KGDr. Kathryn Gray4:57

      Yeah. I mean, I think that's, uh, and I'm also amazed that, that it ever goes well, pregnancy, that is [laughs] so, um, just, uh, for how many ways that it, it can, um, go wrong. But I think, um, you know, it, you, um, take a, an adult and, um, you know, they, um, they become pregnant, and immediately the increased demands on their body starts to support this developing fetus. And so, um, you know, there's great expansion of the, the blood volume, um, you know, great, uh, alterations in the endocrine and metabolism and, um, those, you know, are extremely dramatic and persist throughout the whole pregnancy. Um, so, um, you know, it's, it's hard to pick just, like, you know, one thing, but I think, you know, we, um- It's a cardiovascular, um, stress test, um, because the plasma volume expands, um, so much. Um, it is, um, a metabolic stress test because there's increased insulin, um, resistance, especially in the second part of pregnancy, um, that causes some people to have gestational diabetes. Um, and it often can unmask, like, future predisposition to disease, um, through, um, this process.

   3. PAPeter Attia6:17

      Well, I want to talk about all of those, but maybe we can just start with the beginning. So shortly after conception, what is sort of the first physiologic interruption that occurs in, in, in the woman's body? And I'm, I'm, I mean, we could think of this through the lens of some- I, I, I, I don't know. Is the... If for a woman who is not planning to get pregnant, is the first observation typically the menses, the, the missed period, or is it morning sickness? Like in your experience, what is the first, uh, sign that a woman's pregnant?

   4. KGDr. Kathryn Gray6:51

      Yeah, I think for people who have regular periods, like the missed period is often the first, um, first sign before other s-

   5. PAPeter Attia6:58

      Before an actual symptom.

   6. KGDr. Kathryn Gray6:59

      Yeah.

   7. PAPeter Attia7:00

      Okay. Um, we don't need to explain why that happens. I think that's pretty self-evident. Um, but let's now talk about how the physiology is changing in that first four to six weeks. So, um, the, the implantation has taken place, obviously the placenta is starting to grow. What's happening in her endocrine system, for example?

   8. KGDr. Kathryn Gray7:22

      Yeah, I mean, I think, um, there's, there's certainly different phases of, you know, at first the ovary is actually supporting, um, in an endocrine way the development of the, the pregnancy and then as the placenta develops, the placenta itself, um, starts to secrete the hormones that, um, you know, support the, the pregnancy.

   9. PAPeter Attia7:43

      When, and when does that transition take place?

   10. KGDr. Kathryn Gray7:46

       Uh, between like, you know, eight to 10, 10 weeks of pregnancy. So, um, so that's why when people have IVF, um, and they're, they kind of shut down your own hormone system for that process, that supplementary hormones are given for the first several weeks of pregnancy because that there isn't the natural hormones being produced by the, the ovary.

   11. PAPeter Attia8:08

       Okay, so the ovary before that transition is primarily making estradiol as the dominant estrogen?

   12. KGDr. Kathryn Gray8:14

       And progesterone-

   13. PAPeter Attia8:15

       And progesterone

   14. KGDr. Kathryn Gray8:16

       ... to support the pregnancy.

   15. PAPeter Attia8:16

       Okay. And then what's happening with HCG, uh, during that period of time?

   16. KGDr. Kathryn Gray8:22

       Yeah, I mean that starts to, you know, it goes from being zero to increasing dramatically.

   17. PAPeter Attia8:28

       And what's the purpose of that? I mean, I know it's a lu- it's basically luteinizing hormone, but is it basically the pituitary's way of telling the ovary to make more of these hormones? Is that why it's rising?

   18. KGDr. Kathryn Gray8:40

       That's a good question. [laughs] I, um, uh, I, I haven't thought about that in a while, so.

   19. PAPeter Attia8:47

       Is the rise in HCG part of what's driving the morning sickness or the nausea? Do we, do we know what's causing that?

   20. KGDr. Kathryn Gray8:54

       For a long time people actually thought that, um, but actually, um, there, for people who have extreme nausea and vomiting of pregnancy, so hyperemesis gravidarum, they, um, we have very poor treatments for that and, um, interestingly genetics is something that gave us a, a great insight about that, um, which is when they, they studied folks who had hyperemesis they found a signal that flagged the GDF15 gene as, uh, really important in driving, um, who developed that condition and so that's actually now a developing target for therapeutics in that area and suggests that we haven't really gotten it correct as to why people have that. So it's not that well understood.

   21. PAPeter Attia9:42

       Is it correlated with anything else? For example, is it correlated with, uh, a person who easily gets sick being in a car or on a boat?

   22. KGDr. Kathryn Gray9:50

       That's a good question. I, I don't think all the time that that is the case.

   23. PAPeter Attia9:55

       Is it also something that is predictive of subsequent, I mean if it has a high genetic component I assume the answer is yes, but is it necessarily the case that if a woman's sick during her first pregnancy-

   24. KGDr. Kathryn Gray10:05

       Mm

   25. PAPeter Attia10:05

       ... she's probably in store for this going forward?

   26. KGDr. Kathryn Gray10:08

       We often see people who have hyperemesis in all their pregnancies if they have it with their first, so yes.

   27. PAPeter Attia10:14

       Okay. So again we don't know why it's happening. Um, is the biggest risk of that simply nutrition? Is it that the, you just, it makes it more difficult to get enough nutrition during that period of the pregnancy?

   28. KGDr. Kathryn Gray10:28

       Yeah, I think, I think so and I think it's more, it's more maternally risky, so usually the fetus at that stage will take what it needs from the mother and so, uh, the biggest risk is dehydration and, um, lack of nutrition during that time. Yeah.

   29. PAPeter Attia10:43

       Do you have a rough sense of the prevalence of how often it becomes maybe something that would even require a brief hospitalization or medical, even a medical intervention? And, and by the way is, are your standard, uh, antiemetics, uh, safe during pregnancy? I can't remember. Zofran and things like that, can they be used during pregnancy?

   30. KGDr. Kathryn Gray11:02

       Yeah, we, they can be used during pregnancy. Um, you know, there's various, we could get into the data on that, but in general we do have some, some tools and antiemetics that can be given, but it is, um, but oftentimes they're not helpful enough for folks and they do end up in the hospital needing IV hydration and even IV nutrition sometimes during pregnancy.
4. 14:07 – 22:21

   Early hormonal changes, prenatal nutrition, and neural tube defects

   1. PAPeter Attia14:07

      you talked about this switch from the ovaries providing the sex hormones to now the placenta. You said that takes place, did I s- did you say about eight weeks?

   2. KGDr. Kathryn Gray14:17

      Mm-hmm.

   3. PAPeter Attia14:18

      Okay. Are they just continuing to go up, estrogen, progesterone are continuing to rise? Um, what is their function? How does it differ between a male versus female fetus?

   4. KGDr. Kathryn Gray14:31

      Um, there, there really, there aren't a lot of differences for the, m- in that in, for a male or, or female fetus. Yeah.

   5. PAPeter Attia14:39

      And so the estrogen and progesterone, what are they doing to support the pregnancy specifically?

   6. KGDr. Kathryn Gray14:44

      Yeah, I think, um, [laughs] we're, we're in the domain of the reproductive endocrinologist here and not the maternal fetal medicine doctor, but, um, but you know, they, um, progesterone has many important functions in pregnancy, especially, um, in maintaining the uterine quiescence, right? So it doesn't contract, um, in continuing, um, to support, um, the development of, of the placenta itself.

   7. PAPeter Attia15:08

      Yeah. And, and, and how often do women complain of symptoms from the estrogen rise? Because we, we know from later in life, so when you think about women who are undergoing hormone replacement therapy, um, they can become very symptomatic from the estrogen, but the estrogen that's given during peri and post-menopause is much lower than presumably what she's experiencing in pregnancy, and yet they can still have symptoms like horrible breast tenderness, headaches, and things of that nature. So how often are those occurring in pregnancy as a result of this enormous surge in estrogen?

   8. KGDr. Kathryn Gray15:43

      Yeah, I mean, I think with the dramatic change in the beginning of pregnancy, um, lots of those symptoms are common, like breast tenderness and, um, you know, associated estrogen related symptoms.

   9. PAPeter Attia15:54

      But they abate? Do, does the-

   10. KGDr. Kathryn Gray15:56

       You know, different, everyone experiences it different, but I do think that there is some, uh, adjust- adjustment. Um, but you know, that also, the hormones often also, you know, drive the, you know, other physiologic changes in, in the mother across pregnancy as well.

   11. PAPeter Attia16:12

       Uh, at what point during the pregnancy does the mother's appetite usually start to increase?

   12. KGDr. Kathryn Gray16:19

       Well, I mean-

   13. PAPeter Attia16:20

       No, I mean, I guess it's complicated 'cause you ... Let's, let's take out the case of a, of, of a woman who's got horrible morning sickness, and more I'm asking this through the lens of when does the demand, when does the metabolic demand of the fetus warrant increased intake by the mother?

   14. KGDr. Kathryn Gray16:35

       Hmm. Well, I think that's, that's more like, um, in the second half of pregnancy when the-

   15. PAPeter Attia16:41

       Okay

   16. KGDr. Kathryn Gray16:41

       ... actual amount that the fetus is growing is, is the greatest. There's of- there's of- often, oh, sorry, also, um, increased nutrient demands, which is why, you know, we have folks taking prenatal vitamins, um, and also, um, that in- contain iron 'cause that will also support, like, the developing blood expansion as well. So there are increased nutrient demands.

   17. PAPeter Attia17:05

       So let's talk just specifically about them. I know that many folks probably know what the prenatal stack looks like, but just, and y- maybe we can just state it. What are the most important vitamins and minerals during, fr- from the moment a woman is pregnant or even planning to get pregnant?

   18. KGDr. Kathryn Gray17:19

       Right. Folic acid is really the, one of the things we've really thought about and focused on a lot of having adequate levels prior to conception, so that's part of the reason we tel- tell people to take a prenatal vitamin prior to conception because there's good evidence that folic acid deficiency increases the risk of having a neural tube defect in the baby, and by the time you recognize the pregnancy, it's already kinda too late, um, uh, to bring u- up folic acid levels if they have been deficient. So that's one of the most essential things early on.

   19. PAPeter Attia17:51

       Now you said 50% of pregnancies are unplanned, which suggests that prenatal vitamins should be recommended to all women of childbearing age, correct?

   20. KGDr. Kathryn Gray18:02

       Well, or a healthy diet. So I mean, I think if you have a well-balanced diet and a lot of the food, um- It's now supplemented with, you know, B vitamins and folic acid and things that you want to be replete in with pregnancy. So I think, um, uh, a lot of folks will have adequate levels if they're eating a well-balanced diet with fruits and vegetables and, um, whole grains, so.

   21. PAPeter Attia18:26

       So what is your patient population like? You're in Seattle, um, but you're at, you're at a university hospital, so you serve a very broad population, obviously. How often do you today see a neural tube defect?

   22. KGDr. Kathryn Gray18:38

       Well, we're a, we're a referral center-

   23. PAPeter Attia18:40

       You're a tertiary center-

   24. KGDr. Kathryn Gray18:41

       ... so, you know, we're-

   25. PAPeter Attia18:41

       ... so of course it's, it's, it's concentrating there, but yeah

   26. KGDr. Kathryn Gray18:43

       Right. Yeah. So, um, you know, there, we, we see case of neural tube defects every month-

   27. PAPeter Attia18:49

       Wow

   28. KGDr. Kathryn Gray18:49

       ... you know, that come to our center, but we have, you know, again, we're a, have a wide catchment area.

   29. PAPeter Attia18:55

       Explain to folks what that is, actually. I, I, we're taking that for granted. [laughs]

   30. KGDr. Kathryn Gray18:58

       Yeah. [laughs] Well, um, i- it's a category of, um, uh, defects, like in, in any part of the neural tube where it doesn't form correctly. The most common would be, like, a myelomeningocele where, um, at the base of the spine commonly, the, um, spinal cord is, is actually exposed, so the overlying skin doesn't form properly, and the part of the spinal cord is exposed.
5. 22:21 – 28:29

   Fetal development and the physiology of gestational diabetes

   1. KGDr. Kathryn Gray22:21

      Yeah.

   2. PAPeter Attia22:21

      What are some other very important milestones for the mother and fetus during the first trimester?

   3. KGDr. Kathryn Gray22:27

      Um, well, another really important thing that's happening entirely in the first trimester is formation of all the organs-

   4. PAPeter Attia22:33

      Mm-hmm

   5. KGDr. Kathryn Gray22:33

      ... of the, of the fetus. So by the time the first trimester is done, that's basically complete.

   6. PAPeter Attia22:39

      So the heart has four chambers, the pancreas has considered its little ventral bud rotat- all of that stuff has happened. And, and approximate size of the fetus at the end of the first trimester?

   7. KGDr. Kathryn Gray22:50

      I mean... [laughs]

   8. PAPeter Attia22:51

      So you're, you're f- your whole, for those who are listening to us-

   9. KGDr. Kathryn Gray22:53

      Yeah

   10. PAPeter Attia22:53

       ... basically an inch and a half, two inches. How many, how many grams?

   11. KGDr. Kathryn Gray22:59

       I, I couldn't tell you the number.

   12. PAPeter Attia23:00

       A few, a few, a few almonds.

   13. KGDr. Kathryn Gray23:01

       It's, yes. [laughs]

   14. PAPeter Attia23:01

       Yeah, yeah. So it's miniature, but it's perfectly formed.

   15. KGDr. Kathryn Gray23:05

       Yeah.

   16. PAPeter Attia23:05

       Which is unbelievable.

   17. KGDr. Kathryn Gray23:07

       Yeah.

   18. PAPeter Attia23:08

       Okay. At this point, on average, the mother has gained how much weight?

   19. KGDr. Kathryn Gray23:14

       Zero to 10 pounds. I mean, there's-

   20. PAPeter Attia23:15

       Yeah, so it's relatively small.

   21. KGDr. Kathryn Gray23:17

       Yeah. There's, there's huge variability, as you might imagine.

   22. PAPeter Attia23:20

       Yeah. Okay, so now we enter the second trimester. We are, let me do my math, we're about halfway to that expansion of plasma volume, so we'd be roughly at 25% plasma expansion. Um, tell me what's happening now in terms of the physiology. The hormones, are, are they still going up, or have they plateaued at this point?

   23. KGDr. Kathryn Gray23:42

       That's a good question, and I, I'm not, uh [laughs]

   24. PAPeter Attia23:44

       Sorry, I keep, it's like your board exam here. [laughs]

   25. KGDr. Kathryn Gray23:47

       I do feel like I'm in an oral board exam, just to be very honest, yes. [laughs]

   26. PAPeter Attia23:51

       I'm sorry. I'm sorry. No, I promise you there's no grade at the end of this podcast. Um, okay. So, um, tell m- tell me what else is happening in that second trimester as far as the, the m- the, especially in terms of, like, what the mother's physiology is doing.

   27. KGDr. Kathryn Gray24:06

       Yeah. Well, there's a lot of fetal growth, um, during this period, and, um, really, you know, the, the plasma volume has increased somewhat, but then there's really an acceleration of that, um, in the second part of the, um, uh second trimester, so it's not linear. Um, but I would say that, you know, there's, there's more, um, maternal adaptation to pregnancy. Um, the metabolism might switch from, like, um, being insulin sensitive to being more insulin resistance during that part of the pregnancy, um, given the growth of the placenta. Um, the pregnant person's gonna be, you know, gaining some more weight than the first trimester, usually during this time, and also, you know, they're, they become visibly pregnant during this, this, this part of the pregnancy.

   28. PAPeter Attia24:57

       So let's talk about that fuel partitioning piece, the insulin sensitivity, insulin resistance. Um, there are certain conditions when insulin resistance might be desirable, so one of them is actually fasting. So when a person is fasting for prolonged reasons, the muscles actually become insulin resistant as an adaptive response so that glucose is preferentially spared for the brain. Um, is the insulin resistance that you describe here in the second trimester equally adaptive, or is it necessarily pathologic? And, and obviously at some levels it's pathologic if it develops into frank diabetes, but, but kinda walk me through that.

   29. KGDr. Kathryn Gray25:37

       Yeah, well, I think it can go either way. I mean, the, I think it's meant to be adaptive, right, providing the fuel for the fetus to grow. Um, but for some folks, um, they, um, produce more glucose than is needed, and their glucose levels stay too high, and then they're diagnosed with gestational diabetes.

   30. PAPeter Attia25:57

       When did routine screening for that become the norm?
6. 28:29 – 36:19

   Diagnosing and treating gestational diabetes

   1. PAPeter Attia28:29

      that reason, we've obviously made the wise decision of every woman is [laughs] gonna get screened for this. Uh, remind me when in the pregnancy does that screening take place?

   2. KGDr. Kathryn Gray28:37

      Between 24 and 28 weeks.

   3. PAPeter Attia28:39

      And presumably that's chosen because if you did it any earlier, you would miss people that are gonna present ... Yeah, okay.

   4. KGDr. Kathryn Gray28:46

      Yeah, and actually data shows that when you diagnose it earlier, it might not improve the outcomes at all, so it seems to be the best window for both, like, g- screening and, and identifying people who, who are at risk or have, um, developed, um, gestational diabetes and having the most impact from treatment.

   5. PAPeter Attia29:07

      Tell me the diagnosis is made with an oral glucose tolerance test done at fasting and then two hours. What's the criteria?

   6. KGDr. Kathryn Gray29:14

      So the way it's done is the one-hour glucose test with 50 grams of glucose doesn't have to be a fasting test. So you just come in, you drink 50 grams of glucose, you have your blood drawn an hour later and tested for the glucose level.

   7. PAPeter Attia29:28

      I see.

   8. KGDr. Kathryn Gray29:28

      If, if you don't pass that test, so your glucose is above 130 or 140, depending on which cutoff you're using, um-

   9. PAPeter Attia29:36

      That's actually not that high, Katie.

   10. KGDr. Kathryn Gray29:38

       No. [laughs]

   11. PAPeter Attia29:39

       So, so es- b- 'cause, um, just the way I'm thinking about it is we always do OGTTs on our patients, but they're fasting. Now, we're using 75 grams of glucose-

   12. KGDr. Kathryn Gray29:45

       Right

   13. PAPeter Attia29:45

       ... instead of 50, so I, I'm not sure it's apples to apples. But, um, I can imagine a scenario where a woman comes in from a lunch where she was out at a, you know, she had a, she had pasta for lunch. Her glucose is already 120 or 130, which would be perfectly normal postprandially an hour after 50. I would be surprised if she was back down to 130 or 140.

   14. KGDr. Kathryn Gray30:07

       Yeah.

   15. PAPeter Attia30:07

       So you, you could potentially get into these false positives?

   16. KGDr. Kathryn Gray30:10

       Yes, of, of course. Um, so we do a follow-up, um, a three-hour glucose test where they do have to come in fasting and then, um, drink a larger glucose load and then get tested at one, two, and three hours after that.

   17. PAPeter Attia30:25

       And then what's the criteria on that? Is that 75 grams you do for that one?

   18. KGDr. Kathryn Gray30:28

       Yeah, and then you, um, then you look, there's a, there's a range for each one of those values of what is normal. So if your fasting's elevated from that test, you automatically Are diagnosed with gestational diabetes

   19. PAPeter Attia30:40

       And is, is d- elevated 110 in that fasting state, or 100, or do you ...

   20. KGDr. Kathryn Gray30:46

       Um-

   21. PAPeter Attia30:46

       The, the good news is you are going to get credit. You are gonna, you don't have to take your next board exam.

   22. KGDr. Kathryn Gray30:50

       [laughs]

   23. PAPeter Attia30:50

       This, this podcast is the exam. It's okay [laughs] . So just ...

   24. KGDr. Kathryn Gray30:56

       Um, uh, there [laughs] ...

   25. PAPeter Attia30:58

       We'll put this in the show notes, don't worry. Any- anything you don't know the answer to, just say, "We'll put it in the show notes."

   26. KGDr. Kathryn Gray31:02

       [laughs] Yeah, we're gonna put the values there for you.

   27. PAPeter Attia31:05

       Okay.

   28. KGDr. Kathryn Gray31:06

       Um-

   29. PAPeter Attia31:06

       So there's some, there's a threshold at zero, one hour, two hour, three hour.

   30. KGDr. Kathryn Gray31:09

       Yeah.
7. 36:19 – 48:53

   Preeclampsia: diagnosis, biology, acute risk, and how it’s managed

   1. PAPeter Attia36:19

      about preeclampsia. This is obviously a big one. You mentioned it already, but do you mind just defining it again?

   2. KGDr. Kathryn Gray36:24

      Yeah, so, so preeclampsia is a pregnancy-specific condition where folks develop, um, new onset high blood pressure or hypertension after 20 weeks gestation, and, um, often accompanied by proteinuria, so protein in the urine. And also accompanied by other, um, severe, what we would call, like, severe features, but sometimes other symptoms like right upper quadrant pain, vision changes, headaches.

   3. PAPeter Attia36:50

      And this is obviously screened for because most hypertension is asymptomatic, so that's something that has to be caught during your routine visits, correct?

   4. KGDr. Kathryn Gray36:59

      Yes. Um, and, um, actually, the initial schedule for prenatal care was really set up to detect developing preeclampsia in pregnancy, which is why you see, like, accelerating le- you know, closer visits at the end of pregnancy compared to early pregnancy is really screened for, like, blood pressure.

   5. PAPeter Attia37:19

      Is this defined as blood pressure, like, 135 over 80? Is that the threshold? Where do we consider that?

   6. KGDr. Kathryn Gray37:25

      So, um, one, um, uh, for systolic, it's 140, and for diastolic, it's 105 to one- 110 for, to qualify as, as having.

   7. PAPeter Attia37:37

      Okay.

   8. KGDr. Kathryn Gray37:38

      Yeah.

   9. PAPeter Attia37:38

      And is the diagnosis made in office, or do we accept that there's some white coat syndrome and we have the patient monitor at home?

   10. KGDr. Kathryn Gray37:45

       We're always looking at the whole picture.

   11. PAPeter Attia37:47

       Yeah.

   12. KGDr. Kathryn Gray37:47

       But, uh, a lot of times people will have, uh, some elevateds in the office, and we will send them home with a blood pressure cuff and have them monitoring more. Sometimes people present more, um, uh, robustly w- with, like, very severe blood pressures from the get-go and other symptoms, and then sometimes they get, go straight to being admitted to the hospital. So it can have very different courses for different folks. Like, some people will have hypertension for weeks that doesn't seem to be getting so much worse, and other people will present just in a very severe format from the very first time they present with hypertension.

   13. PAPeter Attia38:20

       And does the diagnosis require both hypertension and proteinuria, or does one of them, if significant enough, uh, warrant the diagnosis?

   14. KGDr. Kathryn Gray38:29

       Yeah, so they've changed the definition over time. So it used to be that to have preeclampsia you needed to have both, um, elevated blood pressures at least two six hours apart and then also proteinuria or another severe symptom. Now they've sort of changed it to say, like, with severe range blood pressures, um, and, um, other, you know, you can get the diagnosis without necessarily having overt, um, proteinuria.

   15. PAPeter Attia38:56

       All comers, what is the incidence of this?

   16. KGDr. Kathryn Gray39:01

       About 5% of pregnancies, 5 to 7% depending on your patient population-

   17. PAPeter Attia39:06

       Okay

   18. KGDr. Kathryn Gray39:06

       ... in the, in the US.

   19. PAPeter Attia39:08

       And then how does that change if we stratify by age? So if we were to limit it to, okay, just women in their 20s versus women in their 40s, does that change things?

   20. KGDr. Kathryn Gray39:17

       Well, the, the highest risk individuals are those folks who are having their first pregnancy and people who are very young or very old.

   21. PAPeter Attia39:26

       So I picked the worst demographic to compare.

   22. KGDr. Kathryn Gray39:28

       [laughs]

   23. PAPeter Attia39:28

       Yeah, yeah, yeah. So, okay, so first of all, why is that?

   24. KGDr. Kathryn Gray39:31

       [laughs] Um, I think we, we don't know. There's lots of reasons why people, like, there's lots of reasons why folks think that the first pregnancy is at highest risk. Um, there may be some, um, a degree of, um, one of the reasons people wonder is if there is, um, less, um, exposure of the mother to the paternal antigens, and it's, and, and that there's some t-

   25. PAPeter Attia39:56

       So it's an autoimmune response?

   26. KGDr. Kathryn Gray39:58

       It's not autoimmune.

   27. PAPeter Attia39:58

       Or immune, I'm sorry, immune.

   28. KGDr. Kathryn Gray39:59

       But there's, um, yeah, there may, there is, can be an i- there's a thinking that there can be an immune component to it, but it's not, it's not just that. Um, but we don't fully understand that.

   29. PAPeter Attia40:09

       Okay, so that would explain the early pregnancy, and then presumably there's a sensitization with a subsequent pregnancy.

   30. KGDr. Kathryn Gray40:15

       Top tolerance, yeah.
8. 48:53 – 55:07

   HELLP syndrome, what genetic studies reveal about preeclampsia, and the antihypertensive medications used to treat it

   1. PAPeter Attia48:53

      platelets, boy, this sounds a lot like HELLP syndrome. So I don't remember what HELLP stands for. I just remember it's really, really bad. Can you, can you remind us what it is?

   2. KGDr. Kathryn Gray49:03

      So HELLP syndrome is where the pregnant patient presents with, it stands for hemolysis, um, elevated liver enzymes, and low platelets. Um, some folks think it's, uh, s- on the spectrum of preeclampsia, like it's this very severe version of preeclampsia. Other folks think s- that it may have a completely, um, different underlying biology but have overlapping features with preeclampsia. Patients with HELLP syndrome may present with severe hypertension like we described for regular preeclampsia, but they also might have just, like, mild range blood pressures and then very severe lab abnormalities. So I've s- we see it present both ways.

   3. PAPeter Attia49:44

      And it can become pretty scary if it occurs, you know, in the 20 weeks, uh, not 20, but in the 20s, right? If it's at 28 weeks, 29 weeks, because you're really balancing the maternal health with maximizing the viability of the fetus, and as you said, the fetus could be compromised based, based on growth. I mean, this gets very complicated very quickly.

   4. KGDr. Kathryn Gray50:05

      Yeah. HELLP syndrome is one of those condit- um, conditions where we often give betamethasone, um, to help mature the baby's lungs, and we wait 48 hours, and then we deliver because we, we don't expectantly manage somebody who has HELLP syndrome.

   5. PAPeter Attia50:22

      How often do women get that diagnosis, um, prior to when they need... Like, in other words, is that something that can be, uh, I guess by definition, you're saying HELLP syndrome implies diagnosis to delivery is a very short window.

   6. KGDr. Kathryn Gray50:37

      Yeah, as long as that, as l- as long as that's actually what's going on, but yes.

   7. PAPeter Attia50:41

      Okay. What's your best guess for the etiology?

   8. KGDr. Kathryn Gray50:44

      Great question. [laughs] We don't, I, we d- we don't, we do not, we do not know what causes HELLP syndrome.

   9. PAPeter Attia50:50

      If we assume that preeclampsia is something distinct or even if it's not, do you have a sense of the, the, I mean, we explained the mechanism of preeclampsia, but do we think that this is somewhat genetic, part, you know, largely genetic, somewhat environmental, not environmental at all? Uh-

   10. KGDr. Kathryn Gray51:06

       Yeah, good questions. Um, well, preeclampsia is heritable, meaning that there is definitely a genetic component. So, um, it, and it comes from both the fetus and placenta, which are the s- considered to be the same, relatively the same genetically, and the, and the maternal genetics. So they're both important. So, um, uh, so there's been a lot done in the past, um, you know, eight years or so that's come out about the underlying genetics of preeclampsia. It was a really understudied field when I started working in this area myself. There were, like, no big cohorts that had genetic data and had had the same type of genome-wide association studies that had been done for many other complex diseases. And so it was really unknown, um, what, um, factors across the genome might contribute. But in the past eight years, there's been a lot more information that's come out about that, um, which I think is, um, really great and fascinating because genetics can really help you get at the underlying causal biology behind something. So when you really don't understand what's causing it or what pathways might be important to target, um, with therapeutics, then genetics can really help, help you understand that.

   11. PAPeter Attia52:21

       Going back to management of preeclampsia, if you're going to use antihypertensives, what are the agents of choice?

   12. KGDr. Kathryn Gray52:27

       Yeah. Um, the, what you'll see used most is nifedipine and labetalol 'cause there's good data about safety, um, in pregnancy. Um, there are other hypertensives that we use sometimes, um, but those are two of two mainstays.

   13. PAPeter Attia52:45

       So interesting 'cause, I mean, we just don't use those outside of pregnancy at all-

   14. KGDr. Kathryn Gray52:49

       Yeah

   15. PAPeter Attia52:49

       ... 'cause they're not that good.

   16. KGDr. Kathryn Gray52:50

       Yeah.

   17. PAPeter Attia52:50

       Um, so does that mean we do not know or we do know that ACE inhibitors or ARBs, which would be first line in someone who's not pregnant, do we know for sure that those are not safe in pregnancy, and is that why they're not chosen?

   18. KGDr. Kathryn Gray53:02

       Correct. We sh- know for sure that they're not safe in pregnancy.

   19. PAPeter Attia53:05

       Yeah. So they have a negative impact on the fetus presumably.

   20. KGDr. Kathryn Gray53:07

       Correct. That's right.

   21. PAPeter Attia53:09

       Got it.

   22. KGDr. Kathryn Gray53:09

       Yeah. But they're good agents postpartum when we're working to control maternal blood pressure, so we often will utilize them after delivery.

   23. PAPeter Attia53:18

       So when we were talking about gestational diabetes, you pointed out that, you know, the woman could be off insulin by the time she goes home.

   24. KGDr. Kathryn Gray53:25

       Oh, yeah.

   25. PAPeter Attia53:26

       Like, that's how quickly it resolves.

   26. KGDr. Kathryn Gray53:27

       Yeah.

   27. PAPeter Attia53:27

       But what you just said makes me think the same is not necessarily true of preeclampsia and the hypertension.

   28. KGDr. Kathryn Gray53:32

       Yeah, that's correct. So, um, some people will have their hypertension resolve, like, very quickly after delivery, but many women need, um, antihypertensive medications for several weeks after delivery. It can take, like, six, 12 weeks to kind of come back to more of a baseline. And there, there are other women who will have persistent hypertension, um, after delivery that never quite resolves, and lots of women who, um, will come back and develop hypertension within the next five to 10 years as well.

   29. PAPeter Attia54:07

       Wow. Um, does the proteinuria respond or resolve quickly? And I assume that's checked until it does.

   30. KGDr. Kathryn Gray54:16

       You know, we don't, we don't check it, but it, and it, and that is because it, it resolves.
9. 55:07 – 1:01:50

   What pregnancy reveals about long-term cardiometabolic health

   1. PAPeter Attia55:07

      is probably a good window to now talk about what you alluded to already, which is something that I was unaware of until, I don't know, nine months ago, 12 months ago, which was this idea that, um, in cohort studies, preeclampsia or more specifically hypertension during pregnancy, even if it resolved, was predictive of later life, um, atherosclerotic cardiovascular disease. Um, how long have, how long has the field of medicine known this, and what do we think is the best explanation other than maybe the obvious one, which is there's a strong genetic component to it and therefore that same genetic component doesn't go away?

   2. KGDr. Kathryn Gray55:47

      Right. Um, so, so good questions there. Um, actually, this has been known for, for quite a while. I just think it hasn't really-

   3. PAPeter Attia55:53

      I'm just late to the party, which is often the case, I can assure you.

   4. KGDr. Kathryn Gray55:56

      Hasn't translated well out of the obstetrics field into, like, primary care and other fields of medicine like w- one, like it should have really.

   5. PAPeter Attia56:05

      Like it should be a question you would ask.

   6. KGDr. Kathryn Gray56:06

      Yeah.

   7. PAPeter Attia56:07

      We now ask this question.

   8. KGDr. Kathryn Gray56:08

      Yes.

   9. PAPeter Attia56:08

      But you should ask this question during a history and physical of any patient, right? You should say, "Have you, oh, I notice you had three kids. Did you have preeclampsia during those pregnancies?"

   10. KGDr. Kathryn Gray56:15

       Yeah. The obstetric history is relevant-

   11. PAPeter Attia56:17

       Yeah

   12. KGDr. Kathryn Gray56:17

       ... and often not asked about. And in fact, that inhibited genetic studies because people would do these large cohort studies and never ask about obstetric history. It wasn't recorded, the data. The data wasn't there. Um, when y- in terms of why, when, when we've looked at these genetic studies, um, on the maternal side, one of the strongest, um, shared genetic architectures between preeclampsia and, um, uh, preeclampsia is, um, essential hypertension, both systolic and diastolic. Um, hypertension is, um, uh, if you have a higher genetic disposition to that, you have a higher risk of preeclampsia. In the very first maternal GWAS of preeclampsia, genome-wide association study, the top hits that were genome-wide significant were some of the top hits in, um, ge- genome-wide association studies of hypertension. So we do know that folks who develop hypertension or preeclampsia are much more likely to have an underlying genetic disposition to hypertension. So that's definitely part of why they have a higher long-term risk, and pregnancy unmasks that predisposition. There's still, um, a component of the exposure to the hypertensive pregnancy that people think may add on top of the underlying genetics to the future risk. So that I think that's an active area of research that people are engaged in, like does the pregnancy itself increase the risk, and if so, how? And then of course there's other factors like, um, social factors, like, uh, otherwise like, uh, other health conditions that contribute to those risks. So it is a multifactorial, um, contributors to long-term disease.

   13. PAPeter Attia57:58

       And remind me, uh, you may have said this and I just missed it. Do women who develop gestational diabetes also have a higher risk for type 2 diabetes? Is that predictive?

   14. KGDr. Kathryn Gray58:09

       Yes. Um, so 50% of patients who have gestational diabetes will develop type 2 diabetes.

   15. PAPeter Attia58:15

       50%?

   16. KGDr. Kathryn Gray58:16

       Yeah. Yeah.

   17. PAPeter Attia58:19

       Interesting. Have there been any intervention studies that have been done, and this would be a difficult study to do, I, I accept, because it would take a long time, so the answer is almost assuredly no. But where you take women who develop gestational diabetes, and then you manage them aggressively, you know, you would randomize them to one intervention versus the other to see if you could delay and/or just outright avoid type 2 diabetes?

   18. KGDr. Kathryn Gray58:43

       Yeah, I think the, the recommendation is that they have frequent follow-up for, um, diabetes screening and also should be very much advised on life, any lifestyle changes that they could make that would impact the risk of type 2 diabetes. So we know that healthier diet and a, um, appropriate body weight and regular exercise all, all are very important there. So, um, it's even more critical for, um, folks who have a history of gestational diabetes to be counseled about, about that to decrease their risk.

   19. PAPeter Attia59:15

       So is that sort of the message you're delivering to a woman? Because you're in a very interesting role as a physician in that you play a profound role in the care of her and her baby, but once that baby's gone, she's, you're not the one that gets to take care of her, and yet you learned something really profound about her because, as you said, you saw her during a very high physiologic stress test that gave you an enormous insight into what the rest of her life has in store for her vis-à-vis metabolic health, cardiovascular disease at a minimum. I mean, by the way, we might discover that there are other diseases we're learning about that are predicted through pregnancy. So what is the relationship between a high risk or any OBGYN and the long-term health of the patient to say, "Look, this is not, your genes are not your destiny, but you need to, we need to really stay on top of managing these things aggressively. And by the way, you, you should live a normal life as a result of the, the, the privilege of modern medicine that we, we wouldn't have been able to do this, you know, 50 years ago."

   20. KGDr. Kathryn Gray1:00:23

       Yeah. Yeah. I mean, I think the counseling is really important and, um, as a high-risk obstetrician, um, you know, some general OBGYNs might see a patient for their pregnancies and then also for their GYN care and have more of a primary care relationship with a patient. Um, with our high-risk obstetric practice, we will only see the patient back in general if they have another pregnancy. Um, and so that transition to a primary care provider with that information, um, transmitted is, is really essential, and I do think lots of patients who are young and taking care of kids and often don't follow up a lot themselves between pregnancies and so, um, you know, stressing the importance of having a primary care provider and following is, is really important, but certainly there could be You know, we can continue to enhance, like, both education and the communication. I mean, electronic health records have helped some, right? 'Cause we can often see now, like, records and, you know, if, if somebody is tuned into that, they can, they can get at what happened. Um, but the, they have to know that it's important.

   21. PAPeter Attia1:01:30

       So if we did nothing else today, if we accomplished only one thing and it was that women and their primary care doctors were really tuned into what was unmasked during pregnancy and used that for aggressive treatment and prevention, that would be a win.

   22. KGDr. Kathryn Gray1:01:47

       Yeah, for sure.

   23. PAPeter Attia1:01:48

       Okay. Do you have a sense

10. 1:01:50 – 1:16:08

    Cesarean delivery, breech presentation, and stillbirth

    1. PAPeter Attia1:01:50

       of... Well, I mean, it sounds like it's, it's a bit of a mixed bag in terms of what's recognized there. Um, okay, so the other thing I wanted to ask you about is C-section versus vaginal. What are the trends? What are the trade-offs? This is an area where I feel like I have heard so many differing stories. I can't tell what's real.

    2. KGDr. Kathryn Gray1:02:10

       Yeah.

    3. PAPeter Attia1:02:10

       Um, so let's, let's kind of walk through what is known and let's acknowledge what is not known.

    4. KGDr. Kathryn Gray1:02:16

       Yeah.

    5. PAPeter Attia1:02:16

       So what, first of all, I don't, from a historical perspective, I assume it wasn't until the late 1800s we were doing the first cesarean sections. I hope we were at least waiting until we had modern anesthetics.

    6. KGDr. Kathryn Gray1:02:25

       [laughs] These are, these are all so good questions that I, I, I don't know all the answers to. Um, but, um, uh, but, uh, certainly even now there's many parts of the world where people don't have great access to, um, uh, you know, surgical intervention during, during labor and delivery, and that can really drive a lot of, um, both stillbirths that people have during the intrapartum phase and, like, long-term maternal complications like fistulas and other complications from prolonged labor. So C-section is certainly, like, a needed and helpful intervention, um, because not, not every baby is gonna deliver vaginally, um.

    7. PAPeter Attia1:03:08

       And do we just have a sense of, again, and I don't expect you to know the answer to this, so don't worry. [laughs] Not on the boards. Um, prehistoric times, right? Or ancestral times. You know, go back 1,000 years. Do we have a sense of what the frequency was of a stillbirth, and was the stillbirth, uh, necessarily going to lead to the maternal demise? Like, if you can't get a dead fetus out of a woman, she's going to die of an infection, correct?

    8. KGDr. Kathryn Gray1:03:34

       Um, I, yes, I think, like, um, I, I think you often will eventually deliver the, the demised fetus, but, you know-

    9. PAPeter Attia1:03:46

       But, but you can't poss- I mean, maybe you could, but it would seem to me that you would be leaving behind some placenta. There, there would be some dead tissue that would remain, wouldn't there?

    10. KGDr. Kathryn Gray1:03:56

        I mean, I wouldn't think of that happening, but, like, the, the, a retained pregnancy is certainly gonna be risky for the patient.

    11. PAPeter Attia1:04:05

        Okay. So C-sections have obviously become important. What, what do we know about the, uh, I don't know what the right word to think of it, is it prevalence or usage or num- you know, what- in whatever metric you would use to determine what percentage of deliveries in the United States are vaginal versus C-section, how has that number changed over the last 50 years?

    12. KGDr. Kathryn Gray1:04:26

        Yeah, it's dramatically increased, you know. So we've, we've gone from, you know, like, 10% C-section rate, say, like, I don't, I, I don't have all the exact numbers in my head, to, like, oftentimes practices have, like, in, in an academic medical center, like, a 30% C-section rate, and that's all comers, right? You're, like, accounting for people who've had, like, previous C-sections and people who can't have a vaginal delivery by, because it's not safe for whatever obstetric reason, so, um, but it has increased, um, increased dramatically.

    13. PAPeter Attia1:04:59

        And what is driving that 3x increase?

    14. KGDr. Kathryn Gray1:05:03

        I think, um, there, there are different drivers. Um, the pregnancies are, are higher risk than they used to. Um, you know, if once you have one C-section, you're more likely to have another one. Um, uh, the, the health of the, the, the patient matters. A lot of people think that, um, maternal obesity increasing has increased the number of women who have, like, um, either, uh, you know, have either larger fetuses or fail, like, labor that doesn't progress normally and therefore leads to a C-section. Um, we have, you know, we went from a time when we were not doing continuous monitoring, so fetal monitoring during labor, to where we monitor, in most hospitals, the baby's being monitored during the active phase of labor continuously, and when the tracing is not reassuring, we, um, you know, move to a C-section. Um, so I think it's, it's a complex issue to understand. Um, uh, and, you know, there is a lot of focus on trying to, um, you know, decrease that number or avoid it getting higher than it is now.

    15. PAPeter Attia1:06:18

        Why is that? Why, why would we be concerned if it's getting too high?

    16. KGDr. Kathryn Gray1:06:21

        So I think the one, um, one consequence, and it's not the only one, but for folks who have prior C-sections, multiple prior C-sections, they're at higher risk for abnormal placentation in the next pregnancy, meaning that, um, the, um, specifically placenta accreta spectrum, so the placenta can invade abnormally into the, to the uterus during pregnancy, and then when it's time to deliver, the placenta does not come, come out after the baby.

    17. PAPeter Attia1:06:53

        Is that the re- is that the main reason why once you have a C-section, your probability of another C-section goes up because of the placenta, or is it because of the pressure on the fascia from the That would be required during the exertion of a vaginal delivery

    18. KGDr. Kathryn Gray1:07:09

        There's a couple different things. So, um, there's a couple different kinds of C-sections, so, um, meaning, um, where you cut on the uterus. So if you cut, if you cut low down on the uterus in a transverse fashion, um, so that's called a low transverse C-section, that is in the, is not in as muscular of a part of the uterus. And so in general it's thought that, um, you are fairly safe to labor in a future pregnancy. Um, it with like a 1%, um, risk or less than 1% that the, that old scar might come apart during labor, so that's called a uterine rupture, which is obviously, um, an emergency, and-

    19. PAPeter Attia1:07:50

        That's an, that's a surgical emergency. Now you're going... Yeah

    20. KGDr. Kathryn Gray1:07:53

        However, if you have had prior surgery on your uterus, either because you had a big fibroid and you, you, um, had it removed from your uterus, or if you had a prior C-section that was what we call a classical C-section where you cut up and down on the uterus, then that cuts through the m- musculature of the uterus, and, um, that type of incision is much more likely to rupture during labor. They say like 10% for someone who've had a classical C-section

    21. PAPeter Attia1:08:19

        Which is too high to even-

    22. KGDr. Kathryn Gray1:08:20

        Which is too high. So we say folks in that group should not labor. So they-

    23. PAPeter Attia1:08:24

        And sorry, remind me why the choice is made between those two incisions in the first place.

    24. KGDr. Kathryn Gray1:08:28

        We try to do a low transverse C-section, and in term patients you almost always can. But if you need to deliver somebody preterm, for example, this is one of the most common reasons we would do a classical C-section, the uterus is not ex- big enough that, or expanded enough that they, the lower uterine segment is not developed and you may not be able to make an incision down in the lower part of the uterine segment and ca- and, um, [lips smack] uh, safely deliver the preterm baby through that. So if, if it's too premature, we often have to do a classical C-section. Sometimes there is other reasons, like, um, surgical complexity, someone's had multiple C-sections, n- you can't-

    25. PAPeter Attia1:09:10

        Scar tissue

    26. KGDr. Kathryn Gray1:09:10

        ... yeah, can't get around the scar tissue, other reasons why we can't, but.

    27. PAPeter Attia1:09:14

        Yeah. And you're not entering the peritoneum when you do this, correct? You're doing this all outside of the abdomen?

    28. KGDr. Kathryn Gray1:09:19

        No, it's in, in the ab-

    29. PAPeter Attia1:09:21

        You, you are. You don't, you don't separate the fascia and keep the uterus outside. Okay. Um, [lips smack] the, um, when you, when-- Okay, so I'm trying to think of reasons where it was a non-negotiable. So a breech delivery would, you wouldn't ever try to deliver a breech vaginally if you, I mean, I assume you know this

    30. KGDr. Kathryn Gray1:09:40

        We generally don't, um, because the biggest, the recommendation by ACOG is that we generally don't, and it's because the biggest part of the baby is the head and it comes last and, and a head entrapment, meaning the head, the rest of the baby comes out and then the head doesn't, is, is very dangerous. So for a singleton, we, um, generally recommend a C-section. If the baby is breech, there's an opportunity to potentially turn, try to turn the baby before labor. That's called an external cephalic version. So sometimes we can turn the baby to cephalic and then the patient can labor, but-
11. 1:16:08 – 1:25:28

    The onset of labor, cervical dilation, and membrane rupture

    1. PAPeter Attia1:16:08

       triggers labor? Why, why, [laughs] what is happening in the bo- how does the body know it's time?

    2. KGDr. Kathryn Gray1:16:12

       Uh, we don't know. [laughs]

    3. PAPeter Attia1:16:14

       Really?

    4. KGDr. Kathryn Gray1:16:15

       Yeah. [laughs]

    5. PAPeter Attia1:16:18

       We, so w- tell me, tell me what is actually happening. What, what is the, what's happening with prolactin and oxytocin and all these other things? Even if we don't know why it's happening, do we, do we at least have a sense of those things?

    6. KGDr. Kathryn Gray1:16:28

       Uh, a, a little bit, but, you know, um, yeah, you know, people have tried to look at the changes that directly precede, um, labor, and, and there's some ... But it's hard to predict, right? Like, you monitor somebody, like, every day to see [laughs] like what's gonna happen up to delivery. So we, we really don't have a great sense. Um, you know, we think something's changing with the HPA axis that's triggering this quiescent state where progesterone is maintaining the uterus not to contract to actually contract, but we really, really don't have, have a good sense of, of what's happening.

    7. PAPeter Attia1:17:03

       Uh, is the contraction of the uterus the first sign? Is that the first thing a woman is actually feeling?

    8. KGDr. Kathryn Gray1:17:09

       Yeah.

    9. PAPeter Attia1:17:11

       Tell me how you coach a woman through that. Like, if, l- let's say you're seeing her in your office, and it's what you believe will be the last time you see her prior to her admission to the labor and delivery ward. It's her first pregnancy. She doesn't know what to expect. [laughs] Uh, her partner is equally clueless, uh, and they're scared senseless. What are you saying?

    10. KGDr. Kathryn Gray1:17:29

        Um, well, with every third trimester patient, we're saying, like, you know, mo- monitor, like, how you're feeling the baby move. Let us know if it's different. Um, look out for leaking fluid, um, and vaginal bleeding. If you have any of those things, come in. And then, um, if you start to have contractions, like, time how frequently they're coming, and if they're coming closer than five minutes apart for, you know, um, more than a, more than an hour or they're increasing in pain and intensity or accompanied by any of those other things I just described, then you should come in to get checked out.

    11. PAPeter Attia1:18:05

        Okay. So that's, that's a pretty logical list. Um, the con- I mean, having experienced contractions yourself, what, what does this con- what does this thing feel like? What does a contraction feel like? Does it feel like a muscle flexing?

    12. KGDr. Kathryn Gray1:18:18

        I think early contractions might kind of be like, or, you know, Braxton Hicks, like practice ones, might be like having a really bad period, like a really bad menstrual cramp. But, like, real contractions, probably more painful than anything else that, you know, uh, I've experienced before.

    13. PAPeter Attia1:18:37

        So it's not subtle. A woman is not, there's no way, she's not thinking to myself, "Is this a contraction?"

    14. KGDr. Kathryn Gray1:18:42

        Well, th- that often comes up, and there are patients who have very high pain tolerances or experience it differently who come in who are quite dilated without a lot of pain. But I think most people experience it as a pretty painful process.

    15. PAPeter Attia1:18:57

        How, so I, explain t- to the listener what you mean by dilation, and what is the, what is the amount of dilation that you would see ... commonly and not be concerned if there still hasn't been any contraction?

    16. KGDr. Kathryn Gray1:19:11

        I think that's a complicated [laughs] question to answer. But, um, so the, what, what I mean by dilation is that, um, you know, at the, at the lower part of the uterus inside, inside the vagina is the cervix, and the cervix is what we're actually monitoring for whether it's dilated or not in pregnancy. In early and mid-pregnancy, you don't want the cervix to be dilated. If it is, that's, like, a sign of premature cervical dilation or preterm... It can be preterm labor. Um, but, um, say you're at term, it would be very common for people to have, um, a cervix that gets thinner and softer and may start to dilate some. That's the body, um, getting ready for, um, labor. Um, and then, um, we y- we digitally check how dilated the cervix is to understand, like, if somebody is in labor and how labor is progressing. It's what we use to monitor the progression of labor, um, when somebody's in the hospital, ready to, getting ready to deliver.

    17. PAPeter Attia1:20:15

        And how many centimeters of dilation is when you start to say, "Okay, you're not... We're, we're sitting here till this baby comes out"?

    18. KGDr. Kathryn Gray1:20:23

        Well, it's, it's, it's not just the dilation by itself. Uh, it's like the-

    19. PAPeter Attia1:20:27

        Right. It's also the frequency of the contraction and-

    20. KGDr. Kathryn Gray1:20:29

        Right. I mean, people can sit around at three to four centimeters dilated for weeks and not be in labor. There can be other people who come in four centimeters dilated who are contracting painfully every three minutes, and they're definitely in labor.

    21. PAPeter Attia1:20:41

        Is it an anatomic difference? Is that a function of the anatomy of the cervix, or is that another mystery of we don't fully understand the whole process of delivery?

    22. KGDr. Kathryn Gray1:20:51

        Well, it's not, it's not the same in everyone, right? It's not like there's this-

    23. PAPeter Attia1:20:54

        Yeah

    24. KGDr. Kathryn Gray1:20:54

        ... then there's this, then there's this. Like, in some people, the water breaks first, and other people, they... You know, that's a smaller percentage of people, but that can happen before any labor, and then, then you either, then they either go into labor or you help them go into labor.

    25. PAPeter Attia1:21:06

        And the, and the, the, quote-unquote, water breaking is the placental fluid coming out because that cer- that membrane at the cervix opens? The, like, what's actually happening when the water breaks?

    26. KGDr. Kathryn Gray1:21:17

        Well, the, the amniotic sac gets a hole, so it can be at any part of it. It's often, um, at the part that's in the lower uterine segment or n- or near where the cervix is opening, but it's that the am- the fluid in the amniotic sac gets, um, released. The bag is no longer-

    27. PAPeter Attia1:21:34

        And it's clear fluid.

    28. KGDr. Kathryn Gray1:21:36

        Uh, you-

    29. PAPeter Attia1:21:36

        Clear yellowish or...?

    30. KGDr. Kathryn Gray1:21:37

        Usually. It, it can, it can contain baby's poop, like meconium staining at-
12. 1:25:28 – 1:29:37

    Vaginal delivery and breastfeeding: benefits versus myths

    1. KGDr. Kathryn Gray1:25:28

       So ...

    2. PAPeter Attia1:25:28

       Going back to the C-section versus vaginal discussion, um, again, my vague recollection is one of the advantages of a vaginal delivery is, uh, related to the bacterial transfer between mother and fetus. Is that real, or is that something that gets over, uh, extrapolated?

    3. KGDr. Kathryn Gray1:25:48

       There's a lot of attention to that for how much we really know [laughs] about it, I would say.

    4. PAPeter Attia1:25:52

       [laughs]

    5. KGDr. Kathryn Gray1:25:52

       There's probably something there, like the microbiome is important.

    6. PAPeter Attia1:25:56

       Yep.

    7. KGDr. Kathryn Gray1:25:56

       It's, like, there's certainly influences and importance across different areas of medicine. Um, but I think, like, there's a lot of popular press about that-

    8. PAPeter Attia1:26:06

       Yeah

    9. KGDr. Kathryn Gray1:26:06

       ... with- without, um, probably a lot more of the, of the, of the basic medical things there.

    10. PAPeter Attia1:26:12

        Th- there seems to be a lot of fear-mongering about it, quite frankly, which is almost like shaming women that have C-sections into believing, like-

    11. KGDr. Kathryn Gray1:26:18

        Right

    12. PAPeter Attia1:26:19

        ... "You have failed to deliver the appropriate gut biome to your child"

    13. KGDr. Kathryn Gray1:26:23

        Right

    14. PAPeter Attia1:26:23

        And, and so is it safe to say that there's j- the science is not suggesting that?

    15. KGDr. Kathryn Gray1:26:28

        Well, I, I'm not saying that there's no helpful component of that.

    16. PAPeter Attia1:26:32

        Yeah.

    17. KGDr. Kathryn Gray1:26:32

        But I would say of all the things that help determine your health and your baby's health, that's probably not the thing to stress about. [laughs]

    18. PAPeter Attia1:26:40

        Is there some epidemiologic data that suggests, which of course would be confound by 100 other things, but is there, is there some on/off, uh, uh, kids that are born via cesarean section are more or less likely to have some gut related ... No. So it's-

    19. KGDr. Kathryn Gray1:26:54

        I, not to my knowledge.

    20. PAPeter Attia1:26:55

        Okay.

    21. KGDr. Kathryn Gray1:26:56

        Yeah.

    22. PAPeter Attia1:26:56

        Um, yeah. So not, yeah, stan- standard, uh, application of, uh, social media there.

    23. KGDr. Kathryn Gray1:27:02

        [laughs]

    24. PAPeter Attia1:27:02

        Um, let's talk about breastfeeding a little bit. So again, one of the things I do remember from medical school is the importance of IgA, if I recall, as ... And, um, so notwithstanding the obvious example of why breastfeeding mattered evolutionarily when we didn't have formula and things like that, uh, w- how, what percentage of women are unable to, for some physiologic reason, breastfeed? Uh, uh, I mean, pick a duration to answer that question, like dr- uh, after X number of weeks or so.

    25. KGDr. Kathryn Gray1:27:33

        I mean, it's such a complicated question, right? Because, um, uh, most people, unless they have had, like, substantial breast surgery or other endocrine disruptors themselves, um, have the physiologic capacity to produce breast milk. Um, there's a lot of, um ... Breastfeeding is complex, right? It's like a both a maternal and a neonatal, like, um, partnership. So for people who have very premature babies, for example, who might not be able to, like, latch and actually breastfeed, the mom would have to, like, pump and produce breast milk, which is always less effective than the baby actually, like, directly breastfeeding in terms of effectiveness and stimulation and also the ability for, like, a mother to keep, keep doing it over time. Um, and, um, you know, uh, then, you know, a breastfeeding mom will have to, you know, be responsible for expressing breast milk every few hours for many, many weeks and being present with, with the baby, which may or may not be possible for, for any given mother. So-

    26. PAPeter Attia1:28:43

        And what's driving that from the endocrine system?

    27. KGDr. Kathryn Gray1:28:46

        Um, you mean, um, what, ab-

    28. PAPeter Attia1:28:49

        The, the production of milk.

    29. KGDr. Kathryn Gray1:28:50

        Yeah. Um, I mean, it's a, it's, again, it's a complex [laughs] hormonal interplay. So, um ...

    30. PAPeter Attia1:28:58

        And in theory, a lactating woman is gonna have a harder time ovulating. I mean, that was generally viewed as one method of birth control.
13. 1:29:37 – 1:36:15

    Exercise during pregnancy, sleep position in the third trimester, and postpartum depression

    1. KGDr. Kathryn Gray1:29:37

       of the, of their cycle. So, yeah.

    2. PAPeter Attia1:29:39

       I wanna talk a- about a couple things you would counsel patients on during pregnancy with respect to three things. So, uh, sleeping position, uh, any nutritional things outside of managing, you know, are there any real big dos and don'ts of what you make- wanna make sure people are eating versus not eating? And then exercise, what restrictions do you place on exercise? So maybe we'll start with exercise.

    3. KGDr. Kathryn Gray1:30:04

       Yeah, I mean, I think exercise is really important. The more data we get, the more we know, like, bed rest is bad. People do better when they exercise. Um, uh, you know, we, um, we tell people not to start, like, a new intensive program during their pregnancy. So if they weren't that physically active prior to pregnancy, it's not the time to, like, start to try to run a marathon. But having, like, regular activity like walking or, um, uh, you know, uh, l- low, low weight weightlifting was, is fine. Um, for patients who've been doing an exercise program, they're generally, if everything in the pregnancy is going fine, it's, like, generally fine for them to continue it. Um, things-

    4. PAPeter Attia1:30:48

       And including s- resistance training if it's-

    5. KGDr. Kathryn Gray1:30:50

       Yes

    6. PAPeter Attia1:30:50

       ... like if they, if they're used to strenuous resistance training-

    7. KGDr. Kathryn Gray1:30:53

       Yeah

    8. PAPeter Attia1:30:53

       ... you would be okay with that until what point in the pregnancy?

    9. KGDr. Kathryn Gray1:30:57

       Well, I think, um, the main risk is, like, the center of gravity changing, the risk of getting injured or, or hurt by whatever you're doing. So you just have to do, um, all the things you're doing in a safe way. So, you know, we don't recommend downhill skiing in the second part of Pregnancy

    10. PAPeter Attia1:31:14

        Yeah

    11. KGDr. Kathryn Gray1:31:14

        Um, you know, we d- you know, horseback riding or, or you know, things where you might incur trauma to your abdomen are, are not good

    12. PAPeter Attia1:31:22

        Yeah. But a Valsalva, a bearing down during a, you know, lifting something heavy is okay if a woman's used to that?

    13. KGDr. Kathryn Gray1:31:28

        Yeah, we haven't ... You know, if she's having like a healthy pregnancy. Now for people who have threatened preterm labor or a short cervix or other things going on, we, um, may tell them to abstain from like heavy lifting and things in, um, during their pregnancy

    14. PAPeter Attia1:31:42

        And a short cervix pres- presumably means you have less resistance to the intraabdominal pressure

    15. KGDr. Kathryn Gray1:31:48

        Yeah, presumably. I'm, I'm not sure. Our data's great, but there-

    16. PAPeter Attia1:31:50

        Yeah

    17. KGDr. Kathryn Gray1:31:50

        ... there's just like, there are certain things where we tell people to have some restrictions

    18. PAPeter Attia1:31:55

        What about running? So if you had a woman who's a runner, lifelong runner, loves to run, it's one of her favorite forms of exercise-

    19. KGDr. Kathryn Gray1:32:01

        Yeah

    20. PAPeter Attia1:32:01

        ... what restrictions do you place on her during pregnancy?

    21. KGDr. Kathryn Gray1:32:03

        I, I wouldn't say that we would place any-

    22. PAPeter Attia1:32:05

        So run to your heart's content and just be mindful of everything you said. At some point, your center of gravity's gonna move

    23. KGDr. Kathryn Gray1:32:10

        Yeah. Don't overdo it. Try not to fall. Stay well hydrated, right?

    24. PAPeter Attia1:32:14

        Yeah

    25. KGDr. Kathryn Gray1:32:14

        Like, you know, like t- maybe take it a little easier than you sometimes would, but yeah, no, we would-

    26. PAPeter Attia1:32:20

        Okay

    27. KGDr. Kathryn Gray1:32:20

        ... people who can ... It might be uncomfortable for people at the end. They might desire to s- to stop, [laughs] but

    28. PAPeter Attia1:32:26

        Yeah, yeah. And then what about, um, a sleeping position? At some point it starts to become pretty uncomfortable. I would imagine side sleeping is probably ideal. Any truth to this idea that you wanna sleep on your left side so you don't compress the vena cava on the right side?

    29. KGDr. Kathryn Gray1:32:43

        Yeah, I mean, at the end of pregnancy when the fetus is pretty big, um, I think, um, it, it, it, to lay completely flat on your back is probably not the best position. To, so to have some tilt, um, if you're laying, um, towards your back, uh, would be good 'cause there is, um, that, that part it, has some truth to it, but I think, um, you know, people sometimes come in panicked that they woke up on their back and, you know, I'm like, "It's, it's gonna be okay." [laughs] Just like, you know? Um, but

    30. PAPeter Attia1:33:13

        Okay
14. 1:36:15 – 1:42:43

    Prenatal genetic screening: the growing role of cell-free DNA and the gap between what is technologically possible and what gets deployed in the clinic

    1. KGDr. Kathryn Gray1:36:15

       feeling this way

    2. PAPeter Attia1:36:16

       Let's go back to the other end of the pregnancy, which is, um, on the sort of genetic screening side of things. So, um, IVF is becoming much more common these days, and with IVF comes prenatal screening. But for, for couples not undergoing IVF, um, who are showing up with a spontaneous pregnancy, what is the current state of the art in screening? Is it mostly done through sampling amniotic fluid? Is that still viewed as kind of an aggressive thing that you wouldn't really do unless you needed to? How, how do you think about that?

    3. KGDr. Kathryn Gray1:36:48

       Yeah, so the, the number of diagnostic or invasive procedures that we're doing that include amniocentesis and then chorionic villus sampling, which we can do even earlier in pregnancy, um, have decreased. Um, and one of the primary drivers of that is how, um, screening for chromosomal disorders like Down syndrome has, um, uh, improved with the advent of cell-free DNA screening. So just a tube of the maternal blood, um, we can find fragments of the placental DNA and therefore, um, screen the pregnancy, um, for chromosomal conditions. Um, that test is best at screening for trisomies 21, 18, 13, and the fetal sex. It's less good for, for other, other things.

    4. PAPeter Attia1:37:38

       And you can do that within how many weeks of pregnancy?

    5. KGDr. Kathryn Gray1:37:40

       As early as nine or 10 weeks of pregnancy, so very early on.

    6. PAPeter Attia1:37:44

       Is that considered routine?

    7. KGDr. Kathryn Gray1:37:46

       Yeah, so it is recommended to be offered to all pregnant patients for screening now.

    8. PAPeter Attia1:37:51

       Okay. Um, so presumably that takes away a lot of the incentive that was present for amniocentesis, correct?

    9. KGDr. Kathryn Gray1:38:00

       Right. So previously, we had what was called a serum screen that looked at three or four protein markers in the maternal blood, and if that screen was positive, meaning that the levels of those proteins for the gestational age were, um, consistent with an increased risk of a chromosomal disorder, then an amniocentesis was recommended. But in those cases, only five... The positive predictive value of a positive test, um, was 5%, meaning that for everyone who screened positive for potentially having a baby with Down syndrome or trisomy 21, only 5% would actually be carrying a baby with Down syndrome.

    10. PAPeter Attia1:38:43

        Now, is that because the prevalence was too low or because the sensitivity and specificity were too low?

    11. KGDr. Kathryn Gray1:38:48

        It's because the sensitivity and specificity were too low.

    12. PAPeter Attia1:38:53

        Got it.

    13. KGDr. Kathryn Gray1:38:53

        Um, and so cell-free DNA has dramatically improved both the sensitivity and the specificity of that testing, so fewer people feel inclined to also pursue a diagnostic procedure. And when the screen is positive, they're, they're not 100% guaranteed to have a fetus with that condition, but they're much more likely to, to have one.

    14. PAPeter Attia1:39:15

        What do you think is the biggest gap in this type of testing? Like, where, where do, where would you like to see things in a decade with respect to prenatal screening or, or in utero screening for that matter?

    15. KGDr. Kathryn Gray1:39:25

        Well, there's different kinds of screening. There's, there's ultrasound, which has developed a lot, so we can actually look structurally at the baby, and then there's genetics. Um, chromosomal disorders that I mentioned that we are currently screening for from cell-free DNA only represent a very small percentage of the, all the genetic disorders that can exist in a baby. And so we're missing many serious and, um, devastating conditions on that cell-free DNA screening. So sometimes people think they've been screened for everything, and it's really only these three things basically. Um, so I think, um, the entire genome is rec- is represented in the cell-free DNA in the maternal blood, so potentially we could detect-

    16. PAPeter Attia1:40:09

        So what's the limit? Do we just not have enough of it? Like, why aren't we doing a whole genome sequence on it for the, you know, or at least screening for 27 different, you know, metabolic diseases that are quasi-common?

    17. KGDr. Kathryn Gray1:40:22

        Well, yeah, um, th- there's many reasons. Um, but, um, you-- when you're thinking about a prenatal screening test, you have to think about, you know, um, what the cost is, um, and, uh, what the implications are in the prenatal space and which things you should be calling out during pregnancy versus, like, what things are only important later in life. Um, to, to really, um, look at all the genes in the whole, um, genome and s-

    18. PAPeter Attia1:40:54

        Well, well, let's simplify it. Let's look at, like, say, the inborn errors of metabolism, which would present early in life.

    19. KGDr. Kathryn Gray1:40:59

        Yes.

    20. PAPeter Attia1:41:00

        That, there, there would probably v- be value in knowing that during the first trimester, right?

    21. KGDr. Kathryn Gray1:41:04

        Correct. Um, so for serious conditions like that, um, folks are working on creating, like, panels of disorders-

    22. PAPeter Attia1:41:12

        Modified panel, yeah

    23. KGDr. Kathryn Gray1:41:12

        ... that might be helpful to screen for. It's still complicated 'cause for any given condition, take, like, cystic fibrosis is a good example. There might be tons of different, um, genetic variants that a patient has that could cause disease. So our ability to understand which genetic changes cause disease in a given gene and which ones don't is essential because there's no other phenotype that we can see prenatally for many of these conditions, right? So for an inborn error of metabolism, the baby within the mom is generally, for most of those, or it's doing just fine. There's no signs. There's no ultrasound features.

    24. PAPeter Attia1:41:55

        Yep.

    25. KGDr. Kathryn Gray1:41:55

        There's nothing else t- that we're testing. So, um, uh, you know, we're, we're getting this genetic result, but if we don't really know with confidence that, like, which things actually cause disease, then it can be really, really tricky and stressful to counsel a patient about that in the prenatal space where they're trying to decide if they should continue the pregnancy or what the implications of that are. So I think there's a big gap between what we can do from a technology standpoint and, and our framework for how we, um, decide which things to screen for, and then the resources of the healthcare system that it will take to actually counsel people about these conditions, um, and their, and their screening results.

    26. PAPeter Attia1:42:42

        What is

15. 1:42:43 – 1:52:41

    Midwifery and the realities of childbirth

    1. PAPeter Attia1:42:43

       the most difficult thing you have to do in your role as a, as a physician? What, what is, what's the thing that just, uh, is so challenging either because of the, um, the resources that are, that are brought to bear or just, quite frankly, the emotional toll it takes on you or, you know, you can answer that in any way that makes sense.

    2. KGDr. Kathryn Gray1:43:05

       There are some really, there are some really hard things that we, um, you know, deal with, um, as physicians. Um, I think from, from a medical standpoint when we see things in pregnancy, um, you know, people who are, uh, who we have to inform of, of devastating diagnoses, whether it be, like, an underlying genetic condition, severe fetal anomalies, a stillborn baby. When you have to, like- Deliver that news and the implications that it has for, for a given family and trying to walk them through that, um, those are, those are really tough, uh, conversations. Um, I also see, like, um, it's just, um, the, the different resources that, that people have that bring them t- to us or that they go back to, I think I, I think are, are very impactful for me to think about too, like patients that we treat and then don't have somewhere to stay or, you know, have really complex other situations that, you know, they're dealing with. So I think, um, there just often feels like you can't do, do a lot about, about that, but you can see, you know, with your p- own patient how much, uh, how much impact it has on, on them and their own, own health and-

    3. PAPeter Attia1:44:20

       Have you ever had the privilege to go and visit another country where the resources are far less and, and participate in, in, in childbirth in a, in a place like that?

    4. KGDr. Kathryn Gray1:44:31

       Yeah, I haven't, I haven't participated in, in childbirth in another country myself. Um, I, um, I spent a lot of time in the, in our own country in, in the Appalachian Mountains as, um, as a, as a high schooler on a service project where we go for a week every summer and fix people's homes. Um, and it was really like being somewhere very different than how I, I thought of at the time, like how our, our country is. And I wasn't participating in childbirth at that time, but I, I've certainly, like, seen a lot of folks who live in very, um, you know, across many circumstances, so.

    5. PAPeter Attia1:45:14

       What percentage of women in the United States, uh, uh, use, um, a midwife for delivery as opposed to an obstetrician?

    6. KGDr. Kathryn Gray1:45:22

       You know, I don't know the exact statistics and it really, there are definite trends by state and r- rural versus urban and area o- of the country. So, um, there's big variations. Um, there is a lot of midwife care prevalent throughout the country. Uh, midwives do a great job providing obstetric care. They, they provide, um, great access in many places where patients don't have other, um, access, and they, their training is a bit different. So f- folks often, they can often reach patients who, um, are otherwise, like, skeptical of the medical system or really don't prefer to have a physician taking care of them. So I think they're a really important, yeah, component of obstetric care.

    7. PAPeter Attia1:46:09

       I assume a midwife doesn't have the other tools with, I'm s- I'm gonna say her because I'm just gonna assume most of them are women, but, um, to, say, pivot to a C-section if something goes wrong in a pregnancy or, or is there ever a scenario where a midwife is there with an anesthesiologist should something change?

    8. KGDr. Kathryn Gray1:46:26

       I mean, usually, um, most practices are set up so that if a, a surgical procedure is needed, then the-

    9. PAPeter Attia1:46:33

       There's a backup.

    10. KGDr. Kathryn Gray1:46:33

        Yeah.

    11. PAPeter Attia1:46:34

        I see. Okay, got it. So it's not like... Because how often does a woman come in for a delivery? So let's just assume it's a woman who's been under your care for the entire pregnancy. She's not high risk. Um, you are therefore expecting to do a vaginal delivery, and one of the many factors we've talked about today that just either there's some rapid deceleration, you'd realize the placenta's a little bit detached, the cord is wrapped three times, any of those things, what percentage of those are converting, to your surprise, to a C-section?

    12. KGDr. Kathryn Gray1:47:05

        Yeah, I mean, of, of anticipated vaginal deliveries, about 20% end up going to C-section.

    13. PAPeter Attia1:47:13

        Wow. So that would imply that even for a woman who's been under great care and wants to go and have a baby at home with a midwife, there's at least, 'cause I would say it might even be higher, but at least a 20% chance that they're gonna need to call in for a, a backup surgical plan.

    14. KGDr. Kathryn Gray1:47:30

        Yeah, and well, there's different reasons why people, if they're delivering in a birthing center or, like, even at home with an attended birth, um, might need to transfer to the hospital. Like, one is that i- it's thought that a surgical delivery is needed, but another might just be that the more pa- like, pain control is needed or that just augmentation with oxytocin is needed to help the labor progress. So we definitely see different d- different, different things.

    15. PAPeter Attia1:47:59

        So how does that work if a woman is having her baby in a place that's very remote? 'Cause you mentioned one of the benefits of midwives is they can access patients that don't have great access to a, a hospital. So how, how does that happen?

    16. KGDr. Kathryn Gray1:48:13

        I sort of meant that in the outpatient setting. I mean, we really do try to encourage people to deliver in a, a birthing center or a place with access to other-

    17. PAPeter Attia1:48:22

        I see. Got it

    18. KGDr. Kathryn Gray1:48:22

        ... like, types of, like, medication and, um, there, there are obviously patients who do choose to have home births, but they are, um, it's not, it's not our recommendation, um-

    19. PAPeter Attia1:48:33

        For this reason, presumably.

    20. KGDr. Kathryn Gray1:48:34

        Well, y- y- and you can't, you can't know when things are gonna go wrong.

    21. PAPeter Attia1:48:37

        Yeah.

    22. KGDr. Kathryn Gray1:48:37

        So you know, you, like, hemorrhage is a big problem and, uh, and often, like, things can change, like, in the, in a second, and then you're very far away from where you need to, to be to, to get care. So yeah, so different obstetrical emergencies can happen, and usually, mostly they don't, but you know, the, the, the risk to the baby is higher at home deliveries, so. And to the mom.

    23. PAPeter Attia1:49:04

        You, you alluded to something earlier when referring to contractions and saying that it, it's the most painful thing you've ever experienced. Um, that's actually kind of, uh, surprising to me. I naively assumed that the most painful part of the delivery was, was actually the stre- like, the vaginal expansion necessary to get the head out, but is it the actual contraction itself that is causing the majority of the pain during labor?

    24. KGDr. Kathryn Gray1:49:29

        Um, well, most of the labor is contractions. The delivery of the head is like A 30-second part of the whole thing. So [laughs] you have something goes on hours, like, uh, not to be too crude, but I had a nurse describe it once as like trying to make a husband understand, like, who didn't want his wife to have an epidural, and she's like, "It's like having your balls slammed in a drawer again and again and again. Think of it that way. That's how painful it is."

    25. PAPeter Attia1:49:53

        Sorry, the husband didn't want her to have an epidural?

    26. KGDr. Kathryn Gray1:49:55

        Right. And-

    27. PAPeter Attia1:49:55

        I see. So she was sort of saying, "I'll make you a deal. If you let me slam your balls in the door for four hours without an epidural-"

    28. KGDr. Kathryn Gray1:50:02

        Right [laughs] .

    29. PAPeter Attia1:50:02

        "... you can, you can do this to me."

    30. KGDr. Kathryn Gray1:50:03

        Yeah. Right. Yeah.
16. 1:52:41 – 2:01:48

    Maternal health in the United States and the need for research investment

    1. PAPeter Attia1:52:41

       when you, when you sort of reflect on this field, um, it's... There probably... I'd need to think about this 'cause I don't know if it's en- entirely true. I mean, medicine has made so much progress over the last 100 years. Um, but I would be hard-pressed to think of a field that has had a greater improvement in mortality in the last 100 years than your field, right? You, you've... I mean, it's had... I think it's had the single biggest impact on a population's longevity, has been fewer mothers and babies dying during this unbelievably hellish process, right?

    2. KGDr. Kathryn Gray1:53:21

       Yeah, I think that's, that's pretty fair to say. [laughs]

    3. PAPeter Attia1:53:24

       So despite that, the United States still doesn't quite stack up to other OECD nations in this arena. Uh, this has been a topic that's come up on other podcasts. I had this discussion with a, a gentleman, a physician, Som Sutaria, um, when we talked about some of the mortality statistics in the United States, and, um, this is a big drag down on our overall mortality, uh, our survival numbers, our life expectancy numbers. Um, there's all the obvious reasons for it. You've talked about many of them today. Do you, do you hold out much hope that th- there's a day, you know, in, in 10 years, in 20 years, the United States is leading the world in, uh, maternal fetal health?

    4. KGDr. Kathryn Gray1:54:14

       It doesn't feel that way right now, honestly. Um, I, I think, um, uh, there's some pretty low-hanging fruit that would help. Um, I think, um, uh, insurance access is a big deal. Um, uh, you know, for states that expanded Medicaid, um, where, um, you know, patients came into pregnancy with better health were, were more willing to come to prenatal care or able because they were, uh, able to get insurance through Medicaid who had extended Medicaid postpartum, um, for care, which is when a lot of mothers die. Um, uh-

    5. PAPeter Attia1:55:00

       You're saying Medicaid previously stopped once you left the hospital?

    6. KGDr. Kathryn Gray1:55:03

       Um, it's been like 60, 60 days, so there's-

    7. PAPeter Attia1:55:06

       Okay

    8. KGDr. Kathryn Gray1:55:06

       ... states that, you know, in, in, who r- in recent years have, um, you know, really expanded access, um, longer postpartum, which is really, really impactful for families. But, you know, I think, um, you know, overall, um, we, um, one of the reasons that our health is poor is because insurance access is, um, piecemeal, and it's not guaranteed, and healthcare is expensive even for those who have insurance. Um, so-

    9. PAPeter Attia1:55:39

       What's typically not covered? Like, if someone was going through The Affordable Care Act, buying their own insurance through, through the program. Um, what's the sort of surprise that they end up getting potentially, financial surprise, where they're saying, "Hey, I h- I, I bought my health insurance. I showed up. This is all taken care of," and then they, they get a bill that says, "Actually, we covered this, but not this"?

    10. KGDr. Kathryn Gray1:56:01

        Yeah, I mean, the system is so complicated that I think most physicians can't actually answer that question because it, um, it's so unpredictable, and there are, it changes every year with any health plan, as we all know. It's like, you know, to have this plan, you have this amount of deductible, or you have this other plan, and then these are the charges, right? It's so complex that it's really, really hard to understand.

    11. PAPeter Attia1:56:22

        So you can't even help a patient navigate the system and try to cater your care to their coverage.

    12. KGDr. Kathryn Gray1:56:29

        No, it's in- incredibly frustrating and difficult, and it, it feels, you feel very powerless because you would like to provide information. That's, like, part of our job. But, like, there's so many differences between so many different plans that, you know, um, it's, it's quite difficult.

    13. PAPeter Attia1:56:46

        Which is interesting because that would seem to me an issue that anyone, e- every- everyone on both sides of the aisle could agree that it's a bad thing to have moms and, and babies not cared for, and nobody should, nobody should really incur, uh, bankruptcy-inducing health, healthcare bills. Um, and everybody's very frustrated with the payers, for sure. Um, it, it, it, it really is the, uh, it is the Achilles' heel of the US healthcare system that does not appear in single-payer solutions. Now, again, the, the challenging thing is there are so many wonderful things about the US healthcare system that are the result of a two-payer system. But at the same time, there are so many things, and this is a classic example, I, I wasn't aware of the, for example, the Medicaid not necessarily extending post, so, um, well, I don't mean to end it on a downer, but that's, uh, this has been a super fascinating discussion, Katie. Um, again, I think this idea that, um, what happens during pregnancy gives you a window into your future health. I think if we, if, again, if the listener, both male and female, for the takes nothing but that which says use this opportunity to learn what your susceptibilities and risks are in the future. Um, any other really big messages you want to make sure people take away from this as far as improving their health?

    14. KGDr. Kathryn Gray1:58:14

        Well, I mean, I think, I think in the, um, pregnancy space, we still, um, really lack interventions and, and treatments because of lack of investment in, in research-

    15. PAPeter Attia1:58:27

        Mm

    16. KGDr. Kathryn Gray1:58:27

        ... in this area, and we, um, haven't spent a, a ton of time talking about that today. But I think that, um, you know, it's been a neglected area in research. It's been an underfunded area of research.

    17. PAPeter Attia1:58:37

        Even at the NIH level?

    18. KGDr. Kathryn Gray1:58:39

        Yes, even at the NIH level. Um, and you know, the, um, the branch of the NIH, the NICHD, the National Institutes of Child, um, Health and Development, um, nothing in that word has the word pregnancy in it. So they're, like, that has been the institute-

    19. PAPeter Attia1:58:56

        That's the closest pregnancy gets to the 17 different-

    20. KGDr. Kathryn Gray1:59:00

        Right, exactly

    21. PAPeter Attia1:59:00

        ... branches of the NIH.

    22. KGDr. Kathryn Gray1:59:01

        So, like, that branch has funded the most pregnancy related research of any branch of the NIH, and yet, like, it's, it's, it's a title that indicates it's about child health, not about the, the moms.

    23. PAPeter Attia1:59:12

        Why do you think that is? It seems obvious. I mean, sorry, what seems obvious is that it should address pregnancy. Do you, I mean, what's, what's your hypothesis? I, I know that the NIH has areas where it's just doubled down and spends endlessly, and then there are gaps, presumably. I mean, there are, I, I'll give you a gap in my world is the investment in geroscience is it's, it's literally basis points of NIH budget. So that's another area that is just completely ignored. Prevention is another area that gets very little funding. Um, so I guess we can add pregnancy to that list, unfortunately.

    24. KGDr. Kathryn Gray1:59:46

        Yeah, and I think, um, it's, um, the recognition of its importance in, um, the whole lifespan has really, has expanded some, um, you know, funding opportunities. And, um, so I think there is more recognition of it now, but really, um, there's need for continued investment in this area 'cause it still remains, like, understudied and under-resourced to really, um, help people the most, most we could if there were more resources.

    25. PAPeter Attia2:00:15

        So if there are philanthropists listening to this now who are saying, "Look, I want to, I'm very interested in fund- funding biomedical research, but I, I like to fund things that are not otherwise crowded," this is an area.

    26. KGDr. Kathryn Gray2:00:26

        Yeah.

    27. PAPeter Attia2:00:26

        How, what would their next steps be? How would they find the right scientists and investigators who are asking the questions that can be answered?

    28. KGDr. Kathryn Gray2:00:35

        Yeah, I think, um, there's, there's some groups that have, um, come around trying to a- advise or advocate for funding. So AAGAS is the American Gynecologic and Obstetric Society. They've put together this women's health collective to try to advocate for women's health funding, and they, lots of the key players in leading in this space across, um, OBGYN are involved in that society. So you can contact leaders of these organizations, and they can help direct people. Um, various folks have different... Sometimes people have areas of very specific interest in giving money to.

    29. PAPeter Attia2:01:14

        Yep.

    30. KGDr. Kathryn Gray2:01:14

        Sometimes, you know, there's, there's lots of ways to make investments that make a big difference for people. So I think-

Episode duration: 2:01:48