#410 ‒ The biology of pregnancy: physiologic adaptation, gestational diabetes, preeclampsia, childbirth, and long-term maternal health | Kathryn Gray, M.D., Ph.D.

Welcome and Episode Overview

0:00Hey, everyone. Welcome to the Drive podcast. I'm your host, Peter Atiyah. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen. It is extremely

0:31important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of a subscription. If you want to learn more about the benefits of our premium membership, head over to peteratiyahmd.com forward slash subscribe.

1:04My guest this week is Dr. Katie Gray, a physician scientist and maternal fetal medicine specialist at the University of Washington School of Medicine, where she serves as division chief of maternal fetal medicine and the director of research in MFM. Katie's clinical work and research focuses on high-risk pregnancy and pregnancy complications with particular expertise in preeclampsia and stillbirth. I wanted to have Katie on because pregnancy is one of the most remarkable physiologic challenges the human body undergoes, and yet I realize there's a lot about this that I certainly

1:39don't understand. So we start with the basic physiology of pregnancy and work our way through many of the complications that can arise from gestational diabetes and preeclampsia to stillbirth and actual complications of delivery. And through this conversation, we talk about many things like how pregnancy changes a woman's cardiovascular system, metabolic system, and hormone physiology. Talk about nutrition during pregnancy, fetal development, and the importance of nutrients such as folate. Talk about gestational diabetes, why it develops, how it's diagnosed and treated,

2:10and what it can mean for both mother and child later on. Talk about preeclampsia, including the role of the placenta, why it can become so dangerous, and how it's managed. Talk about HELP syndrome and other severe complications of pregnancy. We discuss stillbirth and its potential causes and why so many cases remain unexplained even after extensive testing. We discuss the trade-offs between C-sections, vaginal delivery, and how clinicians think about the risk and trade-offs of

2:40each, and how pregnancy complications can affect a woman's health well beyond pregnancy, including her future risk of metabolic, cardiovascular, and kidney disease. And it's this last issue in particular that has me curious as I've been reading more and more literature about what occurs in a woman's pregnancy can be a window into her health later in life. So without further delay, please enjoy my

Dr Katie Gray Background

3:05conversation with Dr. Katie Gray. 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. Yeah, me too. Give folks just a little bit of a background in your, maybe what you're doing today, but also kind of the trajectory that got you here. You're a physician scientist, an MD, PhD. What led you to this field? I guess that's a good question. But I think I've always been interested in science, and I was an undergrad, and I really liked all my classes and all the science classes, and I

3:44was thinking of just going to medical school. And then I had this one advisory meeting with our, that was required at the University of Wisconsin, where in this one meeting, this professor sat down and said, well, my daughter went to medical school, and she really enjoyed it, but I thought she would have been so much happier if she also did a PhD. Have you ever heard of that? And I was like, no, I've never heard of that. But because of that one conversation, I investigated that further, and I thought that that was fascinating and super interesting, and that was the

4:15beginning of me pursuing all the rest of the steps that happened after that. And so what, just briefly, what did you focus on during your PhD? Yeah, so I technically have a PhD in immunology, but what we really did was take this benzodiazepine that was found from a drug screen, and it had been shown by a previous student in the lab to help treat autoimmune lupus, disease in my soul lupus, but they didn't know how it was working. So my PhD was focused on understanding the molecular mechanism of this novel benzodiazepine

4:49and where it bound and how it actually induced apoptosis in cells. And so 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. Did that end up having human clinical benefit? Actually, the drug itself is not very soluble, so it was hard to make into a readily absorbed drug. However, a derivative of that has actually become a treatment that's in trials for inflammatory

5:24bowel disease because it can act just in the gut. Interesting. Yeah. And I assume you did your PhD in the sort of normal MSTP fashion where you did the two years of purely clinical, you went off to the lab, and then you came back for your rotation. So you've come out of your PhD, you've got a couple years left of medical school. What drew you to obstetrics and gynecology? Yeah, I had always been really interested in women's health. I did all the clinical rotations as a third-year medical student. I really liked everything. I liked medicine. I liked surgery. But I really liked pregnant patients

5:58and deliveries. And I thought 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 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? Or why do people have preeclampsia? The answer was, we don't know. And so I thought it was a great

Physiologic Stress Test of Pregnancy

6:27area of medicine to go into. Well, let's just jump into it then. Really, the first place I kind of wanted to start was understanding this sort of physiologic stress test that is pregnancy. Obviously, I have no personal experience, but certainly watched my wife go through it three times, actually more, unfortunately, but three successful pregnancies. And I shared with you some personal stuff that I probably won't disclose on the podcast about, I've seen the most extreme sides of it.

6:59I 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 in whatever way you want to address it, just maybe talk us through the unbelievable demands that are placed on the women

7:30in this species as they have to deal with this essential challenge of our reproduction. Yeah. I mean, I think that's, and I'm also amazed that it ever goes well, pregnancy that is. So just for how many ways that it can go wrong. But I think you take an adult and, you know, they become pregnant and immediately the increased demands on their body starts to support this developing fetus.

8:01And so there's great expansion of the blood volume, great alterations in the endocrine and metabolism. And those, you know, are extremely dramatic and persist throughout the whole pregnancy. So it's hard to pick just like, you know, one thing, but I think, you know, it's a cardiovascular stress test because the plasma volume expands so much. It is a metabolic stress test because there's increased insulin resistance, especially in the second part of pregnancy that

8:36causes some people to have gestational diabetes and it often can unmask like future predisposition to disease through this process. 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 mean, we could think of this through the lens of for a woman who is not planning to get pregnant is the first observation, typically the menses,

9:10the missed period, or is it morning sickness? Like in your experience, what is the first sign that a woman's pregnant? Yeah. I think for people who have regular periods, like the missed period is often the first, first sign before others. Before an actual symptom. Yeah. Okay. We don't need to explain why that happens. I think that's pretty self-evident, but let's now talk about how the physiology is changing in that first four to six weeks. So the implantation has taken place. Obviously the placenta is starting to grow. What's happening in her endocrine system, for example? Yeah. I mean,

9:45I think there's certainly different phases of, you know, at first the ovary is actually supporting in an endocrine way, the development of the pregnancy. And then as the placenta develops, the placenta itself starts to secrete the hormones that support the, the pregnancy. And when does that transition take place? Between like, you know, eight to 10, 10 weeks of pregnancy. So, so that's why when people have IVF and they're, they kind of shut down your own hormone system for that process, that

10:18supplementary hormones are given for the first several weeks of pregnancy, because that there isn't the natural hormones being produced by the ovary. Okay. So the ovary before that transition is primarily making estradiol as the dominant estrogen? And progesterone. And progesterone. Okay. And then what's happening with HCG during that period of time? Yeah. I mean, that starts to, you know, it goes from being zero to increasing dramatically. And what's the purpose of that? I mean, I know it's basically a luteinizing hormone, but is it basically the pituitary's way of telling the ovary to make more

10:55of these hormones? Is that why it's rising? That's a good question. I, um, I haven't thought about that in a while. So, yeah. Is the rise in HCG part of what's driving the morning sickness or the nausea? Or do we, do we know what's causing that? For a long time, people actually thought that, but actually for people who have extreme nausea and vomiting of pregnancy, so hyper amethyst gravidarum, we have very poor treatments for that. And interestingly, genetics is something that gave us a great insight

11:30about that, which is when they studied folks who had hyper amethyst, they found a signal that flagged the GDF15 gene is really important in driving 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. Is it correlated with anything else? For example, is it correlated with a person who easily gets sick being in a car or on a boat?

12:04That's, that's a good question. I don't think all the time that that is the case. 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, she's probably in store for this going forward? We often see people who have hyper amethyst in all their pregnancies if they have it with their first. So yes. Okay. So again, we don't know why it's happening. Is the biggest risk of that simply nutrition? Is it

12:34that the, it makes it more difficult to get enough nutrition during that period of the pregnancy? 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 the biggest risk is dehydration and lack of nutrition during that time. Yeah. 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

13:05intervention? And by the way, is, are your standard antiemetics safe during pregnancy? I can't remember, Zofran and things like that. Can they be used during pregnancy? Yeah, we, they can be used during pregnancy. 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 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. All comers, what's the prevalence of that intervention?

13:35I think it's pretty rare, like less than 1% of folks, but obviously for the folks that have it, it's very severe. Okay. Now I don't remember my embryology well enough to remember exactly what's happening in the fetus at every week. I, obviously we all had to know that in medical school, but the first trimester, the fetus isn't huge, right? Like it's, it's a, it's a pretty non-linear growth pattern is one of my recollections, but a lot of incredibly important things are happening, albeit at a small scale. So you talked about plasma expansion in the mother. How much of that is occurring in the

14:10first trimester? It starts immediately and kind of peaks at being told it, it increased by 50% by 28 weeks. And so it's pretty, it, it starts immediately and it's pretty linear up to the, and really accelerates in the second part of the second trimester and then kind of levels, levels off. So that's pretty remarkable. A 50% increase in plasma volume by 28 weeks. Yeah. Now does, is that accompanied by a 50% increase in oxygen carrying capacity? Is the,

14:44is the hemoglobin concentration expanding to compensate for that? Or is there a relative anemia that's forming? It's a relative anemia that's forming due to that expansion. Okay. Yeah. Again, I suppose because women are young when they have pregnancy, we don't have to worry about things like CHF, but a 50% plasma increase would, would kill some people. Correct. And that there are folks for, who have severe enough cardio or pulmonary disease that they are unable to tolerate that. And then the recommendation is really to, to not be pregnant.

15:16Wow. So there are women whose heart and lung function is poor enough that an abortion might be necessary to save the mother's life. There's, in other words, you couldn't just give them diuretics and treat them the way you would treat someone with CHF. Cause then that would be ineffective. That would be effectively causing the abortion as well. Right. Yeah. That's, and, and presumably, is that a failure of the medical system in the sense that that woman should have known that she was that high risk before? How, like that, that seems like a difficult position for someone to be in. Well, it's, it's complex, right? 50% of pregnancies aren't planned. Uh, oftentimes

15:53folks affected by the most severe medical disease often lack other resources, insurance, access to care. So there's a lot of, there's a lot of barriers. Sometimes disease remains undiagnosed until, um, someone covers it is pregnant. So, um, yeah. Okay. You talked about this switch from the ovaries providing the sex hormones to now the placenta. You said that takes place that I, did you say about eight weeks? Okay. Are they just continuing to go up? Estrogen, progesterone

16:26are continuing to rise. What is their function? How does it differ between a male versus female fetus? There aren't a lot of differences for the, in that in, for a male or, or female fetus. And so the estrogen and progesterone, what are they doing to support the pregnancy specifically? Yeah. I think, um, we're, we're in the domain of the reproductive endocrinologist here and not the maternal fetal medicine doctor, but, but, you know, they, progesterone has many important functions

16:57in pregnancy, especially, um, in maintaining the uterine quiescence, right? So it doesn't contract and continuing to support the development of the placenta. So. Yeah. And how often do women complain of symptoms from the estrogen rise? Because we know from later in life. So when you think about women who are undergoing hormone replacement therapy, they can become very symptomatic from the estrogen, but the estrogen that's given during peri and post menopause is

17:27much 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? Yeah. I mean, I think with the dramatic change in the beginning of pregnancy, lots of those symptoms are common, like breast tenderness and associated estrogen related symptoms. But they abate? Does the, you know, different, everyone experiences it different, but I do think that there is some adjust adjustment, but you know,

17:59that also, the hormones often also, you know, drive the other physiologic changes in the mother across pregnancy as well. At what point during the pregnancy does the mother's appetite usually start to increase? Well, I mean. I mean, I guess it's complicated because 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? Well, I think that's, that's more like in the second half of pregnancy when the actual amount

18:36that the fetus is growing is, is the greatest. There's also increased nutrient demands, which is why, you know, we have folks taking prenatal vitamins and also that didn't contain iron because that will also support like the developing blood expansion as well. So there are increased nutrient

Nutrition and Neural Tube Defects

18:53demands. So let's talk just specifically about them. I know that many folks probably know what the prenatal stack looks like, but just, and maybe we can just state it. What are the most important vitamins and minerals during, from the moment a woman is pregnant or even planning to get pregnant? 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 tell, 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

19:29recognize the pregnancy, it's already kind of too late to bring up folic acid levels if they have been deficient. So that's one of the most essential things early on. Now you said 50% of pregnancies are unplanned, which suggests that prenatal vitamins should be recommended to all women of childbearing age, correct? Well, or a healthy diet. So, I mean, I think if you have a well-balanced diet and a lot of the food is now supplemented with, you know, B vitamins and folic acid and things that you want

20:02to be replete in with pregnancy. So I think a lot of folks will have adequate levels if they're eating a well-balanced diet with fruits and vegetables and whole grains. So what is your patient population? You're in Seattle, but you're at a university hospital, so you serve a very broad population. I'm assuming. How often do you today see a neural tube defect? Well, we're a referral center. You're a tertiary center, so it's concentrating there. Right. Yeah. So, you know, we see case of neural tube defects every month,

20:34you know, that come to our center. But we have, you know, again, we have a wide catchment. Explain to folks what that is, actually. We're taking that for granted. Yeah. Well, it's a category of defects, like, in any part of the neural tube where it doesn't form correctly. The most common would be, like, myelomeningocele, where at the base of the spine, commonly, the spinal cord is actually exposed. So the overlying skin doesn't form properly and the part of the spinal cord is exposed.

21:06And so when that is diagnosed, is there anything that can be done in utero or is it now just a case of knowing what to expect at delivery? Yeah. This is one of the areas where there have been developments in doing in utero surgery. So there, I'm not a fetal interventionist, but there are qualifications that make people eligible or not eligible to have in utero repair. So for some folks that is done in the right cases, it can help improve

21:37long-term ambulatory, like, lower extremity function, bowel and bladder function of the child. So that is why it is done sometimes. And classically, without an intervention, if a child is born with a neural tube defect of the type you've described, how does that impact their life?

21:58Well, it is very variable. There can be mild effects or pretty severe effects. Again, I'm not a pediatrician either, but there can be a lot of effects on walking, lower extremity, strength and function, bowel and bladder function, and also problems with accumulation of fluid in the brain and need for shunting of that fluid lifelong. Now, this is taking another very, very extreme example, but it's one of the ones I really remember from medical school is this condition and encephaly. Is that something that is not seen typically today? Or is that

22:32are there still cases of that? No, we still have cases of that. We have had two this year in our practice that I'm aware of. Can you tell folks what it is? Well, it's also on the spectrum of neural tube defect, but it's the most severe where the brain and cranium does not form at all. And so those are, and I don't think today with the prenatal care that is available to women, children are born in that condition. Although, again, in medical school, we saw countless examples

23:02of this in textbooks and things like that. What determines in the context of a folate deficiency, why one woman might have anencephaly versus, which is obviously not survivable or, you know, whereas another woman might have a baby that has a small neural tube defect down at the other end of the spine, which could be completely survivable. Like, is that a random chance thing or does it speak to some other factor? The overall answer would be that we don't understand it. There are cases of these malformations that are associated with underlying genetic syndromes in the baby, but there are also cases that are sporadic

23:37where there's no underlying genetic defect identified, and we don't know why. Okay. What are some other very important milestones for the mother and fetus during the first trimester? Well, another really important thing that's happening entirely in the first trimester is formation of all the organs of the fetus. So by the time the first trimester is done, that's basically complete. So the heart has four chambers. The pancreas has considered its little ventral bud rotation.

24:08All of that stuff has happened. And approximate size of the fetus at the end of the first trimester? I mean. So for those who are listening to us, basically an inch and a half, two inches. How many grams? I couldn't tell you the number. A few almonds. Yeah. Yeah. So it's miniature, but it's perfectly formed. Yeah. Which is unbelievable. Yeah. Okay. At this point, on average, the mother has gained how much weight? Zero to 10 pounds.

24:39Yes. It's relatively small. Yeah. There's huge variability, as you might imagine.

Second Trimester and Gestational Diabetes

24:44Yeah.

Second Trimester and Gestational Diabetes

24:45Yeah. 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. Tell me what's happening now in terms of the physiology. The hormones, are they still going up or have they plateaued at this point? That's a good question. And I'm not... Yeah. Sorry. I keep... It's like your board exam here. I do feel like I'm in an oral board exam, just to be very honest. I'm sorry. I'm sorry. No, I promise you there's no grade at the end of this podcast.

25:16Okay. So tell me what else is happening in that second trimester as far as the... Especially in terms of what the mother's physiology is doing. Yeah. Well, there's a lot of fetal growth during this period. And really, the plasma volume has increased somewhat, but then there's really an acceleration of that in the second part of the second trimester. So it's not linear. But I would say that, you know, there's more maternal adaptation

25:47to pregnancy. The metabolism might switch from like being insulin sensitive to being more insulin resistance during that part of the pregnancy. Given the growth of the placenta, the pregnant person's going to be, you know, gaining some more weight than the first trimester usually during this time. And also, you know, they become visibly pregnant during this part of the pregnancy. So let's talk about that fuel partitioning piece, the insulin sensitivity, insulin resistance. There are certain conditions when insulin resistance might be desirable. So one of them is actually

26:21fasting. 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. Is the insulin resistance that you describe here in the second trimester equally adaptive? Or is it necessarily pathologic? And obviously, at some levels, it's pathologic if it develops into frank diabetes. But kind of walk me through that. Yeah, well, I think it can go either way. I mean, I think it's meant to be adaptive, right? Providing enough

26:55fuel for the fetus to grow. But for some folks, they produce more glucose than is needed. And their glucose levels stay too high. And then they're diagnosed with gestational diabetes. When did routine screening for that become the norm? As long as I have been practicing, because the reason it became the norm is that by risk factors, we missed half the people who developed gestational diabetes. And so the reason that routine screening started was because you couldn't predict very well who was going to develop gestational diabetes.

27:28And what were the consequences of that? And just how significant was it? Like a woman would show up with a glucose? Would this carry its way all the pregnancy? Or would she present prior to delivery in the way that a person with type 1 diabetes might present with glucose urea and all sorts of other things? Yeah. I mean, it's not like type 1 diabetes. It's more like a type 2 diabetic. But they would present with glucose in the urine. And they may be having other maternal symptoms like polyuria and polydipsia

27:58from high glucose if it was uncontrolled enough. I think the short term of pregnancy is not so much too concerning otherwise from a maternal level, from like a short term mild elevation. But really, for the fetus, that's very consequential to see that high level of glucose. And so if the fetus sees that, they can have excessive growth. So you get fetal macrosomia. There's higher risk of developing complications of pregnancy like preeclampsia, where you get high blood pressure and protein in your

28:31urine if you have gestational diabetes, especially if it's not well treated. And then there's all the consequences at delivery of having a baby that is bigger than it should be, which increased risk of c-section and shoulder dystocia. And then the baby would be at increased risk for having hypoglycemia as the baby ramps up its own insulin production to try to bring the levels of glucose down, then gets detached from the mother and the placenta and then is making too much insulin and then

29:01has low glucose come after. And then does the fact that the baby had to be effectively locally hyperinsulinemic to manage this during the pregnancy, does that have implications for their long-term health vis-a-vis insulin resistance and diabetes later in life? And if so, is it epigenetic? Do we know why? Yeah, I think, yes, they have a higher risk of metabolic issues long-term. And I think we don't fully understand all the reasons why that is the case.

29:32So for that reason, we've obviously made the wise decision of every woman is going to get screened for this. Remind me, when in the pregnancy does that screening take place? Between 24 and 28 weeks. And presumably that's chosen because if you did it any earlier, you would miss people that are going to present. Yeah. 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 screening and identifying people who are at risk

30:05or have developed gestational diabetes and having the most impact from treatment. Tell me, the diagnosis is made with an oral glucose tolerance test done at fasting and then two hours. What's the criteria? 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. I see it. If you don't pass that test, so your glucose is above 130 or 140, depending on which cutoff you're using.

30:41That's actually not that high, Katie. No. So because I'm 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 instead of 50. So I'm not sure it's apples to apples, but I can imagine a scenario where a woman comes in from a lunch where she was out at a, you know, 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. So you could potentially get into these false positives?

31:13Yeah. So yes, of course. So we do a follow-up three-hour glucose test where they do have to come in fasting and then drink a larger glucose load and then get tested at one, two, and three hours after that. And then what's the criteria on that? Is that 75 grams you do for that one? Yeah. And then there's a range for each one of those values of what is normal. So if your fasting is elevated from that test, you automatically are diagnosed as gestational. And is it elevated 110 in that fasting state or 100?

31:43The good news is you are going to get credit. You don't have to take your next board exam. This podcast is the exam. It's okay. We'll put this in the show notes. Don't worry. Anything you don't know the answer to, just say, we'll put it in the show notes. Yeah. We're going to put the values there for you. Okay. So there's a threshold at zero, one hour, two hour, three hour. But relatively speaking, do these compare to what we would use on a person who we're trying to diagnose type two diabetes in

32:18if we don't want to just rely on the A1C? Is it that high? Yeah. Well, if the one hour is over 200, you don't do the three hour. So I think that's similar to outside of pregnancy. And then there are ranges for each of the other ones. And you have to have two elevateds to actually be diagnosed if the fasting is normal. So what is standard of care in this situation? So a woman shows up, I was going to say passes the test, but fails the test, however we want to say it. What is first line? What is second line?

32:52When do we ever rely on insulin? And I'm assuming this is in a woman who is not a type two diabetic outside of pregnancy. So we can put that category to the side for a moment. But this is someone who was metabolically healthy prior to, and now is not. Are you going right to, are you trying to do this with nutrition first? Are you saying, no, we're going to go straight to metformin or some other agent? Yeah, no. First line is actually to do dietary modifications, meet with nutrition, monitor the glucose levels, fasting and postprandial. And with these modifications, see if the glucose is

33:26is well controlled. So like fasting under 95, one hour postprandial, like, you know, less than 140. And so then we monitor that at first, and then we go to medications when more than half the values are above where we'd like to see them. Insulin is really first line. So that's different than outside of pregnancy. With type two diabetics, there may be some differences in management, but in general, we often just go next to insulin. And what's interesting is if you're doing this test at 28

34:00weeks, you also have to be very quick. I mean, you're not going to give lifestyle that long. You're not going to say, well, let's do this lifestyle thing for three months because no, in three months you're having the baby. So how much time are you giving that first lifestyle intervention? Is that two weeks basically? Yeah. I mean, it depends on the patient, right? If everything is elevated in the first week, you're not going to keep going for another week. But yeah, you have close follow-up and lots of communication about what the values are. And is the reason you go to insulin as first line because of time, or is it because there's concern that drugs could have a negative effect

34:35on the fetus? Yeah. Well, there's not good data on a lot of the medications for both efficacy and safety. So metformin we think of as fairly safe in pregnancy and potentially helpful, but really insulin is most effective and we have good safety data and it has the best influence on improving the neonatal outcomes. How long after delivery does this metabolic pattern return to normal? In other

35:07words, if a woman is actually initiating insulin, how long does she have to continue this post-delivery? Does it fix like that? Yeah. If you diagnose them with potentially having undiagnosed type 2 diabetes, this might not be the case. But if you really think it's gestational diabetes, then once they deliver, it seems to, for most folks, be resolved. So we usually check a finger stick while they're still in the hospital. And then the recommendation is also at the six-week postpartum visit to do another two-hour glucose test to screen for type 2 diabetes because some people will have type 2 diabetes and

35:43then they should also be surveilled for type 2 diabetes more closely following a pregnancy because they're at higher risk. Is it an oversimplification to say that every woman to some extent has to become insulin resistant during pregnancy because that's the adaptive response to preferentially direct nutrients to the fetus? There are probably genetic factors that amplify this in some women. And then there are going to be environmental factors that would also amplify it. And that could be stress,

36:13sleep, nutrition, et cetera. Is that the risk of oversimplifying it? Is that sort of the playbook? No, I think that's a great framework for it. So if a woman is diagnosed with gestational diabetes, goes through treatment, et cetera, et cetera, would you counsel her prior to her next pregnancy and say, look, you don't have to go through this again? You might, because we don't know how much each of those things was a contributor. It might be that your genes overwhelmingly made this happen and you're destined for it. But let's see if we can avoid it by doing A, B, and C. Or is it basically the case that once it happens during a pregnancy,

36:46you almost assume it's going to happen with subsequent pregnancies? No, interestingly, it doesn't always recur in every pregnancy. And I don't think we fully understand it. Like almost everything in medicine, if you've had it before, you're more likely to have it again. But not everyone gets it again.

Preeclampsia Mechanics and Management

37:03Okay. Let's talk about preeclampsia. This is obviously a big one. You mentioned it already, but do you mind just defining it again? Yeah. So preeclampsia is a pregnancy-specific condition where folks develop new-onset high blood pressure or hypertension after 20 weeks gestation and often accompanied by proteinuria, proteinuria, so protein in the urine, and also accompanied by other severe, what we would call like severe features, but sometimes other symptoms like right upper quadrant pain, vision changes, headaches.

37:34And this is obviously screened for because most hypertension is asymptomatic. So that's something that has to be caught during your routine visits, correct? Yes. And actually the initial schedule for prenatal care was really set up to detect developing preeclampsia in pregnancy, which is why you see like accelerating, you know, closer visits at the end of pregnancy compared to early pregnancy is really screened for like blood pressure. And is this defined as blood pressure, like 135 over 80? Is that the threshold? Where do we

38:08consider that? So for systolic, it's 140. And for diastolic, it's 105 to 110 to qualify as having. Okay. 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? So we're always looking at the whole picture, but a lot of times people will have 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 robustly with like very severe blood pressures from the get-go

38:44and other symptoms. And then sometimes they 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. And does the diagnosis require both hypertension and proteinuria or is one of them, if significant enough, warrant the diagnosis? Yeah. So they've changed the definition over time. So it used to be that to have preeclampsia,

39:16you needed to have both 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 and other, you know, you can get the diagnosis without necessarily having overt proteinuria. All comers, what is the incidence of this? It's about 5% of pregnancies, 5 to 7% depending on your patient population in the U.S.

39:48And then how does that change if we stratify by age? So if we were to limit it to, okay, just women in the 20s versus women in their 40s. Does that change things? Well, the highest risk individuals are those folks who are having their first pregnancy and people who are very young or very old. So I picked the worst demographic to compare. Yeah, yeah, yeah. So, okay. So first of all, why is that? I think we don't know. There's lots of reasons why people, like, there's lots of reasons why folks

40:18think that the first pregnancy is at highest risk. There may be some degree of, one of the reasons people wonder is if there is less exposure of the mother to the paternal antigens and it's, and there's some- It's an autoimmune response? It's not autoimmune, I'm sorry, it's immune. But there's, yeah, there may, there is, can be an, there's a thinking that there can be an immune component to it, but it's not, it's not just that, but we don't fully understand. Okay. So that would explain the early pregnancy. And then presumably there's a sensitization with

40:50a subsequent pregnancy.

40:53Tolerance, yeah. Okay. I'm talking to an immunologist. I have to be careful with, I have to be accurate. I mean, I'm not really. No, no, I'm just teasing you. I'm just teasing you. I'm just teasing you. But that, so then what do you think explains the other end of that barbell, which is the women over 40, for example? Yeah, I think women over 40 have just increased cardiometabolic disease slash intolerance to more cardiovascular demand. So I think it's really maternal physiologic changes by the time that you're that age that really drive the increased incidence.

41:24Yeah, because the plasma volume alone could drive the hypertension, although I don't know that that would drive the proteinuria, right? That seems to be like, I mean, yeah, tell me more about why that's happening. Because we see that in kidney disease. I mean, that's what we're monitoring is for GFR. So how do we tie those two things together that don't necessarily seem obviously related? Well, that has to, in pregnancy, both the hypertension and proteinuria have to do with angiogenic imbalance. So classically, the classic model of preeclampsia, which may not be true for

41:58everyone, is that the early in pregnancy, the placenta, the placental trophoblasts, which should invade into the maternal spiral or arteries and allow them to become wider and lower pressure vessels to supply the placenta with adequate blood flow. If that is not adequate enough, then the placenta has some degree of hypoxia. And the placenta itself then releases this anti-angiogenic factor called S-split into the maternal circulation. And that molecule soaks up the VEGF, an important

42:35growth factor for maintaining vessel endothelial cell function. And that affects both the endothelial cells of the maternal vessels and the endothelial cells in the glomerulus of the kidney. And so that connects what's happening physiologically. Super interesting. I had never heard that before. So that makes sense. When was that level of understanding brought to the field? Is that something in the last 25 years or? Ooh, the timing. Like something you learned during your career? Or did you know that from, was that taught in medical

43:08school and I just missed that day?

43:11Well, Ananth Karamanji, who was a nephrologist at Beth Israel in Boston, was very interested in preeclampsia. And he actually went around collecting folks' placentas who had preeclampsia and did microarrays on them looking for upregulation of different genes that might be involved in this syndrome. And what he found was this incredible upregulation of S-split. And then, you know,

43:43they did a lot more experiments to show that what was happening with that protein and why it could be causally involved in the trajectory of preeclampsia. And so I always thought that story was fascinating and worked in very, you know, Ananth was one of my early mentors in Boston. And I really, like, he's just, was always so inspirational in thinking about the science in this area. Yeah. It's just a great example of why we just must have scientists working alongside physicians.

44:17Otherwise, we just don't learn. Like, we can't, we can't learn this stuff. And of course, Judah Folkman was also at Harvard working, of course, on anti-VEGF for cancer, which is kind of another way to tie that together. So what is the natural history of preeclampsia if left untreated? So in other words, before we knew what the heck was going on, how did this manifest itself? So pregnant people would develop severe hypertension that would progress to seizures and even death and other maternal complications like stroke and organ, organ failure.

44:51Wow. So in other words, this is a totally different type of hypertension because, you know, in my practice, for example, if somebody shows up with hypertension, it could be, they may have had it for 10 years already. And they clearly have some renal compromise as a result of it and some coronary artery disease as a result of it. But, you know, it wasn't, it wasn't going to kill them in nine months. So there's something about this degree of hypertension that is far more accelerated and far more extreme if it's producing this type of outcome. The treatment option is to reduce, is to give

45:23antihypertensive agents? For the hypertension, when women present with preeclampsia, we do give antihypertensive agents. That can help us expectantly manage a lot of patients, meaning that they can present with hypertension at 30 weeks and we can treat their hypertension and monitor them closely and they may get several more weeks in the, in the pregnancy. But ultimately it won't go away until the baby is delivered. There's nothing that we can do besides that to actually cure it. So what is the, I don't

45:59want to say the earliest because there's always going to be some edge case, but what would you consider to be a very early presentation of preeclampsia and therefore potentially risky case because it's, you have to wait longer till you get to the point where you can deliver the fetus to ultimately render the cure is, is would 25 weeks be considered very early for this to show up? Yeah. So the earliest we think of it as showing up is, is 20 weeks. It is very rare to see it at that point of pregnancy. So we

46:29consider early onset to be preeclampsia that shows up before 34 weeks because most of it will show up in the third trimester and actually most of it shows up near term. So. And sorry, just to do my math, third trimester starts around 27 weeks, right? Yeah. Like 28 weeks. Yeah. So it's like halfway into the third trimester would be the sort of standard case of preeclampsia where your tech, you could, if the woman got into trouble, you could induce and, and safely deliver a fetus at 33, 34 weeks, right?

46:59Yeah. I mean, we have, um, it's not the gestational age of the fetus per se that drives when we decide when to deliver somebody. It has to do about the severity of their disease. So we do make different decisions about delivery, balancing the maternal and the fetal risks based on where they are in gestation. But, um, like a term, we would always deliver somebody who was showing up with even mild hypertension. That would be a recommendation. And is term considered 36? 37 weeks and greater.

47:30Okay. Are you ever making this decision based on the severity of the proteinuria for fear of renal damage? Or is it always based on the hypertension? We don't make decisions based on the proteinuria. We often make decisions based on the severity of the hypertension, but there's off, there's also lab abnormalities that can go along with preeclampsia, like elevated liver function tests and low platelets. There's also fetal concerns that can develop. So the fetus is more likely to be growth restricted. It might have abnormal testing. So sometimes we get into a space where like the mom

48:06is doing okay, but the baby's testing is not reassuring and we need to deliver. So there's many reasons why we stop expectantly managing and move towards delivery. And so all those things have to be considered when we're making that decision. Is the mother ever at risk for residual or lasting kidney damage? Yeah, that's a good question. For patients who start out with normal kidney function, they generally have recovered their kidney function after the pregnancy is done. However, people who have

48:42experienced severe preeclampsia have a longer term risk of kidney disease as well as cardiovascular disease. So long, long term. I want to come back to this topic because it's become a very interesting recent discussion, which we should spend some time on. LFTs, platelets, boy, this sounds a lot like HELP syndrome. So I don't remember what HELP stands for. I just remember it's really, really bad. Can you remind us what it is? Yeah. So HELP syndrome is where the pregnant patient presents with,

49:12it stands for hemolysis, elevated liver enzymes, and low platelets. Some folks think it's on the spectrum of preeclampsia, like it's a very severe version of preeclampsia. Other folks think that it may have a completely different underlying biology, but have overlapping features with preeclampsia. Patients with HELP 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

49:43very severe lab abnormalities. So we see it present both ways. And it can become pretty scary if it occurs, you know, in the 20 weeks, 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 on growth. I mean, this gets very complicated very quickly. Yeah. HELP syndrome is one of those conditions where we often give betamethasone

50:14to help mature the baby's lungs and we wait 48 hours and then we deliver because we don't expectantly manage somebody who has HELP syndrome. How often do women get that diagnosis prior to when they need, like, in other words, is that something that can be, I guess by definition, you're saying HELP syndrome implies diagnosis to delivery is a very short window. Yeah. As long as that, as long as that's actually what's going on, but yes. Okay. What's your best guess for the etiology?

50:47Great question. We do not know what causes HELP syndrome. If we assume that preeclampsia is something distinct, or even if it's not, do you have a sense of 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? Yeah. Good question. Well, preeclampsia is heritable, meaning that there is definitely a genetic component. So, and it comes from both the fetus and placenta, which are considered to be

51:21the same, relatively the same genetically and the maternal genetics. So, they're both important. So, there's been a lot done in the past, 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 what factors across the genome might contribute. But in the past eight years, there's

51:55been a lot more information that's come out about that, which I think is 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 with therapeutics, then genetics can really help you understand that. Going back to management of preeclampsia, if you're going to use antihypertensives, what are the agents of choice? Yeah. What you'll see used most is nifedipine and libidolol because there's good data about

52:31safety in pregnancy. There are other hypertensives that we use sometimes, but those are two mainstays. So interesting because, I mean, we just don't use those outside of pregnancy at all because they're not that good. 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? Correct. We know for sure that they're not safe in pregnancy. Yeah. So, they have a negative impact on the fetus, presumably.

53:01Correct. That's right. Got it. Yeah. But they're good agents postpartum when we're working to control maternal blood pressures. So, we often will utilize them after delivery. So, when we were talking about gestational diabetes, you pointed out that the woman could be off insulin by the time she goes home. Oh, yeah. That's how quickly it resolves. But what you just said makes me think the same is not necessarily true of preeclampsia and the hypertension. Yeah, that's correct. So, some people will have their hypertension resolved like very quickly after

53:31delivery, but many women need antihypertensive medications for several weeks after delivery. It can take like 6, 12 weeks to kind of come back to more of a baseline. And there are other women who will have persistent hypertension after delivery that never quite resolves. And lots of women who will come back and develop hypertension within the next 5 to 10 years as well. Wow. Does the proteinuria respond or resolve quickly? And I assume that's checked until it does?

54:04You know, we don't check it, and that is because it resolves. And is that sort of just because once the placenta is out, you've sort of solved the problem that's driving that? Yeah. Yeah. Yeah. So, unless someone, when we screen their metabolic labs, has evidence of renal dysfunction in elevation of their creatinine, then we would be monitoring that. But most folks just have the proteinuria. And for folks without kidney disease, that resolves.

54:35By the way, if a woman has significant proteinuria, does she also have a bump in her creatinine or cystatin C during the pregnancy? Not in, we don't check cystatin C, but the creatinine tends not to bump. But when it does, if it does get elevated with preeclampsia, then that's also a severe feature of the disease. So, this 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, 9 months ago, 12 months ago, which was this idea

55:06idea that in cohort studies, preeclampsia, or more specifically, hypertension during pregnancy, even if it resolved, was predictive of later life atherosclerotic cardiovascular disease. How long has the field of medicine known this? And what do we think is the best explanation,

Cardiovascular Risks Later in Life

55:26other 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? Right. So, good questions there. Actually, this has been known for quite a while. I just think it hasn't really- I'm just late to the party, which is often the case, I can assure you. Hasn't translated well out of the obstetrics field into primary care and other fields of medicine, like it should have, really. Like it should be a question you would ask. We now ask this question, but you should ask this question during a history and physical of any patient, right? You should say, oh, I noticed you

55:57had three kids. Did you have preeclampsia during those pregnancies? Yeah. The obstetric history is relevant 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. If it wasn't recorded, the data wasn't there. In terms of why, when we've looked at these genetic studies on the maternal side, one of the strongest shared genetic architectures between preeclampsia and preeclampsia is essential hypertension, both systolic and diastolic hypertension is, if you have a higher genetic

56:30disposition 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 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 a component of

57:04the exposure to the hypertensive pregnancy that people think may add on top of the underlying genetics to the future risks. So 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 social factors, like otherwise, like other health conditions that contribute to those risks. So it is a multifactorial contributor to long-term disease. Remind me, you may have said this and I just missed it, do women who develop gestational diabetes

57:37diabetes also have a higher risk for type 2 diabetes? Is that predictive? Yes. So 50% of patients who have gestational diabetes will develop type 2 diabetes. 50%? Yeah. Interesting. Have there been any intervention studies that have been done, and this would be a difficult study to do, 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

58:10could delay and or just outright avoid type 2 diabetes? Yeah. I think that the recommendation is that they have frequent follow-up for 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 appropriate body weight and regular exercise all are very important there. So it's even more critical for folks who have a history of gestational diabetes to be

58:42counseled about that to decrease their risk. 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, 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

59:14enormous insight into what the rest of her life has in store for her vis-a-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 should live a normal life as a result of the privilege of

59:49modern medicine that we wouldn't have been able to do this, you know, 50 years ago. Yeah. I mean, I think the counseling is really important. And as a high risk obstetrician, 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. With our high risk obstetric practice, we will only see the patient back in general if they have another pregnancy. And so that transition to a primary care provider with that information transmitted is really essential. And I do think

1:00:22lots of patients who are young and taking care of kids and often don't follow up a lot themselves between pregnancies. And so stressing the importance of having a primary care provider and following 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? Because we can often see now like records and, you know, if somebody is tuned into that, they can get at what

1:00:53happened. But they have to know that it's important. 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. Yeah, for sure. Okay. Do you have a sense of, well, I mean, it sounds like it's a bit of a mixed bag in terms of what's recognized there. Okay. So the other thing I wanted to ask you about is C-section versus vaginal.

1:01:27What 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. So let's kind of walk through what is known and let's acknowledge what is not known. 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. These are all so good questions that I don't know all the answers to. But certainly even now there's many parts of the world where people don't have

1:02:02great access to, you know, surgical intervention during labor and delivery. And that can really drive a lot of 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 because not every baby is going to deliver vaginally. 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, not on the boards, prehistoric times, right? Or ancestral times, you know,

1:02:35go back a thousand years. Do we have a sense of what the frequency was of a stillbirth? And was the stillbirth 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? Yes. I think like, I think you often will eventually deliver the demised fetus, but you know. But you can't possibly, I mean, maybe you could, but it would seem to me that you would be leaving behind some placenta or there would be some dead tissue that would remain, wouldn't there?

C-Section Trends and Trade-Offs

1:03:10I mean, I wouldn't think of that happening, but like a retained pregnancy is certainly going to be risky for the patient. Yeah. Okay. So C-sections have obviously become important. What do we know about the, I don't know what the right word to think of it, is it prevalence or usage or, you know, 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? Yeah. It's dramatically increased, you know, so we've, we've gone from, you know, like 10%

1:03:47C-section rate, say like, I don't, I don't have all the exact numbers in my head to like oftentimes practices have like 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, but it has increased, increased dramatically. And what is driving that 3x increase? I think there are different drivers. The pregnancies are, are higher risk than they used to.

1:04:21Once you have one C-section, you're more likely to have another one that the health of the, the, the patient matters. A lot of people think that maternal obesity increasing has increased the number of women who have like either larger fetuses or feel like labor that doesn't progress normally and therefore leads to a C-section. 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 babies being

1:04:54monitored during the active phase of labor continuously. And when the tracing is not reassuring, we moved to a C-section. So I think it's, it's a complex issue to understand. And, you know, there is a lot of focus on trying to decrease that number or avoid it getting higher than it is now. Why is that? Why would we be concerned if it's getting too high? Yeah. So I think the one consequence, and it's not the only one, but for folks who have prior C-sections,

1:05:25multiple prior C-sections, they're at higher risk for abnormal placentation in the next pregnancy, meaning that 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 out after the baby. 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

1:05:56from, that would be required during the exertion of a vaginal delivery? There's a couple of different things. So there's a couple of different kinds of C-sections. So meaning where you cut on the uterus. So if you cut, if you cut low down on the uterus in a transverse fashion, 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 you are fairly safe to labor in a future pregnancy. It would like a 1% risk or less than 1% that the, that old scar might come apart during labor. So

1:06:33that's called a uterine rupture, which is obviously an emergency. And, um, that's an, that's a surgical emergency. Now you're going, yeah. However, if you have had prior surgery on your uterus either because you had a big fibroid and 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 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

1:07:06a classical C-section. Which is too high to even. Which is too high. So we've saved folks in that group should not labor. I'm sorry. Remind me why the choice is made between those two incisions in the first place. 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 big enough that expanded enough that they, the lower uterine segment is not developed and you may not be able

1:07:37to make an incision down in the lower part of the urine segment and, and 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's other reasons like surgical complexity. Someone's had multiple C-sections. You can't. Scar tissue. Yeah. I can't get around the scar tissue. Other reasons why we can't, but. Yeah. And you're not entering the peritoneum when you do this, correct? You're doing this all outside of the abdomen? No, it's in, in the abdomen. You, you are, you don't, you don't separate the fascia and keep the uterus outside. Okay.

1:08:10When you, okay. So I'm trying to think of reasons where it was a non-negotiable. So a breach delivery would, you wouldn't ever try to deliver a breach vaginally if you, I mean, I assume you know this. We generally don't 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 generally recommend a C-section. If the

1:08:41baby is breached, 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. And how, like you would do that in the days leading up to. Yeah. We try to do it closer to 37 weeks because if somebody actually goes into labor or breaks their water, then, then you really can't like turn the baby anymore. How successful is that procedure? 50%. Painful, I'm guessing. Yeah, it can be. You can get anesthesia for it.

1:09:13I'm going to guess the answer is we have no idea why some babies are breached. Yeah. In general, we don't. There are cases where, there are cases where like the head might be very big and it makes sense that the baby was in that position the whole time. Sometimes we do a delivery and we find out the cord was wrapped around the neck like four times and then it made sense that the baby couldn't really turn around. So sometimes we see things that, you know, make us kind of think that's why it was. But a lot of the time we don't know. How often does the cord wrap around the neck at all?

1:09:45Well, like a third of the time the baby comes out with a cord around the neck. It's very common. It usually doesn't cause a problem. When does it cause a problem? Well, you can't predict when it's going to cause a problem. It can be very tight. Sometimes in certain stillbirths, we think it might have been the cause, but we don't really know. More common of something we would see is that, you know, we're monitoring this fetal tracing during labor. We have patients sometimes who have like recurrent big like variables, like a type of deceleration on the fetal heart rate. And then they come out and we discover that

1:10:19there was a cord around the neck. So sometimes it just causes like stressful, non-reassuring fetal heart tracings, but doesn't really ultimately cause any problems.

Stillbirths and Labor Triggers

1:10:28What's the frequency of stillbirth in the U.S.? One in 160. That much? Yeah. I thought you were going to say one in 106,000. One in 160 is startling. It's pretty common. And just to make sure, the definition of a stillbirth implies it went to near term? No. Stillbirth means any fetal demise after 20 weeks gestation. So it can be any time after 20 weeks. Okay. But after 20 weeks, you've largely, I assume, eliminated a lot of the really

1:11:03lethal trisomies, the trisomy 18 and things like that. Those probably, we've already taken care of those. So these are usually chromosomally normal fetuses? I mean, it depends. I mean, there's many, there's patients who don't do testing. There's patients who choose to continue their pregnancies. But you're right that like a lot of people who have choice and access to those choices do terminate their pregnancies earlier. But there are many patients carrying pregnancies with various anomalies and other genetic conditions.

1:11:35Hoping that things will work out, but maybe they don't. So what would you say are the most common drivers of a still pregnancy? Yeah. I mean, I think there's different categories, but many of them remain unexplained. At the time of delivery, the things that helped give us the most information about what might have happened was doing pathology of the placenta, doing a fetal autopsy, and doing genetics. So those are the three most useful tests. Also like describing like the baby and the placenta at delivery, like

1:12:07just what you see in terms of, you know, you might see a big abruption, like the placenta came off the uterus. There might be like a really tight cord there. So there might be things that you actually see in the delivery room that, you know, help you. But even with the standard workup, we don't understand the cause in a big percentage of cases. Meaning even when you know the genetics, you've pathologically examined the placenta and there's been an autopsy done on the fetus.

1:12:38You're saying about half the time you still wouldn't be able to identify a cause of death. Yeah. And a lot of them, there might be contributors, right? So a big, there's a substantial fraction that we may find out are growth restricted and there may a lot have some component of placental insufficiency, but it doesn't really explain, like that might've been the proximal cause of then what, why the baby passed away, but it doesn't really explain like what causes that and why that

1:13:09happened at the end of pregnancy, you know, and everything had looked okay up until that point. Because I'm just trying to understand one of these late stage events. So let's just say a woman's had normal prenatal care. She's not high risk, but she's still doing all the normal stuff. Every time she goes in for an ultrasound, you obviously see the heartbeat. Presumably you can tell that the placenta is still attached to the uterus. Is it standard to also do duplex on placental blood vessels or is that not, we wouldn't do that level of inquiry? We're only doing like

1:13:39Doppler monitoring on ultrasound when the baby is growth restricted. So when we know that there's fetal growth restriction, or if there's a few other indications, then, then we monitor blood flow through the umbilical cord. But we don't do that in general because it's not been shown to be a helpful like test otherwise. Yeah. So it's just mind boggling to me that they're, they're from a tragic standpoint that a couple could come in to think everything is fine. Would their labor pains

1:14:10and labor signs and symptoms under stillbirth conditions resemble that of non-stillbirth? Yeah. So let's talk a little bit about that. What triggers labor? Why, why, what is happening in the body? How does the body know it's time? We don't know. Really? Yeah. We, so 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? A little bit, but you know, yeah, you know, people have tried to look at the changes

1:14:44that directly precede labor and there's some, but it's hard to predict, right? Like you monitor somebody like every day to see what's going to happen up to delivery. So we, we really don't have a great sense. 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. Is the contraction of the uterus the first

1:15:15sign? Is that the first thing a woman is actually feeling? Yeah. And tell me how you coach a woman through that. Like if, 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. Her partner is equally clueless and they're scared senseless. What are you saying? Well, with every third trimester patient, we're saying like, you know, monitor, like how you're feeling the baby move. Let us know if it's different. Look out for

1:15:47leaking fluid and vaginal bleeding. If you have any of those things come in. And then if you start to have contractions, like time, how frequently they're coming. And if they're coming closer than five minutes apart for 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. Okay. So that's, that's a pretty logical list. Having experienced contractions yourself, what, what does this, what does this thing feel like? What does a contraction feel like? Does it

1:16:19feel like a muscle flexing? Well, 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, I've experienced before. So it's not subtle. A woman is not, there's no, she's not thinking to myself, is this a contraction? Well, that often comes up and there are patients who have very high pain

1:16:52tolerances 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. How, so I explained 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? Well, I think that's a complicated question to answer, but so the, what, what I mean by dilation

1:17:25is that, 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, but say you're at term, it would be very common for people to have a cervix that gets thinner and softer and may start to dilate

1:17:57some. That's the body getting ready for labor. And then 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 when somebody is in the hospital ready to, getting ready to deliver. And how many centimeters of dilation is when you start to say, okay, you're not, we're, we're sitting here until this baby comes out? Well, it's, it's, it's not just the dilation by itself.

1:18:28Right. It's also the frequency of the contraction. 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. Is that 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? Well, it's not, it's not the same in everyone, right? It's not like there's this, then there's this, then there's this. Like in some people, the water breaks first and other

1:18:58people, 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. And the quote unquote water breaking is the placental fluid coming out because that, that membrane at the cervix opens the, like what's actually happening when the water breaks? Well, the, the amniotic sac gets a hole. So it can be at any part of it. It's often at the part that's in the lower uterine segment or, or near where the cervix is opening, but it's that the,

1:19:30the fluid in the amniotic sac gets released. And it's clear fluid, clear yellowish or? Usually it can contain baby's poop, like meconium staining at term. So, um, or it can be bloody if there's a placental abruption, but it's like, ideally it's clear. Okay. If it's not, if it has blood in it and the placenta has just started to separate, that's not a problem necessarily. It just means you got to get on with things. You know, it, it may be, or it might not be like if it stays, if, if the majority of it stays attached

1:20:04long enough for the labor to progress, which it often does quickly, if that's what's happening, then you potentially can have a vaginal delivery. But if it continues to progress, you know, you're monitoring the baby's heart rate tracing closely and the bleeding closely. So if things become non-reassuring, you may have to move to a C-section. What is the, the clock? There's a clock that sort of starts once the water breaks because there's a risk of infection, correct? Yeah. I mean, you, you're mindful of, of, of how long it's been.

1:20:35What, what do you start to say is too long? Well, there's a few steps. Like one, when somebody's water breaks, we do recommend that they come in, even if they're not contracting because of that risk of the longer the water's broken. We're talking like in a term patient also here, if the water's broken and we don't help induce the labor, then there's the risk of infection. So we recommend coming in, getting started on some Pitocin and helping the labor progress. We want to see like labor and progression and ideally delivery within like 24 hours, but there's no absolute clock. Like if everything's

1:21:09fine, there's not an infection. The mom's fine. The baby's fine. Labor's progressing. It's not like we just stop it. So what do you do if the, or how often does the water break before a woman is, I don't know, like when she's in 28 weeks or something like that? That's called P-Prom, like premature, preterm rupture of the membranes. So people who have P-Prom, they will come into the hospital. About half of patients who have that will deliver in the next seven days, they will go into spontaneous labor, a lot, like a fraction

1:21:42of them. Some people will not. They will sit there with their membranes ruptured and we will monitor them in the hospital all the way up until 34 weeks if everything looks reassuring. And you are, your highest concern is an infection, I assume? That's one of the concerns. Infection is a high concern. Progressing rapidly into labor, once the bag of water is broken, can be very common. If the patient is not cephalic, so not head down, there's a risk of like cord prolapse or another body part, like the cervix dilating and

1:22:15then some part of the pregnancy or cord starting to come through the cervix, which can be an emergency. And I guess I'm still confused. If a woman comes in in this situation, does she still retain or just make more amniotic fluid, but she's just now making it at a high rate and it's leaking? Right. They will often continue to have quite low fluid for the rest of the pregnancy, but they will continue to make the fluid and leak the fluid. Got it. Do you ever give antibiotics in that situation or is that a no-no?

1:22:47We do. So it's not continuous. So the recommendation is to give antibiotics at the time they present, and that's because it helps prolong latency. It doesn't ultimately necessarily prevent all infections, but it helps prolong the duration of the pregnancy in that situation. So we do give some antibiotics at the start and then like no more after that. Going back to the C-section versus vaginal discussion, again, my vague recollection is

1:23:22one of the advantages of a vaginal delivery is related to the bacterial transfer between mother and fetus. Is that real or is that something that gets over extrapolated? There's a lot of attention to that for how much we really know about it, I would say. There's probably something there, like the microbiome is important. Like there's certainly influences and importance across different areas of medicine, but I think like there's a lot of popular press about that without probably a lot more of the basic medical

1:23:56things there. 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 you have failed to deliver the appropriate gut biome to your child. And so is it safe to say that the science is not suggesting that? Well, I'm not saying that there's no helpful component of that, 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. Is there some epidemiologic data that suggests, which of course would be confounded by a hundred

1:24:29other things, but is there some on-off kids that are born via cesarean section are more or less likely to have some gut-related? No. Not to my knowledge. Okay. Yeah. Standard application of social media there. 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. So notwithstanding the obvious example of why breastfeeding mattered evolutionarily when

1:25:00we didn't have formula and things like that, what percentage of women are unable to, for some physiologic reason, breastfeed? I mean, pick a duration to answer that question, like after X number of weeks. I mean, it's such a complicated question, right? Because most people, unless they have had like substantial breast surgery or other endocrine disruptors themselves, have the physiologic capacity to produce breast milk. There's a lot of, breastfeeding is complex, right? It's like both

1:25:32a maternal and a neonatal like 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 doing it over time. And, you know, then, you know, a breastfeeding mom will have to, you know, be responsible for

1:26:05expressing breast milk every few hours for many, many weeks and being present with the baby, which may or may not be possible for, for any given mother. So what's driving that from the endocrine system? You mean, um, the production of milk? Yeah. I mean, it's, it's, again, it's a complex hormonal interplay. So. And in theory, a lactating woman is going to have a harder time ovulating. I mean, that was generally viewed as one method of birth control. Correct. But you only have to miss

1:26:37one feeding to make it not be a good form of birth control. Really? So yes. That's an important message. It is. Don't rely on this for birth control. Definitely not. So it's true that like a lactating woman will have very suppressed levels of estrogen and progesterone and is often doesn't lactate when they're, but if they skip any of the feeds, then they stop that suppression of the,

Exercise, Sleep, and Postpartum Depression

1:27:02of their cycle. I want to talk about a couple of things you would counsel patients on during pregnancy with respect to three things. So sleeping position, any nutritional things outside of managing, you know, are there any real big do's and don'ts of what you make, want to 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. 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. You know, we tell people

1:27:36not 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 low weight, weightlifting was, is fine. 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. Including resistance training. If it's like, if they're used to strenuous

1:28:07resistance training, you would be okay with that until what point in the pregnancy? Well, I think 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 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. You know, we, you know, horseback riding or, or, you know, things where you might incur trauma to your abdomen are, are not good. But, but a Valsalva, a bearing down during a, you know, lifting something heavy is okay if a woman's used to

1:28:42that. 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 may tell them to abstain from like heavy lifting and things in, um, during the rest. And a short cervix presumably means you have less resistance to the intra-abdominal pressure. Yeah. Presumably. I'm not sure our data's great, but there, there's just like, there are certain things where we tell people to have some restrictions. What about running? So if you had a woman who's a runner, lifelong runner, loves to run,

1:29:13that's one of her favorite forms of exercise, what restrictions do you place on her during pregnancy? I wouldn't say that we would. So run to your heart's content and just be mindful of everything you said. At some point, your center of gravity is going to move. Don't overdo it. Try not to fall. Stay well hydrated, right? Like maybe take it a little easier than you sometimes would, but yeah, no, we would. Okay. People who can, it might be uncomfortable for people at the end. They might desire to stop. Yeah. Yeah. And then what about, um, sleeping position? At some point

1:29:45it starts to become pretty uncomfortable. I would imagine side sleeping is probably ideal. Any truth to this idea that you want to sleep on your left side so you don't compress the vena cava on the right side? Yeah. I mean, at the end of pregnancy when the fetus is pretty big, I think it, to lay completely flat on your back is probably not the best position to, so to have some tilt if you're laying, um, towards your back would be good because there is, that part has some truth to it. But I think people sometimes come in panicked that they woke up on their back and, you know, I'm like,

1:30:17it's, it's going to be okay. Okay. Yeah. I know that you're not the one as the obstetrician who's taking care of the mom months and months following her pregnancy, but what's your understanding of postpartum depression? How often is it showing up even in the hospital? What's our, what's our understanding of what's driving that? Yeah. So, so postpartum blues are really common, like having dramatic changes in the mood in the first two weeks after delivery. There's just the most tremendous collapse of the estrogen and progesterone levels, which are sky high during,

1:30:51at the end of pregnancy and then drop to like extremely low levels. And also a lot of, you know, changes that are going on in the HPA axis. And so those things really do cause emotional changes in, in most patients, but postpartum depression is when those like baby blues, like persist beyond that short term and, you know, lead to depressive symptoms for weeks afterwards. We do have standard screening that's recommended during, you know, both during pregnancy for depression

1:31:23and postpartum. And so we really do work hard to do that at the postpartum visit. And we identify patients who might be at higher risk of postpartum depression due to social stressors and other things and try to hook them up with resources and social work. But I think as we all know, across all of healthcare, like the mental health system is stretched thin. People often don't have providers or the access that they need. Obviously mothers who are caring for newborns, like don't, don't have a lot of time.

1:31:54They may have difficulty getting to appointments. They may have hesitancy to ask for help. They may be told that their feelings are normal. So it's definitely can be very serious and under-recognized and under-treated for all those reasons. And do you think that the biggest source of under-treatment is the failure to differentiate between what is maybe normal in this short-term response to what becomes maladaptive and or persists in an abnormal way? And then it just sort of gets turned into like there's so much going on

1:32:28that this kind of gets, you know, shoved under the rug? Yeah. I mean, I think it might be a lot of mother's instincts just to focus on the baby and not like necessarily take care, great care of themselves. So we need a lot of advocacy and encouragement for, you know, mothers to like present to care, get help, like not feel shame and guilt that, you know, that I think a lot of that goes in, like I have a new baby, like society tells me I should be really happy and excited and I feel terrible. Like, so then people don't present

1:32:58to care because of feelings that, you know, they're, it's somehow their fault that they're feeling this

Prenatal Genetic Screening

1:33:04way. Let's go back to the other end of the pregnancy, which is on the sort of genetic screening side of things. So IVF is becoming much more common these days and with IVF comes prenatal screening. But for, for couples not undergoing IVF 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 do you think about that? Yeah. So the, the number of diagnostic or invasive procedures

1:33:38that we're doing that include amniocentesis and then chorionic villus sampling, which we can do even earlier in pregnancy, have decreased. And one of the primary drivers of that is how screening for chromosomal disorders like Down syndrome has improved with the advent of cell-free DNA screening. So just a tube of the maternal blood, we can find fragments of the placental DNA and therefore screen the pregnancy for chromosomal conditions. That test is best at screening for trisomies 21, 18, 13, and the

1:34:15fetal sex. It's less good for, for other, other things. And you can do that within how many weeks of pregnancy? As early as nine or 10 weeks of pregnancy. So very early on. Is that considered routine? Yeah. So it is recommended to be offered to all pregnant patients for screening now. Okay. So presumably that takes away a lot of the incentive that was present for amniocentesis, correct? Right. So previously we had what was called a serum screen that looked at three or four protein

1:34:47markers in the maternal blood. And if that screen was positive, meaning that the levels of those proteins for the gestational age were 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 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.

1:35:23Now, is that because the prevalence was too low or because the sensitivity and specificity were too low? It's because the sensitivity and specificity were too low. Got it. 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 not 100% guaranteed to have a fetus with that condition, but they're much more likely to have one.

1:35:55What do you think is the biggest gap in this type of testing? Like where would you like to see things in a decade with respect to prenatal screening or in utero screening for that matter? Yeah. Well, there's different kinds of screening. There's ultrasound, which has developed a lot so we can actually look structurally at the baby. And then there's genetics. Chromosomal disorders that I mentioned that we are currently screening for from cell-free DNA only represent a very small percentage of all the genetic disorders that can exist in a baby. And so we're missing many

1:36:28serious and 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. So I think the entire genome is represented in the cell-free DNA in the maternal blood. So potentially we could detect... So what's the limit? Do we just not have enough of it? 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?

1:36:59Yeah. Well, there's many reasons. But when you're thinking about a prenatal screening test, you have to think about what the cost is and 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. To really look at all the genes in the whole genome and... Well, let's simplify it. Let's look at like, say, the inborn errors of metabolism, which would present early in life. There would probably be

1:37:29value in knowing that during the first trimester, right? Correct. So for serious conditions like that, folks are working on creating like panels of disorders that might be helpful to screen for. It's still complicated because for any given condition, take like cystic fibrosis is a good example. There might be tons of different 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

1:38:05is 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, it's doing just fine. There's no signs. There's no ultrasound features. There's nothing else that we're testing. So 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

1:38:35and 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 our framework for how we 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 and their screening results.

1:39:06So what is the most difficult thing you have to do in your role as a physician? What's the thing that just is so challenging, either because of the resources 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. Yeah. There's some really hard things that we, you know, deal with as physicians. I think from a medical standpoint, when we see things in pregnancy, you know, people who we have to inform of devastating

1:39:42diagnoses, 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 a given family and trying to walk them through that, those are really tough conversations. I also see, like, it's just the different resources that people have that bring them to us or that they go back to, I think are very

1:40:14impactful for me to think about to, 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 there's often feels like you can't do a lot about that, but you can see, you know, with your own patient how much impact it has on them and their own health. Have you ever had the privilege to go and visit another country where the resources are far less and participate in childbirth in a place like that?

1:40:47Yeah, I haven't participated in childbirth in another country myself. I spent a lot of time in our own country and in the Appalachian Mountains as a high schooler on a service project where we go for a week every summer and fix people's homes. And it was really, like, being somewhere very different than how I thought of at the time, like, how our country is. And I wasn't participating in childbirth at that time, but I've certainly, like, seen a lot of folks who live in very,

1:41:21you know, across many circumstances. What percentage of women in the United States use a midwife for delivery as opposed to an obstetrician? You know, I don't know the exact statistics and it really, there are definite trends by state and rural versus urban and area of the country. So there's big variations. There is a lot of midwife care prevalent throughout the country. Midwives do a great job providing obstetric care. They provide

1:41:54great access in many places where patients don't have other access and they, their training is a bit different. So folks often, they can often reach patients who 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, you know, component of obstetric care. I assume a midwife doesn't have the other tools with, I'm going to say her because I'm just going to assume

1:42:24most of them are women, but to say pivot to a C-section if something goes wrong in the pregnancy or is there ever a scenario where a midwife is there with an anesthesiologist should something change? I mean, usually most practices are set up so that if a surgical procedure is needed, then the- There's a backup. Yeah. 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. You are therefore expecting to do a vaginal delivery. And one of the many factors we've talked

1:42:57about today that just either there's some rapid deceleration, you'd realize the placenta is a little bit detached, the cord is wrapped through, any of those things, what percentage of those are converting to your surprise to a C-section? Yeah. I mean, of anticipated vaginal deliveries, about 20% end up going to C-section. 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, because I would

1:43:29say it might even be higher, but at least a 20% chance that they're going to need to call in for a backup surgical plan. 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, might need to transfer to the hospital. Like one is that it's thought that a surgical delivery is needed, but another might just be that the more like pain control is needed or that just augmentation with oxytocin is needed to help the labor progress. So we definitely see different things. So how does that work if a

1:44:05woman is having her baby in a place that's very remote? Because you mentioned one of the benefits of midwives is they can access patients that don't have great access to a hospital. So how does that work? Well, I mean, I sort of meant that in the outpatient setting. I mean, we really do try to encourage people to deliver in a birthing center or a place with access to other like types of like medication. And they're obviously patients who do choose to have home births, but they are, it's not our recommendation. For this reason, presumably. Well, and you can't, you can't know

1:44:39when things are going to go wrong. 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 risk to the baby is higher at home deliveries and to the mom. You, you alluded to something earlier when referring to contractions and saying that it's the most

1:45:11painful thing you've ever experienced. That's actually kind of surprising to me. I naively assumed that the most painful part of the delivery was actually the stretch, 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? Well, most of the labor is contractions. The delivery of the head is like a 32nd part of the whole thing. So you have something goes on hours, like 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

1:45:46his 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. Sorry, the husband didn't want her to have an epidural. Right. 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, you can, you can do this to me. Right. Yeah. Yeah. Got it. But I mean, it's, I only say that to say like really people don't understand how. And all kidding aside, that's describing a very deep visceral pain. Right. That's how it is. That's, that's what I, cause yeah, every guy listening to this has been kicked

1:46:19in that region. So they know what that feels like. Yeah. Yeah. No, it is. And it goes on for so long, right? So yes, the delivery of the head is like very, very painful. I mean, I had, I had an epidural with all three of my labors and on the third one, they were trying out this new thing where the medicine was more dilute and it was supposed to spread around better to give you better coverage. But apparently there was no coverage like right at the perineum. So I was fine, fine, fine. And then the head was about to come out and it was my third delivery and,

1:46:52and I could feel everything. And it was like the first time you'd experienced that because like in the sense that that was, yeah. So let me ask another question about a term that I've heard, I don't know what it means, which is called back labor. Yeah. What, and is that because, well, anyway, explain what it is. Well, it's just that it, that we have many patients who in the first part of labor, especially, or, or even throughout labor may feel more, a lot of pain in their back in addition, or, or instead of feeling a lot of pain in the front where the,

1:47:23where the uterus is. So that's not uncommon. I think menstrual pain can commonly be both in the, in the front and the back. And I think for patients whose babies might be facing like sunny side up, that there seems to be like more pain in the, in the back during labor. So normal delivery is head out first, face down, correct? Right. That's the most common. That's the most common position that, yeah. Does the mother's body make opioids or other

1:47:55pain suppressing molecules, exot, endogenously to help? Make you have amnesia. Yeah, yeah, yeah. Well, it's, it's kind of a joke, right? Which is, it's, it's described as the single most painful thing a person can undergo. And yet women are, it seems that that pain immediately vanishes when that baby is out. And then to your point, there's a little bit of amnesia. As you say, I can't wait to do this again. I'm not sure most of us think that right away, but yeah, that's a good question. But I, maybe you

1:48:26should, at an interview, an anesthesiologist about it, so.

US Maternal Health and Research Gaps

1:48:30Yeah, interesting. When you, when you sort of reflect on this field, it's, they're probably, I need to think about this because I don't know if it's entirely true. I mean, medicine has made so much progress over the last hundred years, but I would be hard pressed to think of a field that has had a greater improvement in mortality in the last hundred years than your field, right? You've, I mean, it's had, I think it's had the single biggest impact on the population's

1:49:00longevity has been fewer mothers and babies dying during this unbelievably hellish process, right? Yeah. I think that's, that's pretty fair to say. So despite that, the United States still doesn't quite stack up to other OECD nations in this arena. This has been a topic that's come up on other podcasts. I had this discussion with a gentleman, a physician, Sam Sutaria, when we talked

1:49:30about some of the mortality statistics in the United States. And this is a big drag down on our overall mortality, our survival numbers or life expectancy numbers. 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 there, there's a day, you know, in, in 10 years, in 20 years, the United States is leading the world in maternal fetal health? It doesn't feel that way right now, honestly.

1:50:00Absolutely. I think there's some pretty low hanging fruit that would help. I think insurance access is a big deal, you know, for states that expanded Medicaid, where, you know, patients came into pregnancy with better health, were, were more willing to come to prenatal care or ABLE because they were able to get insurance through Medicaid who had extended Medicaid postpartum for care, which is when a lot of mothers die. You're saying Medicaid previously stopped once you left the

1:50:34hospital? It's been like 60, 60 days. So there's states who in recent years have, you know, really expanded access longer postpartum, which is really, really impactful for families. But, you know, I think overall, one of the reasons that our health is poor is because insurance access is piecemeal and it's not guaranteed. And health care is expensive, even for those who have insurance. What's typically not covered? Like if someone was going through the Affordable Care Act, buying their

1:51:09own insurance through, through the program, what's the sort of surprise that they end up getting, potentially financial surprise, where they're saying, hey, 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. Yeah. I mean, the system is so complicated that I think most physicians can't actually answer that question because, 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

1:51:43that it's really, really hard to understand. But you can't even help a patient navigate the system and try to cater your care to their coverage. No, it's 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 it's quite difficult. Which is interesting because that would seem to me an issue that anyone, everyone on both sides of the aisle could agree that it's a bad thing to have moms and,

1:52:16and babies not cared for. And nobody should, nobody should really incur bankruptcy inducing health, healthcare bills. And everybody's very frustrated with the payers for sure. It, it, it, really is the, it is the Achilles heel of the U S healthcare system that does not appear in single payer solutions. Now, again, the challenging thing is there are so many wonderful things about the U S healthcare system that are the result of a two payer system. But at the same time, there are so many

1:52:47things, and this is a classic example. I wasn't aware of the, for example, the Medicaid, not necessarily extending post. So, well, I don't mean to end it on a downer, but that's, this has been a super fascinating discussion, Katie. Again, I think this idea that 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

1:53:17and risks are in the future. Any other really big messages you want to make sure people take away from this as far as improving their health? Well, I mean, I think, I think in the pregnancy space, we still really lack interventions and treatments because of lack of investment in, in research in this area. And we haven't spent a ton of time talking about that today, but I think that, you know, it's been a neglected area in research. It's been an underfunded area of research. Even at the NIH

1:53:49level? Yes. Even at the NIH level. And, you know, the branch of the NIH, the NICHD, the National Institutes of Child Health and Development, nothing in that word has the word pregnancy in it. So they're like, that has been the institute. That's the closest pregnancy gets to the 17 different branches of the NIH. Right, exactly. 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 mom. So. Why do you think that is? It seems obvious. I mean,

1:54:23sorry, what seems obvious is that it should address pregnancy. Do you, I mean, what's, what's your hypothesis? I know that the NIH has areas where it's just doubled down and spends endlessly. Right. And then there are gaps, presumably. I mean, there are, I'll give you a gap in my world is the investment in gyroscience 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. Yes. So I guess we can add pregnancy to that list, unfortunately.

1:54:53Yeah. And I think it's the recognition of its importance in the whole lifespan has really, has expanded some, you know, funding opportunities. And so I think there is more recognition of it now, but really there's need for continued investment in this area because it still remains like understudied and under resourced to really help people the most, most we could if there were more resources. So if there were philanthropists listening to this now who are saying, look, I want to, I'm very interested in finding biomedical research, but I, I like to fund things

1:55:26that are not otherwise crowded. This is an area. Yeah. What would their next steps be? How would they find the right scientists and investigators who are asking the questions that can be answered? Yeah. I think there's some groups that have come around trying to advise or advocate for funding. So AGOS as 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

1:55:57leading in this space across OBGYN are involved in that society. So you can contact leaders of these organizations and they can help direct people. Various folks have different, sometimes people have areas of very specific interest in giving money to sometimes, you know, there's, there's lots of ways to make investments that make a big difference for people. So I think. But going to that organization is a place where you could find the investigators and basically figure out who's doing the work you're interested in. Well, Katie, thank you so much. I appreciate it. And apologies for the board exam,

1:56:29but on the positive side, you don't, you get to sit the next years out. Thanks. Thank you for listening to this week's episode of The Drive. Head over to peteratiamd.com forward slash show notes. If you want to dig deeper into this episode, you can also find me on YouTube, Instagram, and Twitter, all with the handle peteratiamd. You can also leave us review on Apple podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not

1:57:02constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take all conflicts of interest very seriously. For all of my

1:57:37disclosures and the companies I invest in or advise, please visit peteratiamd.com forward slash about where I keep an up-to-date and active list of all disclosures.