00:05:35.040you went off to the lab, and then you came back for your rotation. So you've come out of your PhD,
00:05:40.020you've got a couple years left of medical school. What drew you to obstetrics and gynecology?
00:05:45.420Yeah, I had always been really interested in women's health. I did all the clinical rotations
00:05:51.180as a third-year medical student. I really liked everything. I liked medicine, I liked surgery,
00:05:56.140but I really liked pregnant patients and deliveries. And I thought it was such a unique
00:06:02.100patient population to take care of because I found people were uniquely motivated about their
00:06:07.040health during that time in a way that you didn't find in other parts of medicine. And thinking with
00:06:12.180the research, half of my interest, I also was fascinated that we didn't understand anything.
00:06:17.680Like, why do people go into labor? Why do people have preterm labor? Why do people have preeclampsia?
00:06:23.140The answer was, we don't know. And so I thought it was a great area of medicine to go into.
00:06:29.200Well, let's just jump into it then. Really the first place I kind of wanted to start was
00:06:34.740understanding the sort of physiologic stress test that is pregnancy. Obviously, I have no
00:06:41.800personal experience, but certainly watched my wife go through it three times, actually more
00:06:46.620unfortunately, but three successful pregnancies. And I shared with you some personal stuff that
00:06:52.860I probably won't disclose on the podcast. I've seen the most extreme sides of it. I have to be
00:06:59.800honest with you. There's a part of me that thinks, how did our species propagate? I don't understand
00:07:05.560how all the women and children didn't just die. I know we talk about how infant and maternal0.95
00:07:12.220mortality was such a huge driver of short life expectancy prior to the modernity of medicine.
00:07:18.340I'm still surprised it was as successful as it was. So in whatever way you want to address it,
00:07:24.880just maybe talk us through the unbelievable demands that are placed on the women in this0.73
00:07:31.040species as they have to deal with this essential challenge of our reproduction.1.00
00:07:37.320Yeah. I mean, I think that's, and I'm also amazed that it ever goes well, pregnancy that is. So
00:07:44.940just for how many ways that it can go wrong.0.99
00:07:49.560But I think you take an adult and, you know, they become pregnant
00:07:55.460and immediately the increased demands on their body starts to support this developing fetus.
00:08:01.800And so there's great expansion of the blood volume,
00:08:06.460great alterations in the endocrine and metabolism.
00:08:10.580And 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.
00:08:28.280It is a metabolic stress test because there's increased insulin resistance, especially in the
00:08:34.380second part of pregnancy. It causes some people to have gestational diabetes, and it often can
00:08:39.800unmask future predisposition to disease through this process. Well, I want to talk about all of
00:08:47.540those, but maybe we can just start with the beginning. So shortly after conception, what is
00:08:54.320sort of the first physiologic interruption that occurs in the woman's body? And I mean,
00:09:01.880we could think of this through the lens of, for a woman who is not planning to get pregnant,
00:09:06.880is the first observation typically the menses, the missed period? Or is it morning sickness?
00:09:13.440Like in your experience, what is the first sign that a woman's pregnant?
00:09:18.020Yeah, I think for people who have regular periods, like the missed period is often the first
00:09:22.860first sign before others. Before an actual symptom. Yeah. Okay. We don't need to explain
00:09:27.720why that happens. I think that's pretty self-evident, but let's now talk about how
00:09:31.680the physiology is changing in that first four to six weeks. So the implantation has taken place,
00:09:38.760obviously the placenta is starting to grow. What's happening in her endocrine system,
00:09:43.660for example? Yeah. I mean, I think there's certainly different phases of, you know,
00:09:48.360at first the ovary is actually supporting in an endocrine way the development of the
00:09:54.620pregnancy. And then as the placenta develops, the placenta itself starts to secrete the hormones
00:10:01.000that support the pregnancy. And when does that transition take place?
00:10:05.780Between like, you know, eight to 10 weeks of pregnancy. So that's why when people have IVF
00:10:13.580and they kind of shut down your own hormone system for that process that supplementary hormones are
00:10:20.260given for the first several weeks of pregnancy because there isn't the natural hormones being0.98
00:10:25.820produced by the ovary. Okay. So the ovary before that transition is primarily making estradiol as
00:10:32.180the dominant estrogen? And progesterone. And progesterone. Okay. And then what's happening
00:10:37.360with HCG during that period of time? Yeah. I mean, that starts to, you know, it goes from
00:10:43.260being zero to increasing dramatically. And what's the purpose of that? I mean,
00:10:48.200I know it's basically a luteinizing hormone, but is it basically the pituitary's way of telling
00:10:54.740the ovary to make more of these hormones? Is that why it's rising? That's a good question.
00:10:59.600And I haven't thought about that in a while.
00:11:12.840For a long time, people actually thought that.
00:11:16.060But actually, for people who have extreme nausea and vomiting of pregnancy, so hyperamesis gravidarum, we have very poor treatments for that.
00:11:25.720And interestingly, genetics is something that gave us a great insight about that, which is when they studied folks who had hyperemesis, they found a signal that flagged the GDF15 gene is really important in driving who developed that condition.
00:11:43.920And 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.
00:11:55.100Is 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?
00:12:04.360That's a good question. I don't think all the time that that is the case.
00:12:08.940Is it also something that is predictive of subsequent? I mean, if it has a high genetic component, I assume the answer is yes.
00:12:15.080But is it necessarily the case that if a woman's sick during her first pregnancy, she's probably in store for this going forward?
00:12:22.000We often see people who have hyperamysis in all their pregnancies if they have it with their first. So yes.
00:12:28.280Okay. So again, we don't know why it's happening. Is the biggest risk of that simply nutrition? Is it that it makes it more difficult to get enough nutrition during that period of the pregnancy?
00:12:40.140Yeah, I think so. And I think 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.
00:12:55.980Do you have a rough sense of the prevalence of how often it becomes maybe something that would even require a brief hospitalization or even a medical intervention?
00:13:06.500And by the way, are your standard anti-emetics safe during pregnancy?
00:18:14.860I mean, I guess it's complicated because you...
00:18:16.180Let's take out the case of a woman who's got horrible morning sickness.
00:18:21.240And more, I'm asking this through the lens of when does the demand...
00:18:25.360When does the metabolic demand of the fetus warrant increased intake by the mother?
00:18:29.060Hmm. Well, I think that's more like in the second half of pregnancy when the actual amount that the fetus is growing is the greatest. There's also increased nutrient demands, which is why we have folks taking prenatal vitamins and also that contain iron because that will also support the developing blood expansion as well. So there are increased nutrient demands.
00:18:54.320So let's talk just specifically about them. I know that many folks probably know what the prenatal stack looks like, but just maybe we can just state it. What are the most important vitamins and minerals from the moment a woman is pregnant or even planning to get pregnant?
00:19:08.580Right. Folic acid is really 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 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.
00:19:28.020And by the time you recognize the pregnancy, it's already kind of too late to bring up folic acid levels if they have been deficient.
00:19:37.000So that's one of the most essential things early on.
00:19:39.860Now, you said 50% of pregnancies are unplanned, which suggests that prenatal vitamins should be recommended to all women of childbearing age, correct?
00:19:52.640So, 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 to be replete in with pregnancy.
00:20:03.800So 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.
00:24:40.740Yeah. There's huge variability, as you might imagine.
00:24:43.840Okay. So now we enter the second trimester. Let me do my math. We're about halfway to that
00:24:51.940expansion of plasma volume. So we'd be roughly at 25% plasma expansion. Tell me what's happening
00:24:58.000now in terms of the physiology? The hormones, are they still going up or have they plateaued
00:25:02.560at this point? That's a good question and I'm not... Sorry, it's like your board exam here.
00:25:08.940I do feel like I'm in an oral board exam, just to be very honest. I'm sorry. I'm sorry. I promise
00:25:14.460you there's no grade at the end of this podcast. Okay. So tell me what else is happening in that
00:25:21.040second trimester as far as the, especially in terms of like what the mother's physiology is0.89
00:25:26.900doing? Yeah. Well, there's a lot of fetal growth during this period. And really, the plasma volume1.00
00:25:34.660has increased somewhat, but then there's really an acceleration of that in the second part of the
00:25:40.160second trimester. So it's not linear. But I would say that there's more maternal adaptation
00:25:47.940to pregnancy. The metabolism might switch from being insulin sensitive to being more insulin
00:25:54.880resistance during that part of the pregnancy, given the growth of the placenta, the pregnant
00:26:01.440person's going to be, you know, gaining some more weight than the first trimester, usually during
00:26:06.200this time. And also, you know, they become visibly pregnant during this, this, this part of the
00:26:12.120pregnancy. So let's talk about that fuel partitioning piece, the insulin sensitivity,
00:26:15.620insulin resistance. There are certain conditions when insulin resistance might be desirable. So
00:26:20.820one of them is actually fasting. So when a person is fasting for prolonged reasons,
00:26:25.260the muscles actually become insulin resistant as an adaptive response so that glucose is
00:26:31.640preferentially spared for the brain. Is the insulin resistance that you describe here in
00:26:37.440the second trimester equally adaptive or is it necessarily pathologic? And obviously at some
00:26:44.380levels it's pathologic if it develops into frank diabetes, but kind of walk me through that.
00:26:48.780Yeah, well, I think it can go either way. I mean, I think it's meant to be adaptive, right, providing enough fuel 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.
00:27:08.780When did routine screening for that become the norm?
00:27:11.240As 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.
00:27:22.120And so the reason that routine screening started was because you couldn't predict very well who was going to develop gestational diabetes.
00:27:28.680And what were the consequences of that?
00:27:30.480And just how significant was it? Like a woman would show up with a glucose, would this carry
00:27:36.380its way all the pregnancy or would she present prior to delivery in the way that a person with
00:27:41.860type 1 diabetes might present with glucose urea and all sorts of other things? Yeah. I mean,
00:27:46.140it's not like type 1 diabetes. It's more like a type 2 diabetic, but they would present with
00:27:52.620glucose in the urine and they may be having other maternal symptoms like polyuria and polydipsia
00:27:58.920from high glucose if it was uncontrolled enough. I think the short term of pregnancy is not so much
00:28:07.360too concerning otherwise from a maternal level, from like a short term mild elevation, but really
00:28:13.860for the fetus, that's very consequential to see that high level of glucose. And so
00:28:19.320if the fetus sees that, they can have excessive growth. So you get fetal macrosomia. There's
00:28:24.780higher risk of developing complications of pregnancy, like preeclampsia, where you get
00:28:29.620high blood pressure and protein in your urine if you have gestational diabetes, especially
00:28:33.820if it's not well treated. And then there's all the consequences at delivery of having a baby that is
00:28:40.180bigger than it should be, which increased risk of C-section and shoulder dystocia.
00:28:46.040And then the baby would be at increased risk for having hypoglycemia as the baby ramps up its own
00:28:52.700insulin production to try to bring the levels of glucose down, then gets detached from the mother
00:28:58.440and the placenta and then is making too much insulin and then has low glucose come after.
00:29:04.040And then does the fact that the baby had to be effectively locally hyperinsulinemic to manage
00:29:10.520this during the pregnancy, does that have implications for their long-term health vis-a-vis
00:29:16.840insulin resistance and diabetes later in life? And if so, is it epigenetic? Do we know why?
00:29:22.220Yeah, I think, yes, they have a higher risk of metabolic issues long term.
00:29:27.460And I think we don't fully understand all the reasons why that is the case.0.98
00:29:32.440So for that reason, we've obviously made the wise decision of every woman is going to get screened for this.
00:29:39.900Remind me, when in the pregnancy does that screening take place?
00:34:15.080I mean, it depends on the patient, right?
00:34:16.540If everything is elevated in the first week, you're not going to keep going for another week.
00:34:21.700But, yeah, you have close follow-up and lots of communication about what the values are.
00:34:26.740And 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 on the fetus?
00:34:36.480Yeah, 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.
00:35:00.260How long after delivery does this metabolic pattern return to normal? In other words,
00:35:07.560if a woman is actually initiating insulin, how long does she have to continue this
00:35:12.780post-delivery? Does it fix like that? Yeah. If you diagnose them with potentially0.98
00:35:16.880having undiagnosed type 2 diabetes, this might not be the case. But if you really think it's
00:35:21.860gestational diabetes, then once they deliver, it seems to, for most folks, be resolved. So we
00:35:28.400usually check a finger stick while they're still in the hospital. And then the recommendation is
00:35:33.340also at the six-week postpartum visit to do another two-hour glucose test to screen for
00:35:39.560type 2 diabetes because some people will have type 2 diabetes and then they should also be
00:35:44.760surveilled for type 2 diabetes more closely following a pregnancy because they're at higher
00:35:49.640risk. Is it an oversimplification to say that every woman to some extent has to become insulin
00:35:57.060resistant during pregnancy, because that's the adaptive response to preferentially direct
00:36:01.980nutrients to the fetus. There are probably genetic factors that amplify this in some women. And then
00:36:09.000there are going to be environmental factors that would also amplify it. And that could be stress,
00:36:13.380sleep, nutrition, et cetera. Is that the risk of oversimplifying it? Is that sort of the playbook?
00:36:18.040No, I think that's a great framework for it.
00:36:20.140So if a woman is diagnosed with gestational diabetes, goes through treatment, et cetera,
00:36:24.600et cetera, would you counsel her prior to her next pregnancy and say, look, this is not,
00:36:29.540you don't have to go through this again. You might, because we don't know how much
00:36:32.720each of those things was a contributor. It might be that your genes overwhelmingly made this happen
00:36:36.780and you're destined for it, but let's see if we can avoid it by doing A, B, and C,
00:36:42.580or is it basically the case that once it happens during a pregnancy, you almost assume it's going
00:36:47.540to happen with subsequent pregnancies? No, interestingly, it doesn't always
00:36:51.420recur in every pregnancy. And I don't think we fully understand it. Like almost everything in
00:36:57.840medicine, if you've had it before, you're more likely to have it again. But not everyone gets
00:37:02.180it again. Okay. Let's talk about preeclampsia. This is obviously a big one. You mentioned it
00:37:07.480already, but do you mind just defining it again? Yeah. So preeclampsia is a pregnancy-specific
00:37:12.800condition where folks develop new onset high blood pressure or hypertension after 20 weeks
00:37:19.580gestation and often accompanied by proteinuria, so protein in the urine, and also accompanied by
00:37:26.160other severe, what we would call like severe features, but sometimes other symptoms like
00:37:31.220right upper quadrant pain, vision changes, headaches. And this is obviously screened for
00:37:36.720because most hypertension is asymptomatic. So that's something that has to be caught during
00:37:41.340your routine visits, correct? Yes. And actually the initial schedule for prenatal care was really
00:37:47.860set up to detect developing preeclampsia in pregnancy, which is why you see like accelerating
00:37:53.720leave, you know, closer visits at the end of pregnancy compared to early pregnancy is really
00:37:59.400screened for like blood pressure. And is this defined as blood pressure,
00:38:05.600like 135 over 80? Is that the threshold? Where do we consider that?
00:38:09.600So for systolic, it's 140, and for diastolic, it's 105 to 110 to qualify as having.
00:41:00.700So then what do you think explains the other end of that barbell, which is the women over 40,0.95
00:41:06.980for example? Yeah, I think women over 40 have just increased cardiometabolic0.95
00:41:12.040disease slash intolerance to more cardiovascular demand. So I think it's really
00:41:19.180maternal physiologic changes by the time that you're that age that really drive the increased
00:41:24.420incidence. Yeah, because the plasma volume alone could drive the hypertension, although I don't
00:41:28.300know that that would drive the proteinuria, right? That seems to be like, I mean, yeah, tell me more
00:41:33.520about why that's happening because we see that in kidney disease. I mean, that's what we're
00:41:37.960monitoring is for GFR. So how do we tie those two things together that don't necessarily seem
00:41:44.660obviously related? Well, that has to, in pregnancy, both the hypertension and proteinuria have to do
00:41:51.220with angiogenic imbalance. So classically, the classic model of preeclampsia, which may not be
00:41:58.060true for everyone, is that the early in pregnancy, the placenta, the placental trophoblasts, which
00:42:06.260should invade into the maternal spiral or arteries and allow them to become wider and lower pressure
00:42:14.020vessels to supply the placenta with adequate blood flow. If that is not adequate enough,
00:42:19.820then the placenta has some degree of hypoxia. And the placenta itself then releases this
00:42:26.700anti-angiogenic factor called S-split into the maternal circulation. And that molecule soaks up
00:42:34.160the VEGF, an important growth factor for maintaining vessel endothelial cell function.
00:42:41.240And that affects both the endothelial cells of the maternal vessels and the endothelial cells
00:42:47.220in the glomerulus of the kidney. And so that connects like the, what's happening physiologically.
00:42:53.020Super interesting. I had never heard that before. So that, that makes sense. When was that level
00:42:58.200of understanding brought to the field? Is that something in the last 25 years or?
00:43:02.380Um, who is the timing? Like something you learned during your career? Or did you know that from,
00:43:08.160was that taught in medical school and I just missed that day?
00:43:10.100Well, Ananth Karamanchi, who was a nephrologist at Beth Israel in Boston, was very interested in preeclampsia.
00:43:22.540And 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.
00:43:35.580And what he found was this incredible upregulation of S-FLIT. And then, you know, they 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.
00:43:53.620And so I always thought that story was fascinating and worked in very, you know, Anant was one of my early mentors in Boston.
00:44:03.900And I really like he's just was always so inspirational in thinking about the science in this area.
00:44:11.520Yeah, it's just a great example of why we just must have scientists working alongside physicians.
00:44:20.200And 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.
00:44:27.340So what is the natural history of preeclampsia if left untreated?
00:44:32.520In other words, before we knew what the heck was going on, how did this manifest itself?
00:44:37.260So pregnant people would develop severe hypertension that would progress to seizures and even death and other maternal complications like stroke and organ failure.
00:44:50.460year. Wow. So in other words, this is a totally different type of hypertension because in my
00:44:57.580practice, for example, if somebody shows up with hypertension, they may have had it for 10 years
00:45:02.760already. And they clearly have some renal compromise as a result of it and some coronary
00:45:08.240artery disease as a result of it. But it wasn't going to kill them in nine months. So there's
00:45:13.920something about this degree of hypertension that is far more accelerated and far more extreme if
00:45:18.220it's producing this type of outcome. The treatment option is to reduce, is to give
00:45:23.900antihypertensive agents? For the hypertension, when women present with preeclampsia, we do give
00:45:29.640antihypertensive agents. That can help us expectantly manage a lot of patients, meaning that
00:45:35.440they can present with hypertension at 30 weeks, and we can treat their hypertension and monitor
00:45:41.260them closely, and they may get several more weeks in the pregnancy. But ultimately, it won't go away
00:45:49.240until the baby is delivered. There's nothing that we can do besides that to actually cure it.
00:45:55.700So what is the, I don't want to say the earliest because there's always going to be some edge case,
00:46:02.120but what would you consider to be a very early presentation of preeclampsia and therefore
00:46:06.880potentially risky case because you have to wait longer till you get to the point where you can
00:46:13.100deliver the fetus to ultimately render the cure. Would 25 weeks be considered very early for this
00:46:19.640to show up? Yeah. So the earliest we think of it as showing up is 20 weeks. It is very rare to see
00:46:27.360it at that point of pregnancy. So we consider early onset to be preeclampsia that shows up
00:46:32.440before 34 weeks because most of it will show up in the third trimester. And actually, most of it
00:46:37.860shows up near term. And sorry, just to do my math, third trimester starts around 27 weeks, right?
00:46:43.780Yeah, like 28 weeks. Yeah. So it's like halfway into the third trimester would be the sort of
00:46:48.640standard case of preeclampsia where if the woman got into trouble, you could induce and safely
00:46:56.300deliver a fetus at 33, 34 weeks, right? Yeah. I mean, it's not the gestational age of the fetus0.53
00:47:05.780per se that drives when we decide when to deliver somebody. It has to do about the severity of their
00:47:12.020disease. So we do make different decisions about delivery, balancing the maternal and the fetal
00:47:17.620risks based on where they are in gestation. But like a term, we would always deliver somebody who
00:47:23.980was showing up with even mild hypertension.
00:47:37.940Or is it always based on the hypertension?
00:47:39.800We don't make decisions based on the proteinuria.
00:47:42.500We often make decisions based on the severity of the hypertension.
00:47:48.420But there's also lab abnormalities that can go along with preeclampsia, like elevated
00:47:53.600liver function tests and low platelets. There's also fetal concerns that can develop. So the
00:47:58.900fetus is more likely to be growth restricted. It might have abnormal testing. So sometimes we get
00:48:04.840into a space where like the mom is doing okay, but the baby's testing is not reassuring and we
00:48:09.540need to deliver. So there's many reasons why we stop expectantly managing and move towards delivery.
00:48:17.160And so all those things have to be considered when we're making that decision.
00:48:20.300Is the mother ever at risk for residual or lasting kidney damage?
00:48:27.160Yeah, that's a good question. For patients who start out with normal kidney function,
00:48:33.340they generally have recovered their kidney function after the pregnancy is done. However,
00:48:41.360people who have experienced severe preeclampsia have a longer-term risk of kidney disease as well
00:48:47.680as cardiovascular disease. So long term. I want to come back to this topic because it's become a
00:48:53.760very interesting recent discussion, which we should spend some time on. LFTs, platelets. Boy,
00:48:59.840this sounds a lot like HELP syndrome. So I don't remember what HELP stands for. I just remember
00:49:05.020it's really, really bad. Can you remind us what it is? Yeah. So HELP syndrome is where the pregnant
00:49:11.440patient presents with, it stands for hemolysis, elevated liver enzymes, and low platelets.
00:49:18.100Some folks think it's on the spectrum of preeclampsia, like it's a very severe
00:49:22.320version of preeclampsia. Other folks think that it may have a completely different underlying
00:49:28.520biology, but have overlapping features with preeclampsia. Patients with HELP syndrome may
00:49:35.100present with severe hypertension, like we described for regular preeclampsia, but they also might have
00:49:40.720just like mild range blood pressures and then very severe lab abnormalities. So we see it present
00:49:46.280both ways. And it can become pretty scary if it occurs, you know, in the 20 weeks, not 20,
00:49:55.120but in the 20s, right? If it's at 28 weeks, 29 weeks, because you're really balancing the
00:50:00.120maternal health with maximizing the viability of the fetus. And as you said, the fetus could
00:50:05.080be compromised based on growth. I mean, this gets very complicated very quickly.
00:50:09.320Yeah, HELP syndrome is one of those conditions where we often give betamethasone to 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.
00:50:23.420How often do women get that diagnosis prior to when they need?
00:50:29.840Like, 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.
00:50:37.640Yeah. As long as that's actually what's going on, but yes.
00:50:41.780Okay. What's your best guess for the etiology?
00:50:47.300Great question. We do not know what causes Hope syndrome.
00:50:54.240If we assume that preeclampsia is something distinct, or even if it's not, do you have a
00:50:58.140sense of the... I mean, we explained the mechanism of preeclampsia, but do we think that this is
00:51:03.400somewhat genetic, largely genetic, somewhat environmental, not environmental at all?
00:51:10.700Yeah, good questions. Well, preeclampsia is heritable, meaning that there is definitely
00:51:15.540a genetic component. And it comes from both the fetus and placenta, which are considered to be
00:51:21.380relatively the same genetically and the maternal genetics. So they're both important. So there's
00:51:27.820been a lot done in the past, you know, eight years or so that's come out about the underlying
00:51:32.840genetics of preeclampsia. It was a really understudied field when I started working
00:51:37.300in this area myself. There were like no big cohorts that had genetic data and had had the
00:51:42.720same type of genome-wide association studies that had been done for many other complex diseases.
00:51:49.140And so it was really unknown what factors across the genome might contribute. But in the past eight
00:51:54.880years, there's been a lot more information that's come out about that, which I think is really great
00:51:59.980and fascinating because genetics can really help you get at the underlying causal biology behind
00:52:06.320something. So when you really don't understand what's causing it or what pathways might be
00:52:10.660important to target with therapeutics, then genetics can really help you understand that.
00:52:17.860Going back to management of preeclampsia, if you're going to use antihypertensives,
00:52:23.240what are the agents of choice? Yeah, what you'll see used most is nifedipine and libidolol because
00:52:29.720there's good data about safety in pregnancy. There are other hypertensives that we use
00:52:35.660sometimes, but those are two mainstays. So interesting because, I mean, we just don't
00:52:40.940use those outside of pregnancy at all because they're not that good. So does that mean we do
00:52:45.740not know or we do know that ACE inhibitors or ARBs, which would be first line in someone who's
00:52:51.100not pregnant, do we know for sure that those are not safe in pregnancy? And is that why they're
00:52:54.880not chosen? Correct. We know for sure that they're not safe in pregnancy. Yeah. So they have a
00:52:59.360negative impact on the fetus, presumably. Correct. That's right. Got it. Yeah. But they're good
00:53:03.740agents postpartum when we're working to control maternal blood pressures. So we often will
00:53:09.180utilize them after delivery. So when we were talking about gestational diabetes, you pointed
00:53:13.840out that the woman could be off insulin by the time she goes home. Oh, yeah. That's how quickly
00:53:19.540it resolves. But what you just said makes me think the same is not necessarily true of preeclampsia
00:53:24.320and the hypertension. Yeah, that's correct. So some people will have their hypertension resolved
00:53:29.800like very quickly after delivery, but many women need antihypertensive medications for
00:53:35.720several weeks after delivery. It can take like six, 12 weeks to kind of come back to more of0.98
00:53:43.200a baseline. And there are other women who will have persistent hypertension after delivery that
00:53:50.720never quite resolves. And lots of women who will come back and develop hypertension within the next
00:53:56.280five to 10 years as well. Wow. Does the proteinuria respond or resolve quickly? And I assume that's
00:54:03.280checked until it does? You know, we don't check it, and that is because it resolves.
00:54:09.720And is that because once the placenta is out, you've sort of solved the problem that's driving
00:57:51.620Have there been any intervention studies that have been done, and this would be a difficult
00:57:55.640study to do, I accept, because it would take a long time, so the answer is almost assuredly
00:57:59.840no, but where you take women who develop gestational diabetes and then you manage them
00:58:06.140aggressively, you know, you would randomize them to one intervention versus the other
00:58:09.760to see if you could delay and or just outright avoid type 2 diabetes?
00:58:13.640Yeah, I think that the recommendation is that they have frequent follow-up for diabetes screening and also should be very much advised on any lifestyle changes that they could make that would impact the risk of type 2 diabetes.
00:58:28.600So we know that healthier diet and appropriate body weight and regular exercise all are very important there.
00:58:36.560So it's even more critical for folks who have a history of gestational diabetes to be counseled about that to decrease their risk.
00:58:45.260So is that sort of the message you're delivering to a woman? Because you're in a very interesting
00:58:50.300role as a physician in that you play a profound role in the care of her and her baby. But once
00:58:59.180that baby's gone, you're not the one that gets to take care of her. And yet you learned something
00:59:05.220really profound about her because, as you said, you saw her during a very high physiologic stress
00:59:12.480test that gave you an enormous insight into what the rest of her life has in store for her vis-a-vis
00:59:18.200metabolic health, cardiovascular disease at a minimum. I mean, by the way, we might discover
00:59:23.000that there are other diseases we're learning about that are predicted through pregnancy.
00:59:27.240So what is the relationship between a high risk or any OBGYN and the long-term health of the patient
00:59:35.100to say, look, this is not, your genes are not your destiny, but you need to, we need to really stay
00:59:42.180on top of managing these things aggressively. And by the way, you should live a normal life
00:59:46.720as a result of the privilege of modern medicine that we wouldn't have been able to do this,
00:59:51.860you know, 50 years ago. Yeah. I mean, I think the counseling is really important. And as a
00:59:56.860high risk obstetrician, you know, some general OBGYNs might see a patient for their pregnancies
01:00:02.060and then also for their GYN care and have more of a primary care relationship with a patient.
01:00:07.720With our high-risk obstetric practice, we will only see the patient back in general if they
01:00:13.000have another pregnancy. And so that transition to a primary care provider with that information
01:00:19.180transmitted is really essential. And I do think lots of patients who are young and taking care
01:00:25.940of kids and often don't follow up a lot themselves between pregnancies and so stressing the
01:00:31.900importance of having a primary care provider and following is really important, but certainly there
01:00:36.840could be, you know, we can continue to enhance, like, both education and the communication. I
01:00:43.580mean, electronic health records have helped some, right, because we can often see now, like, records
01:00:48.520and, you know, if somebody is tuned into that, they can get at what happened, but they have to
01:00:54.840know that it's important. So if we did nothing else today, if we accomplished only one thing,
01:01:00.480and it was that women and their primary care doctors were really tuned into what was unmasked0.64
01:01:08.620during pregnancy and used that for aggressive treatment and prevention, that would be a win.
01:01:14.780Okay. Do you have a sense of, well, I mean, it sounds like it's a bit of a mixed bag in terms
01:01:20.100of what's recognized there. Okay. So the other thing I wanted to ask you about is C-section
01:01:25.860versus vaginal? What are the trends? What are the trade-offs? This is an area where I feel like I
01:01:31.480have heard so many differing stories. I can't tell what's real. So let's kind of walk through
01:01:38.280what is known and let's acknowledge what is not known. So first of all, from a historical
01:01:43.440perspective, I assume it wasn't until the late 1800s we were doing the first cesarean sections.
01:01:48.820I hope we were at least waiting until we had modern anesthetics.
01:01:51.420These are also 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 great access to, you know, surgical intervention during labor and delivery.
01:02:06.880And 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.
01:02:18.840So C-section is certainly like a needed and helpful intervention because not every baby is going to deliver vaginally.
01:02:28.160And 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, go back a thousand years.
01:02:37.820Do we have a sense of what the frequency was of a stillbirth and was the stillbirth necessarily going to lead to the maternal demise?
01:02:46.080Like, if you can't get a dead fetus out of a woman, she's going to die of an infection, correct?
01:03:19.840So C-sections have obviously become important.
01:03:24.240What do we know about the, I don't know what the right word to think of it, is it prevalence
01:03:28.860or usage or, you know, in whatever metric you would use to determine what percentage
01:03:34.120of deliveries in the United States are vaginal versus C-section.
01:03:37.400How has that number changed over the last 50 years?
01:03:40.660Yeah, it's dramatically increased, you know, so we've we've gone from, you know, like 10 percent C-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 percent C-section rate.
01:03:58.220And 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.
01:04:14.900I think there are different drivers. The pregnancies are higher risk than they used to. Once you have one C-section, you're more likely to have another one. The health of the patient matters. A lot of people think that maternal obesity increasing has increased the number of women who have either larger fetuses or feel like labor that doesn't progress normally and therefore leads to a C-section.
01:04:43.700You 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 monitored during the active phase of labor continuously.
01:04:57.800And when the tracing is not reassuring, we move to a C-section.
01:05:02.180So I think it's a complex issue to understand.
01:05:06.920And, you know, there is a lot of focus on trying to decrease that number or avoid it
01:09:19.440There are cases where the head might be very big and it makes sense that the baby was in that position the whole time.
01:09:27.380Sometimes 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.
01:09:34.580So sometimes we see things that, you know, make us kind of think that's why it was.
01:11:15.320I mean, there's many, there's patients who don't do testing.
01:11:17.780There's patients who choose to continue their pregnancy.
01:11:20.200But you're right that, like, a lot of people who have choice and access to those choices do terminate their pregnancies earlier.
01:11:28.880But there are many patients carrying pregnancies with various anomalies and other genetic conditions.
01:11:35.160Hoping that things will work out, but maybe they don't.
01:11:37.580So what would you say are the most common drivers of a still pregnancy?
01:11:42.820Yeah, I mean, I think there's different categories, but many of them remain unexplained.
01:11:48.620At 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.
01:12:00.720So those are the three most useful tests.
01:12:03.060Also, like describing like the baby and the placenta at delivery, like just what you see in terms of, you know, you might see a big abruption, like the placenta came off the uterus.
01:12:14.300There might be like a really tight cord there.
01:12:17.380So there might be things that you actually see in the delivery room that, you know, help you.
01:12:22.580But even with the standard workup, we don't understand the cause in a big percentage of cases.
01:12:29.260Meaning even when you know the genetics, you've pathologically examined the placenta and there's been an autopsy done on the fetus.
01:12:38.600You're saying about half the time you still wouldn't be able to identify a cause of death.
01:12:42.740Yeah. 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 have been the proximal cause of then what, why the baby passed away.
01:13:05.800but it doesn't really explain like what causes that and why that happened at the end of pregnancy,
01:13:11.020you know, and everything had looked okay up until that point.
01:13:14.940Because I'm just trying to understand one of these late stage events. So let's just say a
01:13:18.820woman's had normal prenatal care. She's not high risk, but she's still doing all the normal stuff.
01:13:23.660Every time she goes in for an ultrasound, you obviously see the heart beat. Presumably you0.59
01:13:28.380can tell that the placenta is still attached to the uterus. Is it standard to also do duplex on
01:13:35.000placental blood vessels or is that not we wouldn't do that level of we're only doing like doppler
01:13:40.440monitoring on ultrasound when the baby is growth restricted so um so when we know that there's
01:13:45.960fetal growth restriction or if there's a few other indications then then we monitor blood flow through
01:13:52.100the umbilical cord but in we don't do that in general because it's not been shown to be a
01:13:56.840helpful like test otherwise yeah so it's just mind-boggling to me that they're they're from a
01:14:03.180tragic standpoint that a couple could come in to think everything is fine. Would their labor pains
01:14:10.280and labor signs and symptoms under stillbirth conditions resemble that of non-stillbirth?
01:14:16.160Yeah. So let's talk a little bit about that. What triggers labor? What is happening in the
01:14:22.280body? How does the body know it's time? We don't know. Really? Yeah.
01:14:26.640we so tell me tell me what is actually happening what what is the what's happening with prolactin
01:14:32.920and oxytocin and all these other things even if we don't know why it's happening do we do we at
01:14:36.420least have a sense of those things uh a little bit but you know um yeah you know people have
01:14:42.920tried to look at the changes that directly precede labor and and there's some but it's
01:14:48.600hard to predict right like you monitor somebody like every day to see what's going to happen up
01:14:53.200of delivery. So we really don't have a great sense. We think something's changing with the HPA
01:14:59.680axis that's triggering this quiescent state where progesterone is maintaining the uterus not to
01:15:05.280contract to actually contract. But we really, really don't have a good sense of what's happening.
01:15:12.700Is the contraction of the uterus the first sign? Is that the first thing a woman is actually
01:15:17.940feeling. Yeah. And tell me how you coach a woman through that. Like if let's say you're seeing her
01:15:24.360in your office and it's what you believe will be the last time you see her prior to her admission
01:15:29.340to the labor and delivery ward. It's her first pregnancy. She doesn't know what to expect.
01:15:33.840Her partner is equally clueless and they're scared senseless. What are you saying?
01:15:39.000Well, with every third trimester patient, we're saying like, you know, monitor like how you're
01:15:44.080feeling the baby move, let us know if it's different. Look out for leaking fluid and
01:15:49.720vaginal bleeding if you have any of those things come in. And then if you start to have contractions
01:15:55.640like time, how frequently they're coming, and if they're coming closer than five minutes apart for
01:16:00.940more than an hour or they're increasing in pain and intensity or accompanied by any of those
01:16:06.180other things I just described, then you should come in to get checked out.
01:16:09.980okay so that's that's a pretty logical list having experienced contractions yourself what
01:16:16.180what does this what does this thing feel like what does a contraction feel like does it feel
01:16:19.540like a muscle flexing um well i think early contractions might kind of be like or you know
01:16:28.320braxton hicks like practice ones might be like having a really bad period like a really bad
01:16:33.280menstrual cramp. But like real contractions, probably more painful than anything else that
01:16:39.960I've experienced before. So it's not subtle. A woman is not, there's no, she's not thinking to
01:16:46.100myself, is this a contraction? Well, that often comes up and there are patients who have very
01:16:51.500high pain tolerances or experience it differently who come in who are quite dilated without a lot
01:16:57.000of pain, but I think most people experience it as a pretty painful process.
01:17:02.420How, so I explained to the listener what you mean by dilation and what is the, what is
01:17:09.100the amount of dilation that you would see commonly and not be concerned if there still
01:21:45.060They 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.
01:21:53.400And you are, your highest concern is an infection, I assume?
01:21:57.560That's one of the concerns. Infection is a high concern. Progressing rapidly into labor once the
01:22:03.000bag of water is broken is, can be very common. If the patient is not cephalic, so not head down,
01:22:09.920there's a risk of like cord prolapse or another body part, like the cervix dilating, and then
01:22:16.020some part of the pregnancy or cord starting to come through the cervix, which can be an emergency.
01:22:21.720And 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?
01:22:32.880Right. 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.0.95
01:22:44.420Got it. Do you ever give antibiotics in that situation or is that a no-no?
01:22:47.760We 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.
01:23:14.960Going back to the C-section versus vaginal discussion, again, my vague recollection is
01:23:22.120one of the advantages of a vaginal delivery is related to the bacterial transfer between
01:23:28.580mother and fetus. Is that real or is that something that gets over extrapolated?
01:23:34.100There's a lot of attention to that for how much we really know about it, I would say.
01:23:37.860There's probably something there, like the microbiome is important. There's certainly
01:23:42.900influences and importance across different areas of medicine. But I think there's a lot of popular
01:23:50.200press about that without probably a lot more of the basic medical... There seems to be a lot of
01:23:57.280fear-mongering about it, quite frankly, which is almost like shaming women that have C-sections
01:24:02.020into believing like, you have failed to deliver the appropriate gut biome to your child. And so
01:24:08.320Is it safe to say that the science is not suggesting that?
01:24:12.400Well, I'm not saying that there's no helpful component of that, but I would say of all
01:24:18.140the things that help determine your health and your baby's health, that's probably not
01:26:47.220Definitely 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, of their cycle.
01:27:03.360I 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 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.
01:27:26.680Yeah, I mean, I think exercise is really important.
01:27:29.620The more data we get, the more we know, like, bed rest is bad.
01:27:35.080You know, we tell people not to start, like, a new intensive program during their pregnancy.
01:27:40.640So if they weren't that physically active prior to pregnancy, it's not the time to, like, start to try to run a marathon.
01:27:47.940But having, like, regular activity, like walking or low weight, weightlifting is fine.
01:27:54.800For 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.
01:28:03.740Including resistance training if it's like if they're used to strenuous resistance training, you would be okay with that until what point in the pregnancy?
01:28:12.280Well, I think the main risk is like the center of gravity changing, the risk of getting injured or hurt by whatever you're doing.
01:28:21.380So you just have to do all the things you're doing in a safe way.
01:28:24.580So, you know, we don't recommend downhill skiing in the second part of pregnancy.
01:28:29.480You know, we, you know, horseback riding or, you know, things where you might incur trauma to your abdomen are not good.
01:28:36.920But a valsalva, a bearing down during a, you know, lifting something heavy is okay if a woman's used to that.
01:28:42.980Yeah, we haven't, you know, if she's having like a healthy pregnancy.
01:28:46.000Now, 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 during the rest.
01:28:57.100And a short cervix presumably means you have less resistance to the intra-abdominal pressure.
01:29:56.400Yeah, I mean, at the end of pregnancy, when the fetus is pretty big, I think to lay completely
01:30:02.320flat on your back is probably not the best position.
01:30:04.920So to have some tilt if you're laying towards your back would be good because there is
01:30:10.500that part has some truth to it. But I think people sometimes come in panicked that they woke up on
01:30:15.640their back and, you know, I'm like, it's going to be OK. OK. Yeah. I know that you're not the one
01:30:22.500as the obstetrician who's taking care of the mom months and months following her pregnancy. But
01:30:27.500what's your understanding of postpartum depression? How often is it showing up
01:30:33.140even in the hospital? What's our understanding of what's driving that?
01:30:36.920Yeah. 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 at the end of pregnancy and then drop to like extremely low levels.
01:30:55.780And 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 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.
01:31:17.860We do have standard screening that's recommended during, you know, both during pregnancy for depression and 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.
01:31:39.720But I think as we all know, across all of health care, 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. They 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.
01:32:08.840And do you think that the biggest source of undertreatment is the failure to differentiate between what is maybe normal in this short-term response to what becomes maladaptive or persists in an abnormal way?
01:32:24.580And then it just sort of gets turned into like there's so much going on that this kind of gets shoved under the rug?
01:32:30.360Yeah, 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, 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.
01:32:55.620So then people don't present to care because of feelings that it's somehow their fault that they're feeling this way.
01:33:05.160Let's go back to the other end of the pregnancy, which is on the sort of genetic screening side of things.
01:33:10.540So IVF is becoming much more common these days, and with IVF comes prenatal screening.
01:33:16.000But for couples not undergoing IVF who are showing up with a spontaneous pregnancy, what is the current state of the art in screening?
01:33:26.360Is it mostly done through sampling amniotic fluid?
01:33:29.860Is that still viewed as kind of an aggressive thing that you wouldn't really do unless you needed to?
01:34:33.960Okay. So presumably that takes away a lot of the incentive that was present for amniocentesis,
01:34:40.520correct? Right. So previously we had what was called a serum screen that looked at three or
01:34:47.040four protein markers in the maternal blood. And if that screen was positive, meaning that the
01:34:54.580levels of those proteins for the gestational age were consistent with an increased risk of
01:35:00.960a chromosomal disorder, then an amniocentesis was recommended. But in those cases, the positive
01:35:08.340predictive value of a positive test was 5%, meaning that for everyone who screened positive
01:35:14.920for potentially having a baby with Down syndrome or trisomy 21, only 5% would actually be carrying
01:35:21.620a baby with Down syndrome. Now, is that because the prevalence was too low or because the
01:35:26.480sensitivity and specificity were too low? It's because the sensitivity and specificity were
01:35:31.600too low. Got it. And so cell-free DNA has dramatically improved both the sensitivity
01:35:37.140and the specificity of that testing. So fewer people feel inclined to also pursue a diagnostic
01:35:45.300procedure. And when the screen is positive, they're not 100% guaranteed to have a fetus
01:35:51.700with that condition, but they're much more likely to have one. What do you think is the biggest gap
01:35:56.980in this type of testing? Like where would you like to see things in a decade with respect to
01:36:02.060prenatal screening or in utero screening for that matter? Yeah. Well, there's different kinds of
01:36:08.120screening. There's ultrasound, which has developed a lot so we can actually look structurally at the
01:36:13.000baby. And then there's genetics. Chromosomal disorders that I mentioned that we are currently
01:36:17.980screening for from cell-free DNA only represent a very small percentage of all the genetic
01:36:23.880disorders that can exist in a baby. And so we're missing many serious and devastating conditions
01:36:31.180on that cell-free DNA screening. So sometimes people think they've been screened for everything,
01:36:36.020and it's really only these three things, basically. So I think the entire genome is
01:36:42.040represented in the cell-free DNA in the maternal blood. So potentially we could detect...
01:36:47.300So what's the limit? Do we just not have enough of it? Why aren't we doing a whole genome sequence
01:36:52.040on it for the, you know, or at least screening for 27 different, you know, metabolic diseases
01:36:58.040that are quasi-common? Yeah. Well, there's many reasons, but when you're thinking about a prenatal
01:37:04.400screening test, you have to think about what the cost is and what the implications are in the
01:37:10.820prenatal space and which things you should be calling out during pregnancy versus like what
01:37:15.640things are only important later in life, to really look at all the genes in the whole
01:37:21.660genome. Well, let's simplify it. Let's look at, like, say, the inborn errors of metabolism,
01:37:26.020which would present early in life. There would probably be value in knowing that
01:37:31.240during the first trimester, right? Correct. So for serious conditions like that,
01:37:35.900folks are working on creating panels of disorders that might be helpful to screen for.
01:37:42.340it's still complicated because for any given condition, take like cystic fibrosis is a good
01:37:49.120example. There might be tons of different genetic variants that a patient has that could cause
01:37:56.340disease. So our ability to understand which genetic changes cause disease in a given gene
01:38:03.940and which ones don't is essential because there's no other phenotype that we can see prenatally for
01:38:10.220many of these conditions, right? So for an inborn era of metabolism, the baby within the mom is
01:38:16.980generally, for most of those, it's doing just fine. There's no signs. There's no ultrasound features.
01:38:22.040There's nothing else that we're testing. So we're getting this genetic result. But if we don't
01:38:28.500really know with confidence that, like, which things actually cause disease, then it can be
01:38:34.040really, really tricky and stressful to counsel a patient about that in the prenatal space where
01:38:39.740they're trying to decide if they should continue the pregnancy or what the implications of that
01:38:45.440are. So I think there's a big gap between what we can do from a technology standpoint and our
01:38:52.680framework for how we decide which things to screen for and then the resources of the healthcare
01:38:58.720system that it will take to actually counsel people about these conditions and their screening
01:39:05.200results. So what is the most difficult thing you have to do in your role as a physician? What's
01:39:14.140the thing that just is so challenging, either because of the resources that are brought to
01:39:21.240bear or just, quite frankly, the emotional toll it takes on you? You can answer that in any way
01:39:25.940that makes sense. Yeah. There's some really hard things that we deal with as physicians.
01:39:33.020I think from from a medical standpoint, when we see things in pregnancy, you know, people who are who we have to inform of devastating diagnoses, whether it be like an underlying genetic condition, severe fetal anomalies, a stillborn baby, when you have to like deliver that news and the implications that it has for for a given family and trying to walk them through that.
01:40:00.840those are really tough conversations. I also see it's just the different resources that people
01:40:08.620have that bring them to us or that they go back to, I think are very impactful for me to think
01:40:15.820about to patients that we treat and then don't have somewhere to stay or have really complex
01:40:21.840other situations that they're dealing with. So I think there's often feels like you can't do
01:40:27.300do a lot about that, but you can see with your own patient how much impact it has on them and
01:40:35.040their own health. Have you ever had the privilege to go and visit another country where the resources
01:40:41.640are far less and participate in childbirth in a place like that? Yeah, I haven't participated in
01:40:49.580childbirth in another country myself. I spent a lot of time in our own country, in the Appalachian
01:40:57.920Mountains, as a high schooler on a service project where we go for a week every summer and fix
01:41:04.120people's homes. And it was really like being somewhere very different than how I thought of
01:41:11.020at the time, like how our country is. And I wasn't participating in childbirth at that time,
01:41:17.240But I've certainly seen a lot of folks who live in very, you know, across many circumstances.
01:41:25.820What percentage of women in the United States use a midwife for delivery as opposed to an obstetrician?
01:41:33.000You 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.
01:41:45.940There is a lot of midwife care prevalent throughout the country. Midwives do a great job providing obstetric care. They provide great access in many places where patients don't have other access and their training is a bit different.
01:42:01.860So 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 component of obstetric care.
01:42:17.580I assume a midwife doesn't have the other tools with, I'm going to say her because I'm just going to assume most 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?
01:42:34.660I mean, usually most practices are set up so that if a surgical procedure is needed, then the-0.64
01:47:25.940I think menstrual pain can commonly be both in the front and the back.
01:47:31.100And I think for patients whose babies might be facing, like, sunny side up, that there seems to be, like, more pain in the back during labor.
01:47:41.420So normal delivery is head out first, face down, correct?
01:48:31.420When you sort of reflect on this field, it's, they're probably, I need to think about this
01:48:39.460because I don't know if it's entirely true.
01:48:41.000I mean, medicine has made so much progress over the last hundred years.
01:48:44.720but I would be hard-pressed to think of a field that has had a greater improvement in mortality
01:48:51.180in the last hundred years than your field, right? I think it's had the single biggest impact on the
01:48:59.300population's longevity has been fewer mothers and babies dying during this unbelievably hellish
01:49:07.180process, right? Yeah, I think that's pretty fair to say. So despite that, the United States still0.72
01:49:16.700doesn't quite stack up to other OECD nations in this arena. This has been a topic that's come up
01:49:24.300on other podcasts. I had this discussion with a gentleman, a physician, Sam Sutaria, when we
01:49:30.080talked about some of the mortality statistics in the United States. And this is a big drag
01:49:36.980down on our overall mortality, our survival numbers or life expectancy numbers. There's
01:49:43.000all the obvious reasons for it. You've talked about many of them today. Do you hold out much
01:49:49.700hope that in 10 years, in 20 years, the United States is leading the world in maternal fetal
01:49:57.700health? It doesn't feel that way right now, honestly. I think there's some pretty low-hanging
01:50:05.100fruit that would help. I think insurance access is a big deal. You know, for states that expanded
01:50:11.860Medicaid, where, you know, patients came into pregnancy with better health, were more willing
01:50:18.760to come to prenatal care or ABLE because they were able to get insurance through Medicaid,
01:50:24.660who had extended Medicaid postpartum for care, which is when a lot of mothers die.
01:50:32.040You're saying Medicaid previously stopped once you left the hospital?
01:50:35.100It'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.
01:51:03.520What's typically not covered? Like if someone was going through the Affordable Care Act,
01:51:09.000buying their own insurance through the program, what's the sort of surprise that they end up
01:51:14.360getting potentially, financial surprise, where they're saying, hey, I bought my health insurance,
01:51:18.920I showed up, this is all taken care of. And then they get a bill that says, actually,
01:51:22.260we covered this, but not this. Yeah. I mean, the system is so complicated that I think most
01:51:27.240physicians can't actually answer that question because it's so unpredictable and it changes
01:51:33.920every year with any health plan. As we all know, it's like, you know, to have this plan, you have
01:51:38.580this amount of deductible or you have this other plan and then these are the charges, right? It's
01:51:42.760so complex that it's really, really hard to understand. But you can't even help a patient
01:51:47.060navigate the system and try to cater your care to their coverage. No, it's incredibly frustrating
01:51:54.420and difficult. And it feels, you feel very powerless because you would like to provide
01:51:59.380information. That's like part of our job. But like, there's so many differences between so
01:52:04.560many different plans that it's quite difficult. Which is interesting because that would seem to
01:52:10.040me an issue that anyone, everyone on both sides of the aisle could agree that it's a bad thing to
01:52:15.660have moms and babies not cared for. And nobody should, nobody should really incur bankruptcy
01:52:21.880inducing health healthcare bills. And everybody's very frustrated with the payers for sure. It really
01:52:28.780is the Achilles heel of the US healthcare system that does not appear in single payer solutions.
01:52:38.480Now, again, the challenging thing is there are so many wonderful things about the US healthcare
01:52:42.180system that are the result of a two payer system. But at the same time, there are so many things,
01:52:48.100and this is a classic example. I wasn't aware of the, for example, the Medicaid not necessarily
01:52:52.560extending post. Well, I don't mean to end it on a downer, but this has been a super fascinating
01:52:58.000discussion, Katie. Again, I think this idea that what happens during pregnancy gives you a window
01:53:05.360into your future health. I think, again, if the listener, both male and female, takes nothing but
01:53:12.820that, which says, use this opportunity to learn what your susceptibilities and risks are in the
01:53:18.760future. Any other really big messages you want to make sure people take away from this as far
01:53:24.600as improving their health? Well, I mean, I think in the pregnancy space, we still really lack
01:53:32.860interventions and treatments because of lack of investment in research in this area. And we
01:53:38.840haven't spent a ton of time talking about that today, but I think that it's been a neglected
01:53:45.480area in research. It's been an underfunded area of research. Even at the NIH level?
01:53:50.080Yes, even at the NIH level. And the branch of the NIH, the NICHD, the National Institutes of Child
01:53:57.420Health and Development, nothing in that word has the word pregnancy in it. So that has been the
01:54:03.900That's the closest pregnancy gets to the 17 different branches of the NIH.