#410 ‒ 妊娠的生物学：生理适应、妊娠期糖尿病、子痫前期、分娩及长期母体健康 | Kathryn Gray, M.D., Ph.D.

就像

like

二型

type

更像二型

two More like a type

糖尿病。

two.

但他们会出现尿糖，如果血糖控制得不好，可能还会有其他母体症状，比如多尿和烦渴。

But they would present with glucose in the urine, and they may be having other maternal symptoms like polyuria and polydipsia from high glucose if it was uncontrolled enough.

我觉得短期内，轻度的血糖升高对母体来说不是太令人担心，但对胎儿来说，高血糖水平影响很大。

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.

如果胎儿暴露在高血糖下，可能会过度生长，导致巨大儿。

And so if the fetus sees that, they can have excessive growth, so you get fetal macrosomia.

如果患有妊娠期糖尿病，尤其是治疗不当的话，发生妊娠并发症的风险更高，比如子痫前期，会出现高血压和尿蛋白。

There's higher risk of developing complications of pregnancy, like preeclampsia, where you get high blood pressure and protein in your urine if you have gestational diabetes, especially if it's not well treated.

然后分娩时，如果宝宝比正常体型大，会有各种后果，比如增加剖腹产和肩难产的风险。

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.

然后宝宝自身会增加胰岛素分泌来降低血糖，但一旦脱离母体的胎盘，它还在分泌过多的胰岛素，之后就会出现低血糖。

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 in the placenta, and then is making too much insulin, and then has low glucose after.

那么，宝宝在孕期为了应对高血糖而局部高胰岛素血症，这种情况对他们长期健康，比如胰岛素抵抗和以后得糖尿病，有没有影响呢？

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?

如果有的话，是表观遗传学的原因吗？

And if so, is it epigenetic?

我们知道具体原因吗？

Do we know why?

是的，我认为他们长期代谢问题的风险确实更高，但具体原因我们还没有完全弄清楚。

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.

所以，正因为如此，我们显然做出了明智的决定，让每位孕妇都接受筛查。

So for that reason, we've obviously made the wise decision of every woman is going to get screened for this.

提醒我一下，孕期什么时候做这个筛查？

Remind me when in the pregnancy does that screening take place?

在24到28周之间。

Between twenty four and twenty eight weeks.

大概是因为如果更早做的话，会漏掉那些后来才会出现症状的人。

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

对。

Yep.

好的。

Okay.

而且实际上数据显示，如果更早诊断出来，可能根本不会改善结果。

And actually data shows that when you diagnose it earlier, it might not improve the outcomes at all.

所以这似乎是筛查和识别有风险或已经患上妊娠期糖尿病的人的最佳窗口，也是治疗最能发挥作用的时间。

So it seems to be the best window for both screening and identifying people who are at risk or have developed gestational diabetes and having the most impact from treatment.

跟我说说，诊断是通过口服葡萄糖耐量测试进行的，空腹测一次，然后两小时后再测一次。

Tell me, the diagnosis is made with an oral glucose tolerance test, done at fasting, and then two hours.

标准是什么？

What's the criteria?

具体做法是，先做一小时血糖测试，喝50克葡萄糖，这个不需要空腹。

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.

你直接来，喝下50克葡萄糖，一小时后抽血测血糖水平。

So you just come in, you drink 50 of glucose, you have your blood drawn an hour later and tested for the glucose level.

明白了。

I see.

如果这个测试没过，血糖值超过130或140，具体看用的标准。

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

凯蒂，这个数值其实不算高。

That's actually not that high, Katie.

对。

No.

我之所以这么想，是因为我们给病人做OGTT时都是空腹的。

So because I'm just the way I'm thinking about it is we always do OGTTs on our patients, but they're fasting.

现在我们用的是75克葡萄糖，而不是50克，所以我觉得这不太能直接比较。

Now we're using seventy five grams of glucose instead of fifty, so I'm not sure it's apples to apples.

但我能想象一个场景，一位女士吃完午饭回来，比如她中午吃了意大利面。

But I can imagine a scenario where a woman comes in from a lunch where she was out at a, you know, she pasta for lunch.

她的血糖已经是120或130了，这在餐后是完全正常的。

Her glucose is already 120 or 130, which would be perfectly normal postprandially.

喝完50克葡萄糖一小时后，如果她还能降到130或140，我会很惊讶。

An hour after 50, I would be surprised if she was back down to 130 or 140.

所以这可能会导致假阳性，对吧？

So you could potentially get into these false positives?

是的，当然。

So yes, of course.

所以我们会做后续的三小时糖耐量测试，这次需要空腹来，喝更大剂量的葡萄糖，然后在一小时、两小时、三小时后分别抽血检测。

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.

那这个测试的标准是什么？

And then what's the criteria on that?

那个测试用的是75克葡萄糖吗？

Is that 75 grams you do for that one?

然后每一项数值都有一个正常范围。

And then there's a range for each one of those values of what is normal.

所以如果空腹血糖偏高，就直接诊断为妊娠期糖尿病了。

So if your fasting's elevated from that test, you automatically are diagnosed with gestational.

空腹状态下偏高是110还是100？好消息是你会有加分。

Elevated one ten in that fasting state or 100, or do you The good news is you are going to get credit.

你本来要……

You were gonna...

你不需要再参加下一次的执业考试了。

You don't have to take your next board exam.

这个播客就是考试。

This this podcast is the exam.

没关系。

It's okay.

所以就是

So just

那里

There

我们会把这个放在节目说明里。

We'll put this in the show notes.

别担心。

Don't worry.

任何...

Any...

任何你不知道答案的问题，就说我们会把它放在节目说明里。

Anything you don't know the answer to, just say we'll put it in the show notes.

对，我们会把那些数值放在那里给你。

Yeah, we're going to put the values there for you.

好的。

Okay.

所以有一个阈值，分别在零小时、一小时、两小时、三小时的时候。

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

但相对而言，这些数值和我们用来诊断非妊娠期2型糖尿病患者的数值相比，怎么样？如果我们不想只依赖糖化血红蛋白的话。

But relatively speaking, do these compare to what we would use on a person who we're trying to diagnose type two diabetes in if we don't want to just rely on the A1C?

有那么高吗？

Is it that high?

嗯，如果你曾经超过……

Well, if you ever are over...

如果一小时血糖超过200，就不用做三小时的了。

If the one hour is over 200, you don't do the three hour.

对。

Yep.

所以我觉得这和妊娠期外的标准是类似的。

So I think that's similar to outside of pregnancy.

然后其他各项也都有各自的参考范围。

And then there are ranges for each of the other ones.

而且如果空腹血糖正常，你需要有两项升高才能确诊。

And you have to have two elevators to actually be diagnosed if the fasting is normal.

那在这种情况下，标准治疗方案是什么？

So what is standard of care in this situation?

所以女性来了，你知道，我本来想说通过了测试，但没通过测试，不管我们怎么说。

So woman shows up, you know, I was going to say passes the test, but fails the test, however we want say it.

一线治疗是什么？

What is first line?

二线治疗是什么？

What is second line?

我们什么时候会依赖胰岛素？

When do we ever rely on insulin?

我假设这个女性在怀孕前不是二型糖尿病患者，我们可以先不考虑那一类情况。

And I'm assuming this is in a woman who is not a type two diabetic outside of pregnancy, that we can put that category to the side for a moment.

但这个人之前代谢健康，现在却不健康了。

But this is someone who was metabolically healthy prior to and now is not.

你是直接开始用……

Are you going right to...

你是想先通过营养来调理吗？

Are you trying to do this with nutrition first?

你是说，不，我们直接上二甲双胍或者其他药物？

Are you saying, no, we're going go straight to metformin or some other agent?

不是。

No.

一线治疗其实是调整饮食，见营养师，监测血糖，包括空腹和餐后，通过这些调整，看看血糖能不能控制好。

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 well controlled.

比如空腹低于95，餐后一小时，你知道的，低于140。

So like fasting under 95, one hour postprandial, like, you know, less than 140.

所以一开始我们先监测这些，当超过一半的数值高于我们期望的范围时，再开始用药。

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.

胰岛素其实是一线治疗，这和怀孕外的情况不一样。

Insulin is really first line, so that's different than outside of pregnancy.

对于二型糖尿病患者，管理上可能有些不同，但一般来说，我们通常接下来就直接用胰岛素了。

With type two diabetics, there may be some differences in management, but in general, we often just go next to insulin.

有趣的是，如果你在28周做这个测试，你也得非常快。

And what's interesting is if you're doing this test at twenty eight weeks, you also have to be very quick.

我的意思是，你不可能给生活方式干预那么长时间。

I mean, you're not going to give lifestyle that long.

你不会说，好吧，我们试试生活方式干预三个月，因为三个月后你就要生孩子了。

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.

那你给第一次生活方式干预多长时间？

So how much time are you giving that first lifestyle intervention?

基本上就是两周，对吧？

Is that two weeks, basically?

这要看病人情况，对吧？

I mean, it depends on the patient, right?

如果第一周所有数值都偏高，你就不会继续再等一周。

If everything is elevated in the first week, you're not gonna keep going for another week.

是的，但你要密切随访，多沟通数值情况。

But yeah, you have close follow-up and lots of communication about what the values are.

那你们选择胰岛素作为一线治疗，是因为时间紧迫，还是担心药物对胎儿有不良影响？

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 on the fetus?

是的，很多药物在疗效和安全性方面都缺乏可靠的数据。

Yeah, well, there's not good data on a lot of the medications for both efficacy and safety.

二甲双胍我们一般认为在孕期相对安全，可能也有帮助。

So metformin, we think of as fairly safe in pregnancy and potentially helpful.

但胰岛素确实最有效，安全性数据也充分，而且对改善新生儿结局效果最好。

But really, insulin is most effective and we have good safety data and it has the best influence on improving the neonatal outcomes.

分娩后，这种代谢异常多久能恢复正常？

How long after delivery does this metabolic pattern return to normal?

换句话说，就是……

In other words, how...

如果一位女性真的开始用胰岛素了，产后她需要继续用多久？

If a woman is actually initiating insulin, how long does she have to continue this post delivery?

是不是马上就能停？

Does it fix like that?

如果你诊断她们可能患有未确诊的2型糖尿病，那情况可能就不是这样了。

If you diagnose them with potentially having undiagnosed type two diabetes, this might not be the case.

但如果你真的认为是妊娠期糖尿病，那么一旦她们分娩，对大多数人来说，这个问题似乎就解决了。

But if you really think it's gestational diabetes, then once they deliver, it seems to, you know, for most folks be resolved.

所以我们通常会在她们还在医院的时候测一下指尖血糖。

So we usually check a finger stick while they're still in the hospital.

然后建议在产后六周复查时再做一次两小时糖耐量测试，筛查2型糖尿病，因为有些人会有2型糖尿病，而且她们在怀孕后应该更密切地监测2型糖尿病，因为她们的风险更高。

And then the recommendation is also at the six week postpartum visit to do another two hour glucose test to screen for type two diabetes, because some people will have type two diabetes, and then they should also be surveilled for type two diabetes more closely following a pregnancy because they're at higher risk.

如果说每个女性在怀孕期间都会有一定程度的胰岛素抵抗，因为这是优先将营养输送给胎儿的适应性反应，这样说是不是太简单化了？

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?

可能有些遗传因素会放大这种情况，还有一些环境因素也会放大，比如压力、睡眠、营养等等。

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, sleep, nutrition, etcetera.

这样简化是不是有风险？

Is the risk of oversimplifying it?

这大概就是关键点吧？

Is that sort of the point?

不，我觉得这个框架很好。

No, I think that's a great framework for it.

所以，如果一个女性被诊断出妊娠糖尿病，经过治疗等等，你会不会在她下次怀孕前建议她，说，听着，这不是……

So if a woman is diagnosed with gestational diabetes, goes through treatment, etcetera, etcetera, would you counsel her prior to her next pregnancy and say, Look, this is not a...

你不必再经历一次。

You don't have to go through this again.

你可能会，因为我们不知道每个因素贡献了多少。

You might, because we don't know how much each of those things was a contributor.

可能是你的基因在很大程度上导致了这种情况，你注定会这样。

It might be that your genes overwhelmingly made this happen and you're destined for it.

但让我们看看能不能通过做A、B和C来避免，或者基本上，一旦在怀孕期间发生，你几乎可以假设它会在后续怀孕中再次发生？

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, you almost assume it's going to happen with subsequent pregnancies?

不，有趣的是，它并不总是在每次怀孕中复发。

No, interestingly, it doesn't always recur in every pregnancy.

所以，我觉得我们并没有完全理解它。

So, and I don't think we fully understand it.

就像医学里几乎所有的情况一样，如果你以前得过，复发的可能性会更高，但也不是每个人都会再得。

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.

好的。

Okay.

我们来聊聊子痫前期吧。

Let's talk about preeclampsia.

这显然是个大问题。

This is obviously a big one.

你之前提到过，但你能再定义一下吗？

You mentioned it already, but do you mind just defining it again?

好的，子痫前期是怀孕特有的一种情况，指怀孕二十周后出现新发的高血压，通常还伴有蛋白尿，也就是尿里有蛋白，同时可能还有其他严重的表现，比如右上腹疼痛、视力变化、头痛等症状。

Yeah, so preeclampsia is a pregnancy specific condition where folks develop new onset high blood pressure or hypertension after twenty weeks gestation, and often accompanied by 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.

这显然是需要筛查的，因为大多数高血压没有症状，所以必须在常规产检中发现，对吧？

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

是的，实际上，产前检查的初始安排就是为了发现孕期子痫前期的发展，这就是为什么你会看到孕晚期检查频率比孕早期更高，主要就是为了筛查血压。

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 leap, you know, closer visits at the end of pregnancy compared to early pregnancy, is really screened for blood pressure.

那这个定义是血压135/80吗？

And is this defined as blood pressure, like 135 over 80?

这是标准吗？

Is that the threshold?

我们怎么界定这个？

Where do we consider that?

收缩压是140，舒张压是105到110，达到这个标准才算。

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

好的。

Okay.

那诊断是在诊所里做的，还是我们接受有白大褂高血压的情况，让病人回家自己监测？

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?

我们总是看整体情况，但很多时候人们在诊所里血压会有点高，我们会让他们带个血压计回家，多监测一下。

So we're always looking at the whole picture, but a lot of times people will have some elevators in the office, and we will send them home with a blood pressure cuff and have them monitoring more.

有时候人们一开始就表现出很严重的血压和其他症状，那他们可能就直接被收住院了。

Sometimes people present more robustly with like very severe blood pressures from the get go and other symptoms, and then sometimes they get go straight to being admitted to the hospital.

所以每个人的情况可能差别很大。

So it can have very different courses different folks.

比如有些人高血压会持续几周，看起来没有变得更严重，而另一些人第一次出现高血压时就已经非常严重了。

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.

那诊断是需要同时满足高血压和蛋白尿，还是只要其中一个足够严重就可以确诊？

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

是的，这个定义随着时间一直在变。

Yeah, so they've changed the definition over time.

以前要诊断子痫前期，需要至少两次间隔六小时的血压升高，同时还要有蛋白尿或者其他严重症状。

So it used to be that to have preeclampsia, you needed to have both elevated blood pressures at least two, six hours apart, and then also proteinuria or another severe symptom.

现在他们改成了，如果血压达到严重范围，再加上其他一些情况，即使没有明显的蛋白尿，也可以确诊。

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.

总体来看，这种情况的发生率是多少？

All comers, what is the incidence of this?

大约占怀孕的百分之五，具体是百分之五到七，取决于美国的患者群体。

It's about five percent of pregnancies, five to seven percent, depending on your patient population in US.

那如果按年龄分层，情况会有什么变化？

And then how does that change if we stratify by age?

如果我们只看二十多岁的女性和四十多岁的女性，结果会不一样吗？

So if we were to limit it to, okay, just women in the 20s versus women in their 40s, does that change things?

风险最高的人群是第一次怀孕的人，以及年龄很小或很大的人。

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

所以我选了个最差的年龄段来比较。

So I picked the worst demographic to compare.

所以……

So...

好。

Okay.

那首先，这是为什么呢？

So first of all, why is that?

我觉得我们也不太清楚。

I think we we don't know.

人们有很多原因……

There's lots of reasons why people...

比如，很多人认为第一次怀孕风险最高，原因有很多。

Like, there's lots of reasons why folks think that the first pregnancy is at highest risk.

其中一个原因可能是，母亲对父亲抗原的暴露程度较低，而这些抗原存在于儿子的体内。

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 in their son's

所以这是自身免疫反应吗？

So it's an autoimmune response?

不是自身免疫。

It's not autoimmune.

或者说是自身免疫，

Or autoimmune,

抱歉，

I'm sorry,

是免疫反应。

it's immune.

对，有人认为这可能跟免疫有关，但不仅仅是这个原因，我们还没有完全搞清楚。

Yeah, there's a thinking that there can be an immune component to it, but it's not just that, but we don't fully understand

好的。

Okay.

所以这就能解释为什么初次怀孕风险高，然后大概在后续怀孕中会产生敏感化。

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

是耐受。

Tolerance.

好的。

Okay.

我在跟一位免疫学家说话。

I'm talking to an immunologist.

我得小心措辞。

I have to be careful with that.

其实我也不是真正的免疫学家。

I mean, I'm not really.

不是。

No.

不是。

No.

就是这些免疫学家。

Just these immunologists.

但是那……

But that...

那你怎么解释这个杠铃的另一端，比如40岁的女性？

So then what do you think explains the other end of that barbell, which is the women 40, for example?

我觉得40岁的女性只是心血管代谢疾病增加，或者对心血管需求的耐受性下降。

I think women 40 have just increased cardiometabolic disease slash intolerance to more cardiovascular demand.

所以我认为，到了那个年龄，母体的生理变化才是真正导致风险增加的原因。

So I think it's really maternal physiologic changes by the time that you're that age that really drive the increased

发病率。是的，血浆容量本身就可能引发高血压，虽然我不确定那会不会导致蛋白尿，对吧？

incidence Yeah, in that the plasma volume alone could drive the hypertension, although I don't know that that would drive the proteinuria, right?

这看起来像是……

That seems to be like...

我是说，对，跟我说说为什么会这样，因为我们在肾病里也看到这种情况。

I mean, yeah, tell me more about why that's happening, because we see that in kidney disease.

我是说，我们监测的就是肾小球滤过率。

I mean, that's what we're monitoring is for GFR.

所以

So

我们怎么把这两件看起来不太相关的事情联系起来呢？

how do we tie those two things together that don't necessarily seem obviously related?

嗯，在怀孕期间，高血压和蛋白尿都与血管生成失衡有关。

Well, that has to in pregnancy, both the hypertension and proteinuria have to do with angiogenic imbalance.

所以经典地，先兆子痫的经典模型——虽然可能不是对每个人都适用——是怀孕早期，胎盘滋养细胞应该侵入母体螺旋动脉，让它们变得更宽、压力更低的血管，为胎盘提供足够的血流。

So classically, the classic model of preeclampsia, which may not be true for everyone, is that the early in pregnancy, the placenta, the placental trophoblasts, which should invade into the maternal spiral arteries and allow them to become wider and lower pressure vessels to supply the placenta with adequate blood flow.

如果这个过程不够充分，胎盘就会出现一定程度的缺氧。

If that is not adequate enough, then the placenta has some degree of hypoxia.

然后胎盘本身会释放一种叫做SFLT的抗血管生成因子，进入母体循环。

And the placenta itself then releases this anti angiogenic factor called S FLT into the maternal circulation.

这种分子会吸收VEGF，而VEGF是维持血管内皮细胞功能的重要生长因子。

And that molecule soaks up the VEGF, an important growth factor for maintaining vessel endothelial cell function.

这会影响母体血管的内皮细胞，也会影响肾小球里的内皮细胞，所以这就把……

And that affects both the endothelial cells of the maternal vessels and the endothelial cells in the glomerulus Glomerular of the And so that connects, like, the...

生理上发生的情况联系起来了。

What's happening physiologically.

非常有意思。

Super interesting.

我以前从来没听说过这个，这样讲就说得通了。

I had never heard that before, so that that makes sense.

这种认识是什么时候进入这个领域的？

When was that level of understanding brought to the field?

是最近二十五年内的事吗？

Is that something in the last twenty five years?

还是？

Or?

哦，时间点的问题。

Oh, the timing.

是你职业生涯中学到的吗？

Like something you learned during your career?

还是你早就知道了……

Or did you know that from...

这是医学院教的，还是我那天刚好没去上课？

Was that taught in medical school and I just missed that day?

嗯，波士顿贝斯以色列医院的肾脏科医生Ananth Karamanshi对子痫前期非常感兴趣。

Well, Ananth Karamanshi, who was a nephrologist at Beth Israel in Boston, was very interested in preeclampsia.

他实际上到处收集子痫前期患者的胎盘，然后做基因芯片分析，寻找可能与该综合征相关的基因上调。

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.

他发现S FLT的表达显著上调。

And what he found was this incredible upregulation of S FLT.

然后，你知道，他们做了很多实验来证明那种蛋白质的作用，以及它为什么可能与子痫前期的病程有因果关系。

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.

所以我一直觉得那个故事特别吸引人，而且它和很多方面都有关联，你知道……

And so I always thought that story was fascinating and worked in very, you know...

阿南特是我在波士顿早期的导师之一，他真的，就是……

Anant was one of my early mentors in Boston, and really, like, he's just...

他在思考这个领域的科学问题时，总是那么鼓舞人心。

Was always so inspirational in thinking about the science in this area.

这正好说明了为什么我们必须让科学家和医生并肩工作。

It's just a great example of why we just must have scientists working alongside physicians.

否则，我们根本学不到这些。

Otherwise, we just don't learn.

就是说，我们不可能，我们不可能自己搞懂这些东西。

Like, we can't we can't learn this stuff.

当然，犹大·福克曼也在哈佛，他当时研究的是抗VEGF治疗癌症，这正好是另一个把这一切联系起来的例子。

And of course, Judah Folkman was also at Harvard working, of course, on anti VEGF for cancer, which is just kind of another way to tie that together.

那么，如果不治疗，先兆子痫的自然病程是怎样的？

So what is the natural history of preeclampsia if left untreated?

也就是说，在我们搞清楚到底怎么回事之前，它是怎么表现出来的？

So in other words, before we knew what the heck was going on, how did this manifest itself?

孕妇会出现严重的高血压，然后进展为抽搐甚至死亡，还有其他母体并发症，比如中风和器官衰竭。

So pregnant people would develop severe hypertension that would progress to seizures and even death and other maternal complications like stroke and organ failure.

哇。

Wow.

所以，这是一种完全不同的高血压类型，因为，你知道，在我的临床实践中，如果有人出现高血压，可能是……

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...

他们可能已经患有高血压十年了，并且因此有明显的肾功能损害，还有冠状动脉疾病，但是，你知道，这不会在九个月内要他们的命。

They may have had it for ten 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 going to kill them in nine months.

所以，这种程度的高血压，如果会导致这样的后果，那它肯定有某种更快速、更极端的特点。

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.

治疗选择是降低血压，就是给降压药吗？

The treatment option is to reduce, is to give antihypertensive agents?

对于高血压，当孕妇出现子痫前期时，我们确实会使用降压药。

The hypertension, when women present with preeclampsia, we do give antihypertensive agents.

这能帮助我们期待性地管理很多患者，也就是说，她们可能在怀孕30周时出现高血压，我们可以治疗她们的高血压并密切监测，这样她们可能能多维持几周的孕期。

That can help us expectantly manage a lot of patients, meaning that they can present with hypertension at thirty weeks, and we can treat their hypertension and monitor them closely, and they may get several more weeks in the pregnancy.

但最终，只有分娩后，病情才会消失。

But ultimately, it won't go away until the baby is delivered.

除此之外，我们没有办法真正治愈它。

There's nothing that we can do besides that to actually cure it.

那么什么是……

So what is the...

我不想说最早，因为总会有一些边缘案例，但你认为子痫前期非常早的表现是什么，因此可能是有风险的病例，因为……

I don't wanna say the earliest because there's always gonna 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...

你必须等待更长时间，直到能够分娩胎儿，最终实现治愈。

You you have to wait longer till you get to the point where you can deliver the fetus to ultimately render the cure.

是不是……

Is is...

二十五周出现这个算不算很早？

Would twenty five weeks be considered very early for this to show up?

我们一般认为最早出现是在二十周。

So the earliest we think of it as showing up is is twenty weeks.

在那个孕周出现非常罕见，所以我们把三十四周之前出现的子痫前期称为早发型，因为大多数病例是在孕晚期出现的。

It is very rare to see it at that point of pregnancy, so we consider early onset to be preeclampsia that shows up before thirty four weeks, because most of it will show up in the third trimester.

实际上，大多数病例是在接近足月时出现的。

And actually, most of it shows up near term.

抱歉，我算一下，孕晚期大概从二十七周开始，对吧？

And sorry, just to do my math, third trimester starts around twenty seven weeks, right?

对，差不多二十八周。

Yeah, like twenty eight weeks.

对，所以孕晚期过了一半的时候，大概是子痫前期的典型情况，如果孕妇情况危急，可以在三十三、三十四周引产，安全分娩，对吧？

Yeah, so it's like halfway into the third trimester would be the sort of standard case of preeclampsia where you're tech you could if the woman got into trouble, you could induce and safely deliver a fetus at thirty three, thirty four weeks, right?

是的，我们确实有这种情况。

Yeah, I mean, we have.

其实决定什么时候分娩，并不是看胎儿的孕周本身。

It's not the gestational age of the fetus per se that drives when we decide when to deliver somebody.

而是取决于病情的严重程度。

It has to do about the severity of their disease.

所以我们会根据孕周，权衡母亲和胎儿的风险，做出不同的分娩决定。

So we do make different decisions about delivery, balancing the maternal and the fetal risks based on where they are in gestation.

但是，比如到了足月，即使只是轻度高血压，我们也会建议分娩。

But, like at term, we would always deliver somebody who was showing up with even mild hypertension.

那才是正确的做法。

That would be the correct question.

36周算吗？

Considered 36?

37周及以上才算足月。

Thirty seven weeks and greater.

好的。

Okay.

你们做这个决定的时候，会不会因为担心肾脏损伤而看蛋白尿的严重程度？还是说我们总是根据……

Are you ever making this decision based on the severity of the proteinuria for fear of renal damage, or is We it always based on the

我们不会根据蛋白尿来做决定。

don't make decisions based on the proteinuria.

我们经常根据高血压的严重程度来做决定，但子痫前期还可能伴随一些实验室指标异常，比如肝功能升高和血小板降低。

We often make decisions based on the severity of the hypertension, but there's also lab abnormalities that can go along with preeclampsia, like elevated liver function tests and low platelets.

胎儿方面也可能出现问题。

There's also fetal concerns that can develop.

比如胎儿更可能出现生长受限。

So the fetus is more likely to be growth restricted.

胎儿的检测结果也可能异常。

It might have abnormal testing.

所以有时候我们会遇到这种情况：妈妈情况还好，但胎儿的检测结果不让人放心，那就需要终止妊娠。

So sometimes we get into a space where, like, the mom is doing okay, but the baby's testing is not reassuring and we need to deliver.

所以，我们停止期待疗法、转向分娩的原因有很多。

So there's many reasons why we stop expectantly managing and move towards delivery.

所以做决定的时候，所有这些因素都得考虑进去。

And so all those things have to be considered when we're making that decision.

母亲有没有可能留下永久性的肾脏损伤？

Is the is the mother ever at risk for residual or lasting kidney damage?

对，这个问题问得好。

Yeah, that's a good question.

对于一开始肾功能正常的患者来说，怀孕结束后肾功能一般都能恢复。

For patients who start out with normal kidney function, they generally have recovered their kidney function after the pregnancy is done.

但是，经历过重度子痫前期的人，长期来看患肾病和心血管疾病的风险会更高。

However, people who have experienced severe preeclampsia have a longer term risk of kidney disease as well as cardiovascular disease.

所以从长远来看，

So long term,

这个话题我想回头再聊，因为最近讨论得挺有意思，值得花点时间。

Which they I want to come back to this topic because it's become a very interesting recent discussion, which we should spend some time on.

肝功能指标、血小板，哎呀，这听起来很像HELLP综合征啊。

LFTs, platelets, boy, this sounds a lot like HELLP syndrome.

我不记得HELLP代表什么了。

So I don't remember what HELLP stands for.

我只记得它非常非常严重。

I just remember it's really, really bad.

你能提醒我们一下它是什么吗？

Can you remind us what it is?

HELLP综合征是指孕妇出现的一些症状。

So HELLP syndrome is where the pregnant patient presents with.

它代表溶血、肝酶升高和血小板减少。

It stands for hemolysis, elevated liver enzymes and low platelets.

有些人认为它是先兆子痫的一种表现，像是先兆子痫的严重版本。

Some folks think it's on the spectrum of preeclampsia, like it's this very severe version of preeclampsia.

另一些人则认为它可能有完全不同的潜在生物学机制，但症状与先兆子痫有重叠。

Other folks think that it may have a completely different underlying biology but have overlapping features with preeclampsia.

患有HELLP综合征的患者可能会出现严重的高血压，就像我们描述的普通先兆子痫一样，但也可能血压只是轻度升高，而实验室检查结果却非常异常。

Patients with HELLP syndrome may present with severe hypertension like we described for regular preeclampsia, but they also might have just like mild range blood pressures and then very severe lab abnormalities.

所以我们看到它有两种表现方式。

So we see it present both ways.

而且如果发生在二十周，不是二十，而是二十几周的时候，可能会变得很吓人，对吧？

And it can become pretty scary if it occurs, you know, in the twenty weeks, not twenty, but in the 20s, right?

如果是在二十八周、二十九周，因为你真的要在母亲健康和胎儿存活率最大化之间做权衡。

If it's at twenty eight weeks, twenty nine weeks, because you're really balancing the maternal health with maximizing the viability of the fetus.

就像你说的，胎儿可能会因为生长问题而受到影响。

As you said, the fetus could be compromised based on growth.

我是说，这种情况很快就会变得非常复杂。

I mean, this gets very complicated very quickly.

HELLP综合征是那种我们经常给倍他米松来帮助胎儿肺部成熟的疾病之一，然后我们等四十八小时，再分娩，因为我们不会对患有HELLP综合征的人进行期待管理。

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

女性在需要之前多久会得到这个诊断？

How often do women get that diagnosis prior to when they need...

换句话说，这是不是可以……

Like, other words, is that something that can be...

按你的定义，HELLP综合征从诊断到分娩的时间窗口非常短。

I guess by definition, you're saying HELLP syndrome implies diagnosis to delivery is a very short window.

对，只要确实是这种情况，但没错。

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

好的。

Okay.

你觉得病因最可能是什么？

What's your best guess for the etiology?

好问题。

Great question.

我们确实不知道HELLP综合征的病因。

We do not know what causes HELLP syndrome.

如果我们假设子痫前期是独立的，或者即使不是，你对此有什么看法……

If we assume that preeclampsia is something distinct, or even if it's not, do you have a sense of the...

我们解释了子痫前期的机制，但你认为这有遗传因素吗？主要是遗传，还是环境因素，或者完全不是环境因素？

I mean, we explained the mechanism of preeclampsia, but do we think that this is somewhat genetic, largely genetic, somewhat environmental, not environmental at all?

是的，问得好。

Yeah, good questions.

嗯，先兆子痫是有遗传性的，也就是说肯定有基因方面的因素。

Well, preeclampsia is heritable, meaning that there is definitely a genetic component.

它既来自胎儿和胎盘——这两者在基因上基本一致——也来自母体的基因。

And it comes from both the fetus and placenta, which are considered to be the same, relatively the same genetically, and the maternal genetics.

所以两者都很重要。

So they're both important.

过去八年左右，关于先兆子痫的潜在基因研究出了很多成果。

So there's been a lot done in the past eight years or so that's come out about the underlying genetics of preeclampsia.

我自己刚开始研究这个领域的时候，这真的是个研究很少的方向。

It was a really understudied field when I started working in this area myself.

当时几乎没有大型队列研究有基因数据，也没有像其他复杂疾病那样做过全基因组关联分析。

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.

所以当时真的不清楚整个基因组里哪些因素可能起作用。

And so it was really unknown what factors across the genome might contribute.

但在过去的八年里，关于这方面的信息多了很多，我觉得这真的很棒，也很吸引人，因为遗传学真的能帮你找到背后的因果生物学机制。

But in the past eight years, there's been 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.

所以当你真的不清楚病因，或者不知道哪些通路可能对治疗有重要影响时，遗传学真的能帮你理解这些。

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.

回到子痫前期的管理，如果要用降压药，首选药物是什么？

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

对，最常用的是硝苯地平和拉贝洛尔，因为有很好的孕期安全性数据。

Yeah, what you'll see used most is nifedipine and labetalol, because there's good data about safety in pregnancy.

我们有时也会用其他降压药，但这两个是主要的。

There are other hypertensives that we use sometimes, but those are two mainstays.

真有意思，因为我们在非孕期根本不用这些药。

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

因为它们效果不太好。

Because they're not that good.

那这是否意味着我们不知道，或者我们确实知道ACE抑制剂或ARBs（这些在非孕期是一线用药）在孕期不安全，所以不选它们？

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?

对。

Correct.

我们确定它们在孕期不安全。

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

是的，所以它们大概对胎儿有负面影响。

Yeah, so they have a negative impact on the fetus, presumably.

对，没错。

Correct, that's right.

明白了。

Got it.

但产后控制母亲血压时，它们是好用的药物。

But they're good agents postpartum when we're working to control maternal blood pressure.

所以我们经常在分娩后使用它们。

So we often will utilize them after delivery.

刚才我们聊到妊娠期糖尿病时，你提到产妇出院时可能已经不需要胰岛素了。

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

哦，对。

Oh, yeah.

就是这么快就恢复了。

That's how quickly it resolves.

但你刚才说的让我觉得，子痫前期和高血压的情况可能就不一样了。

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

对，没错。

Yeah, that's correct.

有些人产后血压很快就恢复正常了，但很多女性产后还需要吃降压药好几个星期。

So some people will have their hypertension resolve very quickly after delivery, but many women need antihypertensive medications for several weeks after delivery.

可能需要六到十二周才能慢慢回到比较正常的水平。

It can take like six, twelve weeks to kind of come back to more of a baseline.

还有些女性产后血压一直高，好不了，而且很多女性在接下来五到十年里还会再出现高血压。

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 five to ten years as well.

哇。

Wow.

蛋白尿会很快好转或者消失吗？

Does the proteinuria respond or resolve quickly?

我猜你们会一直检查直到它消失吧。

And I assume that's checked until it does.

你知道吗，我们其实不检查这个，但它……

You know, we don't we don't check it, but it...

这是因为它会自己消失。

And and and that is because it it resolves.

那是不是……

And is that...

抱歉。

Sorry.

就是说……

Just be...

是不是因为胎盘一出来，导致这个问题的根源就解决了？

Is that because once the placenta is out, you've sort of solved the problem that's driving that?

所以除非我们在筛查代谢指标时发现肾功能异常，比如肌酐升高，否则我们不会去监测这个。

So unless someone, when we screen their metabolic labs, has evidence of renal dysfunction, you know, in elevation of their creatinine, then we would be monitoring that.

但大多数人只是有蛋白尿。

But most folks just have the proteinuria.

对于没有肾脏疾病的人来说，蛋白尿会自行消退。

And for folks without kidney disease, that resolves.

顺便问一下，那个……

By the way, does the...

如果一位女性有显著的蛋白尿，她在怀孕期间肌酐或胱抑素C也会升高吗？

If a woman has significant proteinuria, does she also have a bump in her creatinine or cystatin C during the pregnancy?

不会……

Not in...

我们不查胱抑素C，但肌酐通常不会升高，不过一旦升高……

We don't check cystatin C, but the creatinine tends not to bump, but when it does...

如果子痫前期导致肌酐升高，那也属于疾病的严重表现。

If it does get elevated with preeclampsia, then that's also a severe feature of the disease.

所以现在是个好时机，来聊聊你之前提到的那个话题。这个话题我直到大概九个月或十二个月前才知道，就是关于队列研究中，先兆子痫，或者更具体地说，孕期高血压，即使后来好了，也预示着以后得动脉粥样硬化性心血管疾病的风险会增加。

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, nine months ago, twelve months ago, which was this idea that in cohort studies, preeclampsia, or more specifically, hypertension during pregnancy, even if it resolved, was predictive of later life atherosclerotic cardiovascular disease?

医学界知道这个有多久了？除了那个显而易见的解释，比如有很强的遗传因素，而且这个遗传因素不会消失，我们觉得最好的解释是什么？

How long has the field of medicine known this, and what do we think is the best explanation other than maybe the obvious one, which is there's a strong genetic component to it, and therefore that same genetic component doesn't go away?

这些问题问得很好。

So good questions there.

其实，这个早就知道了。

Actually, this has been known for quite a while.

我觉得只是这个知识

I just think it hasn't

我确实知道得太晚了，经常这样，我保证。

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

没有很好地从产科领域传播到初级保健和其他医学领域，就像它应该的那样，对吧？

Hasn't translated well out of the obstetrics field into, like, primary care and other fields of medicine like like it should have, right?

就像它应该成为一个你会问的问题。

Like it should be a question you would ask.

我们现在会问这个问题，但你在给任何病人做病史采集和体格检查时都应该问这个问题，对吧？

We now ask this question, but you should ask this question during a history and physical of any patient, right?

你应该说，哦，你注意到你生了三个孩子。

You should say, Oh, you noticed you had three kids.

你怀孕期间有没有得过子痫前期？

Did you have preeclampsia during those pregnancies?

对，产科病史很重要，但常常没人问。

Yeah, the obstetric history is relevant and often not asked about.

事实上，这阻碍了遗传学研究，因为人们做大型队列研究时从不询问产科病史。

And in fact, that inhibited genetic studies because people would do these large cohort studies and never ask about obstetric history.

如果没有记录，数据就不存在。

If it wasn't recorded, the data wasn't there.

有意思。

Interesting.

至于原因，当我们研究母体方面的遗传学时，子痫前期与子痫前期之间共享的最强遗传结构之一是原发性高血压，包括收缩压和舒张压。

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.

高血压的话，如果你有更高的遗传倾向，你患子痫前期的风险就更高。

Hypertension is, if you have a higher genetic disposition to that, you have a higher risk of preeclampsia.

在最早的全基因组关联研究中，针对子痫前期的母体研究，达到全基因组显著水平的主要发现，与高血压全基因组关联研究中的主要发现是一致的。

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.

所以我们确实知道，那些患上高血压或子痫前期的人，更有可能有潜在的高血压遗传倾向。

So we do know that folks who develop hypertension or preeclampsia are much more likely to have an underlying genetic disposition to hypertension.

所以这肯定就是为什么他们长期风险更高的原因之一，而怀孕会暴露这种倾向。

So that's definitely part of why they have a higher long term risk and pregnancy unmasks that predisposition.

还有一部分人认为，妊娠期高血压的暴露本身，可能会在原有遗传基础上，进一步增加未来的风险。

There's still a component of the exposure to the hypertensive pregnancy that people think may add on top of the underlying genetics to the future risks.

所以我觉得这是一个大家都在积极研究的方向，比如怀孕本身是否会增加风险？

So I think that's an active area of research that people are engaged in, like does the pregnancy itself increase the risk?

如果会，又是怎么增加的？

And if so, how?

当然，还有其他因素，比如社会因素，以及其他健康状况，这些都会影响那些风险。

And then of course, there's other factors like social factors, like otherwise, like other health conditions that contribute to those risks.

所以，长期疾病的风险是多因素共同作用的结果。

So it is a multifactorial contributor as to long term disease.

提醒我一下，你可能说过但我没听到，患有妊娠期糖尿病的女性，患2型糖尿病的风险也更高吗？

Remind me, you may have said this and I just missed it, do women who develop gestational diabetes also have a higher risk for type two diabetes?

这是有预测性的吗？

Is that predictive?

是的。

Yes.

有百分之五十的妊娠期糖尿病患者会发展成2型糖尿病。

So fifty percent of patients who have gestational diabetes will develop type two diabetes.

百分之五十？

Fifty percent?

有意思。

Interesting.

有没有做过干预研究？我知道这个研究很难做，因为需要很长时间，所以答案几乎肯定是没有，但就是针对那些患有妊娠期糖尿病的女性，然后积极管理她们，你知道，随机分组，一组用一种干预，另一组用另一种，看看能不能延迟或者完全避免2型糖尿病的发生？

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 could delay and or just outright avoid type two diabetes?

是的，我觉得建议是她们要经常随访做糖尿病筛查，同时也要充分告知她们可以做出哪些生活方式上的改变来降低患二型糖尿病的风险。

Yeah, I think 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 two diabetes.

我们知道，更健康的饮食、合适的体重和规律的运动都非常重要。

So we know that healthier diet and appropriate body weight and regular exercise all are very important there.

所以对于有妊娠糖尿病史的人来说，更要重视这些方面的指导，以降低风险。

So it's even more critical for folks who have a history of gestational diabetes to be counseled about about that to decrease their risk.

所以这就是你给女性的建议吗？

So is that sort of the message you're delivering to a woman?

因为作为医生，你的角色很特别，你在她和宝宝的健康中起着非常重要的作用。

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.

但一旦宝宝出生了，她就不再由你照顾了。

But once that baby's gone, she's...

你不再是负责照顾她的人。

You're not the one that gets to take care of her.

然而，你确实了解到了关于她的重要信息，因为正如你所说，你在她经历高度生理压力测试时看到了她，这让你对她未来的代谢健康和心血管疾病风险有了深刻的洞察。

And yet you learned something really profound about her because, as you said, you saw her during a very high physiologic stress test that gave you an enormous insight into what the rest of her life has in store for her vis a vis metabolic health, cardiovascular disease at a minimum.

顺便说一句，我们可能会发现还有其他疾病可以通过怀孕来预测。

I mean, by the way, we might discover that there are other diseases we're learning about that are predicted through pregnancy.

那么，高危产科或任何妇产科医生与患者的长期健康之间是什么关系呢？比如说，你的基因不是你的命运，但你需要我们真的需要积极管理这些事情。

So what is the relationship between high risk or any OBGYN and the long term health of the patient to say, Look, your genes are not your destiny, but you need to we need to really stay on top of managing these things aggressively.

而且，顺便说一句，你应该因为现代医学的特权而过上正常的生活，这在五十年前是不可能的。

And by the way, you you should live a normal life as a result of the privilege of modern medicine that we we wouldn't have been able to do this, you know, fifty years ago.

是的，我觉得咨询非常重要。

Yeah, I mean, I think the counseling is really important.

作为高危产科医生，你知道，一些普通妇产科医生可能会在患者怀孕期间以及妇科护理中见到她们，并与患者建立更类似初级保健的关系。

And as a high risk obstetrician, you know, some general OBGYNs might see a patient for their pregnancies and then also for their gyne care and have more of a primary care relationship with the patient.

而我们的高危产科实践，通常只有在患者再次怀孕时才会再见到她们。

With our high risk obstetric practice, we will only see the patient back in general if they have another pregnancy.

因此，将信息传递给初级保健提供者是非常关键的。

And so that transition to a primary care provider with that information transmitted is really essential.

而且我确实认为很多年轻患者，既要照顾孩子，往往在两次怀孕之间不会经常自我随访。

And I do think lots of patients who are young and taking care of kids and often don't follow-up a lot themselves between pregnancies.

所以强调拥有一个初级保健医生并持续跟进非常重要。

And so stressing the importance of having a primary care provider and following is really important.

但当然，我们也可以继续加强教育和沟通。

But certainly there could be, you know, we can continue to enhance like both education and the communication.

电子健康档案确实帮了一些忙，对吧？

I mean, electronic health records have helped some, right?

因为我们现在通常能看到记录，如果某人关注这些，他们就能了解发生了什么，但他们必须知道这很重要。

Because we can often see now like records and, you know, if somebody is tuned into that, they can they can get at what happened, but they have to know that it's important.

如果我们今天只做一件事，那就是让女性和她们的初级保健医生真正关注怀孕期间暴露出的问题，并利用这些信息进行积极的治疗和预防，那就算赢了。

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.

是的，当然。

Yeah, for sure.

好的。

Okay.

你有没有感觉到……

Do you have a sense of...

嗯，听起来在这方面的情况有点复杂，既有认识到的，也有没认识到的。

Well, I mean, it sounds like it's a bit of a mixed bag in terms of what's recognized there.

好的。

Okay.

那么，我还想问你另一个问题，就是剖腹产和顺产。

So the other thing I wanted to ask you about is C section versus vaginal.

现在的趋势是什么？

What are the trends?

各自的利弊是什么？

What are the trade offs?

在这个领域，我感觉听到了太多不同的说法。

This is an area where I feel like I have heard so many differing stories.

我都不知道哪个是真的。

I can't tell what's real.

那我们就来梳理一下已知的情况，同时也承认哪些是未知的。

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

那么，什么……

So what...

首先，我不……

First of all, I don't...

从历史的角度来看，我猜我们直到十九世纪末才开始做第一次剖腹产。

From a historical perspective, I assume it wasn't until the late eighteen hundreds we were doing the first cesarean sections.

我希望我们至少是等到有了现代麻醉剂之后才做的。

I hope we were at least waiting until we had modern anesthetics.

这些问题也都很好，但有些答案我也不太清楚。

These these are also good questions that I I I don't know all the answers to.

不过，即使在现在，世界上很多地方的人在分娩时仍然无法获得良好的手术干预，这确实会导致很多死产，尤其是在分娩过程中，以及长期的产妇并发症，比如瘘管和其他因产程延长引起的问题。

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, and that can really drive a lot of both stillbirths that people have during the intra partum phase and long term maternal complications, like fistulas and other complications from prolonged labor.

所以剖腹产确实是一种必要且有益的干预措施，因为不是每个宝宝都能顺产。

So C section is certainly a needed and helpful intervention because not every baby is going to deliver vaginally.

那我们是不是大概知道……

And do we just have a sense of...

再说，我也不指望你知道答案，所以别担心。

Again, and I don't expect you to know the answer to this, so don't worry.

考试不会考的。

Not on the boards.

史前时代，对吧，或者远古时代。

Prehistoric times, right, or ancestral times.

你知道，回到一千年前。

You know, go back a thousand years.

我们有没有概念，那时候死产的发生率是多少？

Do we have a sense of what the frequency was of a stillbirth?

而且死产是不是必然会导致产妇死亡？

And was the stillbirth necessarily going to lead to the maternal demise?

比如说，如果死胎取不出来，产妇就会因为感染而死，对吧？

Like, if you can't get a dead fetus out of a woman, she's going to die of an infection, correct?

是的，我觉得通常最终还是会娩出死胎的。

Yes, I think like I think you often will eventually deliver the demised fetus.

但是，你知道的。

But, you know.

但是，你就是排不出来。

But but you can't pass.

我的意思是，也许可以，但在我看来，总会留下一些胎盘或者死组织，对吧？

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?

我觉得这种情况不太可能发生，但稽留流产对患者来说肯定是有风险的。

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

好的。

Okay.

所以，剖腹产显然变得很重要了。

So, C sections have obviously become important.

关于这个，我们了解多少呢？我不知道该用什么词来形容，是发生率还是使用率，或者用其他什么指标来衡量美国分娩中顺产和剖腹产的比例，这个数字在过去五十年里是怎么变化的？

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 fifty years?

是的，这个比例大幅上升了，你知道的。

Yeah, it's dramatically increased, you know.

所以，我们从大概百分之十的剖腹产率，比如说，我脑子里没有确切的数字，到如今，在学术医疗中心，剖腹产率常常能达到百分之三十。

So we've gone from, you know, like ten percent C section rate, say, like, I don't have all the exact numbers in my head, to like, oftentimes practices have, in an academic medical center, like a thirty percent C section rate.

而且这是所有情况都算在内的，对吧？

And that's all comers, right?

你还要考虑到那些之前做过剖腹产的，以及那些因为某些原因不能顺产的……

You're like accounting for people who've had previous C sections and people who can't have a vaginal delivery by...

因为出于某种产科原因，顺产不安全。

Because it's not safe for whatever obstetric reason.

所以……

So...

但剖腹产率确实大幅上升了。

But it has increased increased dramatically.

那是什么导致了这三倍的增长呢？

And what is driving that three x increase?

我觉得有不同的因素。

I think there are different drivers.

现在的怀孕比以前风险更高了。

The pregnancies are higher risk than they used to.

一旦做过一次剖腹产，就更容易再做一次。

Once you have one C section, you're more likely to have another one.

患者的健康状况也很重要。

The health of the patient matters.

很多人认为，孕妇肥胖率上升，导致胎儿偏大或者产程进展不顺利的情况增多，从而增加了剖腹产的比例。

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.

我们以前不进行持续监测，也就是分娩过程中的胎儿监测，而现在大多数医院在活跃期都会持续监测胎儿。

We went from a time when we were not doing continuous monitoring, so fetal monitoring during labor, to where we monitor in most hospitals, the baby's being monitored during the active phase of labor continuously.

当胎心监护图显示不理想时，我们就会选择剖腹产。

And when the tracing is not reassuring, we move to a C section.

所以我觉得这是个复杂的问题。

So I think it's a complex issue to understand.

而且，现在有很多努力在尝试降低这个数字，或者避免它比现在更高。

And, you know, there is a lot of focus on trying to decrease that number or avoid it getting higher than it is now.

这是为什么呢？

Why is that?

为什么我们会担心剖腹产率太高呢？

Why would we be concerned if it's getting too high?

我觉得一个后果，当然不是唯一的后果，就是对于之前有过剖腹产，尤其是多次剖腹产的女性来说，下一次怀孕时胎盘异常的风险会更高，具体来说就是胎盘植入谱系疾病，也就是说胎盘在怀孕期间可能会异常侵入子宫，到了分娩的时候，胎盘不会在宝宝出生后自然脱落。

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

这是不是一旦做过剖腹产，下次剖腹产概率就会上升的主要原因，是因为胎盘的问题，还是因为阴道分娩用力时对筋膜的压力？

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 that would be required during the exertion of a vaginal delivery?

这里面有好几个不同的因素。

There's a couple of different things.

剖腹产其实有好几种不同的方式，指的是在子宫上切口的位置。

So there's a couple of different kinds of C section, so meaning where you cut on the uterus.

如果在子宫下段做横向切口，也就是低位横切口，那这个位置不是子宫肌肉最厚的部分。

So if you cut low down on the uterus in a transverse fashion, so that's called a low transverse C section, that is not in as muscular of a part of the uterus.

所以一般来说，下次怀孕尝试顺产被认为是比较安全的，旧切口在分娩过程中裂开的风险大约只有百分之一，甚至更低。

And so in general, it's thought that you are fairly safe to labor in a future pregnancy, with like a one percent risk or less than one percent that that old scar might come apart during labor.

这就是所谓的子宫破裂，显然是个紧急情况。

So that's called a uterine rupture, which is obviously an emergency.

那是外科急症。

That's a surgical emergency.

现在你明白了，对。

Now you're going, yeah.

不过，

However,

如果你之前做过子宫手术，比如因为大肌瘤切除过，或者之前做过我们所说的古典式剖宫产，就是子宫上竖着切的那种，那就会切到子宫的肌肉层。

if you have had prior surgery on your uterus, either because you had a big fibroid and you 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.

那种切口在分娩时更容易破裂。

And that type of incision is much more likely to rupture during labor.

据说做过古典式剖宫产的人，风险大约有百分之十。

They say like ten percent for someone who've had a classical C section.

那太高了，甚至……

Which is too high to Which is even

太高了。

too high.

所以我们说，这类人群不应该尝试顺产。

So we say folks in that group should not labor.

他们——抱歉。

They I'm sorry.

提醒我一下，当初为什么要在那两种切口之间做选择？

Remind me why the choice is made between those two incisions in the first place.

我们尽量做低位横切口剖腹产，对于足月产妇，几乎总是能做到。

We try to do a low transverse C section, section, and in term patients, you almost always can.

但如果需要早产分娩，比如，这是做古典式剖腹产最常见的原因之一。

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.

子宫还不够大，没有充分扩张，子宫下段还没发育好，你可能无法在子宫下段做切口，安全地让早产儿通过那里分娩。

The uterus is not big enough, that it expanded enough that the lower uterine segment is not developed, and you may not be able to make an incision down in the lower part of the urine segment and safely deliver the preterm baby through that.

所以如果太早产，我们常常不得不做古典式剖腹产。

So if it's too premature, we often have to do a classical C section.

有时候还有其他原因，比如手术比较复杂。

Sometimes there is other reasons like surgical complexity.

比如有的人做过多次剖腹产。

Someone's had multiple C sections.

疤痕组织。

Scar tissue.

对，疤痕组织绕不开，还有其他原因导致我们没法做低位横切口，但是……

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

你做这个手术的时候不进入腹膜，对吧？

And you're not entering the peritoneum when you do this, correct?

你都是在腹腔外操作的吗？

You're doing this all outside of the abdomen?

不是。

No.

是在腹腔内的。

It's in the abdomen.

是的。

You are.

你不会把筋膜分开，让子宫留在外面。

You don't separate the fascia and keep the uterus outside.

好的。

Okay.

当你……

When you...

好的。

Okay.

所以我在想有哪些情况是绝对不能做的。

So I'm trying to think of reasons where it was a nonnegotiable.

所以臀位分娩会……

So a breech delivery would...

你绝不会尝试经阴道分娩臀位胎儿，如果你……

You wouldn't ever try to deliver a breech vaginally if you...

我的意思是，我猜你，我们知道

Mean, I assume you We know

通常不会，因为最大的……

generally don't because the biggest...

ACOG的建议是我们通常不这样做。

The recommendation by ACOG is that we generally don't.

这是因为宝宝最大的部分是头部，而且最后出来。

And it's because the biggest part of the baby is the head and it comes last.

如果头部被卡住，也就是说宝宝身体出来了但头没出来，那非常危险。

And a head entrapment, meaning the rest of the baby comes out and then the head doesn't, very dangerous.

所以对于单胎，我们通常建议剖腹产。

So for a singleton, we generally recommend a C section.

如果宝宝是臀位，有机会在分娩前尝试转位。

If the baby is breeched, there's an opportunity to potentially turn, try to turn the baby before labor.

这叫做外倒转术。

That's called an external cephalic version.

所以有时候我们可以把宝宝转成头位，然后产妇就可以顺产了。

So sometimes we can turn the baby to cephalic, and then the patient can recover.

那怎么，

And how,

比如，在临产前几天做这个吗？

like, would do that in the days leading up to?

对，我们尽量在接近三十七周的时候做，因为如果产妇真的临产或者破水了，那就真的不行了。是的。

Yeah, we try to do it closer to thirty seven weeks because if somebody actually goes into labor or breaks their water, then then you really can't Yep.

再转宝宝就不行了。

Turn the baby anymore.

这个手术成功率有多高？

How successful is that procedure?

百分之五十。

Fifty percent.

我猜会很疼吧？

Painful, I'm guessing?